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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. T-screen to quantify functional potentiating, antagonistic and thyroid hormone-like activities of poly halogenated aromatic hydrocarbons (PHAHs)

    NARCIS (Netherlands)

    Schriks, M.; Vrabie, C.M.; Gutleb, A.C.; Faassen, E.J.; Rietjens, I.M.C.M.; Murk, A.J.

    2006-01-01

    The present study investigates chemical thyroid hormone disruption at the level of thyroid hormone receptor (TR) functioning. To this end the (ant)agonistic action of a series of xenobiotics was tested in the newly developed T-screen. This assay makes use of a GH3 rat pituitary cell line, that

  3. 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

    . 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...

  4. Drug screening using model systems: some basics

    Directory of Open Access Journals (Sweden)

    Ross Cagan

    2016-11-01

    Full Text Available An increasing number of laboratories that focus on model systems are considering drug screening. Executing a drug screen is complicated enough. But the path for moving initial hits towards the clinic requires a different knowledge base and even a different mindset. In this Editorial I discuss the importance of doing some homework before you start screening. 'Lead hits', 'patentable chemical space' and 'druggability' are all concepts worth exploring when deciding which screening path to take. I discuss some of the lessons I learned that may be useful as you navigate the screening matrix.

  5. 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.

  6. Stochastic modeling for environmental stress screening

    OpenAIRE

    Cha, Ji Hwan; Finkelstein, Maxim

    2014-01-01

    Environmental stress screening (ESS) of manufactured items is used to reduce the occurrence of future failures that are caused by latent defects by eliminating the items with these defects. Some practical descriptions of the relevant ESS procedures can be found in the literature; however, the appropriate stochastic modeling and the corresponding thorough analysis have not been reported. In this paper we develop a stochastic model for the ESS, analyze the effect of this operation o...

  7. How does early detection by screening affect disease progression?: Modeling estimated benefits in prostate cancer screening

    NARCIS (Netherlands)

    E.M. Wever (Elisabeth); G. Draisma (Gerrit); E.A.M. Heijnsdijk (Eveline); H.J. de Koning (Harry)

    2011-01-01

    textabstractBackground. Simulation models are essential tools for estimating benefits of cancer screening programs. Such models include a screening-effect model that represents how early detection by screening followed by treatment affects disease-specific survival. Two commonly used

  8. Resilience of a FIT screening programme against screening fatigue: a modelling study

    Directory of Open Access Journals (Sweden)

    Marjolein J. E. Greuter

    2016-09-01

    Full Text Available Abstract Background Repeated participation is important in faecal immunochemical testing (FIT screening for colorectal cancer (CRC. However, a large number of screening invitations over time may lead to screening fatigue and consequently, decreased participation rates. We evaluated the impact of screening fatigue on overall screening programme effectiveness. Methods Using the ASCCA model, we simulated the Dutch CRC screening programme consisting of biennial FIT screening in individuals aged 55–75. We studied the resilience of the programme against heterogeneity in screening attendance and decrease in participation rate due to screening fatigue. Outcomes were reductions in CRC incidence and mortality compared to no screening. Results Assuming a homogenous 63 % participation, i.e., each round each individual was equally likely to attend screening, 30 years of screening reduced CRC incidence and mortality by 39 and 53 %, respectively, compared to no screening. When assuming clustered participation, i.e., three subgroups of individuals with a high (95 %, moderate (65 % and low (5 % participation rate, screening was less effective; reductions were 33 % for CRC incidence and 43 % for CRC mortality. Screening fatigue considerably reduced screening effectiveness; if individuals refrained from screening after three negative screens, model-predicted incidence reductions decreased to 25 and 18 % under homogenous and clustered participation, respectively. Figures were 34 and 25 % for mortality reduction. Conclusions Screening will substantially decrease CRC incidence and mortality. However, screening effectiveness can be seriously compromised if screening fatigue occurs. This warrants careful monitoring of individual screening behaviour and consideration of targeted invitation systems in individuals who have (repeatedly missed screening rounds.

  9. 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...

  10. Screening design for model sensitivity studies

    Science.gov (United States)

    Welsh, James P.; Koenig, George G.; Bruce, Dorothy

    1997-07-01

    This paper describes a different approach to sensitivity studies for environmental, including atmospheric, physics models. The sensitivity studies were performed on a multispectral environmental data and scene generation capability. The capability includes environmental physics models that are used to generate data and scenes for simulation of environmental materials, features, and conditions, such as trees, clouds, soils, and snow. These studies were performed because it is difficult to obtain input data for many of the environmental variables. The problem to solve is to determine which of the 100 or so input variables, used by the generation capability, are the most important. These sensitivity studies focused on the generation capabilities needed to predict and evaluate the performance of sensor systems operating in the infrared portions of the electromagnetic spectrum. The sensitivity study approach described uses a screening design. Screening designs are analytical techniques that use a fraction of all of the combinations of the potential input variables and conditions to determine which are the most important. Specifically a 20-run Plackett-Burman screening design was used to study the sensitivity of eight data and scene generation capability computed response variables to 11 selected input variables. This is a two-level design, meaning that the range of conditions is represented by two different values for each of the 11 selected variables. The eight response variables used were maximum, minimum, range, and mode of the model-generated temperature and radiance values. The result is that six of the 11 input variables (soil moisture, solar loading, roughness length, relative humidity, surface albedo, and surface emissivity) had a statistically significant effect on the response variables.

  11. How does early detection by screening affect disease progression? Modeling estimated benefits in prostate cancer screening.

    Science.gov (United States)

    Wever, Elisabeth M; Draisma, Gerrit; Heijnsdijk, Eveline A M; de Koning, Harry J

    2011-01-01

    Simulation models are essential tools for estimating benefits of cancer screening programs. Such models include a screening-effect model that represents how early detection by screening followed by treatment affects disease-specific survival. Two commonly used screening-effect models are the stage-shift model, where mortality benefits are explained by the shift to more favorable stages, and the cure model, where early detection enhances the chances of cure from disease. This article describes commonly used screening-effect models and analyses their predicted mortality benefit in a model for prostate cancer screening. The MISCAN simulation model was used to predict the reduction of prostate cancer mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC) Rotterdam. The screening-effect models were included in the model. For each model the predictions of prostate cancer mortality reduction were calculated. The study compared 4 screening-effect models, which are versions of the stage-shift model or the cure model. The stage-shift models predicted, after a follow-up of 9 years, reductions in prostate cancer mortality varying from 38% to 63% for ERSPC-Rotterdam compared with a 27% reduction observed in the ERSPC. The cure models predicted reductions in prostate cancer mortality varying from 21% to 27%. The differences in predicted mortality reductions show the importance of validating models to observed trial mortality data. The stage-shift models considerably overestimated the mortality reduction. Therefore, the stage-shift models should be used with care, especially when modeling the effect of screening for cancers with long lead times, such as prostate cancer.

  12. Screening for prostatic cancer. Investigational models

    DEFF Research Database (Denmark)

    Iversen, P; Torp-Pedersen, S T

    1991-01-01

    features of the disease, which make the possible gain from screening programs questionable. Thus, before embarking on expensive community or national screening programs, the beneficial effect of such an effort on morbidity and mortality must be demonstrated in large-scale trials comparing a screened...

  13. 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

  14. A Drosophila Model for Screening Antiobesity Agents

    Directory of Open Access Journals (Sweden)

    Tran Thanh Men

    2016-01-01

    Full Text Available Although triacylglycerol, the major component for lipid storage, is essential for normal physiology, its excessive accumulation causes obesity in adipose tissue and is associated with organ dysfunction in nonadipose tissue. Here, we focused on the Drosophila model to develop therapeutics for preventing obesity. The brummer (bmm gene in Drosophila melanogaster is known to be homologous with human adipocyte triglyceride lipase, which is related to the regulation of lipid storage. We established a Drosophila model for monitoring bmm expression by introducing the green fluorescent protein (GFP gene as a downstream reporter of the bmm promoter. The third-instar larvae of Drosophila showed the GFP signal in all tissues observed and specifically in the salivary gland nucleus. To confirm the relationship between bmm expression and obesity, the effect of oral administration of glucose diets on bmm promoter activity was analyzed. The Drosophila flies given high-glucose diets showed higher lipid contents, indicating the obesity phenotype; this was suggested by a weaker intensity of the GFP signal as well as reduced bmm mRNA expression. These results demonstrated that the transgenic Drosophila model established in this study is useful for screening antiobesity agents. We also report the effects of oral administration of histone deacetylase inhibitors and some vegetables on the bmm promoter activity.

  15. Cancer risk models and preselection for screening

    NARCIS (Netherlands)

    Stegeman, Inge; Bossuyt, Patrick M.

    2012-01-01

    Objective: The invitation to population screening is based on age criteria in many countries. Screening is not offered to younger or older participants, because the benefits in these age groups do not outweigh the harms. One could argue that it is not so much age that determines the benefits but the

  16. 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.

  17. Screening for prostatic cancer. Investigational models

    DEFF Research Database (Denmark)

    Iversen, P; Torp-Pedersen, S T

    1991-01-01

    Prostatic cancer has a long natural history and a significant preclinical period, during which the disease is detectable. Thus, this common malignancy in males fulfills some of the most important criteria for initiating screening programs. However, the still enigmatic epidemiology also includes...

  18. 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

  19. 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.

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

    NARCIS (Netherlands)

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

    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

  1. HYDROCARBON SPILL SCREENING MODEL (HSSM) VOLUME 1: USER'S GUIDE

    Science.gov (United States)

    This users guide describes the Hydrocarbon Spill Screening Model (HSSM). The model is intended for simulation of subsurface releases of light nonaqueous phase liquids (LNAPLs). The model consists of separate modules for LNAPL flow through the vadose zone, spreading in the capil...

  2. 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

  3. Item Screening in Graphical Loglinear Rasch Models

    DEFF Research Database (Denmark)

    Kreiner, Svend; Christensen, Karl Bang

    2011-01-01

    In behavioural sciences, local dependence and DIF are common, and purification procedures that eliminate items with these weaknesses often result in short scales with poor reliability. Graphical loglinear Rasch models (Kreiner & Christensen, in Statistical Methods for Quality of Life Studies, ed....... by M. Mesbah, F.C. Cole & M.T. Lee, Kluwer Academic, pp. 187–203, 2002) where uniform DIF and uniform local dependence are permitted solve this dilemma by modelling the local dependence and DIF. Identifying loglinear Rasch models by a stepwise model search is often very time consuming, since...... the initial item analysis may disclose a great deal of spurious and misleading evidence of DIF and local dependence that has to disposed of during the modelling procedure. Like graphical models, graphical loglinear Rasch models possess Markov properties that are useful during the statistical analysis...

  4. 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.

  5. Simulation Model Development for Mail Screening Process

    National Research Council Canada - National Science Library

    Vargo, Trish; Marvin, Freeman; Kooistra, Scott

    2005-01-01

    STUDY OBJECTIVE: Provide decision analysis support to the Homeland Defense Business Unit, Special Projects Team, in developing a simulation model to help determine the most effective way to eliminate backlog...

  6. A QSAR Model for Thyroperoxidase Inhibition and Screening ...

    Science.gov (United States)

    Thyroid hormones (THs) are critical modulators of a wide range of biological processes from neurodevelopment to metabolism. Well regulated levels of THs are critical during development and even moderate changes in maternal or fetal TH levels produce irreversible neurological deficits in children. The enzyme thyroperoxidase (TPO) plays a key role in the synthesis of THs. Inhibition of TPO by xenobiotics leads to decreased TH synthesis and, depending on the degree of synthesis inhibition, may result in adverse developmental outcomes. Recently, a high-throughput screening assay for TPO inhibition (AUR-TPO) was developed and used to screen the ToxCast Phase I and II chemicals. In the present study, we used the results from the AUR-TPO screening to develop a Quantitative Structure-Activity Relationship (QSAR) model for TPO inhibition in Leadscope®. The training set consisted of 898 discrete organic chemicals: 134 positive and 764 negative for TPO inhibition. A 10 times two-fold 50% cross-validation of the model was performed, yielding a balanced accuracy of 78.7% within its defined applicability domain. More recently, an additional ~800 chemicals from the US EPA Endocrine Disruption Screening Program (EDSP21) were screened using the AUR-TPO assay. This data was used for external validation of the QSAR model, demonstrating a balanced accuracy of 85.7% within its applicability domain. Overall, the cross- and external validations indicate a model with a high predictiv

  7. 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.

  8. Multi-Tasking vs. Screening: A Model of Academic Tenure

    OpenAIRE

    Kou, Zonglai; Zhou, Min

    2009-01-01

    The paper develops a model of academic tenure based on multi-tasking and screening. A professor has two tasks, researching and teaching. We assume that researching performance is easy to measure but teaching performance is immeasurable. Then Holmtrom and Milgrom's (1991) classical muli-task principal-agent model implies that the only way for the the university to "incentivize" teaching activity is decreasing the incentive power to researching activity. This justifies the low-powered contract ...

  9. 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.

  10. 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.

  11. Resilience of a FIT screening programme against screening fatigue: a modelling study

    NARCIS (Netherlands)

    Greuter, Marjolein J. E.; Berkhof, Johannes; Canfell, Karen; Lew, Jie-Bin; Dekker, Evelien; Coupé, Veerle M. H.

    2016-01-01

    Repeated participation is important in faecal immunochemical testing (FIT) screening for colorectal cancer (CRC). However, a large number of screening invitations over time may lead to screening fatigue and consequently, decreased participation rates. We evaluated the impact of screening fatigue on

  12. Cardiff sciSCREEN: A model for using film screenings to engage publics in University research

    OpenAIRE

    Lewis, Jamie Thornton; Bisson, Susan; Swaden Lewis, Katie; Reyes-Galindo, Luis; Baldwin, Amy Joy

    2017-01-01

    Cardiff sciSCREEN is a public engagement programme that brings together local experts and publics to discuss issues raised by contemporary cinema. Since 2010, Cardiff sciSCREEN (short for science on screen) has exhibited more than 50 films alongside short talks and discussions that draw on a range of disciplinary perspectives to explore the broad repertoire of themes found within different film genres. The aim of Cardiff sciSCREEN is to increase the local community's access to university rese...

  13. [Biomarker screening of rat pulmonary hypertension model by transcriptome sequencing].

    Science.gov (United States)

    Hu, F; Xie, L; Yu, L; Chen, J; Liu, H M

    2016-04-01

    To screen relative gene and pathway of rat severe pulmonary hypertension by transcriptome sequencing. Pulmonary hypertension animal model of SD rats was established by left lung resection and hypodermic injection of monocrotaline.Monocrotaline was injected subcutaneously one week after left lung resection.Eight rats at 1, 3, 5 weeks after the injection of monocrotaline respectively were named group M1, group M2 and group M3.Eight normal rats were assigned into control group (group C). The right lung tissue was used for transcriptome sequencing to screen the differentially expressed genes.KEGG pathway analysis was performed to screen the pathways with enriched differentially expressed genes. The animal model was established successfully.The pulmonary artery pressure was as follows: group C (28.6±3.0) mmHg(1 mmHg=0.133 kPa), group M1 (38.9±3.3) mmHg, group M2 (50.8±3.9) mmHg, group M3 (51.5±3.5) mmHg.The pressure elevated in group M1 compared with group C (P=0.007). The pressure in M2 and M3 elevated compared with M1(P=0.002 and Ppulmonary hypertension were epithelial specific receptor tyrosine kinase(Tie2) and thrombospondin-1(TSP-1). Tie2 was down-regulated (qpulmonary hypertension and up-regulated (qpulmonary hypertension.TSP-1 was up-regulated (qpulmonary hypertension and down-regulated (qpulmonary hypertension.In the stage of severe pulmonary hypertension, the differentially expressed genes were enriched mainly in the pathways of phosphatidylinostitol 3-kinase, focal adhesion kinase and extracellular matrix receptor interaction. The study provides transcriptome information of rat pulmonary hypertension model and normal rat.Possible mechanisms of pulmonary hypertension are found.These genes and pathways might be new precursor for the diagnosis and treatment of pulmonary hypertension.

  14. Development and weighting of a life cycle assessment screening model

    Science.gov (United States)

    Bates, Wayne E.; O'Shaughnessy, James; Johnson, Sharon A.; Sisson, Richard

    2004-02-01

    Nearly all life cycle assessment tools available today are high priced, comprehensive and quantitative models requiring a significant amount of data collection and data input. In addition, most of the available software packages require a great deal of training time to learn how to operate the model software. Even after this time investment, results are not guaranteed because of the number of estimations and assumptions often necessary to run the model. As a result, product development, design teams and environmental specialists need a simplified tool that will allow for the qualitative evaluation and "screening" of various design options. This paper presents the development and design of a generic, qualitative life cycle screening model and demonstrates its applicability and ease of use. The model uses qualitative environmental, health and safety factors, based on site or product-specific issues, to sensitize the overall results for a given set of conditions. The paper also evaluates the impact of different population input ranking values on model output. The final analysis is based on site or product-specific variables. The user can then evaluate various design changes and the apparent impact or improvement on the environment, health and safety, compliance cost and overall corporate liability. Major input parameters can be varied, and factors such as materials use, pollution prevention, waste minimization, worker safety, product life, environmental impacts, return of investment, and recycle are evaluated. The flexibility of the model format will be discussed in order to demonstrate the applicability and usefulness within nearly any industry sector. Finally, an example using audience input value scores will be compared to other population input results.

  15. An oral multispecies biofilm model for high content screening applications.

    Directory of Open Access Journals (Sweden)

    Nadine Kommerein

    Full Text Available Peri-implantitis caused by multispecies biofilms is a major complication in dental implant treatment. The bacterial infection surrounding dental implants can lead to bone loss and, in turn, to implant failure. A promising strategy to prevent these common complications is the development of implant surfaces that inhibit biofilm development. A reproducible and easy-to-use biofilm model as a test system for large scale screening of new implant surfaces with putative antibacterial potency is therefore of major importance. In the present study, we developed a highly reproducible in vitro four-species biofilm model consisting of the highly relevant oral bacterial species Streptococcus oralis, Actinomyces naeslundii, Veillonella dispar and Porphyromonas gingivalis. The application of live/dead staining, quantitative real time PCR (qRT-PCR, scanning electron microscopy (SEM and urea-NaCl fluorescence in situ hybridization (urea-NaCl-FISH revealed that the four-species biofilm community is robust in terms of biovolume, live/dead distribution and individual species distribution over time. The biofilm community is dominated by S. oralis, followed by V. dispar, A. naeslundii and P. gingivalis. The percentage distribution in this model closely reflects the situation in early native plaques and is therefore well suited as an in vitro model test system. Furthermore, despite its nearly native composition, the multispecies model does not depend on nutrient additives, such as native human saliva or serum, and is an inexpensive, easy to handle and highly reproducible alternative to the available model systems. The 96-well plate format enables high content screening for optimized implant surfaces impeding biofilm formation or the testing of multiple antimicrobial treatment strategies to fight multispecies biofilm infections, both exemplary proven in the manuscript.

  16. Considering Planetary Constraints and Dynamic Screening in Solar Evolution Modeling

    Science.gov (United States)

    Wood, Suzannah R.; Mussack, Katie; Guzik, Joyce A.

    2018-01-01

    The ‘faint early sun problem’ remains unsolved. This problem consists of the apparent contradiction between the standard solar model prediction of lower luminosity (70% of current luminosity) and the observations of liquid water on early Earth and Mars. The presence of liquid water on early Earth and Mars should not be neglected and should be used as a constraint for solar evolution modeling. In addition, modifications to standard solar models are needed to address the discrepancy with solar structure inferred from helioseismology given the latest solar abundance determinations. Here, we will utilize the three different solar abundances: GN93 (Grevesse & Noels, 1993), AGS05 (Asplund et al., 2005), AGSS09 (Asplund et al., 2009). Here, we propose an early mass loss model with an initial solar mass between 1.07 and 1.15 solar masses and an exponentially decreasing mass-loss rate to meet conditions in the early solar system (Wood et al, submitted). Additionally, we investigate the effects of dynamic screening and the new OPLIB opacities from Los Alamos (Colgan et al., 2016). We show the effects of these modifications to the standard solar evolution models on the interior structure, neutrino fluxes, sound speed, p-mode frequencies, convection zone depth, and envelope helium and element abundance of the model sun at the present day.

  17. A computer simulation model for the practical planning of cervical cancer screening programmes.

    OpenAIRE

    Parkin, D. M.

    1985-01-01

    There is ample evidence of the efficacy of cytological screening in the prevention of cervical cancer but disagreement on the form which screening programmes should take. Simulation models have been used as a convenient and rapid method of exploring the outcome of different screening policies and of demonstrating the importance and interrelationships of the variables concerned. However, most such models are either too abstract or too simplistic to be of practical value in planning screening p...

  18. 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.

  19. 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

  20. A screening-level modeling approach to estimate nitrogen ...

    Science.gov (United States)

    This paper presents a screening-level modeling approach that can be used to rapidly estimate nutrient loading and assess numerical nutrient standard exceedance risk of surface waters leading to potential classification as impaired for designated use. It can also be used to explore best management practice (BMP) implementation to reduce loading. The modeling framework uses a hybrid statistical and process based approach to estimate source of pollutants, their transport and decay in the terrestrial and aquatic parts of watersheds. The framework is developed in the ArcGIS environment and is based on the total maximum daily load (TMDL) balance model. Nitrogen (N) is currently addressed in the framework, referred to as WQM-TMDL-N. Loading for each catchment includes non-point sources (NPS) and point sources (PS). NPS loading is estimated using export coefficient or event mean concentration methods depending on the temporal scales, i.e., annual or daily. Loading from atmospheric deposition is also included. The probability of a nutrient load to exceed a target load is evaluated using probabilistic risk assessment, by including the uncertainty associated with export coefficients of various land uses. The computed risk data can be visualized as spatial maps which show the load exceedance probability for all stream segments. In an application of this modeling approach to the Tippecanoe River watershed in Indiana, USA, total nitrogen (TN) loading and risk of standard exce

  1. Using an Ocean of Data, Researchers Model Real-Life Benefits of Cancer Screening

    Science.gov (United States)

    Using the results of screening trials, the NCI Cancer Intervention and Surveillance Modeling Network is trying to estimate the true benefit of cancer screening in the general population and identify the optimal way to implement screening within the health care system.

  2. Breast cancer risk prediction model: a nomogram based on common mammographic screening findings

    NARCIS (Netherlands)

    Timmers, J.M.H.; Verbeek, A.L.M.; Hout, J. in't; Pijnappel, R.M.; Broeders, M.J.M.; Heeten, G.J. den

    2013-01-01

    OBJECTIVES: To develop a prediction model for breast cancer based on common mammographic findings on screening mammograms aiming to reduce reader variability in assigning BI-RADS. METHODS: We retrospectively reviewed 352 positive screening mammograms of women participating in the Dutch screening

  3. Breast cancer risk prediction model: a nomogram based on common mammographic screening findings

    NARCIS (Netherlands)

    Timmers, J. M. H.; Verbeek, A. L. M.; Inthout, J.; Pijnappel, R. M.; Broeders, M. J. M.; den Heeten, G. J.

    2013-01-01

    To develop a prediction model for breast cancer based on common mammographic findings on screening mammograms aiming to reduce reader variability in assigning BI-RADS. We retrospectively reviewed 352 positive screening mammograms of women participating in the Dutch screening programme (Nijmegen

  4. Validation of a model to estimate personalised screening frequency to monitor diabetic retinopathy.

    Science.gov (United States)

    van der Heijden, Amber A W A; Walraven, Iris; van 't Riet, Esther; Aspelund, Thor; Lund, Sigrún H; Elders, Petra; Polak, Bettine C P; Moll, Annette C; Keunen, Jan E E; Dekker, Jacqueline M; Nijpels, Giel

    2014-07-01

    Our study aimed to validate a model to determine a personalised screening frequency for diabetic retinopathy. A model calculating a personalised screening interval for monitoring retinopathy based on patients' risk profile was validated using the data of 3,319 type 2 diabetic patients in the Diabetes Care System West-Friesland, the Netherlands. Two-field fundus photographs were graded according to the EURODIAB coding system. Sight-threatening retinopathy (STR) was considered to be grades 3-5. Validity of the model was assessed using calibration and discrimination measures. We compared model-based time of screening with time of STR diagnosis and calculated the differences in the number of fundus photographs using the model compared with those in annual or biennial screening. During a mean of 53 months of follow-up, 76 patients (2.3%) developed STR. Using the model, the mean screening interval was 31 months, leading to a reduced screening frequency of 61% compared with annual screening and 23% compared with biennial screening. STR incidence occurred after a mean of 26 months after the model-based time of screening in 67 patients (88.2%). In nine patients (11.8%), STR had developed before the model-based time of screening. The discriminatory ability of the model was good (C-statistic 0.83; 95% CI 0.74, 0.92). Calibration showed that the model overestimated STR risk. A large reduction in retinopathy screening was achieved using the model in this population of patients with a very low incidence of retinopathy. Considering the number of potentially missed cases of STR, there is room for improvement in the model. Use of the model for personalised screening may eventually help to reduce healthcare use and costs of diabetes care.

