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Sample records for models screen tscreen

  1. Use of external metabolizing systems when testing for endocrine disruption in the T-screen assay

    International Nuclear Information System (INIS)

    Taxvig, Camilla; Olesen, Pelle Thonning; Nellemann, Christine

    2011-01-01

    Although, it is well-established that information on the metabolism of a substance is important in the evaluation of its toxic potential, there is limited experience with incorporating metabolic aspects into in vitro tests for endocrine disrupters. The aim of the current study was a) to study different in vitro systems for biotransformation of ten known endocrine disrupting chemicals (EDs): five azole fungicides, three parabens and 2 phthalates, b) to determine possible changes in the ability of the EDs to bind and activate the thyroid receptor (TR) in the in vitro T-screen assay after biotransformation and c) to investigate the endogenous metabolic capacity of the GH3 cells, the cell line used in the T-screen assay, which is a proliferation assay used for the in vitro detection of agonistic and antagonistic properties of compounds at the level of the TR. The two in vitro metabolizing systems tested the human liver S9 mix and the PCB-induced rat microsomes gave an almost complete metabolic transformation of the tested parabens and phthalates. No marked difference the effects in the T-screen assay was observed between the parent compounds and the effects of the tested metabolic extracts. The GH3 cells themselves significantly metabolized the two tested phthalates dimethyl phthalate (DMP) and diethyl phthalate (DEP). Overall the results and qualitative data from the current study show that an in vitro metabolizing system using liver S9 or microsomes could be a convenient method for the incorporation of metabolic and toxicokinetic aspects into in vitro testing for endocrine disrupting effects.

  2. Use of external metabolizing systems when testing for endocrine disruption in the T-screen assay

    DEFF Research Database (Denmark)

    Taxvig, Camilla; Olesen, Pelle Thonning; Nellemann, Christine Lydia

    2011-01-01

    Although, it is well-established that information on the metabolism of a substance is important in the evaluation of its toxic potential, there is limited experience with incorporating metabolic aspects into in vitro tests for endocrine disrupters. The aim of the current study was a) to study...

  3. Screening for Prediabetes Using Machine Learning Models

    Directory of Open Access Journals (Sweden)

    Soo Beom Choi

    2014-01-01

    Full Text Available The global prevalence of diabetes is rapidly increasing. Studies support the necessity of screening and interventions for prediabetes, which could result in serious complications and diabetes. This study aimed at developing an intelligence-based screening model for prediabetes. Data from the Korean National Health and Nutrition Examination Survey (KNHANES were used, excluding subjects with diabetes. The KNHANES 2010 data (n=4685 were used for training and internal validation, while data from KNHANES 2011 (n=4566 were used for external validation. We developed two models to screen for prediabetes using an artificial neural network (ANN and support vector machine (SVM and performed a systematic evaluation of the models using internal and external validation. We compared the performance of our models with that of a screening score model based on logistic regression analysis for prediabetes that had been developed previously. The SVM model showed the areas under the curve of 0.731 in the external datasets, which is higher than those of the ANN model (0.729 and the screening score model (0.712, respectively. The prescreening methods developed in this study performed better than the screening score model that had been developed previously and may be more effective method for prediabetes screening.

  4. Mechanistic modeling for mammography screening risks

    International Nuclear Information System (INIS)

    Bijwaard, Harmen

    2008-01-01

    Full text: Western populations show a very high incidence of breast cancer and in many countries mammography screening programs have been set up for the early detection of these cancers. Through these programs large numbers of women (in the Netherlands, 700.000 per year) are exposed to low but not insignificant X-ray doses. ICRP based risk estimates indicate that the number of breast cancer casualties due to mammography screening can be as high as 50 in the Netherlands per year. The number of lives saved is estimated to be much higher, but for an accurate calculation of the benefits of screening a better estimate of these risks is indispensable. Here it is attempted to better quantify the radiological risks of mammography screening through the application of a biologically based model for breast tumor induction by X-rays. The model is applied to data obtained from the National Institutes of Health in the U.S. These concern epidemiological data of female TB patients who received high X-ray breast doses in the period 1930-1950 through frequent fluoroscopy of their lungs. The mechanistic model that is used to describe the increased breast cancer incidence is based on an earlier study by Moolgavkar et al. (1980), in which the natural background incidence of breast cancer was modeled. The model allows for a more sophisticated extrapolation of risks to the low dose X-ray exposures that are common in mammography screening and to the higher ages that are usually involved. Furthermore, it allows for risk transfer to other (non-western) populations. The results have implications for decisions on the frequency of screening, the number of mammograms taken at each screening, minimum and maximum ages for screening and the transfer to digital equipment. (author)

  5. Evaluation of Endocrine Disrupting Effects of Nitrate after In Utero Exposure in Rats and of Nitrate and Nitrite in the H295R and T-Screen Assay

    DEFF Research Database (Denmark)

    Hansen, Pernille Reimer; Taxvig, Camilla; Christiansen, Sofie

    2009-01-01

    /l. At GD21, fetuses were examined for anogenital distance, plasma thyroxine levels, testicular and plasma levels of testosterone and progesterone, and testicular testosterone production and histopathology. In addition, endocrine disrupting activity of nitrate and nitrite were studied in two in vitro assays......Animal studies have shown that nitrate acts as an endocrine disrupter affecting the androgen production in adult males. This raises a concern for more severe endocrine disrupting effects after exposure during the sensitive period of prenatal male sexual development. As there are no existing studies...... of effects of nitrate on male sexual development, the aim of the study was to examine how in utero exposure to nitrate would affect male rat fetuses. Pregnant dams were dosed with nitrate in the drinking water from gestational day (GD) 7 to GD21 at the following dose levels 17.5, 50, 150, 450, and 900 mg...

  6. Mathematical Models of the Sinusoidal Screen Family

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    Tajana Koren

    2011-06-01

    Full Text Available In this paper we will define a family of sinusoidal screening elements and explore the possibilities of their application in graphic arts, securities printing and design solutions in photography and typography editing. For this purpose mathematical expressions of sinusoidal families were converted into a Postscript language. The introduction of a random variable results in a countless number of various mutations which cannot be repeated without knowing the programming code itself. The use of the family of screens in protection of securities is thus of great importance. Other possible application of modulated sinusoidal screens is related to the large format color printing. This paper will test the application of sinusoidal screens in vector graphics, pixel graphics and typography. The development of parameters in the sinusoidal screen element algorithms gives new forms defined within screening cells with strict requirements of coverage implementation. Individual solutions include stochastic algorithms, as well as the autonomy of screening forms in regard to multicolor printing channels.

  7. Genetic screens in Caenorhabditis elegans models for neurodegenerative diseases

    NARCIS (Netherlands)

    Alvarenga Fernandes Sin, Olga; Michels, Helen; Nollen, Ellen A. A.

    2014-01-01

    Caenorhabditis elegans comprises unique features that make it an attractive model organism in diverse fields of biology. Genetic screens are powerful to identify genes and C. elegans can be customized to forward or reverse genetic screens and to establish gene function. These genetic screens can be

  8. High-throughput screening (HTS) and modeling of the retinoid ...

    Science.gov (United States)

    Presentation at the Retinoids Review 2nd workshop in Brussels, Belgium on the application of high throughput screening and model to the retinoid system Presentation at the Retinoids Review 2nd workshop in Brussels, Belgium on the application of high throughput screening and model to the retinoid system

  9. A Multiscale Model Evaluates Screening for Neoplasia in Barrett's Esophagus.

    Directory of Open Access Journals (Sweden)

    Kit Curtius

    2015-05-01

    Full Text Available Barrett's esophagus (BE patients are routinely screened for high grade dysplasia (HGD and esophageal adenocarcinoma (EAC through endoscopic screening, during which multiple esophageal tissue samples are removed for histological analysis. We propose a computational method called the multistage clonal expansion for EAC (MSCE-EAC screening model that is used for screening BE patients in silico to evaluate the effects of biopsy sampling, diagnostic sensitivity, and treatment on disease burden. Our framework seamlessly integrates relevant cell-level processes during EAC development with a spatial screening process to provide a clinically relevant model for detecting dysplastic and malignant clones within the crypt-structured BE tissue. With this computational approach, we retain spatio-temporal information about small, unobserved tissue lesions in BE that may remain undetected during biopsy-based screening but could be detected with high-resolution imaging. This allows evaluation of the efficacy and sensitivity of current screening protocols to detect neoplasia (dysplasia and early preclinical EAC in the esophageal lining. We demonstrate the clinical utility of this model by predicting three important clinical outcomes: (1 the probability that small cancers are missed during biopsy-based screening, (2 the potential gains in neoplasia detection probabilities if screening occurred via high-resolution tomographic imaging, and (3 the efficacy of ablative treatments that result in the curative depletion of metaplastic and neoplastic cell populations in BE in terms of the long-term impact on reducing EAC incidence.

  10. Screens

    OpenAIRE

    2016-01-01

    This Sixth volume in the series The Key Debates. Mutations and Appropriations in European Film Studies investigates the question of screens in the context both of the dematerialization due to digitalization and the multiplication of media screens. Scholars offer various infomations and theories of topics such as the archeology of screen, film and media theories, contemporary art, pragmatics of new ways of screening (from home video to street screening).

  11. Screen or not to screen for peripheral arterial disease: guidance from a decision model.

    Science.gov (United States)

    Vaidya, Anil; Joore, Manuela A; Ten Cate-Hoek, Arina J; Ten Cate, Hugo; Severens, Johan L

    2014-01-29

    Asymptomatic Peripheral Arterial Disease (PAD) is associated with greater risk of acute cardiovascular events. This study aims to determine the cost-effectiveness of one time only PAD screening using Ankle Brachial Index (ABI) test and subsequent anti platelet preventive treatment (low dose aspirin or clopidogrel) in individuals at high risk for acute cardiovascular events compared to no screening and no treatment using decision analytic modelling. A probabilistic Markov model was developed to evaluate the life time cost-effectiveness of the strategy of selective PAD screening and consequent preventive treatment compared to no screening and no preventive treatment. The analysis was conducted from the Dutch societal perspective and to address decision uncertainty, probabilistic sensitivity analysis was performed. Results were based on average values of 1000 Monte Carlo simulations and using discount rates of 1.5% and 4% for effects and costs respectively. One way sensitivity analyses were performed to identify the two most influential model parameters affecting model outputs. Then, a two way sensitivity analysis was conducted for combinations of values tested for these two most influential parameters. For the PAD screening strategy, life years and quality adjusted life years gained were 21.79 and 15.66 respectively at a lifetime cost of 26,548 Euros. Compared to no screening and treatment (20.69 life years, 15.58 Quality Adjusted Life Years, 28,052 Euros), these results indicate that PAD screening and treatment is a dominant strategy. The cost effectiveness acceptability curves show 88% probability of PAD screening being cost effective at the Willingness To Pay (WTP) threshold of 40000 Euros. In a scenario analysis using clopidogrel as an alternative anti-platelet drug, PAD screening strategy remained dominant. This decision analysis suggests that targeted ABI screening and consequent secondary prevention of cardiovascular events using low dose aspirin or

  12. Systematic review of model-based cervical screening evaluations.

    Science.gov (United States)

    Mendes, Diana; Bains, Iren; Vanni, Tazio; Jit, Mark

    2015-05-01

    Optimising population-based cervical screening policies is becoming more complex due to the expanding range of screening technologies available and the interplay with vaccine-induced changes in epidemiology. Mathematical models are increasingly being applied to assess the impact of cervical cancer screening strategies. We systematically reviewed MEDLINE®, Embase, Web of Science®, EconLit, Health Economic Evaluation Database, and The Cochrane Library databases in order to identify the mathematical models of human papillomavirus (HPV) infection and cervical cancer progression used to assess the effectiveness and/or cost-effectiveness of cervical cancer screening strategies. Key model features and conclusions relevant to decision-making were extracted. We found 153 articles meeting our eligibility criteria published up to May 2013. Most studies (72/153) evaluated the introduction of a new screening technology, with particular focus on the comparison of HPV DNA testing and cytology (n = 58). Twenty-eight in forty of these analyses supported HPV DNA primary screening implementation. A few studies analysed more recent technologies - rapid HPV DNA testing (n = 3), HPV DNA self-sampling (n = 4), and genotyping (n = 1) - and were also supportive of their introduction. However, no study was found on emerging molecular markers and their potential utility in future screening programmes. Most evaluations (113/153) were based on models simulating aggregate groups of women at risk of cervical cancer over time without accounting for HPV infection transmission. Calibration to country-specific outcome data is becoming more common, but has not yet become standard practice. Models of cervical screening are increasingly used, and allow extrapolation of trial data to project the population-level health and economic impact of different screening policy. However, post-vaccination analyses have rarely incorporated transmission dynamics. Model calibration to country

  13. Evaluation of atmospheric dispersion/consequence models supporting safety analysis

    International Nuclear Information System (INIS)

    O'Kula, K.R.; Lazaro, M.A.; Woodard, K.

    1996-01-01

    Two DOE Working Groups have completed evaluation of accident phenomenology and consequence methodologies used to support DOE facility safety documentation. The independent evaluations each concluded that no one computer model adequately addresses all accident and atmospheric release conditions. MACCS2, MATHEW/ADPIC, TRAC RA/HA, and COSYMA are adequate for most radiological dispersion and consequence needs. ALOHA, DEGADIS, HGSYSTEM, TSCREEN, and SLAB are recommended for chemical dispersion and consequence applications. Additional work is suggested, principally in evaluation of new models, targeting certain models for continued development, training, and establishing a Web page for guidance to safety analysts

  14. Screening fifth forces in k-essence and DBI models

    Energy Technology Data Exchange (ETDEWEB)

    Brax, Philippe [Institut de Physique Théorique, CEA, IPhT, CNRS, URA2306, F-91191 Gif-sur-Yvette cédex (France); Burrage, Clare [School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2RD (United Kingdom); Davis, Anne-Christine, E-mail: Philippe.Brax@cea.fr, E-mail: Clare.Burrage@nottingham.ac.uk, E-mail: A.C.Davis@damtp.cam.ac.uk [Department of Applied Mathematics and Theoretical Physics, Centre for Mathematical Sciences, Cambridge CB3 0WA (United Kingdom)

    2013-01-01

    New fifth forces have not yet been detected in the laboratory or in the solar system, hence it is typically difficult to introduce new light scalar fields that would mediate such forces. In recent years it has been shown that a number of non-linear scalar field theories allow for a dynamical mechanism, such as the Vainshtein and chameleon ones, that suppresses the strength of the scalar fifth force in experimental environments. This is known as screening, however it is unclear how common screening is within non-linear scalar field theories. k-essence models are commonly studied examples of non-linear models, with DBI as the best motivated example, and so we ask whether these non-linearities are able to screen a scalar fifth force. We find that a Vainshtein-like screening mechanism exists for such models although with limited applicability. For instance, we cannot find a screening mechanism for DBI models. On the other hand, we construct a large class of k-essence models which lead to the acceleration of the Universe in the recent past for which the fifth force mediated by the scalar can be screened.

  15. In Vivo RNAi-Based Screens: Studies in Model Organisms

    Directory of Open Access Journals (Sweden)

    Miki Yamamoto-Hino

    2013-11-01

    Full Text Available RNA interference (RNAi is a technique widely used for gene silencing in organisms and cultured cells, and depends on sequence homology between double-stranded RNA (dsRNA and target mRNA molecules. Numerous cell-based genome-wide screens have successfully identified novel genes involved in various biological processes, including signal transduction, cell viability/death, and cell morphology. However, cell-based screens cannot address cellular processes such as development, behavior, and immunity. Drosophila and Caenorhabditis elegans are two model organisms whose whole bodies and individual body parts have been subjected to RNAi-based genome-wide screening. Moreover, Drosophila RNAi allows the manipulation of gene function in a spatiotemporal manner when it is implemented using the Gal4/UAS system. Using this inducible RNAi technique, various large-scale screens have been performed in Drosophila, demonstrating that the method is straightforward and valuable. However, accumulated results reveal that the results of RNAi-based screens have relatively high levels of error, such as false positives and negatives. Here, we review in vivo RNAi screens in Drosophila and the methods that could be used to remove ambiguity from screening results.

  16. Simulation models in population breast cancer screening: A systematic review.

    Science.gov (United States)

    Koleva-Kolarova, Rositsa G; Zhan, Zhuozhao; Greuter, Marcel J W; Feenstra, Talitha L; De Bock, Geertruida H

    2015-08-01

    The aim of this review was to critically evaluate published simulation models for breast cancer screening of the general population and provide a direction for future modeling. A systematic literature search was performed to identify simulation models with more than one application. A framework for qualitative assessment which incorporated model type; input parameters; modeling approach, transparency of input data sources/assumptions, sensitivity analyses and risk of bias; validation, and outcomes was developed. Predicted mortality reduction (MR) and cost-effectiveness (CE) were compared to estimates from meta-analyses of randomized control trials (RCTs) and acceptability thresholds. Seven original simulation models were distinguished, all sharing common input parameters. The modeling approach was based on tumor progression (except one model) with internal and cross validation of the resulting models, but without any external validation. Differences in lead times for invasive or non-invasive tumors, and the option for cancers not to progress were not explicitly modeled. The models tended to overestimate the MR (11-24%) due to screening as compared to optimal RCTs 10% (95% CI - 2-21%) MR. Only recently, potential harms due to regular breast cancer screening were reported. Most scenarios resulted in acceptable cost-effectiveness estimates given current thresholds. The selected models have been repeatedly applied in various settings to inform decision making and the critical analysis revealed high risk of bias in their outcomes. Given the importance of the models, there is a need for externally validated models which use systematical evidence for input data to allow for more critical evaluation of breast cancer screening. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Modeling granular phosphor screens by Monte Carlo methods

    International Nuclear Information System (INIS)

    Liaparinos, Panagiotis F.; Kandarakis, Ioannis S.; Cavouras, Dionisis A.; Delis, Harry B.; Panayiotakis, George S.

    2006-01-01

    The intrinsic phosphor properties are of significant importance for the performance of phosphor screens used in medical imaging systems. In previous analytical-theoretical and Monte Carlo studies on granular phosphor materials, values of optical properties, and light interaction cross sections were found by fitting to experimental data. These values were then employed for the assessment of phosphor screen imaging performance. However, it was found that, depending on the experimental technique and fitting methodology, the optical parameters of a specific phosphor material varied within a wide range of values, i.e., variations of light scattering with respect to light absorption coefficients were often observed for the same phosphor material. In this study, x-ray and light transport within granular phosphor materials was studied by developing a computational model using Monte Carlo methods. The model was based on the intrinsic physical characteristics of the phosphor. Input values required to feed the model can be easily obtained from tabulated data. The complex refractive index was introduced and microscopic probabilities for light interactions were produced, using Mie scattering theory. Model validation was carried out by comparing model results on x-ray and light parameters (x-ray absorption, statistical fluctuations in the x-ray to light conversion process, number of emitted light photons, output light spatial distribution) with previous published experimental data on Gd 2 O 2 S:Tb phosphor material (Kodak Min-R screen). Results showed the dependence of the modulation transfer function (MTF) on phosphor grain size and material packing density. It was predicted that granular Gd 2 O 2 S:Tb screens of high packing density and small grain size may exhibit considerably better resolution and light emission properties than the conventional Gd 2 O 2 S:Tb screens, under similar conditions (x-ray incident energy, screen thickness)

  18. Cost Effective Community Based Dementia Screening: A Markov Model Simulation

    Directory of Open Access Journals (Sweden)

    Erin Saito

    2014-01-01

    Full Text Available Background. Given the dementia epidemic and the increasing cost of healthcare, there is a need to assess the economic benefit of community based dementia screening programs. Materials and Methods. Markov model simulations were generated using data obtained from a community based dementia screening program over a one-year period. The models simulated yearly costs of caring for patients based on clinical transitions beginning in pre dementia and extending for 10 years. Results. A total of 93 individuals (74 female, 19 male were screened for dementia and 12 meeting clinical criteria for either mild cognitive impairment (n=7 or dementia (n=5 were identified. Assuming early therapeutic intervention beginning during the year of dementia detection, Markov model simulations demonstrated 9.8% reduction in cost of dementia care over a ten-year simulation period, primarily through increased duration in mild stages and reduced time in more costly moderate and severe stages. Discussion. Community based dementia screening can reduce healthcare costs associated with caring for demented individuals through earlier detection and treatment, resulting in proportionately reduced time in more costly advanced stages.

  19. Unifying screening processes within the PROSPR consortium: a conceptual model for breast, cervical, and colorectal cancer screening.

    Science.gov (United States)

    Beaber, Elisabeth F; Kim, Jane J; Schapira, Marilyn M; Tosteson, Anna N A; Zauber, Ann G; Geiger, Ann M; Kamineni, Aruna; Weaver, Donald L; Tiro, Jasmin A

    2015-06-01

    General frameworks of the cancer screening process are available, but none directly compare the process in detail across different organ sites. This limits the ability of medical and public health professionals to develop and evaluate coordinated screening programs that apply resources and population management strategies available for one cancer site to other sites. We present a trans-organ conceptual model that incorporates a single screening episode for breast, cervical, and colorectal cancers into a unified framework based on clinical guidelines and protocols; the model concepts could be expanded to other organ sites. The model covers four types of care in the screening process: risk assessment, detection, diagnosis, and treatment. Interfaces between different provider teams (eg, primary care and specialty care), including communication and transfer of responsibility, may occur when transitioning between types of care. Our model highlights across each organ site similarities and differences in steps, interfaces, and transitions in the screening process and documents the conclusion of a screening episode. This model was developed within the National Cancer Institute-funded consortium Population-based Research Optimizing Screening through Personalized Regimens (PROSPR). PROSPR aims to optimize the screening process for breast, cervical, and colorectal cancer and includes seven research centers and a statistical coordinating center. Given current health care reform initiatives in the United States, this conceptual model can facilitate the development of comprehensive quality metrics for cancer screening and promote trans-organ comparative cancer screening research. PROSPR findings will support the design of interventions that improve screening outcomes across multiple cancer sites. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Printer model for dot-on-dot halftone screens

    Science.gov (United States)

    Balasubramanian, Raja

    1995-04-01

    A printer model is described for dot-on-dot halftone screens. For a given input CMYK signal, the model predicts the resulting spectral reflectance of the printed patch. The model is derived in two steps. First, the C, M, Y, K dot growth functions are determined which relate the input digital value to the actual dot area coverages of the colorants. Next, the reflectance of a patch is predicted as a weighted combination of the reflectances of the four solid C, M, Y, K patches and their various overlays. This approach is analogous to the Neugebauer model, with the random mixing equations being replaced by dot-on-dot mixing equations. A Yule-Neilsen correction factor is incorporated to account for light scattering within the paper. The dot area functions and Yule-Neilsen parameter are chosen to optimize the fit to a set of training data. The model is also extended to a cellular framework, requiring additional measurements. The model is tested with a four color xerographic printer employing a line-on-line halftone screen. CIE L*a*b* errors are obtained between measurements and model predictions. The Yule-Neilsen factor significantly decreases the model error. Accuracy is also increased with the use of a cellular framework.

  1. Comparing deep learning models for population screening using chest radiography

    Science.gov (United States)

    Sivaramakrishnan, R.; Antani, Sameer; Candemir, Sema; Xue, Zhiyun; Abuya, Joseph; Kohli, Marc; Alderson, Philip; Thoma, George

    2018-02-01

    According to the World Health Organization (WHO), tuberculosis (TB) remains the most deadly infectious disease in the world. In a 2015 global annual TB report, 1.5 million TB related deaths were reported. The conditions worsened in 2016 with 1.7 million reported deaths and more than 10 million people infected with the disease. Analysis of frontal chest X-rays (CXR) is one of the most popular methods for initial TB screening, however, the method is impacted by the lack of experts for screening chest radiographs. Computer-aided diagnosis (CADx) tools have gained significance because they reduce the human burden in screening and diagnosis, particularly in countries that lack substantial radiology services. State-of-the-art CADx software typically is based on machine learning (ML) approaches that use hand-engineered features, demanding expertise in analyzing the input variances and accounting for the changes in size, background, angle, and position of the region of interest (ROI) on the underlying medical imagery. More automatic Deep Learning (DL) tools have demonstrated promising results in a wide range of ML applications. Convolutional Neural Networks (CNN), a class of DL models, have gained research prominence in image classification, detection, and localization tasks because they are highly scalable and deliver superior results with end-to-end feature extraction and classification. In this study, we evaluated the performance of CNN based DL models for population screening using frontal CXRs. The results demonstrate that pre-trained CNNs are a promising feature extracting tool for medical imagery including the automated diagnosis of TB from chest radiographs but emphasize the importance of large data sets for the most accurate classification.

  2. ScreenBEAM: a novel meta-analysis algorithm for functional genomics screens via Bayesian hierarchical modeling.

    Science.gov (United States)

    Yu, Jiyang; Silva, Jose; Califano, Andrea

    2016-01-15

    Functional genomics (FG) screens, using RNAi or CRISPR technology, have become a standard tool for systematic, genome-wide loss-of-function studies for therapeutic target discovery. As in many large-scale assays, however, off-target effects, variable reagents' potency and experimental noise must be accounted for appropriately control for false positives. Indeed, rigorous statistical analysis of high-throughput FG screening data remains challenging, particularly when integrative analyses are used to combine multiple sh/sgRNAs targeting the same gene in the library. We use large RNAi and CRISPR repositories that are publicly available to evaluate a novel meta-analysis approach for FG screens via Bayesian hierarchical modeling, Screening Bayesian Evaluation and Analysis Method (ScreenBEAM). Results from our analysis show that the proposed strategy, which seamlessly combines all available data, robustly outperforms classical algorithms developed for microarray data sets as well as recent approaches designed for next generation sequencing technologies. Remarkably, the ScreenBEAM algorithm works well even when the quality of FG screens is relatively low, which accounts for about 80-95% of the public datasets. R package and source code are available at: https://github.com/jyyu/ScreenBEAM. ac2248@columbia.edu, jose.silva@mssm.edu, yujiyang@gmail.com Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Screening important inputs in models with strong interaction properties

    International Nuclear Information System (INIS)

    Saltelli, Andrea; Campolongo, Francesca; Cariboni, Jessica

    2009-01-01

    We introduce a new method for screening inputs in mathematical or computational models with large numbers of inputs. The method proposed here represents an improvement over the best available practice for this setting when dealing with models having strong interaction effects. When the sample size is sufficiently high the same design can also be used to obtain accurate quantitative estimates of the variance-based sensitivity measures: the same simulations can be used to obtain estimates of the variance-based measures according to the Sobol' and the Jansen formulas. Results demonstrate that Sobol' is more efficient for the computation of the first-order indices, while Jansen performs better for the computation of the total indices.

  4. Screening important inputs in models with strong interaction properties

    Energy Technology Data Exchange (ETDEWEB)

    Saltelli, Andrea [European Commission, Joint Research Centre, 21020 Ispra, Varese (Italy); Campolongo, Francesca [European Commission, Joint Research Centre, 21020 Ispra, Varese (Italy)], E-mail: francesca.campolongo@jrc.it; Cariboni, Jessica [European Commission, Joint Research Centre, 21020 Ispra, Varese (Italy)

    2009-07-15

    We introduce a new method for screening inputs in mathematical or computational models with large numbers of inputs. The method proposed here represents an improvement over the best available practice for this setting when dealing with models having strong interaction effects. When the sample size is sufficiently high the same design can also be used to obtain accurate quantitative estimates of the variance-based sensitivity measures: the same simulations can be used to obtain estimates of the variance-based measures according to the Sobol' and the Jansen formulas. Results demonstrate that Sobol' is more efficient for the computation of the first-order indices, while Jansen performs better for the computation of the total indices.

  5. Modeling screening, prevention, and delaying of Alzheimer's disease: an early-stage decision analytic model

    Directory of Open Access Journals (Sweden)

    Siemers Eric R

    2010-04-01

    Full Text Available Abstract Background Alzheimer's Disease (AD affects a growing proportion of the population each year. Novel therapies on the horizon may slow the progress of AD symptoms and avoid cases altogether. Initiating treatment for the underlying pathology of AD would ideally be based on biomarker screening tools identifying pre-symptomatic individuals. Early-stage modeling provides estimates of potential outcomes and informs policy development. Methods A time-to-event (TTE simulation provided estimates of screening asymptomatic patients in the general population age ≥55 and treatment impact on the number of patients reaching AD. Patients were followed from AD screen until all-cause death. Baseline sensitivity and specificity were 0.87 and 0.78, with treatment on positive screen. Treatment slowed progression by 50%. Events were scheduled using literature-based age-dependent incidences of AD and death. Results The base case results indicated increased AD free years (AD-FYs through delays in onset and a reduction of 20 AD cases per 1000 screened individuals. Patients completely avoiding AD accounted for 61% of the incremental AD-FYs gained. Total years of treatment per 1000 screened patients was 2,611. The number-needed-to-screen was 51 and the number-needed-to-treat was 12 to avoid one case of AD. One-way sensitivity analysis indicated that duration of screening sensitivity and rescreen interval impact AD-FYs the most. A two-way sensitivity analysis found that for a test with an extended duration of sensitivity (15 years the number of AD cases avoided was 6,000-7,000 cases for a test with higher sensitivity and specificity (0.90,0.90. Conclusions This study yielded valuable parameter range estimates at an early stage in the study of screening for AD. Analysis identified duration of screening sensitivity as a key variable that may be unavailable from clinical trials.

  6. Modeling screening, prevention, and delaying of Alzheimer's disease: an early-stage decision analytic model.

    Science.gov (United States)

    Furiak, Nicolas M; Klein, Robert W; Kahle-Wrobleski, Kristin; Siemers, Eric R; Sarpong, Eric; Klein, Timothy M

    2010-04-30

    Alzheimer's Disease (AD) affects a growing proportion of the population each year. Novel therapies on the horizon may slow the progress of AD symptoms and avoid cases altogether. Initiating treatment for the underlying pathology of AD would ideally be based on biomarker screening tools identifying pre-symptomatic individuals. Early-stage modeling provides estimates of potential outcomes and informs policy development. A time-to-event (TTE) simulation provided estimates of screening asymptomatic patients in the general population age > or =55 and treatment impact on the number of patients reaching AD. Patients were followed from AD screen until all-cause death. Baseline sensitivity and specificity were 0.87 and 0.78, with treatment on positive screen. Treatment slowed progression by 50%. Events were scheduled using literature-based age-dependent incidences of AD and death. The base case results indicated increased AD free years (AD-FYs) through delays in onset and a reduction of 20 AD cases per 1000 screened individuals. Patients completely avoiding AD accounted for 61% of the incremental AD-FYs gained. Total years of treatment per 1000 screened patients was 2,611. The number-needed-to-screen was 51 and the number-needed-to-treat was 12 to avoid one case of AD. One-way sensitivity analysis indicated that duration of screening sensitivity and rescreen interval impact AD-FYs the most. A two-way sensitivity analysis found that for a test with an extended duration of sensitivity (15 years) the number of AD cases avoided was 6,000-7,000 cases for a test with higher sensitivity and specificity (0.90,0.90). This study yielded valuable parameter range estimates at an early stage in the study of screening for AD. Analysis identified duration of screening sensitivity as a key variable that may be unavailable from clinical trials.

  7. Modeling sequential context effects in diagnostic interpretation of screening mammograms.

    Science.gov (United States)

    Alamudun, Folami; Paulus, Paige; Yoon, Hong-Jun; Tourassi, Georgia

    2018-07-01

    Prior research has shown that physicians' medical decisions can be influenced by sequential context, particularly in cases where successive stimuli exhibit similar characteristics when analyzing medical images. This type of systematic error is known to psychophysicists as sequential context effect as it indicates that judgments are influenced by features of and decisions about the preceding case in the sequence of examined cases, rather than being based solely on the peculiarities unique to the present case. We determine if radiologists experience some form of context bias, using screening mammography as the use case. To this end, we explore correlations between previous perceptual behavior and diagnostic decisions and current decisions. We hypothesize that a radiologist's visual search pattern and diagnostic decisions in previous cases are predictive of the radiologist's current diagnostic decisions. To test our hypothesis, we tasked 10 radiologists of varied experience to conduct blind reviews of 100 four-view screening mammograms. Eye-tracking data and diagnostic decisions were collected from each radiologist under conditions mimicking clinical practice. Perceptual behavior was quantified using the fractal dimension of gaze scanpath, which was computed using the Minkowski-Bouligand box-counting method. To test the effect of previous behavior and decisions, we conducted a multifactor fixed-effects ANOVA. Further, to examine the predictive value of previous perceptual behavior and decisions, we trained and evaluated a predictive model for radiologists' current diagnostic decisions. ANOVA tests showed that previous visual behavior, characterized by fractal analysis, previous diagnostic decisions, and image characteristics of previous cases are significant predictors of current diagnostic decisions. Additionally, predictive modeling of diagnostic decisions showed an overall improvement in prediction error when the model is trained on additional information about

  8. Melanoma screening: Informing public health policy with quantitative modelling.

    Directory of Open Access Journals (Sweden)

    Stephen Gilmore

    Full Text Available Australia and New Zealand share the highest incidence rates of melanoma worldwide. Despite the substantial increase in public and physician awareness of melanoma in Australia over the last 30 years-as a result of the introduction of publicly funded mass media campaigns that began in the early 1980s -mortality has steadily increased during this period. This increased mortality has led investigators to question the relative merits of primary versus secondary prevention; that is, sensible sun exposure practices versus early detection. Increased melanoma vigilance on the part of the public and among physicians has resulted in large increases in public health expenditure, primarily from screening costs and increased rates of office surgery. Has this attempt at secondary prevention been effective? Unfortunately epidemiologic studies addressing the causal relationship between the level of secondary prevention and mortality are prohibitively difficult to implement-it is currently unknown whether increased melanoma surveillance reduces mortality, and if so, whether such an approach is cost-effective. Here I address the issue of secondary prevention of melanoma with respect to incidence and mortality (and cost per life saved by developing a Markov model of melanoma epidemiology based on Australian incidence and mortality data. The advantages of developing a methodology that can determine constraint-based surveillance outcomes are twofold: first, it can address the issue of effectiveness; and second, it can quantify the trade-off between cost and utilisation of medical resources on one hand, and reduced morbidity and lives saved on the other. With respect to melanoma, implementing the model facilitates the quantitative determination of the relative effectiveness and trade-offs associated with different levels of secondary and tertiary prevention, both retrospectively and prospectively. For example, I show that the surveillance enhancement that began in

  9. A Computational model for compressed sensing RNAi cellular screening

    Directory of Open Access Journals (Sweden)

    Tan Hua

    2012-12-01

    Full Text Available Abstract Background RNA interference (RNAi becomes an increasingly important and effective genetic tool to study the function of target genes by suppressing specific genes of interest. This system approach helps identify signaling pathways and cellular phase types by tracking intensity and/or morphological changes of cells. The traditional RNAi screening scheme, in which one siRNA is designed to knockdown one specific mRNA target, needs a large library of siRNAs and turns out to be time-consuming and expensive. Results In this paper, we propose a conceptual model, called compressed sensing RNAi (csRNAi, which employs a unique combination of group of small interfering RNAs (siRNAs to knockdown a much larger size of genes. This strategy is based on the fact that one gene can be partially bound with several small interfering RNAs (siRNAs and conversely, one siRNA can bind to a few genes with distinct binding affinity. This model constructs a multi-to-multi correspondence between siRNAs and their targets, with siRNAs much fewer than mRNA targets, compared with the conventional scheme. Mathematically this problem involves an underdetermined system of equations (linear or nonlinear, which is ill-posed in general. However, the recently developed compressed sensing (CS theory can solve this problem. We present a mathematical model to describe the csRNAi system based on both CS theory and biological concerns. To build this model, we first search nucleotide motifs in a target gene set. Then we propose a machine learning based method to find the effective siRNAs with novel features, such as image features and speech features to describe an siRNA sequence. Numerical simulations show that we can reduce the siRNA library to one third of that in the conventional scheme. In addition, the features to describe siRNAs outperform the existing ones substantially. Conclusions This csRNAi system is very promising in saving both time and cost for large-scale RNAi

  10. Mathematic model analysis of Gaussian beam propagation through an arbitrary thickness random phase screen.

    Science.gov (United States)

    Tian, Yuzhen; Guo, Jin; Wang, Rui; Wang, Tingfeng

    2011-09-12

    In order to research the statistical properties of Gaussian beam propagation through an arbitrary thickness random phase screen for adaptive optics and laser communication application in the laboratory, we establish mathematic models of statistical quantities, which are based on the Rytov method and the thin phase screen model, involved in the propagation process. And the analytic results are developed for an arbitrary thickness phase screen based on the Kolmogorov power spectrum. The comparison between the arbitrary thickness phase screen and the thin phase screen shows that it is more suitable for our results to describe the generalized case, especially the scintillation index.

  11. The German cervical cancer screening model: development and validation of a decision-analytic model for cervical cancer screening in Germany.

    Science.gov (United States)

    Siebert, Uwe; Sroczynski, Gaby; Hillemanns, Peter; Engel, Jutta; Stabenow, Roland; Stegmaier, Christa; Voigt, Kerstin; Gibis, Bernhard; Hölzel, Dieter; Goldie, Sue J

    2006-04-01

    We sought to develop and validate a decision-analytic model for the natural history of cervical cancer for the German health care context and to apply it to cervical cancer screening. We developed a Markov model for the natural history of cervical cancer and cervical cancer screening in the German health care context. The model reflects current German practice standards for screening, diagnostic follow-up and treatment regarding cervical cancer and its precursors. Data for disease progression and cervical cancer survival were obtained from the literature and German cancer registries. Accuracy of Papanicolaou (Pap) testing was based on meta-analyses. We performed internal and external model validation using observed epidemiological data for unscreened women from different German cancer registries. The model predicts life expectancy, incidence of detected cervical cancer cases, lifetime cervical cancer risks and mortality. The model predicted a lifetime cervical cancer risk of 3.0% and a lifetime cervical cancer mortality of 1.0%, with a peak cancer incidence of 84/100,000 at age 51 years. These results were similar to observed data from German cancer registries, German literature data and results from other international models. Based on our model, annual Pap screening could prevent 98.7% of diagnosed cancer cases and 99.6% of deaths due to cervical cancer in women completely adherent to screening and compliant to treatment. Extending the screening interval from 1 year to 2, 3 or 5 years resulted in reduced screening effectiveness. This model provides a tool for evaluating the long-term effectiveness of different cervical cancer screening tests and strategies.

  12. Screening model for nanowire surface-charge sensors in liquid

    DEFF Research Database (Denmark)

    Sørensen, Martin Hedegård; Mortensen, Asger; Brandbyge, Mads

    2007-01-01

    The conductance change of nanowire field-effect transistors is considered a highly sensitive probe for surface charge. However, Debye screening of relevant physiological liquid environments challenge device performance due to competing screening from the ionic liquid and nanowire charge carriers....

  13. Screen or not to screen for peripheral arterial disease: Guidance from a decision model

    NARCIS (Netherlands)

    A. Vaidya (Anil); M.A. Joore (Manuela); A.J. Ten Cate-Hoek (Arina J); H. ten Cate (Hugo); J.L. Severens (Hans)

    2014-01-01

    markdownabstract__Abstract__ Background: Asymptomatic Peripheral Arterial Disease (PAD) is associated with greater risk of acute cardiovascular events. This study aims to determine the cost-effectiveness of one time only PAD screening using Ankle Brachial Index (ABI) test and subsequent anti

  14. ND and NB systems in quark delocalization color screening model

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Lifang [Nanjing College of Information Technology, Department of Quality-Oriented Education, Nanjing (China); Huang, Hongxia; Ping, Jialun [Nanjing Normal University, Department of Physics, Nanjing (China)

    2017-02-15

    The ND and NB systems with I = 0 and 1, J{sup P} = (1)/(2){sup ±}, (3)/(2){sup ±}, and (5)/(2){sup ±} are investigated within the framework of the quark delocalization color screening model. The results show that all the positive-parity states are unbound. By coupling to the ND* channel, the state ND with I = 0, J{sup P} = (1)/(2){sup -} can form a bound state, which can be invoked to explain the observed Σ(2800) state. The mass of the ND* with I = 0, J{sup P} = (3)/(2){sup -} is close to that of the reported Λ{sub c}(2940){sup +}, which indicates that Λ{sub c}(2940){sup +} can be explained as a ND* molecular state in QDCSM. Besides, the ΔD* with I = 1, J{sup P} = (5)/(2){sup -} is also a possible resonance state. The results of the bottom case of the NB system are similar to those of the ND system. Searching for these states will be a challenging subject of experiments. (orig.)

  15. THE MODEL FOR DIEGETIC ANALYSIS OF SOUNDS IN SCREEN MEDIA

    Directory of Open Access Journals (Sweden)

    Denikin Anton A.

    2013-12-01

    Full Text Available This article includes the analysis of the relationship between representational visual spaces and sounds in screen media. The methodology presented in this paper can be used for the accurate classification and differentiation for screen sounds, as well as for the general analysis of the specific sound of screen media. For this, the concept of «diegesis» is used. It allows us to analyze the spatial specificity of audiovisual images in cinematographic works and the spatial-functional interactive action in video games and others multimedia.

  16. COSMO-RS-based extractant screening for phenol extraction as model system

    NARCIS (Netherlands)

    Burghoff, B.; Goetheer, E.L.V.; Haan, A.B. de

    2008-01-01

    The focus of this investigation is the development of a fast and reliable extractant screening approach. Phenol extraction is selected as the model process. A quantum chemical conductor-like screening model for real solvents (COSMO-RS) is combined with molecular design considerations. For this

  17. Color screening effect in the quark potential model

    International Nuclear Information System (INIS)

    Zhang Zongye; Yu Youwen; Shen Pengnian; Shen Xiaoyan; Dong Yubin

    1993-01-01

    By using the color confinement potential which includes the color screening effect, we studied the baryon spectra and the nucleon-nucleon interaction. The results show that the color screening effect not only improves the baryon spectrum calculation, but also can solve the long-tail problem of the color Van der Waals force. A part of the medium attraction of the nuclear force can be obtained from the color Van der Waals force. (orig.)

  18. Modeling a point-source release of 1,1,1-trichloroethane using EPA's SCREEN model

    International Nuclear Information System (INIS)

    Henriques, W.D.; Dixon, K.R.

    1994-01-01

    Using data from the Environmental Protection Agency's Toxic Release Inventory 1988 (EPA TRI88), pollutant concentration estimates were modeled for a point source air release of 1,1,1-trichloroethane at the Savannah River Plant located in Aiken, South Carolina. Estimates were calculating using the EPA's SCREEN model utilizing typical meteorological conditions to determine maximum impact of the plume under different mixing conditions for locations within 100 meters of the stack. Input data for the SCREEN model were then manipulated to simulate the impact of the release under urban conditions (for the purpose of assessing future landuse considerations) and under flare release options to determine if these parameters lessen or increase the probability of human or wildlife exposure to significant concentrations. The results were then compared to EPA reference concentrations (RfC) in order to assess the size of the buffer around the stack which may potentially have levels that exceed this level of safety

  19. Discrete Event Simulation for Decision Modeling in Health Care: Lessons from Abdominal Aortic Aneurysm Screening

    Science.gov (United States)

    Jones, Edmund; Masconi, Katya L.; Sweeting, Michael J.; Thompson, Simon G.; Powell, Janet T.

    2018-01-01

    Markov models are often used to evaluate the cost-effectiveness of new healthcare interventions but they are sometimes not flexible enough to allow accurate modeling or investigation of alternative scenarios and policies. A Markov model previously demonstrated that a one-off invitation to screening for abdominal aortic aneurysm (AAA) for men aged 65 y in the UK and subsequent follow-up of identified AAAs was likely to be highly cost-effective at thresholds commonly adopted in the UK (£20,000 to £30,000 per quality adjusted life-year). However, new evidence has emerged and the decision problem has evolved to include exploration of the circumstances under which AAA screening may be cost-effective, which the Markov model is not easily able to address. A new model to handle this more complex decision problem was needed, and the case of AAA screening thus provides an illustration of the relative merits of Markov models and discrete event simulation (DES) models. An individual-level DES model was built using the R programming language to reflect possible events and pathways of individuals invited to screening v. those not invited. The model was validated against key events and cost-effectiveness, as observed in a large, randomized trial. Different screening protocol scenarios were investigated to demonstrate the flexibility of the DES. The case of AAA screening highlights the benefits of DES, particularly in the context of screening studies.

  20. Effects of screening and partner notification on Chlamydia positivity in the United States: a modeling study.

    Science.gov (United States)

    Kretzschmar, Mirjam; Satterwhite, Catherine; Leichliter, Jami; Berman, Stuart

    2012-05-01

    Model impact of increasing screening and partner notification (PN) on chlamydia positivity. We used a stochastic simulation model describing pair formation and dissolution in an age-structured heterosexual population. The model accounts for steady, casual, and concurrent partnerships and a highly sexually active core group. The model used existing sexual behavior data from the United States and was validated using chlamydia positivity data from Region X (Alaska, Idaho, Oregon, Washington). A screening program with a coverage rate of 20% was implemented among women aged 15 to 24 years. After 10 years, we increased screening coverage to 35%, 50%, and 65% and partner treatment rates from 20% to 40% and 55%. Finally, we included male screening (aged 15-24, screening coverage: 20% and 35%, partner treatment: 25% and 40%). We analyzed the effects on chlamydia positivity in women and the frequency of reinfection 6 months after treatment. The model described the decline in positivity observed from 1988 to 1997 in Region X, given screening coverage of 20% and a 25% partner treatment rate. Increasing screening coverage from 35% to 65% resulted in incremental decreases in positivity as did increasing the PN rate; a 23% reduction in positivity was achieved by either increasing screening by 3-fold or PN by 2-fold. Adding male screening to the program had less impact than increasing screening coverage or PN among women. Increased PN and treatment reduced reinfection rates considerably. Increasing efforts in PN may contribute at least as much to control of chlamydia infection as increasing screening coverage rates.

  1. Choosing algorithms for TB screening: a modelling study to compare yield, predictive value and diagnostic burden.

    Science.gov (United States)

    Van't Hoog, Anna H; Onozaki, Ikushi; Lonnroth, Knut

    2014-10-19

    To inform the choice of an appropriate screening and diagnostic algorithm for tuberculosis (TB) screening initiatives in different epidemiological settings, we compare algorithms composed of currently available methods. Of twelve algorithms composed of screening for symptoms (prolonged cough or any TB symptom) and/or chest radiography abnormalities, and either sputum-smear microscopy (SSM) or Xpert MTB/RIF (XP) as confirmatory test we model algorithm outcomes and summarize the yield, number needed to screen (NNS) and positive predictive value (PPV) for different levels of TB prevalence. Screening for prolonged cough has low yield, 22% if confirmatory testing is by SSM and 32% if XP, and a high NNS, exceeding 1000 if TB prevalence is ≤0.5%. Due to low specificity the PPV of screening for any TB symptom followed by SSM is less than 50%, even if TB prevalence is 2%. CXR screening for TB abnormalities followed by XP has the highest case detection (87%) and lowest NNS, but is resource intensive. CXR as a second screen for symptom screen positives improves efficiency. The ideal algorithm does not exist. The choice will be setting specific, for which this study provides guidance. Generally an algorithm composed of CXR screening followed by confirmatory testing with XP can achieve the lowest NNS and highest PPV, and is the least amenable to setting-specific variation. However resource requirements for tests and equipment may be prohibitive in some settings and a reason to opt for symptom screening and SSM. To better inform disease control programs we need empirical data to confirm the modeled yield, cost-effectiveness studies, transmission models and a better screening test.

  2. SCREENING CHEMICALS FOR ESTROGEN RECEPTOR BIOACTIVITY USING A COMPUTATIONAL MODEL

    Science.gov (United States)

    The U.S. Environmental Protection Agency (EPA) is considering the use high-throughput and computational methods for regulatory applications in the Endocrine Disruptor Screening Program (EDSP). To use these new tools for regulatory decision making, computational methods must be a...

  3. Steroidogenesis in vitro : towards relevant models for endocrine disruptor screening

    NARCIS (Netherlands)

    Roelofs, M.J.E.

    2016-01-01

    Starting our search for in vitro alternative methods to screen for steroidogenesis toxicity, we focused on the effects of (suggested) endocrine disrupting compounds (EDCs) on cytochrome P450 17 (CYP17) enzyme activity. CYP17 is responsible for conversion of progestagens to dehydroepiandrosterone

  4. Modelling of hysteresis in thin superconducting screens for mixed-mu suspension systems

    International Nuclear Information System (INIS)

    Asher, G.M.; Williams, J.T.; Walters, C.R.; Joyce, H.; Paul, R.J.A.

    1982-01-01

    Mixed-mu levitation is the principle whereby iron is levitated in a magnetic field and stabilized by the proximity of diamagnetic superconducting screens. In a dynamic environment, the screens are subject to changing magnetic fields thus causing hysteresis losses in the superconducting material. This paper is concerned with the modeling of such hysteresis. A finite difference approximation to the current and field distributions is employed, the current distribution being made consistent with critical current values by iteration. Square and disc shaped screen samples are studied and hysteresis curves computed. It is shown that the method represents a fair approximation to the hysteresis behavior of thin superconducting screens. 8 refs

  5. Independent screening for single-index hazard rate models with ultrahigh dimensional features

    DEFF Research Database (Denmark)

    Gorst-Rasmussen, Anders; Scheike, Thomas

    2013-01-01

    can be viewed as the natural survival equivalent of correlation screening. We state conditions under which the method admits the sure screening property within a class of single-index hazard rate models with ultrahigh dimensional features and describe the generally detrimental effect of censoring...

  6. [Economic impact of lung cancer screening in France: A modeling study].

    Science.gov (United States)

    Gendarme, S; Perrot, É; Reskot, F; Bhoowabul, V; Fourre, G; Souquet, P-J; Milleron, B; Couraud, S

    2017-09-01

    The National Lung Screening Trial found that, in a selected population with a high risk of lung cancer, an annual low-dose CT-scan decreased lung cancer mortality by 20% and overall mortality by 7% compared to annual chest X-Ray. In France, a work group stated that individual screening should be considered in this setting. However, the economic impact of an organized and generalized (to all eligible individuals) screening in France was never reported. This is a modeling study using French population demographic data and published data from randomized screening trials. We used the same selection criteria as NLST: 55-74-year-old smokers for at least 30 pack-years, current smoker or quit less than 15 years. We computed a second model including also 50-54-year-old individuals. Then, we used different participation rates: 65%, 45%, and 32%. According to the considered model, there would be 1,650,588 to 2,283,993 subjects eligible to screening in France. According to the model and participation rate, lung cancer screening would diagnose 3600 to 10,118 stages 1/2 lung cancer each year. There would be 5991 to 16,839 false-positives, of whom 1416 to 3981 would undergo unnecessary surgery. Screening policy would cost 105 to 215 € million per year. However, increasing the price of a cigarette pack by 0.05 to 0.10 € would fully cover the screening costs. Participation rate is a key point for screening impact. Screening could be easily funded by a small increase in cigarette prices. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  7. The Effect of Lead Intensification Screens on Film: Modeling and Experiment

    International Nuclear Information System (INIS)

    Wendt, S.; Gray, J.; Zhou, C.

    2004-01-01

    A physics-based, intensification screen model, using lead as an example, has been developed. Comparisons to experimental results are shown. The dominant effect in producing the intensification is from photoelectrons ejected from a 24 - 40 micron layer of lead near the film with Compton electrons and the lead fluorescence x-rays contributing less than 10% to the intensification for settings below 300 kvp. The thickness of lead screen for optimal intensification is between 15 and 70 microns depending upon the energy of the photon. This is less than the traditional practice of a 130 microns front screen and 260 microns back screen. The model computes the intensifying effect of lead screens placed in front or in back of a sheet of radiographic film and accounts for the strong energy dependent effects contributing to the intensification. The lead screen model is independent of film type, so the user can select any type of film and any combination of lead thickness for the front and back screens. The model uses energy dependent x-ray photon absorption cross-sections to compute the production of electrons in the lead. A Monte Carlo calculation was used to determine energy dependent electron penetration in the lead and the film. The model calculates electron attenuation in the film emulsion, the film substrate and both front and back lead screens and determines the intensification effect as a function of the energy deposited in the film. For model validation, lead screen intensification was studied with x-ray generator settings ranging from 75 to 320 kvp and using various thicknesses of aluminum and iron attenuators to filter the x-ray beam. A high precision motion control system coupled with a high purity germanium detector was used to study the energy spectra

  8. FOOTPRINT: A Screening Model for Estimating the Area of a Plume Produced From Gasoline Containing Ethanol

    Science.gov (United States)

    FOOTPRINT is a screening model used to estimate the length and surface area of benzene, toluene, ethylbenzene, and xylene (BTEX) plumes in groundwater, produced from a gasoline spill that contains ethanol.

  9. Which risk models perform best in selecting ever-smokers for lung cancer screening?

    Science.gov (United States)

    A new analysis by scientists at NCI evaluates nine different individualized lung cancer risk prediction models based on their selections of ever-smokers for computed tomography (CT) lung cancer screening.

  10. Radiation-Induced Breast Cancer Incidence and Mortality From Digital Mammography Screening: A Modeling Study.

    Science.gov (United States)

    Miglioretti, Diana L; Lange, Jane; van den Broek, Jeroen J; Lee, Christoph I; van Ravesteyn, Nicolien T; Ritley, Dominique; Kerlikowske, Karla; Fenton, Joshua J; Melnikow, Joy; de Koning, Harry J; Hubbard, Rebecca A

    2016-02-16

    Estimates of risk for radiation-induced breast cancer from mammography screening have not considered variation in dose exposure or diagnostic work-up after abnormal screening results. To estimate distributions of radiation-induced breast cancer incidence and mortality from digital mammography screening while considering exposure from screening and diagnostic mammography and dose variation among women. 2 simulation-modeling approaches. U.S. population. Women aged 40 to 74 years. Annual or biennial digital mammography screening from age 40, 45, or 50 years until age 74 years. Lifetime breast cancer deaths averted (benefits) and radiation-induced breast cancer incidence and mortality (harms) per 100,000 women screened. Annual screening of 100,000 women aged 40 to 74 years was projected to induce 125 breast cancer cases (95% CI, 88 to 178) leading to 16 deaths (CI, 11 to 23), relative to 968 breast cancer deaths averted by early detection from screening. Women exposed at the 95th percentile were projected to develop 246 cases of radiation-induced breast cancer leading to 32 deaths per 100,000 women. Women with large breasts requiring extra views for complete examination (8% of population) were projected to have greater radiation-induced breast cancer risk (266 cancer cases and 35 deaths per 100,000 women) than other women (113 cancer cases and 15 deaths per 100,000 women). Biennial screening starting at age 50 years reduced risk for radiation-induced cancer 5-fold. Life-years lost from radiation-induced breast cancer could not be estimated. Radiation-induced breast cancer incidence and mortality from digital mammography screening are affected by dose variability from screening, resultant diagnostic work-up, initiation age, and screening frequency. Women with large breasts may have a greater risk for radiation-induced breast cancer. Agency for Healthcare Research and Quality, U.S. Preventive Services Task Force, National Cancer Institute.

  11. Lung Cancer Screening Participation: Developing a Conceptual Model to Guide Research.

    Science.gov (United States)

    Carter-Harris, Lisa; Davis, Lorie L; Rawl, Susan M

    2016-11-01

    To describe the development of a conceptual model to guide research focused on lung cancer screening participation from the perspective of the individual in the decision-making process. Based on a comprehensive review of empirical and theoretical literature, a conceptual model was developed linking key psychological variables (stigma, medical mistrust, fatalism, worry, and fear) to the health belief model and precaution adoption process model. Proposed model concepts have been examined in prior research of either lung or other cancer screening behavior. To date, a few studies have explored a limited number of variables that influence screening behavior in lung cancer specifically. Therefore, relationships among concepts in the model have been proposed and future research directions presented. This proposed model is an initial step to support theoretically based research. As lung cancer screening becomes more widely implemented, it is critical to theoretically guide research to understand variables that may be associated with lung cancer screening participation. Findings from future research guided by the proposed conceptual model can be used to refine the model and inform tailored intervention development.

  12. Validation of Models Used to Inform Colorectal Cancer Screening Guidelines: Accuracy and Implications.

    Science.gov (United States)

    Rutter, Carolyn M; Knudsen, Amy B; Marsh, Tracey L; Doria-Rose, V Paul; Johnson, Eric; Pabiniak, Chester; Kuntz, Karen M; van Ballegooijen, Marjolein; Zauber, Ann G; Lansdorp-Vogelaar, Iris

    2016-07-01

    Microsimulation models synthesize evidence about disease processes and interventions, providing a method for predicting long-term benefits and harms of prevention, screening, and treatment strategies. Because models often require assumptions about unobservable processes, assessing a model's predictive accuracy is important. We validated 3 colorectal cancer (CRC) microsimulation models against outcomes from the United Kingdom Flexible Sigmoidoscopy Screening (UKFSS) Trial, a randomized controlled trial that examined the effectiveness of one-time flexible sigmoidoscopy screening to reduce CRC mortality. The models incorporate different assumptions about the time from adenoma initiation to development of preclinical and symptomatic CRC. Analyses compare model predictions to study estimates across a range of outcomes to provide insight into the accuracy of model assumptions. All 3 models accurately predicted the relative reduction in CRC mortality 10 years after screening (predicted hazard ratios, with 95% percentile intervals: 0.56 [0.44, 0.71], 0.63 [0.51, 0.75], 0.68 [0.53, 0.83]; estimated with 95% confidence interval: 0.56 [0.45, 0.69]). Two models with longer average preclinical duration accurately predicted the relative reduction in 10-year CRC incidence. Two models with longer mean sojourn time accurately predicted the number of screen-detected cancers. All 3 models predicted too many proximal adenomas among patients referred to colonoscopy. Model accuracy can only be established through external validation. Analyses such as these are therefore essential for any decision model. Results supported the assumptions that the average time from adenoma initiation to development of preclinical cancer is long (up to 25 years), and mean sojourn time is close to 4 years, suggesting the window for early detection and intervention by screening is relatively long. Variation in dwell time remains uncertain and could have important clinical and policy implications. © The

  13. Quality assurance target for community-based breast cancer screening in China: a model simulation.

    Science.gov (United States)

    Yang, Lan; Wang, Jing; Cheng, Juan; Wang, Yuan; Lu, Wenli

    2018-03-07

    We aimed to clarify the feasibility of a community-based screening strategy for breast cancer in Tianjin, China; to identify the factors that most significantly influenced its feasibility; and to identify the reference range for quality control. A state-transition Markov model simulated a hypothetical cohort of 100,000 healthy women, the start aged was set at 35 years and the time horizon was set to 50 years. The primary outcome for the model was the incremental cost-utility ratio (ICUR), defined as the program's cost per quality-adjusted life year (QALY) gained. Three screening strategies providing by community health service for women aged 35 to 69 years was compared regarding to different intervals. The probability of the ICUR being below 20 272USD (i.e., triple the annual gross domestic product [3 GDPs]) per QALY saved was 100% for annual screening strategy and screening every three years. Only when the attendance rate was > 50%, the probability for annual screening would be cost effective > 95%. The probability for the annual screening strategy being cost effective could reach to 95% for a willingness-to-pay (WTP) of 2 GDPs when the compliance rate for transfer was > 80%. When 10% stage I tumors were detected by screening, the probability of the annual screening strategy being cost effective would be up to 95% for a WTP > 3 GDPs. Annual community-based breast cancer screening was cost effective for a WTP of 3 GDP based on the incidence of breast cancer in Tianjin, China. Measures are needed to ensure performance indicators to a desirable level for the cost-effectiveness of breast cancer screening.

  14. A System Dynamics Model of Serum Prostate-Specific Antigen Screening for Prostate Cancer.

    Science.gov (United States)

    Palma, Anton; Lounsbury, David W; Schlecht, Nicolas F; Agalliu, Ilir

    2016-02-01

    Since 2012, US guidelines have recommended against prostate-specific antigen (PSA) screening for prostate cancer. However, evidence of screening benefit from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening trial and the European Randomized Study of Screening for Prostate Cancer has been inconsistent, due partly to differences in noncompliance and contamination. Using system dynamics modeling, we replicated the PLCO trial and extrapolated follow-up to 20 years. We then simulated 3 scenarios correcting for contamination in the PLCO control arm using Surveillance, Epidemiology, and End Results (SEER) incidence and survival data collected prior to the PSA screening era (scenario 1), SEER data collected during the PLCO trial period (1993-2001) (scenario 2), and data from the European trial's control arm (1991-2005) (scenario 3). In all scenarios, noncompliance was corrected using incidence and survival rates for men with screen-detected cancer in the PLCO screening arm. Scenarios 1 and 3 showed a benefit of PSA screening, with relative risks of 0.62 (95% confidence interval: 0.53, 0.72) and 0.70 (95% confidence interval: 0.59, 0.83) for cancer-specific mortality after 20 years, respectively. In scenario 2, however, there was no benefit of screening. This simulation showed that after correcting for noncompliance and contamination, there is potential benefit of PSA screening in reducing prostate cancer mortality. It also demonstrates the utility of system dynamics modeling for synthesizing epidemiologic evidence to inform public policy. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. A comparison of scoring models for computerised mental health screening for federal prison inmates.

    Science.gov (United States)

    Martin, Michael S; Wamboldt, Ashley D; O'Connor, Shannon L; Fortier, Julie; Simpson, Alexander I F

    2013-02-01

    There are high rates of mental disorder in correctional environments, so effective mental health screening is needed. Implementation of the computerised mental health screen of the Correctional Service of Canada has led to improved identification of offenders with mental health needs but with high rates of false positives. The goal of this study is to evaluate the use of an iterative classification tree (ICT) approach to mental health screening compared with a simple binary approach using cut-off scores on screening tools. A total of 504 consecutive admissions to federal prison completed the screen and were also interviewed by a mental health professional. Relationships between screening results and more extended assessment and clinical team discussion were tested. The ICT was more parsimonious in identifying probable 'cases' than standard binary screening. ICT was also highly accurate at detecting mental health needs (AUC=0.87, 95% CI 0.84-0.90). The model identified 118 (23.4%) offenders as likely to need further assessment or treatment, 87% of whom were confirmed cases at clinical interview. Of the 244 (48.4%) offenders who were screened out, only 9% were clinically assessed as requiring further assessment or treatment. Standard binary screening was characterised by more false positives and a comparable false negative rate. The use of ICTs to interpret screening data on the mental health of prisoners needs further evaluation in independent samples in Canada and elsewhere. This first evaluation of the application of such an approach offers the prospect of more effective and efficient use of the scarce resource of mental health services in prisons. Although not required, the use of computers can increase the ease of implementing an ICT model. Copyright © 2013 John Wiley & Sons, Ltd.

  16. Cost-effectiveness of community screening for glaucoma in rural India: a decision analytical model.

    Science.gov (United States)

    John, D; Parikh, R

    2018-02-01

    Studies in several countries have demonstrated the cost-effectiveness of population-based screening for glaucoma when targeted at high-risk groups such as older adults and with familial history of disease. This study conducts a cost-effective analysis of a hypothetical community screening and subsequent treatment programme in comparison to opportunistic case finding for glaucoma in rural India. A hypothetical screening programme for both primary open-angle glaucoma and angle-closure disease was built for a population aged between 40 and 69 years in rural areas of India. A decision analytical model was built to model events, costs and treatment pathways with and without a hypothetical screening programme for glaucoma for a rural-based population aged between 40 and 69 years in India. The treatment pathway included both primary open-angle glaucoma and angle-closure disease. The data on costs of screening and treatment were provided by an administrator of a tertiary eye hospital in Eastern India. The probabilities for the screening and treatment pathway were derived from published literature and a glaucoma specialist. The glaucoma prevalence rates were adapted from the Chennai Glaucoma Study findings. An incremental cost-effectiveness ratio value of ₹7292.30 per quality-adjusted life-year was calculated for a community-screening programme for glaucoma in rural India. The community screening for glaucoma would treat an additional 2872 cases and prevent 2190 person-years of blindness over a 10-year period. Community screening for glaucoma in rural India appears to be cost-effective when judged by a ratio of willingness-to-pay thresholds as per WHO-CHOICE guidelines. For community screening to be cost-effective, adequate resources, such as trained medical personnel and equipment would need to be made available. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  17. Creation of a National, At-home Model for Ashkenazi Jewish Carrier Screening.

    Science.gov (United States)

    Grinzaid, Karen Arnovitz; Page, Patricia Zartman; Denton, Jessica Johnson; Ginsberg, Jessica

    2015-06-01

    Ethnicity-based carrier screening for the Ashkenazi Jewish population has been available and encouraged by advocacy and community groups since the early 1970's. Both the American College of Medical Genetics and the American Congress of Obstetricians and Gynecologists recommend carrier screening for this population (Obstetrics and Gynecology, 114(4), 950-953, 2009; Genetics in Medicine, 10(1), 55-56, 2008). While many physicians inquire about ethnic background and offer appropriate carrier screening, studies show that a gap remains in implementing recommendations (Genetic testing and molecular biomarkers, 2011). In addition, education and outreach efforts targeting Jewish communities have had limited success in reaching this at-risk population. Despite efforts by the medical and Jewish communities, many Jews of reproductive age are not aware of screening, and remain at risk for having children with preventable diseases. Reaching this population, preferably pre-conception, and facilitating access to screening is critically important. To address this need, genetic counselors at Emory University developed JScreen, a national Jewish genetic disease screening program. The program includes a national marketing and PR campaign, online education, at-home saliva-based screening, post-test genetic counseling via telephone or secure video conferencing, and referrals for face-to-face genetic counseling as needed. Our goals are to create a successful education and screening program for this population and to develop a model that could potentially be used for other at-risk populations.

  18. Generalized model screening potentials for Fermi-Dirac plasmas

    International Nuclear Information System (INIS)

    Akbari-Moghanjoughi, M.

    2016-01-01

    In this paper, some properties of relativistically degenerate quantum plasmas, such as static ion screening, structure factor, and Thomson scattering cross-section, are studied in the framework of linearized quantum hydrodynamic theory with the newly proposed kinetic γ-correction to Bohm term in low frequency limit. It is found that the correction has a significant effect on the properties of quantum plasmas in all density regimes, ranging from solid-density up to that of white dwarf stars. It is also found that Shukla-Eliasson attractive force exists up to a few times the density of metals, and the ionic correlations are seemingly apparent in the radial distribution function signature. Simplified statically screened attractive and repulsive potentials are presented for zero-temperature Fermi-Dirac plasmas, valid for a wide range of quantum plasma number-density and atomic number values. Moreover, it is observed that crystallization of white dwarfs beyond a critical core number-density persists with this new kinetic correction, but it is shifted to a much higher number-density value of n_0 ≃ 1.94 × 10"3"7 cm"−"3 (1.77 × 10"1"0 gr cm"−"3), which is nearly four orders of magnitude less than the nuclear density. It is found that the maximal Thomson scattering with the γ-corrected structure factor is a remarkable property of white dwarf stars. However, with the new γ-correction, the maximal scattering shifts to the spectrum region between hard X-ray and low-energy gamma-rays. White dwarfs composed of higher atomic-number ions are observed to maximally Thomson-scatter at slightly higher wavelengths, i.e., they maximally scatter slightly low-energy photons in the presence of correction.

  19. Generalized model screening potentials for Fermi-Dirac plasmas

    Science.gov (United States)

    Akbari-Moghanjoughi, M.

    2016-04-01

    In this paper, some properties of relativistically degenerate quantum plasmas, such as static ion screening, structure factor, and Thomson scattering cross-section, are studied in the framework of linearized quantum hydrodynamic theory with the newly proposed kinetic γ-correction to Bohm term in low frequency limit. It is found that the correction has a significant effect on the properties of quantum plasmas in all density regimes, ranging from solid-density up to that of white dwarf stars. It is also found that Shukla-Eliasson attractive force exists up to a few times the density of metals, and the ionic correlations are seemingly apparent in the radial distribution function signature. Simplified statically screened attractive and repulsive potentials are presented for zero-temperature Fermi-Dirac plasmas, valid for a wide range of quantum plasma number-density and atomic number values. Moreover, it is observed that crystallization of white dwarfs beyond a critical core number-density persists with this new kinetic correction, but it is shifted to a much higher number-density value of n0 ≃ 1.94 × 1037 cm-3 (1.77 × 1010 gr cm-3), which is nearly four orders of magnitude less than the nuclear density. It is found that the maximal Thomson scattering with the γ-corrected structure factor is a remarkable property of white dwarf stars. However, with the new γ-correction, the maximal scattering shifts to the spectrum region between hard X-ray and low-energy gamma-rays. White dwarfs composed of higher atomic-number ions are observed to maximally Thomson-scatter at slightly higher wavelengths, i.e., they maximally scatter slightly low-energy photons in the presence of correction.

  20. Generalized model screening potentials for Fermi-Dirac plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Akbari-Moghanjoughi, M. [Faculty of Sciences, Department of Physics, Azarbaijan Shahid Madani University, 51745-406 Tabriz, Iran and International Centre for Advanced Studies in Physical Sciences and Institute for Theoretical Physics, Ruhr University Bochum, D-44780 Bochum (Germany)

    2016-04-15

    In this paper, some properties of relativistically degenerate quantum plasmas, such as static ion screening, structure factor, and Thomson scattering cross-section, are studied in the framework of linearized quantum hydrodynamic theory with the newly proposed kinetic γ-correction to Bohm term in low frequency limit. It is found that the correction has a significant effect on the properties of quantum plasmas in all density regimes, ranging from solid-density up to that of white dwarf stars. It is also found that Shukla-Eliasson attractive force exists up to a few times the density of metals, and the ionic correlations are seemingly apparent in the radial distribution function signature. Simplified statically screened attractive and repulsive potentials are presented for zero-temperature Fermi-Dirac plasmas, valid for a wide range of quantum plasma number-density and atomic number values. Moreover, it is observed that crystallization of white dwarfs beyond a critical core number-density persists with this new kinetic correction, but it is shifted to a much higher number-density value of n{sub 0} ≃ 1.94 × 10{sup 37} cm{sup −3} (1.77 × 10{sup 10} gr cm{sup −3}), which is nearly four orders of magnitude less than the nuclear density. It is found that the maximal Thomson scattering with the γ-corrected structure factor is a remarkable property of white dwarf stars. However, with the new γ-correction, the maximal scattering shifts to the spectrum region between hard X-ray and low-energy gamma-rays. White dwarfs composed of higher atomic-number ions are observed to maximally Thomson-scatter at slightly higher wavelengths, i.e., they maximally scatter slightly low-energy photons in the presence of correction.

  1. Application of Poisson random effect models for highway network screening.

    Science.gov (United States)

    Jiang, Ximiao; Abdel-Aty, Mohamed; Alamili, Samer

    2014-02-01

    In recent years, Bayesian random effect models that account for the temporal and spatial correlations of crash data became popular in traffic safety research. This study employs random effect Poisson Log-Normal models for crash risk hotspot identification. Both the temporal and spatial correlations of crash data were considered. Potential for Safety Improvement (PSI) were adopted as a measure of the crash risk. Using the fatal and injury crashes that occurred on urban 4-lane divided arterials from 2006 to 2009 in the Central Florida area, the random effect approaches were compared to the traditional Empirical Bayesian (EB) method and the conventional Bayesian Poisson Log-Normal model. A series of method examination tests were conducted to evaluate the performance of different approaches. These tests include the previously developed site consistence test, method consistence test, total rank difference test, and the modified total score test, as well as the newly proposed total safety performance measure difference test. Results show that the Bayesian Poisson model accounting for both temporal and spatial random effects (PTSRE) outperforms the model that with only temporal random effect, and both are superior to the conventional Poisson Log-Normal model (PLN) and the EB model in the fitting of crash data. Additionally, the method evaluation tests indicate that the PTSRE model is significantly superior to the PLN model and the EB model in consistently identifying hotspots during successive time periods. The results suggest that the PTSRE model is a superior alternative for road site crash risk hotspot identification. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Modeling Accessibility of Screening and Treatment Facilities for Older Adults using Transportation Networks.

