WorldWideScience

Sample records for testing molecular hypotheses

  1. Testing hypotheses in order

    OpenAIRE

    Paul R. Rosenbaum

    2008-01-01

    In certain circumstances, one wishes to test one hypothesis only if certain other hypotheses have been rejected. This ordering of hypotheses simplifies the task of controlling the probability of rejecting any true hypothesis. In an example from an observational study, a treated group is shown to be further from both of two control groups than the two control groups are from each other. Copyright 2008, Oxford University Press.

  2. Testing statistical hypotheses

    CERN Document Server

    Lehmann, E L

    2005-01-01

    The third edition of Testing Statistical Hypotheses updates and expands upon the classic graduate text, emphasizing optimality theory for hypothesis testing and confidence sets. The principal additions include a rigorous treatment of large sample optimality, together with the requisite tools. In addition, an introduction to the theory of resampling methods such as the bootstrap is developed. The sections on multiple testing and goodness of fit testing are expanded. The text is suitable for Ph.D. students in statistics and includes over 300 new problems out of a total of more than 760. E.L. Lehmann is Professor of Statistics Emeritus at the University of California, Berkeley. He is a member of the National Academy of Sciences and the American Academy of Arts and Sciences, and the recipient of honorary degrees from the University of Leiden, The Netherlands and the University of Chicago. He is the author of Elements of Large-Sample Theory and (with George Casella) he is also the author of Theory of Point Estimat...

  3. Phylemon 2.0: a suite of web-tools for molecular evolution, phylogenetics, phylogenomics and hypotheses testing.

    Science.gov (United States)

    Sánchez, Rubén; Serra, François; Tárraga, Joaquín; Medina, Ignacio; Carbonell, José; Pulido, Luis; de María, Alejandro; Capella-Gutíerrez, Salvador; Huerta-Cepas, Jaime; Gabaldón, Toni; Dopazo, Joaquín; Dopazo, Hernán

    2011-07-01

    Phylemon 2.0 is a new release of the suite of web tools for molecular evolution, phylogenetics, phylogenomics and hypotheses testing. It has been designed as a response to the increasing demand of molecular sequence analyses for experts and non-expert users. Phylemon 2.0 has several unique features that differentiates it from other similar web resources: (i) it offers an integrated environment that enables evolutionary analyses, format conversion, file storage and edition of results; (ii) it suggests further analyses, thereby guiding the users through the web server; and (iii) it allows users to design and save phylogenetic pipelines to be used over multiple genes (phylogenomics). Altogether, Phylemon 2.0 integrates a suite of 30 tools covering sequence alignment reconstruction and trimming; tree reconstruction, visualization and manipulation; and evolutionary hypotheses testing.

  4. Phylemon 2.0: a suite of web-tools for molecular evolution, phylogenetics, phylogenomics and hypotheses testing

    Science.gov (United States)

    Sánchez, Rubén; Serra, François; Tárraga, Joaquín; Medina, Ignacio; Carbonell, José; Pulido, Luis; de María, Alejandro; Capella-Gutíerrez, Salvador; Huerta-Cepas, Jaime; Gabaldón, Toni; Dopazo, Joaquín; Dopazo, Hernán

    2011-01-01

    Phylemon 2.0 is a new release of the suite of web tools for molecular evolution, phylogenetics, phylogenomics and hypotheses testing. It has been designed as a response to the increasing demand of molecular sequence analyses for experts and non-expert users. Phylemon 2.0 has several unique features that differentiates it from other similar web resources: (i) it offers an integrated environment that enables evolutionary analyses, format conversion, file storage and edition of results; (ii) it suggests further analyses, thereby guiding the users through the web server; and (iii) it allows users to design and save phylogenetic pipelines to be used over multiple genes (phylogenomics). Altogether, Phylemon 2.0 integrates a suite of 30 tools covering sequence alignment reconstruction and trimming; tree reconstruction, visualization and manipulation; and evolutionary hypotheses testing. PMID:21646336

  5. Systems Biology-Driven Hypotheses Tested In Vivo: The Need to Advancing Molecular Imaging Tools.

    Science.gov (United States)

    Verma, Garima; Palombo, Alessandro; Grigioni, Mauro; La Monaca, Morena; D'Avenio, Giuseppe

    2018-01-01

    Processing and interpretation of biological images may provide invaluable insights on complex, living systems because images capture the overall dynamics as a "whole." Therefore, "extraction" of key, quantitative morphological parameters could be, at least in principle, helpful in building a reliable systems biology approach in understanding living objects. Molecular imaging tools for system biology models have attained widespread usage in modern experimental laboratories. Here, we provide an overview on advances in the computational technology and different instrumentations focused on molecular image processing and analysis. Quantitative data analysis through various open source software and algorithmic protocols will provide a novel approach for modeling the experimental research program. Besides this, we also highlight the predictable future trends regarding methods for automatically analyzing biological data. Such tools will be very useful to understand the detailed biological and mathematical expressions under in-silico system biology processes with modeling properties.

  6. Testing statistical hypotheses of equivalence

    CERN Document Server

    Wellek, Stefan

    2010-01-01

    Equivalence testing has grown significantly in importance over the last two decades, especially as its relevance to a variety of applications has become understood. Yet published work on the general methodology remains scattered in specialists' journals, and for the most part, it focuses on the relatively narrow topic of bioequivalence assessment.With a far broader perspective, Testing Statistical Hypotheses of Equivalence provides the first comprehensive treatment of statistical equivalence testing. The author addresses a spectrum of specific, two-sided equivalence testing problems, from the

  7. Bayesian testing of constrained hypotheses

    NARCIS (Netherlands)

    Mulder, J.; Robertson, J; Kaptein, M

    2016-01-01

    Statistical hypothesis testing plays a central role in applied research to determine whether theories or expectations are supported by the data or not. Such expectations are often formulated using order constraints. For example an executive board may expect that sales representatives who wear a

  8. Data driven smooth tests for composite hypotheses

    NARCIS (Netherlands)

    Inglot, Tadeusz; Kallenberg, Wilbert C.M.; Ledwina, Teresa

    1997-01-01

    The classical problem of testing goodness-of-fit of a parametric family is reconsidered. A new test for this problem is proposed and investigated. The new test statistic is a combination of the smooth test statistic and Schwarz's selection rule. More precisely, as the sample size increases, an

  9. Going to the 'Dogs' to Test Hypotheses.

    Science.gov (United States)

    Kramm, Kenneth R.

    1982-01-01

    Describes an alternative method for using live animals in the classroom. A toy dog, the "Trail Tracker Hound Dog" (manufactured by CPG Products Corporation, Cincinnati, Ohio), is used to encourage development of such skills as observation, hypothesis testing, and collection and analysis of scientific data. (Author/JN)

  10. Parameter estimation and testing of hypotheses

    International Nuclear Information System (INIS)

    Fruhwirth, R.

    1996-01-01

    This lecture presents the basic mathematical ideas underlying the concept of random variable and the construction and analysis of estimators and test statistics. The material presented is based mainly on four books given in the references: the general exposition of estimators and test statistics follows Kendall and Stuart which is a comprehensive review of the field; the book by Eadie et al. contains selecting topics of particular interest to experimental physicist and a host of illuminating examples from experimental high-energy physics; for the presentation of numerical procedures, the Press et al. and the Thisted books have been used. The last section deals with estimation in dynamic systems. In most books the Kalman filter is presented in a Bayesian framework, often obscured by cumbrous notation. In this lecture, the link to classical least-squares estimators and regression models is stressed with the aim of facilitating the access to this less familiar topic. References are given for specific applications to track and vertex fitting and for extended exposition of these topics. In the appendix, the link between Bayesian decision rules and feed-forward neural networks is presented. (J.S.). 10 refs., 5 figs., 1 appendix

  11. Pearce element ratios: A paradigm for testing hypotheses

    Science.gov (United States)

    Russell, J. K.; Nicholls, Jim; Stanley, Clifford R.; Pearce, T. H.

    Science moves forward with the development of new ideas that are encapsulated by hypotheses whose aim is to explain the structure of data sets or to expand existing theory. These hypotheses remain conjecture until they have been tested. In fact, Karl Popper advocated that a scientist's job does not finish with the creation of an idea but, rather, begins with the testing of the related hypotheses. In Popper's [1959] advocation it is implicit that there be tools with which we can test our hypotheses. Consequently, the development of rigorous tests for conceptual models plays a major role in maintaining the integrity of scientific endeavor [e.g., Greenwood, 1989].

  12. Testing hypotheses for differences between linear regression lines

    Science.gov (United States)

    Stanley J. Zarnoch

    2009-01-01

    Five hypotheses are identified for testing differences between simple linear regression lines. The distinctions between these hypotheses are based on a priori assumptions and illustrated with full and reduced models. The contrast approach is presented as an easy and complete method for testing for overall differences between the regressions and for making pairwise...

  13. Mirror bootstrap method for testing hypotheses of one mean

    OpenAIRE

    Varvak, Anna

    2012-01-01

    The general philosophy for bootstrap or permutation methods for testing hypotheses is to simulate the variation of the test statistic by generating the sampling distribution which assumes both that the null hypothesis is true, and that the data in the sample is somehow representative of the population. This philosophy is inapplicable for testing hypotheses for a single parameter like the population mean, since the two assumptions are contradictory (e.g., how can we assume both that the mean o...

  14. Data-driven efficient score tests for deconvolution hypotheses

    NARCIS (Netherlands)

    Langovoy, M.

    2008-01-01

    We consider testing statistical hypotheses about densities of signals in deconvolution models. A new approach to this problem is proposed. We constructed score tests for the deconvolution density testing with the known noise density and efficient score tests for the case of unknown density. The

  15. Testing hypotheses involving Cronbach's alpha using marginal models

    NARCIS (Netherlands)

    Kuijpers, R.E.; van der Ark, L.A.; Croon, M.A.

    2013-01-01

    We discuss the statistical testing of three relevant hypotheses involving Cronbach's alpha: one where alpha equals a particular criterion; a second testing the equality of two alpha coefficients for independent samples; and a third testing the equality of two alpha coefficients for dependent

  16. The revelation effect: A meta-analytic test of hypotheses.

    Science.gov (United States)

    Aßfalg, André; Bernstein, Daniel M; Hockley, William

    2017-12-01

    Judgments can depend on the activity directly preceding them. An example is the revelation effect whereby participants are more likely to claim that a stimulus is familiar after a preceding task, such as solving an anagram, than without a preceding task. We test conflicting predictions of four revelation-effect hypotheses in a meta-analysis of 26 years of revelation-effect research. The hypotheses' predictions refer to three subject areas: (1) the basis of judgments that are subject to the revelation effect (recollection vs. familiarity vs. fluency), (2) the degree of similarity between the task and test item, and (3) the difficulty of the preceding task. We use a hierarchical multivariate meta-analysis to account for dependent effect sizes and variance in experimental procedures. We test the revelation-effect hypotheses with a model selection procedure, where each model corresponds to a prediction of a revelation-effect hypothesis. We further quantify the amount of evidence for one model compared to another with Bayes factors. The results of this analysis suggest that none of the extant revelation-effect hypotheses can fully account for the data. The general vagueness of revelation-effect hypotheses and the scarcity of data were the major limiting factors in our analyses, emphasizing the need for formalized theories and further research into the puzzling revelation effect.

  17. Testing Hypotheses About Glacial Cycles Against the Observational Record

    DEFF Research Database (Denmark)

    Kaufmann, Robert; Juselius, Katarina

    2013-01-01

    We estimate an identified cointegrated vector autoregression (CVAR) model of the climate system to test hypotheses about the physical mechanisms that may drive glacial cycles during the late Pleistocene. Results indicate that a permanent doubling of CO2 generates a 11.1oC rise in Antarctic...

  18. Cancer stem cell hypotheses: Impact on modern molecular

    Indian Academy of Sciences (India)

    basis for the so-called cancer stem cell (CSC) hypotheses. The first exact proof of CSC ... or less equal ability for tumour regeneration and repopulation. (Nowell 1976 .... Also, there are reports that the 'stemness' (stem-like properties) of brain.

  19. Testing evolutionary hypotheses for phenotypic divergence using landscape genetics.

    Science.gov (United States)

    Funk, W Chris; Murphy, Melanie A

    2010-02-01

    Understanding the evolutionary causes of phenotypic variation among populations has long been a central theme in evolutionary biology. Several factors can influence phenotypic divergence, including geographic isolation, genetic drift, divergent natural or sexual selection, and phenotypic plasticity. But the relative importance of these factors in generating phenotypic divergence in nature is still a tantalizing and unresolved problem in evolutionary biology. The origin and maintenance of phenotypic divergence is also at the root of many ongoing debates in evolutionary biology, such as the extent to which gene flow constrains adaptive divergence (Garant et al. 2007) and the relative importance of genetic drift, natural selection, and sexual selection in initiating reproductive isolation and speciation (Coyne & Orr 2004). In this issue, Wang & Summers (2010) test the causes of one of the most fantastic examples of phenotypic divergence in nature: colour pattern divergence among populations of the strawberry poison frog (Dendrobates pumilio) in Panama and Costa Rica (Fig. 1). This study provides a beautiful example of the use of the emerging field of landscape genetics to differentiate among hypotheses for phenotypic divergence. Using landscape genetic analyses, Wang & Summers were able to reject the hypotheses that colour pattern divergence is due to isolation-by-distance (IBD) or landscape resistance. Instead, the hypothesis left standing is that colour divergence is due to divergent selection, in turn driving reproductive isolation among populations with different colour morphs. More generally, this study provides a wonderful example of how the emerging field of landscape genetics, which has primarily been applied to questions in conservation and ecology, now plays an essential role in evolutionary research.

  20. Origin of honeycombs: Testing the hydraulic and case hardening hypotheses

    Science.gov (United States)

    Bruthans, Jiří; Filippi, Michal; Slavík, Martin; Svobodová, Eliška

    2018-02-01

    Cavernous weathering (cavernous rock decay) is a global phenomenon, which occurs in porous rocks around the world. Although honeycombs and tafoni are considered to be the most common products of this complex process, their origin and evolution are as yet not fully understood. The two commonly assumed formation hypotheses - hydraulic and case hardening - were tested to elucidate the origin of honeycombs on sandstone outcrops in a humid climate. Mechanical and hydraulic properties of the lips (walls between adjacent pits) and backwalls (bottoms of pits) of the honeycombs were determined via a set of established and novel approaches. While the case hardening hypothesis was not supported by the determinations of either tensile strength, drilling resistance or porosity, the hydraulic hypothesis was clearly supported by field measurements and laboratory tests. Fluorescein dye visualization of capillary zone, vapor zone, and evaporation front upon their contact, demonstrated that the evaporation front reaches the honeycomb backwalls under low water flow rate, while the honeycomb lips remain dry. During occasional excessive water flow events, however, the evaporation front may shift to the lips, while the backwalls become moist as a part of the capillary zone. As the zone of evaporation corresponds to the zone of potential salt weathering, it is the spatial distribution of the capillary and vapor zones which dictates whether honeycombs are created or the rock surface is smoothed. A hierarchical model of factors related to the hydraulic field was introduced to obtain better insights into the process of cavernous weathering.

  1. Testing competing hypotheses about single trial fMRI

    DEFF Research Database (Denmark)

    Hansen, Lars Kai; Purushotham, Archana; Kim, Seong-Ge

    2002-01-01

    We use a Bayesian framework to compute probabilities of competing hypotheses about functional activation based on single trial fMRI measurements. Within the framework we obtain a complete probabilistic picture of competing hypotheses, hence control of both type I and type II errors....

  2. Using Transcranial tDCS to test cognitive hypotheses

    Directory of Open Access Journals (Sweden)

    Nazbanou Nozari

    2014-04-01

    Full Text Available Transcranial Direct Current Stimulation (tDCS is used increasingly often for testing cognitive hypotheses. It is, however, often ignored that many assumptions regarding how the neural tissue reacts to stimulation have only been verified in the motor domain. Extrapolating these assumptions to the cognitive domain has a set of unique issues which, if ignored, can lead to incorrect interpretations. In this talk I will review a number of common pitfalls in using tDCS for testing a cognitive hypothesis, and discuss some solutions for better-controlled designs. I will address the following issues: 1- Making an incorrect assumption about the nature of the effect: It is often assumed that anodal stimulation has “excitatory” and cathodal stimulation has “inhibitory” effects. Results are then interpreted in light of this assumption. Obviously, if the assumption is incorrect, the interpretation of the results too will be incorrect. I will discuss how the effects of polarity can change as a function of a number of design parameters, and the dangers of making a priori assumptions about the direction of stimulation effects, especially when employing a new design. 2- Choosing an inappropriate montage: By definition, tDCS requires two electrodes, although we are often only interested in stimulating one brain region. Where the second (reference electrode is placed may not be of theoretical interest to us, but it can have serious consequences for our effects of interest. For one thing the path of the direct current changes as a function of where the reference electrode is placed. This affects the density of the current, as well as the regions that undergo stimulation. Moreover, the region directly under the reference electrode is very likely to be affected by stimulation. Therefore, sometimes the changes in behavior may be due to the unanticipated effects at the reference electrode site, as opposed to the hypothesized effects at the target electrode site

  3. Bayes Factor Approaches for Testing Interval Null Hypotheses

    NARCIS (Netherlands)

    Morey, Richard D.; Rouder, Jeffrey N.

    2011-01-01

    Psychological theories are statements of constraint. The role of hypothesis testing in psychology is to test whether specific theoretical constraints hold in data. Bayesian statistics is well suited to the task of finding supporting evidence for constraint, because it allows for comparing evidence

  4. Testing Multimodal Integration Hypotheses with Application to Schizophrenia Data

    DEFF Research Database (Denmark)

    Axelsen, Martin Christian; Bak, Nikolaj; Hansen, Lars Kai

    2015-01-01

    of the present paper is to propose a method for assessing these inter-modality dependencies. The approach is based on two permutations of an analyzed data set, each exploring different dependencies between and within modalities. The method was tested on the Kaggle MLSP 2014 Schizophrenia Classification Challenge...... data set which is composed of features from functional magnetic resonance imaging (MRI) and structural MRI. The results support the use of a permutation strategy for testing conditional dependencies between modalities in a multimodal classification problem....

  5. Ontological Analysis of Integrated Process Models: testing hypotheses

    Directory of Open Access Journals (Sweden)

    Michael Rosemann

    2001-11-01

    Full Text Available Integrated process modeling is achieving prominence in helping to document and manage business administration and IT processes in organizations. The ARIS framework is a popular example for a framework of integrated process modeling not least because it underlies the 800 or more reference models embedded in the world's most popular ERP package, SAP R/3. This paper demonstrates the usefulness of the Bunge-Wand-Weber (BWW representation model for evaluating modeling grammars such as those constituting ARIS. It reports some initial insights gained from pilot testing Green and Rosemann's (2000 evaluative propositions. Even when considering all five views of ARIS, modelers have problems representing business rules, the scope and boundary of systems, and decomposing models. However, even though it is completely ontologically redundant, users still find the function view useful in modeling.

  6. Black/White Differences in Adolescent Drug Use: A Test of Six Hypotheses

    Science.gov (United States)

    Rote, Sunshine M.; Taylor, John

    2014-01-01

    Six specific hypotheses have been developed to account for why Caucasians have higher rates of drug use compared to African-Americans. This article utilizes data from a South Florida-based community study of 893 young adults (1998-2002) to test these hypotheses. Specifically, Caucasians (1) initiate drug use at younger ages than African-Americans…

  7. A priori assumptions about characters as a cause of incongruence between molecular and morphological hypotheses of primate interrelationships.

    Science.gov (United States)

    Tornow, Matthew A; Skelton, Randall R

    2012-01-01

    When molecules and morphology produce incongruent hypotheses of primate interrelationships, the data are typically viewed as incompatible, and molecular hypotheses are often considered to be better indicators of phylogenetic history. However, it has been demonstrated that the choice of which taxa to include in cladistic analysis as well as assumptions about character weighting, character state transformation order, and outgroup choice all influence hypotheses of relationships and may positively influence tree topology, so that relationships between extant taxa are consistent with those found using molecular data. Thus, the source of incongruence between morphological and molecular trees may lie not in the morphological data themselves but in assumptions surrounding the ways characters evolve and their impact on cladistic analysis. In this study, we investigate the role that assumptions about character polarity and transformation order play in creating incongruence between primate phylogenies based on morphological data and those supported by multiple lines of molecular data. By releasing constraints imposed on published morphological analyses of primates from disparate clades and subjecting those data to parsimony analysis, we test the hypothesis that incongruence between morphology and molecules results from inherent flaws in morphological data. To quantify the difference between incongruent trees, we introduce a new method called branch slide distance (BSD). BSD mitigates many of the limitations attributed to other tree comparison methods, thus allowing for a more accurate measure of topological similarity. We find that releasing a priori constraints on character behavior often produces trees that are consistent with molecular trees. Case studies are presented that illustrate how congruence between molecules and unconstrained morphological data may provide insight into issues of polarity, transformation order, homology, and homoplasy.

  8. A criterion for testing hypotheses about the covariance function of a stationary Gaussian stochastic process

    OpenAIRE

    Kozachenko, Yuriy; Troshki, Viktor

    2015-01-01

    We consider a measurable stationary Gaussian stochastic process. A criterion for testing hypotheses about the covariance function of such a process using estimates for its norm in the space $L_p(\\mathbb {T}),\\,p\\geq1$, is constructed.

  9. Testing contingency hypotheses in budgetary research: An evaluation of the use of moderated regression analysis

    NARCIS (Netherlands)

    Hartmann, Frank G.H.; Moers, Frank

    1999-01-01

    In the contingency literature on the behavioral and organizational effects of budgeting, use of the Moderated Regression Analysis (MRA) technique is prevalent. This technique is used to test contingency hypotheses that predict interaction effects between budgetary and contextual variables. This

  10. A Bayesian decision procedure for testing multiple hypotheses in DNA microarray experiments.

    Science.gov (United States)

    Gómez-Villegas, Miguel A; Salazar, Isabel; Sanz, Luis

    2014-02-01

    DNA microarray experiments require the use of multiple hypothesis testing procedures because thousands of hypotheses are simultaneously tested. We deal with this problem from a Bayesian decision theory perspective. We propose a decision criterion based on an estimation of the number of false null hypotheses (FNH), taking as an error measure the proportion of the posterior expected number of false positives with respect to the estimated number of true null hypotheses. The methodology is applied to a Gaussian model when testing bilateral hypotheses. The procedure is illustrated with both simulated and real data examples and the results are compared to those obtained by the Bayes rule when an additive loss function is considered for each joint action and the generalized loss 0-1 function for each individual action. Our procedure significantly reduced the percentage of false negatives whereas the percentage of false positives remains at an acceptable level.

  11. Causal null hypotheses of sustained treatment strategies: What can be tested with an instrumental variable?

    Science.gov (United States)

    Swanson, Sonja A; Labrecque, Jeremy; Hernán, Miguel A

    2018-05-02

    Sometimes instrumental variable methods are used to test whether a causal effect is null rather than to estimate the magnitude of a causal effect. However, when instrumental variable methods are applied to time-varying exposures, as in many Mendelian randomization studies, it is unclear what causal null hypothesis is tested. Here, we consider different versions of causal null hypotheses for time-varying exposures, show that the instrumental variable conditions alone are insufficient to test some of them, and describe additional assumptions that can be made to test a wider range of causal null hypotheses, including both sharp and average causal null hypotheses. Implications for interpretation and reporting of instrumental variable results are discussed.

  12. Exaptation in human evolution: how to test adaptive vs exaptive evolutionary hypotheses.

    Science.gov (United States)

    Pievani, Telmo; Serrelli, Emanuele

    2011-01-01

    Palaeontologists, Stephen J. Gould and Elisabeth Vrba, introduced the term "ex-aptation" with the aim of improving and enlarging the scientific language available to researchers studying the evolution of any useful character, instead of calling it an "adaptation" by default, coming up with what Gould named an "extended taxonomy of fitness". With the extension to functional co-optations from non-adaptive structures ("spandrels"), the notion of exaptation expanded and revised the neo-Darwinian concept of "pre-adaptation" (which was misleading, for Gould and Vrba, suggesting foreordination). Exaptation is neither a "saltationist" nor an "anti-Darwinian" concept and, since 1982, has been adopted by many researchers in evolutionary and molecular biology, and particularly in human evolution. Exaptation has also been contested. Objections include the "non-operationality objection".We analyze the possible operationalization of this concept in two recent studies, and identify six directions of empirical research, which are necessary to test "adaptive vs. exaptive" evolutionary hypotheses. We then comment on a comprehensive survey of literature (available online), and on the basis of this we make a quantitative and qualitative evaluation of the adoption of the term among scientists who study human evolution. We discuss the epistemic conditions that may have influenced the adoption and appropriate use of exaptation, and comment on the benefits of an "extended taxonomy of fitness" in present and future studies concerning human evolution.

  13. Use of Computational Modeling to Evaluate Hypotheses About the Molecular and Cellular Mechanisms of Bystander Effects

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yuchao; Conolly, Rory B; Andersen, Melvin E.

    2006-11-21

    This report describes the development of a computational systems biology approach to evaluate the hypotheses of molecular and cellular mechanisms of adaptive response to low dose ionizing radiation. Our concept is that computational models of signaling pathways can be developed and linked to biologically based dose response models to evaluate the underlying molecular mechanisms which lead to adaptive response. For development of quantitatively accurate, predictive models, it will be necessary to describe tissues consisting of multiple cell types where the different types each contribute in their own way to the overall function of the tissue. Such a model will probably need to incorporate not only cell type-specific data but also spatial information on the architecture of the tissue and on intercellular signaling. The scope of the current model was more limited. Data obtained in a number of different biological systems were synthesized to describe a chimeric, “average” population cell. Biochemical signaling pathways involved in sensing of DNA damage and in the activation of cell cycle checkpoint controls and the apoptotic path were also included. As with any computational modeling effort, it was necessary to develop these simplified initial descriptions (models) that can be iteratively refined. This preliminary model is a starting point which, with time, can evolve to a level of refinement where large amounts of detailed biological information are synthesized and a capability for robust predictions of dose- and time-response behaviors is obtained.

  14. Delinquency and Peer Acceptance in Adolescence: A Within-Person Test of Moffitt's Hypotheses

    Science.gov (United States)

    Rulison, Kelly L.; Kreager, Derek A.; Osgood, D. Wayne

    2014-01-01

    We tested 2 hypotheses derived from Moffitt's (1993) taxonomic theory of antisocial behavior, both of which are central to her explanation for the rise in delinquency during adolescence. We tested whether persistently delinquent individuals become more accepted by their peers during adolescence and whether individuals who abstain from delinquent…

  15. Preliminary testing of flow-ecology hypotheses developed for the GCP LCC region

    Science.gov (United States)

    Brewer, Shannon K.; Davis, Mary

    2014-01-01

    The Ecological Limits of Hydrological Alteration (ELOHA) framework calls for the development of flow-ecology hypotheses to support protection of the flow regime from ecologically harmful alteration due to human activities. As part of a larger instream flow project for the Gulf Coast Prairie Landscape Conservation Cooperative (GCP LCC), regional flow-ecology hypotheses were developed for fish, mussels, birds, and riparian vegetation (Davis and Brewer 20141). The objective of this study was to assess the usefulness of existing ecological and hydrological data to test these hypotheses or others that may be developed in the future. Several databases related to biological collections and hydrologic data from Oklahoma, Texas, and Louisiana were compiled. State fish-community data from Oklahoma and Louisiana were summarized and paired with existing USGS gage data having at least a 40-year period of record that could be separated into reference and current conditions for comparison. The objective of this study was not to conduct exhaustive analyses of these data, the hypotheses, or analyses interpretation, but rather to use these data to determine if existing data were adequate to statistically test the regional flow-ecology hypotheses. The regional flow-ecology hypotheses were developed for the GCP LCC by a committee chaired by Shannon Brewer and Mary Davis (Davis and Brewer 2014). Existing data were useful for informing the hypotheses and suggest support for some hypotheses, but also highlight the need for additional testing and development as some results contradicted hypotheses. Results presented here suggest existing data are adequate to support some flow-ecology hypotheses; however, lack of sampling effort reported with the fish collections and the need for ecoregion-specific analyses suggest more data would be beneficial to analyses in some ecoregions. Additional fish sampling data from Texas and Louisiana will be available for future analyses and may ameliorate

  16. Vestigial Biological Structures: A Classroom-Applicable Test of Creationist Hypotheses

    Science.gov (United States)

    Senter, Phil; Ambrocio, Zenis; Andrade, Julia B.; Foust, Katanya K.; Gaston, Jasmine E.; Lewis, Ryshonda P.; Liniewski, Rachel M.; Ragin, Bobby A.; Robinson, Khanna L.; Stanley, Shane G.

    2015-01-01

    Lists of vestigial biological structures in biology textbooks are so short that some young-Earth creationist authors claim that scientists have lost confidence in the existence of vestigial structures and can no longer identify any verifiable ones. We tested these hypotheses with a method that is easily adapted to biology classes. We used online…

  17. Bullying Victimization and Adolescent Self-Harm: Testing Hypotheses from General Strain Theory

    Science.gov (United States)

    Hay, Carter; Meldrum, Ryan

    2010-01-01

    Self-harm is widely recognized as a significant adolescent social problem, and recent research has begun to explore its etiology. Drawing from Agnew's (1992) social psychological strain theory of deviance, this study considers this issue by testing three hypotheses about the effects of traditional and cyber bullying victimization on deliberate…

  18. Learned Helplessness and Depression in a Clinical Population: A Test of Two Behavioral Hypotheses

    Science.gov (United States)

    And Others; Price, Kenneth P.

    1978-01-01

    This study was undertaken to extend the learned helplessness phenomenon to a clinical population and to test the competing hypotheses of Seligman and Lewinsohn. 96 male hospitalized psychiatric and medical patients were randomly assigned to one of four experimental conditions. Results replicate the learned helplessness phenomenon in a group of…

  19. Testing Alternative Hypotheses Regarding the Association between Behavioral Inhibition and Language Development in Toddlerhood

    Science.gov (United States)

    Watts, Ashley K. Smith; Patel, Deepika; Corley, Robin P.; Friedman, Naomi P.; Hewitt, John K.; Robinson, JoAnn L.; Rhee, Soo H.

    2014-01-01

    Studies have reported an inverse association between language development and behavioral inhibition or shyness across childhood, but the direction of this association remains unclear. This study tested alternative hypotheses regarding this association in a large sample of toddlers. Data on behavioral inhibition and expressive and receptive…

  20. Interactions between domestic and export markets for softwood lumber and plywood: tests of six hypotheses.

    Science.gov (United States)

    David R. Darr

    1981-01-01

    Price formation in export markets and available data on export and domestic markets are discussed. The results of tests of several hypotheses about interactions between domestic and export markets are presented and interpreted from the standpoints of trade promotion and trade policy.

  1. Automatic Bayes Factors for Testing Equality- and Inequality-Constrained Hypotheses on Variances.

    Science.gov (United States)

    Böing-Messing, Florian; Mulder, Joris

    2018-05-03

    In comparing characteristics of independent populations, researchers frequently expect a certain structure of the population variances. These expectations can be formulated as hypotheses with equality and/or inequality constraints on the variances. In this article, we consider the Bayes factor for testing such (in)equality-constrained hypotheses on variances. Application of Bayes factors requires specification of a prior under every hypothesis to be tested. However, specifying subjective priors for variances based on prior information is a difficult task. We therefore consider so-called automatic or default Bayes factors. These methods avoid the need for the user to specify priors by using information from the sample data. We present three automatic Bayes factors for testing variances. The first is a Bayes factor with equal priors on all variances, where the priors are specified automatically using a small share of the information in the sample data. The second is the fractional Bayes factor, where a fraction of the likelihood is used for automatic prior specification. The third is an adjustment of the fractional Bayes factor such that the parsimony of inequality-constrained hypotheses is properly taken into account. The Bayes factors are evaluated by investigating different properties such as information consistency and large sample consistency. Based on this evaluation, it is concluded that the adjusted fractional Bayes factor is generally recommendable for testing equality- and inequality-constrained hypotheses on variances.

  2. Estimating the Proportion of True Null Hypotheses in Multiple Testing Problems

    Directory of Open Access Journals (Sweden)

    Oluyemi Oyeniran

    2016-01-01

    Full Text Available The problem of estimating the proportion, π0, of the true null hypotheses in a multiple testing problem is important in cases where large scale parallel hypotheses tests are performed independently. While the problem is a quantity of interest in its own right in applications, the estimate of π0 can be used for assessing or controlling an overall false discovery rate. In this article, we develop an innovative nonparametric maximum likelihood approach to estimate π0. The nonparametric likelihood is proposed to be restricted to multinomial models and an EM algorithm is also developed to approximate the estimate of π0. Simulation studies show that the proposed method outperforms other existing methods. Using experimental microarray datasets, we demonstrate that the new method provides satisfactory estimate in practice.

  3. Using potential performance theory to test five hypotheses about meta-attribution.

    Science.gov (United States)

    Trafimow, David; Hunt, Gayle; Rice, Stephen; Geels, Kasha

    2011-01-01

    Based on I. Kant's (1991) distinction between perfect and imperfect duties and the attribution literature pertaining to that distinction, the authors proposed and tested 5 hypotheses about meta-attribution. More specifically, violations of perfect duties have been shown to arouse both more negative affect and stronger correspondent inferences than do violations of imperfect duties (e.g., D. Trafimow, I. K. Bromgard, K. A. Finlay, & T. Ketelaar, 2005). But when it comes to making meta-attributions-that is, guessing the attributions others would make-is the affect differential an advantage or a disadvantage? In addition to the null hypothesis of no effect, the authors proposed and tested additional hypotheses about how negative affect might increase or decrease the effectiveness of people's meta-attribution strategies and how even if there is no effect on strategy effectiveness, negative affect could increase or decrease the consistencies with which these strategies could be used.

  4. Can MOND type hypotheses be tested in a free fall laboratory environment?

    Science.gov (United States)

    Das, Saurya; Patitsas, S. N.

    2013-05-01

    The extremely small accelerations of objects required for the onset of modified Newtonian dynamics, or modified Newtonian dynamics (MOND), makes testing the hypothesis in conventional terrestrial laboratories virtually impossible. This is due to the large background acceleration of Earth, which is transmitted to the acceleration of test objects within an apparatus. We show, however, that it may be possible to test MOND-type hypotheses with experiments using a conventional apparatus capable of tracking very small accelerations of its components but performed in locally inertial frames such as artificial satellites and other freely falling laboratories. For example, experiments involving an optical interferometer or a torsion balance in these laboratories would show nonlinear dynamics and displacement amplitudes larger than expected. These experiments may also be able to test potential violations of the strong equivalence principle by MOND and to distinguish between its two possible interpretations (modified inertia and modified gravity).

  5. Risk, innovation, electricity infrastructure and construction cost overruns: Testing six hypotheses

    International Nuclear Information System (INIS)

    Sovacool, Benjamin K.; Gilbert, Alex; Nugent, Daniel

    2014-01-01

    This study investigates the frequency and magnitude of cost and time overruns occurring during the construction of 401 electricity projects built between 1936 and 2014 in 57 countries. In aggregate, these projects required approximately $820 billion in investment, and amounted to 325,515 MW of installed capacity and 8495 km of transmission lines. We use this sample of projects to test six hypotheses about construction cost overruns related to (1) diseconomies of scale, (2) project delays, (3) technological learning, (4) regulation and markets, (5) decentralization and modularity, and (6) normalization of results to scale. We find that nuclear reactors are the riskiest technology in terms of mean cost escalation as a percentage of budget and frequency; that hydroelectric dams stand apart for their mean cost escalation in total dollars; that many of the hypotheses grounded in the literature appear wrong; and that financing, partnerships, modularity, and accountability may have more to do with overruns than technology. - Highlights: • Many hypotheses about construction overruns grounded in the literature appear wrong. • Nuclear reactors are the most prone to cost overruns as a percentage of budget and frequency. • Hydroelectric dams stand apart for their mean cost escalation in total dollars. • Solar and wind energy systems are least at risk to cost overruns

  6. Human female orgasm as evolved signal: a test of two hypotheses.

    Science.gov (United States)

    Ellsworth, Ryan M; Bailey, Drew H

    2013-11-01

    We present the results of a study designed to empirically test predictions derived from two hypotheses regarding human female orgasm behavior as an evolved communicative trait or signal. One hypothesis tested was the female fidelity hypothesis, which posits that human female orgasm signals a woman's sexual satisfaction and therefore her likelihood of future fidelity to a partner. The other was sire choice hypothesis, which posits that women's orgasm behavior signals increased chances of fertilization. To test the two hypotheses of human female orgasm, we administered a questionnaire to 138 females and 121 males who reported that they were currently in a romantic relationship. Key predictions of the female fidelity hypothesis were not supported. In particular, orgasm was not associated with female sexual fidelity nor was orgasm associated with male perceptions of partner sexual fidelity. However, faked orgasm was associated with female sexual infidelity and lower male relationship satisfaction. Overall, results were in greater support of the sire choice signaling hypothesis than the female fidelity hypothesis. Results also suggest that male satisfaction with, investment in, and sexual fidelity to a mate are benefits that favored the selection of orgasmic signaling in ancestral females.

  7. Testing multiple statistical hypotheses resulted in spurious associations: a study of astrological signs and health.

    Science.gov (United States)

    Austin, Peter C; Mamdani, Muhammad M; Juurlink, David N; Hux, Janet E

    2006-09-01

    To illustrate how multiple hypotheses testing can produce associations with no clinical plausibility. We conducted a study of all 10,674,945 residents of Ontario aged between 18 and 100 years in 2000. Residents were randomly assigned to equally sized derivation and validation cohorts and classified according to their astrological sign. Using the derivation cohort, we searched through 223 of the most common diagnoses for hospitalization until we identified two for which subjects born under one astrological sign had a significantly higher probability of hospitalization compared to subjects born under the remaining signs combined (P<0.05). We tested these 24 associations in the independent validation cohort. Residents born under Leo had a higher probability of gastrointestinal hemorrhage (P=0.0447), while Sagittarians had a higher probability of humerus fracture (P=0.0123) compared to all other signs combined. After adjusting the significance level to account for multiple comparisons, none of the identified associations remained significant in either the derivation or validation cohort. Our analyses illustrate how the testing of multiple, non-prespecified hypotheses increases the likelihood of detecting implausible associations. Our findings have important implications for the analysis and interpretation of clinical studies.

  8. On the use of uncertainty analyses to test hypotheses regarding deterministic model predictions of environmental processes

    International Nuclear Information System (INIS)

    Gilbert, R.O.; Bittner, E.A.; Essington, E.H.

    1995-01-01

    This paper illustrates the use of Monte Carlo parameter uncertainty and sensitivity analyses to test hypotheses regarding predictions of deterministic models of environmental transport, dose, risk and other phenomena. The methodology is illustrated by testing whether 238 Pu is transferred more readily than 239+240 Pu from the gastrointestinal (GI) tract of cattle to their tissues (muscle, liver and blood). This illustration is based on a study wherein beef-cattle grazed for up to 1064 days on a fenced plutonium (Pu)-contaminated arid site in Area 13 near the Nevada Test Site in the United States. Periodically, cattle were sacrificed and their tissues analyzed for Pu and other radionuclides. Conditional sensitivity analyses of the model predictions were also conducted. These analyses indicated that Pu cattle tissue concentrations had the largest impact of any model parameter on the pdf of predicted Pu fractional transfers. Issues that arise in conducting uncertainty and sensitivity analyses of deterministic models are discussed. (author)

  9. The evolution of parental care in insects: A test of current hypotheses.

    Science.gov (United States)

    Gilbert, James D J; Manica, Andrea

    2015-05-01

    Which sex should care for offspring is a fundamental question in evolution. Invertebrates, and insects in particular, show some of the most diverse kinds of parental care of all animals, but to date there has been no broad comparative study of the evolution of parental care in this group. Here, we test existing hypotheses of insect parental care evolution using a literature-compiled phylogeny of over 2000 species. To address substantial uncertainty in the insect phylogeny, we use a brute force approach based on multiple random resolutions of uncertain nodes. The main transitions were between no care (the probable ancestral state) and female care. Male care evolved exclusively from no care, supporting models where mating opportunity costs for caring males are reduced-for example, by caring for multiple broods-but rejecting the "enhanced fecundity" hypothesis that male care is favored because it allows females to avoid care costs. Biparental care largely arose by males joining caring females, and was more labile in Holometabola than in Hemimetabola. Insect care evolution most closely resembled amphibian care in general trajectory. Integrating these findings with the wealth of life history and ecological data in insects will allow testing of a rich vein of existing hypotheses. © 2015 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

  10. The evolution of parental care in insects: A test of current hypotheses

    Science.gov (United States)

    Gilbert, James D J; Manica, Andrea

    2015-01-01

    Which sex should care for offspring is a fundamental question in evolution. Invertebrates, and insects in particular, show some of the most diverse kinds of parental care of all animals, but to date there has been no broad comparative study of the evolution of parental care in this group. Here, we test existing hypotheses of insect parental care evolution using a literature-compiled phylogeny of over 2000 species. To address substantial uncertainty in the insect phylogeny, we use a brute force approach based on multiple random resolutions of uncertain nodes. The main transitions were between no care (the probable ancestral state) and female care. Male care evolved exclusively from no care, supporting models where mating opportunity costs for caring males are reduced—for example, by caring for multiple broods—but rejecting the “enhanced fecundity” hypothesis that male care is favored because it allows females to avoid care costs. Biparental care largely arose by males joining caring females, and was more labile in Holometabola than in Hemimetabola. Insect care evolution most closely resembled amphibian care in general trajectory. Integrating these findings with the wealth of life history and ecological data in insects will allow testing of a rich vein of existing hypotheses. PMID:25825047

  11. Confidence Intervals: From tests of statistical significance to confidence intervals, range hypotheses and substantial effects

    Directory of Open Access Journals (Sweden)

    Dominic Beaulieu-Prévost

    2006-03-01

    Full Text Available For the last 50 years of research in quantitative social sciences, the empirical evaluation of scientific hypotheses has been based on the rejection or not of the null hypothesis. However, more than 300 articles demonstrated that this method was problematic. In summary, null hypothesis testing (NHT is unfalsifiable, its results depend directly on sample size and the null hypothesis is both improbable and not plausible. Consequently, alternatives to NHT such as confidence intervals (CI and measures of effect size are starting to be used in scientific publications. The purpose of this article is, first, to provide the conceptual tools necessary to implement an approach based on confidence intervals, and second, to briefly demonstrate why such an approach is an interesting alternative to an approach based on NHT. As demonstrated in the article, the proposed CI approach avoids most problems related to a NHT approach and can often improve the scientific and contextual relevance of the statistical interpretations by testing range hypotheses instead of a point hypothesis and by defining the minimal value of a substantial effect. The main advantage of such a CI approach is that it replaces the notion of statistical power by an easily interpretable three-value logic (probable presence of a substantial effect, probable absence of a substantial effect and probabilistic undetermination. The demonstration includes a complete example.

  12. Studies of brain and cognitive maturation through childhood and adolescence: a strategy for testing neurodevelopmental hypotheses.

    Science.gov (United States)

    Luna, B; Sweeney, J A

    2001-01-01

    Although neurodevelopmental models of schizophrenia are now widely accepted, there is minimal direct human evidence of dysmaturation in schizophrenia to support this theory. This is especially the case regarding maturational changes during late childhood and adolescence, which immediately precede the typical age of onset of the disorder. By integrating new noninvasive methods of functional magnetic resonance imaging with techniques of developmental cognitive neuroscience, it is now possible to begin systematic research programs to directly test hypotheses of neurodevelopmental abnormalities in schizophrenia. In this article, we describe strategies for characterizing developmental changes taking place during the critical period of adolescence that can elucidate dysmaturation processes in schizophrenia. We emphasize the need for studies characterizing normal development before examining at-risk or clinical populations, and the potential value of using neurobehavioral and neuroimaging approaches to directly characterize the dysmaturation associated with schizophrenia.

  13. How do trees die? A test of the hydraulic failure and carbon starvation hypotheses

    Science.gov (United States)

    Sevanto, Sanna; Mcdowell, Nate G; Dickman, L Turin; Pangle, Robert; Pockman, William T

    2014-01-01

    Despite decades of research on plant drought tolerance, the physiological mechanisms by which trees succumb to drought are still under debate. We report results from an experiment designed to separate and test the current leading hypotheses of tree mortality. We show that piñon pine (Pinus edulis) trees can die of both hydraulic failure and carbon starvation, and that during drought, the loss of conductivity and carbohydrate reserves can also co-occur. Hydraulic constraints on plant carbohydrate use determined survival time: turgor loss in the phloem limited access to carbohydrate reserves, but hydraulic control of respiration prolonged survival. Our data also demonstrate that hydraulic failure may be associated with loss of adequate tissue carbohydrate content required for osmoregulation, which then promotes failure to maintain hydraulic integrity. PMID:23730972

  14. Science from evaluation: testing hypotheses about differential effects of three youth-focused suicide prevention trainings.

    Science.gov (United States)

    Coleman, Daniel; Del Quest, Aisling

    2015-01-01

    As part of an evaluation component of a youth suicide prevention, a quasi-experimental repeated measures design tested hypotheses about two brief suicide prevention gatekeeper trainings (Question, Persuade, Refer [QPR] and RESPONSE) and one longer suicide intervention skills training (Applied Suicide Intervention Skills Training [ASIST]). All three trainings showed large changes in prevention attitudes and self-efficacy, largely maintained at follow-up. ASIST trainees had large increases in asking at-risk youth about suicide at follow-up. Convergent with other research, modeling and role-play in training are crucial to increased prevention behaviors. Practice and research implications are discussed, including social work roles in suicide prevention and research.

  15. Age and motives for volunteering: testing hypotheses derived from socioemotional selectivity theory.

    Science.gov (United States)

    Okun, Morris A; Schultz, Amy

    2003-06-01

    Following a meta-analysis of the relations between age and volunteer motives (career, understanding, enhancement, protective, making friends, social, and values), the authors tested hypotheses derived from socioemotional selectivity theory regarding the effects of age on these volunteer motives. The Volunteer Functions Inventory was completed by 523 volunteers from 2 affiliates of the International Habitat for Humanity. Multiple regression analyses revealed, as predicted, that as age increases, career and understanding volunteer motivation decrease and social volunteer motivation increases. Contrary to expectations, age did not contribute to the prediction of enhancement, protective, and values volunteer motivations and the relation between age and making friends volunteer motivation was nonlinear. The results were discussed in the context of age-differential and age-similarity perspectives on volunteer motivation.

  16. Factors that encourage females to pursue physical science careers: Testing five common hypotheses

    Science.gov (United States)

    Hazari, Zahra; Potvin, Geoff; Lock, Robynne M.; Lung, Florin; Sadler, Philip M.; Sonnert, Gerhard

    2012-03-01

    There are many hypotheses regarding factors that may encourage female students to pursue careers in the physical sciences. Using Propensity Score Matching (PSM) on national data (n=7505) drawn from the Persistence Research in Science and Engineering (PRiSE) project, we test five commonly held beliefs including having a single-sex physics class, having a female physics teacher, having female scientist guest speakers in physics class, discussing the work of women scientists in physics class, and discussing the under-representation of women in physics class. The effect of these experiences is compared for female students who are matched on several factors, including parental education, prior science/math interests, and academic background, thereby controlling for the effect of many confounding variables.

  17. Can manipulations of cognitive load be used to test evolutionary hypotheses?

    Science.gov (United States)

    Barrett, H Clark; Frederick, David A; Haselton, Martie G; Kurzban, Robert

    2006-09-01

    D. DeSteno, M. Y. Bartlett, J. Braverman, and P. Salovey proposed that if sex-differentiated responses to infidelity are evolved, then they should be automatic, and therefore cognitive load should not attenuate them. DeSteno et al. found smaller sex differences in response to sexual versus emotional infidelity among participants under cognitive load, an effect interpreted as evidence against the evolutionary hypothesis. This logic is faulty. Cognitive load probably affects mechanisms involved in simulating infidelity experiences, thus seriously challenging the usefulness of cognitive load manipulations in testing hypotheses involving simulation. The method also entails the assumption that evolved jealousy mechanisms are necessarily automatic, an assumption not supported by theory or evidence. Regardless of how the jealousy debate is eventually settled, cognitive load manipulations cannot rule out the operation of evolved mechanisms. ((c) 2006 APA, all rights reserved).

  18. Do macroeconomic contractions induce or 'harvest' suicides? A test of competing hypotheses.

    Science.gov (United States)

    Gemmill, Alison; Falconi, April; Karasek, Deborah; Hartig, Terry; Anderson, Elizabeth; Catalano, Ralph

    2015-11-01

    Researchers often invoke a mortality displacement or 'harvesting' mechanism to explain mortality patterns, such that those with underlying health vulnerabilities die sooner than expected in response to environmental phenomena, such as heat waves, cold spells and air pollution. It is unclear if this displacement mechanism might also explain observed increases in suicide following economic contraction, or if suicides are induced in persons otherwise unlikely to engage in self-destructive behaviour. Here, we test two competing hypotheses explaining an observed increase in suicides following unemployment-induction or displacement. We apply time series methods to monthly suicide and unemployment data from Sweden for the years 2000-2011. Tests are conducted separately for working age (20-64 years old) men and women as well as older (aged 65 years and older) men and women. Displacement appeared among older men and women; an unexpected rise in unemployment predicted an increase in suicides 6 months later, followed by a significant decrease 8 months later. Induction appeared among working age men, but not among working age women; an unexpected rise in unemployment predicted an increase in suicides 4-6 months later. Displacement and induction both appear to have operated following unexpected labour market contractions in Sweden, though with different population segments. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  19. Over the top: Experiment and the testing of hypotheses in the search for the top quark

    Science.gov (United States)

    Staley, Kent Wade

    1998-07-01

    This study presents a historical account of experiments, performed by the Collider Detector at Fermilab (CDF) collaboration, which led to the discovery of the top quark, and a discussion of philosophical issues raised by that episode. The historical discussion is based on published and unpublished documents and oral history interviews, and is presented in two parts: First, the formation of the collaboration and construction of the detector are described. The activities of the collaborators during the period of detector construction are described in terms of the development of resources for a general experimental programme. Second, the development of the means of analyzing the data for the top quark search is described, particularly aspects of the analysis that were disputed. The hypothesis that collaboration researchers have come to regard the social process of resolving disputes as a matter of methodological importance is suggested. The philosophical discussion of the experiment employs the hierarchy of models approach of Patrick Suppes and Deborah Mayo in order to examine the logic of hypothesis testing and draw some conclusions regarding the nature of scientific evidence. In an extension of an argument presented by Peter Achinstein, the account of hypothesis testing given by hypothetico-deductivist philosophers such as Karl Popper and R. B. Braithwaite is examined in light of the reasoning employed in the top search, and is found wanting. The prediction based on the hypothesis being tested in the top search is found to have been inferred inductively from the experimental data. Finally, a discussion is presented of tuning on the signal, a form of bias in the testing of hypotheses. The proscription of this form of bias resembles John Worrall's requirement of use novelty, but is shown instead to serve the aim of devising a test of the hypothesis that is severe, in the sense articulated by Deborah Mayo. It is shown that the evaluation of evidence claims, as it

  20. Violent media exposure, aggression and CU traits in adolescence: Testing the selection and socialization hypotheses.

    Science.gov (United States)

    Rydell, Ann-Margret

    2016-10-01

    We investigated the role of exposure to violent action for later aggression and for later callous-unemotional traits in a sample of Swedish adolescents (N = 77-85), testing the selection and socialization hypotheses. Adolescents reported on violent delinquency and on callous-unemotional (CU) traits at age 15, on their media habits at age 16 and on reactive and proactive aggression and CU traits at age 18. The socialization hypothesis was supported with regard to aggression, that is, violent delinquency did not affect consumption of violent action, but controlling for violent delinquency, consumption of violent action added to proactive aggression and, marginally, to reactive aggression. The selection hypothesis was supported with regard to CU traits, that is, high levels of CU traits predicted frequent consumption of violent action, but consumption of violent action did not affect later levels of CU traits. Frequent violent media use was associated with later aggression. The associations between CU traits and violent media need further study. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  1. Testing Adaptive Hypotheses of Convergence with Functional Landscapes: A Case Study of Bone-Cracking Hypercarnivores

    Science.gov (United States)

    Tseng, Zhijie Jack

    2013-01-01

    Morphological convergence is a well documented phenomenon in mammals, and adaptive explanations are commonly employed to infer similar functions for convergent characteristics. I present a study that adopts aspects of theoretical morphology and engineering optimization to test hypotheses about adaptive convergent evolution. Bone-cracking ecomorphologies in Carnivora were used as a case study. Previous research has shown that skull deepening and widening are major evolutionary patterns in convergent bone-cracking canids and hyaenids. A simple two-dimensional design space, with skull width-to-length and depth-to-length ratios as variables, was used to examine optimized shapes for two functional properties: mechanical advantage (MA) and strain energy (SE). Functionality of theoretical skull shapes was studied using finite element analysis (FEA) and visualized as functional landscapes. The distribution of actual skull shapes in the landscape showed a convergent trend of plesiomorphically low-MA and moderate-SE skulls evolving towards higher-MA and moderate-SE skulls; this is corroborated by FEA of 13 actual specimens. Nevertheless, regions exist in the landscape where high-MA and lower-SE shapes are not represented by existing species; their vacancy is observed even at higher taxonomic levels. Results highlight the interaction of biomechanical and non-biomechanical factors in constraining general skull dimensions to localized functional optima through evolution. PMID:23734244

  2. Celebrities: From Teachers to Friends : A Test of Two Hypotheses on the Adaptiveness of Celebrity Gossip.

    Science.gov (United States)

    De Backer, Charlotte J S; Nelissen, Mark; Vyncke, Patrick; Braeckman, Johan; McAndrew, Francis T

    2007-12-01

    In this paper we present two compatible hypotheses to explain interest in celebrity gossip. The Learning Hypothesis explains interest in celebrity gossip as a by-product of an evolved mechanism useful for acquiring fitness-relevant survival information. The Parasocial Hypothesis sees celebrity gossip as a diversion of this mechanism, which leads individuals to misperceive celebrities as people who are part of their social network. Using two preliminary studies, we tested our predictions. In a survey with 838 respondents and in-depth interviews with 103 individuals, we investigated how interest in celebrity gossip was related to several dimensions of the participants' social lives. In support of the Learning Hypothesis, age proved to be a strong predictor of interest in celebrities. In partial support of the Parasocial Hypothesis, media exposure, but not social isolation, was a strong predictor of interest in celebrities. The preliminary results support both theories, indicate that across our life span celebrities move from being teachers to being friends, and open up a list of future research opportunities.

  3. Testing adaptive hypotheses of convergence with functional landscapes: a case study of bone-cracking hypercarnivores.

    Directory of Open Access Journals (Sweden)

    Zhijie Jack Tseng

    Full Text Available Morphological convergence is a well documented phenomenon in mammals, and adaptive explanations are commonly employed to infer similar functions for convergent characteristics. I present a study that adopts aspects of theoretical morphology and engineering optimization to test hypotheses about adaptive convergent evolution. Bone-cracking ecomorphologies in Carnivora were used as a case study. Previous research has shown that skull deepening and widening are major evolutionary patterns in convergent bone-cracking canids and hyaenids. A simple two-dimensional design space, with skull width-to-length and depth-to-length ratios as variables, was used to examine optimized shapes for two functional properties: mechanical advantage (MA and strain energy (SE. Functionality of theoretical skull shapes was studied using finite element analysis (FEA and visualized as functional landscapes. The distribution of actual skull shapes in the landscape showed a convergent trend of plesiomorphically low-MA and moderate-SE skulls evolving towards higher-MA and moderate-SE skulls; this is corroborated by FEA of 13 actual specimens. Nevertheless, regions exist in the landscape where high-MA and lower-SE shapes are not represented by existing species; their vacancy is observed even at higher taxonomic levels. Results highlight the interaction of biomechanical and non-biomechanical factors in constraining general skull dimensions to localized functional optima through evolution.

  4. Testing hypotheses that link wood anatomy to cavitation resistance and hydraulic conductivity in the genus Acer.

    Science.gov (United States)

    Lens, Frederic; Sperry, John S; Christman, Mairgareth A; Choat, Brendan; Rabaey, David; Jansen, Steven

    2011-05-01

    • Vulnerability to cavitation and conductive efficiency depend on xylem anatomy. We tested a large range of structure-function hypotheses, some for the first time, within a single genus to minimize phylogenetic 'noise' and maximize detection of functionally relevant variation. • This integrative study combined in-depth anatomical observations using light, scanning and transmission electron microscopy of seven Acer taxa, and compared these observations with empirical measures of xylem hydraulics. • Our results reveal a 2 MPa range in species' mean cavitation pressure (MCP). MCP was strongly correlated with intervessel pit structure (membrane thickness and porosity, chamber depth), weakly correlated with pit number per vessel, and not related to pit area per vessel. At the tissue level, there was a strong correlation between MCP and mechanical strength parameters, and some of the first evidence is provided for the functional significance of vessel grouping and thickenings on inner vessel walls. In addition, a strong trade-off was observed between xylem-specific conductivity and MCP. Vessel length and intervessel wall characteristics were implicated in this safety-efficiency trade-off. • Cavitation resistance and hydraulic conductivity in Acer appear to be controlled by a very complex interaction between tissue, vessel network and pit characteristics. © 2010 The Authors. New Phytologist © 2010 New Phytologist Trust.

  5. Computer-mediated communication and interpersonal attraction: an experimental test of two explanatory hypotheses.

    Science.gov (United States)

    Antheunis, Marjolijn L; Valkenburg, Patti M; Peter, Jochen

    2007-12-01

    The aims of this study were (a) to investigate the influence of computer-mediated communication (CMC) on interpersonal attraction and (b) to examine two underlying processes in the CMC-interpersonal attraction relationship. We identified two variables that may mediate the influence of CMC on interpersonal attraction: self-disclosure and direct questioning. Focusing on these potential mediating variables, we tested two explanatory hypotheses: the CMC-induced direct questioning hypothesis and the CMC-induced self-disclosure hypothesis. Eighty-one cross-sex dyads were randomly assigned to one of three experimental conditions: text-only CMC, visual CMC, and face-to-face communication. We did not find a direct effect of CMC on interpersonal attraction. However, we did find two positive indirect effects of text-only CMC on interpersonal attraction: text-only CMC stimulated both self-disclosure and direct questioning, both of which in turn enhanced interpersonal attraction. Results are discussed in light of uncertainty reduction theory and CMC theories.

  6. Testing competing hypotheses for chronology and intensity of lesser scaup molt during winter and spring migration

    Science.gov (United States)

    Anteau, M.J.; Anteau, A.C.E.; Afton, A.D.

    2011-01-01

    We examined chronology and intensity of molt and their relationships to nutrient reserves (lipid and protein) of Lesser Scaup (Aythya affinis) to test predictions of two competing hypotheses. The "staggered cost" hypothesis states that contour-feather molt is nutritionally costly and should not occur during nutritionally costly periods of the annual cycle unless adequate nutrients are available. The "breeding plumage" hypothesis states that prealternate molt must be complete prior to nesting, regardless of nutrient availability. Males and females were completing prebasic molt during winter (Louisiana) and had similar molt intensities. Females underwent prealternate molt during spring migration (Illinois and Minnesota) and prebreeding (Manitoba) periods; 53% and 93% of females were in moderate to heavy molt in Minnesota and Manitoba, respectively, despite experiencing other substantial nutritional costs. Intensity of prealternate molt was not correlated with lipid reserves even though females, on average, were nutritionally stressed. Molt intensity was not negatively correlated with protein reserves at any location. Chronology and intensity of prealternate molt varied little and were not temporally staggered from other nutritionally costly events. Prealternate molt did not influence nutrient reserves, and nutrient reserves likely were not the ultimate factor influencing chronology or intensity of prealternate molt of females. We surmise that nutrients required for prealternate molt come from exogenous sources and that the "staggered cost" hypothesis does not explain chronology of prealternate molt in female Lesser Scaup; rather, it appears that molt must be complete prior to nesting, consistent with the "breeding plumage" hypothesis. ?? The Cooper Ornithological Society 2011.

  7. Factors that affect the physical science career interest of female students: Testing five common hypotheses

    Science.gov (United States)

    Hazari, Zahra; Potvin, Geoff; Lock, Robynne M.; Lung, Florin; Sonnert, Gerhard; Sadler, Philip M.

    2013-12-01

    There are many hypotheses regarding factors that may encourage female students to pursue careers in the physical sciences. Using multivariate matching methods on national data drawn from the Persistence Research in Science and Engineering (PRiSE) project (n=7505), we test the following five commonly held beliefs regarding what factors might impact females’ physical science career interest: (i) having a single-sex physics class, (ii) having a female physics teacher, (iii) having female scientist guest speakers in physics class, (iv) discussing the work of female scientists in physics class, and (v) discussing the underrepresentation of women in physics class. The effect of these experiences on physical science career interest is compared for female students who are matched on several factors, including prior science interests, prior mathematics interests, grades in science, grades in mathematics, and years of enrollment in high school physics. No significant effects are found for single-sex classes, female teachers, female scientist guest speakers, and discussing the work of female scientists. However, discussions about women’s underrepresentation have a significant positive effect.

  8. Testing competing hypotheses for chronology and intensity of lesser scaup molt during winter and spring migration

    Science.gov (United States)

    Anteau, Michael J.; Anteau, Andrea C.E.; Afton, Alan D.

    2011-01-01

    We examined chronology and intensity of molt and their relationships to nutrient reserves (lipid and protein) of Lesser Scaup (Aythya affinisK/i>) to test predictions of two competing hypotheses. The "staggered cost" hypothesis states that contour-feather molt is nutritionally costly and should not occur during nutritionally costly periods of the annual cycle unless adequate nutrients are available. The "breeding plumage" hypothesis states that prealternate molt must be complete prior to nesting, regardless of nutrient availability. Males and females were completing prebasic molt during winter (Louisiana) and had similar molt intensities. Females underwent prealternate molt during spring migration (Illinois and Minnesota) and prebreeding (Manitoba) periods; 53% and 93% of females were in moderate to heavy molt in Minnesota and Manitoba, respectively, despite experiencing other substantial nutritional costs. Intensity of prealternate molt was not correlated with lipid reserves even though females, on average, were nutritionally stressed. Molt intensity was not negatively correlated with protein reserves at any location. Chronology and intensity of prealternate molt varied little and were not temporally staggered from other nutritionally costly events. Prealternate molt did not influence nutrient reserves, and nutrient reserves likely were not the ultimate factor influencing chronology or intensity of prealternate molt of females. We surmise that nutrients required for prealternate molt come from exogenous sources and that the "staggered cost" hypothesis does not explain chronology of prealternate molt in female Lesser Scaup; rather, it appears that molt must be complete prior to nesting, consistent with the "breeding plumage" hypothesis.

  9. Basal tissue structure in the earliest euconodonts: Testing hypotheses of developmental plasticity in euconodont phylogeny

    Science.gov (United States)

    Dong, X.-P.; Donoghue, P.C.J.; Repetski, J.E.

    2005-01-01

    The hypothesis that conodonts are vertebrates rests solely on evidence of soft tissue anatomy. This has been corroborated by microstructural, topological and developmental evidence of homology between conodont and vertebrate hard tissues. However, these conclusions have been reached on the basis of evidence from highly derived euconodont taxa and the degree to which they are representative of plesiomorphic euconodonts remains an open question. Furthermore, the range of variation in tissue types comprising the euconodont basal body has been used to establish a hypothesis of developmental plasticity early in the phylogeny of the clade, and a model of diminishing potentiality in the evolution of development systems. The microstructural fabrics of the basal tissues of the earliest euconodonts (presumed to be the most plesiomorphic) are examined to test these two hypotheses. It is found that the range of microstructural variation observed hitherto was already apparent among plesiomorphic euconodonts. Thus, established histological data are representative of the most plesiomorphic euconodonts. However, although there is evidence of a range in microstructural fabrics, these are compatible with the dentine tissue system alone, and the degree of variation is compatible with that seen in clades of comparable diversity. ?? The Palaeontological Association.

  10. 3D tooth microwear texture analysis in fishes as a test of dietary hypotheses of durophagy

    Science.gov (United States)

    Purnell, Mark A.; Darras, Laurent P. G.

    2016-03-01

    differentiate between fishes with different diets even when they range widely in size, habitat, and in the structure of their trophic apparatus. The approach thus has great potential as an additional tool for dietary analysis in extant fishes, and for testing dietary hypotheses in ancient and extinct species.

  11. 3D tooth microwear texture analysis in fishes as a test of dietary hypotheses of durophagy

    International Nuclear Information System (INIS)

    Purnell, Mark A; Darras, Laurent P G

    2016-01-01

    differentiate between fishes with different diets even when they range widely in size, habitat, and in the structure of their trophic apparatus. The approach thus has great potential as an additional tool for dietary analysis in extant fishes, and for testing dietary hypotheses in ancient and extinct species. (paper)

  12. Kinetics of cancer: a method to test hypotheses of genetic causation

    Directory of Open Access Journals (Sweden)

    Lipkin Steven M

    2005-12-01

    Full Text Available Abstract Background Mouse studies have recently compared the age-onset patterns of cancer between different genotypes. Genes associated with earlier onset are tentatively assigned a causal role in carcinogenesis. These standard analyses ignore the great amount of information about kinetics contained in age-onset curves. We present a method for analyzing kinetics that measures quantitatively the causal role of candidate genes in cancer progression. We use our method to demonstrate a clear association between somatic mutation rates of different DNA mismatch repair (MMR genotypes and the kinetics of cancer progression. Methods Most experimental studies report age-onset curves as the fraction diagnosed with tumors at each age for each group. We use such data to estimate smoothed survival curves, then measure incidence rates at each age by the slope of the fitted curve divided by the fraction of mice that remain undiagnosed for tumors at that age. With the estimated incidence curves, we compare between different genotypes the median age of cancer onset and the acceleration of cancer, which is the rate of increase in incidence with age. Results The direction of change in somatic mutation rate between MMR genotypes predicts the direction of change in the acceleration of cancer onset in all 7 cases (p ˜ 0.008, with the same result for the association between mutation rate and the median age of onset. Conclusion Many animal experiments compare qualitatively the onset curves for different genotypes. If such experiments were designed to analyze kinetics, the research could move to the next stage in which the mechanistic consequences of particular genetic pathways are related to the dynamics of carcinogenesis. The data we analyzed here were not collected to test mechanistic and quantitative hypotheses about kinetics. Even so, a simple reanalysis revealed significant insights about how DNA repair genotypes affect separately the age of onset and the

  13. Serial Learning Process: Test of Chaining, Position, and Dual-Process Hypotheses

    Science.gov (United States)

    Giurintano, S. L.

    1973-01-01

    The chaining, position, and dual-process hypotheses of serial learning (SL) as well as serial recall, reordering, and relearning of paired-associate learning were examined to establish learning patterns. Results provide evidence for dual-process hypothesis. (DS)

  14. Using Bioinformatics to Develop and Test Hypotheses: E. coli-Specific Virulence Determinants

    Directory of Open Access Journals (Sweden)

    Joanna R. Klein

    2012-09-01

    Full Text Available Bioinformatics, the use of computer resources to understand biological information, is an important tool in research, and can be easily integrated into the curriculum of undergraduate courses. Such an example is provided in this series of four activities that introduces students to the field of bioinformatics as they design PCR based tests for pathogenic E. coli strains. A variety of computer tools are used including BLAST searches at NCBI, bacterial genome searches at the Integrated Microbial Genomes (IMG database, protein analysis at Pfam and literature research at PubMed. In the process, students also learn about virulence factors, enzyme function and horizontal gene transfer. Some or all of the four activities can be incorporated into microbiology or general biology courses taken by students at a variety of levels, ranging from high school through college. The activities build on one another as they teach and reinforce knowledge and skills, promote critical thinking, and provide for student collaboration and presentation. The computer-based activities can be done either in class or outside of class, thus are appropriate for inclusion in online or blended learning formats. Assessment data showed that students learned general microbiology concepts related to pathogenesis and enzyme function, gained skills in using tools of bioinformatics and molecular biology, and successfully developed and tested a scientific hypothesis.

  15. Educational Transitions in Israel: A Test of the Industrialization and Credentialism Hypotheses.

    Science.gov (United States)

    Shavit, Yossi; Kraus, Vered

    1990-01-01

    Explores the industrialization and credentialism hypotheses and predictions of educational attainment levels. Finds the effects of the father's education and occupation were stable for those attending school in the 1940s, 1950s, and 1960s. Notes that the effects of ethnicity declined in the transition from primary to secondary school. (NL)

  16. INFLUENCES ON AND FROM THE SEGMENTATION OF NETWORKS - HYPOTHESES AND TESTS

    NARCIS (Netherlands)

    BAERVELDT, C; SNIJDERS, T

    This article discusses (a) the influence of network structure on the diffusion of (new) cultural behavior within the network and (b) the influence of external events, especially of social programs, on the diffusion of (new) cultural behavior, and on the network structure. Hypotheses are formulated

  17. The Association between Relational Aggression and Perceived Popularity in Early Adolescence: A Test of Competing Hypotheses

    Science.gov (United States)

    Gangel, Meghan J.; Keane, Susan P.; Calkins, Susan D.; Shanahan, Lilly; O'Brien, Marion

    2017-01-01

    This study examined two competing hypotheses regarding the moderators of the association between relational aggression and peer status in early adolescence. The "mitigation relational aggression" hypothesis examined whether positive social behaviors reduced the negative effects of relational aggression, thus amplifying the association…

  18. The Ranschburg Effect: Tests of the Guessing-Bias and Proactive Interference Hypotheses

    Science.gov (United States)

    Walsh, Michael F.; Schwartz, Marian

    1977-01-01

    The guessing-bias and proactive interference hypotheses of the Ranschburg Effect were investigated by giving three groups different instructions as to guessing during recall. Results failed to support the prediction that the effect should be reduced or eliminated on shift trials. Neither hypothesis received significant support. (CHK)

  19. Mechanistic Mathematical Modeling Tests Hypotheses of the Neurovascular Coupling in fMRI.

    Directory of Open Access Journals (Sweden)

    Karin Lundengård

    2016-06-01

    Full Text Available Functional magnetic resonance imaging (fMRI measures brain activity by detecting the blood-oxygen-level dependent (BOLD response to neural activity. The BOLD response depends on the neurovascular coupling, which connects cerebral blood flow, cerebral blood volume, and deoxyhemoglobin level to neuronal activity. The exact mechanisms behind this neurovascular coupling are not yet fully investigated. There are at least three different ways in which these mechanisms are being discussed. Firstly, mathematical models involving the so-called Balloon model describes the relation between oxygen metabolism, cerebral blood volume, and cerebral blood flow. However, the Balloon model does not describe cellular and biochemical mechanisms. Secondly, the metabolic feedback hypothesis, which is based on experimental findings on metabolism associated with brain activation, and thirdly, the neurotransmitter feed-forward hypothesis which describes intracellular pathways leading to vasoactive substance release. Both the metabolic feedback and the neurotransmitter feed-forward hypotheses have been extensively studied, but only experimentally. These two hypotheses have never been implemented as mathematical models. Here we investigate these two hypotheses by mechanistic mathematical modeling using a systems biology approach; these methods have been used in biological research for many years but never been applied to the BOLD response in fMRI. In the current work, model structures describing the metabolic feedback and the neurotransmitter feed-forward hypotheses were applied to measured BOLD responses in the visual cortex of 12 healthy volunteers. Evaluating each hypothesis separately shows that neither hypothesis alone can describe the data in a biologically plausible way. However, by adding metabolism to the neurotransmitter feed-forward model structure, we obtained a new model structure which is able to fit the estimation data and successfully predict new

  20. Attachment and parental divorce: a test of the diffusion and sensitive period hypotheses.

    Science.gov (United States)

    Fraley, R Chris; Heffernan, Marie E

    2013-09-01

    One of the assumptions of attachment theory is that disruptions in parental relationships are prospectively related to insecure attachment patterns in adulthood. The majority of research that has evaluated this hypothesis, however, has been based on retrospective reports of the quality of relationships with parents-research that is subject to retrospective biases. In the present research, the authors examined the impact of parental divorce-an event that can be assessed relatively objectively-on attachment patterns in adulthood across two samples. The data indicate that parental divorce has selective rather than diffuse implications for insecure attachment. Namely, parental divorce was more strongly related to insecure relationships with parents in adulthood than insecure relationships with romantic partners or friends. In addition, parental insecurity was most pronounced when parental divorce took place in early childhood. This finding is consistent with hypotheses about sensitive periods in attachment development.

  1. ITSSOIN Hypotheses

    NARCIS (Netherlands)

    Anheier, H.K.; Krlev, G.; Preuss, S.; Mildenberger, G.; Bekkers, R.H.F.P.; Brink Lund, A.

    2014-01-01

    This report brings together findings from the first ITSSOIN project working steps to formulate empirically testable hypotheses on the impact of the third sector and social innovation – in particular regarding the role of the third sector in generating social innovation but also with reference to

  2. Teaching the Fluctuation Test "In Silico" by Using Mutate: A Program to Distinguish between the Adaptive and Spontaneous Mutation Hypotheses

    Science.gov (United States)

    Carvajal-Rodriguez, Antonio

    2012-01-01

    Mutate is a program developed for teaching purposes to impart a virtual laboratory class for undergraduate students of Genetics in Biology. The program emulates the so-called fluctuation test whose aim is to distinguish between spontaneous and adaptive mutation hypotheses in bacteria. The plan is to train students in certain key multidisciplinary…

  3. What drove reversions to quadrupedality in ornithischian dinosaurs? Testing hypotheses using centre of mass modelling.

    Science.gov (United States)

    Maidment, Susannah C R; Henderson, Donald M; Barrett, Paul M

    2014-11-01

    The exceptionally rare transition to quadrupedalism from bipedal ancestors occurred on three independent occasions in ornithischian dinosaurs. The possible driving forces behind these transitions remain elusive, but several hypotheses-including the development of dermal armour and the expansion of head size and cranial ornamentation-have been proposed to account for this major shift in stance. We modelled the position of the centre of mass (CoM) in several exemplar ornithischian taxa and demonstrate that the anterior shifts in CoM position associated with the development of an enlarged skull ornamented with horns and frills for display/defence may have been one of the drivers promoting ceratopsian quadrupedality. A posterior shift in CoM position coincident with the development of extensive dermal armour in thyreophorans demonstrates this cannot have been a primary causative mechanism for quadrupedality in this clade. Quadrupedalism developed in response to different selective pressures in each ornithischian lineage, indicating different evolutionary pathways to convergent quadrupedal morphology.