  5. 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

  6. 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

  7. Modelling the Effects and Costs of Colorectal Cancer Screening

    NARCIS (Netherlands)

    S.L. Goede (Luuk)

    2015-01-01

    markdownabstract__Abstract__ The thesis focused on the potential effects and costs of population-based colorectal cancer (CRC) screening by considering two overarching questions. In the first part of the thesis the potential impact of current screening policies on the CRC disease burden and costs

  8. 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....

  9. 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.)

  10. 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.

  11. [Factors associated with gastric cancer screening of Koreans based on a socio-ecological model].

    Science.gov (United States)

    Bae, Sang Soo; Jo, Heui Sug; Kim, Dong-Hyun; Choi, Yong-Jun; Lee, Hun Jae; Lee, Tae Jin; Lee, Hye Jean

    2008-03-01

    We measured behavioral factors associated with Koreans receiving gastric cancer screening based on a socio-ecological model, in part to develop strategies to improve cancer screening rates. A telephone survey was conducted with 2,576 people chosen through stratified random sampling from April 1--May 31, 2004. Collected information included gastric cancer screening, socio-demographic factors, and socio-ecological factors at intrapersonal, interpersonal, community, and public policy levels. Among 985 survey respondents (380 men and 605 women), 402 had received gastric cancer screening. Logistic analysis was performed to compare those screened and unscreened. 'Age' was the only demographic factor that showed a statistically significant association with getting screening. People in their fifties (OR=1.731, 95% CI=1.190-2.520) and sixties (OR=2.098, 95% CI=1.301-3.385) showed a higher likelihood of getting screened, compared to those in the forties. 'Accessibility to a medical institution' was a significant factor related to having gastric cancer screening at the intrapersonal level. At the interpersonal level, recommendations by family members to be screened and a family practice of routine cancer screening were significantly related. People with frequent education about cancer screening or with stronger social feelings that cancer screening is necessary also demonstrated significantly higher tendencies to be screened. In conclusion, a socio-ecological model seems appropriate for explaining gastric cancer screening behavior and associated factors. Health planners should develop integrated strategies to improve cancer screening rates based on socio-ecological factors, especially at the interpersonal and community levels.

  12. Customizing G Protein-coupled receptor models for structure-based virtual screening

    NARCIS (Netherlands)

    de Graaf, C.; Rognan, D.

    2009-01-01

    This review will focus on the construction, refinement, and validation of G Protein-coupled receptor models for the purpose of structure-based virtual screening. Practical tips and tricks derived from concrete modeling and virtual screening exercises to overcome the problems and pitfalls associated

  13. Cross-Cultural Validation of the Preventive Health Model for Colorectal Cancer Screening: An Australian Study

    Science.gov (United States)

    Flight, Ingrid H.; Wilson, Carlene J.; McGillivray, Jane; Myers, Ronald E.

    2010-01-01

    We investigated whether the five-factor structure of the Preventive Health Model for colorectal cancer screening, developed in the United States, has validity in Australia. We also tested extending the model with the addition of the factor Self-Efficacy to Screen using Fecal Occult Blood Test (SESFOBT). Randomly selected men and women aged between…

  14. Validation of a model to estimate personalised screening frequency to monitor diabetic retinopathy

    NARCIS (Netherlands)

    Heijden, A.A. van der; Walraven, I.; Riet, E. van 't; Aspelund, T.; Lund, S.H.; Elders, P.; Polak, B.C.P.; Moll, A.C.; Keunen, J.E.E.; Dekker, J.M.; Nijpels, G.

    2014-01-01

    AIMS/HYPOTHESIS: Our study aimed to validate a model to determine a personalised screening frequency for diabetic retinopathy. METHODS: A model calculating a personalised screening interval for monitoring retinopathy based on patients' risk profile was validated using the data of 3,319 type 2

  15. Validation of a model to estimate personalised screening frequency to monitor diabetic retinopathy

    NARCIS (Netherlands)

    van der Heijden, A.A.W.A.; Walraven, I.; van 't Riet, E.; Aspelund, T.; Lund, S.H.; Elders, P.J.M.; Polak, B.C.P.; Moll, A.C.; Keunen, J.E.E.; Dekker, J.M.; Nijpels, G.

    2014-01-01

    Aims/hypothesis: Our study aimed to validate a model to determine a personalised screening frequency for diabetic retinopathy. Methods: A model calculating a personalised screening interval for monitoring retinopathy based on patients' risk profile was validated using the data of 3,319 type 2

  16. Screening for gestational diabetes mellitus by a model based on risk indicators: a prospective study

    DEFF Research Database (Denmark)

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

    2003-01-01

    This study was performed to prospectively evaluate a screening model for gestational diabetes mellitus on the basis of clinical risk indicators.......This study was performed to prospectively evaluate a screening model for gestational diabetes mellitus on the basis of clinical risk indicators....

  17. A Model Strategy and Policy for Screening Firefighter Candidates

    National Research Council Canada - National Science Library

    Pope, Christopher M

    2006-01-01

    ... and motivated by the desire to serve their community and country. Reasons for and evidence of the need for a new firefighter candidate screening strategy to support this new mission are addressed in this thesis...

  18. Socio-psychological factors in the Expanded Health Belief Model and subsequent colorectal cancer screening.

    Science.gov (United States)

    Sohler, Nancy L; Jerant, Anthony; Franks, Peter

    2015-07-01

    CRC screening interventions tailored to the Expanded Health Belief Model (EHBM) socio-psychological factors have been developed, but the contributions of individual factors to screening outcomes are unclear. In observational analyses of data from a randomized intervention trial, we examined the independent associations of five EHBM factors - CRC screening knowledge, self-efficacy, stage of readiness, barriers, and discussion with a provider - with objectively measured CRC screening after one year. When all five factors were added simultaneously to a base model including other patient and visit characteristics, three of the factors were associated with CRC screening: self-efficacy (OR=1.32, p=0.001), readiness (OR=2.72, pmodel improved prediction of CRC screening (area under the curve) by 7.7%. Patient CRC screening self-efficacy, readiness, and discussion with a provider each independently predicted subsequent screening. Self-efficacy and readiness measures might be helpful in parsimoniously predicting which patients are most likely to engage in CRC screening. The importance of screening discussion with a provider suggests the potential value of augmenting patient-focused EHBM-tailored interventions with provider-focused elements. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Prenatal maternal plasma DNA screening for cystic fibrosis: A computer modelling study of screening performance [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Robert W. Old

    2017-10-01

    Full Text Available Background: Prenatal cystic fibrosis (CF screening is currently based on determining the carrier status of both parents. We propose a new method based only on the analysis of DNA in maternal plasma. Methods: The method relies on the quantitative amplification of the CF gene to determine the percentage of DNA fragments in maternal plasma at targeted CF mutation sites that carry a CF mutation. Computer modelling was carried out to estimate the distributions of these percentages in pregnancies with and without a fetus affected with CF. This was done according to the number of DNA fragments counted and fetal fraction, using the 23 CF mutations recommended by the American College of Medical Genetics for parental carrier testing. Results: The estimated detection rate (sensitivity is 70% (100% of those detected using the 23 mutations, the false-positive rate 0.002%, and the odds of being affected given a positive screening result 14:1, compared with 70%, 0.12%, and 1:3, respectively, with current prenatal screening based on parental carrier testing. Conclusions: Compared with current screening practice based on parental carrier testing, the proposed method would substantially reduce the number of invasive diagnostic procedures (amniocentesis or chorionic villus sampling without reducing the CF detection rate. The expected advantages of the proposed method justify carrying out the necessary test development for use in a clinical validation study.

  20. The sociocultural health behavioral model and disparities in colorectal cancer screening among Chinese Americans.

    Science.gov (United States)

    Ma, Grace X; Wang, Min Qi; Ma, Xiang S; Kim, Giyeon; Toubbeh, Jamil; Shive, Steven

    2013-01-01

    The purpose of this study was to validate a Sociocultural Health Behavior Model using a structural equation analysis to determine the direction and magnitude of the interdependence of model components in relation to health behavior associated with colorectal cancer (CRC) screening among Chinese Americans. A cross-sectional design included a sample of 311 Chinese American men and women age 50 and older. The initial step involved use of confirmatory factor analysis which included the following variables: access/satisfaction with health care, enabling, predisposing, cultural, and health belief factors. Structural equation modeling analyses were conducted on factors for CRC screening. Education and health insurance status were significantly related to CRC screening. Those with less than a high school education and without health insurance were more likely to be "never screened" for CRC than those having more education and health insurance. The path analysis findings also lend support for components of the Sociocultural Health Belief Model and indicated that there was a positive and significant relationship between CRC screening and the enabling factors, between cultural factors and predisposing, enabling, and access/satisfaction with health care factors and between enabling factors and access/satisfaction with health care. The model highlights the significance that sociocultural factors play in relation to CRC screening and reinforced the need to assist Chinese with poor English proficiency in translation and awareness of the importance of CRC screening. The use of community organizations may play a role in assisting Chinese to enhance colorectal cancer screening rates.

  1. 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.

  2. Down Syndrome Health Screening--The Fife Model

    Science.gov (United States)

    Jones, Jill; Hathaway, Dorothy; Gilhooley, Mary; Leech, Amanda; MacLeod, Susan

    2010-01-01

    People with Down syndrome have a greater risk of developing a range of health problems, including cardiac problems, thyroid disorders, sensory impairments, reduced muscle tone (hypotonia) and Alzheimer's disease. Despite this increased risk, regular screening is not typically offered to individuals with Down syndrome. A multidisciplinary health…

  3. High-throughput screening, predictive modeling and computational embryology

    Science.gov (United States)

    High-throughput screening (HTS) studies are providing a rich source of data that can be applied to profile thousands of chemical compounds for biological activity and potential toxicity. EPA’s ToxCast™ project, and the broader Tox21 consortium, in addition to projects worldwide,...

  4. High-throughput screening, predictive modeling and computational embryology - Abstract

    Science.gov (United States)

    High-throughput screening (HTS) studies are providing a rich source of data that can be applied to chemical profiling to address sensitivity and specificity of molecular targets, biological pathways, cellular and developmental processes. EPA’s ToxCast project is testing 960 uniq...

  5. 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

  6. Model for the brightness uniformity of fluorescence screen of image intensifier

    Science.gov (United States)

    Qiu, YaFeng; Chang, BenKang; Qian, YunSheng; Fu, RongGuo; Gao, Youtang; Si, Tian

    2007-01-01

    The three elements of photoelectrical cathode, microchannel plate and fluorescence screen are important parts to imaging quality of low light and ultraviolet Image intensifier. To do research and analysis work on the Fluorescence screen parameter testing have practical significance to the understanding of the performance of fluorescence screen and then can help to know where improvement should be made and then achieve a best performance entire tube, This article mainly introduce the testing theory of the brightness uniformity of fluorescence screen of Image Intensifier and how to build a mathematic model.

  7. Modeling the impact of population screening on breast cancer mortality in the United States.

    Science.gov (United States)

    Mandelblatt, Jeanne S; Cronin, Kathleen A; Berry, Donald A; Chang, Yaojen; de Koning, Harry J; Lee, Sandra J; Plevritis, Sylvia K; Schechter, Clyde B; Stout, Natasha K; van Ravesteyn, Nicolien T; Zelen, Marvin; Feuer, Eric J

    2011-10-01

    Optimal US screening strategies remain controversial. We use six simulation models to evaluate screening outcomes under varying strategies. The models incorporate common data on incidence, mammography characteristics, and treatment effects. We evaluate varying initiation and cessation ages applied annually or biennially and calculate mammograms, mortality reduction (vs. no screening), false-positives, unnecessary biopsies and over-diagnosis. The lifetime risk of breast cancer death starting at age 40 is 3% and is reduced by screening. Screening biennially maintains 81% (range 67% to 99%) of annual screening benefits with fewer false-positives. Biennial screening from 50-74 reduces the probability of breast cancer death from 3% to 2.3%. Screening annually from 40 to 84 only lowers mortality an additional one-half of one percent to 1.8% but requires substantially more mammograms and yields more false-positives and over-diagnosed cases. Decisions about screening strategy depend on preferences for benefits vs. potential harms and resource considerations. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

    Gorst-Rasmussen, Anders; Scheike, Thomas

    2013-01-01

    on performance. An iterative variant of the method is also described which combines screening with penalized regression to handle more complex feature covariance structures. The methodology is evaluated through simulation studies and through application to a real gene expression data set.......In data sets with many more features than observations, independent screening based on all univariate regression models leads to a computationally convenient variable selection method. Recent efforts have shown that, in the case of generalized linear models, independent screening may suffice...... to capture all relevant features with high probability, even in ultrahigh dimension. It is unclear whether this formal sure screening property is attainable when the response is a right-censored survival time. We propose a computationally very efficient independent screening method for survival data which...

  9. [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.

  10. 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.

  11. A globally applicable screening model for detecting individuals with undiagnosed diabetes

    DEFF Research Database (Denmark)

    Vistisen, Dorte; Lee, Crystal M Y; Colagiuri, Stephen

    2012-01-01

    Current risk scores for undiagnosed diabetes are additive in structure. We sought to derive a globally applicable screening model based on established non-invasive risk factors for diabetes but with a more flexible structure....

  12. Evaluating predictive modeling's potential to improve teleretinal screening participation in urban safety net clinics.

    Science.gov (United States)

    Ogunyemi, Omolola; Teklehaimanot, Senait; Patty, Lauren; Moran, Erin; George, Sheba

    2013-01-01

    Screening guidelines for diabetic patients recommend yearly eye examinations to detect diabetic retinopathy and other forms of diabetic eye disease. However, annual screening rates for retinopathy in US urban safety net settings remain low. Using data gathered from a study of teleretinal screening in six urban safety net clinics, we assessed whether predictive modeling could be of value in identifying patients at risk of developing retinopathy. We developed and examined the accuracy of two predictive modeling approaches for diabetic retinopathy in a sample of 513 diabetic individuals, using routinely available clinical variables from retrospective medical record reviews. Bayesian networks and radial basis function (neural) networks were learned using ten-fold cross-validation. The predictive models were modestly predictive with the best model having an AUC of 0.71. Using routinely available clinical variables to predict patients at risk of developing retinopathy and to target them for annual eye screenings may be of some usefulness to safety net clinics.

  13. Optimal healthcare decision making under multiple mathematical models: application in prostate cancer screening.

    Science.gov (United States)

    Bertsimas, Dimitris; Silberholz, John; Trikalinos, Thomas

    2018-03-01

    Important decisions related to human health, such as screening strategies for cancer, need to be made without a satisfactory understanding of the underlying biological and other processes. Rather, they are often informed by mathematical models that approximate reality. Often multiple models have been made to study the same phenomenon, which may lead to conflicting decisions. It is natural to seek a decision making process that identifies decisions that all models find to be effective, and we propose such a framework in this work. We apply the framework in prostate cancer screening to identify prostate-specific antigen (PSA)-based strategies that perform well under all considered models. We use heuristic search to identify strategies that trade off between optimizing the average across all models' assessments and being "conservative" by optimizing the most pessimistic model assessment. We identified three recently published mathematical models that can estimate quality-adjusted life expectancy (QALE) of PSA-based screening strategies and identified 64 strategies that trade off between maximizing the average and the most pessimistic model assessments. All prescribe PSA thresholds that increase with age, and 57 involve biennial screening. Strategies with higher assessments with the pessimistic model start screening later, stop screening earlier, and use higher PSA thresholds at earlier ages. The 64 strategies outperform 22 previously published expert-generated strategies. The 41 most "conservative" ones remained better than no screening with all models in extensive sensitivity analyses. We augment current comparative modeling approaches by identifying strategies that perform well under all models, for various degrees of decision makers' conservativeness.

  14. Development and Validation of Risk Models to Select Ever-Smokers for CT Lung Cancer Screening.

    Science.gov (United States)

    Katki, Hormuzd A; Kovalchik, Stephanie A; Berg, Christine D; Cheung, Li C; Chaturvedi, Anil K

    2016-06-07

    The US Preventive Services Task Force (USPSTF) recommends computed tomography (CT) lung cancer screening for ever-smokers aged 55 to 80 years who have smoked at least 30 pack-years with no more than 15 years since quitting. However, selecting ever-smokers for screening using individualized lung cancer risk calculations may be more effective and efficient than current USPSTF recommendations. Comparison of modeled outcomes from risk-based CT lung-screening strategies vs USPSTF recommendations. Empirical risk models for lung cancer incidence and death in the absence of CT screening using data on ever-smokers from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO; 1993-2009) control group. Covariates included age; education; sex; race; smoking intensity, duration, and quit-years; body mass index; family history of lung cancer; and self-reported emphysema. Model validation in the chest radiography groups of the PLCO and the National Lung Screening Trial (NLST; 2002-2009), with additional validation of the death model in the National Health Interview Survey (NHIS; 1997-2001), a representative sample of the United States. Models were applied to US ever-smokers aged 50 to 80 years (NHIS 2010-2012) to estimate outcomes of risk-based selection for CT lung screening, assuming screening for all ever-smokers, yield the percent changes in lung cancer detection and death observed in the NLST. Annual CT lung screening for 3 years beginning at age 50 years. For model validity: calibration (number of model-predicted cases divided by number of observed cases [estimated/observed]) and discrimination (area under curve [AUC]). For modeled screening outcomes: estimated number of screen-avertable lung cancer deaths and estimated screening effectiveness (number needed to screen [NNS] to prevent 1 lung cancer death). Lung cancer incidence and death risk models were well calibrated in PLCO and NLST. The lung cancer death model calibrated and discriminated well for US

  15. Evaluation of parameters of color profile models of LCD and LED screens

    Science.gov (United States)

    Zharinov, I. O.; Zharinov, O. O.

    2017-12-01

    The purpose of the research relates to the problem of parametric identification of the color profile model of LCD (liquid crystal display) and LED (light emitting diode) screens. The color profile model of a screen is based on the Grassmann’s Law of additive color mixture. Mathematically the problem is to evaluate unknown parameters (numerical coefficients) of the matrix transformation between different color spaces. Several methods of evaluation of these screen profile coefficients were developed. These methods are based either on processing of some colorimetric measurements or on processing of technical documentation data.

  16. Prostate cancer screening using risk stratification based on a multi-state model of genetic variants.

    Science.gov (United States)

    Yen, Amy Ming-Fang; Auvinen, Anssi; Schleutker, Johanna; Wu, Yi-Ying; Fann, Jean Ching-Yuan; Tammela, Teuvo; Chen, Sam Li-Sheng; Chiu, Sherry Yueh-Hsia; Chen, Hsiu-Hsi

    2015-06-01

    Risk-stratified screening for prostate cancer (PCa) with prostate-specific antigen (PSA) testing incorporating genetic variants has received some attention but has been scarcely investigated. We developed a model to stratify the Finnish population by different risk profiles related to genetic variants to optimize the screening policy. Data from the Finnish randomized controlled trial on screening for PCa with PSA testing were used to estimate a six-state Markov model of disease progression. Blood samples from Finnish men were used to assess the risk of PCa related to three genetic variants (rs4242382, rs138213197, and rs200331695). A risk score-based approach combined with a series of computer simulation models was applied to optimize individual screening policies. The 10-year risk of having progressive prostate cancer detected ranged from 43% in the top 5% risk group to approximately 11% in the bottom half of the population. Using the median group, with screening every four years beginning at 55 years-old, as the reference group, the recommended age beginning screening was approximately 47 years-old for the top 5% risk group and 55 years-old for those in the lower 60% risk group. The recommended interscreening interval has been shortened for individuals in the high risk group. The increased availability of genomic information allows the proposed multistate model to be more discriminating with respect to risk stratification and the suggested screening policy, particularly for the lowest risk groups-. -- A multi-state genetic variant-based model was developed for further application to population risk stratification to optimize the interscreening interval and the age at which to begin screening for PSA. A small sub-group of the population is likely to benefit from more intensive screening with early start and short interval, while half of the population is unlikely to benefit from such protocol (compared with four-year interval after age 55 years). © 2015 Wiley

  17. Early detection of idiopathic scoliosis - analysis of three screening models.

    Science.gov (United States)

    Kowalski, Ireneusz M; Dwornik, Michał; Lewandowski, Roman; Pierożyński, Bogusław; Raistenskis, Juozas; J Krzych, Łukasz; Kiebzak, Wojciech

    2015-10-12

    The prevalence of lateral curvatures of the spine ranges from 0.3% to 15.3% in the general population. The aim of the study was to develop and compare three different screening tests for idiopathic scoliosis (IS) with respect to their effectiveness and costs. The Delphi method was used to assess the efficacy of each screening algorithm in detecting IS in the population. An economic analysis was also performed. Diagnostic Algorithm 1 for IS comprised a screening examination performed by nurses and a general practitioner (GP) with verification by specialists. The unit cost of carrying out diagnostic work-up for IS in Algorithm 1 was €94 per child. The second algorithm involved the use of the moiré computer method, followed by verification by a specialist. The lower unit cost of €86 per child of diagnostic work-up according to Algorithm 2 was due to fewer stages compared to Algorithm 1. The highest effectiveness with the highest costs were found for the third algorithm, with only one stage, a specialist's consultation (cost €153 per child). The number of stages in an algorithm does not correlate positively with its efficacy or cost. The recommended scheme is Algorithm 3, where children are examined by rehabilitation specialists or a physiotherapist using a scoliometer and an inclinometer. The use of the apparently most expensive scheme (Algorithm 3) should result in lowering the costs of treatment of established idiopathic scoliosis and, in the long term, prove to be the most cost-effective solution for the health care system.

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

    Science.gov (United States)

    Sloot, F; Heijnsdijk, Eam; Groenewoud, J H; Goudsmit, F; Steyerberg, E W; de Koning, H J; Simonsz, H J

    2017-09-01

    Objective 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 little. Methods We developed a micro-simulation model that approximated the birth-cohort data from the previous study, in which 2964 children had completed follow-up at age 7, and 100 amblyopia cases were detected. Detailed data on screens, referrals, and orthoptic follow-up, including the cause of amblyopia, were available. The model predicted the number of amblyopia cases detected for each screen and for the entire screening programme, and the effect of omitting screens. Incidence curves for all types of amblyopia caused by strabismus, refractive anomalies or by both were estimated by approximation of the observational data, in conjunction with experts' estimations and the literature. Results We calculated mean actual sensitivity per screen per type of amblyopia, and the effect per screen. Screening at 24 months was found to be least effective. The impact on the screening programme, estimated by summing the effectiveness per screen, omitting the 24-month screen, was a reduction of 3.4% (57 vs. 59 cases) in the number of detected cases of amblyopia at age 5. Conclusion The effectiveness of the Dutch vision screening programme would hardly be affected by omission of the 24-month screening examination. A disinvestment study is warranted.