    Science.gov (United States)

    Zhang, Qiuyi; Northridge, Mary E; Jin, Zhu; Metcalf, Sara S

    2018-04-01

    Increased lifespans and population growth have resulted in an older U.S. society that must reckon with the complex oral health needs that arise as adults age. Understanding accessibility to screening and treatment facilities for older adults is necessary in order to provide them with preventive and restorative services. This study uses an agent-based model to examine the accessibility of screening and treatment facilities via transportation networks for older adults living in the neighborhoods of northern Manhattan, New York City. Older adults are simulated as socioeconomically distinct agents who move along a GIS-based transportation network using transportation modes that mediate their access to screening and treatment facilities. This simulation model includes four types of mobile agents as a simplifying assumption: walk, by car, by bus, or by van (i.e., a form of transportation assistance for older adults). These mobile agents follow particular routes: older adults who travel by car, bus, and van follow street roads, whereas pedestrians follow walkways. The model enables the user to focus on one neighborhood at a time for analysis. The spatial dimension of an older adult's accessibility to screening and treatment facilities is simulated through the travel costs (indicated by travel time or distance) incurred in the GIS-based model environment, where lower travel costs to screening and treatment facilities imply better access. This model provides a framework for representing health-seeking behavior that is contextualized by a transportation network in a GIS environment.

  3. Modeling fiber motion in a pulp pressure screen: the effect of slot shape

    International Nuclear Information System (INIS)

    Dong, S.; Salcudean, M.; Gartshore, I.

    2003-01-01

    A pressure screen is a piece of equipment in the pulp and paper industry used either to remove contaminants from the pulp suspension or to separate fibers having different properties. Contaminants such as fiber bundles, bark and plastic specks are introduced when fibers are separated from the wood by mechanical or chemical pulping processes. Contaminants significantly affect the strength and smoothness of the paper and must be removed before the final paper is produced. The screen plate is a critical part of the pressure screen and its design is the key to screen performance. This paper uses a new and comprehensive CFD simulation tool to examine the flow and fiber behavior in a single slot screen having any reasonable slot shape. -This simulation tool includes three coupled models: first, the flow model solves the Reynolds Averaged Navier-Stokes (RANS) equation using the standard k - ε turbulence model to predict the flow field in the equipment. Second, a three-dimensional flexible fiber model is used to track the fiber trajectory in the screen. Third, a very general wall model is used to deal with the case when a fiber touches the equipment wall. The simulated results show that the slot shape has a critical influence on fiber behavior and screen performance. Three general slot shapes were investigated: the smooth slot, the step-step contour slot and slope-slope contour slot. Of these the slope-slope contour slot provides the best passage for the fibers with a length of 1mm and 3mm. (author)

  4. Analytical model for screening potential CO2 repositories

    Science.gov (United States)

    Okwen, R.T.; Stewart, M.T.; Cunningham, J.A.

    2011-01-01

    Assessing potential repositories for geologic sequestration of carbon dioxide using numerical models can be complicated, costly, and time-consuming, especially when faced with the challenge of selecting a repository from a multitude of potential repositories. This paper presents a set of simple analytical equations (model), based on the work of previous researchers, that could be used to evaluate the suitability of candidate repositories for subsurface sequestration of carbon dioxide. We considered the injection of carbon dioxide at a constant rate into a confined saline aquifer via a fully perforated vertical injection well. The validity of the analytical model was assessed via comparison with the TOUGH2 numerical model. The metrics used in comparing the two models include (1) spatial variations in formation pressure and (2) vertically integrated brine saturation profile. The analytical model and TOUGH2 show excellent agreement in their results when similar input conditions and assumptions are applied in both. The analytical model neglects capillary pressure and the pressure dependence of fluid properties. However, simulations in TOUGH2 indicate that little error is introduced by these simplifications. Sensitivity studies indicate that the agreement between the analytical model and TOUGH2 depends strongly on (1) the residual brine saturation, (2) the difference in density between carbon dioxide and resident brine (buoyancy), and (3) the relationship between relative permeability and brine saturation. The results achieved suggest that the analytical model is valid when the relationship between relative permeability and brine saturation is linear or quasi-linear and when the irreducible saturation of brine is zero or very small. ?? 2011 Springer Science+Business Media B.V.

  5. Validation of periodontitis screening model using sociodemographic, systemic, and molecular information in a Korean population.

    Science.gov (United States)

    Kim, Hyun-Duck; Sukhbaatar, Munkhzaya; Shin, Myungseop; Ahn, Yoo-Been; Yoo, Wook-Sung

    2014-12-01

    This study aims to evaluate and validate a periodontitis screening model that includes sociodemographic, metabolic syndrome (MetS), and molecular information, including gingival crevicular fluid (GCF), matrix metalloproteinase (MMP), and blood cytokines. The authors selected 506 participants from the Shiwha-Banwol cohort: 322 participants from the 2005 cohort for deriving the screening model and 184 participants from the 2007 cohort for its validation. Periodontitis was assessed by dentists using the community periodontal index. Interleukin (IL)-6, IL-8, and tumor necrosis factor-α in blood and MMP-8, -9, and -13 in GCF were assayed using enzyme-linked immunosorbent assay. MetS was assessed by physicians using physical examination and blood laboratory data. Information about age, sex, income, smoking, and drinking was obtained by interview. Logistic regression analysis was applied to finalize the best-fitting model and validate the model using sensitivity, specificity, and c-statistics. The derived model for periodontitis screening had a sensitivity of 0.73, specificity of 0.85, and c-statistic of 0.86 (P validated model were 0.64, 0.91, and 0.83 (P <0.001), respectively. The model that included age, sex, income, smoking, drinking, and blood and GCF biomarkers could be useful in screening for periodontitis. A future prospective study is indicated for evaluating this model's ability to predict the occurrence of periodontitis.

  6. THE HYDROCARBON SPILL SCREENING MODEL (HSSM), VOLUME 2: THEORETICAL BACKGROUND AND SOURCE CODES

    Science.gov (United States)

    A screening model for subsurface release of a nonaqueous phase liquid which is less dense than water (LNAPL) is presented. The model conceptualizes the release as consisting of 1) vertical transport from near the surface to the capillary fringe, 2) radial spreading of an LNAPL l...

  7. Modeling the cost-benefit of nerve conduction studies in pre-employment screening for carpal tunnel syndrome.

    Science.gov (United States)

    Evanoff, Bradley; Kymes, Steve

    2010-06-01

    The aim of this study was to evaluate the costs associated with pre-employment nerve conduction testing as a screening tool for carpal tunnel syndrome (CTS) in the workplace. We used a Markov decision analysis model to compare the costs associated with a strategy of screening all prospective employees for CTS and not hiring those with abnormal nerve conduction, versus a strategy of not screening for CTS. The variables included in our model included employee turnover rate, the incidence of CTS, the prevalence of median nerve conduction abnormalities, the relative risk of developing CTS conferred by abnormal nerve conduction screening, the costs of pre-employment screening, and the worker's compensation costs to the employer for each case of CTS. In our base case, total employer costs for CTS from the perspective of the employer (cost of screening plus costs for workers' compensation associated with CTS) were higher when screening was used. Median costs per employee position over five years were US$503 for the screening strategy versus US$200 for a no-screening strategy. A sensitivity analysis showed that a strategy of screening was cost-beneficial from the perspective of the employer only under a few circumstances. Using Monte Carlo simulation varying all parameters, we found a 30% probability that screening would be cost-beneficial. A strategy of pre-employment screening for CTS should be carefully evaluated for yield and social consequences before being implemented. Our model suggests such screening is not appropriate for most employers.

  8. METHOD FOR NUMERICAL MODELING OF UNSTEADY SEPARATED FLOW AROUND AIRFOILS MOVING CLOSE TO FLAT SCREEN

    Directory of Open Access Journals (Sweden)

    V. Pogrebnaya Tamara

    2017-01-01

    Full Text Available In this article an attempt is made to explain the nature of differences in measurements of forces and moments, which influence an aircraft at take-off and landing when testing on different types of stands. An algorithm for numerical simulation of unsteady separated flow around airfoil is given. The algorithm is based on the combination of discrete vortex method and turbulent boundary layer equations. An unsteady flow separation modeling has been used. At each interval vortex method was used to calculate the potential flow around airfoils located near a screen. Calculated pressures and velocities were then used in boundary layer calculations to determine flow separation points and separated vortex in- tensities. After that calculation were made to determine free vortex positions to next time step and the process was fulfilled for next time step. The proposed algorithm allows using numeric visualization to understand physical picture of flow around airfoil moving close to screen. Three different ways of flow modeling (mirror method, fixed or movable screens were tested. In each case the flow separation process, which determines pressure distribution over airfoil surface and influ- ences aerodynamic performance, was viewed. The results of the calculations showed that at low atitudes of airfoil over screen mirror method over predicts lift force compared with movable screen, while fixed screen under predicts it. The data obtained can be used when designing equipment for testing in wind tunnels.

  9. Simple model for taking into account the effects of plasma screening in thermonuclear reactions

    International Nuclear Information System (INIS)

    Shalybkov, D.A.; Yakovlev, D.G.

    1988-01-01

    In the Thomas-Fermi model of high-density matter analytic calculation is made of the factor by which the rate of the thermonuclear reactions is enhanced by the effects of plasma screening in a degenerate weakly non-ideal electron gas and a strongly nonideal two-component ion liquid with large charge of the ions. The regions of densities and temperatures in which screening due to compressibility of the electron gas plays an important part are found. It is noted that the screening due to this compressibility may be influenced by strong magnetic fields B /approximately/ 10 12 -10 13 G, which quantize the motion of the electrons and change the electron charge screening length in the plasma. The results can be used for the degenerate cores of white dwarfs and shells of neutron stars

  10. Including ethical considerations in models for first-trimester screening for pre-eclampsia

    DEFF Research Database (Denmark)

    Jørgensen, Jennifer Maureen; Hedley, Paula L.; Gjerris, Mickey

    2014-01-01

    Recent efforts to develop reliable and efficient early pregnancy screening programmes for pre-eclampsia have focused on com-bining clinical, biochemical and biophysical markers. The same model has been used for first-trimester screening for fetal aneuploidies i.e. prenatal diagnosis (PD), which...... is routinely offered to all pregnant women in many developed countries. Some studies suggest combining PD and pre-eclampsia screening, so women can be offered testing for a number of conditions at the same clinical visit. A combination of these tests may be practical in terms of saving time and resources......; however, the combination raises ethical issues. First-trimester PD and pre-eclampsia screening entail qualitative differences which alter the requirements for disclosure, non-directedness and consent with regard to the informed consent process. This article explores the differences related to the ethical...

  11. Validation of the Colorado Retinopathy of Prematurity Screening Model.

    Science.gov (United States)

    McCourt, Emily A; Ying, Gui-Shuang; Lynch, Anne M; Palestine, Alan G; Wagner, Brandie D; Wymore, Erica; Tomlinson, Lauren A; Binenbaum, Gil

    2018-04-01

    The Colorado Retinopathy of Prematurity (CO-ROP) model uses birth weight, gestational age, and weight gain at the first month of life (WG-28) to predict risk of severe retinopathy of prematurity (ROP). In previous validation studies, the model performed very well, predicting virtually all cases of severe ROP and potentially reducing the number of infants who need ROP examinations, warranting validation in a larger, more diverse population. To validate the performance of the CO-ROP model in a large multicenter cohort. This study is a secondary analysis of data from the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study, a retrospective multicenter cohort study conducted in 29 hospitals in the United States and Canada between January 2006 and June 2012 of 6351 premature infants who received ROP examinations. Sensitivity and specificity for severe (early treatment of ROP [ETROP] type 1 or 2) ROP, and reduction in infants receiving examinations. The CO-ROP model was applied to the infants in the G-ROP data set with all 3 data points (infants would have received examinations if they met all 3 criteria: birth weight, large validation cohort. The model requires all 3 criteria to be met to signal a need for examinations, but some infants with a birth weight or gestational age above the thresholds developed severe ROP. Most of these infants who were not detected by the CO-ROP model had obvious deviation in expected weight trajectories or nonphysiologic weight gain. These findings suggest that the CO-ROP model needs to be revised before considering implementation into clinical practice.

  12. Maternal Serologic Screening to Prevent Congenital Toxoplasmosis: A Decision-Analytic Economic Model

    Science.gov (United States)

    Stillwaggon, Eileen; Carrier, Christopher S.; Sautter, Mari; McLeod, Rima

    2011-01-01

    Objective To determine a cost-minimizing option for congenital toxoplasmosis in the United States. Methodology/Principal Findings A decision-analytic and cost-minimization model was constructed to compare monthly maternal serological screening, prenatal treatment, and post-natal follow-up and treatment according to the current French (Paris) protocol, versus no systematic screening or perinatal treatment. Costs are based on published estimates of lifetime societal costs of developmental disabilities and current diagnostic and treatment costs. Probabilities are based on published results and clinical practice in the United States and France. One- and two-way sensitivity analyses are used to evaluate robustness of results. Universal monthly maternal screening for congenital toxoplasmosis with follow-up and treatment, following the French protocol, is found to be cost-saving, with savings of $620 per child screened. Results are robust to changes in test costs, value of statistical life, seroprevalence in women of childbearing age, fetal loss due to amniocentesis, and to bivariate analysis of test costs and incidence of primary T. gondii infection in pregnancy. Given the parameters in this model and a maternal screening test cost of $12, screening is cost-saving for rates of congenital infection above 1 per 10,000 live births. If universal testing generates economies of scale in diagnostic tools—lowering test costs to about $2 per test—universal screening is cost-saving at rates of congenital infection well below the lowest reported rates in the United States of 1 per 10,000 live births. Conclusion/Significance Universal screening according to the French protocol is cost saving for the US population within broad parameters for costs and probabilities. PMID:21980546

  13. A nutritional risk screening model for patients with liver cirrhosis established using discriminant analysis

    Directory of Open Access Journals (Sweden)

    ZHU Binghua

    2017-06-01

    Full Text Available ObjectiveTo establish a nutritional risk screening model for patients with liver cirrhosis using discriminant analysis. MethodsThe clinical data of 273 patients with liver cirrhosis who were admitted to Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from August 2015 to March 2016 were collected. Body height, body weight, upper arm circumference, triceps skinfold thickness, subscapular skinfold thickness, and hand grip strength were measured and recorded, and then body mass index (BMI and upper arm muscle circumference were calculated. Laboratory markers including liver function parameters, renal function parameters, and vitamins were measured. The patients were asked to complete Nutritional Risk Screening 2002 and Malnutrition Universal Screening Tool (MUST, and a self-developed nutritional risk screening pathway was used for nutritional risk classification. Observation scales of the four diagnostic methods in traditional Chinese medicine were used to collect patients′ symptoms and signs. Continuous data were expressed as mean±SD (x±s; an analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. Discriminant analysis was used for model establishment, and cross validation was used for model verification. ResultsThe nutritional risk screening pathway for patients with liver cirrhosis was used for the screening of respondents, and there were 49 patients (17.95% in non-risk group, 49 (17.95% in possible-risk group, and 175 (64.10% in risk group. The distance criterion function was used to establish the nutritional risk screening model for patients with liver cirrhosis: D1=-11.885+0.310×BMI+0150×MAC+0.005×P-Alb-0.001×Vit B12+0.103×Vit D-0.89×ascites-0.404×weakness-0.560×hypochondriac pain+0035×dysphoria with feverish sensation (note: if a patient has ascites, weakness, hypochondriac pain

  14. Cellular and molecular modifier pathways in tauopathies: the big picture from screening invertebrate models.

    Science.gov (United States)

    Hannan, Shabab B; Dräger, Nina M; Rasse, Tobias M; Voigt, Aaron; Jahn, Thomas R

    2016-04-01

    Abnormal tau accumulations were observed and documented in post-mortem brains of patients affected by Alzheimer's disease (AD) long before the identification of mutations in the Microtubule-associated protein tau (MAPT) gene, encoding the tau protein, in a different neurodegenerative disease called Frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). The discovery of mutations in the MAPT gene associated with FTDP-17 highlighted that dysfunctions in tau alone are sufficient to cause neurodegeneration. Invertebrate models have been diligently utilized in investigating tauopathies, contributing to the understanding of cellular and molecular pathways involved in disease etiology. An important discovery came with the demonstration that over-expression of human tau in Drosophila leads to premature mortality and neuronal dysfunction including neurodegeneration, recapitulating some key neuropathological features of the human disease. The simplicity of handling invertebrate models combined with the availability of a diverse range of experimental resources make these models, in particular Drosophila a powerful invertebrate screening tool. Consequently, several large-scale screens have been performed using Drosophila, to identify modifiers of tau toxicity. The screens have revealed not only common cellular and molecular pathways, but in some instances the same modifier has been independently identified in two or more screens suggesting a possible role for these modifiers in regulating tau toxicity. The purpose of this review is to discuss the genetic modifier screens on tauopathies performed in Drosophila and C. elegans models, and to highlight the common cellular and molecular pathways that have emerged from these studies. Here, we summarize results of tau toxicity screens providing mechanistic insights into pathological alterations in tauopathies. Key pathways or modifiers that have been identified are associated with a broad range of processes

  15. A scoring model for predicting advanced colorectal neoplasia in a screened population of asymptomatic Japanese individuals.

    Science.gov (United States)

    Sekiguchi, Masau; Kakugawa, Yasuo; Matsumoto, Minori; Matsuda, Takahisa

    2018-01-22

    Risk stratification of screened populations could help improve colorectal cancer (CRC) screening. Use of the modified Asia-Pacific Colorectal Screening (APCS) score has been proposed in the Asia-Pacific region. This study was performed to build a new useful scoring model for CRC screening. Data were reviewed from 5218 asymptomatic Japanese individuals who underwent their first screening colonoscopy. Multivariate logistic regression was used to investigate risk factors for advanced colorectal neoplasia (ACN), and a new scoring model for the prediction of ACN was developed based on the results. The discriminatory capability of the new model and the modified APCS score were assessed and compared. Internal validation was also performed. ACN was detected in 225 participants. An 8-point scoring model for the prediction of ACN was developed using five independent risk factors for ACN (male sex, higher age, presence of two or more first-degree relatives with CRC, body mass index of > 22.5 kg/m 2 , and smoking history of > 18.5 pack-years). The prevalence of ACN was 1.6% (34/2172), 5.3% (127/2419), and 10.2% (64/627) in participants with scores of statistic of the scoring model was 0.70 (95% confidence interval, 0.67-0.73) in both the development and internal validation sets, and this value was higher than that of the modified APCS score [0.68 (95% confidence interval, 0.65-0.71), P = 0.03]. We built a new simple scoring model for prediction of ACN in a Japanese population that could stratify the screened population into low-, moderate-, and high-risk groups.

  16. Economic model of a birth cohort screening program for hepatitis C virus.

    Science.gov (United States)

    McGarry, Lisa J; Pawar, Vivek S; Panchmatia, Hemangi R; Rubin, Jaime L; Davis, Gary L; Younossi, Zobair M; Capretta, James C; O'Grady, Michael J; Weinstein, Milton C

    2012-05-01

    Recent research has identified high hepatitis C virus (HCV) prevalence among older U.S. residents who contracted HCV decades ago and may no longer be recognized as high risk. We assessed the cost-effectiveness of screening 100% of U.S. residents born 1946-1970 over 5 years (birth-cohort screening), compared with current risk-based screening, by projecting costs and outcomes of screening over the remaining lifetime of this birth cohort. A Markov model of the natural history of HCV was developed using data synthesized from surveillance data, published literature, expert opinion, and other secondary sources. We assumed eligible patients were treated with pegylated interferon plus ribavirin, with genotype 1 patients receiving a direct-acting antiviral in combination. The target population is U.S. residents born 1946-1970 with no previous HCV diagnosis. Among the estimated 102 million (1.6 million chronically HCV infected) eligible for screening, birth-cohort screening leads to 84,000 fewer cases of decompensated cirrhosis, 46,000 fewer cases of hepatocellular carcinoma, 10,000 fewer liver transplants, and 78,000 fewer HCV-related deaths. Birth-cohort screening leads to higher overall costs than risk-based screening ($80.4 billion versus $53.7 billion), but yields lower costs related to advanced liver disease ($31.2 billion versus $39.8 billion); birth-cohort screening produces an incremental cost-effectiveness ratio (ICER) of $37,700 per quality-adjusted life year gained versus risk-based screening. Sensitivity analyses showed that reducing the time horizon during which health and economic consequences are evaluated increases the ICER; similarly, decreasing the treatment rates and efficacy increases the ICER. Model results were relatively insensitive to other inputs. Birth-cohort screening for HCV is likely to provide important health benefits by reducing lifetime cases of advanced liver disease and HCV-related deaths and is cost-effective at conventional willingness

  17. Tailoring Breast Cancer Screening Intervals by Breast Density and Risk for Women Aged 50 Years or Older: Collaborative Modeling of Screening Outcomes.

    Science.gov (United States)

    Trentham-Dietz, Amy; Kerlikowske, Karla; Stout, Natasha K; Miglioretti, Diana L; Schechter, Clyde B; Ergun, Mehmet Ali; van den Broek, Jeroen J; Alagoz, Oguzhan; Sprague, Brian L; van Ravesteyn, Nicolien T; Near, Aimee M; Gangnon, Ronald E; Hampton, John M; Chandler, Young; de Koning, Harry J; Mandelblatt, Jeanne S; Tosteson, Anna N A

    2016-11-15

    Biennial screening is generally recommended for average-risk women aged 50 to 74 years, but tailored screening may provide greater benefits. To estimate outcomes for various screening intervals after age 50 years based on breast density and risk for breast cancer. Collaborative simulation modeling using national incidence, breast density, and screening performance data. United States. Women aged 50 years or older with various combinations of breast density and relative risk (RR) of 1.0, 1.3, 2.0, or 4.0. Annual, biennial, or triennial digital mammography screening from ages 50 to 74 years (vs. no screening) and ages 65 to 74 years (vs. biennial digital mammography from ages 50 to 64 years). Lifetime breast cancer deaths, life expectancy and quality-adjusted life-years (QALYs), false-positive mammograms, benign biopsy results, overdiagnosis, cost-effectiveness, and ratio of false-positive results to breast cancer deaths averted. Screening benefits and overdiagnosis increase with breast density and RR. False-positive mammograms and benign results on biopsy decrease with increasing risk. Among women with fatty breasts or scattered fibroglandular density and an RR of 1.0 or 1.3, breast cancer deaths averted were similar for triennial versus biennial screening for both age groups (50 to 74 years, median of 3.4 to 5.1 vs. 4.1 to 6.5 deaths averted; 65 to 74 years, median of 1.5 to 2.1 vs. 1.8 to 2.6 deaths averted). Breast cancer deaths averted increased with annual versus biennial screening for women aged 50 to 74 years at all levels of breast density and an RR of 4.0, and those aged 65 to 74 years with heterogeneously or extremely dense breasts and an RR of 4.0. However, harms were almost 2-fold higher. Triennial screening for the average-risk subgroup and annual screening for the highest-risk subgroup cost less than $100 000 per QALY gained. Models did not consider women younger than 50 years, those with an RR less than 1, or other imaging methods. Average-risk women

  18. The Dynamics of an HIV/AIDS Model with Screened Disease Carriers

    Directory of Open Access Journals (Sweden)

    S. D. Hove-Musekwa

    2009-01-01

    Full Text Available The presence of carriers usually complicates the dynamics and prevention of a disease. They are not recognized as disease cases themselves unless they are screened and they usually spread the infection without them being aware. We argue that this has been one of the major causes of the spread of human immunodeficiency virus (HIV. We propose, in this paper, a model for the heterogeneous transmission of HIV/acquired immunodeficiency syndrome in the presence of disease carriers. The model allows us to assess the role of screening, as an intervention program that can slow the epidemic. A threshold value ψ*, for the screening rate is obtained. It is shown numerically that if 80% or more of the carrier population is screened, the epidemic can be contained. The qualitative analysis is done in terms of the model reproduction number R. The model has two equilibria, the disease free equilibrium and a unique endemic equilibrium. The disease free equilibrium is globally stable of R  1. A detailed discussion of the model reproduction number is given and numerical simulations are done to show the role of some of the important model parameters.

  19. Estimation of the applicability domain of kernel-based machine learning models for virtual screening

    Directory of Open Access Journals (Sweden)

    Fechner Nikolas

    2010-03-01

    Full Text Available Abstract Background The virtual screening of large compound databases is an important application of structural-activity relationship models. Due to the high structural diversity of these data sets, it is impossible for machine learning based QSAR models, which rely on a specific training set, to give reliable results for all compounds. Thus, it is important to consider the subset of the chemical space in which the model is applicable. The approaches to this problem that have been published so far mostly use vectorial descriptor representations to define this domain of applicability of the model. Unfortunately, these cannot be extended easily to structured kernel-based machine learning models. For this reason, we propose three approaches to estimate the domain of applicability of a kernel-based QSAR model. Results We evaluated three kernel-based applicability domain estimations using three different structured kernels on three virtual screening tasks. Each experiment consisted of the training of a kernel-based QSAR model using support vector regression and the ranking of a disjoint screening data set according to the predicted activity. For each prediction, the applicability of the model for the respective compound is quantitatively described using a score obtained by an applicability domain formulation. The suitability of the applicability domain estimation is evaluated by comparing the model performance on the subsets of the screening data sets obtained by different thresholds for the applicability scores. This comparison indicates that it is possible to separate the part of the chemspace, in which the model gives reliable predictions, from the part consisting of structures too dissimilar to the training set to apply the model successfully. A closer inspection reveals that the virtual screening performance of the model is considerably improved if half of the molecules, those with the lowest applicability scores, are omitted from the screening

  20. Estimation of the applicability domain of kernel-based machine learning models for virtual screening.

    Science.gov (United States)

    Fechner, Nikolas; Jahn, Andreas; Hinselmann, Georg; Zell, Andreas

    2010-03-11

    The virtual screening of large compound databases is an important application of structural-activity relationship models. Due to the high structural diversity of these data sets, it is impossible for machine learning based QSAR models, which rely on a specific training set, to give reliable results for all compounds. Thus, it is important to consider the subset of the chemical space in which the model is applicable. The approaches to this problem that have been published so far mostly use vectorial descriptor representations to define this domain of applicability of the model. Unfortunately, these cannot be extended easily to structured kernel-based machine learning models. For this reason, we propose three approaches to estimate the domain of applicability of a kernel-based QSAR model. We evaluated three kernel-based applicability domain estimations using three different structured kernels on three virtual screening tasks. Each experiment consisted of the training of a kernel-based QSAR model using support vector regression and the ranking of a disjoint screening data set according to the predicted activity. For each prediction, the applicability of the model for the respective compound is quantitatively described using a score obtained by an applicability domain formulation. The suitability of the applicability domain estimation is evaluated by comparing the model performance on the subsets of the screening data sets obtained by different thresholds for the applicability scores. This comparison indicates that it is possible to separate the part of the chemspace, in which the model gives reliable predictions, from the part consisting of structures too dissimilar to the training set to apply the model successfully. A closer inspection reveals that the virtual screening performance of the model is considerably improved if half of the molecules, those with the lowest applicability scores, are omitted from the screening. The proposed applicability domain formulations

  1. Conceptual design of a regional water quality screening model

    International Nuclear Information System (INIS)

    Davis, M.J.

    1981-01-01

    This water quality assessment methodology is intended to predict concentrations at future times and to estimate the impacts on water quality of energy-related activities (including industrial boilers). Estimates of impacts on water quality at future times are based on incremental changes in pollutant inputs to the body water. Important features of the model are: use of measured concentrations to account for existing conditions; consideration of incremental changes in pollutant loads; emphasis on the energy sector and industrial boilers; analysis restricted to streams only; no attempt to fully account for pollutant behavior; and flexible design, so that future improvements can be incorporated. The basic approach is very similar to the one used by Argonne's ARQUAL model but will allow more complex pollutant behavior and more flexibility in use

  2. Cost Effectiveness of Screening Colonoscopy Depends on Adequate Bowel Preparation Rates - A Modeling Study.

    Directory of Open Access Journals (Sweden)

    James Kingsley

    Full Text Available Inadequate bowel preparation during screening colonoscopy necessitates repeating colonoscopy. Studies suggest inadequate bowel preparation rates of 20-60%. This increases the cost of colonoscopy for our society.The aim of this study is to determine the impact of inadequate bowel preparation rate on the cost effectiveness of colonoscopy compared to other screening strategies for colorectal cancer (CRC.A microsimulation model of CRC screening strategies for the general population at average risk for CRC. The strategies include fecal immunochemistry test (FIT every year, colonoscopy every ten years, sigmoidoscopy every five years, or stool DNA test every 3 years. The screening could be performed at private practice offices, outpatient hospitals, and ambulatory surgical centers.At the current assumed inadequate bowel preparation rate of 25%, the cost of colonoscopy as a screening strategy is above society's willingness to pay (<$50,000/QALY. Threshold analysis demonstrated that an inadequate bowel preparation rate of 13% or less is necessary before colonoscopy is considered more cost effective than FIT. At inadequate bowel preparation rates of 25%, colonoscopy is still more cost effective compared to sigmoidoscopy and stool DNA test. Sensitivity analysis of all inputs adjusted by ±10% showed incremental cost effectiveness ratio values were influenced most by the specificity, adherence, and sensitivity of FIT and colonoscopy.Screening colonoscopy is not a cost effective strategy when compared with fecal immunochemical test, as long as the inadequate bowel preparation rate is greater than 13%.

  3. Foam Assisted WAG, Snorre Revisit with New Foam Screening Model

    DEFF Research Database (Denmark)

    Spirov, Pavel; Rudyk, Svetlana Nikolayevna; Khan, Arif

    2012-01-01

    This study deals with simulation model of Foam Assisted Water Alternating Gas (FAWAG) method that had been implemented to two Norwegian Reservoirs. Being studied on number of pilot projects, the method proved successful, but Field Scale simulation was never understood properly. New phenomenological...... of the simulation contributes to more precise planning of the schedule of water and gas injection, prediction of the injection results and evaluation of the method efficiency. The testing of the surfactant properties allows making grounded choice of surfactant to use. The analysis of the history match gives insight...

  4. Lead-Time Models Should Not Be Used to Estimate Overdiagnosis in Cancer Screening

    DEFF Research Database (Denmark)

    Zahl, Per-Henrik; Jørgensen, Karsten Juhl; Gøtzsche, Peter C

    2014-01-01

    screening--the excess-incidence approach and the lead-time approach--that rely on two different lead-time definitions. Overdiagnosis when screening with mammography has varied from 0 to 75 %. We have explained that these differences are mainly caused by using different definitions and methods......Lead-time can mean two different things: Clinical lead-time is the lead-time for clinically relevant tumors; that is, those that are not overdiagnosed. Model-based lead-time is a theoretical construct where the time when the tumor would have caused symptoms is not limited by the person's death....... It is the average time at which the diagnosis is brought forward for both clinically relevant and overdiagnosed cancers. When screening for breast cancer, clinical lead-time is about 1 year, while model-based lead-time varies from 2 to 7 years. There are two different methods to calculate overdiagnosis in cancer...

  5. Suomi NPP VIIRS solar diffuser screen transmittance model and its applications.

    Science.gov (United States)

    Lei, Ning; Xiong, Xiaoxiong; Mcintire, Jeff

    2017-11-01

    The visible infrared imaging radiometer suite on the Suomi National Polar-orbiting Partnership satellite calibrates its reflective solar bands through observations of a sunlit solar diffuser (SD) panel. Sunlight passes through a perforated plate, referred to as the SD screen, before reaching the SD. It is critical to know whether the SD screen transmittance measured prelaunch is accurate. Several factors such as misalignments of the SD panel and the measurement apparatus could lead to errors in the measured transmittance and thus adversely impact on-orbit calibration quality through the SD. We develop a mathematical model to describe the transmittance as a function of the angles that incident light makes with the SD screen, and apply the model to fit the prelaunch measured transmittance. The results reveal that the model does not reproduce the measured transmittance unless the size of the apertures in the SD screen is quite different from the design value. We attribute the difference to the orientation alignment errors for the SD panel and the measurement apparatus. We model the alignment errors and apply our transmittance model to fit the prelaunch transmittance to retrieve the "true" transmittance. To use this model correctly, we also examine the finite source size effect on the transmittance. Furthermore, we compare the product of the retrieved "true" transmittance and the prelaunch SD bidirectional reflectance distribution function (BRDF) value to the value derived from on-orbit data to determine whether the prelaunch SD BRDF value is relatively accurate. The model is significant in that it can evaluate whether the SD screen transmittance measured prelaunch is accurate and help retrieve the true transmittance from the transmittance with measurement errors, consequently resulting in a more accurate sensor data product by the same amount.

  6. Abnormal screening in the quantum disordered phases of nonlinear σ-models

    International Nuclear Information System (INIS)

    Wen, X.G.; Zee, A.

    1989-01-01

    We study some properties of the quantum disordered phase of nonlinear σ-models, focussing on the quantum numbers of the quasi-particles and possible experimental implications. We find that the quasi-particles in the quantum disordered phase may, in many cases, carry new quantum numbers which do not appear in any finite combination of the fundamental fields. We call this phenomenon abnormal screening. Abnormal screening is shown to appear in (1+1)-dimensional systems. Using a large N mean field approach to the quantum disordered state, we show that abnormal screening may also appear in (1+2)-dimensional nonlinear σ-models. In 1+2 dimensions abnormal screening is closely related to spin-charge separation, which was proposed to occur in the spin liquid state relevant in some theories of high T c superconductivity. We compare the mean field approach with bosonization and other exact results for (1+1)-dimensional systems and find exact agreement for the quantum numbers of the quasi-particles. This suggests that mean field analysis of high T c superconductivity may yield a qualitatively reliable picture. Our result also gives an alternative way of understanding some novel properties of the antiferromagnetic spin chain. We estimate the density and temperature at which deconfinement and abnormal screening occur. Finally, we suggest some experimental signatures for this phenomenon. (orig.)

  7. Screening enterprising personality in youth: an empirical model.

    Science.gov (United States)

    Suárez-Álvarez, Javier; Pedrosa, Ignacio; García-Cueto, Eduardo; Muñiz, José

    2014-02-20

    Entrepreneurial attitudes of individuals are determined by different variables, some of them related to the cognitive and personality characteristics of the person, and others focused on contextual aspects. The aim of this study is to review the essential dimensions of enterprising personality and develop a test that will permit their thorough assessment. Nine dimensions were identified: achievement motivation, risk taking, innovativeness, autonomy, internal locus of control, external locus of control, stress tolerance, self-efficacy and optimism. For the assessment of these dimensions, 161 items were developed which were applied to a sample of 416 students, 54% male and 46% female (M = 17.89 years old, SD = 3.26). After conducting several qualitative and quantitative analyses, the final test was composed of 127 items with acceptable psychometric properties. Alpha coefficients for the subscales ranged from .81 to .98. The validity evidence relative to the content was provided by experts (V = .71, 95% CI = .56 - .85). Construct validity was assessed using different factorial analyses, obtaining a dimensional structure in accordance with the proposed model of nine interdependent dimensions as well as a global factor that groups these nine dimensions (explained variance = 49.07%; χ2/df = 1.78; GFI= .97; SRMR = .07). Nine out of the 127 items showed Differential Item Functioning as a function of gender (p .035). The results obtained are discussed and future lines of research analyzed.

  8. Life-Stage Physiologically-Based Pharmacokinetic (PBPK) Model Applications to Screen Environmental Hazards.

    Science.gov (United States)

    This presentation discusses methods used to extrapolate from in vitro high-throughput screening (HTS) toxicity data for an endocrine pathway to in vivo for early life stages in humans, and the use of a life stage PBPK model to address rapidly changing physiological parameters. A...

  9. Footprint (A Screening Model for Estimating the Area of a Plume Produced from Gasoline Containing Ethanol

    Science.gov (United States)

    FOOTPRINT is a simple and user-friendly screening model to estimate the length and surface area of BTEX plumes in ground water produced from a spill of gasoline that contains ethanol. Ethanol has a potential negative impact on the natural biodegradation of BTEX compounds in groun...

  10. Risk prediction models for selection of lung cancer screening candidates: A retrospective validation study

    NARCIS (Netherlands)

    K. ten Haaf (Kevin); J. Jeon (Jihyoun); M.C. Tammemagi (Martin); S.S. Han (Summer); C.Y. Kong (Chung Yin); S.K. Plevritis (Sylvia); E. Feuer (Eric); H.J. de Koning (Harry); E.W. Steyerberg (Ewout W.); R. Meza (Rafael)

    2017-01-01

    textabstractBackground: Selection of candidates for lung cancer screening based on individual risk has been proposed as an alternative to criteria based on age and cumulative smoking exposure (pack-years). Nine previously established risk models were assessed for their ability to identify those most

  11. Using the Cascade Model to Improve Antenatal Screening for the Hemoglobin Disorders

    Science.gov (United States)

    Gould, Dinah; Papadopoulos, Irena; Kelly, Daniel

    2012-01-01

    Introduction: The inherited hemoglobin disorders constitute a major public health problem. Facilitators (experienced hemoglobin counselors) were trained to deliver knowledge and skills to "frontline" practitioners to enable them to support parents during antenatal screening via a cascade (train-the-trainer) model. Objectives of…

  12. Current levels of gonorrhoea screening in MSM in Belgium may have little effect on prevalence: a modelling study.

    Science.gov (United States)

    Buyze, J; Vanden Berghe, W; Hens, N; Kenyon, C

    2018-02-01

    There is considerable uncertainty as to the effectiveness of Neisseria gonorrhoeae (NG) screening in men who have sex with men. It is important to ensure that screening has benefits that outweigh the risks of increased antibiotics resistance. We develop a mathematical model to estimate the effectiveness of screening on prevalence. Separable Temporal Exponential family Random Graph Models are used to model the sexual relationships network, both with main and casual partners. Next, the transmission of Gonorrhoea is simulated on this network. The models are implemented using the R package 'statnet', which we adapted among other things to incorporate infection status at the pharynx, urethra and rectum separately and to distinguish between anal sex, oral sex and rimming. The different screening programmes compared are no screening, 3.5% of the population screened, 32% screened and 50% screened. The model simulates day-by-day evolution for 10 years of a population of 10 000. If half of the population would be screened, the prevalence in the pharynx decreases from 11.9% to 10.2%. We conclude that the limited impact of screening on NG prevalence may not outweigh the increased risk of antibiotic resistance.

  13. Screening for a Chronic Disease: A Multiple Stage Duration Model with Partial Observability.

    Science.gov (United States)

    Mroz, Thomas A; Picone, Gabriel; Sloan, Frank; Yashkin, Arseniy P

    2016-08-01

    We estimate a dynamic multi-stage duration model to investigate how early detection of diabetes can delay the onset of lower extremity complications and death. We allow for partial observability of the disease stage, unmeasured heterogeneity, and endogenous timing of diabetes screening. Timely diagnosis appears important. We evaluate the effectiveness of two potential policies to reduce the monetary costs of frequent screening in terms of lost longevity. Compared to the status quo, the more restrictive policy yields an implicit value for an additional year of life of about $50,000, while the less restrictive policy implies a value of about $120,000.

  14. The value of models in informing resource allocation in colorectal cancer screening – 1 the case of the Netherlands

    Science.gov (United States)

    van Hees, Frank; Zauber, Ann G.; van Veldhuizen, Harriët; Heijnen, Marie-Louise A.; Penning, Corine; de Koning, Harry J.; van Ballegooijen, Marjolein; Lansdorp-Vogelaar, Iris

    2015-01-01

    In May 2011, the Dutch government decided to implement a national programme for colorectal cancer (CRC) screening using biennial faecal immunochemical test (FIT) screening between ages 55 and 75.[1] Decision modelling played an important role in informing this decision, as well as in the planning and implementation of the programme afterwards. In this overview, we illustrate the value of models in informing resource allocation in CRC screening, using the role that decision modelling has played in the Dutch CRC screening programme as an example. PMID:26063755

  15. Stem cells: a model for screening, discovery and development of drugs

    Directory of Open Access Journals (Sweden)

    Kitambi SS

    2011-09-01

    Full Text Available Satish Srinivas Kitambi1, Gayathri Chandrasekar21Department of Medical Biochemistry and Biophysics; 2Department of Biosciences, Karolinska Institutet, Stockholm, SwedenAbstract: The identification of normal and cancerous stem cells and the recent advances made in isolation and culture of stem cells have rapidly gained attention in the field of drug discovery and regenerative medicine. The prospect of performing screens aimed at proliferation, directed differentiation, and toxicity and efficacy studies using stem cells offers a reliable platform for the drug discovery process. Advances made in the generation of induced pluripotent stem cells from normal or diseased tissue serves as a platform to perform drug screens aimed at developing cell-based therapies against conditions like Parkinson's disease and diabetes. This review discusses the application of stem cells and cancer stem cells in drug screening and their role in complementing, reducing, and replacing animal testing. In addition to this, target identification and major advances in the field of personalized medicine using induced pluripotent cells are also discussed.Keywords: therapeutics, stem cells, cancer stem cells, screening models, drug development, high throughput screening

  16. On the Estimation of Disease Prevalence by Latent Class Models for Screening Studies Using Two Screening Tests with Categorical Disease Status Verified in Test Positives Only

    Science.gov (United States)

    Chu, Haitao; Zhou, Yijie; Cole, Stephen R.; Ibrahim, Joseph G.

    2010-01-01

    Summary To evaluate the probabilities of a disease state, ideally all subjects in a study should be diagnosed by a definitive diagnostic or gold standard test. However, since definitive diagnostic tests are often invasive and expensive, it is generally unethical to apply them to subjects whose screening tests are negative. In this article, we consider latent class models for screening studies with two imperfect binary diagnostic tests and a definitive categorical disease status measured only for those with at least one positive screening test. Specifically, we discuss a conditional independent and three homogeneous conditional dependent latent class models and assess the impact of misspecification of the dependence structure on the estimation of disease category probabilities using frequentist and Bayesian approaches. Interestingly, the three homogeneous dependent models can provide identical goodness-of-fit but substantively different estimates for a given study. However, the parametric form of the assumed dependence structure itself is not “testable” from the data, and thus the dependence structure modeling considered here can only be viewed as a sensitivity analysis concerning a more complicated non-identifiable model potentially involving heterogeneous dependence structure. Furthermore, we discuss Bayesian model averaging together with its limitations as an alternative way to partially address this particularly challenging problem. The methods are applied to two cancer screening studies, and simulations are conducted to evaluate the performance of these methods. In summary, further research is needed to reduce the impact of model misspecification on the estimation of disease prevalence in such settings. PMID:20191614

  17. Formalize clinical processes into electronic health information systems: Modelling a screening service for diabetic retinopathy.

    Science.gov (United States)

    Eguzkiza, Aitor; Trigo, Jesús Daniel; Martínez-Espronceda, Miguel; Serrano, Luis; Andonegui, José

    2015-08-01

    Most healthcare services use information and communication technologies to reduce and redistribute the workload associated with follow-up of chronic conditions. However, the lack of normalization of the information handled in and exchanged between such services hinders the scalability and extendibility. The use of medical standards for modelling and exchanging information, especially dual-model based approaches, can enhance the features of screening services. Hence, the approach of this paper is twofold. First, this article presents a generic methodology to model patient-centered clinical processes. Second, a proof of concept of the proposed methodology was conducted within the diabetic retinopathy (DR) screening service of the Health Service of Navarre (Spain) in compliance with a specific dual-model norm (openEHR). As a result, a set of elements required for deploying a model-driven DR screening service has been established, namely: clinical concepts, archetypes, termsets, templates, guideline definition rules, and user interface definitions. This model fosters reusability, because those elements are available to be downloaded and integrated in any healthcare service, and interoperability, since from then on such services can share information seamlessly. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Implications of Nine Risk Prediction Models for Selecting Ever-Smokers for Computed Tomography Lung Cancer Screening.

    Science.gov (United States)

    Katki, Hormuzd A; Kovalchik, Stephanie A; Petito, Lucia C; Cheung, Li C; Jacobs, Eric; Jemal, Ahmedin; Berg, Christine D; Chaturvedi, Anil K

    2018-05-15

    Lung cancer screening guidelines recommend using individualized risk models to refer ever-smokers for screening. However, different models select different screening populations. The performance of each model in selecting ever-smokers for screening is unknown. To compare the U.S. screening populations selected by 9 lung cancer risk models (the Bach model; the Spitz model; the Liverpool Lung Project [LLP] model; the LLP Incidence Risk Model [LLPi]; the Hoggart model; the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model 2012 [PLCOM2012]; the Pittsburgh Predictor; the Lung Cancer Risk Assessment Tool [LCRAT]; and the Lung Cancer Death Risk Assessment Tool [LCDRAT]) and to examine their predictive performance in 2 cohorts. Population-based prospective studies. United States. Models selected U.S. screening populations by using data from the National Health Interview Survey from 2010 to 2012. Model performance was evaluated using data from 337 388 ever-smokers in the National Institutes of Health-AARP Diet and Health Study and 72 338 ever-smokers in the CPS-II (Cancer Prevention Study II) Nutrition Survey cohort. Model calibration (ratio of model-predicted to observed cases [expected-observed ratio]) and discrimination (area under the curve [AUC]). At a 5-year risk threshold of 2.0%, the models chose U.S. screening populations ranging from 7.6 million to 26 million ever-smokers. These disagreements occurred because, in both validation cohorts, 4 models (the Bach model, PLCOM2012, LCRAT, and LCDRAT) were well-calibrated (expected-observed ratio range, 0.92 to 1.12) and had higher AUCs (range, 0.75 to 0.79) than 5 models that generally overestimated risk (expected-observed ratio range, 0.83 to 3.69) and had lower AUCs (range, 0.62 to 0.75). The 4 best-performing models also had the highest sensitivity at a fixed specificity (and vice versa) and similar discrimination at a fixed risk threshold. These models showed better agreement on size of the

  19. Which strategies reduce breast cancer mortality most? Collaborative modeling of optimal screening, treatment, and obesity prevention.

    Science.gov (United States)

    Mandelblatt, Jeanne; van Ravesteyn, Nicolien; Schechter, Clyde; Chang, Yaojen; Huang, An-Tsun; Near, Aimee M; de Koning, Harry; Jemal, Ahmedin

    2013-07-15

    US breast cancer mortality is declining, but thousands of women still die each year. Two established simulation models examine 6 strategies that include increased screening and/or treatment or elimination of obesity versus continuation of current patterns. The models use common national data on incidence and obesity prevalence, competing causes of death, mammography characteristics, treatment effects, and survival/cure. Parameters are modified based on obesity (defined as BMI  ≥  30 kg/m(2) ). Outcomes are presented for the year 2025 among women aged 25+ and include numbers of cases, deaths, mammograms and false-positives; age-adjusted incidence and mortality; breast cancer mortality reduction and deaths averted; and probability of dying of breast cancer. If current patterns continue, the models project that there would be about 50,100-57,400 (range across models) annual breast cancer deaths in 2025. If 90% of women were screened annually from ages 40 to 54 and biennially from ages 55 to 99 (or death), then 5100-6100 fewer deaths would occur versus current patterns, but incidence, mammograms, and false-positives would increase. If all women received the indicated systemic treatment (with no screening change), then 11,400-14,500 more deaths would be averted versus current patterns, but increased toxicity could occur. If 100% received screening plus indicated therapy, there would be 18,100-20,400 fewer deaths. Eliminating obesity yields 3300-5700 fewer breast cancer deaths versus continuation of current obesity levels. Maximal reductions in breast cancer deaths could be achieved through optimizing treatment use, followed by increasing screening use and obesity prevention. © 2013 American Cancer Society.

  20. The cost-effectiveness of neonatal screening for Cystic Fibrosis: an analysis of alternative scenarios using a decision model

    Directory of Open Access Journals (Sweden)

    Tu Karen

    2005-08-01

    Full Text Available Abstract Background The use of neonatal screening for cystic fibrosis is widely debated in the United Kingdom and elsewhere, but the evidence available to inform policy is limited. This paper explores the cost-effectiveness of adding screening for cystic fibrosis to an existing routine neonatal screening programme for congenital hypothyroidism and phenylketonuria, under alternative scenarios and assumptions. Methods The study is based on a decision model comparing screening to no screening in terms of a number of outcome measures, including diagnosis of cystic fibrosis, life-time treatment costs, life years and QALYs gained. The setting is a hypothetical UK health region without an existing neonatal screening programme for cystic fibrosis. Results Under initial assumptions, neonatal screening (using an immunoreactive trypsin/DNA two stage screening protocol costs £5,387 per infant diagnosed, or £1.83 per infant screened (1998 costs. Neonatal screening for cystic fibrosis produces an incremental cost-effectiveness of £6,864 per QALY gained, in our base case scenario (an assumed benefit of a 6 month delay in the emergence of symptoms. A difference of 11 months or more in the emergence of symptoms (and mean survival means neonatal screening is both less costly and produces better outcomes than no screening. Conclusion Neonatal screening is expensive as a method of diagnosis. Neonatal screening may be a cost-effective intervention if the hypothesised delays in the onset of symptoms are confirmed. Implementing both antenatal and neonatal screening would undermine potential economic benefits, since a reduction in the birth incidence of cystic fibrosis would reduce the cost-effectiveness of neonatal screening.

  1. Knowledgeable Neighbors: a mobile clinic model for disease prevention and screening in underserved communities.

    Science.gov (United States)

    Hill, Caterina; Zurakowski, David; Bennet, Jennifer; Walker-White, Rainelle; Osman, Jamie L; Quarles, Aaron; Oriol, Nancy

    2012-03-01

    The Family Van mobile health clinic uses a "Knowledgeable Neighbor" model to deliver cost-effective screening and prevention activities in underserved neighborhoods in Boston, MA. We have described the Knowledgeable Neighbor model and used operational data collected from 2006 to 2009 to evaluate the service. The Family Van successfully reached mainly minority low-income men and women. Of the clients screened, 60% had previously undetected elevated blood pressure, 14% had previously undetected elevated blood glucose, and 38% had previously undetected elevated total cholesterol. This represents an important model for reaching underserved communities to deliver proven cost-effective prevention activities, both to help control health care costs and to reduce health disparities.

  2. Methodological considerations for economic modelling of latent tuberculous infection screening in migrants.

    Science.gov (United States)

    Shedrawy, J; Siroka, A; Oxlade, O; Matteelli, A; Lönnroth, K

    2017-09-01

    Tuberculosis (TB) in migrants from endemic to low-incidence countries results mainly from the reactivation of latent tuberculous infection (LTBI). LTBI screening policies for migrants vary greatly between countries, and the evidence on the cost-effectiveness of the different approaches is weak and heterogeneous. The aim of this review was to assess the methodology used in published economic evaluations of LTBI screening among migrants to identify critical methodological options that must be considered when using modelling to determine value for money from different economic perspectives. Three electronic databases were searched and 10 articles were included. There was considerable variation across this small number of studies with regard to economic perspective, main outcomes, modelling technique, screening options and target populations considered, as well as in parameterisation of the epidemiological situation, test accuracy, efficacy, safety and programme performance. Only one study adopted a societal perspective; others adopted a health care or wider government perspective. Parameters representing the cascade of screening and treating LTBI varied widely, with some studies using highly aspirational scenarios. This review emphasises the need for a more harmonised approach for economic analysis, and better transparency in how policy options and economic perspectives influence methodological choices. Variability is justifiable for some parameters. However, sufficient data are available to standardise others. A societal perspective is ideal, but can be challenging due to limited data. Assumptions about programme performance should be based on empirical data or at least realistic assumptions. Results should be interpreted within specific contexts and policy options, with cautious generalisations.

  3. Does brain slices from pentylenetetrazole-kindled mice provide a more predictive screening model for antiepileptic drugs?

    DEFF Research Database (Denmark)

    Hansen, Suzanne L.; Sterjev, Zoran; Werngreen, Marie

    2012-01-01

    The cortical wedge is a commonly applied model for in vitro screening of new antiepileptic drugs (AEDs) and has been extensively used in characterization of well-known AEDs. However, the predictive validity of this model as a screening model has been questioned as, e.g., carbamazepine has been...... screening model for AEDs. To this end, we compared the in vitro and in vivo pharmacological profile of several selected AEDs (phenobarbital, phenytoin, tiagabine, fosphenytoin, valproate, and carbamazepine) along with citalopram using the PTZ-kindled model and brain slices from naïve, saline...

  4. Withdrawing low risk women from cervical screening programmes: mathematical modelling study.

    Science.gov (United States)

    Sherlaw-Johnson, C; Gallivan, S; Jenkins, D

    1999-02-06

    To evaluate the impact of policies for removing women before the recommended age of 64 from screening programmes for cervical cancer in the United Kingdom. A mathematical model of the clinical course of precancerous lesions which accounts for the influence of infection with the human papillomavirus, the effects of screening on the progression of disease, and the accuracy of the testing procedures. Two policies are compared: one in which women are withdrawn from the programme if their current smear is negative and they have a recent history of regular, negative results and one in which women are withdrawn if their current smear test is negative and a simultaneous test is negative for exposure to high risk types of human papillomavirus. United Kingdom cervical screening programme. The incidence of invasive cervical cancer and the use of resources. Early withdrawal of selected women from the programme is predicted to give rise to resource savings of up to 25% for smear tests and 18% for colposcopies when withdrawal occurs from age 50, the youngest age considered in the study. An increase in the incidence of invasive cervical cancer, by up to 2 cases/100 000 women each year is predicted. Testing for human papillomavirus infection to determine which women should be withdrawn from the programme makes little difference to outcome. This model systematically analyses the consequences of screening options using available data and the clinical course of precancerous lesions. If further audit studies confirm the model's forecasts, a policy of early withdrawal might be considered. This would be likely to release substantial resources which could be channelled into other aspects of health care or may be more effectively used within the cervical screening programme to counteract the possible increase in cancer incidence that early withdrawal might bring.

  5. Collaborative Modeling of the Benefits and Harms Associated With Different U.S. Breast Cancer Screening Strategies.

    Science.gov (United States)

    Mandelblatt, Jeanne S; Stout, Natasha K; Schechter, Clyde B; van den Broek, Jeroen J; Miglioretti, Diana L; Krapcho, Martin; Trentham-Dietz, Amy; Munoz, Diego; Lee, Sandra J; Berry, Donald A; van Ravesteyn, Nicolien T; Alagoz, Oguzhan; Kerlikowske, Karla; Tosteson, Anna N A; Near, Aimee M; Hoeffken, Amanda; Chang, Yaojen; Heijnsdijk, Eveline A; Chisholm, Gary; Huang, Xuelin; Huang, Hui; Ergun, Mehmet Ali; Gangnon, Ronald; Sprague, Brian L; Plevritis, Sylvia; Feuer, Eric; de Koning, Harry J; Cronin, Kathleen A

    2016-02-16

    Controversy persists about optimal mammography screening strategies. To evaluate screening outcomes, taking into account advances in mammography and treatment of breast cancer. Collaboration of 6 simulation models using national data on incidence, digital mammography performance, treatment effects, and other-cause mortality. United States. Average-risk U.S. female population and subgroups with varying risk, breast density, or comorbidity. Eight strategies differing by age at which screening starts (40, 45, or 50 years) and screening interval (annual, biennial, and hybrid [annual for women in their 40s and biennial thereafter]). All strategies assumed 100% adherence and stopped at age 74 years. Benefits (breast cancer-specific mortality reduction, breast cancer deaths averted, life-years, and quality-adjusted life-years); number of mammograms used; harms (false-positive results, benign biopsies, and overdiagnosis); and ratios of harms (or use) and benefits (efficiency) per 1000 screens. Biennial strategies were consistently the most efficient for average-risk women. Biennial screening from age 50 to 74 years avoided a median of 7 breast cancer deaths versus no screening; annual screening from age 40 to 74 years avoided an additional 3 deaths, but yielded 1988 more false-positive results and 11 more overdiagnoses per 1000 women screened. Annual screening from age 50 to 74 years was inefficient (similar benefits, but more harms than other strategies). For groups with a 2- to 4-fold increased risk, annual screening from age 40 years had similar harms and benefits as screening average-risk women biennially from 50 to 74 years. For groups with moderate or severe comorbidity, screening could stop at age 66 to 68 years. Other imaging technologies, polygenic risk, and nonadherence were not considered. Biennial screening for breast cancer is efficient for average-risk populations. Decisions about starting ages and intervals will depend on population characteristics and the

  6. Human iPSC-derived cardiomyocytes and tissue engineering strategies for disease modeling and drug screening.

    Science.gov (United States)

    Smith, Alec S T; Macadangdang, Jesse; Leung, Winnie; Laflamme, Michael A; Kim, Deok-Ho

    Improved methodologies for modeling cardiac disease phenotypes and accurately screening the efficacy and toxicity of potential therapeutic compounds are actively being sought to advance drug development and improve disease modeling capabilities. To that end, much recent effort has been devoted to the development of novel engineered biomimetic cardiac tissue platforms that accurately recapitulate the structure and function of the human myocardium. Within the field of cardiac engineering, induced pluripotent stem cells (iPSCs) are an exciting tool that offer the potential to advance the current state of the art, as they are derived from somatic cells, enabling the development of personalized medical strategies and patient specific disease models. Here we review different aspects of iPSC-based cardiac engineering technologies. We highlight methods for producing iPSC-derived cardiomyocytes (iPSC-CMs) and discuss their application to compound efficacy/toxicity screening and in vitro modeling of prevalent cardiac diseases. Special attention is paid to the application of micro- and nano-engineering techniques for the development of novel iPSC-CM based platforms and their potential to advance current preclinical screening modalities. Published by Elsevier Inc.

  7. Nonlinear Model of Vibrating Screen to Determine Permissible Spring Deterioration for Proper Separation

    Directory of Open Access Journals (Sweden)

    Cristian G. Rodriguez

    2016-01-01

    Full Text Available Springs of vibrating screens are prone to fatigue induced failure because they operate in a heavy duty environment, with abrasive dust and under heavy cyclic loads. If a spring breaks, the stiffness at supporting positions changes, and therefore the amplitude of motion and the static and dynamic angular inclination of deck motion also change. This change in the amplitude and in the inclination of motion produces a reduction in separation efficiency. Available models are useful to determine motion under nominal operating conditions when angular displacement is not significant. However in practice there is significant angular motion during startup, during shutdown, or under off-design operating conditions. In this article, a two-dimensional three-degree-of-freedom nonlinear model that considers significant angular motion and damping is developed. The proposed model allows the prediction of vibrating screen behavior when there is a reduction in spring stiffness. Making use of this model for an actual vibrating screen in operation in industry has permitted determining a limit for spring’s failure before separation efficiency is affected. This information is of practical value for operation and maintenance staff helping to determine whether or not it is necessary to change springs, and hence optimizing stoppage time.

  8. Risk prediction models for selection of lung cancer screening candidates: A retrospective validation study.

    Directory of Open Access Journals (Sweden)

    Kevin Ten Haaf

    2017-04-01

    Full Text Available Selection of candidates for lung cancer screening based on individual risk has been proposed as an alternative to criteria based on age and cumulative smoking exposure (pack-years. Nine previously established risk models were assessed for their ability to identify those most likely to develop or die from lung cancer. All models considered age and various aspects of smoking exposure (smoking status, smoking duration, cigarettes per day, pack-years smoked, time since smoking cessation as risk predictors. In addition, some models considered factors such as gender, race, ethnicity, education, body mass index, chronic obstructive pulmonary disease, emphysema, personal history of cancer, personal history of pneumonia, and family history of lung cancer.Retrospective analyses were performed on 53,452 National Lung Screening Trial (NLST participants (1,925 lung cancer cases and 884 lung cancer deaths and 80,672 Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO ever-smoking participants (1,463 lung cancer cases and 915 lung cancer deaths. Six-year lung cancer incidence and mortality risk predictions were assessed for (1 calibration (graphically by comparing the agreement between the predicted and the observed risks, (2 discrimination (area under the receiver operating characteristic curve [AUC] between individuals with and without lung cancer (death, and (3 clinical usefulness (net benefit in decision curve analysis by identifying risk thresholds at which applying risk-based eligibility would improve lung cancer screening efficacy. To further assess performance, risk model sensitivities and specificities in the PLCO were compared to those based on the NLST eligibility criteria. Calibration was satisfactory, but discrimination ranged widely (AUCs from 0.61 to 0.81. The models outperformed the NLST eligibility criteria over a substantial range of risk thresholds in decision curve analysis, with a higher sensitivity for all models and a

  9. Screening for gestational diabetes mellitus by a model based on risk indicators

    DEFF Research Database (Denmark)

    Jensen, Dorte Møller; Mølsted-Pedersen, Lars; Beck-Nielsen, Henning

    2003-01-01

    OBJECTIVE: This study was performed to prospectively evaluate a screening model for gestational diabetes mellitus on the basis of clinical risk indicators. STUDY DESIGN: In a prospective multicenter study with 5235 consecutive pregnant women, diagnostic testing with a 2-hour 75-g oral glucose...... of the results from tested women to the whole group in question, a 2.4% prevalence of gestational diabetes mellitus was calculated. Sensitivity and specificity of the model was 80.6 (73.7-87.6) and 64.8 (63.5-66.1), respectively (95% CIs). CONCLUSION: Under ideal conditions, sensitivity of the model...

  10. Generic Screening Models for Assessing Exposures to the Public and ICRP Reference Animals and Plants

    Energy Technology Data Exchange (ETDEWEB)

    Yankovich, Tamara L.; Proehl, Gerhard; Telleria, Diego [International Atomic Energy Agency, P.O. Box 100, 1400 Vienna (Austria); Berkovskyy, Volodymyr [Ukrainian Radiation Protection Institute (RPI), 53, Melnikova Street, 04050, Kiev (Ukraine)

    2014-07-01

    With the update of the IAEA Fundamental Safety Principles (SF-1) stating the objective to protect people and the environment from harmful effects of ionizing radiation, it has been necessary to update International Basic Safety Standards (BSS) on Radiation Protection and Safety of Radiation Sources and the underlying safety guides and technical documents to provide guidance on how this could be achieved in practice. The current paper provides an update on the status and plans to revise the IAEA Safety Report 'Generic Models for Use in Assessing the Impact of Discharges of Radioactive Substances to the Environment' (SRS 19) that was published in 2001. The models of SRS 19 (2001), which was focused on assessment of exposures to the public, is being expanded into three volumes that provide methodologies for screening assessments for the public, as well as for flora and fauna. The revised SRS 19 guide will ultimately facilitate the application of screening models for different levels of assessment using updated parameter values from database that have been developed as part of the IAEA's EMRAS (Environmental Modelling for Radiation Safety) and EMRAS II international model validation programmes. The scope of the revised SRS 19 covers prospective screening assessment of doses to the representative person and Reference Animals and Plants (RAPs), and will provide simple and robust assessment methods for radiological assessment related to planning and design, applying a graded approach. Tabulated screening coefficients and environmental dilution factors will be included for 825 radionuclides. The screening coefficients are developed assuming equilibrium conditions; they can be used to assess radiological impacts arising from routine discharges of radionuclides to terrestrial and aquatic receptors for planned exposure situations. Volumes 1 and 2 of the revised SRS 19 are at an advanced stage of completion and are focused on 'Screening Assessment of Public

  11. COLA with scale-dependent growth: applications to screened modified gravity models

    Energy Technology Data Exchange (ETDEWEB)

    Winther, Hans A.; Koyama, Kazuya; Wright, Bill S. [Institute of Cosmology and Gravitation, University of Portsmouth, Dennis Sciama Building, Burnaby Road, Portsmouth, PO1 3FX (United Kingdom); Manera, Marc [Centre for Theoretical Cosmology, Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Wilberforce Road, Cambridge CB3 0WA (United Kingdom); Zhao, Gong-Bo, E-mail: hans.a.winther@gmail.com, E-mail: kazuya.koyama@port.ac.uk, E-mail: manera.work@gmail.com, E-mail: bill.wright@port.ac.uk, E-mail: gong-bo.Zhao@port.ac.uk [National Astronomy Observatories, Chinese Academy of Science, Beijing, 100012 (China)

    2017-08-01

    We present a general parallelized and easy-to-use code to perform numerical simulations of structure formation using the COLA (COmoving Lagrangian Acceleration) method for cosmological models that exhibit scale-dependent growth at the level of first and second order Lagrangian perturbation theory. For modified gravity theories we also include screening using a fast approximate method that covers all the main examples of screening mechanisms in the literature. We test the code by comparing it to full simulations of two popular modified gravity models, namely f ( R ) gravity and nDGP, and find good agreement in the modified gravity boost-factors relative to ΛCDM even when using a fairly small number of COLA time steps.

  12. Measurement and Monte Carlo modeling of the spatial response of scintillation screens

    Energy Technology Data Exchange (ETDEWEB)

    Pistrui-Maximean, S.A. [CNDRI (NDT using Ionizing Radiation) Laboratory, INSA-Lyon, 69621 Villeurbanne (France)], E-mail: spistrui@gmail.com; Letang, J.M. [CNDRI (NDT using Ionizing Radiation) Laboratory, INSA-Lyon, 69621 Villeurbanne (France)], E-mail: jean-michel.letang@insa-lyon.fr; Freud, N. [CNDRI (NDT using Ionizing Radiation) Laboratory, INSA-Lyon, 69621 Villeurbanne (France); Koch, A. [Thales Electron Devices, 38430 Moirans (France); Walenta, A.H. [Detectors and Electronics Department, FB Physik, Siegen University, 57068 Siegen (Germany); Montarou, G. [Corpuscular Physics Laboratory, Blaise Pascal University, 63177 Aubiere (France); Babot, D. [CNDRI (NDT using Ionizing Radiation) Laboratory, INSA-Lyon, 69621 Villeurbanne (France)

    2007-11-01

    In this article, we propose a detailed protocol to carry out measurements of the spatial response of scintillation screens and to assess the agreement with simulated results. The experimental measurements have been carried out using a practical implementation of the slit method. A Monte Carlo simulation model of scintillator screens, implemented with the toolkit Geant4, has been used to study the influence of the acquisition setup parameters and to compare with the experimental results. An algorithm of global stochastic optimization based on a localized random search method has been implemented to adjust the optical parameters (optical scattering and absorption coefficients). The algorithm has been tested for different X-ray tube voltages (40, 70 and 100 kV). A satisfactory convergence between the results simulated with the optimized model and the experimental measurements is obtained.

  13. Using a 3-d model system to screen for drugs effective on solid tumors

    OpenAIRE

    Fayad, Walid

    2011-01-01

    There is a large medical need for the development of effective anticancer agents with minimal side effects. The present thesis represents an attempt to identify potent drugs for treatment of solid tumors. We used a strategy where 3-D multicellular tumor spheroids (cancer cells grown in three dimensional culture) were utilized as in vitro models for solid tumors. Drug libraries were screened using spheroids as targets and using apoptosis induction and loss of cell viability as endpoints. The h...

  14. E-commerce between a large firm and a SME supplier: a screening model

    OpenAIRE

    Veronica, Alderete Maria

    2009-01-01

    This paper derives a model of screening contracts in the presence of positive network effects when building an electronic commerce network (e-commerce) between a large firm and a small and medium sized enterprise (SME) supplier based on Compte (2008). Compte (2008) main insight is that when several potential candidates compete for the task, the principal will in general improve the performance of his firm by inducing the member candidates to assess their competence before signing the contract...

  15. Cost-effectiveness of screening for HIV in primary care: a health economics modelling analysis

    OpenAIRE

    Baggaley, R. F.; Irvine, M. A.; Leber, W.; Cambiano, V.; Figueroa, J.; McMullen, H.; Anderson, J.; Santos, A. C.; Terris-Prestholt, F.; Miners, A.; Hollingsworth, T. D.; Griffiths, C. J.

    2017-01-01

    BACKGROUND: Early HIV diagnosis reduces morbidity, mortality, the probability of onward transmission, and their associated costs, but might increase cost because of earlier initiation of antiretroviral treatment (ART). We investigated this trade-off by estimating the cost-effectiveness of HIV screening in primary care. METHODS: We modelled the effect of the four-times higher diagnosis rate observed in the intervention arm of the RHIVA2 randomised controlled trial done in Hackney, London (UK),...

  16. Cost-effectiveness of screening for HIV in primary care: a health economics modelling analysis

    OpenAIRE

    Baggaley, Rebecca F; Irvine, Michael A; Leber, Werner; Cambiano, Valentina; Figueroa, Jose; McMullen, Heather; Anderson, Jane; Santos, Andreia C; Terris-Prestholt, Fern; Miners, Alec; Hollingsworth, T Déirdre; Griffiths, Chris J

    2017-01-01

    Summary Background Early HIV diagnosis reduces morbidity, mortality, the probability of onward transmission, and their associated costs, but might increase cost because of earlier initiation of antiretroviral treatment (ART). We investigated this trade-off by estimating the cost-effectiveness of HIV screening in primary care. Methods We modelled the effect of the four-times higher diagnosis rate observed in the intervention arm of the RHIVA2 randomised controlled trial done in Hackney, London...

  17. Fishing for Nature's Hits: Establishment of the Zebrafish as a Model for Screening Antidiabetic Natural Products.

    Science.gov (United States)

    Tabassum, Nadia; Tai, Hongmei; Jung, Da-Woon; Williams, Darren R

    2015-01-01

    Diabetes mellitus affects millions of people worldwide and significantly impacts their quality of life. Moreover, life threatening diseases, such as myocardial infarction, blindness, and renal disorders, increase the morbidity rate associated with diabetes. Various natural products from medicinal plants have shown potential as antidiabetes agents in cell-based screening systems. However, many of these potential "hits" fail in mammalian tests, due to issues such as poor pharmacokinetics and/or toxic side effects. To address this problem, the zebrafish (Danio rerio) model has been developed as a "bridge" to provide an experimentally convenient animal-based screening system to identify drug candidates that are active in vivo. In this review, we discuss the application of zebrafish to drug screening technologies for diabetes research. Specifically, the discovery of natural product-based antidiabetes compounds using zebrafish will be described. For example, it has recently been demonstrated that antidiabetic natural compounds can be identified in zebrafish using activity guided fractionation of crude plant extracts. Moreover, the development of fluorescent-tagged glucose bioprobes has allowed the screening of natural product-based modulators of glucose homeostasis in zebrafish. We hope that the discussion of these advances will illustrate the value and simplicity of establishing zebrafish-based assays for antidiabetic compounds in natural products-based laboratories.

  18. CHAM: a fast algorithm of modelling non-linear matter power spectrum in the sCreened HAlo Model

    Science.gov (United States)

    Hu, Bin; Liu, Xue-Wen; Cai, Rong-Gen

    2018-05-01

    We present a fast numerical screened halo model algorithm (CHAM, which stands for the sCreened HAlo Model) for modelling non-linear power spectrum for the alternative models to Λ cold dark matter. This method has three obvious advantages. First of all, it is not being restricted to a specific dark energy/modified gravity model. In principle, all of the screened scalar-tensor theories can be applied. Secondly, the least assumptions are made in the calculation. Hence, the physical picture is very easily understandable. Thirdly, it is very predictable and does not rely on the calibration from N-body simulation. As an example, we show the case of the Hu-Sawicki f(R) gravity. In this case, the typical CPU time with the current parallel PYTHON script (eight threads) is roughly within 10 min. The resulting spectra are in a good agreement with N-body data within a few percentage accuracy up to k ˜ 1 h Mpc-1.

  19. Evaluation of Cannabidiol in Animal Seizure Models by the Epilepsy Therapy Screening Program (ETSP).

    Science.gov (United States)

    Klein, Brian D; Jacobson, Catherine A; Metcalf, Cameron S; Smith, Misty D; Wilcox, Karen S; Hampson, Aidan J; Kehne, John H

    2017-07-01

    Cannabidiol (CBD) is a cannabinoid component of marijuana that has no significant activity at cannabinoid receptors or psychoactive effects. There is considerable interest in CBD as a therapy for epilepsy. Almost a third of epilepsy patients are not adequately controlled by clinically available anti-seizure drugs (ASDs). Initial studies appear to demonstrate that CBD preparations may be a useful treatment for pharmacoresistant epilepsy. The National Institute of Neurological Disorders and Stroke (NINDS) funded Epilepsy Therapy Screening Program (ETSP) investigated CBD in a battery of seizure models using a refocused screening protocol aimed at identifying pharmacotherapies to address the unmet need in pharmacoresistant epilepsy. Applying this new screening workflow, CBD was investigated in mouse 6 Hz 44 mA, maximal electroshock (MES), corneal kindling models and rat MES and lamotrigine-resistant amygdala kindling models. Following intraperitoneal (i.p.) pretreatment, CBD produced dose-dependent protection in the acute seizure models; mouse 6 Hz 44 mA (ED 50 164 mg/kg), mouse MES (ED 50 83.5 mg/kg) and rat MES (ED 50 88.9 mg/kg). In chronic models, CBD produced dose-dependent protection in the corneal kindled mouse (ED 50 119 mg/kg) but CBD (up to 300 mg/kg) was not protective in the lamotrigine-resistant amygdala kindled rat. Motor impairment assessed in conjunction with the acute seizure models showed that CBD exerted seizure protection at non-impairing doses. The ETSP investigation demonstrates that CBD exhibits anti-seizure properties in acute seizure models and the corneal kindled mouse. However, further preclinical and clinical studies are needed to determine the potential for CBD to address the unmet needs in pharmacoresistant epilepsy.