  4. Testing Biological Hypotheses with Embodied Robots: Adaptations, Accidents, and By-Products in the Evolution of Vertebrates

    OpenAIRE

    Roberts, Sonia F.; Hirokawa, Jonathan; Rosenblum, Hannah G.; Sakhtah, Hassan; Gutierrez, Andres A.; Porter, Marianne E.; Long, John H.

    2014-01-01

    Evolutionary robotics allows biologists to test hypotheses about extinct animals. In our case, we modeled some of the first vertebrates, jawless fishes, in order to study the evolution of the trait after which vertebrates are named: vertebrae. We tested the hypothesis that vertebrae are an adaptation for enhanced feeding and fleeing performance. We created a population of autonomous embodied robots, Preyro, in which the number of vertebrae, N, were free to evolve. In addition, two other trait...

  5. Testing Hypotheses on Risk Factors for Scientific Misconduct via Matched-Control Analysis of Papers Containing Problematic Image Duplications.

    Science.gov (United States)

    Fanelli, Daniele; Costas, Rodrigo; Fang, Ferric C; Casadevall, Arturo; Bik, Elisabeth M

    2018-02-19

    It is commonly hypothesized that scientists are more likely to engage in data falsification and fabrication when they are subject to pressures to publish, when they are not restrained by forms of social control, when they work in countries lacking policies to tackle scientific misconduct, and when they are male. Evidence to test these hypotheses, however, is inconclusive due to the difficulties of obtaining unbiased data. Here we report a pre-registered test of these four hypotheses, conducted on papers that were identified in a previous study as containing problematic image duplications through a systematic screening of the journal PLoS ONE. Image duplications were classified into three categories based on their complexity, with category 1 being most likely to reflect unintentional error and category 3 being most likely to reflect intentional fabrication. We tested multiple parameters connected to the hypotheses above with a matched-control paradigm, by collecting two controls for each paper containing duplications. Category 1 duplications were mostly not associated with any of the parameters tested, as was predicted based on the assumption that these duplications were mostly not due to misconduct. Categories 2 and 3, however, exhibited numerous statistically significant associations. Results of univariable and multivariable analyses support the hypotheses that academic culture, peer control, cash-based publication incentives and national misconduct policies might affect scientific integrity. No clear support was found for the "pressures to publish" hypothesis. Female authors were found to be equally likely to publish duplicated images compared to males. Country-level parameters generally exhibited stronger effects than individual-level parameters, because developing countries were significantly more likely to produce problematic image duplications. This suggests that promoting good research practices in all countries should be a priority for the international

  6. Does functional trait diversity predict aboveground biomass and productivity of tropical forests? Testing three alternative hypotheses

    NARCIS (Netherlands)

    Finegan, B.; Pena Claros, M.; Silva de Oliveira, A.; Ascarrunz, N.; Bret-Harte, M.S.; Carreño Rocabado, I.G.; Casanoves, F.; Diaz, S.; Eguiguren Velepucha, P.; Fernandez, F.; Licona, J.C.; Lorenzo, L.; Salgado Negret, B.; Vaz, M.; Poorter, L.

    2014-01-01

    1. Tropical forests are globally important, but it is not clear whether biodiversity enhances carbon storage and sequestration in them. We tested this relationship focusing on components of functional trait biodiversity as predictors. 2. Data are presented for three rain forests in Bolivia, Brazil

  7. Does functional trait diversity predict aboveground biomass and productivity of tropical forests? Testing three alternative hypotheses

    NARCIS (Netherlands)

    Finegan, B.; Peña Claros, M.; Oliviera, de A.; Alarcón, A.; Ascarrunz, N.; Bret-Harte, M.S.; Carreño-Rocabado, G.; Casanoves, F.; Díaz, S.; Eguiguren Velepucha, P.; Fernandez, F.; Licona, J.C.; Lorenzo, L.; Salgado Negret, B.; Vaz, M.; Poorter, L.

    2015-01-01

    Tropical forests are globally important, but it is not clear whether biodiversity enhances carbon storage and sequestration in them. We tested this relationship focusing on components of functional trait biodiversity as predictors. Data are presented for three rain forests in Bolivia, Brazil and

  8. Does functional trait diversity predict aboveground biomass and productivity of tropical forests? Testing three alternative hypotheses

    OpenAIRE

    Finegan, B.; Pena Claros, M.; Silva de Oliveira, A.; Ascarrunz, N.; Bret-Harte, M.S.; Carreño Rocabado, I.G.; Casanoves, F.; Diaz, S.; Eguiguren Velepucha, P.; Fernandez, F.; Licona, J.C.; Lorenzo, L.; Salgado Negret, B.; Vaz, M.; Poorter, L.

    2014-01-01

    1. Tropical forests are globally important, but it is not clear whether biodiversity enhances carbon storage and sequestration in them. We tested this relationship focusing on components of functional trait biodiversity as predictors. 2. Data are presented for three rain forests in Bolivia, Brazil and Costa Rica. Initial above-ground biomass and biomass increments of survivors, recruits and survivors + recruits (total) were estimated for trees ≥10 cm d.b.h. in 62 and 21 1.0-ha plots, respecti...

  9. Evaluating the attractiveness of a new light rail extension: Testing simple change and displacement change hypotheses.

    Science.gov (United States)

    Werner, Carol M; Brown, Barbara B; Tribby, Calvin P; Tharp, Doug; Flick, Kristi; Miller, Harvey J; Smith, Ken R; Jensen, Wyatt

    2016-01-01

    Many communities in the United States have been adding new light rail to bus-predominant public transit systems. However, there is disagreement as to whether opening light rail lines attracts new ridership or merely draws ridership from existing transit users. We study a new light rail line in Salt Lake City, Utah, USA, which is part of a complete street redevelopment. We utilize a pre-test post-test control group quasi-experimental design to test two different measures of ridership change. The first measure is calculated from stops along the light rail route; the second assumes that nearby bus stops might be displaced by the rail and calculates ridership change with those stops included as baseline. Both the simple measure (transit use changes on the complete street light rail corridor) and the "displacement" measure (transit use changes in the one-quarter mile catchment areas around new light rail stops) showed significant ( p rail bus users. In particular, the displacement analysis discredits a common challenge that when a new light rail line opens, most passengers are simply former bus riders whose routes were canceled in favor of light rail. The study suggests that light rail services can attract additional ridership to public transit systems. In addition, although pre-post control-group designs require time and effort, this project underscores the benefits of such quasi-experimental designs in terms of the strength of the inferences that can be drawn about the impacts of new transit infrastructure and services.

  10. Testing hypotheses about management to enhance habitat for feeding birds in a freshwater wetland.

    Science.gov (United States)

    Lindegarth, M; Chapman, M G

    2001-08-01

    The level of water was manipulated in a freshwater wetland, with the aim of enhancing abundances of benthic animals and, ultimately, improving habitat for feeding birds (Japanese Snipe, Gallinago hardwickii). We tested whether these actions had the predicted and desired effects on benthic animals, by contrasting changes in two managed locations to one control location which was left unmanipulated. The number of taxa and abundances of chironomids decreased strongly and significantly in the manipulated locations, while the abundance of oligochaetes appeared to vary in a seasonal manner. Temporal variability of the structure and composition of assemblages was also increased in manipulated locations. Such effects have previously been suggested to indicate stress in benthic assemblages. Therefore, in contrast to what was predicted, managerial actions made benthic fauna less abundant and thus, less suitable as habitat for feeding birds. Several general lessons can be learned from these results. (1) Effects of managerial actions like these are difficult to predict a priori and can only be reliably evaluated with an experimental framework. (2) Because abundances of animals vary naturally, evaluations of managerial actions must include appropriate spatial replication. (3) Sampling at hierarchical temporal scales is important, because abundances of animals may vary in an unpredictable manner at short temporal scales and because changes in temporal variability may be a symptom of stress. (4) Combined use of uni- and multivariate techniques provides a comprehensive set of tools to assess the effects of restoration and creation of new habitats. Finally, these results emphasise the need for clear predictions about desired outcomes and specific experimental plans about how to test whether the desired results were achieved, before managerial actions are taken. Although this is often very difficult to achieve in real situations, it is necessary for practices of management to evolve

  11. Testing hypotheses and the advancement of science: recent attempts to falsify the equilibrium point hypothesis.

    Science.gov (United States)

    Feldman, Anatol G; Latash, Mark L

    2005-02-01

    Criticisms of the equilibrium point (EP) hypothesis have recently appeared that are based on misunderstandings of some of its central notions. Starting from such interpretations of the hypothesis, incorrect predictions are made and tested. When the incorrect predictions prove false, the hypothesis is claimed to be falsified. In particular, the hypothesis has been rejected based on the wrong assumptions that it conflicts with empirically defined joint stiffness values or that it is incompatible with violations of equifinality under certain velocity-dependent perturbations. Typically, such attempts use notions describing the control of movements of artificial systems in place of physiologically relevant ones. While appreciating constructive criticisms of the EP hypothesis, we feel that incorrect interpretations have to be clarified by reiterating what the EP hypothesis does and does not predict. We conclude that the recent claims of falsifying the EP hypothesis and the calls for its replacement by EMG-force control hypothesis are unsubstantiated. The EP hypothesis goes far beyond the EMG-force control view. In particular, the former offers a resolution for the famous posture-movement paradox while the latter fails to resolve it.

  12. Using landscape ecology to test hypotheses about large-scale abundance patterns in migratory birds

    Science.gov (United States)

    Flather, C.H.; Sauer, J.R.

    1996-01-01

    The hypothesis that Neotropical migrant birds may be undergoing widespread declines due to land use activities on the breeding grounds has been examined primarily by synthesizing results from local studies. Growing concern for the cumulative influence of land use activities on ecological systems has heightened the need for large-scale studies to complement what has been observed at local scales. We investigated possible landscape effects on Neotropical migrant bird populations for the eastern United States by linking two large-scale inventories designed to monitor breeding-bird abundances and land use patterns. The null hypothesis of no relation between landscape structure and Neotropical migrant abundance was tested by correlating measures of landscape structure with bird abundance, while controlling for the geographic distance among samples. Neotropical migrants as a group were more 'sensitive' to landscape structure than either temperate migrants or permanent residents. Neotropical migrants tended to be more abundant in landscapes with a greater proportion of forest and wetland habitats, fewer edge habitats, large forest patches, and with forest habitats well dispersed throughout the scene. Permanent residents showed few correlations with landscape structure and temperate migrants were associated with habitat diversity and edge attributes rather than with the amount, size, and dispersion of forest habitats. The association between Neotropical migrant abundance and forest fragmentation differed among physiographic strata, suggesting that land-scape context affects observed relations between bird abundance and landscape structure. Finally, associations between landscape structure and temporal trends in Neotropical migrant abundance were negatively correlated with forest habitats. These results suggest that extrapolation of patterns observed in some landscapes is not likely to hold regionally, and that conservation policies must consider the variation in landscape

  13. Family Stress and Parental Responses to Children’s Negative Emotions: Tests of the Spillover, Crossover, and Compensatory Hypotheses

    Science.gov (United States)

    Nelson, Jackie A.; O’Brien, Marion; Blankson, A. Nayena; Calkins, Susan D.; Keane, Susan P.

    2010-01-01

    The relations between 4 sources of family stress (marital dissatisfaction, home chaos, parental depressive symptoms, and job role dissatisfaction) and the emotion socialization practice of mothers’ and fathers’ responses to children’s negative emotions were examined. Participants included 101 couples with 7-year-old children. Dyadic analyses were conducted using the Actor–Partner Interdependence Model and relations were tested in terms of the spillover, crossover, and compensatory hypotheses. Results suggest that measures of family stress relate to supportive and nonsupportive parental responses, though many of these relations differ by parent gender. The results are discussed in terms of the 3 theoretical hypotheses, all of which are supported to some degree depending on the family stressor examined. PMID:19803603

  14. Family stress and parental responses to children's negative emotions: tests of the spillover, crossover, and compensatory hypotheses.

    Science.gov (United States)

    Nelson, Jackie A; O'Brien, Marion; Blankson, A Nayena; Calkins, Susan D; Keane, Susan P

    2009-10-01

    The relations between 4 sources of family stress (marital dissatisfaction, home chaos, parental depressive symptoms, and job role dissatisfaction) and the emotion socialization practice of mothers' and fathers' responses to children's negative emotions were examined. Participants included 101 couples with 7-year-old children. Dyadic analyses were conducted using the Actor-Partner Interdependence Model and relations were tested in terms of the spillover, crossover, and compensatory hypotheses. Results suggest that measures of family stress relate to supportive and nonsupportive parental responses, though many of these relations differ by parent gender. The results are discussed in terms of the 3 theoretical hypotheses, all of which are supported to some degree depending on the family stressor examined.

  15. Teaching the fluctuation test in silico by using mutate: a program to distinguish between the adaptive and spontaneous mutation hypotheses.

    Science.gov (United States)

    Carvajal-Rodríguez, Antonio

    2012-07-01

    Mutate is a program developed for teaching purposes to impart a virtual laboratory class for undergraduate students of Genetics in Biology. The program emulates the so-called fluctuation test whose aim is to distinguish between spontaneous and adaptive mutation hypotheses in bacteria. The plan is to train students in certain key multidisciplinary aspects of current genetics such as sequence databases, DNA mutations, and hypothesis testing, while introducing the fluctuation test. This seminal experiment was originally performed studying Escherichia coli resistance to the infection by bacteriophage T1. The fluctuation test initiated the modern bacterial genetics that 25 years later ushered in the era of the recombinant DNA. Nowadays we know that some deletions in fhuA, the gene responsible for E. coli membrane receptor of T1, could cause the E. coli resistance to this phage. For the sake of simplicity, we will introduce the assumption that a single mutation generates the resistance to T1. During the practical, the students use the program to download some fhuA gene sequences, manually introduce some stop codon mutations, and design a fluctuation test to obtain data for distinguishing between preadaptative (spontaneous) and induced (adaptive) mutation hypotheses. The program can be launched from a browser or, if preferred, its executable file can be downloaded from http://webs.uvigo.es/acraaj/MutateWeb/Mutate.html. It requires the Java 5.0 (or higher) Runtime Environment (freely available at http://www.java.com). Copyright © 2012 Wiley Periodicals, Inc.

  16. Molecular Testing for Gastrointestinal Cancer

    Directory of Open Access Journals (Sweden)

    Hye Seung Lee

    2017-03-01

    Full Text Available With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC and colorectal cancer (CRC. Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4. A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2 and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.

  17. Sexual videos in Internet: a test of 11 hypotheses about intimate practices and gender interactions in Latin America

    OpenAIRE

    Monge-Nájera, Julián; Corrales, Karla Vega

    2015-01-01

    There is a marked lack of literature on user-submitted sexual videos from Latin America. To start filling that gap, we present a formal statistical testing of several hypotheses about the characteristics of 214 videos from Nereliatube.com posted from the inauguration of the site until December 2010. We found that in most cases the video was made consensually and the camera was operated by the man. The most frequent practice shown was fellatio, followed by vaginal penetration.  The great major...

  18. Replicated population divergence caused by localized coevolution? A test of three hypotheses in the red crossbill-lodgepole pine system.

    Science.gov (United States)

    Edelaar, P; Benkman, C W

    2006-09-01

    Several lines of evidence support the hypothesis that local populations of red crossbills (Loxia curvirostra complex) enter into a predator-prey arms race with lodgepole pine (Pinus contorta latifolia) in the absence of competing pine squirrels (Tamiasciurus hudsonicus). Nevertheless, the alternative hypotheses that neutral evolution or factors other than squirrels have caused crossbill population differentiation have not been thoroughly tested. We compared crossbill and pine cone morphology between island populations where squirrels are absent or present, and mainland sites where squirrels are present, in order to distinguish among these hypotheses. All comparisons supported an effect of squirrel absence, not island status, on crossbill and cone morphology. Hence our results provide further evidence that strong localized coevolutionary interactions in a geographic mosaic have driven adaptive population differentiation. In addition, vocal differentiation of crossbills was related to the absence of squirrels, but not to island status. As morphological and vocal differentiation is correlated with reproductive isolation in crossbills, the geographic mosaic of coevolution also seems to promote ecological speciation.

  19. Is the modern koala ( Phascolarctos cinereus) a derived dwarf of a Pleistocene giant? Implications for testing megafauna extinction hypotheses

    Science.gov (United States)

    Price, Gilbert J.

    2008-12-01

    The modern Australian koala ( Phascolarctos cinereus) is commonly regarded as a dwarf descendent of a Late Pleistocene giant koala ( Ph. stirtoni). The implication of that hypothesis is that the giant koala survived the Late Pleistocene megafaunal extinction "event", albeit as a smaller body-sized form. It is important to be able to constrain rates of Late Pleistocene faunal turnover, an aspect reliant on having accurate taxonomic information of extinct species. The koala dwarfing hypothesis is tested here by using a temporally-constrained biogeographical record of fossil koalas, and a morphological character analysis. The contemporary occurrence of both taxa in pre-Late Pleistocene deposits and significant differences in dental morphologies between those forms suggests that the modern koala is not a derived dwarf of the Pleistocene giant koala. Thus, the giant-form was among a number of other giant mammals, lizards and birds that suffered extinction sometime during the Late Pleistocene. The potential phenomenon of dwarfing of other Late Pleistocene and Recent faunas, such as grey kangaroos, is commonly used as a test for or against various megafaunal extinction hypotheses. However, the results of this study also demonstrate that the dwarfing hypothesis has not been adequately tested for a suite of other taxa. Thus, until the dwarfing hypothesis can be more fully tested, a clear understanding of the fate of Late Pleistocene faunas that apparently survived the extinction "event", and the origins of many extant forms will remain elusive.

  20. Molecular Diagnostic Tests for Microsporidia

    Directory of Open Access Journals (Sweden)

    Kaya Ghosh

    2009-01-01

    Full Text Available The Microsporidia are a ubiquitous group of eukaryotic obligate intracellular parasites which were recognized over 100 years ago with the description of Nosema bombycis, a parasite of silkworms. It is now appreciated that these organisms are related to the Fungi. Microsporidia infect all major animal groups most often as gastrointestinal pathogens; however they have been reported from every tissue and organ, and their spores are common in environmental sources such as ditch water. Several different genera of these organisms infect humans, but the majority of infections are due to either Enterocytozoon bieneusi or Encephalitozoon species. These pathogens can be difficult to diagnose, but significant progress has been made in the last decade in the development of molecular diagnostic reagents for these organisms. This report reviews the molecular diagnostic tests that have been described for the identification of the microsporidia that infect humans.

  1. Stigma models: Testing hypotheses of how images of Nevada are acquired and values are attached to them

    Energy Technology Data Exchange (ETDEWEB)

    Jenkins-Smith, H.C. [New Mexico Univ., Albuquerque, NM (United States)

    1994-12-01

    This report analyzes data from surveys on the effects that images associated with nuclear power and waste (i.e., nuclear images) have on people`s preference to vacation in Nevada. The analysis was stimulated by a model of imagery and stigma which assumes that information about a potentially hazardous facility generates signals that elicit negative images about the place in which it is located. Individuals give these images negative values (valences) that lessen their desire to vacation, relocate, or retire in that place. The model has been used to argue that the proposed Yucca Mountain high-level nuclear waste repository could elicit images of nuclear waste that would stigmatize Nevada and thus impose substantial economic losses there. This report proposes a revised model that assumes that the acquisition and valuation of images depend on individuals` ideological and cultural predispositions and that the ways in which new images will affect their preferences and behavior partly depend on these predispositions. The report tests these hypotheses: (1) individuals with distinct cultural and ideological predispositions have different propensities for acquiring nuclear images, (2) these people attach different valences to these images, (3) the variations in these valences are important, and (4) the valences of the different categories of images within an individual`s image sets for a place correlate very well. The analysis largely confirms these hypotheses, indicating that the stigma model should be revised to (1) consider the relevant ideological and cultural predispositions of the people who will potentially acquire and attach value to the image, (2) specify the kinds of images that previously attracted people to the host state, and (3) consider interactions between the old and potential new images of the place. 37 refs., 18 figs., 17 tabs.

  2. Testing Cort-Fitness and Cort-Adaptation hypotheses in a habitat suitability gradient for roe deer

    Science.gov (United States)

    Escribano-Avila, Gema; Pettorelli, Nathalie; Virgós, Emilio; Lara-Romero, Carlos; Lozano, Jorge; Barja, Isabel; Cuadra, Felipe S.; Puerta, Marisa

    2013-11-01

    According to the Cort-Fitness Hypothesis, higher stress levels (glucocorticoids) in vertebrates are correlated to lower fitness. However, recent studies have failed to validate this hypothesis. A proposed wider framework suggests that reproduction can be perceived as an overload adds up to other environmental challenges that individuals must adjust to. In this case, elevated glucocorticoids could help individuals to allocate resources to reproduction without comprising other functions, leading to the expectation of a positive cort-fitness relationship. This has been proposed as the Cort-Adaptation Hypothesis. Stress levels result from a complex interaction between the environment and the neuroendocrine system of animals. Accounting for physiological functions involved in how animals cope with their environment would help to clarify the relationship between glucocorticoids and animal performance. We used roe deer (Capreolus capreolus) inhabiting diverse habitats in the Iberian Peninsula to: i) test the Cort-Fitness and Cort-Adaptation hypotheses by indexing fitness using a comprehensive physiological approach which takes into account fundamental physiological functions and their trade-offs; and ii) evaluate the link between primary productivity and individuals' condition in a seasonal environment. We evaluated spatial and temporal variation in stress levels, reproductive hormone levels, nutritional status and immune function from fecal samples collected in 2010. Lower stress levels were related to better condition in non-reproductive seasons but not to higher primary productivity. In contrast, stress levels were always positively related to reproductive condition, which was better in most productive habitats. Summer and winter were the less productive seasons and the more challenging for the species in the habitat gradient studied. In winter, reproductive condition traded off against immune function being biased toward immune function in less productive habitats. In

  3. Stigma models: Testing hypotheses of how images of Nevada are acquired and values are attached to them

    International Nuclear Information System (INIS)

    Jenkins-Smith, H.C.

    1994-12-01

    This report analyzes data from surveys on the effects that images associated with nuclear power and waste (i.e., nuclear images) have on people's preference to vacation in Nevada. The analysis was stimulated by a model of imagery and stigma which assumes that information about a potentially hazardous facility generates signals that elicit negative images about the place in which it is located. Individuals give these images negative values (valences) that lessen their desire to vacation, relocate, or retire in that place. The model has been used to argue that the proposed Yucca Mountain high-level nuclear waste repository could elicit images of nuclear waste that would stigmatize Nevada and thus impose substantial economic losses there. This report proposes a revised model that assumes that the acquisition and valuation of images depend on individuals' ideological and cultural predispositions and that the ways in which new images will affect their preferences and behavior partly depend on these predispositions. The report tests these hypotheses: (1) individuals with distinct cultural and ideological predispositions have different propensities for acquiring nuclear images, (2) these people attach different valences to these images, (3) the variations in these valences are important, and (4) the valences of the different categories of images within an individual's image sets for a place correlate very well. The analysis largely confirms these hypotheses, indicating that the stigma model should be revised to (1) consider the relevant ideological and cultural predispositions of the people who will potentially acquire and attach value to the image, (2) specify the kinds of images that previously attracted people to the host state, and (3) consider interactions between the old and potential new images of the place. 37 refs., 18 figs., 17 tabs

  4. Sources of organisational resiliency during the Thailand floods of 2011: a test of the bonding and bridging hypotheses.

    Science.gov (United States)

    Andrew, Simon; Arlikatti, Sudha; Siebeneck, Laura; Pongponrat, Kannapa; Jaikampan, Kraiwuth

    2016-01-01

    Based on the Institutional Collective Action framework, this research tests the impact of two competing hypotheses--bonding and bridging--on enhancing organisational resiliency. The bonding hypothesis posits that organisational resiliency can be achieved if an organisation works closely with others, whereas the bridging hypothesis argues that such a structure places considerable stress on an organisation and advocates for an organisation to position itself as a central actor to gain access to novel resources from a diverse set of entities to achieve resiliency. The paper analyses data gathered from semi-structured interviews with 44 public, private, and non-profit organisations serving communities affected by the Great Floods of 2011 in the Thai capital, Bangkok (urban), and in Pathum Thani (suburban) and Ayutthaya (rural) provinces. The findings suggest that: organisational resiliency was associated with the bridging effect; organisations in the rural province were more resilient than those in the suburban and urban centres; and private and non-governmental organisations generally were more resilient than public sector organisations. The findings highlight the importance of fostering multi-sector partnerships to enhance organisational resiliency for disaster response. © 2016 The Author(s). Disasters © Overseas Development Institute, 2016.

  5. A multilocus evaluation of ermine (Mustela erminea) across the Holarctic, testing hypotheses of Pleistocene diversification in response to climate change

    Science.gov (United States)

    Dawson, Natalie G.; Hope, Andrew G.; Talbot, Sandra L.; Cook, Joseph A.

    2013-01-01

    Aim: We examined data for ermine (Mustela erminea) to test two sets of diversification hypotheses concerning the number and location of late Pleistocene refugia, the timing and mode of diversification, and the evolutionary influence of insularization. Location: Temperate and sub-Arctic Northern Hemisphere. Methods: We used up to two mitochondrial and four nuclear loci from 237 specimens for statistical phylogeographical and demographic analyses. Coalescent species-tree estimation used a Bayesian approach for clade divergence based on external mutation rate calibrations. Approximate Bayesian methods were used to assess population size, timing of divergence and gene flow. Results: Limited structure coupled with evidence of population growth across broad regions, including previously ice-covered areas, indicated expansion from multiple centres of differentiation, but high endemism along the North Pacific coast (NPC). A bifurcating model of diversification with recent growth spanning three glacial cycles best explained the empirical data. Main conclusions: A newly identified clade in North America indicated a fourth refugial area for ermine. The shallow coalescence of all extant ermine reflects a recent history of diversification overlying a deeper fossil record. Post-glacial colonization has led to potential contact zones for multiple lineages in north-western North America. A model of diversification of ermine accompanied by recent gene flow was marginally less well supported than a model of divergence of major clades in response to the most recent glacial cycles.

  6. Specialization and generalization in the diversification of phytophagous insects: tests of the musical chairs and oscillation hypotheses

    Science.gov (United States)

    Hardy, Nate B.; Otto, Sarah P.

    2014-01-01

    Evolutionary biologists have often assumed that ecological generalism comes at the expense of less intense exploitation of specific resources and that this trade-off will promote the evolution of ecologically specialized daughter species. Using a phylogenetic comparative approach with butterflies as a model system, we test hypotheses that incorporate changes in niche breadth and location into explanations of the taxonomic diversification of insect herbivores. Specifically, we compare the oscillation hypothesis, where speciation is driven by host-plant generalists giving rise to specialist daughter species, to the musical chairs hypothesis, where speciation is driven by host-plant switching, without changes in niche breadth. Contrary to the predictions of the oscillation hypothesis, we recover a negative relationship between host-plant breadth and diversification rate and find that changes in host breadth are seldom coupled to speciation events. By contrast, we present evidence for a positive relationship between rates of host switching and butterfly diversification, consonant with the musical chairs hypothesis. These results suggest that the costs of trophic generalism in plant-feeding insects may have been overvalued and that transitions from generalists to ecological specialists may not be an important driver of speciation in general. PMID:25274368

  7. Seasonal patterns in reproductive success of temperate-breeding birds: Experimental tests of the date and quality hypotheses.

    Science.gov (United States)

    Harriman, Vanessa B; Dawson, Russell D; Bortolotti, Lauren E; Clark, Robert G

    2017-04-01

    For organisms in seasonal environments, individuals that breed earlier in the season regularly attain higher fitness than their late-breeding counterparts. Two primary hypotheses have been proposed to explain these patterns: The quality hypothesis contends that early breeders are of better phenotypic quality or breed on higher quality territories, whereas the date hypothesis predicts that seasonally declining reproductive success is a response to a seasonal deterioration in environmental quality. In birds, food availability is thought to drive deteriorating environmental conditions, but few experimental studies have demonstrated its importance while also controlling for parental quality. We tested predictions of the date hypothesis in tree swallows ( Tachycineta bicolor ) over two breeding seasons and in two locations within their breeding range in Canada. Nests were paired by clutch initiation date to control for parental quality, and we delayed the hatching date of one nest within each pair. Subsequently, brood sizes were manipulated to mimic changes in per capita food abundance, and we examined the effects of manipulations, as well as indices of environmental and parental quality, on nestling quality, fledging success, and return rates. Reduced reproductive success of late-breeding individuals was causally related to a seasonal decline in environmental quality. Declining insect biomass and enlarged brood sizes resulted in nestlings that were lighter, in poorer body condition, structurally smaller, had shorter and slower growing flight feathers and were less likely to survive to fledge. Our results provide evidence for the importance of food resources in mediating seasonal declines in offspring quality and survival.

  8. Adaptive x-ray threat detection using sequential hypotheses testing with fan-beam experimental data (Conference Presentation)

    Science.gov (United States)

    Thamvichai, Ratchaneekorn; Huang, Liang-Chih; Ashok, Amit; Gong, Qian; Coccarelli, David; Greenberg, Joel A.; Gehm, Michael E.; Neifeld, Mark A.

    2017-05-01

    We employ an adaptive measurement system, based on sequential hypotheses testing (SHT) framework, for detecting material-based threats using experimental data acquired on an X-ray experimental testbed system. This testbed employs 45-degree fan-beam geometry and 15 views over a 180-degree span to generate energy sensitive X-ray projection data. Using this testbed system, we acquire multiple view projection data for 200 bags. We consider an adaptive measurement design where the X-ray projection measurements are acquired in a sequential manner and the adaptation occurs through the choice of the optimal "next" source/view system parameter. Our analysis of such an adaptive measurement design using the experimental data demonstrates a 3x-7x reduction in the probability of error relative to a static measurement design. Here the static measurement design refers to the operational system baseline that corresponds to a sequential measurement using all the available sources/views. We also show that by using adaptive measurements it is possible to reduce the number of sources/views by nearly 50% compared a system that relies on static measurements.

  9. Testing biological hypotheses with embodied robots: adaptations, accidents, and by-products in the evolution of vertebrates

    Directory of Open Access Journals (Sweden)

    Sonia F Roberts

    2014-11-01

    Full Text Available Evolutionary robotics allows biologists to test hypotheses about extinct animals. We modeled some of the first vertebrates, jawless fishes, in order to study the evolution of the trait after which vertebrates are named: vertebrae. We tested the hypothesis that vertebrae are an adaptation for enhanced feeding and fleeing performance. We created a population of autonomous embodied robots, Preyro, in which the number of vertebrae, N, were free to evolve. In addition, two other traits, the span of the caudal fin, b, and the predator detection threshold, ζ, a proxy for the lateral line sensory system, were also allowed to evolve. These three traits were chosen because they evolved early in vertebrates, are all potentially important in feeding and fleeing, and vary in form among species. Preyro took on individual identities in a given generation as defined by the population’s six diploid genotypes, Gi. Each Gi was a 3-tuple, with each element an integer specifying N, b, and, ζ. The small size of the population allowed for genetic drift to operate in concert with random mutation and mating; the presence of these mechanisms of chance provided an opportunity for N to evolve by accident. The presence of three evolvable traits provided an opportunity for direct selection on b and/or ζ to evolve N as a by-product linked trait correlation. In selection trials, different Gi embodied in Preyro attempted to feed at a light source and then flee to avoid a predator robot in pursuit. The fitness of each Gi was calculated from five different types of performance: speed, acceleration, distance to the light, distance to the predator, and the number of predator escapes initiated. In each generation, we measured the selection differential, the selection gradient, the strength of chance, and the indirect correlation selection gradient. These metrics allowed us to understand the relative contributions of the three mechanisms: direct selection, chance, and indirect

  10. Do Job Demands of Chinese Manufacturing Employees Predict Positive or Negative Outcomes? A Test of Competing Hypotheses.

    Science.gov (United States)

    Cheung, Janelle H; Sinclair, Robert R; Shi, Junqi; Wang, Mo

    2015-12-01

    Karasek's job demands-control (JDC) model posits that job control can buffer against the harmful effects of demands experienced by employees. A large volume of JDC research has obtained support for the main effects of demands and control, but not the interactive effects. Recent research on the challenge-hindrance stressors framework, however, found that work stressors may not always be deleterious, suggesting alternative hypotheses about the effects of demands and control. The present study therefore examined competing hypotheses concerning the effects of job demands on occupational health outcomes. Using a sample of 316 employees in a Chinese manufacturing company, we found that, consistent with the challenge-hindrance framework, production demands were challenge stressors associated with favourable outcomes (i.e. job satisfaction and psychological well-being). In addition, results showed that the interactive role of job control depended on the nature of outcome variables. Future recommendations and implications of findings are discussed. Copyright © 2014 John Wiley & Sons, Ltd.

  11. Molecular testing practices and perceptions among dermatopathologists.

    Science.gov (United States)

    Torre, Kristin; Jhorar, Preeti; Wu, Rong; Pfeifer, John; Elaba, Zendee; Murphy, Michael

    2018-02-13

    We evaluated how dermatopathologists are employing molecular testing in the setting of neoplastic skin diseases, and assessed their opinions of the broader role and utility of molecular technologies in clinical practice. A 15-question online survey was sent to Fellows of the American Society of Dermatopathology in April 2017. One hundred and thirty-six dermatopathologists completed the survey (response rate = 16%). A majority (94%) of respondents reported experience with one or more molecular testing strategies. Sixty-two percent of dermatopathologists order 12 or more molecular tests per year, while 5% of respondents order 2 or fewer assays per year. More frequent utilization of molecular testing is associated with relevant instruction during residency training (P = .009), primary board certification in pathology (P = .008), academic medical center affiliation (P = molecular pathology/cytogenetics laboratory (P = .007), and greater physician confidence incorporating test results into histopathological assessments (P = molecular testing in dermatopathology may be limited by factors such as physician training, test costs/insurance coverage, logistical issues and lack of evidence-based clinical practice guidelines. Dermatopathologists have concerns regarding clinical validity/utility and inappropriate/overuse of some molecular tests. The importance of longitudinal education in molecular technologies and their applications for trainee and practicing physicians is highlighted. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. COVAR: Computer Program for Multifactor Relative Risks and Tests of Hypotheses Using a Variance-Covariance Matrix from Linear and Log-Linear Regression

    Directory of Open Access Journals (Sweden)

    Leif E. Peterson

    1997-11-01

    Full Text Available A computer program for multifactor relative risks, confidence limits, and tests of hypotheses using regression coefficients and a variance-covariance matrix obtained from a previous additive or multiplicative regression analysis is described in detail. Data used by the program can be stored and input from an external disk-file or entered via the keyboard. The output contains a list of the input data, point estimates of single or joint effects, confidence intervals and tests of hypotheses based on a minimum modified chi-square statistic. Availability of the program is also discussed.

  13. Integrating evolutionary and functional tests of adaptive hypotheses: a case study of altitudinal differentiation in hemoglobin function in an Andean Sparrow, Zonotrichia capensis.

    Science.gov (United States)

    Cheviron, Zachary A; Natarajan, Chandrasekhar; Projecto-Garcia, Joana; Eddy, Douglas K; Jones, Jennifer; Carling, Matthew D; Witt, Christopher C; Moriyama, Hideaki; Weber, Roy E; Fago, Angela; Storz, Jay F

    2014-11-01

    In air-breathing vertebrates, the physiologically optimal blood-O2 affinity is jointly determined by the prevailing partial pressure of atmospheric O2, the efficacy of pulmonary O2 transfer, and internal metabolic demands. Consequently, genetic variation in the oxygenation properties of hemoglobin (Hb) may be subject to spatially varying selection in species with broad elevational distributions. Here we report the results of a combined functional and evolutionary analysis of Hb polymorphism in the rufous-collared sparrow (Zonotrichia capensis), a species that is continuously distributed across a steep elevational gradient on the Pacific slope of the Peruvian Andes. We integrated a population genomic analysis that included all postnatally expressed Hb genes with functional studies of naturally occurring Hb variants, as well as recombinant Hb (rHb) mutants that were engineered through site-directed mutagenesis. We identified three clinally varying amino acid polymorphisms: Two in the α(A)-globin gene, which encodes the α-chain subunits of the major HbA isoform, and one in the α(D)-globin gene, which encodes the α-chain subunits of the minor HbD isoform. We then constructed and experimentally tested single- and double-mutant rHbs representing each of the alternative α(A)-globin genotypes that predominate at different elevations. Although the locus-specific patterns of altitudinal differentiation suggested a history of spatially varying selection acting on Hb polymorphism, the experimental tests demonstrated that the observed amino acid mutations have no discernible effect on respiratory properties of the HbA or HbD isoforms. These results highlight the importance of experimentally validating the hypothesized effects of genetic changes in protein function to avoid the pitfalls of adaptive storytelling. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please

  14. Properties of hypothesis testing techniques and (Bayesian) model selection for exploration-based and theory-based (order-restricted) hypotheses.

    Science.gov (United States)

    Kuiper, Rebecca M; Nederhoff, Tim; Klugkist, Irene

    2015-05-01

    In this paper, the performance of six types of techniques for comparisons of means is examined. These six emerge from the distinction between the method employed (hypothesis testing, model selection using information criteria, or Bayesian model selection) and the set of hypotheses that is investigated (a classical, exploration-based set of hypotheses containing equality constraints on the means, or a theory-based limited set of hypotheses with equality and/or order restrictions). A simulation study is conducted to examine the performance of these techniques. We demonstrate that, if one has specific, a priori specified hypotheses, confirmation (i.e., investigating theory-based hypotheses) has advantages over exploration (i.e., examining all possible equality-constrained hypotheses). Furthermore, examining reasonable order-restricted hypotheses has more power to detect the true effect/non-null hypothesis than evaluating only equality restrictions. Additionally, when investigating more than one theory-based hypothesis, model selection is preferred over hypothesis testing. Because of the first two results, we further examine the techniques that are able to evaluate order restrictions in a confirmatory fashion by examining their performance when the homogeneity of variance assumption is violated. Results show that the techniques are robust to heterogeneity when the sample sizes are equal. When the sample sizes are unequal, the performance is affected by heterogeneity. The size and direction of the deviations from the baseline, where there is no heterogeneity, depend on the effect size (of the means) and on the trend in the group variances with respect to the ordering of the group sizes. Importantly, the deviations are less pronounced when the group variances and sizes exhibit the same trend (e.g., are both increasing with group number). © 2014 The British Psychological Society.

  15. The effect of dislike of school on risk of teenage pregnancy: testing of hypotheses using longitudinal data from a randomised trial of sex education

    OpenAIRE

    Bonell, C; Allen, E; Strange, V; Copas, A; Oakley, A; Stephenson, J; Johnson, A

    2005-01-01

    Study objective: To examine whether attitude to school is associated with subsequent risk of teenage pregnancy. To test two hypotheses that attitude to school is linked to pregnancy via pathways involving young people having "alternative" expectations or deficits in sexual health knowledge and confidence.

  16. Properties of hypothesis testing techniques and (Bayesian) model selection for exploration-based and theory-based (order-restricted) hypotheses

    NARCIS (Netherlands)

    Kuiper, Rebecca M.; Nederhoff, Tim; Klugkist, Irene

    2015-01-01

    In this paper, the performance of six types of techniques for comparisons of means is examined. These six emerge from the distinction between the method employed (hypothesis testing, model selection using information criteria, or Bayesian model selection) and the set of hypotheses that is

  17. Plot of expected distributions of the test statistics q=log(L(0^+)/L(2^+)) for the spin-0 and spin-2 (produced by gluon fusion) hypotheses

    CERN Multimedia

    ATLAS, Collaboration

    2013-01-01

    Expected distributions of the test statistics q=log(L(0^+)/L(2^+)) for the spin-0 and spin-2 (produced by gluon fusion) hypotheses. The observed value is indicated by a vertical line. The coloured areas correspond to the integrals of the expected distributions used to compute the p-values for the rejection of each hypothesis.

  18. Alternative glacial-interglacial refugia demographic hypotheses tested on Cephalocereus columna-trajani (Cactaceae) in the intertropical Mexican drylands.

    Science.gov (United States)

    Cornejo-Romero, Amelia; Vargas-Mendoza, Carlos Fabián; Aguilar-Martínez, Gustavo F; Medina-Sánchez, Javier; Rendón-Aguilar, Beatriz; Valverde, Pedro Luis; Zavala-Hurtado, Jose Alejandro; Serrato, Alejandra; Rivas-Arancibia, Sombra; Pérez-Hernández, Marco Aurelio; López-Ortega, Gerardo; Jiménez-Sierra, Cecilia

    2017-01-01

    Historic demography changes of plant species adapted to New World arid environments could be consistent with either the Glacial Refugium Hypothesis (GRH), which posits that populations contracted to refuges during the cold-dry glacial and expanded in warm-humid interglacial periods, or with the Interglacial Refugium Hypothesis (IRH), which suggests that populations contracted during interglacials and expanded in glacial times. These contrasting hypotheses are developed in the present study for the giant columnar cactus Cephalocereus columna-trajani in the intertropical Mexican drylands where the effects of Late Quaternary climatic changes on phylogeography of cacti remain largely unknown. In order to determine if the historic demography and phylogeographic structure of the species are consistent with either hypothesis, sequences of the chloroplast regions psbA-trnH and trnT-trnL from 110 individuals from 10 populations comprising the full distribution range of this species were analysed. Standard estimators of genetic diversity and structure were calculated. The historic demography was analysed using a Bayesian approach and the palaeodistribution was derived from ecological niche modelling to determine if, in the arid environments of south-central Mexico, glacial-interglacial cycles drove the genetic divergence and diversification of this species. Results reveal low but statistically significant population differentiation (FST = 0.124, P < 0.001), although very clear geographic clusters are not formed. Genetic diversity, haplotype network and Approximate Bayesian Computation (ABC) demographic analyses suggest a population expansion estimated to have taken place in the Last Interglacial (123.04 kya, 95% CI 115.3-130.03). The species palaeodistribution is consistent with the ABC analyses and indicates that the potential area of palaedistribution and climatic suitability were larger during the Last Interglacial and Holocene than in the Last Glacial Maximum. Overall

  19. Molecular dynamics simulation of impact test

    International Nuclear Information System (INIS)

    Akahoshi, Y.; Schmauder, S.; Ludwig, M.

    1998-01-01

    This paper describes an impact test by molecular dynamics (MD) simulation to evaluate embrittlement of bcc Fe at different temperatures. A new impact test model is developed for MD simulation. The typical fracture behaviors show transition from brittle to ductile fracture, and a history of the impact loads also demonstrates its transition. We conclude that the impact test by MD could be feasible. (orig.)

  20. Molecular dynamics simulation of impact test

    Energy Technology Data Exchange (ETDEWEB)

    Akahoshi, Y. [Kyushu Inst. of Tech., Kitakyushu, Fukuoka (Japan); Schmauder, S.; Ludwig, M. [Stuttgart Univ. (Germany). Staatliche Materialpruefungsanstalt

    1998-11-01

    This paper describes an impact test by molecular dynamics (MD) simulation to evaluate embrittlement of bcc Fe at different temperatures. A new impact test model is developed for MD simulation. The typical fracture behaviors show transition from brittle to ductile fracture, and a history of the impact loads also demonstrates its transition. We conclude that the impact test by MD could be feasible. (orig.)

  1. The Effect of Multicollinearity and the Violation of the Assumption of Normality on the Testing of Hypotheses in Regression Analysis.

    Science.gov (United States)

    Vasu, Ellen S.; Elmore, Patricia B.

    The effects of the violation of the assumption of normality coupled with the condition of multicollinearity upon the outcome of testing the hypothesis Beta equals zero in the two-predictor regression equation is investigated. A monte carlo approach was utilized in which three differenct distributions were sampled for two sample sizes over…

  2. Substance use and misuse in burn patients: Testing the classical hypotheses of the interaction between post-traumatic symptomatology and substance use.

    Science.gov (United States)

    Eiroa-Orosa, Francisco Jose; Giannoni-Pastor, Anna; Fidel-Kinori, Sara Guila; Argüello, José María

    2016-01-01

    The authors aimed to test whether the three classical hypotheses of the interaction between post-traumatic symptomatology and substance use (high risk of trauma exposure, susceptibility for post-traumatic symptomatology, and self-medication of symptoms), may be useful in the understanding of substance use among burn patients. Substance use data (nicotine, alcohol, cannabis, amphetamines, cocaine, opiates, and tranquilizers) and psychopathology measures among burn patients admitted to a burn unit and enrolled in a longitudinal observational study were analyzed. Lifetime substance use information (n = 246) was incorporated to analyses aiming to test the high risk hypothesis. Only patients assessed for psychopathology in a 6-month follow-up (n = 183) were included in prospective analyses testing the susceptibility and self-medication hypotheses. Regarding the high risk hypothesis, results show a higher proportion of heroin and tranquilizer users compared to the general population. Furthermore, in line with the susceptibility hypothesis, higher levels of symptomatology were found in lifetime alcohol, tobacco, and drug users during recovery. The self-medication hypothesis could be tested partially due to the hospital stay "cleaning" effect, but severity of symptoms was linked to the amount of caffeine, nicotine, alcohol, and cannabis use after discharge. It was found that the 3 classical hypotheses could be used to understand the link between traumatic experiences and substance use explaining different patterns of burn patient's risk for trauma exposure and emergence of symptomatology.

  3. Genetic variation of Lymnaea stagnalis tolerance to copper: A test of selection hypotheses and its relevance for ecological risk assessment.

    Science.gov (United States)

    Côte, Jessica; Bouétard, Anthony; Pronost, Yannick; Besnard, Anne-Laure; Coke, Maïra; Piquet, Fabien; Caquet, Thierry; Coutellec, Marie-Agnès

    2015-10-01

    The use of standardized monospecific testing to assess the ecological risk of chemicals implicitly relies on the strong assumption that intraspecific variation in sensitivity is negligible or irrelevant in this context. In this study, we investigated genetic variation in copper sensitivity of the freshwater snail Lymnaea stagnalis, using lineages stemming from eight natural populations or strains found to be genetically differentiated at neutral markers. Copper-induced mortality varied widely among populations, as did the estimated daily death rate and time to 50% mortality (LT50). Population genetic divergence in copper sensitivity was compared to neutral differentiation using the QST-FST approach. No evidence for homogenizing selection could be detected. This result demonstrates that species-level extrapolations from single population studies are highly unreliable. The study provides a simple example of how evolutionary principles could be incorporated into ecotoxicity testing in order to refine ecological risk assessment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Environmental isotopes to test hypotheses for fluid mud (mud bank) generation mechanisms along the southwest coast of India

    Digital Repository Service at National Institute of Oceanography (India)

    Jacob, N.; Ansari, M.A.; Revichandran, C.

    the sea (Mallik et al., 1988). Fluidmud has high socio-economic importance as it is considered responsible for the enormous fish catch during monsoon. Fluid mud is associated with high biological productivity as it is rich in organic matter, phytoplankton... tritium (3H), sourced from the fallout of thermo nuclear weapons testing, carried out in the atmosphere during 1950e1963, could be effectively used to identify the recent recharge (estimate residence time) from precipitation or surface water bodies...

  5. Genetic variation of Lymnaea stagnalis tolerance to copper: A test of selection hypotheses and its relevance for ecological risk assessment

    International Nuclear Information System (INIS)

    Côte, Jessica; Bouétard, Anthony; Pronost, Yannick; Besnard, Anne-Laure; Coke, Maïra; Piquet, Fabien; Caquet, Thierry; Coutellec, Marie-Agnès

    2015-01-01

    The use of standardized monospecific testing to assess the ecological risk of chemicals implicitly relies on the strong assumption that intraspecific variation in sensitivity is negligible or irrelevant in this context. In this study, we investigated genetic variation in copper sensitivity of the freshwater snail Lymnaea stagnalis, using lineages stemming from eight natural populations or strains found to be genetically differentiated at neutral markers. Copper-induced mortality varied widely among populations, as did the estimated daily death rate and time to 50% mortality (LT50). Population genetic divergence in copper sensitivity was compared to neutral differentiation using the Q ST -F ST approach. No evidence for homogenizing selection could be detected. This result demonstrates that species-level extrapolations from single population studies are highly unreliable. The study provides a simple example of how evolutionary principles could be incorporated into ecotoxicity testing in order to refine ecological risk assessment. - Highlights: • Genetic variation in copper tolerance occurs between Lymnaea stagnalis populations. • We used the Q ST -F ST approach to test evolutionary patterns in copper tolerance. • No evidence for uniform selection was found. • Results suggest that extrapolations to the species level are not safe. • A method is proposed to refine ecological risk assessment using genetic parameters. - Genetic variation in copper tolerance occurs in Lymnaea stagnalis. A method is proposed for considering evolutionary parameters in ecological risk assessment

  6. Testing hypotheses in an I(2) model with applications to the persistent long swings in the Dmk/$ rate

    DEFF Research Database (Denmark)

    Johansen, Søren; Juselius, Katarina; Frydman, Roman

    long-term interest rates and two short-term interest rates over the 1975-1999 period. One important aim of the paper is to demonstrate that by structuring the data with the help of the I(2) model one can achieve a better understanding of the empirical regularities underlying the persistent swings...... components in the I(2) model is discussed at some length. Model specification and tests are illustrated with an empirical analysis of long and persistent swings in the foreign exchange market between Germany and USA. The data analyzed consist of nominal exchange rates, relative prices, US inflation rate, two...... in nominal exchange rates, typical in periods of floating exchange rates....

  7. Using Landscape Analysis to Test Hypotheses about Drivers of Tick Abundance and Infection Prevalence with Borrelia burgdorferi.

    Science.gov (United States)

    Ferrell, A Michelle; Brinkerhoff, R Jory

    2018-04-12

    Patterns of vector-borne disease risk are changing globally in space and time and elevated disease risk of vector-borne infection can be driven by anthropogenic modification of the environment. Incidence of Lyme disease, caused by the bacterium Borrelia burgdorferi sensu stricto, has risen in a number of locations in North America and this increase may be driven by spatially or numerically expanding populations of the primary tick vector, Ixodes scapularis . We used a model selection approach to identify habitat fragmentation and land-use/land cover variables to test the hypothesis that the amount and configuration of forest cover at spatial scales relevant to deer, the primary hosts of adult ticks, would be the predominant determinants of tick abundance. We expected that land cover heterogeneity and amount of forest edge, a habitat thought to facilitate deer foraging and survival, would be the strongest driver of tick density and that larger spatial scales (5-10 km) would be more important than smaller scales (1 km). We generated metrics of deciduous and mixed forest fragmentation using Fragstats 4.4 implemented in ArcMap 10.3 and found, after adjusting for multicollinearity, that total forest edge within a 5 km buffer had a significant negative effect on tick density and that the proportion of forested land cover within a 10 km buffer was positively associated with density of I. scapularis nymphs. None of the 1 km fragmentation metrics were found to significantly improve the fit of the model. Elevation, previously associated with increased density of I. scapularis nymphs in Virginia, while significantly predictive in univariate analysis, was not an important driver of nymph density relative to fragmentation metrics. Our results suggest that amount of forest cover (i.e., lack of fragmentation) is the most important driver of I. scapularis density in our study system.

  8. Migrating Seals on Shifting Sands: Testing Alternate Hypotheses for Holocene Ecological and Cultural Change on the California Coast

    Science.gov (United States)

    Koch, P. L.; Newsome, S. D.; Gifford-Gonzalez, D.

    2001-12-01

    The coast of California presented Holocene humans with a diverse set of ecosystems and geomorphic features, from large islands off a semi-desert mainland in the south, to a mix of sandy and rocky beaches abutting grassland and oak forest in central California, to a rocky coast hugged by dense coniferous forest in the north. Theories explaining trends in human resource use, settlement patterns, and demography are equally diverse, but can be categorized as 1) driven by diffusion of technological innovations from outside the region, 2) driven by population growth leading to more intensive extraction of resources, or 3) driven by climatic factors that affect the resource base. With respect to climatic shifts, attention has focused on a possible regime shift ca. 5500 BP, following peak Holocene warming, and on evidence for massive droughts and a drop in marine productivity ca. 1000 BP. While evidence for a coincidence between climatic, cultural, and ecological change is present, albeit complex, in southern California, similar data are largely lacking from central and northern California. We are using isotopic and archaeofaunal analysis to test ideas for ecological and cultural change in central California. Three features of the archaeological record are relevant. First, overall use of marine resources by coastal communities declined after 1000 BP. Second, northern fur seals, which are common in earlier sites, drop in abundance relative to remaining marine animals. We have previously established that Holocene humans in central California were hunting gregariously-breeding northern fur seals from mainland rookeries. These seals breed exclusively on offshore islands today, typically at high latitudes. Their restriction to these isolated sites today may be a response to human overexploitation of their mainland rookeries prehistorically. Finally, collection of oxygen and carbon isotope data from mussels at the archaeological sites, while still in a preliminary phase, has

  9. [Strategy for molecular testing in pulmonary carcinoma].

    Science.gov (United States)

    Penault-Llorca, Frédérique; Tixier, Lucie; Perrot, Loïc; Cayre, Anne

    2016-01-01

    Nowadays, the analysis of theranostic molecular markers is central in the management of lung cancer. As those tumors are diagnosed in two third of the cases at an advanced stage, molecular screening is frequently performed on "small samples". The screening strategy starts by an accurate histopathological characterization, including on biopsies or cytological specimens. WHO 2015 provided a new classification for small biopsy and cytology, defining categories such as non-small cell carcinoma (NSCC), favor adenocarcinoma (TTF1 positive), or favor squamous cell carcinoma (p40 positive). Only the NSCC tumors, non-squamous, are eligible to molecular testing. A strategy aiming at tissue sparing for the small biopsies has to be organized. Tests corresponding to available drugs are prioritized. Blank slides will be prepared for immunohistochemistry and in situ hybridization based tests such as ALK. DNA will then be extracted for the other tests, EGFR mutation screening first associated or not to KRAS. Then, the emerging biomarkers (HER2, ROS1, RET, BRAF…) as well as potentially other markers in case of clinical trials, can been tested. The spread of next generation sequencing technologies, with a very sensitive all-in-one approach will allow the identification of minority clones. Eventually, the development of liquid biopsies will provide the opportunity to monitor the apparition of resistance clones during treatment. This non-invasive approach allows patients with a contraindication to perform biopsy or with non-relevant biopsies to access to molecular screening. Copyright © 2016. Published by Elsevier Masson SAS.

  10. Two hypotheses were tested, namely:

    African Journals Online (AJOL)

    Referee

    anthelmintic thereby indirectly controlling blowfly strike. A.J. Scholtz ... monetary terms and because of the stress associated with flystrike (Waghorn et al., 1999). Gastro- ... Barger, 1988; Waller, 1994) in combination with managerial practices.

  11. Utility of molecular tests in cytopathology

    Directory of Open Access Journals (Sweden)

    Arthur David Somoza

    2014-01-01

    Full Text Available With the popularity of interventional radiology, diagnostic material obtained can be limited requiring critical decisions on making the best use of it. Molecular testing using nanogram amounts of tissue can add useful diagnostic information by improving sensitivity and/or specificity of the diagnosis. This review examines the use of molecular tests in cervical cytology, "indeterminate" thyroid cytology specimens, pancreatic cyst fluid, urinary tract and pulmonary adenocarcinoma cytologic material. Molecular human papillomavirus (HPV testing combined with cervical cytology increases sensitivity of detection of high grade lesions. In cytologically negative cases, the HPV negative predictive value endorses longer screening intervals. With the high prevalence of benign thyroid nodules, cytology plays a vital role in screening. However, 10-40% of the specimens obtained are cytologically indeterminate. Molecular analysis of these specimens can predict the malignant risk in these cases. Increased detection of pancreatic cysts has necessitated accurate pre-operative diagnosis delineating non-mucinous from mucinous cysts, which have a potential for progression to adenocarcinoma. Multimodal diagnosis of pancreatic cysts and molecular analysis help to clarify neoplastic risk; and in cases of limited fluid, may be the only available diagnostic information. Urothelial carcinoma (UC of the bladder, a common cancer with frequent recurrences, requires lifelong surveillance. The UroVysion ™ test kit can increase the sensitivity of detection of UC especially in cases of residual/recurrent carcinoma after therapy. Subsets of lung adenocarcinomas are now commonly targeted by therapies based on molecular mutation results of epidermal growth factor receptor, KRAS or echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase re-arrangements. The move toward standardization of reporting of cytology specimens commencing with cervical smears and more

  12. In silico generation of alternative hypotheses using causal mapping (CMAP.

    Directory of Open Access Journals (Sweden)

    Gabriel E Weinreb

    Full Text Available Previously, we introduced causal mapping (CMAP as an easy to use systems biology tool for studying the behavior of biological processes that occur at the cellular and molecular level. CMAP is a coarse-grained graphical modeling approach in which the system of interest is modeled as an interaction map between functional elements of the system, in a manner similar to portrayals of signaling pathways commonly used by molecular cell biologists. CMAP describes details of the interactions while maintaining the simplicity of other qualitative methods (e.g., Boolean networks.In this paper, we use the CMAP methodology as a tool for generating hypotheses about the mechanisms that regulate molecular and cellular systems. Furthermore, our approach allows competing hypotheses to be ranked according to a fitness index and suggests experimental tests to distinguish competing high fitness hypotheses. To motivate the CMAP as a hypotheses generating tool and demonstrate the methodology, we first apply this protocol to a simple test-case of a three-element signaling module. Our methods are next applied to the more complex phenomenon of cortical oscillations observed in spreading cells. This analysis produces two high fitness hypotheses for the mechanism that underlies this dynamic behavior and suggests experiments to distinguish the hypotheses. The method can be widely applied to other cellular systems to generate and compare alternative hypotheses based on experimentally observed data and using computer simulations.

  13. The power of gene-based rare variant methods to detect disease-associated variation and test hypotheses about complex disease.

    Directory of Open Access Journals (Sweden)

    Loukas Moutsianas

    2015-04-01

    Full Text Available Genome and exome sequencing in large cohorts enables characterization of the role of rare variation in complex diseases. Success in this endeavor, however, requires investigators to test a diverse array of genetic hypotheses which differ in the number, frequency and effect sizes of underlying causal variants. In this study, we evaluated the power of gene-based association methods to interrogate such hypotheses, and examined the implications for study design. We developed a flexible simulation approach, using 1000 Genomes data, to (a generate sequence variation at human genes in up to 10K case-control samples, and (b quantify the statistical power of a panel of widely used gene-based association tests under a variety of allelic architectures, locus effect sizes, and significance thresholds. For loci explaining ~1% of phenotypic variance underlying a common dichotomous trait, we find that all methods have low absolute power to achieve exome-wide significance (~5-20% power at α = 2.5 × 10(-6 in 3K individuals; even in 10K samples, power is modest (~60%. The combined application of multiple methods increases sensitivity, but does so at the expense of a higher false positive rate. MiST, SKAT-O, and KBAC have the highest individual mean power across simulated datasets, but we observe wide architecture-dependent variability in the individual loci detected by each test, suggesting that inferences about disease architecture from analysis of sequencing studies can differ depending on which methods are used. Our results imply that tens of thousands of individuals, extensive functional annotation, or highly targeted hypothesis testing will be required to confidently detect or exclude rare variant signals at complex disease loci.

  14. New media applications and their potential for the advancement of public perceptions of archaeoastronomy and for the testing of archaeoastronomical hypotheses.

    Science.gov (United States)

    MacDonald, J.

    This paper looks at the use of astronomical programmes and the development of new media modeling techniques as a means to better understand archaeoastronomy. The paper also suggests that these new methods and technologies are a means of furthering the public perceptions of archaeoastronomy and the important role that 'astronomy' played in the history and development of human culture. This discussion is rooted in a computer simulation of Stonehenge and its land and skyscape. The integration of the astronomy software allows viewing horizon astronomical lignments in relation to digitally recreated Neolithic/Early Bronze Age (EBA) monumental architecture. This work shows how modern virtual modelling techniques can be a tool for testing archaeoastronomical hypotheses, as well as a demonstrative tool for teaching and promoting archaeoastronomy in mainstream media.

  15. Compensation or inhibitory failure? Testing hypotheses of age-related right frontal lobe involvement in verbal memory ability using structural and diffusion MRI

    Science.gov (United States)

    Cox, Simon R.; Bastin, Mark E.; Ferguson, Karen J.; Allerhand, Mike; Royle, Natalie A.; Maniega, Susanna Muñoz; Starr, John M.; MacLullich, Alasdair M.J.; Wardlaw, Joanna M.; Deary, Ian J.; MacPherson, Sarah E.

    2015-01-01

    Functional neuroimaging studies report increased right prefrontal cortex (PFC) involvement during verbal memory tasks amongst low-scoring older individuals, compared to younger controls and their higher-scoring contemporaries. Some propose that this reflects inefficient use of neural resources through failure of the left PFC to inhibit non-task-related right PFC activity, via the anterior corpus callosum (CC). For others, it indicates partial compensation – that is, the right PFC cannot completely supplement the failing neural network, but contributes positively to performance. We propose that combining structural and diffusion brain MRI can be used to test predictions from these theories which have arisen from fMRI studies. We test these hypotheses in immediate and delayed verbal memory ability amongst 90 healthy older adults of mean age 73 years. Right hippocampus and left dorsolateral prefrontal cortex (DLPFC) volumes, and fractional anisotropy (FA) in the splenium made unique contributions to verbal memory ability in the whole group. There was no significant effect of anterior callosal white matter integrity on performance. Rather, segmented linear regression indicated that right DLPFC volume was a significantly stronger positive predictor of verbal memory for lower-scorers than higher-scorers, supporting a compensatory explanation for the differential involvement of the right frontal lobe in verbal memory tasks in older age. PMID:25241394

  16. Compensation or inhibitory failure? Testing hypotheses of age-related right frontal lobe involvement in verbal memory ability using structural and diffusion MRI.

    Science.gov (United States)

    Cox, Simon R; Bastin, Mark E; Ferguson, Karen J; Allerhand, Mike; Royle, Natalie A; Maniega, Susanna Muñoz; Starr, John M; MacLullich, Alasdair M J; Wardlaw, Joanna M; Deary, Ian J; MacPherson, Sarah E

    2015-02-01

    Functional neuroimaging studies report increased right prefrontal cortex (PFC) involvement during verbal memory tasks amongst low-scoring older individuals, compared to younger controls and their higher-scoring contemporaries. Some propose that this reflects inefficient use of neural resources through failure of the left PFC to inhibit non-task-related right PFC activity, via the anterior corpus callosum (CC). For others, it indicates partial compensation - that is, the right PFC cannot completely supplement the failing neural network, but contributes positively to performance. We propose that combining structural and diffusion brain MRI can be used to test predictions from these theories which have arisen from fMRI studies. We test these hypotheses in immediate and delayed verbal memory ability amongst 90 healthy older adults of mean age 73 years. Right hippocampus and left dorsolateral prefrontal cortex (DLPFC) volumes, and fractional anisotropy (FA) in the splenium made unique contributions to verbal memory ability in the whole group. There was no significant effect of anterior callosal white matter integrity on performance. Rather, segmented linear regression indicated that right DLPFC volume was a significantly stronger positive predictor of verbal memory for lower-scorers than higher-scorers, supporting a compensatory explanation for the differential involvement of the right frontal lobe in verbal memory tasks in older age. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  17. First insights into the social organisation of Goodman's mouse lemur (Microcebus lehilahytsara)--testing predictions from socio-ecological hypotheses in the Masoala hall of Zurich Zoo.

    Science.gov (United States)

    Jürges, Vivian; Kitzler, Johanne; Zingg, Robert; Radespiel, Ute

    2013-01-01

    Following current socio-ecological hypotheses, the social organisation of a species is mainly determined by resource quality and distribution. In the case of Microcebus spp., a taxon-specific socio-ecological model was formulated earlier to explain their variable social organisation. The aim of this study was to test predictions from this model in Goodman's mouse lemur based on a data set from animals living in the semi-free colony of Zurich Zoo. During a 2-month study, we observed 5 females and 5 males using radiotelemetry. We collected data on space use and social behaviour, on sleeping sites and on sleeping group composition. Predictions were only partly confirmed. As expected, Goodman's mouse lemurs were solitary foragers with an increased level of sociality due to crowding effects at the feeding stations. In contrast to the prediction, females and males formed unisexual sleeping groups, which were stable in females and of a fission-fusion type in males. Whereas the formation of sleeping groups by both sexes may be triggered by thermoregulatory benefits, the formation of unisexual sleeping groups may result from divergent interests of the sexes. We conclude that the existing model for the evolution of mouse lemur social organisation needs to be refined. Copyright © 2013 S. Karger AG, Basel.

  18. Testing the 'hybrid susceptibility' and 'phenological sink' hypotheses using the P. balsamifera - P. deltoides hybrid zone and septoria leaf spot [Septoria musiva].

    Science.gov (United States)

    LeBoldus, Jared M; Isabel, Nathalie; Floate, Kevin D; Blenis, Peter; Thomas, Barb R

    2013-01-01

    Hybrid genotypes that arise between plant species frequently have increased susceptibility to arthropod pests and fungal pathogens. This pattern has been attributed to the breakdown of plant defenses ('Hybrid susceptibility' hypothesis) and (or) to extended periods of susceptibility attributed to plant phenologies in zones of species overlap and (or) hybridization ('phenological sink' hypothesis). We examined these hypotheses by assessing the susceptibility of parental and hybrid Populus host genotypes to a leaf spot disease caused by the fungal pathogen Septoria musiva. For this purpose, 214 genotypes were obtained from morphologically pure zones of P. balsamifera and P. deltoides, and from an intervening zone of overlap and hybridization on the drainage of the Red Deer River, Alberta, Canada. Genotypes were identified as P. balsamifera, P. deltoides, or hybrid using a suite of 27 species-specific SNP markers. Initially the genetic structure of the hybrid zone was characterized with 27.7% of trees classified as admixed individuals. To test the hybrid susceptibility hypothesis, a subset of 52 genotypes was inoculated with four isolates of S. musiva. Levels of susceptibility were P. balsamifera > F1 hybrid > P. deltoides. A further 53 genotypes were grown in a common garden to assess the effect of genotype on variation in leaf phenology. Leaf phenology was more variable within the category of hybrid genotypes than within categories of either parental species. Leaf phenology was also more variable for the category of trees originating in the hybrid (P. balsamifera - P. deltoides [hybrid and parental genotypes combined]) zone than in adjacent pure zones of the parental species. The results from the inoculation experiment support the hybrid intermediacy hypothesis. The results from the common garden experiment support the 'phenological sink' hypothesis. These findings have greatly increased our understanding of the epidemiology and ecology of fungal pathogens in plant

  19. Stress, coping, and depression: testing new hypotheses in a prospectively studied general population sample of U.S. born Whites and Blacks

    Science.gov (United States)

    Keyes, K.M.; Barnes, D.; Bates, L.M.

    2010-01-01

    The scarcity of empirically supported explanations for the Black/White prevalence difference in depression in the U.S. is a conspicuous gap in the literature. Recent evidence suggests that the paradoxical observation of decreased risk of depression but elevated rates of physical illness among Blacks in the U.S. compared with Whites may be accounted for by the use of coping behaviors (e.g., alcohol and nicotine consumption, overeating) among Blacks exposed to high stress levels. Such coping behaviors may mitigate deleterious effects of stressful exposures on mental health while increasing the risk of physical ailments. The racial patterning in mental and physical health outcomes could therefore be explained by this mechanism if a) these behaviors were more prevalent among Blacks than Whites and/or b) the effect of these behavioral responses to stress was differential by race. The present study challenges this hypothesis using longitudinal, nationally-representative data with comprehensive DSM-IV diagnoses. Data are drawn from 34,653 individuals sampled in Waves 1 (2001-2002) and 2 (2004-2005) as part of the US National Epidemiologic Survey on Alcohol and Related Conditions. Results showed that a) Blacks were less likely to engage in alcohol or nicotine consumption at low, moderate, and high levels of stress compared to Whites, and b) there was a significant three-way interaction between race, stress, and coping behavior for BMI only (F=2.11, df=12, p=0.03), but, contrary to the hypothesis, elevated BMI was protective against depression in Blacks at low, not high, levels of stress. Further, engagement in unhealthy behaviors, especially at pathological levels, did not protect against depression in Blacks or in Whites. In sum, the impact of stress and coping processes on depression do not appear to operate differently in Blacks versus Whites. Further research testing innovative hypotheses that would explain the difference in Black/White depression prevalence is

  20. Testing the 'hybrid susceptibility' and 'phenological sink' hypotheses using the P. balsamifera - P. deltoides hybrid zone and septoria leaf spot [Septoria musiva].

    Directory of Open Access Journals (Sweden)

    Jared M LeBoldus

    Full Text Available Hybrid genotypes that arise between plant species frequently have increased susceptibility to arthropod pests and fungal pathogens. This pattern has been attributed to the breakdown of plant defenses ('Hybrid susceptibility' hypothesis and (or to extended periods of susceptibility attributed to plant phenologies in zones of species overlap and (or hybridization ('phenological sink' hypothesis. We examined these hypotheses by assessing the susceptibility of parental and hybrid Populus host genotypes to a leaf spot disease caused by the fungal pathogen Septoria musiva. For this purpose, 214 genotypes were obtained from morphologically pure zones of P. balsamifera and P. deltoides, and from an intervening zone of overlap and hybridization on the drainage of the Red Deer River, Alberta, Canada. Genotypes were identified as P. balsamifera, P. deltoides, or hybrid using a suite of 27 species-specific SNP markers. Initially the genetic structure of the hybrid zone was characterized with 27.7% of trees classified as admixed individuals. To test the hybrid susceptibility hypothesis, a subset of 52 genotypes was inoculated with four isolates of S. musiva. Levels of susceptibility were P. balsamifera > F1 hybrid > P. deltoides. A further 53 genotypes were grown in a common garden to assess the effect of genotype on variation in leaf phenology. Leaf phenology was more variable within the category of hybrid genotypes than within categories of either parental species. Leaf phenology was also more variable for the category of trees originating in the hybrid (P. balsamifera - P. deltoides [hybrid and parental genotypes combined] zone than in adjacent pure zones of the parental species. The results from the inoculation experiment support the hybrid intermediacy hypothesis. The results from the common garden experiment support the 'phenological sink' hypothesis. These findings have greatly increased our understanding of the epidemiology and ecology of fungal

  1. A PORTRAIT OF COLD GAS IN GALAXIES AT 60 pc RESOLUTION AND A SIMPLE METHOD TO TEST HYPOTHESES THAT LINK SMALL-SCALE ISM STRUCTURE TO GALAXY-SCALE PROCESSES

    International Nuclear Information System (INIS)

    Leroy, Adam K.; Hughes, Annie; Schruba, Andreas; Rosolowsky, Erik; Blanc, Guillermo A.; Escala, Andres; Bolatto, Alberto D.; Colombo, Dario; Kramer, Carsten; Kruijssen, J. M. Diederik; Meidt, Sharon; Querejeta, Miguel; Schinnerer, Eva; Sliwa, Kazimierz; Pety, Jerome; Sandstrom, Karin

    2016-01-01

    The cloud-scale density, velocity dispersion, and gravitational boundedness of the interstellar medium (ISM) vary within and among galaxies. In turbulent models, these properties play key roles in the ability of gas to form stars. New high-fidelity, high-resolution surveys offer the prospect to measure these quantities across galaxies. We present a simple approach to make such measurements and to test hypotheses that link small-scale gas structure to star formation and galactic environment. Our calculations capture the key physics of the Larson scaling relations, and we show good correspondence between our approach and a traditional “cloud properties” treatment. However, we argue that our method is preferable in many cases because of its simple, reproducible characterization of all emission. Using, low- J 12 CO data from recent surveys, we characterize the molecular ISM at 60 pc resolution in the Antennae, the Large Magellanic Cloud (LMC), M31, M33, M51, and M74. We report the distributions of surface density, velocity dispersion, and gravitational boundedness at 60 pc scales and show galaxy-to-galaxy and intragalaxy variations in each. The distribution of flux as a function of surface density appears roughly lognormal with a 1 σ width of ∼0.3 dex, though the center of this distribution varies from galaxy to galaxy. The 60 pc resolution line width and molecular gas surface density correlate well, which is a fundamental behavior expected for virialized or free-falling gas. Varying the measurement scale for the LMC and M31, we show that the molecular ISM has higher surface densities, lower line widths, and more self-gravity at smaller scales.