  19. Cost-Effectiveness of a Community Pharmacist-Led Sleep Apnea Screening Program - A Markov Model.

    Directory of Open Access Journals (Sweden)

    Clémence Perraudin

    Full Text Available Despite the high prevalence and major public health ramifications, obstructive sleep apnea syndrome (OSAS remains underdiagnosed. In many developed countries, because community pharmacists (CP are easily accessible, they have been developing additional clinical services that integrate the services of and collaborate with other healthcare providers (general practitioners (GPs, nurses, etc.. Alternative strategies for primary care screening programs for OSAS involving the CP are discussed.To estimate the quality of life, costs, and cost-effectiveness of three screening strategies among patients who are at risk of having moderate to severe OSAS in primary care.Markov decision model.Published data.Hypothetical cohort of 50-year-old male patients with symptoms highly evocative of OSAS.The 5 years after initial evaluation for OSAS.Societal.Screening strategy with CP (CP-GP collaboration, screening strategy without CP (GP alone and no screening.Quality of life, survival and costs for each screening strategy.Under almost all modeled conditions, the involvement of CPs in OSAS screening was cost effective. The maximal incremental cost for "screening strategy with CP" was about 455€ per QALY gained.Our results were robust but primarily sensitive to the treatment costs by continuous positive airway pressure, and the costs of untreated OSAS. The probabilistic sensitivity analysis showed that the "screening strategy with CP" was dominant in 80% of cases. It was more effective and less costly in 47% of cases, and within the cost-effective range (maximum incremental cost effectiveness ratio at €6186.67/QALY in 33% of cases.CP involvement in OSAS screening is a cost-effective strategy. This proposal is consistent with the trend in Europe and the United States to extend the practices and responsibilities of the pharmacist in primary care.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Circuit models for Salisbury screens made from unidirectional carbon fiber composite sandwich structures

    Science.gov (United States)

    Riley, Elliot J.; Lenzing, Erik H.; Narayanan, Ram M.

    2016-05-01

    Carbon fiber composite materials have many useful structural material properties. The electromagnetic perfor- mance of these materials is of great interest for future applications. The work presented in this paper deals with the construction of Salisbury screen microwave absorbers made from unidirectional carbon fiber composite sand- wich structures. Specifically, absorbers centered at 7.25 GHz and 12.56 GHz are investigated. Circuit models are created to match the measured performance of the carbon fiber Salisbury screens using a genetic algorithm to extract lumped element circuit values. The screens presented in this paper utilize unidirectional carbon fiber sheets in place of the resistive sheet utilized in the classic Salisbury screen. The theory, models, prototypes, and measurements of these absorbers are discussed.

  5. 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.

  6. 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)

  7. The sociocultural health behavioral model and disparities in colorectal cancer screening among Chinese Americans

    Science.gov (United States)

    Ma, Grace X; Wang, Min Qi; Ma, Xiang S; Kim, Giyeon; Toubbeh, Jamil; Shive, Steven

    2013-01-01

    Objective The purpose of this study was to validate a Sociocultural Health Behavior Model using a structural equation analysis to determine the direction and magnitude of the interdependence of model components in relation to health behavior associated with colorectal cancer (CRC) screening among Chinese Americans. Methods A cross-sectional design included a sample of 311 Chinese American men and women age 50 and older. The initial step involved use of confirmatory factor analysis which included the following variables: access/satisfaction with health care, enabling, predisposing, cultural, and health belief factors. Structural equation modeling analyses were conducted on factors for CRC screening. Results Education and health insurance status were significantly related to CRC screening. Those with less than a high school education and without health insurance were more likely to be “never screened” for CRC than those having more education and health insurance. The path analysis findings also lend support for components of the Sociocultural Health Belief Model and indicated that there was a positive and significant relationship between CRC screening and the enabling factors, between cultural factors and predisposing, enabling, and access/satisfaction with health care factors and between enabling factors and access/satisfaction with health care. Conclusions The model highlights the significance that sociocultural factors play in relation to CRC screening and reinforced the need to assist Chinese with poor English proficiency in translation and awareness of the importance of CRC screening. The use of community organizations may play a role in assisting Chinese to enhance colorectal cancer screening rates. PMID:25364475

  8. 'Inside-out', back-to-front: a model for clinical population genetic screening.

    Science.gov (United States)

    Shickle, D; Harvey, I

    1993-07-01

    Developments in DNA technology have resulted in a dramatic increase in the number of genes identified. With the localisation of a gene it is possible to devise procedures suitable for mass carrier screening programmes. Until recently mass carrier screening was only possible for a limited number of disorders, for example, Tay-Sachs disease and haemoglobinopathies. Counselling possible carriers was based on estimations of risk. The momentum towards mass carrier screening is likely to be increased by gene therapy. Carrier screening for cystic fibrosis alone will have dramatic implications for genetic service provision as 4 to 5% of the UK population carry the CF gene. The potential for genetic screening of multifactorial diseases, for example, cancers, should also be considered. The existing organisation of genetic services is likely to be inadequate. A new specialty of clinical population genetics is required. A model is proposed of clinical population genetic screening programmes, organised under a 'common umbrella' led by a public health physician, while screening and follow up will remain the responsibility of the appropriate clinician.

  9. 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.

  10. 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...

  11. Analysis, Modeling, and Simulation (AMS) testbed initial screening report.

    Science.gov (United States)

    2013-11-01

    Analysis Modeling and Simulation (AMS) Testbeds can make significant contributions in identifying the benefits of more effective, more active systems management, resulting from integrating transformative applications enabled by new data from wireless...

  12. 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.

  13. Por La Vida model intervention enhances use of cancer screening tests among Latinas.

    Science.gov (United States)

    Navarro, A M; Senn, K L; McNicholas, L J; Kaplan, R M; Roppé, B; Campo, M C

    1998-07-01

    To describe the short-term impact of the intervention known as Por La Vida (PLV) on cancer screening for Latinas in San Diego, California. Thirty-six lay community workers (consejeras) were recruited and trained to conduct educational group sessions. Each consejera recruited approximately 14 peers from the community to participate in the program. The consejeras were randomly assigned to either a twelve-week cancer screening intervention group or a control group in which they participated in an equally engaging program entitled "Community Living Skills." Pre- and post-intervention self-report information was obtained from project participants on the use of cancer screening examinations. Outcome measures were changes in the percentages of women who had breast and cervical cancer screening test within the past year before and after the intervention occurred. Experimental and control groups were compared using t-tests. Analyses were conducted using both consejeras and participants as the unit of analysis. The increase in the use of the cancer screening test was higher in the PLV cancer intervention group in comparison to women in the community living skills control group. Key to the PLV intervention model is the identification of natural helpers in the Latino community and their subsequent training in intervention based on social learning theory using culturally appropriate educational materials. The model is an effective and viable approach for increasing the use of cancer screening tests in Latinas of low socioeconomic level and low level of acculturation.

  14. 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

    . 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...... 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...... and not by variations in data. High levels of overdiagnosis of cancer have usually been explained by detection of many slow-growing tumors with long lead-times. This theory can be tested by studying if slow-growing tumors accumulate in the absence of screening, which they don't. Thus, it is likely that the natural...

  15. Screening model for assessing doses from radiological accidents

    International Nuclear Information System (INIS)

    Sjoreen, A.L.; Athey, G.F.; Sakenas, C.A.; McKenna, T.J.

    1988-01-01

    A new dose assessment model, called RASCAL, has been written for the US Nuclear Regulatory Commission (NRC) for use during response to emergencies. RASCAL is designed to provide rough estimates of the health effects from a radiological accident in progress and only limited information is available. RASCAL will be used by the NRC personnel who report to the site of a nuclear accident to conduct an independent evaluation of dose projections. It was written to correct the technical and operational problems in NRC's previous model and to be more appropriate to the personal computers presently in use by the NRC. The model has been constructed to be easy to modify, with separate modules for estimation of the quantity of radioactivity released, its transport through the atmosphere, and the resulting radiologic dose to man. RASCAL results can be displayed in graphical or ASCII form. 4 refs

  16. 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

  17. Maternal serologic screening to prevent congenital toxoplasmosis: a decision-analytic economic model.

    Directory of Open Access Journals (Sweden)

    Eileen Stillwaggon

    2011-09-01

    Full Text Available To determine a cost-minimizing option for congenital toxoplasmosis in the United States.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.Universal screening according to the French protocol is cost saving for the US population within broad parameters for costs and probabilities.

  18. 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 phenomenologic...

  19. Erythrocytes as a biological model for screening of xenobiotics toxicity.

    Science.gov (United States)

    Farag, Mayada Ragab; Alagawany, Mahmoud

    2018-01-05

    Erythrocytes are the main cells in circulation. They are devoid of internal membrane structures and easy to be isolated and handled providing a good model for different assays. Red blood cells (RBCs) plasma membrane is a multi-component structure that keeps the cell morphology, elasticity, flexibility and deformability. Alteration of membrane structure upon exposure to xenobiotics could induce various cellular abnormalities and releasing of intracellular components. Therefore the morphological changes and extracellular release of haemoglobin [hemolysis] and increased content of extracellular adenosine triphosphate (ATP) [as signs of membrane stability] could be used to evaluate the cytotoxic effects of various molecules. The nucleated RBCs from birds, fish and amphibians can be used to evaluate genotoxicity of different xenobiotics using comet, DNA fragmentation and micronucleus assays. The RBCs could undergo programmed cell death (eryptosis) in response to injury providing a useful model to analyze some mechanisms of toxicity that could be implicated in apoptosis of nucleated cells. Erythrocytes are vulnerable to peroxidation making it a good biological membrane model for analyzing the oxidative stress and lipid peroxidation of various xenobiotics. The RBCs contain a large number of enzymatic and non-enzymatic antioxidants. The changes of the RBCs antioxidant capacity could reflect the capability of xenobiotics to generate reactive oxygen species (ROS) resulting in oxidative damage of tissue. These criteria make RBCs a valuable in vitro model to evaluate the cytotoxicity of different natural or synthetic and organic or inorganic molecules by cellular damage measures. Copyright © 2017. Published by Elsevier B.V.

  20. Simple Screened Hydrogen Model of Excitons in Two-Dimensional Materials

    DEFF Research Database (Denmark)

    Olsen, Thomas; Latini, Simone; Rasmussen, Filip Anselm

    2016-01-01

    We present a generalized hydrogen model for the binding energies (EB) and radii of excitons in two-dimensional (2D) materials that sheds light on the fundamental differences between excitons in two and three dimensions. In contrast to the well-known hydrogen model of three-dimensional (3D) excitons......, the description of 2D excitons is complicated by the fact that the screening cannot be assumed to be local. We show that one can consistently define an effective 2D dielectric constant by averaging the screening over the extend of the exciton. For an ideal 2D semiconductor this leads to a simple expression for EB...

  1. 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.

  2. 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

  3. 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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...... foam model was tested with sensitivity analysis on foam properties to provide a guideline for the history matching process (GOR alteration) of FAWAG Pilot of Snorre Field (Statoil). The aim was to check the authenticity of presented new foam model in commercial software whether it is implementable...... of the fluid flows control inside reservoir. The way; how specific properties control the time of gas arrival and values of GOR are described. The analyses of the improvements in the injection schedule are shown. With increasing number of CO2 and FAWAG methods in preparation worldwide, the use...

  5. 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

  6. Hydration of nail plate: a novel screening model for transungual drug permeation enhancers.

    Science.gov (United States)

    Chouhan, P; Saini, T R

    2012-10-15

    Drug delivery by topical route for the treatment of onychomycosis, a nail fungal infection, is challenging due to the unique barrier properties of the nail plate which imparts high resistance to the passage of antifungal drugs. Permeation enhancers are used in transungual formulations to improve the drug flux across the nail plate. Selection of the effective permeation enhancer among the available large pool of permeation enhancers is a difficult task. Screening the large number of permeation enhancers using conventional Franz diffusion cells is laborious and expensive. The objective of present study was to evolve a simple, accurate and rapid method for screening of transungual drug permeation enhancers based on the principle of hydration of nail plate. The permeation enhancer which affects the structural or physicochemical properties of nail plate would also affect their hydration capacity. Two screening procedures namely primary and secondary screenings were evolved wherein hydration and uptake of ciclopirox olamine by nail plates were measured. Hydration enhancement factor, HEF(24) and drug uptake enhancement factor, UEF(24) were determined for screening of 23 typical permeation enhancers. The Pearson's correlation coefficient between HEF(24) and UEF(24) was determined. A good agreement between the HEF(24) and UEF(24) data proved the validity of the proposed nail plate hydration model as a screening technique for permeation enhancers. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. A team care model of cervical 
screening in a general practice.

    Science.gov (United States)

    Rennie, Darryn; Boxsell, Jennifer; Pedretti, Kaye

    2015-07-01

    Cervical screening reduces the incidence and mortality rate of cervical cancer. General practices have opportunities to increase screening rates by modifying the model of service provided. We provide an example of team-based cervical screening in a general practice and report the effectiveness of invitation letters for women with no record of a Pap smear. The practice sent invitation letters to women with no record of a Pap smear (or reason for not requiring one) to attend a visit to a women's health clinic comprising a visit to a GP of choice and then a nurse to perform the smear. Practice cervical screening data were collected over 45 months to investigate the impact of invitation letters. The quality of Pap smears performed by nurses was recorded. The biennial cervical screening rate improved by 11%. The percentage of women with no Pap smear recorded was reduced from 41.71% to 27.99%. The quality of the smears taken by the nurses was above the nationwide average. The data show that invitation letters contributed to improved cervical screening and that nurses were highly effective team members in the collection of Pap smears.

  8. 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%.

  9. Utilizing high throughput screening data for predictive toxicology models: protocols and application to MLSCN assays

    Science.gov (United States)

    Guha, Rajarshi; Schürer, Stephan C.

    2008-06-01

    Computational toxicology is emerging as an encouraging alternative to experimental testing. The Molecular Libraries Screening Center Network (MLSCN) as part of the NIH Molecular Libraries Roadmap has recently started generating large and diverse screening datasets, which are publicly available in PubChem. In this report, we investigate various aspects of developing computational models to predict cell toxicity based on cell proliferation screening data generated in the MLSCN. By capturing feature-based information in those datasets, such predictive models would be useful in evaluating cell-based screening results in general (for example from reporter assays) and could be used as an aid to identify and eliminate potentially undesired compounds. Specifically we present the results of random forest ensemble models developed using different cell proliferation datasets and highlight protocols to take into account their extremely imbalanced nature. Depending on the nature of the datasets and the descriptors employed we were able to achieve percentage correct classification rates between 70% and 85% on the prediction set, though the accuracy rate dropped significantly when the models were applied to in vivo data. In this context we also compare the MLSCN cell proliferation results with animal acute toxicity data to investigate to what extent animal toxicity can be correlated and potentially predicted by proliferation results. Finally, we present a visualization technique that allows one to compare a new dataset to the training set of the models to decide whether the new dataset may be reliably predicted.

  10. Applying Statistical Models to Mammographic Screening Data to Understand Growth and Progression of Ductal Carcinoma in Situ

    National Research Council Canada - National Science Library

    Gertig, Dorota M; Erbas, Bircan; Bymes, Gram; Dowty, James

    2005-01-01

    ... IS. Similar results were found for histological grade. We have developed a computer simulation for mammographic screening data which models progression and detection of Ductal carcinoma in situ...

  11. A Three-groups Model for High Throughput Survival Screens

    Science.gov (United States)

    Shaby, Benjamin A.; Skibinski, Gaia; Ando, Michael; LaDow, Eva S.; Finkbeiner, Steven

    2016-01-01

    Summary Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by the progressive deterioration of motor neurons in the cortex and spinal cord. Using an automated robotic microscope platform that enables the longitudinal tracking of thousands of single neurons, we examine the effects a large library of compounds on modulating the survival of primary neurons expressing a mutation known to cause ALS. The goal of our analysis is to identify the few potentially beneficial compounds among the many assayed, the vast majority of which do not extend neuronal survival. This resembles the large-scale simultaneous inference scenario familiar from microarray analysis, but transferred to the survival analysis setting due to the novel experimental setup. We apply a three component mixture model to censored survival times of thousands of individual neurons subjected to hundreds of different compounds. The shrinkage induced by our model significantly improves performance in simulations relative to performing treatment-wise survival analysis and subsequent multiple testing adjustment. Our analysis identified compounds that provide insight into potential novel therapeutic strategies for ALS. PMID:26821783

  12. 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.

  13. Turkish translation and adaptation of Champion's Health Belief Model Scales for breast cancer mammography screening.

    Science.gov (United States)

    Yilmaz, Meryem; Sayin, Yazile Yazici

    2014-07-01

    To examine the translation and adaptation process from English to Turkish and the validity and reliability of the Champion's Health Belief Model Scales for Mammography Screening. Its aim (1) is to provide data about and (2) to assess Turkish women's attitudes and behaviours towards mammography. The proportion of women who have mammography is lower in Turkey. The Champion's Health Belief Model Scales for Mammography Screening-Turkish version can be helpful to determine Turkish women's health beliefs, particularly about mammography. Cross-sectional design was used to collect survey data from Turkish women: classical measurement method. The Champion's Health Belief Model Scales for Mammography Screening was translated from English to Turkish. Again, it was back translated into English. Later, the meaning and clarity of the scale items were evaluated by a bilingual group representing the culture of the target population. Finally, the tool was evaluated by two bilingual professional researchers in terms of content validity, translation validity and psychometric estimates of the validity and reliability. The analysis included a total of 209 Turkish women. The validity of the scale was confirmed by confirmatory factor analysis and criterion-related validity testing. The Champion's Health Belief Model Scales for Mammography Screening aligned to four factors that were coherent and relatively independent of each other. There was a statistically significant relationship among all of the subscale items: the positive and high correlation of the total item test score and high Cronbach's α. The scale has a strong stability over time: the Champion's Health Belief Model Scales for Mammography Screening demonstrated acceptable preliminary values of reliability and validity. The Champion's Health Belief Model Scales for Mammography Screening is both a reliable and valid instrument that can be useful in measuring the health beliefs of Turkish women. It can be used to provide data

  14. Targeted screening of individuals at high risk for pancreatic cancer: results of a simulation model.

    Science.gov (United States)

    Pandharipande, Pari V; Heberle, Curtis; Dowling, Emily C; Kong, Chung Yin; Tramontano, Angela; Perzan, Katherine E; Brugge, William; Hur, Chin

    2015-04-01

    To identify when, from the standpoint of relative risk, magnetic resonance (MR) imaging-based screening may be effective in patients with a known or suspected genetic predisposition to pancreatic cancer. The authors developed a Markov model of pancreatic ductal adenocarcinoma (PDAC). The model was calibrated to National Cancer Institute Surveillance, Epidemiology, and End Results registry data and informed by the literature. A hypothetical screening strategy was evaluated in which all population individuals underwent one-time MR imaging screening at age 50 years. Screening outcomes for individuals with an average risk for PDAC ("base case") were compared with those for individuals at an increased risk to assess for differential benefits in populations with a known or suspected genetic predisposition. Effects of varying key inputs, including MR imaging performance, surgical mortality, and screening age, were evaluated with a sensitivity analysis. RESULTS In the base case, screening resulted in a small number of cancer deaths averted (39 of 100 000 men, 38 of 100 000 women) and a net decrease in life expectancy (-3 days for men, -4 days for women), which was driven by unnecessary pancreatic surgeries associated with false-positive results. Life expectancy gains were achieved if an individual's risk for PDAC exceeded 2.4 (men) or 2.7 (women) times that of the general population. When relative risk increased further, for example to 30 times that of the general population, averted cancer deaths and life expectancy gains increased substantially (1219 of 100 000 men, life expectancy gain: 65 days; 1204 of 100 000 women, life expectancy gain: 71 days). In addition, results were sensitive to MR imaging specificity and the surgical mortality rate. Although PDAC screening with MR imaging for the entire population is not effective, individuals with even modestly increased risk may benefit. © RSNA, 2014 Online supplemental material is available for this article.

  15. 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.

  16. Towards modelling cost and risks of infrequent events in the cargo screening process

    OpenAIRE

    Sherman, Galina; Menachof, David; Siebers, Peer-Olaf; Aickelin, Uwe

    2013-01-01

    We introduce a simulation model of the port of Calais with a focus on the operation of immigration controls. Our aim is to compare the cost and benefits of different screening policies. Methodologically, we are trying to understand the limits of discrete event simulation of rare events. When will they become 'too rare' for simulation to give meaningful results?

  17. 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...

  18. Screening and vaccination as determined by the Social Ecological Model and the Theory of Triadic Influence

    NARCIS (Netherlands)

    Nyambe, Anayawa; Hal, Van Guido; Kampen, Jarl K.

    2016-01-01

    Background: Vaccination and screening are forms of primary and secondary prevention methods. These methods are recommended for controlling the spread of a vast number of diseases and conditions. To determine the most effective preventive methods to be used by a society, multi-level models have

  19. 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

  20. 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...

  1. 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…

  2. 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.

  3. 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 periodontitis. A future prospective study is indicated for evaluating this model's ability to predict the occurrence of periodontitis.

  4. 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.

  5. A prediction model for advanced colorectal neoplasia in an asymptomatic screening population.

    Directory of Open Access Journals (Sweden)

    Sung Noh Hong

    Full Text Available An electronic medical record (EMR database of a large unselected population who received screening colonoscopies may minimize sampling error and represent real-world estimates of risk for screening target lesions of advanced colorectal neoplasia (CRN. Our aim was to develop and validate a prediction model for assessing the probability of advanced CRN using a clinical data warehouse.A total of 49,450 screenees underwent their first colonoscopy as part of a health check-up from 2002 to 2012 at Samsung Medical Center, and the dataset was constructed by means of natural language processing from the computerized EMR system. The screenees were randomized into training and validation sets. The prediction model was developed using logistic regression. The model performance was validated and compared with existing models using area under receiver operating curve (AUC analysis.In the training set, age, gender, smoking duration, drinking frequency, and aspirin use were identified as independent predictors for advanced CRN (adjusted P < .01. The developed model had good discrimination (AUC = 0.726 and was internally validated (AUC = 0.713. The high-risk group had a 3.7-fold increased risk of advanced CRN compared to the low-risk group (1.1% vs. 4.0%, P < .001. The discrimination performance of the present model for high-risk patients with advanced CRN was better than that of the Asia-Pacific Colorectal Screening score (AUC = 0.678, P < .001 and Schroy's CAN index (AUC = 0.672, P < .001.The present 5-item risk model can be calculated readily using a simple questionnaire and can identify the low- and high-risk groups of advanced CRN at the first screening colonoscopy. This model may increase colorectal cancer risk awareness and assist healthcare providers in encouraging the high-risk group to undergo a colonoscopy.

  6. Breast cancer screening behaviors among Korean American immigrant women: findings from the Health Belief Model.

    Science.gov (United States)

    Lee, Hee Yun; Stange, Mia Ju; Ahluwalia, Jasjit S

    2015-11-01

    This study examined the utilization of clinical breast examinations (CBEs) and mammograms among Korean American immigrant women and investigated how the six constructs of Health Belief Model (HBM) are associated with the receipt of breast cancer screening. Using a quota sampling strategy, 202 Korean American immigrant women were recruited in metropolitan areas in the northeastern United States. Approximately 64% of the participants reported having had at least one CBE in their lifetime, and about 81% of the sample had undergone at least one mammogram in their lifetime. Women who perceived themselves to be susceptible to breast cancer were more likely to have undergone a CBE, and women who had lower barriers to screening or demonstrated a higher level of confidence were more likely than their counterparts to undergo a mammogram. Findings suggest that HBM constructs such as susceptibility, barriers, and confidence should be considered when designing interventions aimed at promoting breast cancer screening. © The Author(s) 2014.

  7. Pharmacophore modeling improves virtual screening for novel peroxisome proliferator-activated receptor-gamma ligands

    Science.gov (United States)

    Lewis, Stephanie N.; Garcia, Zulma; Hontecillas, Raquel; Bassaganya-Riera, Josep; Bevan, David R.

    2015-05-01

    Peroxisome proliferator-activated receptor-gamma (PPARγ) is a nuclear hormone receptor involved in regulating various metabolic and immune processes. The PPAR family of receptors possesses a large binding cavity that imparts promiscuity of ligand binding not common to other nuclear receptors. This feature increases the challenge of using computational methods to identify PPAR ligands that will dock favorably into a structural model. Utilizing both ligand- and structure-based pharmacophore methods, we sought to improve agonist prediction by grouping ligands according to pharmacophore features, and pairing models derived from these features with receptor structures for docking. For 22 of the 33 receptor structures evaluated we observed an increase in true positive rate (TPR) when screening was restricted to compounds sharing molecular features found in rosiglitazone. A combination of structure models used for docking resulted in a higher TPR (40 %) when compared to docking with a single structure model (marketed drug database verified the predictive ability of the selected structure models. This study highlights the steps necessary to improve screening for PPARγ ligands using multiple structure models, ligand-based pharmacophore data, evaluation of protein-ligand interactions, and comparison of docking datasets. The unique combination of methods presented here holds potential for more efficient screening of compounds with unknown affinity for PPARγ that could serve as candidates for therapeutic development.

