645 research outputs found

    Advances in item response theory and applications: an introduction

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    Test theories can be divided roughly into two categories. The first is classical test theory, which dates back to Spearman’s conception of the observed test score as a composite of true and error components, and which was introduced to psychologists at the beginning of this century. Important milestones in its long and venerable tradition are Gulliksen’s Theory of Mental Tests (1950) and Lord and Novick’s Statistical Theories of Mental Test Scores (1968). The second is item response theory, or latent trait theory, as it has been called until recently. At the present time, item response theory (IRT) is having a major impact on the field of testing. Models derived from IRT are being used to develop tests, to equate scores from nonparallel tests, to investigate item bias, and to report scores, as well as to address many other pressing measurement problems (see, e.g., Hambleton, 1983; Lord, 1980). IRT differs from classical test theory in that it assumes a different relation of the test score to the variable measured by the test. Although there are parallels between models from IRT and psychophysical models formulated around the turn of the century, only in the last 10 years has IRT had any impact on psychometricians and test users. Work by Rasch (1980/1960), Fischer (1974), 9 Birnbaum (1968), ivrighi and Panchapakesan (1969), Bock (1972), and Lord (1974) has been especially influential in this turnabout; and Lazarsfeld’s pioneering work on latent structure analysis in sociology (Lazarsfeld, 1950; Lazarsfeld & Henry, 1968) has also provided impetus. One objective of this introduction is to review the conceptual differences between classical test theory and IRT. A second objective is to introduce the goals of this special issue on item response theory and the seven papers. Some basic problems with classical test theory are reviewed in the next section. Then, IRT approaches to educational and psychological measurement are presented and compared to classical test theory. The final two sections present the goals for this special issue and an outline of the seven invited papers

    Shotgun Cloning of Transposon Insertions in the Genome of Caenorhabditis elegans

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    We present a strategy to identify and map large numbers of transposon insertions in the genome of Caenorhabditis elegans. Our approach makes use of the mutator strain mut-7, which has germline-transposition activity of the Tc1/mariner family of transposons, a display protocol to detect new transposon insertions, and the availability of the genomic sequence of C. elegans. From a pilot insertional mutagenesis screen, we have obtained 351 new Tc1 transposons inserted in or near 219 predicted C. elegans genes. The strategy presented provides an approach to isolate insertions of natural transposable elements in many C. elegans genes and to create a large-scale collection of C. elegans mutants

    Come fly with us: services provided by the Space Weather Education Centre

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    The Solar-Terrestrial Centre of Excellence brings together and supports sun-space-earth research and services present at the federal level in Belgium. In 2019, the STCE was a founding member of a European network, PECASUS, that provides space weather services for civil aviation. Our expertise in solar observations and research combined with the experience of our Global Navigation Satellite System and solar particle radiation group proved to be crucial. The STCE also strongly invests in education and training as these are a backbone of quality research and services, and therefore created the Space Weather Education Centre. This centre offers the Space Weather Introductory Course covering the Sun, solar storms, heliosphere, ionosphere, magnetosphere, instruments and methods to observe solar and space weather activity, as well as reading and interpreting our space weather bulletins. This course is taught to future space weather advisory staff, both military and civilian. It is based upon the STCE’s expertise gained through scientific research, involvement in space missions and space weather monitoring, and on its forecasting capabilities. The course is given by qualified staff. In addition to the Space Weather Introductory Course, the STCE has been and remains involved in a wide range of outreach activities, from public lectures, over dedicated classes and workshops at schools, organization of public events like open doors, publications in popular journals and on online media, scientific newsletters and press releases, to the participation in science festivals and the organization of events for the scientific community. In this paper, we present more details of our educational programme, reflect on the methodologies used, and provide an overview of the obtained result

    Hyperactivation of the G12-Mediated Signaling Pathway in Caenorhabditis elegans Induces a Developmental Growth Arrest via Protein Kinase C