  2. A PORTRAIT OF COLD GAS IN GALAXIES AT 60 pc RESOLUTION AND A SIMPLE METHOD TO TEST HYPOTHESES THAT LINK SMALL-SCALE ISM STRUCTURE TO GALAXY-SCALE PROCESSES

    Energy Technology Data Exchange (ETDEWEB)

    Leroy, Adam K. [Department of Astronomy, The Ohio State University, 140 West 18th Avenue, Columbus, OH 43210 (United States); Hughes, Annie [CNRS, IRAP, 9 av. du Colonel Roche, BP 44346, F-31028 Toulouse cedex 4 (France); Schruba, Andreas [Max-Planck-Institut für extraterrestrische Physik, Giessenbachstrasse 1, D-85748 Garching (Germany); Rosolowsky, Erik [Department of Physics, University of Alberta, Edmonton, AB (Canada); Blanc, Guillermo A.; Escala, Andres [Departamento de Astronomía, Universidad de Chile, Casilla 36-D, Santiago (Chile); Bolatto, Alberto D. [Department of Astronomy, Laboratory for Millimeter-wave Astronomy, and Joint Space Institute, University of Maryland, College Park, MD 20742 (United States); Colombo, Dario [Max-Planck-Institut für Radioastronomie, Auf dem Hügel 69, D-53121 Bonn (Germany); Kramer, Carsten [Instituto Radioastronomía Milimétrica (IRAM), Av. Divina Pastora 7, Nucleo Central, E-18012 Granada (Spain); Kruijssen, J. M. Diederik [Astronomisches Rechen-Institut, Zentrum für Astronomie der Universität Heidelberg, Mönchhofstrasse 12-14, D-69120 Heidelberg (Germany); Meidt, Sharon; Querejeta, Miguel; Schinnerer, Eva; Sliwa, Kazimierz [Max Planck Institute für Astronomie, Königstuhl 17, D-69117, Heidelberg (Germany); Pety, Jerome [Institut de Radioastronomie Millimtrique (IRAM), 300 Rue de la Piscine, F-38406 Saint-Martin-d’Hères (France); Sandstrom, Karin [Center for Astrophysics and Space Sciences, Department of Physics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (United States); and others

    2016-11-01

    The cloud-scale density, velocity dispersion, and gravitational boundedness of the interstellar medium (ISM) vary within and among galaxies. In turbulent models, these properties play key roles in the ability of gas to form stars. New high-fidelity, high-resolution surveys offer the prospect to measure these quantities across galaxies. We present a simple approach to make such measurements and to test hypotheses that link small-scale gas structure to star formation and galactic environment. Our calculations capture the key physics of the Larson scaling relations, and we show good correspondence between our approach and a traditional “cloud properties” treatment. However, we argue that our method is preferable in many cases because of its simple, reproducible characterization of all emission. Using, low- J {sup 12}CO data from recent surveys, we characterize the molecular ISM at 60 pc resolution in the Antennae, the Large Magellanic Cloud (LMC), M31, M33, M51, and M74. We report the distributions of surface density, velocity dispersion, and gravitational boundedness at 60 pc scales and show galaxy-to-galaxy and intragalaxy variations in each. The distribution of flux as a function of surface density appears roughly lognormal with a 1 σ width of ∼0.3 dex, though the center of this distribution varies from galaxy to galaxy. The 60 pc resolution line width and molecular gas surface density correlate well, which is a fundamental behavior expected for virialized or free-falling gas. Varying the measurement scale for the LMC and M31, we show that the molecular ISM has higher surface densities, lower line widths, and more self-gravity at smaller scales.

  3. Testing Proximate Cause Hypotheses for the End-Ordovician Mass Extinction: Do Patterns of Change in Biomarker Signatures Support a Linkage Between Graptolite and Phytoplankton Community Changes?

    Science.gov (United States)

    Marshall, N.; Thomas, E.; Mitchell, C. E.; Aga, D.; Wombacher, R.

    2017-12-01

    The goal of our study is to analyze the biomarkers in the Vinini Creek section based on a set of samples in which graptolite community change has been identified. The study will test several competing hypotheses about the cause of the observed changes in the environmental proxies and the graptolite community structure and composition. The study interval in the Late Ordovician (444.7-443.4 Ma) was a glacial period with varying climate and sea level changes that are marked by geochemical signatures. Climate change drove changes in deep-ocean circulation and upwelling zones during the concomitant mass extinction and it appears that the graptolites inhabiting the mesopelagic zone were the most vulnerable during these events. Due to the high vulnerability of the graptolites in the Vinini Creek section, biomarkers in the section are especially important for interpreting changing ocean conditions. Changing productivity in the upwelling zones of modern oceans is reflected in the microbial community, which forms the base of the food chain and drives biogeochemical cycles. Moreover, microbes can be traced using organism-specific biomarkers. Steranes (C27-C29) are biomarkers for eukaryotic organisms (e.g., green algae) and hopanes (C27-C35) are biomarkers for bacteria. We will determine hopane-sterane ratios, which reflect measurable relative contributions of bacteria and eukaryotes to sedimentary organic matter as a result of fluctuations in the strength of the oxygen minimum zone and associated denitrification processes. Previous work at lower resolution in this section suggests a decrease in denitrification and increase in abundance of eukaryotes (e.g., green algae) relative to bacteria within the Hirnantian glacial lowstand interval, roughly synchronously with the mass extinction. These relationships suggest that climatically driven changes in nutrient cycling and phytoplankton communities drove the mass extinction. If this is so, then changes in graptolite community

  4. Ancestral state reconstructions require biological evidence to test evolutionary hypotheses: A case study examining the evolution of reproductive mode in squamate reptiles.

    Science.gov (United States)

    Griffith, Oliver W; Blackburn, Daniel G; Brandley, Matthew C; Van Dyke, James U; Whittington, Camilla M; Thompson, Michael B

    2015-09-01

    To understand evolutionary transformations it is necessary to identify the character states of extinct ancestors. Ancestral character state reconstruction is inherently difficult because it requires an accurate phylogeny, character state data, and a statistical model of transition rates and is fundamentally constrained by missing data such as extinct taxa. We argue that model based ancestral character state reconstruction should be used to generate hypotheses but should not be considered an analytical endpoint. Using the evolution of viviparity and reversals to oviparity in squamates as a case study, we show how anatomical, physiological, and ecological data can be used to evaluate hypotheses about evolutionary transitions. The evolution of squamate viviparity requires changes to the timing of reproductive events and the successive loss of features responsible for building an eggshell. A reversal to oviparity requires that those lost traits re-evolve. We argue that the re-evolution of oviparity is inherently more difficult than the reverse. We outline how the inviability of intermediate phenotypes might present physiological barriers to reversals from viviparity to oviparity. Finally, we show that ecological data supports an oviparous ancestral state for squamates and multiple transitions to viviparity. In summary, we conclude that the first squamates were oviparous, that frequent transitions to viviparity have occurred, and that reversals to oviparity in viviparous lineages either have not occurred or are exceedingly rare. As this evidence supports conclusions that differ from previous ancestral state reconstructions, our paper highlights the importance of incorporating biological evidence to evaluate model-generated hypotheses. © 2015 Wiley Periodicals, Inc.

  5. In vivo strains in the femur of the Virginia opossum (Didelphis virginiana) during terrestrial locomotion: testing hypotheses of evolutionary shifts in mammalian bone loading and design.

    Science.gov (United States)

    Butcher, Michael T; White, Bartholomew J; Hudzik, Nathan B; Gosnell, W Casey; Parrish, John H A; Blob, Richard W

    2011-08-01

    Terrestrial locomotion can impose substantial loads on vertebrate limbs. Previous studies have shown that limb bones from cursorial species of eutherian mammals experience high bending loads with minimal torsion, whereas the limb bones of non-avian reptiles (and amphibians) exhibit considerable torsion in addition to bending. It has been hypothesized that these differences in loading regime are related to the difference in limb posture between upright mammals and sprawling reptiles, and that the loading patterns observed in non-avian reptiles may be ancestral for tetrapod vertebrates. To evaluate whether non-cursorial mammals show loading patterns more similar to those of sprawling lineages, we measured in vivo strains in the femur during terrestrial locomotion of the Virginia opossum (Didelphis virginiana), a marsupial that uses more crouched limb posture than most mammals from which bone strains have been recorded, and which belongs to a clade phylogenetically between reptiles and the eutherian mammals studied previously. The presence of substantial torsion in the femur of opossums, similar to non-avian reptiles, would suggest that this loading regime likely reflects an ancestral condition for tetrapod limb bone design. Strain recordings indicate the presence of both bending and appreciable torsion (shear strain: 419.1 ± 212.8 με) in the opossum femur, with planar strain analyses showing neutral axis orientations that placed the lateral aspect of the femur in tension at the time of peak strains. Such mediolateral bending was unexpected for a mammal running with near-parasagittal limb kinematics. Shear strains were similar in magnitude to peak compressive axial strains, with opossum femora experiencing similar bending loads but higher levels of torsion compared with most previously studied mammals. Analyses of peak femoral strains led to estimated safety factor ranges of 5.1-7.2 in bending and 5.5-7.3 in torsion, somewhat higher than typical mammalian values

  6. Molecular diagnostic testing for primary biliary cholangitis.

    Science.gov (United States)

    Gatselis, Nikolaos K; Dalekos, George N

    2016-09-01

    A reliable liver autoimmune serology for the diagnosis of primary biliary cholangitis (PBC) is of particular importance. Recognition of patients at early stages and prompt treatment initiation may alter the outcome, slow progression, delays liver failure, and improves survival. In this review, we summarize and discuss the published data obtained from literature searches from PubMed and The National Library of Medicine (USA) and our own experience on the current and potential molecular based approaches to the diagnosis of PBC. Expert commentary: Standardization of liver diagnostic serology and clinical governance are two major points as antimitochondrial antibodies are the diagnostic hallmark of the disease and PBC-specific antinuclear antibodies could assist in the diagnosis and estimation of prognosis. New biomarkers such as novel autoantibodies, genetic polymorphisms, metabolomic profiling, micro-RNA and epigenetics may assist to the understanding, diagnosis and management of the disease.

  7. Testing Mediators Hypothesized to Account for the Effects of a Dissonance-Based Eating Disorder Prevention Program over Longer Term Follow-Up

    Science.gov (United States)

    Stice, Eric; Marti, C. Nathan; Rohde, Paul; Shaw, Heather

    2011-01-01

    Objective: Test the hypothesis that reductions in thin-ideal internalization and body dissatisfaction mediate the effects of a dissonance-based eating disorder prevention program on reductions in eating disorder symptoms over 1-year follow-up. Method: Data were drawn from a randomized effectiveness trial in which 306 female high school students…

  8. Immigrant self-employment : testing hypotheses about the role of origin- and host country human capital and bonding and bridging social capital

    NARCIS (Netherlands)

    Kanas, A.M.; Tubergen, F.A. van; Lippe, T. van der

    2009-01-01

    Using large-scale data on immigrants in the Netherlands, the authors tested competing arguments about the role of origin- and host-country human capital and bonding and bridging social capital in immigrants’ self-employment. When taking job-skill level into account, immigrants with a higher level of

  9. Quantitative linking hypotheses for infant eye movements.

    Directory of Open Access Journals (Sweden)

    Daniel Yurovsky

    Full Text Available The study of cognitive development hinges, largely, on the analysis of infant looking. But analyses of eye gaze data require the adoption of linking hypotheses: assumptions about the relationship between observed eye movements and underlying cognitive processes. We develop a general framework for constructing, testing, and comparing these hypotheses, and thus for producing new insights into early cognitive development. We first introduce the general framework--applicable to any infant gaze experiment--and then demonstrate its utility by analyzing data from a set of experiments investigating the role of attentional cues in infant learning. The new analysis uncovers significantly more structure in these data, finding evidence of learning that was not found in standard analyses and showing an unexpected relationship between cue use and learning rate. Finally, we discuss general implications for the construction and testing of quantitative linking hypotheses. MATLAB code for sample linking hypotheses can be found on the first author's website.

  10. Origin and evolution of Petrocosmea (Gesneriaceae) inferred from both DNA sequence and novel findings in morphology with a test of morphology-based hypotheses.

    Science.gov (United States)

    Qiu, Zhi-Jing; Lu, Yuan-Xue; Li, Chao-Qun; Dong, Yang; Smith, James F; Wang, Yin-Zheng

    2015-07-03

    Petrocosmea Oliver (Gesneriaceae) currently comprises 38 species with four non-nominate varieties, nearly all of which have been described solely from herbarium specimens. However, the dried specimens have obscured the full range of extremely diverse morphological variation that exists in the genus and has resulted in a poor subgeneric classification system that does not reflect the evolutionary history of this group. It is important to develop innovative methods to find new morphological traits and reexamine and reevaluate the traditionally used morphological data based on new hypothesis. In addition, Petrocosmea is a mid-sized genus but exhibits extreme diverse floral variants. This makes the genus of particular interest in addressing the question whether there are any key factors that is specifically associated with their evolution and diversification. Here we present the first phylogenetic analyses of the genus based on dense taxonomic sampling and multiple genes combined with a comprehensive morphological investigation. Maximum-parsimony, maximum likelihood and Bayesian analyses of molecular data from two nuclear DNA and six cpDNA regions support the monophyly of Petrocosmea and recover five major clades within the genus, which is strongly corroborated by the reconstruction of ancestral states for twelve new morphological characters directly observed from living material. Ancestral area reconstruction shows that its most common ancestor was likely located east and southeast of the Himalaya-Tibetan plateau. The origin of Petrocosmea from a potentially Raphiocarpus-like ancestor might have involved a series of morphological modifications from caulescent to acaulescent habit as well as from a tetrandrous flower with a long corolla-tube to a diandrous flower with a short corolla-tube, also evident in the vestigial caulescent habit and transitional floral form in clade A that is sister to the remainder of the genus. Among the five clades in Petrocosmea, the

  11. Testing hypotheses in an I(2) model with piecewise linear trends. An analysis of the persistent long swings in the Dmk/$ rate

    DEFF Research Database (Denmark)

    Johansen, Søren; Juselius, Katarina; Frydman, Roman

    2010-01-01

    This paper discusses the I(2) model with breaks in the deterministic component and illustrates with an analysis of German and US prices, exchange rates, and interest rates in 1975--1999. It provides new results on the likelihood ratio test of overidentifying restrictions on the cointegrating...... relations when they contain piecewise linear trends. One important aim of the paper is to demonstrate that a structured I(2) analysis is useful for a better understanding of the empirical regularities underlying the persistent swings in nominal exchange rates, typical in periods of floating exchange rates....

  12. Individual wealth rank, community wealth inequality, and self-reported adult poor health: a test of hypotheses with panel data (2002-2006) from native Amazonians, Bolivia.

    Science.gov (United States)

    Undurraga, Eduardo A; Nyberg, Colleen; Eisenberg, Dan T A; Magvanjav, Oyunbileg; Reyes-García, Victoria; Huanca, Tomás; Leonard, William R; McDade, Thomas W; Tanner, Susan; Vadez, Vincent; Godoy, Ricardo

    2010-12-01

    Growing evidence suggests that economic inequality in a community harms the health of a person. Using panel data from a small-scale, preindustrial rural society, we test whether individual wealth rank and village wealth inequality affects self-reported poor health in a foraging-farming native Amazonian society. A person's wealth rank was negatively but weakly associated with self-reported morbidity. Each step up/year in the village wealth hierarchy reduced total self-reported days ill by 0.4 percent. The Gini coefficient of village wealth inequality bore a positive association with self-reported poor health that was large in size, but not statistically significant. We found small village wealth inequality, and evidence that individual economic rank did not change. The modest effects may have to do with having used subjective rather than objective measures of health, having small village wealth inequality, and with the possibly true modest effect of a person's wealth rank on health in a small-scale, kin-based society. Finally, we also found that an increase in mean individual wealth by village was related to worse self-reported health. As the Tsimane' integrate into the market economy, their possibilities of wealth accumulation rise, which may affect their well-being. Our work contributes to recent efforts in biocultural anthropology to link the study of social inequalities, human biology, and human-environment interactions.

  13. Improving Molecular Genetic Test Utilization through Order Restriction, Test Review, and Guidance.

    Science.gov (United States)

    Riley, Jacquelyn D; Procop, Gary W; Kottke-Marchant, Kandice; Wyllie, Robert; Lacbawan, Felicitas L

    2015-05-01

    The ordering of molecular genetic tests by health providers not well trained in genetics may have a variety of untoward effects. These include the selection of inappropriate tests, the ordering of panels when the assessment of individual or fewer genes would be more appropriate, inaccurate result interpretation and inappropriate patient guidance, and significant unwarranted cost expenditure. We sought to improve the utilization of molecular genetic tests by requiring providers without specialty training in genetics to use genetic counselors and molecular genetic pathologists to assist in test selection. We used a genetic and genomic test review process wherein the laboratory-based genetic counselor performed the preanalytic assessment of test orders and test triage. Test indication and clinical findings were evaluated against the test panel composition, methods, and test limitations under the supervision of the molecular genetic pathologist. These test utilization management efforts resulted in a decrease in genetic test ordering and a gross cost savings of $1,531,913 since the inception of these programs in September 2011 through December 2013. The combination of limiting the availability of complex genetic tests and providing guidance regarding appropriate test strategies is an effective way to improve genetic tests, contributing to judicious use of limited health care resources. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  14. Structures of Bordered Pits Potentially Contributing to Isolation of a Refilled Vessel from Negative Xylem Pressure in Stems of Morus australis Poir.: Testing of the Pit Membrane Osmosis and Pit Valve Hypotheses.

    Science.gov (United States)

    Ooeda, Hiroki; Terashima, Ichiro; Taneda, Haruhiko

    2017-02-01

    Two hypotheses have been proposed to explain the mechanism preventing the refilling vessel water from being drained to the neighboring functional vessels under negative pressure. The pit membrane osmosis hypothesis proposes that the xylem parenchyma cells release polysaccharides that are impermeable to the intervessel pit membranes into the refilling vessel; this osmotically counteracts the negative pressure, thereby allowing the vessel to refill. The pit valve hypothesis proposes that gas trapped within intervessel bordered pits isolates the refilling vessel water from the surrounding functional vessels. Here, using the single-vessel method, we assessed these hypotheses in shoots of mulberry (Morus australis Poir.). First, we confirmed the occurrence of xylem refilling under negative pressure in the potted mulberry saplings. To examine the pit membrane osmosis hypothesis, we estimated the semi-permeability of pit membranes for molecules of various sizes and found that the pit membranes were not semi-permeable to polyethylene glycol of molecular mass osmosis mechanism in mulberry would be unrealistically large. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  15. Scientific 'Laws', 'Hypotheses' and 'Theories'

    Indian Academy of Sciences (India)

    theories, defines a hypothesis as "any supposition which we may ... about the origin of the solar system are also hypotheses of this type. They are about the birth of the planets, an event, which has happened, in the past history of our Universe.

  16. Scientific 'Laws', 'Hypotheses' and 'Theories'

    Indian Academy of Sciences (India)

    verified, the hypothesis changes from the status of a 'mere' hypothesis, and ... a pre-existing law and the body of facts upon which that law is based. Hypotheses .... implicit belief that order objectively exists in nature, and that scientific laws ...

  17. Overdiagnosis of Clostridium difficile Infection in the Molecular Test Era.

    Science.gov (United States)

    Polage, Christopher R; Gyorke, Clare E; Kennedy, Michael A; Leslie, Jhansi L; Chin, David L; Wang, Susan; Nguyen, Hien H; Huang, Bin; Tang, Yi-Wei; Lee, Lenora W; Kim, Kyoungmi; Taylor, Sandra; Romano, Patrick S; Panacek, Edward A; Goodell, Parker B; Solnick, Jay V; Cohen, Stuart H

    2015-11-01

    Clostridium difficile is a major cause of health care-associated infection, but disagreement between diagnostic tests is an ongoing barrier to clinical decision making and public health reporting. Molecular tests are increasingly used to diagnose C difficile infection (CDI), but many molecular test-positive patients lack toxins that historically defined disease, making it unclear if they need treatment. To determine the natural history and need for treatment of patients who are toxin immunoassay negative and polymerase chain reaction (PCR) positive (Tox-/PCR+) for CDI. Prospective observational cohort study at a single academic medical center among 1416 hospitalized adults tested for C difficile toxins 72 hours or longer after admission between December 1, 2010, and October 20, 2012. The analysis was conducted in stages with revisions from April 27, 2013, to January 13, 2015. Patients undergoing C difficile testing were grouped by US Food and Drug Administration-approved toxin and PCR tests as Tox+/PCR+, Tox-/PCR+, or Tox-/PCR-. Toxin results were reported clinically. Polymerase chain reaction results were not reported. The main study outcomes were duration of diarrhea during up to 14 days of treatment, rate of CDI-related complications (ie, colectomy, megacolon, or intensive care unit care) and CDI-related death within 30 days. Twenty-one percent (293 of 1416) of hospitalized adults tested for C difficile were positive by PCR, but 44.7% (131 of 293) had toxins detected by the clinical toxin test. At baseline, Tox-/PCR+ patients had lower C difficile bacterial load and less antibiotic exposure, fecal inflammation, and diarrhea than Tox+/PCR+ patients (P difficile by either method. Exclusive reliance on molecular tests for CDI diagnosis without tests for toxins or host response is likely to result in overdiagnosis, overtreatment, and increased health care costs.

  18. Update on Molecular Testing for Cytologically Indeterminate Thyroid Nodules.

    Science.gov (United States)

    Nishino, Michiya; Nikiforova, Marina

    2018-04-01

    - Approximately 15% to 30% of thyroid nodules that undergo fine-needle aspiration are classified as cytologically indeterminate, presenting management challenges for patients and clinicians alike. During the past several years, several molecular tests have been developed to reduce the diagnostic uncertainty of indeterminate thyroid fine-needle aspirations. - To review the methodology, clinical validation, and recent peer-reviewed literature for 4 molecular tests that are currently marketed for cytologically indeterminate thyroid fine-needle aspiration specimens: Afirma, ThyroSeq, ThyGenX/ThyraMIR, and RosettaGX Reveal. - Peer-reviewed literature retrieved from PubMed search, data provided by company websites and representatives, and authors' personal experiences. - The 4 commercially available molecular tests for thyroid cytology offer unique approaches to improve the risk stratification of thyroid nodules. Familiarity with data from the validation studies as well as the emerging literature about test performance in the postvalidation setting can help users to select and interpret these tests in a clinically meaningful way.

  19. Commercially available molecular tests for human papillomaviruses (HPV): 2015 update.

    Science.gov (United States)

    Poljak, Mario; Kocjan, Boštjan J; Oštrbenk, Anja; Seme, Katja

    2016-03-01

    Commercial molecular tests for human papillomaviruses (HPV) are invaluable diagnostic tools in cervical carcinoma screening and management of women with cervical precancerous lesions as well as important research tools for epidemiological studies, vaccine development, and implementation and monitoring of vaccination programs. In this third inventory of commercial HPV tests, we identified 193 distinct commercial HPV tests and at least 127 test variants available on the market in 2015, which represents a 54% and 79% increase in the number of distinct HPV tests and variants, respectively, in comparison to our last inventory performed in 2012. Identified HPV tests were provisionally divided into eight main groups and several subgroups. Among the 193 commercial HPV tests, all but two target alpha-HPV types only. Although the number of commercial HPV tests with at least one published study in peer-reviewed literature has increased significantly in the last three years, several published performance evaluations are still not in line with agreed-upon standards in the HPV community. Manufacturers should invest greater effort into evaluating their products and publishing validation/evaluation results in peer-reviewed journals. To achieve this, more clinically oriented external quality-control panels and initiatives are required. For evaluating the analytical performance of the entire range of HPV tests currently on the market, more diverse and reliable external quality-control programs based on international standards for all important HPV types are indispensable. The performance of a wider range of HPV tests must be promptly evaluated on a variety of alternative clinical specimens. In addition, more complete HPV assays containing validated sample-extraction protocols and appropriate internal controls are urgently needed. Provision of a broader range of automated systems allowing large-scale HPV testing as well as the development of reliable, rapid, and affordable molecular

  20. QED Tests and Search for New Physics in Molecular Hydrogen

    Science.gov (United States)

    Salumbides, E. J.; Niu, M. L.; Dickenson, G. D.; Eikema, K. S. E.; Komasa, J.; Pachucki, K.; Ubachs, W.

    2013-06-01

    The hydrogen molecule has been the benchmark system for quantum chemistry, and may provide a test ground for new physics. We present our high-resolution spectroscopic studies on the X ^1Σ^+_g electronic ground state rotational series and fundamenal vibrational tones in molecular hydrogen. In combination with recent accurate ab initio calculations, we demonstrate systematic tests of quantum electrodynamical (QED) effects in molecules. Moreover, the precise comparison between theory and experiment can provide stringent constraints on possible new interactions that extend beyond the Standard Model. E. J. Salumbides, G. D. Dickenson, T. I. Ivanov and W. Ubachs, Phys. Rev. Lett. 107, 043005 (2011).

  1. Predictive hypotheses are ineffectual in resolving complex biochemical systems.

    Science.gov (United States)

    Fry, Michael

    2018-03-20

    Scientific hypotheses may either predict particular unknown facts or accommodate previously-known data. Although affirmed predictions are intuitively more rewarding than accommodations of established facts, opinions divide whether predictive hypotheses are also epistemically superior to accommodation hypotheses. This paper examines the contribution of predictive hypotheses to discoveries of several bio-molecular systems. Having all the necessary elements of the system known beforehand, an abstract predictive hypothesis of semiconservative mode of DNA replication was successfully affirmed. However, in defining the genetic code whose biochemical basis was unclear, hypotheses were only partially effective and supplementary experimentation was required for its conclusive definition. Markedly, hypotheses were entirely inept in predicting workings of complex systems that included unknown elements. Thus, hypotheses did not predict the existence and function of mRNA, the multiple unidentified components of the protein biosynthesis machinery, or the manifold unknown constituents of the ubiquitin-proteasome system of protein breakdown. Consequently, because of their inability to envision unknown entities, predictive hypotheses did not contribute to the elucidation of cation theories remained the sole instrument to explain complex bio-molecular systems, the philosophical question of alleged advantage of predictive over accommodative hypotheses became inconsequential.

  2. [Malignant Melanoma - from Classical Histology towards Molecular Genetic Testing].

    Science.gov (United States)

    Ryška, A; Horký, O; Berkovcová, J; Tichá, I; Kalinová, M; Matějčková, M; Bóday, Á; Drábek, J; Martínek, P; Šimová, J; Sieglová, K; Vošmiková, H

    Malignant melanoma is - in comparison with other skin tumors - a relatively rare malignant neoplasm with highly aggressive biologic behavior and variable prognosis. Recent data in pathology and molecular diagnostics indicate that malignant melanoma is in fact not a single entity but a group of different neoplasms with variable etiopathogenesis, biologic behavior and prognosis. New therapeutic options using targeted treatment blocking MAPK signaling pathway require testing of BRAF gene mutation status. This helps to select patients with highest probability of benefit from this treatment. This article summarizes information on the correlation of morphological findings with genetic changes, discusses the representation of individual genetic types in various morphological subgroups and deals with the newly proposed genetic classification of melanoma and the current possibilities, pitfalls and challenges in BRAF testing of malignant melanoma. It also describes the current testing situation in the Czech Republic - the methods used, the representation of BRAF mutations in the tested population and the future of testing. It also shows the limitations of the BRAF and MEK targeted treatment concept resulting from the heterogeneity of the tumor population. Mechanisms of acquired resistance to MAPK pathway inhibitors, possibilities of their detection, and issues of combination of targeted therapy and immunotherapy are discussed.Key words: malignant melanoma - BRAF - mutation - molecular targeted therapy - tumor microenvironment - tumor heterogeneity This work was supported by projects PROGRES Q40/11, BBMRICZ LM2015089, SVV 260398 and GACR 17-10331S. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 28. 3. 2017Accepted: 16. 5. 2017.

  3. [Pilot tests using molecular diagnostic assay cervicovaginal infection during pregnancy].

    Science.gov (United States)

    Beltrán-Montoya, J; Escudero-Gontes, S; Martínez-Huerta, N E; Ávila-Vergara, M A; Morales-Hernández, V; Canchola-Sotelo, C; Palacios-González, B; Vadillo-Ortega, F

    2016-08-01

    The prevalence of cervicovaginal infections during pregnancy has been associated with adverse perinatal outcomes however, the actual approach used for diagnosis is not effective. The aim of this study was to compare the diagnosis of vaginal infections in pregnant women using clinical, molecular diagnostic and traditional microbiological culture in a pilot study, to determine the prevalence and association with the development of preterm labor. We performed a nested cross-sectional study composed by 54 women in a cohort of pregnant women in Mexico City. Cervicovaginal infections were evaluated by clinical methods, microbiology culture and a commercially available molecular biology test. Prevalence of cervicovaginal infections during pregnancy was estimated between 28% and 50% according to methodologies. Considering the clinical diagnosis of preterm labor as the gold standard, all diagnostic tests were poor as predictors of preterm labor. Traditional approaches to establish the significance of cervicovaginal infection in pregnancy are exhausted, so be sought new ways to understand this complex relationship. Meanwhile it is recommended to continue to use traditional methods to identify infections during pregnancy in both knowledge of new methods aimed at understanding these relationships are sophisticated.

  4. Molecular testing of human papillomavirus in cervical specimens

    International Nuclear Information System (INIS)

    Gazzaz, Faten Salah B.

    2007-01-01

    Objective was to improve the diagnosis of cervical neoplasia by early detection of human papillomavirus (HPV) in uterine cervix, by adding molecular testing of HPV using hybrid capture 2 (HC2) and polymerase chain reaction (PCR) tests to Papanicoalou (Pap) test. One hundred women were enrolled in this study. The mean age (mean+-SD) was 41.97+- 8.76 years and range was 27-65 years. All women had undergone cervical cytological screening with cervical cytology, HPV DNA testing by HC2 and PCR, during the period from January to December 2006, at King Abdul-Aziz University Hospital (KAAUH) and King Fahd research Center, Jeddah, Saudi Arabia. The results were obtained by HC2 for detection of HPV were 5(5%) high-risk HPV, one low-risk HPV (1%) and 94(94%) negative cases. The PCR detected only 4(4%) cases. Using the HC2 test as a reference, sensitivity, specificity, positive predictive, negative predictive values and accuracy of base line Pap were 50, 85, 17.7, 96.4 and 83%; of final Pap smear were 100, 96.8, 66.7, 100, and 97% and for PCR were 66.7, 100, 100, 97.9 and 98%. The Pap test was repeated within a year for patients with abnormal Pap test with positive HPV DNA. Combined screening by cytology and HPV testing using both HC2 and PCR sensitively detects women with existing disease. The absence of HPV DNA provides reassurance that patients are unlikely to develop cancer for several years. We suggest using Pap with HC2 and PCR in screening programs to ensure that women with the double negative result at baseline might safely be screened at longer intervals. (author)

  5. Advancing molecular-guided surgery through probe development and testing in a moderate cost evaluation pipeline

    Science.gov (United States)

    Pogue, Brian W.; Paulsen, Keith D.; Hull, Sally M.; Samkoe, Kimberley S.; Gunn, Jason; Hoopes, Jack; Roberts, David W.; Strong, Theresa V.; Draney, Daniel; Feldwisch, Joachim

    2015-03-01

    Molecular guided oncology surgery has the potential to transform the way decisions about resection are done, and can be critically important in areas such as neurosurgery where the margins of tumor relative to critical normal tissues are not readily apparent from visual or palpable guidance. Yet there are major financial barriers to advancing agents into clinical trials with commercial backing. We observe that development of these agents in the standard biological therapeutic paradigm is not viable, due to the high up front financial investment needed and the limitations in the revenue models of contrast agents for imaging. The hypothesized solution to this problem is to develop small molecular biologicals tagged with an established fluorescent reporter, through the chemical agent approval pathway, targeting a phase 0 trials initially, such that the initial startup phase can be completely funded by a single NIH grant. In this way, fast trials can be completed to de-risk the development pipeline, and advance the idea of fluorescence-guided surgery (FGS) reporters into human testing. As with biological therapies the potential successes of each agent are still moderate, but this process will allow the field to advance in a more stable and productive manner, rather than relying upon isolated molecules developed at high cost and risk. The pathway proposed and tested here uses peptide synthesis of an epidermal growth factor receptor (EGFR)-binding Affibody molecules, uniquely conjugated to IRDye 800CW, developed and tested in academic and industrial laboratories with well-established records for GMP production, fill and finish, toxicity testing, and early phase clinical trials with image guidance.

  6. Biomarker assessment and molecular testing for prognostication in breast cancer.

    Science.gov (United States)

    Kos, Zuzana; Dabbs, David J

    2016-01-01

    Current treatment of breast cancer incorporates clinical, pathological and molecular data. Oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) define prognosis and identify tumours for targeted therapy, and remain the sole established single-molecule biomarkers defining the minimum breast cancer pathology data set. Ki67 remains one of the most promising yet controversial biomarkers in breast cancer, implemented routinely in some, but not all, pathology departments. Beyond the single-molecule biomarkers, a host of multigene expression tests have been developed to interrogate the driver pathways and biology of individual breast cancers to predict clinical outcome more accurately. A minority of these assays have entered into clinical practice. This review focuses on the established biomarkers of ER, PR and HER2, the controversial but clinically implemented biomarker Ki67 and the currently marketed gene expression signatures. © 2015 John Wiley & Sons Ltd.

  7. Development of a molecular test of Paget's disease of bone.

    Science.gov (United States)

    Guay-Bélanger, Sabrina; Simonyan, David; Bureau, Alexandre; Gagnon, Edith; Albert, Caroline; Morissette, Jean; Siris, Ethel S; Orcel, Philippe; Brown, Jacques P; Michou, Laëtitia

    2016-03-01

    Depending on populations, 15 to 40% of patients have a familial form of Paget's disease of bone (PDB), which is transmitted in an autosomal-dominant mode of inheritance with incomplete penetrance. To date, only SQSTM1 gene mutations have been linked to the disease. Several single nucleotide polymorphisms (SNPs) have been associated with PDB in patient non-carriers of SQSTM1 mutations, but they have minor size effects. The current clinical practice guidelines still recommend to measure total serum alkaline phosphatase (sALP) for PDB screening. However, genetic or bone biomarkers alone may lack sensitivity to detect PDB. Thus, the objective of this study was to develop a molecular test of PDB, combining genetic and bone biomarkers, in order to detect PDB, which is frequently asymptomatic. We genotyped 35 SNPs previously associated with PDB in 305 patients, and 292 healthy controls. In addition, serum levels of 14 bone biomarkers were assayed in 51 patients and 151 healthy controls. Bivariate and multivariate logistic regression models with adjustment for age and sex were fitted to search for a combination of SNPs and/or bone biomarkers that could best detect PDB in patient non-carriers of SQSTM1 mutations. First, a combination of five genetic markers gave rise to the highest area under the ROC curve (AUC) with 95% confidence interval [95% CI] of 0.731 [0.688; 0.773], which allowed us to detect 81.5% of patients with PDB. Second, a combination of two bone biomarkers had an AUC of 0.822 [0.726; 0.918], and was present in 81.5% of patients with PDB. Then, the combination of the five genetic markers and the two bone biomarkers increased the AUC up to 0.892 [0.833; 0.951], and detected 88.5% of patients with PDB. These results suggested that an algorithm integrating first a screen for SQSTM1 gene mutations, followed by either a genetic markers combination or a combined genetic and biochemical markers test in patients non-carrier of any SQSTM1 mutation, may detect the PDB

  8. Testing the molecular clock using mechanistic models of fossil preservation and molecular evolution.

    Science.gov (United States)

    Warnock, Rachel C M; Yang, Ziheng; Donoghue, Philip C J

    2017-06-28

    Molecular sequence data provide information about relative times only, and fossil-based age constraints are the ultimate source of information about absolute times in molecular clock dating analyses. Thus, fossil calibrations are critical to molecular clock dating, but competing methods are difficult to evaluate empirically because the true evolutionary time scale is never known. Here, we combine mechanistic models of fossil preservation and sequence evolution in simulations to evaluate different approaches to constructing fossil calibrations and their impact on Bayesian molecular clock dating, and the relative impact of fossil versus molecular sampling. We show that divergence time estimation is impacted by the model of fossil preservation, sampling intensity and tree shape. The addition of sequence data may improve molecular clock estimates, but accuracy and precision is dominated by the quality of the fossil calibrations. Posterior means and medians are poor representatives of true divergence times; posterior intervals provide a much more accurate estimate of divergence times, though they may be wide and often do not have high coverage probability. Our results highlight the importance of increased fossil sampling and improved statistical approaches to generating calibrations, which should incorporate the non-uniform nature of ecological and temporal fossil species distributions. © 2017 The Authors.

  9. Electroconvulsive therapy's mechanism of action: neuroendocrine hypotheses.

    Science.gov (United States)

    Haskett, Roger F

    2014-06-01

    Despite a range of etiological theories since the introduction of electroconvulsive therapy (ECT) more than 75 years ago, its mechanism of action remains poorly understood. The neuroendocrine hypothesis is based on the seizure-related release of hypothalamic hormones into the blood and cerebrospinal fluid and evidence of endocrine dysfunction in many patients with severe mood disorder. The specific effect of ECT was hypothesized to result from the transverse passage of current through the brain with direct stimulation of axial structures including the diencephalon. The prompt release of adrenocorticotropic hormone, cortisol, and prolactin into blood followed ECT with a return to pretreatment baseline levels in several hours. The elevated levels of hormones were absorbed by the cerebrospinal fluid, providing contact with brain cells and central nervous system structures. An apparently specific pattern of ECT-induced hormone changes, limited to prolactin and cortisol, suggested that ECT released a substance with dopaminergic antagonist and antipsychotic properties. As hypothalamic dysfunction is a key finding in endogenomorphic depression and the abnormal endocrine and physiological functions usually normalize with recovery, this led to a search for biological markers that would supplement clinical assessment of diagnosis and treatment response. One of these, the overnight dexamethasone suppression test found that 40% to 50% of melancholic depressed patients had abnormal results, whereas 90% of control patients suppressed normally. This was followed by a period of uncritical overenthusiasm followed by wholesale rejection of the clinical neuroendocrine strategies. Several key methodological issues received inadequate attention, and there have been calls to revisit this topic.

  10. Limits on hypothesizing new quantum numbers

    International Nuclear Information System (INIS)

    Goldstein, G.R.; Moravcsik, M.J.

    1986-01-01

    According to a recent theorem, for a general quantum-mechanical system undergoing a process, one can tell from measurements on this system whether or not it is characterized by a quantum number, the existence of which is unknown to the observer, even though the detecting equipment used by the observer is unable to distinguish among the various possible values of the ''secret'' quantum number and hence always averages over them. The present paper deals with situations in which this averaging is avoided and hence the ''secret'' quantum number remains ''secret.'' This occurs when a new quantum number is hypothesized in such a way that all the past measurements pertain to the system with one and the same value of the ''secret'' quantum number, or when the new quantum number is related to the old ones by a specific dynamical model providing a one-to-one correspondence. In the first of these cases, however, the one and the same state of the ''secret'' quantum number needs to be a nondegenerate one. If it is degenerate, the theorem can again be applied. This last feature provides a tool for experimentally testing symmetry breaking and the reestablishment of symmetries in asymptotic regions. The situation is illustrated on historical examples like isospin and strangeness, as well as on some contemporary schemes involving spaces of higher dimensionality

  11. Biomineralization Patterns of Intracellular Carbonatogenesis in Cyanobacteria: Molecular Hypotheses

    Directory of Open Access Journals (Sweden)

    Jinhua Li

    2016-02-01

    Full Text Available The recent discovery of intracellular carbonatogenesis in several cyanobacteria species has challenged the traditional view that this process was extracellular and not controlled. However, a detailed analysis of the size distribution, chemical composition and 3-D-arrangement of carbonates in these cyanobacteria is lacking. Here, we characterized these features in Candidatus Gloeomargarita lithophora C7 and Candidatus Synechococcus calcipolaris G9 by conventional transmission electron microscopy, tomography, ultramicrotomy, and scanning transmission X-ray microscopy (STXM. Both Ca. G. lithophora C7 and Ca. S. calcipolaris G9 formed numerous polyphosphate granules adjacent or engulfing Ca-carbonate inclusions when grown in phosphate-rich solutions. Ca-carbonates were scattered within Ca. G. lithophora C7 cells under these conditions, but sometimes arranged in one or several chains. In contrast, Ca-carbonates formed at cell septa in Ca. S. calcipolaris G9 and were segregated equally between daughter cells after cell division, arranging as distorted disks at cell poles. The size distribution of carbonates evolved from a positively to a negatively skewed distribution as particles grew. Conventional ultramicrotomy did not preserve Ca-carbonates explaining partly why intracellular calcification has been overlooked in the past. All these new observations allow discussing with unprecedented insight some nucleation and growth processes occurring in intracellularly calcifying cyanobacteria with a particular emphasis on the possible involvement of intracellular compartments and cytoskeleton.

  12. Diagnostic Accuracy of Molecular Amplification Tests for Human African Trypanosomiasis-Systematic Review

    NARCIS (Netherlands)

    Mugasa, Claire M.; Adams, Emily R.; Boer, Kimberly R.; Dyserinck, Heleen C.; Büscher, Philippe; Schallig, Henk D. H. F.; Leeflang, Mariska M. G.

    2012-01-01

    Background: A range of molecular amplification techniques have been developed for the diagnosis of Human African Trypanosomiasis (HAT); however, careful evaluation of these tests must precede implementation to ensure their high clinical accuracy. Here, we investigated the diagnostic accuracy of

  13. EMQN/CMGS best practice guidelines for the molecular genetic testing of Huntington disease

    OpenAIRE

    Losekoot, Monique; van Belzen, Martine J; Seneca, Sara; Bauer, Peter; Stenhouse, Susan A R; Barton, David E

    2012-01-01

    Huntington disease (HD) is caused by the expansion of an unstable polymorphic trinucleotide (CAG)n repeat in exon 1 of the HTT gene, which translates into an extended polyglutamine tract in the protein. Laboratory diagnosis of HD involves estimation of the number of CAG repeats. Molecular genetic testing for HD is offered in a wide range of laboratories both within and outside the European community. In order to measure the quality and raise the standard of molecular genetic testing in these ...

  14. Twelve testable hypotheses on the geobiology of weathering

    Science.gov (United States)

    S.L. Brantley; J.P. Megonigal; F.N. Scatena; Z. Balogh-Brunstad; R.T. Barnes; M.A. Bruns; P. van Cappelen; K. Dontsova; H.E. Hartnett; A.S. Hartshorn; A. Heimsath; E. Herndon; L. Jin; C.K. Keller; J.R. Leake; W.H. McDowell; F.C. Meinzer; T.J. Mozdzer; S. Petsch; J. Pett-Ridge; K.S. Pretziger; P.A. Raymond; C.S. Riebe; K. Shumaker; A. Sutton-Grier; R. Walter; K. Yoo

    2011-01-01

    Critical Zone (CZ) research investigates the chemical, physical, and biological processes that modulate the Earth's surface. Here, we advance 12 hypotheses that must be tested to improve our understanding of the CZ: (1) Solar-to-chemical conversion of energy by plants regulates flows of carbon, water, and nutrients through plant-microbe soil networks, thereby...

  15. Development and assessment of molecular diagnostic tests for 15 enteropathogens causing childhood diarrhoea: a multicentre study.

    Science.gov (United States)

    Liu, Jie; Kabir, Furqan; Manneh, Jainaba; Lertsethtakarn, Paphavee; Begum, Sharmin; Gratz, Jean; Becker, Steve M; Operario, Darwin J; Taniuchi, Mami; Janaki, Lalitha; Platts-Mills, James A; Haverstick, Doris M; Kabir, Mamun; Sobuz, Shihab U; Nakjarung, Kaewkanya; Sakpaisal, Pimmada; Silapong, Sasikorn; Bodhidatta, Ladaporn; Qureshi, Shahida; Kalam, Adil; Saidi, Queen; Swai, Ndealilia; Mujaga, Buliga; Maro, Athanasia; Kwambana, Brenda; Dione, Michel; Antonio, Martin; Kibiki, Gibson; Mason, Carl J; Haque, Rashidul; Iqbal, Najeeha; Zaidi, Anita K M; Houpt, Eric R

    2014-08-01

    Childhood diarrhoea can be caused by many pathogens that are difficult to assay in the laboratory. Molecular diagnostic techniques provide a uniform method to detect and quantify candidate enteropathogens. We aimed to develop and assess molecular tests for identification of enteropathogens and their association with disease. We developed and assessed molecular diagnostic tests for 15 enteropathogens across three platforms-PCR-Luminex, multiplex real-time PCR, and TaqMan array card-at five laboratories worldwide. We judged the analytical and clinical performance of these molecular techniques against comparator methods (bacterial culture, ELISA, and PCR) using 867 diarrhoeal and 619 non-diarrhoeal stool specimens. We also measured molecular quantities of pathogens to predict the association with diarrhoea, by univariate logistic regression analysis. The molecular tests showed very good analytical and clinical performance at all five laboratories. Comparator methods had limited sensitivity compared with the molecular techniques (20-85% depending on the target) but good specificity (median 97·3%, IQR 96·5-98·9; mean 95·2%, SD 9·1). Positive samples by comparator methods usually had higher molecular quantities of pathogens than did negative samples, across almost all platforms and for most pathogens (pMolecular diagnostic tests can be implemented successfully and with fidelity across laboratories around the world. In the case of diarrhoea, these techniques can detect pathogens with high sensitivity and ascribe diarrhoeal associations based on quantification, including in mixed infections, providing rich and unprecedented measurements of infectious causes. Bill & Melinda Gates Foundation Next Generation Molecular Diagnostics Project. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. EMQN/CMGS best practice guidelines for the molecular genetic testing of Huntington disease.

    Science.gov (United States)

    Losekoot, Monique; van Belzen, Martine J; Seneca, Sara; Bauer, Peter; Stenhouse, Susan A R; Barton, David E

    2013-05-01

    Huntington disease (HD) is caused by the expansion of an unstable polymorphic trinucleotide (CAG)n repeat in exon 1 of the HTT gene, which translates into an extended polyglutamine tract in the protein. Laboratory diagnosis of HD involves estimation of the number of CAG repeats. Molecular genetic testing for HD is offered in a wide range of laboratories both within and outside the European community. In order to measure the quality and raise the standard of molecular genetic testing in these laboratories, the European Molecular Genetics Quality Network has organized a yearly external quality assessment (EQA) scheme for molecular genetic testing of HD for over 10 years. EQA compares a laboratory's output with a fixed standard both for genotyping and reporting of the results to the referring physicians. In general, the standard of genotyping is very high but the clarity of interpretation and reporting of the test result varies more widely. This emphasizes the need for best practice guidelines for this disorder. We have therefore developed these best practice guidelines for genetic testing for HD to assist in testing and reporting of results. The analytical methods and the potential pitfalls of molecular genetic testing are highlighted and the implications of the different test outcomes for the consultand and his or her family members are discussed.

  17. Adaptive hatching hypotheses do not explain asynchronous ...

    African Journals Online (AJOL)

    At the core of the suite of adaptive hatching hypotheses advanced to explain asynchronous hatching in birds is the assumption that if food is not limited then all the hatchlings will develop normally to adulthood. In this study Brown-headed Parrot Poicephalus cryptoxanthus chicks were hand fed and weighed on a daily basis.

  18. Scientific'Laws','Hypotheses' and'Theories'

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 3; Issue 12. Scientific 'Laws', 'Hypotheses' and 'Theories' - How are They Related? J R Lakshmana Rao. General Article Volume 3 Issue 12 December 1998 pp 55-61. Fulltext. Click here to view fulltext PDF. Permanent link:

  19. Using molecular diagnostic testing to personalize the treatment of patients with gastrointestinal stromal tumors.

    Science.gov (United States)

    Bannon, Amber E; Klug, Lillian R; Corless, Christopher L; Heinrich, Michael C

    2017-05-01

    The diagnosis and treatment of gastrointestinal stromal tumor (GIST) has emerged as a paradigm for modern cancer treatment ('precision medicine'), as it highlights the importance of matching molecular defects with specific therapies. Over the past two decades, the molecular classification and diagnostic work up of GIST has been radically transformed, accompanied by the development of molecular therapies for specific subgroups of GIST. This review summarizes the developments in the field of molecular diagnosis of GIST, particularly as they relate to optimizing medical therapy. Areas covered: Based on an extensive literature search of the molecular and clinical aspects of GIST, the authors review the most important developments in this field with an emphasis on the differential diagnosis of GIST including mutation testing, therapeutic implications of each molecular subtype, and emerging technologies relevant to the field. Expert commentary: The use of molecular diagnostics to classify GIST has been shown to be successful in optimizing patient treatment, but these methods remain under-utilized. In order to facilitate efficient and comprehensive molecular testing, the authors have developed a decision tree to aid clinicians.

  20. Current evidence for universal molecular testing for colorectal cancer patients

    Directory of Open Access Journals (Sweden)

    Fábio Guilherme Campos

    2017-07-01

    Full Text Available Background: Risk assessment for Lynch Syndrome may be a complex and challenging task. Demonstration of germline mutations has the benefits of confirming Lynch Syndrome diagnosis and may also provide screening and surgical orientation for affected members and relief for non-affected relatives. Objective: The present paper aimed to critically review the criteria to diagnose Lynch Syndrome, focusing the attention on the new perspective of adopting universal screening for patients diagnosed with colorectal cancer. Methods: We performed a literature review about the rationale and preliminary results of universal testing for Lynch Syndrome. Results: The use of selective eligibility criteria to determine who should undergo Lynch Syndrome testing may fail in a substantial proportion of cases. Moreover, universal strategy is feasible, cost-effective and more sensitive than previous methods. However, there still exist problems regarding clinical practice implementation and compliance either by medical doctors and patients. Conclusions: Standard guidelines for colorectal cancer screening are not ideal to provide early detection of Lynch Syndrome patients. And although universal screening has been associated with an increased identification of Lynch Syndrome patients, a successful implementation of this approach is still limited by the lack of clinical expertise among physicians, and also requires standardization of the existing protocols for routine genetic screening. Resumo: Introdução: A avaliação de risco para síndrome de Lynch (SL pode ser tarefa complexa e desafiadora. A demonstração de mutações na linha germinal resulta em benefícios, como a confirmação do diagnóstico de SL e também pode proporcionar orientações para a triagem e procedimentos cirúrgicos para os membros afetados, além de trazer alívio para os parentes não afetados. Objetivo: Este artigo teve por objetivo oferecer uma revisão crítica dos critérios para o diagn

  1. Singularity hypotheses a scientific and philosophical assessment

    CERN Document Server

    Moor, James; Søraker, Johnny; Steinhart, Eric

    2012-01-01

    Singularity Hypotheses: A Scientific and Philosophical Assessment offers authoritative, jargon-free essays and critical commentaries on accelerating technological progress and the notion of technological singularity. It focuses on conjectures about the intelligence explosion, transhumanism, and whole brain emulation. Recent years have seen a plethora of forecasts about the profound, disruptive impact that is likely to result from further progress in these areas. Many commentators however doubt the scientific rigor of these forecasts, rejecting them as speculative and unfounded. We therefore invited prominent computer scientists, physicists, philosophers, biologists, economists and other thinkers to assess the singularity hypotheses. Their contributions go beyond speculation, providing deep insights into the main issues and a balanced picture of the debate.

  2. New hypotheses regarding the Danish health puzzle.

    Science.gov (United States)

    Bakah, May; Raphael, Dennis

    2017-12-01

    Nordic welfare states have achieved admirable population health profiles as a result of public policies that provide economic and social security across the life course. Denmark has been an exception to this rule, as its life expectancies and infant mortality rates since the mid-1970s have lagged behind the other Nordic nations and, in the case of life expectancy, behind most Organisation for Economic Co-operation and Development nations. In this review paper, we identify a number of new hypotheses for why this may be the case. These hypotheses concern the health effects of neo-liberal restructuring of the economy and its institutions, the institution of flexi-security in Denmark's labour market and the influence of Denmark's tobacco and alcohol industries. Also of note is that Denmark experienced higher unemployment rates during its initial period of health stagnation, as well as its treatment of non-Western immigrants and high wealth inequality and, until recently, the fact that Denmark did not systematically address the issue of health inequalities. These hypotheses may serve as covering explanations for the usually provided accounts of elevated behavioural risks and psychosocial stress as being responsible for Denmark's health profile.

  3. Higher Quality of Molecular Testing, an Unfulfilled Priority: Results from External Quality Assessment for KRAS Mutation Testing in Colorectal Cancer

    NARCIS (Netherlands)

    Tembuyser, L.; Ligtenberg, M.J.L.; Normanno, N.; Delen, S.; Krieken, J.H.J.M. van; Dequeker, E.M.

    2014-01-01

    Precision medicine is now a key element in clinical oncology. RAS mutational status is a crucial predictor of responsiveness to anti-epidermal growth factor receptor agents in metastatic colorectal cancer. In an effort to guarantee high-quality testing services in molecular pathology, the European

  4. The molecular anatomy of spontaneous germline mutations in human testes.

    Directory of Open Access Journals (Sweden)

    Jian Qin

    2007-09-01

    Full Text Available The frequency of the most common sporadic Apert syndrome mutation (C755G in the human fibroblast growth factor receptor 2 gene (FGFR2 is 100-1,000 times higher than expected from average nucleotide substitution rates based on evolutionary studies and the incidence of human genetic diseases. To determine if this increased frequency was due to the nucleotide site having the properties of a mutation hot spot, or some other explanation, we developed a new experimental approach. We examined the spatial distribution of the frequency of the C755G mutation in the germline by dividing four testes from two normal individuals each into several hundred pieces, and, using a highly sensitive PCR assay, we measured the mutation frequency of each piece. We discovered that each testis was characterized by rare foci with mutation frequencies 10(3 to >10(4 times higher than the rest of the testis regions. Using a model based on what is known about human germline development forced us to reject (p < 10(-6 the idea that the C755G mutation arises more frequently because this nucleotide simply has a higher than average mutation rate (hot spot model. This is true regardless of whether mutation is dependent or independent of cell division. An alternate model was examined where positive selection acts on adult self-renewing Ap spermatogonial cells (SrAp carrying this mutation such that, instead of only replacing themselves, they occasionally produce two SrAp cells. This model could not be rejected given our observed data. Unlike the disease site, similar analysis of C-to-G mutations at a control nucleotide site in one testis pair failed to find any foci with high mutation frequencies. The rejection of the hot spot model and lack of rejection of a selection model for the C755G mutation, along with other data, provides strong support for the proposal that positive selection in the testis can act to increase the frequency of premeiotic germ cells carrying a mutation

  5. Comparison of molecular tests for the diagnosis of malaria in Honduras.

    Science.gov (United States)

    Fontecha, Gustavo A; Mendoza, Meisy; Banegas, Engels; Poorak, Mitra; De Oliveira, Alexandre M; Mancero, Tamara; Udhayakumar, Venkatachalam; Lucchi, Naomi W; Mejia, Rosa E

    2012-04-18

    Honduras is a tropical country with more than 70% of its population living at risk of being infected with either Plasmodium vivax or Plasmodium falciparum. Laboratory diagnosis is a very important factor for adequate treatment and management of malaria. In Honduras, malaria is diagnosed by both, microscopy and rapid diagnostic tests and to date, no molecular methods have been implemented for routine diagnosis. However, since mixed infections, and asymptomatic and low-parasitaemic cases are difficult to detect by light microscopy alone, identifying appropriate molecular tools for diagnostic applications in Honduras deserves further study. The present study investigated the utility of different molecular tests for the diagnosis of malaria in Honduras. A total of 138 blood samples collected as part of a clinical trial to assess the efficacy of chloroquine were used: 69 microscopically confirmed P. falciparum positive samples obtained on the day of enrollment and 69 follow-up samples obtained 28 days after chloroquine treatment and shown to be malaria negative by microscopy. Sensitivity and specificity of microscopy was compared to an 18 s ribosomal RNA gene-based nested PCR, two single-PCR reactions designed to detect Plasmodium falciparum infections, one single-PCR to detect Plasmodium vivax infections, and one multiplex one-step PCR reaction to detect both parasite species. Of the 69 microscopically positive P. falciparum samples, 68 were confirmed to be P. falciparum-positive by two of the molecular tests used. The one sample not detected as P. falciparum by any of the molecular tests was shown to be P. vivax-positive by a reference molecular test indicating a misdiagnosis by microscopy. The reference molecular test detected five cases of P. vivax/P. falciparum mixed infections, which were not recognized by microscopy as mixed infections. Only two of these mixed infections were recognized by a multiplex test while a P. vivax-specific polymerase chain reaction (PCR

  6. Higher quality of molecular testing, an unfulfilled priority: Results from external quality assessment for KRAS mutation testing in colorectal cancer.

    Science.gov (United States)

    Tembuyser, Lien; Ligtenberg, Marjolijn J L; Normanno, Nicola; Delen, Sofie; van Krieken, J Han; Dequeker, Elisabeth M C

    2014-05-01

    Precision medicine is now a key element in clinical oncology. RAS mutational status is a crucial predictor of responsiveness to anti-epidermal growth factor receptor agents in metastatic colorectal cancer. In an effort to guarantee high-quality testing services in molecular pathology, the European Society of Pathology has been organizing an annual KRAS external quality assessment program since 2009. In 2012, 10 formalin-fixed, paraffin-embedded samples, of which 8 from invasive metastatic colorectal cancer tissue and 2 artificial samples of cell line material, were sent to more than 100 laboratories from 26 countries with a request for routine KRAS testing. Both genotyping and clinical reports were assessed independently. Twenty-seven percent of the participants genotyped at least 1 of 10 samples incorrectly. In total, less than 5% of the distributed specimens were genotyped incorrectly. Genotyping errors consisted of false negatives, false positives, and incorrectly genotyped mutations. Twenty percent of the laboratories reported a technical error for one or more samples. A review of the written reports showed that several essential elements were missing, most notably a clinical interpretation of the test result, the method sensitivity, and the use of a reference sequence. External quality assessment serves as a valuable educational tool in assessing and improving molecular testing quality and is an important asset for monitoring quality assurance upon incorporation of new biomarkers in diagnostic services. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  7. Origin of honeycombs: Testing the hydraulic and case hardening hypotheses

    Czech Academy of Sciences Publication Activity Database

    Bruthans, J.; Filippi, Michal; Slavík, M.; Svobodová, E.

    2018-01-01

    Roč. 303, 15 February (2018), s. 68-83 ISSN 0169-555X R&D Projects: GA ČR(CZ) GA16-19459S Institutional support: RVO:67985831 Keywords : tafoni * moisture * cavernous weathering * salt Subject RIV: DB - Geology ; Mineralogy OBOR OECD: Geology Impact factor: 2.958, year: 2016

  8. Educational mismatches and skills: New empirical tests of old hypotheses

    NARCIS (Netherlands)

    Levels, M.; van der Velden, R.K.W.; Allen, J.P.

    2013-01-01

    In this paper, we empirically explore how the often reported relationship between overeducation and wages can best be understood. Exploiting the newly published Programme for International Assessment of Adult Competencies (PIAAC) data (OECD 2013), we are able to achieve a better estimation of the

  9. Testing hypotheses on frequency effects in first language acquisition

    DEFF Research Database (Denmark)

    Kjærbæk, Laila; Basbøll, Hans

    2015-01-01

    On the basis of extensive literature studies, Ambridge, Kidd, Rowland and Theakston (2015) present five theses on frequency effects on language acquisition: i) the Levels and Kinds Thesis argues that frequency effects exist at all levels and are of many different kinds (e.g., type and token...... frequency effects as well as absolute and relative frequency effects); ii) the Age of Acquisition Thesis argues that all other things being equal, frequent forms will be acquired before less frequent forms. Since all other things are not equal, this claim does not entail a one-to-one relationship between...... frequency and age of acquisition; iii) the Prevent Error Thesis argues that high-frequency forms prevent (or reduce) errors in contexts in which they are the target; iv) the Cause Error Thesis argues that high-frequency forms also cause errors in contexts in which a competing, related lower-frequency form...

  10. Development of a molecular diagnostic test for Retinitis Pigmentosa in the Japanese population.

    Science.gov (United States)

    Maeda, Akiko; Yoshida, Akiko; Kawai, Kanako; Arai, Yuki; Akiba, Ryutaro; Inaba, Akira; Takagi, Seiji; Fujiki, Ryoji; Hirami, Yasuhiko; Kurimoto, Yasuo; Ohara, Osamu; Takahashi, Masayo

    2018-05-21

    Retinitis Pigmentosa (RP) is the most common form of inherited retinal dystrophy caused by different genetic variants. More than 60 causative genes have been identified to date. The establishment of cost-effective molecular diagnostic tests with high sensitivity and specificity can be beneficial for patients and clinicians. Here, we developed a clinical diagnostic test for RP in the Japanese population. Evaluation of diagnostic technology, Prospective, Clinical and experimental study. A panel of 39 genes reported to cause RP in Japanese patients was established. Next generation sequence (NGS) technology was applied for the analyses of 94 probands with RP and RP-related diseases. After interpretation of detected genetic variants, molecular diagnosis based on a study of the genetic variants and a clinical phenotype was made by a multidisciplinary team including clinicians, researchers and genetic counselors. NGS analyses found 14,343 variants from 94 probands. Among them, 189 variants in 83 probands (88.3% of all cases) were selected as pathogenic variants and 64 probands (68.1%) have variants which can cause diseases. After the deliberation of these 64 cases, molecular diagnosis was made in 43 probands (45.7%). The final molecular diagnostic rate with the current system combining supplemental Sanger sequencing was 47.9% (45 of 94 cases). The RP panel provides the significant advantage of detecting genetic variants with a high molecular diagnostic rate. This type of race-specific high-throughput genotyping allows us to conduct a cost-effective and clinically useful genetic diagnostic test.

  11. The role of molecular diagnostic testing in the management of thyroid nodules.

    Science.gov (United States)

    Moore, Maureen D; Panjwani, Suraj; Gray, Katherine D; Finnerty, Brendan M; Zarnegar, Rasa; Fahey, Thomas J

    2017-06-01

    Fine needle aspiration (FNA) with cytologic examination remains the standard of care for investigation of thyroid nodules. However, as many as 30% of FNA samples are cytologically indeterminate for malignancy, which confounds clinical management. To reduce the burden of repeat diagnostic testing and unnecessary surgery, there has been extensive investigation into molecular markers that can be detected on FNA specimens to more accurately stratify a patient's risk of malignancy. Areas covered: In this review, the authors discuss recent evidence and progress in molecular markers used in the diagnosis of thyroid cancer highlighting somatic gene alterations, molecular technologies and microRNA analysis. Expert commentary: The goal of molecular markers is to improve diagnostic accuracy and aid clinicians in the preoperative management of thyroid lesions. Modalities such as direct mutation analysis, mRNA gene expression profiling, next-generation sequencing, and miRNA expression profiling have been explored to improve the diagnostic accuracy of thyroid nodule FNA. Although no perfect test has been discovered, molecular diagnostic testing has revolutionized the management of thyroid nodules.

  12. Constant conditional entropy and related hypotheses

    International Nuclear Information System (INIS)

    Ferrer-i-Cancho, Ramon; Dębowski, Łukasz; Moscoso del Prado Martín, Fermín

    2013-01-01

    Constant entropy rate (conditional entropies must remain constant as the sequence length increases) and uniform information density (conditional probabilities must remain constant as the sequence length increases) are two information theoretic principles that are argued to underlie a wide range of linguistic phenomena. Here we revise the predictions of these principles in the light of Hilberg’s law on the scaling of conditional entropy in language and related laws. We show that constant entropy rate (CER) and two interpretations for uniform information density (UID), full UID and strong UID, are inconsistent with these laws. Strong UID implies CER but the reverse is not true. Full UID, a particular case of UID, leads to costly uncorrelated sequences that are totally unrealistic. We conclude that CER and its particular cases are incomplete hypotheses about the scaling of conditional entropies. (letter)

  13. Assessing hypotheses about nesting site occupancy dynamics

    Science.gov (United States)

    Bled, Florent; Royle, J. Andrew; Cam, Emmanuelle

    2011-01-01

    Hypotheses about habitat selection developed in the evolutionary ecology framework assume that individuals, under some conditions, select breeding habitat based on expected fitness in different habitat. The relationship between habitat quality and fitness may be reflected by breeding success of individuals, which may in turn be used to assess habitat quality. Habitat quality may also be assessed via local density: if high-quality sites are preferentially used, high density may reflect high-quality habitat. Here we assessed whether site occupancy dynamics vary with site surrogates for habitat quality. We modeled nest site use probability in a seabird subcolony (the Black-legged Kittiwake, Rissa tridactyla) over a 20-year period. We estimated site persistence (an occupied site remains occupied from time t to t + 1) and colonization through two subprocesses: first colonization (site creation at the timescale of the study) and recolonization (a site is colonized again after being deserted). Our model explicitly incorporated site-specific and neighboring breeding success and conspecific density in the neighborhood. Our results provided evidence that reproductively "successful'' sites have a higher persistence probability than "unsuccessful'' ones. Analyses of site fidelity in marked birds and of survival probability showed that high site persistence predominantly reflects site fidelity, not immediate colonization by new owners after emigration or death of previous owners. There is a negative quadratic relationship between local density and persistence probability. First colonization probability decreases with density, whereas recolonization probability is constant. This highlights the importance of distinguishing initial colonization and recolonization to understand site occupancy. All dynamics varied positively with neighboring breeding success. We found evidence of a positive interaction between site-specific and neighboring breeding success. We addressed local

  14. Causes of bat fatalities at wind turbines: Hypotheses and predictions

    Science.gov (United States)

    Cryan, P.M.; Barclay, R.M.R.

    2009-01-01

    Thousands of industrial-scale wind turbines are being built across the world each year to meet the growing demand for sustainable energy. Bats of certain species are dying at wind turbines in unprecedented numbers. Species of bats consistently affected by turbines tend to be those that rely on trees as roosts and most migrate long distances. Although considerable progress has been made in recent years toward better understanding the problem, the causes of bat fatalities at turbines remain unclear. In this synthesis, we review hypothesized causes of bat fatalities at turbines. Hypotheses of cause fall into 2 general categoriesproximate and ultimate. Proximate causes explain the direct means by which bats die at turbines and include collision with towers and rotating blades, and barotrauma. Ultimate causes explain why bats come close to turbines and include 3 general types: random collisions, coincidental collisions, and collisions that result from attraction of bats to turbines. The random collision hypothesis posits that interactions between bats and turbines are random events and that fatalities are representative of the bats present at a site. Coincidental hypotheses posit that certain aspects of bat distribution or behavior put them at risk of collision and include aggregation during migration and seasonal increases in flight activity associated with feeding or mating. A surprising number of attraction hypotheses suggest that bats might be attracted to turbines out of curiosity, misperception, or as potential feeding, roosting, flocking, and mating opportunities. Identifying, prioritizing, and testing hypothesized causes of bat collisions with wind turbines are vital steps toward developing practical solutions to the problem. ?? 2009 American Society of Mammalogists.

  15. Dental Hypotheses: Seeks to Publish Hypotheses from All Areas of Dentistry

    Directory of Open Access Journals (Sweden)

    Edward F. Rossomando

    2010-07-01

    Full Text Available Starting a new open access journal in a rapid growing scientific panorama is a severe challenge. However, the first issue of dental hypotheses is now history and the even skeptics can appreciate that dental hypotheses is a success - it is a journal of high quality that provides an outlet for publication of articles that encourage readers to question dental paradigms. But dental hypotheses readers might have noticed that the majority of the articles published in the first issue of dental hypotheses concern clinical dentistry. However, dental hypotheses editors recognize that there are many other areas in dentistry that present challenges and that our readers may offer suggestions for their solution. Some of these challenges relate to: dental education; digital dental technology; teledentistry and access to dental care; dental practice issues, such as, dental office design, dental office management, the slow rate of acceptance of innovative technology in the dental office; and issues related to innovation and dental entrepreneurship including intellectual property protection. Nevertheless, the dental profession faces many challenges - in many areas - and with the publication of dental hypotheses our profession has a venue for presentation of possible solutions. If you have developed a hypothesis that might help, please share it with your colleagues. As many have noted, the intellectual power of the global village in which we now live is formidable. The internet has provided the technology to bring us together and dental hypotheses has provided the venue. Please use it. New radical, speculative and non-mainstream scientific ideas are always welcome.

  16. The identification of carbapenemase types in Enterobacteriaceae by using molecular assay and phenotyping confirmation tests.

    Science.gov (United States)

    Genc, Ozlem; Aksu, Evrim; Gulcan, Aynur

    2016-06-01

    In this study, we aimed to identify the molecular carbapenemase types of the Enterobacteriaceae isolates and to evaluate the performance of manually prepared and commercially available combination disc methods and the modified Hodge test. One hundred and forty carbapenemase producing isolates and 45 isolates as control group were included in our study. The Xpert CARBA-R test was used as the molecular method. Antibiotic susceptibility tests were performed using combined discs, manually prepared with APBA (3-aminophenyl boronic acid), DPA (dipicolinic acid), EDTA (Ethylene diamine tetra acetic acid), cloxacillin supplements and Mastdiscs Combi-D70C that includes four antibiotic discs with specific inhibitors and temocillin discs. The modified Hodge test was performed on all isolates. OXA-48 gene was identified in 129 isolates , the NDM gene was identified in 10 isolates and VIM in one isolate. Thirty inaccurate results (30/185, 16%) were detected by using the manually prepared confirmation test. The sensitivity and specificity of this test were identified respectively 85% and 73%. Also, the sensitivity and specificity of the Mastdiscs Combi-D70C were identified as 100%. Negative results were detected in 3 NDM isolates with the use of a modified Hodge test. Sensitivity and specificity were calculated for the modified Hodge test respectively 97% and 100%. Finally, molecular methods provide results rapidly but they are not always easily accessible. The modified Hodge test can be used only for screening as a first step test and is not one of the tests that can identify the type of the carbapenemase. When carbapenem-resistant Enterobacteriaceae are detected, a commercial kit like Mastdiscs Combi-D70 may be preferred instead of the manually prepared phenotypic verification tests. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Pre-examination factors affecting molecular diagnostic test results and interpretation: A case-based approach.

    Science.gov (United States)

    Payne, Deborah A; Baluchova, Katarina; Peoc'h, Katell H; van Schaik, Ron H N; Chan, K C Allen; Maekawa, Masato; Mamotte, Cyril; Russomando, Graciela; Rousseau, François; Ahmad-Nejad, Parviz

    2017-04-01

    Multiple organizations produce guidance documents that provide opportunities to harmonize quality practices for diagnostic testing. The International Organization for Standardization ISO 15189 standard addresses requirements for quality in management and technical aspects of the clinical laboratory. One technical aspect addresses the complexities of the pre-examination phase prior to diagnostic testing. The Committee for Molecular Diagnostics of the International Federation for Clinical Chemistry and Laboratory Medicine (also known as, IFCC C-MD) conducted a survey of international molecular laboratories and determined ISO 15189 to be the most referenced guidance document. In this review, the IFCC C-MD provides case-based examples illustrating the value of select pre-examination processes as these processes relate to molecular diagnostic testing. Case-based examples in infectious disease, oncology, inherited disease and pharmacogenomics address the utility of: 1) providing information to patients and users, 2) designing requisition forms, 3) obtaining informed consent and 4) maintaining sample integrity prior to testing. The pre-examination phase requires extensive and consistent communication between the laboratory, the healthcare provider and the end user. The clinical vignettes presented in this paper illustrate the value of applying select ISO 15189 recommendations for general laboratory to the more specialized area of Molecular Diagnostics. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Evaluation of the generalized likelihood ratio test of hypotheses on the genetic control of continuous traits/ Avaliação da razão de verossimilhança generalizada em teste de hipóteses sobre o controle genético de características contínuas

    Directory of Open Access Journals (Sweden)

    Daniel Furtado Ferreira

    2004-05-01

    Full Text Available Studies of genetic control in plants are carried out to characterize genetic effects and detect the existence of a major gene and/or genes of minor effects (polygenes. If the trait of interest is continuous, the likelihood can be constructed based on a model with mixtures of normal densities. Once exact tests are not evident with such models, the likelihood ratio test is generally used, using the chi-square approximation. This work aimed at evaluating such test statistic using computer simulation. Data sets were simulated using generations typical in plant studies, under two conditions of null hypothesis, without a major gene, and without polygenes. The power of the test was evaluated with both types of genes present. Different sample sizes and values of heritability were considered. Results showed that, although the empirical densities of the test statistic departed significantly from a chi-square distribution, under null hypotheses, there was a reasonable control of type I error, with a significance level of 5%. The power of the test was generally high to detect polygenes and major genes. Power is low to detect a major gene only when it explains a low fraction of genetic variation.Estudos de herança genética em plantas são realizados para caracterizar os efeitos genéticos e verificar a existência de um gene de efeito maior e/ou de genes de pequeno efeito (“poligenes”. Quando a característica de interesse é contínua, a verossimilhança é baseada em modelos de misturas de densidades normais. Uma vez que não há testes exatos evidentes para julgar a existência de um gene de efeito maior, a razão de verossimilhança generalizada é em geral utilizada, considerando a aproximação de qui-quadrado. Este trabalho objetivou avaliar esta estatística de teste através de simulação em computador. Dados foram simulados, considerando particularidades de genealogia típicas de tais estudos, e duas condições sob a hipótese de nulidade

  19. Exploring the Benefits of Molecular Testing for Gonorrhoea Antibiotic Resistance Surveillance in Remote Settings.

    Directory of Open Access Journals (Sweden)

    Ben B Hui

    Full Text Available Surveillance for gonorrhoea antimicrobial resistance (AMR is compromised by a move away from culture-based testing in favour of more convenient nucleic acid amplification test (NAAT tests. We assessed the potential benefit of a molecular resistance test in terms of the timeliness of detection of gonorrhoea AMR.An individual-based mathematical model was developed to describe the transmission of gonorrhoea in a remote Indigenous population in Australia. We estimated the impact of the molecular test on the time delay between first importation and the first confirmation that the prevalence of gonorrhoea AMR (resistance proportion has breached the WHO-recommended 5% threshold (when a change in antibiotic should occur. In the remote setting evaluated in this study, the model predicts that when culture is the only available means of testing for AMR, the breach will only be detected when the actual prevalence of AMR in the population has already reached 8 - 18%, with an associated delay of ~43 - 69 months between first importation and detection. With the addition of a molecular resistance test, the number of samples for which AMR can be determined increases facilitating earlier detection at a lower resistance proportion. For the best case scenario, where AMR can be determined for all diagnostic samples, the alert would be triggered at least 8 months earlier than using culture alone and the resistance proportion will have only slightly exceeded the 5% notification threshold.Molecular tests have the potential to provide more timely warning of the emergence of gonorrhoea AMR. This in turn will facilitate earlier treatment switching and more targeted treatment, which has the potential to reduce the population impact of gonorrhoea AMR.