  8. 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.

  9. Partial Atomic Charges and Screened Charge Models of the Electrostatic Potential.

    Science.gov (United States)

    Wang, Bo; Truhlar, Donald G

    2012-06-12

    We propose a new screened charge method for calculating partial atomic charges in molecules by electrostatic potential (ESP) fitting. The model, called full density screening (FDS), is used to approximate the screening effect of full charge densities of atoms in molecules. The results are compared to the conventional ESP fitting method based on point charges and to our previously proposed outer density screening (ODS) method, in which the parameters are reoptimized for the present purpose. In ODS, the charge density of an atom is represented by the sum of a point charge and a smeared negative charge distributed in a Slater-type orbital (STO). In FDS, the charge density of an atom is taken to be the sum of the charge density of the neutral atom and a partial atomic charge (of either sign) distributed in an STO. The ζ values of the STOs used in these two models are optimized in the present study to best reproduce the electrostatic potentials. The quality of the fit to the electrostatics is improved in the screened charge methods, especially for the regions that are within one van der Waals radius of the centers of atoms. It is also found that the charges derived by fitting electrostatic potentials with screened charges are less sensitive to the positions of the fitting points than are those derived with conventional electrostatic fitting. Moreover, we found that the electrostatic-potential-fitted (ESP) charges from the screened charge methods are similar to those from the point-charge method except for molecules containing the methyl group, where we have explored the use of restraints on nonpolar H atoms. We recommend the FDS model if the only goal is ESP fitting to obtain partial atomic charges or a fit to the ESP field. However, the ODS model is more accurate for electronic embedding in combined quantum mechanical and molecular mechanical (QM/MM) modeling and is more accurate than point-charge models for ESP fitting, and it is recommended for applications

  10. Cost savings from a teledentistry model for school dental screening: an Australian health system perspective.

    Science.gov (United States)

    Estai, Mohamed; Bunt, Stuart; Kanagasingam, Yogesan; Tennant, Marc

    2017-06-05

    Objective The aim of the present study was to compare the costs of teledentistry and traditional dental screening approaches in Australian school children. Methods A cost-minimisation analysis was performed from the perspective of the oral health system, comparing the cost of dental screening in school children using a traditional visual examination approach with the cost of mid-level dental practitioners (MLDPs), such as dental therapists, screening the same cohort of children remotely using teledentistry. A model was developed to simulate the costs (over a 12-month period) of the two models of dental screening for all school children (2.7million children) aged 5-14 years across all Australian states and territories. The fixed costs and the variable costs, including staff salary, travel and accommodation costs, and cost of supply were calculated. All costs are given in Australian dollars. Results The total estimated cost of the teledentistry model was $50million. The fixed cost of teledentistry was $1million and that of staff salaries (tele-assistants, charters and their supervisors, as well as information technology support was estimated to be $49million. The estimated staff salary saved with the teledentistry model was $56million, and the estimated travel allowance and supply expenses avoided were $16million and $14million respectively; an annual reduction of $85million in total. Conclusions The present study shows that the teledentistry model of dental screening can minimise costs. The estimated savings were due primarily to the low salaries of dental therapists and the avoidance of travel and accommodation costs. Such savings could be redistributed to improve infrastructure and oral health services in rural or other underserved areas. What is known about the topic? Caries is a preventable disease, which, if it remains untreated, can cause significant morbidity requiring costly treatment. Regular dental screening and oral health education have the great

  11. 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.

  12. Modeling of high-frequency wave propagation in the heterogenous Earth using screen method

    Science.gov (United States)

    Ding, Y.; Zheng, Y.

    2017-12-01

    High-frequency (1Hz) wave propagation modeling in the heterogenous Earth is difficult due to computation cost. We have developed one alternative method to do high-frequency wave propagation locally in the Earth. First, we divide the heterogeneous Earth model into two parts: the background gradient velocity model, and the velocity perturbation. Then we trace rays from the source to the Earth surface and make screens perpendicular to the rays. We propagate the wavefield in each screen by Kirchhoff surface integral and account for the velocity perturbations with a phase shift. Recursively, the algorithm will propagate the wavefield locally from the source to the surface. The result is compared with that from the finite difference method.

  13. 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

    2018-02-01

    We present a fast numerical screened halo model algorithm (CHAM) for modeling non-linear power spectrum for the alternative models to ΛCDM. 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. Second, the least assumptions are made in the calculation. Hence, the physical picture is very easily understandable. Third, it is very predictable and does not rely on the calibration from N-body simulation. As an example, we show the case of Hu-Sawicki f(R) gravity. In this case, the typical CPU time with the current parallel Python script (8 threads) is roughly within 10 minutes. The resulting spectra are in a good agreement with N-body data within a few percentage accuracy up to k ˜ 1 h/Mpc.

  14. High-Throughput Screening and Prediction Model Building for Novel Hemozoin Inhibitors Using Physicochemical Properties.

    Science.gov (United States)

    Huy, Nguyen Tien; Chi, Pham Lan; Nagai, Jun; Dang, Tran Ngoc; Mbanefo, Evaristus Chibunna; Ahmed, Ali Mahmoud; Long, Nguyen Phuoc; Thoa, Le Thi Bich; Hung, Le Phi; Titouna, Afaf; Kamei, Kaeko; Ueda, Hiroshi; Hirayama, Kenji

    2017-02-01

    It is essential to continue the search for novel antimalarial drugs due to the current spread of resistance against artemisinin by Plasmodium falciparum parasites. In this study, we developed in silico models to predict hemozoin inhibitors as a potential first-step screening for novel antimalarials. An in vitro colorimetric high-throughput screening assay of hemozoin formation was used to identify hemozoin inhibitors from 9,600 structurally diverse compounds. The physicochemical properties of positive hits and randomly selected compounds were extracted from the ChemSpider database; they were used for developing prediction models to predict hemozoin inhibitors using two different approaches, i.e., traditional multivariate logistic regression and Bayesian model averaging. Our results showed that a total of 224 positive-hit compounds exhibited the ability to inhibit hemozoin formation, with 50% inhibitory concentrations (IC 50 s) ranging from 3.1 μM to 199.5 μM. The best model according to traditional multivariate logistic regression included the three variables octanol-water partition coefficient, number of hydrogen bond donors, and number of atoms of hydrogen, while the best model according to Bayesian model averaging included the three variables octanol-water partition coefficient, number of hydrogen bond donors, and index of refraction. Both models had a good discriminatory power, with area under the curve values of 0.736 and 0.781 for the traditional multivariate model and Bayesian model averaging, respectively. In conclusion, the prediction models can be a new, useful, and cost-effective approach for the first screen of hemozoin inhibition-based antimalarial drug discovery. Copyright © 2017 American Society for Microbiology.

  15. LOCAL INDEPENDENCE FEATURE SCREENING FOR NONPARAMETRIC AND SEMIPARAMETRIC MODELS BY MARGINAL EMPIRICAL LIKELIHOOD

    Science.gov (United States)

    Chang, Jinyuan; Tang, Cheng Yong; Wu, Yichao

    2015-01-01

    We consider an independence feature screening technique for identifying explanatory variables that locally contribute to the response variable in high-dimensional regression analysis. Without requiring a specific parametric form of the underlying data model, our approach accommodates a wide spectrum of nonparametric and semiparametric model families. To detect the local contributions of explanatory variables, our approach constructs empirical likelihood locally in conjunction with marginal nonparametric regressions. Since our approach actually requires no estimation, it is advantageous in scenarios such as the single-index models where even specification and identification of a marginal model is an issue. By automatically incorporating the level of variation of the nonparametric regression and directly assessing the strength of data evidence supporting local contribution from each explanatory variable, our approach provides a unique perspective for solving feature screening problems. Theoretical analysis shows that our approach can handle data dimensionality growing exponentially with the sample size. With extensive theoretical illustrations and numerical examples, we show that the local independence screening approach performs promisingly. PMID:27242388

  16. PBT assessment and prioritization by PBT Index and consensus modeling: comparison of screening results from structural models.

    Science.gov (United States)

    Gramatica, Paola; Cassani, Stefano; Sangion, Alessandro

    2015-04-01

    The limited availability of comprehensive data for Persistence, Bioaccumulation and Toxicity (PBT) of chemicals is a serious hindrance to the assignment of compounds to the categories of PBT and vPvB; REACH regulation requires authorization for the use of such chemicals, and additionally plans for safer alternatives. In the context of screening and priority-setting tools for PBT-assessment, the cumulative PBT Index model, implemented in QSARINS (QSAR-INSUBRIA), new software tool for the development and validation of multiple linear regression QSAR models, offers a new holistic approach for the identification of chemicals with cumulative PBT properties directly from their molecular structure. In this study the Insubria PBT Index in QSARINS is applied to the screening and prioritization of various data sets, containing a large variety of chemicals of heterogeneous molecular structure, previously screened by various authors by different methods, for their potential PBT behavior. Particular attention is devoted to the model Applicability Domain, using different approaches such as Descriptor Range, Leverage, and Principal Component Analysis (PCA) of the modeling molecular descriptors, in order to discriminate between interpolated and extrapolated predictions. The results of this screening, which is based only on the molecular structure features and is not dependent on single threshold values for P, B and T, are compared with those obtained by the on-line US-EPA PBT Profiler. Good agreement between the various approaches is found, supporting the utility of a consensus approach in priority-setting studies. The main discrepancies are highlighted and commented on. Moreover, a priority list containing the most hazardous compounds identified in agreement between the two tools is drafted. The PBT Index, implemented in QSARINS, which was demonstrated to be a practical, precautionary and reliable screening tool for PBT-behavior directly from the molecular structure, can be

  17. Comparative analysis of 5 lung cancer natural history and screening models that reproduce outcomes of the NLST and PLCO trials.

    Science.gov (United States)

    Meza, Rafael; ten Haaf, Kevin; Kong, Chung Yin; Erdogan, Ayca; Black, William C; Tammemagi, Martin C; Choi, Sung Eun; Jeon, Jihyoun; Han, Summer S; Munshi, Vidit; van Rosmalen, Joost; Pinsky, Paul; McMahon, Pamela M; de Koning, Harry J; Feuer, Eric J; Hazelton, William D; Plevritis, Sylvia K

    2014-06-01

    The National Lung Screening Trial (NLST) demonstrated that low-dose computed tomography screening is an effective way of reducing lung cancer (LC) mortality. However, optimal screening strategies have not been determined to date and it is uncertain whether lighter smokers than those examined in the NLST may also benefit from screening. To address these questions, it is necessary to first develop LC natural history models that can reproduce NLST outcomes and simulate screening programs at the population level. Five independent LC screening models were developed using common inputs and calibration targets derived from the NLST and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). Imputation of missing information regarding smoking, histology, and stage of disease for a small percentage of individuals and diagnosed LCs in both trials was performed. Models were calibrated to LC incidence, mortality, or both outcomes simultaneously. Initially, all models were calibrated to the NLST and validated against PLCO. Models were found to validate well against individuals in PLCO who would have been eligible for the NLST. However, all models required further calibration to PLCO to adequately capture LC outcomes in PLCO never-smokers and light smokers. Final versions of all models produced incidence and mortality outcomes in the presence and absence of screening that were consistent with both trials. The authors developed 5 distinct LC screening simulation models based on the evidence in the NLST and PLCO. The results of their analyses demonstrated that the NLST and PLCO have produced consistent results. The resulting models can be important tools to generate additional evidence to determine the effectiveness of lung cancer screening strategies using low-dose computed tomography. © 2014 American Cancer Society.

  18. 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

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

    Science.gov (United States)

    Ten Haaf, Kevin; Jeon, Jihyoun; Tammemägi, Martin C; Han, Summer S; Kong, Chung Yin; Plevritis, Sylvia K; Feuer, Eric J; de Koning, Harry J; Steyerberg, Ewout W; Meza, Rafael

    2017-04-01

    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 slightly

  20. 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...

  1. Impact of template choice on homology model efficiency in virtual screening.

    Science.gov (United States)

    Rataj, Krzysztof; Witek, Jagna; Mordalski, Stefan; Kosciolek, Tomasz; Bojarski, Andrzej J

    2014-06-23

    Homology modeling is a reliable method of predicting the three-dimensional structures of proteins that lack NMR or X-ray crystallographic data. It employs the assumption that a structural resemblance exists between closely related proteins. Despite the availability of many crystal structures of possible templates, only the closest ones are chosen for homology modeling purposes. To validate the aforementioned approach, we performed homology modeling of four serotonin receptors (5-HT1AR, 5-HT2AR, 5-HT6R, 5-HT7R) for virtual screening purposes, using 10 available G-Protein Coupled Receptors (GPCR) templates with diverse evolutionary distances to the targets, with various approaches to alignment construction and model building. The resulting models were further validated in two steps by means of ligand docking and enrichment calculation, using Glide software. The final quality of the models was determined in virtual screening-like experiments by the AUROC score of the resulting ROC curves. The outcome of this research showed that no correlation between sequence identity and model quality was found, leading to the conclusion that the closest phylogenetic relative is not always the best template for homology modeling.

  2. 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.

  3. Virtual Screening Models for Prediction of HIV-1 RT Associated RNase H Inhibition

    DEFF Research Database (Denmark)

    Poongavanam, Vasanthanathan; Kongsted, Jacob

    2013-01-01

    of choice in terms of best retrieval of active from inactive compounds and efficiency and efficacy schemes. Moreover, shape similarity, machine learning and FLAP models could also be used for further validation or filtration in virtual screening processes. The best models could potentially be use...... reverse transcriptase associated ribonuclease H (RNase H) function provides a novel target for anti-HIV chemotherapy. Here we report on the applicability of conceptually different in silico approaches as virtual screening (VS) tools in order to efficiently identify RNase H inhibitors from large chemical...... 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...

  4. Diagnostic performance and costs of contingent screening models for trisomy 21 incorporating non-invasive prenatal testing.

    Science.gov (United States)

    Maxwell, Susannah; O'Leary, Peter; Dickinson, Jan E; Suthers, Graeme K

    2017-08-01

    Contingent screening for trisomy 21 using non-invasive prenatal testing has the potential to reduce invasive diagnostic testing and increase the detection of trisomy 21. To describe the diagnostic and economic performance of prenatal screening models for trisomy 21 that use non-invasive prenatal testing as a contingent screen across a range of combined first trimester screening risk cut-offs from a public health system perspective. Using a hypothetical cohort of 300 000 pregnancies, we modelled the outcomes of 25 contingent non-invasive prenatal testing screening models and compared these to conventional screening, offering women with a high-risk (1 > 300) combined first trimester screening result an invasive test. The 25 models used a range of risk cut-offs. High-risk women were offered invasive testing. Intermediate-risk women were offered non-invasive prenatal testing. We report the cost of each model, detection rate, costs per diagnosis, invasive tests per diagnosis and the number of fetal losses per diagnosis. The cost per prenatal diagnosis of trisomy 21 using the conventional model was $51 876 compared to the contingent models which varied from $49 309-66 686. The number of diagnoses and cost per diagnosis increased as the intermediate-risk threshold was lowered. Results were sensitive to trisomy 21 incidence, uptake of testing and cost of non-invasive prenatal testing. Contingent non-invasive prenatal testing models using more sensitive combined first trimester screening risk cut-offs than conventional screening improved the detection rate of trisomy 21, reduced procedure-related fetal loss and could potentially be provided at a lower cost per diagnosis than conventional screening. © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  5. Homology model-based virtual screening for GPCR ligands using docking and target-biased scoring.

    Science.gov (United States)

    Radestock, Sebastian; Weil, Tanja; Renner, Steffen

    2008-05-01

    The current study investigates the combination of two recently reported techniques for the improvement of homology model-based virtual screening for G-protein coupled receptor (GPCR) ligands. First, ligand-supported homology modeling was used to generate receptor models that were in agreement with mutagenesis data and structure-activity relationship information of the ligands. Second, interaction patterns from known ligands to the receptor were applied for scoring and rank ordering compounds from a virtual library using ligand-receptor interaction fingerprint-based similarity (IFS). Our approach was evaluated in retrospective virtual screening experiments for antagonists of the metabotropic glutamate receptor (mGluR) subtype 5. The results of our approach were compared to the results obtained by conventional scoring functions (Dock-Score, PMF-Score, Gold-Score, ChemScore, and FlexX-Score). The IFS lead to significantly higher enrichment rates, relative to the competing scoring functions. Though using a target-biased scoring approach, the results were not biased toward the chemical classes of the reference structures. Our results indicate that the presented approach has the potential to serve as a general setup for successful structure-based GPCR virtual screening.

  6. Health Beliefs and Breast Cancer Screening in Rural Appalachia: An Evaluation of the Health Belief Model.

    Science.gov (United States)

    VanDyke, Santana D; Shell, Madelynn D

    2017-09-01

    This study explored the role of the Health Belief Model in predicting breast cancer screening among women in rural Appalachia. Health beliefs (perceived susceptibility to breast cancer, severity of breast cancer, and benefits and barriers to screening) were used to predict health behavior (mammogram frequency). A total of 170 women aged 18-78 were recruited at a free health clinic in central Appalachia. Women completed surveys that assessed demographic characteristics, mammogram frequency, and perceived susceptibility, severity, and benefits and barriers to mammography. Consistent with expectations, women with objectively elevated risks for breast cancer (history of abnormal mammograms or family history of breast cancer) perceived themselves to be at higher risk for breast cancer, and those with a history of abnormal mammograms were more likely to receive mammograms regularly. In addition, older women expected their prognosis to be marginally poorer following a diagnosis, perceived greater benefits and fewer barriers to mammography, and were significantly more likely to receive mammograms regularly. Consistent with the Health Belief Model, fewer perceived barriers to mammography predicted greater mammogram frequency. However, the model was not fully supported because perceived susceptibility, severity, and benefits to mammography did not predict mammogram frequency. Results highlight the importance of reducing real and perceived barriers to screening in order to improve mammography rates among rural populations. © 2016 National Rural Health Association.

  7. 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.

  8. Factors affecting breast cancer screening behavior in Japan--assessment using the health belief model and conjoint analysis.

    Science.gov (United States)

    Tsunematsu, Miwako; Kawasaki, Hiromi; Masuoka, Yuko; Kakehashi, Masayuki

    2013-01-01

    Japanese women in their 40s or older have been encouraged to attend breast cancer screening. However, the breast cancer screening rate in Japan is not as high as in Europe and the United States. The aim of this study was to identify psychological and personal characteristics of women concerning their participation in breast cancer screening using the Health Belief Model (HBM). In addition, the attributes of screening more easily accepted by participants were analyzed by conjoint analysis. In this cross sectional study of 3,200 age 20-69 women, data were collected by an anonymous questionnaire. Questions were based on HBM and personal characteristics, and included attitudes on hypothetical screening attributes. Data of women aged 40-69 were analyzed by logistic regression and conjoint analysis to clarify the factors affecting their participation in breast cancer screening. Among responses collected from 1,280 women of age 20-69, the replies of 993 women of age 40-69 were used in the analysis. Regarding the psychological characteristics based on HBM, the odds ratios were significantly higher in "importance of cancer screening" (95%CI: 1.21-2.47) and "benefits of cancer screening" (95%CI: 1.09-2.49), whereas the odds ratio was significantly lower in "barriers to participation before cancer screening" (95%CI: 0.27-0.51). Conjoint analysis revealed that the respondents, overall, preferred screening to be low cost and by female staff members. Furthermore, it was also clarified that attributes of screening dominant in decision-making were influenced by the employment status and the type of medical insurance of the women. In order to increase participation in breast cancer screening, it is necessary to disseminate accurate knowledge on cancer screening and to reduce barriers to participation. In addition, the attributes of screening more easily accepted were inexpensive, provided by female staff, executed in a hospital and finished in a short time.

  9. 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

  10. Influence of Screen-Based Peer Modeling on Preschool Children's Vegetable Consumption and Preferences.

    Science.gov (United States)

    Staiano, Amanda E; Marker, Arwen M; Frelier, Johannah M; Hsia, Daniel S; Martin, Corby K

    2016-05-01

    To determine the influence of screen-based peer modeling on children's vegetable consumption and preference. A total of 42 children aged 3-5 years were randomly assigned to view individually a video segment of peers consuming a modeled vegetable (bell pepper), vs a nonfood video segment or no video. Analysis of covariance models examined bell pepper preference and consumption during initial video exposure (day 1) and without video exposure (days 2 and 7), adjusted for age, sex, body mass index, and initial bell pepper consumption. Children in the vegetable condition ate more bell peppers (15.5 g) than did those in the control condition (5.9 g; P = .04; model η(2) = 0.85) on day 7, with no differences on days 1 or 2. Among children who ate the modeled vegetable, those in the vegetable DVD condition reported greater preference for eating the vegetable again (P = .01). Screen-based peer modeling is a promising tool to influence children's vegetable consumption. Copyright © 2016 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

  11. Gene expression profiling in a mouse model identifies fetal liver- and placenta-derived potential biomarkers for Down syndrome screening

    NARCIS (Netherlands)

    Pennings, J.L.A.; Rodenburg, W.; Imholz, S.; Koster, M.P.H.; van Oostrom, C.T.M.; Breit, T.M.; Schielen, P.C.J.I.; de Vries, A.

    2011-01-01

    Background: As a first step to identify novel potential biomarkers for prenatal Down Syndrome screening, we analyzed gene expression in embryos of wild type mice and the Down Syndrome model Ts1Cje. Since current Down Syndrome screening markers are derived from placenta and fetal liver, these tissues

  12. Uncertainty Quantification in High Throughput Screening: Applications to Models of Endocrine Disruption, Cytotoxicity, and Zebrafish Development (GRC Drug Safety)

    Science.gov (United States)

    Using uncertainty quantification, we aim to improve the quality of modeling data from high throughput screening assays for use in risk assessment. ToxCast is a large-scale screening program that analyzes thousands of chemicals using over 800 assays representing hundreds of bioche...

  13. 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

  14. Curating and Preparing High-Throughput Screening Data for Quantitative Structure-Activity Relationship Modeling.

    Science.gov (United States)

    Kim, Marlene T; Wang, Wenyi; Sedykh, Alexander; Zhu, Hao

    2016-01-01

    Publicly available bioassay data often contains errors. Curating massive bioassay data, especially high-throughput screening (HTS) data, for Quantitative Structure-Activity Relationship (QSAR) modeling requires the assistance of automated data curation tools. Using automated data curation tools are beneficial to users, especially ones without prior computer skills, because many platforms have been developed and optimized based on standardized requirements. As a result, the users do not need to extensively configure the curation tool prior to the application procedure. In this chapter, a freely available automatic tool to curate and prepare HTS data for QSAR modeling purposes will be described.

  15. Novel use of zebrafish as a vertebrate model to screen radiation protectors and sensitizers

    International Nuclear Information System (INIS)

    Purpose: Zebrafish (Danio rerio) embryos provide a unique vertebrate model to screen therapeutic agents easily and rapidly because of their relatively close genetic relationship to humans, ready abundance and accessibility, short embryonal development, and optical clarity. To validate zebrafish embryos as a screen for radiation modifiers, we evaluated the effects of ionizing radiation in combination with a known radioprotector (free radical scavenger Amifostine) or radiosensitizing agent (tyrosine kinase inhibitor AG1478). Methods and materials: Viable zebrafish embryos were exposed to 0-10 Gy single-fraction 250 kVp X-rays with or without either Amifostine (0-4 mM) or AG1478 (0-10 μM) at defined developmental stages from 1-24 h postfertilization (hpf). Embryos were examined for morphologic abnormalities and viability until 144 hpf. Results: Radiation alone produced a time- and dose-dependent perturbation of normal embryonic development and survival with maximal sensitivity at doses ≥4 Gy delivered before 4 hpf. Amifostine markedly attenuated this effect, whereas AG1478 enhanced teratogenicity and lethality, particularly at therapeutically relevant (2-6 Gy) radiation doses. Conclusions: Collectively, these data validate the use of zebrafish as a vertebrate model to assess the effect of radiation alone or with radiation response modulators. Zebrafish embryos may thus provide a rapid, facile system to screen novel agents ultimately intended for human use in the context of therapeutic or accidental radiation exposure

  16. A Markov Decision Process Model for Cervical Cancer Screening Policies in Colombia.

    Science.gov (United States)

    Akhavan-Tabatabaei, Raha; Sánchez, Diana Marcela; Yeung, Thomas G

    2017-02-01

    Cervical cancer is the second most common cancer in women around the world, and the human papillomavirus (HPV) is universally known as the necessary agent for developing this disease. Through early detection of abnormal cells and HPV virus types, cervical cancer incidents can be reduced and disease progression prevented. We propose a finite-horizon Markov decision process model to determine the optimal screening policies for cervical cancer prevention. The optimal decision is given in terms of when and what type of screening test to be performed on a patient based on her current diagnosis, age, HPV contraction risk, and screening test results. The cost function considers the tradeoff between the cost of prevention and treatment procedures and the risk of taking no action while taking into account a cost assigned to loss of life quality in each state. We apply the model to data collected from a representative sample of 1141 affiliates at a health care provider located in Bogotá, Colombia. To track the disease incidence more effectively and avoid higher cancer rates and future costs, the optimal policies recommend more frequent colposcopies and Pap tests for women with riskier profiles.