  20. An Analysis of Mass Screening Strategies Using a Mathematical Model: Comparison of Breast Cancer Screening in Japan and the United States

    Science.gov (United States)

    Tsunematsu, Miwako; Kakehashi, Masayuki

    2015-01-01

    Background Although the United States Preventive Services Task Force (USPSTF) downgraded their recommendation for breast cancer screening for women aged 40–49 years in 2009, Japanese women in their 40s have been encouraged to attend breast cancer screenings since 2004. The aim of this study is to examine whether these different mass-screening strategies are justifiable by the different situations of these countries and to provide evidence for suitable judgment. Methods Performance of screening strategies (annual/biennial intervals; initiating/terminating ages) was evaluated using a mathematical model based on the natural history of breast cancer and the transition between its stages. Benefits (reduced number of deaths and extended average life expectancy) and harm (false-positives) associated with these strategies were calculated. Results Additional average life expectancy by including women in their 40s as participants were 13 days (26%) and 25 days (22%) in Japan and the United States, respectively, under the biennial screening condition; however, the respective increases in numbers of false-positive cases were 65% and 53% in Japan and the United States. Moreover, the number of screenings needed to detect one diagnosis or to avert one death was smaller when participants were limited to women of age 50 or over than when women in their 40s were included. The validity of including women in their 40s in Japan could not be determined without specifying the weight of harms compared to benefits. Conclusions Whether screening of women in their 40s in Japan is justifiable must be carefully determined based the quantitative balance of benefits and harms. PMID:25483105

  1. Risk modeling and screening for BRCA1 mutations among Filipino breast cancer patients

    International Nuclear Information System (INIS)

    Nato, Alejandro Q. Jr.

    2003-03-01

    Breast cancer susceptibility gene, type 1(BRCA1) has been thought to be responsible for ∼45% of families with multiple breast carcinomas and for ∼80% of breast and ovarian cancer families. In this study, we investigated 34 familial Filipino breast cancer (BC) patients to: (a) estimate breast cancer risks and BRCA1/2 mutation carrier probabilities using risk assessment and prior probability models, respectively; (b) screen for putative polymorphisms at selected smaller exons of BRCA1 by single-strand conformation polymorphism (SSCP) analysis; (c) screen for truncated mutations at BRCA1 exon 11 by radioactive protein truncation test (PTT); and (d) estimate posterior probabilities upon incorporation of screening results. SSCP analysis revealed 8 unique putative polymorphisms. Low prevalence of unique putative polymorphisms at exon 2, 5, 17, and 22 may indicate probable mutations. Contrastingly, high prevalence of unique putative polymorphisms at exons 13, 15, and 16 may suggest true polymorphisms which are biologically insignificant. PTT, DHPLC, and sequence analyses revealed a novel mutation in exon 11 involving GT insertion that resulted to a stop codon which generated a 29.7 kDa truncated protein product. This is the second documented mutation in BRCA1 exon 11 in a Filipino BC patient since 1998. Initial genotype-phenotype correlations in Filipino BC patients may be elucidated based on screening tests performed. Our results corroborate the findings of a study on unselected incident Filipino BC cases where the reported prevalence of BRCA1 mutation is low. The higher prevalence of putative polypmorphisms may be attributed to the increased stringency in patient prospecting. The Gail, Claus, and BRCAPRO models can be utilized to estimate BC risk in unaffected high-risk individuals but validation is needed. Most of the BRCAPRO and Myriad.com prior probability estimates coincide with the presence of BRCA1 mutation and/or putative polymorphisms. This pioneering

  2. Risk modeling and screening for BRCA1 mutations among Filipino breast cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Nato, Jr, Alejandro Q

    2003-03-01

    Breast cancer susceptibility gene, type 1(BRCA1) has been thought to be responsible for {approx}45% of families with multiple breast carcinomas and for {approx}80% of breast and ovarian cancer families. In this study, we investigated 34 familial Filipino breast cancer (BC) patients to: (a) estimate breast cancer risks and BRCA1/2 mutation carrier probabilities using risk assessment and prior probability models, respectively; (b) screen for putative polymorphisms at selected smaller exons of BRCA1 by single-strand conformation polymorphism (SSCP) analysis; (c) screen for truncated mutations at BRCA1 exon 11 by radioactive protein truncation test (PTT); and (d) estimate posterior probabilities upon incorporation of screening results. SSCP analysis revealed 8 unique putative polymorphisms. Low prevalence of unique putative polymorphisms at exon 2, 5, 17, and 22 may indicate probable mutations. Contrastingly, high prevalence of unique putative polymorphisms at exons 13, 15, and 16 may suggest true polymorphisms which are biologically insignificant. PTT, DHPLC, and sequence analyses revealed a novel mutation in exon 11 involving GT insertion that resulted to a stop codon which generated a 29.7 kDa truncated protein product. This is the second documented mutation in BRCA1 exon 11 in a Filipino BC patient since 1998. Initial genotype-phenotype correlations in Filipino BC patients may be elucidated based on screening tests performed. Our results corroborate the findings of a study on unselected incident Filipino BC cases where the reported prevalence of BRCA1 mutation is low. The higher prevalence of putative polypmorphisms may be attributed to the increased stringency in patient prospecting. The Gail, Claus, and BRCAPRO models can be utilized to estimate BC risk in unaffected high-risk individuals but validation is needed. Most of the BRCAPRO and Myriad.com prior probability estimates coincide with the presence of BRCA1 mutation and/or putative polymorphisms. This

  3. Debye screening and a Thomas - Fermi model of a dyonic atom in a two potential theory of electromagnetism

    International Nuclear Information System (INIS)

    Wolf, C.

    1993-01-01

    We study the screening of a central Abelian dyon by a surrounding dyon cloud in a two potential theory of electromagnetism. A generalized formula for the Debye screening length is obtained and a Thomas - Fermi Model for a charged cloud surrounding a central Dyonic Core is studied. 20 refs

  4. Polyglutamine Disease Modeling: Epitope Based Screen for Homologous Recombination using CRISPR/Cas9 System.

    Science.gov (United States)

    An, Mahru C; O'Brien, Robert N; Zhang, Ningzhe; Patra, Biranchi N; De La Cruz, Michael; Ray, Animesh; Ellerby, Lisa M

    2014-04-15

    We have previously reported the genetic correction of Huntington's disease (HD) patient-derived induced pluripotent stem cells using traditional homologous recombination (HR) approaches. To extend this work, we have adopted a CRISPR-based genome editing approach to improve the efficiency of recombination in order to generate allelic isogenic HD models in human cells. Incorporation of a rapid antibody-based screening approach to measure recombination provides a powerful method to determine relative efficiency of genome editing for modeling polyglutamine diseases or understanding factors that modulate CRISPR/Cas9 HR.

  5. Modeling human papillomavirus and cervical cancer in the United States for analyses of screening and vaccination

    Directory of Open Access Journals (Sweden)

    Ortendahl Jesse

    2007-10-01

    Full Text Available Abstract Background To provide quantitative insight into current U.S. policy choices for cervical cancer prevention, we developed a model of human papillomavirus (HPV and cervical cancer, explicitly incorporating uncertainty about the natural history of disease. Methods We developed a stochastic microsimulation of cervical cancer that distinguishes different HPV types by their incidence, clearance, persistence, and progression. Input parameter sets were sampled randomly from uniform distributions, and simulations undertaken with each set. Through systematic reviews and formal data synthesis, we established multiple epidemiologic targets for model calibration, including age-specific prevalence of HPV by type, age-specific prevalence of cervical intraepithelial neoplasia (CIN, HPV type distribution within CIN and cancer, and age-specific cancer incidence. For each set of sampled input parameters, likelihood-based goodness-of-fit (GOF scores were computed based on comparisons between model-predicted outcomes and calibration targets. Using 50 randomly resampled, good-fitting parameter sets, we assessed the external consistency and face validity of the model, comparing predicted screening outcomes to independent data. To illustrate the advantage of this approach in reflecting parameter uncertainty, we used the 50 sets to project the distribution of health outcomes in U.S. women under different cervical cancer prevention strategies. Results Approximately 200 good-fitting parameter sets were identified from 1,000,000 simulated sets. Modeled screening outcomes were externally consistent with results from multiple independent data sources. Based on 50 good-fitting parameter sets, the expected reductions in lifetime risk of cancer with annual or biennial screening were 76% (range across 50 sets: 69–82% and 69% (60–77%, respectively. The reduction from vaccination alone was 75%, although it ranged from 60% to 88%, reflecting considerable parameter

  6. A groundwater mass flux model for screening the groundwater-to-indoor-air exposure pathway

    Energy Technology Data Exchange (ETDEWEB)

    McHugh, T.; Blanc, P.C. de; Connor, J. [Groundwater Services Inc, Houston, TX (United States)

    2003-07-01

    The potential for human exposure via volatilisation of groundwater contaminants into indoor air has been a focus of increasing concern in recent years. At a small number of sites, elevated indoor vapour concentrations have been measured within buildings overlying shallow groundwater contaminated with chlorinated solvents, causing public concern over the potential for similar problems at other corrective action sites. In addition, use of the screening-levelmodel developed by Johnson and Ettinger (1991) for the groundwater-to-indoor-air exposure pathway has suggested that low microgram per litre (ug/L)-range concentrations of either chlorinated or non-chlorinated volatile organic compounds dissolved in groundwater could result in indoor vapour concentrations in excess of applicable risk-based exposure limits. As an alternative screening tool, this paper presents a groundwater mass flux model for evaluation of transport to indoor air. The mass flux model is intended to serve as a highly conservative screening tool that over-predicts groundwater-to-indoor-air mass flux, yet still provides sufficient sensitivity to identify sites for which the groundwater-to-indoor air exposure pathway is not a concern. (orig.)

  7. The vortex free energy in the screening phase of the Z(2) Higgs model

    International Nuclear Information System (INIS)

    Meyer, H.

    1983-06-01

    The vortex free energy was proposed to distinguish between the confinement - and the Higgs phase (in the sense of 't Hooft) in lattice gauge theory, when matter fields are present that transform according to an arbitrary representation of the gauge group. In this paper I consider the Z(2) Higgs model and calculate the vortex free energy in the screening part of the confining/screening phase of Fradkin and Shenker. The result does not agree with the expected behavior that corresponds to the structure of the phase diagram. Therefore the vortex free energy is no longer a good indicator for confinement when matter fields transform nontrivially under the center of the gauge group (such as Z(2) Higgs scalars). (orig.)

  8. Simulation of reactive geochemical transport in groundwater using a semi-analytical screening model

    Science.gov (United States)

    McNab, Walt W.

    1997-10-01

    A reactive geochemical transport model, based on a semi-analytical solution to the advective-dispersive transport equation in two dimensions, is developed as a screening tool for evaluating the impact of reactive contaminants on aquifer hydrogeochemistry. Because the model utilizes an analytical solution to the transport equation, it is less computationally intensive than models based on numerical transport schemes, is faster, and it is not subject to numerical dispersion effects. Although the assumptions used to construct the model preclude consideration of reactions between the aqueous and solid phases, thermodynamic mineral saturation indices are calculated to provide qualitative insight into such reactions. Test problems involving acid mine drainage and hydrocarbon biodegradation signatures illustrate the utility of the model in simulating essential hydrogeochemical phenomena.

  9. Enhanced hexose fermentation by Saccharomyces cerevisiae through integration of stoichiometric modeling and genetic screening.

    Science.gov (United States)

    Quarterman, Josh; Kim, Soo Rin; Kim, Pan-Jun; Jin, Yong-Su

    2015-01-20

    In order to determine beneficial gene deletions for ethanol production by the yeast Saccharomyces cerevisiae, we performed an in silico gene deletion experiment based on a genome-scale metabolic model. Genes coding for two oxidative phosphorylation reactions (cytochrome c oxidase and ubiquinol cytochrome c reductase) were identified by the model-based simulation as potential deletion targets for enhancing ethanol production and maintaining acceptable overall growth rate in oxygen-limited conditions. Since the two target enzymes are composed of multiple subunits, we conducted a genetic screening study to evaluate the in silico results and compare the effect of deleting various portions of the respiratory enzyme complexes. Over two-thirds of the knockout mutants identified by the in silico study did exhibit experimental behavior in qualitative agreement with model predictions, but the exceptions illustrate the limitation of using a purely stoichiometric model-based approach. Furthermore, there was a substantial quantitative variation in phenotype among the various respiration-deficient mutants that were screened in this study, and three genes encoding respiratory enzyme subunits were identified as the best knockout targets for improving hexose fermentation in microaerobic conditions. Specifically, deletion of either COX9 or QCR9 resulted in higher ethanol production rates than the parental strain by 37% and 27%, respectively, with slight growth disadvantages. Also, deletion of QCR6 led to improved ethanol production rate by 24% with no growth disadvantage. The beneficial effects of these gene deletions were consistently demonstrated in different strain backgrounds and with four common hexoses. The combination of stoichiometric modeling and genetic screening using a systematic knockout collection was useful for narrowing a large set of gene targets and identifying targets of interest. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Competing risks model in screening for preeclampsia by maternal characteristics and medical history.

    Science.gov (United States)

    Wright, David; Syngelaki, Argyro; Akolekar, Ranjit; Poon, Leona C; Nicolaides, Kypros H

    2015-07-01

    The purpose of this study was to develop a model for preeclampsia based on maternal demographic characteristics and medical history. This was a screening study of 120,492 singleton pregnancies at 11-13 weeks' gestation, including 2704 pregnancies (2.2%) that experienced preeclampsia. A survival-time model for the gestational age at delivery with preeclampsia was developed from variables of maternal characteristics and history. This approach assumes that, if the pregnancy was to continue indefinitely, all women would experience preeclampsia and that whether they do so or not before a specified gestational age depends on competition between delivery before or after development of preeclampsia. A 5-fold cross validation study was conducted to compare the performance of the new model with the National Institute for Health and Clinical Excellence (NICE) guidelines. In the new model, increased risk for preeclampsia, with a consequent shift in the Gaussian distribution of the gestational age at delivery with preeclampsia to the left, is provided by advancing maternal age, increasing weight, Afro-Caribbean and South Asian racial origin, medical history of chronic hypertension, diabetes mellitus and systemic lupus erythematosus or antiphospholipid syndrome, family history and personal history of preeclampsia, and conception by in vitro fertilization. The risk for preeclampsia decreases with increasing maternal height and in parous women with no previous preeclampsia; in the latter, the protective effect, which is related inversely to the interpregnancy interval, persists beyond 15 years. At a screen-positive rate of 11%, as defined by NICE, the new model predicted 40%, 48%, and 54% of cases of total preeclampsia and preeclampsia requiring delivery at preeclampsia. Such estimation of the a priori risk for preeclampsia is an essential first step in the use of Bayes theorem to combine maternal factors with biomarkers for the continuing development of more effective methods of

  11. Identifiability in N-mixture models: a large-scale screening test with bird data.

    Science.gov (United States)

    Kéry, Marc

    2018-02-01

    Binomial N-mixture models have proven very useful in ecology, conservation, and monitoring: they allow estimation and modeling of abundance separately from detection probability using simple counts. Recently, doubts about parameter identifiability have been voiced. I conducted a large-scale screening test with 137 bird data sets from 2,037 sites. I found virtually no identifiability problems for Poisson and zero-inflated Poisson (ZIP) binomial N-mixture models, but negative-binomial (NB) models had problems in 25% of all data sets. The corresponding multinomial N-mixture models had no problems. Parameter estimates under Poisson and ZIP binomial and multinomial N-mixture models were extremely similar. Identifiability problems became a little more frequent with smaller sample sizes (267 and 50 sites), but were unaffected by whether the models did or did not include covariates. Hence, binomial N-mixture model parameters with Poisson and ZIP mixtures typically appeared identifiable. In contrast, NB mixtures were often unidentifiable, which is worrying since these were often selected by Akaike's information criterion. Identifiability of binomial N-mixture models should always be checked. If problems are found, simpler models, integrated models that combine different observation models or the use of external information via informative priors or penalized likelihoods, may help. © 2017 by the Ecological Society of America.

  12. Breast cancer screening (BCS) chart: a basic and preliminary model for making screening mammography more productive and efficient.

    Science.gov (United States)

    Poorolajal, Jalal; Akbari, Mohammad Esmaeil; Ziaee, Fatane; Karami, Manoochehr; Ghoncheh, Mahshid

    2017-05-15

    The breast cancer screening (BCS) chart is suggested as a basic and preliminary tool to improve efficiency of screening mammography. We conducted this case-control study in 2016 and enrolled 1422 women aged 30-75 years, including 506 women with breast cancer (cases) and 916 women without breast cancer (controls). We developed the BCS chart using a multiple logistic regression analysis. We combined the risks of breast cancer to predict the individual risk of breast cancer. Then, we stratified and colored the predicted risk probabilities as follows: green), 05-09% (yellow), 10-14% (orange), 15-19% (red), 20-24% (brown) and ≥25% (black). The BCS chart provides the risk probability of breast cancer, based on age, body mass index, late menopause, having a benign breast disease and a positive family history of breast cancer among the first-degree or the second/third-degree relatives. According to this chart, an individual can be classified in a category of low risk (green), medium risk (yellow and orange), high risk (red and brown) and very high risk (black) for breast cancer. This chart is a flexible and easy to use tool that can detect high-risk subjects and make the screening program more efficient and productive. © The Author 2017. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  13. Benefits and harms of prostate cancer screening – predictions of the ONCOTYROL prostate cancer outcome and policy model

    Directory of Open Access Journals (Sweden)

    Nikolai Mühlberger

    2017-06-01

    Full Text Available Abstract Background A recent recalibration of the ONCOTYROL Prostate Cancer Outcome and Policy (PCOP Model, assuming that latent prostate cancer (PCa detectable at autopsy might be detectable by screening as well, resulted in considerable worsening of the benefit-harm balance of screening. In this study, we used the recalibrated model to assess the effects of familial risk, quality of life (QoL preferences, age, and active surveillance. Methods Men with average and elevated familial PCa risk were simulated in separate models, differing in familial risk parameters. Familial risk was assumed to affect PCa onset and progression simultaneously in the base-case, and separately in scenario analyses. Evaluated screening strategies included one-time screening at different ages, and screening at different intervals and age ranges. Optimal screening strategies were identified depending on age and individual QoL preferences. Strategies were additionally evaluated with active surveillance by biennial re-biopsy delaying treatment of localized cancer until grade progression to Gleason score ≥ 7. Results Screening men with average PCa risk reduced quality-adjusted life expectancy (QALE even under favorable assumptions. Men with elevated familial risk, depending on age and disutilities, gained QALE. While for men with familial risk aged 55 and 60 years annual screening to age 69 was the optimal strategy over most disutility ranges, no screening was the preferred option for 65 year-old men with average and above disutilities. Active surveillance greatly reduced overtreatment, but QALE gains by averted adverse events were opposed by losses due to delayed treatment and additional biopsies. The effect of active surveillance on the benefit-harm balance of screening differed between populations, as net losses and gains in QALE predicted for screening without active surveillance in men with average and familial PCa risk, respectively, were both reduced

  14. Determining the optimal screening interval for type 2 diabetes mellitus using a risk prediction model.

    Directory of Open Access Journals (Sweden)

    Andrei Brateanu

    Full Text Available Progression to diabetes mellitus (DM is variable and the screening time interval not well defined. The American Diabetes Association and US Preventive Services Task Force suggest screening every 3 years, but evidence is limited. The objective of the study was to develop a model to predict the probability of developing DM and suggest a risk-based screening interval.We included non-diabetic adult patients screened for DM in the Cleveland Clinic Health System if they had at least two measurements of glycated hemoglobin (HbA1c, an initial one less than 6.5% (48 mmol/mol in 2008, and another between January, 2009 and December, 2013. Cox proportional hazards models were created. The primary outcome was DM defined as HbA1C greater than 6.4% (46 mmol/mol. The optimal rescreening interval was chosen based on the predicted probability of developing DM.Of 5084 participants, 100 (4.4% of the 2281 patients with normal HbA1c and 772 (27.5% of the 2803 patients with prediabetes developed DM within 5 years. Factors associated with developing DM included HbA1c (HR per 0.1 units increase 1.20; 95%CI, 1.13-1.27, family history (HR 1.31; 95%CI, 1.13-1.51, smoking (HR 1.18; 95%CI, 1.03-1.35, triglycerides (HR 1.01; 95%CI, 1.00-1.03, alanine aminotransferase (HR 1.07; 95%CI, 1.03-1.11, body mass index (HR 1.06; 95%CI, 1.01-1.11, age (HR 0.95; 95%CI, 0.91-0.99 and high-density lipoproteins (HR 0.93; 95% CI, 0.90-0.95. Five percent of patients in the highest risk tertile developed DM within 8 months, while it took 35 months for 5% of the middle tertile to develop DM. Only 2.4% percent of the patients in the lowest tertile developed DM within 5 years.A risk prediction model employing commonly available data can be used to guide screening intervals. Based on equal intervals for equal risk, patients in the highest risk category could be rescreened after 8 months, while those in the intermediate and lowest risk categories could be rescreened after 3 and 5 years

  15. In vitro microfluidic models of tumor microenvironment to screen transport of drugs and nanoparticles.

    Science.gov (United States)

    Ozcelikkale, Altug; Moon, Hye-Ran; Linnes, Michael; Han, Bumsoo

    2017-09-01

    Advances in nanotechnology have enabled numerous types of nanoparticles (NPs) to improve drug delivery to tumors. While many NP systems have been proposed, their clinical translation has been less than anticipated primarily due to failure of current preclinical evaluation techniques to adequately model the complex interactions between the NP and physiological barriers of tumor microenvironment. This review focuses on microfluidic tumor models for characterization of delivery efficacy and toxicity of cancer nanomedicine. Microfluidics offer significant advantages over traditional macroscale cell cultures by enabling recapitulation of tumor microenvironment through precise control of physiological cues such as hydrostatic pressure, shear stress, oxygen, and nutrient gradients. Microfluidic systems have recently started to be adapted for screening of drugs and NPs under physiologically relevant settings. So far the two primary application areas of microfluidics in this area have been high-throughput screening using traditional culture settings such as single cells or multicellular tumor spheroids, and mimicry of tumor microenvironment for study of cancer-related cell-cell and cell-matrix interactions. These microfluidic technologies are also useful in modeling specific steps in NP delivery to tumor and characterize NP transport properties and outcomes by systematic variation of physiological conditions. Ultimately, it will be possible to design drug-screening platforms uniquely tailored for individual patient physiology using microfluidics. These in vitro models can contribute to development of precision medicine by enabling rapid and patient-specific evaluation of cancer nanomedicine. WIREs Nanomed Nanobiotechnol 2017, 9:e1460. doi: 10.1002/wnan.1460 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

  16. The SSI TOOLBOX Source Term Model SOSIM - Screening for important radionuclides and parameter sensitivity analysis

    Energy Technology Data Exchange (ETDEWEB)

    Avila Moreno, R.; Barrdahl, R.; Haegg, C.

    1995-05-01

    The main objective of the present study was to carry out a screening and a sensitivity analysis of the SSI TOOLBOX source term model SOSIM. This model is a part of the SSI TOOLBOX for radiological impact assessment of the Swedish disposal concept for high-level waste KBS-3. The outputs of interest for this purpose were: the total released fraction, the time of total release, the time and value of maximum release rate, the dose rates after direct releases of the biosphere. The source term equations were derived and simple equations and methods were proposed for calculation of these. A literature survey has been performed in order to determine a characteristic variation range and a nominal value for each model parameter. In order to reduce the model uncertainties the authors recommend a change in the initial boundary condition for solution of the diffusion equation for highly soluble nuclides. 13 refs.

  17. Using model-based screening to help discover unknown environmental contaminants.

    Science.gov (United States)

    McLachlan, Michael S; Kierkegaard, Amelie; Radke, Michael; Sobek, Anna; Malmvärn, Anna; Alsberg, Tomas; Arnot, Jon A; Brown, Trevor N; Wania, Frank; Breivik, Knut; Xu, Shihe

    2014-07-01

    Of the tens of thousands of chemicals in use, only a small fraction have been analyzed in environmental samples. To effectively identify environmental contaminants, methods to prioritize chemicals for analytical method development are required. We used a high-throughput model of chemical emissions, fate, and bioaccumulation to identify chemicals likely to have high concentrations in specific environmental media, and we prioritized these for target analysis. This model-based screening was applied to 215 organosilicon chemicals culled from industrial chemical production statistics. The model-based screening prioritized several recognized organosilicon contaminants and generated hypotheses leading to the selection of three chemicals that have not previously been identified as potential environmental contaminants for target analysis. Trace analytical methods were developed, and the chemicals were analyzed in air, sewage sludge, and sediment. All three substances were found to be environmental contaminants. Phenyl-tris(trimethylsiloxy)silane was present in all samples analyzed, with concentrations of ∼50 pg m(-3) in Stockholm air and ∼0.5 ng g(-1) dw in sediment from the Stockholm archipelago. Tris(trifluoropropyl)trimethyl-cyclotrisiloxane and tetrakis(trifluoropropyl)tetramethyl-cyclotetrasiloxane were found in sediments from Lake Mjøsa at ∼1 ng g(-1) dw. The discovery of three novel environmental contaminants shows that models can be useful for prioritizing chemicals for exploratory assessment.

  18. Calculation of radiative opacity of plasma mixtures using a relativistic screened hydrogenic model

    International Nuclear Information System (INIS)

    Mendoza, M.A.; Rubiano, J.G.; Gil, J.M.; Rodríguez, R.; Florido, R.; Espinosa, G.; Martel, P.; Mínguez, E.

    2014-01-01

    We present the code ATMED based on an average atom model and conceived for fast computing the population distribution and radiative properties of hot and dense single and multicomponent plasmas under LTE conditions. A relativistic screened hydrogenic model (RSHM), built on a new set of universal constants considering j-splitting, is used to calculate the required atomic data. The opacity model includes radiative bound–bound, bound–free, free–free, and scattering processes. Bound–bound line-shape function has contributions from natural, Doppler and electron-impact broadenings. An additional dielectronic broadening to account for fluctuations in the average level populations has been included, which improves substantially the Rosseland mean opacity results. To illustrate the main features of the code and its capabilities, calculations of several fundamental quantities of one-component plasmas and mixtures are presented, and a comparison with previously published data is performed. Results are satisfactorily compared with those predicted by more elaborate codes. - Highlights: • A new opacity code, ATMED, based on the average atom approximation is presented. • Atomic data are computed by means of a relativistic screened hydrogenic model. • An effective bound level degeneracy is included for accounting pressure ionization. • A new dielectronic line broadening is included to improve the mean opacities. • ATMED has the possibility to handle with single element and multicomponent plasmas

  19. Data Sources for the Model-based Small Area Estimates of Cancer Risk Factors and Screening Behaviors - Small Area Estimates

    Science.gov (United States)

    The model-based estimates of important cancer risk factors and screening behaviors are obtained by combining the responses to the Behavioral Risk Factor Surveillance System (BRFSS) and the National Health Interview Survey (NHIS).

  20. Process of Integrating Screening and Detailed Risk-based Modeling Analyses to Ensure Consistent and Scientifically Defensible Results

    International Nuclear Information System (INIS)

    Buck, John W.; McDonald, John P.; Taira, Randal Y.

    2002-01-01

    To support cleanup and closure of these tanks, modeling is performed to understand and predict potential impacts to human health and the environment. Pacific Northwest National Laboratory developed a screening tool for the United States Department of Energy, Office of River Protection that estimates the long-term human health risk, from a strategic planning perspective, posed by potential tank releases to the environment. This tool is being conditioned to more detailed model analyses to ensure consistency between studies and to provide scientific defensibility. Once the conditioning is complete, the system will be used to screen alternative cleanup and closure strategies. The integration of screening and detailed models provides consistent analyses, efficiencies in resources, and positive feedback between the various modeling groups. This approach of conditioning a screening methodology to more detailed analyses provides decision-makers with timely and defensible information and increases confidence in the results on the part of clients, regulators, and stakeholders

  1. Dual Binding Site and Selective Acetylcholinesterase Inhibitors Derived from Integrated Pharmacophore Models and Sequential Virtual Screening

    Directory of Open Access Journals (Sweden)

    Shikhar Gupta

    2014-01-01

    Full Text Available In this study, we have employed in silico methodology combining double pharmacophore based screening, molecular docking, and ADME/T filtering to identify dual binding site acetylcholinesterase inhibitors that can preferentially inhibit acetylcholinesterase and simultaneously inhibit the butyrylcholinesterase also but in the lesser extent than acetylcholinesterase. 3D-pharmacophore models of AChE and BuChE enzyme inhibitors have been developed from xanthostigmine derivatives through HypoGen and validated using test set, Fischer’s randomization technique. The best acetylcholinesterase and butyrylcholinesterase inhibitors pharmacophore hypotheses Hypo1_A and Hypo1_B, with high correlation coefficient of 0.96 and 0.94, respectively, were used as 3D query for screening the Zinc database. The screened hits were then subjected to the ADME/T and molecular docking study to prioritise the compounds. Finally, 18 compounds were identified as potential leads against AChE enzyme, showing good predicted activities and promising ADME/T properties.

  2. Effectiveness of screening hospital admissions to detect asymptomatic carriers of Clostridium difficile: a modeling evaluation.

    Science.gov (United States)

    Lanzas, Cristina; Dubberke, Erik R

    2014-08-01

    Both asymptomatic and symptomatic Clostridium difficile carriers contribute to new colonizations and infections within a hospital, but current control strategies focus only on preventing transmission from symptomatic carriers. Our objective was to evaluate the potential effectiveness of methods targeting asymptomatic carriers to control C. difficile colonization and infection (CDI) rates in a hospital ward: screening patients at admission to detect asymptomatic C. difficile carriers and placing positive patients into contact precautions. We developed an agent-based transmission model for C. difficile that incorporates screening and contact precautions for asymptomatic carriers in a hospital ward. We simulated scenarios that vary according to screening test characteristics, colonization prevalence, and type of strain present at admission. In our baseline scenario, on average, 42% of CDI cases were community-onset cases. Within the hospital-onset (HO) cases, approximately half were patients admitted as asymptomatic carriers who became symptomatic in the ward. On average, testing for asymptomatic carriers reduced the number of new colonizations and HO-CDI cases by 40%-50% and 10%-25%, respectively, compared with the baseline scenario. Test sensitivity, turnaround time, colonization prevalence at admission, and strain type had significant effects on testing efficacy. Testing for asymptomatic carriers at admission may reduce both the number of new colonizations and HO-CDI cases. Additional reductions could be achieved by preventing disease in patients who are admitted as asymptomatic carriers and developed CDI during the hospital stay.

  3. High Throughput Screen for Novel Antimicrobials using a Whole Animal Infection Model

    Science.gov (United States)

    Moy, Terence I.; Conery, Annie L.; Larkins-Ford, Jonah; Wu, Gang; Mazitschek, Ralph; Casadei, Gabriele; Lewis, Kim; Carpenter, Anne E.; Ausubel, Frederick M.

    2009-01-01

    The nematode Caenorhabditis elegans is a unique whole animal model system for identifying small molecules with in vivo anti-infective properties. C. elegans can be infected with a broad range of human pathogens, including Enterococcus faecalis, an important human nosocomial pathogen with a mortality rate of up to 37% that is increasingly acquiring resistance to antibiotics. Here, we describe an automated, high throughput screen of 37,200 compounds and natural product extracts for those that enhance survival of C. elegans infected with E. faecalis. The screen uses a robot to accurately dispense live, infected animals into 384-well plates, and automated microscopy and image analysis to generate quantitative, high content data. We identified 28 compounds and extracts that were not previously reported to have antimicrobial properties, including 6 structural classes that cure infected C. elegans animals but do not affect the growth of the pathogen in vitro, thus acting by a mechanism of action distinct from antibiotics currently in clinical use. Our versatile and robust screening system can be easily adapted for other whole animal assays to probe a broad range of biological processes. PMID:19572548

  4. Improving virtual screening predictive accuracy of Human kallikrein 5 inhibitors using machine learning models.

    Science.gov (United States)

    Fang, Xingang; Bagui, Sikha; Bagui, Subhash

    2017-08-01

    The readily available high throughput screening (HTS) data from the PubChem database provides an opportunity for mining of small molecules in a variety of biological systems using machine learning techniques. From the thousands of available molecular descriptors developed to encode useful chemical information representing the characteristics of molecules, descriptor selection is an essential step in building an optimal quantitative structural-activity relationship (QSAR) model. For the development of a systematic descriptor selection strategy, we need the understanding of the relationship between: (i) the descriptor selection; (ii) the choice of the machine learning model; and (iii) the characteristics of the target bio-molecule. In this work, we employed the Signature descriptor to generate a dataset on the Human kallikrein 5 (hK 5) inhibition confirmatory assay data and compared multiple classification models including logistic regression, support vector machine, random forest and k-nearest neighbor. Under optimal conditions, the logistic regression model provided extremely high overall accuracy (98%) and precision (90%), with good sensitivity (65%) in the cross validation test. In testing the primary HTS screening data with more than 200K molecular structures, the logistic regression model exhibited the capability of eliminating more than 99.9% of the inactive structures. As part of our exploration of the descriptor-model-target relationship, the excellent predictive performance of the combination of the Signature descriptor and the logistic regression model on the assay data of the Human kallikrein 5 (hK 5) target suggested a feasible descriptor/model selection strategy on similar targets. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Cervical cancer screening in Australia: modelled evaluation of the impact of changing the recommended interval from two to three years

    Directory of Open Access Journals (Sweden)

    Howard Kirsten

    2010-11-01

    Full Text Available Abstract Background The National Cervical Screening Program in Australia currently recommends that sexually active women between the ages of 18-70 years attend routine screening every 2 years. The publically funded National HPV Vaccination Program commenced in 2007, with catch-up in females aged 12-26 years conducted until 2009; and this may prompt consideration of whether the screening interval and other aspects of the organized screening program could be reviewed. The aim of the current evaluation was to assess the epidemiologic outcomes and cost implications of changing the recommended screening interval in Australia to 3 years. Methods We used a modelling approach to evaluate the effects of moving to a 3-yearly recommended screening interval. We used data from the Victorian Cervical Cytology Registry over the period 1997-2007 to model compliance with routine screening under current practice, and registry data from other countries with 3-yearly recommendations to inform assumptions about future screening behaviour under two alternative systems for screening organisation - retention of a reminder-based system (as in New Zealand, or a move to a call-and-recall system (as in England. Results A 3-yearly recommendation is predicted to be of similar effectiveness to the current 2-yearly recommendation, resulting in no substantial change to the total number of incident cervical cancer cases or cancer deaths, or to the estimated 0.68% average cumulative lifetime risk of cervical cancer in unvaccinated Australian women. However, a 3-yearly screening policy would be associated with decreases in the annual number of colposcopy and biopsy procedures performed (by 4-10% and decreases in the number of treatments for pre-invasive lesions (by 2-4%. The magnitude of the decrease in the number of diagnostic procedures and treatments would depend on the method of screening organization, with call-and-recall screening associated with the highest reductions. The

  6. Computer-Aided Evaluation of Screening Mammograms Based on Local Texture Models

    Czech Academy of Sciences Publication Activity Database

    Grim, Jiří; Somol, Petr; Haindl, Michal; Daneš, J.

    2009-01-01

    Roč. 18, č. 4 (2009), s. 765-773 ISSN 1057-7149 R&D Projects: GA ČR GA102/07/1594; GA ČR GA102/08/0593; GA MŠk 1M0572 Grant - others:GA MŠk(CZ) 2C06019 Institutional research plan: CEZ:AV0Z10750506 Keywords : Screening mammography * texture information * local statistical model * Gaussian mixture Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.848, year: 2009

  7. Cost-effectiveness of screening for HIV in primary care: a health economics modelling analysis.

    Science.gov (United States)

    Baggaley, Rebecca F; Irvine, Michael A; Leber, Werner; Cambiano, Valentina; Figueroa, Jose; McMullen, Heather; Anderson, Jane; Santos, Andreia C; Terris-Prestholt, Fern; Miners, Alec; Hollingsworth, T Déirdre; Griffiths, Chris J

    2017-10-01

    Early HIV diagnosis reduces morbidity, mortality, the probability of onward transmission, and their associated costs, but might increase cost because of earlier initiation of antiretroviral treatment (ART). We investigated this trade-off by estimating the cost-effectiveness of HIV screening in primary care. We modelled the effect of the four-times higher diagnosis rate observed in the intervention arm of the RHIVA2 randomised controlled trial done in Hackney, London (UK), a borough with high HIV prevalence (≥0·2% adult prevalence). We constructed a dynamic, compartmental model representing incidence of infection and the effect of screening for HIV in general practices in Hackney. We assessed cost-effectiveness of the RHIVA2 trial by fitting model diagnosis rates to the trial data, parameterising with epidemiological and behavioural data from the literature when required, using trial testing costs and projecting future costs of treatment. Over a 40 year time horizon, incremental cost-effectiveness ratios were £22 201 (95% credible interval 12 662-132 452) per quality-adjusted life-year (QALY) gained, £372 207 (268 162-1 903 385) per death averted, and £628 874 (434 902-4 740 724) per HIV transmission averted. Under this model scenario, with UK cost data, RHIVA2 would reach the upper National Institute for Health and Care Excellence cost-effectiveness threshold (about £30 000 per QALY gained) after 33 years. Scenarios using cost data from Canada (which indicate prolonged and even higher health-care costs for patients diagnosed late) suggest this threshold could be reached in as little as 13 years. Screening for HIV in primary care has important public health benefits as well as clinical benefits. We predict it to be cost-effective in the UK in the medium term. However, this intervention might be cost-effective far sooner, and even cost-saving, in settings where long-term health-care costs of late-diagnosed patients in high

  8. An in vitro model for screening estrogen activity of environmental samples after metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Chahbane, N.; Schramm, K.W. [GSF - Forschungszentrum fuer Umwelt und Gesundheit Neuherberg GmbH, Oberschleissheim (Germany). Inst. fuer Oekologische Chemie; Kettrup, A. [Technische Univ. Muenchen, Freising (Germany). Lehrstuhl fuer Oekologische Chemie

    2004-09-15

    For a few years, yeast estrogen assay (YES) was accepted as a reliable and economic model for screening of environmental estrogens. Though the chemicals directly act with estrogen receptor (ER) can be filtered out by this model, there are still chemicals act with ER only after metabolism and some chemicals eliminate their estrogen activities after metabolism. That is to say, their metabolites exert or have stronger estrogen activities than themselves, which can be called bio-activation. In this case, for the lack of the metabolism enzyme system as human and other animals, only the assay with recombinant yeast cells is insufficient. So, it is necessary to combine the YES with metabolism procedure to evaluate the estrogen activities of these chemicals. The most common method used currently for in vitro metabolic activation in mutagenicity testing and also be applied to the estrogen screening field is S-9 mixture. Also, there is an attempt to develop a chemical model for cytochrome P450 as a bio-mimetic metabolic activation system. All these methods can be used as in vitro models for metabolism. Compare with these models, using whole H4II E cells for metabolism is an alternative and with superiorities. It has the excellence of short experiment period as all other in vitro models, but is much more close to the real surroundings as in vivo. Furthermore, the activity of 7-ethoxyresorufin-O-deethylase (EROD) can be easily measured during the whole incubation period for us to discuss the metabolic activities in a quantitative foundation, not only in qualitative. Methoxychlor is one of the chemicals with bio-activation ability. When directly used in the YES, it shows weak estrogen activity. But a main metabolite of methoxychlor, 2,2-bis (p-hydroxyphenyl) - 1,1,1-trichloroethane (HPTE) is a known estrogen mimic. For the long time using methoxychlor as a pesticide and its clear background, it is an ideal chemical to establish this in vitro system.

  9. Generalized Linear Mixed Model Analysis of Urban-Rural Differences in Social and Behavioral Factors for Colorectal Cancer Screening

    Science.gov (United States)

    Wang, Ke-Sheng; Liu, Xuefeng; Ategbole, Muyiwa; Xie, Xin; Liu, Ying; Xu, Chun; Xie, Changchun; Sha, Zhanxin

    2017-09-27

    Objective: Screening for colorectal cancer (CRC) can reduce disease incidence, morbidity, and mortality. However, few studies have investigated the urban-rural differences in social and behavioral factors influencing CRC screening. The objective of the study was to investigate the potential factors across urban-rural groups on the usage of CRC screening. Methods: A total of 38,505 adults (aged ≥40 years) were selected from the 2009 California Health Interview Survey (CHIS) data - the latest CHIS data on CRC screening. The weighted generalized linear mixed-model (WGLIMM) was used to deal with this hierarchical structure data. Weighted simple and multiple mixed logistic regression analyses in SAS ver. 9.4 were used to obtain the odds ratios (ORs) and their 95% confidence intervals (CIs). Results: The overall prevalence of CRC screening was 48.1% while the prevalence in four residence groups - urban, second city, suburban, and town/rural, were 45.8%, 46.9%, 53.7% and 50.1%, respectively. The results of WGLIMM analysis showed that there was residence effect (pregression analysis revealed that age, race, marital status, education level, employment stats, binge drinking, and smoking status were associated with CRC screening (p<0.05). Stratified by residence regions, age and poverty level showed associations with CRC screening in all four residence groups. Education level was positively associated with CRC screening in second city and suburban. Infrequent binge drinking was associated with CRC screening in urban and suburban; while current smoking was a protective factor in urban and town/rural groups. Conclusions: Mixed models are useful to deal with the clustered survey data. Social factors and behavioral factors (binge drinking and smoking) were associated with CRC screening and the associations were affected by living areas such as urban and rural regions. Creative Commons Attribution License

  10. The Effect of Treatment Advances on the Mortality Results of Breast Cancer Screening Trials: A Microsimulation Model.

    Science.gov (United States)

    Birnbaum, Jeanette; Gadi, Vijayakrishna K; Markowitz, Elan; Etzioni, Ruth

    2016-02-16

    Mammography trials, which are the primary sources of evidence for screening benefit, were conducted decades ago. Whether advances in systemic therapies have rendered previously observed benefits of screening less significant is unknown. To compare the outcomes of breast cancer screening trials had they been conducted using contemporary systemic treatments with outcomes of trials conducted with previously used treatments. Computer simulation model of 3 virtual screening trials with similar reductions in advanced-stage cancer cases but reflecting treatment patterns in 1975 (prechemotherapy era), 1999, or 2015 (treatment according to receptor status). Meta-analyses of screening and treatment trials; study of dissemination of primary systemic treatments; SEER (Surveillance, Epidemiology, and End Results) registry. U.S. women aged 50 to 74 years. 10 and 25 years. Population. Mammography, chemotherapy, tamoxifen, aromatase inhibitors, and trastuzumab. Breast cancer mortality rate ratio (MRR) and absolute risk reduction (ARR) obtained by the difference in cumulative breast cancer mortality between control and screening groups. At 10 years, screening in a 1975 trial yielded an MRR of 90% and an ARR of 5 deaths per 10,000 women. A 2015 screening trial yielded a 10-year MRR of 90% and an ARR of 3 deaths per 10,000 women. Greater reductions in advanced-stage disease yielded a greater screening effect, but MRRs remained similar across trials. However, ARRs were consistently lower under contemporary treatments. When contemporary treatments were available only for early-stage cases, the MRR was 88%. Disease models simplify reality and cannot capture all breast cancer subtypes. Advances in systemic therapies for breast cancer have not substantively reduced the relative benefits of screening but have likely reduced the absolute benefits because of their positive effect on breast cancer survival. University of Washington and National Cancer Institute.

  11. Pharmacophore modeling, virtual screening and molecular docking of ATPase inhibitors of HSP70.

    Science.gov (United States)

    Sangeetha, K; Sasikala, R P; Meena, K S

    2017-10-01

    Heat shock protein 70 is an effective anticancer target as it influences many signaling pathways. Hence the study investigated the important pharmacophore feature required for ATPase inhibitors of HSP70 by generating a ligand based pharmacophore model followed by virtual based screening and subsequent validation by molecular docking in Discovery studio V4.0. The most extrapolative pharmacophore model (hypotheses 8) consisted of four hydrogen bond acceptors. Further validation by external test set prediction identified 200 hits from Mini Maybridge, Drug Diverse, SCPDB compounds and Phytochemicals. Consequently, the screened compounds were refined by rule of five, ADMET and molecular docking to retain the best competitive hits. Finally Phytochemical compounds Muricatetrocin B, Diacetylphiladelphicalactone C, Eleutheroside B and 5-(3-{[1-(benzylsulfonyl)piperidin-4-yl]amino}phenyl)- 4-bromo-3-(carboxymethoxy)thiophene-2-carboxylic acid were obtained as leads to inhibit the ATPase activity of HSP70 in our findings and thus can be proposed for further in vitro and in vivo evaluation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease.

    Science.gov (United States)

    Potter, Paul K; Bowl, Michael R; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E; Simon, Michelle M; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V; Law, Gemma; MacLaren, Robert E; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H; Foster, Russell G; Jackson, Ian J; Peirson, Stuart N; Thakker, Rajesh V; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D M

    2016-08-18

    Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss.

  13. Genetic screening and testing in an episode-based payment model: preserving patient autonomy.

    Science.gov (United States)

    Sutherland, Sharon; Farrell, Ruth M; Lockwood, Charles

    2014-11-01

    The State of Ohio is implementing an episode-based payment model for perinatal care. All costs of care will be tabulated for each live birth and assigned to the delivering provider, creating a three-tiered model for reimbursement for care. Providers will be reimbursed as usual for care that is average in cost and quality, while instituting rewards or penalties for those outside the expected range in either domain. There are few exclusions, and all methods of genetic screening and diagnostic testing are included in the episode cost calculation as proposed. Prenatal ultrasonography, genetic screening, and diagnostic testing are critical components of the delivery of high-quality, evidence-based prenatal care. These tests provide pregnant women with key information about the pregnancy, which, in turn, allows them to work closely with their health care provider to determine optimal prenatal care. The concepts of informed consent and decision-making, cornerstones of the ethical practice of medicine, are founded on the principles of autonomy and respect for persons. These principles recognize that patients' rights to make choices and take actions are based on their personal beliefs and values. Given the personal nature of such decisions, it is critical that patients have unbarred access to prenatal genetic tests if they elect to use them as part of their prenatal care. The proposed restructuring of reimbursement creates a clear conflict between patient autonomy and physician financial incentives.

  14. High-throughput migration modelling for estimating exposure to chemicals in food packaging in screening and prioritization tools

    DEFF Research Database (Denmark)

    Ernstoff, Alexi S; Fantke, Peter; Huang, Lei

    2017-01-01

    Specialty software and simplified models are often used to estimate migration of potentially toxic chemicals from packaging into food. Current models, however, are not suitable for emerging applications in decision-support tools, e.g. in Life Cycle Assessment and risk-based screening and prioriti...... to uncertainty and dramatically decreased model performance (R2 = 0.4, Se = 1). In all, this study provides a rapid migration modelling approach to estimate exposure to chemicals in food packaging for emerging screening and prioritization approaches....

  15. Cost-effectiveness of HIV and syphilis antenatal screening: a modelling study.

    Science.gov (United States)

    Bristow, Claire C; Larson, Elysia; Anderson, Laura J; Klausner, Jeffrey D

    2016-08-01

    The WHO called for the elimination of maternal-to-child transmission (MTCT) of HIV and syphilis, a harmonised approach for the improvement of health outcomes for mothers and children. Testing early in pregnancy, treating seropositive pregnant women and preventing syphilis reinfection can prevent MTCT of HIV and syphilis. We assessed the health and economic outcomes of a dual testing strategy in a simulated cohort of 100 000 antenatal care patients in Malawi. We compared four screening algorithms: (1) HIV rapid test only, (2) dual HIV and syphilis rapid tests, (3) single rapid tests for HIV and syphilis and (4) HIV rapid and syphilis laboratory tests. We calculated the expected number of adverse pregnancy outcomes, the expected costs and the expected newborn disability-adjusted life years (DALYs) for each screening algorithm. The estimated costs and DALYs for each screening algorithm were assessed from a societal perspective using Markov progression models. Additionally, we conducted a Monte Carlo multiway sensitivity analysis, allowing for ranges of inputs. Our cohort decision model predicted the lowest number of adverse pregnancy outcomes in the dual HIV and syphilis rapid test strategy. Additionally, from the societal perspective, the costs of prevention and care using a dual HIV and syphilis rapid testing strategy was both the least costly ($226.92 per pregnancy) and resulted in the fewest DALYs (116 639) per 100 000 pregnancies. In the Monte Carlo simulation the dual HIV and syphilis algorithm was always cost saving and almost always reduced DALYs compared with HIV testing alone. The results of the cost-effectiveness analysis showed that a dual HIV and syphilis test was cost saving compared with all other screening strategies. Updating existing prevention of mother-to-child HIV transmission programmes in Malawi and similar countries to include dual rapid testing for HIV and syphilis is likely to be advantageous. Published by the BMJ Publishing Group

  16. Selection of low-level radioactive waste disposal sites using screening models versus more complex methodologies

    International Nuclear Information System (INIS)

    Uslu, I.; Fields, D.E.

    1993-01-01

    The task of choosing a waste-disposal site from a set of candidate sites requires an approach capable of objectively handling many environmental variables for each site. Several computer methodologies have been developed to assist in the process of choosing a site for the disposal of low-level radioactive waste; however, most of these models are costly to apply, in terms of computer resources and the time and effort required by professional modelers, geologists, and waste-disposal experts. The authors describe how the relatively simple DRASTIC methodology (a standardized system for evaluating groundwater pollution potential using hydrogeologic settings) may be used for open-quotes pre-screeningclose quotes of sites to determine which subset of candidate sites is worthy of more detailed screening. Results of site comparisons made with DRASTIC are compared with results obtained using PRESTO-II methodology, which is representative of the more complex release-transport-human exposure methodologies. 6 refs., 1 fig., 1 tab

  17. Characterization of three human cell line models for high-throughput neuronal cytotoxicity screening.

    Science.gov (United States)

    Tong, Zhi-Bin; Hogberg, Helena; Kuo, David; Sakamuru, Srilatha; Xia, Menghang; Smirnova, Lena; Hartung, Thomas; Gerhold, David

    2017-02-01

    More than 75 000 man-made chemicals contaminate the environment; many of these have not been tested for toxicities. These chemicals demand quantitative high-throughput screening assays to assess them for causative roles in neurotoxicities, including Parkinson's disease and other neurodegenerative disorders. To facilitate high throughput screening for cytotoxicity to neurons, three human neuronal cellular models were compared: SH-SY5Y neuroblastoma cells, LUHMES conditionally-immortalized dopaminergic neurons, and Neural Stem Cells (NSC) derived from human fetal brain. These three cell lines were evaluated for rapidity and degree of differentiation, and sensitivity to 32 known or candidate neurotoxicants. First, expression of neural differentiation genes was assayed during a 7-day differentiation period. Of the three cell lines, LUHMES showed the highest gene expression of neuronal markers after differentiation. Both in the undifferentiated state and after 7 days of neuronal differentiation, LUHMES cells exhibited greater cytotoxic sensitivity to most of 32 suspected or known neurotoxicants than SH-SY5Y or NSCs. LUHMES cells were also unique in being more susceptible to several compounds in the differentiating state than in the undifferentiated state; including known neurotoxicants colchicine, methyl-mercury (II), and vincristine. Gene expression results suggest that differentiating LUHMES cells may be susceptible to apoptosis because they express low levels of anti-apoptotic genes BCL2 and BIRC5/survivin, whereas SH-SY5Y cells may be resistant to apoptosis because they express high levels of BCL2, BIRC5/survivin, and BIRC3 genes. Thus, LUHMES cells exhibited favorable characteristics for neuro-cytotoxicity screening: rapid differentiation into neurons that exhibit high level expression neuronal marker genes, and marked sensitivity of LUHMES cells to known neurotoxicants. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Curcumin Based Drug Screening for Inhibitors of NF kappa B in a Cell Model of Prostate Cancer Progression

    Science.gov (United States)

    2008-02-01

    identify new and structurally diverse chemical analogs of the polyphenolic phytochemical Curcumin from the Indian herb Curcuma longa (family...AD_________________ Award Number: W81XWH-07-1-0081 TITLE: Curcumin Based Drug Screening for... Curcumin Based Drug Screening for Inhibitors of NF kappa B in a Cell Model of Prostate Cancer Progression 5b. GRANT NUMBER W81XWH-07-1-0081 5c

  19. Cost-effectiveness of enhanced syphilis screening among HIV-positive men who have sex with men: a microsimulation model.

    Directory of Open Access Journals (Sweden)

    Ashleigh R Tuite

    Full Text Available Syphilis co-infection risk has increased substantially among HIV-infected men who have sex with men (MSM. Frequent screening for syphilis and treatment of men who test positive might be a practical means of controlling the risk of infection and disease sequelae in this population.We evaluated the cost-effectiveness of strategies that increased the frequency and population coverage of syphilis screening in HIV-infected MSM receiving HIV care, relative to current standard of care.We developed a state-transition microsimulation model of syphilis natural history and medical care in HIV-infected MSM receiving care for HIV. We performed Monte Carlo simulations using input data derived from a large observational cohort in Ontario, Canada, and from published biomedical literature. Simulations compared usual care (57% of the population screened annually to different combinations of more frequent (3- or 6-monthly screening and higher coverage (100% screened. We estimated expected disease-specific outcomes, quality-adjusted survival, costs, and cost-effectiveness associated with each strategy from the perspective of a public health care payer.Usual care was more costly and less effective than strategies with more frequent or higher coverage screening. Higher coverage strategies (with screening frequency of 3 or 6 months were expected to be cost-effective based on usually cited willingness-to-pay thresholds. These findings were robust in the face of probabilistic sensitivity analyses, alternate cost-effectiveness thresholds, and alternate assumptions about duration of risk, program characteristics, and management of underlying HIV.We project that higher coverage and more frequent syphilis screening of HIV-infected MSM would be a highly cost-effective health intervention, with many potentially viable screening strategies projected to both save costs and improve health when compared to usual care. The baseline requirement for regular blood testing in this

  20. Cost-Effectiveness of Enhanced Syphilis Screening among HIV-Positive Men Who Have Sex with Men: A Microsimulation Model

    Science.gov (United States)

    Tuite, Ashleigh R.; Burchell, Ann N.; Fisman, David N.

    2014-01-01

    Background Syphilis co-infection risk has increased substantially among HIV-infected men who have sex with men (MSM). Frequent screening for syphilis and treatment of men who test positive might be a practical means of controlling the risk of infection and disease sequelae in this population. Purpose We evaluated the cost-effectiveness of strategies that increased the frequency and population coverage of syphilis screening in HIV-infected MSM receiving HIV care, relative to current standard of care. Methods We developed a state-transition microsimulation model of syphilis natural history and medical care in HIV-infected MSM receiving care for HIV. We performed Monte Carlo simulations using input data derived from a large observational cohort in Ontario, Canada, and from published biomedical literature. Simulations compared usual care (57% of the population screened annually) to different combinations of more frequent (3- or 6-monthly) screening and higher coverage (100% screened). We estimated expected disease-specific outcomes, quality-adjusted survival, costs, and cost-effectiveness associated with each strategy from the perspective of a public health care payer. Results Usual care was more costly and less effective than strategies with more frequent or higher coverage screening. Higher coverage strategies (with screening frequency of 3 or 6 months) were expected to be cost-effective based on usually cited willingness-to-pay thresholds. These findings were robust in the face of probabilistic sensitivity analyses, alternate cost-effectiveness thresholds, and alternate assumptions about duration of risk, program characteristics, and management of underlying HIV. Conclusions We project that higher coverage and more frequent syphilis screening of HIV-infected MSM would be a highly cost-effective health intervention, with many potentially viable screening strategies projected to both save costs and improve health when compared to usual care. The baseline requirement

  1. Costs and cost effectiveness of different strategies for chlamydia screening and partner notification: an economic and mathematical modelling study.

    Science.gov (United States)

    Turner, Katy; Adams, Elisabeth; Grant, Arabella; Macleod, John; Bell, Gill; Clarke, Jan; Horner, Paddy

    2011-01-04

    To compare the cost, cost effectiveness, and sex equity of different intervention strategies within the English National Chlamydia Screening Programme. To develop a tool for calculating cost effectiveness of chlamydia control programmes at a local, national, or international level. An economic and mathematical modelling study with cost effectiveness analysis. Costs were restricted to those of screening and partner notification from the perspective of the NHS and excluded patient costs, the costs of reinfection, and costs of complications arising from initial infection. England. Population Individuals eligible for the National Chlamydia Screening Programme. Cost effectiveness of National Chlamydia Screening Programme in 2008-9 (as cost per individual tested, cost per positive diagnosis, total cost of screening, number screened, number infected, sex ratio of those tested and treated). Comparison of baseline programme with two different interventions-(i) increased coverage of primary screening in men and (ii) increased efficacy of partner notification. In 2008-9 screening was estimated to cost about £46.3m in total and £506 per infection treated. Provision for partner notification within the screening programme cost between £9 and £27 per index case, excluding treatment and testing. The model results suggest that increasing male screening coverage from 8% (baseline value) to 24% (to match female coverage) would cost an extra £22.9m and increase the cost per infection treated to £528. In contrast, increasing partner notification efficacy from 0.4 (baseline value) to 0.8 partners per index case would cost an extra £3.3m and would reduce the cost per infection diagnosed to £449. Increasing screening coverage to 24% in men would cost over six times as much as increasing partner notification to 0.8 but only treat twice as many additional infections. In the English National Chlamydia Screening Programme increasing the effectiveness of partner notification is likely

  2. Performance of third-trimester combined screening model for prediction of adverse perinatal outcome.

    Science.gov (United States)

    Miranda, J; Triunfo, S; Rodriguez-Lopez, M; Sairanen, M; Kouru, H; Parra-Saavedra, M; Crovetto, F; Figueras, F; Crispi, F; Gratacós, E

    2017-09-01

    To explore the potential value of third-trimester combined screening for the prediction of adverse perinatal outcome (APO) in the general population and among small-for-gestational-age (SGA) fetuses. This was a nested case-control study within a prospective cohort of 1590 singleton gestations undergoing third-trimester evaluation (32 + 0 to 36 + 6 weeks' gestation). Maternal baseline characteristics, mean arterial blood pressure, fetoplacental ultrasound and circulating biochemical markers (placental growth factor (PlGF), lipocalin-2, unconjugated estriol and inhibin A) were assessed in all women who subsequently had an APO (n = 148) and in a control group without perinatal complications (n = 902). APO was defined as the occurrence of stillbirth, umbilical artery cord blood pH < 7.15, 5-min Apgar score < 7 or emergency operative delivery for fetal distress. Logistic regression models were developed for the prediction of APO in the general population and among SGA cases (defined as customized birth weight < 10 th centile). The prevalence of APO was 9.3% in the general population and 27.4% among SGA cases. In the general population, a combined screening model including a-priori risk (maternal characteristics), estimated fetal weight (EFW) centile, umbilical artery pulsatility index (UA-PI), estriol and PlGF achieved a detection rate for APO of 26% (area under receiver-operating characteristics curve (AUC), 0.59 (95% CI, 0.54-0.65)), at a 10% false-positive rate (FPR). Among SGA cases, a model including a-priori risk, EFW centile, UA-PI, cerebroplacental ratio, estriol and PlGF predicted 62% of APO (AUC, 0.86 (95% CI, 0.80-0.92)) at a FPR of 10%. The use of fetal ultrasound and maternal biochemical markers at 32-36 weeks provides a poor prediction of APO in the general population. Although it remains limited, the performance of the screening model is improved when applied to fetuses with suboptimal fetal growth. Copyright © 2016 ISUOG. Published by John Wiley & Sons

  3. Models of Community-Based Hepatitis B Surface Antigen Screening Programs in the U.S. and Their Estimated Outcomes and Costs

    Science.gov (United States)

    Rein, David B.; Lesesne, Sarah B.; Smith, Bryce D.; Weinbaum, Cindy M.

    2011-01-01

    Objectives Information on the process and method of service delivery is sparse for hepatitis B surface antigen (HBsAg) testing, and no systematic study has evaluated the relative effectiveness or cost-effectiveness of different HBsAg screening models. To address this need, we compared five specific community-based screening programs. Methods We funded five HBsAg screening programs to collect information on their design, costs, and outcomes of participants during a six-month observation period. We categorized programs into four types of models. For each model, we calculated the number screened, the number screened as per Centers for Disease Control and Prevention (CDC) recommendations, and the cost per screening. Results The models varied by cost per person screened and total number of people screened, but they did not differ meaningfully in the proportion of people screened following CDC recommendations, the proportion of those screened who tested positive, or the proportion of those who newly tested positive. Conclusions Integrating screening into outpatient service settings is the most cost-effective method but may not reach all people needing to be screened. Future research should examine cost-effective methods that expand the reach of screening into communities in outpatient settings. PMID:21800750

  4. Revisiting EOR Projects in Indonesia through Integrated Study: EOR Screening, Predictive Model, and Optimisation

    KAUST Repository

    Hartono, A. D.; Hakiki, Farizal; Syihab, Z.; Ambia, F.; Yasutra, A.; Sutopo, S.; Efendi, M.; Sitompul, V.; Primasari, I.; Apriandi, R.

    2017-01-01

    EOR preliminary analysis is pivotal to be performed at early stage of assessment in order to elucidate EOR feasibility. This study proposes an in-depth analysis toolkit for EOR preliminary evaluation. The toolkit incorporates EOR screening, predictive, economic, risk analysis and optimisation modules. The screening module introduces algorithms which assimilates statistical and engineering notions into consideration. The United States Department of Energy (U.S. DOE) predictive models were implemented in the predictive module. The economic module is available to assess project attractiveness, while Monte Carlo Simulation is applied to quantify risk and uncertainty of the evaluated project. Optimization scenario of EOR practice can be evaluated using the optimisation module, in which stochastic methods of Genetic Algorithms (GA), Particle Swarm Optimization (PSO) and Evolutionary Strategy (ES) were applied in the algorithms. The modules were combined into an integrated package of EOR preliminary assessment. Finally, we utilised the toolkit to evaluate several Indonesian oil fields for EOR evaluation (past projects) and feasibility (future projects). The attempt was able to update the previous consideration regarding EOR attractiveness and open new opportunity for EOR implementation in Indonesia.

  5. Effective screening length and quasiuniversality for the restricted primitive model of an electrolyte solution.

    Science.gov (United States)

    Janecek, Jirí; Netz, Roland R

    2009-02-21

    Monte Carlo simulations for the restricted primitive model of an electrolyte solution above the critical temperature are performed at a wide range of concentrations and temperatures. Thermodynamic properties such as internal energy, osmotic coefficient, activity coefficient, as well as spatial correlation functions are determined. These observables are used to investigate whether quasiuniversality in terms of an effective screening length exists, similar to the role played by the effective electron mass in solid-state physics. To that end, an effective screening length is extracted from the asymptotic behavior of the Fourier-transformed charge-correlation function and plugged into the Debye-Huckel limiting expressions for various thermodynamic properties. Comparison with numerical results is favorable, suggesting that correlation and other effects not captured on the Debye-Huckel limiting level can be successfully incorporated by a single effective parameter while keeping the functional form of Debye-Huckel expressions. We also compare different methods to determine mean ionic activity coefficient in molecular simulations and check the internal consistency of the numerical data.

  6. Revisiting EOR Projects in Indonesia through Integrated Study: EOR Screening, Predictive Model, and Optimisation

    KAUST Repository

    Hartono, A. D.

    2017-10-17

    EOR preliminary analysis is pivotal to be performed at early stage of assessment in order to elucidate EOR feasibility. This study proposes an in-depth analysis toolkit for EOR preliminary evaluation. The toolkit incorporates EOR screening, predictive, economic, risk analysis and optimisation modules. The screening module introduces algorithms which assimilates statistical and engineering notions into consideration. The United States Department of Energy (U.S. DOE) predictive models were implemented in the predictive module. The economic module is available to assess project attractiveness, while Monte Carlo Simulation is applied to quantify risk and uncertainty of the evaluated project. Optimization scenario of EOR practice can be evaluated using the optimisation module, in which stochastic methods of Genetic Algorithms (GA), Particle Swarm Optimization (PSO) and Evolutionary Strategy (ES) were applied in the algorithms. The modules were combined into an integrated package of EOR preliminary assessment. Finally, we utilised the toolkit to evaluate several Indonesian oil fields for EOR evaluation (past projects) and feasibility (future projects). The attempt was able to update the previous consideration regarding EOR attractiveness and open new opportunity for EOR implementation in Indonesia.

  7. BioSig3D: High Content Screening of Three-Dimensional Cell Culture Models.

    Directory of Open Access Journals (Sweden)

    Cemal Cagatay Bilgin

    Full Text Available BioSig3D is a computational platform for high-content screening of three-dimensional (3D cell culture models that are imaged in full 3D volume. It provides an end-to-end solution for designing high content screening assays, based on colony organization that is derived from segmentation of nuclei in each colony. BioSig3D also enables visualization of raw and processed 3D volumetric data for quality control, and integrates advanced bioinformatics analysis. The system consists of multiple computational and annotation modules that are coupled together with a strong use of controlled vocabularies to reduce ambiguities between different users. It is a web-based system that allows users to: design an experiment by defining experimental variables, upload a large set of volumetric images into the system, analyze and visualize the dataset, and either display computed indices as a heatmap, or phenotypic subtypes for heterogeneity analysis, or download computed indices for statistical analysis or integrative biology. BioSig3D has been used to profile baseline colony formations with two experiments: (i morphogenesis of a panel of human mammary epithelial cell lines (HMEC, and (ii heterogeneity in colony formation using an immortalized non-transformed cell line. These experiments reveal intrinsic growth properties of well-characterized cell lines that are routinely used for biological studies. BioSig3D is being released with seed datasets and video-based documentation.

  8. Development of a green fluorescent protein metastatic-cancer chick-embryo drug-screen model.

    Science.gov (United States)

    Bobek, Vladimir; Plachy, Jiri; Pinterova, Daniela; Kolostova, Katarina; Boubelik, Michael; Jiang, Ping; Yang, Meng; Hoffman, Robert M

    2004-01-01

    The chick-embryo model has been an important tool to study tumor growth, metastasis, and angiogenesis. However, an imageable model with a genetic fluorescent tag in the growing and spreading cancer cells that is stable over time has not been developed. We report here the development of such an imageable fluorescent chick-embryo metastatic cancer model with the use of green fluorescent protein (GFP). Lewis lung carcinoma cells, stably expressing GFP, were injected on the 12th day of incubation in the chick embryo. GFP-Lewis lung carcinoma metastases were visualized by fluorescence, after seven days additional incubation, in the brain, heart, and sternum of the developing chick embryo, with the most frequent site being the brain. The combination of streptokinase and gemcitabine was evaluated in this GFP metastatic model. Twelve-day-old chick embryos were injected intravenously with GFP-Lewis lung cancer cells, along with these two agents either alone or in combination. The streptokinase-gemcitabine combination inhibited metastases at all sites. The effective dose of gemcitabine was found to be 10 mg/kg and streptokinase 2000 IU per embryo. The data in this report suggest that this new stably fluorescent imageable metastatic-cancer chick-embryo model will enable rapid screening of new antimetastatic agents.

  9. A globally applicable location-specific screening model for assessing the relative risk of pesticide leaching

    International Nuclear Information System (INIS)

    Whelan, M.J.; Davenport, E.J.; Smith, B.G.

    2007-01-01

    A screening model of pesticide leaching loss is described which forms part of a multi-criteria risk-based indicator system called PRoMPT (Pesticide Risk Management and Profiling Tool). The leaching model evaluates pesticide fate in soil for any application rate and time of application (including multiple applications), for any land-based location in the world. It considers a generic evaluative environment with fixed dimensions and soil properties. The soil profile is conceptualised as a number of discrete layers. Equilibrium partitioning between adsorbed and dissolved chemical (based on the organic carbon-water partition coefficient [K OC ]) is assumed in each time step, in each layer. Non-leaching losses are described using first order kinetics. Drainage is assumed to be uniform throughout the soil profile but varies temporally. The drainage rate, which can be augmented by evapotranspiration-adjusted irrigation, is derived from long-term mean monthly water balance model calculations performed for 30 arc-minute grid cells across the entire ice-free land surface of the earth. Although, such predictions are approximate, they do capture the seasonality and relative magnitude of drainage and allow the model to be applied anywhere, without the need for extensive data compilation. PRoMPT predictions are shown to be consistent with those made by more sophisticated models (PRZM, PELMO and PEARL) for the FOCUS groundwater scenarios

  10. A globally applicable location-specific screening model for assessing the relative risk of pesticide leaching

    Energy Technology Data Exchange (ETDEWEB)

    Whelan, M.J. [Unilever Safety and Environmental Assurance Centre, Colworth House, Sharnbrook, Bedfordshire, MK44 1LQ (United Kingdom)]. E-mail: mick.whelan@unilever.com; Davenport, E.J. [Unilever Safety and Environmental Assurance Centre, Colworth House, Sharnbrook, Bedfordshire, MK44 1LQ (United Kingdom); Smith, B.G. [Unilever Sustainable Agriculture Team, Colworth House, Sharnbrook, Bedfordshire, MK44 1LQ (United Kingdom)

    2007-05-15

    A screening model of pesticide leaching loss is described which forms part of a multi-criteria risk-based indicator system called PRoMPT (Pesticide Risk Management and Profiling Tool). The leaching model evaluates pesticide fate in soil for any application rate and time of application (including multiple applications), for any land-based location in the world. It considers a generic evaluative environment with fixed dimensions and soil properties. The soil profile is conceptualised as a number of discrete layers. Equilibrium partitioning between adsorbed and dissolved chemical (based on the organic carbon-water partition coefficient [K {sub OC}]) is assumed in each time step, in each layer. Non-leaching losses are described using first order kinetics. Drainage is assumed to be uniform throughout the soil profile but varies temporally. The drainage rate, which can be augmented by evapotranspiration-adjusted irrigation, is derived from long-term mean monthly water balance model calculations performed for 30 arc-minute grid cells across the entire ice-free land surface of the earth. Although, such predictions are approximate, they do capture the seasonality and relative magnitude of drainage and allow the model to be applied anywhere, without the need for extensive data compilation. PRoMPT predictions are shown to be consistent with those made by more sophisticated models (PRZM, PELMO and PEARL) for the FOCUS groundwater scenarios.

  11. Development of a whole-organism model to screen new compounds for sun protection.

    Science.gov (United States)

    Wang, Yun-Hsin; Wen, Chi-Chung; Yang, Zhi-Shiang; Cheng, Chien-Chung; Tsai, Jen-Ning; Ku, Chia-Chen; Wu, Hsin-Ju; Chen, Yau-Hung

    2009-01-01

    We used zebrafish as a whole-organism model to screen new compounds for sun protection activity. First of all, we designed a series of UVB exposure experiments and recorded the phenotypic changes of zebrafish embryos. Results showed that 100 mJ/cm(2) of UVB given six times separated by 30 min intervals is the best condition. Fin malformation (reduced and/or absent fin) phenotypes are the most evident consequences after exposure to UVB. Each fin was affected by UVB, including pelvic, ventral, caudal, and dorsal fin, but pelvic fin seemed to be the most sensitive target after UVB exposure. We furthermore carried out "prevention" and "treatment" experiments using green tea extract and/or (-)-epigallocatechin (EGCG) to test this whole-organism model by observing the morphological changes of all fins (especially pelvic fin) after UVB exposure. Effects of UVB, green tea extract and EGCG on fin development were assessed using the Kaplan-Meier analysis, log-rank test and Cox proportional hazards regression. Results showed that a zebrafish pelvic fin in the UVB + green tea (treatment) group is 5.51 (range from 2.39 to 14.90) times, one in the UVB + green tea (prevention) group is 7.04 (range from 3.11 to 18.92) times, and one in the 25 ppm of EGCG (prevention) group is 22.19 (range from 9.40 to 61.50) times more likely to return to normal fin than one in the UVB only group. On the basis of these observations, we believe this model is effective for screening the higher stability and lower toxicity of new compounds, such as small chemicals which are derivative from EGCG or other dietary agents for sun protection.