  20. Exploring the Benefits of Molecular Testing for Gonorrhoea Antibiotic Resistance Surveillance in Remote Settings.

    Science.gov (United States)

    Hui, Ben B; Ryder, Nathan; Su, Jiunn-Yih; Ward, James; Chen, Marcus Y; Donovan, Basil; Fairley, Christopher K; Guy, Rebecca J; Lahra, Monica M; Law, Mathew G; Whiley, David M; Regan, David G

    2015-01-01

    Surveillance for gonorrhoea antimicrobial resistance (AMR) is compromised by a move away from culture-based testing in favour of more convenient nucleic acid amplification test (NAAT) tests. We assessed the potential benefit of a molecular resistance test in terms of the timeliness of detection of gonorrhoea AMR. An individual-based mathematical model was developed to describe the transmission of gonorrhoea in a remote Indigenous population in Australia. We estimated the impact of the molecular test on the time delay between first importation and the first confirmation that the prevalence of gonorrhoea AMR (resistance proportion) has breached the WHO-recommended 5% threshold (when a change in antibiotic should occur). In the remote setting evaluated in this study, the model predicts that when culture is the only available means of testing for AMR, the breach will only be detected when the actual prevalence of AMR in the population has already reached 8 - 18%, with an associated delay of ~43 - 69 months between first importation and detection. With the addition of a molecular resistance test, the number of samples for which AMR can be determined increases facilitating earlier detection at a lower resistance proportion. For the best case scenario, where AMR can be determined for all diagnostic samples, the alert would be triggered at least 8 months earlier than using culture alone and the resistance proportion will have only slightly exceeded the 5% notification threshold. Molecular tests have the potential to provide more timely warning of the emergence of gonorrhoea AMR. This in turn will facilitate earlier treatment switching and more targeted treatment, which has the potential to reduce the population impact of gonorrhoea AMR.

  1. Diagnostic Performance of a Molecular Test versus Clinician Assessment of Vaginitis.

    Science.gov (United States)

    Schwebke, Jane R; Gaydos, Charlotte A; Nyirjesy, Paul; Paradis, Sonia; Kodsi, Salma; Cooper, Charles K

    2018-06-01

    Vaginitis is a common complaint, diagnosed either empirically or using Amsel's criteria and wet mount microscopy. This study sought to determine characteristics of an investigational test (a molecular test for vaginitis), compared to reference, for detection of bacterial vaginosis, Candida spp., and Trichomonas vaginalis Vaginal specimens from a cross-sectional study were obtained from 1,740 women (≥18 years old), with vaginitis symptoms, during routine clinic visits (across 10 sites in the United States). Specimens were analyzed using a commercial PCR/fluorogenic probe-based investigational test that detects bacterial vaginosis, Candida spp., and Trichomonas vaginalis Clinician diagnosis and in-clinic testing (Amsel's test, potassium hydroxide preparation, and wet mount) were also employed to detect the three vaginitis causes. All testing methods were compared to the respective reference methods (Nugent Gram stain for bacterial vaginosis, detection of the Candida gene its2 , and Trichomonas vaginalis culture). The investigational test, clinician diagnosis, and in-clinic testing were compared to reference methods for bacterial vaginosis, Candida spp., and Trichomonas vaginalis The investigational test resulted in significantly higher sensitivity and negative predictive value than clinician diagnosis or in-clinic testing. In addition, the investigational test showed a statistically higher overall percent agreement with each of the three reference methods than did clinician diagnosis or in-clinic testing. The investigational test showed significantly higher sensitivity for detecting vaginitis, involving more than one cause, than did clinician diagnosis. Taken together, these results suggest that a molecular investigational test can facilitate accurate detection of vaginitis. Copyright © 2018 Schwebke et al.

  2. A Report on Molecular Diagnostic Testing for Inherited Retinal Dystrophies by Targeted Genetic Analyses.

    Science.gov (United States)

    Ramkumar, Hema L; Gudiseva, Harini V; Kishaba, Kameron T; Suk, John J; Verma, Rohan; Tadimeti, Keerti; Thorson, John A; Ayyagari, Radha

    2017-02-01

    To test the utility of targeted sequencing as a method of clinical molecular testing in patients diagnosed with inherited retinal degeneration (IRD). After genetic counseling, peripheral blood was drawn from 188 probands and 36 carriers of IRD. Single gene testing was performed on each patient in a Clinical Laboratory Improvement Amendment (CLIA) certified laboratory. DNA was isolated, and all exons in the gene of interest were analyzed along with 20 base pairs of flanking intronic sequence. Genetic testing was most often performed on ABCA4, CTRP5, ELOV4, BEST1, CRB1, and PRPH2. Pathogenicity of novel sequence changes was predicted by PolyPhen2 and sorting intolerant from tolerant (SIFT). Of the 225 genetic tests performed, 150 were for recessive IRD, and 75 were for dominant IRD. A positive molecular diagnosis was made in 70 (59%) of probands with recessive IRD and 19 (26%) probands with dominant IRD. Analysis confirmed 12 (34%) of individuals as carriers of familial mutations associated with IRD. Thirty-two novel variants were identified; among these, 17 sequence changes in four genes were predicted to be possibly or probably damaging including: ABCA4 (14), BEST1 (2), PRPH2 (1), and TIMP3 (1). Targeted analysis of clinically suspected genes in 225 subjects resulted in a positive molecular diagnosis in 26% of patients with dominant IRD and 59% of patients with recessive IRD. Novel damaging mutations were identified in four genes. Single gene screening is not an ideal method for diagnostic testing given the phenotypic and genetic heterogeneity among IRD cases. High-throughput sequencing of all genes associated with retinal degeneration may be more efficient for molecular diagnosis.

  3. Avoiding Pitfalls in Molecular Genetic Testing: Case Studies of High-Resolution Array Comparative Genomic Hybridization Testing in the Definitive Diagnosis of Mowat-Wilson Syndrome

    OpenAIRE

    Kluk, Michael Joseph; An, Yu; James, Philip; Coulter, David; Harris, David; Wu, Bai-Lin; Shen, Yiping

    2011-01-01

    The molecular testing options available for the diagnosis of genetic disorders are numerous and include a variety of different assay platforms. The consultative input of molecular pathologists and cytogeneticists, working closely with the ordering clinicians, is often important for definitive diagnosis. Herein, we describe two patients who had long histories of unexplained signs and symptoms with a high clinical suspicion of an underlying genetic etiology. Initial molecular testing in both ca...

  4. A molecular diagnostic test for persistent Müllerian duct syndrome in miniature schnauzer dogs.

    Science.gov (United States)

    Pujar, S; Meyers-Wallen, V N

    2009-01-01

    In persistent Müllerian duct syndrome (PMDS), Müllerian ducts fail to regress in males during sexual differentiation. In the canine miniature schnauzer model, PMDS is caused by a C to T transition in exon 3 of the Müllerian inhibiting substance type II receptor (MISRII), which introduces a DdeI restriction site. Here we report a molecular diagnostic test for PMDS in the miniature schnauzer to identify affected dogs and carriers. As our test results suggest that the mutation is identical by descent in affected dogs of this breed, the test could be used to eliminate this mutation from the miniature schnauzer breed worldwide.

  5. Seed dormancy and germination - Emerging mechanisms and new hypotheses

    Directory of Open Access Journals (Sweden)

    Hiroyuki eNonogaki

    2014-05-01

    Full Text Available Seed dormancy has played a significant role in adaptation and evolution of seed plants. While its biological significance is clear, molecular mechanisms underlying seed dormancy induction, maintenance and alleviation still remain elusive. Intensive efforts have been made to investigate gibberellin and abscisic acid metabolism in seeds, which greatly contributed to the current understanding of seed dormancy mechanisms. Other mechanisms, which might be independent of hormones, or specific to the seed dormancy pathway, are also emerging from genetic analysis of seed dormancy mutants. These studies suggest that chromatin remodeling through histone ubiquitination, methylation and acetylation, which could lead to transcription elongation or gene silencing, may play a significant role in seed dormancy regulation. Small interfering RNA and/or long non-coding RNA might be a trigger of epigenetic changes at the seed dormancy or germination loci, such as DELAY OF GERMINATION1. While new mechanisms are emerging from genetic studies of seed dormancy, novel hypotheses are also generated from seed germination study with high throughput gene expression analysis. Recent studies on tissue-specific gene expression in tomato and Arabidopsis seeds, which suggested possible mechanosensing in the regulatory mechanisms, advanced our understanding of embryo-endosperm interaction and have potential to re-draw the traditional hypotheses or integrate them into a comprehensive scheme. The progress in basic seed science will enable knowledge translation, another frontier of research to be expanded for food and fuel production.

  6. Transfer factor - hypotheses for its structure and function.

    Science.gov (United States)

    Shifrine, M; Scibienski, R

    1975-01-01

    Transfer factor (TF) is a dialyzable extract from primed lymphocytes that is able to transfer specific delayed hypersensitivity from one animal to another. On the basis of available data we suggest that TF is a polypeptide with a molecular weight below 15,000 daltons. We hypothesize that TF is the variable light or heavy chain domain of immunoglobulin: such a molecule conforms with the accepted properties of TF and also has the necessary specificity requirements. We also hypothesize that TF is part of a receptor site. beta-2-microglobulin, a molecule that is an integral part of cell surfaces, could be the anchor for TF. beta-2-microglobulin has homologies with the constant portion of immunoglobulin light or heavy chain and thus would combine with the variable domain (TF) to form a complete receptor site for a specific antigen. The properties of TF suggest its mode of action, which is discussed in detail in the text. The biologic advantages of TF is its ability to confer immediate (immunologie specific) protection while the 'normal' immune response develops.

  7. Sudden venting test of an emergency bearing for the magnet bearing type compound molecular pump

    International Nuclear Information System (INIS)

    Hiroki, Seiji; Abe, Tetsuya; Murakami, Yoshio; Okamoto, Masatomo; Iguchi, Masashi; Nakamura, Jyunichi; Nakazeki, Tsugito.

    1995-01-01

    The vacuum evacuation system for nuclear fusion reactors bears the role of exhausting hydrogen isotopes in large quantity together with helium continuously for long hours, and as the high vacuum pumps for this purpose, the mechanical pumps which can do continuous evacuation and decrease the quantity of staying radioactive tritium, such as turbo molecular pumps and compound molecular pumps, are promising. Because of the compatibility with tritium, oil lubrication is not desirable, accordingly, the pumps with ceramic rotating vanes and magnetic bearings are demanded. As a part of the development of a magnetic bearing type mechanical pump which can be used for nuclear fusion reactors, the compound molecular pump, in which emergency bearings were incorporated, was made for trial, and the test of sudden air intrusion was carried out, as the results, various knowledges were obtained. The constitution of the testing setup, and the test results are reported. When air was injected at the pressure rise of 3.3x10 4 Pa/s from exhaust port side, after about 2.5 s, the maximum lift of 4.2x10 3 N arose. When air was injected at the pressure rise of 2.7x10 5 Pa/s from the suction part side, after about 0.4s, the maximum lift of 6.9x10 3 N arose. In the air injection alternately from the suction port and exhaust port sides, the emergency bearings functioned normally in 10 times of the test. (K.I.)

  8. Sensitivity of field tests, serological and molecular techniques for Plum Pox Virus detection in various tissues

    Directory of Open Access Journals (Sweden)

    Mojca VIRŠČEK MARN

    2015-12-01

    Full Text Available Sensitivity of field tests (AgriStrip  and Immunochromato, DAS-ELISA, two step RT-PCR and real-time RT-PCR for Plum pox virus (PPV detection was tested in various tissues of apricot, peach, plum and damson plum trees infected with isolates belonging to PPV-D, PPV-M or PPV-Rec, the three strains present in Slovenia. Flowers of apricot and plum in full bloom proved to be a very good source for detection of PPV. PPV could be detected with all tested techniques in symptomatic parts of leaves in May and with one exception even in the beginning of August, but it was not detected in asymptomatic leaves using field tests, DAS-ELISA and partly also molecular techniques. PPV was detected only in some of the samples of asymptomatic parts of the leaves with symptoms and of stalks by field tests and DAS-ELISA. Infections were not detected in buds in August using field tests or DAS-ELISA. Field tests are useful for confirmation of the PPV infection in symptomatic leaves, but in tissues without symptoms DAS-ELISA should be combined or replaced by molecular techniques.

  9. Testing the Molecular Clock Using the Best Fossil Record: Case Studies from the Planktic Foraminifera

    Science.gov (United States)

    Steel, B. A.; Kucera, M.; Darling, K.

    2004-12-01

    Criticism of molecular clock studies often centres on inadequate calibration and a perceived lack of correlation between reproductive isolation and recognisable morphological evolution. Since many major groups (e.g. birds, mammals, reptiles) have a poor fossil record, it is often difficult to test and refute these limitations. Planktic foraminifera represent an exception to this rule. Deep-sea sediments are super-abundant in foraminifera, and large numbers of specimens and occurrences are easily garnered from Ocean Drilling Programme cores. Planktic foraminifera therefore represent an ideal model group with which to test and refine molecular clock studies. Since the 1990AƒAøAøâ_sA¬Aøâ_zAøs, genetic sequences (principally 18S r-RNA) have been extracted from living planktic foraminifera, and a large genetic library has developed. Our study attempts to contextualise and test molecular data, particularly AƒAøAøâ_sA¬Agenetic studies have suggested that these two AƒAøAøâ_sA¬A<Å"super-speciesAƒAøAøâ_sA¬Aøâ_zAø in fact consist of a number of isolated forms, with contrasting ecologies and longevities, which in Recent and sub-Recent sediments can be distinguished either on the basis of pore ultrastructure (Gl. siphonifera) or test colouration (Gs. ruber). In both cases, molecular clock estimates are indicative of ancient (7-11 Ma) intra-species cryptic divergences, which seem to be considerably older than fossil dates. In particular, the calculated molecular split between the two forms of Gs. ruber (AƒAøAøâ_sA¬A<Å"whiteAƒAøAøâ_sA¬Aøâ_zAø and AƒAøAøâ_sA¬A<Å"pinkAƒAøAøâ_sA¬Aøâ_zAø) of around 11 Ma is considerably discordant with the fossil date of around 0.7 Ma. At first glance, this may appear to be a classic case of molecular over-estimation, often a feature of clock models, especially where, as in the foraminifera, substitution rates may vary widely. However, there is good reason to suspect that fossil range of the

  10. Testing advances in molecular discrimination among Chinook salmon life histories: evidence from a blind test.

    Science.gov (United States)

    Banks, Michael A; Jacobson, David P; Meusnier, Isabelle; Greig, Carolyn A; Rashbrook, Vanessa K; Ardren, William R; Smith, Christian T; Bernier-Latmani, Jeremiah; Van Sickle, John; O'Malley, Kathleen G

    2014-06-01

    The application of DNA-based markers toward the task of discriminating among alternate salmon runs has evolved in accordance with ongoing genomic developments and increasingly has enabled resolution of which genetic markers associate with important life-history differences. Accurate and efficient identification of the most likely origin for salmon encountered during ocean fisheries, or at salvage from fresh water diversion and monitoring facilities, has far-reaching consequences for improving measures for management, restoration and conservation. Near-real-time provision of high-resolution identity information enables prompt response to changes in encounter rates. We thus continue to develop new tools to provide the greatest statistical power for run identification. As a proof of concept for genetic identification improvements, we conducted simulation and blind tests for 623 known-origin Chinook salmon (Oncorhynchus tshawytscha) to compare and contrast the accuracy of different population sampling baselines and microsatellite loci panels. This test included 35 microsatellite loci (1266 alleles), some known to be associated with specific coding regions of functional significance, such as the circadian rhythm cryptochrome genes, and others not known to be associated with any functional importance. The identification of fall run with unprecedented accuracy was demonstrated. Overall, the top performing panel and baseline (HMSC21) were predicted to have a success rate of 98%, but the blind-test success rate was 84%. Findings for bias or non-bias are discussed to target primary areas for further research and resolution. © 2014 The Authors. Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.

  11. Whole Genome Sequencing Increases Molecular Diagnostic Yield Compared with Current Diagnostic Testing for Inherited Retinal Disease.

    Science.gov (United States)

    Ellingford, Jamie M; Barton, Stephanie; Bhaskar, Sanjeev; Williams, Simon G; Sergouniotis, Panagiotis I; O'Sullivan, James; Lamb, Janine A; Perveen, Rahat; Hall, Georgina; Newman, William G; Bishop, Paul N; Roberts, Stephen A; Leach, Rick; Tearle, Rick; Bayliss, Stuart; Ramsden, Simon C; Nemeth, Andrea H; Black, Graeme C M

    2016-05-01

    To compare the efficacy of whole genome sequencing (WGS) with targeted next-generation sequencing (NGS) in the diagnosis of inherited retinal disease (IRD). Case series. A total of 562 patients diagnosed with IRD. We performed a direct comparative analysis of current molecular diagnostics with WGS. We retrospectively reviewed the findings from a diagnostic NGS DNA test for 562 patients with IRD. A subset of 46 of 562 patients (encompassing potential clinical outcomes of diagnostic analysis) also underwent WGS, and we compared mutation detection rates and molecular diagnostic yields. In addition, we compared the sensitivity and specificity of the 2 techniques to identify known single nucleotide variants (SNVs) using 6 control samples with publically available genotype data. Diagnostic yield of genomic testing. Across known disease-causing genes, targeted NGS and WGS achieved similar levels of sensitivity and specificity for SNV detection. However, WGS also identified 14 clinically relevant genetic variants through WGS that had not been identified by NGS diagnostic testing for the 46 individuals with IRD. These variants included large deletions and variants in noncoding regions of the genome. Identification of these variants confirmed a molecular diagnosis of IRD for 11 of the 33 individuals referred for WGS who had not obtained a molecular diagnosis through targeted NGS testing. Weighted estimates, accounting for population structure, suggest that WGS methods could result in an overall 29% (95% confidence interval, 15-45) uplift in diagnostic yield. We show that WGS methods can detect disease-causing genetic variants missed by current NGS diagnostic methodologies for IRD and thereby demonstrate the clinical utility and additional value of WGS. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  12. A Molecular Diagnostic Test for Persistent Müllerian Duct Syndrome in Miniature Schnauzer Dogs

    OpenAIRE

    Pujar, S.; Meyers-Wallen, V.N.

    2009-01-01

    In persistent Müllerian duct syndrome (PMDS), Müllerian ducts fail to regress in males during sexual differentiation. In the canine miniature schnauzer model, PMDS is caused by a C to T transition in exon 3 of the Müllerian inhibiting substance type II receptor (MISRII), which introduces a DdeI restriction site. Here we report a molecular diagnostic test for PMDS in the miniature schnauzer to identify affected dogs and carriers. As our test results suggest that the mutation is identical by de...

  13. Avoiding pitfalls in molecular genetic testing: case studies of high-resolution array comparative genomic hybridization testing in the definitive diagnosis of Mowat-Wilson syndrome.

    Science.gov (United States)

    Kluk, Michael Joseph; An, Yu; James, Philip; Coulter, David; Harris, David; Wu, Bai-Lin; Shen, Yiping

    2011-05-01

    The molecular testing options available for the diagnosis of genetic disorders are numerous and include a variety of different assay platforms. The consultative input of molecular pathologists and cytogeneticists, working closely with the ordering clinicians, is often important for definitive diagnosis. Herein, we describe two patients who had long histories of unexplained signs and symptoms with a high clinical suspicion of an underlying genetic etiology. Initial molecular testing in both cases was negative, but the application of high-resolution array comparative genomic hybridization technology lead to definitive diagnosis in both cases. We summarize the clinical findings and molecular testing in each case, discuss the differential diagnoses, and review the clinical and pathological findings of Mowat-Wilson syndrome. This report highlights the importance for those involved in molecular testing to know the nature of the underlying genetic abnormalities associated with the suspected diagnosis, to recognize the limitations of each testing platform, and to persistently pursue repeat testing using high-resolution technologies when indicated. This concept is applicable to both germline and somatic molecular genetic testing. Copyright © 2011 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  14. Cost-effectiveness of using a molecular diagnostic test to improve preoperative diagnosis of thyroid cancer.

    Science.gov (United States)

    Najafzadeh, Mehdi; Marra, Carlo A; Lynd, Larry D; Wiseman, Sam M

    2012-12-01

    Fine-needle aspiration biopsy (FNAB) is a safe and inexpensive diagnostic procedure for evaluating thyroid nodules.Up to 25% of the results from an FNAB, however, may not be diagnostic or may be indeterminate, leading to a subsequent diagnostic thyroid surgery. A new molecularly based diagnostic test could potentially reduce indeterminate cytological results and, with high accuracy, provide a definitive diagnosis for cancer in thyroid nodules. The aim of the study was to estimate the cost-effectiveness of utilizing a molecular diagnostic (DX) test as an adjunct to FNAB, compared with NoDX, to improve the preoperative diagnosis of thyroid nodules. We constructed a patient-level simulation model to estimate the clinical and economic outcomes of using a DX test compared with current practice (NoDX) for the diagnosis of thyroid nodules. By using a cost-effectiveness framework, we measured incremental clinical benefits in terms of quality-adjusted life-years and incremental costs over a 10-year time horizon. Assuming 95% sensitivity and specificity of the Dx test when used as an adjunct to FNAB, the utilization of the DX test resulted in a gain of 0.046 quality-adjusted life-years (95% confidence interval 0.019-0.078) and a saving of $1087 (95% confidence interval $691-$1533) in direct costs per patient. If the cost of the Dx test is less than $1087 per test, we expect to save quality-adjusted life-years and reduce costs when it is utilized. Sensitivity of the DX test, compared with specificity, had a larger influence on the overall outcomes. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  15. A classical Ehlers-Danlos syndrome family with incomplete presentation diagnosed by molecular testing.

    Science.gov (United States)

    Colombi, Marina; Dordoni, Chiara; Cinquina, Valeria; Venturini, Marina; Ritelli, Marco

    2018-01-01

    The 2017 EDS revised nosology indicates that minimal criteria suggestive for classical Ehlers-Danlos syndrome (cEDS) are skin hyperextensibility plus atrophic scarring together with either generalized joint hypermobility (gJHM) and/or at least three minor criteria that include cutaneous features and gJHM complications. Confirmatory molecular testing is obligatory to reach a final diagnosis. Although the large majority of the patients presents with these clinical features, some do not and might remain undiagnosed or misdiagnosed. Here we describe a family with 2 affected members, a 23-year-old proposita and her 51-year-old mother, who presented subtle cutaneous signs, including a variable degree of skin hyperextensibility without extensive widened atrophic scars that apparently better fitted with the overlapping hypermobile EDS. The proposita also presented gastrointestinal symptoms secondary to aberrant mast cells mediators release, making the clinical picture even more puzzling. Both patients were diagnosed by molecular testing that revealed a COL5A1 splice mutation. This report highlights the relevance of molecular analysis in patients presenting rather mild signs of EDS, especially in familial cases, and the importance of clinical expertise to make such a diagnosis. Copyright © 2017. Published by Elsevier Masson SAS.

  16. Fireballs Masses and Densities: Hypotheses and Reality

    Science.gov (United States)

    Gritsevich, Maria

    data on the deceleration and ablation of meteoroids provide objective information on the basic parameters of fireballs and the accompanying physical processes. Cases will be presented where the discrepancy between the dynamic and photometric estimates cannot be explained even by the above-mentioned reasons. In particular, large fireballs with dynamic masses exceeding the photometric mass by more than an order of magnitude were observed. Furthermore the detail calculations clearly show that the major part of the luminous segment of the trajectories of large fireballs corresponds to continuous medium flow, while the condition of a free molecular flow holds outside this segment. The maximum brightness altitude is smaller than that at which a strong bow shock is formed. Therefore, we can assume that the fireball brightness under these conditions is mainly due to the emission from air in the compressed shock layer rather than due to the emission from evaporated meteoroid matter which is necessary for the validity of the well-known photometric formula.

  17. Ordering molecular genetic tests and reporting results: practices in laboratory and clinical settings.

    Science.gov (United States)

    Lubin, Ira M; Caggana, Michele; Constantin, Carolyn; Gross, Susan J; Lyon, Elaine; Pagon, Roberta A; Trotter, Tracy L; Wilson, Jean Amos; McGovern, Margaret M

    2008-09-01

    Previous studies have suggested that patient care may be compromised as a consequence of poor communication between clinicians and laboratory professionals in cases in which molecular genetic test results are reported. To understand better the contributing factors to such compromised care, we investigated both pre- and postanalytical processes using cystic fibrosis mutation analysis as our model. We found that although the majority of test requisition forms requested patient/family information that was necessary for the proper interpretation of test results, in many cases, these data were not provided by the individuals filling out the forms. We found instances in which result reports for simulated diagnostic testing described individuals as carriers where only a single mutation was found with no comment pertaining to a diagnosis of cystic fibrosis. Similarly, reports based on simulated scenarios for carrier testing were problematic when no mutations were identified, and the patient's race/ethnicity and family history were not discussed in reference to residual risk of disease. Remarkably, a pilot survey of obstetrician-gynecologists revealed that office staff, including secretaries, often helped order genetic tests and reported test results to patients, raising questions about what efforts are undertaken to ensure personnel competency. These findings are reviewed in light of what efforts should be taken to improve the quality of test-ordering and result-reporting practices.

  18. Baseline staging tests based on molecular subtype is necessary for newly diagnosed breast cancer.

    Science.gov (United States)

    Chen, Xuesong; Sun, Lichun; Cong, Yingying; Zhang, Tingting; Lin, Qiushi; Meng, Qingwei; Pang, Hui; Zhao, Yanbin; Li, Yu; Cai, Li; Dong, Xiaoqun

    2014-03-17

    Bone scanning (BS), liver ultrasonography (LUS), and chest radiography (CXR) are commonly recommended for baseline staging in patients with newly diagnosed breast cancer. The purpose of this study is to demonstrate whether these tests are indicated for specific patient subpopulation based on clinical staging and molecular subtype. A retrospective study on 5406 patients with newly diagnosed breast cancer was conducted to identify differences in occurrence of metastasis based on clinical staging and molecular subtypes. All patients had been evaluated by BS, LUS and CXR at diagnosis. Complete information on clinical staging was available in 5184 patients. For stage I, II, and III, bone metastasis rate was 0%, 0.6% and 2.7%, respectively (P diagnosed breast cancer.

  19. Evolution of microgastropods (Ellobioidea, Carychiidae): integrating taxonomic, phylogenetic and evolutionary hypotheses

    Science.gov (United States)

    2013-01-01

    Background Current biodiversity patterns are considered largely the result of past climatic and tectonic changes. In an integrative approach, we combine taxonomic and phylogenetic hypotheses to analyze temporal and geographic diversification of epigean (Carychium) and subterranean (Zospeum) evolutionary lineages in Carychiidae (Eupulmonata, Ellobioidea). We explicitly test three hypotheses: 1) morphospecies encompass unrecognized evolutionary lineages, 2) limited dispersal results in a close genetic relationship of geographical proximally distributed taxa and 3) major climatic and tectonic events had an impact on lineage diversification within Carychiidae. Results Initial morphospecies assignments were investigated by different molecular delimitation approaches (threshold, ABGD, GMYC and SP). Despite a conservative delimitation strategy, carychiid morphospecies comprise a great number of unrecognized evolutionary lineages. We attribute this phenomenon to historic underestimation of morphological stasis and phenotypic variability amongst lineages. The first molecular phylogenetic hypothesis for the Carychiidae (based on COI, 16S and H3) reveals Carychium and Zospeum to be reciprocally monophyletic. Geographical proximally distributed lineages are often closely related. The temporal diversification of Carychiidae is best described by a constant rate model of diversification. The evolution of Carychiidae is characterized by relatively few (long distance) colonization events. We find support for an Asian origin of Carychium. Zospeum may have arrived in Europe before extant members of Carychium. Distantly related Carychium clades inhabit a wide spectrum of the available bioclimatic niche and demonstrate considerable niche overlap. Conclusions Carychiid taxonomy is in dire need of revision. An inferred wide distribution and variable phenotype suggest underestimated diversity in Zospeum. Several Carychium morphospecies are results of past taxonomic lumping. By collecting

  20. Evaluation of the Effect of Diagnostic Molecular Testing on the Surgical Decision-Making Process for Patients With Thyroid Nodules.

    Science.gov (United States)

    Noureldine, Salem I; Najafian, Alireza; Aragon Han, Patricia; Olson, Matthew T; Genther, Dane J; Schneider, Eric B; Prescott, Jason D; Agrawal, Nishant; Mathur, Aarti; Zeiger, Martha A; Tufano, Ralph P

    2016-07-01

    Diagnostic molecular testing is used in the workup of thyroid nodules. While these tests appear to be promising in more definitively assigning a risk of malignancy, their effect on surgical decision making has yet to be demonstrated. To investigate the effect of diagnostic molecular profiling of thyroid nodules on the surgical decision-making process. A surgical management algorithm was developed and published after peer review that incorporated individual Bethesda System for Reporting Thyroid Cytopathology classifications with clinical, laboratory, and radiological results. This algorithm was created to formalize the decision-making process selected herein in managing patients with thyroid nodules. Between April 1, 2014, and March 31, 2015, a prospective study of patients who had undergone diagnostic molecular testing of a thyroid nodule before being seen for surgical consultation was performed. The recommended management undertaken by the surgeon was then prospectively compared with the corresponding one in the algorithm. Patients with thyroid nodules who did not undergo molecular testing and were seen for surgical consultation during the same period served as a control group. All pertinent treatment options were presented to each patient, and any deviation from the algorithm was recorded prospectively. To evaluate the appropriateness of any change (deviation) in management, the surgical histopathology diagnosis was correlated with the surgery performed. The study cohort comprised 140 patients who underwent molecular testing. Their mean (SD) age was 50.3 (14.6) years, and 75.0% (105 of 140) were female. Over a 1-year period, 20.3% (140 of 688) had undergone diagnostic molecular testing before surgical consultation, and 79.7% (548 of 688) had not undergone molecular testing. The surgical management deviated from the treatment algorithm in 12.9% (18 of 140) with molecular testing and in 10.2% (56 of 548) without molecular testing (P = .37). In the group with

  1. From themes to hypotheses: following up with quantitative methods.

    Science.gov (United States)

    Morgan, David L

    2015-06-01

    One important category of mixed-methods research designs consists of quantitative studies that follow up on qualitative research. In this case, the themes that serve as the results from the qualitative methods generate hypotheses for testing through the quantitative methods. That process requires operationalization to translate the concepts from the qualitative themes into quantitative variables. This article illustrates these procedures with examples that range from simple operationalization to the evaluation of complex models. It concludes with an argument for not only following up qualitative work with quantitative studies but also the reverse, and doing so by going beyond integrating methods within single projects to include broader mutual attention from qualitative and quantitative researchers who work in the same field. © The Author(s) 2015.

  2. Hypotheses about geoglyphs at Nasca, Peru: new discoveries

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    Jaroslav Klokočník

    2016-07-01

    Full Text Available The known hypotheses about the reasons why the geoglyphs in the Nasca and Palpa region of Peru were created are many: roads/paths, rituals/ceremonials, use of hallucinogens, astronomical meaning, influence of extraterrestrials, underground water… and so on. We present a new hypothesis, formulated by J. Sonnek (first published in 2011 in the context of all previous hypotheses.1 Sonnek explains the geoglyphs as tidied work areas for the production of rope and nets, although he goes much further than Stierlin. This eccentric hypothesis now has not only experimental but also archaeological and ethnographical support, which is presented here. Geoglyphs of a special shape were discovered in the pampas; they may represent technical objects – different types of ‘rope twisters’. Following this idea, Sonnek made technical devices (using today’s materials and tested them in practice; they work perfectly, see his YouTube videos.2 In November 2012, wooden pieces, which may be the remnants of ropemaking, were collected from the pampa near the towns of Nasca and Palpa, in vicinity of these hypothetic ropemaking places. Radiocarbon testing by 14C standardized radio-carbon age according to Stuiver-Polach convention and Accelerator Mass Spectroscopy (AMS of these wood pieces shows the age to be in a wide range from Early Nasca to the 17th century (and to our epoch with a fake geoglyph, too, thus supporting (but surely not proving the new hypothesis. Moreover, in the Quechua language, the word huasca, waskha (read: uasca means a rope or cord or place where these are produced. This word is very similar to ‘nasca’.

  3. Development and performance of prototype serologic and molecular tests for hepatitis delta infection.

    Science.gov (United States)

    Coller, Kelly E; Butler, Emily K; Luk, Ka-Cheung; Rodgers, Mary A; Cassidy, Michael; Gersch, Jeffrey; McNamara, Anne L; Kuhns, Mary C; Dawson, George J; Kaptue, Lazare; Bremer, Birgit; Wedemeyer, Heiner; Cloherty, Gavin A

    2018-02-01

    Worldwide, an estimated 5% of hepatitis B virus (HBV) infected people are coinfected with hepatitis delta virus (HDV). HDV infection leads to increased mortality over HBV mono-infection, yet HDV diagnostics are not widely available. Prototype molecular (RNA) and serologic (IgG) assays were developed for high-throughput testing on the Abbott m2000 and ARCHITECT systems, respectively. RNA detection was achieved through amplification of a ribozyme region target, with a limit of detection of 5 IU/ml. The prototype serology assay (IgG) was developed using peptides derived from HDV large antigen (HDAg), and linear epitopes were further identified by peptide scan. Specificity of an HBV negative population was 100% for both assays. A panel of 145 HBsAg positive samples from Cameroon with unknown HDV status was tested using both assays: 16 (11.0%) had detectable HDV RNA, and 23 (15.7%) were sero-positive including the 16 HDV RNA positive samples. Additionally, an archival serial bleed panel from an HDV superinfected chimpanzee was tested with both prototypes; data was consistent with historic testing data using a commercial total anti-Delta test. Overall, the two prototype assays provide sensitive and specific methods for HDV detection using high throughput automated platforms, allowing opportunity for improved diagnosis of HDV infected patients.

  4. A Novel Molecular Test to Diagnose Canine Visceral Leishmaniasis at the Point of Care

    Science.gov (United States)

    Castellanos-Gonzalez, Alejandro; Saldarriaga, Omar A.; Tartaglino, Lilian; Gacek, Rosana; Temple, Elissa; Sparks, Hayley; Melby, Peter C.; Travi, Bruno L.

    2015-01-01

    Dogs are the principal reservoir hosts of zoonotic visceral leishmaniasis (VL) but current serological methods are not sensitive enough to detect all subclinically infected animals, which is crucial to VL control programs. Polymerase chain reaction (PCR) methods have greater sensitivity but require expensive equipment and trained personnel, impairing its implementation in endemic areas. We developed a diagnostic test that uses isothermal recombinase polymerase amplification (RPA) to detect Leishmania infantum. This method was coupled with lateral flow (LF) reading with the naked eye to be adapted as a point-of-care test. The L. infantum RPA-LF had an analytical sensitivity similar to real time-PCR, detecting DNA of 0.1 parasites spiked in dog blood, which was equivalent to 40 parasites/mL. There was no cross amplification with dog or human DNA or with Leishmania braziliensis, Leishmania amazonensis, or Trypanosoma cruzi. The test also amplified Leishmania donovani strains (N = 7). In a group of clinically normal dogs (N = 30), RPA-LF detected more subclinical infections than rK39 strip test, a standard serological method (50% versus 13.3% positivity, respectively; P = 0.005). Also, RPA-LF detected L. infantum in noninvasive mucosal samples of dogs with a sensitivity comparable to blood samples. This novel molecular test may have a positive impact in leishmaniasis control programs. PMID:26240156

  5. In Vitro Drug Sensitivity Tests to Predict Molecular Target Drug Responses in Surgically Resected Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Ryohei Miyazaki

    Full Text Available Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs and anaplastic lymphoma kinase (ALK inhibitors have dramatically changed the strategy of medical treatment of lung cancer. Patients should be screened for the presence of the EGFR mutation or echinoderm microtubule-associated protein-like 4 (EML4-ALK fusion gene prior to chemotherapy to predict their clinical response. The succinate dehydrogenase inhibition (SDI test and collagen gel droplet embedded culture drug sensitivity test (CD-DST are established in vitro drug sensitivity tests, which may predict the sensitivity of patients to cytotoxic anticancer drugs. We applied in vitro drug sensitivity tests for cyclopedic prediction of clinical responses to different molecular targeting drugs.The growth inhibitory effects of erlotinib and crizotinib were confirmed for lung cancer cell lines using SDI and CD-DST. The sensitivity of 35 cases of surgically resected lung cancer to erlotinib was examined using SDI or CD-DST, and compared with EGFR mutation status.HCC827 (Exon19: E746-A750 del and H3122 (EML4-ALK cells were inhibited by lower concentrations of erlotinib and crizotinib, respectively than A549, H460, and H1975 (L858R+T790M cells were. The viability of the surgically resected lung cancer was 60.0 ± 9.8 and 86.8 ± 13.9% in EGFR-mutants vs. wild types in the SDI (p = 0.0003. The cell viability was 33.5 ± 21.2 and 79.0 ± 18.6% in EGFR mutants vs. wild-type cases (p = 0.026 in CD-DST.In vitro drug sensitivity evaluated by either SDI or CD-DST correlated with EGFR gene status. Therefore, SDI and CD-DST may be useful predictors of potential clinical responses to the molecular anticancer drugs, cyclopedically.

  6. The impact of new trends in POCTs for companion diagnostics, non-invasive testing and molecular diagnostics.

    Science.gov (United States)

    Huckle, David

    2015-06-01

    Point-of-care diagnostics have been slowly developing over several decades and have taken on a new importance in current healthcare delivery for both diagnostics and development of new drugs. Molecular diagnostics have become a key driver of technology change and opened up new areas in companion diagnostics for use alongside pharmaceuticals and in new clinical approaches such as non-invasive testing. Future areas involving smartphone and other information technology advances, together with new developments in molecular biology, microfluidics and surface chemistry are adding to advances in the market. The focus for point-of-care tests with molecular diagnostic technologies is focused on advancing effective applications.

  7. Colorimetric test-systems for creatinine detection based on composite molecularly imprinted polymer membranes.

    Science.gov (United States)

    Sergeyeva, T A; Gorbach, L A; Piletska, E V; Piletsky, S A; Brovko, O O; Honcharova, L A; Lutsyk, O D; Sergeeva, L M; Zinchenko, O A; El'skaya, A V

    2013-04-03

    An easy-to-use colorimetric test-system for the efficient detection of creatinine in aqueous samples was developed. The test-system is based on composite molecularly imprinted polymer (MIP) membranes with artificial receptor sites capable of creatinine recognition. A thin MIP layer was created on the surface of microfiltration polyvinylidene fluoride (PVDF) membranes using method of photo-initiated grafting polymerization. The MIP layer was obtained by co-polymerization of a functional monomer (e.g. 2-acrylamido-2-methyl-1-propanesulfonic acid, itaconic acid or methacrylic acid) with N, N'-methylenebisacrylamide as a cross-linker. The choice of the functional monomer was based on the results of computational modeling. The creatinine-selective composite MIP membranes were used for measuring creatinine in aqueous samples. Creatinine molecules were selectively adsorbed by the MIP membranes and quantified using color reaction with picrates. The intensity of MIP membranes staining was proportional to creatinine concentration in an analyzed sample. The colorimetric test-system based on the composite MIP membranes was characterized with 0.25 mM detection limit and 0.25-2.5mM linear dynamic range. Storage stability of the MIP membranes was estimated as at least 1 year at room temperature. As compared to the traditional methods of creatinine detection the developed test-system is characterized by simplicity of operation, small size and low cost. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Quality assurance practices in Europe: a survey of molecular genetic testing laboratories

    Science.gov (United States)

    Berwouts, Sarah; Fanning, Katrina; Morris, Michael A; Barton, David E; Dequeker, Elisabeth

    2012-01-01

    In the 2000s, a number of initiatives were taken internationally to improve quality in genetic testing services. To contribute to and update the limited literature available related to this topic, we surveyed 910 human molecular genetic testing laboratories, of which 291 (32%) from 29 European countries responded. The majority of laboratories were in the public sector (81%), affiliated with a university hospital (60%). Only a minority of laboratories was accredited (23%), and 26% was certified. A total of 22% of laboratories did not participate in external quality assessment (EQA) and 28% did not use reference materials (RMs). The main motivations given for accreditation were to improve laboratory profile (85%) and national recognition (84%). Nearly all respondents (95%) would prefer working in an accredited laboratory. In accredited laboratories, participation in EQA (Pquality assurance (Pquality implementation score (QIS), we showed that accredited laboratories (average score 92) comply better than certified laboratories (average score 69, Pquality indicators. We conclude that quality practices vary widely in European genetic testing laboratories. This leads to a potentially dangerous situation in which the quality of genetic testing is not consistently assured. PMID:22739339

  9. Test-beds for molecular electronics: metal-molecules-metal junctions based on Hg electrodes.

    Science.gov (United States)

    Simeone, Felice Carlo; Rampi, Maria Anita

    2010-01-01

    produced results, are convenient test-beds for molecular electronics and represent a useful complement to physics-based experimental methods.

  10. Role of molecular testing in the multidisciplinary diagnostic approach of ichthyosis.

    Science.gov (United States)

    Diociaiuti, Andrea; El Hachem, May; Pisaneschi, Elisa; Giancristoforo, Simona; Genovese, Silvia; Sirleto, Pietro; Boldrini, Renata; Angioni, Adriano

    2016-01-13

    The term ichthyosis describes a generalized disorder of cornification characterized by scaling and/or hyperkeratosis of different skin regions. Mutations in a broad group of genes related to keratinocyte differentiation and epidermal barrier function have been demonstrated to play a causative role in disease development. Ichthyosis may be classified in syndromic or non-syndromic forms based on the occurrence or absence of extracutaneous signs. In this setting, the diagnosis of ichthyosis is an integrated multistep process requiring a multidisciplinary approach in order to formulate the appropriate diagnostic hypothesis and to address the genetic testing. Due to the complex features of the different ichthyoses and the high number of genes involved we have investigated a group of 64 patients, affected by syndromic and non-syndromic diseases, using Next Generation Sequencing as a new tool for the molecular diagnosis. Using this innovative molecular approach we were able to find pathogenic mutations in 53 out of 64 patients resulting in 82.8 % total detection rate. An interesting result from the analysis of the data is the high rate of novel sequence variations found compared to known mutations and the relevant rate of homozygous mutations. The possibility to analyze a large number of genes associated with various diseases allows to study cases with phenotypes not well-determined, giving the opportunity to make new genotype-phenotype correlation. In some cases there were discrepancies between clinical features and histology or electron microscopy and only molecular analysis allowed to definitively resolve the diagnostic dilemma. The genetic diagnosis of ichthyosis leads to a more accurate and effective genetic counseling, allowing correct evaluation of the risk of recurrence, particularly in families with consanguineous background.

  11. Cancer Stem Cells and Molecular Biology Test in Colorectal Cancer: Therapeutic Implications.

    Science.gov (United States)

    Effendi-Ys, Rustam

    2017-10-01

    Colorectal cancer (CRC) is the third most frequent cancer in males, the second in females, and is the second leading cause of cancer related death worldwide. Within Indonesia's 250 million population, the incidence rates for CRC per 100,000 population were 15.2 for males and 10.2 for females, and estimated 63,500 cases per year.  More than 50% of colorectal cancer patients will develop metastasis. CRC is still the main cause of tumor-related death, and although most CRC patients are treated with surgery to remove the tumor tissue, some of the CRC patients recurred. Chemotherapy used as adjuvant or neoadjuvant therapy also has several problems, in which these treatments are useless in tumor cells with chemo-resistance. Molecular testing of CRC from tumor tissues has important implications for the selection of treatment. Biomarkers can be used as prognostic value, molecular predictive factors, and targeted therapy. Recent research reported that, cancer stem cells (CSCs) are considered as the origin of tumorigenesis, development, metastasis and recurrence. At present, it has been shown that CSCs existed in many tumors including CRC. This review aims to summarize the issue on CSCs, and the future development of drugs that target colorectal cancer stem cells.

  12. Funções estimáveis e hipóteses testáveis nos delineamentos ortogonais e parcialmente ortogonais com três fatores Estimable functions and testable hypotheses in orthogonal and partially orthogonal designs with three factors

    Directory of Open Access Journals (Sweden)

    Denise Garcia de Santana

    2002-06-01

    Full Text Available Em situações experimentais, não raro, o pesquisador depara-se com a impossibilidade de planejar experimentos balanceados. Um grave problema surge imediatamente, no tocante à interpretação das hipóteses testadas através dos sistemas estatísticos, principalmente quando há vários fatores envolvidos e se faz presente um alto grau de desbalanceamento. Diante disso, o objetivo deste trabalho foi o estudo das funções estimáveis e das hipóteses testáveis em delineamentos ortogonais e parcialmente ortogonais com três fatores, à luz do procedimento GLM do sistema estatístico SAS. Os efeitos principais para os quais o subespaço gerado é ortogonal a cada outro subespaço inerente aos demais fatores são estimáveis e, portanto, as hipóteses correspondentes são testáveis nos modelos sem interações. Na presença de interações, as funções estimáveis apresentam, além de parâmetros do próprio fator, parâmetros das interações nas quais o fator está presente. Para esses casos, independentemente do modelo conter ou não interações, as hipóteses sobre médias ponderadas (tipo I são equivalentes às hipóteses sobre médias ponderadas ajustadas (tipo II e, como conjunto completo é condição necessária para a ortogonalidade parcial ou plena, ocorre também a equivalência entre as hipóteses sobre médias não ponderadas ajustadas (tipos III e IV. A igualdade entre as hipóteses dos tipos I e II ocorre para todas as interações, nos delineamentos ortogonais, mas nos delineamentos parcialmente ortogonais, ocorre para as interações formadas pelos fatores que não forem ortogonais entre si. Nessas interações as funções estimáveis apresentam parâmetros da própria interação e parâmetros da interação tripla.In experimental situations, not rarely, the scientist faces the impossibility of planning balanced experiments. A serious problem arises immediately concerning the interpretation of the hypothesis tested with

  13. Tests of potential functional barriers for laminated multilayer food packages. Part I: Low molecular weight permeants.

    Science.gov (United States)

    Simal-Gándara, J; Sarria-Vidal, M; Koorevaar, A; Rijk, R

    2000-08-01

    The advent of the functional barrier concept in food packaging has brought with it a requirement for fast tests of permeation through potential barrier materials. In such tests it would be convenient for both foodstuffs and materials below the functional barrier (sub-barrier materials) to be represented by standard simulants. By means of inverse gas chromatography, liquid paraffin spiked with appropriate permeants was considered as a potential simulant of sub-barrier materials based on polypropylene (PP) or similar polyolefins. Experiments were performed to characterize the kinetics of the permeation of low molecular weight model permeants (octene, toluene and isopropanol) from liquid paraffin, through a surrogate potential functional barrier (25 microns-thick oriented PP) into the food stimulants olive oil and 3% (w/v) acetic acid. These permeation results were interpreted in terms of three permeation kinetic models regarding the solubility of a particular model permeant in the post-barrier medium (i.e. the food simulant). The results obtained justify the development and evaluation of liquid sub-barrier simulants that would allow flexible yet rigorous testing of new laminated multilayer packaging materials.

  14. [Clinical parameters for molecular testing of Maturity Onset Diabetes of the Young (MODY)].

    Science.gov (United States)

    Datz, N; Nestoris, C; von Schütz, W; Danne, T; Driesel, A J; Maringa, M; Kordonouri, O

    2011-05-01

    Monogenic forms of diabetes are often diagnosed by chance, due to the variety of clinical presentation and limited experience of the diabetologists with this kind of diabetes. Aim of this study was to evaluate clinical parameters for an efficient screening. Clinical parameters were: negative diabetes-specific antibodies at onset of diabetes, positive family history of diabetes, and low to moderate insulin requirements after one year of diabetes treatment. Molecular testing was performed through sequencing of the programming regions of HNF-4alpha (MODY 1), glucokinase (MODY 2) and HNF-1alpha/TCF1 (MODY 3) and in one patient the HNF-1beta/TCF2 region (MODY 5). 39 of 292 patients treated with insulin were negative for GADA and IA2A, and 8 (20.5%) patients fulfilled both other criteria. Positive molecular results were found in five (63%) patients (two with MODY 2, two with MODY 3, one with MODY 5). At diabetes onset, the mean age of the 5 patients with MODY was 10.6 ± 5.3 yrs (range 2.6-15 yrs), HbA(1c) was 8.4 ± 3.1 % (6.5-13.9%), mean diabetes duration until diagnosis of MODY was 3.3 ± 3.6 yrs (0.8-9.6 yrs) with insulin requirements of 0.44 ± 0.17 U/kg/d (0.2-0.6 U/kg/d). Patients with MODY 3 were changed from insulin to repaglinide, those with MODY 2 were recommended discontinuing insulin treatment. In patients with negative diabetes-specific antibodies at onset of diabetes, with a positive family history, and low to moderate insulin needs a genetic screening for MODY is indicated. Watchful consideration of these clinical parameters may lead to an early genetic testing, and to an adequate treatment. © Georg Thieme Verlag KG Stuttgart · New York.

  15. An Innovative Field-Applicable Molecular Test to Diagnose Cutaneous Leishmania Viannia spp. Infections.

    Directory of Open Access Journals (Sweden)

    Omar A Saldarriaga

    2016-04-01

    Full Text Available Cutaneous and mucosal leishmaniasis is widely distributed in Central and South America. Leishmania of the Viannia subgenus are the most frequent species infecting humans. L. (V. braziliensis, L. (V. panamensis are also responsible for metastatic mucosal leishmaniasis. Conventional or real time PCR is a more sensitive diagnostic test than microscopy, but the cost and requirement for infrastructure and trained personnel makes it impractical in most endemic regions. Primary health systems need a sensitive and specific point of care (POC diagnostic tool. We developed a novel POC molecular diagnostic test for cutaneous leishmaniasis caused by Leishmania (Viannia spp. Parasite DNA was amplified using isothermal Recombinase Polymerase Amplification (RPA with primers and probes that targeted the kinetoplast DNA. The amplification product was detected by naked eye with a lateral flow (LF immunochromatographic strip. The RPA-LF had an analytical sensitivity equivalent to 0.1 parasites per reaction. The test amplified the principal L. Viannia species from multiple countries: L. (V. braziliensis (n = 33, L. (V. guyanensis (n = 17, L. (V. panamensis (n = 9. The less common L. (V. lainsoni, L. (V. shawi, and L. (V. naiffi were also amplified. No amplification was observed in parasites of the L. (Leishmania subgenus. In a small number of clinical samples (n = 13 we found 100% agreement between PCR and RPA-LF. The high analytical sensitivity and clinical validation indicate the test could improve the efficiency of diagnosis, especially in chronic lesions with submicroscopic parasite burdens. Field implementation of the RPA-LF test could contribute to management and control of cutaneous and mucosal leishmaniasis.

  16. Evaluating enzootic bovine leukemia virus infection by means of molecular probe compared with the results of serological tests

    International Nuclear Information System (INIS)

    Reichert, M.; Grundbock, J.; Rulka, J.; Kozaczynska, B.; Stec, J.

    1994-01-01

    The present studies were aimed at determining the relation between the finding obtained by means of serological tests and the specific molecular probe. Serological tests were performed according to the methods recommended by the Polish Ministry of Agriculture; ELISA was run with ''Bioveta'' and ''Rhone Merieux'' kits and the AGID test was performed with EBL antigen made in our laboratory. The molecular probe was prepared from the previously cloned provirus DNA of EBL virus. The EBL provirus was detected in 28 samples taken from 44 randomly selected cows in three herds on which a leukemia eradication programme was in process. Three sera out of 28 positive reacting animals were negative in AGID test and only one serum in ELISA. The results indicate that the use of a specific molecular probe has some advantages in the diagnosis of latent virus infections. Besides, it can be applied in the studies on the pathogenesis of enzootic bovine leukemia. (author). 13 refs, 1 fig., 1 tab

  17. Evaluating the accuracy of molecular diagnostic testing for canine visceral leishmaniasis using latent class analysis.

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    Manuela da Silva Solcà

    Full Text Available Host tissues affected by Leishmania infantum have differing degrees of parasitism. Previously, the use of different biological tissues to detect L. infantum DNA in dogs has provided variable results. The present study was conducted to evaluate the accuracy of molecular diagnostic testing (qPCR in dogs from an endemic area for canine visceral leishmaniasis (CVL by determining which tissue type provided the highest rate of parasite DNA detection. Fifty-one symptomatic dogs were tested for CVL using serological, parasitological and molecular methods. Latent class analysis (LCA was performed for accuracy evaluation of these methods. qPCR detected parasite DNA in 100% of these animals from at least one of the following tissues: splenic and bone marrow aspirates, lymph node and skin fragments, blood and conjunctival swabs. Using latent variable as gold standard, the qPCR achieved a sensitivity of 95.8% (CI 90.4-100 in splenic aspirate; 79.2% (CI 68-90.3 in lymph nodes; 77.3% (CI 64.5-90.1 in skin; 75% (CI 63.1-86.9 in blood; 50% (CI 30-70 in bone marrow; 37.5% (CI 24.2-50.8 in left-eye; and 29.2% (CI 16.7-41.6 in right-eye conjunctival swabs. The accuracy of qPCR using splenic aspirates was further evaluated in a random larger sample (n = 800, collected from dogs during a prevalence study. The specificity achieved by qPCR was 76.7% (CI 73.7-79.6 for splenic aspirates obtained from the greater sample. The sensitivity accomplished by this technique was 95% (CI 93.5-96.5 that was higher than those obtained for the other diagnostic tests and was similar to that observed in the smaller sampling study. This confirms that the splenic aspirate is the most effective type of tissue for detecting L. infantum infection. Additionally, we demonstrated that LCA could be used to generate a suitable gold standard for comparative CVL testing.

  18. Incidence of sarcoma histotypes and molecular subtypes in a prospective epidemiological study with central pathology review and molecular testing.

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    Françoise Ducimetière

    Full Text Available BACKGROUND: The exact overall incidence of sarcoma and sarcoma subtypes is not known. The objective of the present population-based study was to determine this incidence in a European region (Rhone-Alpes of six million inhabitants, based on a central pathological review of the cases. METHODOLOGY/PRINCIPAL FINDINGS: From March 2005 to February 2007, pathology reports and tumor blocks were prospectively collected from the 158 pathologists of the Rhone-Alpes region. All diagnosed or suspected cases of sarcoma were collected, reviewed centrally, examined for molecular alterations and classified according to the 2002 World Health Organization classification. Of the 1287 patients screened during the study period, 748 met the criteria for inclusion in the study. The overall crude and world age-standardized incidence rates were respectively 6.2 and 4.8 per 100,000/year. Incidence rates for soft tissue, visceral and bone sarcomas were respectively 3.6, 2.0 and 0.6 per 100,000. The most frequent histological subtypes were gastrointestinal stromal tumor (18%; 1.1/100,000, unclassified sarcoma (16%; 1/100,000, liposarcoma (15%; 0.9/100,000 and leiomyosarcoma (11%; 0.7/100,000. CONCLUSIONS/SIGNIFICANCE: The observed incidence of sarcomas was higher than expected. This study is the first detailed investigation of the crude incidence of histological and molecular subtypes of sarcomas.

  19. Integrative taxonomy of ciliates: Assessment of molecular phylogenetic content and morphological homology testing.

    Science.gov (United States)

    Vďačný, Peter

    2017-10-01

    The very diverse and comparatively complex morphology of ciliates has given rise to numerous taxonomic concepts. However, the information content of the utilized molecular markers has seldom been explored prior to phylogenetic analyses and taxonomic decisions. Likewise, robust testing of morphological homology statements and the apomorphic nature of diagnostic characters of ciliate taxa is rarely carried out. Four phylogenetic techniques that may help address these issues are reviewed. (1) Split spectrum analysis serves to determine the exact number and quality of nucleotide positions supporting individual nodes in phylogenetic trees and to discern long-branch artifacts that cause spurious phylogenies. (2) Network analysis can depict all possible evolutionary trajectories inferable from the dataset and locate and measure the conflict between them. (3) A priori likelihood mapping tests the suitability of data for reconstruction of a well resolved tree, visualizes the tree-likeness of quartets, and assesses the support of an internal branch of a given tree topology. (4) Reconstruction of ancestral morphologies can be applied for analyzing homology and apomorphy statements without circular reasoning. Since these phylogenetic tools are rarely used, their principles and interpretation are introduced and exemplified using various groups of ciliates. Finally, environmental sequencing data are discussed in this light. Copyright © 2017 The Author. Published by Elsevier GmbH.. All rights reserved.

  20. A survey of etiologic hypotheses among testicular cancer researchers.

    Science.gov (United States)

    Stang, A; Trabert, B; Rusner, C; Poole, C; Almstrup, K; Rajpert-De Meyts, E; McGlynn, K A

    2015-01-01

    Basic research results can provide new ideas and hypotheses to be examined in epidemiological studies. We conducted a survey among testicular cancer researchers on hypotheses concerning the etiology of this malignancy. All researchers on the mailing list of Copenhagen Testis Cancer Workshops and corresponding authors of PubMed-indexed articles identified by the search term 'testicular cancer' and published within 10 years (in total 2750 recipients) were invited to respond to an e-mail-based survey. Participants of the 8th Copenhagen Testis Cancer Workshop in May 2014 were subsequently asked to rate the plausibility of the suggested etiologic hypotheses on a scale of 1 (very implausible) to 10 (very plausible). This report describes the methodology of the survey, the score distributions by individual hypotheses, hypothesis group, and the participants' major research fields, and discuss the hypotheses that scored as most plausible. We also present plans for improving the survey that may be repeated at a next international meeting of experts in testicular cancer. Overall 52 of 99 (53%) registered participants of the 8th Copenhagen Testis Cancer Workshop submitted the plausibility rating form. Fourteen of 27 hypotheses were related to exposures during pregnancy. Hypotheses with the highest mean plausibility ratings were either related to pre-natal exposures or exposures that might have an effect during pregnancy and in post-natal life. The results of the survey may be helpful for triggering more specific etiologic hypotheses that include factors related to endocrine disruption, DNA damage, inflammation, and nutrition during pregnancy. The survey results may stimulate a multidisciplinary discussion about new etiologic hypotheses of testicular cancer. Published 2014. This article is a U. S. Government work and is in the public domain in the USA.

  1. Masticatory-stress hypotheses and the supraorbital region of primates.

    Science.gov (United States)

    Hylander, W L; Picq, P G; Johnson, K R

    1991-09-01

    The purpose of this study is to test various masticatory-stress hypotheses about the evolution and function of well-developed browridges of higher primates. This was done by measuring and analyzing patterns of in vivo bone strain recorded from three-element rosette strain gages bonded to the supraorbital region and to other portions of the bony face of Macaca fascicularis and Papio anubis during mastication and incision. The magnitude and direction of the principal strains recorded support Endo's hypothesis that the supraorbital region during mastication and incision is bent in the frontal plane (Endo, 1966). Our data do not, however, support his hypothesis that the supraorbital region is bent more during incision than during mastication. The data also demonstrate that overall levels of supraorbital strain are not larger in more prognathic subjects. Most importantly, the data indicate that the supraorbital region of nonhuman catarrhines is strained very little during mastication and incision. This indicates that there is much more supraorbital bone than is necessary both to counter masticatory loads and to provide an adequate safety factor to failure for these loads. This in turn suggests that the macaque and baboon browridges can be considerably reduced in size and still maintain these required structural characteristics. Thus, our experiments provide no support whatsoever for those hypotheses that directly link browridge morphology to masticatory stress (cf. Endo, 1966; Russell, 1983, 1985). A recent review of Endo's original work indicates that this latter statement is also true for humans (Picq and Hylander, 1989). We conclude, therefore, that there is no good reason to believe that enlarged browridges in living and/or fossil primates are structural adaptations to counter intense masticatory forces. The evolution of browridge morphology in primates is best explained on the basis of factors related to the position of the brain relative to the orbits (Moss and

  2. Use of hypotheses for analysis of variance Models: Challenging the current practice

    NARCIS (Netherlands)

    van Wesel, F.; Boeije, H.R.; Hoijtink, H

    2013-01-01

    In social science research, hypotheses about group means are commonly tested using analysis of variance. While deemed to be formulated as specifically as possible to test social science theory, they are often defined in general terms. In this article we use two studies to explore the current

  3. Red cell antigen prevalence predicted by molecular testing in ethnic groups of South Texas blood donors.

    Science.gov (United States)

    Aranda, Lorena I; Smith, Linda A; Jones, Scott; Beddard, Rachel

    2015-01-01

    Alloimmunization to red blood cell antigens is seen in patients receiving chronic blood transfusion. Knowing the prevalence of blood group antigens of the different ethnicities of South Texas donors can provide better management of rare blood inventory for patients in this geographical area. A total of 4369 blood donors were tested and analyzed for various antigens in the following blood group systems: ABO, Rh, Kell, Duffy, Kidd, MNS, Lutheran, Dombrock, Landsteiner-Wiener, Diego, Colton, and Scianna. Donors tested to be group 0 or A were serologically tested for the Rh (C, E, c, e) antigens. Those that tested as presumably R1R1, R2R2, or Ror were then genotyped. Donors constituted three major ethnicities: black (18.3%), Hispanic (36.3%), and Caucasian (41.1%); ethnicities comprised of Asian, American Indian, multiracial, and other accounted for the remaining donors (4.3%). The most likely common Rh phenotype for each ethnicity is as follows: black -Ror (44.4%), Hispanic -R1R1 (59.0%), and Caucasian -R1R1 (38.9%). The prevalence of Kell, Duffy, and Kidd blood group system antigens in black and Caucasian donors is comparable with published reports for the entire U.S. The black South Texas donor population had an 8.8 percent increase in prevalence of the Fy(a+b-) phenotype as compared with these published reports; the Hispanic South Texas donor population had a prevalence of 36.1 percent of the Fy(a+b-) phenotype. Regarding the Diego blood group system, the Hispanic donor population in South Texas had a prevalence of 93.5 percent for the Di(a-b+) phenotype as compared with published reports for the entire U.S. (>99.9%). The Hispanic population had a prevalence of 7.9 percent of donors testing as M-N+S-s+ as compared with 20.2 percent and 15.6 percent for black and Caucasian donors, respectively. This study helped us determine the prevalence of each of the blood group antigens in the South Texas donor population to establish and maintain adequate rare inventory of

  4. Using rapid diagnostic tests as source of malaria parasite DNA for molecular analyses in the era of declining malaria prevalence

    DEFF Research Database (Denmark)

    Ishengoma, Deus S; Lwitiho, Sudi; Madebe, Rashid A

    2011-01-01

    was conducted to examine if sufficient DNA could be successfully extracted from malaria rapid diagnostic tests (RDTs), used and collected as part of routine case management services in health facilities, and thus forming the basis for molecular analyses, surveillance and quality control (QC) testing of RDTs....... continued molecular surveillance of malaria parasites is important to early identify emerging anti-malarial drug resistance, it is becoming increasingly difficult to obtain parasite samples from ongoing studies, such as routine drug efficacy trials. To explore other sources of parasite DNA, this study...

  5. Audit of Trichomonas vaginalis test requesting by community referrers after a change from culture to molecular testing, including a cost analysis.

    Science.gov (United States)

    Bissessor, Liselle; Wilson, Janet; McAuliffe, Gary; Upton, Arlo

    2017-06-16

    Trichomonas vaginalis (TV) prevalence varies among different communities and peoples. The availability of robust molecular platforms for the detection of TV has advanced diagnosis; however, molecular tests are more costly than phenotypic methodologies, and testing all urogenital samples is costly. We recently replaced culture methods with the Aptima Trichomonas vaginalis nucleic acid amplification test on specific request and as reflex testing by the laboratory, and have audited this change. Data were collected from August 2015 (microbroth culture and microscopy) and August 2016 (Aptima TV assay) including referrer, testing volumes, results and test cost estimates. In August 2015, 10,299 vaginal swabs, and in August 2016, 2,189 specimens (urogenital swabs and urines), were tested. The positivity rate went from 0.9% to 5.3%, and overall more TV infections were detected in 2016. The number needed to test and cost for one positive TV result respectively was 111 and $902.55 in 2015, and 19 and $368.92 in 2016. Request volumes and positivity rates differed among referrers. The methodology change was associated with higher overall detection of TV, and reductions in the numbers needed to test/cost for one TV diagnosis. Our audit suggests that there is room for improvement with TV test requesting in our community.

  6. Preappointment testing for BRAF/KIT mutation in advanced melanoma: a model in molecular data delivery for individualized medicine.

    Science.gov (United States)

    Mounajjed, Taofic; Brown, Char L; Stern, Therese K; Bjorheim, Annette M; Bridgeman, Andrew J; Rumilla, Kandelaria M; McWilliams, Robert R; Flotte, Thomas J

    2014-11-01

    The emergence of individualized medicine is driven by developments in precision diagnostics, epitomized by molecular testing. Because treatment decisions are being made based on such molecular data, data management is gaining major importance. Among data management challenges, creating workflow solutions for timely delivery of molecular data has become pivotal. This study aims to design and implement a scalable process that permits preappointment BRAF/KIT mutation analysis in melanoma patients, allowing molecular results necessary for treatment plans to be available before the patient's appointment. Process implementation aims to provide a model for efficient molecular data delivery for individualized medicine. We examined the existing process of BRAF/KIT testing in melanoma patients visiting our institution for oncology consultation. We created 5 working groups, each designing a specific segment of an alternative process that would allow preappointment BRAF/KIT testing and delivery of results. Data were captured and analyzed to evaluate the success of the alternative process. For 1 year, 35 (59%) of 55 patients had prior BRAF/KIT testing. The remaining 20 patients went through the new process of preappointment testing; results were available at the time of appointment for 12 patients (overall preappointment results availability, 85.5%). The overall process averaged 13.4 ± 4.7 days. In conclusion, we describe the successful implementation of a scalable workflow solution that permits preappointment BRAF/KIT mutation analysis and result delivery in melanoma patients. This sets the stage for further applications of this model to other conditions, answering an increasing demand for robust delivery of molecular data for individualized medicine. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Molecular dynamics test of the Brownian description of Na+ motion in water

    International Nuclear Information System (INIS)

    Wilson, M.A.; Pohorille, A.; Pratt, L.R.

    1985-01-01

    The autocorrelation function of the velocity of an infinitely dilute Na + ion in aqueous solution, and the autocorrelation function of the force exerted on a stationary Na + under the same conditions are evaluated by molecular dynamics calculations. The results are used to test the accuracy of Brownian motion assumptions which are basic to hydrodynamic models of ion dynamics in solution. The self-diffusion coefficient of the Na + ion predicted by Brownian motion theory is (0.65 +- 0.1) x 10 -5 cm 2 /s. This value is about 60% greater than the one obtained for the proper dynamics of the finite mass ion, (0.4 +- 0.1) x 10 -5 cm 2 /s. The numerically correct velocity autocorrelation function is nonexponential, and the autocorrelation of the force on the stationary ion does not decay faster than the ion velocity autocorrelation function. Motivated by previous hydrodynamic modeling of friction kernels, we examine the approximation in which the memory function for the velocity autocorrelation function is identified with the autocorrelation function of the force on the stationary ion. The overall agreement between this approximation for the velocity autocorrelation function and the numerically correct answer is quite good

  8. Costs of genetic testing: Supporting Brazilian Public Policies for the incorporating of molecular diagnostic technologies

    Directory of Open Access Journals (Sweden)

    Rosane Paixão Schlatter

    2015-09-01

    Full Text Available This study identifies and describes the operating costs associated with the molecular diagnosis of diseases, such as hereditary cancer. To approximate the costs associated with these tests, data informed by Standard Operating Procedures for various techniques was collected from hospital software and a survey of market prices. Costs were established for four scenarios of capacity utilization to represent the possibility of suboptimal use in research laboratories. Cost description was based on a single site. The results show that only one technique was not impacted by rising costs due to underutilized capacity. Several common techniques were considerably more expensive at 30% capacity, including polymerase chain reaction (180%, microsatellite instability analysis (181%, gene rearrangement analysis by multiplex ligation probe amplification (412%, non-labeled sequencing (173%, and quantitation of nucleic acids (169%. These findings should be relevant for the definition of public policies and suggest that investment of public funds in the establishment of centralized diagnostic research centers would reduce costs to the Public Health System.

  9. Molecular Line Emission from Multifluid Shock Waves. I. Numerical Methods and Benchmark Tests

    Science.gov (United States)

    Ciolek, Glenn E.; Roberge, Wayne G.

    2013-05-01

    We describe a numerical scheme for studying time-dependent, multifluid, magnetohydrodynamic shock waves in weakly ionized interstellar clouds and cores. Shocks are modeled as propagating perpendicular to the magnetic field and consist of a neutral molecular fluid plus a fluid of ions and electrons. The scheme is based on operator splitting, wherein time integration of the governing equations is split into separate parts. In one part, independent homogeneous Riemann problems for the two fluids are solved using Godunov's method. In the other, equations containing the source terms for transfer of mass, momentum, and energy between the fluids are integrated using standard numerical techniques. We show that, for the frequent case where the thermal pressures of the ions and electrons are Lt magnetic pressure, the Riemann problems for the neutral and ion-electron fluids have a similar mathematical structure which facilitates numerical coding. Implementation of the scheme is discussed and several benchmark tests confirming its accuracy are presented, including (1) MHD wave packets ranging over orders of magnitude in length- and timescales, (2) early evolution of multifluid shocks caused by two colliding clouds, and (3) a multifluid shock with mass transfer between the fluids by cosmic-ray ionization and ion-electron recombination, demonstrating the effect of ion mass loading on magnetic precursors of MHD shocks. An exact solution to an MHD Riemann problem forming the basis for an approximate numerical solver used in the homogeneous part of our scheme is presented, along with derivations of the analytic benchmark solutions and tests showing the convergence of the numerical algorithm.

  10. MOLECULAR LINE EMISSION FROM MULTIFLUID SHOCK WAVES. I. NUMERICAL METHODS AND BENCHMARK TESTS

    International Nuclear Information System (INIS)

    Ciolek, Glenn E.; Roberge, Wayne G.

    2013-01-01

    We describe a numerical scheme for studying time-dependent, multifluid, magnetohydrodynamic shock waves in weakly ionized interstellar clouds and cores. Shocks are modeled as propagating perpendicular to the magnetic field and consist of a neutral molecular fluid plus a fluid of ions and electrons. The scheme is based on operator splitting, wherein time integration of the governing equations is split into separate parts. In one part, independent homogeneous Riemann problems for the two fluids are solved using Godunov's method. In the other, equations containing the source terms for transfer of mass, momentum, and energy between the fluids are integrated using standard numerical techniques. We show that, for the frequent case where the thermal pressures of the ions and electrons are << magnetic pressure, the Riemann problems for the neutral and ion-electron fluids have a similar mathematical structure which facilitates numerical coding. Implementation of the scheme is discussed and several benchmark tests confirming its accuracy are presented, including (1) MHD wave packets ranging over orders of magnitude in length- and timescales, (2) early evolution of multifluid shocks caused by two colliding clouds, and (3) a multifluid shock with mass transfer between the fluids by cosmic-ray ionization and ion-electron recombination, demonstrating the effect of ion mass loading on magnetic precursors of MHD shocks. An exact solution to an MHD Riemann problem forming the basis for an approximate numerical solver used in the homogeneous part of our scheme is presented, along with derivations of the analytic benchmark solutions and tests showing the convergence of the numerical algorithm.

  11. EMQN best practice guidelines for the molecular genetic testing and reporting of chromosome 11p15 imprinting disorders

    DEFF Research Database (Denmark)

    Eggermann, Katja; Bliek, Jet; Brioude, Frédéric

    2016-01-01

    of these disorders and the demand for molecular testing, it turned out that there is an urgent need for a standardized molecular diagnostic testing and reporting strategy. Based on the results from the first external pilot quality assessment schemes organized by the European Molecular Quality Network (EMQN) in 2014...... and in context with activities of the European Network of Imprinting Disorders (EUCID.net) towards a consensus in diagnostics and management of SRS and BWS, best practice guidelines have now been developed. Members of institutions working in the field of SRS and BWS diagnostics were invited to comment......, and in the light of their feedback amendments were made. The final document was ratified in the course of an EMQN best practice guideline meeting and is in accordance with the general SRS and BWS consensus guidelines, which are in preparation. These guidelines are based on the knowledge acquired from peer...

  12. The identification of new substrates of human DHRS7 by molecular modeling and in vitro testing

    Czech Academy of Sciences Publication Activity Database

    Zemanová, L.; Palani, Kirubakaran; Pato, I. H.; Štambergová, H.; Vondrášek, Jiří

    2017-01-01

    Roč. 105, č. 1 (2017), s. 171-182 ISSN 0141-8130 R&D Projects: GA MŠk(CZ) LM2015047 Institutional support: RVO:61388963 Keywords : DHRS7 * SDR superfamily * SDR34C1 * homology modeling * molecular modeling Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 3.671, year: 2016

  13. Molecular Population Genetics.

    Science.gov (United States)

    Casillas, Sònia; Barbadilla, Antonio

    2017-03-01

    Molecular population genetics aims to explain genetic variation and molecular evolution from population genetics principles. The field was born 50 years ago with the first measures of genetic variation in allozyme loci, continued with the nucleotide sequencing era, and is currently in the era of population genomics. During this period, molecular population genetics has been revolutionized by progress in data acquisition and theoretical developments. The conceptual elegance of the neutral theory of molecular evolution or the footprint carved by natural selection on the patterns of genetic variation are two examples of the vast number of inspiring findings of population genetics research. Since the inception of the field, Drosophila has been the prominent model species: molecular variation in populations was first described in Drosophila and most of the population genetics hypotheses were tested in Drosophila species. In this review, we describe the main concepts, methods, and landmarks of molecular population genetics, using the Drosophila model as a reference. We describe the different genetic data sets made available by advances in molecular technologies, and the theoretical developments fostered by these data. Finally, we review the results and new insights provided by the population genomics approach, and conclude by enumerating challenges and new lines of inquiry posed by increasingly large population scale sequence data. Copyright © 2017 Casillas and Barbadilla.

  14. Molecular phylogeny of selected species of the order Dinophysiales (Dinophyceae) - testing the hypothesis of a Dinophysioid radiation

    DEFF Research Database (Denmark)

    Jensen, Maria Hastrup; Daugbjerg, Niels

    2009-01-01

    additional information on morphology and ecology to these evolutionary lineages. We have for the first time combined morphological information with molecular phylogenies to test the dinophysioid radiation hypothesis in a modern context. Nuclear-encoded LSU rDNA sequences including domains D1-D6 from 27...

  15. Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a TBNET/RESIST-TB consensus statement

    NARCIS (Netherlands)

    Domínguez, J.; Boettger, E. C.; Cirillo, D.; Cobelens, F.; Eisenach, K. D.; Gagneux, S.; Hillemann, D.; Horsburgh, R.; Molina-Moya, B.; Niemann, S.; Tortoli, E.; Whitelaw, A.; Lange, C.

    2016-01-01

    The emergence of drug-resistant strains of Mycobacterium tuberculosis is a challenge to global tuberculosis (TB) control. Although culture-based methods have been regarded as the gold standard for drug susceptibility testing (DST), molecular methods provide rapid information on mutations in the M.