  17. Addressing the Global Zika Epidemic Locally: An Interprofessional Model of Universal Screening at One Center.

    Science.gov (United States)

    Forman, Rosha N; Mehta, Pooja K; Louis, Kettie R; Finneseth, Molly K; Yarrington, Christina D

    Escalating evidence for the fetal impact of Zika virus infection required a change in care by all prenatal providers. This article describes an effective model of rapid implementation of universal prenatal screening at one hospital and its network of community health centers for a large and diverse immigrant population exploring the challenges, experiences, and lessons learned. Implementation of national recommendations required a workflow change, challenging a system with a heterogeneity of settings and providers. Using a physician clinical champion and advanced practice nurses in the roles of logistical coordinator and liaison to the network, Zika screening was embedded into prenatal intake visits at both the hospital and community health centers. Challenges addressed include varied medical record systems, acceptance by patients, providers, and community health center leadership, as well as culturally appropriate outreach to diverse ethnic and linguistic communities. In 6 months, the prenatal screening rates increased from 20% to 88%, which resulted in the identification of more than 300 pregnant patients at risk of exposure to Zika virus. This model offers key lessons for emergency preparedness in heterogeneous, safety net hospital settings.

  18. 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.

  19. 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.)

  20. 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.

  1. 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

  2. Development of small scale cell culture models for screening poloxamer 188 lot-to-lot variation.

    Science.gov (United States)

    Peng, Haofan; Hall, Kaitlyn M; Clayton, Blake; Wiltberger, Kelly; Hu, Weiwei; Hughes, Erik; Kane, John; Ney, Rachel; Ryll, Thomas

    2014-01-01

    Shear protectants such as poloxamer 188 play a critical role in protecting cells during cell culture bioprocessing. Lot-to-lot variation of poloxamer 188 was experienced during a routine technology transfer across sites of similar scale and equipment. Cell culture medium containing a specific poloxamer 188 lot resulted in an unusual drop in cell growth, viability, and titer during manufacturing runs. After switching poloxamer lots, culture performance returned to the expected level. In order to control the quality of poloxamer 188 and thus maintain better consistency in manufacturing, multiple small scale screening models were developed. Initially, a 5L bioreactor model was established to evaluate cell damage by high sparge rates with different poloxamer 188 lots. Subsequently, a more robust, simple, and efficient baffled shake flask model was developed. The baffled shake flask model can be performed in a high throughput manner to investigate the cell damage in a bubbling environment. The main cause of the poor performance was the loss of protection, rather than toxicity. It was also suggested that suspicious lots can be identified using different cell line and media. The screening methods provide easy, yet remarkable models for understanding and controlling cell damage due to raw material lot variation as well as studying the interaction between poloxamer 188 and cells. © 2014 American Institute of Chemical Engineers.

  3. A sparse QSRR model for predicting retention indices of essential oils based on robust screening approach.

    Science.gov (United States)

    Al-Fakih, A M; Algamal, Z Y; Lee, M H; Aziz, M

    2017-08-01

    A robust screening approach and a sparse quantitative structure-retention relationship (QSRR) model for predicting retention indices (RIs) of 169 constituents of essential oils is proposed. The proposed approach is represented in two steps. First, dimension reduction was performed using the proposed modified robust sure independence screening (MR-SIS) method. Second, prediction of RIs was made using the proposed robust sparse QSRR with smoothly clipped absolute deviation (SCAD) penalty (RSQSRR). The RSQSRR model was internally and externally validated based on [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], Y-randomization test, [Formula: see text], [Formula: see text], and the applicability domain. The validation results indicate that the model is robust and not due to chance correlation. The descriptor selection and prediction performance of the RSQSRR for training dataset outperform the other two used modelling methods. The RSQSRR shows the highest [Formula: see text], [Formula: see text], and [Formula: see text], and the lowest [Formula: see text]. For the test dataset, the RSQSRR shows a high external validation value ([Formula: see text]), and a low value of [Formula: see text] compared with the other methods, indicating its higher predictive ability. In conclusion, the results reveal that the proposed RSQSRR is an efficient approach for modelling high dimensional QSRRs and the method is useful for the estimation of RIs of essential oils that have not been experimentally tested.

  4. Development of a receptor model for efficient in silico screening of HIV-1 integrase inhibitors.

    Science.gov (United States)

    Quevedo, Mario A; Ribone, Sergio R; Briñón, Margarita C; Dehaen, Wim

    2014-07-01

    Integrase (IN) is a key viral enzyme for the replication of the type-1 human immunodeficiency virus (HIV-1), and as such constitutes a relevant therapeutic target for the development of anti-HIV agents. However, the lack of crystallographic data of HIV IN complexed with the corresponding viral DNA has historically hindered the application of modern structure-based drug design techniques to the discovery of new potent IN inhibitors (INIs). Consequently, the development and validation of reliable HIV IN structural models that may be useful for the screening of large databases of chemical compounds is of particular interest. In this study, four HIV-1 IN homology models were evaluated respect to their capability to predict the inhibition potency of a training set comprising 36 previously reported INIs with IC50 values in the low nanomolar to the high micromolar range. Also, 9 inactive structurally related compounds were included in this training set. In addition, a crystallographic structure of the IN-DNA complex corresponding to the prototype foamy virus (PFV) was also evaluated as structural model for the screening of inhibitors. The applicability of high throughput screening techniques, such as blind and ligand-guided exhaustive rigid docking was assessed. The receptor models were also refined by molecular dynamics and clustering techniques to assess protein sidechain flexibility and solvent effect on inhibitor binding. Among the studied models, we conclude that the one derived from the X-ray structure of the PFV integrase exhibited the best performance to rank the potencies of the compounds in the training set, with the predictive power being further improved by explicitly modeling five water molecules within the catalytic side of IN. Also, accounting for protein sidechain flexibility enhanced the prediction of inhibition potencies among the studied compounds. Finally, an interaction fingerprint pattern was established for the fast identification of potent IN

  5. An alternative screening model for the estimation of outdoor air concentration at large contaminated sites

    Science.gov (United States)

    Verginelli, Iason; Nocentini, Massimo; Baciocchi, Renato

    2017-09-01

    Simplified analytical solutions of fate and transport models are often used to carry out risk assessment on contaminated sites, to evaluate the long-term air quality in relation to volatile organic compounds in either soil or groundwater. Among the different assumptions employed to develop these solutions, in this work we focus on those used in the ASTM-RBCA ;box model; for the evaluation of contaminant dispersion in the atmosphere. In this simple model, it is assumed that the contaminant volatilized from the subsurface is dispersed in the atmosphere within a mixing height equal to two meters, i.e. the height of the breathing zone. In certain cases, this simplification could lead to an overestimation of the outdoor air concentration at the point of exposure. In this paper we first discuss the maximum source lengths (in the wind direction) for which the application of the ;box model; can be considered acceptable. Specifically, by comparing the results of ;box model; with the SCREEN3 model of U.S.EPA we found that under very stable atmospheric conditions (class F) the ASTM-RBCA approach provides acceptable results for source lengths up to 200 m while for very unstable atmospheric conditions (class A and B) the overestimation of the concentrations at the point of the exposure can be already observed for source lengths of only 10 m. In the latter case, the overestimation of the ;box model; can be of more than one order of magnitude for source lengths above 500 m. To overcome this limitation, in this paper we introduce a simple analytical solution that can be used for the calculation of the concentration at the point of exposure for large contaminated sites. The method consists in the introduction of an equivalent mixing zone height that allows to account for the dispersion of the contaminants along the source length while keeping the simplistic ;box model; approach that is implemented in most of risk assessment tools that are based on the ASTM-RBCA standard (e.g. RBCA

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

    International Nuclear Information System (INIS)

    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

  7. Ligand Based Pharmacophore Modeling and Virtual Screening Studies to Design Novel HDAC2 Inhibitors

    Directory of Open Access Journals (Sweden)

    Naresh Kandakatla

    2014-01-01

    Full Text Available Histone deacetylases 2 (HDAC2, Class I histone deacetylase (HDAC family, emerged as an important therapeutic target for the treatment of various cancers. A total of 48 inhibitors of two different chemotypes were used to generate pharmacophore model using 3D QSAR pharmacophore generation (HypoGen algorithm module in Discovery Studio. The best HypoGen model consists of four pharmacophore features namely, one hydrogen bond acceptor (HBA, and one hydrogen donor (HBD, one hydrophobic (HYP and one aromatic centres, (RA. This model was validated against 20 test set compounds and this model was utilized as a 3D query for virtual screening to validate against NCI and Maybridge database and the hits further screened by Lipinski’s rule of 5, and a total of 382 hit compounds from NCI and 243 hit compounds from Maybridge were found and were subjected to molecular docking in the active site of HDAC2 (PDB: 3MAX. Finally eight hit compounds, NSC108392, NSC127064, NSC110782, and NSC748337 from NCI database and MFCD01935795, MFCD00830779, MFCD00661790, and MFCD00124221 from Maybridge database, were considered as novel potential HDAC2 inhibitors.

  8. 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.

  9. The transtheoretical model, health belief model, and breast cancer screening among Iranian women with a family history of breast cancer.

    Science.gov (United States)

    Farajzadegan, Ziba; Fathollahi-Dehkordi, Fariba; Hematti, Simin; Sirous, Reza; Tavakoli, Neda; Rouzbahani, Reza

    2016-01-01

    Participation of Iranian women with a family history of breast cancer in breast cancer screening programs is low. This study evaluates the compliance of women having a family history of breast cancer with clinical breast exam (CBE) according to the stage of transtheoretical model (TTM) and health belief model (HBM). In this cross-sectional study, we used Persian version of champion's HBM scale to collect factors associated with TTM stages applied to screening from women over 20 years and older. The obtained data were analyzed by SPSS, using descriptive statistics, Chi-square test, independent t -test, and analysis of covariance. Final sample size was 162 women. Thirty-three percent were in action/maintenance stage. Older women, family history of breast cancer in first-degree relatives, personal history of breast disease, insurance coverage, and a history of breast self-examination were associated with action/maintenance stage. Furthermore, women in action/maintenance stages had significantly fewer perceived barriers in terms of CBE in comparison to women in other stages ( P 0.05). The finding indicates that the rate of women in action/maintenance stage of CBE is low. Moreover, results show a strong association between perceived barriers and having a regular CBE. These clarify the necessity of promoting national target programs for breast cancer screening, which should be considered as the first preference for reducing CBE barriers.

  10. 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.

  11. Microglia-Based Phenotypic Screening Identifies a Novel Inhibitor of Neuroinflammation Effective in Alzheimer's Disease Models.

    Science.gov (United States)

    Zhou, Wei; Zhong, Guifa; Fu, Sihai; Xie, Hui; Chi, Tianyan; Li, Luyi; Rao, Xiurong; Zeng, Shaogao; Xu, Dengfeng; Wang, Hao; Sheng, Guoqing; Ji, Xing; Liu, Xiaorong; Ji, Xuefei; Wu, Donghai; Zou, Libo; Tortorella, Micky; Zhang, Kejian; Hu, Wenhui

    2016-11-16

    Currently, anti-AD drug discovery using target-based approaches is extremely challenging due to unclear etiology of AD and absence of validated therapeutic protein targets. Neuronal death, regardless of causes, plays a key role in AD progression, and it is directly linked to neuroinflammation. Meanwhile, phenotypic screening is making a resurgence in drug discovery process as an alternative to target-focused approaches. Herein, we employed microglia-based phenotypic screenings to search for small molecules that modulate the release of detrimental proinflammatory cytokines. The identified novel pharmacological inhibitor of neuroinflammation (named GIBH-130) was validated to alter phenotypes of neuroinflammation in AD brains. Notably, this molecule exhibited comparable in vivo efficacy of cognitive impairment relief to donepezil and memantine respectively in both β amyloid-induced and APP/PS1 double transgenic Alzheimer's murine models at a substantially lower dose (0.25 mg/kg). Therefore, GIBH-130 constitutes a unique chemical probe for pathogenesis research and drug development of AD, and it also suggests microglia-based phenotypic screenings that target neuroinflammation as an effective and feasible strategy to identify novel anti-AD agents.

  12. 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

  13. Survey of breast cancer mammography screening behaviors in Eastern Taiwan based on a health belief model

    Directory of Open Access Journals (Sweden)

    Wen-Li Wang

    2014-08-01

    Full Text Available Breast cancer is the main form of cancer affecting women and the fourth most common cause of cancer mortality in women. The aim of this study was to explore regular mammography screening in Hualien women and to identify the factors that influence its uptake based on a health belief model. This cross-sectional study was performed between July 2012 and December 2012. A total of 776 women aged 45–69 years were enrolled in the study. The results of crude and adjusted analyses showed that there were significant differences in the prevalence of regular mammography screening, which were related to different age groups, residence areas, educational levels, hormone replacement therapy status, and history of breast cancer. Women in the older age groups, with a higher educational level, in receipt of hormone replacement therapy, and with a personal history of breast cancer had significantly higher odds ratios for regular mammography screening (2.75, 1.68, 1.75, and 1.98, respectively; all p < 0.05.

  14. Screening, brief intervention and referral to treatment (SBIRT): implementation barriers, facilitators and model migration.

    Science.gov (United States)

    Vendetti, Janice; Gmyrek, Amanda; Damon, Donna; Singh, Manu; McRee, Bonnie; Del Boca, Frances

    2017-02-01

    To identify barriers and facilitators associated with initial implementation of a US alcohol and other substance use Screening, Brief Intervention, and Referral to Treatment (SBIRT) grant program, and to identify modifications in program design that addressed implementation challenges. A mixed-method approach used quantitative and qualitative data, including SBIRT provider ratings of implementation barriers and facilitators, staff interview responses and program documentation. Multiple sites within the first seven programs funded in a national demonstration program in the United States. One hundred and two SBIRT providers were surveyed; 221 SBIRT stakeholders and staff were interviewed. Mean ratings of barriers and facilitators were calculated using provider survey responses. An inductive content analysis of interview responses identified factors perceived to support and challenge implementation; program modifications that occurred over time were recorded. Providers rated pre-selected implementation facilitators higher than barriers. Content analysis of interview responses revealed six themes: committed leaders; intra- and inter-organizational communication/collaboration; provider buy-in and model acceptance; contextual factors; quality assurance; and grant requirements. Over time, programs tended to: adopt more efficient 'pre-screen' item sets; screen for risk factors in addition to alcohol/substance use; use contracted specialists to deliver SBIRT services; conduct services in high-volume emergency department and trauma center settings; and implement on-site and telephonic treatment delivery. Screening, Brief Intervention and Referral to Treatment program implementation in the United States is facilitated by committed leadership and the use of substance use specialists, rather than medical generalists, to deliver services. Many implementation challenges can be addressed by an adequate start-up phase focused on comprehensive education and training, and on the

  15. Ionic screening of charged impurities in electrolytically gated graphene: A partially linearized Poisson-Boltzmann model.

    Science.gov (United States)

    Sharma, P; Mišković, Z L

    2015-10-07

    We present a model describing the electrostatic interactions across a structure that consists of a single layer of graphene with large area, lying above an oxide substrate of finite thickness, with its surface exposed to a thick layer of liquid electrolyte containing salt ions. Our goal is to analyze the co-operative screening of the potential fluctuation in a doped graphene due to randomness in the positions of fixed charged impurities in the oxide by the charge carriers in graphene and by the mobile ions in the diffuse layer of the electrolyte. In order to account for a possibly large potential drop in the diffuse later that may arise in an electrolytically gated graphene, we use a partially linearized Poisson-Boltzmann (PB) model of the electrolyte, in which we solve a fully nonlinear PB equation for the surface average of the potential in one dimension, whereas the lateral fluctuations of the potential in graphene are tackled by linearizing the PB equation about the average potential. In this way, we are able to describe the regime of equilibrium doping of graphene to large densities for arbitrary values of the ion concentration without restrictions to the potential drop in the electrolyte. We evaluate the electrostatic Green's function for the partially linearized PB model, which is used to express the screening contributions of the graphene layer and the nearby electrolyte by means of an effective dielectric function. We find that, while the screened potential of a single charged impurity at large in-graphene distances exhibits a strong dependence on the ion concentration in the electrolyte and on the doping density in graphene, in the case of a spatially correlated two-dimensional ensemble of impurities, this dependence is largely suppressed in the autocovariance of the fluctuating potential.

  16. A model for screening and prioritizing consumer nanoproduct risks: A case study from South Africa.

    Science.gov (United States)

    Musee, Ndeke

    2017-03-01

    The potential risks of the increasing variety and volume of engineered nanomaterials (ENMs) entering into the ecosystem remain poorly quantified. In recent years, information essential to evaluate the ecological risks of ENMs has increased. However, the data are highly fragmented, limited, or severely lacking. This limits the usefulness of the information to support holistic screening and prioritization of potentially harmful ENMs. To screen and prioritize ENMs risks, we adopted a two-phased approach. First, a holistic framework model was developed to integrate a diverse set of factors aimed to assess the potential hazard, exposure, and in turn, risk to the ecosystem of ENMs from a given consumer nanoproduct. Secondly, using published literature we created a database of consumer nanoproduct categories, and types based on embedded ENMs type. The database consisted of eight consumer product categories, eleven different types of ENMs, and twenty-three nanoproduct types. The model results indicates the largest quantities of ENMs were released from sunscreens, textiles, cosmetics and paints with dominant ENMs quantities in descending order (based on quantity) as nTiO 2 >nZnO>nSiO 2 >nAg, and nFe 2 O 3 . In addition, according to the results from this study, nAg from washing machine were found to likely the highest risk to the environment. Overall, our model-derived results based on the case study illustrated: (i) the holistic framework's ability to screen, prioritize, rank, and compare ENMs potential exposure and risks among different nanoproducts categories and types, (ii) the derived risk estimations could support nanowastes classification with likelihood of non-uniformity of nanowastes classes even from the same nanoproduct category (e.g. cosmetics), and (iii) the lack of a mass-based criteria specific for EMNs impedes realistic exposure and risk evaluation in the ecological systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Effect of HPV vaccination and cervical cancer screening in England by ethnicity: a modelling study.

    Science.gov (United States)

    Johnson, Helen C; Lafferty, Erin I; Eggo, Rosalind M; Louie, Karly; Soldan, Kate; Waller, Jo; Edmunds, W John

    2018-01-01

    Health equality is increasingly being considered alongside overall health gain when assessing public health interventions. However, the trade-off between the direct effects of vaccination and herd immunity could lead to unintuitive consequences for the distribution of disease burden within a population. We used a transmission dynamic model of human papillomavirus (HPV) to investigate the effect of ethnic disparities in vaccine and cervical screening uptake on inequality in disease incidence in England. We developed an individual-based model of HPV transmission and disease, parameterising it with the latest data for sexual behaviour (from National Survey of Sexual Attitudes and Lifestyles [Natsal-3]) and vaccine and screening uptake by ethnicity (from Public Health England [PHE]) and fitting it to data for HPV prevalence (from ARTISTIC, PHE, Natsal-3) and HPV-related disease incidence (from National Cancer Registry [ONS]). The outcome of interest was the age-adjusted incidence of HPV-related cancer (both cervical and non-cervical) in all women in England in view of differences and changes in vaccination and screening uptake by ethnicity in England, over time. We also studied three potential public health interventions aimed at reducing inequality in HPV-related disease incidence: increasing uptake in black and Asian females to match that in whites for vaccination; cervical screening in women who turn 25 in 2018 or later; and cervical screening in all ages. In the pre-vaccination era, before 2008, women from ethnic minorities in England reported a disproportionate share of cervical disease. Our model suggests that Asian women were 1·7 times (95% credibility interval [CI] 1·1-2·7) more likely to be diagnosed with cervical cancer than white women (22·8 vs 13·4 cases per 100 000 women). Because HPV vaccination uptake is lower in ethnic minorities, we predict an initial widening of this gap, with cervical cancer incidence in Asian women up to 2·5 times higher (95

  18. 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

  19. Uncle Tony's computer: order-of-magnitude modelling as a screening tool in environmental analysis

    CSIR Research Space (South Africa)

    Scholes, RJ

    2002-09-01

    Full Text Available : order-of-magnitude modelling as a screening tool in environmental analysis R.J. Scholes Introduction When Tony Starfield took up his position at the University of Minnesota, he wanted to stay in contact with his young nephews in South Africa... study. The method assumes a good, but not highly quantitative, knowledge of the system, and does not apply to cumulative effects. *CSIR Environmentek, P.O. Box 395, Pretoria 0001, South Africa. E-mail: bscholes@csir.co.za. production sources or loss...

  20. Experimental validation of a phase screen propagation model for nanosecond laser pulses travelling through turbulent atmospheres

    Science.gov (United States)

    Burgess, Christopher; Westgate, Christopher

    2017-10-01

    Applications involving the outdoor use of pulsed lasers systems can be affected by atmospheric turbulence and scintillation. In particular, deterministic prediction of the risk of injury or damage due to pulsed laser radiation can be difficult due to uncertainty over the focal plane fluence of radiation that has traversed through a turbulent medium. In this study, focussed beam profiles of nanosecond laser pulses are recorded for visible laser pulses that have traversed 1400m paths through turbulent atmospheres. Beam profiles are also taken under laboratory conditions. These pulses are characterised in terms of their peak focal plane fluence, total collected energy and Strehl ratio. Measured pulses are then compared statistically to pulse profiles generated by a two-dimensional phase screen propagation model based on the Von Karman power spectrum distribution. The model takes into account the refractive index structure constant (𝐶𝑛2), the wavelength, the path geometry and macroscopic beam steering. Analysis shows good correlation between the measured and simulated data, inferring that the Von Karman phase screen model can be used to predict focal plane fluence distributions for outdoor applications.

  1. 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

  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

    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...... developed two global quantitative structure-activity relationship (QSAR) models for TPO inhibition in vitro. Rigorous cross- and blinded external validations demonstrated that the first model, QSAR1, built from a training set of 877 chemicals, was robust and highly predictive with balanced accuracies of 80......Thyroperoxidase (TPO) is the enzyme that synthesizes thyroid hormones (THs). TPO inhibition by chemicals can result in decreased TH levels and developmental neurotoxicity, and therefore identification of TPO inhibition is of high relevance in safety evaluation of chemicals. In the present study, we...

  3. 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.

  4. Combination of Biological Screening in a Cellular Model of Viral Latency and Virtual Screening Identifies Novel Compounds That Reactivate HIV-1

    Science.gov (United States)

    Gallastegui, Edurne; Marshall, Brett; Vidal, David; Sanchez-Duffhues, Gonzalo; Collado, Juan A.; Alvarez-Fernández, Carmen; Luque, Neus; Terme, Jean-Michel; Gatell, Josep M.; Sánchez-Palomino, Sonsoles; Muñoz, Eduardo; Mestres, Jordi; Verdin, Eric

    2012-01-01

    Although highly active antiretroviral therapy (HAART) has converted HIV into a chronic disease, a reservoir of HIV latently infected resting T cells prevents the eradication of the virus from patients. To achieve eradication, HAART must be combined with drugs that reactivate the dormant viruses. We examined this problem in an established model of HIV postintegration latency by screening a library of small molecules. Initially, we identified eight molecules that reactivated latent HIV. Using them as templates, additional hits were identified by means of similarity-based virtual screening. One of those hits, 8-methoxy-6-methylquinolin-4-ol (MMQO), proved to be useful to reactivate HIV-1 in different cellular models, especially in combination with other known reactivating agents, without causing T-cell activation and with lower toxicity than that of the initial hits. Interestingly, we have established that MMQO produces Jun N-terminal protein kinase (JNK) activation and enhances the T-cell receptor (TCR)/CD3 stimulation of HIV-1 reactivation from latency but inhibits CD3-induced interleukin-2 (IL-2) and tumor necrosis factor alpha (TNF-α) gene transcription. Moreover, MMQO prevents TCR-induced cell cycle progression and proliferation in primary T cells. The present study documents that the combination of biological screening in a cellular model of viral latency with virtual screening is useful for the identification of novel agents able to reactivate HIV-1. Moreover, we set the bases for a hypothetical therapy to reactivate latent HIV by combining MMQO with physiological or pharmacological TCR/CD3 stimulation. PMID:22258251

  5. 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

  6. A Screening-Level Hydroeconomic Model of South Florida Water Resources System

    Science.gov (United States)

    Mirchi, A.; Watkins, D. W., Jr.; Flaxman, M.; Wiesmann, D.