  12. Mutation-Guided Unbiased Modeling of the Fat Sensor GPR119 for High-Yield Agonist Screening

    DEFF Research Database (Denmark)

    Norn, Christoffer; Pedersen, Maria Hauge; Engelstoft, Maja S.

    2015-01-01

    and is consistent with the structure-activity relationship for a large no. of AR231453 analogs. Another key property of the refined models is their success in sepg. active ligands from decoys in a large-scale virtual screening. These results demonstrate that mutation-guided receptor modeling can provide predictions...

  13. Predictive Models and Tools for Screening Chemicals under TSCA: Consumer Exposure Models 1.5

    Science.gov (United States)

    CEM contains a combination of models and default parameters which are used to estimate inhalation, dermal, and oral exposures to consumer products and articles for a wide variety of product and article use categories.

  14. A screening model for depleted uranium testing using environmental radiation monitoring data

    International Nuclear Information System (INIS)

    Dunfrund, F.L.; Ebinger, M.H.; Hansen, W.R.

    1996-01-01

    Information from an ecological risk assessment of depleted uranium test areas at Yuma Proving Ground (YPG) was used to update the required environmental radiation monitoring (ERM) plan. Data to be collected for the ERM can also be used to evaluate the potential for adverse radiological and toxicological effects to terrestrial reptiles and mammals in the affected areas. We developed a spreadsheet-based screening model that incorporates the ERM data and associated uncertainties. The purpose of the model is to provide a conservative estimate of radiological exposure of terrestrial, biota to DU using the ERM data. The uncertainty in the estimate is also predicted so that the variation in the radiological exposure can be used in assessing potential adverse effects from DU testing. Toxicological effects are evaluated as well as radiological effects in the same program using the same data. Our presentation shows an example data set, model calculations, and the report of expected radiation dose rates and probable kidney burdens of select mammals and reptiles. The model can also be used in an inverse mode to calculate the soil concentration required to give either a radiological dose that would produce a potential adverse effect such as fatal cancer or a toxicological dose that would result in nephrotoxic effects in mammals

  15. New radio model in the fourth screen: radiovision, the radio that you can watch

    Directory of Open Access Journals (Sweden)

    Sandra CAVIA FRAILE

    2016-12-01

    Full Text Available The traditional radio is not strange to the social revolution that Internet and new technologies are raising. In recent years, the fourth screen has led the emergence of new models of radio, including Radiovision. The «radio that you can watch» intends to change and innovate the radio broadcasting media to offer a product that meets the multimedia requirements of users. However, currently, the Radiovisión is still at an early stage and it has many aspects that it should improve and care, as the contents and the staging. It is a big chance for the radio that poses challenges and opportunities both for journalism and journalists.

  16. A theoretical model evaluating the angular distribution of luminescence emission in X-ray scintillating screens

    International Nuclear Information System (INIS)

    Kandarakis, I.; Cavouras, D.; Nikolopoulos, D.; Episkopakis, A.; Kalivas, N.; Liaparinos, P.; Valais, I.; Kagadis, G.; Kourkoutas, K.; Sianoudis, I.; Dimitropoulos, N.; Nomicos, C.; Panayiotakis, G.

    2006-01-01

    The aim of this study was to examine the angular distribution of the light emitted from radiation-excited scintillators in medical imaging detectors. This distribution diverges from Lambert's cosine law and affects the light emission efficiency of scintillators, hence it also affects the dose burden to the patient. In the present study, the angular distribution was theoretically modeled and was used to fit experimental data on various scintillator materials. Results of calculations revealed that the angular distribution is more directional than that predicted by Lambert's law. Divergence from this law is more pronounced for high values of light attenuation coefficient and thick scintillator layers (screens). This type of divergence reduces light emission efficiency and hence it increases the incident X-ray flux required for a given level of image brightness

  17. High-throughput screen for novel antimicrobials using a whole animal infection model.

    Science.gov (United States)

    Moy, Terence I; Conery, Annie L; Larkins-Ford, Jonah; Wu, Gang; Mazitschek, Ralph; Casadei, Gabriele; Lewis, Kim; Carpenter, Anne E; Ausubel, Frederick M

    2009-07-17

    The nematode Caenorhabditis elegans is a unique whole animal model system for identifying small molecules with in vivo anti-infective properties. C. elegans can be infected with a broad range of human pathogens, including Enterococcus faecalis, an important human nosocomial pathogen. Here, we describe an automated, high-throughput screen of 37,200 compounds and natural product extracts for those that enhance survival of C. elegans infected with E. faecalis. Using a robot to dispense live, infected animals into 384-well plates and automated microscopy and image analysis, we identified 28 compounds and extracts not previously reported to have antimicrobial properties, including six structural classes that cure infected C. elegans animals but do not affect the growth of the pathogen in vitro, thus acting by a mechanism of action distinct from antibiotics currently in clinical use.

  18. Understanding the Harms and Benefits of Cancer Screening: A Model of Factors That Shape Informed Decision Making.

    Science.gov (United States)

    Petrova, Dafina; Garcia-Retamero, Rocio; Cokely, Edward T

    2015-10-01

    Decisions about cancer screenings often involve the consideration of complex and counterintuitive evidence. We investigated psychological factors that promote the comprehension of benefits and harms associated with common cancer screenings and their influence on shared decision making. In experiment 1, 256 men received information about PSA-based prostate cancer screening. In experiment 2, 355 women received information about mammography-based breast cancer screening. In both studies, information about potential screening outcomes was provided in 1 of 3 formats: text, a fact box, or a visual aid (e.g., mortality with and without screening and rate of overdiagnosis). We modeled the interplay of comprehension, perceived risks and benefits, intention to participate in screening, and desire for shared decision making. Generally, visual aids were the most effective format, increasing comprehension by up to 18%. Improved comprehension was associated with 1) superior decision making (e.g., fewer intentions to participate in screening when it offered no benefit) and 2) more desire to share in decision making. However, comprehension of the evidence had a limited effect on experienced emotions, risk perceptions, and decision making among those participants who felt that the consequences of cancer were extremely severe. Even when information is counterintuitive and requires the integration of complex harms and benefits, user-friendly risk communications can facilitate comprehension, improve high-stakes decisions, and promote shared decision making. However, previous beliefs about the effectiveness of screening or strong fears about specific cancers may interfere with comprehension and informed decision making. © The Author(s) 2015.

  19. Adolescent idiopathic scoliosis screening for school, community, and clinical health promotion practice utilizing the PRECEDE-PROCEED model

    Directory of Open Access Journals (Sweden)

    Wyatt Lawrence A

    2005-11-01

    Full Text Available Abstract Background Screening for adolescent idiopathic scoliosis (AIS is a commonly performed procedure for school children during the high risk years. The PRECEDE-PROCEDE (PP model is a health promotion planning model that has not been utilized for the clinical diagnosis of AIS. The purpose of this research is to study AIS in the school age population using the PP model and its relevance for community, school, and clinical health promotion. Methods MEDLINE was utilized to locate AIS data. Studies were screened for relevance and applicability under the auspices of the PP model. Where data was unavailable, expert opinion was utilized based on consensus. Results The social assessment of quality of life is limited with few studies approaching the long-term effects of AIS. Epidemiologically, AIS is the most common form of scoliosis and leading orthopedic problem in children. Behavioral/environmental studies focus on discovering etiologic relationships yet this data is confounded because AIS is not a behavioral. Illness and parenting health behaviors can be appreciated. The educational diagnosis is confounded because AIS is an orthopedic disorder and not behavioral. The administration/policy diagnosis is hindered in that scoliosis screening programs are not considered cost-effective. Policies are determined in some schools because 26 states mandate school scoliosis screening. There exists potential error with the Adam's test. The most widely used measure in the PP model, the Health Belief Model, has not been utilized in any AIS research. Conclusion The PP model is a useful tool for a comprehensive study of a particular health concern. This research showed where gaps in AIS research exist suggesting that there may be problems to the implementation of school screening. Until research disparities are filled, implementation of AIS screening by school, community, and clinical health promotion will be compromised. Lack of data and perceived importance by

  20. Neuronal models for evaluation of proliferation in vitro using high content screening

    International Nuclear Information System (INIS)

    Mundy, William R.; Radio, Nicholas M.; Freudenrich, Theresa M.

    2010-01-01

    In vitro test methods can provide a rapid approach for the screening of large numbers of chemicals for their potential to produce toxicity (hazard identification). In order to identify potential developmental neurotoxicants, a battery of in vitro tests for neurodevelopmental processes such as cell proliferation, differentiation, growth, and synaptogenesis has been proposed. The development of in vitro approaches for toxicity testing will require choosing a model system that is appropriate to the endpoint of concern. This study compared several cell lines as models for neuronal proliferation. The sensitivities of neuronal cell lines derived from three species (PC12, rat; N1E-115, mouse; SH-SY5Y, human) to chemicals known to affect cell proliferation were assessed using a high content screening system. After optimizing conditions for cell growth in 96-well plates, proliferation was measured as the incorporation of 5-bromo-2'-deoxyuridine (BrdU) into replicating DNA during S phase. BrdU-labeled cells were detected by immunocytochemistry and cell counts were obtained using automated image acquisition and analysis. The three cell lines showed approximately 30-40% of the population in S phase after a 4 h pulse of BrdU. Exposure to the DNA polymerase inhibitor aphidicolin for 20 h prior to the 4 h pulse of BrdU significantly decreased proliferation in all three cell lines. The sensitivities of the cell lines were compared by exposure to eight chemicals known to affect proliferation (positive controls) and determination of the concentration inhibiting proliferation by 50% of control (I 50 ). PC12 cells were the most sensitive to chemicals; 6 out of 8 chemicals (aphidicolin, cadmium, cytosine arabinoside, dexamethasone, 5-fluorouracil, and methylmercury) inhibited proliferation at the concentrations tested. SH-SY5Y cells were somewhat less sensitive to chemical effects, with five out of eight chemicals inhibiting proliferation; dexamethasone had no effect, and cadmium

  1. Prospective identification of adolescent suicide ideation using classification tree analysis: Models for community-based screening.

    Science.gov (United States)

    Hill, Ryan M; Oosterhoff, Benjamin; Kaplow, Julie B

    2017-07-01

    Although a large number of risk markers for suicide ideation have been identified, little guidance has been provided to prospectively identify adolescents at risk for suicide ideation within community settings. The current study addressed this gap in the literature by utilizing classification tree analysis (CTA) to provide a decision-making model for screening adolescents at risk for suicide ideation. Participants were N = 4,799 youth (Mage = 16.15 years, SD = 1.63) who completed both Waves 1 and 2 of the National Longitudinal Study of Adolescent to Adult Health. CTA was used to generate a series of decision rules for identifying adolescents at risk for reporting suicide ideation at Wave 2. Findings revealed 3 distinct solutions with varying sensitivity and specificity for identifying adolescents who reported suicide ideation. Sensitivity of the classification trees ranged from 44.6% to 77.6%. The tree with greatest specificity and lowest sensitivity was based on a history of suicide ideation. The tree with moderate sensitivity and high specificity was based on depressive symptoms, suicide attempts or suicide among family and friends, and social support. The most sensitive but least specific tree utilized these factors and gender, ethnicity, hours of sleep, school-related factors, and future orientation. These classification trees offer community organizations options for instituting large-scale screenings for suicide ideation risk depending on the available resources and modality of services to be provided. This study provides a theoretically and empirically driven model for prospectively identifying adolescents at risk for suicide ideation and has implications for preventive interventions among at-risk youth. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  2. Phenotypic Screening Identifies Modulators of Amyloid Precursor Protein Processing in Human Stem Cell Models of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Philip W. Brownjohn

    2017-04-01

    Full Text Available Summary: Human stem cell models have the potential to provide platforms for phenotypic screens to identify candidate treatments and cellular pathways involved in the pathogenesis of neurodegenerative disorders. Amyloid precursor protein (APP processing and the accumulation of APP-derived amyloid β (Aβ peptides are key processes in Alzheimer's disease (AD. We designed a phenotypic small-molecule screen to identify modulators of APP processing in trisomy 21/Down syndrome neurons, a complex genetic model of AD. We identified the avermectins, commonly used as anthelmintics, as compounds that increase the relative production of short Aβ peptides at the expense of longer, potentially more toxic peptides. Further studies demonstrated that this effect is not due to an interaction with the core γ-secretase responsible for Aβ production. This study demonstrates the feasibility of phenotypic drug screening in human stem cell models of Alzheimer-type dementia, and points to possibilities for indirectly modulating APP processing, independently of γ-secretase modulation. : In this article, Livesey and colleagues perform a phenotypic drug screen in a human stem cell model of Alzheimer's disease. The anthelminthic avermectins are identified as a family of compounds that increase the production of short Aβ peptides over longer more toxic Aβ forms. The effect is analogous to existing γ-secretase modulators, but is independent of the core γ-secretase complex. Keywords: neural stem cells, Alzheimer's disease, phenotypic screening, iPSCs, human neurons, dementia, Down syndrome, amyloid beta, ivermectin, selamectin

  3. The Clinical and Economic Benefits of Co-Testing Versus Primary HPV Testing for Cervical Cancer Screening: A Modeling Analysis.

    Science.gov (United States)

    Felix, Juan C; Lacey, Michael J; Miller, Jeffrey D; Lenhart, Gregory M; Spitzer, Mark; Kulkarni, Rucha

    2016-06-01

    Consensus United States cervical cancer screening guidelines recommend use of combination Pap plus human papillomavirus (HPV) testing for women aged 30 to 65 years. An HPV test was approved by the Food and Drug Administration in 2014 for primary cervical cancer screening in women age 25 years and older. Here, we present the results of clinical-economic comparisons of Pap plus HPV mRNA testing including genotyping for HPV 16/18 (co-testing) versus DNA-based primary HPV testing with HPV 16/18 genotyping and reflex cytology (HPV primary) for cervical cancer screening. A health state transition (Markov) model with 1-year cycling was developed using epidemiologic, clinical, and economic data from healthcare databases and published literature. A hypothetical cohort of one million women receiving triennial cervical cancer screening was simulated from ages 30 to 70 years. Screening strategies compared HPV primary to co-testing. Outcomes included total and incremental differences in costs, invasive cervical cancer (ICC) cases, ICC deaths, number of colposcopies, and quality-adjusted life years for cost-effectiveness calculations. Comprehensive sensitivity analyses were performed. In a simulation cohort of one million 30-year-old women modeled up to age 70 years, the model predicted that screening with HPV primary testing instead of co-testing could lead to as many as 2,141 more ICC cases and 2,041 more ICC deaths. In the simulation, co-testing demonstrated a greater number of lifetime quality-adjusted life years (22,334) and yielded $39.0 million in savings compared with HPV primary, thereby conferring greater effectiveness at lower cost. Model results demonstrate that co-testing has the potential to provide improved clinical and economic outcomes when compared with HPV primary. While actual cost and outcome data are evaluated, these findings are relevant to U.S. healthcare payers and women's health policy advocates seeking cost-effective cervical cancer screening

  4. VR-SCOSMO: A smooth conductor-like screening model with charge-dependent radii for modeling chemical reactions.

    Science.gov (United States)

    Kuechler, Erich R; Giese, Timothy J; York, Darrin M

    2016-04-28

    To better represent the solvation effects observed along reaction pathways, and of ionic species in general, a charge-dependent variable-radii smooth conductor-like screening model (VR-SCOSMO) is developed. This model is implemented and parameterized with a third order density-functional tight binding quantum model, DFTB3/3OB-OPhyd, a quantum method which was developed for organic and biological compounds, utilizing a specific parameterization for phosphate hydrolysis reactions. Unlike most other applications with the DFTB3/3OB model, an auxiliary set of atomic multipoles is constructed from the underlying DFTB3 density matrix which is used to interact the solute with the solvent response surface. The resulting method is variational, produces smooth energies, and has analytic gradients. As a baseline, a conventional SCOSMO model with fixed radii is also parameterized. The SCOSMO and VR-SCOSMO models shown have comparable accuracy in reproducing neutral-molecule absolute solvation free energies; however, the VR-SCOSMO model is shown to reduce the mean unsigned errors (MUEs) of ionic compounds by half (about 2-3 kcal/mol). The VR-SCOSMO model presents similar accuracy as a charge-dependent Poisson-Boltzmann model introduced by Hou et al. [J. Chem. Theory Comput. 6, 2303 (2010)]. VR-SCOSMO is then used to examine the hydrolysis of trimethylphosphate and seven other phosphoryl transesterification reactions with different leaving groups. Two-dimensional energy landscapes are constructed for these reactions and calculated barriers are compared to those obtained from ab initio polarizable continuum calculations and experiment. Results of the VR-SCOSMO model are in good agreement in both cases, capturing the rate-limiting reaction barrier and the nature of the transition state.

  5. A theoretical model predicting the intensity of emitted light per unit of x-ray exposure in radiographic screens

    Energy Technology Data Exchange (ETDEWEB)

    Tsoukos, S; Kateris, A; Kalivas, N; Spyrou, G; Panayiotakis, G [Department of Medical Physics, School of Medicine, University of Patras, 265 00 pAtras (Greece); Kandarakis, I; Gavouras, D [Department of Medical Instrumentation Technology, Technological Educational Institution of Athens (Greece)

    1999-12-31

    A theoretical model predicting the intensity of light emitted by x-ray imaging phosphor screens per unit of area and time over incident x-ray flux (absolute efficiency) was developed. The model takes into account : A) the structure of the screens which consists of luminescent grains embedded in a binding matrix. B) the direct deposition of energy by x-ray absorption effects.. C) the re-absorption of K fluorescence characteristic x-rays produced when the x-ray energy exceeds the energy of the K absorption edge of the phosphor material. To test the model a set of (Gd,La)2O2S:Tb phosphor screens was prepared by sedimentation in the laboratory. Experimental absolute efficiency data were obtained at x-ray tube voltage range from 40 to 160 kVp. The coincidence between experimental and theoretical results were satisfactory. (authors) 7 refs., 4 figs.

  6. Screening of metal-organic frameworks for carbon dioxide capture from flue gas using a combined experimental and modeling approach.

    Science.gov (United States)

    Yazaydin, A Ozgür; Snurr, Randall Q; Park, Tae-Hong; Koh, Kyoungmoo; Liu, Jian; Levan, M Douglas; Benin, Annabelle I; Jakubczak, Paulina; Lanuza, Mary; Galloway, Douglas B; Low, John J; Willis, Richard R

    2009-12-30

    A diverse collection of 14 metal-organic frameworks (MOFs) was screened for CO(2) capture from flue gas using a combined experimental and modeling approach. Adsorption measurements are reported for the screened MOFs at room temperature up to 1 bar. These data are used to validate a generalized strategy for molecular modeling of CO(2) and other small molecules in MOFs. MOFs possessing a high density of open metal sites are found to adsorb significant amounts of CO(2) even at low pressure. An excellent correlation is found between the heat of adsorption and the amount of CO(2) adsorbed below 1 bar. Molecular modeling can aid in selection of adsorbents for CO(2) capture from flue gas by screening a large number of MOFs.

  7. Cost-Effectiveness of HBV and HCV Screening Strategies – A Systematic Review of Existing Modelling Techniques

    Science.gov (United States)

    Geue, Claudia; Wu, Olivia; Xin, Yiqiao; Heggie, Robert; Hutchinson, Sharon; Martin, Natasha K.; Fenwick, Elisabeth; Goldberg, David

    2015-01-01

    Introduction Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers. PMID:26689908

  8. Disease modeling and phenotypic drug screening for diabetic cardiomyopathy using human induced pluripotent stem cells.

    Science.gov (United States)

    Drawnel, Faye M; Boccardo, Stefano; Prummer, Michael; Delobel, Frédéric; Graff, Alexandra; Weber, Michael; Gérard, Régine; Badi, Laura; Kam-Thong, Tony; Bu, Lei; Jiang, Xin; Hoflack, Jean-Christophe; Kiialainen, Anna; Jeworutzki, Elena; Aoyama, Natsuyo; Carlson, Coby; Burcin, Mark; Gromo, Gianni; Boehringer, Markus; Stahlberg, Henning; Hall, Benjamin J; Magnone, Maria Chiara; Kolaja, Kyle; Chien, Kenneth R; Bailly, Jacques; Iacone, Roberto

    2014-11-06

    Diabetic cardiomyopathy is a complication of type 2 diabetes, with known contributions of lifestyle and genetics. We develop environmentally and genetically driven in vitro models of the condition using human-induced-pluripotent-stem-cell-derived cardiomyocytes. First, we mimic diabetic clinical chemistry to induce a phenotypic surrogate of diabetic cardiomyopathy, observing structural and functional disarray. Next, we consider genetic effects by deriving cardiomyocytes from two diabetic patients with variable disease progression. The cardiomyopathic phenotype is recapitulated in the patient-specific cells basally, with a severity dependent on their original clinical status. These models are incorporated into successive levels of a screening platform, identifying drugs that preserve cardiomyocyte phenotype in vitro during diabetic stress. In this work, we present a patient-specific induced pluripotent stem cell (iPSC) model of a complex metabolic condition, showing the power of this technique for discovery and testing of therapeutic strategies for a disease with ever-increasing clinical significance. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Evaluating skin-protective materials against contact irritants and allergens. An in vivo screening human model.

    Science.gov (United States)

    Zhai, H; Willard, P; Maibach, H I

    1998-03-01

    2 acute irritants and 1 allergen were selected: sodium lauryl sulfate (SLS) representative of irritant household and occupational contact dermatitis, the combination of ammonium hydroxide (NH4OH) and urea to simulate diaper dermatitis, and Rhus to evaluate the effect of model protective materials. The putative protective materials and vehicle were applied to both ventral forearms of 10 subjects in each group, according to a randomized code. Test materials were spread over a marked 2.0 cm2 area, massaged in, allowed to dry for 30 min, and reapplied with another 30 min drying period. The model irritants and allergen were then applied (0.025 ml) to an Al-test occlusive patch, which in turn was placed for 24 h over each of the 8 designated sites. Inflammation was scored according to a clinical scale 72 h post-application. Paraffin wax plus Acetulan in cetyl alcohol, and beeswax plus Acetulan in cetyl alcohol, markedly (p < 0.001) suppressed SLS irritation. Paraffin wax plus beeswax in cetyl alcohol, and Acetulan in cetyl alcohol reduced NH4OH and urea irritation (p < 0.05), paraffin wax in cetyl alcohol significantly (p < 0.01) decreasing Rhus allergic contact dermatitis. This model, provides an easy approach to screening protectants. Its clinical significance requires comparison with an open rather than an occluded challenge.

  10. Bioprospecting of Thermostable Cellulolytic Enzymes through Modeling and Virtual Screening Method

    Directory of Open Access Journals (Sweden)

    R. Navanietha Krishnaraj

    2017-04-01

    Full Text Available Cellulolytic enzymes are promising candidates for the use of cellulose in any bioprocess operations and for the disposal of the cellulosic wastes in an environmentally benign manner. Cellulases from thermophiles have the advantage of hydrolyzing cellulose at wider range of operating conditions unlike the normal enzymes. Herein we report the modeled structures of cellulolytic enzymes (endoglucanase, cellobiohydrolase and ß-glucosidase from a thermophilic bacterium,Clostridium thermocellumand their validation using Root Mean Square Deviation (RMSD and Ramachandran plot analyses. Further, the molecular interactions of the modeled enzyme with cellulose were analyzed using molecular docking technique. The results of molecular docking showed that the endoglucanase, cellobiohydrolase and ß-glucosidase had the binding affinities of -10.7, -9.0 and -10.8 kcal/mol, respectively. A correlation between the binding affinity of the endoglucanase with cellulose and the enzyme activity was also demonstrated. The results showed that the binding affinities of cellulases with cellulose could be used as a tool to assess the hydrolytic activity of cellulases. The results obtained could be used in virtual screening of cellulolytic enzymes based on the molecular interactions with the substrate, and aid in developing systems biology models of thermophiles for industrial biotechnology applications.

  11. Disease Modeling and Phenotypic Drug Screening for Diabetic Cardiomyopathy using Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Faye M. Drawnel

    2014-11-01

    Full Text Available Diabetic cardiomyopathy is a complication of type 2 diabetes, with known contributions of lifestyle and genetics. We develop environmentally and genetically driven in vitro models of the condition using human-induced-pluripotent-stem-cell-derived cardiomyocytes. First, we mimic diabetic clinical chemistry to induce a phenotypic surrogate of diabetic cardiomyopathy, observing structural and functional disarray. Next, we consider genetic effects by deriving cardiomyocytes from two diabetic patients with variable disease progression. The cardiomyopathic phenotype is recapitulated in the patient-specific cells basally, with a severity dependent on their original clinical status. These models are incorporated into successive levels of a screening platform, identifying drugs that preserve cardiomyocyte phenotype in vitro during diabetic stress. In this work, we present a patient-specific induced pluripotent stem cell (iPSC model of a complex metabolic condition, showing the power of this technique for discovery and testing of therapeutic strategies for a disease with ever-increasing clinical significance.

  12. The use of graph theory in the sensitivity analysis of the model output: a second order screening method

    International Nuclear Information System (INIS)

    Campolongo, Francesca; Braddock, Roger

    1999-01-01

    Sensitivity analysis screening methods aim to isolate the most important factors in experiments involving a large number of significant factors and interactions. This paper extends the one-factor-at-a-time screening method proposed by Morris. The new method, in addition to the 'overall' sensitivity measures already provided by the traditional Morris method, offers estimates of the two-factor interaction effects. The number of model evaluations required is O(k 2 ), where k is the number of model input factors. The efficient sampling strategy in the parameter space is based on concepts of graph theory and on the solution of the 'handcuffed prisoner problem'

  13. An in vivo C. elegans model system for screening EGFR-inhibiting anti-cancer drugs.

    Directory of Open Access Journals (Sweden)

    Young-Ki Bae

    Full Text Available The epidermal growth factor receptor (EGFR is a well-established target for cancer treatment. EGFR tyrosine kinase (TK inhibitors, such as gefinitib and erlotinib, have been developed as anti-cancer drugs. Although non-small cell lung carcinoma with an activating EGFR mutation, L858R, responds well to gefinitib and erlotinib, tumors with a doubly mutated EGFR, T790M-L858R, acquire resistance to these drugs. The C. elegans EGFR homolog LET-23 and its downstream signaling pathway have been studied extensively to provide insight into regulatory mechanisms conserved from C. elegans to humans. To develop an in vivo screening system for potential cancer drugs targeting specific EGFR mutants, we expressed three LET-23 chimeras in which the TK domain was replaced with either the human wild-type TK domain (LET-23::hEGFR-TK, a TK domain with the L858R mutation (LET-23::hEGFR-TK[L858R], or a TK domain with the T790M-L858R mutations (LET-23::hEGFR-TK[T790M-L858R] in C. elegans vulval cells using the let-23 promoter. The wild-type hEGFR-TK chimeric protein rescued the let-23 mutant phenotype, and the activating mutant hEGFR-TK chimeras induced a multivulva (Muv phenotype in a wild-type C. elegans background. The anti-cancer drugs gefitinib and erlotinib suppressed the Muv phenotype in LET-23::hEGFR-TK[L858R]-expressing transgenic animals, but not in LET-23::hEGFR-TK[T790M-L858R] transgenic animals. As a pilot screen, 8,960 small chemicals were tested for Muv suppression, and AG1478 (an EGFR-TK inhibitor and U0126 (a MEK inhibitor were identified as potential inhibitors of EGFR-mediated biological function. In conclusion, transgenic C. elegans expressing chimeric LET-23::hEGFR-TK proteins are a model system that can be used in mutation-specific screens for new anti-cancer drugs.

  14. Screening of nanoparticulate delivery systems for the photodetection of cancer in a simple and cost-effective model.

    Science.gov (United States)

    Zeisser-Labouèbe, Magali; Delie, Florence; Gurny, Robert; Lange, Norbert

    2009-02-01

    In urology, fluorescence-based imaging methods have been proven to significantly improve the detection of small, barely visible tumors and reduce the recurrence rate. Under ethical and economical pressure, new effective screening systems have to be developed to exploit and assess novel strategies for fluorescence photodetection in other areas. For this purpose, the chorioallantoic membrane (CAM) of the developing chick embryo is an attractive alternative model to the mammalian models. Hypericin encapsulated into nanoparticles for the photodetection of ovarian metastases was evaluated in the CAM model with respect to vascular extravazation and tumor targeting and compared with free drug following intravenous administration. To validate the CAM model as a valuable screening system for photodetection of cancer, we drew a comparison with results obtained on a conventional rodent model. Rodent and CAM models led to the same conclusion regarding the benefits of nanoencapsulation to improve selective accumulation of drug in ovarian micrometastases.

  15. On various metrics used for validation of predictive QSAR models with applications in virtual screening and focused library design.

    Science.gov (United States)

    Roy, Kunal; Mitra, Indrani

    2011-07-01

    Quantitative structure-activity relationships (QSARs) have important applications in drug discovery research, environmental fate modeling, property prediction, etc. Validation has been recognized as a very important step for QSAR model development. As one of the important objectives of QSAR modeling is to predict activity/property/toxicity of new chemicals falling within the domain of applicability of the developed models and QSARs are being used for regulatory decisions, checking reliability of the models and confidence of their predictions is a very important aspect, which can be judged during the validation process. One prime application of a statistically significant QSAR model is virtual screening for molecules with improved potency based on the pharmacophoric features and the descriptors appearing in the QSAR model. Validated QSAR models may also be utilized for design of focused libraries which may be subsequently screened for the selection of hits. The present review focuses on various metrics used for validation of predictive QSAR models together with an overview of the application of QSAR models in the fields of virtual screening and focused library design for diverse series of compounds with citation of some recent examples.

  16. DockoMatic 2.0: high throughput inverse virtual screening and homology modeling.

    Science.gov (United States)

    Bullock, Casey; Cornia, Nic; Jacob, Reed; Remm, Andrew; Peavey, Thomas; Weekes, Ken; Mallory, Chris; Oxford, Julia T; McDougal, Owen M; Andersen, Timothy L

    2013-08-26

    DockoMatic is a free and open source application that unifies a suite of software programs within a user-friendly graphical user interface (GUI) to facilitate molecular docking experiments. Here we describe the release of DockoMatic 2.0; significant software advances include the ability to (1) conduct high throughput inverse virtual screening (IVS); (2) construct 3D homology models; and (3) customize the user interface. Users can now efficiently setup, start, and manage IVS experiments through the DockoMatic GUI by specifying receptor(s), ligand(s), grid parameter file(s), and docking engine (either AutoDock or AutoDock Vina). DockoMatic automatically generates the needed experiment input files and output directories and allows the user to manage and monitor job progress. Upon job completion, a summary of results is generated by Dockomatic to facilitate interpretation by the user. DockoMatic functionality has also been expanded to facilitate the construction of 3D protein homology models using the Timely Integrated Modeler (TIM) wizard. The wizard TIM provides an interface that accesses the basic local alignment search tool (BLAST) and MODELER programs and guides the user through the necessary steps to easily and efficiently create 3D homology models for biomacromolecular structures. The DockoMatic GUI can be customized by the user, and the software design makes it relatively easy to integrate additional docking engines, scoring functions, or third party programs. DockoMatic is a free comprehensive molecular docking software program for all levels of scientists in both research and education.

  17. Depression Screening

    Science.gov (United States)

    ... Depression Screening Substance Abuse Screening Alcohol Use Screening Depression Screening (PHQ-9) - Instructions The following questions are ... this tool, there is also text-only version . Depression Screening - Manual Instructions The following questions are a ...

  18. High throughput ADME screening: practical considerations, impact on the portfolio and enabler of in silico ADME models.

    Science.gov (United States)

    Hop, Cornelis E C A; Cole, Mark J; Davidson, Ralph E; Duignan, David B; Federico, James; Janiszewski, John S; Jenkins, Kelly; Krueger, Suzanne; Lebowitz, Rebecca; Liston, Theodore E; Mitchell, Walter; Snyder, Mark; Steyn, Stefan J; Soglia, John R; Taylor, Christine; Troutman, Matt D; Umland, John; West, Michael; Whalen, Kevin M; Zelesky, Veronica; Zhao, Sabrina X

    2008-11-01

    Evaluation and optimization of drug metabolism and pharmacokinetic data plays an important role in drug discovery and development and several reliable in vitro ADME models are available. Recently higher throughput in vitro ADME screening facilities have been established in order to be able to evaluate an appreciable fraction of synthesized compounds. The ADME screening process can be dissected in five distinct steps: (1) plate management of compounds in need of in vitro ADME data, (2) optimization of the MS/MS method for the compounds, (3) in vitro ADME experiments and sample clean up, (4) collection and reduction of the raw LC-MS/MS data and (5) archival of the processed ADME data. All steps will be described in detail and the value of the data on drug discovery projects will be discussed as well. Finally, in vitro ADME screening can generate large quantities of data obtained under identical conditions to allow building of reliable in silico models.

  19. A model-based cost-effectiveness analysis of osteoporosis screening and treatment strategy for postmenopausal Japanese women.

    Science.gov (United States)

    Yoshimura, M; Moriwaki, K; Noto, S; Takiguchi, T

    2017-02-01

    Although an osteoporosis screening program has been implemented as a health promotion project in Japan, its cost-effectiveness has yet to be elucidated fully. We performed a cost-effectiveness analysis and found that osteoporosis screening and treatment would be cost-effective for Japanese women over 60 years. The purpose of this study was to estimate the cost-effectiveness of osteoporosis screening and drug therapy in the Japanese healthcare system for postmenopausal women with no history of fracture. A patient-level state transition model was developed to predict the outcomes of Japanese women with no previous fracture. Lifetime costs and quality-adjusted life years (QALYs) were estimated for women who receive osteoporosis screening and alendronate therapy for 5 years and those who do not receive the screening and treatments. The incremental cost-effectiveness ratio (ICER) of the screening option compared with the no screening option was estimated. Sensitivity analyses were performed to examine the influence of parameter uncertainty on the base case results. The ICERs of osteoporosis screening and treatments for Japanese women aged 50-54, 55-59, 60-64, 65-69, 70-74, and 75-79 years were estimated to be $89,242, $64,010, $40,596, $27,697, $17,027, and $9771 per QALY gained, respectively. Deterministic sensitivity analyses showed that several parameters such as the disutility due to vertebral fracture had a significant influence on the base case results. Applying a willingness to pay of $50,000 per QALY gained, the probability that the screening option became cost-effectiveness estimated to 50.9, 56.3, 59.1, and 64.7 % for women aged 60-64, 65-69, 70-74, and 75-79 years, respectively. Scenario analyses showed that the ICER for women aged 55-59 years with at least one clinical risk factor was below $50,000 per QALY. In conclusion, dual energy X-ray absorptiometry (DXA) screening and alendronate therapy for osteoporosis would be cost-effective for

  20. A joint model of persistent human papillomavirus infection and cervical cancer risk: Implications for cervical cancer screening.

    Science.gov (United States)

    Katki, Hormuzd A; Cheung, Li C; Fetterman, Barbara; Castle, Philip E; Sundaram, Rajeshwari

    2015-10-01

    New cervical cancer screening guidelines in the US and many European countries recommend that women get tested for human papillomavirus (HPV). To inform decisions about screening intervals, we calculate the increase in precancer/cancer risk per year of continued HPV infection. However, both time to onset of precancer/cancer and time to HPV clearance are interval-censored, and onset of precancer/cancer strongly informatively censors HPV clearance. We analyze this bivariate informatively interval-censored data by developing a novel joint model for time to clearance of HPV and time to precancer/cancer using shared random-effects, where the estimated mean duration of each woman's HPV infection is a covariate in the submodel for time to precancer/cancer. The model was fit to data on 9,553 HPV-positive/Pap-negative women undergoing cervical cancer screening at Kaiser Permanente Northern California, data that were pivotal to the development of US screening guidelines. We compare the implications for screening intervals of this joint model to those from population-average marginal models of precancer/cancer risk. In particular, after 2 years the marginal population-average precancer/cancer risk was 5%, suggesting a 2-year interval to control population-average risk at 5%. In contrast, the joint model reveals that almost all women exceeding 5% individual risk in 2 years also exceeded 5% in 1 year, suggesting that a 1-year interval is better to control individual risk at 5%. The example suggests that sophisticated risk models capable of predicting individual risk may have different implications than population-average risk models that are currently used for informing medical guideline development.

  1. The dynamic modeling and design improvement of a piezoelectric exciter of a touch screen device for efficient tactile feedback

    International Nuclear Information System (INIS)

    Park, Young-Min; Kim, Kwang-Joon

    2011-01-01

    Piezoelectric exciters have been receiving greater attention recently as a vibration source for tactile feedback in devices with touch screens, such as a mobile phones, in place of DC motors due to lower energy consumption and smaller volume. Their insufficient excitation level, however, still remains a problem. In this paper, dynamic modeling and design improvement of a piezoelectric exciter are presented. The excitation performance is defined as the acceleration response at the center of a touch screen per electric power and to be maximized around 250 Hz where the index finger is most sensitive. The piezoelectric exciter consists of a z-shaped metal beam, a piezoelectric layer on the long horizontal segment and an adhesive layer between the short horizontal segment and the touch screen. Assuming that the piezoelectric exciter is attached onto a rigid ground due to its low mechanical impedance compared with that of the touch screen, the piezoelectric exciter is dynamically modeled by applying Hamilton's principle, where the adhesive layer is treated as a distributed stiffness. The touch screen is modeled approximately as a simply supported beam such that it may have the same fundamental natural frequency and bending stiffness as the screen based on measurements. The performance improvement is focused on the change of five geometric parameters of the piezoelectric exciter: length of the long horizontal segment, thickness of the piezoelectric layer, thickness of the elastic metal layer, width of the beams and tip mass. The procedure to improve the performance of the piezoelectric exciter via dynamic modeling is presented together with experimental results on a prototype. Effectiveness of the design modification and limitations in practice are further discussed as well

  2. QSAR Models for Thyroperoxidase Inhibition and Screening of U.S. and EU Chemical Inventories

    DEFF Research Database (Denmark)

    Abildgaard Rosenberg, Sine; D. Watt, Eric; Judson, Richard S.

    2017-01-01

    to QSAR1. Of the substances predicted within QSAR2’s applicability domain, 8,790 (19.3%) REACH substances and 7,166 (19.0%) U.S. EPA substances, respectively, were predicted to be TPO inhibitors. A case study on butyl hydroxyanisole (BHA), which is extensively used as an antioxidant, was included.......6% (SD = 4.6%) and 85.3%, respectively. The external validation test set was subsequently merged with the training set to constitute a larger training set totaling 1,519 chemicals for a second model, QSAR2, which underwent robust cross-validation with a balanced accuracy of 82.7% (SD = 2.2%). An analysis...... of QSAR2 identified the ten most discriminating structural features for TPO inhibition and non-inhibition, respectively. Both models were used to screen 72,524 REACH substances and 32,197 U.S. EPA substances, and QSAR2 with the expanded training set had an approximately 10% larger coverages compared...

  3. Environmental fate and transport of chemical signatures from buried landmines -- Screening model formulation and initial simulations

    Energy Technology Data Exchange (ETDEWEB)

    Phelan, J.M.; Webb, S.W.

    1997-06-01

    The fate and transport of chemical signature molecules that emanate from buried landmines is strongly influenced by physical chemical properties and by environmental conditions of the specific chemical compounds. Published data have been evaluated as the input parameters that are used in the simulation of the fate and transport processes. A one-dimensional model developed for screening agricultural pesticides was modified and used to simulate the appearance of a surface flux above a buried landmine, estimate the subsurface total concentration, and show the phase specific concentrations at the ground surface. The physical chemical properties of TNT cause a majority of the mass released to the soil system to be bound to the solid phase soil particles. The majority of the transport occurs in the liquid phase with diffusion and evaporation driven advection of soil water as the primary mechanisms for the flux to the ground surface. The simulations provided herein should only be used for initial conceptual designs of chemical pre-concentration subsystems or complete detection systems. The physical processes modeled required necessary simplifying assumptions to allow for analytical solutions. Emerging numerical simulation tools will soon be available that should provide more realistic estimates that can be used to predict the success of landmine chemical detection surveys based on knowledge of the chemical and soil properties, and environmental conditions where the mines are buried. Additional measurements of the chemical properties in soils are also needed before a fully predictive approach can be confidently applied.

  4. A Model for determination of screening levels for radioactive elements in soil

    International Nuclear Information System (INIS)

    Peres, Ana C.; Hiromoto, Goro

    2008-01-01

    Full text: At the present, decision about clean-up of Brazilian sites contaminated with radioactive isotopes is addressed on a case-by-case basis, since there is no general guidance or recommendation to support actions in early phases of the problem identification. For chemicals, CETESB - the governmental organization responsible for preventing and controlling environmental pollution in Sao Paulo State - established quality reference values for prevention and intervention, as the first step to implement a remediation policy based on human health risk assessment. The aim of this study is to develop a methodology for the establishment of target values for radioactive soil contamination, as far as possible consistent and compatible with the approach adopted by CETESB for sites contaminated with chemicals. The following steps have been addressed in this study: conceptual scenario and model development; codification of the equations in an electronic spreadsheet; selection of proper input values; derivation of the intervention levels for selected radionuclides using Monte Carlo methods. The mathematical model developed was mainly based on the equations used by the U.S. Environmental Protection Agency and by the National Council on Radiation Protection and Measurements for soil screening purposes. Results are presented for selected natural and man-made radioactive isotopes. (author)

  5. Targeting Dengue Virus NS-3 Helicase by Ligand based Pharmacophore Modeling and Structure based Virtual Screening

    Science.gov (United States)

    Halim, Sobia A.; Khan, Shanza; Khan, Ajmal; Wadood, Abdul; Mabood, Fazal; Hussain, Javid; Al-Harrasi, Ahmed

    2017-10-01

    Dengue fever is an emerging public health concern, with several million viral infections occur annually, for which no effective therapy currently exist. Non-structural protein 3 (NS-3) Helicase encoded by the dengue virus (DENV) is considered as a potential drug target to design new and effective drugs against dengue. Helicase is involved in unwinding of dengue RNA. This study was conducted to design new NS-3 Helicase inhibitor by in silico ligand- and structure based approaches. Initially ligand-based pharmacophore model was generated that was used to screen a set of 1201474 compounds collected from ZINC Database. The compounds matched with the pharmacophore model were docked into the active site of NS-3 helicase. Based on docking scores and binding interactions, twenty five compounds are suggested to be potential inhibitors of NS3 Helicase. The pharmacokinetic properties of these hits were predicted. The selected hits revealed acceptable ADMET properties. This study identified potential inhibitors of NS-3 Helicase in silico, and can be helpful in the treatment of Dengue.

  6. Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 11-13 weeks gestation.

    Science.gov (United States)

    O'Gorman, Neil; Wright, David; Syngelaki, Argyro; Akolekar, Ranjit; Wright, Alan; Poon, Leona C; Nicolaides, Kypros H

    2016-01-01

    Preeclampsia affects approximately 3% of all pregnancies and is a major cause of maternal and perinatal morbidity and death. In the last decade, extensive research has been devoted to early screening for preeclampsia with the aim of reducing the prevalence of the disease through pharmacologic intervention in the high-risk group starting from the first trimester of pregnancy. The purpose of this study was to develop a model for preeclampsia based on maternal demographic characteristics and medical history (maternal factors) and biomarkers. The data for this study were derived from prospective screening for adverse obstetric outcomes in women who attended for their routine first hospital visit at 11-13 weeks gestation in 2 maternity hospitals in England. We screened 35,948 singleton pregnancies that included 1058 pregnancies (2.9%) that experienced preeclampsia. Bayes theorem was used to combine the a priori risk from maternal factors with various combinations of uterine artery pulsatility index, mean arterial pressure, serum pregnancy-associated plasma protein-A, and placental growth factor multiple of the median values. Five-fold cross validation was used to assess the performance of screening for preeclampsia that delivered at preeclampsia) and ≥37 weeks gestation (term-preeclampsia) by models that combined maternal factors with individual biomarkers and their combination with screening by maternal factors alone. In pregnancies that experienced preeclampsia, the values of uterine artery pulsatility index and mean arterial pressure were increased, and the values of serum pregnancy-associated plasma protein-A and placental growth factor were decreased. For all biomarkers, the deviation from normal was greater for early than late preeclampsia; therefore, the performance of screening was related inversely to the gestational age at which delivery became necessary for maternal and/or fetal indications. Combined screening by maternal factors, uterine artery pulsatility

  7. The Quick Peek Program: A Model for Developmental Screening within Underserved Communities

    Science.gov (United States)

    Harris, Jill; Norton, Amy

    2016-01-01

    Developmental screening of young children is important in all populations, especially underserved communities with known health care disparities. The American Academy of Pediatrics created guidelines and a toolkit for pediatricians to conduct developmental surveillance and screening, yet these guidelines are not uniformly implemented within…

  8. Neural progenitor cells as models for high-throughput screens of developmental neurotoxicity: State of the science

    NARCIS (Netherlands)

    Breier, J.M.; Gassmann, K.; Kayser, R.; Stegeman, H.; Groot, D.de; Fritsche, E.; Shafer, T.J.

    2010-01-01

    In vitro, high-throughput methods have been widely recommended as an approach to screen chemicals for the potential to cause developmental neurotoxicity and prioritize them for additional testing. The choice of cellular models for such an approach will have important ramifications for the accuracy,

  9. Methodology for the Model-based Small Area Estimates of Cancer Risk Factors and Screening Behaviors - Small Area Estimates

    Science.gov (United States)

    This model-based approach uses data from both the Behavioral Risk Factor Surveillance System (BRFSS) and the National Health Interview Survey (NHIS) to produce estimates of the prevalence rates of cancer risk factors and screening behaviors at the state, health service area, and county levels.

  10. A Model for Screening Twice-Exceptional Students (Gifted with Learning Disabilities) within a Response to Intervention Paradigm

    Science.gov (United States)

    McCallum, R. Steve; Bell, Sherry Mee; Coles, Jeremy Thomas; Miller, Kelli Caldwell; Hopkins, Michael B.; Hilton-Prillhart, Angela

    2013-01-01

    The purpose of this article is to present a model for screening for twice-exceptional status (i.e., gifted students who have a learning disability). Curriculum-based measures (Monitoring Instructional Responsiveness: Reading and Monitoring Instructional Responsiveness: Math) were administered to 1,242 third-grade students within a Response to…

  11. Screening models for releases of radionuclides to atmosphere, surface water, and ground -- Work sheets

    International Nuclear Information System (INIS)

    1996-01-01

    Three levels of screening for the atmospheric transport pathways and two levels for surface water are presented. The ground has only one screening level. Level 1 is the simplest approach and incorporates a high degree of conservatism. The estimate of the effective dose for this level assumes a concentration based upon the radionuclide concentration at the point of emission to the environment, i.e., at the stack for atmospheric emissions, at the end of the effluent pipe for liquid effluent releases, and at a well because of the buried radioactive material. Levels 2 and 3 are presented for atmospheric releases, and Level 2 for surface water releases only and are more detailed and correspondingly less conservative. Level 2 screening accounts for dispersion in the atmosphere and in surface waters and combines all recognized pathways into the screening factor. For the atmospheric pathway, Level 3 screening includes more definitive pathways analysis. Should the user be found in compliance on the basis of Level 1 screening, no further calculations are required. If the user fails Level 1, the user proceeds to the next level and checks for compliance. This process is repeated until the user passes screening (is in compliance) or no further screening levels exist. If the user fails the final level, professional assistance should be obtained in environmental radiological assessment. Work sheets are designed to lead the user through screening in a step-by-step manner until compliance is demonstrated or it is determined that more sophisticated methods or expertise are needed. Flow diagrams are provided as a guide to identify key steps in the screening process

  12. A model for determination of screening level for radioactive elements in soil

    International Nuclear Information System (INIS)

    Peres, Ana Claudia

    2007-01-01

    At the present, decision about clean-up of Brazilian sites contaminated with radioactive isotopes is addressed on a case-by-case basis, since there is no general guidance or recommendation to support actions in early phases of the problem identification. For chemicals, CETESB - the governmental organization responsible for preventing and controlling environmental pollution in Sao Paulo State - established background values, prevention and intervention, as the first step to implement a remediation actions based on human health risk assessment. The aim of this study was to develop a methodology for the establishment of target values for radioactive soil contamination, as far as possible consistent and compatible with the approach adopted by CETESB for sites contaminated with chemicals. The following steps have been addressed in this study: conceptual scenario and model development; codification of the equations in an electronic spreadsheet; selection of proper range and statistical distribution of the input values; derivation of the intervention levels for selected radionuclides using Monte Carlo methods. The mathematical model developed was mainly based on the equations used by the U.S. Environmental Protection Agency (EPA) and by the National Council on Radiation Protection and Measurements (NCRP) for soil screening purposes. Intervention and prevention values are presented for adult and 10 years old child, for each 3 exposure scenarios: agricultural, residential and industrial; the following radionuclides were considered: 3 H, 14 C, 32 P, 35 S, 45 Ca, 51 Cr, 90 Sr, 125 I, 131 I, 134 Cs, 137 Cs, 210 Pb, 226 Ra, 228 Ra, 232 Th, 238 U, 239 Pu and 241 Am. Quality reference values were determined for 40 K, 137 Cs, 210 Pb, 226 Ra, 228 Ra, 228 Th, Th-nat e U-nat. Results obtained in this study showed a good agreement with those reported by NCRP, considering that the equations and the input data used in both models are not the same ones.(author)

  13. Simulation modeling for stratified breast cancer screening - a systematic review of cost and quality of life assumptions.

    Science.gov (United States)

    Arnold, Matthias

    2017-12-02

    The economic evaluation of stratified breast cancer screening gains momentum, but produces also very diverse results. Systematic reviews so far focused on modeling techniques and epidemiologic assumptions. However, cost and utility parameters received only little attention. This systematic review assesses simulation models for stratified breast cancer screening based on their cost and utility parameters in each phase of breast cancer screening and care. A literature review was conducted to compare economic evaluations with simulation models of personalized breast cancer screening. Study quality was assessed using reporting guidelines. Cost and utility inputs were extracted, standardized and structured using a care delivery framework. Studies were then clustered according to their study aim and parameters were compared within the clusters. Eighteen studies were identified within three study clusters. Reporting quality was very diverse in all three clusters. Only two studies in cluster 1, four studies in cluster 2 and one study in cluster 3 scored high in the quality appraisal. In addition to the quality appraisal, this review assessed if the simulation models were consistent in integrating all relevant phases of care, if utility parameters were consistent and methodological sound and if cost were compatible and consistent in the actual parameters used for screening, diagnostic work up and treatment. Of 18 studies, only three studies did not show signs of potential bias. This systematic review shows that a closer look into the cost and utility parameter can help to identify potential bias. Future simulation models should focus on integrating all relevant phases of care, using methodologically sound utility parameters and avoiding inconsistent cost parameters.

  14. Development of a Clinical Forecasting Model to Predict Comorbid Depression Among Diabetes Patients and an Application in Depression Screening Policy Making

    OpenAIRE

    Jin, Haomiao; Wu, Shinyi; Di Capua, Paul

    2015-01-01

    Introduction Depression is a common but often undiagnosed comorbid condition of people with diabetes. Mass screening can detect undiagnosed depression but may require significant resources and time. The objectives of this study were 1) to develop a clinical forecasting model that predicts comorbid depression among patients with diabetes and 2) to evaluate a model-based screening policy that saves resources and time by screening only patients considered as depressed by the clinical forecasting...

  15. Screening Applications to Test Cellular Fitness in Transwell® Models After Nanoparticle Treatment.

    Science.gov (United States)

    Christ, Bastian; Fey, Christina; Cubukova, Alevtina; Walles, Heike; Dembski, Sofia; Metzger, Marco

    2017-01-01

    Nanoparticles (NPs) in biotechnology hold great promise for revolutionizing medical treatments and therapies. In order to bring NPs into clinical application there is a number of preclinical in vitro and in vivo tests, which have to be applied before. The initial in vitro evaluation includes a detailed physicochemical characterization as well as biocompatibility tests, among others. For determination of biocompatibility at the cellular level, the correct choice of the in vitro assay as well as NP pretreatment is absolutely essential. There are a variety of assay technologies available that use standard plate readers to measure metabolic markers to estimate the number of viable cells in culture. Each cell viability assay has its own set of advantages and disadvantages. Regardless of the assay method chosen, the major factors critical for reproducibility and success include: (1) choosing the right assay after comparing optical NP properties with the read-out method of the assay, (2) verifying colloidal stability of NPs in cell culture media, (3) preparing a sterile and stable NP dispersion in cell culture media used in the assay, (4) using a tightly controlled and consistent cell model allowing appropriate characterization of NPs. This chapter will briefly summarize these different critical points, which can occur during biocompatibility screening applications of NPs.

  16. Perfusion of tumor-bearing kidneys as a model for scintigraphic screening of monoclonal antibodies

    International Nuclear Information System (INIS)

    van Dijk, J.; Oosterwijk, E.; van Kroonenburgh, M.J.; Jonas, U.; Fleuren, G.J.; Pauwels, E.K.; Warnaar, S.O.

    1988-01-01

    Tumor-bearing human kidneys were used in an ex vivo perfusion model to screen monoclonal antibodies, recognizing renal cell carcinoma-associated antigens for diagnostic potential in vivo. Perfusion of tumor-bearing kidneys with /sup 99m/Tc-labeled G250 and RC38 antibody resulted in visualization of the tumor, whereas perfusion with two other monoclonal antibodies, RC2 and RC4, did not lead to tumor visualization. Uptake of radiolabel in normal kidney tissue was low for G250 and RC38 antibody. Tumor-to-kidney tissue ratios after perfusion with G250 and RC38 antibody were 2.7 and 2.2, respectively. After rinsing for 3 hr with unlabeled perfusion fluid the tumor-to-kidney tissue ratios increased to 8.6 for G250 antibody and to 2.7 for RC38 antibody. We conclude that perfusion of tumor-bearing human kidneys with radiolabeled monoclonal antibodies is a relatively simple way to evaluate renal cell carcinoma associated monoclonal antibodies as diagnostic agents in vivo

  17. Compound toxicity screening and structure-activity relationship modeling in Escherichia coli.

    Science.gov (United States)

    Planson, Anne-Gaëlle; Carbonell, Pablo; Paillard, Elodie; Pollet, Nicolas; Faulon, Jean-Loup

    2012-03-01

    Synthetic biology and metabolic engineering are used to develop new strategies for producing valuable compounds ranging from therapeutics to biofuels in engineered microorganisms. When developing methods for high-titer production cells, toxicity is an important element to consider. Indeed the production rate can be limited due to toxic intermediates or accumulation of byproducts of the heterologous biosynthetic pathway of interest. Conversely, highly toxic molecules are desired when designing antimicrobials. Compound toxicity in bacteria plays a major role in metabolic engineering as well as in the development of new antibacterial agents. Here, we screened a diversified chemical library of 166 compounds for toxicity in Escherichia coli. The dataset was built using a clustering algorithm maximizing the chemical diversity in the library. The resulting assay data was used to develop a toxicity predictor that we used to assess the toxicity of metabolites throughout the metabolome. This new tool for predicting toxicity can thus be used for fine-tuning heterologous expression and can be integrated in a computational-framework for metabolic pathway design. Many structure-activity relationship tools have been developed for toxicology studies in eukaryotes [Valerio (2009), Toxicol Appl Pharmacol, 241(3): 356-370], however, to the best of our knowledge we present here the first E. coli toxicity prediction web server based on QSAR models (EcoliTox server: http://www.issb.genopole.fr/∼faulon/EcoliTox.php). Copyright © 2011 Wiley Periodicals, Inc.

  18. A mouse model of hereditary coproporphyria identified in an ENU mutagenesis screen

    Directory of Open Access Journals (Sweden)

    Ashlee J. Conway

    2017-08-01

    Full Text Available A genome-wide ethyl-N-nitrosourea (ENU mutagenesis screen in mice was performed to identify novel regulators of erythropoiesis. Here, we describe a mouse line, RBC16, which harbours a dominantly inherited mutation in the Cpox gene, responsible for production of the haem biosynthesis enzyme, coproporphyrinogen III oxidase (CPOX. A premature stop codon in place of a tryptophan at amino acid 373 results in reduced mRNA expression and diminished protein levels, yielding a microcytic red blood cell phenotype in heterozygous mice. Urinary and faecal porphyrins in female RBC16 heterozygotes were significantly elevated compared with that of wild-type littermates, particularly coproporphyrinogen III, whereas males were biochemically normal. Attempts to induce acute porphyric crises were made using fasting and phenobarbital treatment on females. While fasting had no biochemical effect on RBC16 mice, phenobarbital caused significant elevation of faecal coproporphyrinogen III in heterozygous mice. This is the first known investigation of a mutagenesis mouse model with genetic and biochemical parallels to hereditary coproporphyria.

  19. Induced pluripotent stem cell-derived cardiomyocytes for cardiovascular disease modeling and drug screening.

    Science.gov (United States)

    Sharma, Arun; Wu, Joseph C; Wu, Sean M

    2013-12-24

    Human induced pluripotent stem cells (hiPSCs) have emerged as a novel tool for drug discovery and therapy in cardiovascular medicine. hiPSCs are functionally similar to human embryonic stem cells (hESCs) and can be derived autologously without the ethical challenges associated with hESCs. Given the limited regenerative capacity of the human heart following myocardial injury, cardiomyocytes derived from hiPSCs (hiPSC-CMs) have garnered significant attention from basic and translational scientists as a promising cell source for replacement therapy. However, ongoing issues such as cell immaturity, scale of production, inter-line variability, and cell purity will need to be resolved before human clinical trials can begin. Meanwhile, the use of hiPSCs to explore cellular mechanisms of cardiovascular diseases in vitro has proven to be extremely valuable. For example, hiPSC-CMs have been shown to recapitulate disease phenotypes from patients with monogenic cardiovascular disorders. Furthermore, patient-derived hiPSC-CMs are now providing new insights regarding drug efficacy and toxicity. This review will highlight recent advances in utilizing hiPSC-CMs for cardiac disease modeling in vitro and as a platform for drug validation. The advantages and disadvantages of using hiPSC-CMs for drug screening purposes will be explored as well.

  20. Reliability and validity of Champion's Health Belief Model Scale for breast cancer screening among Malaysian women.

    Science.gov (United States)

    Parsa, P; Kandiah, M; Mohd Nasir, M T; Hejar, A R; Nor Afiah, M Z

    2008-11-01

    Breast cancer is the leading cause of cancer deaths in Malaysian women, and the use of breast self-examination (BSE), clinical breast examination (CBE) and mammography remain low in Malaysia. Therefore, there is a need to develop a valid and reliable tool to measure the beliefs that influence breast cancer screening practices. The Champion's Health Belief Model Scale (CHBMS) is a valid and reliable tool to measure beliefs about breast cancer and screening methods in the Western culture. The purpose of this study was to translate the use of CHBMS into the Malaysian context and validate the scale among Malaysian women. A random sample of 425 women teachers was taken from 24 secondary schools in Selangor state, Malaysia. The CHBMS was translated into the Malay language, validated by an expert's panel, back translated, and pretested. Analyses included descriptive statistics of all the study variables, reliability estimates, and construct validity using factor analysis. The mean age of the respondents was 37.2 (standard deviation 7.1) years. Factor analysis yielded ten factors for BSE with eigenvalue greater than 1 (four factors more than the original): confidence 1 (ability to differentiate normal and abnormal changes in the breasts), barriers to BSE, susceptibility for breast cancer, benefits of BSE, health motivation 1 (general health), seriousness 1 (fear of breast cancer), confidence 2 (ability to detect size of lumps), seriousness 2 (fear of long-term effects of breast cancer), health motivation 2 (preventive health practice), and confidence 3 (ability to perform BSE correctly). For CBE and mammography scales, seven factors each were identified. Factors for CBE scale include susceptibility, health motivation 1, benefits of CBE, seriousness 1, barriers of CBE, seriousness 2 and health motivation 2. For mammography the scale includes benefits of mammography, susceptibility, health motivation 1, seriousness 1, barriers to mammography seriousness 2 and health

  1. Discovery of DPP IV inhibitors by pharmacophore modeling and QSAR analysis followed by in silico screening.

    Science.gov (United States)

    Al-Masri, Ihab M; Mohammad, Mohammad K; Taha, Mutasem O

    2008-11-01

    Dipeptidyl peptidase IV (DPP IV) deactivates the natural hypoglycemic incretin hormones. Inhibition of this enzyme should restore glucose homeostasis in diabetic patients making it an attractive target for the development of new antidiabetic drugs. With this in mind, the pharmacophoric space of DPP IV was explored using a set of 358 known inhibitors. Thereafter, genetic algorithm and multiple linear regression analysis were employed to select an optimal combination of pharmacophoric models and physicochemical descriptors that yield selfconsistent and predictive quantitative structure-activity relationships (QSAR) (r(2) (287)=0.74, F-statistic=44.5, r(2) (BS)=0.74, r(2) (LOO)=0.69, r(2) (PRESS) against 71 external testing inhibitors=0.51). Two orthogonal pharmacophores (of cross-correlation r(2)=0.23) emerged in the QSAR equation suggesting the existence of at least two distinct binding modes accessible to ligands within the DPP IV binding pocket. Docking experiments supported the binding modes suggested by QSAR/pharmacophore analyses. The validity of the QSAR equation and the associated pharmacophore models were established by the identification of new low-micromolar anti-DPP IV leads retrieved by in silico screening. One of our interesting potent anti-DPP IV hits is the fluoroquinolone gemifloxacin (IC(50)=1.12 muM). The fact that gemifloxacin was recently reported to potently inhibit the prodiabetic target glycogen synthase kinase 3beta (GSK-3beta) suggests that gemifloxacin is an excellent lead for the development of novel dual antidiabetic inhibitors against DPP IV and GSK-3beta.

  2. Energy metabolism and biotransformation as endpoints to pre-screen hepatotoxicity using a liver spheroid model

    International Nuclear Information System (INIS)

    Xu Jinsheng; Purcell, Wendy M.

    2006-01-01

    The current study investigated liver spheroid culture as an in vitro model to evaluate the endpoints relevant to the status of energy metabolism and biotransformation after exposure to test toxicants. Mature rat liver spheroids were exposed to diclofenac, galactosamine, isoniazid, paracetamol, m-dinitrobenzene (m-DNB) and 3-nitroaniline (3-NA) for 24 h. Pyruvate uptake, galactose biotransformation, lactate release and glucose secretion were evaluated after exposure. The results showed that pyruvate uptake and lactate release by mature liver spheroids in culture were maintained at a relatively stable level. These endpoints, together with glucose secretion and galactose biotransformation, were related to and could reflect the status of energy metabolism and biotransformation in hepatocytes. After exposure, all of the test agents significantly reduced glucose secretion, which was shown to be the most sensitive endpoint of those evaluated. Diclofenac, isoniazid, paracetamol and galactosamine reduced lactate release (P < 0.01), but m-DNB increased lactate release (P < 0.01). Diclofenac, isoniazid and paracetamol also reduced pyruvate uptake (P < 0.01), while galactosamine had little discernible effect. Diclofenac, galactosamine, paracetamol and m-DNB also reduced galactose biotransformation (P < 0.01), by contrast, isoniazid did not. The metabolite of m-DNB, 3-NA, which served as a negative control, did not cause significant changes in lactate release, pyruvate uptake or galactose biotransformation. It is concluded that pyruvate uptake, galactose biotransformation, lactate release and glucose secretion can be used as endpoints for evaluating the status of energy metabolism and biotransformation after exposure to test agents using the liver spheroid model to pre-screen hepatotoxicity

  3. Computed tomographic colonography to screen for colorectal cancer, extracolonic cancer, and aortic aneurysm: model simulation with cost-effectiveness analysis.

    Science.gov (United States)

    Hassan, Cesare; Pickhardt, Perry J; Pickhardt, Perry; Laghi, Andrea; Kim, Daniel H; Kim, Daniel; Zullo, Angelo; Iafrate, Franco; Di Giulio, Lorenzo; Morini, Sergio

    2008-04-14

    In addition to detecting colorectal neoplasia, abdominal computed tomography (CT) with colonography technique (CTC) can also detect unsuspected extracolonic cancers and abdominal aortic aneurysms (AAA).The efficacy and cost-effectiveness of this combined abdominal CT screening strategy are unknown. A computerized Markov model was constructed to simulate the occurrence of colorectal neoplasia, extracolonic malignant neoplasm, and AAA in a hypothetical cohort of 100,000 subjects from the United States who were 50 years of age. Simulated screening with CTC, using a 6-mm polyp size threshold for reporting, was compared with a competing model of optical colonoscopy (OC), both without and with abdominal ultrasonography for AAA detection (OC-US strategy). In the simulated population, CTC was the dominant screening strategy, gaining an additional 1458 and 462 life-years compared with the OC and OC-US strategies and being less costly, with a savings of $266 and $449 per person, respectively. The additional gains for CTC were largely due to a decrease in AAA-related deaths, whereas the modeled benefit from extracolonic cancer downstaging was a relatively minor factor. At sensitivity analysis, OC-US became more cost-effective only when the CTC sensitivity for large polyps dropped to 61% or when broad variations of costs were simulated, such as an increase in CTC cost from $814 to $1300 or a decrease in OC cost from $1100 to $500. With the OC-US approach, suboptimal compliance had a strong negative influence on efficacy and cost-effectiveness. The estimated mortality from CT-induced cancer was less than estimated colonoscopy-related mortality (8 vs 22 deaths), both of which were minor compared with the positive benefit from screening. When detection of extracolonic findings such as AAA and extracolonic cancer are considered in addition to colorectal neoplasia in our model simulation, CT colonography is a dominant screening strategy (ie, more clinically effective and more cost

  4. Population Screening for Hereditary Haemochromatosis in Australia: Construction and Validation of a State-Transition Cost-Effectiveness Model.

    Science.gov (United States)

    de Graaff, Barbara; Si, Lei; Neil, Amanda L; Yee, Kwang Chien; Sanderson, Kristy; Gurrin, Lyle C; Palmer, Andrew J

    2017-03-01

    HFE-associated haemochromatosis, the most common monogenic disorder amongst populations of northern European ancestry, is characterised by iron overload. Excess iron is stored in parenchymal tissues, leading to morbidity and mortality. Population screening programmes are likely to improve early diagnosis, thereby decreasing associated disease. Our aim was to develop and validate a health economics model of screening using utilities and costs from a haemochromatosis cohort. A state-transition model was developed with Markov states based on disease severity. Australian males (aged 30 years) and females (aged 45 years) of northern European ancestry were the target populations. The screening strategy was the status quo approach in Australia; the model was run over a lifetime horizon. Costs were estimated from the government perspective and reported in 2015 Australian dollars ($A); costs and quality-adjusted life-years (QALYs) were discounted at 5% annually. Model validity was assessed using goodness-of-fit analyses. Second-order Monte-Carlo simulation was used to account for uncertainty in multiple parameters. For validity, the model reproduced mortality, life expectancy (LE) and prevalence rates in line with published data. LE for C282Y homozygote males and females were 49.9 and 40.2 years, respectively, slightly lower than population rates. Mean (95% confidence interval) QALYS were 15.7 (7.7-23.7) for males and 14.4 (6.7-22.1) for females. Mean discounted lifetime costs for C282Y homozygotes were $A22,737 (3670-85,793) for males and $A13,840 (1335-67,377) for females. Sensitivity analyses revealed discount rates and prevalence had the greatest impacts on outcomes. We have developed a transparent, validated health economics model of C282Y homozygote haemochromatosis. The model will be useful to decision makers to identify cost-effective screening strategies.

  5. Refined Dummy Atom Model of Mg(2+) by Simple Parameter Screening Strategy with Revised Experimental Solvation Free Energy.

    Science.gov (United States)

    Jiang, Yang; Zhang, Haiyang; Feng, Wei; Tan, Tianwei

    2015-12-28

    Metal ions play an important role in the catalysis of metalloenzymes. To investigate metalloenzymes via molecular modeling, a set of accurate force field parameters for metal ions is highly imperative. To extend its application range and improve the performance, the dummy atom model of metal ions was refined through a simple parameter screening strategy using the Mg(2+) ion as an example. Using the AMBER ff03 force field with the TIP3P model, the refined model accurately reproduced the experimental geometric and thermodynamic properties of Mg(2+). Compared with point charge models and previous dummy atom models, the refined dummy atom model yields an enhanced performance for producing reliable ATP/GTP-Mg(2+)-protein conformations in three metalloenzyme systems with single or double metal centers. Similar to other unbounded models, the refined model failed to reproduce the Mg-Mg distance and favored a monodentate binding of carboxylate groups, and these drawbacks needed to be considered with care. The outperformance of the refined model is mainly attributed to the use of a revised (more accurate) experimental solvation free energy and a suitable free energy correction protocol. This work provides a parameter screening strategy that can be readily applied to refine the dummy atom models for metal ions.

  6. NCCN Guidelines as a Model of Extended Criteria for Lung Cancer Screening.

    Science.gov (United States)

    McKee, Brady J; Regis, Shawn; Borondy-Kitts, Andrea K; Hashim, Jeffrey A; French, Robert J; Wald, Christoph; McKee, Andrea B

    2018-04-01

    Background: This review assessed the performance of patients in NCCN high-risk group 2 in a clinical CT lung screening (CTLS) program. Methods: We retrospectively reviewed screening results for all patients from our institution undergoing clinical CTLS from January 2012 through December 2016, with follow-up through June 2017. To qualify for screening, patients had to meet the NCCN Guidelines high-risk criteria for CTLS, have a physician order for screening, be asymptomatic, be lung cancer-free for 5 years, and have no known metastatic disease. We compared demographics and screening performance of NCCN high-risk groups 1 and 2 across >4 rounds of screening. Screening metrics assessed included rates of positive and suspicious examinations, significant incidental and infectious/inflammatory findings, false negatives, and cancer detection. We also compared cancer stage and histology detected in each NCCN high-risk group. Results: A total of 2,927 individuals underwent baseline screening, of which 698 (24%) were in NCCN group 2. On average, group 2 patients were younger (60.6 vs 63.1 years), smoked less (38.8 vs 50.8 pack-years), had quit longer (18.1 vs 6.3 years), and were more often former smokers (61.4% vs 44.2%). Positive and suspicious examination rates, false negatives, and rates of infectious/inflammatory findings were equivalent in groups 1 and 2 across all rounds of screening. An increased rate of cancer detection was observed in group 2 during the second annual (T2) screening round (2.7% vs 0.5%; P =.005), with no difference in the other screening rounds: baseline (T0; 2% vs 2.3%; P =.61), first annual (T1; 1.2% vs 1.7%; P =.41), and third annual and beyond (≥T3; 1.2% vs 1.1%; P =1.00). Conclusions: CTLS appears to be equally effective in both NCCN high-risk groups. Copyright © 2018 by the National Comprehensive Cancer Network.

  7. Discovering Novel Alternaria solani Succinate Dehydrogenase Inhibitors by in Silico Modeling and Virtual Screening Strategies to Combat Early Blight

    Directory of Open Access Journals (Sweden)

    Sehrish Iftikhar

    2017-11-01

    Full Text Available Alternaria blight is an important foliage disease caused by Alternaria solani. The enzyme Succinate dehydrogenase (SDH is a potential drug target because of its role in tricarboxylic acid cycle. Hence targeting Alternaria solani SDH enzyme could be efficient tool to design novel fungicides against A. solani. We employed computational methodologies to design new SDH inhibitors using homology modeling; pharmacophore modeling and structure based virtual screening. The three dimensional SDH model showed good stereo-chemical and structural properties. Based on virtual screening results twelve commercially available compounds were purchased and tested in vitro and in vivo. The compounds were found to inhibit mycelial growth of A. solani. Moreover in vitro trials showed that inhibitory effects were enhanced with increase in concentrations. Similarly increased disease control was observed in pre-treated potato tubers. Hence the applied in silico strategy led us to identify novel fungicides.