  16. Quality control in diagnostic molecular pathology in the Netherlands; proficiency testing for patient identification in tissue samples

    NARCIS (Netherlands)

    Thunnissen, F. B. J. M.; Tilanus, M. G. J.; Ligtenberg, M. J. L.; Nederlof, P. M.; Dinjens, W. N. M.; Meulemans, E.; van den Brule, A. J. C.; van Noesel, C. J. M.; de Leeuw, W. J. F.; Schuuring, E.

    2004-01-01

    Aims: To describe the evolution of proficiency testing for molecular diagnostic pathology with respect to determining unambiguously the patient identity of tissue samples by microsatellite analysis. Method: Four rounds of quality control exchanges of samples from different patients were sent with

  17. Evaluation of molecular markers for Phytophthora ramorum detection and identification: Testing for specificity using a standardized library of isolates

    Science.gov (United States)

    F.N. Martin; M.D. Coffey; K. Zeller; R.C. Hamelin; P. Tooley; M. Garbelotto; K.J.D. Hughes; T. Kubisiak; G.J. Bilodeau; L. Levy; C. Blomquist; P.H. Berger

    2009-01-01

    Given the importance of Phytophthora ramorum from a regulatory standpoint, it is imperative that molecular markers for pathogen detection are fully tested to evaluate their specificity in detection of the pathogen. In an effort to evaluate 11 reported diagnostic techniques, we assembled a standardized DNA library using accessions from the World...

  18. HyQue: evaluating hypotheses using Semantic Web technologies

    Science.gov (United States)

    2011-01-01

    Background Key to the success of e-Science is the ability to computationally evaluate expert-composed hypotheses for validity against experimental data. Researchers face the challenge of collecting, evaluating and integrating large amounts of diverse information to compose and evaluate a hypothesis. Confronted with rapidly accumulating data, researchers currently do not have the software tools to undertake the required information integration tasks. Results We present HyQue, a Semantic Web tool for querying scientific knowledge bases with the purpose of evaluating user submitted hypotheses. HyQue features a knowledge model to accommodate diverse hypotheses structured as events and represented using Semantic Web languages (RDF/OWL). Hypothesis validity is evaluated against experimental and literature-sourced evidence through a combination of SPARQL queries and evaluation rules. Inference over OWL ontologies (for type specifications, subclass assertions and parthood relations) and retrieval of facts stored as Bio2RDF linked data provide support for a given hypothesis. We evaluate hypotheses of varying levels of detail about the genetic network controlling galactose metabolism in Saccharomyces cerevisiae to demonstrate the feasibility of deploying such semantic computing tools over a growing body of structured knowledge in Bio2RDF. Conclusions HyQue is a query-based hypothesis evaluation system that can currently evaluate hypotheses about the galactose metabolism in S. cerevisiae. Hypotheses as well as the supporting or refuting data are represented in RDF and directly linked to one another allowing scientists to browse from data to hypothesis and vice versa. HyQue hypotheses and data are available at http://semanticscience.org/projects/hyque. PMID:21624158

  19. HyQue: evaluating hypotheses using Semantic Web technologies.

    Science.gov (United States)

    Callahan, Alison; Dumontier, Michel; Shah, Nigam H

    2011-05-17

    Key to the success of e-Science is the ability to computationally evaluate expert-composed hypotheses for validity against experimental data. Researchers face the challenge of collecting, evaluating and integrating large amounts of diverse information to compose and evaluate a hypothesis. Confronted with rapidly accumulating data, researchers currently do not have the software tools to undertake the required information integration tasks. We present HyQue, a Semantic Web tool for querying scientific knowledge bases with the purpose of evaluating user submitted hypotheses. HyQue features a knowledge model to accommodate diverse hypotheses structured as events and represented using Semantic Web languages (RDF/OWL). Hypothesis validity is evaluated against experimental and literature-sourced evidence through a combination of SPARQL queries and evaluation rules. Inference over OWL ontologies (for type specifications, subclass assertions and parthood relations) and retrieval of facts stored as Bio2RDF linked data provide support for a given hypothesis. We evaluate hypotheses of varying levels of detail about the genetic network controlling galactose metabolism in Saccharomyces cerevisiae to demonstrate the feasibility of deploying such semantic computing tools over a growing body of structured knowledge in Bio2RDF. HyQue is a query-based hypothesis evaluation system that can currently evaluate hypotheses about the galactose metabolism in S. cerevisiae. Hypotheses as well as the supporting or refuting data are represented in RDF and directly linked to one another allowing scientists to browse from data to hypothesis and vice versa. HyQue hypotheses and data are available at http://semanticscience.org/projects/hyque.

  20. HyQue: evaluating hypotheses using Semantic Web technologies

    Directory of Open Access Journals (Sweden)

    Callahan Alison

    2011-05-01

    Full Text Available Abstract Background Key to the success of e-Science is the ability to computationally evaluate expert-composed hypotheses for validity against experimental data. Researchers face the challenge of collecting, evaluating and integrating large amounts of diverse information to compose and evaluate a hypothesis. Confronted with rapidly accumulating data, researchers currently do not have the software tools to undertake the required information integration tasks. Results We present HyQue, a Semantic Web tool for querying scientific knowledge bases with the purpose of evaluating user submitted hypotheses. HyQue features a knowledge model to accommodate diverse hypotheses structured as events and represented using Semantic Web languages (RDF/OWL. Hypothesis validity is evaluated against experimental and literature-sourced evidence through a combination of SPARQL queries and evaluation rules. Inference over OWL ontologies (for type specifications, subclass assertions and parthood relations and retrieval of facts stored as Bio2RDF linked data provide support for a given hypothesis. We evaluate hypotheses of varying levels of detail about the genetic network controlling galactose metabolism in Saccharomyces cerevisiae to demonstrate the feasibility of deploying such semantic computing tools over a growing body of structured knowledge in Bio2RDF. Conclusions HyQue is a query-based hypothesis evaluation system that can currently evaluate hypotheses about the galactose metabolism in S. cerevisiae. Hypotheses as well as the supporting or refuting data are represented in RDF and directly linked to one another allowing scientists to browse from data to hypothesis and vice versa. HyQue hypotheses and data are available at http://semanticscience.org/projects/hyque.

  1. Development of a molecular method for testing the effectiveness of UV systems on-site.

    Science.gov (United States)

    Nizri, Limor; Vaizel-Ohayon, Dalit; Ben-Amram, Hila; Sharaby, Yehonatan; Halpern, Malka; Mamane, Hadas

    2017-12-15

    We established a molecular method for quantifying ultraviolet (UV) disinfection efficacy using total bacterial DNA in a water sample. To evaluate UV damage to the DNA, we developed the "DNA damage" factor, which is a novel cultivation-independent approach that reveals UV-exposure efficiency by applying a simple PCR amplification method. The study's goal was to prove the feasibility of this method for demonstrating the efficiency of UV systems in the field using flow-through UV reactors. In laboratory-based experiments using seeded bacteria, the DNA damage tests demonstrated a good correlation between PCR products and UV dose. In the field, natural groundwater sampled before and after being subjected to the full-scale UV reactors was filtered, and the DNA extracted from the filtrate was subjected to PCR amplification for a 900-bp fragment of the 16S rRNA gene with initial DNA concentrations of 0.1 and 1 ng/μL. In both cases, the UV dose predicted and explained a significant proportion of the variance in the log inactivation ratio and DNA damage factor. Log inactivation ratio was very low, as expected in groundwater due to low initial bacterial counts, whereas the DNA damage factor was within the range of values obtained in the laboratory-based experiments. Consequently, the DNA damage factor reflected the true performance of the full-scale UV system during operational water flow by using the indigenous bacterial array present in a water sample. By applying this method, we were able to predict with high confidence, the UV reactor inactivation potential. For method validation, laboratory and field iterations are required to create a practical field calibration curve that can be used to determine the expected efficiency of the full-scale UV system in the field under actual operation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Biomechanical testing of new meniscal repair techniques containing ultra high-molecular weight polyethylene suture.

    Science.gov (United States)

    Barber, F Alan; Herbert, Morley A; Schroeder, F Alexander; Aziz-Jacobo, Jorge; Sutker, Michael J

    2009-09-01

    To evaluate the biomechanical characteristics of current meniscal repair techniques containing ultra high-molecular weight polyethylene (UHMWPE) suture with and without cyclic loading. Vertical longitudinal cuts made in porcine menisci were secured with a single repair device. Noncycled and cycled (500 cycles) biomechanical tests were performed on the following groups: group 1, No. 2-0 Mersilene vertical suture (Ethicon, Somerville, NJ); group 2, No. 2-0 Orthocord vertical suture (DePuy Mitek, Westwood, MA); group 3, No. 0 Ultrabraid vertical suture (Smith & Nephew Endoscopy, Andover, MA); group 4, No. 2-0 FiberWire vertical suture (Arthrex, Naples, FL); group 5, vertically oriented mattress suture by use of an Ultra FasT-Fix device (Smith & Nephew Endoscopy) with No. 0 Ultrabraid; group 6, vertically oriented mattress suture by use of a RapidLoc A2 device (DePuy Mitek) with No. 2-0 Orthocord suture; group 7, vertically oriented stitch by use of a MaxFire device with MaxBraid PE suture (Biomet Sports Medicine, Warsaw, IN); and group 8, an obliquely oriented stitch of No. 0 UHMWPE suture inserted by use of a CrossFix device (Cayenne Medical, Scottsdale, AZ). Endpoints were failure loads, failure modes, stiffness, and cyclic displacement. Mean single-pull loads were calculated for Ultra FasT-Fix (121 N), FiberWire (110 N), MaxFire (130 N), Mersilene (84 N), Orthocord (124 N), RapidLoc A2 (86 N), CrossFix (77 N), and Ultrabraid (109 N). After 500 cyclic loads, the Orthocord (222 N) repair was stronger than the others: Ultra FasT-Fix (110 N), FiberWire (117 N), MaxFire (132 N), Mersilene (89 N), RapidLoc A2 (108 N), CrossFix (95 N), and Ultrabraid (126 N) (P Fix, RapidLoc A2, and MaxFire) were comparable to the isolated UHMWPE-containing suture repairs on single-failure load testing. UHMWPE-containing suture repairs are stronger than braided polyester suture repairs, but pure UHMWPE suture (Ultrabraid) elongated more during cycling. Orthocord suture is significantly

  3. High frequency circular translation pin-on-disk method for accelerated wear testing of ultrahigh molecular weight polyethylene as a bearing material in total hip arthroplasty.

    Science.gov (United States)

    Saikko, Vesa

    2015-01-21

    The temporal change of the direction of sliding relative to the ultrahigh molecular weight polyethylene (UHMWPE) component of prosthetic joints is known to be of crucial importance with respect to wear. One complete revolution of the resultant friction vector is commonly called a wear cycle. It was hypothesized that in order to accelerate the wear test, the cycle frequency may be substantially increased if the circumference of the slide track is reduced in proportion, and still the wear mechanisms remain realistic and no overheating takes place. This requires an additional slow motion mechanism with which the lubrication of the contact is maintained and wear particles are conveyed away from the contact. A three-station, dual motion high frequency circular translation pin-on-disk (HF-CTPOD) device with a relative cycle frequency of 25.3 Hz and an average sliding velocity of 27.4 mm/s was designed. The pins circularly translated at high frequency (1.0 mm per cycle, 24.8 Hz, clockwise), and the disks at low frequency (31.4mm per cycle, 0.5 Hz, counter-clockwise). In a 22 million cycle (10 day) test, the wear rate of conventional gamma-sterilized UHMWPE pins against polished CoCr disks in diluted serum was 1.8 mg per 24 h, which was six times higher than that in the established 1 Hz CTPOD device. The wear mechanisms were similar. Burnishing of the pin was the predominant feature. No overheating took place. With the dual motion HF-CTPOD method, the wear testing of UHMWPE as a bearing material in total hip arthroplasty can be substantially accelerated without concerns of the validity of the wear simulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Molecular genetics of Mycobacterium tuberculosis resistant to aminoglycosides and cyclic peptide testing by MTBDRsl in Armenia

    Directory of Open Access Journals (Sweden)

    Hasmik Margaryan

    2016-01-01

    Conclusion: Isolates with rrs structural gene mutations were cross-resistant to streptomycin, KAN, CAP, and AMK. Detection of the A1401G mutation appeared to be 100% specific for the detection of resistance to KAN and AMK. Being the first assessment, these data establish the presence of phenotypic drug-resistant and extensively drug-resistant strains using molecular profiling and are helpful in understanding aminoglycoside resistance on a molecular level.

  5. Techniques for Maximizing the Performance of Molecular Pathology Testing: Responsibilities of All Pathologists

    Directory of Open Access Journals (Sweden)

    Evren UZUN

    2018-05-01

    Full Text Available Molecular pathological analysis has an expanding role in patient diagnosis and management. The performance of these techniques relies on excellent laboratory procedures. However, the crucial step is obtaining the best samples for molecular analysis. Archiving and selection of these are the responsibilities of all pathologists even if they are not working at a center with molecular pathological facilities. This review focuses on the features of different types of materials for molecular pathological analysis. Many steps that might affect the results, including communication between the pathologist and the oncology team, features of different types of materials (cytological, tissue blocks, biopsy, circulating tumor cells (CTCs and cell-free circulating nucleic acids, effects of tissue processing, methods for selecting the best material, and tissue saving and tumor enrichment methods are discussed. The procedures for referral to a center for molecular pathological analysis are also mentioned. Awareness of the importance of the cytopathological and histopathological material of the patients for future molecular pathological analysis by pathologists is of the utmost importance.

  6. Testing the universality of the star-formation efficiency in dense molecular gas

    Science.gov (United States)

    Shimajiri, Y.; André, Ph.; Braine, J.; Könyves, V.; Schneider, N.; Bontemps, S.; Ladjelate, B.; Roy, A.; Gao, Y.; Chen, H.

    2017-08-01

    Context. Recent studies with, for example, Spitzer and Herschel have suggested that star formation in dense molecular gas may be governed by essentially the same "law" in Galactic clouds and external galaxies. This conclusion remains controversial, however, in large part because different tracers have been used to probe the mass of dense molecular gas in Galactic and extragalactic studies. Aims: We aimed to calibrate the HCN and HCO+ lines commonly used as dense gas tracers in extragalactic studies and to test the possible universality of the star-formation efficiency in dense gas (≳104 cm-3), SFEdense. Methods: We conducted wide-field mapping of the Aquila, Ophiuchus, and Orion B clouds at 0.04 pc resolution in the J = 1 - 0 transition of HCN, HCO+, and their isotopomers. For each cloud, we derived a reference estimate of the dense gas mass MHerschelAV > 8, as well as the strength of the local far-ultraviolet (FUV) radiation field, using Herschel Gould Belt survey data products, and estimated the star-formation rate from direct counting of the number of Spitzer young stellar objects. Results: The H13CO+(1-0) and H13CN(1-0) lines were observed to be good tracers of the dense star-forming filaments detected with Herschel. Comparing the luminosities LHCN and LHCO+ measured in the HCN and HCO+ lines with the reference masses MHerschelAV > 8, the empirical conversion factors αHerschel - HCN (=MHerschelAV > 8/LHCN) and αHerschel - HCO+ (=MHerschelAV > 8/LHCO+) were found to be significantly anti-correlated with the local FUV strength. In agreement with a recent independent study of Orion B by Pety et al., the HCN and HCO+ lines were found to trace gas down to AV ≳ 2. As a result, published extragalactic HCN studies must be tracing all of the moderate density gas down to nH2 ≲ 103 cm-3. Estimating the contribution of this moderate density gas from the typical column density probability distribution functions in nearby clouds, we obtained the following G0

  7. Support for major hypotheses in invasion biology is uneven and declining

    Czech Academy of Sciences Publication Activity Database

    Jeschke, J.M.; Aparicio, L.G.; Haider, S.; Heger, T.; Lortie, C. J.; Pyšek, Petr; Strayer, D.L.

    2012-01-01

    Roč. 2012, č. 14 (2012), s. 1-20 ISSN 1619-0033 R&D Projects: GA ČR(CZ) GAP504/11/1028 Institutional support: RVO:67985939 Keywords : biological invasions * hypotheses * testing Subject RIV: EF - Botanics

  8. Message and source factors, market uncertainty and extrafunctional information processing : hypotheses and empirical evidence

    NARCIS (Netherlands)

    Song, X.M.

    2001-01-01

    This article examines how the perceived quality of extrafunctional information improves the innovation management process and contributes to success with innovations. Data collected from 420 Japanese managers and 270 US managers are used to test hypotheses about the antecedents of satisfaction with

  9. Landscape moderation of biodiversity patterns and processes - eight hypotheses

    NARCIS (Netherlands)

    Tscharntke, T.; Tylianakis, J.M.; Rand, T.A.; Didham, R.K.; Fahrig, L.; Batary, P.; Bengtsson, J.; Clough, Y.; Crist, T.O.; Dormann, C.; Ewers, R.M.; Frund, J.; Holt, R.D.; Holzschuh, A.; Klein, A.M.; Kleijn, D.; Kremen, C.; Landis, D.A.; Laurance, W.F.; Lindenmayer, D.B.; Scherber, C.; Sodhi, N.; Steffan-Dewenter, I.; Thies, C.; Putten, van der W.H.; Westphal, C.

    2012-01-01

    Understanding how landscape characteristics affect biodiversity patterns and ecological processes at local and landscape scales is critical for mitigating effects of global environmental change. In this review, we use knowledge gained from human-modified landscapes to suggest eight hypotheses, which

  10. What Is the Problem of Ad Hoc Hypotheses?

    Science.gov (United States)

    Bamford, Greg

    1999-01-01

    Philosophers' attempts to convincingly explicate the received view of an ad hoc hypothesis--that it accounts for only the observations it was designed to account for--have been unsuccessful. Familiar and firmer criteria for evaluating the hypotheses or modified theories so classified are characteristically available. Contains 41 references.…

  11. Editorial: hypotheses about protein folding - the proteomic code and wonderfolds

    Directory of Open Access Journals (Sweden)

    Agutter Paul S

    2009-12-01

    Full Text Available Abstract Theoretical biology journals can contribute in many ways to the progress of knowledge. They are particularly well-placed to encourage dialogue and debate about hypotheses addressing problematical areas of research. An online journal provides an especially useful forum for such debate because of the option of posting comments within days of the publication of a contentious article.

  12. Toward Valid Measurement of Stephen Pepper's World Hypotheses.

    Science.gov (United States)

    Johnson, John A.

    Two measures of the "world hypotheses" of Stephen Pepper were mailed to 100 sociobiologists, 87 behaviorists, 79 personality psychologists, and 45 human developmentalists. The World Hypothesis Scale (WHS) was designed to measure Pepper's four world views: (1) formism; (2) mechanism; (3) organicism; and (4) contextualism. The…

  13. A test of systematic coarse-graining of molecular dynamics simulations: Thermodynamic properties

    Science.gov (United States)

    Fu, Chia-Chun; Kulkarni, Pandurang M.; Scott Shell, M.; Gary Leal, L.

    2012-10-01

    Coarse-graining (CG) techniques have recently attracted great interest for providing descriptions at a mesoscopic level of resolution that preserve fluid thermodynamic and transport behaviors with a reduced number of degrees of freedom and hence less computational effort. One fundamental question arises: how well and to what extent can a "bottom-up" developed mesoscale model recover the physical properties of a molecular scale system? To answer this question, we explore systematically the properties of a CG model that is developed to represent an intermediate mesoscale model between the atomistic and continuum scales. This CG model aims to reduce the computational cost relative to a full atomistic simulation, and we assess to what extent it is possible to preserve both the thermodynamic and transport properties of an underlying reference all-atom Lennard-Jones (LJ) system. In this paper, only the thermodynamic properties are considered in detail. The transport properties will be examined in subsequent work. To coarse-grain, we first use the iterative Boltzmann inversion (IBI) to determine a CG potential for a (1-ϕ)N mesoscale particle system, where ϕ is the degree of coarse-graining, so as to reproduce the radial distribution function (RDF) of an N atomic particle system. Even though the uniqueness theorem guarantees a one to one relationship between the RDF and an effective pairwise potential, we find that RDFs are insensitive to the long-range part of the IBI-determined potentials, which provides some significant flexibility in further matching other properties. We then propose a reformulation of IBI as a robust minimization procedure that enables simultaneous matching of the RDF and the fluid pressure. We find that this new method mainly changes the attractive tail region of the CG potentials, and it improves the isothermal compressibility relative to pure IBI. We also find that there are optimal interaction cutoff lengths for the CG system, as a function of

  14. Practical-scale tests of cryogenic molecular sieve for separating low-concentration hydrogen isotopes from helium

    International Nuclear Information System (INIS)

    Willms, R.S.; Taylor, D.J.; Enoeda, Mikio; Okuno, Kenji

    1994-01-01

    Earlier bench-scale work at the Tritium Systems Test Assembly (TSTA) at Los Alamos National Laboratory examined a number of adsorbents for their suitability for separating low-concentration hydrogen (no tritium) from helium. One of the effective adsorbents was Linde 5A molecular sieve. Recently, experiments including tritium were conducted using practical-scale adsorbers. These tests used existing cryogenic molecular sieve beds (CMSB's) which each contain about 1.6 kg of Linde 5A molecular sieve. They are part of the TSTA integrated tritium processing system. Gas was fed to each CMSB at about 13 SLPM with a nominal composition of 99% He, 0.98% H 2 and 0.02% HT. In all cases, for an extended period of time, the beds allowed no detectable (via Raman spectroscopy) hydrogen isotopes to escape in the bed effluent. Thereafter, the hydrogen isotopes appeared in the bed exit with a relatively sharp breakthrough curve. This work concludes that cryogenic molecular sieve adsorption is an practical and effective means of separating low-concentration hydrogen isotopes from a helium carrier

  15. Tests of potential functional barriers for laminated multilayer food packages. Part II: Medium molecular weight permeants.

    Science.gov (United States)

    Simal-Gándara, J; Sarria-Vidal, M; Rijk, R

    2000-09-01

    Experiments were performed to characterize the kinetics of the permeation of different medium molecular weight model permeants: bisphenol A, warfarin and anthracene, from liquid paraffin, through a surrogate potential functional barrier (25 microns-thick orientated polypropylene--OPP) into the food simulants olive oil and 3% (w/v) acetic acid. The characterization of permeation kinetics generally observed the permeation models previously reported to explain the experimental permeation results obtained for a low molecular weight group of model permeants. In general, the model permeants exhibited behaviour consistent with their relative molecular weights with respect to (a) the time taken to attain steady-state permeation into the food simulant in which they were more soluble, (b) their subsequent steady-state permeation rates, and (c) their partition between liquid paraffin and the OPP membrane.

  16. Effect of molecular weight and testing rate on adhesion property of pressure-sensitive adhesives prepared from epoxidized natural rubber

    International Nuclear Information System (INIS)

    Khan, Imran; Poh, B.T.

    2011-01-01

    Research highlights: → Elucidation of adhesion property of epoxidized natural rubber (ENR 25). → Correlation of peel and shear strength with molecular weight and rate of testing. → Confirmation of miscibility of tackifier and ENR 25 by DSC and FTIR study. → Applicability of Fox equation in ENR 25/coumarone-indene resin system. -- Abstract: The dependence of peel strength and shear strength of epoxidized natural rubber (ENR 25)-based pressure-sensitive adhesive on molecular weight and rate of testing was investigated using coumarone-indene as the tackifying resin. Toluene and polyethylene terephthalate (PET) were used as the solvent and substrate respectively throughout the study. A SHEEN hand coater was used to coat the adhesive on the substrate at a coating thickness of 120 μm. All the adhesion properties were determined by a Llyod Adhesion Tester operating at different rates of testing. Result shows that peel strength and shear strength increases up to an optimum molecular weight of 6.5 x 10 4 of ENR 25. For peel strength, the observation is attributed to the combined effects of wettability and mechanical strength of rubber at the optimum molecular weight, whereas for the shear strength, it is ascribed to the increasing amount of adhesive present in the coating layer which enhances the shear resistance of the adhesive. Peel strength and shear strength also increases with increase in rate of testing, an observation which is associated to the viscoeslastic response of the adhesive. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) study confirms the miscibility of tackifier and the ENR 25.

  17. Comparison between the diagnostic accuracy of clinico-pathological and molecular tests for feline infectious peritonitis (FIP

    Directory of Open Access Journals (Sweden)

    Angelica Stranieri

    2015-07-01

    Full Text Available The aim of this study was to compare the diagnostic accuracy for feline infectious peritonitis (FIP of conventional clinic-pathological tests with that of molecular tests such as routine PCR and PCR followed by the sequencing of the Spike (S gene. Blood, effusion and tissues specimens were collected from 21 FIP suspected cats. In vivo examination consisted of CBC, serum protein electrophoresis, AGP measurement, cytological and biochemical examination and the evaluation of the ΔTNC on effusions, and of molecular tests such the screening PCR (target: 3’UTR region and the PCR directed towards the S gene followed by the amplification products sequencing in order to detect the aminoacidic substitution recently considered diagnostic for FIP1. These molecular techniques were applied to tissues collected during necropsy, which also allowed forming an FIP group (13 cats and a non-FIP group (5 cats based on histology and immunohistochemistry. The best test on tissues was immunohistochemistry (sens: 92.3%; spec: 100%, while the screening PCR suffered of low specificity (spec: 33.3% and the S gene sequencing showed low sensitivity (sens: 69.2%.On effusions, the best tests resulted screening PCR and cytology (sens and spec: 100% in comparison with the ΔTNC measurement (sens: 85.7 %; spec: 100% and the S gene sequencing (sens: 42.8%; spec: 100%.On blood, the best test resulted AGP measurement (sens: 81.8%; spec: 100%, while serum protein electrophoresis showed a surprisingly low sensitivity (sens: 41.7%. Screening PCR (sens: 55.6%; spec: 100% and S gene sequencing (sens: 33.3%; spec: 100% proved again low accuracy.

  18. Kolmogorov's refined similarity hypotheses for turbulence and general stochastic processes

    International Nuclear Information System (INIS)

    Stolovitzky, G.; Sreenivasan, K.R.

    1994-01-01

    Kolmogorov's refined similarity hypotheses are shown to hold true for a variety of stochastic processes besides high-Reynolds-number turbulent flows, for which they were originally proposed. In particular, just as hypothesized for turbulence, there exists a variable V whose probability density function attains a universal form. Analytical expressions for the probability density function of V are obtained for Brownian motion as well as for the general case of fractional Brownian motion---the latter under some mild assumptions justified a posteriori. The properties of V for the case of antipersistent fractional Brownian motion with the Hurst exponent of 1/3 are similar in many details to those of high-Reynolds-number turbulence in atmospheric boundary layers a few meters above the ground. The one conspicuous difference between turbulence and the antipersistent fractional Brownian motion is that the latter does not possess the required skewness. Broad implications of these results are discussed

  19. A survey of etiologic hypotheses among testicular cancer researchers

    DEFF Research Database (Denmark)

    Stang, A; Trabert, B; Rusner, C

    2015-01-01

    Basic research results can provide new ideas and hypotheses to be examined in epidemiological studies. We conducted a survey among testicular cancer researchers on hypotheses concerning the etiology of this malignancy. All researchers on the mailing list of Copenhagen Testis Cancer Workshops...... and corresponding authors of PubMed-indexed articles identified by the search term 'testicular cancer' and published within 10 years (in total 2750 recipients) were invited to respond to an e-mail-based survey. Participants of the 8th Copenhagen Testis Cancer Workshop in May 2014 were subsequently asked to rate...... that scored as most plausible. We also present plans for improving the survey that may be repeated at a next international meeting of experts in testicular cancer. Overall 52 of 99 (53%) registered participants of the 8th Copenhagen Testis Cancer Workshop submitted the plausibility rating form. Fourteen of 27...

  20. Explanatory hypotheses formation and the anomalous β spectrum

    Energy Technology Data Exchange (ETDEWEB)

    Gauderis, Tjerk [Centre for Logic and Philosophy of Science, Ghent University (Belgium)

    2013-07-01

    Between 1928 and 1934, a persevering anomaly mystified the physics community: while alpha decay behaved perfectly according to the new quantum mechanics, the energy of electrons emitted in beta decay displayed a broad continuous spectrum. This puzzle invoked a lively debate among the most established physicists at the time. But the curious thing was that they all suggested hypotheses of very different formal types: Rutherford and Chadwick thought of varying internal energies, Bohr suggested to restrict the energy conservation principle, Heisenberg tinkered with a new quantization of space, and Pauli suggested the existence of a new elementary particle - all these hypotheses being radical and highly controversial. In physics, an anomalous experimental result can trigger the formation of formally very different hypotheses. A scientist confronted with such a result has no strict guidelines to help her decide whether she should explain this result by withdrawing or adapting a constraint (e.g. a law) of the current theory, or by presupposing the existence of a hitherto unobserved entity (e.g. a particle) that makes the anomaly fit within that theory. In this talk I aim to gain some insights how scientists make this choice, by examining in the above case study how the choice of the various mentioned physicists depended on their previous experiences and their specific perception of the problem.

  1. Cytological preparations for molecular analysis: A review of technical procedures, advantages and limitations for referring samples for testing.

    Science.gov (United States)

    da Cunha Santos, G; Saieg, M A; Troncone, G; Zeppa, P

    2018-04-01

    Minimally invasive procedures such as endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) must yield not only good quality and quantity of material for morphological assessment, but also an adequate sample for analysis of molecular markers to guide patients to appropriate targeted therapies. In this context, cytopathologists worldwide should be familiar with minimum requirements for refereeing cytological samples for testing. The present manuscript is a review with comprehensive description of the content of the workshop entitled Cytological preparations for molecular analysis: pre-analytical issues for EBUS TBNA, presented at the 40th European Congress of Cytopathology in Liverpool, UK. The present review emphasises the advantages and limitations of different types of cytology substrates used for molecular analysis such as archival smears, liquid-based preparations, archival cytospin preparations and FTA (Flinders Technology Associates) cards, as well as their technical requirements/features. These various types of cytological specimens can be successfully used for an extensive array of molecular studies, but the quality and quantity of extracted nucleic acids rely directly on adequate pre-analytical assessment of those samples. In this setting, cytopathologists must not only be familiar with the different types of specimens and associated technical procedures, but also correctly handle the material provided by minimally invasive procedures, ensuring that there is sufficient amount of material for a precise diagnosis and correct management of the patient through personalised care. © 2018 John Wiley & Sons Ltd.

  2. The solid-state terahertz spectrum of MDMA (Ecstasy) - A unique test for molecular modeling assignments

    Science.gov (United States)

    Allis, Damian G.; Hakey, Patrick M.; Korter, Timothy M.

    2008-10-01

    The terahertz (THz, far-infrared) spectrum of 3,4-methylene-dioxymethamphetamine hydrochloride (Ecstasy) is simulated using solid-state density functional theory. While a previously reported isolated-molecule calculation is noteworthy for the precision of its solid-state THz reproduction, the solid-state calculation predicts that the isolated-molecule modes account for only half of the spectral features in the THz region, with the remaining structure arising from lattice vibrations that cannot be predicted without solid-state molecular modeling. The molecular origins of the internal mode contributions to the solid-state THz spectrum, as well as the proper consideration of the protonation state of the molecule, are also considered.

  3. A survey of physician receptivity to molecular diagnostic testing and readiness to act on results for early-stage colon cancer patients.

    Science.gov (United States)

    Myers, Ronald E; Wolf, Thomas; Shwae, Phillip; Hegarty, Sarah; Peiper, Stephen C; Waldman, Scott A

    2016-10-03

    We sought to assess physician interest in molecular prognosic testing for patients with early stage colon cancer, and identify factors associated with the likelihood of test adoption. We identified physicians who care for patients with early-stage (pN0) colon cancer patients, mailed them a survey, and analyzed survey responses to assess clinician receptivity to the use of a new molecular test (GUCY2C) that identifies patients at risk for recurrence, and clinician readiness to act on abnormal test results. Of 104 eligible potential respondents, 41 completed and returned the survey. Among responding physicians, 56 % were receptive to using the new prognostic test. Multivariable analyses showed that physicians in academic medical centers were significantly more receptive to molecular test use than those in non-academic settings. Forty-one percent of respondents were ready to act on abnormal molecular test results. Physicians who viewed current staging methods as inaccurate and were confident in their capacity to incorporate molecular testing in practice were more likely to say they would act on abnormal test results. Physician receptivity to molecular diagnostic testing for early-stage colon cancer patients is likely to be influenced by practice setting and perceptions related to delivering quality care to patients. ClinicalTrials.gov Identifier: NCT01972737.

  4. Testing the molecular-hydrogen Kennicutt-Schmidt law in the low-density environments of extended ultraviolet disc galaxies

    Science.gov (United States)

    Watson, Linda C.; Martini, Paul; Lisenfeld, Ute; Böker, Torsten; Schinnerer, Eva

    2016-01-01

    Studying star formation beyond the optical radius of galaxies allows us to test empirical relations in extreme conditions with low average gas density and low molecular fraction. Previous studies discovered galaxies with extended ultraviolet (XUV) discs, which often contain star-forming regions with lower Hα-to-far-UV (FUV) flux ratios compared to inner disc star-forming regions. However, most previous studies lack measurements of molecular gas, which is presumably the component of the interstellar medium out of which stars form. We analysed published CO measurements and upper limits for 15 star-forming regions in the XUV or outer disc of three nearby spiral galaxies and a new CO upper limit from the IRAM (Institut de Radioastronomie Millimétrique) 30 m telescope in one star-forming region at r = 3.4r25 in the XUV disc of NGC 4625. We found that the star-forming regions are in general consistent with the same molecular-hydrogen Kennicutt-Schmidt law that applies within the optical radius, independent of whether we used Hα or FUV as the star formation rate (SFR) tracer. However, a number of the CO detections are significantly offset towards higher SFR surface density for their molecular-hydrogen surface density. Deeper CO data may enable us to use the presence or absence of molecular gas as an evolutionary probe to break the degeneracy between age and stochastic sampling of the initial mass function as the explanation for the low Hα-to-FUV flux ratios in XUV discs.

  5. Multiplex molecular testing for management of infectious gastroenteritis in a hospital setting: a comparative diagnostic and clinical utility study.

    Science.gov (United States)

    Halligan, E; Edgeworth, J; Bisnauthsing, K; Bible, J; Cliff, P; Aarons, E; Klein, J; Patel, A; Goldenberg, S

    2014-08-01

    Laboratory diagnosis and clinical management of inpatients with diarrhoea is complex and time consuming. Tests are often requested sequentially and undertaken in different laboratories. This causes prolonged unnecessary presumptive isolation of patients, because most cases are non-infectious. A molecular multiplex test (Luminex(®) Gastrointestinal Pathogen Panel (GPP)) was compared with conventional testing over 8 months to determine diagnostic accuracy, turnaround times, laboratory costs, use of isolation facilities and user acceptability. A total of 262 (12%) patients had a pathogen detected by conventional methods compared with 483 (22.1%) by GPP. Most additional cases were detected in patients developing symptoms in the first 4 days of admission. Additional cases were detected because of presumed improved diagnostic sensitivity but also because clinicians had not requested the correct pathogen. Turnaround time (41.8 h) was faster than bacterial culture (66.5 h) and parasite investigation (66.5 h) but slower than conventional testing for Clostridium difficile (17.3 h) and viruses (27 h). The test could allow simplified requesting by clinicians and a consolidated laboratory workflow, reducing the overall number of specimens received by the laboratory. A total of 154 isolation days were saved at an estimated cost of £30 800. Consumables and labour were estimated at £150 641 compared with £63 431 for conventional testing. Multiplex molecular testing using a panel of targets allowed enhanced detection and a consolidated laboratory workflow. This is likely to be of greater benefit to cases that present within the first 4 days of hospital admission. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

  6. A decade of molecular genetic testing for MODY: a retrospective study of utilization in The Netherlands.

    Science.gov (United States)

    Weinreich, Stephanie S; Bosma, Astrid; Henneman, Lidewij; Rigter, Tessel; Spruijt, Carla M J; Grimbergen, Anneliese J E M A; Breuning, Martijn H; de Koning, Eelco J P; Losekoot, Monique; Cornel, Martina C

    2015-01-01

    Genetic testing for maturity-onset diabetes of the young (MODY) may be relevant for treatment and prognosis in patients with usually early-onset, non-ketotic, insulin-sensitive diabetes and for monitoring strategies in non-diabetic mutation carriers. This study describes the first 10 years of genetic testing for MODY in The Netherlands in terms of volume and test positive rate, medical setting, purpose of the test and age of patients tested. Some analyses focus on the most prevalent subtype, HNF1A MODY. Data were retrospectively extracted from a laboratory database. In total, 502 individuals were identified with a pathogenic mutation in HNF4A, GCK or HNF1A between 2001 and 2010. Although mutation scanning for MODY was used at an increasing rate, cascade testing was only used for one relative, on average, per positive index patient. Testing for HNF1A MODY was mostly requested by internists and paediatricians, often from regional hospitals. Primary care physicians and clinical geneticists rarely requested genetic testing for HNF1A MODY. Clinical geneticists requested cascade testing relatively more often than other health professionals. A substantial proportion (currently 29%) of HNF1A MODY probands was at least 40 years old at the time of testing. In conclusion, the number of individuals genetically tested for MODY so far in The Netherlands is low compared with previously predicted numbers of patients. Doctors' valuation of the test and patients' and family members' response to (an offer of) genetic testing on the other hand need to be investigated. Efforts may be needed to develop and implement translational guidelines.

  7. Hypothesized eye movements of neurolinguistic programming: a statistical artifact.

    Science.gov (United States)

    Farmer, A; Rooney, R; Cunningham, J R

    1985-12-01

    Neurolinguistic programming's hypothesized eye-movements were measured independently from videotapes of 30 subjects, aged 15 to 76 yr., who were asked to recall visual pictures, recorded audio sounds, and textural objects. chi 2 indicated that subjects' responses were significantly different from those predicted. When chi 2 comparisons were weighted by number of eye positions assigned to each modality (3 visual, 3 auditory, 1 kinesthetic), subjects' responses did not differ significantly from the expected pattern. These data indicate that the eye-movement hypothesis may represent randomly occurring rather than sensory-modality-related positions.

  8. Systematic review, meta-analysis and economic modelling of molecular diagnostic tests for antibiotic resistance in tuberculosis.

    Science.gov (United States)

    Drobniewski, Francis; Cooke, Mary; Jordan, Jake; Casali, Nicola; Mugwagwa, Tendai; Broda, Agnieszka; Townsend, Catherine; Sivaramakrishnan, Anand; Green, Nathan; Jit, Mark; Lipman, Marc; Lord, Joanne; White, Peter J; Abubakar, Ibrahim

    2015-05-01

    Drug-resistant tuberculosis (TB), especially multidrug-resistant (MDR, resistance to rifampicin and isoniazid) disease, is associated with a worse patient outcome. Drug resistance diagnosed using microbiological culture takes days to weeks, as TB bacteria grow slowly. Rapid molecular tests for drug resistance detection (1 day) are commercially available and may promote faster initiation of appropriate treatment. To (1) conduct a systematic review of evidence regarding diagnostic accuracy of molecular genetic tests for drug resistance, (2) conduct a health-economic evaluation of screening and diagnostic strategies, including comparison of alternative models of service provision and assessment of the value of targeting rapid testing at high-risk subgroups, and (3) construct a transmission-dynamic mathematical model that translates the estimates of diagnostic accuracy into estimates of clinical impact. A standardised search strategy identified relevant studies from EMBASE, PubMed, MEDLINE, Bioscience Information Service (BIOSIS), System for Information on Grey Literature in Europe Social Policy & Practice (SIGLE) and Web of Science, published between 1 January 2000 and 15 August 2013. Additional 'grey' sources were included. Quality was assessed using quality assessment of diagnostic accuracy studies version 2 (QUADAS-2). For each diagnostic strategy and population subgroup, a care pathway was constructed to specify which medical treatments and health services that individuals would receive from presentation to the point where they either did or did not complete TB treatment successfully. A total cost was estimated from a health service perspective for each care pathway, and the health impact was estimated in terms of the mean discounted quality-adjusted life-years (QALYs) lost as a result of disease and treatment. Costs and QALYs were both discounted at 3.5% per year. An integrated transmission-dynamic and economic model was used to evaluate the cost-effectiveness of

  9. Systematic review, meta-analysis and economic modelling of molecular diagnostic tests for antibiotic resistance in tuberculosis.

    Science.gov (United States)

    Drobniewski, Francis; Cooke, Mary; Jordan, Jake; Casali, Nicola; Mugwagwa, Tendai; Broda, Agnieszka; Townsend, Catherine; Sivaramakrishnan, Anand; Green, Nathan; Jit, Mark; Lipman, Marc; Lord, Joanne; White, Peter J; Abubakar, Ibrahim

    2015-01-01

    BACKGROUND Drug-resistant tuberculosis (TB), especially multidrug-resistant (MDR, resistance to rifampicin and isoniazid) disease, is associated with a worse patient outcome. Drug resistance diagnosed using microbiological culture takes days to weeks, as TB bacteria grow slowly. Rapid molecular tests for drug resistance detection (1 day) are commercially available and may promote faster initiation of appropriate treatment. OBJECTIVES To (1) conduct a systematic review of evidence regarding diagnostic accuracy of molecular genetic tests for drug resistance, (2) conduct a health-economic evaluation of screening and diagnostic strategies, including comparison of alternative models of service provision and assessment of the value of targeting rapid testing at high-risk subgroups, and (3) construct a transmission-dynamic mathematical model that translates the estimates of diagnostic accuracy into estimates of clinical impact. REVIEW METHODS AND DATA SOURCES A standardised search strategy identified relevant studies from EMBASE, PubMed, MEDLINE, Bioscience Information Service (BIOSIS), System for Information on Grey Literature in Europe Social Policy & Practice (SIGLE) and Web of Science, published between 1 January 2000 and 15 August 2013. Additional 'grey' sources were included. Quality was assessed using quality assessment of diagnostic accuracy studies version 2 (QUADAS-2). For each diagnostic strategy and population subgroup, a care pathway was constructed to specify which medical treatments and health services that individuals would receive from presentation to the point where they either did or did not complete TB treatment successfully. A total cost was estimated from a health service perspective for each care pathway, and the health impact was estimated in terms of the mean discounted quality-adjusted life-years (QALYs) lost as a result of disease and treatment. Costs and QALYs were both discounted at 3.5% per year. An integrated transmission-dynamic and

  10. Barcoding a quantified food web: crypsis, concepts, ecology and hypotheses.

    Directory of Open Access Journals (Sweden)

    M Alex Smith

    Full Text Available The efficient and effective monitoring of individuals and populations is critically dependent on correct species identification. While this point may seem obvious, identifying the majority of the more than 100 natural enemies involved in the spruce budworm (Choristoneura fumiferana--SBW food web remains a non-trivial endeavor. Insect parasitoids play a major role in the processes governing the population dynamics of SBW throughout eastern North America. However, these species are at the leading edge of the taxonomic impediment and integrating standardized identification capacity into existing field programs would provide clear benefits. We asked to what extent DNA barcoding the SBW food web would alter our understanding of the diversity and connectence of the food web and the frequency of generalists vs. specialists in different forest habitats. We DNA barcoded over 10% of the insects collected from the SBW food web in three New Brunswick forest plots from 1983 to 1993. For 30% of these specimens, we amplified at least one additional nuclear region. When the nodes of the food web were estimated based on barcode divergences (using molecular operational taxonomic units (MOTU or phylogenetic diversity (PD--the food web became much more diverse and connectence was reduced. We tested one measure of food web structure (the "bird feeder effect" and found no difference compared to the morphologically based predictions. Many, but not all, of the presumably polyphagous parasitoids now appear to be morphologically-cryptic host-specialists. To our knowledge, this project is the first to barcode a food web in which interactions have already been well-documented and described in space, time and abundance. It is poised to be a system in which field-based methods permit the identification capacity required by forestry scientists. Food web barcoding provided an effective tool for the accurate identification of all species involved in the cascading effects of

  11. Barcoding a quantified food web: crypsis, concepts, ecology and hypotheses.

    Science.gov (United States)

    Smith, M Alex; Eveleigh, Eldon S; McCann, Kevin S; Merilo, Mark T; McCarthy, Peter C; Van Rooyen, Kathleen I

    2011-01-01

    The efficient and effective monitoring of individuals and populations is critically dependent on correct species identification. While this point may seem obvious, identifying the majority of the more than 100 natural enemies involved in the spruce budworm (Choristoneura fumiferana--SBW) food web remains a non-trivial endeavor. Insect parasitoids play a major role in the processes governing the population dynamics of SBW throughout eastern North America. However, these species are at the leading edge of the taxonomic impediment and integrating standardized identification capacity into existing field programs would provide clear benefits. We asked to what extent DNA barcoding the SBW food web would alter our understanding of the diversity and connectence of the food web and the frequency of generalists vs. specialists in different forest habitats. We DNA barcoded over 10% of the insects collected from the SBW food web in three New Brunswick forest plots from 1983 to 1993. For 30% of these specimens, we amplified at least one additional nuclear region. When the nodes of the food web were estimated based on barcode divergences (using molecular operational taxonomic units (MOTU) or phylogenetic diversity (PD)--the food web became much more diverse and connectence was reduced. We tested one measure of food web structure (the "bird feeder effect") and found no difference compared to the morphologically based predictions. Many, but not all, of the presumably polyphagous parasitoids now appear to be morphologically-cryptic host-specialists. To our knowledge, this project is the first to barcode a food web in which interactions have already been well-documented and described in space, time and abundance. It is poised to be a system in which field-based methods permit the identification capacity required by forestry scientists. Food web barcoding provided an effective tool for the accurate identification of all species involved in the cascading effects of future budworm

  12. Japanese Society of Medical Oncology Clinical Guidelines: Molecular Testing for Colorectal Cancer Treatment, Third Edition.

    Science.gov (United States)

    Yamazaki, Kentaro; Taniguchi, Hiroya; Yoshino, Takayuki; Akagi, Kiwamu; Ishida, Hideyuki; Ebi, Hiromichi; Nakatani, Kaname; Muro, Kei; Yatabe, Yasushi; Yamaguchi, Kensei; Tsuchihara, Katsuya

    2018-06-01

    The Japanese Society of Medical Oncology (JSMO) previously published 2 editions of the clinical guidelines: "Japanese guidelines for testing of KRAS gene mutation in colorectal cancer" in 2008 and "Japanese Society of Medical Oncology Clinical Guidelines: RAS (KRAS/NRAS) mutation testing in colorectal cancer patients" in 2014. These guidelines have contributed to the proper use of KRAS and RAS mutation testing, respectively. Recently, clinical utility, particularly for colorectal cancer (CRC) patients with BRAF V600E mutation or DNA mismatch-repair (MMR) deficiency, has been established. Therefore, the guideline members decided these genetic alterations should also be involved. The aim of this revision is to properly carry out testing for BRAF V600E mutation and MMR deficiency in addition to RAS mutation. The revised guidelines include the basic requirements for testing for these genetic alterations based on recent scientific evidence. Furthermore, because clinical utility of comprehensive genetic testing using next-generation sequencing and somatic gene testing of analyzing circulating tumor DNA has increasingly evolved with recent advancements in testing technology, we noted the current situation and prospects for these testing technologies and their clinical implementation in the revised guidelines. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  13. Method for efficient storage and transportation of sputum specimens for molecular testing of tuberculosis.

    Science.gov (United States)

    Guio, H; Okayama, H; Ashino, Y; Saitoh, H; Xiao, P; Miki, M; Yoshihara, N; Nakanowatari, S; Hattori, T

    2006-08-01

    The polymerase chain reaction (PCR) is a highly sensitive method for the detection of Mycobacterium tuberculosis and is available in most countries, though to a lesser extent in rural areas. To amplify M. tuberculosis DNA sequences of sputum spotted on FTA cards and compare them with the results of microscopic examination among culture-positive samples. A total of 102 sputum specimens of TB patients in treatment were spotted on FTA cards and stored at room temperature until DNA analysis. We assessed the IS6110 region of M. tuberculosis. The efficacy of the PCR assay for the direct detection of M. tuberculosis was evaluated and compared with the results of cultures (Middlebrook 7H9 broth) and smears of fresh sputum specimens. We were able to detect 10 fg/microl of mycobacterial DNA even after 6 months in storage. The PCR sensitivity and specificity using the FTA card system were 82% and 96%, while microscopic examination showed 41% and 95%, respectively. The FTA card system for the storage of bacterial DNA from sputum samples should be considered for the molecular diagnosis of tuberculosis. Samples can easily be obtained from geographically isolated populations and shipped by mail for accurate molecular diagnosis.

  14. Political Participation Online: The Replacement and the Mobilisation Hypotheses Revisited

    DEFF Research Database (Denmark)

    Jensen, Jakob Linaa

    2013-01-01

    This article discusses the state of political participation online more than ten years after the Internet’s great popular breakthrough as an everyday medium. Denmark is used as a case study to critically re-examine the frequently discussed replacement and mobilisation hypotheses on behalf of the ...... participation, efficacy and social capital seem to have less impact on online political participation. In the end, these findings are related to more overall discussions on the democratising potential of the Internet.......This article discusses the state of political participation online more than ten years after the Internet’s great popular breakthrough as an everyday medium. Denmark is used as a case study to critically re-examine the frequently discussed replacement and mobilisation hypotheses on behalf...... of the Internet. The pure replacement hypothesis is rejected. Instead, it is found that the Internet still supplements rather than replaces other media, even among heavy Internet users. The Internet is one among several media used by ‘media omnivores’, and political participation online supplements rather than...

  15. Experienced physicians benefit from analyzing initial diagnostic hypotheses

    Science.gov (United States)

    Bass, Adam; Geddes, Colin; Wright, Bruce; Coderre, Sylvain; Rikers, Remy; McLaughlin, Kevin

    2013-01-01

    Background Most incorrect diagnoses involve at least one cognitive error, of which premature closure is the most prevalent. While metacognitive strategies can mitigate premature closure in inexperienced learners, these are rarely studied in experienced physicians. Our objective here was to evaluate the effect of analytic information processing on diagnostic performance of nephrologists and nephrology residents. Methods We asked nine nephrologists and six nephrology residents at the University of Calgary and Glasgow University to diagnose ten nephrology cases. We provided presenting features along with contextual information, after which we asked for an initial diagnosis. We then primed participants to use either hypothetico-deductive reasoning or scheme-inductive reasoning to analyze the remaining case data and generate a final diagnosis. Results After analyzing initial hypotheses, both nephrologists and residents improved the accuracy of final diagnoses (31.1% vs. 65.6%, p inductive reasoning (odds ratio [95% confidence interval] 5.69 [1.59, 20.33], p = 0.07), whereas the performance of experienced nephrologists did not differ between strategies (odds ratio 0.57 [0.23, 1.39], p = 0.20). Discussion Experienced nephrologists and nephrology residents can improve their performance by analyzing initial diagnostic hypotheses. The explanation of the interaction between experience and the effect of different reasoning strategies is unclear, but may relate to preferences in reasoning strategy, or the changes in knowledge structure with experience. PMID:26451203

  16. Real-world utilization of molecular diagnostic testing and matched drug therapies in the treatment of metastatic cancers.

    Science.gov (United States)

    Chawla, Anita; Peeples, Miranda; Li, Nanxin; Anhorn, Rachel; Ryan, Jason; Signorovitch, James

    2018-06-01

    To assess the frequency of biopsies and molecular diagnostic testing (human DNA/RNA analysis), anti-cancer drug use (genomically-matched targeted therapy [GMTT], unmatched targeted therapy [UTT], endocrine therapy [ET], and chemotherapy [CT]), and medical service costs among adults with metastatic cancer. Adults diagnosed with metastatic breast, non-small cell lung (NSCLC), colorectal, head and neck, ovarian, and uterine cancer (2010Q1-2015Q1) were identified in the OptumHealth Care Solutions claims database and followed from first metastatic diagnosis for ≥1 month and until the end of data availability. Utilization was assessed for each cancer cohort (all and patients aged ≥65 years); per-patient-per-month (PPPM) medical service costs were assessed for all patients. Testing frequency estimates were applied to Surveillance, Epidemiology, and End Results Program data to estimate the number of untested patients (2010-2014). Patients with metastatic cancer (n = 8,193; breast [n = 3,414], NSCLC [n = 2,231], colorectal [n = 1,611], head and neck [n = 511], ovarian [n = 275], and uterine [n = 151]) were 63 years old (mean), with 11.1-22.2 months of observation. Biopsy and molecular diagnostic testing frequencies ranged from 7% (uterine) to 73% (ovarian), and from 34% (head and neck) to 52% (breast), respectively. Few were treated with GMTT (breast, 11%; NSCLC, 9%; colorectal, 6%). Treatment with UTT ranged from 0.7% (uterine) to 21% (colorectal). Biopsy, diagnostic testing, and anti-cancer drug therapy were less frequent for those ≥65 years. Medical service costs (PPPM, mean) ranged from $6,618 (head and neck) to $9,940 (ovarian). The estimated number of untested new patients with metastatic cancer was 636,369 (all) and 341,397 (≥65). In addition to the limitations of claims analyses, diagnostic testing frequency may be under-estimated if patients underwent testing prior to study inclusion. The low frequency of molecular diagnostic

  17. Economic and evolutionary hypotheses for cross-population variation in parochialism.

    Science.gov (United States)

    Hruschka, Daniel J; Henrich, Joseph

    2013-09-11

    Human populations differ reliably in the degree to which people favor family, friends, and community members over strangers and outsiders. In the last decade, researchers have begun to propose several economic and evolutionary hypotheses for these cross-population differences in parochialism. In this paper, we outline major current theories and review recent attempts to test them. We also discuss the key methodological challenges in assessing these diverse economic and evolutionary theories for cross-population differences in parochialism.

  18. Economic and evolutionary hypotheses for cross-population variation in parochialism

    Directory of Open Access Journals (Sweden)

    Daniel Jacob Hruschka

    2013-09-01

    Full Text Available Human populations differ reliably in the degree to which people favor family, friends and community members over strangers and outsiders. In the last decade, researchers have begun to propose several economic and evolutionary hypotheses for these cross-population differences in parochialism. In this paper, we outline major current theories and review recent attempts to test them. We also discuss the key methodological challenges in assessing these diverse economic and evolutionary theories for cross-population differences in parochialism.

  19. Economic and evolutionary hypotheses for cross-population variation in parochialism

    OpenAIRE

    Daniel Jacob Hruschka; Joseph eHenrich

    2013-01-01

    Human populations differ reliably in the degree to which people favor family, friends and community members over strangers and outsiders. In the last decade, researchers have begun to propose several economic and evolutionary hypotheses for these cross-population differences in parochialism. In this paper, we outline major current theories and review recent attempts to test them. We also discuss the key methodological challenges in assessing these diverse economic and evolutionary theories...

  20. CT-guided transthoracic core needle biopsy for small pulmonary lesions: diagnostic performance and adequacy for molecular testing.

    Science.gov (United States)

    Tian, Panwen; Wang, Ye; Li, Lei; Zhou, Yongzhao; Luo, Wenxin; Li, Weimin

    2017-02-01

    Computed tomography (CT)-guided transthoracic needle biopsy is a well-established, minimally invasive diagnostic tool for pulmonary lesions. Few large studies have been conducted on the diagnostic performance and adequacy for molecular testing of transthoracic core needle biopsy (TCNB) for small pulmonary lesions. This study included CT-guided TCNB with 18-gauge cutting needles in 560 consecutive patients with small (≤3 cm) pulmonary lesions from January 2012 to January 2015. There were 323 males and 237 females, aged 51.8±12.7 years. The size of the pulmonary lesions was 1.8±0.6 cm. The sensitivity, specificity, accuracy and complications of the biopsies were investigated. The risk factors of diagnostic failure were assessed using univariate and multivariate analyses. The sample's adequacy for molecular testing of non-small cell lung cancer (NSCLC) was analyzed. The overall sensitivity, specificity, and accuracy for diagnosis of malignancy were 92.0% (311/338), 98.6% (219/222), and 94.6% (530/560), respectively. The incidence of bleeding complications was 22.9% (128/560), and the incidence of pneumothorax was 10.4% (58/560). Logistic multivariate regression analysis showed that the independent risk factors for diagnostic failure were a lesion size ≤1 cm [odds ratio (OR), 3.95; P=0.007], lower lobe lesions (OR, 2.83; P=0.001), and pneumothorax (OR, 1.98; P=0.004). Genetic analysis was successfully performed on 95.45% (168/176) of specimens diagnosed as NSCLC. At least 96.8% of samples with two or more passes from a lesion were sufficient for molecular testing. The diagnostic yield of small pulmonary lesions by CT-guided TCNB is high, and the procedure is relatively safe. A lesion size ≤1 cm, lower lobe lesions, and pneumothorax are independent risk factors for biopsy diagnostic failure. TCNB specimens could provide adequate tissues for molecular testing.

  1. Molecular testing for clinical diagnosis and epidemiological investigations of intestinal parasitic infections.

    Science.gov (United States)

    Verweij, Jaco J; Stensvold, C Rune

    2014-04-01

    Over the past few decades, nucleic acid-based methods have been developed for the diagnosis of intestinal parasitic infections. Advantages of nucleic acid-based methods are numerous; typically, these include increased sensitivity and specificity and simpler standardization of diagnostic procedures. DNA samples can also be stored and used for genetic characterization and molecular typing, providing a valuable tool for surveys and surveillance studies. A variety of technologies have been applied, and some specific and general pitfalls and limitations have been identified. This review provides an overview of the multitude of methods that have been reported for the detection of intestinal parasites and offers some guidance in applying these methods in the clinical laboratory and in epidemiological studies.

  2. Current hypotheses and research milestones in Alzheimer's disease

    National Research Council Canada - National Science Library

    Maccioni, Ricardo B; Perry, George

    2009-01-01

    .... This book contains 20 seminal chapters by authors with different views that in a multidisciplinary approach focus on the main issues of neuroanatomical, neuropathological, neuropsychological, neurological, and molecular biological aspects of AD. The idea for this collection arose during the preparation of the proceedings for the International Summit Meeting...

  3. Development of a blood-based molecular biomarker test for identification of schizophrenia before disease onset

    NARCIS (Netherlands)

    M.K. Chan (Man K.); M.-O. Krebs (M-O); D. Cox; P.C. Guest (Paul); R.H. Yolken; H. Rahmoune (Hassan); M. Rothermundt (Matthias); J. Steiner (Johann); F.M. Leweke (Marcus); N.J.M. van Beveren (Nico); D. Niebuhr (David); N. Weber (Natalya); D. Cowan (David); P. Suarez-Pinilla; B. Crespo-Facorro (Benedicto); C. Mam-Lam-Fook; J. Bourgin; R.J. Wenstrup (Richard); R.R. Kaldate; J.D. Cooper (Jason); S. Bahn (Sabine)

    2015-01-01

    markdownabstractRecent research efforts have progressively shifted towards preventative psychiatry and prognostic identification of individuals before disease onset. We describe the development of a serum biomarker test for the identification of individuals at risk of developing schizophrenia based

  4. A novel automatic molecular test for detection of multidrug resistance tuberculosis in sputum specimen: A case control study.

    Science.gov (United States)

    Li, Qiang; Ou, Xi C; Pang, Yu; Xia, Hui; Huang, Hai R; Zhao, Bing; Wang, Sheng F; Zhao, Yan L

    2017-07-01

    MiniLab tuberculosis (ML TB) assay is a new automatic diagnostic tool for diagnosis of multidrug resistance tuberculosis (MDR-TB). This study was conducted with aims to know the performance of this assay. Sputum sample from 224 TB suspects was collected from tuberculosis suspects seeking medical care at Beijing Chest hospital. The sputum samples were directly used for smear and ML TB test. The left sputum sample was used to conduct Xpert MTB/RIF, Bactec MGIT culture and drug susceptibility test (DST). All discrepancies between the results from DST, molecular and phenotypic methods were confirmed by DNA Sequencing. The sensitivity and specificity of ML TB test for detecting MTBC from TB suspects were 95.1% and 88.9%, respectively. The sensitivity for smear negative TB suspects was 64.3%. For detection of RIF resistance, the sensitivity and specificity of ML TB test were 89.2% and 95.7%, respectively. For detection of INH resistance, the sensitivity and specificity of ML TB test were 78.3% and 98.1%, respectively. ML TB test showed similar performance to Xpert MTB/RIF for detection of MTBC and RIF resistance. In addition, ML TB also had good performance for INH resistance detection. Copyright © 2017. Published by Elsevier Ltd.

  5. About hypotheses and paradigms: exploring the Discreetness-Chance Paradigm.

    Science.gov (United States)

    Kaellis, Eugene

    2006-01-01

    Hypotheses generally conform to paradigms which, over time, change, usually tardily, after they have become increasingly difficult to sustain under the impact of non-conforming evidence and alternative hypotheses, but more important, when they no longer are comfortably ensconced in the surrounding social-economic-political-cultural milieu. It is asserted that this milieu is the most important factor in shaping scientific theorizing. Some examples are cited: the rejection of the evidence that the world orbits around the sun (suspected by Pythagoras) in favor of centuries-long firm adherence to the Ptolemaic geocentric system; the early acceptance of Natural Selection in spite of its tautological essence and only conjectural supporting evidence, because it justified contemporaneous social-political ideologies as typified by, e.g., Spencer and Malthus. Economic, social, and cultural factors are cited as providing the ground, i.e., ideational substrate, for what is cited as the Discreetness-Chance Paradigm (DCP), that has increasingly dominated physics, biology, and medicine for over a century and which invokes small, discrete packets of energy/matter (quanta, genes, microorganisms, aberrant cells) functioning within an environment of statistical, not determined, causality. There is speculation on a possible paradigmatic shift from the DCP, which has fostered the proliferation, parallel with ("splitting") taxonomy, of alleged individual disease entities, their diagnoses, and, when available, their specific remedies, something particularly prominent in, e.g., psychiatry's Diagnostic and Statistical Manual, a codified compendium of alleged mental and behavioral disorders, but evident in any textbook of diagnosis and treatment of physical ailments. This presumed paradigm shift may be reflected in Western medicine, presently increasingly empirical and atomized, towards a growing acceptance of a more generalized, subject-oriented, approach to health and disease, a non

  6. Experienced physicians benefit from analyzing initial diagnostic hypotheses

    Directory of Open Access Journals (Sweden)

    Adam Bass

    2013-03-01

    Full Text Available Background: Most incorrect diagnoses involve at least one cognitive error, of which premature closure is the most prevalent. While metacognitive strategies can mitigate premature closure in inexperienced learners, these are rarely studied in experienced physicians. Our objective here was to evaluate the effect of analytic information processing on diagnostic performance of nephrologists and nephrology residents. Methods: We asked nine nephrologists and six nephrology residents at the University of Calgary and Glasgow University to diagnose ten nephrology cases. We provided presenting features along with contextual information, after which we asked for an initial diagnosis. We then primed participants to use either hypothetico-deductive reasoning or scheme-inductive reasoning to analyze the remaining case data and generate a final diagnosis. Results: After analyzing initial hypotheses, both nephrologists and residents improved the accuracy of final diagnoses (31.1% vs. 65.6%, p < 0.001, and 40.0% vs. 70.0%, p < 0.001, respectively. We found a significant interaction between experience and analytic processing strategy (p = 0.002: nephrology residents had significantly increased odds of diagnostic success when using scheme-inductive reasoning (odds ratio [95% confidence interval] 5.69 [1.59, 20.33], p = 0.007, whereas the performance of experienced nephrologists did not differ between strategies (odds ratio 0.57 [0.23, 1.39], p = 0.2. Discussion: Experienced nephrologists and nephrology residents can improve their performance by analyzing initial diagnostic hypotheses. The explanation of the interaction between experience and the effect of different reasoning strategies is unclear, but may relate to preferences in reasoning strategy, or the changes in knowledge structure with experience.

  7. Global mtDNA genetic structure and hypothesized invasion history of a major pest of citrus, Diaphorina citri (Hemiptera: Liviidae).

    Science.gov (United States)

    Luo, Yufa; Agnarsson, Ingi

    2018-01-01

    The Asian citrus psyllid Diaphorina citri Kuwayama is a key pest of citrus as the vector of the bacterium causing the "huanglongbing" disease (HLB). To assess the global mtDNA population genetic structure, and possible dispersal history of the pest, we investigated genetic variation at the COI gene collating newly collected samples with all previously published data. Our dataset consists of 356 colonies from 106 geographic sites worldwide. High haplotype diversity (H-mean = 0.702 ± 0.017), low nucleotide diversity (π-mean = 0.003), and significant positive selection (Ka/Ks = 32.92) were observed. Forty-four haplotypes (Hap) were identified, clustered into two matrilines: Both occur in southeastern and southern Asia, North and South America, and Africa; lineages A and B also occur in eastern and western Asia, respectively. The most abundant haplotypes were Hap4 in lineage A (35.67%), and Hap9 in lineage B (41.29%). The haplotype network identified them as the ancestral haplotypes within their respective lineages. Analysis of molecular variance showed significant genetic structure ( F ST  = 0.62, p  analysis suggests geographic structuring. We hypothesize a southern and/or southeastern Asia origin, three dispersal routes, and parallel expansions of two lineages. The hypothesized first route involved the expansion of lineage B from southern Asia into North America via West Asia. The second, the expansion of some lineage A individuals from Southeast Asia into East Asia, and the third involved both lineages from Southeast Asia spreading westward into Africa and subsequently into South America. To test these hypotheses and gain a deeper understanding of the global history of D. citri , more data-rich approaches will be necessary from the ample toolkit of next-generation sequencing (NGS). However, this study may serve to guide such sampling and in the development of biological control programs against the global pest D. citri .

  8. Molecular and Culture-Based Bronchoalveolar Lavage Fluid Testing for the Diagnosis of Cytomegalovirus Pneumonitis.

    Science.gov (United States)

    Tan, Susanna K; Burgener, Elizabeth B; Waggoner, Jesse J; Gajurel, Kiran; Gonzalez, Sarah; Chen, Sharon F; Pinsky, Benjamin A

    2016-01-01

    Background.  Cytomegalovirus (CMV) is a major cause of morbidity and mortality in immunocompromised patients, with CMV pneumonitis among the most severe manifestations of infection. Although bronchoalveolar lavage (BAL) samples are frequently tested for CMV, the clinical utility of such testing remains uncertain. Methods.  Retrospective analysis of adult patients undergoing BAL testing via CMV polymerase chain reaction (PCR), shell vial culture, and conventional viral culture between August 2008 and May 2011 was performed. Cytomegalovirus diagnostic methods were compared with a comprehensive definition of CMV pneumonitis that takes into account signs and symptoms, underlying host immunodeficiency, radiographic findings, and laboratory results. Results.  Seven hundred five patients underwent 1077 bronchoscopy episodes with 1090 BAL specimens sent for CMV testing. Cytomegalovirus-positive patients were more likely to be hematopoietic cell transplant recipients (26% vs 8%, P definition, the sensitivity and specificity of PCR, shell vial culture, and conventional culture were 91.3% and 94.6%, 54.4% and 97.4%, and 28.3% and 96.5%, respectively. Compared with culture, PCR provided significantly higher sensitivity and negative predictive value (P ≤ .001), without significantly lower positive predictive value. Cytomegalovirus quantitation did not improve test performance, resulting in a receiver operating characteristic curve with an area under the curve of 0.53. Conclusions.  Cytomegalovirus PCR combined with a comprehensive clinical definition provides a pragmatic approach for the diagnosis of CMV pneumonitis.

  9. Molecular tools for diagnosis of visceral leishmaniasis: systematic review and meta-analysis of diagnostic test accuracy.

    Science.gov (United States)

    de Ruiter, C M; van der Veer, C; Leeflang, M M G; Deborggraeve, S; Lucas, C; Adams, E R

    2014-09-01

    Molecular methods have been proposed as highly sensitive tools for the detection of Leishmania parasites in visceral leishmaniasis (VL) patients. Here, we evaluate the diagnostic accuracy of these tools in a meta-analysis of the published literature. The selection criteria were original studies that evaluate the sensitivities and specificities of molecular tests for diagnosis of VL, adequate classification of study participants, and the absolute numbers of true positives and negatives derivable from the data presented. Forty studies met the selection criteria, including PCR, real-time PCR, nucleic acid sequence-based amplification (NASBA), and loop-mediated isothermal amplification (LAMP). The sensitivities of the individual studies ranged from 29 to 100%, and the specificities ranged from 25 to 100%. The pooled sensitivity of PCR in whole blood was 93.1% (95% confidence interval [CI], 90.0 to 95.2), and the specificity was 95.6% (95% CI, 87.0 to 98.6). The specificity was significantly lower in consecutive studies, at 63.3% (95% CI, 53.9 to 71.8), due either to true-positive patients not being identified by parasitological methods or to the number of asymptomatic carriers in areas of endemicity. PCR for patients with HIV-VL coinfection showed high diagnostic accuracy in buffy coat and bone marrow, ranging from 93.1 to 96.9%. Molecular tools are highly sensitive assays for Leishmania detection and may contribute as an additional test in the algorithm, together with a clear clinical case definition. We observed wide variety in reference standards and study designs and now recommend consecutively designed studies. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  10. Molecular Tools for Diagnosis of Visceral Leishmaniasis: Systematic Review and Meta-Analysis of Diagnostic Test Accuracy

    Science.gov (United States)

    de Ruiter, C. M.; van der Veer, C.; Leeflang, M. M. G.; Deborggraeve, S.; Lucas, C.

    2014-01-01

    Molecular methods have been proposed as highly sensitive tools for the detection of Leishmania parasites in visceral leishmaniasis (VL) patients. Here, we evaluate the diagnostic accuracy of these tools in a meta-analysis of the published literature. The selection criteria were original studies that evaluate the sensitivities and specificities of molecular tests for diagnosis of VL, adequate classification of study participants, and the absolute numbers of true positives and negatives derivable from the data presented. Forty studies met the selection criteria, including PCR, real-time PCR, nucleic acid sequence-based amplification (NASBA), and loop-mediated isothermal amplification (LAMP). The sensitivities of the individual studies ranged from 29 to 100%, and the specificities ranged from 25 to 100%. The pooled sensitivity of PCR in whole blood was 93.1% (95% confidence interval [CI], 90.0 to 95.2), and the specificity was 95.6% (95% CI, 87.0 to 98.6). The specificity was significantly lower in consecutive studies, at 63.3% (95% CI, 53.9 to 71.8), due either to true-positive patients not being identified by parasitological methods or to the number of asymptomatic carriers in areas of endemicity. PCR for patients with HIV-VL coinfection showed high diagnostic accuracy in buffy coat and bone marrow, ranging from 93.1 to 96.9%. Molecular tools are highly sensitive assays for Leishmania detection and may contribute as an additional test in the algorithm, together with a clear clinical case definition. We observed wide variety in reference standards and study designs and now recommend consecutively designed studies. PMID:24829226

  11. Integrated Testing of a 4-Bed Molecular Sieve, Air-Cooled Temperature Swing Adsorption Compressor, and Sabatier Engineering Development Unit

    Science.gov (United States)

    Knox, James C.; Miller, Lee; Campbell, Melissa; Mulloth, Lila; Varghese, Mini

    2006-01-01

    Accumulation and subsequent compression of carbon dioxide that is removed from the space cabin are two important processes involved in a closed-loop air revitalization scheme of the International Space Station (ISS). The 4-Bed Molecular Sieve (4BMS) of ISS currently operates in an open loop mode without a compressor. The Sabatier Engineering Development Unit (EDU) processes waste CO2 to provide water to the crew. This paper reports the integrated 4BMS, air-cooled Temperature Swing Adsorption Compressor (TSAC), and Sabatier EDU testing. The TSAC prototype was developed at NASA Ames Research Center (ARC). The 4BMS was modified to a functionally flight-like condition at NASA Marshall Space Flight Center (MSFC). Testing was conducted at MSFC. The paper provides details of the TSAC operation at various CO2 loadings and corresponding performance of the 4BMS and Sabatier.

  12. A molecular phylogeny of the Cephinae (Hymenoptera, Cephidae based on mtDNA COI gene: a test of traditional classification

    Directory of Open Access Journals (Sweden)

    Mahir Budak

    2011-09-01

    Full Text Available Cephinae is traditionally divided into three tribes and about 24 genera based on morphology and host utilization. There has been no study testing the monophyly of taxa under a strict phylogenetic criterion. A molecular phylogeny of Cephinae based on a total of 68 sequences of mtDNA COI gene, representing seven genera of Cephinae, is reconstructed to test the traditional limits and relationships of taxa. Monophyly of the traditional tribes is not supported. Monophyly of the genera are largely supported except for Pachycephus. A few host shift events are suggested based on phylogenetic relationships among taxa. These results indicate that a more robust phylogeny is required for a more plausible conclusion. We also report two species of Cephus for the first time from Turkey.

  13. Development of molecular tests for the detection of ILAR and latent viruses in fruit trees.

    Science.gov (United States)

    Roussel, S; Kummert, J; Dutrecq, O; Lepoivre, P; Jijakli, M H

    2004-01-01

    The detection throughout the year of latent and ILAR viruses in fruit tress by classical serological tests appear to be unreliable. We have developed RT-PCR tests for a reliable detection of latent and ILAR viruses in fruit trees. These assays were then simplified to allow the direct use of crude plant extracts instead of total RNA preparations, and the analyses of pooled samples. In this way, such RT-PCR protocols are suitable for a routine diagnosis of latent and ILAR viruses in fruit tree certification.

  14. BIOMEX Experiment: Ultrastructural Alterations, Molecular Damage and Survival of the Fungus Cryomyces antarcticus after the Experiment Verification Tests

    Science.gov (United States)

    Pacelli, Claudia; Selbmann, Laura; Zucconi, Laura; De Vera, Jean-Pierre; Rabbow, Elke; Horneck, Gerda; de la Torre, Rosa; Onofri, Silvano

    2017-06-01

    The search for traces of extinct or extant life in extraterrestrial environments is one of the main goals for astrobiologists; due to their ability to withstand stress producing conditions, extremophiles are perfect candidates for astrobiological studies. The BIOMEX project aims to test the ability of biomolecules and cell components to preserve their stability under space and Mars-like conditions, while at the same time investigating the survival capability of microorganisms. The experiment has been launched into space and is being exposed on the EXPOSE-R2 payload, outside of the International Space Station (ISS) over a time-span of 1.5 years. Along with a number of other extremophilic microorganisms, the Antarctic cryptoendolithic black fungus Cryomyces antarcticus CCFEE 515 has been included in the experiment. Before launch, dried colonies grown on Lunar and Martian regolith analogues were exposed to vacuum, irradiation and temperature cycles in ground based experiments (EVT1 and EVT2). Cultural and molecular tests revealed that the fungus survived on rock analogues under space and simulated Martian conditions, showing only slight ultra-structural and molecular damage.