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    AbstractThe G12 type of heterotrimeric G-proteins play an important role in development and behave as potent oncogenes in cultured cells [1–5]. However, little is known about the molecular nature of the components that act in the G12-signaling pathway in an organism. We characterized a C. elegans Gα subunit gene, gpa-12, which is a homolog of mammalian G12/G13α, and found that animals defective in gpa-12 are viable. Expression of activated GPA-12 (G12QL) results in a developmental growth arrest caused by a feeding behavior defect that is due to a dramatic reduction in pharyngeal pumping. To elucidate the molecular nature of the signaling pathways in which G12 participates, we screened for suppressors of the G12QL phenotype. We isolated 50 suppressors that contain mutations in tpa-1, which encodes two protein kinase C isoforms, TPA-1A and TPA-1B, most similar to PKCΞ/ÎŽ. TPA-1 mediates the action of the tumor promoter PMA [6]. Expression of G12QL and treatment of wild-type animals with PMA induce an identical growth arrest caused by inhibition of larval feeding, which is dependent on TPA-1A and TPA-1B function. These results suggest that TPA-1 is a downstream target of both G12 signaling and PMA in modulating feeding and growth in C. elegans. Taken together, our findings provide a potential molecular mechanism for the transforming capability of G12 proteins

    Identification of genes transcriptionally responsive to the loss of MLL fusions in MLL-rearranged acute lymphoblastic leukemia

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    MLL-rearranged acute lymphoblastic leukemia (ALL) in infants (<1 year) is characterized by high relapse rates and a dismal prognosis. To facilitate the discovery of novel therapeutic targets, we here searched for genes directly influenced by the repression of various MLL fusions. Methods For this, we performed gene expression profiling after siRNA-mediated repression of MLLAF4, MLL-ENL, and AF4-MLL in MLL -rearranged ALL cell line models. The obtained results were compared with various already established gene signatures including those consisting of known MLL-AF4 target genes, or those associated with primary MLL-rearranged infant ALL samples. Results Genes that were down-regulated in response to the repression of MLL-AF4 and MLL-ENL appeared characteristically expressed in primary MLL-rearranged infant ALL samples, and often represented known MLL-AF4 targets genes. Genes that were up-regulated in response to the repression of MLL-AF4 and MLL-ENL often represented genes typically silenced by promoter hypermethylation in MLL-rearranged infant ALL. Genes that were aff

    External validation of a model to predict the survival of patients presenting with a spinal epidural metastasis

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    The surgical treatment of spinal metastases is evolving. The major problem is the selection of patients who may benefit from surgical treatment. One of the criteria is an expected survival of at least 3 months. A prediction model has been previously developed. The present study has been performed in order to validate externally the model and to demonstrate that this model can be generalized to other institutions and other countries than the Netherlands. Data of 356 patients from five centers in Germany, Spain, Sweden, and the Netherlands who were treated for metastatic epidural spinal cord compression were collected. Hazard ratios in the test population corresponded with those of the developmental population. However, the observed and the expected survival were different. Analysis revealed that the baseline hazard function was significantly different. This tempted us to combine the data and develop a new prediction model. Estimating iteratively, a baseline hazard was composed. An adapted prediction model is presented. External validation of a prediction model revealed a difference in expected survival, although the relative contribution of the specific hazard ratios was the same as in the developmental population. This study emphasized the need to check the baseline hazard function in external validation. A new model has been developed using an estimated baseline hazar

    COVID-19 in health-care workers in three hospitals in the south of the Netherlands:A cross-sectional study