  8. The Importance of Non-neuronal Cell Types in hiPSC-Based Disease Modeling and Drug Screening

    Directory of Open Access Journals (Sweden)

    David M. Gonzalez

    2017-12-01

    Full Text Available Current applications of human induced pluripotent stem cell (hiPSC technologies in patient-specific models of neurodegenerative and neuropsychiatric disorders tend to focus on neuronal phenotypes. Here, we review recent efforts toward advancing hiPSCs toward non-neuronal cell types of the central nervous system (CNS and highlight their potential use for the development of more complex in vitro models of neurodevelopment and disease. We present evidence from previous works in both rodents and humans of the importance of these cell types (oligodendrocytes, microglia, astrocytes in neurological disease and highlight new hiPSC-based models that have sought to explore these relationships in vitro. Lastly, we summarize efforts toward conducting high-throughput screening experiments with hiPSCs and propose methods by which new screening platforms could be designed to better capture complex relationships between neural cell populations in health and disease.

  9. High-throughput migration modelling for estimating exposure to chemicals in food packaging in screening and prioritization tools.

    Science.gov (United States)

    Ernstoff, Alexi S; Fantke, Peter; Huang, Lei; Jolliet, Olivier

    2017-11-01

    Specialty software and simplified models are often used to estimate migration of potentially toxic chemicals from packaging into food. Current models, however, are not suitable for emerging applications in decision-support tools, e.g. in Life Cycle Assessment and risk-based screening and prioritization, which require rapid computation of accurate estimates for diverse scenarios. To fulfil this need, we develop an accurate and rapid (high-throughput) model that estimates the fraction of organic chemicals migrating from polymeric packaging materials into foods. Several hundred step-wise simulations optimised the model coefficients to cover a range of user-defined scenarios (e.g. temperature). The developed model, operationalised in a spreadsheet for future dissemination, nearly instantaneously estimates chemical migration, and has improved performance over commonly used model simplifications. When using measured diffusion coefficients the model accurately predicted (R 2  = 0.9, standard error (S e ) = 0.5) hundreds of empirical data points for various scenarios. Diffusion coefficient modelling, which determines the speed of chemical transfer from package to food, was a major contributor to uncertainty and dramatically decreased model performance (R 2  = 0.4, S e  = 1). In all, this study provides a rapid migration modelling approach to estimate exposure to chemicals in food packaging for emerging screening and prioritization approaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Effects of Interventions Based on Health Behavior Models on Breast Cancer Screening Behaviors of Migrant Women in Turkey.

    Science.gov (United States)

    Tuzcu, Ayla; Bahar, Zuhal; Gözüm, Sebahat

    2016-01-01

    Antalya is a city receiving internal and external migration in Turkey, including migrant women in need of developing breast cancer screening behaviors. The aim of this study was to develop breast cancer screening behaviors of migrant women through nursing interventions based on the Health Belief Model and the Health Promotion Model. This quasi-experimental study was conducted with 200 women (100 women in the intervention group, 100 women in the control group) in Antalya. The intervention group received training, consultancy service, and reminders and was followed up at 3 and 6 months after interventions. The rates of breast self-examination, clinical breast examination and mammography were higher at months 3 and 6 in women in the intervention group compared with the women in the control group. In the intervention group, perceptions of susceptibility and barriers decreased after the interventions, and benefit, health motivation, and self-efficacy perceptions increased. According to month 6 data, in the intervention group, the decrease of each unit in perception of barriers increased the rate of breast self-examination 0.8 times and the rate of mammography 0.7 times. An increase of each unit in health motivation increased the rate of clinical breast examination 1.3 times and the rate of mammography 1.5 times. Interventions based on health behavior models positively affected breast cancer screening behaviors of migrant women. Health motivations and perceptions of barriers are determinants in performing the screening behaviors. Migrant women should be supported more by healthcare professionals regarding recognition of breast health and disease and in transportation to screening centers in their new location.

  11. Assessment of pyrrolizidine alkaloid-induced toxicity in an in vitro screening model.

    Science.gov (United States)

    Li, Yan Hong; Kan, Winnie Lai Ting; Li, Na; Lin, Ge

    2013-11-25

    and directly compared for the first time. The results suggested that the developed model has a great potential to be applied for the quick screening of the toxicity of PAs and PA-containing natural products. © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. Impact of screening and early detection of impaired fasting glucose tolerance and type 2 diabetes in Canada: a Markov model simulation

    Directory of Open Access Journals (Sweden)

    Badawi A

    2012-04-01

    Full Text Available Soroush Mortaz*, Christine Wessman*, Ross Duncan, Rachel Gray, Alaa Badawi Office of Biotechnology Genomics and Population Health, Public Health Agency of Canada, Toronto, Ontario, Canada*Both authors contributed equally to this workBackground: Type 2 diabetes mellitus (T2DM is a major global health problem. An estimated 20%–50% of diabetic subjects in Canada are currently undiagnosed, and around 20%–30% have already developed complications. Screening for high blood glucose levels can identify people with prediabetic conditions and permit introduction of timely and effective prevention. This study examines the benefit of screening for impaired fasting glucose (IFG and T2DM. If intervention is introduced at this prediabetic stage, it can be most effective in delaying the onset and complications of T2DM.Methods: Using a Markov model simulation, we compare the cost-effectiveness of screening for prediabetes (IFG and T2DM with the strategy of no screening. An initial cohort of normoglycemic, prediabetic, or undiagnosed diabetic adults with one or more T2DM risk factors was used to model the strategies mentioned over a 10-year period. Subjects without known prediabetes or diabetes are screened every 3 years and persons with prediabetes were tested for diabetes on an annual basis. The model weighs the increase in quality-adjusted life-years (QALYs associated with early detection of prediabetes and earlier diagnosis of T2DM due to lifestyle intervention and early treatment in asymptomatic subjects.Results: Costs for each QALY gained were $2281 for conventional screening compared with $2890 for no screening. Thus, in this base-case analysis, conventional screening with a frequency of once every 3 years was favored over no screening. Furthermore, conventional screening was more favorable compared with no screening over a wide range of willingness-to-pay thresholds. Changing the frequency of screening did not affect the overall results. Screening

  13. Overlapping gene expression profiles of model compounds provide opportunities for immunotoxicity screening

    International Nuclear Information System (INIS)

    Baken, Kirsten A.; Pennings, Jeroen L.A.; Jonker, Martijs J.; Schaap, Mirjam M.; Vries, Annemieke de; Steeg, Harry van; Breit, Timo M.; Loveren, Henk van

    2008-01-01

    In order to investigate immunotoxic effects of a set of model compounds in mice, a toxicogenomics approach was combined with information on macroscopical and histopathological effects on spleens and on modulation of immune function. Bis(tri-n-butyltin)oxide (TBTO), cyclosporin A (CsA), and benzo[a]pyrene (B[a]P) were administered to C57BL/6 mice at immunosuppressive dose levels. Acetaminophen (APAP) was included in the study since indications of immunomodulating properties of this compound have appeared in the literature. TBTO exposure caused the most pronounced effect on gene expression and also resulted in the most severe reduction of body weight gain and induction of splenic irregularities. All compounds caused inhibition of cell division in the spleen as shown by microarray analysis as well as by suppression of lymphocyte proliferation after application of a contact sensitizer as demonstrated in an immune function assay that was adapted from the local lymph node assay. The immunotoxicogenomics approach applied in this study thus pointed to immunosuppression through cell cycle arrest as a common mechanism of action of immunotoxicants, including APAP. Genes related to cell division such as Ccna2, Brca1, Birc5, Incenp, and Cdkn1a (p21) were identified as candidate genes to indicate anti-proliferative effects of xenobiotics in immune cells for future screening assays. The results of our experiments also show the value of group wise pathway analysis for detection of more subtle transcriptional effects and the potency of evaluation of effects in the spleen to demonstrate immunotoxicity

  14. ILP-2 modeling and virtual screening of an FDA-approved library:a possible anticancer therapy.

    Science.gov (United States)

    Khalili, Saeed; Mohammadpour, Hemn; Shokrollahi Barough, Mahideh; Kokhaei, Parviz

    2016-06-23

    The members of the inhibitors of apoptosis protein (IAP) family inhibit diverse components of the caspase signaling pathway, notably caspase 3, 7, and 9. ILP-2 (BIRC-8) is the most recently identified member of the IAPs, mainly interacting with caspase 9. This interaction would eventually lead to death resistance in the case of cancerous cells. Therefore, structural modeling of ILP-2 and finding applicable inhibitors of its interaction with caspase 9 are a compelling challenge. Three main protein modeling approaches along with various model refinement measures were harnessed to achieve a reliable 3D model, using state-of-the-art software. Thereafter, the selected model was employed to perform virtual screening of an FDA approved library. A model built by a combinatorial approach (homology and ab initio approaches) was chosen as the best model. Model refinement processes successfully bolstered the model quality. Virtual screening of the compound library introduced several high affinity inhibitor candidates that interact with functional residues of ILP2. Given the 3D structure of the ILP2 molecule, we found promising inhibitory molecules. In addition to high affinity towards the ILP2 molecule, these molecules interact with residues that play pivotal rules in ILP2-caspase interaction. These molecules would inhibit ILP2-caspase interaction and consequently would lead to reactivated cell apoptosis through the caspases pathway.

  15. Development of a Clinical Forecasting Model to Predict Comorbid Depression Among Diabetes Patients and an Application in Depression Screening Policy Making.

    Science.gov (United States)

    Jin, Haomiao; Wu, Shinyi; Di Capua, Paul

    2015-09-03

    Depression is a common but often undiagnosed comorbid condition of people with diabetes. Mass screening can detect undiagnosed depression but may require significant resources and time. The objectives of this study were 1) to develop a clinical forecasting model that predicts comorbid depression among patients with diabetes and 2) to evaluate a model-based screening policy that saves resources and time by screening only patients considered as depressed by the clinical forecasting model. We trained and validated 4 machine learning models by using data from 2 safety-net clinical trials; we chose the one with the best overall predictive ability as the ultimate model. We compared model-based policy with alternative policies, including mass screening and partial screening, on the basis of depression history or diabetes severity. Logistic regression had the best overall predictive ability of the 4 models evaluated and was chosen as the ultimate forecasting model. Compared with mass screening, the model-based policy can save approximately 50% to 60% of provider resources and time but will miss identifying about 30% of patients with depression. Partial-screening policy based on depression history alone found only a low rate of depression. Two other heuristic-based partial screening policies identified depression at rates similar to those of the model-based policy but cost more in resources and time. The depression prediction model developed in this study has compelling predictive ability. By adopting the model-based depression screening policy, health care providers can use their resources and time better and increase their efficiency in managing their patients with depression.

  16. Is computer aided detection (CAD) cost effective in screening mammography? A model based on the CADET II study

    Science.gov (United States)

    2011-01-01

    provides updated estimates of CAD costs in a full-field digital system and assessment cost for women who are re-called after initial screening. However, the model is highly sensitive to various parameters e.g. reading time, reader qualification, and equipment cost. PMID:21241473

  17. Predictive models for anti-tubercular molecules using machine learning on high-throughput biological screening datasets.

    Science.gov (United States)

    Periwal, Vinita; Rajappan, Jinuraj K; Jaleel, Abdul Uc; Scaria, Vinod

    2011-11-18

    Tuberculosis is a contagious disease caused by Mycobacterium tuberculosis (Mtb), affecting more than two billion people around the globe and is one of the major causes of morbidity and mortality in the developing world. Recent reports suggest that Mtb has been developing resistance to the widely used anti-tubercular drugs resulting in the emergence and spread of multi drug-resistant (MDR) and extensively drug-resistant (XDR) strains throughout the world. In view of this global epidemic, there is an urgent need to facilitate fast and efficient lead identification methodologies. Target based screening of large compound libraries has been widely used as a fast and efficient approach for lead identification, but is restricted by the knowledge about the target structure. Whole organism screens on the other hand are target-agnostic and have been now widely employed as an alternative for lead identification but they are limited by the time and cost involved in running the screens for large compound libraries. This could be possibly be circumvented by using computational approaches to prioritize molecules for screening programmes. We utilized physicochemical properties of compounds to train four supervised classifiers (Naïve Bayes, Random Forest, J48 and SMO) on three publicly available bioassay screens of Mtb inhibitors and validated the robustness of the predictive models using various statistical measures. This study is a comprehensive analysis of high-throughput bioassay data for anti-tubercular activity and the application of machine learning approaches to create target-agnostic predictive models for anti-tubercular agents.

  18. Predictive models for anti-tubercular molecules using machine learning on high-throughput biological screening datasets

    Directory of Open Access Journals (Sweden)

    Periwal Vinita

    2011-11-01

    Full Text Available Abstract Background Tuberculosis is a contagious disease caused by Mycobacterium tuberculosis (Mtb, affecting more than two billion people around the globe and is one of the major causes of morbidity and mortality in the developing world. Recent reports suggest that Mtb has been developing resistance to the widely used anti-tubercular drugs resulting in the emergence and spread of multi drug-resistant (MDR and extensively drug-resistant (XDR strains throughout the world. In view of this global epidemic, there is an urgent need to facilitate fast and efficient lead identification methodologies. Target based screening of large compound libraries has been widely used as a fast and efficient approach for lead identification, but is restricted by the knowledge about the target structure. Whole organism screens on the other hand are target-agnostic and have been now widely employed as an alternative for lead identification but they are limited by the time and cost involved in running the screens for large compound libraries. This could be possibly be circumvented by using computational approaches to prioritize molecules for screening programmes. Results We utilized physicochemical properties of compounds to train four supervised classifiers (Naïve Bayes, Random Forest, J48 and SMO on three publicly available bioassay screens of Mtb inhibitors and validated the robustness of the predictive models using various statistical measures. Conclusions This study is a comprehensive analysis of high-throughput bioassay data for anti-tubercular activity and the application of machine learning approaches to create target-agnostic predictive models for anti-tubercular agents.

  19. Target specific proteochemometric model development for BACE1 - protein flexibility and structural water are critical in virtual screening.

    Science.gov (United States)

    Manoharan, Prabu; Chennoju, Kiranmai; Ghoshal, Nanda

    2015-07-01

    BACE1 is an attractive target in Alzheimer's disease (AD) treatment. A rational drug design effort for the inhibition of BACE1 is actively pursued by researchers in both academic and pharmaceutical industries. This continued effort led to the steady accumulation of BACE1 crystal structures, co-complexed with different classes of inhibitors. This wealth of information is used in this study to develop target specific proteochemometric models and these models are exploited for predicting the prospective BACE1 inhibitors. The models developed in this study have performed excellently in predicting the computationally generated poses, separately obtained from single and ensemble docking approaches. The simple protein-ligand contact (SPLC) model outperforms other sophisticated high end models, in virtual screening performance, developed during this study. In an attempt to account for BACE1 protein active site flexibility information in predictive models, we included the change in the area of solvent accessible surface and the change in the volume of solvent accessible surface in our models. The ensemble and single receptor docking results obtained from this study indicate that the structural water mediated interactions improve the virtual screening results. Also, these waters are essential for recapitulating bioactive conformation during docking study. The proteochemometric models developed in this study can be used for the prediction of BACE1 inhibitors, during the early stage of AD drug discovery.

  20. Modelling the cost-effectiveness of mass screening and treatment for reducing Plasmodium falciparum malaria burden

    Directory of Open Access Journals (Sweden)

    Crowell Valerie

    2013-01-01

    Full Text Available Abstract Background Past experience and modelling suggest that, in most cases, mass treatment strategies are not likely to succeed in interrupting Plasmodium falciparum malaria transmission. However, this does not preclude their use to reduce disease burden. Mass screening and treatment (MSAT is preferred to mass drug administration (MDA, as the latter involves massive over-use of drugs. This paper reports simulations of the incremental cost-effectiveness of well-conducted MSAT campaigns as a strategy for P. falciparum malaria disease-burden reduction in settings with varying receptivity (ability of the combined vector population in a setting to transmit disease and access to case management. Methods MSAT incremental cost-effectiveness ratios (ICERs were estimated in different sub-Saharan African settings using simulation models of the dynamics of malaria and a literature-based MSAT cost estimate. Imported infections were simulated at a rate of two per 1,000 population per annum. These estimates were compared to the ICERs of scaling up case management or insecticide-treated net (ITN coverage in each baseline health system, in the absence of MSAT. Results MSAT averted most episodes, and resulted in the lowest ICERs, in settings with a moderate level of disease burden. At a low pre-intervention entomological inoculation rate (EIR of two infectious bites per adult per annum (IBPAPA MSAT was never more cost-effective than scaling up ITNs or case management coverage. However, at pre-intervention entomological inoculation rates (EIRs of 20 and 50 IBPAPA and ITN coverage levels of 40 or 60%, respectively, the ICER of MSAT was similar to that of scaling up ITN coverage further. Conclusions In all the transmission settings considered, achieving a minimal level of ITN coverage is a “best buy”. At low transmission, MSAT probably is not worth considering. Instead, MSAT may be suitable at medium to high levels of transmission and at moderate ITN coverage

  1. FieldChopper, a new tool for automatic model generation and virtual screening based on molecular fields.

    Science.gov (United States)

    Kalliokoski, Tuomo; Ronkko, Toni; Poso, Antti

    2008-06-01

    Algorithms were developed for ligand-based virtual screening of molecular databases. FieldChopper (FC) is based on the discretization of the electrostatic and van der Waals field into three classes. A model is built from a set of superimposed active molecules. The similarity of the compounds in the database to the model is then calculated using matrices that define scores for comparing field values of different categories. The method was validated using 12 publicly available data sets by comparing the method to the electrostatic similarity comparison program EON. The results suggest that FC is competitive with more complex descriptors and could be used as a molecular sieve in virtual screening experiments when multiple active ligands are known.

  2. Health behavior change models and their socio-cultural relevance for breast cancer screening in African American women.

    Science.gov (United States)

    Ashing-Giwa, K

    1999-01-01

    Models of health behavior provide the conceptual bases for most of the breast cancer screening intervention studies. These models were not designed for and have not been adequately tested with African American women. The models discussed in this paper are: The Health Belief Model, the Theory of Reasoned Action/Theory of Planned Behavior, and the Transtheoretical Model. This paper will examine the socio-cultural relevance of these health behavior models, and discuss specific socio-cultural dimensions that are not accounted for by these paradigms. It is critical that researchers include socio-cultural dimensions, such as interconnectedness, health socialization, ecological factors and health care system factors into their intervention models with African American women. Comprehensive and socio-culturally based investigations are necessary to guide the scientific and policy challenge for reducing breast cancer mortality in African American women.

  3. Stem cells: a model for screening, discovery and development of drugs.

    Science.gov (United States)

    Kitambi, Satish Srinivas; Chandrasekar, Gayathri

    2011-01-01

    The identification of normal and cancerous stem cells and the recent advances made in isolation and culture of stem cells have rapidly gained attention in the field of drug discovery and regenerative medicine. The prospect of performing screens aimed at proliferation, directed differentiation, and toxicity and efficacy studies using stem cells offers a reliable platform for the drug discovery process. Advances made in the generation of induced pluripotent stem cells from normal or diseased tissue serves as a platform to perform drug screens aimed at developing cell-based therapies against conditions like Parkinson's disease and diabetes. This review discusses the application of stem cells and cancer stem cells in drug screening and their role in complementing, reducing, and replacing animal testing. In addition to this, target identification and major advances in the field of personalized medicine using induced pluripotent cells are also discussed.

  4. Modelling of the mammographic exposure conditions for radiological detriment study in the Valencian Breast Cancer Screening Programme

    International Nuclear Information System (INIS)

    Ferrer, S.; Ramos, M.; Villaescusa, J. I.; Verdu, G.; Salas, M. D.; Cuevas, M. D.

    2005-01-01

    Breast screening programmes are the best weapon to fight against breast cancer. Nevertheless, despite the benefits, this practice supposes a radiological risk that cannot be forgotten. In order to calculate breast glandular doses, different MCNP-4C2 models have been developed, simulating the exposure conditions. Radiological detriments have been transported from the population under study in the UNSCEAR 2000 to the Valencian Community, obtaining the detection-induced cancer ratio (DICR) for this population. (authors)

  5. High-throughput screening for novel anti-infectives using a C. elegans pathogenesis model.

    Science.gov (United States)

    Conery, Annie L; Larkins-Ford, Jonah; Ausubel, Frederick M; Kirienko, Natalia V

    2014-03-14

    In recent history, the nematode Caenorhabditis elegans has provided a compelling platform for the discovery of novel antimicrobial drugs. In this protocol, we present an automated, high-throughput C. elegans pathogenesis assay, which can be used to screen for anti-infective compounds that prevent nematodes from dying due to Pseudomonas aeruginosa. New antibiotics identified from such screens would be promising candidates for treatment of human infections, and also can be used as probe compounds to identify novel targets in microbial pathogenesis or host immunity. Copyright © 2014 John Wiley & Sons, Inc.

  6. A prediction model-based algorithm for computer-assisted database screening of adverse drug reactions in the Netherlands.

    Science.gov (United States)

    Scholl, Joep H G; van Hunsel, Florence P A M; Hak, Eelko; van Puijenbroek, Eugène P

    2018-02-01

    The statistical screening of pharmacovigilance databases containing spontaneously reported adverse drug reactions (ADRs) is mainly based on disproportionality analysis. The aim of this study was to improve the efficiency of full database screening using a prediction model-based approach. A logistic regression-based prediction model containing 5 candidate predictors was developed and internally validated using the Summary of Product Characteristics as the gold standard for the outcome. All drug-ADR associations, with the exception of those related to vaccines, with a minimum of 3 reports formed the training data for the model. Performance was based on the area under the receiver operating characteristic curve (AUC). Results were compared with the current method of database screening based on the number of previously analyzed associations. A total of 25 026 unique drug-ADR associations formed the training data for the model. The final model contained all 5 candidate predictors (number of reports, disproportionality, reports from healthcare professionals, reports from marketing authorization holders, Naranjo score). The AUC for the full model was 0.740 (95% CI; 0.734-0.747). The internal validity was good based on the calibration curve and bootstrapping analysis (AUC after bootstrapping = 0.739). Compared with the old method, the AUC increased from 0.649 to 0.740, and the proportion of potential signals increased by approximately 50% (from 12.3% to 19.4%). A prediction model-based approach can be a useful tool to create priority-based listings for signal detection in databases consisting of spontaneous ADRs. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

  7. Screening for Adverse Childhood Experiences (ACEs) in an Integrated Pediatric Care Model

    Science.gov (United States)

    Purewal, Sukhdip K.; Bucci, Monica; Wang, Lisa Gutiérrez; Koita, Kadiatou; Marques, Sara Silvério; Oh, Debora; Harris, Nadine Burke

    2016-01-01

    Adverse childhood experiences (ACEs) are stressful or traumatic events that place children at risk of negative health, mental health, and behavioral outcomes. The Center for Youth Wellness (CYW), working in partnership with the Bayview Child Health Center (BCHC), pioneered ACE screening for children and adolescents. This article describes the…

  8. Systematic screening for Chlamydia trachomatis : Estimating cost-effectiveness using dynamic modeling and Dutch data

    NARCIS (Netherlands)

    de Vries, R.; Van Bergen, J.E.A.M.; de Jong-van den Berg, Lolkje; Postma, Maarten

    2006-01-01

    To estimate the cost-effectiveness of a systematic one-off Chlamydia trachomatis (CT) screening program including partner treatment for Dutch young adults. Data on infection prevalence, participation rates, and sexual behavior were obtained from a large pilot study conducted in The Netherlands.

  9. Systematic screening for Chlamydia trachomatis: estimating cost-effectiveness using dynamic modeling and Dutch data

    NARCIS (Netherlands)

    de Vries, Robin; van Bergen, Jan E. A. M.; de Jong-van den Berg, Lolkje T. W.; Postma, Maarten J.

    2006-01-01

    To estimate the cost-effectiveness of a systematic one-off Chlamydia trachomatis (CT) screening program including partner treatment for Dutch young adults. Data on infection prevalence, participation rates, and sexual behavior were obtained from a large pilot study conducted in The Netherlands.

  10. Direct and indirect effects of screening for Chlamydia trachomatis on the prevention of pelvic inflammatory disease: a mathematical modeling study.

    Science.gov (United States)

    Herzog, Sereina A; Heijne, Janneke C M; Scott, Pippa; Althaus, Christian L; Low, Nicola

    2013-11-01

    Pelvic inflammatory disease (PID) results from the ascending spread of microorganisms, including Chlamydia trachomatis, to the upper genital tract. Screening could improve outcomes by identifying and treating chlamydial infections before they progress to PID (direct effect) or by reducing chlamydia transmission (indirect effect). We developed a compartmental model that represents a hypothetical heterosexual population and explicitly incorporates progression from chlamydia to clinical PID. Chlamydia screening was introduced, with coverage increasing each year for 10 years. We estimated the separate contributions of the direct and indirect effects of screening on PID cases prevented per 100,000 women. We explored the influence of varying the time point at which clinical PID could occur and of increasing the risk of PID after repeated chlamydial infections. The probability of PID at baseline was 3.1% by age 25 years. After 5 years, the intervention scenario had prevented 187 PID cases per 100,000 women and after 10 years 956 PID cases per 100,000 women. At the start of screening, most PID cases were prevented by the direct effect. The indirect effect produced a small net increase in PID cases, which was outweighed by the effect of reduced chlamydia transmission after 2.2 years. The later that progression to PID occurs, the greater the contribution of the direct effect. Increasing the risk of PID with repeated chlamydial infection increases the number of PID cases prevented by screening. This study shows the separate roles of direct and indirect PID prevention and potential harms, which cannot be demonstrated in observational studies.

  11. Long-Term Impact of the Dutch Colorectal Cancer Screening Program on Cancer Incidence and Mortality-Model-Based Exploration of the Serrated Pathway

    NARCIS (Netherlands)

    Greuter, Marjolein J. E.; Demirel, Erhan; Lew, Jie-Bin; Berkhof, Johannes; Xu, Xiang-Ming; Canfell, Karen; Dekker, Evelien; Meijer, Gerrit A.; Coupé, Veerle M. H.

    2016-01-01

    We aimed to predict the long-term colorectal cancer incidence, mortality, and colonoscopy demand of the recently implemented Dutch colorectal cancer screening program. The Adenoma and Serrated pathway to Colorectal Cancer model was set up to simulate the Dutch screening program consisting of

  12. Hsp90 inhibitors, part 1: definition of 3-D QSAutogrid/R models as a tool for virtual screening.

    Science.gov (United States)

    Ballante, Flavio; Caroli, Antonia; Wickersham, Richard B; Ragno, Rino

    2014-03-24

    The multichaperone heat shock protein (Hsp) 90 complex mediates the maturation and stability of a variety of oncogenic signaling proteins. For this reason, Hsp90 has emerged as a promising target for anticancer drug development. Herein, we describe a complete computational procedure for building several 3-D QSAR models used as a ligand-based (LB) component of a comprehensive ligand-based (LB) and structure-based (SB) virtual screening (VS) protocol to identify novel molecular scaffolds of Hsp90 inhibitors. By the application of the 3-D QSAutogrid/R method, eight SB PLS 3-D QSAR models were generated, leading to a final multiprobe (MP) 3-D QSAR pharmacophoric model capable of recognizing the most significant chemical features for Hsp90 inhibition. Both the monoprobe and multiprobe models were optimized, cross-validated, and tested against an external test set. The obtained statistical results confirmed the models as robust and predictive to be used in a subsequent VS.

  13. A model to evaluate the costs and clinical effectiveness of human papilloma virus screening compared with annual papanicolaou cytology in Germany.

    Science.gov (United States)

    Petry, Karl Ulrich; Barth, Cordula; Wasem, Jürgen; Neumann, Anja

    2017-05-01

    We modelled human papilloma virus (HPV) primary screening scenarios compared with Pap cytology to evaluate clinical effectiveness and projected annual costs in Germany. A Markov cohort model was built to compare the budget impact of annual Pap cytology with different 5-yearly HPV screening scenarios: (1) a positive HPV test followed by Pap cytology; (2) a positive HPV test followed by p16/Ki-67 dual-stained cytology; (3) a positive HPV test followed by colposcopy if HPV-16/18-positive or p16/Ki-67 dual-stained cytology if positive for other subtypes; (4) co-testing with HPV and Pap. Screening scenarios were based on a 10-year horizon. All HPV screening scenarios in the model were associated with fewer deaths from missed diagnosis of cervical cancer compared with Pap screening; 10-year totals n=172-344 (1.5-3 per 100,000) versus n=477 (4.1 per 100,000), respectively. Total annual costs were lower with HPV screening than Pap cytology. The projected average annual cost for HPV screening ranged from €117 million to €136 million compared with €177 million for Pap screening, representing annual savings of €41-60 million. The greatest clinical impact was achieved with primary HPV screening (with genotyping) followed by colposcopy for HPV 16/18-positive women or p16/Ki-67 dual-stained cytology for women positive for other HPV subtypes. Screening strategies including primary HPV testing for high-risk subtypes (HPV-16/18) in conjunction with p16/Ki-67 dual-stained cytology can improve the detection of cervical cancer at a lower total annual cost than conventional Pap cytology screening. Copyright © 2017. Published by Elsevier B.V.

  14. Air Pollution Dispersion Modeling of Abadan oil Refinery Using SCREEN3

    International Nuclear Information System (INIS)

    Hedayati Rad, F.; Salman-Mahini, A.; Mirkarimi, H.

    2016-01-01

    Air pollution is a major problem that has been recognized throughout the world. Refineriers normally create environmental pollution through emissions of pollutants gaseous from a variety of sources. Analysing air pollution distribution and dispersion can help in reducing the negative effects. In this study NO_X and SO_2 emissions and distributions were investigated for Abadan oil refinery using SCREEN3 software. In this softweare, wind speed and direction, air temperature, location and physical characteristics of chimnies and atmospheric stability were taken into consideration.The concentration of pollutants in different distances from the stacks in the range 25 km were predicted and mapped in Idrisi software. The output from software SCREEN3 for emissions from stacks were also examined and compared with the standard output of the refineries. According to our results, the concentration of pollutants in summer and autumn seasons exceeds of the environmental standards.

  15. Modeling nanoscale gas sensors under realistic conditions: Computational screening of metal-doped carbon nanotubes

    DEFF Research Database (Denmark)

    García Lastra, Juan Maria; Mowbray, Duncan; Thygesen, Kristian Sommer

    2010-01-01

    We use computational screening to systematically investigate the use of transition-metal-doped carbon nanotubes for chemical-gas sensing. For a set of relevant target molecules (CO, NH3, and H2S) and the main components of air (N2, O2, and H2O), we calculate the binding energy and change in condu......We use computational screening to systematically investigate the use of transition-metal-doped carbon nanotubes for chemical-gas sensing. For a set of relevant target molecules (CO, NH3, and H2S) and the main components of air (N2, O2, and H2O), we calculate the binding energy and change...... the change in the nanotube resistance per doping site as a function of the target molecule concentration assuming charge transport in the diffusive regime. Our analysis points to Ni-doped nanotubes as candidates for CO sensors working under typical atmospheric conditions....

  16. Stem cells: a model for screening, discovery and development of drugs

    OpenAIRE

    Kitambi, Satish Srinivas; Chandrasekar, Gayathri

    2011-01-01

    Satish Srinivas Kitambi1, Gayathri Chandrasekar21Department of Medical Biochemistry and Biophysics; 2Department of Biosciences, Karolinska Institutet, Stockholm, SwedenAbstract: The identification of normal and cancerous stem cells and the recent advances made in isolation and culture of stem cells have rapidly gained attention in the field of drug discovery and regenerative medicine. The prospect of performing screens aimed at proliferation, directed differentiation, and toxicity and efficac...

  17. Modelling and comparison studies of packed screen regenerators for active magnetocaloric refrigeration

    DEFF Research Database (Denmark)

    Lei, Tian; Engelbrecht, Kurt; Nielsen, K. K.

    2011-01-01

    In active magnetic regeneration (AMR) systems, not only the magnetocaloric properties of materials, but also the regenerator geometry plays an important role in the system performance. Packed sphere regenerators are often employed in existing prototypes, however, the characteristics such as relat...... is improved and applied to simulate the regenerators. The performance of the new regenerators is studied and compared with that of the packed sphere regenerators. Possible fabrication methods of the packed screen regenerators are also discussed....

  18. Modelling and comparison studies of packed screen regenerators for active magnetocaloric refrigeration

    DEFF Research Database (Denmark)

    Lei, Tian; Engelbrecht, Kurt; Nielsen, Kaspar Kirstein

    2014-01-01

    In active magnetic regeneration (AMR) systems, not only the magnetocaloric properties of materials, but also the regenerator geometry plays an important role in the system performance. Packed sphere regenerators are often employed in existing prototypes, however, the characteristics such as relat...... is improved and applied to simulate the regenerators. The performance of the new regenerators is studied and compared with that of the packed sphere regenerators. Possible fabrication methods of the packed screen regenerators are also discussed....

  19. Role of Chemical Reactivity and Transition State Modeling for Virtual Screening.

    Science.gov (United States)

    Karthikeyan, Muthukumarasamy; Vyas, Renu; Tambe, Sanjeev S; Radhamohan, Deepthi; Kulkarni, Bhaskar D

    2015-01-01

    Every drug discovery research program involves synthesis of a novel and potential drug molecule utilizing atom efficient, economical and environment friendly synthetic strategies. The current work focuses on the role of the reactivity based fingerprints of compounds as filters for virtual screening using a tool ChemScore. A reactant-like (RLS) and a product- like (PLS) score can be predicted for a given compound using the binary fingerprints derived from the numerous known organic reactions which capture the molecule-molecule interactions in the form of addition, substitution, rearrangement, elimination and isomerization reactions. The reaction fingerprints were applied to large databases in biology and chemistry, namely ChEMBL, KEGG, HMDB, DSSTox, and the Drug Bank database. A large network of 1113 synthetic reactions was constructed to visualize and ascertain the reactant product mappings in the chemical reaction space. The cumulative reaction fingerprints were computed for 4000 molecules belonging to 29 therapeutic classes of compounds, and these were found capable of discriminating between the cognition disorder related and anti-allergy compounds with reasonable accuracy of 75% and AUC 0.8. In this study, the transition state based fingerprints were also developed and used effectively for virtual screening in drug related databases. The methodology presented here provides an efficient handle for the rapid scoring of molecular libraries for virtual screening.

  20. Sensitivity of ecological soil-screening levels for metals to exposure model parameterization and toxicity reference values.

    Science.gov (United States)

    Sample, Bradley E; Fairbrother, Anne; Kaiser, Ashley; Law, Sheryl; Adams, Bill

    2014-10-01

    Ecological soil-screening levels (Eco-SSLs) were developed by the United States Environmental Protection Agency (USEPA) for the purposes of setting conservative soil screening values that can be used to eliminate the need for further ecological assessment for specific analytes at a given site. Ecological soil-screening levels for wildlife represent a simplified dietary exposure model solved in terms of soil concentrations to produce exposure equal to a no-observed-adverse-effect toxicity reference value (TRV). Sensitivity analyses were performed for 6 avian and mammalian model species, and 16 metals/metalloids for which Eco-SSLs have been developed. The relative influence of model parameters was expressed as the absolute value of the range of variation observed in the resulting soil concentration when exposure is equal to the TRV. Rank analysis of variance was used to identify parameters with greatest influence on model output. For both birds and mammals, soil ingestion displayed the broadest overall range (variability), although TRVs consistently had the greatest influence on calculated soil concentrations; bioavailability in food was consistently the least influential parameter, although an important site-specific variable. Relative importance of parameters differed by trophic group. Soil ingestion ranked 2nd for carnivores and herbivores, but was 4th for invertivores. Different patterns were exhibited, depending on which parameter, trophic group, and analyte combination was considered. The approach for TRV selection was also examined in detail, with Cu as the representative analyte. The underlying assumption that generic body-weight-normalized TRVs can be used to derive protective levels for any species is not supported by the data. Whereas the use of site-, species-, and analyte-specific exposure parameters is recommended to reduce variation in exposure estimates (soil protection level), improvement of TRVs is more problematic. © 2014 The Authors

  1. A partial exponential lumped parameter model to evaluate groundwater age distributions and nitrate trends in long-screened wells

    Science.gov (United States)

    Jurgens, Bryant; Böhlke, John Karl; Kauffman, Leon J.; Belitz, Kenneth; Esser, Bradley K.

    2016-01-01

    A partial exponential lumped parameter model (PEM) was derived to determine age distributions and nitrate trends in long-screened production wells. The PEM can simulate age distributions for wells screened over any finite interval of an aquifer that has an exponential distribution of age with depth. The PEM has 3 parameters – the ratio of saturated thickness to the top and bottom of the screen and mean age, but these can be reduced to 1 parameter (mean age) by using well construction information and estimates of the saturated thickness. The PEM was tested with data from 30 production wells in a heterogeneous alluvial fan aquifer in California, USA. Well construction data were used to guide parameterization of a PEM for each well and mean age was calibrated to measured environmental tracer data (3H, 3He, CFC-113, and 14C). Results were compared to age distributions generated for individual wells using advective particle tracking models (PTMs). Age distributions from PTMs were more complex than PEM distributions, but PEMs provided better fits to tracer data, partly because the PTMs did not simulate 14C accurately in wells that captured varying amounts of old groundwater recharged at lower rates prior to groundwater development and irrigation. Nitrate trends were simulated independently of the calibration process and the PEM provided good fits for at least 11 of 24 wells. This work shows that the PEM, and lumped parameter models (LPMs) in general, can often identify critical features of the age distributions in wells that are needed to explain observed tracer data and nonpoint source contaminant trends, even in systems where aquifer heterogeneity and water-use complicate distributions of age. While accurate PTMs are preferable for understanding and predicting aquifer-scale responses to water use and contaminant transport, LPMs can be sensitive to local conditions near individual wells that may be inaccurately represented or missing in an aquifer-scale flow model.

  2. The health system and population health implications of large-scale diabetes screening in India: a microsimulation model of alternative approaches.

    Directory of Open Access Journals (Sweden)

    Sanjay Basu

    2015-05-01

    Full Text Available Like a growing number of rapidly developing countries, India has begun to develop a system for large-scale community-based screening for diabetes. We sought to identify the implications of using alternative screening instruments to detect people with undiagnosed type 2 diabetes among diverse populations across India.We developed and validated a microsimulation model that incorporated data from 58 studies from across the country into a nationally representative sample of Indians aged 25-65 y old. We estimated the diagnostic and health system implications of three major survey-based screening instruments and random glucometer-based screening. Of the 567 million Indians eligible for screening, depending on which of four screening approaches is utilized, between 158 and 306 million would be expected to screen as "high risk" for type 2 diabetes, and be referred for confirmatory testing. Between 26 million and 37 million of these people would be expected to meet international diagnostic criteria for diabetes, but between 126 million and 273 million would be "false positives." The ratio of false positives to true positives varied from 3.9 (when using random glucose screening to 8.2 (when using a survey-based screening instrument in our model. The cost per case found would be expected to be from US$5.28 (when using random glucose screening to US$17.06 (when using a survey-based screening instrument, presenting a total cost of between US$169 and US$567 million. The major limitation of our analysis is its dependence on published cohort studies that are unlikely fully to capture the poorest and most rural areas of the country. Because these areas are thought to have the lowest diabetes prevalence, this may result in overestimation of the efficacy and health benefits of screening.Large-scale community-based screening is anticipated to produce a large number of false-positive results, particularly if using currently available survey-based screening

  3. The Gap-Startle Paradigm for Tinnitus Screening in Animal Models: Limitations and Optimization

    Science.gov (United States)

    Lobarinas, Edward; Hayes, Sarah H.; Allman, Brian L.

    2012-01-01

    In 2006, Turner and colleagues (Behav Neurosci, 120:188–195) introduced the gap-startle paradigm as a high-throughput method for tinnitus screening in rats. Under this paradigm, gap detection ability was assessed by determining the level of inhibition of the acoustic startle reflex produced by a short silent gap inserted in an otherwise continuous background sound prior to a loud startling stimulus. Animals with tinnitus were expected to show impaired gap detection ability (i.e., lack of inhibition of the acoustic startle reflex) if the background sound containing the gap was qualitatively similar to the tinnitus pitch. Thus, for the gap-startle paradigm to be a valid tool to screen for tinnitus, a robust startle response from which to inhibit must be present. Because recent studies have demonstrated that the acoustic startle reflex could be dramatically reduced following noise exposure, we endeavored to 1) modify the gap-startle paradigm to be more resilient in the presence of hearing loss, and 2) evaluate whether a reduction in startle reactivity could confound the interpretation of gap prepulse inhibition and lead to errors in screening for tinnitus. In the first experiment, the traditional broadband noise (BBN) startle stimulus was replaced by a bandpass noise in which the sound energy was concentrated in the lower frequencies (5–10 kHz) in order to maintain audibility of the startle stimulus after unilateral high frequency noise exposure (16 kHz). However, rats still showed a 57% reduction in startle amplitude to the bandpass noise post-noise exposure. A follow-up experiment on a separate group of rats with transiently-induced conductive hearing loss revealed that startle reactivity was better preserved when the BBN startle stimulus was replaced by a rapid airpuff to the back of the rats neck. Furthermore, it was found that transient unilateral conductive hearing loss, which was not likely to induce tinnitus, caused an impairment in gap prepulse inhibition

  4. A DPSIR model for ecological security assessment through indicator screening: a case study at Dianchi Lake in China.

    Directory of Open Access Journals (Sweden)

    Zhen Wang

    Full Text Available Given the important role of lake ecosystems in social and economic development, and the current severe environmental degradation in China, a systematic diagnosis of the ecological security of lakes is essential for sustainable development. A Driving-force, Pressure, Status, Impact, and Risk (DPSIR model, combined with data screening for lake ecological security assessment was developed to overcome the disadvantages of data selection in existing assessment methods. Correlation and principal component analysis were used to select independent and representative data. The DPSIR model was then applied to evaluate the ecological security of Dianchi Lake in China during 1988-2007 using an ecological security index. The results revealed a V-shaped trend. The application of the DPSIR model with data screening provided useful information regarding the status of the lake's ecosystem, while ensuring information efficiency and eliminating multicollinearity. The modeling approach described here is practical and operationally efficient, and provides an attractive alternative approach to assess the ecological security of lakes.

  5. Budget Impact Analysis of Switching to Digital Mammography in a Population-Based Breast Cancer Screening Program: A Discrete Event Simulation Model

    Science.gov (United States)

    Comas, Mercè; Arrospide, Arantzazu; Mar, Javier; Sala, Maria; Vilaprinyó, Ester; Hernández, Cristina; Cots, Francesc; Martínez, Juan; Castells, Xavier

    2014-01-01

    Objective To assess the budgetary impact of switching from screen-film mammography to full-field digital mammography in a population-based breast cancer screening program. Methods A discrete-event simulation model was built to reproduce the breast cancer screening process (biennial mammographic screening of women aged 50 to 69 years) combined with the natural history of breast cancer. The simulation started with 100,000 women and, during a 20-year simulation horizon, new women were dynamically entered according to the aging of the Spanish population. Data on screening were obtained from Spanish breast cancer screening programs. Data on the natural history of breast cancer were based on US data adapted to our population. A budget impact analysis comparing digital with screen-film screening mammography was performed in a sample of 2,000 simulation runs. A sensitivity analysis was performed for crucial screening-related parameters. Distinct scenarios for recall and detection rates were compared. Results Statistically significant savings were found for overall costs, treatment costs and the costs of additional tests in the long term. The overall cost saving was 1,115,857€ (95%CI from 932,147 to 1,299,567) in the 10th year and 2,866,124€ (95%CI from 2,492,610 to 3,239,638) in the 20th year, representing 4.5% and 8.1% of the overall cost associated with screen-film mammography. The sensitivity analysis showed net savings in the long term. Conclusions Switching to digital mammography in a population-based breast cancer screening program saves long-term budget expense, in addition to providing technical advantages. Our results were consistent across distinct scenarios representing the different results obtained in European breast cancer screening programs. PMID:24832200

  6. Model for screened, charge-regulated electrostatics of an eye lens protein: Bovine gammaB-crystallin

    Science.gov (United States)

    Wahle, Christopher W.; Martini, K. Michael; Hollenbeck, Dawn M.; Langner, Andreas; Ross, David S.; Hamilton, John F.; Thurston, George M.

    2017-09-01

    We model screened, site-specific charge regulation of the eye lens protein bovine gammaB-crystallin (γ B ) and study the probability distributions of its proton occupancy patterns. Using a simplified dielectric model, we solve the linearized Poisson-Boltzmann equation to calculate a 54 ×54 work-of-charging matrix, each entry being the modeled voltage at a given titratable site, due to an elementary charge at another site. The matrix quantifies interactions within patches of sites, including γ B charge pairs. We model intrinsic p K values that would occur hypothetically in the absence of other charges, with use of experimental data on the dependence of p K values on aqueous solution conditions, the dielectric model, and literature values. We use Monte Carlo simulations to calculate a model grand-canonical partition function that incorporates both the work-of-charging and the intrinsic p K values for isolated γ B molecules and we calculate the probabilities of leading proton occupancy configurations, for 4 Debye screening lengths from 6 to 20 Å. We select the interior dielectric value to model γ B titration data. At p H 7.1 and Debye length 6.0 Å, on a given γ B molecule the predicted top occupancy pattern is present nearly 20% of the time, and 90% of the time one or another of the first 100 patterns will be present. Many of these occupancy patterns differ in net charge sign as well as in surface voltage profile. We illustrate how charge pattern probabilities deviate from the multinomial distribution that would result from use of effective p K values alone and estimate the extents to which γ B charge pattern distributions broaden at lower p H and narrow as ionic strength is lowered. These results suggest that for accurate modeling of orientation-dependent γ B -γ B interactions, consideration of numerous pairs of proton occupancy patterns will be needed.

  7. Model for screening-level assessment of near-field human exposure to neutral organic chemicals released indoors.

    Science.gov (United States)

    Zhang, Xianming; Arnot, Jon A; Wania, Frank

    2014-10-21

    Screening organic chemicals for hazard and risk to human health requires near-field human exposure models that can be readily parametrized with available data. The integration of a model of human exposure, uptake, and bioaccumulation into an indoor mass balance model provides a quantitative framework linking emissions in indoor environments with human intake rates (iRs), intake fractions (iFs) and steady-state concentrations in humans (C) through consideration of dermal permeation, inhalation, and nondietary ingestion exposure pathways. Parameterized based on representative indoor and adult human characteristics, the model is applied here to 40 chemicals of relevance in the context of human exposure assessment. Intake fractions and human concentrations (C(U)) calculated with the model based on a unit emission rate to air for these 40 chemicals span 2 and 5 orders of magnitude, respectively. Differences in priority ranking based on either iF or C(U) can be attributed to the absorption, biotransformation and elimination processes within the human body. The model is further applied to a large data set of hypothetical chemicals representative of many in-use chemicals to show how the dominant exposure pathways, iF and C(U) change as a function of chemical properties and to illustrate the capacity of the model for high-throughput screening. These simulations provide hypotheses for the combination of chemical properties that may result in high exposure and internal dose. The model is further exploited to highlight the role human contaminant uptake plays in the overall fate of certain chemicals indoors and consequently human exposure.

  8. A Modeling Study of the Spatial Structure of Electric Fields Generated by Electrified Clouds with Screening Layers

    Science.gov (United States)

    Biagi, C. J.; Cummins, K. L.

    2015-12-01

    The growing possibility of inexpensive airborne observations of electric fields using one or more small UAVs increases the importance of understanding what can be determined about cloud electrification and associated electric fields outside cloud boundaries. If important information can be inferred from carefully selected flight paths outside of a cloud, then the aircraft and its instrumentation will be much cheaper to develop and much safer to operate. These facts have led us to revisit this long-standing topic using quasi-static, finite-element modeling inside and outside arbitrarily shaped clouds with a variety of internal charge distributions. In particular, we examine the effect of screening layers on electric fields outside of electrified clouds by comparing modeling results for charged clouds having electrical conductivities that are both equal to and lower than the surrounding clear air. The comparisons indicate that the spatial structure of the electric field is approximately the same regardless of the difference in the conductivities between the cloud and clear air and the formation of a screening layer, even for altitude-dependent electrical conductivities. This result is consistent with the numerical modeling results reported by Driscoll et al [1992]. The similarity of the spatial structure of the electric field outside of clouds with and without a screening layer suggests that "bulk" properties related to cloud electrification might be determined using measurements of the electric field at multiple locations in space outside the cloud, particularly at altitude. Finally, for this somewhat simplified model, the reduction in electric field magnitude outside the cloud due to the presence of a screening layer exhibits a simple dependence on the difference in conductivity between the cloud and clear air. These results are particularly relevant for studying clouds that are not producing lightning, such as developing thunderstorms and decaying anvils

  9. Multistate transitional models for measuring adherence to breast cancer screening: A population-based longitudinal cohort study with over two million women.

    Science.gov (United States)

    Sutradhar, R; Gu, S; Paszat, L F

    2017-06-01

    Objective Prior work on the disparities among women in breast cancer screening adherence has been methodologically limited. This longitudinal study determines and examines the factors associated with becoming adherent. Methods In a cohort of Canadian women aged 50-74, a three-state transitional model was used to examine adherence to screening for breast cancer. The proportion of time spent being non-adherent with screening was calculated for each woman during her observation window. Using age as the time scale, a relative rate multivariable regression was implemented under the three-state transitional model, to examine the association between covariates (all time-varying) and the rate of becoming adherent. Results The cohort consisted of 2,537,960 women with a median follow-up of 8.46 years. Nearly 31% of women were continually up-to-date with breast screening. Once a woman was non-adherent, the rate of becoming adherent was higher among longer term residents (relative rate = 1.289, 95% confidence interval 1.275-1.302), those from wealthier neighbourhoods, and those who had an identifiable primary care provider who was female or had graduated in Canada. Conclusion Individual and physician-level characteristics play an important role in a woman's adherence to screening. This work improves the quality of evidence regarding disparities among women in adherence to breast cancer screening and provides a novel methodological foundation to investigate adherence for other types of screening, including cervix and colorectal cancer screening.

  10. Evaluating the impacts of screening and smoking cessation programmes on lung cancer in a high-burden region of the USA: a simulation modelling study.

    Science.gov (United States)

    Tramontano, Angela C; Sheehan, Deirdre F; McMahon, Pamela M; Dowling, Emily C; Holford, Theodore R; Ryczak, Karen; Lesko, Samuel M; Levy, David T; Kong, Chung Yin

    2016-02-29

    While the US Preventive Services Task Force has issued recommendations for lung cancer screening, its effectiveness at reducing lung cancer burden may vary at local levels due to regional variations in smoking behaviour. Our objective was to use an existing model to determine the impacts of lung cancer screening alone or in addition to increased smoking cessation in a US region with a relatively high smoking prevalence and lung cancer incidence. Computer-based simulation model. Simulated population of individuals 55 and older based on smoking prevalence and census data from Northeast Pennsylvania. Hypothetical lung cancer control from 2014 to 2050 through (1) screening with CT, (2) intensified smoking cessation or (3) a combination strategy. Primary outcomes were lung cancer mortality rates. Secondary outcomes included number of people eligible for screening and number of radiation-induced lung cancers. Combining lung cancer screening with increased smoking cessation would yield an estimated 8.1% reduction in cumulative lung cancer mortality by 2050. Our model estimated that the number of screening-eligible individuals would progressively decrease over time, indicating declining benefit of a screening-only programme. Lung cancer screening achieved a greater mortality reduction in earlier years, but was later surpassed by smoking cessation. Combining smoking cessation programmes with lung cancer screening would provide the most benefit to a population, especially considering the growing proportion of patients ineligible for screening based on current recommendations. 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. Prediction of Phase Behavior of Spray-Dried Amorphous Solid Dispersions: Assessment of Thermodynamic Models, Standard Screening Methods and a Novel Atomization Screening Device with Regard to Prediction Accuracy

    Directory of Open Access Journals (Sweden)

    Aymeric Ousset

    2018-03-01

    Full Text Available The evaluation of drug–polymer miscibility in the early phase of drug development is essential to ensure successful amorphous solid dispersion (ASD manufacturing. This work investigates the comparison of thermodynamic models, conventional experimental screening methods (solvent casting, quench cooling, and a novel atomization screening device based on their ability to predict drug–polymer miscibility, solid state properties (Tg value and width, and adequate polymer selection during the development of spray-dried amorphous solid dispersions (SDASDs. Binary ASDs of four drugs and seven polymers were produced at 20:80, 40:60, 60:40, and 80:20 (w/w. Samples were systematically analyzed using modulated differential scanning calorimetry (mDSC and X-ray powder diffraction (XRPD. Principal component analysis (PCA was used to qualitatively assess the predictability of screening methods with regards to SDASD development. Poor correlation was found between theoretical models and experimentally-obtained results. Additionally, the limited ability of usual screening methods to predict the miscibility of SDASDs did not guarantee the appropriate selection of lead excipient for the manufacturing of robust SDASDs. Contrary to standard approaches, our novel screening device allowed the selection of optimal polymer and drug loading and established insight into the final properties and performance of SDASDs at an early stage, therefore enabling the optimization of the scaled-up late-stage development.

  12. Feasibility and patient acceptability of a novel artificial intelligence-based screening model for diabetic retinopathy at endocrinology outpatient services: a pilot study.

    Science.gov (United States)

    Keel, Stuart; Lee, Pei Ying; Scheetz, Jane; Li, Zhixi; Kotowicz, Mark A; MacIsaac, Richard J; He, Mingguang

    2018-03-12

    The purpose of this study is to evaluate the feasibility and patient acceptability of a novel artificial intelligence (AI)-based diabetic retinopathy (DR) screening model within endocrinology outpatient settings. Adults with diabetes were recruited from two urban endocrinology outpatient clinics and single-field, non-mydriatic fundus photographs were taken and graded for referable DR ( ≥ pre-proliferative DR). Each participant underwent; (1) automated screening model; where a deep learning algorithm (DLA) provided real-time reporting of results; and (2) manual model where retinal images were transferred to a retinal grading centre and manual grading outcomes were distributed to the patient within 2 weeks of assessment. Participants completed a questionnaire on the day of examination and 1-month following assessment to determine overall satisfaction and the preferred model of care. In total, 96 participants were screened for DR and the mean assessment time for automated screening was 6.9 minutes. Ninety-six percent of participants reported that they were either satisfied or very satisfied with the automated screening model and 78% reported that they preferred the automated model over manual. The sensitivity and specificity of the DLA for correct referral was 92.3% and 93.7%, respectively. AI-based DR screening in endocrinology outpatient settings appears to be feasible and well accepted by patients.

  13. Risk-based high-throughput chemical screening and prioritization using exposure models and in vitro bioactivity assays

    DEFF Research Database (Denmark)

    Shin, Hyeong-Moo; Ernstoff, Alexi; Arnot, Jon

    2015-01-01

    We present a risk-based high-throughput screening (HTS) method to identify chemicals for potential health concerns or for which additional information is needed. The method is applied to 180 organic chemicals as a case study. We first obtain information on how the chemical is used and identify....../oral contact, or dermal exposure. The method provides high-throughput estimates of exposure and important input for decision makers to identify chemicals of concern for further evaluation with additional information or more refined models....

  14. The effect of omitting an early population-based vision screen in the Netherlands : A micro-simulation model approach

    NARCIS (Netherlands)

    F. Sloot; E. Heijnsdijk; F. Goudsmit; E.W. Steyerberg; H.J. de Koning; H.J. Simonsz; Dr. J.H. Groenewoud

    2016-01-01

    To estimate the effect of omitting an individual screen from a child vision screening programme on the detection of amblyopia in the Netherlands. A previous study (Rotterdam Amblyopia Screening Effectiveness Study) suggested that the three screens carried out between 6 and 24 months contributed

  15. A potential model for drug screening by simulating the effect of shear stress in vivo on endothelium.

    Science.gov (United States)

    Xu, Yingqian; Wang, Bochu; Deng, Jia; Liu, Zerong; Zhu, Liancai

    2013-01-01

    The purpose of this paper was to research the potential of a dynamic cell model in drug screening by studying the influence of microvascular wall shear stress on the drug absorption of endothelial cells compared to that in the static state. The cells were grown and seeded on gelatin-coated glass slides and were pretreated with extracts of Salviae miltiorrhizae (200 μg/ml) for 1 h. Then oxidative stress damage was produced by H2O2 (300 μmol/l) for 0.5 h under the 1.5 dyn/cm2 shear stress incorporated in a parallel plate flow chamber. Morphological analysis was conducted with an inverted microscope and image analysis software, and high performance liquid chromatography-mass spectrometry was used for the detection of active compounds. We compared the drug absorption in the dynamic group with that in the static group. In the dynamic model, five compounds and two new metabolite peaks were detected. However, in the static model, four compounds were absorbed by cells, and one metabolite peak was found. This study indicated that there were some effects on the absorption and metabolism of drugs under the microvascular shear stress compared to that under stasis. We infer that shear stress in the microcirculation situation in vivo played a role in causing the differences between drug screening in vitro and in vivo.

  16. Identification of Alternative Vapor Intrusion Pathways Using Controlled Pressure Testing, Soil Gas Monitoring, and Screening Model Calculations.

    Science.gov (United States)

    Guo, Yuanming; Holton, Chase; Luo, Hong; Dahlen, Paul; Gorder, Kyle; Dettenmaier, Erik; Johnson, Paul C

    2015-11-17

    Vapor intrusion (VI) pathway assessment and data interpretation have been guided by an historical conceptual model in which vapors originating from contaminated soil or groundwater diffuse upward through soil and are swept into a building by soil gas flow induced by building underpressurization. Recent studies reveal that alternative VI pathways involving neighborhood sewers, land drains, and other major underground piping can also be significant VI contributors, even to buildings beyond the delineated footprint of soil and groundwater contamination. This work illustrates how controlled-pressure-method testing (CPM), soil gas sampling, and screening-level emissions calculations can be used to identify significant alternative VI pathways that might go undetected by conventional sampling under natural conditions at some sites. The combined utility of these tools is shown through data collected at a long-term study house, where a significant alternative VI pathway was discovered and altered so that it could be manipulated to be on or off. Data collected during periods of natural and CPM conditions show that the alternative pathway was significant, but its presence was not identifiable under natural conditions; it was identified under CPM conditions when measured emission rates were 2 orders of magnitude greater than screening-model estimates and subfoundation vertical soil gas profiles changed and were no longer consistent with the conventional VI conceptual model.

  17. 3D Printing of Tissue Engineered Constructs for in vitro Modeling of Disease Progression and Drug Screening

    Science.gov (United States)

    Vanderburgh, Joseph; Sterling, Julie A.

    2016-01-01

    2D cell culture and preclinical animal models have traditionally been implemented for investigating the underlying cellular mechanisms of human disease progression. However, the increasing significance of 3D versus 2D cell culture has initiated a new era in cell culture research in which 3D in vitro models are emerging as a bridge between traditional 2D cell culture and in vivo animal models. Additive manufacturing (AM, also known as 3D printing), defined as the layer-by-layer fabrication of parts directed by digital information from a 3D computer-aided design (CAD) file, offers the advantages of simultaneous rapid prototyping and biofunctionalization as well as the precise placement of cells and extracellular matrix with high resolution. In this review, we highlight recent advances in 3D printing of tissue engineered constructs (TECs) that recapitulate the physical and cellular properties of the tissue microenvironment for investigating mechanisms of disease progression and for screening drugs. PMID:27169894

  18. Plasma nitriding monitoring reactor: A model reactor for studying plasma nitriding processes using an active screen

    Science.gov (United States)

    Hamann, S.; Börner, K.; Burlacov, I.; Spies, H.-J.; Strämke, M.; Strämke, S.; Röpcke, J.

    2015-12-01

    A laboratory scale plasma nitriding monitoring reactor (PLANIMOR) has been designed to study the basics of active screen plasma nitriding (ASPN) processes. PLANIMOR consists of a tube reactor vessel, made of borosilicate glass, enabling optical emission spectroscopy (OES) and infrared absorption spectroscopy. The linear setup of the electrode system of the reactor has the advantages to apply the diagnostic approaches on each part of the plasma process, separately. Furthermore, possible changes of the electrical field and of the heat generation, as they could appear in down-scaled cylindrical ASPN reactors, are avoided. PLANIMOR has been used for the nitriding of steel samples, achieving similar results as in an industrial scale ASPN reactor. A compact spectrometer using an external cavity quantum cascade laser combined with an optical multi-pass cell has been applied for the detection of molecular reaction products. This allowed the determination of the concentrations of four stable molecular species (CH4, C2H2, HCN, and NH3). With the help of OES, the rotational temperature of the screen plasma could be determined.

  19. Plasma nitriding monitoring reactor: A model reactor for studying plasma nitriding processes using an active screen

    International Nuclear Information System (INIS)

    Hamann, S.; Röpcke, J.; Börner, K.; Burlacov, I.; Spies, H.-J.; Strämke, M.; Strämke, S.

    2015-01-01

    A laboratory scale plasma nitriding monitoring reactor (PLANIMOR) has been designed to study the basics of active screen plasma nitriding (ASPN) processes. PLANIMOR consists of a tube reactor vessel, made of borosilicate glass, enabling optical emission spectroscopy (OES) and infrared absorption spectroscopy. The linear setup of the electrode system of the reactor has the advantages to apply the diagnostic approaches on each part of the plasma process, separately. Furthermore, possible changes of the electrical field and of the heat generation, as they could appear in down-scaled cylindrical ASPN reactors, are avoided. PLANIMOR has been used for the nitriding of steel samples, achieving similar results as in an industrial scale ASPN reactor. A compact spectrometer using an external cavity quantum cascade laser combined with an optical multi-pass cell has been applied for the detection of molecular reaction products. This allowed the determination of the concentrations of four stable molecular species (CH 4 , C 2 H 2 , HCN, and NH 3 ). With the help of OES, the rotational temperature of the screen plasma could be determined

  20. Screening for new brewing yeasts in the non-Saccharomyces sector with Torulaspora delbrueckii as model.

    Science.gov (United States)

    Michel, Maximilian; Kopecká, Jana; Meier-Dörnberg, Tim; Zarnkow, Martin; Jacob, Fritz; Hutzler, Mathias

    2016-04-01

    This study describes a screening system for future brewing yeasts focusing on non-Saccharomyces yeasts. The aim was to find new yeast strains that can ferment beer wort into a respectable beer. Ten Torulaspora delbrueckii strains were put through the screening system, which included sugar utilization tests, hop resistance tests, ethanol resistance tests, polymerase chain reaction fingerprinting, propagation tests, amino acid catabolism and anabolism, phenolic off-flavour tests and trial fermentations. Trial fermentations were analysed for extract reduction, pH drop, yeast concentration in bulk fluid and fermentation by-products. All investigated strains were able to partly ferment wort sugars and showed high tolerance to hop compounds and ethanol. One of the investigated yeast strains fermented all the wort sugars and produced a respectable fruity flavour and a beer of average ethanol content with a high volatile flavour compound concentration. Two other strains could possibly be used for pre-fermentation as a bio-flavouring agent for beers that have been post-fermented by Saccharomyces strains as a consequence of their low sugar utilization but good flavour-forming properties. Copyright © 2015 John Wiley & Sons, Ltd.

  1. Plasma nitriding monitoring reactor: A model reactor for studying plasma nitriding processes using an active screen

    Energy Technology Data Exchange (ETDEWEB)

    Hamann, S., E-mail: hamann@inp-greifswald.de; Röpcke, J. [INP-Greifswald, Felix-Hausdorff-Str. 2, 17489 Greifswald (Germany); Börner, K.; Burlacov, I.; Spies, H.-J. [TU Bergakademie Freiberg, Institute of Materials Engineering, Gustav-Zeuner-Str. 5, 09599 Freiberg (Germany); Strämke, M.; Strämke, S. [ELTRO GmbH, Arnold-Sommerfeld-Ring 3, 52499 Baesweiler (Germany)

    2015-12-15

    A laboratory scale plasma nitriding monitoring reactor (PLANIMOR) has been designed to study the basics of active screen plasma nitriding (ASPN) processes. PLANIMOR consists of a tube reactor vessel, made of borosilicate glass, enabling optical emission spectroscopy (OES) and infrared absorption spectroscopy. The linear setup of the electrode system of the reactor has the advantages to apply the diagnostic approaches on each part of the plasma process, separately. Furthermore, possible changes of the electrical field and of the heat generation, as they could appear in down-scaled cylindrical ASPN reactors, are avoided. PLANIMOR has been used for the nitriding of steel samples, achieving similar results as in an industrial scale ASPN reactor. A compact spectrometer using an external cavity quantum cascade laser combined with an optical multi-pass cell has been applied for the detection of molecular reaction products. This allowed the determination of the concentrations of four stable molecular species (CH{sub 4}, C{sub 2}H{sub 2}, HCN, and NH{sub 3}). With the help of OES, the rotational temperature of the screen plasma could be determined.

  2. Application of the Perceptual Factors, Enabling and Reinforcing Model on Pap Smaear Screening in Iranian Northern Woman

    Directory of Open Access Journals (Sweden)

    Abolhassan Naghibi

    2016-03-01

    Full Text Available Background and Purpose: Cervical cancer is the most prevalent cancer among women in the world. Cervical cancer is no symptoms and can be treated if diagnosed in the first stage of the disease. The aim of this study was to survey the affecting factors of the Pap smears test on perceptual factors, enabling and reinforcing (PEN-3 model constructs in women. Materials and Methods: This study was a descriptive cross-sectional study. The sample size was 416 married women with random sampling. The questionnaire had 50 questions based on PEN-3 model structures. Data were analyzed by descriptive statistics and logistic regression method in software SPSS 20. Results: The mean age of women was 32.70 ± 21.00 years. The knowledge of risk factors and screening methods for cervical cancer was 37.2. About 40% of women had a history of Pap smears. The most important of perception factors were effective, family history of the disease, encourage people to Pap smear, and fear of detecting of cervical cancer. The most important enabling factors were the presence of expert health personnel to provide training and Pap smear test (50.3%, lack of time and too busy to do Pap smear test (23.2%. The reinforcing factors were the media advice (41.3%, doctor’s advice (32.5% and neglect and forgetfulness (36.2%. Conclusion: This study has shown the Pap smear screening behavior affected by personal factors, family, cultural and economic. Application of PEN-3 can effective in planning and designing intervention programs for cervical cancer screening.

  3. An actor-based model of social network influence on adolescent body size, screen time, and playing sports.

    Directory of Open Access Journals (Sweden)

    David A Shoham

    Full Text Available Recent studies suggest that obesity may be "contagious" between individuals in social networks. Social contagion (influence, however, may not be identifiable using traditional statistical approaches because they cannot distinguish contagion from homophily (the propensity for individuals to select friends who are similar to themselves or from shared environmental influences. In this paper, we apply the stochastic actor-based model (SABM framework developed by Snijders and colleagues to data on adolescent body mass index (BMI, screen time, and playing active sports. Our primary hypothesis was that social influences on adolescent body size and related behaviors are independent of friend selection. Employing the SABM, we simultaneously modeled network dynamics (friendship selection based on homophily and structural characteristics of the network and social influence. We focused on the 2 largest schools in the National Longitudinal Study of Adolescent Health (Add Health and held the school environment constant by examining the 2 school networks separately (N = 624 and 1151. Results show support in both schools for homophily on BMI, but also for social influence on BMI. There was no evidence of homophily on screen time in either school, while only one of the schools showed homophily on playing active sports. There was, however, evidence of social influence on screen time in one of the schools, and playing active sports in both schools. These results suggest that both homophily and social influence are important in understanding patterns of adolescent obesity. Intervention efforts should take into consideration peers' influence on one another, rather than treating "high risk" adolescents in isolation.

  4. ScreenBEAM: a novel meta-analysis algorithm for functional genomics screens via Bayesian hierarchical modeling | Office of Cancer Genomics

    Science.gov (United States)

    Functional genomics (FG) screens, using RNAi or CRISPR technology, have become a standard tool for systematic, genome-wide loss-of-function studies for therapeutic target discovery. As in many large-scale assays, however, off-target effects, variable reagents' potency and experimental noise must be accounted for appropriately control for false positives.

  5. Discovery of novel PPAR ligands by a virtual screening approach based on pharmacophore modeling, 3D shape, and electrostatic similarity screening

    DEFF Research Database (Denmark)

    Markt, Patrick; Petersen, Rasmus K; Flindt, Esben N

    2008-01-01

    Peroxisome proliferator-activated receptors (PPARs) are important targets for drugs used in the treatment of atherosclerosis, dyslipidaemia, obesity, type 2 diabetes, and other diseases caused by abnormal regulation of the glucose and lipid metabolism. We applied a virtual screening workflow base...

  6. Screening to prevent spontaneous preterm birth: systematic reviews of accuracy and effectiveness literature with economic modelling.

    Science.gov (United States)

    Honest, H; Forbes, C A; Durée, K H; Norman, G; Duffy, S B; Tsourapas, A; Roberts, T E; Barton, P M; Jowett, S M; Hyde, C J; Khan, K S

    2009-09-01

    To identify combinations of tests and treatments to predict and prevent spontaneous preterm birth. Searches were run on the following databases up to September 2005 inclusive: MEDLINE, EMBASE, DARE, the Cochrane Library (CENTRAL and Cochrane Pregnancy and Childbirth Group trials register) and MEDION. We also contacted experts including the Cochrane Pregnancy and Childbirth Group and checked reference lists of review articles and papers that were eligible for inclusion. Two series of systematic reviews were performed: (1) accuracy of tests for the prediction of spontaneous preterm birth in asymptomatic women in early pregnancy and in women symptomatic with threatened preterm labour in later pregnancy; (2) effectiveness of interventions with potential to reduce cases of spontaneous preterm birth in asymptomatic women in early pregnancy and to reduce spontaneous preterm birth or improve neonatal outcome in women with a viable pregnancy symptomatic of threatened preterm labour. For the health economic evaluation, a model-based analysis incorporated the combined effect of tests and treatments and their cost-effectiveness. Of the 22 tests reviewed for accuracy, the quality of studies and accuracy of tests was generally poor. Only a few tests had LR+ > 5. In asymptomatic women these were ultrasonographic cervical length measurement and cervicovaginal prolactin and fetal fibronectin screening for predicting spontaneous preterm birth before 34 weeks. In this group, tests with LR- 5 were absence of fetal breathing movements, cervical length and funnelling, amniotic fluid interleukin-6 (IL-6), serum CRP for predicting birth within 2-7 days of testing, and matrix metalloprotease-9, amniotic fluid IL-6, cervicovaginal fetal fibronectin and cervicovaginal human chorionic gonadotrophin (hCG) for predicting birth before 34 or 37 weeks. In this group, tests with LR- asymptomatic women. Non-steroidal anti-inflammatory agents were the most effective tocolytic agent for reducing

  7. GPCRs from fusarium graminearum detection, modeling and virtual screening - the search for new routes to control head blight disease.

    Science.gov (United States)

    Bresso, Emmanuel; Togawa, Roberto; Hammond-Kosack, Kim; Urban, Martin; Maigret, Bernard; Martins, Natalia Florencio

    2016-12-15

    Fusarium graminearum (FG) is one of the major cereal infecting pathogens causing high economic losses worldwide and resulting in adverse effects on human and animal health. Therefore, the development of new fungicides against FG is an important issue to reduce cereal infection and economic impact. In the strategy for developing new fungicides, a critical step is the identification of new targets against which innovative chemicals weapons can be designed. As several G-protein coupled receptors (GPCRs) are implicated in signaling pathways critical for the fungi development and survival, such proteins could be valuable efficient targets to reduce Fusarium growth and therefore to prevent food contamination. In this study, GPCRs were predicted in the FG proteome using a manually curated pipeline dedicated to the identification of GPCRs. Based on several successive filters, the most appropriate GPCR candidate target for developing new fungicides was selected. Searching for new compounds blocking this particular target requires the knowledge of its 3D-structure. As no experimental X-Ray structure of the selected protein was available, a 3D model was built by homology modeling. The model quality and stability was checked by 100 ns of molecular dynamics simulations. Two stable conformations representative of the conformational families of the protein were extracted from the 100 ns simulation and were used for an ensemble docking campaign. The model quality and stability was checked by 100 ns of molecular dynamics simulations previously to the virtual screening step. The virtual screening step comprised the exploration of a chemical library with 11,000 compounds that were docked to the GPCR model. Among these compounds, we selected the ten top-ranked nontoxic molecules proposed to be experimentally tested to validate the in silico simulation. This study provides an integrated process merging genomics, structural bioinformatics and drug design for proposing innovative

  8. Screening of effective pharmacological treatments for MELAS syndrome using yeasts, fibroblasts and cybrid models of the disease.