    2014-12-01

    South Florida's water resources management is characterized by system-wide tradeoffs associated with maintaining the ecological integrity of natural environments such as the Everglades while meeting the water demands of the agricultural sector and growing urban areas. As these tradeoffs become more pronounced due to pressures from climate change, sea level rise, and population growth, it will be increasingly challenging for policy makers and stakeholders to reach consensus on water resources management objectives and planning horizons. A hydroeconomic optimization model of south Florida's water resources system is developed to incorporate the value of water for preserving ecosystem services alongside water supplies to the Everglades Agricultural Area and urban areas. Results of this screening-level network flow model facilitate quantitative analysis and provide insights for long-term adaptive management strategies for the region's water resources.

  7. A Screening Model to Predict Microalgae Biomass Growth in Photobioreactors and Raceway Ponds

    Energy Technology Data Exchange (ETDEWEB)

    Huesemann, Michael H.; Van Wagenen, Jonathan M.; Miller, Tyler W.; Chavis, Aaron R.; Hobbs, Watts B.; Crowe, Braden J.

    2013-06-01

    A microalgae biomass growth model was developed for screening novel strains for their potential to exhibit high biomass productivities under nutrient-replete conditions in photobioreactors or outdoor ponds. Growth is modeled by first estimating the light attenuation by biomass according to Beer-Lambert’s law, and then calculating the specific growth rate in discretized culture volume slices that receive declining light intensities due to attenuation. The model requires only two physical and two species-specific biological input parameters, all of which are relatively easy to determine: incident light intensity, culture depth, as well as the biomass light absorption coefficient and the specific growth rate as a function of light intensity. Roux bottle culture experiments were performed with Nannochloropsis salina at constant temperature (23 °C) at six different incident light intensities (5, 10, 25, 50, 100, 250, and 850 μmol/m2∙ sec) to determine both the specific growth rate under non-shading conditions and the biomass light absorption coefficient as a function of light intensity. The model was successful in predicting the biomass growth rate in these Roux bottle cultures during the light-limited linear phase at different incident light intensities. Model predictions were moderately sensitive to minor variations in the values of input parameters. The model was also successful in predicting the growth performance of Chlorella sp. cultured in LED-lighted 800 L raceway ponds operated at constant temperature (30 °C) and constant light intensity (1650 μmol/m2∙ sec). Measurements of oxygen concentrations as a function of time demonstrated that following exposure to darkness, it takes at least 5 seconds for cells to initiate dark respiration. As a result, biomass loss due to dark respiration in the aphotic zone of a culture is unlikely to occur in highly mixed small-scale photobioreactors where cells move rapidly in and out of the light. By contrast, as

  8. A screening model to predict microalgae biomass growth in photobioreactors and raceway ponds.

    Science.gov (United States)

    Huesemann, M H; Van Wagenen, J; Miller, T; Chavis, A; Hobbs, S; Crowe, B

    2013-06-01

    A microalgae biomass growth model was developed for screening novel strains for their potential to exhibit high biomass productivities under nutrient-replete conditions in photobioreactors or outdoor ponds. Growth is modeled by first estimating the light attenuation by biomass according to Beer-Lambert's Law, and then calculating the specific growth rate in discretized culture volume slices that receive declining light intensities due to attenuation. The model uses only two physical and two species-specific biological input parameters, all of which are relatively easy to determine: incident light intensity, culture depth, as well as the biomass light absorption coefficient and the specific growth rate as a function of light intensity. Roux bottle culture experiments were performed with Nannochloropsis salina at constant temperature (23°C) at six different incident light intensities (10, 25, 50, 100, 250, and 850 µmol/m(2)  s) to determine both the specific growth rate under non-shading conditions and the biomass light absorption coefficient as a function of light intensity. The model was successful in predicting the biomass growth rate in these Roux bottle batch cultures during the light-limited linear phase at different incident light intensities. Model predictions were moderately sensitive to minor variations in the values of input parameters. The model was also successful in predicting the growth performance of Chlorella sp. cultured in LED-lighted 800 L raceway ponds operated in batch mode at constant temperature (30°C) and constant light intensity (1,650 µmol/m(2)  s). Measurements of oxygen concentrations as a function of time demonstrated that following exposure to darkness, it takes at least 5 s for cells to initiate dark respiration. As a result, biomass loss due to dark respiration in the aphotic zone of a culture is unlikely to occur in highly mixed small-scale photobioreactors where cells move rapidly in and out of the light. By contrast

  9. 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

  10. 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

  11. 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

  12. In silico screening of estrogen-like chemicals based on different nonlinear classification models.

    Science.gov (United States)

    Liu, Huanxiang; Papa, Ester; Walker, John D; Gramatica, Paola

    2007-07-01

    Increasing concern is being shown by the scientific community, government regulators, and the public about endocrine-disrupting chemicals that are adversely affecting human and wildlife health through a variety of mechanisms. There is a great need for an effective means of rapidly assessing endocrine-disrupting activity, especially estrogen-simulating activity, because of the large number of such chemicals in the environment. In this study, quantitative structure activity relationship (QSAR) models were developed to quickly and effectively identify possible estrogen-like chemicals based on 232 structurally-diverse chemicals (training set) by using several nonlinear classification methodologies (least-square support vector machine (LS-SVM), counter-propagation artificial neural network (CP-ANN), and k nearest neighbour (kNN)) based on molecular structural descriptors. The models were externally validated by 87 chemicals (prediction set) not included in the training set. All three methods can give satisfactory prediction results both for training and prediction sets, and the most accurate model was obtained by the LS-SVM approach through the comparison of performance. In addition, our model was also applied to about 58,000 discrete organic chemicals; about 76% were predicted not to bind to Estrogen Receptor. The obtained results indicate that the proposed QSAR models are robust, widely applicable and could provide a feasible and practical tool for the rapid screening of potential estrogens.

  13. Construction of protein profile classification model and screening of proteomic signature of acute leukemia.

    Science.gov (United States)

    Xu, Yun; Zhuo, Jiacai; Duan, Yonggang; Shi, Benhang; Chen, Xuhong; Zhang, Xiaoli; Xiao, Liang; Lou, Jin; Huang, Ruihong; Zhang, Qiongli; Du, Xin; Li, Ming; Wang, Daping; Shi, Dunyun

    2014-01-01

    The French-American-British (FAB) and WHO classifications provide important guidelines for the diagnosis, treatment, and prognostic prediction of acute leukemia, but are incapable of accurately differentiating all subtypes, and not well correlated with the clinical outcomes. In this study, we performed the protein profiling of the bone marrow mononuclear cells from the patients with acute leukemia and the health volunteers (control) by surface enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI_TOF_MS). The patients with acute leukemia were analyzed as unitary by the profiling that were grouped into acute promyelocytic leukemia (APL), acute myeloid leukemia-granulocytic (AML-Gran), acute myeloid leukemia-monocytic (AML-Mon) acute lymphocytic leukemia (ALL), and control. Based on 109 proteomic signatures, the classification models of acute leukemia were constructed to screen the predictors by the improvement of the proteomic signatures and to detect their expression characteristics. According to the improvement and the expression characteristics of the predictors, the proteomic signatures (M3829, M1593, M2121, M2536, M1016) characterized successively each group (CON, APL, AML-Gra, AML-Mon, ALL) were screened as target molecules for identification. Meanwhile, the proteomic-based class of determinant samples could be made by the classification models. The credibility of the proteomic-based classification passed the evaluation of Biomarker Patterns Software 5.0 (BPS 5.0) scoring and validated application in clinical practice. The results suggested that the proteomic signatures characterized by different blasts were potential for developing new treatment and monitoring approaches of leukemia blasts. Moreover, the classification model was potential in serving as new diagnose approach of leukemia.

  14. Role of charge screening and delocalization for lipophilic cation permeability of model and mitochondrial membranes.

    Science.gov (United States)

    Trendeleva, Tatiana A; Sukhanova, Evgenia I; Rogov, Anton G; Zvyagilskaya, Renata A; Seveina, Inna I; Ilyasova, Tatiana M; Cherepanov, Dmitry A; Skulachev, Vladimir P

    2013-09-01

    The effects of the mitochondria-targeted lipophilic cation dodecyltriphenylphosphonium (C12TPP, the charge is delocalized and screened by bulky hydrophobic residues) and those of lipophilic cations decyltriethylammonium bromide and cetyltrimethylammonium bromide (C10TEA and C16TMA, the charges are localized and screened by less bulky residues) on bilayer planar phospholipid membranes and tightly-coupled mitochondria from the yeast Yarrowia lipolytica have been compared. In planar membranes, C12TPP was found to generate a diffusion potential as if it easily penetrates these membranes. In the presence of palmitate, C12TPP induced H(+) permeability like plastoquinonyl decyltriphenilphosphonium that facilitates transfer of fatty acid anions (Severin et al., PNAS, 2010, 107, 663-668). C12TPP was shown to stimulate State 4 respiration of mitochondria and caused a mitochondrial membrane depolarization with a half-maximal effect at 6μM. Besides, C12TPP profoundly potentiated the uncoupling effect of endogenous or added fatty acids. C10TEA and C16TMA inhibited State 4 respiration and decreased the membrane potential, though at much higher concentrations than C12TPP, and they did not promote the uncoupling action of fatty acids. These relationships were modeled by molecular dynamics. They can be explained by different membrane permeabilities for studied cations, which in turn are due to different availabilities of the positive charge in these cations to water dipoles. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. 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.

  16. 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.

  17. 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

    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...

  18. Local health departments implement a theory-based model to increase breast and cervical cancer screening.

    Science.gov (United States)

    Suarez, L; Nichols, D C; Pulley, L; Brady, C A; McAlister, A

    1993-01-01

    Su Vida, Su Salud/Your Life, Your Health is a community program to increase participation in breast and cervical cancer screening. This program illustrates the diffusion of an innovative outreach strategy from a research environment to two local health departments. The program uses A Su Salud, the communication model in which positive role models are featured in the media, and community volunteers who give positive social reinforcement. Local health departments in Galveston and Corpus Christi, TX, were selected to implement the model because of excessive mortality rates in the region and the departments' adequate level of resources and commitment. Over an 18-month period, 54 stories of role models appeared in the media in Corpus Christi, and 60 appeared in Galveston. There were 490 volunteers active in Corpus Christi and 279 in Galveston. Of 365 inquiries to the Corpus Christi program, 35 percent were from the Mexican American target group of women ages 40-70. Of 1,457 women who contacted the Galveston program, 9 percent were from the African American target group ages 40-70. Local health departments are well-suited to participation in cancer control research applications because they have direct access to high-risk populations and have the authority to institutionalize effective interventions.

  19. Screening of persistent organic pollutants by QSPR classification models: a comparative study.

    Science.gov (United States)

    Papa, Ester; Gramatica, Paola

    2008-08-01

    A Quantitative Structure-Property Relationships (QSPRs) study for the prediction of the environmental persistence of a set of 250 heterogeneous organic compounds is here presented. Three a priori defined classes of environmental persistence were generated, by Hierarchical Cluster Analysis, from the combination of half-life data in air, water, soil and sediment available for all the studied compounds. QSPR classification models were successfully developed using different techniques (k-NN, CART and CP-ANN) and three interpretable theoretical molecular descriptors. Robust external validation was provided by statistical splitting and also on completely new data. The good performances of all these models were compared and their structural domains were analyzed. The analysis of the errors highlights a slight tendency of persistence overestimation, misclassifying chemicals from a lower to a higher class of persistence, in line with the precautionary principle. Finally, the reliability of the proposed QSPR models was verified further with new data from the literature. The structure-based classification models, applicable for the prediction of potential persistence of heterogeneous organic compounds, could be useful as preliminary support tools for the identification and prioritization of new potential POPs among already existing chemicals as well as "screening prior to synthesis" procedures to avoid the production, and consequent release into the environment, of new POPs.

  20. QSAR classification models for the screening of the endocrine-disrupting activity of perfluorinated compounds.

    Science.gov (United States)

    Kovarich, S; Papa, E; Li, J; Gramatica, P

    2012-01-01

    Perfluorinated compounds (PFCs) are a class of emerging pollutants still widely used in different materials as non-adhesives, waterproof fabrics, fire-fighting foams, etc. Their toxic effects include potential for endocrine-disrupting activity, but the amount of experimental data available for these pollutants is limited. The use of predictive strategies such as quantitative structure-activity relationships (QSARs) is recommended under the REACH regulation, to fill data gaps and to screen and prioritize chemicals for further experimentation, with a consequent reduction of costs and number of tested animals. In this study, local classification models for PFCs were developed to predict their T4-TTR (thyroxin-transthyretin) competing potency. The best models were selected by maximizing the sensitivity and external predictive ability. These models, characterized by robustness, good predictive power and a defined applicability domain, were applied to predict the activity of 33 other PFCs of environmental concern. Finally, classification models recently published by our research group for T4-TTR binding of brominated flame retardants and for estrogenic and anti-androgenic activity were applied to the studied perfluorinated chemicals to compare results and to further evaluate the potential for these PFCs to cause endocrine disruption.

  1. 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.

  2. Robust ridge regression estimators for nonlinear models with applications to high throughput screening assay data.

    Science.gov (United States)

    Lim, Changwon

    2015-03-30

    Nonlinear regression is often used to evaluate the toxicity of a chemical or a drug by fitting data from a dose-response study. Toxicologists and pharmacologists may draw a conclusion about whether a chemical is toxic by testing the significance of the estimated parameters. However, sometimes the null hypothesis cannot be rejected even though the fit is quite good. One possible reason for such cases is that the estimated standard errors of the parameter estimates are extremely large. In this paper, we propose robust ridge regression estimation procedures for nonlinear models to solve this problem. The asymptotic properties of the proposed estimators are investigated; in particular, their mean squared errors are derived. The performances of the proposed estimators are compared with several standard estimators using simulation studies. The proposed methodology is also illustrated using high throughput screening assay data obtained from the National Toxicology Program. Copyright © 2014 John Wiley & Sons, Ltd.

  3. 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

  4. Target discovery screens using pooled shRNA libraries and next-generation sequencing: A model workflow and analytical algorithm.

    Directory of Open Access Journals (Sweden)

    Christiane Schaefer

    Full Text Available In the search for novel therapeutic targets, RNA interference screening has become a valuable tool. High-throughput technologies are now broadly accessible but their assay development from baseline remains resource-intensive and challenging. Focusing on this assay development process, we here describe a target discovery screen using pooled shRNA libraries and next-generation sequencing (NGS deconvolution in a cell line model of Ewing sarcoma. In a strategy designed for comparative and synthetic lethal studies, we screened for targets specific to the A673 Ewing sarcoma cell line. Methods, results and pitfalls are described for the entire multi-step screening procedure, from lentiviral shRNA delivery to bioinformatics analysis, illustrating a complete model workflow. We demonstrate that successful studies are feasible from the first assay performance and independent of specialized screening units. Furthermore, we show that a resource-saving screen depth of 100-fold average shRNA representation can suffice to generate reproducible target hits despite heterogeneity in the derived datasets. Because statistical analysis methods are debatable for such datasets, we created ProFED, an analysis package designed to facilitate descriptive data analysis and hit calling using an aim-oriented profile filtering approach. In its versatile design, this open-source online tool provides fast and easy analysis of shRNA and other count-based datasets to complement other analytical algorithms.

  5. 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

  6. 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).

  7. [Model concept of the health economic evaluation of low-dose CT lung cancer screening in Hungary].

    Science.gov (United States)

    Vokó, Zoltán; Barra, Magdolna; Molnár, Anett; Kerpel-Fronius, Anna; Bajzik, Gábor; Horváth, Ildikó; Moizs, Mariann; Nagy, Balázs

    2017-06-01

    Lung cancer is a rapidly progressing, often life-threatening disease that constitutes a huge societal burden. Because of the scarce resources of the Hungarian health care system, the cost-effectiveness of introducing low-dose computed tomography screening is a relevant health policy matter. The aim of this study is to design a model concept for assessing the cost-effectiveness of low-dose computed tomography lung cancer screening in Hungary, and to define the required steps for performing the analysis. A targeted literature review was conducted to identify and synthesize the evidence on efficacy and effectiveness of screening, and results were evaluated based on adaptability to Hungarian settings. We also summarized the available Hungarian scientific evidence and reconstructed the potential patient pathways. In accordance with these findings, we recommend to perform the full health-economic evaluation of low-dose computed tomography lung cancer screening using a complex model structure that consists of several sub-models and is capable to follow the population at risk on life-time horizon. The proposed cost-effectiveness model will be suitable to provide data for further analyses that support decision-making on introducing low-dose computed tomography lung cancer screening as public health program. Orv Hetil. 2017; 158(25): 963-975.

  8. 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

  9. A modelling study to evaluate the costs and effects of lowering the starting age of population breast cancer screening.

    Science.gov (United States)

    Koleva-Kolarova, Rositsa G; Daszczuck, Alicja M; de Jonge, Chris; Abu Hantash, Mohd Kahlil; Zhan, Zhuozhao Z; Postema, Erik Jan; Feenstra, Talitha L; Pijnappel, Ruud M; Greuter, Marcel J W; de Bock, Geertruida H

    2018-03-01

    Because the incidence of breast cancer increases between 45 and 50years of age, a reconsideration is required of the current starting age (typically 50years) for routine mammography. Our aim was to evaluate the quantitative benefits, harms, and cost-effectiveness of lowering the starting age of breast cancer screening in the Dutch general population. Economic modelling with a lifelong perspective compared biennial screening for women aged 48-74years and for women aged 46-74years with the current Dutch screening programme, which screen women between the ages of 50 and 74years. Tumour deaths prevented, years of life saved (YOLS), false-positive rates, radiation-induced tumours, costs and incremental cost-effectiveness ratios (ICERs) were evaluated. Starting the screening at 48 instead of 50 years of age led to increases in: the number of small tumours detected (4.0%), tumour deaths prevented (5.6%), false positives (9.2%), YOLS (5.6%), radiation-induced tumours (14.7%), and costs (4.1%). Starting the screening at 46 instead of 48 years of age increased the number of small tumours detected (3.3%), tumour deaths prevented (4.2%), false positives (8.8%), YOLS (3.7%), radiation-induced tumours (15.2%), and costs (4.0%). The ICER was €5600/YOLS for the 48-74 scenario and €5600/YOLS for the 46-74 scenario. Women could benefit from lowering the starting age of screening as more breast cancer deaths would be averted. Starting regular breast cancer screening earlier is also cost-effective. As the number of additional expected harms is relatively small in both the scenarios examined, and the difference in ICERs is not large, introducing two additional screening rounds is justifiable. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Estimating the coverage of a targeted mobile tuberculosis screening programme among illicit drug users and homeless persons with truncated models.

    Science.gov (United States)

    van Hest, N A H; De Vries, G; Smit, F; Grant, A D; Richardus, J H

    2008-05-01

    Truncated models are indirect methods to estimate the size of a hidden population which, in contrast to the capture-recapture method, can be used on a single information source. We estimated the coverage of a tuberculosis screening programme among illicit drug users and homeless persons with a mobile digital X-ray unit between 1 January 2003 and 31 December 2005 in Rotterdam, The Netherlands, using truncated models. The screening programme reached about two-third of the estimated target population at least once annually. The intended coverage (at least two chest X-rays per person per year) was about 23%. We conclude that simple truncated models can be used relatively easily on available single-source routine data to estimate the size of a population of illicit drug users and homeless persons. We assumed that the most likely overall bias in this study would be overestimation and therefore the coverage of the targeted mobile tuberculosis screening programme would be higher.

  11. Modeling indoor TV/screen viewing and adult physical and mental health: Health Survey for England, 2012.

    Science.gov (United States)

    Shiue, Ivy

    2016-06-01

    The aim of the present study was to model indoor TV/screen viewing and a series of adult health conditions and cognitive performance in a country-wide, population-based setting in recent years. Data was retrieved from Health Survey for England, 2012. Information on demographics, lifestyle factors, self-reported health conditions, and TV and/or screen watching hours in adults was collected by household interviews. Chi-square test and survey-weighted logistic and multi-nominal modeling were performed. Of 8114 English adults aged 18-98, 4138 people (51.1 %) watched TV and/or screen daily for 2 h or more on average. Two thousand five-hundred people (30.9 %) watched for 3 h or more. TV and/or screening watching for 2+ hours was associated with endocrine or metabolic disorders, diabetes, mental disorders (including poor scores in General Health Questionnaire and Warwick-Edinburgh Mental Well-being Scale), nervous system disorders, eye complaints, circulatory system disorders, respiratory system disorders, musculoskeletal system disorders, and self-rated health. TV and/or screen watching for 3+ hours was associated with digestive disorders and clotting disorder. TV and/or screen watching for 5+ hours was associated with cancer. TV and/or screen watching for 6+, 8+, or 11+ hours was associated with bladder disease, genito-urinary system disorders or bowel disease, respectively. There were no risk associations (within 20 h) found with ear complaints, infectious disease, and blood system disorders. Future educational and public health programs minimizing TV and/or screen viewing in order to protect from physical inactivity and X-radiation might be needed while research on the combined effect of physical inactivity and X-radiation should be explored.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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'

  17. Cost-Effectiveness of HIV Screening in STD Clinics, Emergency Departments, and Inpatient Units: A Model-Based Analysis

    Science.gov (United States)

    Prabhu, Vimalanand S.; Farnham, Paul G.; Hutchinson, Angela B.; Soorapanth, Sada; Heffelfinger, James D.; Golden, Matthew R.; Brooks, John T.; Rimland, David; Sansom, Stephanie L.

    2011-01-01

    Background Identifying and treating persons with human immunodeficiency virus (HIV) infection early in their disease stage is considered an effective means of reducing the impact of the disease. We compared the cost-effectiveness of HIV screening in three settings, sexually transmitted disease (STD) clinics serving men who have sex with men, hospital emergency departments (EDs), settings where patients are likely to be diagnosed early, and inpatient diagnosis based on clinical manifestations. Methods and Findings We developed the Progression and Transmission of HIV/AIDS model, a health state transition model that tracks index patients and their infected partners from HIV infection to death. We used program characteristics for each setting to compare the incremental cost per quality-adjusted life year gained from early versus late diagnosis and treatment. We ran the model for 10,000 index patients for each setting, examining alternative scenarios, excluding and including transmission to partners, and assuming HAART was initiated at a CD4 count of either 350 or 500 cells/µL. Screening in STD clinics and EDs was cost-effective compared with diagnosing inpatients, even when including only the benefits to the index patients. Screening patients in STD clinics, who have less-advanced disease, was cost-effective compared with ED screening when treatment with HAART was initiated at a CD4 count of 500 cells/µL. When the benefits of reduced transmission to partners from early diagnosis were included, screening in settings with less-advanced disease stages was cost-saving compared with screening later in the course of infection. The study was limited by a small number of observations on CD4 count at diagnosis and by including transmission only to first generation partners of the index patients. Conclusions HIV prevention efforts can be advanced by screening in settings where patients present with less-advanced stages of HIV infection and by initiating treatment with HAART

  18. 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.

  19. Aneuploidy screening during pregnancy by a three-dimensional Advanced First Trimester Screening model: description of the AFS-3D algorithm.