  15. In vitro evaluation of microbial contamination of orthodontic brackets as received from the manufacturer using microbiological and molecular tests.

    Science.gov (United States)

    Dos Santos Gerzson, Darlene R; Simon, Daniel; Dos Anjos, Aline Lima; Freitas, Maria Perpétua Mota

    2015-11-01

    To test the null hypothesis that orthodontic brackets as supplied by manufacturers do not have microbial contamination. The sample comprised 140 brackets of four different commercially available brands, used directly from the manufacturer's packaging, divided into 14 groups (n  =  10 brackets each). Of the 140 pieces, 60 were full cases and 80 were replacement brackets. Materials were tested to detect bacterial growth, analyze types of bacteria present (biochemical test), and identify bacteria (molecular test with polymerase chain reaction [PCR]). In two of 12 groups the brackets showed microbial contamination: group 1, Morelli full case brackets, and group 12, Abzil-3M Unitek replacement brackets. Staphylococcus aureus and Staphylococcus epidermidis were the bacteria identified in groups 1 and 12, respectively (suggested by the biochemical test and confirmed by PCR). Brackets of two brands (Morelli and Abzil-3M Unitek) were found to be contaminated by bacteria in the original packages supplied by the manufacturers, which suggests a risk for patient contamination. These data suggest that the manufacturers of these materials should improve the quality control of the packaging used, including sterilization, for the security of patient health.

  16. Evaluation of a New Test, GenoType HelicoDR, for Molecular Detection of Antibiotic Resistance in Helicobacter pylori▿

    Science.gov (United States)

    Cambau, Emmanuelle; Allerheiligen, Vera; Coulon, Céline; Corbel, Céline; Lascols, Christine; Deforges, Lionel; Soussy, Claude-James; Delchier, Jean-Charles; Megraud, Francis

    2009-01-01

    The eradication rate of Helicobacter pylori by standard therapy is decreasing due to antibiotic resistance, mainly to clarithromycin. Our aim was to provide a new molecular test to guide the treatment of new and relapsed cases. We first studied 126 H. pylori strains for phenotypic (MIC) and genotypic resistance to clarithromycin (rrl mutation) and levofloxacin (gyrA mutation) and then developed a DNA strip genotyping test on the basis of the correlation results and literature data. Clinical strains (n = 92) and gastric biopsy specimens containing H. pylori (n = 105) were tested blindly with the new molecular test GenoType HelicoDR. The presence of mutations or the absence of hybridization with wild-type sequences was predictive, in rrl for clarithromycin resistance in 91 cases (mostly the A2147G mutation) and in gyrA for levofloxacin resistance in 58 cases (mutations at codon 87 or 91). Genotyping revealed a mix of genotypes in 33% of the cases, reflecting a coinfection or selection for resistant mutants. The sensitivity and specificity of detecting resistance were 94% and 99% for clarithromycin and 87% and 98.5% for levofloxacin, respectively. The concordance scores were 0.96 for clarithromycin and 0.94 for levofloxacin. With global resistance rates of 46% for clarithromycin and 25% for levofloxacin, which were observed for consecutive positive biopsy specimens from 2007 and 2008, the positive and negative predictive values for detecting resistance were 99% and 94% for clarithromycin and 96% and 96% for fluoroquinolone. GenoType HelicoDR is efficient at detecting mutations predictive of antibiotic resistance in H. pylori when applied to strains or directly to gastric biopsy specimens. PMID:19759218

  17. Evaluation of a new test, genotype HelicoDR, for molecular detection of antibiotic resistance in Helicobacter pylori.

    Science.gov (United States)

    Cambau, Emmanuelle; Allerheiligen, Vera; Coulon, Céline; Corbel, Céline; Lascols, Christine; Deforges, Lionel; Soussy, Claude-James; Delchier, Jean-Charles; Megraud, Francis

    2009-11-01

    The eradication rate of Helicobacter pylori by standard therapy is decreasing due to antibiotic resistance, mainly to clarithromycin. Our aim was to provide a new molecular test to guide the treatment of new and relapsed cases. We first studied 126 H. pylori strains for phenotypic (MIC) and genotypic resistance to clarithromycin (rrl mutation) and levofloxacin (gyrA mutation) and then developed a DNA strip genotyping test on the basis of the correlation results and literature data. Clinical strains (n = 92) and gastric biopsy specimens containing H. pylori (n = 105) were tested blindly with the new molecular test GenoType HelicoDR. The presence of mutations or the absence of hybridization with wild-type sequences was predictive, in rrl for clarithromycin resistance in 91 cases (mostly the A2147G mutation) and in gyrA for levofloxacin resistance in 58 cases (mutations at codon 87 or 91). Genotyping revealed a mix of genotypes in 33% of the cases, reflecting a coinfection or selection for resistant mutants. The sensitivity and specificity of detecting resistance were 94% and 99% for clarithromycin and 87% and 98.5% for levofloxacin, respectively. The concordance scores were 0.96 for clarithromycin and 0.94 for levofloxacin. With global resistance rates of 46% for clarithromycin and 25% for levofloxacin, which were observed for consecutive positive biopsy specimens from 2007 and 2008, the positive and negative predictive values for detecting resistance were 99% and 94% for clarithromycin and 96% and 96% for fluoroquinolone. GenoType HelicoDR is efficient at detecting mutations predictive of antibiotic resistance in H. pylori when applied to strains or directly to gastric biopsy specimens.

  18. Testing the new animal phylogeny: a phylum level molecular analysis of the animal kingdom.

    Science.gov (United States)

    Bourlat, Sarah J; Nielsen, Claus; Economou, Andrew D; Telford, Maximilian J

    2008-10-01

    The new animal phylogeny inferred from ribosomal genes some years ago has prompted a number of radical rearrangements of the traditional, morphology based metazoan tree. The two main bilaterian clades, Deuterostomia and Protostomia, find strong support, but the protostomes consist of two sister groups, Ecdysozoa and Lophotrochozoa, not seen in morphology based trees. Although widely accepted, not all recent molecular phylogenetic analyses have supported the tripartite structure of the new animal phylogeny. Furthermore, even if the small ribosomal subunit (SSU) based phylogeny is correct, there is a frustrating lack of resolution of relationships between the phyla that make up the three clades of this tree. To address this issue, we have assembled a dataset including a large number of aligned sequence positions as well as a broad sampling of metazoan phyla. Our dataset consists of sequence data from ribosomal and mitochondrial genes combined with new data from protein coding genes (5139 amino acid and 3524 nucleotide positions in total) from 37 representative taxa sampled across the Metazoa. Our data show strong support for the basic structure of the new animal phylogeny as well as for the Mandibulata including Myriapoda. We also provide some resolution within the Lophotrochozoa, where we confirm support for a monophyletic clade of Echiura, Sipuncula and Annelida and surprising evidence of a close relationship between Brachiopoda and Nemertea.

  19. Testing thermal gradient driving force for grain boundary migration using molecular dynamics simulations

    International Nuclear Information System (INIS)

    Bai, Xian-Ming; Zhang, Yongfeng; Tonks, Michael R.

    2015-01-01

    Strong thermal gradients in low-thermal-conductivity ceramics may drive extended defects, such as grain boundaries and voids, to migrate in preferential directions. In this work, molecular dynamics simulations are conducted to study thermal gradient driven grain boundary migration and to verify a previously proposed thermal gradient driving force equation, using uranium dioxide as a model system. It is found that a thermal gradient drives grain boundaries to migrate up the gradient and the migration velocity increases under a constant gradient owing to the increase in mobility with temperature. Different grain boundaries migrate at very different rates due to their different intrinsic mobilities. The extracted mobilities from the thermal gradient driven simulations are compared with those calculated from two other well-established methods and good agreement between the three different methods is found, demonstrating that the theoretical equation of the thermal gradient driving force is valid, although a correction of one input parameter should be made. The discrepancy in the grain boundary mobilities between modeling and experiments is also discussed.

  20. Comparative evaluation of molecular diagnostic tests for Nucleospora salmonis and prevalence in migrating juvenile salmonids from the Snake River, USA

    Science.gov (United States)

    Badil, Samantha; Elliott, Diane G.; Kurobe, Tomofumi; Hedrick, Ronald P.; Clemens, Kathy; Blair, Marilyn; Purcell, Maureen K.

    2011-01-01

    Nucleospora salmonis is an intranuclear microsporidian that primarily infects lymphoblast cells and contributes to chronic lymphoblastosis and a leukemia-like condition in a range of salmonid species. The primary goal of this study was to evaluate the prevalence of N. salmonis in out-migrating juvenile hatchery and wild Chinook salmon Oncorhynchus tshawytscha and steelhead O. mykiss from the Snake River in the U.S. Pacific Northwest. To achieve this goal, we first addressed the following concerns about current molecular diagnostic tests for N. salmonis: (1) nonspecific amplification patterns by the published nested polymerase chain reaction (nPCR) test, (2) incomplete validation of the published quantitative PCR (qPCR) test, and (3) whether N. salmonis can be detected reliably from nonlethal samples. Here, we present an optimized nPCR protocol that eliminates nonspecific amplification. During validation of the published qPCR test, our laboratory developed a second qPCR test that targeted a different gene sequence and used different probe chemistry for comparison purposes. We simultaneously evaluated the two different qPCR tests for N. salmonis and found that both assays were highly specific, sensitive, and repeatable. The nPCR and qPCR tests had good overall concordance when DNA samples derived from both apparently healthy and clinically diseased hatchery rainbow trout were tested. Finally, we demonstrated that gill snips were a suitable tissue for nonlethal detection of N. salmonis DNA in juvenile salmonids. Monitoring of juvenile salmonid fish in the Snake River over a 3-year period revealed low prevalence of N. salmonis in hatchery and wild Chinook salmon and wild steelhead but significantly higher prevalence in hatchery-derived steelhead. Routine monitoring of N. salmonis is not performed for all hatchery steelhead populations. At present, the possible contribution of this pathogen to delayed mortality of steelhead has not been determined.

  1. Use of FTA gene guard filter paper for the storage and transportation of tumor cells for molecular testing.

    Science.gov (United States)

    Dobbs, Larry J; Madigan, Merle N; Carter, Alexis B; Earls, Lori

    2002-01-01

    Efficient methods of storing tumor specimens for molecular testing are needed in the modern surgical pathology laboratory. The FTA Gene Guard system is a novel method for the collection and room temperature storage of blood samples for DNA testing. The method uses index card-sized filter papers that provide an ideal medium on which to store tumor specimens for DNA testing. To determine whether FTA filter paper can be used in the surgical pathology laboratory to store tumor cells for DNA testing. Cell suspensions were prepared from 60 surgical specimens, and DNA was extracted either immediately or after storage on FTA paper. The DNA extracted by each method was tested by polymerase chain reaction (PCR) for the beta-globin and interferon gamma genes, and the results were compared. Fifteen lymph node specimens stored on FTA paper were then tested for immunoglobulin heavy chain (IgH) gene rearrangement by PCR, and these results were compared with those obtained for immediately extracted DNA. University medical center. The DNA extracted from cells stored on FTA paper performed as well in the PCR as the freshly extracted DNA in nearly all cases (>95%). The results of tests for IgH gene rearrangements showed 100% concordance between the 2 methods of DNA extraction.Conclusion.-Cells from surgical specimens can be stored on FTA paper for extended lengths of time, and DNA can be extracted from these cells for PCR-based testing. FTA filter paper is a reliable medium for the storage and/or transport of tumor cells for PCR-based DNA analysis.

  2. A decade of molecular genetic testing for MODY: a retrospective study of utilization in The Netherlands

    NARCIS (Netherlands)

    Weinreich, S.S.; Bosma, A.R.; Henneman, L.; Rigter, T.; Spruijt, C.M.J.; Grimbergen, A.J.E.M.; Breuning, M.H.; de Koning, E.J.P.; Losekoot, M.; Cornel, M.C.

    2015-01-01

    Genetic testing for maturity-onset diabetes of the young (MODY) may be relevant for treatment and prognosis in patients with usually early-onset, non-ketotic, insulin-sensitive diabetes and for monitoring strategies in non-diabetic mutation carriers. This study describes the first 10 years of

  3. Evaluation of Extremal Hypotheses as a Criterion to Resolve Channel Indeterminacy

    Science.gov (United States)

    Tranmer, A.

    2012-12-01

    Design criteria for river restoration and sustainable development have significantly advanced in recent decades, yet complete deterministic formulations to address channel form and sinuosity still prove elusive. Many hypotheses have been presented to ascertain the dynamic-equilibrium of a stream at both the cross sectional and reach level. These efforts to better understand the functioning of alluvial systems include regime theory, stability theory, perturbation analysis, threshold theory, reference reach comparison, downstream hydraulic geometry, and extremal hypotheses. The latter of these theories, the extremal hypothesis, is based on optimizing one variable or criterion in the alluvial system in order to find closure to the channel design problem. Currently, there is no method to directly compare the various hypotheses at the system scale, understanding of their sensitivity to the various formulae employed or consensus regarding which hypothesis is most appropriate. This study analyzed the various extremal hypotheses in as close to a pristine environment as exists (a remote part of Patagonia, Chile), in order to assess which hypothesis (or collective hypotheses) is most appropriate for channel design. Extremal hypotheses were applied in the longitudinal direction, under the assumption of a space-for-time substitution, to evaluate the geomorphic trends of a river evolving during deglaciation. The space-for-time model assumes the watershed reaches stable, dynamic-equilibrium in its lower meandering reaches and the point of equilibrium extends upstream through its braiding reaches as the watershed adapts to new climatic and environmental conditions. Extremal hypotheses applied in a downstream fashion are then expected to predict chaotic and oversized channel characteristics in the upstream reaches and trend towards a point of equilibrium (minimum/maximum of tested hypothesis). Initial findings indicate that many hypotheses predict similar geometry and sinuosity

  4. Molecular diagnostic testing for Klinefelter syndrome and other male sex chromosome aneuploidies

    Directory of Open Access Journals (Sweden)

    Hager Karl

    2012-04-01

    Full Text Available Abstract Background Male sex chromosome aneuploidies are underdiagnosed despite concomitant physical and behavioral manifestations. Objective To develop a non-invasive, rapid and high-throughput molecular diagnostic assay for detection of male sex chromosome aneuploidies, including 47,XXY (Klinefelter, 47,XYY, 48,XXYY and 48,XXXY syndromes. Methods The assay utilizes three XYM and four XA markers to interrogate Y:X and X:autosome ratios, respectively. The seven markers were PCR amplified using genomic DNA isolated from a cohort of 323 males with aneuploid (n = 117 and 46,XY (n = 206 karyotypes. The resulting PCR products were subjected to Pyrosequencing, a quantitative DNA sequencing method. Results Receiver operator characteristic (ROC curves were used to establish thresholds for the discrimination of aneuploid from normal samples. The XYM markers permitted the identification of 47,XXY, 48,XXXY and 47,XYY syndromes with 100% sensitivity and specificity in both purified DNA and buccal swab samples. The 48,XXYY karyotype was delineated by XA marker data from 46,XY; an X allele threshold of 43% also permitted detection of 48,XXYY with 100% sensitivity and specificity. Analysis of X chromosome-specific biallelic SNPs demonstrated that 43 of 45 individuals (96% with 48,XXYY karyotype had two distinct X chromosomes, while 2 (4% had a duplicate X, providing evidence that 48,XXYY may result from nondisjunction during early mitotic divisions of a 46,XY embryo. Conclusions Quantitative Pyrosequencing, with high-throughput potential, can detect male sex chromosome aneuploidies with 100% sensitivity.

  5. Landscape moderation of biodiversity patterns and processes - eight hypotheses.

    Science.gov (United States)

    Tscharntke, Teja; Tylianakis, Jason M; Rand, Tatyana A; Didham, Raphael K; Fahrig, Lenore; Batáry, Péter; Bengtsson, Janne; Clough, Yann; Crist, Thomas O; Dormann, Carsten F; Ewers, Robert M; Fründ, Jochen; Holt, Robert D; Holzschuh, Andrea; Klein, Alexandra M; Kleijn, David; Kremen, Claire; Landis, Doug A; Laurance, William; Lindenmayer, David; Scherber, Christoph; Sodhi, Navjot; Steffan-Dewenter, Ingolf; Thies, Carsten; van der Putten, Wim H; Westphal, Catrin

    2012-08-01

    Understanding how landscape characteristics affect biodiversity patterns and ecological processes at local and landscape scales is critical for mitigating effects of global environmental change. In this review, we use knowledge gained from human-modified landscapes to suggest eight hypotheses, which we hope will encourage more systematic research on the role of landscape composition and configuration in determining the structure of ecological communities, ecosystem functioning and services. We organize the eight hypotheses under four overarching themes. Section A: 'landscape moderation of biodiversity patterns' includes (1) the landscape species pool hypothesis-the size of the landscape-wide species pool moderates local (alpha) biodiversity, and (2) the dominance of beta diversity hypothesis-landscape-moderated dissimilarity of local communities determines landscape-wide biodiversity and overrides negative local effects of habitat fragmentation on biodiversity. Section B: 'landscape moderation of population dynamics' includes (3) the cross-habitat spillover hypothesis-landscape-moderated spillover of energy, resources and organisms across habitats, including between managed and natural ecosystems, influences landscape-wide community structure and associated processes and (4) the landscape-moderated concentration and dilution hypothesis-spatial and temporal changes in landscape composition can cause transient concentration or dilution of populations with functional consequences. Section C: 'landscape moderation of functional trait selection' includes (5) the landscape-moderated functional trait selection hypothesis-landscape moderation of species trait selection shapes the functional role and trajectory of community assembly, and (6) the landscape-moderated insurance hypothesis-landscape complexity provides spatial and temporal insurance, i.e. high resilience and stability of ecological processes in changing environments. Section D: 'landscape constraints on

  6. An automated framework for hypotheses generation using literature

    Directory of Open Access Journals (Sweden)

    Abedi Vida

    2012-08-01

    Full Text Available Abstract Background In bio-medicine, exploratory studies and hypothesis generation often begin with researching existing literature to identify a set of factors and their association with diseases, phenotypes, or biological processes. Many scientists are overwhelmed by the sheer volume of literature on a disease when they plan to generate a new hypothesis or study a biological phenomenon. The situation is even worse for junior investigators who often find it difficult to formulate new hypotheses or, more importantly, corroborate if their hypothesis is consistent with existing literature. It is a daunting task to be abreast with so much being published and also remember all combinations of direct and indirect associations. Fortunately there is a growing trend of using literature mining and knowledge discovery tools in biomedical research. However, there is still a large gap between the huge amount of effort and resources invested in disease research and the little effort in harvesting the published knowledge. The proposed hypothesis generation framework (HGF finds “crisp semantic associations” among entities of interest - that is a step towards bridging such gaps. Methodology The proposed HGF shares similar end goals like the SWAN but are more holistic in nature and was designed and implemented using scalable and efficient computational models of disease-disease interaction. The integration of mapping ontologies with latent semantic analysis is critical in capturing domain specific direct and indirect “crisp” associations, and making assertions about entities (such as disease X is associated with a set of factors Z. Results Pilot studies were performed using two diseases. A comparative analysis of the computed “associations” and “assertions” with curated expert knowledge was performed to validate the results. It was observed that the HGF is able to capture “crisp” direct and indirect associations, and provide knowledge

  7. An automated framework for hypotheses generation using literature.

    Science.gov (United States)

    Abedi, Vida; Zand, Ramin; Yeasin, Mohammed; Faisal, Fazle Elahi

    2012-08-29

    In bio-medicine, exploratory studies and hypothesis generation often begin with researching existing literature to identify a set of factors and their association with diseases, phenotypes, or biological processes. Many scientists are overwhelmed by the sheer volume of literature on a disease when they plan to generate a new hypothesis or study a biological phenomenon. The situation is even worse for junior investigators who often find it difficult to formulate new hypotheses or, more importantly, corroborate if their hypothesis is consistent with existing literature. It is a daunting task to be abreast with so much being published and also remember all combinations of direct and indirect associations. Fortunately there is a growing trend of using literature mining and knowledge discovery tools in biomedical research. However, there is still a large gap between the huge amount of effort and resources invested in disease research and the little effort in harvesting the published knowledge. The proposed hypothesis generation framework (HGF) finds "crisp semantic associations" among entities of interest - that is a step towards bridging such gaps. The proposed HGF shares similar end goals like the SWAN but are more holistic in nature and was designed and implemented using scalable and efficient computational models of disease-disease interaction. The integration of mapping ontologies with latent semantic analysis is critical in capturing domain specific direct and indirect "crisp" associations, and making assertions about entities (such as disease X is associated with a set of factors Z). Pilot studies were performed using two diseases. A comparative analysis of the computed "associations" and "assertions" with curated expert knowledge was performed to validate the results. It was observed that the HGF is able to capture "crisp" direct and indirect associations, and provide knowledge discovery on demand. The proposed framework is fast, efficient, and robust in

  8. Exploration of miRNA families for hypotheses generation.

    KAUST Repository

    Kamanu, T.K.

    2013-10-15

    Technological improvements have resulted in increased discovery of new microRNAs (miRNAs) and refinement and enrichment of existing miRNA families. miRNA families are important because they suggest a common sequence or structure configuration in sets of genes that hint to a shared function. Exploratory tools to enhance investigation of characteristics of miRNA families and the functions of family-specific miRNA genes are lacking. We have developed, miRNAVISA, a user-friendly web-based tool that allows customized interrogation and comparisons of miRNA families for hypotheses generation, and comparison of per-species chromosomal distribution of miRNA genes in different families. This study illustrates hypothesis generation using miRNAVISA in seven species. Our results unveil a subclass of miRNAs that may be regulated by genomic imprinting, and also suggest that some miRNA families may be species-specific, as well as chromosome- and/or strand-specific.

  9. Fear of knowledge: Clinical hypotheses in diagnostic and prognostic reasoning.

    Science.gov (United States)

    Chiffi, Daniele; Zanotti, Renzo

    2017-10-01

    Patients are interested in receiving accurate diagnostic and prognostic information. Models and reasoning about diagnoses have been extensively investigated from a foundational perspective; however, for all its importance, prognosis has yet to receive a comparable degree of philosophical and methodological attention, and this may be due to the difficulties inherent in accurate prognostics. In the light of these considerations, we discuss a considerable body of critical thinking on the topic of prognostication and its strict relations with diagnostic reasoning, pointing out the distinction between nosographic and pathophysiological types of diagnosis and prognosis, underlying the importance of the explication and explanation processes. We then distinguish between various forms of hypothetical reasoning applied to reach diagnostic and prognostic judgments, comparing them with specific forms of abductive reasoning. The main thesis is that creative abduction regarding clinical hypotheses in diagnostic process is very unlikely to occur, whereas this seems to be often the case for prognostic judgments. The reasons behind this distinction are due to the different types of uncertainty involved in diagnostic and prognostic judgments. © 2016 John Wiley & Sons, Ltd.

  10. Host Lipid Mediators in Leprosy: The Hypothesized Contributions to Pathogenesis

    Directory of Open Access Journals (Sweden)

    Carlos A. M. Silva

    2018-02-01

    Full Text Available The spectrum of clinical forms observed in leprosy and its pathogenesis are dictated by the host’s immune response against Mycobacterium leprae, the etiological agent of leprosy. Previous results, based on metabolomics studies, demonstrated a strong relationship between clinical manifestations of leprosy and alterations in the metabolism of ω3 and ω6 polyunsaturated fatty acids (PUFAs, and the diverse set of lipid mediators derived from PUFAs. PUFA-derived lipid mediators provide multiple functions during acute inflammation, and some lipid mediators are able to induce both pro- and anti-inflammatory responses as determined by the cell surface receptors being expressed, as well as the cell type expressing the receptors. However, little is known about how these compounds influence cellular immune activities during chronic granulomatous infectious diseases, such as leprosy. Current evidence suggests that specialized pro-resolving lipid mediators (SPMs are involved in the down-modulation of the innate and adaptive immune response against M. leprae and that alteration in the homeostasis of pro-inflammatory lipid mediators versus SPMs is associated with dramatic shifts in the pathogenesis of leprosy. In this review, we discuss the possible consequences and present new hypotheses for the involvement of ω3 and ω6 PUFA metabolism in the pathogenesis of leprosy. A specific emphasis is placed on developing models of lipid mediator interactions with the innate and adaptive immune responses and the influence of these interactions on the outcome of leprosy.

  11. [The evolution of plant life span: facts and hypotheses].

    Science.gov (United States)

    2006-01-01

    There are two different views on the evolution of life forms in Cormophyta: from woody plants to herbaceous ones or in opposite direction - from herbs to trees. In accordance with these views it is supposed that life span in plants changed in the course of evolution from many years (perennials) to few years (annuals, biennials), or went in reverse - from few years to many years. The author discusses the problems of senescence and longevity in Cormophyta in the context of various hypotheses of ageing (programmed death theory, mutation accumulation, antagonistic pleiotropy, disposable soma, genes of ageing, genes of longevity). Special attention is given to bio-morphological aspects of longevity and cases of non-ageing plants ("negative senescence", "potential immortality"). It is proposed to distinguish seven models of simple ontogenesis in Cormophyta that can exemplify the diversity of mechanisms of ageing and longevity. The evolution of life span in plants is considered as an indirect result of natural selection of other characteristics of organisms or as a consequence of fixation of modifications (episelectional evolution). It seems that short life span could emerge several times during evolution of one group of plants, thus favoring its adaptive radiation.

  12. Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers

    Directory of Open Access Journals (Sweden)

    Fei Tang

    2017-07-01

    Full Text Available Epilepsy is a common neurological disorder that affects over 70 million people worldwide. Despite the recent introduction of new antiseizure drugs (ASDs, about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early identification of patients who will become refractory to ASDs could help direct such patients to appropriate non-pharmacological treatment, but the complexity in the temporal patterns of epilepsy could make such identification difficult. The target hypothesis and transporter hypothesis are the most cited theories trying to explain refractory epilepsy, but neither theory alone fully explains the neurobiological basis of pharmacoresistance. This review summarizes evidence for and against several major theories, including the pharmacokinetic hypothesis, neural network hypothesis, intrinsic severity hypothesis, gene variant hypothesis, target hypothesis, and transporter hypothesis. The discussion is mainly focused on the transporter hypothesis, where clinical and experimental data are discussed on multidrug transporter overexpression, substrate profiles of ASDs, mechanism of transporter upregulation, polymorphisms of transporters, and the use of transporter inhibitors. Finally, future perspectives are presented for the improvement of current hypotheses and the development of treatment strategies as guided by the current understanding of refractory epilepsy.

  13. [Identification of Candida dubliniensis strains using heat tolerance tests, morphological characteristics and molecular methods].

    Science.gov (United States)

    Arikan, Sevtap; Darka, Ozge; Hasçelik, Gülşen; Günalp, Ayfer

    2003-01-01

    Described in 1995, Candida dubliniensis is a novel Candida species closely related to Candida albicans due primarily to its ability to produce germ tube and chlamydospores. Given these phenotypic similarities between the two species, C. dubliniensis cannot be readily distinguished from Candida albicans by routine laboratory work-up. We explored the frequency of isolation of C. dubliniensis among 213 strains previously defined as C. albicans based on their ability to produce germ tube. The test isolates were initially examined for their morphological features on cornmeal tween 80 agar, inability to grow at 45 degrees C, and the biochemical assimilation profile (ID 32C system, bioMerieux, France). Among all, 2 (0.9%) of the isolates were identified as C. dubliniensis based on the production of numerous chlamydospores in chains on cornmeal tween 80 agar and the lack of growth at 45 degrees C. The assimilation profile of these isolates was found to be in accordance with this identification. In an effort to confirm the identification, polymerase chain reaction (PCR) studies were carried out by using the C. dubliniensis specific primer set, DUBF and DUBR. Both of the isolates yielded C. dubliniensis-specific 288 base pair amplification products, confirming the previous identification obtained with the initial screening tests. The isolates were found to be susceptible to fluconazole and itraconazole, and generated amphotericin B minimal inhibitory concentrations of 0.5-1 microgram/ml by NCCLS M27-A2 microdilution method. These data suggest that the isolation rate of C. dubliniensis among our clinical isolates is low. The morphological features on cornmeal tween 80 agar and the lack of ability to grow at 45 degrees C appear as reliable, cheap, and practical screening tests in initial identification of C. dubliniensis among germ tube-producing Candida strains.

  14. Early Bronchus-Associated Lymphoid Tissue Lymphoma Diagnosed with Immunoglobulin Heavy Chain Molecular Testing

    Directory of Open Access Journals (Sweden)

    Pen Li

    2016-01-01

    Full Text Available When extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue (MALT, a low grade B-cell lymphoma, arises in the lung it is referred to as bronchus-associated lymphoid tissue (BALT lymphoma. We describe a patient with a history of Sjögren’s syndrome and rheumatoid arthritis with dyspnea and imaging consistent with lymphoid interstitial pneumonia (LIP. However, while histology and immunohistochemistry lacked definitive features of a lymphoma, immunoglobulin heavy chain (IgH polymerase chain reaction testing demonstrated B-cell monoclonality, consistent with an early BALT lymphoma.

  15. Prenatal molecular testing for Beckwith-Wiedemann and Silver-Russell syndromes

    DEFF Research Database (Denmark)

    Eggermann, Thomas; Brioude, Frédéric; Russo, Silvia

    2016-01-01

    Beckwith-Wiedemann and Silver-Russell syndromes (BWS/SRS) are two imprinting disorders (IDs) associated with disturbances of the 11p15.5 chromosomal region. In BWS, epimutations and genomic alterations within 11p15.5 are observed in >70% of patients, whereas in SRS they are observed in about 60% ......, the consequences for prenatal genetic testing and counseling and our cumulative experience in dealing with these disorders.European Journal of Human Genetics advance online publication, 28 October 2015; doi:10.1038/ejhg.2015.224....

  16. Molecular Dynamics Simulations on the solvation and interfacial behaviour of hydrophobic species. Applications to the TATB hypothesis and to the liquid/liquid extraction of cations to supercritical CO{sub 2}; Simulations par dynamique moleculaire de la solvatation et du comportement interfacial d'especes hydrophobes: application a l'hypothese TATB et a l'extraction liquide/liquide de cations par le CO{sub 2} supercritique

    Energy Technology Data Exchange (ETDEWEB)

    Schurhammer, R

    2001-12-15

    We report molecular dynamics studies on the solvation of charged hydrophobic molecules in pure liquids and at liquid / liquid interfaces. The first part of the thesis deals with the TATB hypothesis according to which the As{phi}{sub 4}{sup +} (TA{sup +}) and B{phi}{sub 4}{sup -} (TB{sup -}) ions have the same free energy of solvation in any solvent. The two ions are found to be solvated differently in pure liquids (water, chloroform, acetonitrile) as at a chloroform / water interface. These results are confirmed by free energy calculations and by simulations on iso-volume spherical S{sup +} and S{sup -} ions, which perfectly meet the TATB criteria. The many methodological tests performed show the importance of (i) the corrected treatment of 'long range interactions' (ii) the precise repartition of atomic charges (iii) the solvent models, especially for water, on the + / - charge discrimination by solvent. In the second part, in relation to the liquid / liquid extraction of cations from water to supercritical CO{sub 2}, we report the behaviour of ions (Cs{sup +}, UO{sub 2}{sup 2+}, Eu{sup 3+}), of un-complexed extractants molecules (tri-n-butylphosphate, calixarene), of their complexes with the cations and nitric acid at a preformed chloroform / water interface and during de-mixing simulations which started from a perfectly mixed CO{sub 2} / water solutions. These studies demonstrate the importance of interfacial phenomena, of simulation conditions and acid and extractant concentrations, in assisted ion extraction to supercritical CO{sub 2}. (author)

  17. Ultrasonic, Molecular and Mechanical Testing Diagnostics in Natural Fibre Reinforced, Polymer-Stabilized Earth Blocks

    Directory of Open Access Journals (Sweden)

    C. Galán-Marín

    2013-01-01

    Full Text Available The aim of this research study was to evaluate the influence of utilising natural polymers as a form of soil stabilization, in order to assess their potential for use in building applications. Mixtures were stabilized with a natural polymer (alginate and reinforced with wool fibres in order to improve the overall compressive and flexural strength of a series of composite materials. Ultrasonic pulse velocity (UPV and mechanical strength testing techniques were then used to measure the porous properties of the manufactured natural polymer-soil composites, which were formed into earth blocks. Mechanical tests were carried out for three different clays which showed that the polymer increased the mechanical resistance of the samples to varying degrees, depending on the plasticity index of each soil. Variation in soil grain size distributions and Atterberg limits were assessed and chemical compositions were studied and compared. X-ray diffraction (XRD, X-ray fluorescence spectroscopy (XRF, and energy dispersive X-ray fluorescence (EDXRF techniques were all used in conjunction with qualitative identification of the aggregates. Ultrasonic wave propagation was found to be a useful technique for assisting in the determination of soil shrinkage characteristics and fibre-soil adherence capacity and UPV results correlated well with the measured mechanical properties.

  18. Molecular Tagging Velocimetry Development for In-situ Measurement in High-Temperature Test Facility

    Science.gov (United States)

    Andre, Matthieu A.; Bardet, Philippe M.; Burns, Ross A.; Danehy, Paul M.

    2015-01-01

    The High Temperature Test Facility, HTTF, at Oregon State University (OSU) is an integral-effect test facility designed to model the behavior of a Very High Temperature Gas Reactor (VHTR) during a Depressurized Conduction Cooldown (DCC) event. It also has the ability to conduct limited investigations into the progression of a Pressurized Conduction Cooldown (PCC) event in addition to phenomena occurring during normal operations. Both of these phenomena will be studied with in-situ velocity field measurements. Experimental measurements of velocity are critical to provide proper boundary conditions to validate CFD codes, as well as developing correlations for system level codes, such as RELAP5 (http://www4vip.inl.gov/relap5/). Such data will be the first acquired in the HTTF and will introduce a diagnostic with numerous other applications to the field of nuclear thermal hydraulics. A laser-based optical diagnostic under development at The George Washington University (GWU) is presented; the technique is demonstrated with velocity data obtained in ambient temperature air, and adaptation to high-pressure, high-temperature flow is discussed.

  19. Molecular imaging with {sup 99m}Tc-MIBI and molecular testing for mutations in differentiating benign from malignant follicular neoplasm: a prospective comparison

    Energy Technology Data Exchange (ETDEWEB)

    Giovanella, L.; Treglia, G.; Ceriani, L. [Oncology Institute of Southern Switzerland, Department of Nuclear Medicine and Thyroid Centre, Bellinzona (Switzerland); Campenni, A. [Policlinico Universitario, Istituto di Medicina Nucleare, Messina (Italy); Verburg, F.A. [RWTH University Hospital Aachen, Department of Nuclear Medicine, Aachen (Germany); Trimboli, P. [Oncology Institute of Southern Switzerland, Department of Nuclear Medicine and Thyroid Centre, Bellinzona (Switzerland); Ospedale Israelitico, Sezione di Endocrinologia e Diabetologia, Roma (Italy); Bongiovanni, M. [Centre Hopitalier Universitaire Vaudouise, Institut de Pathologie, Lausanne (Switzerland)

    2016-06-15

    To compare mutation analysis of cytology specimens and {sup 99m}Tc-MIBI thyroid scintigraphy for differentiating benign from malignant thyroid nodules in patients with a cytological reading of follicular neoplasm. Patients ≥18 years of age with a solitary hypofunctioning thyroid nodule (≥10 mm), normal thyrotropin and calcitonin levels, and a cytological diagnosis of follicular neoplasm were prospectively enrolled. Mutation analysis and {sup 99m}Tc-MIBI scintigraphy were performed and patients were subsequently operated on to confirm or exclude a malignant lesion. Mutations for KRAS, HRAS and NRAS and for BRAF and translocations of PAX8/PPARγ, RET/PTC1 and RET/PTC3 were investigated. Static thyroid scintigraphic images were acquired 10 and 60 min after intravenous injection of 200 MBq of {sup 99m}Tc-MIBI and visually assessed. Additionally, the MIBI washout index was calculated using a semiquantitative method. In our series, 26 % of nodules with a follicular pattern on cytology were malignant with a prevalence of follicular carcinomas. {sup 99m}Tc-MIBI scintigraphy was found to be significantly more accurate (positive likelihood ratio 4.56 for visual assessment and 12.35 for semiquantitative assessment) than mutation analysis (positive likelihood ratio 1.74). A negative {sup 99m}Tc-MIBI scan reliably excluded malignancy. In patients with a thyroid nodule cytologically diagnosed as a follicular proliferation, semiquantitative analysis of {sup 99m}Tc-MIBI scintigraphy should be the preferred method for differentiating benign from malignant nodules. It is superior to molecular testing for the presence of differentiated thyroid cancer-associated mutations in fine-needle aspiration cytology sample material. (orig.)

  20. Molecular imaging with (99m)Tc-MIBI and molecular testing for mutations in differentiating benign from malignant follicular neoplasm: a prospective comparison.

    Science.gov (United States)

    Giovanella, L; Campenni, A; Treglia, G; Verburg, F A; Trimboli, P; Ceriani, L; Bongiovanni, M

    2016-06-01

    To compare mutation analysis of cytology specimens and (99m)Tc-MIBI thyroid scintigraphy for differentiating benign from malignant thyroid nodules in patients with a cytological reading of follicular neoplasm. Patients ≥18 years of age with a solitary hypofunctioning thyroid nodule (≥10 mm), normal thyrotropin and calcitonin levels, and a cytological diagnosis of follicular neoplasm were prospectively enrolled. Mutation analysis and (99m)Tc-MIBI scintigraphy were performed and patients were subsequently operated on to confirm or exclude a malignant lesion. Mutations for KRAS, HRAS and NRAS and for BRAF and translocations of PAX8/PPARγ, RET/PTC1 and RET/PTC3 were investigated. Static thyroid scintigraphic images were acquired 10 and 60 min after intravenous injection of 200 MBq of (99m)Tc-MIBI and visually assessed. Additionally, the MIBI washout index was calculated using a semiquantitative method. In our series, 26 % of nodules with a follicular pattern on cytology were malignant with a prevalence of follicular carcinomas. (99m)Tc-MIBI scintigraphy was found to be significantly more accurate (positive likelihood ratio 4.56 for visual assessment and 12.35 for semiquantitative assessment) than mutation analysis (positive likelihood ratio 1.74). A negative (99m)Tc-MIBI scan reliably excluded malignancy. In patients with a thyroid nodule cytologically diagnosed as a follicular proliferation, semiquantitative analysis of (99m)Tc-MIBI scintigraphy should be the preferred method for differentiating benign from malignant nodules. It is superior to molecular testing for the presence of differentiated thyroid cancer-associated mutations in fine-needle aspiration cytology sample material.

  1. Molecular and Morphological Differentiation of Common Dolphins (Delphinus sp.) in the Southwestern Atlantic: Testing the Two Species Hypothesis in Sympatry

    Science.gov (United States)

    Cunha, Haydée A.; de Castro, Rocio Loizaga; Secchi, Eduardo R.; Crespo, Enrique A.; Lailson-Brito, José; Azevedo, Alexandre F.; Lazoski, Cristiano; Solé-Cava, Antonio M.

    2015-01-01

    The taxonomy of common dolphins (Delphinus sp.) has always been controversial, with over twenty described species since the original description of the type species of the genus (Delphinus delphis Linnaeus, 1758). Two species and four subspecies are currently accepted, but recent molecular data have challenged this view. In this study we investigated the molecular taxonomy of common dolphins through analyses of cytochrome b sequences of 297 individuals from most of their distribution. We included 37 novel sequences from the Southwestern Atlantic Ocean, a region where the short- and long-beaked morphotypes occur in sympatry, but which had not been well sampled before. Skulls of individuals from the Southwestern Atlantic were measured to test the validity of the rostral index as a diagnostic character and confirmed the presence of the two morphotypes in our genetic sample. Our genetic results show that all common dolphins in the Atlantic Ocean belong to a single species, Delphinus delphis. According to genetic data, the species Delphinus capensis is invalid. Long-beaked common dolphins from the Northeastern Pacific Ocean may constitute a different species. Our conclusions prompt the need for revision of currently accepted common dolphin species and subspecies and of Delphinus delphis distribution. PMID:26559411

  2. Unravelling the Complexity of Inherited Retinal Dystrophies Molecular Testing: Added Value of Targeted Next-Generation Sequencing

    Directory of Open Access Journals (Sweden)

    Isabella Bernardis

    2016-01-01

    Full Text Available To assess the clinical utility of targeted Next-Generation Sequencing (NGS for the diagnosis of Inherited Retinal Dystrophies (IRDs, a total of 109 subjects were enrolled in the study, including 88 IRD affected probands and 21 healthy relatives. Clinical diagnoses included Retinitis Pigmentosa (RP, Leber Congenital Amaurosis (LCA, Stargardt Disease (STGD, Best Macular Dystrophy (BMD, Usher Syndrome (USH, and other IRDs with undefined clinical diagnosis. Participants underwent a complete ophthalmologic examination followed by genetic counseling. A custom AmpliSeq™ panel of 72 IRD-related genes was designed for the analysis and tested using Ion semiconductor Next-Generation Sequencing (NGS. Potential disease-causing mutations were identified in 59.1% of probands, comprising mutations in 16 genes. The highest diagnostic yields were achieved for BMD, LCA, USH, and STGD patients, whereas RP confirmed its high genetic heterogeneity. Causative mutations were identified in 17.6% of probands with undefined diagnosis. Revision of the initial diagnosis was performed for 9.6% of genetically diagnosed patients. This study demonstrates that NGS represents a comprehensive cost-effective approach for IRDs molecular diagnosis. The identification of the genetic alterations underlying the phenotype enabled the clinicians to achieve a more accurate diagnosis. The results emphasize the importance of molecular diagnosis coupled with clinic information to unravel the extensive phenotypic heterogeneity of these diseases.

  3. Molecular and Morphological Differentiation of Common Dolphins (Delphinus sp. in the Southwestern Atlantic: Testing the Two Species Hypothesis in Sympatry.

    Directory of Open Access Journals (Sweden)

    Haydée A Cunha

    Full Text Available The taxonomy of common dolphins (Delphinus sp. has always been controversial, with over twenty described species since the original description of the type species of the genus (Delphinus delphis Linnaeus, 1758. Two species and four subspecies are currently accepted, but recent molecular data have challenged this view. In this study we investigated the molecular taxonomy of common dolphins through analyses of cytochrome b sequences of 297 individuals from most of their distribution. We included 37 novel sequences from the Southwestern Atlantic Ocean, a region where the short- and long-beaked morphotypes occur in sympatry, but which had not been well sampled before. Skulls of individuals from the Southwestern Atlantic were measured to test the validity of the rostral index as a diagnostic character and confirmed the presence of the two morphotypes in our genetic sample. Our genetic results show that all common dolphins in the Atlantic Ocean belong to a single species, Delphinus delphis. According to genetic data, the species Delphinus capensis is invalid. Long-beaked common dolphins from the Northeastern Pacific Ocean may constitute a different species. Our conclusions prompt the need for revision of currently accepted common dolphin species and subspecies and of Delphinus delphis distribution.

  4. Nearly Complete 28S rRNA Gene Sequences Confirm New Hypotheses of Sponge Evolution

    Science.gov (United States)

    Thacker, Robert W.; Hill, April L.; Hill, Malcolm S.; Redmond, Niamh E.; Collins, Allen G.; Morrow, Christine C.; Spicer, Lori; Carmack, Cheryl A.; Zappe, Megan E.; Pohlmann, Deborah; Hall, Chelsea; Diaz, Maria C.; Bangalore, Purushotham V.

    2013-01-01

    The highly collaborative research sponsored by the NSF-funded Assembling the Porifera Tree of Life (PorToL) project is providing insights into some of the most difficult questions in metazoan systematics. Our understanding of phylogenetic relationships within the phylum Porifera has changed considerably with increased taxon sampling and data from additional molecular markers. PorToL researchers have falsified earlier phylogenetic hypotheses, discovered novel phylogenetic alliances, found phylogenetic homes for enigmatic taxa, and provided a more precise understanding of the evolution of skeletal features, secondary metabolites, body organization, and symbioses. Some of these exciting new discoveries are shared in the papers that form this issue of Integrative and Comparative Biology. Our analyses of over 300 nearly complete 28S ribosomal subunit gene sequences provide specific case studies that illustrate how our dataset confirms new hypotheses of sponge evolution. We recovered monophyletic clades for all 4 classes of sponges, as well as the 4 major clades of Demospongiae (Keratosa, Myxospongiae, Haploscleromorpha, and Heteroscleromorpha), but our phylogeny differs in several aspects from traditional classifications. In most major clades of sponges, families within orders appear to be paraphyletic. Although additional sampling of genes and taxa are needed to establish whether this pattern results from a lack of phylogenetic resolution or from a paraphyletic classification system, many of our results are congruent with those obtained from 18S ribosomal subunit gene sequences and complete mitochondrial genomes. These data provide further support for a revision of the traditional classification of sponges. PMID:23748742

  5. Endocardial tip cells in the human embryo - facts and hypotheses.

    Directory of Open Access Journals (Sweden)

    Mugurel C Rusu

    Full Text Available Experimental studies regarding coronary embryogenesis suggest that the endocardium is a source of endothelial cells for the myocardial networks. As this was not previously documented in human embryos, we aimed to study whether or not endothelial tip cells could be correlated with endocardial-dependent mechanisms of sprouting angiogenesis. Six human embryos (43-56 days were obtained and processed in accordance with ethical regulations; immunohistochemistry was performed for CD105 (endoglin, CD31, CD34, α-smooth muscle actin, desmin and vimentin antibodies. Primitive main vessels were found deriving from both the sinus venosus and aorta, and were sought to be the primordia of the venous and arterial ends of cardiac microcirculation. Subepicardial vessels were found branching into the outer ventricular myocardium, with a pattern of recruiting α-SMA+/desmin+ vascular smooth muscle cells and pericytes. Endothelial sprouts were guided by CD31+/CD34+/CD105+/vimentin+ endothelial tip cells. Within the inner myocardium, we found endothelial networks rooted from endocardium, guided by filopodia-projecting CD31+/CD34+/CD105+/ vimentin+ endocardial tip cells. The myocardial microcirculatory bed in the atria was mostly originated from endocardium, as well. Nevertheless, endocardial tip cells were also found in cardiac cushions, but they were not related to cushion endothelial networks. A general anatomical pattern of cardiac microvascular embryogenesis was thus hypothesized; the arterial and venous ends being linked, respectively, to the aorta and sinus venosus. Further elongation of the vessels may be related to the epicardium and subepicardial stroma and the intramyocardial network, depending on either endothelial and endocardial filopodia-guided tip cells in ventricles, or mostly on endocardium, in atria.

  6. Molecular docking.

    Science.gov (United States)

    Morris, Garrett M; Lim-Wilby, Marguerita

    2008-01-01

    Molecular docking is a key tool in structural molecular biology and computer-assisted drug design. The goal of ligand-protein docking is to predict the predominant binding mode(s) of a ligand with a protein of known three-dimensional structure. Successful docking methods search high-dimensional spaces effectively and use a scoring function that correctly ranks candidate dockings. Docking can be used to perform virtual screening on large libraries of compounds, rank the results, and propose structural hypotheses of how the ligands inhibit the target, which is invaluable in lead optimization. The setting up of the input structures for the docking is just as important as the docking itself, and analyzing the results of stochastic search methods can sometimes be unclear. This chapter discusses the background and theory of molecular docking software, and covers the usage of some of the most-cited docking software.

  7. How doctors generate diagnostic hypotheses: a study of radiological diagnosis with functional magnetic resonance imaging.

    Directory of Open Access Journals (Sweden)

    Marcio Melo

    Full Text Available In medical practice, diagnostic hypotheses are often made by physicians in the first moments of contact with patients; sometimes even before they report their symptoms. We propose that generation of diagnostic hypotheses in this context is the result of cognitive processes subserved by brain mechanisms that are similar to those involved in naming objects or concepts in everyday life.To test this proposal we developed an experimental paradigm with functional magnetic resonance imaging (fMRI using radiological diagnosis as a model. Twenty-five radiologists diagnosed lesions in chest X-ray images and named non-medical targets (animals embedded in chest X-ray images while being scanned in a fMRI session. Images were presented for 1.5 seconds; response times (RTs and the ensuing cortical activations were assessed. The mean response time for diagnosing lesions was 1.33 (SD ±0.14 seconds and 1.23 (SD ±0.13 seconds for naming animals. 72% of the radiologists reported cogitating differential diagnoses during trials (3.5 seconds. The overall pattern of cortical activations was remarkably similar for both types of targets. However, within the neural systems shared by both stimuli, activation was significantly greater in left inferior frontal sulcus and posterior cingulate cortex for lesions relative to animals.Generation of diagnostic hypotheses and differential diagnoses made through the immediate visual recognition of clinical signs can be a fast and automatic process. The co-localization of significant brain activation for lesions and animals suggests that generating diagnostic hypotheses for lesions and naming animals are served by the same neuronal systems. Nevertheless, diagnosing lesions was cognitively more demanding and associated with more activation in higher order cortical areas. These results support the hypothesis that medical diagnoses based on prompt visual recognition of clinical signs and naming in everyday life are supported by similar

  8. Kolmogorov similarity hypotheses for scalar fields: sampling intermittent turbulent mixing in the ocean and galaxy

    International Nuclear Information System (INIS)

    Gibson, C.H.

    1991-01-01

    Kolmogorov's three universal similarity hypotheses are extrapolated to describe scalar fields like temperature mixed by turbulence. The analogous first and second hypotheses for scalars include the effects of Prandtl number and rate-of-strain mixing. Application of velocity and scalar similarity hypotheses to the ocean must take into account the damping of active turbulence by density stratification and the Earth's rotation to form fossil turbulence. By the analogous Kolmogorov third hypothesis for scalars, temperature dissipation rates χ averaged over lengths r > L K should be lognormally distributed with intermittency factors σ 2 that increase with increasing turbulence energy length scales L O as σ ln r 2 approx = μ θ ln(L O /r). Tests of kolmogorovian velocity and scalar universal similarity hypotheses for very large ranges of turbulence length and timescales are provided by data from the ocean and the galactic interstellar medium. These ranges are from 1 to 9 decades in the ocean, and over 12 decades in the interstellar medium. The universal constant for turbulent mixing intermittency μ θ is estimated from oceanic data to be 0.44±0.01, which is remarkably close to estimates for Kolmorgorov's turbulence intermittency constant μ of 0.45±0.05 from galactic as well as atmospheric data. Extreme intermittency complicates the oceanic sampling problem, and may lead to quantitative and qualitative undersampling errors in estimates of mean oceanic dissipation rates and fluxes. Intermittency of turbulence and mixing in the interstellar medium may be a factor in the formation of stars. (author)

  9. The Relevance of External Quality Assessment for Molecular Testing for ALK Positive Non-Small Cell Lung Cancer : Results from Two Pilot Rounds Show Room for Optimization

    NARCIS (Netherlands)

    Tembuyser, Lien; Tack, Veronique; Zwaenepoel, Karen; Pauwels, Patrick; Miller, Keith; Bubendorf, Lukas; Kerr, Keith; Schuuring, Ed; Thunnissen, Erik; Dequeker, Elisabeth M. C.

    2014-01-01

    Background and Purpose: Molecular profiling should be performed on all advanced non-small cell lung cancer with non-squamous histology to allow treatment selection. Currently, this should include EGFR mutation testing and testing for ALK rearrangements. ROS1 is another emerging target. ALK

  10. Curie's hypotheses concerning radioactivity and the origin of the elements

    International Nuclear Information System (INIS)

    Kuroda, P.K.

    1999-01-01

    Pierre Curie gave two hypotheses at first; (1) It can be supposed that the radioactive substances borrow the energy, which they release, from an external radiation, and their radiation would then be a secondary radiation, (2) It can be supposed that the radioactive substances draw from themselves the energy which they release. The second hypothesis has shown the more fertile in explaining the properties of the radioactive substances. Consequently, the first hypothesis became more or less forgotten. It appears, however, the first hypothesis should play an important role in explaining the phenomena concerning the origin of the elements. The Oklo Phenomenon has demonstrated that a nuclear fire had once existed on our planet earth and formation of heavy elements was occurring in nature. The author pointed out that the difference in the isotopic compositions of xenon found in meteorites, lunar samples and in the earth's atmosphere can only be explained as due to the alterations of the isotropic compositions of xenon by combined effect of (a) mass-fractionation, (b) spallation, and (c) stellar temperature neutron-capture reactions. The strange xenon components are not isotopically pure substance. Instead, xenon-HL is a mixture of the 244 Pu fission xenon and the xenon whose isotopic compositions is severely altered by a combined effect of the processes (a), (b) and (c) mentioned above. These results also indicate that C1 carbonaceous chondrites, which is generally as the most primitive sample of the solar system material, began to retain its xenon 5.1 billion years ago, when the plutonium to uranium ratio in the solar system was as high as almost 0.6 (atom/atom), while the C2 carbonaceous chondrite began to retain their xenon about 150 million years later and the ordinary chondrites and achondrite about 500 to 600 million years later. This means that the birth of the solar system began soon after the last supernova exploded about 5.1 billion years ago, and the generally

  11. Point -of -care testing (POCT) in molecular diagnostics: Performance evaluation of GeneXpert HCV RNA test in diagnosing and monitoring of HCV infection.

    Science.gov (United States)

    Gupta, Ekta; Agarwala, Pragya; Kumar, Guresh; Maiwall, Rakhi; Sarin, Shiv Kumar

    2017-03-01

    Molecular testing at the point-of-care may turn out to be game changer for HCV diagnosis and treatment monitoring, through increased sensitivity, reduced turnaround time, and ease of performance. One such assay GeneXpert ® has recently been released. Comparative analysis between performances of GeneXpert ® and Abbott HCV-RNA was done. 174 HCV infected patients were recruited and, one time plasma samples from 154 patients and repeated samples from 20 patients, obtained at specific treatment time-points (0, 4, 12 and 24) weeks were serially re-tested on Xpert ® . Genotype 3 was the commonest, seen in 80 (66%) of the cases, genotype 1 in 34 (28.3%), genotype 4 in 4 (3.3%) and genotypes 2 and 5 in 1 (0.8%) each. Median HCV RNA load was 4.69 log 10 (range: 0-6.98log 10 ) IU/ml. Overall a very good correlation was seen between the two assays (R 2 =0.985), concordance of the results between the assays was seen in 138 samples (89.6%). High and low positive standards were tested ten times on Xpert ® to evaluate the precision and the coefficient of variation was 0.01 for HPC and 0.07 for the LPC. Monitoring of patients on two different regimes of treatment, pegylated interferon plus ribavirin and sofosbuvir plus ribavirin was done by both the systems at baseline, 4, 12 and 24 weeks. Perfect correlation between the assays in the course of therapy at different treatment time- point in genotypes 3 and 1 was seen. The study demonstrates excellent performance of the Xpert ® HCV assay in viral load assessment and in treatment course monitoring consistency. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. How the mainstream limits the spreading of alternative hypotheses

    Science.gov (United States)

    Kalenda, Pavel

    2014-05-01

    that prof. Djuric had tried for more than 10 years to publish this article in various peer-reviewed journals. So, prof. Djuric got into the official book (list) of "scientific dissidents" among hundreds of other professors and doctors of science (De Climont 2012). These "scientific dissidents" do not have access to established journals and may possibly publish privately or at best on the web in marginal journals whose list was published by De Climont (2012). Such a marginal journal in the field of geophysics and geology is New Concepts in Global Tectonics. This journal has been established because the current hypothesis about the movement of the continents due to convection currents in the mantle becomes under the weight of new observation quite untenable. 4) Scientific consensus History has known many hypotheses that were accepted as proven truth but later, in the light of new knowledge, they completely failed. - No one has the right to decide which scientific hypotheses will be accepted and which will not get into print. Perhaps the worst situation is in climatology (due to global effects and impacts), when the plenary session of IPCC consensually stated that the current global warming was mainly due to the human activity. References De Climont, J. (2012): The worldwide list of dissident scientists. http://astrojan.hostei.com/droa.htm. Djurič, J. (2006): Unification Of Gravitation And Electromagnetism. http://jovandjuric.tripod.com/ David H. Douglass, John R. Christy, Benjamin D. Pearson and S. Fred Singer (2007): A comparison of tropical temperature trends with model predictions. International Journal of Climatology, Volume 28, Issue 13, 15 November 2008, Pages: 1693-1701. http://onlinelibrary.wiley.com/doi/10.1002/joc.1651/pdf. Einstein, A. : List of scientific publications by Albert Einstein. /wiki/List_of_scientific_publications_by_Albert_Einstein. Kolínský, P., Valenta, J. and Gaždová, R. (2012): Seismicity, groundwater level variations and earth tides in

  13. Cognitive diagnostic assessment via Bayesian evaluation of informative diagnostic hypotheses.

    NARCIS (Netherlands)

    Hoijtink, Herbert; Béland, Sébastien; Vermeulen, Jorine A.

    2014-01-01

    There exist diverse approaches that can be used for cognitive diagnostic assessment, such as mastery testing, constrained latent class analysis, rule space methodology, diagnostic cognitive modeling, and person-fit analysis. Each of these approaches can be used within 1 of the 4 psychometric

  14. Cognitive Diagnostic Assessment via Bayesian Evaluation of Informative Diagnostic Hypotheses

    NARCIS (Netherlands)

    Hoitink, Herbert; Beland, Sebastien; Vermeulen, Jorine

    2014-01-01

    There exist diverse approaches that can be used for cognitive diagnostic assessment, such as mastery testing, constrained latent class analysis, rule space methodology, diagnostic cognitive modeling, and person-fit analysis. Each of these approaches can be used within 1 of the 4 psychometric

  15. Utilization of Cell-Transfer Technique for Molecular Testing on Hematoxylin-Eosin-Stained Sections: A Viable Option for Small Biopsies That Lack Tumor Tissues in Paraffin Block.

    Science.gov (United States)

    Wu, Howard H; Jovonovich, Stephen M; Randolph, Melissa; Post, Kristin M; Sen, Joyashree D; Curless, Kendra; Cheng, Liang

    2016-12-01

    - In some instances the standard method of doing molecular testing from formalin-fixed, paraffin-embedded block is not possible because of limited tissue. Tumor cell-enriched cell-transfer technique has been proven useful for performing immunocytochemistry and molecular testing on cytologic smears. - To establish the cell-transfer technique as a viable option for isolating tumor cells from hematoxylin-eosin (H&E)-stained slides. - Molecular testing was performed by using the cell-transfer technique on 97 archived H&E-stained slides from a variety of different tumors. Results were compared to the conventional method of molecular testing. - Polymerase chain reaction-based molecular testing via the cell-transfer technique was successfully performed on 82 of 97 samples (85%). This included 39 of 47 cases for EGFR, 10 of 11 cases for BRAF, and 33 of 39 cases for KRAS mutations. Eighty-one of 82 cell-transfer technique samples (99%) showed agreement with previous standard method results, including 4 mutations and 35 wild-type alleles for EGFR, 4 mutations and 6 wild-type alleles for BRAF, and 11 mutations and 21 wild-type alleles for KRAS. There was only 1 discrepancy: a cell-transfer technique with a false-negative >KRAS result (wild type versus G12C). - Molecular testing performed on H&E-stained sections via cell-transfer technique is useful when tissue from cell blocks and small surgical biopsy samples is exhausted and the only available material for testing is on H&E-stained slides.

  16. Design of a tablet computer app for facilitation of a molecular blood culture test in clinical microbiology and preliminary usability evaluation

    DEFF Research Database (Denmark)

    Samson, Lasse L.; Pape-Haugaard, Louise; Meltzer, Michelle C.

    2016-01-01

    through specialized applications (apps) while supporting the mobility of the users. The use of apps for mobile phones and tablet computers may support workflow of complex tasks, for example, molecular-based diagnostic tests in clinical microbiology. Multiplex Blood Culture Test (MuxBCT) is a molecular......-based diagnostic test used for rapid identification of pathogens in positive blood cultures. To facilitate the workflow of the MuxBCT, a specialized tablet computer app was developed as an accessory to the diagnostic test. The app aims to reduce the complexity of the test by step-by-step guidance of microscopy...... and to assist users in reaching an exact bacterial or fungal diagnosis based on blood specimen observations and controls. Additionally, the app allows for entry of test results, and communication thereof to the laboratory information system (LIS). OBJECTIVE: The objective of the study was to describe the design...

  17. Evaluating Hypotheses of Plant Species Invasions on Mediterranean Islands: Inverse Patterns between Alien and Endemic Species

    Directory of Open Access Journals (Sweden)

    Alexander Bjarnason

    2017-08-01

    Full Text Available Invasive alien species cause major changes to ecosystem functioning and patterns of biodiversity, and the main factors involved in invasion success remain contested. Using the Mediterranean island of Crete, Greece as a case study, we suggest a framework for analyzing spatial data of alien species distributions, based on environmental predictors, aiming to gain an understanding of their spatial patterns and spread. Mediterranean islands are under strong ecological pressure from invading species due to their restricted size and increased human impact. Four hypotheses of invasibility, the “propagule pressure hypothesis” (H1, “biotic resistance hypothesis vs. acceptance hypothesis” (H2, “disturbance-mediated hypothesis” (H3, and “environmental heterogeneity hypothesis” (H4 were tested. Using data from alien, native, and endemic vascular plant species, the propagule pressure, biotic resistance vs. acceptance, disturbance-mediated, and environmental heterogeneity hypotheses were tested with Generalized Additive Modeling (GAM of 39 models. Based on model selection, the optimal model includes the positive covariates of native species richness, the negative covariates of endemic species richness, and land area. Variance partitioning between the four hypotheses indicated that the biotic resistance vs. acceptance hypothesis explained the vast majority of the total variance. These results show that areas of high species richness have greater invasibility and support the acceptance hypothesis and “rich-get-richer” distribution of alien species. The negative correlation between alien and endemic species appears to be predominantly driven by altitude, with fewer alien and more endemic species at greater altitudes, and habitat richness. The negative relationship between alien and endemic species richness provides potential for understanding patterns of endemic and alien species on islands, contributing to more effective conservation

  18. Molecular Testing for Fragile X: Analysis of 5062 Tests from 1105 Fragile X Families—Performed in 12 Clinical Laboratories in Spain

    Directory of Open Access Journals (Sweden)

    María-Isabel Tejada

    2014-01-01

    Full Text Available Fragile X syndrome is the most common inherited form of intellectual disability. Here we report on a study based on a collaborative registry, involving 12 Spanish centres, of molecular diagnostic tests in 1105 fragile X families comprising 5062 individuals, of whom, 1655 carried a full mutation or were mosaic, three cases had deletions, 1840 had a premutation, and 102 had intermediate alleles. Two patients with the full mutation also had Klinefelter syndrome. We have used this registry to assess the risk of expansion from parents to children. From mothers with premutation, the overall rate of allele expansion to full mutation is 52.5%, and we found that this rate is higher for male than female offspring (63.6% versus 45.6%; P<0.001. Furthermore, in mothers with intermediate alleles (45–54 repeats, there were 10 cases of expansion to a premutation allele, and for the smallest premutation alleles (55–59 repeats, there was a 6.4% risk of expansion to a full mutation, with 56 repeats being the smallest allele that expanded to a full mutation allele in a single meiosis. Hence, in our series the risk for alleles of <59 repeats is somewhat higher than in other published series. These findings are important for genetic counselling.

  19. Molecular profiling of cancer--the future of personalized cancer medicine: a primer on cancer biology and the tools necessary to bring molecular testing to the clinic.

    Science.gov (United States)

    Stricker, Thomas; Catenacci, Daniel V T; Seiwert, Tanguy Y

    2011-04-01

    Cancers arise as a result of an accumulation of genetic aberrations that are either acquired or inborn. Virtually every cancer has its unique set of molecular changes. Technologies have been developed to study cancers and derive molecular characteristics that increasingly have implications for clinical care. Indeed, the identification of key genetic aberrations (molecular drivers) may ultimately translate into dramatic benefit for patients through the development of highly targeted therapies. With the increasing availability of newer, more powerful, and cheaper technologies such as multiplex mutational screening, next generation sequencing, array-based approaches that can determine gene copy numbers, methylation, expression, and others, as well as more sophisticated interpretation of high-throughput molecular information using bioinformatics tools like signatures and predictive algorithms, cancers will routinely be characterized in the near future. This review examines the background information and technologies that clinicians and physician-scientists will need to interpret in order to develop better, personalized treatment strategies. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. The RNA-world and co-evolution hypotheses and the origin of life: Implications, research strategies and perspectives

    Science.gov (United States)

    Lahav, Noam

    1993-12-01

    The applicability of the RNA-world and co-evolution hypotheses to the study of the very first stages of the origin of life is discussed. The discussion focuses on the basic differences between the two hypotheses and their implications, with regard to the reconstruction methodology, ribosome emergence, balance between ribozymes and protein enzymes, and their major difficulties. Additional complexities of the two hypotheses, such as membranes and the energy source of the first reactions, are not treated in the present work. A central element in the proposed experimental strategies is the study of the catalytic activities of very small peptides and RNA-like oligomers, according to existing, as well as to yet-to-be-invented scenarios of the two hypotheses under consideration. It is suggested that the noveldirected molecular evolution technology, andmolecular computational modeling, can be applied to this research. This strategy is assumed to be essential for the suggested goal of future studies of the origin of life, namely, the establishment of a ‘Primordial Darwinian entity’.

  1. Facebook Use and the Tendency to Ruminate among College Students: Testing Mediational Hypotheses

    Science.gov (United States)

    Locatelli, Sara M.; Kluwe, Katharina; Bryant, Fred B.

    2012-01-01

    Studies have found that general use of Facebook influences subjective well-being. However, fewer studies have explored the impact of specific use behaviors, such as information posted in status updates. The current study uses data collected from 251 Facebook-using undergraduate students through an online survey, and examines the valence and…

  2. Stereotypes of emotional expressiveness of northerners and southerners: a cross-cultural test of Montesquieu's hypotheses.

    Science.gov (United States)

    Pennebaker, J W; Rimé, B; Blankenship, V E

    1996-02-01

    Montesquieu argued that residents of warmer climates are more emotionally expressive than those living in cooler ones. More than 2,900 college students from 26 countries completed a brief questionnaire assessing the degree to which they considered Northerners and Southerners within their own countries to be emotionally expressive. In addition, individuals rated themselves on their own degree of expressiveness. In partial confirmation of Montesquieu's hypothesis, it was found that large within-country North-South stereotypes exist. Especially in Old World countries, Northerners are viewed as less emotionally expressive than Southerners. Regression and other analyses revealed that self-ratings of expressiveness were, in fact, related to being from the South and to warmer mean temperatures. Several possible explanations for these effects are discussed.

  3. Determinants of Domestic Private Investment: Test of Alternative Hypotheses for Pakistan

    Directory of Open Access Journals (Sweden)

    Abdul Waheed

    2015-12-01

    Full Text Available This paper analyzes the determinants of domestic private investment in Pakistan using long time series data for the period 1982 to 2012. The conventional variable such as output is not significant in explaining the domestic private investment but the interest rate has significant negative effect on private investment in the long run. The results of the study confirm the validity of crowding in hypothesis and debt overhang hypothesis for Pakistan. This study did not find any support for Mackinnon-Shaw hypothesis. The improvement in law and order condition and existence of democratic political regime in the country has significant positive effect on domestic private investment in the long run. The focus on non-conventional variables could restore investors’ confidence and may result in the recovery of domestic private investment in the country.

  4. An Intersectional Analysis of Gender and Ethnic Stereotypes: Testing Three Hypotheses

    Science.gov (United States)

    Ghavami, Negin; Peplau, Letitia Anne

    2013-01-01

    We compared perceived cultural stereotypes of diverse groups varying by gender and ethnicity. Using a free-response procedure, we asked 627 U.S. undergraduates to generate 10 attributes for 1 of 17 groups: Asian Americans, Blacks, Latinos, Middle Eastern Americans, or Whites; men or women; or 10 gender-by-ethnic groups (e.g., Black men or Latina…

  5. Rewards and Creative Performance: A Meta-Analytic Test of Theoretically Derived Hypotheses

    Science.gov (United States)

    Byron, Kris; Khazanchi, Shalini

    2012-01-01

    Although many scholars and practitioners are interested in understanding how to motivate individuals to be more creative, whether and how rewards affect creativity remain unclear. We argue that the conflicting evidence may be due to differences between studies in terms of reward conditions and the context in which rewards are offered.…

  6. Physiological reactivity in a community sample of sexually aggressive young men: a test of competing hypotheses.

    Science.gov (United States)

    Peterson, Zoë D; Janssen, Erick; Goodrich, David; Heiman, Julia R

    2014-01-01

    Men's sexually aggressive behavior potentially could relate to either physiological hyporeactivity or hyperreactivity, and these two different physiological profiles could be associated with different underlying causes of sexual aggression. Thus, measurement of physiological reactivity could provide insight into mechanisms relevant to the etiology of sexual aggression. The relationship between sexual aggression and physiological reactivity was investigated in 78 community men (38 sexually aggressive and 40 non-aggressive men). In a laboratory protocol, the men were exposed to neutral, negative-affect-inducing, and positive-affect-inducing stimuli. Men's salivary cortisol concentrations and electrodermal activity (EDA) were measured throughout the laboratory procedure. Sexually aggressive men demonstrated (1) lower overall cortisol levels and (2) lower EDA reactivity in some conditions as compared to non-aggressive men. Results of this study were consistent with the idea that men's sexual aggression is associated with physiological hyporeactivity, a physiological profile that has been found to be associated with externalizing behaviors and psychopathic traits. © 2013 Wiley Periodicals, Inc.

  7. Rényi statistics for testing composite hypotheses in general exponential models

    Czech Academy of Sciences Publication Activity Database

    Morales, D.; Pardo, L.; Pardo, M. C.; Vajda, Igor

    2004-01-01

    Roč. 38, č. 2 (2004), s. 133-147 ISSN 0233-1888 R&D Projects: GA ČR GA201/02/1391 Grant - others:BMF(ES) 2003-00892; BMF(ES) 2003-04820 Institutional research plan: CEZ:AV0Z1075907 Keywords : natural exponential models * Levy processes * generalized Wald statistics Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 0.323, year: 2004

  8. Sex differences in subjective distress to unfaithfulness: testing competing evolutionary and violation of infidelity expectations hypotheses.

    Science.gov (United States)

    Cramer, Robert Ervin; Lipinski, Ryan E; Meteer, John D; Houska, Jeremy Ashton

    2008-08-01

    According to an evolutionary psychology perspective, men's and women's processing of threats to their sex-linked mate selection strategies cause sex differences in infidelity distress. An alternative account assumes that the distress results from men's and women's processing of expectation violations regarding the content of an unfaithful partner's actions with a rival. Logistic regressions supported the conclusion that the participant's sex-but not the processing of expectation violations-was the best predictor of the most distressing infidelity presented in forced-choice, mutually exclusive, and combined formats. Our results also indicated that the sex differences in infidelity distress were neither limited to using data from a forced-choice response format nor caused by the distinct inferences that men and women draw about the relation between love and sex.

  9. Testing Dietary Hypotheses of East African Hominines Using Buccal Dental Microwear Data.

    Directory of Open Access Journals (Sweden)

    Laura Mónica Martínez

    Full Text Available There is much debate on the dietary adaptations of the robust hominin lineages during the Pliocene-Pleistocene transition. It has been argued that the shift from C3 to C4 ecosystems in Africa was the main factor responsible for the robust dental and facial anatomical adaptations of Paranthropus taxa, which might be indicative of the consumption of fibrous, abrasive plant foods in open environments. However, occlusal dental microwear data fail to provide evidence of such dietary adaptations and are not consistent with isotopic evidence that supports greater C4 food intake for the robust clades than for the gracile australopithecines. We provide evidence from buccal dental microwear data that supports softer dietary habits than expected for P. aethiopicus and P. boisei based both on masticatory apomorphies and isotopic analyses. On one hand, striation densities on the buccal enamel surfaces of paranthropines teeth are low, resembling those of H. habilis and clearly differing from those observed on H. ergaster, which display higher scratch densities indicative of the consumption of a wide assortment of highly abrasive foodstuffs. Buccal dental microwear patterns are consistent with those previously described for occlusal enamel surfaces, suggesting that Paranthropus consumed much softer diets than previously presumed and thus calling into question a strict interpretation of isotopic evidence. On the other hand, the significantly high buccal scratch densities observed in the H. ergaster specimens are not consistent with a highly specialized, mostly carnivorous diet; instead, they support the consumption of a wide range of highly abrasive food items.

  10. Substance abuse and criminal thinking: testing the countervailing, mediation, and specificity hypotheses.

    Science.gov (United States)

    Walters, Glenn D

    2012-12-01

    The purpose of this study was to determine (a) which of 2 dimensions of criminal thinking (proactive and/or reactive) correlates with prior substance abuse; (b) whether criminal thinking mediates the relationship between prior substance abuse and recidivism; (c) if a direct relationship exists between specific drugs of abuse and specific criminal thinking styles. First, the reconstructed Proactive (Prc) and Reactive (Rrc) Criminal Thinking scores from the Psychological Inventory of Criminal Thinking Styles (PICTS; Walters, 1995) were correlated with a dichotomous measure of prior substance abuse and a continuous measure of the number of substances abused in a sample of 2877 male federal prisoners (age: M = 34.96, SD = 9.89, range = 18-84; race: 63.6% Black, 17.3% White, 17.6% Hispanic, 1.4% other). The results indicated that only the Rrc score correlated significantly with prior substance abuse when the effect of the alternative measure (Prc in the case of Rrc and Rrc in the case of the Prc) was controlled through partial correlations. Second, reactive criminal thinking was found to mediate the relationship between a history of prior substance abuse and subsequent recidivism in a subsample of 1101 inmates who were released from prison during a 1- to 76-month follow-up. Third, both specific (alcohol with cutoff; marijuana with cognitive indolence) and global (heroin, cocaine, and amphetamine with cutoff, cognitive indolence, and discontinuity) drug-criminal thinking correlations were obtained. These results suggest that reactive criminal thinking plays a potentially important role in the drug-crime relationship.