    Science.gov (United States)

    Garrido-Maraver, Juan; Cordero, Mario D; Moñino, Irene Domínguez; Pereira-Arenas, Sheila; Lechuga-Vieco, Ana V; Cotán, David; De la Mata, Mario; Oropesa-Ávila, Manuel; De Miguel, Manuel; Bautista Lorite, Juan; Rivas Infante, Eloy; Alvarez-Dolado, Manuel; Navas, Plácido; Jackson, Sandra; Francisci, Silvia; Sánchez-Alcázar, José A

    2012-11-01

    MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) is a mitochondrial disease most usually caused by point mutations in tRNA genes encoded by mitochondrial DNA (mtDNA). Approximately 80% of cases of MELAS syndrome are associated with a m.3243A > G mutation in the MT-TL1 gene, which encodes the mitochondrial tRNALeu (UUR). Currently, no effective treatments are available for this chronic progressive disorder. Treatment strategies in MELAS and other mitochondrial diseases consist of several drugs that diminish the deleterious effects of the abnormal respiratory chain function, reduce the presence of toxic agents or correct deficiencies in essential cofactors. We evaluated the effectiveness of some common pharmacological agents that have been utilized in the treatment of MELAS, in yeast, fibroblast and cybrid models of the disease. The yeast model harbouring the A14G mutation in the mitochondrial tRNALeu(UUR) gene, which is equivalent to the A3243G mutation in humans, was used in the initial screening. Next, the most effective drugs that were able to rescue the respiratory deficiency in MELAS yeast mutants were tested in fibroblasts and cybrid models of MELAS disease. According to our results, supplementation with riboflavin or coenzyme Q(10) effectively reversed the respiratory defect in MELAS yeast and improved the pathologic alterations in MELAS fibroblast and cybrid cell models. Our results indicate that cell models have great potential for screening and validating the effects of novel drug candidates for MELAS treatment and presumably also for other diseases with mitochondrial impairment. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  9. The Investigate Factors on Screening of the Breast Cancer Based on PEN-3 Model in Iranian Northern Women

    Directory of Open Access Journals (Sweden)

    Seyed Abolhassan Naghibi

    2015-09-01

    Materials and Methods: The present study was cross-sectional. The samples studied were women above 20 years and the sample size was 1416 people. The method of sampling was a random cluster. The tools of data collection questionnaire with 70 questions which approved its content validity and reliability. Data were analyzed by using software of SPSS Ver. 20. Results: The average age of samples was 35.71±6.1. Only 14.3% of samples are regularly conducted to the self-examination. Also, 38.5% of women had a history of the clinical examination. The difference of observed in performance the breast self-examination and clinical breast examination were the statistical significant by variables of rural or urban (P= 0.005, the marital status (P = 0.013 and a background of having breast cancer (P <0.001. The results of the study based on PEN-3 model were showed that there were a statistical significant relationship between the structure of perceptual factors and reinforcing factors (P=0.002 and between the perceptual factors and enabling factors (P=0.006. Conclusion: According to the results of presented, the women`s performance in using the screening was low. Also, the components status of the PEN-3 Model (factors of perceptual, enabling, and reinforcing for the breast cancer screening in women studied were not suitable.

  10. Soil-plant transfer models for metals to improve soil screening value guidelines valid for São Paulo, Brazil.

    Science.gov (United States)

    Dos Santos-Araujo, Sabrina N; Swartjes, Frank A; Versluijs, Kees W; Moreno, Fabio Netto; Alleoni, Luís R F

    2017-11-07

    In Brazil, there is a lack of combined soil-plant data attempting to explain the influence of specific climate, soil conditions, and crop management on heavy metal uptake and accumulation by plants. As a consequence, soil-plant relationships to be used in risk assessments or for derivation of soil screening values are not available. Our objective in this study was to develop empirical soil-plant models for Cd, Cu, Pb, Ni, and Zn, in order to derive appropriate soil screening values representative of humid tropical regions such as the state of São Paulo (SP), Brazil. Soil and plant samples from 25 vegetable species in the production areas of SP were collected. The concentrations of metals found in these soil samples were relatively low. Therefore, data from temperate regions were included in our study. The soil-plant relations derived had a good performance for SP conditions for 8 out of 10 combinations of metal and vegetable species. The bioconcentration factor (BCF) values for Cd, Cu, Ni, Pb, and Zn in lettuce and for Cd, Cu, Pb, and Zn in carrot were determined under three exposure scenarios at pH 5 and 6. The application of soil-plant models and the BCFs proposed in this study can be an important tool to derive national soil quality criteria. However, this methodological approach includes data assessed under different climatic conditions and soil types and need to be carefully considered.

  11. Prediction of fetal growth restriction using estimated fetal weight vs a combined screening model in the third trimester.

    Science.gov (United States)

    Miranda, J; Rodriguez-Lopez, M; Triunfo, S; Sairanen, M; Kouru, H; Parra-Saavedra, M; Crovetto, F; Figueras, F; Crispi, F; Gratacós, E

    2017-11-01

    To compare the performance of third-trimester screening, based on estimated fetal weight centile (EFWc) vs a combined model including maternal baseline characteristics, fetoplacental ultrasound and maternal biochemical markers, for the prediction of small-for-gestational-age (SGA) neonates and late-onset fetal growth restriction (FGR). This was a nested case-control study within a prospective cohort of 1590 singleton gestations undergoing third-trimester (32 + 0 to 36 + 6 weeks' gestation) evaluation. Maternal baseline characteristics, mean arterial pressure, fetoplacental ultrasound and circulating biochemical markers (placental growth factor (PlGF), lipocalin-2, unconjugated estriol and inhibin A) were assessed in all women who subsequently delivered a SGA neonate (n = 175), defined as birth weight < 10 th centile according to customized standards, and in a control group (n = 875). Among SGA cases, those with birth weight < 3 rd centile and/or abnormal uterine artery pulsatility index (UtA-PI) and/or abnormal cerebroplacental ratio (CPR) were classified as FGR. Logistic regression predictive models were developed for SGA and FGR, and their performance was compared with that obtained using EFWc alone. In SGA cases, EFWc, CPR Z-score and maternal serum concentrations of unconjugated estriol and PlGF were significantly lower, while mean UtA-PI Z-score and lipocalin-2 and inhibin A concentrations were significantly higher, compared with controls. Using EFWc alone, 52% (area under receiver-operating characteristics curve (AUC), 0.82 (95% CI, 0.77-0.85)) of SGA and 64% (AUC, 0.86 (95% CI, 0.81-0.91)) of FGR cases were predicted at a 10% false-positive rate. A combined screening model including a-priori risk (maternal characteristics), EFWc, UtA-PI, PlGF and estriol (with lipocalin-2 for SGA) achieved a detection rate of 61% (AUC, 0.86 (95% CI, 0.83-0.89)) for SGA cases and 77% (AUC, 0.92 (95% CI, 0.88-0.95)) for FGR. The combined model for the

  12. Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules description.

    Science.gov (United States)

    Spyrakis, Francesca; Cavasotto, Claudio N

    2015-10-01

    Structure-based virtual screening is currently an established tool in drug lead discovery projects. Although in the last years the field saw an impressive progress in terms of algorithm development, computational performance, and retrospective and prospective applications in ligand identification, there are still long-standing challenges where further improvement is needed. In this review, we consider the conceptual frame, state-of-the-art and recent developments of three critical "structural" issues in structure-based drug lead discovery: the use of homology modeling to accurately model the binding site when no experimental structures are available, the necessity of accounting for the dynamics of intrinsically flexible systems as proteins, and the importance of considering active site water molecules in lead identification and optimization campaigns. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. The link between women's body image disturbances and body-focused cancer screening behaviors: a critical review of the literature and a new integrated model for women.

    Science.gov (United States)

    Ridolfi, Danielle R; Crowther, Janis H

    2013-03-01

    A large body of literature demonstrates the association between body image disturbances and health compromising behaviors among women (e.g., pathological eating, substance use, inappropriate exercise). However, given that disturbed body image is a pervasive problem, it is likely inversely related to health maintenance behaviors. Cancer screenings for breast, skin, and cervical cancer represent an important type of health maintenance behavior, yet adherence rates are low. Given the body-focused nature of these screenings, body image may be a salient predictor. This paper reviews the literature on the relationship between body image disturbances and cancer screening behaviors among women culminating in the proposal of a theoretical model. This model posits that body shame and body avoidance predict performance of cancer screenings and that variables drawn from the cancer literature, including risk perception, health anxiety, subjective norms, and self-efficacy, may moderate this relationship. Clinical implications and suggestions for research are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Improved continuum lowering calculations in screened hydrogenic model with l-splitting for high energy density systems

    Science.gov (United States)

    Ali, Amjad; Shabbir Naz, G.; Saleem Shahzad, M.; Kouser, R.; Aman-ur-Rehman; Nasim, M. H.

    2018-03-01

    The energy states of the bound electrons in high energy density systems (HEDS) are significantly affected due to the electric field of the neighboring ions. Due to this effect bound electrons require less energy to get themselves free and move into the continuum. This phenomenon of reduction in potential is termed as ionization potential depression (IPD) or the continuum lowering (CL). The foremost parameter to depict this change is the average charge state, therefore accurate modeling for CL is imperative in modeling atomic data for computation of radiative and thermodynamic properties of HEDS. In this paper, we present an improved model of CL in the screened hydrogenic model with l-splitting (SHML) proposed by G. Faussurier and C. Blancard, P. Renaudin [High Energy Density Physics 4 (2008) 114] and its effect on average charge state. We propose the level charge dependent calculation of CL potential energy and inclusion of exchange and correlation energy in SHML. By doing this, we made our model more relevant to HEDS and free from CL empirical parameter to the plasma environment. We have implemented both original and modified model of SHML in our code named OPASH and benchmark our results with experiments and other state-of-the-art simulation codes. We compared our results of average charge state for Carbon, Beryllium, Aluminum, Iron and Germanium against published literature and found a very reasonable agreement between them.

  15. A Combined Pharmacophore Modeling, 3D QSAR and Virtual Screening Studies on Imidazopyridines as B-Raf Inhibitors

    Directory of Open Access Journals (Sweden)

    Huiding Xie

    2015-05-01

    Full Text Available B-Raf kinase is an important target in treatment of cancers. In order to design and find potent B-Raf inhibitors (BRIs, 3D pharmacophore models were created using the Genetic Algorithm with Linear Assignment of Hypermolecular Alignment of Database (GALAHAD. The best pharmacophore model obtained which was used in effective alignment of the data set contains two acceptor atoms, three donor atoms and three hydrophobes. In succession, comparative molecular field analysis (CoMFA and comparative molecular similarity indices analysis (CoMSIA were performed on 39 imidazopyridine BRIs to build three dimensional quantitative structure-activity relationship (3D QSAR models based on both pharmacophore and docking alignments. The CoMSIA model based on the pharmacophore alignment shows the best result (q2 = 0.621, r2pred = 0.885. This 3D QSAR approach provides significant insights that are useful for designing potent BRIs. In addition, the obtained best pharmacophore model was used for virtual screening against the NCI2000 database. The hit compounds were further filtered with molecular docking, and their biological activities were predicted using the CoMSIA model, and three potential BRIs with new skeletons were obtained.

  16. A Combined Pharmacophore Modeling, 3D QSAR and Virtual Screening Studies on Imidazopyridines as B-Raf Inhibitors.

    Science.gov (United States)

    Xie, Huiding; Chen, Lijun; Zhang, Jianqiang; Xie, Xiaoguang; Qiu, Kaixiong; Fu, Jijun

    2015-05-29

    B-Raf kinase is an important target in treatment of cancers. In order to design and find potent B-Raf inhibitors (BRIs), 3D pharmacophore models were created using the Genetic Algorithm with Linear Assignment of Hypermolecular Alignment of Database (GALAHAD). The best pharmacophore model obtained which was used in effective alignment of the data set contains two acceptor atoms, three donor atoms and three hydrophobes. In succession, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on 39 imidazopyridine BRIs to build three dimensional quantitative structure-activity relationship (3D QSAR) models based on both pharmacophore and docking alignments. The CoMSIA model based on the pharmacophore alignment shows the best result (q(2) = 0.621, r(2)(pred) = 0.885). This 3D QSAR approach provides significant insights that are useful for designing potent BRIs. In addition, the obtained best pharmacophore model was used for virtual screening against the NCI2000 database. The hit compounds were further filtered with molecular docking, and their biological activities were predicted using the CoMSIA model, and three potential BRIs with new skeletons were obtained.

  17. Decision-making in healthcare: a practical application of partial least square path modelling to coverage of newborn screening programmes.

    Science.gov (United States)

    Fischer, Katharina E

    2012-08-02

    Decision-making in healthcare is complex. Research on coverage decision-making has focused on comparative studies for several countries, statistical analyses for single decision-makers, the decision outcome and appraisal criteria. Accounting for decision processes extends the complexity, as they are multidimensional and process elements need to be regarded as latent constructs (composites) that are not observed directly. The objective of this study was to present a practical application of partial least square path modelling (PLS-PM) to evaluate how it offers a method for empirical analysis of decision-making in healthcare. Empirical approaches that applied PLS-PM to decision-making in healthcare were identified through a systematic literature search. PLS-PM was used as an estimation technique for a structural equation model that specified hypotheses between the components of decision processes and the reasonableness of decision-making in terms of medical, economic and other ethical criteria. The model was estimated for a sample of 55 coverage decisions on the extension of newborn screening programmes in Europe. Results were evaluated by standard reliability and validity measures for PLS-PM. After modification by dropping two indicators that showed poor measures in the measurement models' quality assessment and were not meaningful for newborn screening, the structural equation model estimation produced plausible results. The presence of three influences was supported: the links between both stakeholder participation or transparency and the reasonableness of decision-making; and the effect of transparency on the degree of scientific rigour of assessment. Reliable and valid measurement models were obtained to describe the composites of 'transparency', 'participation', 'scientific rigour' and 'reasonableness'. The structural equation model was among the first applications of PLS-PM to coverage decision-making. It allowed testing of hypotheses in situations where there

  18. A Tiered Approach to Retinopathy of Prematurity Screening (TARP) Using a Weight Gain Predictive Model and a Telemedicine System.

    Science.gov (United States)

    Gurwin, Jaclyn; Tomlinson, Lauren A; Quinn, Graham E; Ying, Gui-Shuang; Baumritter, Agnieshka; Binenbaum, Gil

    2017-01-05

    The Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study telemedicine system of remote fundus image grading and The Children's Hospital of Philadelphia Retinopathy of Prematurity (CHOP-ROP) postnatal weight gain predictive model are 2 approaches for improving ROP screening efficiency. Current screening has low specificity for severe ROP. To describe a tiered approach to ROP screening (TARP) for identifying children who develop severe ROP using telemedicine and a predictive model synergistically. This investigation was a post hoc analysis of a cohort in the e-ROP Study (a multicenter prospective telemedicine study) and the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study (a multicenter retrospective cohort study). The setting was neonatal intensive care units at The Children's Hospital of Philadelphia and the Hospital of the University of Pennsylvania. Participants in the e-ROP Study were premature infants with a birth weight less than 1251 g and a known ROP outcome enrolled between May 25, 2011, and October 31, 2013. The G-ROP Study enrolled all infants undergoing ROP examinations with a known ROP outcome who were born between January 1, 2006, and December 31, 2011. The mean outcomes were the sensitivity for type 1 ROP, reductions in infants requiring imaging or examinations, numbers of imaging sessions and examinations, and total clinical encounters (imaging sessions and examinations combined). The following 4 screening approaches were evaluated: ROUTINE (only diagnostic examinations by an ophthalmologist), CHOP-ROP (birth weight and gestational age, with weekly weight gain initiating examinations when the risk cut point is surpassed), e-ROP IMAGING (trained reader grading of type 1 or 2 ROP initiates diagnostic examinations), and TARP (CHOP-ROP alarm initiates imaging, and imaging finding of severe ROP initiates diagnostic examinations). A total of 242 infants were included in the study, with a median birth

  19. SWAT Check: A Screening Tool to Assist Users in the Identification of Potential Model Application Problems.

    Science.gov (United States)

    White, Michael J; Harmel, R Daren; Arnold, Jeff G; Williams, Jimmy R

    2014-01-01

    The Soil and Water Assessment Tool (SWAT) is a basin-scale hydrologic model developed by the United States Department of Agriculture Agricultural Research Service. SWAT's broad applicability, user-friendly model interfaces, and automatic calibration software have led to a rapid increase in the number of new users. These advancements also allow less experienced users to conduct SWAT modeling applications. In particular, the use of automated calibration software may produce simulated values that appear appropriate because they adequately mimic measured data used in calibration and validation. Autocalibrated model applications (and often those of unexperienced modelers) may contain input data errors and inappropriate parameter adjustments not readily identified by users or the autocalibration software. The objective of this research was to develop a program to assist users in the identification of potential model application problems. The resulting "SWAT Check" is a stand-alone Microsoft Windows program that (i) reads selected SWAT output and alerts users of values outside the typical range; (ii) creates process-based figures for visualization of the appropriateness of output values, including important outputs that are commonly ignored; and (iii) detects and alerts users of common model application errors. By alerting users to potential model application problems, this software should assist the SWAT community in developing more reliable modeling applications. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  20. Toxicology screen

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003578.htm Toxicology screen To use the sharing features on this page, please enable JavaScript. A toxicology screen refers to various tests that determine the ...

  1. The Cost and Cost-Effectiveness of Scaling up Screening and Treatment of Syphilis in Pregnancy: A Model

    Science.gov (United States)

    Kahn, James G.; Jiwani, Aliya; Gomez, Gabriela B.; Hawkes, Sarah J.; Chesson, Harrell W.; Broutet, Nathalie; Kamb, Mary L.; Newman, Lori M.

    2014-01-01

    Background Syphilis in pregnancy imposes a significant global health and economic burden. More than half of cases result in serious adverse events, including infant mortality and infection. The annual global burden from mother-to-child transmission (MTCT) of syphilis is estimated at 3.6 million disability-adjusted life years (DALYs) and $309 million in medical costs. Syphilis screening and treatment is simple, effective, and affordable, yet, worldwide, most pregnant women do not receive these services. We assessed cost-effectiveness of scaling-up syphilis screening and treatment in existing antenatal care (ANC) programs in various programmatic, epidemiologic, and economic contexts. Methods and Findings We modeled the cost, health impact, and cost-effectiveness of expanded syphilis screening and treatment in ANC, compared to current services, for 1,000,000 pregnancies per year over four years. We defined eight generic country scenarios by systematically varying three factors: current maternal syphilis testing and treatment coverage, syphilis prevalence in pregnant women, and the cost of healthcare. We calculated program and net costs, DALYs averted, and net costs per DALY averted over four years in each scenario. Program costs are estimated at $4,142,287 – $8,235,796 per million pregnant women (2010 USD). Net costs, adjusted for averted medical care and current services, range from net savings of $12,261,250 to net costs of $1,736,807. The program averts an estimated 5,754 – 93,484 DALYs, yielding net savings in four scenarios, and a cost per DALY averted of $24 – $111 in the four scenarios with net costs. Results were robust in sensitivity analyses. Conclusions Eliminating MTCT of syphilis through expanded screening and treatment in ANC is likely to be highly cost-effective by WHO-defined thresholds in a wide range of settings. Countries with high prevalence, low current service coverage, and high healthcare cost would benefit most. Future analyses can be

  2. Discovery of Novel Inhibitors for Nek6 Protein through Homology Model Assisted Structure Based Virtual Screening and Molecular Docking Approaches

    Directory of Open Access Journals (Sweden)

    P. Srinivasan

    2014-01-01

    Full Text Available Nek6 is a member of the NIMA (never in mitosis, gene A-related serine/threonine kinase family that plays an important role in the initiation of mitotic cell cycle progression. This work is an attempt to emphasize the structural and functional relationship of Nek6 protein based on homology modeling and binding pocket analysis. The three-dimensional structure of Nek6 was constructed by molecular modeling studies and the best model was further assessed by PROCHECK, ProSA, and ERRAT plot in order to analyze the quality and consistency of generated model. The overall quality of computed model showed 87.4% amino acid residues under the favored region. A 3 ns molecular dynamics simulation confirmed that the structure was reliable and stable. Two lead compounds (Binding database ID: 15666, 18602 were retrieved through structure-based virtual screening and induced fit docking approaches as novel Nek6 inhibitors. Hence, we concluded that the potential compounds may act as new leads for Nek6 inhibitors designing.

  3. Generation of a homology model of the human histamine H3 receptor for ligand docking and pharmacophore-based screening

    Science.gov (United States)

    Schlegel, Birgit; Laggner, Christian; Meier, Rene; Langer, Thierry; Schnell, David; Seifert, Roland; Stark, Holger; Höltje, Hans-Dieter; Sippl, Wolfgang

    2007-08-01

    The human histamine H3 receptor (hH3R) is a G-protein coupled receptor (GPCR), which modulates the release of various neurotransmitters in the central and peripheral nervous system and therefore is a potential target in the therapy of numerous diseases. Although ligands addressing this receptor are already known, the discovery of alternative lead structures represents an important goal in drug design. The goal of this work was to study the hH3R and its antagonists by means of molecular modelling tools. For this purpose, a strategy was pursued in which a homology model of the hH3R based on the crystal structure of bovine rhodopsin was generated and refined by molecular dynamics simulations in a dipalmitoylphosphatidylcholine (DPPC)/water membrane mimic before the resulting binding pocket was used for high-throughput docking using the program GOLD. Alternatively, a pharmacophore-based procedure was carried out where the alleged bioactive conformations of three different potent hH3R antagonists were used as templates for the generation of pharmacophore models. A pharmacophore-based screening was then carried out using the program Catalyst. Based upon a database of 418 validated hH3R antagonists both strategies could be validated in respect of their performance. Seven hits obtained during this screening procedure were commercially purchased, and experimentally tested in a [3H]Nα-methylhistamine binding assay. The compounds tested showed affinities at hH3R with K i values ranging from 0.079 to 6.3 μM.

  4. Developing, Applying, and Evaluating Models for Rapid Screening of Chemical Exposures

    DEFF Research Database (Denmark)

    Arnot, J.; Shin, H.; Ernstoff, Alexi

    2015-01-01

    provides an introduction to underlying principles of some models used for exposure- and risk-based HTS for chemical prioritization for human health, including tools used in the ExpoDat project (USEtox, RAIDAR, CalTox) and other initiatives (SHEDS-HT). Case study examples of HTS include(i) model...

  5. Decision-making in healthcare: a practical application of partial least square path modelling to coverage of newborn screening programmes

    Directory of Open Access Journals (Sweden)

    Fischer Katharina E

    2012-08-01

    Full Text Available Abstract Background Decision-making in healthcare is complex. Research on coverage decision-making has focused on comparative studies for several countries, statistical analyses for single decision-makers, the decision outcome and appraisal criteria. Accounting for decision processes extends the complexity, as they are multidimensional and process elements need to be regarded as latent constructs (composites that are not observed directly. The objective of this study was to present a practical application of partial least square path modelling (PLS-PM to evaluate how it offers a method for empirical analysis of decision-making in healthcare. Methods Empirical approaches that applied PLS-PM to decision-making in healthcare were identified through a systematic literature search. PLS-PM was used as an estimation technique for a structural equation model that specified hypotheses between the components of decision processes and the reasonableness of decision-making in terms of medical, economic and other ethical criteria. The model was estimated for a sample of 55 coverage decisions on the extension of newborn screening programmes in Europe. Results were evaluated by standard reliability and validity measures for PLS-PM. Results After modification by dropping two indicators that showed poor measures in the measurement models’ quality assessment and were not meaningful for newborn screening, the structural equation model estimation produced plausible results. The presence of three influences was supported: the links between both stakeholder participation or transparency and the reasonableness of decision-making; and the effect of transparency on the degree of scientific rigour of assessment. Reliable and valid measurement models were obtained to describe the composites of ‘transparency’, ‘participation’, ‘scientific rigour’ and ‘reasonableness’. Conclusions The structural equation model was among the first applications of PLS-PM to

  6. Positioning graphical objects on computer screens: a three-phase model.

    Science.gov (United States)

    Pastel, Robert

    2011-02-01

    This experiment identifies and models phases during the positioning of graphical objects (called cursors in this article) on computer displays. The human computer-interaction community has traditionally used Fitts' law to model selection in graphical user interfaces, whereas human factors experiments have found the single-component Fitts' law inadequate to model positioning of real objects. Participants (N=145) repeatedly positioned variably sized square cursors within variably sized rectangular targets using computer mice. The times for the cursor to just touch the target, for the cursor to enter the target, and for participants to indicate positioning completion were observed. The positioning tolerances were varied from very precise and difficult to imprecise and easy. The time for the cursor to touch the target was proportional to the initial cursor-target distance. The time for the cursor to completely enter the target after touching was proportional to the logarithms of cursor size divided by target tolerances. The time for participants to indicate positioning after entering was inversely proportional to the tolerance. A three-phase model defined by regions--distant, proximate, and inside the target--was proposed and could model the positioning tasks. The three-phase model provides a framework for ergonomists to evaluate new positioning techniques and can explain their deficiencies. The model provides a means to analyze tasks and enhance interaction during positioning.

  7. Targeting acetylcholinesterase: identification of chemical leads by high throughput screening, structure determination and molecular modeling.

    Directory of Open Access Journals (Sweden)

    Lotta Berg

    Full Text Available Acetylcholinesterase (AChE is an essential enzyme that terminates cholinergic transmission by rapid hydrolysis of the neurotransmitter acetylcholine. Compounds inhibiting this enzyme can be used (inter alia to treat cholinergic deficiencies (e.g. in Alzheimer's disease, but may also act as dangerous toxins (e.g. nerve agents such as sarin. Treatment of nerve agent poisoning involves use of antidotes, small molecules capable of reactivating AChE. We have screened a collection of organic molecules to assess their ability to inhibit the enzymatic activity of AChE, aiming to find lead compounds for further optimization leading to drugs with increased efficacy and/or decreased side effects. 124 inhibitors were discovered, with considerable chemical diversity regarding size, polarity, flexibility and charge distribution. An extensive structure determination campaign resulted in a set of crystal structures of protein-ligand complexes. Overall, the ligands have substantial interactions with the peripheral anionic site of AChE, and the majority form additional interactions with the catalytic site (CAS. Reproduction of the bioactive conformation of six of the ligands using molecular docking simulations required modification of the default parameter settings of the docking software. The results show that docking-assisted structure-based design of AChE inhibitors is challenging and requires crystallographic support to obtain reliable results, at least with currently available software. The complex formed between C5685 and Mus musculus AChE (C5685•mAChE is a representative structure for the general binding mode of the determined structures. The CAS binding part of C5685 could not be structurally determined due to a disordered electron density map and the developed docking protocol was used to predict the binding modes of this part of the molecule. We believe that chemical modifications of our discovered inhibitors, biochemical and biophysical

  8. Perspective: Web-based machine learning models for real-time screening of thermoelectric materials properties

    Science.gov (United States)

    Gaultois, Michael W.; Oliynyk, Anton O.; Mar, Arthur; Sparks, Taylor D.; Mulholland, Gregory J.; Meredig, Bryce

    2016-05-01

    The experimental search for new thermoelectric materials remains largely confined to a limited set of successful chemical and structural families, such as chalcogenides, skutterudites, and Zintl phases. In principle, computational tools such as density functional theory (DFT) offer the possibility of rationally guiding experimental synthesis efforts toward very different chemistries. However, in practice, predicting thermoelectric properties from first principles remains a challenging endeavor [J. Carrete et al., Phys. Rev. X 4, 011019 (2014)], and experimental researchers generally do not directly use computation to drive their own synthesis efforts. To bridge this practical gap between experimental needs and computational tools, we report an open machine learning-based recommendation engine (http://thermoelectrics.citrination.com) for materials researchers that suggests promising new thermoelectric compositions based on pre-screening about 25 000 known materials and also evaluates the feasibility of user-designed compounds. We show this engine can identify interesting chemistries very different from known thermoelectrics. Specifically, we describe the experimental characterization of one example set of compounds derived from our engine, RE12Co5Bi (RE = Gd, Er), which exhibits surprising thermoelectric performance given its unprecedentedly high loading with metallic d and f block elements and warrants further investigation as a new thermoelectric material platform. We show that our engine predicts this family of materials to have low thermal and high electrical conductivities, but modest Seebeck coefficient, all of which are confirmed experimentally. We note that the engine also predicts materials that may simultaneously optimize all three properties entering into zT; we selected RE12Co5Bi for this study due to its interesting chemical composition and known facile synthesis.

  9. A BENCHMARKING ANALYSIS FOR FIVE RADIONUCLIDE VADOSE ZONE MODELS (CHAIN, MULTIMED_DP, FECTUZ, HYDRUS, AND CHAIN 2D) IN SOIL SCREENING LEVEL CALCULATIONS

    Science.gov (United States)

    Five radionuclide vadose zone models with different degrees of complexity (CHAIN, MULTIMED_DP, FECTUZ, HYDRUS, and CHAIN 2D) were selected for use in soil screening level (SSL) calculations. A benchmarking analysis between the models was conducted for a radionuclide (99Tc) rele...

  10. Predictive Accuracy of the PanCan Lung Cancer Risk Prediction Model -External Validation based on CT from the Danish Lung Cancer Screening Trial

    NARCIS (Netherlands)

    Wille, M.M.W.; Riel, S.J. van; Saghir, Z.; Dirksen, A.; Pedersen, J.H.; Jacobs, C.; Thomsen, L.H.u.; Scholten, E.T.; Skovgaard, L.T.; Ginneken, B. van

    2015-01-01

    Lung cancer risk models should be externally validated to test generalizability and clinical usefulness. The Danish Lung Cancer Screening Trial (DLCST) is a population-based prospective cohort study, used to assess the discriminative performances of the PanCan models.From the DLCST database, 1,152

  11. Characterization of a novel brain barrier ex vivo insect-based P-glycoprotein screening model

    DEFF Research Database (Denmark)

    Andersson, O.; Badisco, L.; Hansen, A. H.

    2014-01-01

    In earlier studies insects were proposed as suitable models for vertebrate blood–brain barrier (BBB) permeability prediction and useful in early drug discovery. Here we provide transcriptome and functional data demonstrating the presence of a P-glycoprotein (Pgp) efflux transporter in the brain b...... has the potential to act as a robust and convenient model for assessing BBB permeability in early drug discovery.......In earlier studies insects were proposed as suitable models for vertebrate blood–brain barrier (BBB) permeability prediction and useful in early drug discovery. Here we provide transcriptome and functional data demonstrating the presence of a P-glycoprotein (Pgp) efflux transporter in the brain...

  12. Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

    Directory of Open Access Journals (Sweden)

    Millard M

    2017-10-01

    Full Text Available Marie Millard,1,2 Ilya Yakavets,1–3 Vladimir Zorin,3,4 Aigul Kulmukhamedova,1,2,5 Sophie Marchal,1,2 Lina Bezdetnaya1,2 1Centre de Recherche en Automatique de Nancy, Centre National de la Recherche Scientifique UMR 7039, Université de Lorraine, 2Research Department, Institut de Cancérologie de Lorraine, Vandœuvre-lès-Nancy, France; 3Laboratory of Biophysics and Biotechnology, 4International Sakharov Environmental Institute, Belarusian State University, Minsk, Belarus; 5Department of Radiology, Medical Company Sunkar, Almaty, Kazakhstan Abstract: The increasing number of publications on the subject shows that nanomedicine is an attractive field for investigations aiming to considerably improve anticancer chemotherapy. Based on selective tumor targeting while sparing healthy tissue, carrier-mediated drug delivery has been expected to provide significant benefits to patients. However, despite reduced systemic toxicity, most nanodrugs approved for clinical use have been less effective than previously anticipated. The gap between experimental results and clinical outcomes demonstrates the necessity to perform comprehensive drug screening by using powerful preclinical models. In this context, in vitro three-dimensional models can provide key information on drug behavior inside the tumor tissue. The multicellular tumor spheroid (MCTS model closely mimics a small avascular tumor with the presence of proliferative cells surrounding quiescent cells and a necrotic core. Oxygen, pH and nutrient gradients are similar to those of solid tumor. Furthermore, extracellular matrix (ECM components and stromal cells can be embedded in the most sophisticated spheroid design. All these elements together with the physicochemical properties of nanoparticles (NPs play a key role in drug transport, and therefore, the MCTS model is appropriate to assess the ability of NP to penetrate the tumor tissue. This review presents recent developments in MCTS models for a

  13. Model-based Small Area Estimates of Cancer Risk Factors and Screening Behaviors - Small Area Estimates

    Science.gov (United States)

    These model-based estimates use two surveys, the Behavioral Risk Factor Surveillance System (BRFSS) and the National Health Interview Survey (NHIS). The two surveys are combined using novel statistical methodology.

  14. Understanding the stable boron clusters: A bond model and first-principles calculations based on high-throughput screening

    International Nuclear Information System (INIS)

    Xu, Shao-Gang; Liao, Ji-Hai; Zhao, Yu-Jun; Yang, Xiao-Bao

    2015-01-01

    The unique electronic property induced diversified structure of boron (B) cluster has attracted much interest from experimentalists and theorists. B 30–40 were reported to be planar fragments of triangular lattice with proper concentrations of vacancies recently. Here, we have performed high-throughput screening for possible B clusters through the first-principles calculations, including various shapes and distributions of vacancies. As a result, we have determined the structures of B n clusters with n = 30–51 and found a stable planar cluster of B 49 with a double-hexagon vacancy. Considering the 8-electron rule and the electron delocalization, a concise model for the distribution of the 2c–2e and 3c–2e bonds has been proposed to explain the stability of B planar clusters, as well as the reported B cages

  15. Metabolomics-based prediction models of yeast strains for screening of metabolites contributing to ethanol stress tolerance

    Science.gov (United States)

    Hashim, Z.; Fukusaki, E.

    2016-06-01

    The increased demand for clean, sustainable and renewable energy resources has driven the development of various microbial systems to produce biofuels. One of such systems is the ethanol-producing yeast. Although yeast produces ethanol naturally using its native pathways, production yield is low and requires improvement for commercial biofuel production. Moreover, ethanol is toxic to yeast and thus ethanol tolerance should be improved to further enhance ethanol production. In this study, we employed metabolomics-based strategy using 30 single-gene deleted yeast strains to construct multivariate models for ethanol tolerance and screen metabolites that relate to ethanol sensitivity/tolerance. The information obtained from this study can be used as an input for strain improvement via metabolic engineering.

  16. Screening of broad spectrum natural pesticides against conserved target arginine kinase in cotton pests by molecular modeling.

    Science.gov (United States)

    Sakthivel, Seethalakshmi; Habeeb, S K M; Raman, Chandrasekar

    2018-03-12

    Cotton is an economically important crop and its production is challenged by the diversity of pests and related insecticide resistance. Identification of the conserved target across the cotton pest will help to design broad spectrum insecticide. In this study, we have identified conserved sequences by Expressed Sequence Tag profiling from three cotton pests namely Aphis gossypii, Helicoverpa armigera, and Spodoptera exigua. One target protein arginine kinase having a key role in insect physiology and energy metabolism was studied further using homology modeling, virtual screening, molecular docking, and molecular dynamics simulation to identify potential biopesticide compounds from the Zinc natural database. We have identified four compounds having excellent inhibitor potential against the identified broad spectrum target which are highly specific to invertebrates.

  17. A model for color screening in a QCD plasma: the roles of thermal gluons and of confinement

    International Nuclear Information System (INIS)

    Calucci, G.; Cattaruzza, E.

    2006-01-01

    The study of the screening in the q anti q plasma, in a model which takes into account only static interactions, is continued with the introduction of two new dynamical elements: the presence of thermal gluons and a phenomenological description of the confinement. In the first case the qq correlation and the q anti q correlation are similar to each other and also similar to the correlation in the absence of gluons: the decay with the distance deviates slightly from a standard exponential decay. In the second case the two-body confining potential gives rise to correlation functions oscillating with the distance, so that only the total correlation, i.e. the space integral, has a more transparent interpretation; moreover, the qq correlations and the q anti q correlations show very definite differences. (orig.)

  18. Information-sharing to promote informed choice in prenatal screening in the spirit of the SOGC clinical practice guideline: a proposal for an alternative model.

    Science.gov (United States)

    Vanstone, Meredith; Kinsella, Elizabeth Anne; Nisker, Jeff

    2012-03-01

    The 2011 SOGC clinical practice guideline "Prenatal Screening for Fetal Aneuploidy in Singleton Pregnancies" recommends that clinicians offer prenatal screening to all pregnant women and provide counselling in a non-directive manner. Non-directive counselling is intended to facilitate autonomous decision-making and remove the clinician's views regarding a particular course of action. However, recent research in genetic counselling raises concerns that non-directive counselling is neither possible nor desirable, and that it may not be the best way to facilitate informed choice. We propose an alternative model of information-sharing specific to prenatal screening that combines attributes of the models of informative decision-making and shared decision-making. Our proposed model is intended to provide clinicians with a strategy to communicate information about prenatal screening in a way that facilitates a shared deliberative process and autonomous decision-making. Our proposed model may better prepare a pregnant woman to make an informed choice about participating in prenatal screening on the basis of her consideration of the medical information provided by her clinician and her particular circumstances and values.

  19. Risk Profiling May Improve Lung Cancer Screening

    Science.gov (United States)

    A new modeling study suggests that individualized, risk-based selection of ever-smokers for lung cancer screening may prevent more lung cancer deaths and improve the effectiveness and efficiency of screening compared with current screening recommendations

  20. Novel approaches to models of Alzheimer's disease pathology for drug screening and development.

    Science.gov (United States)

    Shaughnessy, Laura; Chamblin, Beth; McMahon, Lori; Nair, Ayyappan; Thomas, Mary Beth; Wakefield, John; Koentgen, Frank; Ramabhadran, Ram

    2004-01-01

    Development of therapeutics for Alzheimer's disease (AD) requires appropriate cell culture models that reflect the errant biochemical pathways and animal models that reflect the pathological hallmarks of the disease as well as the clinical manifestations. In the past two decades AD research has benefited significantly from the use of genetically engineered cell lines expressing components of the amyloid-generating pathway, as well as from the study of transgenic mice that develop the pathological hallmarks of the disease, mainly neuritic plaques. The choice of certain cell types and the choice of mouse as the model organism have been mandated by the feasibility of introduction and expression of foreign genes into these model systems. We describe a universal and efficient gene-delivery system, using lentiviral vectors, that permits the development of relevant cell biological systems using neuronal cells, including primary neurons and animal models in mammalian species best suited for the study of AD. In addition, lentiviral gene delivery provides avenues for creation of novel models by direct and prolonged expression of genes in the brain in any vertebrate animal. TranzVector is a lentiviral vector optimized for efficiency and safety that delivers genes to cells in culture, in tissue explants, and in live animals regardless of the dividing or differentiated status of the cells. Genes can also be delivered efficiently to fertilized single-cell-stage embryos of a wide range of mammalian species, broadening the range of the model organism (from rats to nonhuman primates) for the study of disease mechanism as well as for development of therapeutics. Copyright 2004 Humana Press Inc.

  1. Machine Learning Approaches Toward Building Predictive Models for Small Molecule Modulators of miRNA and Its Utility in Virtual Screening of Molecular Databases.

    Science.gov (United States)

    Periwal, Vinita; Scaria, Vinod

    2017-01-01

    The ubiquitous role of microRNAs (miRNAs) in a number of pathological processes has suggested that they could act as potential drug targets. RNA-binding small molecules offer an attractive means for modulating miRNA function. The availability of bioassay data sets for a variety of biological assays and molecules in public domain provides a new opportunity toward utilizing them to create models and further utilize them for in silico virtual screening approaches to prioritize or assign potential functions for small molecules. Here, we describe a computational strategy based on machine learning for creation of predictive models from high-throughput biological screens for virtual screening of small molecules with the potential to inhibit microRNAs. Such models could be potentially used for computational prioritization of small molecules before performing high-throughput biological assay.

  2. Decision-analytic modeling to evaluate the long-term effectiveness and cost-effectiveness of HPV-DNA testing in primary cervical cancer screening in Germany

    Directory of Open Access Journals (Sweden)

    Krämer, Alexander

    2010-01-01

    Full Text Available Background: Persistent infections with high-risk types of human papillomavirus (HPV are associated with the development of cervical neoplasia. Compared to cytology HPV testing is more sensitive in detecting high-grade cervical cancer precursors, but with lower specificity. HPV based primary screening for cervical cancer is currently discussed in Germany. Decisions should be based on a systematic evaluation of the long-term effectiveness and cost-effectiveness of HPV based primary screening. Research questions: What is the long-term clinical effectiveness (reduction in lifetime risk of cervical cancer and death due to cervical cancer, life years gained of HPV testing and what is the cost-effectiveness in Euro per life year gained (LYG of including HPV testing in primary cervical cancer screening in the German health care context? How can the screening program be improved with respect to test combination, age at start and end of screening and screening interval and which recommendations should be made for the German health care context? Methods: A previously published and validated decision-analytic model for the German health care context was extended and adapted to the natural history of HPV infection and cervical cancer in order to evaluate different screening strategies that differ by screening interval, and tests, including cytology alone, HPV testing alone or in combination with cytology, and HPV testing with cytology triage for HPV-positive women. German clinical, epidemiological and economic data were used. In the absence of individual data, screening adherence was modelled independently from screening history. Test accuracy data were retrieved from international meta-analyses. Predicted outcomes included reduction in lifetime-risk for cervical cancer cases and deaths, life expectancy, lifetime costs, and discounted incremental cost-effectiveness ratios (ICER. The perspective of the third party payer and 3% annual discount rate were

  3. More comprehensive discussion of CRC screening associated with higher screening.

    Science.gov (United States)

    Mosen, David M; Feldstein, Adrianne C; Perrin, Nancy A; Rosales, A Gabriella; Smith, David H; Liles, Elizabeth G; Schneider, Jennifer L; Meyers, Ronald E; Elston-Lafata, Jennifer

    2013-04-01

    Examine association of comprehensiveness of colorectal cancer (CRC) screening discussion by primary care physicians (PCPs) with completion of CRC screening. Observational study in Kaiser Permanente Northwest, a group-model health maintenance organization. A total of 883 participants overdue for CRC screening received an automated telephone call (ATC) between April and June 2009 encouraging CRC screening. Between January and March 2010, participants completed a survey on PCPs' discussion of CRC screening and patient beliefs regarding screening. receipt of CRC screening (assessed by electronic medical record [EMR], 9 months after ATC). Primary independent variable: comprehensiveness of CRC screening discussion by PCPs (7-item scale). Secondary independent variables: perceived benefits of screening (4-item scale assessing respondents' agreement with benefits of timely screening) and primary care utilization (EMR; 9 months after ATC). The independent association of variables with CRC screening was assessed with logistic regression. Average scores for comprehensiveness of CRC discussion and perceived benefits were 0.4 (range 0-1) and 4.0 (range 1-5), respectively. A total of 28.2% (n = 249) completed screening, 84% of whom had survey assessments after their screening date. Of screeners, 95.2% completed the fecal immunochemical test. More comprehensive discussion of CRC screening was associated with increased screening (odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.03-2.21). Higher perceived benefits (OR = 1.46, 95% CI = 1.13-1.90) and 1 or more PCP visits (OR = 5.82, 95% CI = 3.87-8.74) were also associated with increased screening. More comprehensive discussion of CRC screening was independently associated with increased CRC screening. Primary care utilization was even more strongly associated with CRC screening, irrespective of discussion of CRC screening.

  4. High-Resolution Longitudinal Screening with Magnetic Resonance Imaging in a Murine Brain Cancer Model

    Directory of Open Access Journals (Sweden)

    Nicholas A. Bock

    2003-11-01

    Full Text Available One of the main limitations of intracranial models of diseases is our present inability to monitor and evaluate the intracranial compartment noninvasively over time. Therefore, there is a growing need for imaging modalities that provide thorough neuropathological evaluations of xenograft and transgenic models of intracranial pathology. In this study, we have established protocols for multiple-mouse magnetic resonance imaging (MRI to follow the growth and behavior of intracranial xenografts of gliomas longitudinally. We successfully obtained weekly images on 16 mice for a total of 5 weeks on a 7-T multiple-mouse MRI. T2- and Ti-weighted imaging with gadolinium enhancement of vascularity was used to detect tumor margins, tumor size, and growth. These experiments, using 3D whole brain images obtained in four mice at once, demonstrate the feasibility of obtaining repeat radiological images in intracranial tumor models and suggest that MRI should be incorporated as a research modality for the investigation of intracranial pathobiology.

  5. A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction

    Science.gov (United States)

    Bell, Richard L.; Hauser, Sheketha; Rodd, Zachary A.; Liang, Tiebing; Sari, Youssef; McClintick, Jeanette; Rahman, Shafiqur; Engleman, Eric A.

    2016-01-01

    The purpose of this review is to present up-to-date pharmacological, genetic and behavioral findings from the alcohol-preferring P rat and summarize similar past work. Behaviorally, the focus will be on how the P rat meets criteria put forth for a valid animal model of alcoholism with a highlight on its use as an animal model of polysubstance abuse, including alcohol, nicotine and psychostimulants. Pharmacologically and genetically, the focus will be on the neurotransmitter and neuropeptide systems that have received the most attention: cholinergic, dopaminergic, GABAergic, glutamatergic, serotonergic, noradrenergic, corticotrophin releasing hormone, opioid, and neuropeptide Y. Herein we sought to place the P rat’s behavioral and neurochemical phenotypes, and to some extent its genotype, in the context of the clinical literature. After reviewing the findings thus far, this paper discusses future directions for expanding the use of this genetic animal model of alcoholism to identify molecular targets for treating drug addiction in general. PMID:27055615

  6. Cost-effectiveness and budget impact analyses of a colorectal cancer screening programme in a high adenoma prevalence scenario using MISCAN-Colon microsimulation model.

    Science.gov (United States)

    Arrospide, Arantzazu; Idigoras, Isabel; Mar, Javier; de Koning, Harry; van der Meulen, Miriam; Soto-Gordoa, Myriam; Martinez-Llorente, Jose Miguel; Portillo, Isabel; Arana-Arri, Eunate; Ibarrondo, Oliver; Lansdorp-Vogelaar, Iris

    2018-04-25

    The Basque Colorectal Cancer Screening Programme began in 2009 and the implementation has been complete since 2013. Faecal immunological testing was used for screening in individuals between 50 and 69 years old. Colorectal Cancer in Basque country is characterized by unusual epidemiological features given that Colorectal Cancer incidence is similar to other European countries while adenoma prevalence is higher. The object of our study was to economically evaluate the programme via cost-effectiveness and budget impact analyses with microsimulation models. We applied the Microsimulation Screening Analysis (MISCAN)-Colon model to predict trends in Colorectal Cancer incidence and mortality and to quantify the short- and long-term effects and costs of the Basque Colorectal Cancer Screening Programme. The model was calibrated to the Basque demographics in 2008 and age-specific Colorectal Cancer incidence data in the Basque Cancer Registry from 2005 to 2008 before the screening begun. The model was also calibrated to the high adenoma prevalence observed for the Basque population in a previously published study. The multi-cohort approach used in the model included all the cohorts in the programme during 30 years of implementation, with lifetime follow-up. Unit costs were obtained from the Basque Health Service and both cost-effectiveness analysis and budget impact analysis were carried out. The goodness-of-fit of the model adaptation to observed programme data was evidence of validation. In the cost-effectiveness analysis, the savings from treatment were larger than the added costs due to screening. Thus, the Basque programme was dominant compared to no screening, as life expectancy increased by 29.3 days per person. The savings in the budget analysis appeared 10 years after the complete implementation of the programme. The average annual budget was €73.4 million from year 2023 onwards. This economic evaluation showed a screening intervention with a major health gain

  7. A SCREENING MODEL FOR SIMULATING DNAPL FLOW AND TRANSPORT IN POROUS MEDIA: THEORETICAL DEVELOPMENT

    Science.gov (United States)

    There exists a need for a simple tool that will allow us to analyze a DNAPL contamination scenario from free-product release to transport of soluble constituents to downgradient receptor wells. The objective of this manuscript is to present the conceptual model and formulate the ...

  8. SCREENING OF WILD FRUIT TREES WITH GASTROPROTECTIVE ACTIVITY IN DIFFERENT EXPERIMENTAL MODELS.

    Science.gov (United States)

    Nesello, Luciane Angela Nottar; Campos, Adriana; Rosa, Roseane Leandra da; Andrade, Sérgio Faloni de; Cechinel, Valdir

    2017-01-01

    Given the increase of people with gastrointestinal disorders, the search for alternative treatments with fewer side effects is vital, as well as the demand for food or plants that can help protect the stomach. The aim of this study was to evaluate the gastroprotective action of the extracts of wild fruit trees of Myrcianthes pungens (guabiju); Inga vera Willd. (ingá-banana) and Marlierea tomentosa Cambess. (guarapuruna) in in vivo pharmacological models. The different parts of the fruits were separately subjected to a process of extraction by methanol. Two experimental pharmacological models were conducted in mice; the gastric ulcer model induced by non-steroidal anti-inflammatory (indomethacin), and the gastric ulcer model induced by ethanol/HCl, which allowed us to evaluate the gastroprotective activity of the extracts at a dose of 250 mg/kg. Subsequently, the total lesion area (mm2) and relative lesion area (%) were determined. The results showed significant gastroprotective activity against the aggressive agents used - ethanol and indomethacin - for all the extracts tested. It is assumed that the fruits have bioactive compounds such as antioxidant substances that act on the prostaglandin levels, protecting them from the damage caused by ethanol and indomethacin. These results prompt further studies to isolate and identify the active properties.

  9. Surrogate screening models for the low physical activity criterion of frailty.

    Science.gov (United States)

    Eckel, Sandrah P; Bandeen-Roche, Karen; Chaves, Paulo H M; Fried, Linda P; Louis, Thomas A

    2011-06-01

    Low physical activity, one of five criteria in a validated clinical phenotype of frailty, is assessed by a standardized, semiquantitative questionnaire on up to 20 leisure time activities. Because of the time demanded to collect the interview data, it has been challenging to translate to studies other than the Cardiovascular Health Study (CHS), for which it was developed. Considering subsets of activities, we identified and evaluated streamlined surrogate assessment methods and compared them to one implemented in the Women's Health and Aging Study (WHAS). Using data on men and women ages 65 and older from the CHS, we applied logistic regression models to rank activities by "relative influence" in predicting low physical activity.We considered subsets of the most influential activities as inputs to potential surrogate models (logistic regressions). We evaluated predictive accuracy and predictive validity using the area under receiver operating characteristic curves and assessed criterion validity using proportional hazards models relating frailty status (defined using the surrogate) to mortality. Walking for exercise and moderately strenuous household chores were highly influential for both genders. Women required fewer activities than men for accurate classification. The WHAS model (8 CHS activities) was an effective surrogate, but a surrogate using 6 activities (walking, chores, gardening, general exercise, mowing and golfing) was also highly predictive. We recommend a 6 activity questionnaire to assess physical activity for men and women. If efficiency is essential and the study involves only women, fewer activities can be included.

  10. Colon cancer screening

    Science.gov (United States)

    Screening for colon cancer; Colonoscopy - screening; Sigmoidoscopy - screening; Virtual colonoscopy - screening; Fecal immunochemical test; Stool DNA test; sDNA test; Colorectal cancer - screening; Rectal ...

  11. An anatomic risk model to screen post endovascular aneurysm repair patients for aneurysm sac enlargement.

    Science.gov (United States)

    Png, Chien Yi M; Tadros, Rami O; Beckerman, William E; Han, Daniel K; Tardiff, Melissa L; Torres, Marielle R; Marin, Michael L; Faries, Peter L

    2017-09-01

    Follow-up computed tomography angiography (CTA) scans add considerable postimplantation costs to endovascular aneurysm repairs (EVARs) of abdominal aortic aneurysms (AAAs). By building a risk model, we hope to identify patients at low risk for aneurysm sac enlargement to minimize unnecessary CTAs. 895 consecutive patients who underwent EVAR for AAA were reviewed, of which 556 met inclusion criteria. A Probit model was created for aneurysm sac enlargement, with preoperative aneurysm morphology, patient demographics, and operative details as variables. Our final model included 287 patients and had a sensitivity of 100%, a specificity of 68.9%, and an accuracy of 70.4%. Ninety-nine (35%) of patients were assigned to the high-risk group, whereas 188 (65%) of patients were assigned to the low-risk group. Notably, regarding anatomic variables, our model reported that age, pulmonary comorbidities, aortic neck diameter, iliac artery length, and aneurysms were independent predictors of post-EVAR sac enlargement. With the exception of age, all statistically significant variables were qualitatively supported by prior literature. With regards to secondary outcomes, the high-risk group had significantly higher proportions of AAA-related deaths (5.1% versus 1.1%, P = 0.037) and Type 1 endoleaks (9.1% versus 3.2%, P = 0.033). Our model is a decent predictor of patients at low risk for post AAA EVAR aneurysm sac enlargement and associated complications. With additional validation and refinement, it could be applied to practices to cut down on the overall need for postimplantation CTA. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Dosage and dose schedule screening of drug combinations in agent-based models reveals hidden synergies

    Directory of Open Access Journals (Sweden)

    Lisa Corina Barros de Andrade e Sousa1

    2016-01-01

    Full Text Available The fungus Candida albicans is the most common causative agent of human fungal infections and better drugs or drug combination strategies are urgently needed. Here, we present an agent-based model of the interplay of C. albicans with the host immune system and with the microflora of the host. We took into account the morphological change of C. albicans from the yeast to hyphae form and its dynamics during infection. The model allowed us to follow the dynamics of fungal growth and morphology, of the immune cells and of microflora in different perturbing situations. We specifically focused on the consequences of microflora reduction following antibiotic treatment. Using the agent-based model, different drug types have been tested for their effectiveness, namely drugs that inhibit cell division and drugs that constrain the yeast-to-hyphae transition. Applied individually, the division drug turned out to successfully decrease hyphae while the transition drug leads to a burst in hyphae after the end of the treatment. To evaluate the effect of different drug combinations, doses, and schedules, we introduced a measure for the return to a healthy state, the infection score. Using this measure, we found that the addition of a transition drug to a division drug treatment can improve the treatment reliability while minimizing treatment duration and drug dosage. In this work we present a theoretical study. Although our model has not been calibrated to quantitative experimental data, the technique of computationally identifying synergistic treatment combinations in an agent based model exemplifies the importance of computational techniques in translational research.

  13. Effective screening strategy using ensembled pharmacophore models combined with cascade docking: application to p53-MDM2 interaction inhibitors.

    Science.gov (United States)

    Xue, Xin; Wei, Jin-Lian; Xu, Li-Li; Xi, Mei-Yang; Xu, Xiao-Li; Liu, Fang; Guo, Xiao-Ke; Wang, Lei; Zhang, Xiao-Jin; Zhang, Ming-Ye; Lu, Meng-Chen; Sun, Hao-Peng; You, Qi-Dong

    2013-10-28

    Protein-protein interactions (PPIs) play a crucial role in cellular function and form the backbone of almost all biochemical processes. In recent years, protein-protein interaction inhibitors (PPIIs) have represented a treasure trove of potential new drug targets. Unfortunately, there are few successful drugs of PPIIs on the market. Structure-based pharmacophore (SBP) combined with docking has been demonstrated as a useful Virtual Screening (VS) strategy in drug development projects. However, the combination of target complexity and poor binding affinity prediction has thwarted the application of this strategy in the discovery of PPIIs. Here we report an effective VS strategy on p53-MDM2 PPI. First, we built a SBP model based on p53-MDM2 complex cocrystal structures. The model was then simplified by using a Receptor-Ligand complex-based pharmacophore model considering the critical binding features between MDM2 and its small molecular inhibitors. Cascade docking was subsequently applied to improve the hit rate. Based on this strategy, we performed VS on NCI and SPECS databases and successfully discovered 6 novel compounds from 15 hits with the best, compound 1 (NSC 5359), K(i) = 180 ± 50 nM. These compounds can serve as lead compounds for further optimization.

  14. Analysis of risk indicators and issues associated with applications of screening model for hazardous and radioactive waste sites

    International Nuclear Information System (INIS)

    Buck, J.W.; Strenge, D.L.; Droppo, J.G. Jr.

    1990-12-01

    Risk indicators, such as population risk, maximum individual risk, time of arrival of contamination, and maximum water concentrations, were analyzed to determine their effect on results from a screening model for hazardous and radioactive waste sites. The analysis of risk indicators is based on calculations resulting from exposure to air and waterborne contamination predicted with Multimedia Environmental Pollutant Assessment System (MEPAS) model. The different risk indicators were analyzed, based on constituent type and transport and exposure pathways. Three of the specific comparisons that were made are (1) population-based versus maximum individual-based risk indicators, (2) time of arrival of contamination, and (3) comparison of different threshold assumptions for noncarcinogenic impacts. Comparison of indicators for population- and maximum individual-based human health risk suggests that these two parameters are highly correlated, but for a given problem, one may be more important than the other. The results indicate that the arrival distribution for different levels of contamination reaching a receptor can also be helpful in decisions regarding the use of resources for remediating short- and long-term environmental problems. The addition of information from a linear model for noncarcinogenic impacts allows interpretation of results below the reference dose (RfD) levels that might help in decisions for certain applications. The analysis of risk indicators suggests that important information may be lost by the use of a single indicator to represent public health risk and that multiple indicators should be considered. 15 refs., 8 figs., 1 tab

  15. A computer simulation model of the cost-effectiveness of routine Staphylococcus aureus screening and decolonization among lung and heart-lung transplant recipients.

    Science.gov (United States)

    Clancy, C J; Bartsch, S M; Nguyen, M H; Stuckey, D R; Shields, R K; Lee, B Y

    2014-06-01

    Our objective was to model the cost-effectiveness and economic value of routine peri-operative Staphylococcus aureus screening and decolonization of lung and heart-lung transplant recipients from hospital and third-party payer perspectives. We used clinical data from 596 lung and heart-lung transplant recipients to develop a model in TreeAge Pro 2009 (Williamsport, MA, USA). Sensitivity analyses varied S. aureus colonization rate (5-15 %), probability of infection if colonized (10-30 %), and decolonization efficacy (25-90 %). Data were collected from the Cardiothoracic Transplant Program at the University of Pittsburgh Medical Center. Consecutive lung and heart-lung transplant recipients from January 2006 to December 2010 were enrolled retrospectively. Baseline rates of S. aureus colonization, infection and decolonization efficacy were 9.6 %, 36.7 %, and 31.9 %, respectively. Screening and decolonization was economically dominant for all scenarios tested, providing more cost savings and health benefits than no screening. Savings per case averted (2012 $US) ranged from $73,567 to $133,157 (hospital perspective) and $10,748 to $16,723 (third party payer perspective), varying with the probability of colonization, infection, and decolonization efficacy. Using our clinical data, screening and decolonization led to cost savings per case averted of $240,602 (hospital perspective) and averted 6.7 S. aureus infections (4.3 MRSA and 2.4 MSSA); 89 patients needed to be screened to prevent one S. aureus infection. Our data support routine S. aureus screening and decolonization of lung and heart-lung transplant patients. The economic value of screening and decolonization was greater than in previous models of other surgical populations.

  16. Conceptual design of a regional water quality screening model. [RFF; Reach; HANFORD; ARQUAL; SEAS; NASQUAN

    Energy Technology Data Exchange (ETDEWEB)

    Davis, M J

    1981-01-01

    This water quality assessment methodology is intended to predict concentrations at future times and to estimate the impacts on water quality of energy-related activities (including industrial boilers). Estimates of impacts on water quality at future times are based on incremental changes in pollutant inputs to the body water. Important features of the model are: use of measured concentrations to account for existing conditions; consideration of incremental changes in pollutant loads; emphasis on the energy sector and industrial boilers; analysis restricted to streams only; no attempt to fully account for pollutant behavior; and flexible design, so that future improvements can be incorporated. The basic approach is very similar to the one used by Argonne's ARQUAL model but will allow more complex pollutant behavior and more flexibility in use. (PSB)

  17. Speeding up N -body simulations of modified gravity: chameleon screening models

    Energy Technology Data Exchange (ETDEWEB)

    Bose, Sownak; Li, Baojiu; He, Jian-hua; Llinares, Claudio [Institute for Computational Cosmology, Department of Physics, Durham University, Durham DH1 3LE (United Kingdom); Barreira, Alexandre [Max-Planck-Institut für Astrophysik, Karl-Schwarzschild-Str. 1, 85741 Garching (Germany); Hellwing, Wojciech A.; Koyama, Kazuya [Institute of Cosmology and Gravitation, University of Portsmouth, Portsmouth PO1 3FX (United Kingdom); Zhao, Gong-Bo, E-mail: sownak.bose@durham.ac.uk, E-mail: baojiu.li@durham.ac.uk, E-mail: barreira@mpa-garching.mpg.de, E-mail: jianhua.he@durham.ac.uk, E-mail: wojciech.hellwing@port.ac.uk, E-mail: kazuya.koyama@port.ac.uk, E-mail: claudio.llinares@durham.ac.uk, E-mail: gbzhao@nao.cas.cn [National Astronomy Observatories, Chinese Academy of Science, Beijing, 100012 (China)

    2017-02-01

    We describe and demonstrate the potential of a new and very efficient method for simulating certain classes of modified gravity theories, such as the widely studied f ( R ) gravity models. High resolution simulations for such models are currently very slow due to the highly nonlinear partial differential equation that needs to be solved exactly to predict the modified gravitational force. This nonlinearity is partly inherent, but is also exacerbated by the specific numerical algorithm used, which employs a variable redefinition to prevent numerical instabilities. The standard Newton-Gauss-Seidel iterative method used to tackle this problem has a poor convergence rate. Our new method not only avoids this, but also allows the discretised equation to be written in a form that is analytically solvable. We show that this new method greatly improves the performance and efficiency of f ( R ) simulations. For example, a test simulation with 512{sup 3} particles in a box of size 512 Mpc/ h is now 5 times faster than before, while a Millennium-resolution simulation for f ( R ) gravity is estimated to be more than 20 times faster than with the old method. Our new implementation will be particularly useful for running very high resolution, large-sized simulations which, to date, are only possible for the standard model, and also makes it feasible to run large numbers of lower resolution simulations for covariance analyses. We hope that the method will bring us to a new era for precision cosmological tests of gravity.

  18. Speeding up N-body simulations of modified gravity: chameleon screening models

    Science.gov (United States)

    Bose, Sownak; Li, Baojiu; Barreira, Alexandre; He, Jian-hua; Hellwing, Wojciech A.; Koyama, Kazuya; Llinares, Claudio; Zhao, Gong-Bo

    2017-02-01

    We describe and demonstrate the potential of a new and very efficient method for simulating certain classes of modified gravity theories, such as the widely studied f(R) gravity models. High resolution simulations for such models are currently very slow due to the highly nonlinear partial differential equation that needs to be solved exactly to predict the modified gravitational force. This nonlinearity is partly inherent, but is also exacerbated by the specific numerical algorithm used, which employs a variable redefinition to prevent numerical instabilities. The standard Newton-Gauss-Seidel iterative method used to tackle this problem has a poor convergence rate. Our new method not only avoids this, but also allows the discretised equation to be written in a form that is analytically solvable. We show that this new method greatly improves the performance and efficiency of f(R) simulations. For example, a test simulation with 5123 particles in a box of size 512 Mpc/h is now 5 times faster than before, while a Millennium-resolution simulation for f(R) gravity is estimated to be more than 20 times faster than with the old method. Our new implementation will be particularly useful for running very high resolution, large-sized simulations which, to date, are only possible for the standard model, and also makes it feasible to run large numbers of lower resolution simulations for covariance analyses. We hope that the method will bring us to a new era for precision cosmological tests of gravity.

  19. Speeding up N -body simulations of modified gravity: chameleon screening models

    International Nuclear Information System (INIS)

    Bose, Sownak; Li, Baojiu; He, Jian-hua; Llinares, Claudio; Barreira, Alexandre; Hellwing, Wojciech A.; Koyama, Kazuya; Zhao, Gong-Bo

    2017-01-01

    We describe and demonstrate the potential of a new and very efficient method for simulating certain classes of modified gravity theories, such as the widely studied f ( R ) gravity models. High resolution simulations for such models are currently very slow due to the highly nonlinear partial differential equation that needs to be solved exactly to predict the modified gravitational force. This nonlinearity is partly inherent, but is also exacerbated by the specific numerical algorithm used, which employs a variable redefinition to prevent numerical instabilities. The standard Newton-Gauss-Seidel iterative method used to tackle this problem has a poor convergence rate. Our new method not only avoids this, but also allows the discretised equation to be written in a form that is analytically solvable. We show that this new method greatly improves the performance and efficiency of f ( R ) simulations. For example, a test simulation with 512 3 particles in a box of size 512 Mpc/ h is now 5 times faster than before, while a Millennium-resolution simulation for f ( R ) gravity is estimated to be more than 20 times faster than with the old method. Our new implementation will be particularly useful for running very high resolution, large-sized simulations which, to date, are only possible for the standard model, and also makes it feasible to run large numbers of lower resolution simulations for covariance analyses. We hope that the method will bring us to a new era for precision cosmological tests of gravity.

  20. Reliability of IOTA score and ADNEX model in the screening of ovarian malignancy in postmenopausal women.

    Science.gov (United States)

    Nohuz, Erdogan; De Simone, Luisa; Chêne, Gautier

    2018-04-28

    The IOTA (International Ovarian Tumor Analysis) group has developed the ADNEX (Assessment of Different NEoplasias in the adneXa) model to predict the risk that an ovarian mass is benign, borderline or malignant. This study aimed to test reliability of these risks prediction models to improve the performance of pelvic ultrasound and discriminate between benign and malignant cysts. Postmenopausal women with an adnexal mass (including ovarian, para-ovarian and tubal) and who underwent a standardized ultrasound examination before surgery were included. Prospectively and retrospectively collected data and ultrasound appearances of the tumors were described using the terms and definitions of the IOTA group and tested in accordance with the ADNEX model and were compared to the final histological diagnosis. Of the 107 menopausal patients recruited between 2011 and 2016, 14 were excluded (incomplete inclusion criteria). Thus, 93 patients constituted a cohort in whom 89 had benign cysts (83 ovarian and 6 tubal or para-ovarian cysts), 1 had border line tumor and 3 had invasive ovarian cancers (1 at first stage, 1 at advanced stage and 1 metastatic tumor in the ovary). The overall prevalence of malignancy was 4.3%. Every benign ovarian cyst was classified as probably benign by IOTA score which showed also a high specificity with the totality of probably malignant lesion proved malignant by histological exam. The limit of this score was the important rate of not classified or undetermined cysts. However, the malignancy risks calculated by ADNEX model allowed identifying the totality of malignancy. Thus, the combination of the two methods of analysis showed a sensitivity and specificity rates of respectively 100% and 98%. Evaluation of malignancy risks by these 2 tests highlighted a negative predictive value of 100% (there was no case of false negative) and a positive predictive value of 80%. On the basis of our findings, the IOTA classification and the ADNEX multimodal

  1. Screening California Current fishery management scenarios using the Atlantis end-to-end ecosystem model

    Science.gov (United States)

    Kaplan, Isaac C.; Horne, Peter J.; Levin, Phillip S.

    2012-09-01

    End-to-end marine ecosystem models link climate and oceanography to the food web and human activities. These models can be used as forecasting tools, to strategically evaluate management options and to support ecosystem-based management. Here we report the results of such forecasts in the California Current, using an Atlantis end-to-end model. We worked collaboratively with fishery managers at NOAA’s regional offices and staff at the National Marine Sanctuaries (NMS) to explore the impact of fishery policies on management objectives at different spatial scales, from single Marine Sanctuaries to the entire Northern California Current. In addition to examining Status Quo management, we explored the consequences of several gear switching and spatial management scenarios. Of the scenarios that involved large scale management changes, no single scenario maximized all performance metrics. Any policy choice would involve trade-offs between stakeholder groups and policy goals. For example, a coast-wide 25% gear shift from trawl to pot or longline appeared to be one possible compromise between an increase in spatial management (which sacrificed revenue) and scenarios such as the one consolidating bottom impacts to deeper areas (which did not perform substantially differently from Status Quo). Judged on a coast-wide scale, most of the scenarios that involved minor or local management changes (e.g. within Monterey Bay NMS only) yielded results similar to Status Quo. When impacts did occur in these cases, they often involved local interactions that were difficult to predict a priori based solely on fishing patterns. However, judged on the local scale, deviation from Status Quo did emerge, particularly for metrics related to stationary species or variables (i.e. habitat and local metrics of landed value or bycatch). We also found that isolated management actions within Monterey Bay NMS would cause local fishers to pay a cost for conservation, in terms of reductions in landed

  2. Performance and Cost-Effectiveness of Computed Tomography Lung Cancer Screening Scenarios in a Population-Based Setting: A Microsimulation Modeling Analysis in Ontario, Canada.

    Directory of Open Access Journals (Sweden)

    Kevin Ten Haaf

    2017-02-01

    Full Text Available The National Lung Screening Trial (NLST results indicate that computed tomography (CT lung cancer screening for current and former smokers with three annual screens can be cost-effective in a trial setting. However, the cost-effectiveness in a population-based setting with >3 screening rounds is uncertain. Therefore, the objective of this study was to estimate the cost-effectiveness of lung cancer screening in a population-based setting in Ontario, Canada, and evaluate the effects of screening eligibility criteria.This study used microsimulation modeling informed by various data sources, including the Ontario Health Insurance Plan (OHIP, Ontario Cancer Registry, smoking behavior surveys, and the NLST. Persons, born between 1940 and 1969, were examined from a third-party health care payer perspective across a lifetime horizon. Starting in 2015, 576 CT screening scenarios were examined, varying by age to start and end screening, smoking eligibility criteria, and screening interval. Among the examined outcome measures were lung cancer deaths averted, life-years gained, percentage ever screened, costs (in 2015 Canadian dollars, and overdiagnosis. The results of the base-case analysis indicated that annual screening was more cost-effective than biennial screening. Scenarios with eligibility criteria that required as few as 20 pack-years were dominated by scenarios that required higher numbers of accumulated pack-years. In general, scenarios that applied stringent smoking eligibility criteria (i.e., requiring higher levels of accumulated smoking exposure were more cost-effective than scenarios with less stringent smoking eligibility criteria, with modest differences in life-years gained. Annual screening between ages 55-75 for persons who smoked ≥40 pack-years and who currently smoke or quit ≤10 y ago yielded an incremental cost-effectiveness ratio of $41,136 Canadian dollars ($33,825 in May 1, 2015, United States dollars per life-year gained

  3. QSAR Classification Model for Antibacterial Compounds and Its Use in Virtual Screening

    Science.gov (United States)

    2012-09-26

    pertussis (290 000), and tetanus (210 000).1 Considering this staggering number of deaths, there should be a lucrative market for drug therapies for...e Th r e a t R edu c t i o n Ag en c y G r a n t Journal of Chemical Information and Modeling Article dx.doi.org/10.1021/ci300336v | J. Chem. Inf...15, 2012). (32) Knox, C.; Law, V.; Jewison, T.; Liu, P.; Ly, S.; Frolkis, A.; Pon, A.; Banco , K.; Mak, C.; Neveu, V.; Djoumbou, Y.; Eisner, R.; Guo, A

  4. Discovery of a Dipeptide Epimerase Enzymatic Function Guided by Homology Modeling and Virtual Screening

    Energy Technology Data Exchange (ETDEWEB)

    Kalyanaraman, C.; Imker, H; Fedorov, A; Fedorov, E; Glasner, M; Babbitt, P; Almo, S; Gerlt, J; Jacobson, M

    2008-01-01

    We have developed a computational approach to aid the assignment of enzymatic function for uncharacterized proteins that uses homology modeling to predict the structure of the binding site and in silico docking to identify potential substrates. We apply this method to proteins in the functionally diverse enolase superfamily that are homologous to the characterized L-Ala-D/L-Glu epimerase from Bacillus subtilis. In particular, a protein from Thermotoga martima was predicted to have different substrate specificity, which suggests that it has a different, but as yet unknown, biological function. This prediction was experimentally confirmed, resulting in the assignment of epimerase activity for L-Ala-D/L-Phe, L-Ala-D/L-Tyr, and L-Ala-D/L-His, whereas the enzyme is annotated incorrectly in GenBank as muconate cycloisomerase. Subsequently, crystal structures of the enzyme were determined in complex with three substrates, showing close agreement with the computational models and revealing the structural basis for the observed substrate selectivity.