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    Background: 10 days after the first reported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Netherlands (on Feb 27, 2020), 55 (4%) of 1497 health-care workers in nine hospitals located in the south of the Netherlands had tested positive for SARS-CoV-2 RNA. We aimed to gain insight in possible sources of infection in health-care workers. Methods: We did a cross-sectional study at three of the nine hospitals located in the south of the Netherlands. We screened health-care workers at the participating hospitals for SARS-CoV-2 infection, based on clinical symptoms (fever or mild respiratory symptoms) in the 10 days before screening. We obtained epidemiological data through structured interviews with health-care workers and combined this information with data from whole-genome sequencing of SARS-CoV-2 in clinical samples taken from health-care workers and patients. We did an in-depth analysis of sources and modes of transmission of SARS-CoV-2 in health-care workers and patients. Findings: Between March 2 and March 12, 2020, 1796 (15%) of 12 022 health-care workers were screened, of whom 96 (5%) tested positive for SARS-CoV-2. We obtained complete and near-complete genome sequences from 50 health-care workers and ten patients. Most sequences were grouped in three clusters, with two clusters showing local circulation within the region. The noted patterns were consistent with multiple introductions into the hospitals through community-acquired infections and local amplification in the community. Interpretation: Although direct transmission in the hospitals cannot be ruled out, our data do not support widespread nosocomial transmission as the source of infection in patients or health-care workers. Funding: EU Horizon 2020 (RECoVer, VEO, and the European Joint Programme One Health METASTAVA), and the National Institute of Allergy and Infectious Diseases, National Institutes of Health

    Identification strategy for unknown pollutants using high-resolution mass spectrometry: Androgen-disrupting compounds identified through effect-directed analysis

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    Effect-directed analysis has been applied to a river sediment sample of concern to identify the compounds responsible for the observed effects in an in vitro (anti-)androgenicity assay. For identification after non-target analysis performed on a high-resolution LTQ-Orbitrap, we developed a de novo identification strategy including physico-chemical parameters derived from the effect-directed analysis approach. With this identification strategy, we were able to handle the immense amount of data produced by non-target accurate mass analysis. The effect-directed analysis approach, together with the identification strategy, led to the successful identification of eight androgen-disrupting compounds belonging to very diverse compound classes: an oxygenated polyaromatic hydrocarbon, organophosphates, musks, and steroids. This is one of the first studies in the field of environmental analysis dealing with the difficult task of handling the large amount of data produced from non-target analysis. The combination of bioassay activity assessment, accurate mass measurement, and the identification and confirmation strategy is a promising approach for future identification of environmental key toxicants that are not included as priority pollutants in monitoring programs

    EUropean Heliospheric FORecasting Information Asset 2.0

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    Aims: This paper presents a H2020 project aimed at developing an advanced space weather forecasting tool, combining the MagnetoHydroDynamic (MHD) solar wind and coronal mass ejection (CME) evolution modelling with solar energetic particle (SEP) transport and acceleration model(s). The EUHFORIA 2.0 project will address the geoeffectiveness of impacts and mitigation to avoid (part of the) damage, including that of extreme events, related to solar eruptions, solar wind streams, and SEPs, with particular emphasis on its application to forecast geomagnetically induced currents (GICs) and radiation on geospace. Methods: We will apply innovative methods and state-of-the-art numerical techniques to extend the recent heliospheric solar wind and CME propagation model EUHFORIA with two integrated key facilities that are crucial for improving its predictive power and reliability, namely (1) data-driven flux-rope CME models, and (2) physics-based, self-consistent SEP models for the acceleration and transport of particles along and across the magnetic field lines. This involves the novel coupling of advanced space weather models. In addition, after validating the upgraded EUHFORIA/SEP model, it will be coupled to existing models for GICs and atmospheric radiation transport models. This will result in a reliable prediction tool for radiation hazards from SEP events, affecting astronauts, passengers and crew in high-flying aircraft, and the impact of space weather events on power grid infrastructure, telecommunication, and navigation satellites. Finally, this innovative tool will be integrated into both the Virtual Space Weather Modeling Centre (VSWMC, ESA) and the space weather forecasting procedures at the ESA SSCC in Ukkel (Belgium), so that it will be available to the space weather community and effectively used for improved predictions and forecasts of the evolution of CME magnetic structures and their impact on Earth. Results: The results of the first six months of the EU H2020 project are presented here. These concern alternative coronal models, the application of adaptive mesh refinement techniques in the heliospheric part of EUHFORIA, alternative flux-rope CME models, evaluation of data-assimilation based on Karman filtering for the solar wind modelling, and a feasibility study of the integration of SEP models
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