  11. Test of Alternative Hypotheses Explaining the Comorbidity between Attention-Deficit/Hyperactivity Disorder and Conduct Disorder

    Science.gov (United States)

    Rhee, Soo Hyun; Willcutt, Erik G.; Hartman, Christie A.; Pennington, Bruce F.; DeFries, John C.

    2008-01-01

    There is significant comorbidity between attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD). The conclusions of studies that examined the causes of comorbidity between ADHD and CD conflict, with some researchers finding support for the three independent disorders model and others finding support for the correlated risk…

  12. Explaining the reductions in US corn ethanol processing costs: Testing competing hypotheses

    International Nuclear Information System (INIS)

    Chen Xiaoguang; Khanna, Madhu

    2012-01-01

    The processing costs of US corn ethanol have declined by 45% since 1983 as production volumes have increased seventeen-fold. We investigate the role of various factors that could explain this, including economies of scale, cumulative experience, induced innovation in response to rising input prices, an autonomous technological change, and trade induced competition from imported ethanol. Using data on dry-mill ethanol processing costs over the 1983–2005 period, we find evidence to show that US corn ethanol production exhibited decreasing returns to scale, that learning by doing played an important role in reducing these processing costs with a learning rate of 0.25, and that sugarcane ethanol imports contributed to making the corn ethanol industry more competitive. Other factors such as the rising prices of energy and labor did induce lower processing costs, but the effect is not statistically significant. The inclusion of these competing explanations for the reduction in processing costs of US corn ethanol lead to a significantly higher learning rate than otherwise, and this learning rate is found to be robust across specifications. - Highlights: ► We investigate the role of various factors that could explain the reduction in US corn ethanol processing costs over the period 1983–2005. ► We find that US corn ethanol production exhibited decreasing returns to scale. ► Learning by doing played an important role in reducing these costs with a learning rate of 0.25. ► Sugarcane ethanol imports contributed to making the corn ethanol industry more competitive. ► Rising prices of energy and labor did induce lower processing costs, but the effect is not statistically significant.

  13. Coopersmith Self-Esteem: Two Different Hypothesized Factor Models--Both Acceptable for the Same Data Structure.

    Science.gov (United States)

    Hofmann, Rich; Sherman, Larry

    Using data from 135 sixth-, seventh-, and eighth-graders between 11 and 15 years old attending a middle school in a suburban Southwest Ohio school district, two hypothesized models of the factor structures for the Coopersmith Self-Esteem Inventory were tested. One model represents the original Coopersmith factor structure, and the other model is…

  14. Personalized medicine for non-small-cell lung cancer: implications of recent advances in tissue acquisition for molecular and histologic testing.

    Science.gov (United States)

    Moreira, Andre L; Thornton, Raymond H

    2012-09-01

    In light of recent advances in individualized therapy for non-small-cell lung cancer (NSCLC), molecular and histologic profiling is essential for guiding therapeutic decisions. Results of these analyses may have implications for both response (eg, molecular testing for EGFR [epidermal growth factor receptor] mutations) and safety (eg, contraindications for squamous histology) in NSCLC. Most patients with NSCLC present with unresectable advanced disease; therefore, greater emphasis is being placed on minimally invasive tissue acquisition techniques, such as small biopsy and cytology specimens. Due to the need for increasing histologic and molecular information and increasingly smaller tissue sample sizes, efforts must be focused on optimizing tissue acquisition and the development of more sensitive molecular assays. Recent advances in tissue acquisition techniques and specimen preservation may help to address this challenge and lead to enhanced personalized treatment in NSCLC. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. The Italian National External Quality Assessment Program in Molecular Genetic Testing: Results of the VII Round (2010-2011

    Directory of Open Access Journals (Sweden)

    F. Censi

    2013-01-01

    Full Text Available Since 2001 the Istituto Superiore di Sanità established a quality assurance programme for molecular genetic testing that covers four pathologies: Cystic Fibrosis (CF, Beta Thalassemia (BT, Fragile X Syndrome (FX, and Familial Adenomatous Polyposis Coli (APC. Since 2009 this activity is an institutional activity and participation is open to both public and private laboratories. Seven rounds have been performed until now and the eighth is in progress. Laboratories receive 4 DNA samples with mock clinical indications. They analyze the samples using their routine procedures. A panel of assessors review the raw data and the reports; all data are managed through a web utility. In 2010 the number of participants was 43, 17, 15, 5 for CF, BT, FX, APC schemes respectively. Genotyping results were correct in 96%, 98.5%, 100%, and 100% of CF, BT, FX, and APC samples, respectively. Interpretation was correct in 74%, 91%, 88%, and 60% of CF, BT, FX, and APC reports, respectively; however in most of them it was not complete but a referral to genetic counseling was given. Reports were satisfactory in more than 60% of samples in all schemes. This work presents the 2010 results in detail comparing our data with those from other European schemes.

  16. The Italian National External quality assessment program in molecular genetic testing: results of the VII round (2010-2011).

    Science.gov (United States)

    Censi, F; Tosto, F; Floridia, G; Marra, M; Salvatore, M; Baffico, A M; Grasso, M; Melis, M A; Pelo, E; Radice, P; Ravani, A; Rosatelli, C; Resta, N; Russo, S; Seia, M; Varesco, L; Falbo, V; Taruscio, D

    2013-01-01

    Since 2001 the Istituto Superiore di Sanità established a quality assurance programme for molecular genetic testing that covers four pathologies: Cystic Fibrosis (CF), Beta Thalassemia (BT), Fragile X Syndrome (FX), and Familial Adenomatous Polyposis Coli (APC). Since 2009 this activity is an institutional activity and participation is open to both public and private laboratories. Seven rounds have been performed until now and the eighth is in progress. Laboratories receive 4 DNA samples with mock clinical indications. They analyze the samples using their routine procedures. A panel of assessors review the raw data and the reports; all data are managed through a web utility. In 2010 the number of participants was 43, 17, 15, 5 for CF, BT, FX, APC schemes respectively. Genotyping results were correct in 96%, 98.5%, 100%, and 100% of CF, BT, FX, and APC samples, respectively. Interpretation was correct in 74%, 91%, 88%, and 60% of CF, BT, FX, and APC reports, respectively; however in most of them it was not complete but a referral to genetic counseling was given. Reports were satisfactory in more than 60% of samples in all schemes. This work presents the 2010 results in detail comparing our data with those from other European schemes.

  17. "On Clocks and Clouds:" Confirming and Interpreting Climate Models as Scientific Hypotheses (Invited)

    Science.gov (United States)

    Donner, L.

    2009-12-01

    The certainty of climate change projected under various scenarios of emissions using general circulation models is an issue of vast societal importance. Unlike numerical weather prediction, a problem to which general circulation models are also applied, projected climate changes usually lie outside of the range of external forcings for which the models generating these changes have been directly evaluated. This presentation views climate models as complex scientific hypotheses and thereby frames these models within a well-defined process of both advancing scientific knowledge and recognizing its limitations. Karl Popper's Logik der Forschung (The Logic of Scientific Discovery, 1934) and 1965 essay “On Clocks and Clouds” capture well the methodologies and challenges associated with constructing climate models. Indeed, the process of a problem situation generating tentative theories, refined by error elimination, characterizes aptly the routine of general circulation model development. Limitations on certainty arise from the distinction Popper perceived in types of natural processes, which he exemplified by clocks, capable of exact measurement, and clouds, subject only to statistical approximation. Remarkably, the representation of clouds in general circulation models remains the key uncertainty in understanding atmospheric aspects of climate change. The asymmetry of hypothesis falsification by negation and much vaguer development of confidence in hypotheses consistent with some of their implications is an important practical challenge to confirming climate models. The presentation will discuss the ways in which predictions made by climate models for observable aspects of the present and past climate can be regarded as falsifiable hypotheses. The presentation will also include reasons why “passing” these tests does not provide complete confidence in predictions about the future by climate models. Finally, I will suggest that a “reductionist” view, in

  18. Constructional Volcanic Edifices on Mercury: Candidates and Hypotheses of Formation

    Science.gov (United States)

    Wright, Jack; Rothery, David A.; Balme, Matthew R.; Conway, Susan J.

    2018-04-01

    Mercury, a planet with a predominantly volcanic crust, has perplexingly few, if any, constructional volcanic edifices, despite their common occurrence on other solar system bodies with volcanic histories. Using image and topographical data from the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft, we describe two small (Earth and the Moon. Though we cannot definitively conclude that these landforms are volcanic, the paucity of constructional volcanic edifices on Mercury is intriguing in itself. We suggest that this lack is because volcanic eruptions with sufficiently low eruption volumes, rates, and flow lengths, suitable for edifice construction, were highly spatiotemporally restricted during Mercury's geological history. We suggest that volcanic edifices may preferentially occur in association with late-stage, postimpact effusive volcanic deposits. The European Space Agency/Japan Aerospace Exploration Agency BepiColombo mission to Mercury will be able to investigate further our candidate volcanic edifices; search for other, as-yet unrecognized edifices beneath the detection limits of MESSENGER data; and test our hypothesis that edifice construction is favored by late-stage, low-volume effusive eruptions.

  19. Neural reflex pathways in intestinal inflammation: hypotheses to viable therapy.

    Science.gov (United States)

    Willemze, Rose A; Luyer, Misha D; Buurman, Wim A; de Jonge, Wouter J

    2015-06-01

    Studies in neuroscience and immunology have clarified much of the anatomical and cellular basis for bidirectional interactions between the nervous and immune systems. As with other organs, intestinal immune responses and the development of immunity seems to be modulated by neural reflexes. Sympathetic immune modulation and reflexes are well described, and in the past decade the parasympathetic efferent vagus nerve has been added to this immune-regulation network. This system, designated 'the inflammatory reflex', comprises an afferent arm that senses inflammation and an efferent arm that inhibits innate immune responses. Intervention in this system as an innovative principle is currently being tested in pioneering trials of vagus nerve stimulation using implantable devices to treat IBD. Patients benefit from this treatment, but some of the working mechanisms remain to be established, for instance, treatment is effective despite the vagus nerve not always directly innervating the inflamed tissue. In this Review, we will focus on the direct neuronal regulatory mechanisms of immunity in the intestine, taking into account current advances regarding the innervation of the spleen and lymphoid organs, with a focus on the potential for treatment in IBD and other gastrointestinal pathologies.

  20. [Irritable bowel syndrome: New pathophysiological hypotheses and practical issues].

    Science.gov (United States)

    Duboc, H; Dior, M; Coffin, B

    2016-08-01

    In 2015, besides the fact that it still fills the gastroenterologists' offices and impairs patient's quality of life, the irritable bowel syndrome has considerably evolved on several points. The pathophysiology is now organized around a consensual hypothesis called the "brain-gut axis", which gather all the influences of peripheral factors as gut microbiota or local serotonin secretion, on the central pain perception, contributing to visceral hypersensitivity and transit modifications. About the diagnosis, the key message is "avoid over-prescription" of additional tests, and reminds that a positive clinical diagnosis based on Rome III criteria is possible after the elimination of simple clinical warning signs. Finally, the food component, a neglected and historical claim of patients, finally finds a strong scientific rational, with a diet low in fermentable sugar and polyols, that gives positive and reproducible results. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  1. A simple and cost-effective method of DNA extraction from small formalin-fixed paraffin-embedded tissue for molecular oncologic testing.

    Science.gov (United States)

    Snow, Anthony N; Stence, Aaron A; Pruessner, Jonathan A; Bossler, Aaron D; Ma, Deqin

    2014-01-01

    Extraction of DNA from formalin-fixed, paraffin-embedded (FFPE) tissue is a critical step in molecular oncologic testing. As molecular oncology testing becomes more important for prognostic and therapeutic decision making and tissue specimens become smaller due to earlier detection of suspicious lesions and the use of fine needle aspiration methods for tissue collection, it becomes more challenging for the typical molecular pathology laboratory to obtain reliable test results. We developed a DNA extraction method to obtain sufficient quantity and high quality genomic DNA from limited FFPE tissue for molecular oncology testing using a combination of H&E stained slides, a matrix capture method and the Qiagen DNA column. THREE DNA EXTRACTION METHODS WERE COMPARED: our standard procedure of manually scraping tissue from unstained slides followed by DNA extraction using the QIAamp FFPE column (Qiagen, Valencia, CA), a glue capture method (Pinpoint Solution, Zymo Research Corp, Inc) on H&E stained slides followed by DNA extraction using either the QIAamp column or the column included with the Pinpoint kit (Zymo Research). The DNA extraction protocol was optimized. Statistical analysis was performed using the paired two-sample student's t-test. The combination of the matrix capture method with the QIAamp column gave an equivalent amount of DNA as our standard extraction method using the unstained slides and a 4.6-fold higher DNA yield than using the Zymo column included in the Pinpoint Slide Solution kit. Several molecular tests were performed and DNA purified using the new method gave the same results as for the previous methods. Using H&E stained slides allows visual confirmation of tumor cells during microdissection. The Pinpoint solution made removal of specific tissue from the slides easier and reduced the risk of contamination and tissue loss. This DNA extraction method is simple, cost-effective, and blends with our current workflow requiring no additional equipment.

  2. Molecular testing guidelines for lung adenocarcinoma: Utility of cell blocks and concordance between fine-needle aspiration cytology and histology samples

    Science.gov (United States)

    Heymann, Jonas J.; Bulman, William A.; Maxfield, Roger A.; Powell, Charles A.; Halmos, Balazs; Sonett, Joshua; Beaubier, Nike T.; Crapanzano, John P.; Mansukhani, Mahesh M.; Saqi, Anjali

    2014-01-01

    Background: Lung cancer is a leading cause of mortality, and patients often present at a late stage. More recently, advances in screening, diagnosing, and treating lung cancer have been made. For instance, greater numbers of minimally invasive procedures are being performed, and identification of lung adenocarcinoma driver mutations has led to the implementation of targeted therapies. Advances in molecular techniques enable use of scant tissue, including cytology specimens. In addition, per recently published consensus guidelines, cytology-derived cell blocks (CBs) are preferred over direct smears. Yet, limited comparison of molecular testing of fine-needle aspiration (FNA) CBs and corresponding histology specimens has been performed. This study aimed to establish concordance of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (KRAS) virus homolog testing between FNA CBs and histology samples from the same patients. Materials and Methods: Patients for whom molecular testing for EGFR or KRAS was performed on both FNA CBs and histology samples containing lung adenocarcinoma were identified retrospectively. Following microdissection, when necessary, concordance of EGFR and KRAS molecular testing results between FNA CBs and histology samples was evaluated. Results: EGFR and/or KRAS testing was performed on samples obtained from 26 patients. Concordant results were obtained for all EGFR (22/22) and KRAS (17/17) mutation analyses performed. Conclusions: Identification of mutations in lung adenocarcinomas affects clinical decision-making, and it is important that results from small samples be accurate. This study demonstrates that molecular testing on cytology CBs is as sensitive and specific as that on histology. PMID:24987443

  3. Molecular testing guidelines for lung adenocarcinoma: Utility of cell blocks and concordance between fine-needle aspiration cytology and histology samples

    Directory of Open Access Journals (Sweden)

    Jonas J. Heymann

    2014-01-01

    Full Text Available Background: Lung cancer is a leading cause of mortality, and patients often present at a late stage. More recently, advances in screening, diagnosing, and treating lung cancer have been made. For instance, greater numbers of minimally invasive procedures are being performed, and identification of lung adenocarcinoma driver mutations has led to the implementation of targeted therapies. Advances in molecular techniques enable use of scant tissue, including cytology specimens. In addition, per recently published consensus guidelines, cytology-derived cell blocks (CBs are preferred over direct smears. Yet, limited comparison of molecular testing of fine-needle aspiration (FNA CBs and corresponding histology specimens has been performed. This study aimed to establish concordance of epidermal growth factor receptor (EGFR and Kirsten rat sarcoma (KRAS virus homolog testing between FNA CBs and histology samples from the same patients. Materials and Methods: Patients for whom molecular testing for EGFR or KRAS was performed on both FNA CBs and histology samples containing lung adenocarcinoma were identified retrospectively. Following microdissection, when necessary, concordance of EGFR and KRAS molecular testing results between FNA CBs and histology samples was evaluated. Results: EGFR and/or KRAS testing was performed on samples obtained from 26 patients. Concordant results were obtained for all EGFR (22/22 and KRAS (17/17 mutation analyses performed. Conclusions: Identification of mutations in lung adenocarcinomas affects clinical decision-making, and it is important that results from small samples be accurate. This study demonstrates that molecular testing on cytology CBs is as sensitive and specific as that on histology.

  4. Unexplained Graft Dysfunction after Heart Transplantation—Role of Novel Molecular Expression Test Score and QTc-Interval: A Case Report

    Directory of Open Access Journals (Sweden)

    Khurram Shahzad

    2010-01-01

    Full Text Available In the current era of immunosuppressive medications there is increased observed incidence of graft dysfunction in the absence of known histological criteria of rejection after heart transplantation. A noninvasive molecular expression diagnostic test was developed and validated to rule out histological acute cellular rejection. In this paper we present for the first time, longitudinal pattern of changes in this novel diagnostic test score along with QTc-interval in a patient who was admitted with unexplained graft dysfunction. Patient presented with graft failure with negative findings on all known criteria of rejection including acute cellular rejection, antibody mediated rejection and cardiac allograft vasculopathy. The molecular expression test score showed gradual increase and QTc-interval showed gradual prolongation with the gradual decline in graft function. This paper exemplifies that in patients presenting with unexplained graft dysfunction, GEP test score and QTc-interval correlate with the changes in the graft function.

  5. Cancer risks near nuclear facilities: the importance of research design and explicit study hypotheses.

    Science.gov (United States)

    Wing, Steve; Richardson, David B; Hoffmann, Wolfgang

    2011-04-01

    In April 2010, the U.S. Nuclear Regulatory Commission asked the National Academy of Sciences to update a 1990 study of cancer risks near nuclear facilities. Prior research on this topic has suffered from problems in hypothesis formulation and research design. We review epidemiologic principles used in studies of generic exposure-response associations and in studies of specific sources of exposure. We then describe logical problems with assumptions, formation of testable hypotheses, and interpretation of evidence in previous research on cancer risks near nuclear facilities. Advancement of knowledge about cancer risks near nuclear facilities depends on testing specific hypotheses grounded in physical and biological mechanisms of exposure and susceptibility while considering sample size and ability to adequately quantify exposure, ascertain cancer cases, and evaluate plausible confounders. Next steps in advancing knowledge about cancer risks near nuclear facilities require studies of childhood cancer incidence, focus on in utero and early childhood exposures, use of specific geographic information, and consideration of pathways for transport and uptake of radionuclides. Studies of cancer mortality among adults, cancers with long latencies, large geographic zones, and populations that reside at large distances from nuclear facilities are better suited for public relations than for scientific purposes.

  6. Molecular identification and amphotericin B susceptibility testing of clinical isolates of Aspergillus from 11 hospitals in Korea.

    Science.gov (United States)

    Heo, Min Seok; Shin, Jong Hee; Choi, Min Ji; Park, Yeon Joon; Lee, Hye Soo; Koo, Sun Hoe; Lee, Won Gil; Kim, Soo Hyun; Shin, Myung Geun; Suh, Soon Pal; Ryang, Dong Wook

    2015-11-01

    We investigated the species distribution and amphotericin B (AMB) susceptibility of Korean clinical Aspergillus isolates by using two Etests and the CLSI broth microdilution method. A total of 136 Aspergillus isolates obtained from 11 university hospitals were identified by sequencing the internal transcribed spacer (ITS) and β-tubulin genomic regions. Minimal inhibitory concentrations (MICs) of AMB were determined in Etests using Mueller-Hinton agar (Etest-MH) and RPMI agar (Etest-RPG), and categorical agreement with the CLSI method was assessed by using epidemiological cutoff values. ITS sequencing identified the following six Aspergillus species complexes: Aspergillus fumigatus (42.6% of the isolates), A. niger (23.5%), A. flavus (17.6%), A. terreus (11.0%), A. versicolor (4.4%), and A. ustus (0.7%). Cryptic species identifiable by β-tubulin sequencing accounted for 25.7% (35/136) of the isolates. Of all 136 isolates, 36 (26.5%) had AMB MICs of ≥2 μg/mL by the CLSI method. The categorical agreement of Etest-RPG with the CLSI method was 98% for the A. fumigatus, A. niger, and A. versicolor complexes, 87% for the A. terreus complex, and 37.5% for the A. flavus complex. That of Etest-MH was ≤75% for the A. niger, A. flavus, A. terreus, and A. versicolor complexes but was higher for the A. fumigatus complex (98.3%). Aspergillus species other than A. fumigatus constitute about 60% of clinical Aspergillus isolates, and reduced AMB susceptibility is common among clinical isolates of Aspergillus in Korea. Molecular identification and AMB susceptibility testing by Etest-RPG may be useful for characterizing Aspergillus isolates of clinical relevance.

  7. Impact of rapid molecular diagnostic tests on time to treatment initiation and outcomes in patients with multidrug-resistant tuberculosis, Tamil Nadu, India.

    Science.gov (United States)

    Nair, Dina; Navneethapandian, Pooranaganga D; Tripathy, Jaya Prasad; Harries, Anthony D; Klinton, Joel S; Watson, Basilea; Sivaramakrishnan, Gomathi N; Reddy, Devarajulu S; Murali, Lakshmi; Natrajan, Mohan; Swaminathan, Soumya

    2016-09-01

    India is replacing culture and drug sensitivity testing (CDST) with rapid molecular tests for diagnosing MDR-TB. We assessed the impact of rapid tests on time to initiation of treatment and outcomes in patients with MDR-TB compared with CDST. A retrospective cohort study involving MDR-TB patients from six districts in Tamil Nadu state, who underwent CDST (2010-2011) and rapid tests (2012-2013). There were 135 patients in the CDST group and 389 in the rapid diagnostic test group. Median time from sputum receipt at the laboratory to initiation of MDR-TB treatment was 130 days (IQR 75-213) in the CDST group and 22 days (IQR 14-38) in the rapid diagnostic test group (p30% in both groups and missing data were higher in CDST (13%) compared with rapid tests (3%). There were significantly higher risks of unfavourable treatment outcomes in males (aRR 1.3, 95% CI 1.1-1.5) and those with treatment initiation delays >30 days (aRR 1.3, 95% CI 1.0-1.6). Rapid molecular diagnostic tests shortened the time to initiate treatment which was associated with reduced unfavourable outcomes in MDR-TB patients. This supports the policy to scale up these tests in India. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Molecular Testing of Nodules with a Suspicious or Malignant Cytologic Diagnosis in the Setting of Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP).

    Science.gov (United States)

    Strickland, Kyle C; Eszlinger, Markus; Paschke, Ralf; Angell, Trevor E; Alexander, Erik K; Marqusee, Ellen; Nehs, Matthew A; Jo, Vickie Y; Lowe, Alarice; Vivero, Marina; Hollowell, Monica; Qian, Xiaohua; Wieczorek, Tad; French, Christopher A; Teot, Lisa A; Cibas, Edmund S; Lindeman, Neal I; Krane, Jeffrey F; Barletta, Justine A

    2018-03-01

    Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is an indolent thyroid tumor characterized by frequent RAS mutations and an absence of the BRAF V600E mutation commonly seen in classical papillary thyroid carcinoma (cPTC). The ability to differentiate potential NIFTP/follicular variant of papillary thyroid carcinoma (FVPTC) from cPTC at the time of fine-needle aspiration (FNA) can facilitate conservative management of NIFTP. The aim of the current study was to investigate how molecular testing may add to cytologic assessment in the pre-operative differentiation of potential NIFTP/FVPTC and cPTC. We had previously evaluated cytologists' ability to prospectively distinguish potential NIFTP/FVPTC from cPTC in a cohort of 56 consecutive FNAs diagnosed as malignant or suspicious for malignancy. We utilized this cohort to perform molecular analysis. Detected molecular abnormalities were stratified into two groups: (1) those supporting malignancy and (2) those supporting a diagnosis of potential NIFTP/FVPTC. The cytologists' characterization of cases and the detected molecular alterations were correlated with the final histologic diagnoses. Molecular testing was performed in 52 (93%) of the 56 cases. For the 37 cases cytologists favored to be cPTC, 31 (84%) had a molecular result that supported malignancy (28 BRAF V600E mutations, 2 NTRK1 fusions, 1 AGK-BRAF fusion). For the 8 cases that were favored to be NIFTP/FVPTC by cytologists, 7 (88%) had a molecular result that supported conservative management (1 NRAS mutation, 6 wild-type result). Seven cases were designated as cytomorphologically indeterminate for NIFTP/FVPTC or cPTC, of which 6 (86%) had a molecular result that would have aided in the pre-operative assessment of potential NIFTP/FVPTC or cPTC/malignancy. These included 3 BRAF V600E mutations in nodules that were cPTC on resection, an HRAS mutation, and a wild-type result in the 2 nodules that were NIFTP, and a TERT promoter

  9. Agent-Based Modeling in Molecular Systems Biology.

    Science.gov (United States)

    Soheilypour, Mohammad; Mofrad, Mohammad R K

    2018-06-08

    Molecular systems orchestrating the biology of the cell typically involve a complex web of interactions among various components and span a vast range of spatial and temporal scales. Computational methods have advanced our understanding of the behavior of molecular systems by enabling us to test assumptions and hypotheses, explore the effect of different parameters on the outcome, and eventually guide experiments. While several different mathematical and computational methods are developed to study molecular systems at different spatiotemporal scales, there is still a need for methods that bridge the gap between spatially-detailed and computationally-efficient approaches. In this review, we summarize the capabilities of agent-based modeling (ABM) as an emerging molecular systems biology technique that provides researchers with a new tool in exploring the dynamics of molecular systems/pathways in health and disease. © 2018 WILEY Periodicals, Inc.

  10. Why Victory in the War on Cancer Remains Elusive: Biomedical Hypotheses and Mathematical Models

    Directory of Open Access Journals (Sweden)

    Leonid Hanin

    2011-01-01

    Full Text Available We discuss philosophical, methodological, and biomedical grounds for the traditional paradigm of cancer and some of its critical flaws. We also review some potentially fruitful approaches to understanding cancer and its treatment. This includes the new paradigm of cancer that was developed over the last 15 years by Michael Retsky, Michael Baum, Romano Demicheli, Isaac Gukas, William Hrushesky and their colleagues on the basis of earlier pioneering work of Bernard Fisher and Judah Folkman. Next, we highlight the unique and pivotal role of mathematical modeling in testing biomedical hypotheses about the natural history of cancer and the effects of its treatment, elaborate on model selection criteria, and mention some methodological pitfalls. Finally, we describe a specific mathematical model of cancer progression that supports all the main postulates of the new paradigm of cancer when applied to the natural history of a particular breast cancer patient and fit to the observables.

  11. Importance and pitfalls of molecular analysis to parasite epidemiology.

    Science.gov (United States)

    Constantine, Clare C

    2003-08-01

    Molecular tools are increasingly being used to address questions about parasite epidemiology. Parasites represent a diverse group and they might not fit traditional population genetic models. Testing hypotheses depends equally on correct sampling, appropriate tool and/or marker choice, appropriate analysis and careful interpretation. All methods of analysis make assumptions which, if violated, make the results invalid. Some guidelines to avoid common pitfalls are offered here.

  12. The agony of choice in dermatophyte diagnostics-performance of different molecular tests and culture in the detection of Trichophyton rubrum and Trichophyton interdigitale.

    Science.gov (United States)

    Kupsch, C; Ohst, T; Pankewitz, F; Nenoff, P; Uhrlaß, S; Winter, I; Gräser, Y

    2016-08-01

    Dermatophytosis caused by dermatophytes of the genera Trichophyton and Microsporum belong to the most frequent mycoses worldwide. Molecular detection methods proved to be highly sensitive and enable rapid and accurate detection of dermatophyte species from clinical specimens. For the first time, we compare the performance of different molecular methods with each other and with conventional diagnostics in the detection of dermatophytoses caused by Trichophyton rubrum and Trichophyton interdigitale in clinical specimens (nail, skin and hair). The compared molecular methods comprise two already published PCR-ELISAs, a published quantitative RT-PCR as well as a newly developed PCR-ELISA targeting the internal transcribed spacer region. We investigated the sensitivity of the assays by analysing 375 clinical samples. In 148 specimens (39.5%) a positive result was gained in at least one of the four molecular tests or by culture, but the number of detected agents differed significantly between some of the assays. The most sensitive assay, a PCR-ELISA targeting a microsatellite region, detected 81 T. rubrum infections followed by an internal transcribed spacer PCR-ELISA (60), quantitative RT-PCR (52) and a topoisomerase II PCR-ELISA (51), whereas cultivation resulted in T. rubrum identification in 37 samples. The pros and cons of all four tests in routine diagnostics are discussed. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  13. Molecular HIV screening.

    Science.gov (United States)

    Bourlet, Thomas; Memmi, Meriam; Saoudin, Henia; Pozzetto, Bruno

    2013-09-01

    Nuclear acid testing is more and more used for the diagnosis of infectious diseases. This paper focuses on the use of molecular tools for HIV screening. The term 'screening' will be used under the meaning of first-line HIV molecular techniques performed on a routine basis, which excludes HIV molecular tests designed to confirm or infirm a newly discovered HIV-seropositive patient or other molecular tests performed for the follow-up of HIV-infected patients. The following items are developed successively: i) presentation of the variety of molecular tools used for molecular HIV screening, ii) use of HIV molecular tools for the screening of blood products, iii) use of HIV molecular tools for the screening of organs and tissue from human origin, iv) use of HIV molecular tools in medically assisted procreation and v) use of HIV molecular tools in neonates from HIV-infected mothers.

  14. Molecular tools for diagnosis of visceral leishmaniasis: systematic review and meta-analysis of diagnostic test accuracy

    NARCIS (Netherlands)

    de Ruiter, C. M.; van der Veer, C.; Leeflang, M. M. G.; Deborggraeve, S.; Lucas, C.; Adams, E. R.

    2014-01-01

    Molecular methods have been proposed as highly sensitive tools for the detection of Leishmania parasites in visceral leishmaniasis (VL) patients. Here, we evaluate the diagnostic accuracy of these tools in a meta-analysis of the published literature. The selection criteria were original studies that

  15. The Hydrological Open Air Laboratory (HOAL) in Petzenkirchen: a hypotheses driven observatory

    Science.gov (United States)

    Blöschl, G.; Blaschke, A. P.; Broer, M.; Bucher, C.; Carr, G.; Chen, X.; Eder, A.; Exner-Kittridge, M.; Farnleitner, A.; Flores-Orozco, A.; Haas, P.; Hogan, P.; Kazemi Amiri, A.; Oismüller, M.; Parajka, J.; Silasari, R.; Stadler, P.; Strauß, P.; Vreugdenhil, M.; Wagner, W.; Zessner, M.

    2015-07-01

    Hydrological observatories bear a lot of resemblance to the more traditional research catchment concept but tend to differ in providing more long term facilities that transcend the lifetime of individual projects, are more strongly geared towards performing interdisciplinary research, and are often designed as networks to assist in performing collaborative science. This paper illustrates how the experimental and monitoring setup of an observatory, the 66 ha Hydrological Open Air Laboratory (HOAL) in Petzenkirchen, Lower Austria, has been established in a way that allows meaningful hypothesis testing. The overarching science questions guided site selection, identifying dissertation topics and the base monitoring. The specific hypotheses guided the dedicated monitoring and sampling, individual experiments, and repeated experiments with controlled boundary conditions. The purpose of the HOAL is to advance the understanding of water related flow and transport processes involving sediments, nutrients and microbes in small catchments. The HOAL catchment is ideally suited for this purpose, because it features a range of different runoff generation processes (surface runoff, springs, tile drains, wetlands), the nutrient inputs are known, and it is convenient from a logistic point of view as all instruments can be connected to the power grid and a high speed glassfibre Local Area Network. The multitude of runoff generation mechanisms in the catchment provide a genuine laboratory where hypotheses of flow and transport can be tested, either by controlled experiments or by contrasting sub-regions of different characteristics. This diversity also ensures that the HOAL is representative of a range of catchments around the world and the specific process findings from the HOAL are applicable to a variety of agricultural catchment settings. The HOAL is operated jointly by the Vienna University of Technology and the Federal Agency for Water Management and takes advantage of the

  16. Quantitative analysis of dental microwear in hadrosaurid dinosaurs, and the implications for hypotheses of jaw mechanics and feeding

    Science.gov (United States)

    Williams, Vincent S.; Barrett, Paul M.; Purnell, Mark A.

    2009-01-01

    Understanding the feeding mechanisms and diet of nonavian dinosaurs is fundamental to understanding the paleobiology of these taxa and their role in Mesozoic terrestrial ecosystems. Various methods, including biomechanical analysis and 3D computer modeling, have been used to generate detailed functional hypotheses, but in the absence of either direct observations of dinosaur feeding behavior, or close living functional analogues, testing these hypotheses is problematic. Microscopic scratches that form on teeth in vivo during feeding are known to record the relative motion of the tooth rows to each other during feeding and to capture evidence of tooth–food interactions. Analysis of this dental microwear provides a powerful tool for testing hypotheses of jaw mechanics, diet, and trophic niche; yet, quantitative analysis of microwear in dinosaurs has not been attempted. Here, we show that analysis of tooth microwear orientation provides direct evidence for the relative motions of jaws during feeding in hadrosaurid ornithopods, the dominant terrestrial herbivores of the Late Cretaceous. Statistical testing demonstrates that Edmontosaurus teeth preserve 4 distinct sets of scratches in different orientations. In terms of jaw mechanics, these data indicate an isognathic, near-vertical posterodorsal power stroke during feeding; near-vertical jaw opening; and propalinal movements in near anterior and near posterior directions. Our analysis supports the presence of a pleurokinetic hinge, and the straightness and parallelism of scratches indicate a tightly controlled occlusion. The dominance of scratched microwear fabrics suggests that Edmontosaurus was a grazer rather than a browser. PMID:19564603

  17. Molecular evidence of malaria and zoonotic diseases among rapid diagnostic test-negative febrile patients in low-transmission season, Mali

    DEFF Research Database (Denmark)

    Touré, Mahamoudou; Petersen, Pelle T; Bathily, Sidy N'd

    2017-01-01

    From November to December 2012 in Sélingué-Mali, blood samples from 88 febrile patients who tested negative by malaria Paracheck (®) rapid diagnostic tests (RDTs) were used to assess the presence of sub-RDT Plasmodium falciparum as well as Borrelia, Coxiella burnetii, and Babesia applying molecular...... tools. Plasmodium sp. was present among 57 (60.2%) of the 88 malaria RDT-negative patients, whereas the prevalence of Borrelia, C. burnetii, and Babesia were 3.4% (N = 3), 1.1% (N = 1), and 0.0%, respectively. The additional diagnostic use of polymerase chain reaction (PCR) identified a high proportion...

  18. Country-wide surveillance of molecular markers of antimalarial drug resistance in Senegal by use of positive Malaria Rapid Diagnostic Tests

    DEFF Research Database (Denmark)

    Ndiaye, Magatte; Sow, Doudou; Nag, Sidsel

    2017-01-01

    of drug resistance. Therefore, surveillance of drug resistance in the malaria parasites is essential. The objective of this pilot study was to test the feasibility of routinely sampled malaria rapid diagnostic tests (RDTs) at a national scale to assess the temporal changes in the molecular profiles...... of antimalarial drug resistance markers of Plasmodium falciparum parasites. Overall, 9,549 positive malaria RDTs were collected from 14 health facilities across the country. A limited random set of RDTs were analyzed regarding Pfcrt gene polymorphisms at codon 72-76. Overall, a high but varied prevalence (> 50...

  19. The Use of the Molecular Adsorber Coating Technology to Mitigate Vacuum Chamber Contamination During Pathfinder Testing for the James Webb Space Telescope

    Science.gov (United States)

    Abraham, Nithin S.; Hasegawa, Mark M.; Wooldridge, Eve M.; Henderson-Nelson, Kelly A.

    2016-01-01

    As a coating made of highly porous zeolite materials, the Molecular Adsorber Coating (MAC) was developed to capture outgassed molecular contaminants, such as hydrocarbons and silicones. For spaceflight applications, the adsorptive capabilities of the coating can alleviate on-orbit outgassing concerns on or near sensitive surfaces and instruments within the spacecraft. Similarly, this sprayable paint technology has proven to be significantly beneficial for ground based space applications, in particular, for vacuum chamber environments. This paper describes the recent use of the MAC technology during Pathfinder testing of the Optical Ground Support Equipment (OGSE) for the James Webb Space Telescope (JWST) at NASA Johnson Space Center (JSC). The coating was used as a mitigation tool to entrap persistent outgassed contaminants, specifically silicone based diffusion pump oil, from within JSC's cryogenic optical vacuum chamber test facility called Chamber A. This paper summarizes the sample fabrication, installation, laboratory testing, post-test chemical analysis results, and future plans for the MAC technology, which was effectively used to protect the JWST test equipment from vacuum chamber contamination.

  20. Evaluating hypotheses in geolocation on a very large sample of Twitter

    DEFF Research Database (Denmark)

    Salehi, Bahar; Søgaard, Anders

    2017-01-01

    Recent work in geolocation has madeseveral hypotheses about what linguisticmarkers are relevant to detect where peoplewrite from. In this paper, we examinesix hypotheses against a corpus consistingof all geo-tagged tweets from theUS, or whose geo-tags could be inferred,in a 19% sample of Twitter...

  1. Molecular Solutions to Low Vision Resulting from Battlefield Injuries

    National Research Council Canada - National Science Library

    Dartt, Darlene A

    2006-01-01

    We hypothesize that targeted molecular intervention can preserve vision threatened by battlefield trauma-induced corneal andretinal inflammation corneal and retina/optic nerve apoptosis ocular surface...

  2. Test

    DEFF Research Database (Denmark)

    Bendixen, Carsten

    2014-01-01

    Bidrag med en kortfattet, introducerende, perspektiverende og begrebsafklarende fremstilling af begrebet test i det pædagogiske univers.......Bidrag med en kortfattet, introducerende, perspektiverende og begrebsafklarende fremstilling af begrebet test i det pædagogiske univers....

  3. Design of a Tablet Computer App for Facilitation of a Molecular Blood Culture Test in Clinical Microbiology and Preliminary Usability Evaluation.

    Science.gov (United States)

    Samson, Lasse L; Pape-Haugaard, Louise; Meltzer, Michelle C; Fuchs, Martin; Schønheyder, Henrik C; Hejlesen, Ole

    2016-03-18

    User mobility is an important aspect of the development of clinical information systems for health care professionals. Mobile phones and tablet computers have obtained widespread use by health care professionals, offering an opportunity for supporting the access to patient information through specialized applications (apps) while supporting the mobility of the users. The use of apps for mobile phones and tablet computers may support workflow of complex tasks, for example, molecular-based diagnostic tests in clinical microbiology. Multiplex Blood Culture Test (MuxBCT) is a molecular-based diagnostic test used for rapid identification of pathogens in positive blood cultures. To facilitate the workflow of the MuxBCT, a specialized tablet computer app was developed as an accessory to the diagnostic test. The app aims to reduce the complexity of the test by step-by-step guidance of microscopy and to assist users in reaching an exact bacterial or fungal diagnosis based on blood specimen observations and controls. Additionally, the app allows for entry of test results, and communication thereof to the laboratory information system (LIS). The objective of the study was to describe the design considerations of the MuxBCT app and the results of a preliminary usability evaluation. The MuxBCT tablet app was developed and set up for use in a clinical microbiology laboratory. A near-live simulation study was conducted in the clinical microbiology laboratory to evaluate the usability of the MuxBCT app. The study was designed to achieve a high degree of realism as participants carried out a scenario representing the context of use for the MuxBCT app. As the MuxBCT was under development, the scenario involved the use of molecular blood culture tests similar to the MuxBCT for identification of microorganisms from positive blood culture samples. The study participants were observed, and their interactions with the app were recorded. After the study, the participants were debriefed to

  4. Life History theory hypotheses on child growth: Potential implications for short and long-term child growth, development and health.

    Science.gov (United States)

    Said-Mohamed, Rihlat; Pettifor, John M; Norris, Shane A

    2018-01-01

    Life history theory integrates ecological, physiological, and molecular layers within an evolutionary framework to understand organisms' strategies to optimize survival and reproduction. Two life history hypotheses and their implications for child growth, development, and health (illustrated in the South African context) are reviewed here. One hypothesis suggests that there is an energy trade-off between linear growth and brain growth. Undernutrition in infancy and childhood may trigger adaptive physiological mechanisms prioritizing the brain at the expense of body growth. Another hypothesis is that the period from conception to infancy is a critical window of developmental plasticity of linear growth, the duration of which may vary between and within populations. The transition from infancy to childhood may mark the end of a critical window of opportunity for improving child growth. Both hypotheses emphasize the developmental plasticity of linear growth and the potential determinants of growth variability (including the role of parent-offspring conflict in maternal resources allocation). Implications of these hypotheses in populations with high burdens of undernutrition and infections are discussed. In South Africa, HIV/AIDS during pregnancy (associated with adverse birth outcomes, short duration of breastfeeding, and social consequences) may lead to a shortened window of developmental plasticity of growth. Furthermore, undernutrition and infectious diseases in children living in South Africa, a country undergoing a rapid nutrition transition, may have adverse consequences on individuals' cognitive abilities and risks of cardio-metabolic diseases. Studies are needed to identify physiological mechanisms underlying energy allocation between biological functions and their potential impacts on health. © 2017 Wiley Periodicals, Inc.

  5. Confidence judgment in depression and dysphoria: the depressive realism vs. negativity hypotheses.

    Science.gov (United States)

    Szu-Ting Fu, Tiffany; Koutstaal, Wilma; Poon, Lucia; Cleare, Anthony J

    2012-06-01

    According to the negativity hypothesis, depressed individuals are over-pessimistic due to negative self-concepts. In contrast, depressive realism suggests that depressed persons are realistic compared to their nondepressed controls. However, evidence supporting depressive realism predominantly comes from judgment comparisons between controls and nonclinical dysphoric samples when the controls showed overconfident bias. This study aimed to test the validity of the two accounts in clinical depression and dysphoria. Sixty-eight participants, including healthy controls (n = 32), patients with DSM-IV major depression (n = 20), and dysphoric participants with CDC-defined chronic fatigue syndrome (n = 16) performed an adjective recognition task and reported their item-by-item confidence judgments and post-test performance estimate (PTPE). Compared to realistic PTPE made by the controls, patients with major depression showed significant underconfidence. The PTPE of the dysphoric participants was relatively accurate. Both the depressed and dysphoric participants displayed less item-by-item overconfidence as opposed to significant item-by-item overconfidence shown by the controls. The judgment-accuracy patterns of the three groups need to be replicated with larger samples using non-memory task domains. The present study confirms depressive realism in dysphoric individuals. However, toward a more severe depressive emotional state, the findings did not support depressive realism but are in line with the prediction of the negativity hypothesis. It is not possible to determine the validity of the two hypotheses when the controls are overconfident. Dissociation between item-by-item and retrospective confidence judgments is discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Examining competing hypotheses for the effects of diagrams on recall for text.

    Science.gov (United States)

    Ortegren, Francesca R; Serra, Michael J; England, Benjamin D

    2015-01-01

    Supplementing text-based learning materials with diagrams typically increases students' free recall and cued recall of the presented information. In the present experiments, we examined competing hypotheses for why this occurs. More specifically, although diagrams are visual, they also serve to repeat information from the text they accompany. Both visual presentation and repetition are known to aid students' recall of information. To examine to what extent diagrams aid recall because they are visual or repetitive (or both), we had college students in two experiments (n = 320) read a science text about how lightning storms develop before completing free-recall and cued-recall tests over the presented information. Between groups, we manipulated the format and repetition of target pieces of information in the study materials using a 2 (visual presentation of target information: diagrams present vs. diagrams absent) × 2 (repetition of target information: present vs. absent) between-participants factorial design. Repetition increased both the free recall and cued recall of target information, and this occurred regardless of whether that repetition was in the form of text or a diagram. In contrast, the visual presentation of information never aided free recall. Furthermore, visual presentation alone did not significantly aid cued recall when participants studied the materials once before the test (Experiment 1) but did when they studied the materials twice (Experiment 2). Taken together, the results of the present experiments demonstrate the important role of repetition (i.e., that diagrams repeat information from the text) over the visual nature of diagrams in producing the benefits of diagrams for recall.

  7. Prioritizing molecular markers to test for in the initial workup of advanced non-small cell lung cancer: wants versus needs.

    Science.gov (United States)

    West, Howard

    2017-09-01

    The current standard of care for molecular marker testing in patients with advanced non-small cell lung cancer (NSCLC) has been evolving over several years and is a product of the quality of the evidence supporting a targeted therapy for a specific molecular marker, the pre-test probability of that marker in the population, and the magnitude of benefit seen with that treatment. Among the markers that have one or more matched targeted therapies, only a few are in the subset for which they should be considered as most clearly worthy of prioritizing to detect in the first line setting in order to have them supplant other first line alternatives, and in only a subset of patients, as defined currently by NSCLC histology. Specifically, this currently includes testing for an activating epidermal growth factor receptor ( EGFR ) mutation or an anaplastic lymphoma kinase ( ALK ) or ROS1 rearrangement. This article reviews the history and data supporting the prioritization of these markers in patients with non-squamous NSCLC, a histologically selected population in whom the probability of these markers combined with the anticipated efficacy of targeted therapies against them is high enough to favor these treatments in the first line setting. In reviewing the evidence supporting this very limited core subset of most valuable molecular markers to detect in the initial workup of such patients, we can also see the criteria by which other actionable markers need to reach in order to be widely recognized as reliably valuable enough to warrant prioritization to detect in the initial workup of advanced NSCLC as well.

  8. A novel approach to generating CER hypotheses based on mining clinical data.

    Science.gov (United States)

    Zhang, Shuo; Li, Lin; Yu, Yiqin; Sun, Xingzhi; Xu, Linhao; Zhao, Wei; Teng, Xiaofei; Pan, Yue

    2013-01-01

    Comparative effectiveness research (CER) is a scientific method of investigating the effectiveness of alternative intervention methods. In a CER study, clinical researchers typically start with a CER hypothesis, and aim to evaluate it by applying a series of medical statistical methods. Traditionally, the CER hypotheses are defined manually by clinical researchers. This makes the task of hypothesis generation very time-consuming and the quality of hypothesis heavily dependent on the researchers' skills. Recently, with more electronic medical data being collected, it is highly promising to apply the computerized method for discovering CER hypotheses from clinical data sets. In this poster, we proposes a novel approach to automatically generating CER hypotheses based on mining clinical data, and presents a case study showing that the approach can facilitate clinical researchers to identify potentially valuable hypotheses and eventually define high quality CER studies.

  9. Corrigendum to: Bayesian evaluation of informative hypotheses in SEM using Mplus

    NARCIS (Netherlands)

    van de Schoot, R.; Verhoeven, Marjolein; Hoijtink, H.

    2014-01-01

    This paper corrects: van de Schoot, R., Verhoeven, M., & Hoijtink, H. (2013). Bayesian evaluation ofinformative hypotheses in SEM using Mplus: A black bear story. EuropeanJournal of Developmental Psychology, 10, 81 –98.

  10. From existing data to novel hypotheses : design and application of structure-based Molecular Class Specific Information Systems

    NARCIS (Netherlands)

    Kuipers, R.K.P.

    2012-01-01

    As the active component of many biological systems, proteins are of great interest to life scientists. Proteins are used in a large number of different applications such as the production of precursors and compounds, for bioremediation, as drug targets, to diagnose patients suffering from

  11. Functional Testing of SLC26A4 Variants—Clinical and Molecular Analysis of a Cohort with Enlarged Vestibular Aqueduct from Austria

    Science.gov (United States)

    Bernardinelli, Emanuele; Nofziger, Charity; Patsch, Wolfgang; Rasp, Gerd; Paulmichl, Markus; Dossena, Silvia

    2018-01-01

    The prevalence and spectrum of sequence alterations in the SLC26A4 gene, which codes for the anion exchanger pendrin, are population-specific and account for at least 50% of cases of non-syndromic hearing loss associated with an enlarged vestibular aqueduct. A cohort of nineteen patients from Austria with hearing loss and a radiological alteration of the vestibular aqueduct underwent Sanger sequencing of SLC26A4 and GJB2, coding for connexin 26. The pathogenicity of sequence alterations detected was assessed by determining ion transport and molecular features of the corresponding SLC26A4 protein variants. In this group, four uncharacterized sequence alterations within the SLC26A4 coding region were found. Three of these lead to protein variants with abnormal functional and molecular features, while one should be considered with no pathogenic potential. Pathogenic SLC26A4 sequence alterations were only found in 12% of patients. SLC26A4 sequence alterations commonly found in other Caucasian populations were not detected. This survey represents the first study on the prevalence and spectrum of SLC26A4 sequence alterations in an Austrian cohort and further suggests that genetic testing should always be integrated with functional characterization and determination of the molecular features of protein variants in order to unequivocally identify or exclude a causal link between genotype and phenotype. PMID:29320412

  12. Skin Stem Cell Hypotheses and Long Term Clone Survival - Explored Using Agent-based Modelling

    OpenAIRE

    Li, X.; Upadhyay, A.K.; Bullock, A.J.; Dicolandrea, T.; Xu, J.; Binder, R.L.; Robinson, M.K.; Finlay, D.R.; Mills, K.J.; Bascom, C.C.; Kelling, C.K.; Isfort, R.J.; Haycock, J.W.; MacNeil, S.; Smallwood, R.H.

    2013-01-01

    Epithelial renewal in skin is achieved by the constant turnover and differentiation of keratinocytes. Three popular hypotheses have been proposed to explain basal keratinocyte regeneration and epidermal homeostasis: 1) asymmetric division (stem-transit amplifying cell); 2) populational asymmetry (progenitor cell with stochastic fate); and 3) populational asymmetry with stem cells. In this study, we investigated lineage dynamics using these hypotheses with a 3D agent-based model of the epiderm...

  13. Comparison for aphasic and control subjects of eye movements hypothesized in neurolinguistic programming.

    Science.gov (United States)

    Dooley, K O; Farmer, A

    1988-08-01

    Neurolinguistic programming's hypothesized eye movements were measured independently using videotapes of 10 nonfluent aphasic and 10 control subjects matched for age and sex. Chi-squared analysis indicated that eye-position responses were significantly different for the groups. Although earlier research has not supported the hypothesized eye positions for normal subjects, the present findings support the contention that eye-position responses may differ between neurologically normal and aphasic individuals.

  14. Distinctive pattern of expression of spermatogenic molecular markers in testes of azoospermic men with non-mosaic Klinefelter syndrome.

    Science.gov (United States)

    Kleiman, Sandra E; Yogev, Leah; Lehavi, Ofer; Yavetz, Haim; Hauser, Ron

    2016-06-01

    Mature sperm cells can be found in testicular specimens extracted from azoospermic men with non-mosaic Klinefelter syndrome (KS). The present study evaluates the expression of various known molecular markers of spermatogenesis in a population of men with KS and assesses the ability of those markers to predict spermatogenesis. Two groups of men with non-obstructive azoospermia who underwent testicular sperm-retrieval procedures were included in the study: 31 had non-mosaic KS (KS group) and 91 had normal karyotype (NK group). Each group was subdivided into mixed atrophy (containing some mature sperm cells) or Sertoli cell only syndrome according to testicular histology and cytology observations. Semi-quantitative histological morphometric analysis (interstitial hyperplasia and hyalinization, tubules with cells and abnormal thickness of the basement membrane) and expression of spermatogenetic markers (DAZ, RBM, BOLL, and CDY1) were evaluated and compared among those subgroups. Clear differences in the histological morphometry and spermatogenetic marker expression were noted between the KS and NK groups. There was a significant difference in the expression of spermatogenetic markers between the subgroups of the NK group (as expected), while no difference could be discerned between the two subgroups in the KS group. We conclude that molecular spermatogenetic markers have a pattern of expression in men with KS that is distinctively different from that of men with NK, and that it precludes and limits their use for predicting spermatogenesis in the former. It is suggested that this difference might be due to the specific highly abnormal histological morphometric parameters in KS specimens.

  15. Testing the excitation/inhibition imbalance hypothesis in a mouse model of the autism spectrum disorder: in vivo neurospectroscopy and molecular evidence for regional phenotypes.

    Science.gov (United States)

    Gonçalves, Joana; Violante, Inês R; Sereno, José; Leitão, Ricardo A; Cai, Ying; Abrunhosa, Antero; Silva, Ana Paula; Silva, Alcino J; Castelo-Branco, Miguel

    2017-01-01

    Excitation/inhibition (E/I) imbalance remains a widely discussed hypothesis in autism spectrum disorders (ASD). The presence of such an imbalance may potentially define a therapeutic target for the treatment of cognitive disabilities related to this pathology. Consequently, the study of monogenic disorders related to autism, such as neurofibromatosis type 1 (NF1), represents a promising approach to isolate mechanisms underlying ASD-related cognitive disabilities. However, the NF1 mouse model showed increased γ-aminobutyric acid (GABA) neurotransmission, whereas the human disease showed reduced cortical GABA levels. It is therefore important to clarify whether the E/I imbalance hypothesis holds true. We hypothesize that E/I may depend on distinct pre- and postsynaptic push-pull mechanisms that might be are region-dependent. In current study, we assessed two critical components of E/I regulation: the concentration of neurotransmitters and levels of GABA(A) receptors. Measurements were performed across the hippocampi, striatum, and prefrontal cortices by combined in vivo magnetic resonance spectroscopy (MRS) and molecular approaches in this ASD-related animal model, the Nf1 +/- mouse. Cortical and striatal GABA/glutamate ratios were increased. At the postsynaptic level, very high receptor GABA(A) receptor expression was found in hippocampus, disproportionately to the small reduction in GABA levels. Gabaergic tone (either by receptor levels change or GABA/glutamate ratios) seemed therefore to be enhanced in all regions, although by a different mechanism. Our data provides support for the hypothesis of E/I imbalance in NF1 while showing that pre- and postsynaptic changes are region-specific. All these findings are consistent with our previous physiological evidence of increased inhibitory tone. Such heterogeneity suggests that therapeutic approaches to address neurochemical imbalance in ASD may need to focus on targets where convergent physiological mechanisms can be

  16. Three Rounds of External Quality Assessment in France to Evaluate the Performance of 28 Platforms for Multiparametric Molecular Testing in Metastatic Colorectal and Non-Small Cell Lung Cancer

    NARCIS (Netherlands)

    Dequeker, E.M.; Keppens, C.; Egele, C.; Delen, S.; Lamy, A.; Lemoine, A.; Sabourin, J.C.; Andrieu, C.; Ligtenberg, M.; Fetique, D.; Tops, B.; Descarpentries, C.; Blons, H.; Denoux, Y.; Aube, C.; Penault-Llorca, F.; Hofman, P.; Leroy, K.; Marechal, C. Le; Doucet, L.; Duranton-Tanneur, V.; Pedeutour, F.; Soubeyran, I.; Cote, J.F.; Emile, J.F.; Vignaud, J.M.; Monhoven, N.; Haddad, V.; Laurent-Puig, P.; Krieken, H. van; Nowak, F.; Lonchamp, E.; Bellocq, J.P.; Rouleau, E.

    2016-01-01

    Personalized medicine has gained increasing importance in clinical oncology, and several clinically important biomarkers are implemented in routine practice. In an effort to guarantee high quality of molecular testing in France, three subsequent external quality assessment rounds were organized at

  17. What's next? Perspectives and future needs of cervical screening in Europe in the era of molecular testing and vaccination

    DEFF Research Database (Denmark)

    Lynge, Elsebeth; Antilla, Ahti; Arbyn, Marc

    2009-01-01

    controlled trials have found HPV-testing to increase the detection rate of cervical intraepithelial neoplasia grade 2+, CIN2+, compared with cytology. Two studies found a decreased detection rate of CIN3+ in the HPV-testing arm at the subsequent screening. Randomised controlled trials found that women......AIM: To outline the perspectives for future control of cervical cancer in Europe. METHODS: Review of current status for major cervical cancer control tools. The review was based on PubMed searches for cervical cancer prevention, Human Papillomavirus, HPV-test, HPV-vaccination, and treatment...... with large loop excision of the transformation zone, LLETZ. RESULTS: Recent studies suggest that condom use offers some but not complete protection against HPV-infection. High quality cytology screening with good population coverage reduces the incidence and mortality of cervical cancer. Randomised...

  18. Pathways and barriers to genetic testing and screening: Molecular genetics meets the high-risk family. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Duster, T.

    1998-11-01

    The proliferation of genetic screening and testing is requiring increasing numbers of Americans to integrate genetic knowledge and interventions into their family life and personal experience. This study examines the social processes that occur as families at risk for two of the most common autosomal recessive diseases, sickle cell disease (SC) and cystic fibrosis (CF), encounter genetic testing. Each of these diseases is found primarily in a different ethnic/racial group (CF in Americans of North European descent and SC in Americans of West African descent). This has permitted them to have a certain additional lens on the role of culture in integrating genetic testing into family life and reproductive planning. A third type of genetic disorder, the thalassemias was added to the sample in order to extent the comparative frame and to include other ethnic and racial groups.

  19. Integrated Testing of a 4-Bed Molecular Sieve and a Temperature-Swing Adsorption Compressor for Closed-Loop Air Revitalization

    Science.gov (United States)

    Knox, James C.; Mulloth, Lila M.; Affleck, David L.

    2004-01-01

    Accumulation and subsequent compression of carbon dioxide that is removed from space cabin are two important processes involved in a closed-loop air revitalization scheme of the International Space Station (ISS). The 4-Bed Molecular Sieve (4BMS) of ISS currently operates in an open loop mode without a compressor. This paper reports the integrated 4BMS and liquid-cooled TSAC testing conducted during the period of March 3 to April 18, 2003. The TSAC prototype was developed at NASA Ames Research Center (ARC). The 4BMS was modified to a functionally flight-like condition at NASA Marshall Space Flight Center (MSFC). Testing was conducted at MSFC. The paper provides details of the TSAC operation at various CO2 loadings and corresponding performance of CDRA.

  20. Molecular testing of adult Pacific salmon and trout (Oncorhynchus spp.) for several RNA viruses demonstrates widespread distribution of piscine orthoreovirus in Alaska and Washington

    Science.gov (United States)

    Purcell, Maureen; Thompson, Rachel L.; Evered, Joy; Kerwin, John; Meyers, Ted R.; Stewart, Bruce; Winton, James

    2018-01-01

    This research was initiated in conjunction with a systematic, multiagency surveillance effort in the United States (U.S.) in response to reported findings of infectious salmon anaemia virus (ISAV) RNA in British Columbia, Canada. In the systematic surveillance study reported in a companion paper, tissues from various salmonids taken from Washington and Alaska were surveyed for ISAV RNA using the U.S.-approved diagnostic method, and samples were released for use in this present study only after testing negative. Here, we tested a subset of these samples for ISAV RNA with three additional published molecular assays, as well as for RNA from salmonid alphavirus (SAV), piscine myocarditis virus (PMCV) and piscine orthoreovirus (PRV). All samples (n = 2,252; 121 stock cohorts) tested negative for RNA from ISAV, PMCV, and SAV. In contrast, there were 25 stock cohorts from Washington and Alaska that had one or more individuals test positive for PRV RNA; prevalence within stocks varied and ranged from 2% to 73%. The overall prevalence of PRV RNA-positive individuals across the study was 3.4% (77 of 2,252 fish tested). Findings of PRV RNA were most common in coho (Oncorhynchus kisutch Walbaum) and Chinook (O. tshawytscha Walbaum) salmon.

  1. The wings before the bird: an evaluation of flapping-based locomotory hypotheses in bird antecedents

    Directory of Open Access Journals (Sweden)

    T. Alexander Dececchi

    2016-07-01

    Full Text Available Background: Powered flight is implicated as a major driver for the success of birds. Here we examine the effectiveness of three hypothesized pathways for the evolution of the flight stroke, the forelimb motion that powers aerial locomotion, in a terrestrial setting across a range of stem and basal avians: flap running, Wing Assisted Incline Running (WAIR, and wing-assisted leaping. Methods: Using biomechanical mathematical models based on known aerodynamic principals and in vivo experiments and ground truthed using extant avians we seek to test if an incipient flight stroke may have contributed sufficient force to permit flap running, WAIR, or leaping takeoff along the phylogenetic lineage from Coelurosauria to birds. Results: None of these behaviours were found to meet the biomechanical threshold requirements before Paraves. Neither was there a continuous trend of refinement for any of these biomechanical performances across phylogeny nor a signal of universal applicability near the origin of birds. None of these flap-based locomotory models appear to have been a major influence on pre-flight character acquisition such as pennaceous feathers, suggesting non-locomotory behaviours, and less stringent locomotory behaviours such as balancing and braking, played a role in the evolution of the maniraptoran wing and nascent flight stroke. We find no support for widespread prevalence of WAIR in non-avian theropods, but can’t reject its presence in large winged, small-bodied taxa like Microraptor and Archaeopteryx. Discussion: Using our first principles approach we find that “near flight” locomotor behaviors are most sensitive to wing area, and that non-locomotory related selection regimes likely expanded wing area well before WAIR and other such behaviors were possible in derived avians. These results suggest that investigations of the drivers for wing expansion and feather elongation in theropods need not be intrinsically linked to locomotory

  2. Distinguishing 'Higgs' spin hypotheses using {gamma}{gamma} and WW{sup *} decays

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, John [King' s College London, Theoretical Particle Physics and Cosmology Group, Physics Department, London (United Kingdom); CERN, TH Division, Physics Department, Geneva (Switzerland); Fok, Ricky [York University, Department of Physics and Astronomy, Toronto, ON (Canada); Hwang, Dae Sung [Sejong University, Department of Physics, Seoul (Korea, Republic of); Sanz, Veronica [CERN, TH Division, Physics Department, Geneva (Switzerland); York University, Department of Physics and Astronomy, Toronto, ON (Canada); You, Tevong [King' s College London, Theoretical Particle Physics and Cosmology Group, Physics Department, London (United Kingdom)

    2013-07-15

    The new particle X recently discovered by the ATLAS and CMS Collaborations in searches for the Higgs boson has been observed to decay into {gamma}{gamma}, ZZ{sup *} and WW{sup *}, but its spin and parity, J{sup P}, remain a mystery, with J{sup P} = 0{sup +} and 2{sup +} being open possibilities. We use PYTHIA and Delphes to simulate an analysis of the angular distribution of gg {yields} X {yields} {gamma}{gamma} decays in a full 2012 data set, including realistic background levels. We show that this angular distribution should provide strong discrimination between the possibilities of spin zero and spin two with graviton-like couplings: {proportional_to}3 {sigma} if a conservative symmetric interpretation of the log-likelihood ratio (LLR) test statistic is used, and {proportional_to}6 {sigma} if a less conservative asymmetric interpretation is used. The WW and ZZ couplings of the Standard Model Higgs boson and of a 2{sup +} particle with graviton-like couplings are both expected to exhibit custodial symmetry. We simulate the present ATLAS and CMS search strategies for X {yields} WW{sup *} using PYTHIA and Delphes, and show that their efficiencies in the case of a spin-2 particle with graviton-like couplings are a factor {approx_equal} 1.9 smaller than in the spin-0 case. On the other hand, the ratio of X{sub 2{sup +}} {yields} WW{sup *} and ZZ{sup *} branching ratios is larger than that in the 0{sup +} case by a factor {approx_equal} 1.3. We find that the current ATLAS and CMS results for X {yields} WW{sup *} and X {yields} ZZ{sup *} decays are compatible with custodial symmetry under both the spin-0 and -2 hypotheses, and that the data expected to become available during 2012 are unlikely to discriminate significantly between these possibilities. (orig.)

  3. Distinguishing 'Higgs' spin hypotheses using γγ and WW* decays

    International Nuclear Information System (INIS)

    Ellis, John; Fok, Ricky; Hwang, Dae Sung; Sanz, Veronica; You, Tevong

    2013-01-01

    The new particle X recently discovered by the ATLAS and CMS Collaborations in searches for the Higgs boson has been observed to decay into γγ, ZZ * and WW * , but its spin and parity, J P , remain a mystery, with J P = 0 + and 2 + being open possibilities. We use PYTHIA and Delphes to simulate an analysis of the angular distribution of gg → X → γγ decays in a full 2012 data set, including realistic background levels. We show that this angular distribution should provide strong discrimination between the possibilities of spin zero and spin two with graviton-like couplings: ∝3 σ if a conservative symmetric interpretation of the log-likelihood ratio (LLR) test statistic is used, and ∝6 σ if a less conservative asymmetric interpretation is used. The WW and ZZ couplings of the Standard Model Higgs boson and of a 2 + particle with graviton-like couplings are both expected to exhibit custodial symmetry. We simulate the present ATLAS and CMS search strategies for X → WW * using PYTHIA and Delphes, and show that their efficiencies in the case of a spin-2 particle with graviton-like couplings are a factor ≅ 1.9 smaller than in the spin-0 case. On the other hand, the ratio of X 2 + → WW * and ZZ * branching ratios is larger than that in the 0 + case by a factor ≅ 1.3. We find that the current ATLAS and CMS results for X → WW * and X → ZZ * decays are compatible with custodial symmetry under both the spin-0 and -2 hypotheses, and that the data expected to become available during 2012 are unlikely to discriminate significantly between these possibilities. (orig.)

  4. Emergence of nutrient limitation in tropical dry forests: hypotheses from simulation models

    Science.gov (United States)

    Medvigy, D.; Waring, B. G.; Xu, X.; Trierweiler, A.; Werden, L. K.; Wang, G.; Zhu, Q.; Powers, J. S.

    2017-12-01

    It is unclear to what extent tropical dry forest productivity may be limited by nutrients. Direct assessment of nutrient limitation through fertilization experiments has been rare, and paradigms pertaining to other ecosystems may not extend to tropical dry forests. For example, because dry tropical forests have a lower water supply than moist tropical forests, dry forests can have lower decomposition rates, higher soil carbon and nitrogen concentrations, and a more open nitrogen cycle than moist forests. We used a mechanistic, numerical model to generate hypotheses about nutrient limitation in tropical dry forests. The model dynamically couples ED2 (vegetation dynamics), MEND (biogeochemistry), and N-COM (plant-microbe competition for nutrients). Here, the MEND-component of the model has been extended to include nitrogen (N) and phosphorus (P) cycles. We focus on simulation of sixteen 25m x 25m plots in Costa Rica where a fertilization experiment has been underway since 2015. Baseline simulations are characterized by both nitrogen and phosphorus limitation of vegetation. Fertilization with N and P increased vegetation biomass, with N fertilization having a somewhat stronger effect. Nutrient limitation was also sensitive to climate and was more pronounced during drought periods. Overflow respiration was identified as a key process that mitigated nutrient limitation. These results suggest that, despite often having richer soils than tropical moist forests, tropical dry forests can also become nutrient-limited. If the climate becomes drier in the next century, as is expected for Central America, drier soils may decrease microbial activity and exacerbate nutrient limitation. The importance of overflow respiration underscores the need for appropriate treatment of microbial dynamics in ecosystem models. Ongoing and new nutrient fertilization experiments will present opportunities for testing whether, and how, nutrient limitation may indeed be emerging in tropical dry

  5. Dialium seed coprophagy in wild western gorillas: Multiple nutritional benefits and toxicity reduction hypotheses.

    Science.gov (United States)

    Masi, Shelly; Breuer, Thomas

    2018-04-01

    Unraveling the relationship between the unusual feeding behaviors and the nutritional intake of endangered species may provide crucial information for understanding species response to habitat unpredictable changes. Primates occasionally re-ingest fruit seeds alongside ingestion of feces, a behavior called coprophagy. The nutritional benefit is one of the several non-mutual exclusive hypotheses proposed to explain this behavior. We investigated the ecological correlates of coprophagy in wild western gorillas. We tested whether coprophagy occurred during periods of lower fruit availability and whether it led to higher nutrient intake in comparison to the other food. Data integrated phenological, fecal and nutritional analyses of gorilla food with behavioral observations collected at two sites in Central Africa (Mbeli Bai: ad libitum observations on 15 groups/solitary males, October 2002-November 2005; Bai Hokou: 5-min scan on a habituated group, December 2004-December 2005). Coprophagy occurred at the end of the high-fruiting season in association of two Dialium species. Coprophagy correlated positively with the occurrence of Dialium spp. fruit in gorilla feces and in the feeding scans, and showed a positive trend with Dialium availability but not with total fruit availability. Nutritional comparison of Dialium seeds with other important gorilla food showed higher fat and mineral content, particularly of Mg, but also of phenols and tannins in Dialium seeds. We discuss how the effect of gut processing and gut heat via coprophagy may act as cooking-like effect: increasing the ability to maximize nutrient intake by concurrently softening fibers and decreasing the toxic effect of antifeedants, like in human traditional cooking. Our results support both the multiple nutritional benefit hypothesis and the toxicity reduction hypothesis. Since Dialium is precious timber, the importance of this tree for the critically endangered western gorillas should be taken with high

  6. Disrupting self-assembly and toxicity of amyloidogenic protein oligomers by "molecular tweezers" - from the test tube to animal models.

    Science.gov (United States)

    Attar, Aida; Bitan, Gal

    2014-01-01

    Despite decades of research, therapy for diseases caused by abnormal protein folding and aggregation (amyloidoses) is limited to treatment of symptoms and provides only temporary and moderate relief to sufferers. The failure in developing successful disease-modifying drugs for amyloidoses stems from the nature of the targets for such drugs - primarily oligomers of amyloidogenic proteins, which are distinct from traditional targets, such as enzymes or receptors. The oligomers are metastable, do not have well-defined structures, and exist in dynamically changing mixtures. Therefore, inhibiting the formation and toxicity of these oligomers likely will require out-of-the-box thinking and novel strategies. We review here the development of a strategy based on targeting the combination of hydrophobic and electrostatic interactions that are key to the assembly and toxicity of amyloidogenic proteins using lysine (K)-specific "molecular tweezers" (MTs). Our discussion includes a survey of the literature demonstrating the important role of K residues in the assembly and toxicity of amyloidogenic proteins and the development of a lead MT derivative called CLR01, from an inhibitor of protein aggregation in vitro to a drug candidate showing effective amelioration of disease symptoms in animal models of Alzheimer's and Parkinson's diseases.

  7. Molecular and structural changes induced by essential oils treatments in Vicia faba roots detected by genotoxicity testing.

    Science.gov (United States)

    Sturchio, Elena; Boccia, Priscilla; Zanellato, Miriam; Meconi, Claudia; Donnarumma, Lucia; Mercurio, Giuseppe; Mecozzi, Mauro

    2016-01-01

    Over the last few years, there has been an increased interest in exploiting allelopathy in organic agriculture. The aim of this investigation was to examine the effects of essential oil mixtures in order to establish their allelopathic use in agriculture. Two mixtures of essential oils consisting respectively of tea tree oil (TTO) and clove plus rosemary (C + R) oils were tested. Phytotoxicity and genotoxicity tests on the root meristems of Vicia faba minor were performed. A phytotoxic influence was particularly relevant for C + R mixture, while genotoxicity tests revealed significant results with both C + R oil mixture and TTO. Phenotypic analysis on Vicia faba minor primary roots following C + R oil mixture treatment resulted in callose production, an early symptom attributed to lipid peroxidation. The approach described in this study, based on genotoxicity bioassays, might identify specific DNA damage induced by essential oil treatments. These tests may represent a powerful method to evaluate potential adverse effects of different mixtures of essential oils that might be useful in alternative agriculture. Future studies are focusing on the positive synergism of more complex mixtures of essential oils in order to reduce concentrations of potentially toxic components while at the same time maintaining efficacy in antimicrobial and antifungal management.

  8. A simple and inexpensive point-of-care test for hepatitis B surface antigen detection: serological and molecular evaluation.

    Science.gov (United States)

    Gish, R G; Gutierrez, J A; Navarro-Cazarez, N; Giang, K; Adler, D; Tran, B; Locarnini, S; Hammond, R; Bowden, S

    2014-12-01

    Early identification of chronic hepatitis B is important for optimal disease management and prevention of transmission. Cost and lack of access to commercial hepatitis B surface antigen (HBsAg) immunoassays can compromise the effectiveness of HBV screening in resource-limited settings and among marginalized populations. High-quality point-of-care (POC) testing may improve HBV diagnosis in these situations. Currently available POC HBsAg assays are often limited in sensitivity. We evaluated the NanoSign(®) HBs POC chromatographic immunoassay for its ability to detect HBsAg of different genotypes and with substitutions in the 'a' determinant. Thirty-seven serum samples from patients with HBV infection, covering HBV genotypes A-G, were assessed for HBsAg titre with the Roche Elecsys HBsAg II quantification assay and with the POC assay. The POC assay reliably detected HBsAg at a concentration of at least 50 IU/mL for all genotypes, and at lower concentrations for some genotypes. Eight samples with substitutions in the HBV 'a' determinant were reliably detected after a 1/100 dilution. The POC strips were used to screen serum samples from 297 individuals at risk for HBV in local clinical settings (health fairs and outreach events) in parallel with commercial laboratory HBsAg testing (Quest Diagnostics EIA). POC testing was 73.7% sensitive and 97.8% specific for detection of HBsAg. Although the POC test demonstrated high sensitivity over a range of genotypes, false negatives were frequent in a clinical setting. Nevertheless, the POC assay offers advantages for testing in both developed and resource-limited countries due to its low cost (0.50$) and immediately available results. © 2014 John Wiley & Sons Ltd.