  5. Using Collaborative Simulation Modeling to Develop a Web-Based Tool to Support Policy-Level Decision Making About Breast Cancer Screening Initiation Age

    Directory of Open Access Journals (Sweden)

    Elizabeth S. Burnside MD, MPH, MS

    2017-07-01

    Full Text Available Background: There are no publicly available tools designed specifically to assist policy makers to make informed decisions about the optimal ages of breast cancer screening initiation for different populations of US women. Objective: To use three established simulation models to develop a web-based tool called Mammo OUTPuT. Methods: The simulation models use the 1970 US birth cohort and common parameters for incidence, digital screening performance, and treatment effects. Outcomes include breast cancers diagnosed, breast cancer deaths averted, breast cancer mortality reduction, false-positive mammograms, benign biopsies, and overdiagnosis. The Mammo OUTPuT tool displays these outcomes for combinations of age at screening initiation (every year from 40 to 49, annual versus biennial interval, lifetime versus 10-year horizon, and breast density, compared to waiting to start biennial screening at age 50 and continuing to 74. The tool was piloted by decision makers (n = 16 who completed surveys. Results: The tool demonstrates that benefits in the 40s increase linearly with earlier initiation age, without a specific threshold age. Likewise, the harms of screening increase monotonically with earlier ages of initiation in the 40s. The tool also shows users how the balance of benefits and harms varies with breast density. Surveys revealed that 100% of users (16/16 liked the appearance of the site; 94% (15/16 found the tool helpful; and 94% (15/16 would recommend the tool to a colleague. Conclusions: This tool synthesizes a representative subset of the most current CISNET (Cancer Intervention and Surveillance Modeling Network simulation model outcomes to provide policy makers with quantitative data on the benefits and harms of screening women in the 40s. Ultimate decisions will depend on program goals, the population served, and informed judgments about the weight of benefits and harms.

  6. Risk-based high-throughput chemical screening and prioritization using exposure models and in vitro bioactivity assays

    International Nuclear Information System (INIS)

    Shin, Hyeong-Moo; Ernstoff, Alexi; Csiszar, Susan A.

    2015-01-01

    We present a risk-based high-throughput screening (HTS) method to identify chemicals for potential health concerns or for which additional information is needed. The method is applied to 180 organic chemicals as a case study. We first obtain information on how the chemical is used and identify relevant use scenarios (e.g., dermal application, indoor emissions). For each chemical and use scenario, exposure models are then used to calculate a chemical intake fraction, or a product intake fraction, accounting for chemical properties and the exposed population. We then combine these intake fractions with use scenario-specific estimates of chemical quantity to calculate daily intake rates (iR; mg/kg/day). These intake rates are compared to oral equivalent doses (OED; mg/kg/day), calculated from a suite of ToxCast in vitro bioactivity assays using in vitro-to-in vivo extrapolation and reverse dosimetry. Bioactivity quotients (BQs) are calculated as iR/OED to obtain estimates of potential impact associated with each relevant use scenario. Of the 180 chemicals considered, 38 had maximum iRs exceeding minimum OEDs (i.e., BQs > 1). For most of these compounds, exposures are associated with direct intake, food/oral contact, or dermal exposure. The method provides high-throughput estimates of exposure and important input for decision makers to identify chemicals of concern for further evaluation with additional information or more refined models

  7. Primary Screening for Proteins Differentially Expressed in the Myocardium of a Rat Model of Acute Methamphetamine Intoxication

    Directory of Open Access Journals (Sweden)

    Guoqiang Qu

    2016-01-01

    Full Text Available The mechanism of myocardial injury induced by the cardiovascular toxicity of methamphetamine (MA has been shown to depend on alterations in myocardial proteins caused by MA. Primary screening of the expression of myocardial proteins in a rat model of MA intoxication was achieved by combining two-dimensional electrophoresis and mass spectrometry analyses, which revealed a total of 100 differentially expressed proteins. Of these, 13 displayed significantly altered expression. Moreover, Western blotting and real-time reverse transcription quantitative polymerase chain reaction analyses of several relative proteins demonstrated that acute MA intoxication lowers protein expression and mRNA transcription of aldehyde dehydrogenase-2 and NADH dehydrogenase (ubiquinone 1 alpha subcomplex subunit 10. In contrast, MA intoxication elevated the protein expression and mRNA transcription of heat shock protein family B (small member 1. By combining behavioral assessments of experimental rat models with the histological and pathological changes evident in cardiomyocytes, a mechanism accounting for MA myocardial toxicity was suggested. MA alters the regulation of gene transcription and the subsequent expression of certain proteins that participate in myocardial respiration and in responding to oxidative stress, resulting in myocardial dysfunction and structural changes that affect the functioning of the cardiovascular system.

  8. Homology modeling and virtual screening to discover potent inhibitors targeting the imidazole glycerophosphate dehydratase protein in Staphylococcus xylosus

    Science.gov (United States)

    Chen, Xing-Ru; Wang, Xiao-Ting; Hao, Mei-Qi; Zhou, Yong-Hui; Cui, Wen-Qiang; Xing, Xiao-Xu; Xu, Chang-Geng; Bai, Jing-Wen; Li, Yan-Hua

    2017-11-01

    The imidazole glycerophosphate dehydratase (IGPD) protein is a therapeutic target for herbicide discovery. It is also regarded as a possible target in Staphylococcus xylosus (S. xylosus) for solving mastitis in the dairy cow. The 3D structure of IGPD protein is essential for discovering novel inhibitors during high-throughput virtual screening. However, to date, the 3D structure of IGPD protein of S. xylosus has not been solved. In this study, a series of computational techniques including homology modeling, Ramachandran Plots, and Verify 3D were performed in order to construct an appropriate 3D model of IGPD protein of S. xylosus. Nine hits were identified from 2500 compounds by docking studies. Then, these 9 compounds were first tested in vitro in S. xylosus biofilm formation using crystal violet staining. One of the potential compounds, baicalin was shown to significantly inhibit S. xylosus biofilm formation. Finally, the baicalin was further evaluated, which showed better inhibition of biofilm formation capability in S. xylosus by scanning electron microscopy. Hence, we have predicted the structure of IGPD protein of S. xylosus using computational techniques. We further discovered the IGPD protein was targeted by baicalin compound which inhibited the biofilm formation in S. xylosus. Our findings here would provide implications for the further development of novel IGPD inhibitors for the treatment of dairy mastitis.

  9. An Emerging Translational Model to Screen Potential Medicinal Plants for Nephrolithiasis, an Independent Risk Factor for Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    San-Yuan Wu

    2014-01-01

    Full Text Available Pharmacological therapy for urolithiasis using medicinal plants has been increasingly adopted for the prevention of its recurrence. A Drosophila melanogaster model developed for translational research of urolithiasis was applied to evaluate agents with potential antilithic effects and calcium oxalate (CaOx formation. Potential antilithic herbs were prepared in a mixture of food in a diluted concentration of 5,000 from the original extract with 0.5% ethylene glycol (EG as the lithogenic agent. The control group was fed with food only. After 3 weeks, flies (n≥150 for each group were killed using CO2 narcotization, and the Malpighian tubules were dissected, removed, and processed for polarized light microscopy examination of the crystals. The crystal formation rate in the EG group was 100.0%. In the study, 16 tested herbal drugs reached the crystal formation rate of 0.0%, including Salviae miltiorrhizae, Paeonia lactiflora, and Carthami flos. Scutellaria baicalensis enhanced CaOx crystal formation. Two herbal drugs Commiphora molmol and Natrii sulfas caused the death of all flies. Our rapid screening methods provided evidence that some medicinal plants have potential antilithic effects. These useful medicinal plants can be further studied using other animal or human models to verify their effects.

  10. UPF1 silenced cellular model systems for screening of read-through agents active on β039 thalassemia point mutation.

    Science.gov (United States)

    Salvatori, Francesca; Pappadà, Mariangela; Breveglieri, Giulia; D'Aversa, Elisabetta; Finotti, Alessia; Lampronti, Ilaria; Gambari, Roberto; Borgatti, Monica

    2018-05-15

    Nonsense mutations promote premature translational termination, introducing stop codons within the coding region of mRNAs and causing inherited diseases, including thalassemia. For instance, in β 0 39 thalassemia the CAG (glutamine) codon is mutated to the UAG stop codon, leading to premature translation termination and to mRNA destabilization through the well described NMD (nonsense-mediated mRNA decay). In order to develop an approach facilitating translation and, therefore, protection from NMD, ribosomal read-through molecules, such as aminoglycoside antibiotics, have been tested on mRNAs carrying premature stop codons. These findings have introduced new hopes for the development of a pharmacological approach to the β 0 39 thalassemia therapy. While several strategies, designed to enhance translational read-through, have been reported to inhibit NMD efficiency concomitantly, experimental tools for systematic analysis of mammalian NMD inhibition by translational read-through are lacking. We developed a human cellular model of the β 0 39 thalassemia mutation with UPF-1 suppressed and showing a partial NMD suppression. This novel cellular model could be used for the screening of molecules exhibiting preferential read-through activity allowing a great rescue of the mutated transcripts.

  11. Screen-level non-GTS data assimilation in a limited-area mesoscale model

    Directory of Open Access Journals (Sweden)

    M. Milelli

    2010-06-01

    Full Text Available The forecast in areas of very complex topography, as for instance the Alpine region, is still a challenge even for the new generation of numerical weather prediction models which aim at reaching the km-scale. The problem is enhanced by a general lack of standard observations, which is even more evident over the southern side of the Alps. For this reason, it would be useful to increase the performance of the mathematical models by locally assimilating non-conventional data. Since in ARPA Piemonte there is the availability of a great number of non-GTS stations, it has been decided to assimilate the 2 m temperature, coming from this dataset, in the very-high resolution version of the COSMO model, which has a horizontal resolution of about 3 km, more similar to the average resolution of the thermometers. Four different weather situations have been considered, ranging from spring to winter, from cloudy to clear sky. The aim of the work is to investigate the effects of the assimilation of non-GTS data in order to create an operational very high-resolution analysis, but also to test the option of running in the future a very short-range forecast starting from these analyses (RUC or Rapid Update Cycle. The results, in terms of Root Mean Square Error, Mean Error and diurnal cycle of some surface variables such as 2 m temperature, 2 m relative humidity and 10 m wind intensity show a positive impact during the assimilation cycle which tends to dissipate a few hours after the end of it. Moreover, the 2 m temperature assimilation has a slightly positive or neutral impact on the vertical profiles of temperature, eventhough some calibration is needed for the precipitation field which is too much perturbed during the assimilation cycle, while it is unaffected in the forecast period. So the stability of the planetary boundary layer, on the one hand, has not been particularly improved by the new-data assimilation, but, on the other hand, it has not been destroyed

  12. Virtual Screening Models for Prediction of HIV-1 RT Associated RNase H Inhibition

    DEFF Research Database (Denmark)

    Poongavanam, Vasanthanathan; Kongsted, Jacob

    2013-01-01

    The increasing resistance to current therapeutic agents for HIV drug regiment remains a major problem for effective acquired immune deficiency syndrome (AIDS) therapy. Many potential inhibitors have today been developed which inhibits key cellular pathways in the HIV cycle. Inhibition of HIV-1...... databases. The methods used here include machine-learning algorithms (e.g. support vector machine, random forest and kappa nearest neighbor), shape similarity (rapid overlay of chemical structures), pharmacophore, molecular interaction fields-based fingerprints for ligands and protein (FLAP) and flexible...... for identifying structurally diverse and selective RNase H inhibitors from large chemical databases. In addition, pharmacophore models suggest that the inter-distance between hydrogen bond acceptors play a key role in inhibition of the RNase H domain through metal chelation....

  13. Screening of Catalysts for Hydrodeoxygenation of Phenol as Model Compound for Bio-oil

    DEFF Research Database (Denmark)

    Mortensen, Peter Mølgaard; Grunwaldt, Jan-Dierk; Jensen, Peter Arendt

    2013-01-01

    Four groups of catalysts have been tested for hydrodeoxygenation (HDO) of phenol as a model compound of bio-oil, including: oxide catalysts, methanol synthesis catalysts, reduced noble metal catalysts, and reduced non-noble metal catalysts. In total 23 different catalysts were tested at 100 bar H2...... and 275 °C in a batch reactor. The experiments showed that none of the tested oxides and methanol synthesis catalysts had any significant activity for phenol HDO at the given conditions, which were linked to their inability to hydrogenate the phenol. HDO of phenol over reduced metal catalysts could...... on a carbon support, but more active than the carbon supported noble metal catalysts when supported on ZrO2. This observation indicates that the nickel based catalysts require a metal oxide as carrier on which the activation of the phenol for the hydrogenation can take place through heterolytic dissociation...

  14. Combining frozen-density embedding with the conductor-like screening model using Lagrangian techniques for response properties.

    Science.gov (United States)

    Schieschke, Nils; Di Remigio, Roberto; Frediani, Luca; Heuser, Johannes; Höfener, Sebastian

    2017-07-15

    We present the explicit derivation of an approach to the multiscale description of molecules in complex environments that combines frozen-density embedding (FDE) with continuum solvation models, in particular the conductor-like screening model (COSMO). FDE provides an explicit atomistic description of molecule-environment interactions at reduced computational cost, while the outer continuum layer accounts for the effect of long-range isotropic electrostatic interactions. Our treatment is based on a variational Lagrangian framework, enabling rigorous derivations of ground- and excited-state response properties. As an example of the flexibility of the theoretical framework, we derive and discuss FDE + COSMO analytical molecular gradients for excited states within the Tamm-Dancoff approximation (TDA) and for ground states within second-order Møller-Plesset perturbation theory (MP2) and a second-order approximate coupled cluster with singles and doubles (CC2). It is shown how this method can be used to describe vertical electronic excitation (VEE) energies and Stokes shifts for uracil in water and carbostyril in dimethyl sulfoxide (DMSO), respectively. In addition, VEEs for some simplified protein models are computed, illustrating the performance of this method when applied to larger systems. The interaction terms between the FDE subsystem densities and the continuum can influence excitation energies up to 0.3 eV and, thus, cannot be neglected for general applications. We find that the net influence of the continuum in presence of the first FDE shell on the excitation energy amounts to about 0.05 eV for the cases investigated. The present work is an important step toward rigorously derived ab initio multilayer and multiscale modeling approaches. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. Alcohol, Sex, and Screens: Modeling Media Influence on Adolescent Alcohol and Sex Co-Occurrence.

    Science.gov (United States)

    Bleakley, Amy; Ellithorpe, Morgan E; Hennessy, Michael; Khurana, Atika; Jamieson, Patrick; Weitz, Ilana

    2017-10-01

    Alcohol use and sexual behavior are important risk behaviors in adolescent development, and combining the two is common. The reasoned action approach (RAA) is used to predict adolescents' intention to combine alcohol use and sexual behavior based on exposure to alcohol and sex combinations in popular entertainment media. We conducted a content analysis of mainstream (n = 29) and Black-oriented movies (n = 34) from 2014 and 2013-2014, respectively, and 56 television shows (2014-2015 season). Content analysis ratings featuring character portrayals of both alcohol and sex within the same five-minute segment were used to create exposure measures that were linked to online survey data collected from 1,990 adolescents ages 14 to 17 years old (50.3% Black, 49.7% White; 48.1% female). Structural equation modeling (SEM) and group analysis by race were used to test whether attitudes, norms, and perceived behavioral control mediated the effects of media exposure on intention to combine alcohol and sex. Results suggest that for both White and Black adolescents, exposure to media portrayals of alcohol and sex combinations is positively associated with adolescents' attitudes and norms. These relationships were stronger among White adolescents. Intention was predicted by attitude, norms, and control, but only the attitude-intention relationship was different by race group (stronger for Whites).

  16. Disruption of steroidogenesis: Cell models for mechanistic investigations and as screening tools.

    Science.gov (United States)

    Odermatt, Alex; Strajhar, Petra; Engeli, Roger T

    2016-04-01

    In the modern world, humans are exposed during their whole life to a large number of synthetic chemicals. Some of these chemicals have the potential to disrupt endocrine functions and contribute to the development and/or progression of major diseases. Every year approximately 1000 novel chemicals, used in industrial production, agriculture, consumer products or as pharmaceuticals, are reaching the market, often with limited safety assessment regarding potential endocrine activities. Steroids are essential endocrine hormones, and the importance of the steroidogenesis pathway as a target for endocrine disrupting chemicals (EDCs) has been recognized by leading scientists and authorities. Cell lines have a prominent role in the initial stages of toxicity assessment, i.e. for mechanistic investigations and for the medium to high throughput analysis of chemicals for potential steroidogenesis disrupting activities. Nevertheless, the users have to be aware of the limitations of the existing cell models in order to apply them properly, and there is a great demand for improved cell-based testing systems and protocols. This review intends to provide an overview of the available cell lines for studying effects of chemicals on gonadal and adrenal steroidogenesis, their use and limitations, as well as the need for future improvements of cell-based testing systems and protocols. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Breast cancer screening in an era of personalized regimens: a conceptual model and National Cancer Institute initiative for risk-based and preference-based approaches at a population level.

    Science.gov (United States)

    Onega, Tracy; Beaber, Elisabeth F; Sprague, Brian L; Barlow, William E; Haas, Jennifer S; Tosteson, Anna N A; D Schnall, Mitchell; Armstrong, Katrina; Schapira, Marilyn M; Geller, Berta; Weaver, Donald L; Conant, Emily F

    2014-10-01

    Breast cancer screening holds a prominent place in public health, health care delivery, policy, and women's health care decisions. Several factors are driving shifts in how population-based breast cancer screening is approached, including advanced imaging technologies, health system performance measures, health care reform, concern for "overdiagnosis," and improved understanding of risk. Maximizing benefits while minimizing the harms of screening requires moving from a "1-size-fits-all" guideline paradigm to more personalized strategies. A refined conceptual model for breast cancer screening is needed to align women's risks and preferences with screening regimens. A conceptual model of personalized breast cancer screening is presented herein that emphasizes key domains and transitions throughout the screening process, as well as multilevel perspectives. The key domains of screening awareness, detection, diagnosis, and treatment and survivorship are conceptualized to function at the level of the patient, provider, facility, health care system, and population/policy arena. Personalized breast cancer screening can be assessed across these domains with both process and outcome measures. Identifying, evaluating, and monitoring process measures in screening is a focus of a National Cancer Institute initiative entitled PROSPR (Population-based Research Optimizing Screening through Personalized Regimens), which will provide generalizable evidence for a risk-based model of breast cancer screening, The model presented builds on prior breast cancer screening models and may serve to identify new measures to optimize benefits-to-harms tradeoffs in population-based screening, which is a timely goal in the era of health care reform. © 2014 American Cancer Society.

  18. Evaluation of a Stratified National Breast Screening Program in the United Kingdom: An Early Model-Based Cost-Effectiveness Analysis.

    Science.gov (United States)

    Gray, Ewan; Donten, Anna; Karssemeijer, Nico; van Gils, Carla; Evans, D Gareth; Astley, Sue; Payne, Katherine

    2017-09-01

    To identify the incremental costs and consequences of stratified national breast screening programs (stratified NBSPs) and drivers of relative cost-effectiveness. A decision-analytic model (discrete event simulation) was conceptualized to represent four stratified NBSPs (risk 1, risk 2, masking [supplemental screening for women with higher breast density], and masking and risk 1) compared with the current UK NBSP and no screening. The model assumed a lifetime horizon, the health service perspective to identify costs (£, 2015), and measured consequences in quality-adjusted life-years (QALYs). Multiple data sources were used: systematic reviews of effectiveness and utility, published studies reporting costs, and cohort studies embedded in existing NBSPs. Model parameter uncertainty was assessed using probabilistic sensitivity analysis and one-way sensitivity analysis. The base-case analysis, supported by probabilistic sensitivity analysis, suggested that the risk stratified NBSPs (risk 1 and risk-2) were relatively cost-effective when compared with the current UK NBSP, with incremental cost-effectiveness ratios of £16,689 per QALY and £23,924 per QALY, respectively. Stratified NBSP including masking approaches (supplemental screening for women with higher breast density) was not a cost-effective alternative, with incremental cost-effectiveness ratios of £212,947 per QALY (masking) and £75,254 per QALY (risk 1 and masking). When compared with no screening, all stratified NBSPs could be considered cost-effective. Key drivers of cost-effectiveness were discount rate, natural history model parameters, mammographic sensitivity, and biopsy rates for recalled cases. A key assumption was that the risk model used in the stratification process was perfectly calibrated to the population. This early model-based cost-effectiveness analysis provides indicative evidence for decision makers to understand the key drivers of costs and QALYs for exemplar stratified NBSP. Copyright

  19. Effects of Application of Social Marketing Theory and the Health Belief Model in Promoting Cervical Cancer Screening among Targeted Women in Sisaket Province, Thailand.

    Science.gov (United States)

    Wichachai, Suparp; Songserm, Nopparat; Akakul, Theerawut; Kuasiri, Chanapong

    2016-01-01

    Cervical cancer is a major public health problem in Thailand, being ranked second only to breast cancer. Thai women have been reported to have a low rate of cervical cancer screening (27.7% of the 80% goal of WHO). We therefore aimed to apply the social marketing theory and health belief model in promoting cervical cancer screening in Kanthararom District, Sisaket Province. A total of 92 from 974 targeted women aged 3060 years were randomly divided into two groups. The experimental group underwent application of social marketing theory and a health belief model program promoting cervical cancer screening while the control group received normal services. Two research tools were used: (1) application of social marketing theory and health belief model program and (2) questionnaire used to evaluate perceptions of cervical cancer. Descriptive and inferential statistics including paired sample ttest and independent ttest were used to analyze the data. After the program had been used, the mean score of perception of cervical cancer of experimental group was at a higher level (x=4.09; S.D. =0.30), than in the control group (x=3.82; S.D. =0.20) with statistical significance (psocial marketing and the health belief model be used to promote cervical cancer screening in targeted women and it can be promoted as a guideline for other health services, especially in health promotion and disease prevention.

  20. Long-term evaluation of benefits, harms, and cost-effectiveness of the National Bowel Cancer Screening Program in Australia: A modelling study

    NARCIS (Netherlands)

    Lew, J.-B. (Jie-Bin); St John, D.J.B. (D James B); X.-M. Xu (Xiang-Ming); M.J.W. Greuter (Marcel); Caruana, M. (Michael); D.R. Cenin (Dayna R.); He, E. (Emily); Saville, M. (Marion); Grogan, P. (Paul); V.M.H. Coupé (Veerle); K. Canfell (Karen)

    2017-01-01

    textabstractBackground: No assessment of the National Bowel Screening Program (NBCSP) in Australia, which considers all downstream benefits, costs, and harms, has been done. We aimed to use a comprehensive natural history model and the most recent information about cancer treatment costs to estimate

  1. Evaluation of a Stratified National Breast Screening Program in the United Kingdom : An Early Model-Based Cost-Effectiveness Analysis

    NARCIS (Netherlands)

    Gray, Ewan; Donten, Anna; Karssemeijer, Nico; van Gils, Carla; Evans, D. Gareth R.; Astley, Sue; Payne, Katherine

    Objectives: To identify the incremental costs and consequences of stratified national breast screening programs (stratified NBSPs) and drivers of relative cost-effectiveness. Methods: A decision-analytic model (discrete event simulation) was conceptualized to represent four stratified NBSPs (risk 1,

  2. Evaluation of a Stratified National Breast Screening Program in the United Kingdom: An Early Model-Based Cost-Effectiveness Analysis

    NARCIS (Netherlands)

    Gray, E.; Donten, A.; Karssemeijer, N.; Gils, C. van; Evans, D.G.; Astley, S.; Payne, K.

    2017-01-01

    OBJECTIVES: To identify the incremental costs and consequences of stratified national breast screening programs (stratified NBSPs) and drivers of relative cost-effectiveness. METHODS: A decision-analytic model (discrete event simulation) was conceptualized to represent four stratified NBSPs (risk 1,

  3. An acute rat in vivo screening model to predict compounds that alter blood glucose and/or insulin regulation.

    Science.gov (United States)

    Brott, David A; Diamond, Melody; Campbell, Pam; Zuvich, Andy; Cheatham, Letitia; Bentley, Patricia; Gorko, Mary Ann; Fikes, James; Saye, JoAnne

    2013-01-01

    Drug-induced glucose dysregulation and insulin resistance have been associated with weight gain and potential induction and/or exacerbation of diabetes mellitus in the clinic suggesting they may be safety biomarkers when developing antipsychotics. Glucose and insulin have also been suggested as potential efficacy biomarkers for some oncology compounds. The objective of this study was to qualify a medium throughput rat in vivo acute Intravenous Glucose Tolerance Test (IVGTT) for predicting compounds that will induce altered blood glucose and/or insulin levels. Acute and sub-chronic studies were performed to qualify an acute IVGTT model. Double cannulated male rats (Han-Wistar and Sprague-Dawley) were administered vehicle, olanzapine, aripiprazole or other compounds at t=-44min for acute studies and at time=-44min on the last day of dosing for sub-chronic studies, treated with dextrose (time=0min; i.v.) and blood collected using an automated Culex® system for glucose and insulin analysis (time=-45, -1, 2, 10, 15, 30, 45, 60, 75, 90, 120, 150 and 180min). Olanzapine significantly increased glucose and insulin area under the curve (AUC) values while aripiprazole AUC values were similar to control, in both acute and sub-chronic studies. All atypical antipsychotics evaluated were consistent with literature references of clinical weight gain. As efficacy biomarkers, insulin AUC but not glucose AUC values were increased with a compound known to have insulin growth factor-1 (IGF-1) activity, compared to control treatment. These studies qualified the medium throughput acute IVGTT model to more quickly screen compounds for 1) safety - the potential to elicit glucose dysregulation and/or insulin resistance and 2) efficacy - as a surrogate for compounds affecting the glucose and/or insulin regulatory pathways. These data demonstrate that the same in vivo rat model and assays can be used to predict both clinical safety and efficacy of compounds. © 2013.

  4. Screening of inhibitors for remediation of asphaltene deposits: Experimental and modeling study

    Directory of Open Access Journals (Sweden)

    Mehdi Madhi

    2018-06-01

    revelation of the mechanism behind the SDS/asphaltene behavior in various concentrations of inhibitor. Effect of chosen inhibitors on asphaltene precipitation and consequently deposition in porous media was studied, and then experimental data were modeled for evaluation of permeability impairment mechanisms. Permeability revived after inhibitor squeezing and cake formation mechanism played an important role in permeability reduction before and after treatment in porous media. The findings can also be applied to prediction of future behavior of reservoirs in oil field scale and evaluation of formation damage in the different period of production if needed any treatment process. Keywords: Asphaltene, Precipitation, Deposition, Inhibitor, Permeability reduction

  5. Toward the virtual screening of potential drugs in the homology modeled NAD+ dependent DNA ligase from Mycobacterium tuberculosis.

    Science.gov (United States)

    Singh, Vijai; Somvanshi, Pallavi

    2010-02-01

    DNA ligase is an important enzyme and it plays vital role in the replication and repair; also catalyzes nick joining between adjacent bases of DNA. The NAD(+) dependent DNA ligase is selectively present in eubacteria and few viruses; but missing in humans. Homology modeling was used to generate 3-D structure of NAD(+) dependent DNA ligase (LigA) of Mycobacterium tuberculosis using the known template (PDB: 2OWO). Furthermore, the stereochemical quality and torsion angle of 3-D structure was validated. Numerous effective drugs were selected and the active amino acid residue in LigA was targeted and virtual screening through molecular docking was done. In this analysis, four drugs Chloroquine, Hydroxychloroquine, Putrienscine and Adriamycin were found more potent in inhibition of M. tuberculosis through the robust binding affinity between protein-drug interactions in comparison with the other studied drugs. A phylogenetic tree was constructed and it was observed that homology of LigA in M. tuberculosis resembled with other Mycobacterium species. The conserved active amino acids of LigA may be useful to target these drugs. These findings could be used as the starting point of a rational design of novel antibacterial drugs and its analogs.

  6. The cytokine-dependent MUTZ-3 cell line as an in vitro model for the screening of contact sensitizers

    International Nuclear Information System (INIS)

    Azam, Philippe; Peiffer, Jean-Luc; Chamousset, Delphine; Tissier, Marie-Helene; Bonnet, Pierre-Antoine; Vian, Laurence; Fabre, Isabelle; Ourlin, Jean-Claude

    2006-01-01

    Langerhans cells (LC) are key mediators of contact allergenicity in the skin. However, no in vitro methods exist which are based on the activation process of LC to predict the sensitization potential of chemicals. In this study, we have evaluated the performances of MUTZ-3, a cytokine-dependent human monocytic cell line, in its response to sensitizers. First, we compared undifferentiated MUTZ-3 cells with several standard human cells such as THP-1, KG-1, HL-60, K-562, and U-937 in their response to the strong sensitizer DNCB and the irritant SDS by monitoring the expression levels of HLA-DR, CD54, and CD86 by flow cytometry. Only MUTZ-3 and THP-1 cells show a strong and specific response to sensitizer, while other cell lines showed very variable responses. Then, we tested MUTZ-3 cells against a wider panel of sensitizers and irritants on a broader spectrum of cell surface markers (HLA-DR, CD40, CD54, CD80, CD86, B7-H1, B7-H2, B7-DC). Of these markers, CD86 proved to be the most reliable since it detected all sensitizers, including benzocaine, a classical false negative in local lymph node assay (LLNA) but not irritants. We confirmed the MUTZ-3 response to DNCB by real-time PCR analysis. Taken together, our data suggest that undifferentiated MUTZ-3 cells may represent a valuable in vitro model for the screening of potential sensitizers

  7. Screening sensitivity theory

    International Nuclear Information System (INIS)

    Oblow, E.M.; Perey, F.G.

    1984-01-01

    A comprehensive rigorous theory is developed for screening sensitivity coefficients in largescale modeling applications. The theory uses Bayesian inference and group theory to establish a probabilistic framework for solving an underdetermined system of linear equations. The underdetermined problem is directly related to statistical screening sensitivity theory as developed in recent years. Several examples of the new approach to screening are worked out in detail and comparisons are made with statistical approaches to the problem. The drawbacks of these latter methods are discussed at some length

  8. Identification of seniors at risk (ISAR) screening tool in the emergency department: implementation using the plan-do-study-act model and validation results.

    Science.gov (United States)

    Asomaning, Nana; Loftus, Carla

    2014-07-01

    To better meet the needs of older adults in the emergency department, Senior Friendly care processes, such as high-risk screening are recommended. The identification of Seniors at Risk (ISAR) tool is a 6-item validated screening tool for identifying elderly patients at risk of the adverse outcomes post-ED visit. This paper describes the implementation of the tool in the Mount Sinai Hospital emergency department using a Plan-Do-Study-Act model; and demonstrates whether the tool predicts adverse outcomes. An observational study tracked tool implementation. A retrospective chart audit was completed to collect data about elderly ED patients during 2 time periods in 2010 and 2011. Data analysis compared the characteristics of patients with positive and negative screening tool results. The identification of Seniors at Risk tool was completed for 51.6% of eligible patients, with 61.2% of patients having a positive result. Patients with positive screening results were more likely to be over age 79 (P = .003); be admitted to hospital (P Risk tool was challenged by problematic compliance with tool completion. Strategies to address this included tool adaptation; and providing staff with knowledge of ED and inpatient geriatric resources and feedback on completion rates. Positive screening results predicted adverse outcomes in elderly Mount Sinai Hospital ED patients. © 2014. Published by Elsevier Inc. All rights reserved.

  9. South Asian ethnicity, socioeconomic status, and psychological mediators of faecal occult blood colorectal screening participation: A prospective test of a process model.

    Science.gov (United States)

    Orbell, Sheina; Szczepura, Ala; Weller, David; Gumber, Anil; Hagger, Martin S

    2017-12-01

    Although ethnicity and socioeconomic status (SES) correlate with health inequality, efforts to explain variance in health behavior attributable to these factors are limited by difficulties in population sampling. We used ethnicity identification software to test effects of psychological beliefs about screening as mediators of ethnicity and SES on faecal occult blood colorectal screening behavior in a no-cost health care context. Adults aged 50-67 years (N = 1,678), of whom 28% were from minority South Asian religiolinguistic ethnic groups (Hindu-Gujarati/Hindi, Muslim-Urdu and Sikh-Punjabi), participated in a prospective survey study. Subsequent screening participation was determined from medical records. Screening nonparticipation in the most deprived SES quintile was 1.6 times that of the least deprived quintile. Nonparticipation was 1.6 times higher in South Asians compared with non-Asians. A process model in which psychological variables mediated effects of ethnicity and SES on uptake was tested using structural equation modeling. Self-efficacy and perceived psychological costs of screening were, respectively, positive and negative direct predictors of uptake. Paths from Hindu, Muslim, and Sikh ethnicity, and SES on uptake were fully mediated by lower self-efficacy and higher perceived psychological costs. Paths from South Asian ethnicity to participation via self-efficacy and psychological costs were direct, and indirect via SES. SES is implicated, but does not fully account for low colorectal screening uptake among South Asians. Targeting increased self-efficacy and reduced perceived psychological costs may minimize health inequality effects. Future research should test independent effects of SES and ethnicity on lower self-efficacy and higher psychological costs. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  10. Cost-effectiveness of national mandatory screening of all admissions to English National Health Service hospitals for meticillin-resistant Staphylococcus aureus: a mathematical modelling study.

    Science.gov (United States)

    Robotham, Julie V; Deeny, Sarah R; Fuller, Chris; Hopkins, Susan; Cookson, Barry; Stone, Sheldon

    2016-03-01

    In December, 2010, National Health Service (NHS) England introduced national mandatory screening of all admissions for meticillin-resistant Staphylococcus aureus (MRSA). We aimed to assess the effectiveness and cost-effectiveness of this policy, from a regional or national health-care decision makers' perspective, compared with alternative screening strategies. We used an individual-based dynamic transmission model parameterised with national MRSA audit data to assess the effectiveness and cost-effectiveness of admission screening of patients in English NHS hospitals compared with five alternative strategies (including no screening, checklist-activated screening, and high-risk specialty-based screening), accompanied by patient isolation and decolonisation, over a 5 year time horizon. We evaluated strategies for different NHS hospital types (acute, teaching, and specialist), MRSA prevalence, and transmission potentials using probabilistic sensitivity analyses. Compared with no screening, mean cost per quality-adjusted life-year (QALY) of screening all admissions was £89,000-148,000 (range £68,000-222,000), and this strategy was consistently more costly and less effective than alternatives for all hospital types. At a £30,000/QALY willingness-to-pay threshold and current prevalence, only the no-screening strategy was cost effective. The next best strategies were, in acute and teaching hospitals, targeting of high-risk specialty admissions (30-40% chance of cost-effectiveness; mean incremental cost-effectiveness ratios [ICERs] £45,200 [range £35,300-61,400] and £48,000/QALY [£34,600-74,800], respectively) and, in specialist hospitals, screening these patients plus risk-factor-based screening of low-risk specialties (a roughly 20% chance of cost-effectiveness; mean ICER £62,600/QALY [£48,000-89,400]). As prevalence and transmission increased, targeting of high-risk specialties became the optimum strategy at the NHS willingness-to-pay threshold (£30,000/QALY

  11. Screen dealing

    International Nuclear Information System (INIS)

    Barlow, J.W.

    1991-01-01

    The screen dealing system provides a facility whereby buyers and sellers of spot thermal coal can make bids and offers via the medium of the Reuters screen. A sale results when a market participant notifies his acceptance of a price to a central dealing desk. Use of the system is available to all genuine participants in the coal trade. This paper reports that it provides a focus for information and for the visible making of coal prices. For years screen trading has been used successfully to trade other commodities. At last coal is being traded electronically. It makes sense. It works. Users like it

  12. A joint model of persistent human papillomavirus infection and cervical cancer risk: Implications for cervical cancer screening

    OpenAIRE

    Katki, Hormuzd A.; Cheung, Li C.; Fetterman, Barbara; Castle, Philip E.; Sundaram, Rajeshwari

    2015-01-01

    New cervical cancer screening guidelines in the US and many European countries recommend that women get tested for human papillomavirus (HPV). To inform decisions about screening intervals, we calculate the increase in precancer/cancer risk per year of continued HPV infection. However, both time to onset of precancer/cancer and time to HPV clearance are interval-censored, and onset of precancer/cancer strongly informatively censors HPV clearance. We analyze this bivariate informatively interv...

  13. Airport Screening

    Science.gov (United States)

    Health Physics Society Specialists in Radiation Safety Airport Screening Fact Sheet Adopted: May 2011 Photo courtesy of Dan ... a safe level. An American National Standards Institute/Health Physics Society industry standard states that the maxi- mum ...

  14. Hypertension screening

    Science.gov (United States)

    Foulke, J. M.

    1975-01-01

    An attempt was made to measure the response to an announcement of hypertension screening at the Goddard Space Center, to compare the results to those of previous statistics. Education and patient awareness of the problem were stressed.

  15. Carrier Screening

    Science.gov (United States)

    ... How accurate is carrier screening? No test is perfect. In a small number of cases, test results ... in which an egg is removed from a woman’s ovary, fertilized in a laboratory with the man’s ...

  16. Screening diagnostic program breast cancer

    International Nuclear Information System (INIS)

    Portnoj, L.M.; Zhakova, I.I.; Budnikova, N.V.; Rukhlyadko, E.D.

    1995-01-01

    The authors propose their screening program for detection of breast cancer. It includes the entire complex of present-day screening diagnostic methods, starting from an original system for the formation of groups at risk of breast cancer and completed by the direct diagnostic model of detection of the condition, oriented at a differentiated approach to the use of mammographic techniques. The proposed organizational and methodologic screening measures are both economic and diagnostically effective, thus meeting the principal requirements to screening programs. Screening of 8541 risk-groups patients helped detect 867 nodular formations, 244 of which were cancer and 623 benign formations. 8 refs., 3 figs.,

  17. Homology modeling, molecular dynamics, and virtual screening of NorA efflux pump inhibitors of Staphylococcus aureus.

    Science.gov (United States)

    Bhaskar, Baki Vijaya; Babu, Tirumalasetty Muni Chandra; Reddy, Netala Vasudeva; Rajendra, Wudayagiri

    2016-01-01

    Emerging drug resistance in clinical isolates of Staphylococcus aureus might be implicated to the overexpression of NorA efflux pump which is capable of extruding numerous structurally diverse compounds. However, NorA efflux pump is considered as a potential drug target for the development of efflux pump inhibitors. In the present study, NorA model was constructed based on the crystal structure of glycerol-3-phosphate transporter (PDBID: 1PW4). Molecular dynamics (MD) simulation was performed using NAMD2.7 for NorA which is embedded in the hydrated lipid bilayer. Structural design of NorA unveils amino (N)- and carboxyl (C)-terminal domains which are connected by long cytoplasmic loop. N and C domains are composed of six transmembrane α-helices (TM) which exhibits pseudo-twofold symmetry and possess voluminous substrate binding cavity between TM helices. Molecular docking of reserpine, totarol, ferruginol, salvin, thioxanthene, phenothiazine, omeprazole, verapamil, nalidixic acid, ciprofloxacin, levofloxacin, and acridine to NorA found that all the molecules were bound at the large hydrophobic cleft and indicated significant interactions with the key residues. In addition, structure-based virtual screening was employed which indicates that 14 potent novel lead molecules such as CID58685302, CID58685367, CID5799283, CID5578487, CID60028372, ZINC12196383, ZINC72140751, ZINC72137843, ZINC39227983, ZINC43742707, ZINC12196375, ZINC66166948, ZINC39228014, and ZINC14616160 have highest binding affinity for NorA. These lead molecules displayed considerable pharmacological properties as evidenced by Lipinski rule of five and prophecy of toxicity risk assessment. Thus, the present study will be helpful in designing and synthesis of a novel class of NorA efflux pump inhibitors that restore the susceptibilities of drug compounds.

  18. Generation of SNCA Cell Models Using Zinc Finger Nuclease (ZFN) Technology for Efficient High-Throughput Drug Screening.

    Science.gov (United States)

    Dansithong, Warunee; Paul, Sharan; Scoles, Daniel R; Pulst, Stefan M; Huynh, Duong P

    2015-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by loss of dopaminergic neurons of the substantia nigra. The hallmark of PD is the appearance of neuronal protein aggregations known as Lewy bodies and Lewy neurites, of which α-synuclein forms a major component. Familial PD is rare and is associated with missense mutations of the SNCA gene or increases in gene copy number resulting in SNCA overexpression. This suggests that lowering SNCA expression could be therapeutic for PD. Supporting this hypothesis, SNCA reduction was neuroprotective in cell line and rodent PD models. We developed novel cell lines expressing SNCA fused to the reporter genes luciferase (luc) or GFP with the objective to enable high-throughput compound screening (HTS) for small molecules that can lower SNCA expression. Because SNCA expression is likely regulated by far-upstream elements (including the NACP-REP1 located at 8852 bp upstream of the transcription site), we employed zinc finger nuclease (ZFN) genome editing to insert reporter genes in-frame downstream of the SNCA gene in order to retain native SNCA expression control. This ensured full retention of known and unknown up- and downstream genetic elements controlling SNCA expression. Treatment of cells with the histone deacetylase inhibitor valproic acid (VPA) resulted in significantly increased SNCA-luc and SNCA-GFP expression supporting the use of our cell lines for identifying small molecules altering complex modes of expression control. Cells expressing SNCA-luc treated with a luciferase inhibitor or SNCA siRNA resulted in Z'-scores ≥ 0.75, suggesting the suitability of these cell lines for use in HTS. This study presents a novel use of genome editing for the creation of cell lines expressing α-synuclein fusion constructs entirely under native expression control. These cell lines are well suited for HTS for compounds that lower SNCA expression directly or by acting at long-range sites to the SNCA

  19. Nonlinear mixed effects dose response modeling in high throughput drug screens: application to melanoma cell line analysis.

    Science.gov (United States)

    Ding, Kuan-Fu; Petricoin, Emanuel F; Finlay, Darren; Yin, Hongwei; Hendricks, William P D; Sereduk, Chris; Kiefer, Jeffrey; Sekulic, Aleksandar; LoRusso, Patricia M; Vuori, Kristiina; Trent, Jeffrey M; Schork, Nicholas J

    2018-01-12

    Cancer cell lines are often used in high throughput drug screens (HTS) to explore the relationship between cell line characteristics and responsiveness to different therapies. Many current analysis methods infer relationships by focusing on one aspect of cell line drug-specific dose-response curves (DRCs), the concentration causing 50% inhibition of a phenotypic endpoint (IC 50 ). Such methods may overlook DRC features and do not simultaneously leverage information about drug response patterns across cell lines, potentially increasing false positive and negative rates in drug response associations. We consider the application of two methods, each rooted in nonlinear mixed effects (NLME) models, that test the relationship relationships between estimated cell line DRCs and factors that might mitigate response. Both methods leverage estimation and testing techniques that consider the simultaneous analysis of different cell lines to draw inferences about any one cell line. One of the methods is designed to provide an omnibus test of the differences between cell line DRCs that is not focused on any one aspect of the DRC (such as the IC 50 value). We simulated different settings and compared the different methods on the simulated data. We also compared the proposed methods against traditional IC 50 -based methods using 40 melanoma cell lines whose transcriptomes, proteomes, and, importantly, BRAF and related mutation profiles were available. Ultimately, we find that the NLME-based methods are more robust, powerful and, for the omnibus test, more flexible, than traditional methods. Their application to the melanoma cell lines reveals insights into factors that may be clinically useful.

  20. Rapid Screening of Active Components with an Osteoclastic Inhibitory Effect in Herba epimedii Using Quantitative Pattern–Activity Relationships Based on Joint-Action Models

    Directory of Open Access Journals (Sweden)

    Xiao-Yan Yuan

    2017-10-01

    Full Text Available Screening of bioactive components is important for modernization and quality control of herbal medicines, while the traditional bioassay-guided phytochemical approach is time-consuming and laborious. The presented study proposes a strategy for rapid screening of active components from herbal medicines. As a case study, the quantitative pattern–activity relationship (QPAR between compounds and the osteoclastic inhibitory effect of Herba epimedii, a widely used herbal medicine in China, were investigated based on joint models. For model construction, standard mixtures data showed that the joint-action models are better than the partial least-squares (PLS model. Then, the Good2bad value, which could reflect components’ importance based on Monte Carlo sampling, was coupled with the joint-action models for screening of active components. A compound (baohuoside I and a component composed of compounds with retention times in the 6.9–7.9 min range were selected by our method. Their inhibition rates were higher than icariin, the key bioactive compound in Herba epimedii, which could inhibit osteoclast differentiation and bone resorption in a previous study. Meanwhile, the half-maximal effective concentration, namely, EC50 value of the selected component was 7.54 μg/mL, much smaller than that of baohuoside I—77 μg/mL—which indicated that there is synergistic action between compounds in the selected component. The results clearly show our proposed method is simple and effective in screening the most-bioactive components and compounds, as well as drug-lead components, from herbal medicines.

  1. Identification of novel antitubulin agents by using a virtual screening approach based on a 7-point pharmacophore model of the tubulin colchi-site.

    Science.gov (United States)

    Massarotti, Alberto; Theeramunkong, Sewan; Mesenzani, Ornella; Caldarelli, Antonio; Genazzani, Armando A; Tron, Gian Cesare

    2011-12-01

    Tubulin inhibition represents an established target in the field of anticancer research, and over the last 20 years, an intensive search for new antimicrotubule agents has occurred. Indeed, in silico models have been presented that might aid the discovery of novel agents. Among these, a 7-point pharmacophore model has been recently proposed. As a formal proof of this model, we carried out a ligand-based virtual screening on the colchicine-binding site. In vitro testing demonstrated that two compounds displayed a cytotoxic profile on neuroblastoma cancer cells (SH-SY5H) and one had an antitubulinic profile. © 2011 John Wiley & Sons A/S.

  2. CoMiniGut—a small volume in vitro colon model for the screening of gut microbial fermentation processes

    Science.gov (United States)

    Khakimov, Bekzod; Nielsen, Sebastian; Sørensen, Helena; van den Berg, Frans; Nielsen, Dennis Sandris

    2018-01-01

    Driven by the growing recognition of the influence of the gut microbiota (GM) on human health and disease, there is a rapidly increasing interest in understanding how dietary components, pharmaceuticals and pre- and probiotics influence GM. In vitro colon models represent an attractive tool for this purpose. With the dual objective of facilitating the investigation of rare and expensive compounds, as well as an increased throughput, we have developed a prototype in vitro parallel gut microbial fermentation screening tool with a working volume of only 5 ml consisting of five parallel reactor units that can be expanded with multiples of five to increase throughput. This allows e.g., the investigation of interpersonal variations in gut microbial dynamics and the acquisition of larger data sets with enhanced statistical inference. The functionality of the in vitro colon model, Copenhagen MiniGut (CoMiniGut) was first demonstrated in experiments with two common prebiotics using the oligosaccharide inulin and the disaccharide lactulose at 1% (w/v). We then investigated fermentation of the scarce and expensive human milk oligosaccharides (HMOs) 3-Fucosyllactose, 3-Sialyllactose, 6-Sialyllactose and the more common Fructooligosaccharide in fermentations with infant gut microbial communities. Investigations of microbial community composition dynamics in the CoMiniGut reactors by MiSeq-based 16S rRNA gene amplicon high throughput sequencing showed excellent experimental reproducibility and allowed us to extract significant differences in gut microbial composition after 24 h of fermentation for all investigated substrates and fecal donors. Furthermore, short chain fatty acids (SCFAs) were quantified for all treatments and donors. Fermentations with inulin and lactulose showed that inulin leads to a microbiota dominated by obligate anaerobes, with high relative abundance of Bacteroidetes, while the more easily fermented lactulose leads to higher relative abundance of

  3. CoMiniGut-a small volume in vitro colon model for the screening of gut microbial fermentation processes.

    Science.gov (United States)

    Wiese, Maria; Khakimov, Bekzod; Nielsen, Sebastian; Sørensen, Helena; van den Berg, Frans; Nielsen, Dennis Sandris

    2018-01-01

    Driven by the growing recognition of the influence of the gut microbiota (GM) on human health and disease, there is a rapidly increasing interest in understanding how dietary components, pharmaceuticals and pre- and probiotics influence GM. In vitro colon models represent an attractive tool for this purpose. With the dual objective of facilitating the investigation of rare and expensive compounds, as well as an increased throughput, we have developed a prototype in vitro parallel gut microbial fermentation screening tool with a working volume of only 5 ml consisting of five parallel reactor units that can be expanded with multiples of five to increase throughput. This allows e.g., the investigation of interpersonal variations in gut microbial dynamics and the acquisition of larger data sets with enhanced statistical inference. The functionality of the in vitro colon model, Copenhagen MiniGut (CoMiniGut) was first demonstrated in experiments with two common prebiotics using the oligosaccharide inulin and the disaccharide lactulose at 1% (w/v). We then investigated fermentation of the scarce and expensive human milk oligosaccharides (HMOs) 3-Fucosyllactose, 3-Sialyllactose, 6-Sialyllactose and the more common Fructooligosaccharide in fermentations with infant gut microbial communities. Investigations of microbial community composition dynamics in the CoMiniGut reactors by MiSeq-based 16S rRNA gene amplicon high throughput sequencing showed excellent experimental reproducibility and allowed us to extract significant differences in gut microbial composition after 24 h of fermentation for all investigated substrates and fecal donors. Furthermore, short chain fatty acids (SCFAs) were quantified for all treatments and donors. Fermentations with inulin and lactulose showed that inulin leads to a microbiota dominated by obligate anaerobes, with high relative abundance of Bacteroidetes, while the more easily fermented lactulose leads to higher relative abundance of

  4. CoMiniGut—a small volume in vitro colon model for the screening of gut microbial fermentation processes

    Directory of Open Access Journals (Sweden)

    Maria Wiese

    2018-01-01

    Full Text Available Driven by the growing recognition of the influence of the gut microbiota (GM on human health and disease, there is a rapidly increasing interest in understanding how dietary components, pharmaceuticals and pre- and probiotics influence GM. In vitro colon models represent an attractive tool for this purpose. With the dual objective of facilitating the investigation of rare and expensive compounds, as well as an increased throughput, we have developed a prototype in vitro parallel gut microbial fermentation screening tool with a working volume of only 5 ml consisting of five parallel reactor units that can be expanded with multiples of five to increase throughput. This allows e.g., the investigation of interpersonal variations in gut microbial dynamics and the acquisition of larger data sets with enhanced statistical inference. The functionality of the in vitro colon model, Copenhagen MiniGut (CoMiniGut was first demonstrated in experiments with two common prebiotics using the oligosaccharide inulin and the disaccharide lactulose at 1% (w/v. We then investigated fermentation of the scarce and expensive human milk oligosaccharides (HMOs 3-Fucosyllactose, 3-Sialyllactose, 6-Sialyllactose and the more common Fructooligosaccharide in fermentations with infant gut microbial communities. Investigations of microbial community composition dynamics in the CoMiniGut reactors by MiSeq-based 16S rRNA gene amplicon high throughput sequencing showed excellent experimental reproducibility and allowed us to extract significant differences in gut microbial composition after 24 h of fermentation for all investigated substrates and fecal donors. Furthermore, short chain fatty acids (SCFAs were quantified for all treatments and donors. Fermentations with inulin and lactulose showed that inulin leads to a microbiota dominated by obligate anaerobes, with high relative abundance of Bacteroidetes, while the more easily fermented lactulose leads to higher relative

  5. Effects of education based on the health belief model on screening behavior in high risk women for breast cancer, Tehran, Iran.

    Science.gov (United States)

    Hajian, Sepideh; Vakilian, Katayon; Najabadi, Khadijeh Mirzaii; Hosseini, Jalil; Mirzaei, Hamid Reza

    2011-01-01

    Breast cancer is the most common malignancy in women. Early diagnosis allows efficient treatment and increases survival, but the efficacy of breast self examination (BSE) is not sufficiently well established. The American Cancer Society aims to give women the opportunity to recognize the utility, limitations and adverse effects of breast cancer screening through education models based on psychological theories. With the Health Belief Model, people's health perceptions and attitudes influence their practices, for example with screening. The purpose of this randomized controlled clinical trial was to determine the effect of education based on this model on breast cancer screening in high risk Iranian women. Participants were women with a family history of breast cancer (mother, sister, and daughter). After explanation of the study objectives to participants, they were recruited on obtaining oral consent and each filled out the study questionnaire based on the Health Belief Model. Allocation was into two groups by computerized randomization, control and intervention, receiving education on breast cancer screening. Perceived susceptibility to and seriousness of breast cancer, perceived usefulness of and barriers to BSE, clinical breast examination, and mammography, and self-efficacy in the ability to perform these, were assessed, with comparison of scores for BSE practice before and after education and doing mammography and clinical examination by a physician in intervention and control group. The mean age was 37.8 ± 11.7 (range 19-60). The mean rank in the intervention group significantly differed before and after the education, but except for " perceived threat" and "perceived usefulness of breast self examination", we did not find any significant differences from the control group. After educational sessions, breast self examination and clinical examination practice rates were elevated. Health education based on well known psychological theories for breast cancer

  6. Use of risk projection models to estimate mortality and incidence from radiation-induced breast cancer in screening programs

    International Nuclear Information System (INIS)

    Ramos, M; Ferrer, S; Villaescusa, J I; Verdu, G; Salas, M D; Cuevas, M D

    2005-01-01

    The authors report on a method to calculate radiological risks, applicable to breast screening programs and other controlled medical exposures to ionizing radiation. In particular, it has been applied to make a risk assessment in the Valencian Breast Cancer Early Detection Program (VBCEDP) in Spain. This method is based on a parametric approach, through Markov processes, of hazard functions for radio-induced breast cancer incidence and mortality, with mean glandular breast dose, attained age and age-at-exposure as covariates. Excess relative risk functions of breast cancer mortality have been obtained from two different case-control studies exposed to ionizing radiation, with different follow-up time: the Canadian Fluoroscopy Cohort Study (1950-1987) and the Life Span Study (1950-1985 and 1950-1990), whereas relative risk functions for incidence have been obtained from the Life Span Study (1958-1993), the Massachusetts tuberculosis cohorts (1926-1985 and 1970-1985), the New York post-partum mastitis patients (1930-1981) and the Swedish benign breast disease cohort (1958-1987). Relative risks from these cohorts have been transported to the target population undergoing screening in the Valencian Community, a region in Spain with about four and a half million inhabitants. The SCREENRISK software has been developed to estimate radiological detriments in breast screening. Some hypotheses corresponding to different screening conditions have been considered in order to estimate the total risk associated with a woman who takes part in all screening rounds. In the case of the VBCEDP, the total radio-induced risk probability for fatal breast cancer is in a range between [5 x 10 -6 , 6 x 10 -4 ] versus the natural rate of dying from breast cancer in the Valencian Community which is 9.2 x 10 -3 . The results show that these indicators could be included in quality control tests and could be adequate for making comparisons between several screening programs

  7. Luminescent screens

    International Nuclear Information System (INIS)

    Lu, C.-I.

    1982-01-01

    Luminescent screens which are useful for such purposes as intensifying screens for radiographs are comprised of a support bearing a layer of finely divided particles of a phosphor dispersed in a cross-linked polymeric matrix formed by heat-curing of a coating composition comprising an unsaturated cross-linkable polymer, a polymerizable acrylic monomer, a thermoplastic polyurethane elastomer, and a heat-activatable polymerization initiator. The phosphor layer includes voids formed by evaporation of an evaporable component which is present in the coating composition from which such layer is formed. (author)

  8. Long-term evaluation of benefits, harms, and cost-effectiveness of the National Bowel Cancer Screening Program in Australia: a modelling study.

    Science.gov (United States)

    Lew, Jie-Bin; St John, D James B; Xu, Xiang-Ming; Greuter, Marjolein J E; Caruana, Michael; Cenin, Dayna R; He, Emily; Saville, Marion; Grogan, Paul; Coupé, Veerle M H; Canfell, Karen

    2017-07-01

    No assessment of the National Bowel Screening Program (NBCSP) in Australia, which considers all downstream benefits, costs, and harms, has been done. We aimed to use a comprehensive natural history model and the most recent information about cancer treatment costs to estimate long-term benefits, costs, and harms of the NBCSP (2 yearly immunochemical faecal occult blood testing screening at age 50-74 years) and evaluate the incremental effect of improved screening participation under different scenarios. In this modelling study, a microsimulation model, Policy1-Bowel, which simulates the development of colorectal cancer via both the conventional adenoma-carcinoma and serrated pathways was used to simulate the NBCSP in 2006-40, taking into account the gradual rollout of NBCSP in 2006-20. The base-case scenario assumed 40% screening participation (currently observed behaviour) and two alternative scenarios assuming 50% and 60% participation by 2020 were modelled. Aggregate year-by-year screening, diagnosis, treatment and surveillance-related costs, resource utilisation (number of screening tests and colonoscopies), and health outcomes (incident colorectal cancer cases and colorectal cancer deaths) were estimated, as was the cost-effectiveness of the NBCSP. With current levels of participation (40%), the NBCSP is expected to prevent 92 200 cancer cases and 59 000 deaths over the period 2015-40; an additional 24 300 and 37 300 cases and 16 800 and 24 800 deaths would be prevented if participation was increased to 50% and 60%, respectively. In 2020, an estimated 101 000 programme-related colonoscopies will be done, associated with about 270 adverse events; an additional 32 500 and 49 800 colonoscopies and 88 and 134 adverse events would occur if participation was increased to 50% and 60%, respectively. The overall number needed to screen (NNS) is 647-788 per death prevented, with 52-59 colonoscopies per death prevented. The programme is cost

  9. Alcohol Use Screening

    Science.gov (United States)

    ... Depression Screening Substance Abuse Screening Alcohol Use Screening Alcohol Use Screening (AUDIT-C) - Instructions The following questions ... this tool, there is also text-only version . Alcohol Use Screening (AUDIT-C) - Manual Instructions The following ...

  10. Assessment and model guided cancer screening promotion by village doctors in China: a randomized controlled trial protocol.

    Science.gov (United States)

    Feng, Rui; Shen, Xingrong; Chai, Jing; Chen, Penglai; Cheng, Jing; Liang, Han; Zhao, Ting; Sha, Rui; Li, Kaichun; Wang, Debin

    2015-10-12

    Proven cost-effectiveness contrasted by low uptake of cancer screening (CS) calls for new methodologies promoting the service. Contemporary interventions in this regard relies primarily on strategies targeting general or specific groups with limited attention being paid to individualized approaches. This trial tests a novel package promoting CS utilization via continuous and tailored counseling delivered by primary caregivers. It aims at demonstrating that high risk individuals in the intervention arm will, compared to those in the delayed intervention condition, show increased use of CS service. The trial adopts a quasi-randomized controlled trial design and involves 2160 high risk individuals selected, via rapid and detailed risk assessments, from about 72,000 farmers aged 35+ in 36 administrative villages randomized into equal intervention and delayed intervention arms. The CS intervention package uses: a) village doctors and village clinics to deliver personalized and thus relatively sophisticated CS counseling; b) two-stage risk assessment models in identifying high risk individuals to focus the intervention on the most needed; c) standardized operation procedures to guide conduct of counseling; d) real-time effectiveness and quality monitoring to leverage continuous improvement; e) web-based electronic system to enable prioritizing complex determinants of CS uptake and tailoring counseling sessions to the changing needs of individual farmers. The intervention arm receives baseline and semiannual follow up evaluations plus CS counseling for 5 years; while the delayed intervention arm, only the same baseline and follow-up evaluations for the first 5 years and CS counseling starting from the 6th year if the intervention proved effective. Evaluation measures include: CS uptake by high risk farmers and changes in their knowledge, perceptions and self-efficacy about CS. Given the complexity and heterogeneity in the determinant system of individual CS service

  11. Novel Method for Calculating a Nonsubjective Informative Prior for a Bayesian Model in Toxicology Screening: A Theoretical Framework

    NARCIS (Netherlands)

    Woldegebriel, M.

    2015-01-01

    In toxicology screening (forensic, food-safety), due to several analytical errors (e.g., retention time shift, lack of repeatability in m/z scans, etc.), the ability to confidently identify/confirm a compound remains a challenge. Due to these uncertainties, a probabilistic approach is currently

  12. In silico Screening and Evaluation of the Anticonvulsant Activity of Docosahexaenoic Acid-Like Molecules in Experimental Models of Seizures.

    Science.gov (United States)

    Gharibi Loron, Ali; Sardari, Soroush; Narenjkar, Jamshid; Sayyah, Mohammad

    2017-01-01

    Resistance to antiepileptic drugs and the intolerability in 20-30% of the patients raises demand for developing new drugs with improved efficacy and safety. Acceptable anticonvulsant activity, good tolerability, and inexpensiveness of docosahexaenoic acid (DHA) make it as a good candidate for designing and development of the new anticonvulsant medications. Ten DHA-based molecules were screened based on in silico screening of DHA-like molecules by root-mean-square deviation of atomic positions, the biological activity score of Professional Association for SQL Server, and structural requirements suggested by pharmacophore design. Anticonvulsant activity was tested against clonic seizures induced by pentylenetetrazole (PTZ, 60 mg/kg, i.p.) and tonic seizures induced by maximal electroshock (MES, 50 mA, 50 Hz, 1 ms duration) by intracerebroventricular (i.c.v.) injection of the screened compounds to mice. Among screened compounds, 4-Phenylbutyric acid, 4-Biphenylacetic acid, phenylacetic acid, and 2-Phenylbutyric acid showed significant protective activity in pentylenetetrazole test with ED50 values of 4, 5, 78, and 70 mM, respectively. In MES test, shikimic acid and 4-tert-Butylcyclo-hexanecarboxylic acid showed significant activity with ED50 values 29 and 637 mM, respectively. Effective compounds had no mortality in mice up to the maximum i.c.v. injectable dose of 1 mM. Common electrochemical features and three-dimensional spatial structures of the effective compounds suggest the involvement of the anticonvulsant mechanisms similar to the parent compound DHA.

  13. Initial Development of the Teen Screen for Dating Violence: Exploratory Factor Analysis, Rasch Model, and Psychometric Data

    Science.gov (United States)

    Emelianchik-Key, Kelly; Hays, Danica G.; Hill, Tara

    2018-01-01

    The Teen Screen for Dating Violence (TSDV) is an assessment that examines adolescent dating violence perpetration and victimization, perception and exposure to violence, and support systems. Through assessment, adolescents who are at high risk could be identified for prevention and early intervention. This article presents the development,…

  14. Hearing Screening

    Science.gov (United States)

    Johnson-Curiskis, Nanette

    2012-01-01

    Hearing levels are threatened by modern life--headsets for music, rock concerts, traffic noises, etc. It is crucial we know our hearing levels so that we can draw attention to potential problems. This exercise requires that students receive a hearing screening for their benefit as well as for making the connection of hearing to listening.

  15. Vision Screening

    Science.gov (United States)

    ... an efficient and cost-effective method to identify children with visual impairment or eye conditions that are likely to lead ... main goal of vision screening is to identify children who have or are at ... visual impairment unless treated in early childhood. Other problems that ...

  16. Luminescence studies on phosphor screens

    International Nuclear Information System (INIS)

    Panayiotakis, G.; Nomikos, C.; Bakas, A.; Proimos, B.

    1994-01-01

    We report our results on x-ray phosphor screens prepared of some new materials focusing attention on their efficiency under fluoroscopy conditions, on optimization conditions and on comparisons among the various materials. All data are presented in absolute values. A theoretical model is presented, that takes into account the granular structure of the screens, permitting the explanation and prediction of the luminescence properties of the screens. (authors)

  17. Luminescence studies on phosphor screens

    Energy Technology Data Exchange (ETDEWEB)

    Panayiotakis, G; Nomikos, C; Bakas, A; Proimos, B [Medical Physics Department, University of Patras, 265 00 Patras, Greece (Greece)

    1994-12-31

    We report our results on x-ray phosphor screens prepared of some new materials focusing attention on their efficiency under fluoroscopy conditions, on optimization conditions and on comparisons among the various materials. All data are presented in absolute values. A theoretical model is presented, that takes into account the granular structure of the screens, permitting the explanation and prediction of the luminescence properties of the screens. (authors). 12 refs, 3 figs.

  18. Effects of plasticizers and their mixtures on estrogen Receptor and thyroid hormone functions

    DEFF Research Database (Denmark)

    Ghisari, Mandana; Bonefeld-Jørgensen, Eva Cecilie

    2009-01-01

    compounds, but 2-PP, significantly affected the GH3 cell proliferation. tOP, BBP and DBP activated ER transactivity, whereas DEHP antagonized the 17(-estradiol induced ER function. The mixture significantly induced ER transactivity in an additive manner, whereas in the T-screen, the observed mixture effect...

  19. Developing a Screening Model to Establish Human Risk from Glacial Meltwater Release of Legacy Organochlorine Pollutants at the Silvretta Glacier in the Swiss Alps

    Science.gov (United States)

    Miner, K. R.

    2017-12-01

    Organochlorine pollutants (OCPs) banned globally by the Stockholm Convention in 2004 are reemerging from melting glaciers in numerous alpine ecosystems. Despite the known OCP influx from glaciers, a study of human risk from uptake of pesticides in glacial meltwater has never been attempted. Our study qualifies human uptake routes and quantifies risk utilizing published meltwater data from the Silvretta Glacier in the Swiss Alps in combination with methodology established by the US Environmental Protection Agency (EPA). Relatively high concentrations of OCPs in Silvretta glacier meltwater reflect proximity to use near high density populations and provide the best estimate of a 95th percentile human risk scenario. This screening level model assesses direct PCB risk to humans through consumption of fish tissue and meltwater. Our model shows a risk for both cancer and non-cancer disease impacts to children with lifetime exposure to glacial meltwater and an average local fish consumption. For adults with an abbreviated 30 year exposure timeframe, the risk for non-cancer effects is negligible and cancer effects are only barely above screening level. Populations that consume higher quantities of local fish are at greater risk, with additional challenges borne by children. Further direct study into the individual level risk to Swiss residents from glacial meltwater pollution is deemed necessary by our screening study.

  20. Predictive Accuracy of the PanCan Lung Cancer Risk Prediction Model -External Validation based on CT from the Danish Lung Cancer Screening Trial

    DEFF Research Database (Denmark)

    Winkler Wille, Mathilde M.; van Riel, Sarah J.; Saghir, Zaigham

    2015-01-01

    Objectives: Lung cancer risk models should be externally validated to test generalizability and clinical usefulness. The Danish Lung Cancer Screening Trial (DLCST) is a population-based prospective cohort study, used to assess the discriminative performances of the PanCan models. Methods: From...... the DLCST database, 1,152 nodules from 718 participants were included. Parsimonious and full PanCan risk prediction models were applied to DLCST data, and also coefficients of the model were recalculated using DLCST data. Receiver operating characteristics (ROC) curves and area under the curve (AUC) were...... used to evaluate risk discrimination. Results: AUCs of 0.826–0.870 were found for DLCST data based on PanCan risk prediction models. In the DLCST, age and family history were significant predictors (p = 0.001 and p = 0.013). Female sex was not confirmed to be associated with higher risk of lung cancer...

  1. Participant selection for lung cancer screening by risk modelling (the Pan-Canadian Early Detection of Lung Cancer [PanCan] study): a single-arm, prospective study.

    Science.gov (United States)

    Tammemagi, Martin C; Schmidt, Heidi; Martel, Simon; McWilliams, Annette; Goffin, John R; Johnston, Michael R; Nicholas, Garth; Tremblay, Alain; Bhatia, Rick; Liu, Geoffrey; Soghrati, Kam; Yasufuku, Kazuhiro; Hwang, David M; Laberge, Francis; Gingras, Michel; Pasian, Sergio; Couture, Christian; Mayo, John R; Nasute Fauerbach, Paola V; Atkar-Khattra, Sukhinder; Peacock, Stuart J; Cressman, Sonya; Ionescu, Diana; English, John C; Finley, Richard J; Yee, John; Puksa, Serge; Stewart, Lori; Tsai, Scott; Haider, Ehsan; Boylan, Colm; Cutz, Jean-Claude; Manos, Daria; Xu, Zhaolin; Goss, Glenwood D; Seely, Jean M; Amjadi, Kayvan; Sekhon, Harmanjatinder S; Burrowes, Paul; MacEachern, Paul; Urbanski, Stefan; Sin, Don D; Tan, Wan C; Leighl, Natasha B; Shepherd, Frances A; Evans, William K; Tsao, Ming-Sound; Lam, Stephen

    2017-11-01

    Results from retrospective studies indicate that selecting individuals for low-dose CT lung cancer screening on the basis of a highly predictive risk model is superior to using criteria similar to those used in the National Lung Screening Trial (NLST; age, pack-year, and smoking quit-time). We designed the Pan-Canadian Early Detection of Lung Cancer (PanCan) study to assess the efficacy of a risk prediction model to select candidates for lung cancer screening, with the aim of determining whether this approach could better detect patients with early, potentially curable, lung cancer. We did this single-arm, prospective study in eight centres across Canada. We recruited participants aged 50-75 years, who had smoked at some point in their life (ever-smokers), and who did not have a self-reported history of lung cancer. Participants had at least a 2% 6-year risk of lung cancer as estimated by the PanCan model, a precursor to the validated PLCOm2012 model. Risk variables in the model were age, smoking duration, pack-years, family history of lung cancer, education level, body-mass index, chest x-ray in the past 3 years, and history of chronic obstructive pulmonary disease. Individuals were screened with low-dose CT at baseline (T0), and at 1 (T1) and 4 (T4) years post-baseline. The primary outcome of the study was incidence of lung cancer. This study is registered with ClinicalTrials.gov, number NCT00751660. 7059 queries came into the study coordinating centre and were screened for PanCan risk. 15 were duplicates, so 7044 participants were considered for enrolment. Between Sept 24, 2008, and Dec 17, 2010, we recruited and enrolled 2537 eligible ever-smokers. After a median follow-up of 5·5 years (IQR 3·2-6·1), 172 lung cancers were diagnosed in 164 individuals (cumulative incidence 0·065 [95% CI 0·055-0·075], incidence rate 138·1 per 10 000 person-years [117·8-160·9]). There were ten interval lung cancers (6% of lung cancers and 6% of individuals with cancer

  2. An efficient route to selective bio-oxidation catalysts: an iterative approach comprising modeling, diversification, and screening, based on CYP102A1.

    Science.gov (United States)

    Seifert, Alexander; Antonovici, Mihaela; Hauer, Bernhard; Pleiss, Jürgen

    2011-06-14

    Perillyl alcohol is the terminal hydroxylation product of the cheap and readily available terpene, limonene. It has high potential as an anti-tumor substance, but is of limited availability. In principle, cytochrome P450 monooxygenases, such as the self-sufficient CYP102A1, are promising catalysts for the oxidation of limonene or other inert hydrocarbons. The wild-type enzyme converts (4R)-limonene to four different oxidation products; however, terminal hydroxylation at the allylic C7 is not observed. Here we describe a generic strategy to engineer this widely used enzyme to hydroxylate exclusively the exposed, but chemically less reactive, primary C7 in the presence of other reactive positions. The approach presented here turns CYP102A1 into a highly selective catalyst with a shifted product spectra by successive rounds of modeling, the design of small focused libraries, and screening. In the first round a minimal CYP102A1 mutant library was rationally designed. It contained variants with improved or strongly shifted regio-, stereo- and chemoselectivity, compared to wild-type. From this library the variant with the highest perillyl alcohol ratio was fine-tuned by two additional rounds of molecular modeling, diversification, and screening. In total only 29 variants needed to be screened to identify the triple mutant A264V/A238V/L437F that converts (4R)-limonene to perillyl alcohol with a selectivity of 97 %. Focusing mutagenesis on a small number of relevant positions identified by computational approaches is the key for efficient screening for enzyme selectivity. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Constructing and Validating High-Performance MIEC-SVM Models in Virtual Screening for Kinases: A Better Way for Actives Discovery.