    Science.gov (United States)

    Schmidt, Peter; Hörmansdörfer, Cindy; Vaske, Bernhard; Hillemanns, Peter; Scharf, Alexander

    2012-02-01

    A novel screening method for fetal aneuploidies was developed, in which nuchal translucency (NT), pregnancy-associated plasma protein-A (PAPP-A), and free-β human chorionic gonadotropin (free-β hCG) are placed into a three-dimensional scatter plot. Likelihood ratios are directly inferred from the ratio of already observed healthy and diseased fetuses. This method is called 'Three-dimensional Advanced First trimester Screening' (AFS-3D). It was aimed to develop and test a new algorithm based on the results of previous studies. A new static-sized sphere model was developed. Several scaling factors of the axes and the optional application of the modifications 'simulation' (SIM) and 'empty sphere positive' were tested on 15,227 data sets. An additional examination was performed on a second collective (n = 458). The application of the new AFS-3D model with static-sized spheres, a re-sampled ∆NT axis by a scaling factor of 0.125, and the application of SIM and Empty Box Positive resulted in a marked improvement of the test performance (area under curve, AUC = 0.9668). Analogous results (AUC = 0.9807) were found for the second test collective. This novel approach is promising and should be tested on a larger, independent collective. © 2012 John Wiley & Sons, Ltd.

  20. 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 (pmodels 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

  1. Screening Men at Increased Risk for Prostate Cancer Diagnosis: Model Estimates of Benefits and Harms.

    Science.gov (United States)

    Gulati, Roman; Cheng, Heather H; Lange, Paul H; Nelson, Peter S; Etzioni, Ruth

    2017-02-01

    Guidelines for PSA screening in subgroups with increased risk of prostate cancer diagnosis due to race or genotype are underdeveloped. Our goal was to investigate types of increased prostate cancer risk and implications for targeted screening. We investigated computer simulation of subgroups with average and hypothetical increased risk(s) of onset of latent disease, progression, and/or cancer-specific death. For each subgroup, we predicted lifetime probabilities of overdiagnosis and life saved under more and less intensive PSA screening strategies. An application estimated risks of onset among BRCA1/2 mutation carriers in the Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls (IMPACT) study using maximum likelihood. Our simulations implied PSA screening can save more lives among subgroups with increased risk than with average risk, but more intensive screening did not always improve harm-benefit trade-offs. IMPACT data were consistent with increased risks of onset among BRCA1 and BRCA2 mutation carriers [HR = 1.05; 95% confidence interval (CI), 0.63-1.59 and HR = 1.81; 95% CI, 1.14-2.78, respectively]. Our analysis suggests screening BRCA2 mutation carriers earlier and more frequently than the average-risk population, but a lower PSA threshold for biopsy is unlikely to improve outcomes. Effective screening in men with increased prostate cancer risk depends on the manner in which the risk is increased. More intensive screening is not always optimal. Guidelines for screening men at increased prostate cancer risk should consider the mechanism inducing the increased risk. Although the benefit of screening may be greater in men with increased risks, more intensive screening is not always appropriate. Cancer Epidemiol Biomarkers Prev; 26(2); 222-7. ©2016 AACR. ©2016 American Association for Cancer Research.

  2. 'Inside-out', back-to-front: a model for clinical population genetic screening.

    OpenAIRE

    Shickle, D; Harvey, I

    1993-01-01

    Developments in DNA technology have resulted in a dramatic increase in the number of genes identified. With the localisation of a gene it is possible to devise procedures suitable for mass carrier screening programmes. Until recently mass carrier screening was only possible for a limited number of disorders, for example, Tay-Sachs disease and haemoglobinopathies. Counselling possible carriers was based on estimations of risk. The momentum towards mass carrier screening is likely to be increas...

  3. [Drug screening model acting on out-membrane protein OprM in pseudomonas aeruginosa efflux pump system].

    Science.gov (United States)

    Tian, Rui; Yu, Li-yan; Xiao, Chun-ling; Zuo, Lian; Yao, Tian-jue; Yang, Li-xia

    2004-08-01

    To establish an efflux pump inhibitor screening model with the out-membrane protein OprM in Pseudomonas aeruginosa efflux pump system as the target point. Efflux pump out-membrane protein gene oprM was obtained from standard Pseudomonas aeruginosa PA01 strain. Expression of OprM protein was induced in E. coli strain HS151 with T-easy vector as the cloning vector, and pMMB67EH as the expression vector. In order to evaluate the function of OprM protein, we measured intracellular tetracycline concentrations with liquid scintillation counter, measured the diameters of bacteriostatic circles with paper disc, and then established a screening model accordingly. OprM protein was highly expressed. Using Pseudomonas aeruginosa as the main detecting bacteria, we established a drug screening model acting on OprM. A total of 1 600 microbial fermentation samples were screened with this model, among which 56 positive strains were found, with a positive rate of 3.5%. OprM plays an important role in drug efflux. The established model has good specificity and maneuverability.

  4. 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.

  5. Human primary liver cancer-derived organoid cultures for disease modeling and drug screening.

    Science.gov (United States)

    Broutier, Laura; Mastrogiovanni, Gianmarco; Verstegen, Monique Ma; Francies, Hayley E; Gavarró, Lena Morrill; Bradshaw, Charles R; Allen, George E; Arnes-Benito, Robert; Sidorova, Olga; Gaspersz, Marcia P; Georgakopoulos, Nikitas; Koo, Bon-Kyoung; Dietmann, Sabine; Davies, Susan E; Praseedom, Raaj K; Lieshout, Ruby; IJzermans, Jan N M; Wigmore, Stephen J; Saeb-Parsy, Kourosh; Garnett, Mathew J; van der Laan, Luc Jw; Huch, Meritxell

    2017-12-01

    Human liver cancer research currently lacks in vitro models that can faithfully recapitulate the pathophysiology of the original tumor. We recently described a novel, near-physiological organoid culture system, wherein primary human healthy liver cells form long-term expanding organoids that retain liver tissue function and genetic stability. Here we extend this culture system to the propagation of primary liver cancer (PLC) organoids from three of the most common PLC subtypes: hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and combined HCC/CC (CHC) tumors. PLC-derived organoid cultures preserve the histological architecture, gene expression and genomic landscape of the original tumor, allowing for discrimination between different tumor tissues and subtypes, even after long-term expansion in culture in the same medium conditions. Xenograft studies demonstrate that the tumorogenic potential, histological features and metastatic properties of PLC-derived organoids are preserved in vivo. PLC-derived organoids are amenable for biomarker identification and drug-screening testing and led to the identification of the ERK inhibitor SCH772984 as a potential therapeutic agent for primary liver cancer. We thus demonstrate the wide-ranging biomedical utilities of PLC-derived organoid models in furthering the understanding of liver cancer biology and in developing personalized-medicine approaches for the disease.

  6. 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

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

    Science.gov (United States)

    Park, Young-Min; Kim, Kwang-Joon

    2011-05-01

    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.

  8. Mammographic screening in BRCA1 mutation carriers postponed until age 40: Evaluation of benefits, costs and radiation risks using models.

    Science.gov (United States)

    Obdeijn, Inge-Marie; Heijnsdijk, Eveline A M; Hunink, M G Myriam; Tilanus-Linthorst, Madeleine M A; de Koning, Harry J

    2016-08-01

    BRCA1 mutation carriers are offered screening with magnetic resonance imaging (MRI) and mammography. The aim of this study was to weigh benefits and risks of postponing mammographic screening until age 40. With the MISCAN microsimulation model two screening protocols were evaluated: 1) the current Dutch guidelines: annual MRI from age 25-60, annual mammography from age 30-60, and biennial mammography in the nationwide program from age 60-74, and 2) the modified protocol: with annual mammography postponed until age 40. A cost-effectiveness analysis was performed. The risks of radiation-induced breast cancer mortality were estimated with absolute and relative exposure-risk models of the 7th Biological Effects of Ionising Radiation Committee. Current screening guidelines prevent 13,139 breast cancer deaths per 100,000 BRCA1 mutation carriers. Postponing mammography until age 40 would increase breast cancer deaths by 23 (0.17%), but would also reduce radiation-induced breast cancer deaths by 15 or 105 using the absolute and relative risk model respectively per 100,000 women screened. The estimated net effect is an increase of eight or a reduction of 82 breast cancer deaths per 100,000 women screened (depending on the risk model used). The incremental cost of mammograms between age 30-39 is €272,900 per life year gained. The modified protocol may be slightly less effective or even better than the current guidelines. The high cost-savings justify a possible small loss of effectiveness. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. 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

  10. 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 ...

  11. Calculation of the radiative opacity of laser-produced plasmas using a relativistic-screened hydrogenic model

    International Nuclear Information System (INIS)

    Rubiano, J.G.; Florido, R.; Rodriguez, R.; Gil, J.M.; Martel, P.; Minguez, E.

    2004-01-01

    In this work, we use a relativistic-screened hydrogenic model to compute the radiative opacity of laser-produced plasmas. The model is based on a set of screening charges which allow one to easily calculate atomic properties of isolated ions. These screened charges have been fitted to a fourth-order polynomial depending on the nuclear charge Z for ground and single excited states of ions belonging to the isoelectronic sequences comprised between He-like to U-like. In the opacity model used, ionic populations are obtained by solving the Saha equation including degeneracy corrections. Bound-bound transitions are determined using a Voigt profile for line shape, which includes natural, collisional, Doppler and UTA widths. Bound-free and free-free opacities are evaluated using the Kramer cross-sections with appropriate corrections. Scattering processes are computed through the use of the Thomson formula with corrections. The results are compared with other screened hydrogenic models and more sophisticated self-consistent codes

  12. Development and Application of In Vitro Models for Screening Drugs and Environmental Chemicals that Predict Toxicity in Animals and Humans

    Science.gov (United States)

    Development and Application of In Vitro Models for Screening Drugs and Environmental Chemicals that Predict Toxicity in Animals and Humans (Presented by James McKim, Ph.D., DABT, Founder and Chief Science Officer, CeeTox) (5/25/2012)

  13. Implementation of a "Learner-Driven" Curriculum: An Screening, Brief Intervention, and Referral to Treatment (SBIRT) Interdisciplinary Primary Care Model

    Science.gov (United States)

    Stanton, Marina R.; Atherton, W. Leigh; Toriello, Paul J.; Hodgson, Jennifer L.

    2012-01-01

    Although screening, brief intervention, and referral to treatment (SBIRT) has been a popular model to address potential substance abuse issues in primary care, there is a need for innovative approaches for training providers and staff on SBIRT protocols. An interdisciplinary approach to SBIRT training, named ICARE, was implemented at 3 different…

  14. 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.

  15. 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…

  16. 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)

  17. 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

  18. An evaluation of screening policies for cervical cancer in England and Wales using a computer simulation model.

    OpenAIRE

    Parkin, D M; Moss, S M

    1986-01-01

    Several screening policies have been recommended for implementation in England and Wales in the last 20 years, although no evidence as to their relative effectiveness or efficiency has been provided. Using a computer simulation model, the outcomes expected from those policies had they been implemented over a 30 year period (1961-90) have been examined. The original policies based on five-yearly testing of women aged over 35 appear to be the most cost-effective, and extension of screening to y...

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

    Science.gov (United States)

    Wang, Zhen; Zhou, Jingqing; Loaiciga, Hugo; Guo, Huaicheng; Hong, Song

    2015-01-01

    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.

  20. Fault identification using piezoelectric impedance measurement and model-based intelligent inference with pre-screening

    Science.gov (United States)

    Shuai, Q.; Zhou, K.; Zhou, Shiyu; Tang, J.

    2017-04-01

    While piezoelectric impedance/admittance measurements have been used for fault detection and identification, the actual identification of fault location and severity remains to be a challenging topic. On one hand, the approach that uses these measurements entertains high detection sensitivity owing to the high-frequency actuation/sensing nature. On the other hand, high-frequency analysis requires high dimensionality in the model and the subsequent inverse analysis contains a very large number of unknowns which often renders the identification problem under-determined. A new fault identification algorithm is developed in this research for piezoelectric impedance/admittance based measurement. Taking advantage of the algebraic relation between the sensitivity matrix and the admittance change measurement, we devise a pre-screening scheme that can rank the likelihoods of fault locations with estimated fault severity levels, which drastically reduces the fault parameter space. A Bayesian inference approach is then incorporated to pinpoint the fault location and severity with high computational efficiency. The proposed approach is examined and validated through case studies.

  1. Bioreactor process parameter screening utilizing a Plackett-Burman design for a model monoclonal antibody.

    Science.gov (United States)

    Agarabi, Cyrus D; Schiel, John E; Lute, Scott C; Chavez, Brittany K; Boyne, Michael T; Brorson, Kurt A; Khan, Mansoora; Read, Erik K

    2015-06-01

    Consistent high-quality antibody yield is a key goal for cell culture bioprocessing. This endpoint is typically achieved in commercial settings through product and process engineering of bioreactor parameters during development. When the process is complex and not optimized, small changes in composition and control may yield a finished product of less desirable quality. Therefore, changes proposed to currently validated processes usually require justification and are reported to the US FDA for approval. Recently, design-of-experiments-based approaches have been explored to rapidly and efficiently achieve this goal of optimized yield with a better understanding of product and process variables that affect a product's critical quality attributes. Here, we present a laboratory-scale model culture where we apply a Plackett-Burman screening design to parallel cultures to study the main effects of 11 process variables. This exercise allowed us to determine the relative importance of these variables and identify the most important factors to be further optimized in order to control both desirable and undesirable glycan profiles. We found engineering changes relating to culture temperature and nonessential amino acid supplementation significantly impacted glycan profiles associated with fucosylation, β-galactosylation, and sialylation. All of these are important for monoclonal antibody product quality. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  2. Opportunistische screening...

    NARCIS (Netherlands)

    Postma, M.J.; Welte, R.; Van Den Hoek, J.A.R.; Van Doornum, G.J.J.; Coutinho, R.A.; Jager, J.C.

    1999-01-01

    Objective. To estimate the cost effectiveness of Chlamydia trachomatis (CT) screening of young women visiting general practitioners. Design. Economic model analysis. Methods. Data on the health care needs for CT complications were derived from various sources; costing was done using estimated cost

  3. Vapor intrusion screening model for the evaluation of risk-based vertical exclusion distances at petroleum contaminated sites.

    Science.gov (United States)

    Verginelli, Iason; Baciocchi, Renato

    2014-11-18

    The key role of biodegradation in attenuating the migration of petroleum hydrocarbon vapors into the indoor environments has been deeply investigated in the last decades. Very recently, empirical screening levels for the separation distance from the source, above which the potential for vapor intrusion can be considered negligible, were defined. In this paper, an analytical solution that allows one to predict risk-based vertical screening distances for hydrocarbons compounds is presented. The proposed solution relies on a 1-D vapor intrusion model that incorporates a piecewise first-order aerobic biodegradation limited by oxygen availability and accounts also for the effect of the building footprint. The model predictions are shown to be consistent with the results obtained using a 3-D numerical model and with the empirical screening criteria defined by U.S.EPA and CRC care. However, the different simulations carried out show that in some specific cases (e.g., large building footprint, high methane concentration, and low attenuation in the capillary fringe), the respect of these empirical screening criteria could be insufficient to guarantee soil-gas concentrations below acceptable risk-based levels.

  4. Modeling the Impact of School-Based Universal Depression Screening on Additional Service Capacity Needs: A System Dynamics Approach.

    Science.gov (United States)

    Lyon, Aaron R; Maras, Melissa A; Pate, Christina M; Igusa, Takeru; Vander Stoep, Ann

    2016-03-01

    Although it is widely known that the occurrence of depression increases over the course of adolescence, symptoms of mood disorders frequently go undetected. While schools are viable settings for conducting universal screening to systematically identify students in need of services for common health conditions, particularly those that adversely affect school performance, few school districts routinely screen their students for depression. Among the most commonly referenced barriers are concerns that the number of students identified may exceed schools' service delivery capacities, but few studies have evaluated this concern systematically. System dynamics (SD) modeling may prove a useful approach for answering questions of this sort. The goal of the current paper is therefore to demonstrate how SD modeling can be applied to inform implementation decisions in communities. In our demonstration, we used SD modeling to estimate the additional service demand generated by universal depression screening in a typical high school. We then simulated the effects of implementing "compensatory approaches" designed to address anticipated increases in service need through (1) the allocation of additional staff time and (2) improvements in the effectiveness of mental health interventions. Results support the ability of screening to facilitate more rapid entry into services and suggest that improving the effectiveness of mental health services for students with depression via the implementation of an evidence-based treatment protocol may have a limited impact on overall recovery rates and service availability. In our example, the SD approach proved useful in informing systems' decision-making about the adoption of a new school mental health service.

  5. A model of tuberculosis screening for pregnant women in resource-limited settings using Xpert MTB/RIF.

    Science.gov (United States)

    Turnbull, Eleanor R; Kancheya, Nzali G; Harris, Jennifer B; Topp, Stephanie M; Henostroza, German; Reid, Stewart E

    2012-01-01

    Timely diagnosis and treatment of maternal tuberculosis (TB) is important to reduce morbidity and mortality for both the mother and child, particularly in women who are coinfected with HIV. The World Health Organization (WHO) recommends the integration of TB/HIV screening into antenatal services but available diagnostic tools are slow and insensitive, resulting in delays in treatment initiation. Recently the WHO endorsed Xpert MTB/RIF, a highly sensitive, real-time PCR assay for Mycobacterium tuberculosis that simultaneously detects rifampicin resistance directly from sputum and provides results within 100 minutes. We propose a model for same-day TB screening and diagnosis of all pregnant women at antenatal care using Xpert MTB/RIF. Pilot studies are urgently required to evaluate strategies for the integration of TB screening into antenatal clinics using new diagnostic technologies.

  6. A Model of Tuberculosis Screening for Pregnant Women in Resource-Limited Settings Using Xpert MTB/RIF

    Directory of Open Access Journals (Sweden)

    Eleanor R. Turnbull

    2012-01-01

    Full Text Available Timely diagnosis and treatment of maternal tuberculosis (TB is important to reduce morbidity and mortality for both the mother and child, particularly in women who are coinfected with HIV. The World Health Organization (WHO recommends the integration of TB/HIV screening into antenatal services but available diagnostic tools are slow and insensitive, resulting in delays in treatment initiation. Recently the WHO endorsed Xpert MTB/RIF, a highly sensitive, real-time PCR assay for Mycobacterium tuberculosis that simultaneously detects rifampicin resistance directly from sputum and provides results within 100 minutes. We propose a model for same-day TB screening and diagnosis of all pregnant women at antenatal care using Xpert MTB/RIF. Pilot studies are urgently required to evaluate strategies for the integration of TB screening into antenatal clinics using new diagnostic technologies.

  7. Screening of central functions of amino acids and their metabolites for sedative and hypnotic effects using chick models.

    Science.gov (United States)

    Furuse, Mitsuhiro

    2015-09-05

    The chick has a practical advantage in the screening process in that chicks require only small quantities of drugs. The chick separation stress paradigm has traditionally been recognized as a valid form of anxiolytic screening. Further, chick behavior involving standing motionless with eyes closed or sitting motionless with head drooped is nearly always associated with electrophysiological sleep. When centrally administered, some DNA-encoded L-α-amino acids, as well as some DNA-non-encoded amino acids, such as metabolites of L-α-amino acids, D-amino acid and β-amino acid, have shown sedative and/or hypnotic effects in chicks. The effects of some of these amino acids have subsequently been confirmed in humans. In conclusion, the chick model is convenient and useful for screening central functions of amino acids and their metabolites for hypnosis and sedation. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. [Establishment of double targets of high throughput screening model for xanthine oxidase inhibitors and superoxide anion scavengers].

    Science.gov (United States)

    Xie, Tao; Qin, Zhi-Zhen; Zhou, Rui; Zhao, Ying; Du, Guan-hua

    2015-04-01

    A double targets of high throughput screening model for xanthine oxidase inhibitors and superoxide anion scavengers was established. In the reaction system of xanthine oxidase, WST-1 works as the probe for the ultra oxygen anion generation, and product uric acid works as xanthine oxidase activity indicator. By using SpectraMax M5 continuous spectrum enzyme sign reflectoscope reflector, the changes of these indicators' concentration were observed and the influence factors of this reaction system to establish the high throughput screening model were studied. And the model is confirmed by positive drugs. In the reaction system, the final volume of reaction system is 50 μL and the concentrations of xanthine oxidase is 4 mU x mL(-1), xanthine 250 μmol x L(-1) and WST-1 100 μmol x L(-1), separately. The Z'-factor of model for xanthine oxidase inhibitors is 0.537 4, S/N is 47.519 9; the Z'-factor of model for superoxide anion scavengers is 0.507 4, S/N is 5.388 9. This model for xanthine oxidase inhibitors and superoxide anion scavengers has more common characteristics of the good stability, the fewer reagent types and quantity, the good repeatability, and so on. And it can be widely applied in high-throughput screening research.

  9. The Economic Model of Retinopathy of Prematurity (EcROP) Screening and Treatment: Mexico and the United States.

    Science.gov (United States)

    Rothschild, Michael I; Russ, Rebecca; Brennan, Kathryn A; Williams, Christopher J; Berrones, David; Patel, Bhavesh; Martinez-Castellanos, Maria Ana; Fernandes, Alcides; Hubbard, G Baker; Chan, R V Paul; Yang, Zhou; Olsen, Timothy W

    2016-08-01

    To describe an economic (Ec) model for estimating the impact of screening and treatment for retinopathy of prematurity (ROP). EcROP is a cost-effectiveness, cost-utility, and cost-benefit analysis. We surveyed caregivers of 52 children at schools for the blind or pediatric eye clinics in Atlanta, Georgia and 43 in Mexico City. A decision analytic model with sensitivity analysis determined the incremental cost-effectiveness (primary outcome) and incremental monetary benefit (secondary outcome) of an ideal (100% screening) national ROP program as compared to estimates of current practice. Direct costs included screening and treatment expenditures. Indirect costs estimated lost productivity of caretaker(s) and blind individuals as determined by face-to-face surveys. Utility and effectiveness were measured in quality-adjusted life years and benefit in US dollars. EcROP includes a sensitivity analysis to assesses the incremental cost-effectiveness and societal impact of ROP screening and treatment within a country or economic region. Estimates are based on evidence-based clinical data and region-specific economic data acquired from direct field survey. In both Mexico and the United States, an ideal national ROP screening and treatment program was highly cost-saving. The incremental net benefit of an ideal ROP program over current practice is $5556 per child ($206 574 333 annually) and $3628 per child ($205 906 959 annually) in Mexico and the United States, respectively. EcROP demonstrates that ROP screening and treatment is highly beneficial for quality of life, cost saving, and cost-effectiveness in the United States and Mexico. EcROP can be applied to any country or region to provide data for informed allocation of limited health care resources. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Associations of demographic variables and the Health Belief Model constructs with Pap smear screening among urban women in Botswana

    Directory of Open Access Journals (Sweden)

    McFarl

    2013-10-01

    Full Text Available Ditsapelo M McFarland College of Nursing and Public Health, Adelphi University, Garden City, NY, USA Purpose: Papanicolaou (Pap smear services are available in most urban areas in Botswana. Yet most women in such areas do not screen regularly for cancer of the cervix. The purpose of this article is to present findings on the associations of demographic variables and Health Belief Model constructs with Pap smear screening among urban women in Botswana. Sample and methods: The study included a convenience sample of 353 asymptomatic women aged 30 years and older who were living in Gaborone, Botswana. Data were collected using a demographic questionnaire and items of the Health Belief Model. Data analysis included descriptive statistics for demographic variables and bivariate and ordinal (logit regression to determine the associations of demographic variables. Results: Having health insurance and having a regular health care provider were significant predictors of whether or not women had a Pap smear. Women with health insurance were more likely to have had a Pap smear test than women without health insurance (91% vs 36%. Similarly, women who had a regular health care provider were more likely to have had a Pap smear test than women without a regular health care provider (94% vs 42%. Major barriers to screening included what was described as "laziness" for women who had ever had a Pap smear (57% and limited information about Pap smear screening for women who had never had a Pap smear (44%. Conclusion: There is a need for more information about the importance of the Pap smear test and for increased access to screening services in Botswana. Keywords: cervical, screening, barriers, access, beliefs

  11. 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

  12. 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.