  9. Molecular identification and in-vitro antifungal susceptibility testing of Candida species isolated from patients with onychomycosis

    Directory of Open Access Journals (Sweden)

    Keyvan Pakshir

    2015-03-01

    Full Text Available Background and Purpose: Candida species are the most opportunistic fungi affecting the nails and resulting in onychomycosis. In this study, we identified and evaluated in-vitro susceptibility of the recovered isolates against fluconazole (FLC, voriconazole (VRC, and clotrimazole (CLT using the Clinical and Laboratory Standards Institute (CLSI M27-A3 document. Materials and Methods: From patients with either clinically or mycologically proven onychomycosis, 97 isolates comprising of seven Candida species were isolated, which were identified by both conventional and molecular techniques such as polymerase chain reaction-restriction fragment length polymorphism. In addition, Candida dubliniensis was confirmed by restriction endonuclease analysis. Antifungal susceptibility of each isolate against the three azoles applied in this study was determined using the CLSI microdilution reference method M27-A3. Results: Candida parapsilosis (C. parapsilosis was the most frequently isolated species (n=44, followed by C. albicans (n=23, C. tropicalis (n=13, C. glabrata (n=7, C. krusei (n=6, C. guilliermondii (n=3, and C. dubliniensis (n=1. All the isolates were susceptible to CLT. VRC had lower minimum inhibitory concentration (MIC values for the isolates compared to FLC. Geometric mean MIC values of VRC, FLC, and CLT for C. parapsilosis isolates were 0.07 µg/ml, 0.8 µg/ml, and 0.35 µg/ml, respectively. Collectively, all species exhibited greater susceptibility to VRC in comparison to C. albicans (P≤0.001. Conclusion: This study showed that non-albicans Candida species were the most common etiologic agents of non-dermatophyte onychomycosis. The major antifungal agents used in clinics to empirically treat yeast onychomycosis are FLC and CLT. Our data suggested that CLT is a better choice for the treatment of Candida onychomycosis, especially in drug resistant cases.

  10. Comparison of 2 molecular assays and a serologic test in diagnosing Mycoplasma pneumoniae infection in paediatrics patients.

    Science.gov (United States)

    Blanco, Silvia; Fuenzalida, Loreto; Bas, Albert; Prat, Cristina; Ramírez, Aida; Matas, Lurdes; Rodrigo, Carlos; Ausina, Vicente

    2011-12-01

    Two commercial polymerase chain reaction (PCR) assays (a real-time PCR [Cepheid] and an oligochromatographic test [Speed-oligo]) and 1 serology test (Serodia-Myco II) for detecting Mycoplasma pneumoniae in nasopharyngeal aspirates and serum samples were studied. Among the 145 samples, 32 serum pairs were serologically positive for M. pneumoniae. Of these, in 30 nasopharyngeal aspirates, M. pneumoniae was detected using the real-time PCR assay and 25 using Speed-oligo, corresponding to a sensitivity of 93.7% and 78.1%, respectively. Among the 94 samples with negative serology, we only obtained 1 positive result by real-time PCR assay. In the group of samples from healthy children, no positive results were obtained. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Molecular analysis and test of linkage between the FMR-I gene and infantile autism in multiplex families

    Energy Technology Data Exchange (ETDEWEB)

    Hallmayer, J.; Pintado, E.; Lotspeich, L.; Spiker, D.; Kraemer, H.C.; Lee Wong, D.; Lin, A.; Herbert, J.; Cavalli-Sforza, L.L.; Ciaranello, R.D. [Stanford Univ., CA (United States)] [and others

    1994-11-01

    Approximately 2%-5% of autistic children show cytogenetic evidence of the fragile X syndrome. This report tests whether infantile autism in multiplex autism families arises from an unusual manifestion of the fragile X syndrome. This could arise either by expansion of the (CGG)n trinucleotide repeat in FMR-1 or from a mutation elsewhere in the gene. We studied 35 families that met stringent criteria for multiplex autism. Amplification of the trinucleotide repeat and analysis of methylation status were performed in 79 autistic children and in 31 of their unaffected siblings by Southern blot analysis. No examples of amplified repeats were seen in the autistic or control children or in their parents or grandparents. We next examined the hypothesis that there was a mutation elsewhere in the FMR-1 gene, by linkage analysis in 32 of these families. We tested four different dominant models and a recessive model. Linkage to FMR-1 could be excluded (lod score between -24 and -62) in all models by using probes DXS548, FRAXAC1, and FRAXAC2 and the CGG repeat itself. Tests for heterogeneity in this sample were negative, and the occurrence of positive lod scores in this data set could be attributed to chance. Analysis of the data by the affected-sib method also did not show evidence for linkage of any marker to autism. These results enable us to reject the hypothesis that multiplex autism arises from expansion of the (CGG)n trinucleotide repeat in FMR-1. Further, because the overall lod scores for all probes in all models tested were highly negative, linkage to FMR-1 can also be ruled out in multiplex autistic families. 35 refs., 2 figs., 5 tabs.

  12. Bench-top validation testing of selected immunological and molecular Renibacterium salmoninarum diagnostic assays by comparison with quantitative bacteriological culture

    Science.gov (United States)

    Elliott, D.G.; Applegate, L.J.; Murray, A.L.; Purcell, M.K.; McKibben, C.L.

    2013-01-01

    No gold standard assay exhibiting error-free classification of results has been identified for detection of Renibacterium salmoninarum, the causative agent of salmonid bacterial kidney disease. Validation of diagnostic assays for R. salmoninarum has been hindered by its unique characteristics and biology, and difficulties in locating suitable populations of reference test animals. Infection status of fish in test populations is often unknown, and it is commonly assumed that the assay yielding the most positive results has the highest diagnostic accuracy, without consideration of misclassification of results. In this research, quantification of R. salmoninarum in samples by bacteriological culture provided a standardized measure of viable bacteria to evaluate analytical performance characteristics (sensitivity, specificity and repeatability) of non-culture assays in three matrices (phosphate-buffered saline, ovarian fluid and kidney tissue). Non-culture assays included polyclonal enzyme-linked immunosorbent assay (ELISA), direct smear fluorescent antibody technique (FAT), membrane-filtration FAT, nested polymerase chain reaction (nested PCR) and three real-time quantitative PCR assays. Injection challenge of specific pathogen-free Chinook salmon, Oncorhynchus tshawytscha (Walbaum), with R. salmoninarum was used to estimate diagnostic sensitivity and specificity. Results did not identify a single assay demonstrating the highest analytical and diagnostic performance characteristics, but revealed strengths and weaknesses of each test.

  13. HER2 testing of gastro-oesophageal adenocarcinoma: a commentary and guidance document from the Association of Clinical Pathologists Molecular Pathology and Diagnostics Committee.

    Science.gov (United States)

    Wong, Newton A C S; Amary, Fernanda; Butler, Rachel; Byers, Richard; Gonzalez, David; Haynes, Harry R; Ilyas, Mohammad; Salto-Tellez, Manuel; Taniere, Philippe

    2018-05-01

    The use of biologics targeted to the human epidermal growth factor receptor 2 (HER2) protein is the latest addition to the armamentarium used to fight advanced gastric or gastro-oesophageal junction adenocarcinoma. The decision to treat with the biologic trastuzumab is completely dependent on HER2 testing of tumour tissue. In 2017, the College of American Pathologists, American Society for Clinical Pathology and the American Society of Clinical Oncology jointly published guidelines for HER2 testing and clinical decision making in gastro-oesophageal adenocarcinoma. The Association of Clinical Pathologists Molecular Pathology and Diagnostics Committee has issued the following document as a commentary of these guidelines and, in parallel, to provide guidance on HER2 testing in National Health Service pathology departments within the UK. This guidance covers issues related to case selection, preanalytical aspects, analysis and interpretation of such HER2 testing. © 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.

  14. A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders.

    Science.gov (United States)

    Stark, Zornitza; Tan, Tiong Y; Chong, Belinda; Brett, Gemma R; Yap, Patrick; Walsh, Maie; Yeung, Alison; Peters, Heidi; Mordaunt, Dylan; Cowie, Shannon; Amor, David J; Savarirayan, Ravi; McGillivray, George; Downie, Lilian; Ekert, Paul G; Theda, Christiane; James, Paul A; Yaplito-Lee, Joy; Ryan, Monique M; Leventer, Richard J; Creed, Emma; Macciocca, Ivan; Bell, Katrina M; Oshlack, Alicia; Sadedin, Simon; Georgeson, Peter; Anderson, Charlotte; Thorne, Natalie; Melbourne Genomics Health Alliance; Gaff, Clara; White, Susan M

    2016-11-01

    To prospectively evaluate the diagnostic and clinical utility of singleton whole-exome sequencing (WES) as a first-tier test in infants with suspected monogenic disease. Singleton WES was performed as a first-tier sequencing test in infants recruited from a single pediatric tertiary center. This occurred in parallel with standard investigations, including single- or multigene panel sequencing when clinically indicated. The diagnosis rate, clinical utility, and impact on management of singleton WES were evaluated. Of 80 enrolled infants, 46 received a molecular genetic diagnosis through singleton WES (57.5%) compared with 11 (13.75%) who underwent standard investigations in the same patient group. Clinical management changed following exome diagnosis in 15 of 46 diagnosed participants (32.6%). Twelve relatives received a genetic diagnosis following cascade testing, and 28 couples were identified as being at high risk of recurrence in future pregnancies. This prospective study provides strong evidence for increased diagnostic and clinical utility of singleton WES as a first-tier sequencing test for infants with a suspected monogenic disorder. Singleton WES outperformed standard care in terms of diagnosis rate and the benefits of a diagnosis, namely, impact on management of the child and clarification of reproductive risks for the extended family in a timely manner.Genet Med 18 11, 1090-1096.

  15. Isolation, molecular identification and quinolone-susceptibility testing of Arcobacter spp. isolated from fresh vegetables in Spain.

    Science.gov (United States)

    González, Ana; Bayas Morejón, Isidro Favián; Ferrús, María Antonia

    2017-08-01

    Some species of the Arcobacter genus are considered emerging foodborne and waterborne enteropathogens. However, the presence of Arcobacter spp. in vegetables very little is known, because most studies have focused on foods of animal origin. On the other hand, quinolones are considered as first-line drugs for the treatment of infection by campylobacteria in human patients, but few data are currently available about the resistance levels to these antibiotics among Arcobacter species. Therefore, the aim of this study was to investigate the presence and diversity of arcobacters isolated from fresh vegetables such as lettuces, spinaches, chards and cabbages. Resistance to quinolones of the isolates was also investigated. One hundred fresh vegetables samples purchased from seven local retail markets in Valencia (Spain) during eight months were analysed. The study included 41 lettuces, 21 spinaches, 34 chards and 4 cabbages. Samples were analysed by culture and by molecular methods before and after enrichment. By culture, 17 out of 100 analysed samples were Arcobacter positive and twenty-five isolates were obtained from them. Direct detection by PCR was low, with only 4% Arcobacter spp. positive samples. This percentage increased considerably, up 20%, after 48 h enrichment. By polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), 17 out of the 25 isolates were identified as A. butzleri and 8 as A. cryaerophilus. Only two A. butzleri isolates showed resistance to levofloxacin and ciprofloxacin. The sequencing of a fragment of the QRDR region of the gyrA gene from the quinolones-resistant isolates revealed the presence of a mutation in position 254 of this gene (C-T transition). This study is the first report about the presence of pathogenic species of Arcobacter spp. in chards and cabbages and confirms that fresh vegetables can act as transmission vehicle to humans. Moreover, the presence of A. butzleri quinolone resistant in vegetables could

  16. Evaluating hypotheses of basal animal phylogeny using complete sequences of large and small subunit rRNA

    International Nuclear Information System (INIS)

    Medina, Monica; Collins, Allen G.; Silberman, Jeffrey; Sogin, Mitchell L.

    2001-01-01

    We studied the evolutionary relationships among basal metazoan lineages by using complete large subunit (LSU) and small subunit (SSU) ribosomal RNA sequences for 23 taxa. After identifying competing hypotheses, we performed maximum likelihood searches for trees conforming to each hypothesis. Kishino-Hasegawa tests were used to determine whether the data (LSU, SSU, and combined) reject any of the competing hypotheses. We also conducted unconstrained tree searches, compared the resulting topologies, and calculated bootstrap indices. Shimodaira-Hasegawa tests were applied to determine whether the data reject any of the topologies resulting from the constrained and unconstrained tree searches. LSU, SSU, and the combined data strongly contradict two assertions pertaining to sponge phylogeny. Hexactinellid sponges are not likely to be the basal lineage of amonophyletic Porifera or the sister group to all other animals. Instead, Hexactinellida and Demospongia form a well-supported clade of siliceous sponges, Silicea. It remains unclear, on the basis of these data alone, whether the calcarean sponges are more closely related to Silicea or to nonsponge animals. The SSU and combined data reject the hypothesis that Bilateria is more closely related to Ctenophora than it is to Cnidaria, whereas LSU data alone do not refute either hypothesis. LSU and SSU data agree in supporting the monophyly of Bilateria, Cnidaria, Ctenophora, and Metazoa. LSU sequence data reveal phylogenetic structure in a data set with limited taxon sampling. Continued accumulation of LSU sequences should increase our understanding of animal phylogeny

  17. Molecular phylogeny of the Drusinae (Trichoptera: Limnephilidae): preliminary results

    Science.gov (United States)

    Pauls, S.; Lumbsch, T.; Haase, P.

    2005-05-01

    We examine the phylogenetic relationships within the subfamily of the Drusinae using molecular markers. Sequence data from two mitochondrial loci (mitochondrial cytochrome oxidase I, mitochondrial ribosomal large subunit) are used to infer the relationships within and among the genera of the Drusinae. Sequence data were generated for 21 taxa from five genera from the subfamily. The molecular data were analyzed using a Bayesian Markov Chain Monte Carlo and a Maximum Parsimony approach for both single gene and combined data sets. Several hypotheses of relationships previously inferred based on morphological characters were tested. The study revealed a very close relationship between Drusus discolor and D. romanicus suggesting that divergence between these two species occurred recently. The relationships inferred by molecular data suggest that larval morphology may be an important taxonomic character, which has often been neglected. The data also indicate that the genera Ecclisopteryx and Drusus are polyphyletic with respect to one another.

  18. Development, Evaluation, and Integration of a Quantitative Reverse-Transcription Polymerase Chain Reaction Diagnostic Test for Ebola Virus on a Molecular Diagnostics Platform.

    Science.gov (United States)

    Cnops, Lieselotte; Van den Eede, Peter; Pettitt, James; Heyndrickx, Leo; De Smet, Birgit; Coppens, Sandra; Andries, Ilse; Pattery, Theresa; Van Hove, Luc; Meersseman, Geert; Van Den Herrewegen, Sari; Vergauwe, Nicolas; Thijs, Rein; Jahrling, Peter B; Nauwelaers, David; Ariën, Kevin K

    2016-10-15

     The 2013-2016 Ebola epidemic in West Africa resulted in accelerated development of rapid diagnostic tests for emergency outbreak preparedness. We describe the development and evaluation of the Idylla™ prototype Ebola virus test, a fully automated sample-to-result molecular diagnostic test for rapid detection of Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV).  The Idylla™ prototype Ebola virus test can simultaneously detect EBOV and SUDV in 200 µL of whole blood. The sample is directly added to a disposable cartridge containing all reagents for sample preparation, RNA extraction, and amplification by reverse-transcription polymerase chain reaction analysis. The performance was evaluated with a variety of sample types, including synthetic constructs and whole blood samples from healthy volunteers spiked with viral RNA, inactivated virus, and infectious virus.  The 95% limits of detection for EBOV and SUDV were 465 plaque-forming units (PFU)/mL (1010 copies/mL) and 324 PFU/mL (8204 copies/mL), respectively. In silico and in vitro analyses demonstrated 100% correct reactivity for EBOV and SUDV and no cross-reactivity with relevant pathogens. The diagnostic sensitivity was 97.4% (for EBOV) and 91.7% (for SUDV), the specificity was 100%, and the diagnostic accuracy was 95.9%.  The Idylla™ prototype Ebola virus test is a fast, safe, easy-to-use, and near-patient test that meets the performance criteria to detect EBOV in patients with suspected Ebola. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  19. An Attempt to Determine the Construct Validity of Measures Hypothesized to Represent an Orientation to Right, Left, or Integrated Hemispheric Brain Function for a Sample of Primary School Children.

    Science.gov (United States)

    Dumbrower, Jule; And Others

    1981-01-01

    This study attempts to obtain evidence of the construct validity of pupil ability tests hypothesized to represent orientation to right, left, or integrated hemispheric function, and of teacher observation subscales intended to reveal behaviors in school setting that were hypothesized to portray preference for right or left brain function. (Author)

  20. Use of a molecular diagnostic test in AFB smear positive tuberculosis suspects greatly reduces time to detection of multidrug resistant tuberculosis.

    Directory of Open Access Journals (Sweden)

    Nestani Tukvadze

    Full Text Available The WHO has recommended the implementation of rapid diagnostic tests to detect and help combat M/XDR tuberculosis (TB. There are limited data on the performance and impact of these tests in field settings.The performance of the commercially available Genotype MTBDRplus molecular assay was compared to conventional methods including AFB smear, culture and drug susceptibility testing (DST using both an absolute concentration method on Löwenstein-Jensen media and broth-based method using the MGIT 960 system. Sputum specimens were obtained from TB suspects in the country of Georgia who received care through the National TB Program.Among 500 AFB smear-positive sputum specimens, 458 (91.6% had both a positive sputum culture for Mycobacterium tuberculosis and a valid MTBDRplus assay result. The MTBDRplus assay detected isoniazid (INH resistance directly from the sputum specimen in 159 (89.8% of 177 specimens and MDR-TB in 109 (95.6% of 114 specimens compared to conventional methods. There was high agreement between the MTBDRplus assay and conventional DST results in detecting MDR-TB (kappa = 0.95, p<0.01. The most prevalent INH resistance mutation was S315T (78% in the katG codon and the most common rifampicin resistance mutation was S531L (68% in the rpoB codon. Among 13 specimens from TB suspects with negative sputum cultures, 7 had a positive MTBDRplus assay (3 with MDR-TB. The time to detection of MDR-TB was significantly less using the MTBDRplus assay (4.2 days compared to the use of standard phenotypic tests (67.3 days with solid media and 21.6 days with broth-based media.Compared to conventional methods, the MTBDRplus assay had high accuracy and significantly reduced time to detection of MDR-TB in an area with high MDR-TB prevalence. The use of rapid molecular diagnostic tests for TB and drug resistance should increase the proportion of patients promptly placed on appropriate therapy.

  1. Method of Check of Statistical Hypotheses for Revealing of “Fraud” Point of Sale

    Directory of Open Access Journals (Sweden)

    T. M. Bolotskaya

    2011-06-01

    Full Text Available Application method checking of statistical hypotheses fraud Point of Sale working with purchasing cards and suspected of accomplishment of unauthorized operations is analyzed. On the basis of the received results the algorithm is developed, allowing receive an assessment of works of terminals in regime off-line.

  2. De bruikbaarheid van de ‘shaken baby syndroom’-hypothese in het strafproces

    NARCIS (Netherlands)

    Hoving, R.A.

    In het Nederlandse strafproces wordt regelmatig gebruik gemaakt van deskundigenbewijs van deskundigen die uitgaan van de ‘shaken baby syndroom’-hypothese om aan te tonen dat een verdachte een baby heeft mishandeld of gedood. In onder meer de Verenigde Staten en Engeland woedt een felle discussie

  3. Hypotheses on citation practices as revealed in the literature of the ...

    African Journals Online (AJOL)

    Citations found in two historical articles, which appeared in Cancer Research, a top American Journal, were used to show both positive and negative attitudes towards my 22 historical publications on cancer carriage in the body. Therefore, scientific information concepts are cited critically and two hypotheses are advanced ...

  4. ADOPTING SOCIO-DEMOGRAPHIC CHARACTERISTICS IN PROFILING GREEN CONSUMERS: A REVIEW OF HYPOTHESES

    Directory of Open Access Journals (Sweden)

    Arif Hartono

    2009-02-01

    Full Text Available In the last three decades worldwide environmental consciousness has increased dramatically as well as profiling green consumers have gained tremendous attention in the past. Segmenting and targeting markets base on pro-environmental purchase behavior are essential when companies positioning their green products. Socio-demographic characteristics have gained a lot of attention as the key profiling variables. Such characteristics have been employed by many scholars more frequently for the bases of segmenting and profiling green consumers. However, most existing studies of green consumers’ socio-demographic were US based. The present article attempts to review the common hypotheses of socio-demographic characteristics in profiling green consumers. The present article reviews five general hypotheses relating to socio-demographics and environmental consciousness of green consumers, namely the gender, age, education level, income, and occupation hypotheses, as well as the theoretical explanation for each hypothesis. Most previous studies tend to have the same conclusion in the gender, age, education level, and  income characteristics. Critics to socio-demographic characteristics and a need to conduct green marketing research in Indonesia was also reviewed.Key words: profiling, socio-demographic, green consumer, hypotheses.

  5. Improving the Development of Student's Research Questions and Hypotheses in an Introductory Business Research Methods Course

    Science.gov (United States)

    Strangman, Lauria; Knowles, Elizabeth

    2012-01-01

    In an introductory research methods course, students often develop research questions and hypotheses that are vague or confusing, do not contain measurable concepts, and are too narrow in scope or vision. Because of this, the final research projects often fail to provide useful information or address the overall research problem. A Lesson Study…

  6. Utility of Krashen's Five Hypotheses in the Saudi Context of Foreign Language Acquisition/Learning

    Science.gov (United States)

    Gulzar, Malik Ajmal; Gulnaz, Fahmeeda; Ijaz, Attiya

    2014-01-01

    In the last twenty years, the paradigm that has dominated the discipline of language teaching is the SLA theory and Krashen's five hypotheses which are still proving flexible to accommodate earlier reforms. This paper reviews second language acquisition (SLA) theory to establish an understanding of its role in the EFL/ESL classrooms. Other areas…

  7. Williams Syndrome Hypersociability: A Neuropsychological Study of the Amygdala and Prefrontal Cortex Hypotheses

    Science.gov (United States)

    Capitao, Liliana; Sampaio, Adriana; Fernandez, Montse; Sousa, Nuno; Pinheiro, Ana; Goncalves, Oscar F.

    2011-01-01

    Individuals with Williams syndrome display indiscriminate approach towards strangers. Neuroimaging studies conducted so far have linked this social profile to structural and/or functional abnormalities in WS amygdala and prefrontal cortex. In this study, the neuropsychological hypotheses of amygdala and prefrontal cortex involvement in WS…

  8. Coping with the Stigma of Mental Illness: Empirically-Grounded Hypotheses from Computer Simulations

    Science.gov (United States)

    Kroska, Amy; Har, Sarah K.

    2011-01-01

    This research demonstrates how affect control theory and its computer program, "Interact", can be used to develop empirically-grounded hypotheses regarding the connection between cultural labels and behaviors. Our demonstration focuses on propositions in the modified labeling theory of mental illness. According to the MLT, negative societal…

  9. Gender Relations and Economic Development: Hypotheses about the Reversal of Fortune in EurAsia

    NARCIS (Netherlands)

    de Pleijt, A.M.; van Zanden, J.L.; Carmichael, S.G.

    2016-01-01

    This paper develops an interrelated set of hypotheses about the links between gender relations, family systems and economic development in EurAsia. Firstly, we briefly discuss a number of ideas from the recent literature about the links between gender relations and economic development. Secondly, we

  10. Examining Preservice Science Teachers' Skills of Formulating Hypotheses and Identifying Variables

    Science.gov (United States)

    Aydogdu, Bülent

    2015-01-01

    The aim of this study is to examine preservice science teachers' skills of formulating hypotheses and identifying variables. The research has a phenomenological research design. The data was gathered qualitatively. In this study, preservice science teachers were first given two scenarios (Scenario-1 & Scenario-2) containing two different…

  11. Study design, objectives, hypotheses, main findings, health consequences for the population exposed, rationale of future research

    Energy Technology Data Exchange (ETDEWEB)

    Trnovec, T.; Kocan, A. [Slovak Medical Univ., Bratislava (Slovakia); Bencko, V. [Charles Univ., Prague (Czech Republic); Langer, P. [Institute of Experimental Endocrinology SAS, Bratislava (Slovakia); Berg, M. van den [Rijksuniversiteit Utrecht (Netherlands); Bergman, A. [Stockholm Univ. (Sweden); Hustak, M. [Air Force Military Hospital, Kosics (Slovakia)

    2004-09-15

    pesticides, polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) within a population that has been exposed to these chemicals as a result of environmental pollution. The hypotheses tested are closely related to these objectives. The basic hypothesis that can be further developed for a particular compound of interest and health outcome is as follows: ''Is there any association between a certain type of health outcome investigated and the organochlorine exposure?'' Any of the project objectives was targeted at the place of residence as a predictor of any health outcome.

  12. Advancing the literature on designing audit and feedback interventions: identifying theory-informed hypotheses.

    Science.gov (United States)

    Colquhoun, Heather L; Carroll, Kelly; Eva, Kevin W; Grimshaw, Jeremy M; Ivers, Noah; Michie, Susan; Sales, Anne; Brehaut, Jamie C

    2017-09-29

    Audit and feedback (A&F) is a common strategy for helping health providers to implement evidence into practice. Despite being extensively studied, health care A&F interventions remain variably effective, with overall effect sizes that have not improved since 2003. Contributing to this stagnation is the fact that most health care A&F interventions have largely been designed without being informed by theoretical understanding from the behavioral and social sciences. To determine if the trend can be improved, the objective of this study was to develop a list of testable, theory-informed hypotheses about how to design more effective A&F interventions. Using purposive sampling, semi-structured 60-90-min telephone interviews were conducted with experts in theories related to A&F from a range of fields (e.g., cognitive, health and organizational psychology, medical decision-making, economics). Guided by detailed descriptions of A&F interventions from the health care literature, interviewees described how they would approach the problem of designing improved A&F interventions. Specific, theory-informed hypotheses about the conditions for effective design and delivery of A&F interventions were elicited from the interviews. The resulting hypotheses were assigned by three coders working independently into themes, and categories of themes, in an iterative process. We conducted 28 interviews and identified 313 theory-informed hypotheses, which were placed into 30 themes. The 30 themes included hypotheses related to the following five categories: A&F recipient (seven themes), content of the A&F (ten themes), process of delivery of the A&F (six themes), behavior that was the focus of the A&F (three themes), and other (four themes). We have identified a set of testable, theory-informed hypotheses from a broad range of behavioral and social science that suggest conditions for more effective A&F interventions. This work demonstrates the breadth of perspectives about A&F from non

  13. Development of test models to quantify encapsulated bioburden in spacecraft polymer materials by cultivation-dependent and molecular methods

    Science.gov (United States)

    Bauermeister, Anja; Moissl-Eichinger, Christine; Mahnert, Alexander; Probst, Alexander; Flier, Niwin; Auerbach, Anna; Weber, Christina; Haberer, Klaus; Boeker, Alexander

    Bioburden encapsulated in spacecraft polymers (such as adhesives and coatings) poses a potential risk to scientific exploration of other celestial bodies, but it is not easily detectable. In this study, we developed novel testing strategies to estimate the quantity of intrinsic encapsulated bioburden in polymers used frequently on spaceflight hardware. In particular Scotch-Weld (TM) 2216 B/A (Epoxy adhesive); MAP SG121FD (Silicone coating), Solithane (®) 113 (Urethane resin); ESP 495 (Silicone adhesive); and Dow Corning (®) 93-500 (Silicone encapsulant) were investigated. As extraction of bioburden from polymerized (solid) materials did not prove feasible, a method was devised to extract contaminants from uncured polymer precursors by dilution in organic solvents. Cultivation-dependent analyses showed less than 0.1-2.5 colony forming units (cfu) per cm³ polymer, whereas quantitative PCR with extracted DNA indicated considerably higher values, despite low DNA extraction efficiency. Results obtained by this method reflected the most conservative proxy for encapsulated bioburden. To observe the effect of physical and chemical stress occurring during polymerization on the viability of encapsulated contaminants, Bacillus safensis spores were embedded close to the surface in cured polymer, which facilitated access for different analytical techniques. Staining by AlexaFluor succinimidyl ester 488 (AF488), propidium monoazide (PMA), CTC (5-cyano-2,3-diotolyl tetrazolium chloride) and subsequent confocal laser scanning microscopy (CLSM) demonstrated that embedded spores retained integrity, germination and cultivation ability even after polymerization of the adhesive Scotch-Weld™ 2216 B/A.

  14. A molecular diagnostic tool to replace larval culture in conventional faecal egg count reduction testing in sheep.

    Directory of Open Access Journals (Sweden)

    Florian Roeber

    Full Text Available The accurate diagnosis of parasitic nematode infections in livestock (including sheep and goats is central to their effective control and the detection of the anthelmintic resistance. Traditionally, the faecal egg count reduction test (FECRT, combined with the technique of larval culture (LC, has been used widely to assess drug-susceptibility/resistance in strongylid nematodes. However, this approach suffers from a lack of specificity, sensitivity and reliability, and is time-consuming and costly to conduct. Here, we critically assessed a specific PCR assay to support FECRT, in a well-controlled experiment on sheep with naturally acquired strongylid infections known to be resistant to benzimidazoles. We showed that the PCR results were in close agreement with those of total worm count (TWC, but not of LC. Importantly, albendazole resistance detected by PCR-coupled FECRT was unequivocally linked to Teladorsagia circumcincta and, to lesser extent, Trichostrongylus colubriformis, a result that was not achievable by LC. The key findings from this study demonstrate that our PCR-coupled FECRT approach has major merit for supporting anthelmintic resistance in nematode populations. The findings also show clearly that our PCR assay can be used as an alternative to LC, and is more time-efficient and less laborious, which has important practical implications for the effective management and control strongylid nematodes of sheep.

  15. Molecular testing for viral and bacterial enteric pathogens: gold standard for viruses, but don't let culture go just yet?

    Science.gov (United States)

    Bloomfield, Maxim G; Balm, Michelle N D; Blackmore, Timothy K

    2015-04-01

    Contemporary diagnostic microbiology is increasingly adopting molecular methods as front line tests for a variety of samples. This trend holds true for detection of enteric pathogens (EP), where nucleic acid amplification tests (NAAT) for viruses are well established as the gold standard, and an increasing number of commercial multi-target assays are now available for bacteria and parasites. NAAT have significant sensitivity and turnaround time advantages over traditional methods, potentially returning same-day results. Multiplex panels offer an attractive 'one-stop shop' that may provide workflow and cost advantages to laboratories processing large sample volumes. However, there are a number of issues which need consideration. Reflex culture is required for antibiotic susceptibility testing and strain typing when needed for food safety and other epidemiological investigations. Surveillance systems will need to allow for differences in disease incidence due to the enhanced sensitivity of NAAT. Laboratories should be mindful of local epidemiology when selecting which pathogens to include in multiplex panels, and be thoughtful regarding which pathogens will not be detected. Multiplex panels may not be appropriate in certain situations, such as hospital-onset diarrhoea, where Clostridium difficile testing might be all that is required, and laboratories may wish to retain the flexibility to run single tests in such situations. The clinical impact of rapid results is also likely to be relatively minor, as infective diarrhoea is a self-limiting illness in the majority of cases. Laboratories will require strategies to assist users in the interpretation of the results produced by NAAT, particularly where pathogens are detected at low levels with uncertain clinical significance. These caveats aside, faecal NAAT are increasingly being used and introduce a new era of diagnosis of gastrointestinal infection.

  16. Proband-only medical exome sequencing as a cost-effective first-tier genetic diagnostic test for patients without prior molecular tests and clinical diagnosis in a developing country: the China experience.

    Science.gov (United States)

    Hu, Xuyun; Li, Niu; Xu, Yufei; Li, Guoqiang; Yu, Tingting; Yao, Ru-En; Fu, Lijun; Wang, Jiwen; Yin, Lei; Yin, Yong; Wang, Ying; Jin, Xingming; Wang, Xiumin; Wang, Jian; Shen, Yiping

    2017-11-02

    PurposeTo evaluate the performance of proband-only medical exome sequencing (POMES) as a cost-effective first-tier diagnostic test for pediatric patients with unselected conditions.MethodsA total of 1,323 patients were tested by POMES, which targeted 2,742 known disease-causing genes. Clinical relevant variants were Sanger-confirmed in probands and parents. We assessed the diagnostic validity and clinical utility of POMES by means of a survey questionnaire.ResultsPOMES, ordered by 136 physicians, identified 512 pathogenic or likely pathogenic variants associated with over 200 conditions. The overall diagnostic rate was 28.8%, ranging from 10% in neonatal intensive care unit patients to over 35% in pediatric intensive care unit patients. The test results had an impact on the management of the 45.1% of patients for whom there were positive findings. The average turnaround time was 57 days; the cost was $360/case.ConclusionWe adopted a relatively efficient and cost-effective approach in China for the molecular diagnosis of pediatric patients with suspected genetic conditions. While training for clinical geneticists and other specialists is lagging behind in China POMES is serving as a diagnostic equalizer for patients who do not normally receive extensive clinical evaluation and clinical diagnosis prior to testing. This Chinese experience should be applicable to other developing countries that are lacking clinical, financial, and personnel resources.GENETICS in MEDICINE advance online publication, 2 November 2017; doi:10.1038/gim.2017.195.

  17. Molecular Beacons in Diagnostics

    OpenAIRE

    Tyagi, Sanjay; Kramer, Fred Russell

    2012-01-01

    Recent technical advances have begun to realize the potential of molecular beacons to test for diverse infections in clinical diagnostic laboratories. These include the ability to test for, and quantify, multiple pathogens in the same clinical sample, and to detect antibiotic resistant strains within hours. The design principles of molecular beacons have also spawned a variety of allied technologies.

  18. Molecular and morphometric evidence for separate species of Uncinaria (Nematoda: Ancylostomatidae) in California sea lions and northern fur seals: hypothesis testing supplants verification.

    Science.gov (United States)

    Nadler, S A; Adams, B J; Lyons, E T; DeLong, R L; Melin, S R

    2000-10-01

    California sea lions (Zalophus californianus) and northern fur seals (Callorhinus ursinus) are each believed to host distinct hookworm species (Uncinaria spp.). However, a recent morphometric analysis suggested that a single species parasitizes multiple pinniped hosts, and that the observed differences are host-induced. To explore the systematics of these hookworms and test these competing hypotheses, we obtained nucleotide sequences of nuclear ribosomal DNA (D2/D3 28S, D18/D19 28S, and internal transcribed spacer [ITS] regions) from 20 individual hookworms parasitizing California sea lion and northern fur seal pups where their breeding grounds are sympatric. Five individuals from an allopatric population of California sea lions were also sampled for ITS-1 and D18/D19 28S sequences. The 28S D2/D3 sequences showed no diagnostic differences among hookworms sampled from individual sea lions and fur seals, whereas the 28S D18/D19 sequences had one derived (apomorphic) character demarcating hookworms from northern fur seals. ITS sequences were variable for 7 characters, with 4 derived (apomorphic) states in ITS-1 demarcating hookworms from California sea lions. Multivariate analysis of morphometric data also revealed significant differences between nematodes representing these 2 host-associated lineages. These results indicate that these hookworms represent 2 species that are not distributed indiscriminately between these host species, but instead exhibit host fidelity, evolving independently with each respective host species. This evolutionary approach to analyzing sequence data for species delimitation is contrasted with similarity-based methods that have been applied to numerous diagnostic studies of nematode parasites.

  19. Facial markings in the social cuckoo wasp Polistes sulcifer: No support for the visual deception and the assessment hypotheses.

    Science.gov (United States)

    Cini, Alessandro; Ortolani, Irene; Zechini, Luigi; Cervo, Rita

    2015-02-01

    Insect social parasites have to conquer a host colony by overcoming its defensive barriers. In addition to increased fighting abilities, many social parasites evolved sophisticated sensory deception mechanisms to elude host colonies defenses by exploiting host communication channels. Recently, it has been shown that the conspicuous facial markings of a paper wasp social parasite, Polistes sulcifer, decrease the aggressiveness of host foundresses. Two main hypotheses stand as explanations of this phenomenon: visual sensory deception (i.e. the black patterning reduces host aggression by exploiting the host visual communication system) and visual quality assessment (i.e. facial markings reduce aggressiveness as they signal the increased fighting ability of parasites). Through behavioral assays and morphological measurements we tested three predictions resulting from these hypotheses and found no support either for the visual sensory deception or for the quality assessment to explain the reduction in host aggressiveness towards the parasite. Our results suggest that other discrimination processes may explain the observed phenomenon. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Visual functions in phenylketonuria-evaluating the dopamine and long-chain polyunsaturated fatty acids depletion hypotheses.

    Science.gov (United States)

    Gramer, Gwendolyn; Förl, Birgit; Springer, Christina; Weimer, Petra; Haege, Gisela; Mackensen, Friederike; Müller, Edith; Völcker, Hans Eberhard; Hoffmann, Georg Friedrich; Lindner, Martin; Krastel, Hermann; Burgard, Peter

    2013-01-01

    In phenylketonuria presymptomatic treatment following newborn screening prevents severe mental and physical impairment. The reasons for subtle impairments of cerebral functions despite early treatment remain unclear. We assessed a broad spectrum of visual functions in early-treated patients with phenylketonuria and evaluated two hypotheses-the dopamine and the long-chain polyunsaturated fatty acids (LCPUFAs) depletion hypotheses. Contrast sensitivity, colour vision, electroretinography, frequency doubling technology campimetry (FDT), and their relation with blood phenylalanine and docosahexaenoic acid levels were assessed in 36 patients with phenylketonuria and 18 age-matched healthy controls. Contrast sensitivity was significantly lower and total error scores in colour vision significantly higher in patients than controls. Electroretinography results differed significantly between patients and controls. We found a trend for the effect of phenylalanine-levels on contrast sensitivity and a significant effect on colour vision/FDT results. Docosahexaenoic acid levels in erythrocytes were not associated with visual functions. This is the first evaluation of visual functions in phenylketonuria using a comprehensive ophthalmological test battery. We found no evidence supporting the long-chain polyunsaturated fatty acids depletion hypothesis. However, the effect of phenylalanine-levels on visual functions suggests that imbalance between phenylalanine and tyrosine may affect retinal dopamine levels in phenylketonuria. This is supported by the similar patterns of visual functions in patients with phenylketonuria observed in our study and patients with Parkinson's disease. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. High-throughput strategy for molecular identification of Vel- blood donors employing nucleic acids extracted from plasma pools used for viral nucleic acid test screening.

    Science.gov (United States)

    Dezan, Marcia R; Dinardo, Carla L; Bosi, Silvia R A; Vega, Sileni; Salles, Nanci A; Mendrone-Júnior, Alfredo; Levi, José E

    2016-06-01

    Serologic methods to determine the Vel- phenotype require the use of rare human antisera and do not allow for many samples to be tested simultaneously, which limits their application as a tool to search for rare donors. This study developed a low-cost molecular screening strategy using real-time polymerase chain reaction (PCR) and DNA, extracted from plasma pools for viral nucleic acid test (NAT) screening, to identify Vel- and Vel+(W) donors. A total of 4680 blood donors from the Brazilian southeast region were genotyped through real-time PCR targeting the 17-nucleotide (c.64_80del) deletion in the SMIM1 gene, which determines the Vel- phenotype, by using remaining nucleic acid from plasma pools of six donors, routinely discarded after the release of viral NAT results. Twenty pools tested reactive and individual testing of samples from reactive pools identified 19 heterozygous donors with the SMIM1*64_80del deletion (0.40%) and one homozygous donor (0.02%). Fourteen of the 19 donors were confirmed as Vel- or Vel+(W) using anti-Vel human antiserum. The DNA pool genotyping strategy using real-time PCR designed to detect the deletion in the SMIM1 gene proved effective and accurate in identifying donors with the Vel- and Vel+(W) phenotypes. The fact that remaining nucleic acid from routine viral NAT screening was used makes this technique economically attractive and definitely superior to the serologic techniques available to search for this rare phenotype. © 2016 AABB.

  2. Political market orientation and strategic party postures: Some hypotheses regarding profiles and relationship strengths

    DEFF Research Database (Denmark)

    Ormrod, Robert P.; Henneberg, Stephan C. M.

    2007-01-01

    an integrated construct of political marketing strategy which is exemplified by the derivation of hypotheses of the relationships between organizational stances on the one hand, and attitudinal and behavioural aspects of political market orientation on the other. We propose two levels of hypotheses: Firstly......Recently, the areas of strategic political marketing as well as political market orientation have been the subject of several conceptual articles (e.g., Henneberg 2006a; O'Cass 1996; Ormrod 2005, 2007). These have laid the theoretical foundations for further empirical work (e.g., Henneberg 2006b; O......'Cass 1996, 2001a, 2001b; Ormrod et al. 2007; Ormrod and Henneberg 2008 forthcoming). However, despite the close conceptual relatedness between some of these concepts they have yet to be integrated to provide a more nuanced picture which researchers but also political marketing practitioners can utilise...

  3. A set working hypotheses towards a unified view of the universe

    International Nuclear Information System (INIS)

    Kecher, J.-C.; Vigier, J.P.; Centre National de la Recherche Scientifique, 75 - Paris; Paris-6 Univ., 75

    1976-01-01

    Some observation evidence (anisotropy and inhomogeneity of the Hubble constant, abnormal red shifts) led the authors to formulate working hypotheses compatible with these observations. The logics of these hypotheses led to consider the universe as a ''hierarchical'' universe similar to Charlier one, and to find the cause of the apparent expansion in the interactions affecting the path of the photons. As, in some cases, intrinsic red shifts are very important this reduces the distance of the considered objects and their absolute luminosity, and forces to link them with ordinary galaxies; a scheme of evolution of extragalactic objects is suggested, to account for the geometrical location of abnormal objects, and for some aspects of their morphology. Coherent picture of the universe might emerge from the suggested studies

  4. Global changes of climate through human activities. New clues and hypotheses

    Energy Technology Data Exchange (ETDEWEB)

    Grassl, H

    1988-02-01

    New clues to world-wide changes of climate through human activities have been found or corroborated: Precipitation belts have shifted during the last 30 years; ozone over Antarctica in spring has fallen to its lowest level ever (1956); near-ground ozone in our latitudes has at least doubled in this century. Newly discussed hypotheses are: The oxidation capacity and, consequently, the purification capacity of the atmosphere decreases in the southern hemisphere owing above all to the increase in methane. Increased backscatter of solar radiation through low clouds during periods of turbid air in the atmosphere attenuates the greenhouse effect, the increase in icy clouds through condensation trails of jets flying at high altitudes intensifies the greenhouse effect of the atmosphere. The paper analyses these hypotheses and shows that the distinction between change of climate on the one hand and ecological damage on the other is not justifiable any longer. (orig./HSCH).

  5. Skin Stem Cell Hypotheses and Long Term Clone Survival – Explored Using Agent-based Modelling

    Science.gov (United States)

    Li, X.; Upadhyay, A. K.; Bullock, A. J.; Dicolandrea, T.; Xu, J.; Binder, R. L.; Robinson, M. K.; Finlay, D. R.; Mills, K. J.; Bascom, C. C.; Kelling, C. K.; Isfort, R. J.; Haycock, J. W.; MacNeil, S.; Smallwood, R. H.

    2013-01-01

    Epithelial renewal in skin is achieved by the constant turnover and differentiation of keratinocytes. Three popular hypotheses have been proposed to explain basal keratinocyte regeneration and epidermal homeostasis: 1) asymmetric division (stem-transit amplifying cell); 2) populational asymmetry (progenitor cell with stochastic fate); and 3) populational asymmetry with stem cells. In this study, we investigated lineage dynamics using these hypotheses with a 3D agent-based model of the epidermis. The model simulated the growth and maintenance of the epidermis over three years. The offspring of each proliferative cell was traced. While all lineages were preserved in asymmetric division, the vast majority were lost when assuming populational asymmetry. The third hypothesis provided the most reliable mechanism for self-renewal by preserving genetic heterogeneity in quiescent stem cells, and also inherent mechanisms for skin ageing and the accumulation of genetic mutation. PMID:23712735

  6. Skin stem cell hypotheses and long term clone survival--explored using agent-based modelling.

    Science.gov (United States)

    Li, X; Upadhyay, A K; Bullock, A J; Dicolandrea, T; Xu, J; Binder, R L; Robinson, M K; Finlay, D R; Mills, K J; Bascom, C C; Kelling, C K; Isfort, R J; Haycock, J W; MacNeil, S; Smallwood, R H

    2013-01-01

    Epithelial renewal in skin is achieved by the constant turnover and differentiation of keratinocytes. Three popular hypotheses have been proposed to explain basal keratinocyte regeneration and epidermal homeostasis: 1) asymmetric division (stem-transit amplifying cell); 2) populational asymmetry (progenitor cell with stochastic fate); and 3) populational asymmetry with stem cells. In this study, we investigated lineage dynamics using these hypotheses with a 3D agent-based model of the epidermis. The model simulated the growth and maintenance of the epidermis over three years. The offspring of each proliferative cell was traced. While all lineages were preserved in asymmetric division, the vast majority were lost when assuming populational asymmetry. The third hypothesis provided the most reliable mechanism for self-renewal by preserving genetic heterogeneity in quiescent stem cells, and also inherent mechanisms for skin ageing and the accumulation of genetic mutation.

  7. NegaWatt 2011-2050 scenario - Hypotheses and method. Technical report, May 2014

    International Nuclear Information System (INIS)

    2014-05-01

    This report proposes an analysis of the negaWatt 2011 scenario. It describes in detail the methodology adopted to elaborate this prospective scenario, and presents the major part of the hypotheses which structure this scenario. A first part presents the approach and methodology (constraints, scenario, model). The second part addresses the issue of energy saving and energy efficiency through a sector-based analysis (housing and office building, transports, industrial and agricultural production). The third part studies the substitution by renewable energies through a supply analysis: energy production based on biomass, renewable energies, and fissile and fossil energies. It outlines the major role of grids in the supply-demand balance. The results of the negaWatt 2011 scenario are presented in terms of final energy, primary energies, and impact on greenhouse gas emissions. Hypotheses and results related to the different sectors (building, transports, industry and agriculture, energy production) are given in appendix

  8. Towards Self-Learning Based Hypotheses Generation in Biomedical Text Domain.

    Science.gov (United States)

    Gopalakrishnan, Vishrawas; Jha, Kishlay; Xun, Guangxu; Ngo, Hung Q; Zhang, Aidong

    2017-12-26

    The overwhelming amount of research articles in the domain of bio-medicine might cause important connections to remain unnoticed. Literature Based Discovery is a sub-field within biomedical text mining that peruses these articles to formulate high confident hypotheses on possible connections between medical concepts. Although many alternate methodologies have been proposed over the last decade, they still suffer from scalability issues. The primary reason, apart from the dense inter-connections between biological concepts, is the absence of information on the factors that lead to the edge-formation. In this work, we formulate this problem as a collaborative filtering task and leverage a relatively new concept of word-vectors to learn and mimic the implicit edge-formation process. Along with single-class classifier, we prune the search-space of redundant and irrelevant hypotheses to increase the efficiency of the system and at the same time maintaining and in some cases even boosting the overall accuracy. We show that our proposed framework is able to prune up to 90% of the hypotheses while still retaining high recall in top-K results. This level of efficiency enables the discovery algorithm to look for higher-order hypotheses, something that was infeasible until now. Furthermore, the generic formulation allows our approach to be agile to performboth open and closed discovery.We also experimentally validate that the core data-structures upon which the system bases its decision has a high concordance with the opinion of the experts.This coupled with the ability to understand the edge formation process provides us with interpretable results without any manual intervention. The relevant JAVA codes are available at: https://github.com/vishrawas/Medline-Code_v2. vishrawa@buffalo.edukishlayj@buffalo.edu. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email

  9. Statistical analysis of hypotheses on the cointegrating relations in the I(2) model

    DEFF Research Database (Denmark)

    Johansen, Søren

    2006-01-01

    The cointegrated vector autoregressive model for I(2) variables is a non-linear parametric restriction on the linear I(2) regression model for variables of order I(0), I(1) and I(2). In this paper we discuss non-linear submodels given by smooth parametrizations. We give conditions on the parametr......) and the reformulation is applied to show that some hypotheses on the cointegrating coefficients in the cointegrated I(2) model give asymptotic ¿² inference....

  10. Deformational plagiocephaly in normal infants: a systematic review of causes and hypotheses.

    Science.gov (United States)

    De Bock, Freia; Braun, Volker; Renz-Polster, Herbert

    2017-06-01

    Deformational plagiocephaly (DP) is one of the most prevalent abnormal findings in infants and a frequent reason for parents to seek paediatric advice. To systematically review the literature and identify evidence and hypotheses on the aetiology and determinants of DP in otherwise healthy infants. Systematic keyword search in all major biomedical databases to identify peer-reviewed publications reporting (a) empirical research or (b) hypotheses on the aetiology of DP in healthy, term infants. 3150 studies published between 1985 and 2016 and containing relevant keywords were screened. In a two-pronged approach, results were summarised separately for the body of empirical work (22 studies) and the body of hypotheses (110 articles). Only a few empirical studies have examined risk factors in non-selected patient populations on a higher grade methodological level. The most commonly reported risk factors were: male gender, supine sleep position, limited neck rotation or preference in head position, first-born child, lower level of activity and lack of tummy time. Agreement between empirical studies was poor for most exposures, including supine sleep position, tummy time and use of car seats. The articles reporting hypotheses on the aetiology of DP cover a wide field of environmental and biological factors, but include little suggestions as to the potential influence of the everyday care environment of the baby. The evidence on the aetiology of DP is fragmentary and heterogeneous. In addition, factors possibly relevant to the development of DP have not been appreciated in the scientific discussion. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. Five hypotheses concerning the fate of the Singapore issues in the Doha Round

    OpenAIRE

    Evenett, Simon J.

    2017-01-01

    At the Cancún Ministerial Conference, the members of the World Trade Organization (WTO) disagreed on whether to launch negotiations on multilateral disciplines concerning the four areas of government policy collectively known as the ‘Singapore issues'. This amounted to a decision not to expand the WTO's boundaries along these dimensions. In this paper, five hypotheses concerning the treatment of the Singapore issues by the WTO's membership are described and assessed. The implications of this ...

  12. Controversial hypotheses on the relationship between researcher and informant in qualitative research.

    Science.gov (United States)

    Wilde, V

    1992-02-01

    This paper addresses methodological issues that emerged unexpectedly during a qualitative study set up to explore nurses' descriptions of difficult, challenging and satisfying experiences at work. The purpose of the study had been to look for critical factors influencing nurses' perceptions of their performance in specific situations, and their labelling of each event. Ten nurses were asked to describe in detail three events; a difficult situation in which they had coped well, a difficult situation in which they would like to have coped better, and a satisfying or rewarding situation. The critical incident technique was used. Rich descriptions were obtained, tape recorded, transcribed verbatum, and analysed by constant comparative analysis, following the principles of grounded theory. Some suprising hypotheses emerged regarding the methodology of the informal interview in qualitative research. This paper addresses these hypotheses, which focus on the interaction between the researcher and informant, the role conflict facing the nurse researcher, the effect of the researcher's past experience on the interaction, the use of counselling strategies and the principle of self-disclosure. These hypotheses were incidental to the original area of study and were more exciting in their emergence because of this.

  13. Validity of the Environmental Kuznets Curve Hypotheses in Water Pollution A Case Study

    Directory of Open Access Journals (Sweden)

    Hediyeh Alishiri

    2017-03-01

    Full Text Available Among the different environmental pollutions, water pollution is of especial importance due to the rather unchanging supply of this vital resource on a global scale and because of the dire consequences of its pollution for human health. The relationship between water production and its pollution can thus established and used as a measure of environmental degradation. This relationship can then be captured and analyzed in terms of environmental Kuznets hypotheses. It may be claimed that the early stages of economic growth is associated with lower per capita income and water pollution but the trend is reversed with increasing per capita income and improved economic growth. The present study was conducted using the panel data technique and the Kuznets environmental hypotheses were examined for the two groups of developed and developing countries under the two scenarios of using either per capita GDP or the share of industry to the added value in GDP as an indicator of economic growth. Results indicate that under both scenarios, Kuznets hypotheses are confirmed when studying the situation in developing countries but refuted in the case of developed countries.

  14. Intrahost Diversity of Feline Coronavirus: A Consensus between the Circulating Virulent/Avirulent Strains and the Internal Mutation Hypotheses?

    Directory of Open Access Journals (Sweden)

    Aline S. Hora

    2013-01-01

    Full Text Available To evaluate the most controversial issue concerning current feline coronavirus (FCoV virology, the coexisting hypotheses of the intrahost and interhost origins of feline infectious peritonitis virus (FIPV in regard to the pathogenesis of feline infectious peritonitis (FIP, this study aimed to assess the molecular diversity of the membrane gene FCoVs in 190 samples from 10 cats with signs of FIP and in 5 faecal samples from cats without signs of FIP. All samples from the non-FIP cats and 25.26% of the samples from the FIP cats were positive for the FCoV membrane (M gene. Mutations in this gene consisted of SNP changes randomly scattered among the sequences; few mutations resulted in amino acid changes. No geographic pattern was observed. Of the cats without FIP that harboured FECoV, the amino acid sequence identities for the M gene were 100% among cats (Cats 1–3 from the same cattery, and the overall sequence identity for the M gene was ≥91%. In one cat, two different lineages of FCoV, one enteric and one systemic, were found that segregated apart in the M gene tree. In conclusion, the in vivo mutation transition hypothesis and the circulating high virulent-low virulent FCoV hypothesis have been found to be plausible according to the results obtained from sequencing the M gene.

  15. Mismatch between aspects of hearing impairment and hearing disability/handicap in adult/elderly Cantonese speakers: some hypotheses concerning cultural and linguistic influences.

    Science.gov (United States)

    Doyle, J; Wong, L L

    1996-12-01

    This paper addresses the observation that some Cantonese-speaking adults do not perceive a hearing problem even when hearing screening identifies hearing loss. A sample of 49 Cantonese speakers was surveyed about their self-perceptions of hearing prior to a 25 dB HTL pure-tone screening test. All 49 persons failed the screening test, yet 34 (69.4%) reported that they had no problems hearing during conversations. Persons who admitted hearing difficulties tended to have mean hearing levels in excess of 45 dB HTL. A number of hypotheses concerning cultural and linguistic influences are proposed as explanations for the apparent lack of significance of auditory sensitivity loss for some Cantonese speakers. Ways in which these hypotheses might be tested are suggested.

  16. Diversity patterns amongst herbivorous dinosaurs and plants during the Cretaceous: implications for hypotheses of dinosaur/angiosperm co-evolution.

    Science.gov (United States)

    Butler, R J; Barrett, P M; Kenrick, P; Penn, M G

    2009-03-01

    Palaeobiologists frequently attempt to identify examples of co-evolutionary interactions over extended geological timescales. These hypotheses are often intuitively appealing, as co-evolution is so prevalent in extant ecosystems, and are easy to formulate; however, they are much more difficult to test than their modern analogues. Among the more intriguing deep time co-evolutionary scenarios are those that relate changes in Cretaceous dinosaur faunas to the primary radiation of flowering plants. Demonstration of temporal congruence between the diversifications of co-evolving groups is necessary to establish whether co-evolution could have occurred in such cases, but is insufficient to prove whether it actually did take place. Diversity patterns do, however, provide a means for falsifying such hypotheses. We have compiled a new database of Cretaceous dinosaur and plant distributions from information in the primary literature. This is used as the basis for plotting taxonomic diversity and occurrence curves for herbivorous dinosaurs (Sauropodomorpha, Stegosauria, Ankylosauria, Ornithopoda, Ceratopsia, Pachycephalosauria and herbivorous theropods) and major groups of plants (angiosperms, Bennettitales, cycads, cycadophytes, conifers, Filicales and Ginkgoales) that co-occur in dinosaur-bearing formations. Pairwise statistical comparisons were made between various floral and faunal groups to test for any significant similarities in the shapes of their diversity curves through time. We show that, with one possible exception, diversity patterns for major groups of herbivorous dinosaurs are not positively correlated with angiosperm diversity. In other words, at the level of major clades, there is no support for any diffuse co-evolutionary relationship between herbivorous dinosaurs and flowering plants. The diversification of Late Cretaceous pachycephalosaurs (excluding the problematic taxon Stenopelix) shows a positive correlation, but this might be spuriously related to

  17. Pathways to multidrug-resistant tuberculosis diagnosis and treatment initiation: a qualitative comparison of patients' experiences in the era of rapid molecular diagnostic tests.

    Science.gov (United States)

    Naidoo, Pren; van Niekerk, Margaret; du Toit, Elizabeth; Beyers, Nulda; Leon, Natalie

    2015-10-28

    Although new molecular diagnostic tests such as GenoType MTBDRplus and Xpert® MTB/RIF have reduced multidrug-resistant tuberculosis (MDR-TB) treatment initiation times, patients' experiences of diagnosis and treatment initiation are not known. This study aimed to explore and compare MDR-TB patients' experiences of their diagnostic and treatment initiation pathway in GenoType MTBDRplus and Xpert® MTB/RIF-based diagnostic algorithms. The study was undertaken in Cape Town, South Africa where primary health-care services provided free TB diagnosis and treatment. A smear, culture and GenoType MTBDRplus diagnostic algorithm was used in 2010, with Xpert® MTB/RIF phased in from 2011-2013. Participants diagnosed in each algorithm at four facilities were purposively sampled, stratifying by age, gender and MDR-TB risk profiles. We conducted in-depth qualitative interviews using a semi-structured interview guide. Through constant comparative analysis we induced common and divergent themes related to symptom recognition, health-care access, testing for MDR-TB and treatment initiation within and between groups. Data were triangulated with clinical information and health visit data from a structured questionnaire. We identified both enablers and barriers to early MDR-TB diagnosis and treatment. Half the patients had previously been treated for TB; most recognised recurring symptoms and reported early health-seeking. Those who attributed symptoms to other causes delayed health-seeking. Perceptions of poor public sector services were prevalent and may have contributed both to deferred health-seeking and to patient's use of the private sector, contributing to delays. However, once on treatment, most patients expressed satisfaction with public sector care. Two patients in the Xpert® MTB/RIF-based algorithm exemplified its potential to reduce delays, commencing MDR-TB treatment within a week of their first health contact. However, most patients in both algorithms experienced

  18. Molecular dynamics simulation for the test of calibrated OPLS-AA force field for binary liquid mixture of tri-iso-amyl phosphate and n-dodecane

    Science.gov (United States)

    Das, Arya; Ali, Sk. Musharaf

    2018-02-01

    Tri-isoamyl phosphate (TiAP) has been proposed to be an alternative for tri-butyl phosphate (TBP) in the Plutonium Uranium Extraction (PUREX) process. Recently, we have successfully calibrated and tested all-atom optimized potentials for liquid simulations using Mulliken partial charges for pure TiAP, TBP, and dodecane by performing molecular dynamics (MD) simulation. It is of immense importance to extend this potential for the various molecular properties of TiAP and TiAP/n-dodecane binary mixtures using MD simulation. Earlier, efforts were devoted to find out a suitable force field which can explain both structural and dynamical properties by empirical parameterization. Therefore, the present MD study reports the structural, dynamical, and thermodynamical properties with different mole fractions of TiAP-dodecane mixtures at the entire range of mole fraction of 0-1 employing our calibrated Mulliken embedded optimized potentials for liquid simulation (OPLS) force field. The calculated electric dipole moment of TiAP was seen to be almost unaffected by the TiAP concentration in the dodecane diluent. The calculated liquid densities of the TiAP-dodecane mixture are in good agreement with the experimental data. The mixture densities at different temperatures are also studied which was found to be reduced with temperature as expected. The plot of diffusivities for TiAP and dodecane against mole fraction in the binary mixture intersects at a composition in the range of 25%-30% of TiAP in dodecane, which is very much closer to the TBP/n-dodecane composition used in the PUREX process. The excess volume of mixing was found to be positive for the entire range of mole fraction and the excess enthalpy of mixing was shown to be endothermic for the TBP/n-dodecane mixture as well as TiAP/n-dodecane mixture as reported experimentally. The spatial pair correlation functions are evaluated between TiAP-TiAP and TiAP-dodecane molecules. Further, shear viscosity has been computed by

  19. Molecular dynamics simulation for the test of calibrated OPLS-AA force field for binary liquid mixture of tri-iso-amyl phosphate and n-dodecane.

    Science.gov (United States)

    Das, Arya; Ali, Sk Musharaf

    2018-02-21

    Tri-isoamyl phosphate (TiAP) has been proposed to be an alternative for tri-butyl phosphate (TBP) in the Plutonium Uranium Extraction (PUREX) process. Recently, we have successfully calibrated and tested all-atom optimized potentials for liquid simulations using Mulliken partial charges for pure TiAP, TBP, and dodecane by performing molecular dynamics (MD) simulation. It is of immense importance to extend this potential for the various molecular properties of TiAP and TiAP/n-dodecane binary mixtures using MD simulation. Earlier, efforts were devoted to find out a suitable force field which can explain both structural and dynamical properties by empirical parameterization. Therefore, the present MD study reports the structural, dynamical, and thermodynamical properties with different mole fractions of TiAP-dodecane mixtures at the entire range of mole fraction of 0-1 employing our calibrated Mulliken embedded optimized potentials for liquid simulation (OPLS) force field. The calculated electric dipole moment of TiAP was seen to be almost unaffected by the TiAP concentration in the dodecane diluent. The calculated liquid densities of the TiAP-dodecane mixture are in good agreement with the experimental data. The mixture densities at different temperatures are also studied which was found to be reduced with temperature as expected. The plot of diffusivities for TiAP and dodecane against mole fraction in the binary mixture intersects at a composition in the range of 25%-30% of TiAP in dodecane, which is very much closer to the TBP/n-dodecane composition used in the PUREX process. The excess volume of mixing was found to be positive for the entire range of mole fraction and the excess enthalpy of mixing was shown to be endothermic for the TBP/n-dodecane mixture as well as TiAP/n-dodecane mixture as reported experimentally. The spatial pair correlation functions are evaluated between TiAP-TiAP and TiAP-dodecane molecules. Further, shear viscosity has been computed by

  20. Environmental isotopes to test hypotheses for fluid mud (mud bank) generation mechanisms along the southwest coast of India

    Digital Repository Service at National Institute of Oceanography (India)

    Jacob, N.; Ansari, M.A.; Revichandran, C.

    monitor for assessment of radon in coastal ocean waters. J. Radioanal. Nucl. Chem. 249, 167e172. Cable, J.E., Burnett, W.C., Chanton, J.P., Weatherly, G.L., 1996. Modeling groundwater flow into the ocean based on 222Rn. Earth Planet. Sci. Lett. 144, 591e...Anally, W.H., Mehta, A.J. (Eds.), Est. Fine Sed. Proc. Elsevier Science BV, pp. 495e507. N. Jacob et al. / Estuarine, Coastal and Shelf Science 164 (2015) 115e123 123characteristics. Ind. J. Mar. Sci. 3, 105e114. Gopinathan, C.P., Regunathan, A., Rao, D.S...

  1. Transaction cost economics and the role of national culture : a test of hypotheses based on Inglehart and Hofstede

    NARCIS (Netherlands)

    Steenkamp, J.E.B.M.; Geyskens, I.

    2012-01-01

    Transaction cost economics (TCE) is probably the most widely accepted theory on how firms can gain competitive advantage through efficient organization of their economic transactions. However, by focusing on the competitive environment in which companies operate, it abstracts from the cultural

  2. Testing hypotheses for excess flower production and low fruit-to-flower ratios in a pollinating seed-consuming mutualism

    Science.gov (United States)

    Holland, J. Nathaniel; Bronstein, Judith L.; DeAngelis, Donald L.

    2004-01-01

    Pollinator attraction, pollen limitation, resource limitation, pollen donation and selective fruit abortion have all been proposed as processes explaining why hermaphroditic plants commonly produce many more flowers than mature fruit. We conducted a series of experiments in Arizona to investigate low fruit-to-flower ratios in senita cacti, which rely exclusively on pollinating seed-consumers. Selective abortion of fruit based on seed predators is of particular interest in this case because plants relying on pollinating seed-consumers are predicted to have such a mechanism to minimize seed loss. Pollinator attraction and pollen dispersal increased with flower number, but fruit set did not, refuting the hypothesis that excess flowers increase fruit set by attracting more pollinators. Fruit set of natural- and hand-pollinated flowers were not different, supporting the resource, rather than pollen, limitation hypothesis. Senita did abort fruit, but not selectively based on pollen quantity, pollen donors, or seed predators. Collectively, these results are consistent with sex allocation theory in that resource allocation to excess flower production can increase pollen dispersal and the male fitness function of flowers, but consequently results in reduced resources available for fruit set. Inconsistent with sex allocation theory, however, fruit production and the female fitness function of flowers may actually increase with flower production. This is because excess flower production lowers pollinator-to-flower ratios and results in fruit abortion, both of which limit the abundance and hence oviposition rates, of pre-dispersal seed predators.

  3. Maternal age at first birth and offspring criminality: using the children of twins design to test causal hypotheses.

    Science.gov (United States)

    Coyne, Claire A; Långström, Niklas; Rickert, Martin E; Lichtenstein, Paul; D'Onofrio, Brian M

    2013-02-01

    Teenage childbirth is a risk factor for poor offspring outcomes, particularly offspring antisocial behavior. It is not clear, however, if maternal age at first birth (MAFB) is causally associated with offspring antisocial behavior or if this association is due to selection factors that influence both the likelihood that a young woman gives birth early and that her offspring engage in antisocial behavior. The current study addresses the limitations of previous research by using longitudinal data from Swedish national registries and children of siblings and children of twins comparisons to identify the extent to which the association between MAFB and offspring criminal convictions is consistent with a causal influence and confounded by genetic or environmental factors that make cousins similar. We found offspring born to mothers who began childbearing earlier were more likely to be convicted of a crime than offspring born to mothers who delayed childbearing. The results from comparisons of differentially exposed cousins, especially born to discordant monozygotic twin sisters, provide support for a causal association between MAFB and offspring criminal convictions. The analyses also found little evidence for genetic confounding due to passive gene-environment correlation. Future studies are needed to replicate these findings and to identify environmental risk factors that mediate this causal association.

  4. Maternal age at first birth and offspring criminality: Using the children-of-twins design to test causal hypotheses

    Science.gov (United States)

    Coyne, Claire A; Långström, Niklas; Rickert, Martin E; Lichtenstein, Paul; D’Onofrio, Brian M

    2013-01-01

    Teenage childbirth is a risk factor for poor offspring outcomes, particularly offspring antisocial behaviour. It is not clear if maternal age at first birth (MAFB) is causally associated with offspring antisocial behavior or if this association is due to selection factors that influence both the likelihood that a young woman gives birth early and that her offspring engage in antisocial behavior. The current study addresses the limitations of previous research by using longitudinal data from Swedish national registries and children-of-siblings and children-of-twins comparisons to identify the extent to which the association between MAFB and offspring criminal convictions is consistent with a causal influence and confounded by genetic or environmental factors that make cousins similar. We found offspring born to mothers who began childbearing earlier were more likely to be convicted of a crime than offspring born to mothers who delayed childbearing. The results from comparisons of differentially exposed cousins, especially born to discordant MZ twin sisters, provide support for a causal association between MAFB and offspring criminal convictions. The analyses also found little evidence for genetic confounding due to passive gene-environment correlation. Future studies are needed to replicate these findings and to identify environmental risk factors that mediate this causal association. PMID:23398750

  5. Testing aggregation hypotheses among Neotropical trees and shrubs: results from a 50-ha plot over 20 years of sampling.

    Science.gov (United States)

    Myster, Randall W; Malahy, Michael P

    2012-09-01

    Spatial patterns of tropical trees and shrubs are important to understanding their interaction and the resultant structure of tropical rainforests. To assess this issue, we took advantage of previously collected data, on Neotropical tree and shrub stem identified to species and mapped for spatial coordinates in a 50ha plot, with a frequency of every five years and over a 20 year period. These stems data were first placed into four groups, regardless of species, depending on their location in the vertical strata of the rainforest (shrubs, understory trees, mid-sized trees, tall trees) and then used to generate aggregation patterns for each sampling year. We found shrubs and understory trees clumped at small spatial scales of a few meters for several of the years sampled. Alternatively, mid-sized trees and tall trees did not clump, nor did they show uniform (regular) patterns, during any sampling period. In general (1) groups found higher in the canopy did not show aggregation on the ground and (2) the spatial patterns of all four groups showed similarity among different sampling years, thereby supporting a "shifting mosaic" view of plant communities over large areas. Spatial analysis, such as this one, are critical to understanding and predicting tree spaces, tree-tree replacements and the Neotropical forest patterns, such as biodiversity and those needed for sustainability efforts, they produce.

  6. Social deprivation and burden of influenza: Testing hypotheses and gaining insights from a simulation model for the spread of influenza

    Directory of Open Access Journals (Sweden)

    Ayaz Hyder

    2015-06-01

    Full Text Available Factors associated with the burden of influenza among vulnerable populations have mainly been identified using statistical methodologies. Complex simulation models provide mechanistic explanations, in terms of spatial heterogeneity and contact rates, while controlling other factors and may be used to better understand statistical patterns and, ultimately, design optimal population-level interventions. We extended a sophisticated simulation model, which was applied to forecast epidemics and validated for predictive ability, to identify mechanisms for the empirical relationship between social deprivation and the burden of influenza. Our modeled scenarios and associated epidemic metrics systematically assessed whether neighborhood composition and/or spatial arrangement could qualitatively replicate this empirical relationship. We further used the model to determine consequences of local-scale heterogeneities on larger scale disease spread. Our findings indicated that both neighborhood composition and spatial arrangement were critical to qualitatively match the empirical relationship of interest. Also, when social deprivation was fully included in the model, we observed lower age-based attack rates and greater delay in epidemic peak week in the most socially deprived neighborhoods. Insights from simulation models complement current understandings from statistical-based association studies. Additional insights from our study are: (1 heterogeneous spatial arrangement of neighborhoods is a necessary condition for simulating observed disparities in the burden of influenza and (2 unmeasured factors may lead to a better quantitative match between simulated and observed rate ratio in the burden of influenza between the most and least socially deprived populations.

  7. Testing Hypotheses in an I(2) Model with Applications to the Persistent Long Swings in the Dmk/$ Rate

    DEFF Research Database (Denmark)

    Johansen, Søren; Juselius, Katarina; Frydman, Roman

    and persistent swings in the foreign exchange market between Germany and USA. The data analyzed consist of nominal exchange rates, relative prices, US inflation rate, two long-term interest rates and two short-term interest rates over the 1975-1999 period. One important aim of the paper is to demonstrate...... that by structuring the data with the help of the I(2) model one can achieve a better understanding of the empirical regularities underlying the persistent swings in nominal exchange rates, typical in periods of floating exchange rates...

  8. [Non-EC workers in Italy: an overview of the literature and an attempt to test various hypotheses].

    Science.gov (United States)

    Strozza, S

    1995-09-01

    "The essay presents an overview of the interpretations offered in scientific literature about causes and effects of non-EC [European Community] immigrants' integration into the Italian labor market....The essay uses the aggregate data of [the] Labor Ministry integrated by local surveys to answer some questions...[concerning] the link between sex, Italian region, place of origin and sector of activity...and the complementarity or competition with [the] Italian labor force." (SUMMARY IN ENG AND FRE) excerpt

  9. Testing the variability of PSA expression by different human prostate cancer cell lines by means of a new potentiometric device employing molecularly antibody assembled on graphene surface

    International Nuclear Information System (INIS)

    Rebelo, Tânia S.C.R.; Noronha, João P.; Galésio, Marco; Santos, Hugo; Diniz, Mário; Sales, M. Goreti F.; Fernandes, Maria H.; Costa-Rodrigues, João

    2016-01-01

    Prostate Specific Antigen (PSA) is widely used as a biomarker for prostate cancer. Recently, an electrochemical biosensor for PSA detection by means of molecularly imprinted polymers (MIPs) was developed. This work evaluated the performance and the effectiveness of that PSA biosensor in screening the biomarker PSA in biological media with complex composition, collected from different human prostate cell line cultures. For that, the prostate cancer LNCaP and PC3 cells, and the non-cancerous prostate cell line PNT2 were cultured for 2, 7 and 14 days in either α-MEM or RPMI in the presence of 10% or 30% fetal bovine serum. Human gingival fibroblasts were used as a non-cancerous non-prostatic control. The different culture conditions modulated cellular proliferation and the expression of several prostate markers, including PSA. The electrochemical biosensor was able to specifically detect PSA in the culture media and values obtained were similar to those achieved by a commercial Enzyme-Linked Immunosorbent Assay (ELISA) kit, the most commonly used method for PSA quantification in prostate cancer diagnosis. Thus, the tested biosensor may represent a useful alternative as a diagnostic tool for PSA determination in biological samples. - Highlights: • PSA quantification was performed in prostate cancer cell culture media. • Culture media composition and culture period significantly affect PSA production. • The PSA biosensor detected a wide range of PSA levels in complex media. • A high data correlation was observed between the biosensor and the ELISA analysis.

  10. Search for cosmic ray origins by the study of supernova remnants associated with molecular clouds with HESS and test of HESS II sampling system

    International Nuclear Information System (INIS)

    Fiasson, A.

    2008-03-01

    The H.E.S.S. telescope (High energy Stereoscopic System), located in Namibia, is currently the most efficient for the observation of very high energy (VHE) gamma-ray sources. It is composed of 4 large diameter telescopes working in stereoscopic mode and allows an unequaled survey of the galactic plane at these extreme wavelengths. The H.E.S.S. experiment showed the presence of high energy particles up to 100 TeV within supernova remnant. This astrophysical objects are believed to be the main particle accelerator within the Galaxy. However, the particle nature remains unclear. This thesis presents a new observational approach in order to show hadronic particles acceleration through diffusive shock within supernova remnant. A search of supernova remnant associated with molecular cloud have been led within the HESS source catalog and the H.E.S.S. observations. An analysis of the new VHE gamma-ray source in Monoceros and its interpretation are presented. As well, the analysis and interpretation of new observations of the unidentified source HESS J1745-303 are presented. The multi-wavelength analysis of the new source HESS J1714-385, coincident with the supernova remnant CTB37A is presented. A contribution to the H.E.S.S. phase II building is also presented. This second phase consists in the building of a fifth telescope at the center of the existing system. The series tests of the new camera sampling system are reported. (author)

  11. Testing a Low Molecular Mass Fraction of a Mushroom (Lentinus edodes Extract Formulated as an Oral Rinse in a Cohort of Volunteers

    Directory of Open Access Journals (Sweden)

    Caterina Signoretto

    2011-01-01