    Science.gov (United States)

    Sun, Huiyong; Pan, Peichen; Tian, Sheng; Xu, Lei; Kong, Xiaotian; Li, Youyong; Dan Li; Hou, Tingjun

    2016-04-22

    The MIEC-SVM approach, which combines molecular interaction energy components (MIEC) derived from free energy decomposition and support vector machine (SVM), has been found effective in capturing the energetic patterns of protein-peptide recognition. However, the performance of this approach in identifying small molecule inhibitors of drug targets has not been well assessed and validated by experiments. Thereafter, by combining different model construction protocols, the issues related to developing best MIEC-SVM models were firstly discussed upon three kinase targets (ABL, ALK, and BRAF). As for the investigated targets, the optimized MIEC-SVM models performed much better than the models based on the default SVM parameters and Autodock for the tested datasets. Then, the proposed strategy was utilized to screen the Specs database for discovering potential inhibitors of the ALK kinase. The experimental results showed that the optimized MIEC-SVM model, which identified 7 actives with IC50 < 10 μM from 50 purchased compounds (namely hit rate of 14%, and 4 in nM level) and performed much better than Autodock (3 actives with IC50 < 10 μM from 50 purchased compounds, namely hit rate of 6%, and 2 in nM level), suggesting that the proposed strategy is a powerful tool in structure-based virtual screening.

  4. ZNStress: a high-throughput drug screening protocol for identification of compounds modulating neuronal stress in the transgenic mutant sod1G93R zebrafish model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    McGown, Alexander; Shaw, Dame Pamela J; Ramesh, Tennore

    2016-07-26

    Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease with death on average within 2-3 years of symptom onset. Mutations in superoxide dismutase 1 (SOD1) have been identified to cause ALS. Riluzole, the only neuroprotective drug for ALS provides life extension of only 3 months on average. Thishighlights the need for compound screening in disease models to identify new neuroprotective therapies for this disease. Zebrafish is an emerging model system that is well suited for the study of diseasepathophysiology and also for high throughput (HT) drug screening. The mutant sod1 zebrafish model of ALS mimics the hallmark features of ALS. Using a fluorescence based readout of neuronal stress, we developed a high throughput (HT) screen to identify neuroprotective compounds. Here we show that the zebrafish screen is a robust system that can be used to rapidly screen thousands ofcompounds and also demonstrate that riluzole is capable of reducing neuronal stress in this model system. The screen shows optimal quality control, maintaining a high sensitivity and specificity withoutcompromising throughput. Most importantly, we demonstrate that many compounds previously failed in human clinical trials, showed no stress reducing activity in the zebrafish assay. We conclude that HT drug screening using a mutant sod1 zebrafish is a reliable model system which supplemented with secondary assays would be useful in identifying drugs with potential for neuroprotective efficacy in ALS.

  5. Cell-based DNA demethylation detection system for screening of epigenetic drugs in 2D, 3D, and xenograft models

    Czech Academy of Sciences Publication Activity Database

    Agrawal, K.; Das, V.; Otmar, Miroslav; Krečmerová, Marcela; Džubák, P.; Hajdúch, M.

    91A, č. 2 (2017), s. 133-143 ISSN 1552-4922 R&D Projects: GA MZd(CZ) NV15-31984A; GA MŠk(CZ) LO1304; GA MŠk(CZ) LM2015064; GA TA ČR(CZ) TE01020028 Institutional support: RVO:61388963 Keywords : DNA methylation * DNA methylation inhibitors * demethylation detection system * epigenetic drugs * high content screening Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 3.222, year: 2016

  6. Vision Screening

    Science.gov (United States)

    1993-01-01

    The Visi Screen OSS-C, marketed by Vision Research Corporation, incorporates image processing technology originally developed by Marshall Space Flight Center. Its advantage in eye screening is speed. Because it requires no response from a subject, it can be used to detect eye problems in very young children. An electronic flash from a 35 millimeter camera sends light into a child's eyes, which is reflected back to the camera lens. The photorefractor then analyzes the retinal reflexes generated and produces an image of the child's eyes, which enables a trained observer to identify any defects. The device is used by pediatricians, day care centers and civic organizations that concentrate on children with special needs.

  7. [Ideas and methods of two-dimensional zebrafish model combined with chromatographic techniques in high-throughput screening of active anti-osteoporosis components of traditional Chinese medicines].

    Science.gov (United States)

    Wei, Ying-Jie; Jing, Li-Jun; Zhan, Yang; Sun, E; Jia, Xiao-Bin

    2014-05-01

    To break through the restrictions of the evaluation model and the quantity of compounds by using the two-dimensional zebrafish model combined with chromatographic techniques, and establish a new method for the high-throughput screening of active anti-osteoporosis components. According to the research group-related studies and relevant foreign literatures, on the basis of the fact that the zebrafish osteoporosis model could efficiently evaluate the activity, the zebrafish metabolism model could efficiently enrich metabolites and the chromatographic techniques could efficiently separate and analyze components of traditional Chinese medicines, we proposed that the inherent combination of the three methods is expected to efficiently decode in vivo and in vitro efficacious anti-osteoporosis materials of traditional Chinese medicines. The method makes it simple and efficient in the enrichment, separation and analysis on components of traditional Chinese medicines, particularly micro-components and metabolites and the screening anti-osteoporosis activity, fully reflects that efficacious materials of traditional Chinese medicines contain original components and metabolites, with characteristic of "multi-components, multi-targets and integral effect", which provides new ideas and methods for the early and rapid discovery of active anti-osteoporosis components of traditional Chinese medicines.

  8. Urban Adolescents’ Physical Activity Experience, Physical Activity Levels, and Use of Screen-Based Media during Leisure Time: A Structural Model

    Directory of Open Access Journals (Sweden)

    Hui Xie

    2018-01-01

    Full Text Available There is limited understanding of the relationship between physical activity and use of screen-based media, two important behaviors associated with adolescents’ health outcomes. To understand this relationship, researchers may need to consider not only physical activity level but also physical activity experience (i.e., affective experience obtained from doing physical activity. Using a sample predominantly consisting of African and Latino American urban adolescents, this study examined the interrelationships between physical activity experience, physical activity level, and use of screen-based media during leisure time. Data collected using self-report, paper and pencil surveys was analyzed using structural equation modeling. Results showed that physical activity experience was positively associated with physical activity level and had a direct negative relationship with use of non-active video games for males and a direct negative relationship with use of computer/Internet for both genders, after controlling for physical activity level. Physical activity level did not have a direct relationship with use of non-active video games or computer/Internet. However, physical activity level had a direct negative association with use of TV/movies. This study suggests that physical activity experience may play an important role in promoting physical activity and thwarting use of screen-based media among adolescents.

  9. Measuring motivation using the transtheoretical (stages of change) model: A follow-up study of people who failed an online hearing screening.

    Science.gov (United States)

    Ingo, Elisabeth; Brännström, K Jonas; Andersson, Gerhard; Lunner, Thomas; Laplante-Lévesque, Ariane

    2016-07-01

    Acceptance and readiness to seek professional help have shown to be important factors for favourable audiological rehabilitation outcomes. Theories from health psychology such as the transtheoretical (stages-of-change) model could help understand behavioural change in people with hearing impairment. In recent studies, the University of Rhode Island change assessment (URICA) has been found to have good predictive validity. In a previous study, 224 Swedish adults who had failed an online hearing screening completed URICA and two other measures of stages of change. This follow-up aimed to: (1) determine prevalence of help-seeking at a hearing clinic and hearing aid uptake, and (2) explore the predictive validity of the stages of change measures by a follow-up on the 224 participants who had failed a hearing screening 18 months previously. A total of 122 people (54%) completed the follow-up online questionnaire, including the three measures and questions regarding experience with hearing help-seeking and hearing aid uptake. Since failing the online hearing screening, 61% of participants had sought help. A good predictive validity for a one-item measure of stages of change was reported. The Staging algorithm was the stages of change measure with the best ability to predict help-seeking 18 months later.

  10. Urban Adolescents’ Physical Activity Experience, Physical Activity Levels, and Use of Screen-Based Media during Leisure Time: A Structural Model

    Science.gov (United States)

    Xie, Hui; Scott, Jason L.; Caldwell, Linda L.

    2018-01-01

    There is limited understanding of the relationship between physical activity and use of screen-based media, two important behaviors associated with adolescents’ health outcomes. To understand this relationship, researchers may need to consider not only physical activity level but also physical activity experience (i.e., affective experience obtained from doing physical activity). Using a sample predominantly consisting of African and Latino American urban adolescents, this study examined the interrelationships between physical activity experience, physical activity level, and use of screen-based media during leisure time. Data collected using self-report, paper and pencil surveys was analyzed using structural equation modeling. Results showed that physical activity experience was positively associated with physical activity level and had a direct negative relationship with use of non-active video games for males and a direct negative relationship with use of computer/Internet for both genders, after controlling for physical activity level. Physical activity level did not have a direct relationship with use of non-active video games or computer/Internet. However, physical activity level had a direct negative association with use of TV/movies. This study suggests that physical activity experience may play an important role in promoting physical activity and thwarting use of screen-based media among adolescents. PMID:29410634

  11. From positive screen to engagement in treatment: a preliminary study of the impact of a new model of care for prisoners with serious mental illness.

    Science.gov (United States)

    Pillai, Krishna; Rouse, Paul; McKenna, Brian; Skipworth, Jeremy; Cavney, James; Tapsell, Rees; Simpson, Alexander; Madell, Dominic

    2016-01-15

    The high prevalence of serious mental illness (SMI) in prisons remains a challenge for mental health services. Many prisoners with SMI do not receive care. Screening tools have been developed but better detection has not translated to higher rates of treatment. In New Zealand a Prison Model of Care (PMOC) was developed by forensic mental health and correctional services to address this challenge. The PMOC broadened triggers for referrals to mental health teams. Referrals were triaged by mental health nurses leading to multidisciplinary team assessment within specified timeframes. This pathway for screening, referral and assessment was introduced within existing resources. The PMOC was implemented across four prisons. An AB research design was used to explore the extent to which mentally ill prisoners were referred to and accepted by prison in-reach mental health teams and to determine the proportion of prison population receiving specialist mental health care. The number of prisoners in the study in the year before the PMOC (n =  9,349) was similar to the year after (n = 19,421). 24.6 % of prisoners were screened as per the PMOC in the post period. Referrals increased from 491 to 734 in the post period (Z = -7.23, p prison population on in-reach caseloads increased from 5.6 % in the pre period to 7.0 % in the year post implementation while diagnostic patterns did not change, indicating more prisoners with SMI were identified and engaged in treatment. The PMOC led to increased prisoner numbers across screening, referral, treatment and engagement. Gains were achieved without extra resources by consistent processes and improved clarity of professional roles and tasks. The PMOC described a more effective pathway to specialist care for people with SMI entering prison.

  12. Effectiveness of brief interventions as part of the Screening, Brief Intervention and Referral to Treatment (SBIRT) model for reducing the nonmedical use of psychoactive substances: a systematic review.

    Science.gov (United States)

    Young, Matthew M; Stevens, Adrienne; Galipeau, James; Pirie, Tyler; Garritty, Chantelle; Singh, Kavita; Yazdi, Fatemeh; Golfam, Mohammed; Pratt, Misty; Turner, Lucy; Porath-Waller, Amy; Arratoon, Cheryl; Haley, Nancy; Leslie, Karen; Reardon, Rhoda; Sproule, Beth; Grimshaw, Jeremy; Moher, David

    2014-05-24

    The purpose of this systematic review is to assess the effectiveness of brief interventions (BIs) as part of the Screening, Brief Intervention, and Referral to Treatment (SBIRT) model for reducing the nonmedical use of psychoactive substances. Bibliographic databases (including MEDLINE, Embase, The Cochrane Library, CINAHL, and PsycINFO to April 2012) and gray literature sources were searched. We included randomized controlled trials that opportunistically screened adolescents or adults and then provided a one-to-one, verbal BI to those at risk of substance-use harm. Of interest was the nonmedical use of psychoactive substances (for example, drugs prohibited by international law), excluding alcohol, nicotine, and caffeine. Interventions comprised four or fewer sessions and were compared with no/delayed intervention or provision of information only. Studies were assessed for bias using the Cochrane risk of bias tool. Results were synthesized narratively. Evidence was interpreted according to the GRADE framework. We identified 8,836 records. Of these, five studies met our inclusion criteria. Two studies compared BI with no BI, and three studies compared BI with information only. Studies varied in characteristics such as substances targeted, screening procedures, and BI administered. Outcomes were mostly reported by a single study, leading to limited or uncertain confidence in effect estimates. Insufficient evidence exists as to whether BIs, as part of SBIRT, are effective or ineffective for reducing the use of, or harms associated with nonmedical use of, psychoactive substances when these interventions are administered to nontreatment-seeking, screen-detected populations. Updating this review with emerging evidence will be important. CRD42012002414.

  13. Using Decision-Analytic Modeling to Isolate Interventions That Are Feasible, Efficient and Optimal: An Application from the Norwegian Cervical Cancer Screening Program.

    Science.gov (United States)

    Pedersen, Kine; Sørbye, Sveinung Wergeland; Burger, Emily Annika; Lönnberg, Stefan; Kristiansen, Ivar Sønbø

    2015-12-01

    Decision makers often need to simultaneously consider multiple criteria or outcomes when deciding whether to adopt new health interventions. Using decision analysis within the context of cervical cancer screening in Norway, we aimed to aid decision makers in identifying a subset of relevant strategies that are simultaneously efficient, feasible, and optimal. We developed an age-stratified probabilistic decision tree model following a cohort of women attending primary screening through one screening round. We enumerated detected precancers (i.e., cervical intraepithelial neoplasia of grade 2 or more severe (CIN2+)), colposcopies performed, and monetary costs associated with 10 alternative triage algorithms for women with abnormal cytology results. As efficiency metrics, we calculated incremental cost-effectiveness, and harm-benefit, ratios, defined as the additional costs, or the additional number of colposcopies, per additional CIN2+ detected. We estimated capacity requirements and uncertainty surrounding which strategy is optimal according to the decision rule, involving willingness to pay (monetary or resources consumed per added benefit). For ages 25 to 33 years, we eliminated four strategies that did not fall on either efficiency frontier, while one strategy was efficient with respect to both efficiency metrics. Compared with current practice in Norway, two strategies detected more precancers at lower monetary costs, but some required more colposcopies. Similar results were found for women aged 34 to 69 years. Improving the effectiveness and efficiency of cervical cancer screening may necessitate additional resources. Although efficient and feasible, both society and individuals must specify their willingness to accept the additional resources and perceived harms required to increase effectiveness before a strategy can be considered optimal. Copyright © 2015. Published by Elsevier Inc.

  14. One-stop microvascular screening service: an effective model for the early detection of diabetic peripheral neuropathy and the high-risk foot.

    Science.gov (United States)

    Binns-Hall, O; Selvarajah, D; Sanger, D; Walker, J; Scott, A; Tesfaye, S

    2018-04-02

    To evaluate the feasibility of a one-stop microvascular screening service for the early diagnosis of diabetic distal symmetrical polyneuropathy, painful distal symmetrical polyneuropathy and the at-risk diabetic foot. People with diabetes attending retinal screening in hospital and community settings had their feet examined by a podiatrist. Assessment included: Toronto Clinical Neuropathy Score evaluation; a 10-g monofilament test; and two validated, objective and quick measures of neuropathy obtained using the point-of-care devices 'DPN-Check', a hand-held device that measures sural nerve conduction velocity and amplitude, and 'Sudoscan', a device that measures sudomotor function. The diagnostic utility of these devices was assessed against the Toronto Clinical Neuropathy Score as the 'gold standard'. A total of 236 consecutive people attending the retinal screening service, 18.9% of whom had never previously had their feet examined, were evaluated. The prevalence of distal symmetrical polyneuropathy, assessed using the Toronto Clinical Neuropathy Score, was 30.9%, and was underestimated by 10-g monofilament test (14.4%). The prevalence of distal symmetrical polyneuropathy using DPN-check was 51.5% (84.3% sensitivity, 68.3% specificity), 38.2% using Sudoscan foot electrochemical skin conductance (77.4% sensitivity, 68.3% specificity), and 61.9% using abnormality in either of the results (93.2% sensitivity, 52.8% specificity). The results of both devices correlated with Toronto Clinical Neuropathy Score (Peye, foot and renal screening is feasible, has a high uptake, reduces clinic visits, and identifies painful distal symmetrical polyneuropathy and the at-risk foot. Combined large- and small-nerve-fibre assessment using non-invasive, quantitative and quick point-of-care devices may be an effective model for the early diagnosis of distal symmetrical polyneuropathy. © 2018 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

  15. A genetic screen identifies Tor as an interactor of VAPB in a Drosophila model of amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Senthilkumar Deivasigamani

    2014-10-01

    Full Text Available Amyotrophic Lateral Sclerosis (ALS is a progressive neurodegenerative disorder characterized by selective death of motor neurons. In 5–10% of the familial cases, the disease is inherited because of mutations. One such mutation, P56S, was identified in human VAPB that behaves in a dominant negative manner, sequestering wild type protein into cytoplasmic inclusions. We have conducted a reverse genetic screen to identify interactors of Drosophila VAPB. We screened 2635 genes and identified 103 interactors, of which 45 were enhancers and 58 were suppressors of VAPB function. Interestingly, the screen identified known ALS loci – TBPH, alsin2 and SOD1. Also identified were genes involved in cellular energetics and homeostasis which were used to build a gene regulatory network of VAPB modifiers. One key modifier identified was Tor, whose knockdown reversed the large bouton phenotype associated with VAP(P58S expression in neurons. A similar reversal was seen by over-expressing Tuberous Sclerosis Complex (Tsc1,2 that negatively regulates TOR signaling as also by reduction of S6K activity. In comparison, the small bouton phenotype associated with VAP(wt expression was reversed with Tsc1 knock down as well as S6K-CA expression. Tor therefore interacts with both VAP(wt and VAP(P58S, but in a contrasting manner. Reversal of VAP(P58S bouton phenotypes in larvae fed with the TOR inhibitor Rapamycin suggests upregulation of TOR signaling in response to VAP(P58S expression. The VAPB network and further mechanistic understanding of interactions with key pathways, such as the TOR cassette, will pave the way for a better understanding of the mechanisms of onset and progression of motor neuron disease.

  16. A genetic screen identifies Tor as an interactor of VAPB in a Drosophila model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Deivasigamani, Senthilkumar; Verma, Hemant Kumar; Ueda, Ryu; Ratnaparkhi, Anuradha; Ratnaparkhi, Girish S

    2014-10-31

    Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by selective death of motor neurons. In 5-10% of the familial cases, the disease is inherited because of mutations. One such mutation, P56S, was identified in human VAPB that behaves in a dominant negative manner, sequestering wild type protein into cytoplasmic inclusions. We have conducted a reverse genetic screen to identify interactors of Drosophila VAPB. We screened 2635 genes and identified 103 interactors, of which 45 were enhancers and 58 were suppressors of VAPB function. Interestingly, the screen identified known ALS loci - TBPH, alsin2 and SOD1. Also identified were genes involved in cellular energetics and homeostasis which were used to build a gene regulatory network of VAPB modifiers. One key modifier identified was Tor, whose knockdown reversed the large bouton phenotype associated with VAP(P58S) expression in neurons. A similar reversal was seen by over-expressing Tuberous Sclerosis Complex (Tsc1,2) that negatively regulates TOR signaling as also by reduction of S6K activity. In comparison, the small bouton phenotype associated with VAP(wt) expression was reversed with Tsc1 knock down as well as S6K-CA expression. Tor therefore interacts with both VAP(wt) and VAP(P58S), but in a contrasting manner. Reversal of VAP(P58S) bouton phenotypes in larvae fed with the TOR inhibitor Rapamycin suggests upregulation of TOR signaling in response to VAP(P58S) expression. The VAPB network and further mechanistic understanding of interactions with key pathways, such as the TOR cassette, will pave the way for a better understanding of the mechanisms of onset and progression of motor neuron disease. © 2014. Published by The Company of Biologists Ltd.

  17. Chemical-specific screening criteria for interpretation of biomonitoring data for volatile organic compounds (VOCs)--application of steady-state PBPK model solutions.

    Science.gov (United States)

    Aylward, Lesa L; Kirman, Chris R; Blount, Ben C; Hays, Sean M

    2010-10-01

    The National Health and Nutrition Examination Survey (NHANES) generates population-representative biomonitoring data for many chemicals including volatile organic compounds (VOCs) in blood. However, no health or risk-based screening values are available to evaluate these data from a health safety perspective or to use in prioritizing among chemicals for possible risk management actions. We gathered existing risk assessment-based chronic exposure reference values such as reference doses (RfDs), reference concentrations (RfCs), tolerable daily intakes (TDIs), cancer slope factors, etc. and key pharmacokinetic model parameters for 47 VOCs. Using steady-state solutions to a generic physiologically-based pharmacokinetic (PBPK) model structure, we estimated chemical-specific steady-state venous blood concentrations across chemicals associated with unit oral and inhalation exposure rates and with chronic exposure at the identified exposure reference values. The geometric means of the slopes relating modeled steady-state blood concentrations to steady-state exposure to a unit oral dose or unit inhalation concentration among 38 compounds with available pharmacokinetic parameters were 12.0 microg/L per mg/kg-d (geometric standard deviation [GSD] of 3.2) and 3.2 microg/L per mg/m(3) (GSD=1.7), respectively. Chemical-specific blood concentration screening values based on non-cancer reference values for both oral and inhalation exposure range from 0.0005 to 100 microg/L; blood concentrations associated with cancer risk-specific doses at the 1E-05 risk level ranged from 5E-06 to 6E-02 microg/L. The distribution of modeled steady-state blood concentrations associated with unit exposure levels across VOCs may provide a basis for estimating blood concentration screening values for VOCs that lack chemical-specific pharmacokinetic data. The screening blood concentrations presented here provide a tool for risk assessment-based evaluation of population biomonitoring data for VOCs and

  18. Applications of patient-specific induced pluripotent stem cells; focused on disease modeling, drug screening and therapeutic potentials for liver disease.

    Science.gov (United States)

    Chun, Yong Soon; Chaudhari, Pooja; Jang, Yoon-Young

    2010-12-14

    The recent advances in the induced pluripotent stem cell (iPSC) research have significantly changed our perspectives on regenerative medicine by providing researchers with a unique tool to derive disease-specific stem cells for study. In this review, we describe the human iPSC generation from developmentally diverse origins (i.e. endoderm-, mesoderm-, and ectoderm- tissue derived human iPSCs) and multistage hepatic differentiation protocols, and discuss both basic and clinical applications of these cells including disease modeling, drug toxicity screening/drug discovery, gene therapy and cell replacement therapy.

  19. Water screen

    Energy Technology Data Exchange (ETDEWEB)

    Kutepov, A.I.; Fedotov, I.N.; Prokopov, O.I.

    1981-01-01

    The invention refers to ventilation and can be used for repair-fitting operations in a blasting-dangerous gas condition, for example, during elimination of gas-oil gushers, repair of gas-oil pipelines, equipment etc. In order to improve safety of labor, the nozzle adapters of the water collector are oriented towards each other. The collector is installed on a support with the possibility of rotating and vertical movement. The proposed screen excludes the possibility of blasting-dangerous concentrations of gases and guarantees extinguishing of the impact spark during operation of the tool.

  20. RBC Antibody Screen

    Science.gov (United States)

    ... C Cystic Fibrosis (CF) Gene Mutations Testing Cytomegalovirus (CMV) Tests D-dimer Dengue Fever Testing Des-gamma- ... Index of Screening Recommendations Not Listed? Not Listed? Newborn Screening Screening Tests for Infants Screening Tests for ...

  1. Mental Health Screening Center

    Science.gov (United States)

    ... Releases & Announcements Public Service Announcements Partnering with DBSA Mental Health Screening Center These online screening tools are not ... you have any concerns, see your doctor or mental health professional. Depression Screening for Adult Depression Screening for ...

  2. Breast cancer screening

    Science.gov (United States)

    Mammogram - breast cancer screening; Breast exam - breast cancer screening; MRI - breast cancer screening ... is performed to screen women to detect early breast cancer when it is more likely to be cured. ...

  3. Cost-effectiveness of an HPV self-collection campaign in Uganda: comparing models for delivery of cervical cancer screening in a low-income setting.

    Science.gov (United States)

    Campos, Nicole G; Tsu, Vivien; Jeronimo, Jose; Njama-Meya, Denise; Mvundura, Mercy; Kim, Jane J

    2017-09-01

    With the availability of a low-cost HPV DNA test that can be administered by either a healthcare provider or a woman herself, programme planners require information on the costs and cost-effectiveness of implementing cervical cancer screening programmes in low-resource settings under different models of healthcare delivery. Using data from the START-UP demonstration project and a micro-costing approach, we estimated the health and economic impact of once-in-a-lifetime HPV self-collection campaign relative to clinic-based provider-collection of HPV specimens in Uganda. We used an individual-based Monte Carlo simulation model of the natural history of HPV and cervical cancer to estimate lifetime health and economic outcomes associated with screening with HPV DNA testing once in a lifetime (clinic-based provider-collection vs a self-collection campaign). Test performance and cost data were obtained from the START-UP demonstration project using a micro-costing approach. Model outcomes included lifetime risk of cervical cancer, total lifetime costs (in 2011 international dollars [I$]), and life expectancy. Cost-effectiveness ratios were expressed using incremental cost-effectiveness ratios (ICERs). When both strategies achieved 75% population coverage, ICERs were below Uganda's per capita GDP (self-collection: I$80 per year of life saved [YLS]; provider-collection: I$120 per YLS). When the self-collection campaign achieved coverage gains of 15-20%, it was more effective than provider-collection, and had a lower ICER unless coverage with both strategies was 50% or less. Findings were sensitive to cryotherapy compliance among screen-positive women and relative HPV test performance. The primary limitation of this analysis is that self-collection costs are based on a hypothetical campaign but are based on unit costs from Uganda. Once-in-a-lifetime screening with HPV self-collection may be very cost-effective and reduce cervical cancer risk by > 20% if coverage is high

  4. Study protocol for a transversal study to develop a screening model for excessive gambling behaviours on a representative sample of users of French authorised gambling websites.

    Science.gov (United States)

    Perrot, Bastien; Hardouin, Jean-Benoit; Costes, Jean-Michel; Caillon, Julie; Grall-Bronnec, Marie; Challet-Bouju, Gaëlle

    2017-05-17

    Since the legalisation of online gambling in France in 2010, gambling operators must implement responsible gambling measures to prevent excessive gambling practices. However, actually there is no screening procedure for identifying problematic gamblers. Although several studies have already been performed using several data sets from online gambling operators, the authors deplored several methodological and clinical limits that prevent scientifically validating the existence of problematic gambling behaviour. The aim of this study is to develop a model for screening excessive gambling practices based on the gambling behaviours observed on French gambling websites, coupled with a clinical validation. The research is divided into three successive stages. All analyses will be performed for each major type of authorised online gambling in France. The first stage aims at defining a typology of users of French authorised gambling websites based on their gambling behaviour. This analysis will be based on data from the Authority for Regulating Online Gambling (ARJEL) and the Française Des Jeux (FDJ). For the second stage aiming at determining a score to predict whether a gambler is problematic or not, we will cross answers from the Canadian Problem Gambling Index with real gambling data. The objective of the third stage is to clinically validate the score previously developed. Results from the screening model will be compared (using sensitivity, specificity, area under the curve, and positive and negative predictive values) with the diagnosis obtained with a telephone clinical interview, including diagnostic criteria for gambling addiction. This study was approved by the local Research Ethics Committee (GNEDS) on 25 March 2015. Results will be presented in national and international conferences, submitted to peer-reviewed journals and will be part of a PhD thesis. A final report with the study results will be presented to the ARJEL, especially the final screening model

  5. Pharmacophore modeling and in silico / in vitro screening for human cytochrome P450 11B1 & cytochrome P450 11B2 inhibitors

    Science.gov (United States)

    Akram, Muhammad; Waratchareeyakul, Watcharee; Haupenthal, Joerg; Hartmann, Rolf W.; Schuster, Daniela

    2017-12-01

    Cortisol synthase (CYP11B1) is the main enzyme for the endogenous synthesis of cortisol and its inhibition is a potential way for the treatment of diseases associated with increased cortisol levels, such as Cushing’s syndrome, metabolic diseases, and delayed wound healing. Aldosterone synthase (CYP11B2) is the key enzyme for aldosterone biosynthesis and its inhibition is a promising approach for the treatment of congestive heart failure, cardiac fibrosis, and certain forms of hypertension. Both CYP11B1 and CYP11B2 are structurally very similar and expressed in the adrenal cortex. To facilitate the identification of novel inhibitors of these enzymes, ligand-based pharmacophore models of CYP11B1 and CYP11B2 inhibition were developed. A virtual screening of the SPECS database was performed with our pharmacophore queries. Biological evaluation of the selected hits lead to the discovery of three potent novel inhibitors of both CYP11B1 and CYP11B2 in the submicromolar range (compounds 8-10), one selective CYP11B1 inhibitor (Compound 11, IC50 = 2.5 µM), and one selective CYP11B2 inhibitor (compound 12, IC50 = 1.1 µM), respectively. The overall success rate of this prospective virtual screening experiment is 20.8% indicating good predictive power of the pharmacophore models.

  6. Pharmacophore Modeling and in Silico/in Vitro Screening for Human Cytochrome P450 11B1 and Cytochrome P450 11B2 Inhibitors.

    Science.gov (United States)

    Akram, Muhammad; Waratchareeyakul, Watcharee; Haupenthal, Joerg; Hartmann, Rolf W; Schuster, Daniela

    2017-01-01

    Cortisol synthase (CYP11B1) is the main enzyme for the endogenous synthesis of cortisol and its inhibition is a potential way for the treatment of diseases associated with increased cortisol levels, such as Cushing's syndrome, metabolic diseases, and delayed wound healing. Aldosterone synthase (CYP11B2) is the key enzyme for aldosterone biosynthesis and its inhibition is a promising approach for the treatment of congestive heart failure, cardiac fibrosis, and certain forms of hypertension. Both CYP11B1 and CYP11B2 are structurally very similar and expressed in the adrenal cortex. To facilitate the identification of novel inhibitors of these enzymes, ligand-based pharmacophore models of CYP11B1 and CYP11B2 inhibition were developed. A virtual screening of the SPECS database was performed with our pharmacophore queries. Biological evaluation of the selected hits lead to the discovery of three potent novel inhibitors of both CYP11B1 and CYP11B2 in the submicromolar range (compounds 8 - 10 ), one selective CYP11B1 inhibitor (Compound 11 , IC 50 = 2.5 μM), and one selective CYP11B2 inhibitor (compound 12 , IC 50 = 1.1 μM), respectively. The overall success rate of this prospective virtual screening experiment is 20.8% indicating good predictive power of the pharmacophore models.

  7. Pharmacophore Modeling and in Silico/in Vitro Screening for Human Cytochrome P450 11B1 and Cytochrome P450 11B2 Inhibitors

    Directory of Open Access Journals (Sweden)

    Muhammad Akram

    2017-12-01

    Full Text Available Cortisol synthase (CYP11B1 is the main enzyme for the endogenous synthesis of cortisol and its inhibition is a potential way for the treatment of diseases associated with increased cortisol levels, such as Cushing's syndrome, metabolic diseases, and delayed wound healing. Aldosterone synthase (CYP11B2 is the key enzyme for aldosterone biosynthesis and its inhibition is a promising approach for the treatment of congestive heart failure, cardiac fibrosis, and certain forms of hypertension. Both CYP11B1 and CYP11B2 are structurally very similar and expressed in the adrenal cortex. To facilitate the identification of novel inhibitors of these enzymes, ligand-based pharmacophore models of CYP11B1 and CYP11B2 inhibition were developed. A virtual screening of the SPECS database was performed with our pharmacophore queries. Biological evaluation of the selected hits lead to the discovery of three potent novel inhibitors of both CYP11B1 and CYP11B2 in the submicromolar range (compounds 8–10, one selective CYP11B1 inhibitor (Compound 11, IC50 = 2.5 μM, and one selective CYP11B2 inhibitor (compound 12, IC50 = 1.1 μM, respectively. The overall success rate of this prospective virtual screening experiment is 20.8% indicating good predictive power of the pharmacophore models.

  8. Virtual Screening of M3 Protein Antagonists for Finding a Model to Study the Gammaherpesvirus Damaged Immune System and Chemokine Related Diseases

    Directory of Open Access Journals (Sweden)

    Ibrahim Torktaz

    2013-12-01

    Full Text Available Introduction: M3 protein is a chemokine decoy receptor involved in pathogenesis of persistent infection with gammaherpesvirus and complications related to the latency of this pathogen. We proposed that antagonists of the M3 would provide a unique opportunity for studying new therapeutic strategies in disordered immune system, immune-deficient states and role of chemokines in pathogenesis development. Methods: Comparative modeling and fold recognition algorithms have been used for prediction of M3 protein 3-D model. Evaluation of the models using Q-mean and ProSA-web score, has led to choosing predicted model by fold recognition algorithm as the best model which was minimized regarding energy level using Molegro Virtual Docker 2011.4.3.0 (MVD software. Pockets and active sites of model were recognized using MVD cavity detection, and MetaPocket algorithms. Ten thousand compounds accessible on KEGG database were screened; MVD was used for computer simulated docking study; MolDock SE was selected as docking scoring function and final results were evaluated based on MolDock and Re-rank score. Results: Docking data suggested that prilocaine, which is generally applied as a topical anesthetic, binds strongly to 3-D model of M3 protein. Conclusion: This study proposes that prilocaine is a potential inhibitor of M3 protein and possibly has immune enhancing properties.

  9. Investigating ER-Associated Degradation with RNAi Screening - and Searching for Model Proteins to Do It with

    DEFF Research Database (Denmark)

    Jensen, Njal Winther

    Abstract In eukaryotes, secretory proteins are translocated into the endoplasmic reticulum (ER) for folding assistance, acquisition of posttranslational modifications and sorting. Proteins that do not obtain their native conformation are eliminated by ER-associated degradation (ERAD). ERAD...... is a sophisticated pathway that recognizes misfolded proteins and targets them for degradation by the 26S proteasome residing in the cytosol. More than 60 diseases including Alzheimer’s disease, Huntington’s disease and Parkinson’s disease have been linked to the ERAD pathway underscoring its crucial role...... for cellular homeostasis. The aim of this thesis has been to gain insight into ERAD. The experimental approach was RNAi screening, which is a fast and efficient method for initial evaluation of a large pool of genes. Since relatively few proteins routinely are used as ERAD substrates, the first goal...

  10. Design of a micro colorimetric enzyme assay for screening of radioprotectors using the oriental fruit fly Bactrocera Philippine's Model

    International Nuclear Information System (INIS)

    Deocaris, Custer C.; Nato, Jr. Alejandro Q.; Dacanay, Elena T.; Marcelo, Samantha C.; Buenaventura, Dyan M.

    1998-01-01

    Loss of function and expression of a 109kDa protein is observed in the oriental fruit fly, Bactrocera philippinensis, upon exposure to a γ-radiation dose of 100 Gy. Found to possess tyrosinase activity, this marker enzyme is particularly important during quarantine treatment of export fruits. A semi-automated radioprotector screening assay for anti-cancer drug development at PNRI has been developed and optimized. Larvae of B.philippinensis are subjected to relatively high and low doses of standard radioprotectors (L-glutathione (GSH), tert-butylated hydroxyanisole (BHA), garlic bulb extracts), temperature treatments (37 degrees centegrade and 42 degrees centegrade) and relatively high and low radiation doses (10 and 40 Gy) following a 2-factorial design. Using mushroom tyrosinase as standard and 605 nm as reference wavelength, optimum precision, sensitivity and curve linearity are achieved at the 405 nm window within 60-minute reaction time with 2-methyl DOPA yielding dopachrome. Significant radioprotection and tyrosinase activity are observed. Results showed that GSH exhibited the best radioprotection with an emergence rate of 100% (GSHη 42 degrees10). Consequently, GSHη exhibited a high dopachrome level next to garlicη. Garlic approximates the performance of GSH and BHA, but the fact that dopachrome levels or garlich are exceeding high could be correlated with the relatively lower emergence rates observed. Dopachrome level of 0.45-005μg/ml exhibits the optimal radioprotection.Other radioprotectors will be screened in the future using this assay in search of potent and less toxic radioprotectors that could decrease radiation-induced morbidities and improve therapeutic gains in patients undergoing therapy. (Author)

  11. Screening of the anticonvulsant activity of some plants from Fabaceae family in experimental seizure models in mice

    Directory of Open Access Journals (Sweden)

    S Sardari

    2011-10-01

    Full Text Available "n  Background and purpose of the study: Fabaceae is the third largest family of flowering plants. Lack of essential oils in the plants of this family can be an advantage in search for safe and effective medicines. In this study the anticonvulsant effect of the leaves of Albizzia julibrissin, Acacia juliflora, Acacia nubica and aerial parts of Astragalus obtusifolius was evaluated in pentylenetetrazole (PTZ and maximal electroshock (MES seizure tests. "n  Methods: The hydroalcoholic extracts of the plants were obtained by percolation. Different doses of the extracts were injected to the mice intraperitoneally (i.p. and occurrence of clonic seizures induced by PTZ (60 mg/kg, i.p. or tonic seizures induced by MES (50 mA, 50Hz, 1sec were monitored up to 30 min after administration. Acute toxicity of the extracts was also assessed. The safe and effective extract was then fractionated by dichloromethane and anticonvulsant activity of the fractions was determined. Finally, the constituents of the extract and the fractions were screened by thin layer chromatography. "n  Results: Among the extracts, only A. obtusifolius extract showed low toxicity and protective effect against clonic seizures with ED50 value of 3.97 g/kg. Fractionation of the extract led to increase in anticonvulsant activity and ED50 value of 2.86 g/kg was obtained for the aqueous fraction. Phytochemical screening revealed the presence of alkaloids, flavonoids, anthrones and saponins in the aqueous fraction. "n  Major conclusion: The presence of anticonvulsant compounds in A. obtusifolius suggests further activity-guided fractionation and analytical studies to find out the potential of this plant as a source of anticonvulsant agent.

  12. The prostate cancer screening clinic in the Bahamas: a model for low- and middle-income countries.

    Science.gov (United States)

    Roberts, Robin; Mitchell, Corydon; Tancawan, Ana Lourdes; Pedican, Mandi; Jones, Glenn Wayne

    2017-11-01

    Grand Bahama (pop. 51,000) is an island within the Bahamas archipelago. A local chapter of International Us TOO Prostate Cancer Support Group (UTGB) has led an annual community-based prostate cancer screening clinic in Grand Bahama each September since 2009. Features of this initiative, characteristics of attendees, and a description of found cancers were summarized to determine the clinic's value and to guide improvements. We analyzed the established clinic from 2012 to 2015, wherein UTGB attracted corporate funding, volunteers managed clinics, and health professionals provided healthcare services. An explicit algorithm was used to sort clients by age, comorbidities, and findings from digital rectal examinations, and prostate-specific antigen (PSA) values, to determine which clients would undergo secondary assessment and prostate biopsy. Overall, 1,844 males were registered (mean age 57.6 years), and only 149 men attended on more than one occasion for a total of 1,993 clinic visit. The urologist reviewed 315 men in secondary follow-up, for elevated PSA and/or an abnormal digital rectal examination. Of these, 45 men fulfilled criteria for trans-rectal ultrasound biopsy, and there were 40 found cases of prostate cancer, for a positive-predictive value of 89%. By D'Amico risk-stratification, these 40 cases were low (10%), intermediate (40%), and high risk (50%). The urologist counseled all 40 cases and facilitated access to standard care. This study suggests that low-resource countries can advance cost-effective screening clinics, apply policy guidelines, and provide services within acceptable standards of care. It is the expectation, with a sustained effort and community participation over the ensuing years, that earlier disease presentation will occur and, consequently, a concomitant decrease in the disease-specific mortality.

  13. Alginate based 3D hydrogels as an in vitro co-culture model platform for the toxicity screening of new chemical entities

    International Nuclear Information System (INIS)

    Lan, Shih-Feng; Starly, Binil

    2011-01-01

    Prediction of human response to potential therapeutic drugs is through conventional methods of in vitro cell culture assays and expensive in vivo animal testing. Alternatives to animal testing require sophisticated in vitro model systems that must replicate in vivo like function for reliable testing applications. Advancements in biomaterials have enabled the development of three-dimensional (3D) cell encapsulated hydrogels as in vitro drug screening tissue model systems. In this study, we have developed an in vitro platform to enable high density 3D culture of liver cells combined with a monolayer growth of target breast cancer cell line (MCF-7) in a static environment as a representative example of screening drug compounds for hepatotoxicity and drug efficacy. Alginate hydrogels encapsulated with serial cell densities of HepG2 cells (10 5 -10 8 cells/ml) are supported by a porous poly-carbonate disc platform and co-cultured with MCF-7 cells within standard cell culture plates during a 3 day study period. The clearance rates of drug transformation by HepG2 cells are measured using a coumarin based pro-drug. The platform was used to test for HepG2 cytotoxicity 50% (CT 50 ) using commercially available drugs which further correlated well with published in vivo LD 50 values. The developed test platform allowed us to evaluate drug dose concentrations to predict hepatotoxicity and its effect on the target cells. The in vitro 3D co-culture platform provides a scalable and flexible approach to test multiple-cell types in a hybrid setting within standard cell culture plates which may open up novel 3D in vitro culture techniques to screen new chemical entity compounds. - Graphical abstract: Display Omitted Highlights: → A porous support disc design to support the culture of desired cells in 3D hydrogels. → Demonstrated the co-culture of two cell types within standard cell-culture plates. → A scalable, low cost approach to toxicity screening involving multiple cell

  14. Predictive accuracy of the PanCan lung cancer risk prediction model - external validation based on CT from the Danish Lung Cancer Screening Trial

    International Nuclear Information System (INIS)

    Winkler Wille, Mathilde M.; Dirksen, Asger; Riel, Sarah J. van; Jacobs, Colin; Scholten, Ernst T.; Ginneken, Bram van; Saghir, Zaigham; Pedersen, Jesper Holst; Hohwue Thomsen, Laura; Skovgaard, Lene T.

    2015-01-01

    Lung cancer risk models should be externally validated to test generalizability and clinical usefulness. The Danish Lung Cancer Screening Trial (DLCST) is a population-based prospective cohort study, used to assess the discriminative performances of the PanCan models. From the DLCST database, 1,152 nodules from 718 participants were included. Parsimonious and full PanCan risk prediction models were applied to DLCST data, and also coefficients of the model were recalculated using DLCST data. Receiver operating characteristics (ROC) curves and area under the curve (AUC) were used to evaluate risk discrimination. AUCs of 0.826-0.870 were found for DLCST data based on PanCan risk prediction models. In the DLCST, age and family history were significant predictors (p = 0.001 and p = 0.013). Female sex was not confirmed to be associated with higher risk of lung cancer; in fact opposing effects of sex were observed in the two cohorts. Thus, female sex appeared to lower the risk (p = 0.047 and p = 0.040) in the DLCST. High risk discrimination was validated in the DLCST cohort, mainly determined by nodule size. Age and family history of lung cancer were significant predictors and could be included in the parsimonious model. Sex appears to be a less useful predictor. (orig.)

  15. Predictive accuracy of the PanCan lung cancer risk prediction model - external validation based on CT from the Danish Lung Cancer Screening Trial

    Energy Technology Data Exchange (ETDEWEB)

    Winkler Wille, Mathilde M.; Dirksen, Asger [Gentofte Hospital, Department of Respiratory Medicine, Hellerup (Denmark); Riel, Sarah J. van; Jacobs, Colin; Scholten, Ernst T.; Ginneken, Bram van [Radboud University Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen (Netherlands); Saghir, Zaigham [Herlev Hospital, Department of Respiratory Medicine, Herlev (Denmark); Pedersen, Jesper Holst [Copenhagen University Hospital, Department of Thoracic Surgery, Rigshospitalet, Koebenhavn Oe (Denmark); Hohwue Thomsen, Laura [Hvidovre Hospital, Department of Respiratory Medicine, Hvidovre (Denmark); Skovgaard, Lene T. [University of Copenhagen, Department of Biostatistics, Koebenhavn Oe (Denmark)

    2015-10-15

    Lung cancer risk models should be externally validated to test generalizability and clinical usefulness. The Danish Lung Cancer Screening Trial (DLCST) is a population-based prospective cohort study, used to assess the discriminative performances of the PanCan models. From the DLCST database, 1,152 nodules from 718 participants were included. Parsimonious and full PanCan risk prediction models were applied to DLCST data, and also coefficients of the model were recalculated using DLCST data. Receiver operating characteristics (ROC) curves and area under the curve (AUC) were used to evaluate risk discrimination. AUCs of 0.826-0.870 were found for DLCST data based on PanCan risk prediction models. In the DLCST, age and family history were significant predictors (p = 0.001 and p = 0.013). Female sex was not confirmed to be associated with higher risk of lung cancer; in fact opposing effects of sex were observed in the two cohorts. Thus, female sex appeared to lower the risk (p = 0.047 and p = 0.040) in the DLCST. High risk discrimination was validated in the DLCST cohort, mainly determined by nodule size. Age and family history of lung cancer were significant predictors and could be included in the parsimonious model. Sex appears to be a less useful predictor. (orig.)

  16. Ultra-low-dose lung screening CT with model-based iterative reconstruction: an assessment of image quality and lesion conspicuity.

    Science.gov (United States)

    Ju, Yun Hye; Lee, Geewon; Lee, Ji Won; Hong, Seung Baek; Suh, Young Ju; Jeong, Yeon Joo

    2018-05-01

    Background Reducing radiation dose inevitably increases image noise, and thus, it is important in low-dose computed tomography (CT) to maintain image quality and lesion detection performance. Purpose To assess image quality and lesion conspicuity of ultra-low-dose CT with model-based iterative reconstruction (MBIR) and to determine a suitable protocol for lung screening CT. Material and Methods A total of 120 heavy smokers underwent lung screening CT and were randomly and equally assigned to one of five groups: group 1 = 120 kVp, 25 mAs, with FBP reconstruction; group 2 = 120 kVp, 10 mAs, with MBIR; group 3 = 100 kVp, 15 mAs, with MBIR; group 4 = 100 kVp, 10 mAs, with MBIR; and group 5 = 100 kVp, 5 mAs, with MBIR. Two radiologists evaluated intergroup differences with respect to radiation dose, image noise, image quality, and lesion conspicuity using the Kruskal-Wallis test and the Chi-square test. Results Effective doses were 61-87% lower in groups 2-5 than in group 1. Image noises in groups 1 and 5 were significantly higher than in the other groups ( P image quality was best in group 1, but diagnostic acceptability of overall image qualities in groups 1-3 was not significantly different (all P values > 0.05). Lesion conspicuities were similar in groups 1-4, but were significantly poorer in group 5. Conclusion Lung screening CT with MBIR obtained at 100 kVp and 15 mAs enables a ∼60% reduction in radiation dose versus low-dose CT, while maintaining image quality and lesion conspicuity.

  17. Developing multi-cellular tumor spheroid model (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jian-Zheng, E-mail: wppzheng@126.com [Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000 (China); Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000 (China); Zhu, Yu-Xia [Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023 (China); Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000 (China); Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000 (China); Ma, Hui-Chao; Chen, Si-Nan; Chao, Ji-Ye; Ruan, Wen-Ding; Wang, Duo; Du, Feng-guang [Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000 (China); Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000 (China); Meng, Yue-Zhong [State Key Laboratory of Optoelectronic Materials and Technologies, Sun Yat-sen University, Guangzhou 510275 (China)

    2016-05-01

    In this work, a 3D MCTS-CCA system was constructed by culturing multi-cellular tumor spheroid (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening. The CCA scaffolds were fabricated by spray-spinning. The interactions between the components of the spray-spun fibers were evidenced by methods of Coomassie Blue stain, X-ray diffraction (XRD) and Fourier transform-infrared spectroscopy (FTIR). Co-culture indicated that MCF-7 cells showed a spatial growth pattern of multi-cellular tumor spheroid (MCTS) in the CCA fibrous scaffold with increased proliferation rate and drug-resistance to MMC, ADM and 5-Aza comparing with the 2D culture cells. Significant increases of total viable cells were found in 3D MCTS groups after drug administration by method of apoptotic analysis. Glucose–lactate analysis indicated that the metabolism of MCTS in CCA scaffold was closer to the tumor issue in vivo than the monolayer cells. In addition, MCTS showed the characteristic of epithelial mesenchymal transition (EMT) which is subverted by carcinoma cells to facilitate metastatic spread. These results demonstrated that MCTS in CCA scaffold possessed a more conservative phenotype of tumor than monolayer cells, and anticancer drug screening in 3D MCTS-CCA system might be superior to the 2D culture system. - Highlights: • Chitosan/collagen/alginate (CCA) scaffolds were fabricated by spray-spinning. • MCF-7 cells presented a multi-cellular tumor spheroid model (MCTS) in CCA scaffold. • MCTS in CCA possessed a more conservative phenotype of tumor than monolayer cells. • Anticancer drug screening in MCTS-CCA system is superior to 2D culture system.

  18. Developing multi-cellular tumor spheroid model (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening

    International Nuclear Information System (INIS)

    Wang, Jian-Zheng; Zhu, Yu-Xia; Ma, Hui-Chao; Chen, Si-Nan; Chao, Ji-Ye; Ruan, Wen-Ding; Wang, Duo; Du, Feng-guang; Meng, Yue-Zhong

    2016-01-01

    In this work, a 3D MCTS-CCA system was constructed by culturing multi-cellular tumor spheroid (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening. The CCA scaffolds were fabricated by spray-spinning. The interactions between the components of the spray-spun fibers were evidenced by methods of Coomassie Blue stain, X-ray diffraction (XRD) and Fourier transform-infrared spectroscopy (FTIR). Co-culture indicated that MCF-7 cells showed a spatial growth pattern of multi-cellular tumor spheroid (MCTS) in the CCA fibrous scaffold with increased proliferation rate and drug-resistance to MMC, ADM and 5-Aza comparing with the 2D culture cells. Significant increases of total viable cells were found in 3D MCTS groups after drug administration by method of apoptotic analysis. Glucose–lactate analysis indicated that the metabolism of MCTS in CCA scaffold was closer to the tumor issue in vivo than the monolayer cells. In addition, MCTS showed the characteristic of epithelial mesenchymal transition (EMT) which is subverted by carcinoma cells to facilitate metastatic spread. These results demonstrated that MCTS in CCA scaffold possessed a more conservative phenotype of tumor than monolayer cells, and anticancer drug screening in 3D MCTS-CCA system might be superior to the 2D culture system. - Highlights: • Chitosan/collagen/alginate (CCA) scaffolds were fabricated by spray-spinning. • MCF-7 cells presented a multi-cellular tumor spheroid model (MCTS) in CCA scaffold. • MCTS in CCA possessed a more conservative phenotype of tumor than monolayer cells. • Anticancer drug screening in MCTS-CCA system is superior to 2D culture system.

  19. Utilization of the Behavior Change Wheel framework to develop a model to improve cardiometabolic screening for people with severe mental illness

    Directory of Open Access Journals (Sweden)

    Christina Mangurian

    2017-11-01

    Full Text Available Abstract Background Individuals with severe mental illness (e.g., schizophrenia, bipolar disorder die 10–25 years earlier than the general population, primarily from premature cardiovascular disease (CVD. Contributing factors are complex, but include systemic-related factors of poorly integrated primary care and mental health services. Although evidence-based models exist for integrating mental health care into primary care settings, the evidence base for integrating medical care into specialty mental health settings is limited. Such models are referred to as “reverse” integration. In this paper, we describe the application of an implementation science framework in designing a model to improve CVD outcomes for individuals with severe mental illness (SMI who receive services in a community mental health setting. Methods Using principles from the theory of planned behavior, focus groups were conducted to understand stakeholder perspectives of barriers to CVD risk factor screening and treatment identify potential target behaviors. We then applied results to the overarching Behavior Change Wheel framework, a systematic and theory-driven approach that incorporates the COM-B model (capability, opportunity, motivation, and behavior, to build an intervention to improve CVD risk factor screening and treatment for people with SMI. Results Following a stepped approach from the Behavior Change Wheel framework, a model to deliver primary preventive care for people that use community mental health settings as their de facto health home was developed. The CRANIUM (cardiometabolic risk assessment and treatment through a novel integration model for underserved populations with mental illness model focuses on engaging community psychiatrists to expand their scope of practice to become responsible for CVD risk, with significant clinical decision support. Conclusion The CRANIUM model was designed by integrating behavioral change theory and implementation

  20. Utilization of the Behavior Change Wheel framework to develop a model to improve cardiometabolic screening for people with severe mental illness.

    Science.gov (United States)

    Mangurian, Christina; Niu, Grace C; Schillinger, Dean; Newcomer, John W; Dilley, James; Handley, Margaret A

    2017-11-14

    Individuals with severe mental illness (e.g., schizophrenia, bipolar disorder) die 10-25 years earlier than the general population, primarily from premature cardiovascular disease (CVD). Contributing factors are complex, but include systemic-related factors of poorly integrated primary care and mental health services. Although evidence-based models exist for integrating mental health care into primary care settings, the evidence base for integrating medical care into specialty mental health settings is limited. Such models are referred to as "reverse" integration. In this paper, we describe the application of an implementation science framework in designing a model to improve CVD outcomes for individuals with severe mental illness (SMI) who receive services in a community mental health setting. Using principles from the theory of planned behavior, focus groups were conducted to understand stakeholder perspectives of barriers to CVD risk factor screening and treatment identify potential target behaviors. We then applied results to the overarching Behavior Change Wheel framework, a systematic and theory-driven approach that incorporates the COM-B model (capability, opportunity, motivation, and behavior), to build an intervention to improve CVD risk factor screening and treatment for people with SMI. Following a stepped approach from the Behavior Change Wheel framework, a model to deliver primary preventive care for people that use community mental health settings as their de facto health home was developed. The CRANIUM (cardiometabolic risk assessment and treatment through a novel integration model for underserved populations with mental illness) model focuses on engaging community psychiatrists to expand their scope of practice to become responsible for CVD risk, with significant clinical decision support. The CRANIUM model was designed by integrating behavioral change theory and implementation theory. CRANIUM is feasible to implement, is highly acceptable to, and

  1. From Community Laywomen to Breast Health Workers: A Pilot Training Model to Implement Clinical Breast Exam Screening in Malawi.

    Science.gov (United States)

    Gutnik, Lily; Moses, Agnes; Stanley, Christopher; Tembo, Tapiwa; Lee, Clara; Gopal, Satish

    2016-01-01

    Breast cancer burden is high in low-income countries. Inadequate early detection contributes to late diagnosis and increased mortality. We describe the training program for Malawi's first clinical breast exam (CBE) screening effort. Laywomen were recruited as Breast Health Workers (BHWs) with the help of local staff and breast cancer advocates. The four-week training consisted of lectures, online modules, role-playing, case discussions, CBE using simulators and patients, and practice presentations. Ministry of Health trainers taught health communication, promotion, and education skills. Breast cancer survivors shared their experiences. Clinicians taught breast cancer epidemiology, prevention, detection, and clinical care. Clinicians and research staff taught research ethics, informed consent, data collection, and professionalism. Breast cancer knowledge was measured using pre- and post-training surveys. Concordance between BHW and clinician CBE was assessed. Breast cancer talks by BHW were evaluated on a 5-point scale in 22 areas by 3 judges. We interviewed 12 women, and 4 were selected as BHWs including 1 breast cancer survivor. Training was dynamic with modification based on trainee response and progress. A higher-than-anticipated level of comprehension and interest led to inclusion of additional topics like breast reconstruction. Pre-training knowledge increased from 49% to 91% correct (peducational talks was 4.4 (standard deviation 0.7). Malawian laywomen successfully completed training and demonstrated competency to conduct CBE and deliver breast cancer educational talks. Knowledge increased after training, and concordance was high between BHW and clinician CBE.

  2. A constitutive pan-hexose permease for the Plasmodium life cycle and transgenic models for screening of antimalarial sugar analogs.

    Science.gov (United States)

    Blume, Martin; Hliscs, Marion; Rodriguez-Contreras, Dayana; Sanchez, Marco; Landfear, Scott; Lucius, Richard; Matuschewski, Kai; Gupta, Nishith

    2011-04-01

    Glucose is considered essential for erythrocytic stages of the malaria parasite, Plasmodium falciparum. Importance of sugar and its permease for hepatic and sexual stages of Plasmodium, however, remains elusive. Moreover, increasing global resistance to current antimalarials necessitates the search for novel drugs. Here, we reveal that hexose transporter 1 (HT1) of Plasmodium berghei can transport glucose (K(m)~87 μM), mannose (K(i)~93 μM), fructose (K(i)~0.54 mM), and galactose (K(i)~5 mM) in Leishmania mexicana mutant and Xenopus laevis; and, therefore, is functionally equivalent to HT1 of P. falciparum (Glc, K(m)~175 μM; Man, K(i)~276 μM; Fru, K(i)~1.25 mM; Gal, K(i)~5.86 mM). Notably, a glucose analog, C3361, attenuated hepatic (IC(50)~15 μM) and ookinete development of P. berghei. The PbHT1 could be ablated during intraerythrocytic stages only by concurrent complementation with PbHT1-HA or PfHT1. Together; these results signify that PbHT1 and glucose are required for the entire life cycle of P. berghei. Accordingly, PbHT1 is expressed in the plasma membrane during all parasite stages. To permit a high-throughput screening of PfHT1 inhibitors and their subsequent in vivo assessment, we have generated Saccharomyces cerevisiae mutant expressing codon-optimized PfHT1, and a PfHT1-dependent Δpbht1 parasite strain. This work provides a platform to facilitate the development of drugs against malaria, and it suggests a disease-control aspect by reducing parasite transmission.

  3. From Community Laywomen to Breast Health Workers: A Pilot Training Model to Implement Clinical Breast Exam Screening in Malawi.

    Directory of Open Access Journals (Sweden)

    Lily Gutnik

    Full Text Available Breast cancer burden is high in low-income countries. Inadequate early detection contributes to late diagnosis and increased mortality. We describe the training program for Malawi's first clinical breast exam (CBE screening effort.Laywomen were recruited as Breast Health Workers (BHWs with the help of local staff and breast cancer advocates. The four-week training consisted of lectures, online modules, role-playing, case discussions, CBE using simulators and patients, and practice presentations. Ministry of Health trainers taught health communication, promotion, and education skills. Breast cancer survivors shared their experiences. Clinicians taught breast cancer epidemiology, prevention, detection, and clinical care. Clinicians and research staff taught research ethics, informed consent, data collection, and professionalism. Breast cancer knowledge was measured using pre- and post-training surveys. Concordance between BHW and clinician CBE was assessed. Breast cancer talks by BHW were evaluated on a 5-point scale in 22 areas by 3 judges.We interviewed 12 women, and 4 were selected as BHWs including 1 breast cancer survivor. Training was dynamic with modification based on trainee response and progress. A higher-than-anticipated level of comprehension and interest led to inclusion of additional topics like breast reconstruction. Pre-training knowledge increased from 49% to 91% correct (p<0.0001. Clinician and BHW CBE had 88% concordance (kappa 0.43. The mean rating of BHW educational talks was 4.4 (standard deviation 0.7.Malawian laywomen successfully completed training and demonstrated competency to conduct CBE and deliver breast cancer educational talks. Knowledge increased after training, and concordance was high between BHW and clinician CBE.

  4. Primary care colorectal cancer screening correlates with breast cancer screening: implications for colorectal cancer screening improvement interventions.

    Science.gov (United States)

    Weiss, Jennifer M; Pandhi, Nancy; Kraft, Sally; Potvien, Aaron; Carayon, Pascale; Smith, Maureen A

    2018-04-25

    National colorectal cancer (CRC) screening rates have plateaued. To optimize interventions targeting those unscreened, a better understanding is needed of how this preventive service fits in with multiple preventive and chronic care needs managed by primary care providers (PCPs). This study examines whether PCP practices of other preventive and chronic care needs correlate with CRC screening. We performed a retrospective cohort study of 90 PCPs and 33,137 CRC screening-eligible patients. Five PCP quality metrics (breast cancer screening, cervical cancer screening, HgbA1c and LDL testing, and blood pressure control) were measured. A baseline correlation test was performed between these metrics and PCP CRC screening rates. Multivariable logistic regression with clustering at the clinic-level estimated odds ratios and 95% confidence intervals for these PCP quality metrics, patient and PCP characteristics, and their relationship to CRC screening. PCP CRC screening rates have a strong correlation with breast cancer screening rates (r = 0.7414, p < 0.001) and a weak correlation with the other quality metrics. In the final adjusted model, the only PCP quality metric that significantly predicted CRC screening was breast cancer screening (OR 1.25; 95% CI 1.11-1.42; p < 0.001). PCP CRC screening rates are highly concordant with breast cancer screening. CRC screening is weakly concordant with cervical cancer screening and chronic disease management metrics. Efforts targeting PCPs to increase CRC screening rates could be bundled with breast cancer screening improvement interventions to increase their impact and success.

  5. Assessing Interval Estimation Methods for Hill Model Parameters in a High-Throughput Screening Context (IVIVE meeting)

    Science.gov (United States)

    The Hill model of concentration-response is ubiquitous in toxicology, perhaps because its parameters directly relate to biologically significant metrics of toxicity such as efficacy and potency. Point estimates of these parameters obtained through least squares regression or maxi...

  6. Sheet beam model for intense space charge: Application to Debye screening and the distribution of particle oscillation frequencies in a thermal equilibrium beam

    Directory of Open Access Journals (Sweden)

    Steven M. Lund

    2011-05-01

    Full Text Available A one-dimensional Vlasov-Poisson model for sheet beams is reviewed and extended to provide a simple framework for analysis of space-charge effects. Centroid and rms envelope equations including image-charge effects are derived and reasonable parameter equivalences with commonly employed 2D transverse models of unbunched beams are established. This sheet-beam model is then applied to analyze several problems of fundamental interest. A sheet-beam thermal equilibrium distribution in a continuous focusing channel is constructed and shown to have analogous properties to two- and three-dimensional thermal equilibrium models in terms of the equilibrium structure and Debye screening properties. The simpler formulation for sheet beams is exploited to explicitly calculate the distribution of particle oscillation frequencies within a thermal equilibrium beam. It is shown that as space-charge intensity increases, the frequency distribution becomes broad, suggesting that beams with strong space-charge can have improved stability relative to beams with weak space-charge.

  7. Screening of external hazards for NPP with bank type reactor. Modeling of safety related systems and equipment for RBMK. Probabilistic assessment of NPP safety on aircraft impact. Progress report

    International Nuclear Information System (INIS)

    Kostarev, V.

    1999-01-01

    This progress report was produced within the frame of IAEA research project on screening the hazards for NPP with bank type reactor. It covers the following tasks; development of the model for the primary loop system of RBMK; developing the models for safety related equipment of RBMK; developing of models for safety related models of EGP-6 type reactor (Bilibinskaya Nuclear Co-generated heat and Power Plant); and probabilistic assessment of NPP safety on aircraft impact

  8. Malignancy risk estimation of screen-detected nodules at baseline CT: comparison of the PanCan model, Lung-RADS and NCCN guidelines

    Energy Technology Data Exchange (ETDEWEB)

    Riel, Sarah J. van; Ciompi, Francesco; Jacobs, Colin; Scholten, Ernst T.; Prokop, Mathias; Ginneken, Bram van [Radboud University Nijmegen Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen (Netherlands); Winkler Wille, Mathilde M.; Naqibullah, Matiullah [University of Copenhagen, Department of Pulmonology Gentofte Hospital, Hellerup (Denmark); Lam, Stephen [British Columbia Cancer Agency, Department of Integrative Oncology, Vancouver, British Columbia (Canada); Schaefer-Prokop, Cornelia [Radboud University Nijmegen Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen (Netherlands); Meander Medical Center, Department of Radiology, Amersfoort (Netherlands)

    2017-10-15

    To compare the PanCan model, Lung-RADS and the 1.2016 National Comprehensive Cancer Network (NCCN) guidelines for discriminating malignant from benign pulmonary nodules on baseline screening CT scans and the impact diameter measurement methods have on performances. From the Danish Lung Cancer Screening Trial database, 64 CTs with malignant nodules and 549 baseline CTs with benign nodules were included. Performance of the systems was evaluated applying the system's original diameter definitions: D{sup longest-C} (PanCan), D{sup meanAxial} (NCCN), both obtained from axial sections, and D{sup mean3D} (Lung-RADS). Subsequently all diameter definitions were applied uniformly to all systems. Areas under the ROC curves (AUC) were used to evaluate risk discrimination. PanCan performed superiorly to Lung-RADS and NCCN (AUC 0.874 vs. 0.813, p = 0.003; 0.874 vs. 0.836, p = 0.010), using the original diameter specifications. When uniformly applying D{sup longest-C}, D{sup mean3D} and D{sup meanAxial}, PanCan remained superior to Lung-RADS (p < 0.001 - p = 0.001) and NCCN (p < 0.001 - p = 0.016). Diameter definition significantly influenced NCCN's performance with D{sup longest-C} being the worst (D{sup longest-C} vs. D{sup mean3D}, p = 0.005; D{sup longest-C} vs. D{sup meanAxial}, p = 0.016). Without follow-up information, the PanCan model performs significantly superiorly to Lung-RADS and the 1.2016 NCCN guidelines for discriminating benign from malignant nodules. The NCCN guidelines are most sensitive to nodule size definition. (orig.)

  9. Detection of the antiviral activity of epicatechin isolated from Salacia crassifolia (Celastraceae) against Mayaro virus based on protein C homology modelling and virtual screening.

    Science.gov (United States)

    Ferreira, P G; Ferraz, A C; Figueiredo, J E; Lima, C F; Rodrigues, V G; Taranto, A G; Ferreira, J M S; Brandão, G C; Vieira-Filho, S A; Duarte, L P; de Brito Magalhães, C L; de Magalhães, J C

    2018-02-24

    Mayaro fever, caused by Mayaro virus (MAYV) is a sub-lethal disease with symptoms that are easily confused with those of dengue fever, except for polyarthralgia, which may culminate in physical incapacitation. Recently, outbreaks of MAYV have been documented in metropolitan areas, and to date, there is no therapy or vaccine available. Moreover, there is no information regarding the three-dimensional structure of the viral proteins of MAYV, which is important in the search for antivirals. In this work, we constructed a three-dimensional model of protein C of MAYV by homology modelling, and this was employed in a manner similar to that of receptors in virtual screening studies to evaluate 590 molecules as prospective antiviral agents. In vitro bioassays were utilized to confirm the potential antiviral activity of the flavonoid epicatechin isolated from Salacia crassifolia (Celastraceae). The virtual screening showed that six flavonoids were promising ligands for protein C. The bioassays showed potent antiviral action of epicatechin, which protected the cells from almost all of the effects of viral infection. An effective concentration (EC 50 ) of 0.247 μmol/mL was observed with a selectivity index (SI) of 7. The cytotoxicity assay showed that epicatechin has low toxicity, with a 50% cytotoxic concentration (CC 50 ) greater than 1.723 µmol/mL. Epicatechin was found to be twice as potent as the reference antiviral ribavirin. Furthermore, a replication kinetics assay showed a strong inhibitory effect of epicatechin on MAYV growth, with a reduction of at least four logs in virus production. Our results indicate that epicatechin is a promising candidate for further testing as an antiviral agent against Mayaro virus and other alphaviruses.

  10. Skin Cancer Screening

    Science.gov (United States)

    ... Genetics of Skin Cancer Skin Cancer Screening Research Skin Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Skin Cancer Key Points Skin cancer is a disease ...

  11. Screening for Cancer

    Science.gov (United States)

    Cancer screening is checking for cancer in people who don't have symptoms. Screening tests can help doctors find and treat several types of cancer early, but cancer screening can have harms as well as benefits.

  12. Colorectal Cancer Screening

    Science.gov (United States)

    ... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...

  13. Screen time and children

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000355.htm Screen time and children To use the sharing features on ... videos is considered unhealthy screen time. Current Screen Time Guidelines Children under age 2 should have no ...

  14. Stomach (Gastric) Cancer Screening

    Science.gov (United States)

    ... Stomach Cancer Prevention Stomach Cancer Screening Research Stomach (Gastric) Cancer Screening (PDQ®)–Patient Version What is screening? Go ... are called diagnostic tests . General Information About Stomach (Gastric) Cancer Key Points Stomach cancer is a disease in ...

  15. An in vitro transport model for rapid screening and predicting the permeability of candidate compounds at blood-brain barrier.

    Science.gov (United States)

    Yang, Zhi-Hong; Sun, Xiao; Mei, Chao; Sun, Xiao-Bo; Liu, Xiao-Dong; Chang, Qi

    2011-12-01

    The aim of this study was to design and develop a simple in vitro blood-brain barrier (BBB) permeation model for elementarily and rapidly predicting the permeability of candidate compounds at BBB and further evaluating whether P-glycoprotein (P-gp) affects them across BBB. The model was mainly composed of cultured rat brain microvascular endothelial cells (rBMECs), glass contraption, and micropore membrane. First, we evaluated the model by morphological observation. Second, the restriction effects of paracellular transport were verified by measuring marker probes transport, and monitoring transendothelial electrical resistance (TEER) and leakage. Finally, protein expression and activity of P-gp were confirmed by carrying out Western blot analysis and polarized transport of rhodamine-123 (Rho123) in rBMECs. The rBMECs retained both endothelial cells and BBB features. The rBMECs model reproducibly attained approximately 130 Ω cm² on the steady-state TEER value, and displayed a barrier function to marker probes transport by decreasing the permeability. Protein band of 170 kDa manifested the existence of P-gp in the rBMECs, and the findings of cyclosporin A-sensitive decrease of Rho123 efflux confirmed the presence of P-gp activity. A simple, rapid, and convenient in vitro BBB permeation model was successfully established and applied to evaluate the BBB transport profiles of three natural flavonoids: quercetin, naringenin, and rutin.

  16. Implementation of a Model Output Statistics based on meteorological variable screening for short‐term wind power forecast

    DEFF Research Database (Denmark)

    Ranaboldo, Matteo; Giebel, Gregor; Codina, Bernat

    2013-01-01

    A combination of physical and statistical treatments to post‐process numerical weather predictions (NWP) outputs is needed for successful short‐term wind power forecasts. One of the most promising and effective approaches for statistical treatment is the Model Output Statistics (MOS) technique....... The proposed MOS performed well in both wind farms, and its forecasts compare positively with an actual operative model in use at Risø DTU and other MOS types, showing minimum BIAS and improving NWP power forecast of around 15% in terms of root mean square error. Further improvements could be obtained...

  17. The rat subcutaneous air sac model. A new and simple method for in vivo screening of antiangiogenesis

    International Nuclear Information System (INIS)

    Lichtenberg, J.; Abildgaard Hansen, C.; Skak-Nielsen, T.; Bay, C.; Thing Mortensen, J.; Binderup, L.

    1997-01-01

    An experimental rat model, the Subcutaneous Air Sac (SAS) model, was developed to provide an animal model in which neo-vascularisation can be easily assessed in situ and quantified using a radiolabelled plasma marker. The SAS model was designed to replace a previous model where neo-vascularisation was induced by chemical injury of rat or rabbit cornea or by implantation of tumour cells intracorneally, a methodology which is believed to cause severe pain to the animals. In the SAS model the air sac replaces the cornea as a transparent avascular substratum in which vascularisation can be observed. The air sac is induced by injection of air subcutaneously on the back of the animal. After 8 to 10 days a sufficient air sac has been established. The animal is anaesthesized and by a minor operation the cellulose sponge is implanted upon the air sac under the skin. The vaso-proliferative effect of the cellulose sponge caused formation of new vessels which are macroscopically visible 10 days after implantation. The ability of the in vivo SAS model to show an anti-angiogenic effect of a systemically applied test compound was investigated using the fumagilline analogue TNP-470 (o-chloro-acetylcarbomoyl-fumagillol) as a positive control at dose levels of 0, 1, 2.5, 5 and 10 mg/kg/day given subcutaneously for 10 days. The neo-angio genesis was scored both in situ using a subjective point system and by measuring the 125 I-activity of the implant and the membrane after an intravenous injection of 125 I-labelled antibodies. The neo-angio genesis was reduced by approximately 45-50% in animals treated with 5 or 10 mg/kg/day of TNP-470 compared to animals treated with the vehicle. The animals treated with 10 mg/kg/day TNP-470 showed signs of toxicity. The SAS model is considered highly relevant for in vivo testing of potential anti-angiogenci drugs on humane grounds. The high reproducibility, the low cost and the technical simplicity of the method makes it attractive. (au)