  13. Cell cultures from animal models of Alzheimer's disease as a tool for faster screening and testing of drug efficacy.

    Science.gov (United States)

    Trinchese, Fabrizio; Liu, Shumin; Ninan, Ipe; Puzzo, Daniela; Jacob, Joel P; Arancio, Ottavio

    2004-01-01

    Approximately 2 million people in the United States suffer from Alzheimer's disease (AD), which is the most common cause of chronic dementia among the aging population. During the last 7 yr, excellent opportunities to screen drugs against AD have been provided by animal models of the disease. Because even in the fastest model, AD pathology does not start before the end of the second month, it has been necessary to wait at least until that age to inject drugs into the animal to assess whether they prevent, reduce, or revert synaptic impairment, plaque formation, and increase of beta-amyloid (Abeta) levels, the main features of the disease. A solution to the problems mentioned above is achieved by the present fast, efficient, and reproducible cultured cell system from animal models of AD or Abeta-associated diseases, for the screening and testing of compounds for the treatment and therapy of AD or Abeta-associated diseases. Copyright 2004 Humana Press Inc.

  14. 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.

  15. The international endorsement of US distress screening and psychosocial guidelines in oncology: a model for dissemination.

    Science.gov (United States)

    Lazenby, Mark

    2014-02-01

    The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Distress Management have, since 1997, called for routine screening of distress in patients with cancer. Following the example of pain as the fifth vital sign, the case for using the concept of distress as the sixth vital sign was made by leading psycho-oncologists in 2007. Cancer care organizations in Canada and the International Psycho-Oncology Society have adopted the NCCN Guidelines for Distress Management and have named distress screening as the sixth vital sign, thereby encouraging cancer care clinicians to think of screening for distress when they screen for pain and other vital signs. Using the evidence integration triangle, this article explores the dissemination of the notion of distress as the sixth vital sign in an international context. This exploration shows that NCCN and similar organizations can adopt the evidence integration triangle in its next phase of moving toward full implementation of the NCCN Guidelines for Distress Management.

  16. 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.

  17. 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.

  18. Development and application of an aerosol screening model for size-resolved urban aerosols.

    Science.gov (United States)

    Stanier, Charles O; Lee, Sang-Rin

    2014-06-01

    Predictive models of vehicular ultrafine particles less than 0.1 microm in diameter (UFPs*) and other urban pollutants with high spatial and temporal variation are useful and important in applications such as (1) decision support for infrastructure projects, emissions controls, and transportation-mode shifts; (2) the interpretation and enhancement of observations (e.g., source apportionment, extrapolation, interpolation, and gap-filling in space and time); and (3) the generation of spatially and temporally resolved exposure estimates where monitoring is unfeasible. The objective of the current study was to develop, test, and apply the Aerosol Screening Model (ASM), a new physically based vehicular UFP model for use in near-road environments. The ASM simulates hourly average outdoor concentrations of roadway-derived aerosols and gases. Its distinguishing features include user-specified spatial resolution; use of the Weather Research and Forecasting (WRF) meteorologic model for winds estimates; use of a database of more than 100,000 road segments in the Los Angeles, California, region, including freeway ramps and local streets; and extensive testing against more than 9000 hours of observed particle concentrations at 11 sites. After initialization of air parcels at an upwind boundary, the model solves for vehicle emissions, dispersion, coagulation, and deposition using a Lagrangian modeling framework. The Lagrangian parcel of air is subdivided vertically (into 11 levels) and in the crosswind direction (into 3 parcels). It has overall dimensions of 10 m (downwind), 300 m (vertically), and 2.1 km (crosswind). The simulation is typically started 4 km upwind from the receptor, that is, the location at which the exposure is to be estimated. As parcels approach the receptor, depending on the user-specified resolution, step size is decreased, and crosswind resolution is enhanced through subdivision of parcels in the crosswind direction. Hourly concentrations and size

  19. 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

  20. 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

  1. The development and evaluation of a community based model for cervical cancer screening based on self-sampling.

    Science.gov (United States)

    Belinson, Jerome L; Wang, Guixiang; Qu, Xinfeng; Du, Hui; Shen, Jingjing; Xu, Jiajia; Zhong, Liqun; Yi, Ji; Yi, Xin; Wu, Ruifang

    2014-03-01

    To develop and implement a community based model for cervical cancer prevention that allows the communities to manage the screening and the healthcare system to focus resources on evaluation and management of the positives. Using self-sampling and the concepts founded in Community Based Participatory Research (CBPR), we progressively developed a model to efficiently reach the women, especially rural communities; and collect the volume of samples needed to support high throughput centralized low cost per case processing. 8382 eligible women, ages 35 to 59, in 130 rural communities participated. The screening was organized by the local government administration and conducted by the community leaders (CLs). The model used was progressively designed through detailed assessment of key elements at 6 decision points in 26 workshops that were used to train the CLs and the local promoters. The communities were able to accurately conduct the screening; in the final model a local medical worker conducted a 50-minute workshop featuring instructional posters and structured role-play. A manual and a workshop DVD were created for distribution to and implementation by local governments. The average callback rate was 84.3%, without involvement of the local doctors in the management of the positives. An efficient community based model capable of massive screening events was developed. We believe that the callback rate will be further improved when local doctors are trained in the management of the positives. Many elements impact coverage and further research is needed to define the influence of the identified key variables. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. A physical-chemical screening model for anticipating widespread contamination of community water supply wells by gasoline constituents.

    Science.gov (United States)

    Arey, J Samuel; Gschwend, Philip M

    2005-01-01

    Continuing modifications of fuels like gasoline should include evaluations of the proposed constituents for their potential to damage environmental resources such as subsurface water supplies. Consequently, we developed a screening model to estimate well water concentrations and transport times for gasoline components migrating from underground fuel tank (UFT) releases to typical at-risk community water supply wells. Representative fuel release volumes and hydrogeologic characteristics were used to parameterize the transport calculation. Subsurface degradation processes were neglected in the model in order to make risk-conservative assessments. The model was tailored to individual compounds based on their abundances in gasoline, gasoline-water partition coefficients (Kgw), and organic matter-water partition coefficients (Kom). Transport calculations were conducted for 20 polar and 4 nonpolar compounds found in gasoline, including methyl tert-butyl ether (MTBE) and other ether oxygenates, ethanol, methanol, and some aromatic hydrocarbons. With no calibration, the screening model successfully captured the reported magnitude of MTBE contamination of at-risk community supply wells. Such screening indicates that other oxygenates would cause similar widespread problems unless they were biodegradable. Stochastic analysis of field parameter variability concluded that community supply well contamination estimates had order-of-magnitude reliability. This indicated that such pre-manufacturing analyses may reasonably anticipate widespread environmental problems and/or inspire focused investigations into chemical properties (e.g., biodegradability) before industrial adoption of new fuel formulations.

  3. Newborn Screening

    Science.gov (United States)

    ... Laboratory Sciences Office of Public Health Genomics Publications & Articles Newborn Screening Lab Bulletin Laboratory Partners Multimedia Tools Newborn Screening Program – Role of Laboratories Meet the Scientist Newborn Screening: Family Stories Newborn Screening: Public Health ...

  4. 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.

  5. 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......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...

  6. 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.

  7. 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.

  8. Associations of demographic variables and the Health Belief Model constructs with Pap smear screening among urban women in Botswana

    Science.gov (United States)

    McFarland, Ditsapelo M

    2013-01-01

    Purpose Papanicolaou (Pap) smear services are available in most urban areas in Botswana. Yet most women in such areas do not screen regularly for cancer of the cervix. The purpose of this article is to present findings on the associations of demographic variables and Health Belief Model constructs with Pap smear screening among urban women in Botswana. Sample and methods The study included a convenience sample of 353 asymptomatic women aged 30 years and older who were living in Gaborone, Botswana. Data were collected using a demographic questionnaire and items of the Health Belief Model. Data analysis included descriptive statistics for demographic variables and bivariate and ordinal (logit) regression to determine the associations of demographic variables. Results Having health insurance and having a regular health care provider were significant predictors of whether or not women had a Pap smear. Women with health insurance were more likely to have had a Pap smear test than women without health insurance (91% vs 36%). Similarly, women who had a regular health care provider were more likely to have had a Pap smear test than women without a regular health care provider (94% vs 42%). Major barriers to screening included what was described as “laziness” for women who had ever had a Pap smear (57%) and limited information about Pap smear screening for women who had never had a Pap smear (44%). Conclusion There is a need for more information about the importance of the Pap smear test and for increased access to screening services in Botswana. PMID:24179380

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

    Directory of Open Access Journals (Sweden)

    Wallis Matthew G

    2011-01-01

    in UK. This study 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.

  10. 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

  11. Gene expression profiling in a mouse model identifies fetal liver- and placenta-derived potential biomarkers for Down Syndrome screening.

    Directory of Open Access Journals (Sweden)

    Jeroen L A Pennings

    Full Text Available BACKGROUND: As a first step to identify novel potential biomarkers for prenatal Down Syndrome screening, we analyzed gene expression in embryos of wild type mice and the Down Syndrome model Ts1Cje. Since current Down Syndrome screening markers are derived from placenta and fetal liver, these tissues were chosen as target. METHODOLOGY/PRINCIPAL FINDINGS: Placenta and fetal liver at 15.5 days gestation were analyzed by microarray profiling. We confirmed increased expression of genes located at the trisomic chromosomal region. Overall, between the two genotypes more differentially expressed genes were found in fetal liver than in placenta. Furthermore, the fetal liver data are in line with the hematological aberrations found in humans with Down Syndrome as well as Ts1Cje mice. Together, we found 25 targets that are predicted (by Gene Ontology, UniProt, or the Human Plasma Proteome project to be detectable in human serum. CONCLUSIONS/SIGNIFICANCE: Fetal liver might harbor more promising targets for Down Syndrome screening studies. We expect these new targets will help focus further experimental studies on identifying and validating human maternal serum biomarkers for Down Syndrome screening.

  12. A mixture model of ductus venosus pulsatility index in screening for aneuploidies at 11-13 weeks' gestation.

    Science.gov (United States)

    Maiz, Nerea; Wright, David; Ferreira, Ana Fatima A; Syngelaki, Argyro; Nicolaides, Kypros H

    2012-01-01

    To assess the value of ductus venosus pulsatility index for veins (DV PIV) in screening for aneuploidies at 11-13 weeks' gestation. Fetal DV PIV was measured in singleton pregnancies undergoing first-trimester screening for aneuploidies. In euploid (n = 44,756) and aneuploid (202 cases of trisomy 21, 72 cases of trisomy 18 and 30 cases of trisomy 13) fetuses, DV PIV was best described by a mixture model of distributions. Performance of screening for aneuploidies by DV PIV alone and in combination with fetal nuchal translucency (NT) thickness and serum free β-hCG and PAPP-A was estimated. In euploid pregnancies there was a bimodal distribution of DV PIV with a dominant crown-rump length (CRL)-dependent part, accounting for around 97% of cases in Caucasians and around 93% in Afro-Caribbeans, and a smaller CRL-independent distribution. In aneuploidies the dominant part was the CRL-independent distribution, which accounted for around 85% cases of trisomies 21 and 18 and 70% of cases of trisomy 13. In screening for trisomy 21 by maternal age, NT and biochemistry at a risk cutoff of 1 in 100, the detection rate was 89.7% and false positive rate was 2.74%; with addition of DV PIV, the values were 93.5 and 1.63%, respectively. Measurement of DV PIV improves the performance of first-trimester combined test for aneuploidies. Copyright © 2012 S. Karger AG, Basel.

  13. Coupling Numerical and Physical Modeling for Analysis of Flow in a Diversion Structure with Coanda-effect Screens

    Directory of Open Access Journals (Sweden)

    Julie Coonrod

    2011-07-01

    Full Text Available There is an increasing need to screen water in surface water collection systems to remove floating debris and small aquatic organisms to protect receiving water bodies. Recently, the Albuquerque Metropolitan Arroyo Flood Control Authority (AMAFCA, New Mexico, USA has actively introduced structural debris removal from storm-water facilities as a best management practice. In the South Diversion Channel Project, AMAFCA’s objective is to divert the flow at the upstream end of the existing concrete structure and remove debris from this flow using Coanda-effect screens before allowing it to re-enter the channel. Design limitations, such as access to the debris removal site, existing components of the concrete structure, topography of the site, and need for flow-regulating structures complicate the design. This paper shows how numerical modeling tools (Delft3D-FLOW model and physical modeling can be used in conjunction to observe flow patterns in a diversion structure and around Coanda-effect screens, estimate design parameters and thereby provide design recommendations.

  14. Estimating the coverage of a targeted mobile tuberculosis screening programme among illicit drug users and homeless persons with truncated models

    Science.gov (United States)

    VAN HEST, N. A. H.; De VRIES, G.; SMIT, F.; GRANT, A. D.; RICHARDUS, J. H.

    2008-01-01

    SUMMARY Truncated models are indirect methods to estimate the size of a hidden population which, in contrast to the capture–recapture method, can be used on a single information source. We estimated the coverage of a tuberculosis screening programme among illicit drug users and homeless persons with a mobile digital X-ray unit between 1 January 2003 and 31 December 2005 in Rotterdam, The Netherlands, using truncated models. The screening programme reached about two-third of the estimated target population at least once annually. The intended coverage (at least two chest X-rays per person per year) was about 23%. We conclude that simple truncated models can be used relatively easily on available single-source routine data to estimate the size of a population of illicit drug users and homeless persons. We assumed that the most likely overall bias in this study would be overestimation and therefore the coverage of the targeted mobile tuberculosis screening programme would be higher. PMID:17631692

  15. 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.

  16. 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.

  17. Multi-objective vs. single-objective calibration of a hydrologic model using single- and multi-objective screening

    Science.gov (United States)

    Mai, Juliane; Cuntz, Matthias; Shafii, Mahyar; Zink, Matthias; Schäfer, David; Thober, Stephan; Samaniego, Luis; Tolson, Bryan

    2016-04-01

    Hydrologic models are traditionally calibrated against observed streamflow. Recent studies have shown however, that only a few global model parameters are constrained using this kind of integral signal. They can be identified using prior screening techniques. Since different objectives might constrain different parameters, it is advisable to use multiple information to calibrate those models. One common approach is to combine these multiple objectives (MO) into one single objective (SO) function and allow the use of a SO optimization algorithm. Another strategy is to consider the different objectives separately and apply a MO Pareto optimization algorithm. In this study, two major research questions will be addressed: 1) How do multi-objective calibrations compare with corresponding single-objective calibrations? 2) How much do calibration results deteriorate when the number of calibrated parameters is reduced by a prior screening technique? The hydrologic model employed in this study is a distributed hydrologic model (mHM) with 52 model parameters, i.e. transfer coefficients. The model uses grid cells as a primary hydrologic unit, and accounts for processes like snow accumulation and melting, soil moisture dynamics, infiltration, surface runoff, evapotranspiration, subsurface storage and discharge generation. The model is applied in three distinct catchments over Europe. The SO calibrations are performed using the Dynamically Dimensioned Search (DDS) algorithm with a fixed budget while the MO calibrations are achieved using the Pareto Dynamically Dimensioned Search (PA-DDS) algorithm allowing for the same budget. The two objectives used here are the Nash Sutcliffe Efficiency (NSE) of the simulated streamflow and the NSE of the logarithmic transformation. It is shown that the SO DDS results are located close to the edges of the Pareto fronts of the PA-DDS. The MO calibrations are hence preferable due to their supply of multiple equivalent solutions from which the

  18. 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.

  19. 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.

  20. Screening for angiogenic inhibitors in zebrafish to evaluate a predictive model for developmental vascular toxicity

    Science.gov (United States)

    Chemically-induced vascular toxicity during embryonic development may cause a wide range of adverse effects. To identify putative vascular disrupting chemicals (pVDCs), a predictive signature was constructed from U.S. EPA ToxCast high-throughput screening (HTS) assays that map to...

  1. Including Antenna Models in Microwave Imaging for Breast-Cancer Screening

    DEFF Research Database (Denmark)

    Rubæk, Tonny; Meincke, Peter

    2006-01-01

    Microwave imaging is emerging as a tool for screening for breast cancer, but the lack of methods for including the characteristics of the antennas of the imaging systems in the imaging algorithms limits their performance. In this paper, a method for incorporating the full antenna characteristics...

  2. 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…

  3. 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

  4. Molecular modeling on pyruvate phosphate dikinase of Entamoeba histolytica and in silico virtual screening for novel inhibitors.

    Science.gov (United States)

    Stephen, Preyesh; Vijayan, Ramachandran; Bhat, Audesh; Subbarao, N; Bamezai, R N K

    2008-09-01

    Pyruvate phosphate dikinase (PPDK) is the key enzyme essential for the glycolytic pathway in most common and perilous parasite Entamoeba histolytica. Inhibiting the function of this enzyme could control the wide spread of intestinal infections caused by Entamoeba histolytica in humans. With this objective, we modeled the three dimensional structure of the PPDK protein. We used templates with 51% identity and 67% similarity to employ homology-modeling approach. Stereo chemical quality of protein structure was validated by protein structure validation program PROCHECK and VERIFY3D. Experimental proof available in literature along with the in silico studies indicated Lys21, Arg91, Asp323, Glu325 and Gln337 to be the probable active sites in the target protein. Virtual screening was carried out using the genetic docking algorithm GOLD and a consensus scoring function X-Score to substantiate the prediction. The small molecule libraries (ChemDivision database, Diversity dataset, Kinase inhibitor database) were used for screening process. Along with the high scoring results, the interaction studies provided promising ligands for future experimental screening to inhibit the function of PPDK in Entamoeba histolytica. Further, the phylogeny study was carried out to assess the possibility of using the proposed ligands as inhibitors in related pathogens.

  5. Nontarget screening using passive air and water sampling with a level II fugacity model to identify unregulated environmental contaminants.

    Science.gov (United States)

    Chung, In-Young; Park, Yu-Mi; Lee, Hyun-Jeoung; Kim, Hyuk; Kim, Dong-Hoon; Kim, Il-Gyu; Kim, Sang-Min; Do, Young-Sun; Seok, Kwang-Seol; Kwon, Jung-Hwan

    2017-12-01

    It is thought that there are many unregulated anthropogenic chemicals in the environment. For risk assessment of chemicals, it is essential to estimate the predicted environmental concentrations. As an effort of identifying residual organic contaminants in air and water in Korea, nontarget screening using two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOFMS) was conducted at 10 sites using polyurethane foam passive air sampler and at 6 sites using polydimethyl siloxane (PDMS) passive water sampler in three different seasons in 2014. More than 600 chemical peaks were identified satisfying the identification criteria in air and water samples, respectively, providing a list for further investigation. Chemical substances with reported national emission rates in 2014 (n=149) were also screened for potential existence in the environment using a level II fugacity model. Most of chemical substances classified as not detectable were not identified with detection frequency greater than 20% by nontarget screening, indicating that a simple equilibrium model has a strong potential to be used to exclude chemicals that are not likely to remain in the environment after emissions from targeted monitoring. Copyright © 2017. Published by Elsevier B.V.

  6. Molecular modeling on pyruvate phosphate dikinase of Entamoeba histolytica and in silico virtual screening for novel inhibitors

    Science.gov (United States)

    Stephen, Preyesh; Vijayan, Ramachandran; Bhat, Audesh; Subbarao, N.; Bamezai, R. N. K.

    2008-09-01

    Pyruvate phosphate dikinase (PPDK) is the key enzyme essential for the glycolytic pathway in most common and perilous parasite Entamoeba histolytica. Inhibiting the function of this enzyme could control the wide spread of intestinal infections caused by Entamoeba histolytica in humans. With this objective, we modeled the three dimensional structure of the PPDK protein. We used templates with 51% identity and 67% similarity to employ homology-modeling approach. Stereo chemical quality of protein structure was validated by protein structure validation program PROCHECK and VERIFY3D. Experimental proof available in literature along with the in silico studies indicated Lys21, Arg91, Asp323, Glu325 and Gln337 to be the probable active sites in the target protein. Virtual screening was carried out using the genetic docking algorithm GOLD and a consensus scoring function X-Score to substantiate the prediction. The small molecule libraries (ChemDivision database, Diversity dataset, Kinase inhibitor database) were used for screening process. Along with the high scoring results, the interaction studies provided promising ligands for future experimental screening to inhibit the function of PPDK in Entamoeba histolytica. Further, the phylogeny study was carried out to assess the possibility of using the proposed ligands as inhibitors in related pathogens.

  7. The Kidney Disease Screening and Awareness Program (KDSAP): a novel translatable model for increasing interest in nephrology careers.

    Science.gov (United States)

    Hsiao, Li-Li; Wu, Jingshing; Yeh, Albert C; Shieh, Eric C; Cui, Cheryl; Li, Ang; Polding, Laura C; Ahmed, Rayhnuma; Lim, Kenneth; Lu, Tzong-Shi; Rhee, Connie M; Bonventre, Joseph V

    2014-09-01

    Despite the increasing prevalence of CKD in the United States, there is a declining interest among United States medical graduates in nephrology as a career choice. Effective programs are needed to generate interest at early educational stages when career choices can be influenced. The Kidney Disease Screening and Awareness Program (KDSAP) is a novel program initiated at Harvard College that increases student knowledge of and interest in kidney health and disease, interest in nephrology career paths, and participation in kidney disease research. This model, built on physician mentoring, kidney screening of underserved populations, direct interactions with kidney patients, and opportunities to participate in kidney research, can be reproduced and translated to other workforce-challenged subspecialties. Copyright © 2014 by the American Society of Nephrology.

  8. 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.

  9. Diffusional screening in treelike spaces: An exactly solvable diffusion-reaction model

    Science.gov (United States)

    Mayo, Michael; Gheorghiu, Stefan; Pfeifer, Peter

    2012-01-01

    A renormalization approach is used to derive an analytic formula for the total current crossing the reactive surface of a Cayley tree of cylindrical tubes under a Helmholtz-type approximation to the full diffusion-reaction problem. We provide analytic conditions for the emergence of a plateau in the current—a region of maximum insensitivity of the current to variations in either the reaction rate (membrane permeability) or the diffusivity. The occurrence of such a plateau is associated with a partial screening regime wherein most of the active surface is screened to incoming diffusing particles. Large trees trade efficiency for fault tolerance, a valuable feature which may provide robustness to mammalian respiratory systems and tolerance to catalytic poisoning in chemical reactors.

  10. 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.

  11. 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....

  12. Limitations in a frataxin knockdown cell model for Friedreich ataxia in a high-throughput drug screen

    Directory of Open Access Journals (Sweden)

    Haiech Jacques

    2009-08-01

    Full Text Available Abstract Background Pharmacological high-throughput screening (HTS represents a powerful strategy for drug discovery in genetic diseases, particularly when the full spectrum of pathological dysfunctions remains unclear, such as in Friedreich ataxia (FRDA. FRDA, the most common recessive ataxia, results from a generalized deficiency of mitochondrial and cytosolic iron-sulfur cluster (ISC proteins activity, due to a partial loss of frataxin function, a mitochondrial protein proposed to function as an iron-chaperone for ISC biosynthesis. In the absence of measurable catalytic function for frataxin, a cell-based assay is required for HTS assay. Methods Using a targeted ribozyme strategy in murine fibroblasts, we have developed a cellular model with strongly reduced levels of frataxin. We have used this model to screen the Prestwick Chemical Library, a collection of one thousand off-patent drugs, for potential molecules for FRDA. Results The frataxin deficient cell lines exhibit a proliferation defect, associated with an ISC enzyme deficit. Using the growth defect as end-point criteria, we screened the Prestwick Chemical Library. However no molecule presented a significant and reproducible effect on the proliferation rate of frataxin deficient cells. Moreover over numerous passages, the antisense ribozyme fibroblast cell lines revealed an increase in frataxin residual level associated with the normalization of ISC enzyme activities. However, the ribozyme cell lines and FRDA patient cells presented an increase in Mthfd2 transcript, a mitochondrial enzyme that was previously shown to be upregulated at very early stages of the pathogenesis in the cardiac mouse model. Conclusion Although no active hit has been identified, the present study demonstrates the feasibility of using a cell-based approach to HTS for FRDA. Furthermore, it highlights the difficulty in the development of a stable frataxin-deficient cell model, an essential condition for productive

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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 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.

  18. A simulation model investigating the impact of tumor volume doubling time and mammographic tumor detectability on screening outcomes in women aged 40-49 years.

    Science.gov (United States)

    Bailey, Stephanie L; Sigal, Bronislava M; Plevritis, Sylvia K

    2010-08-18

    Compared with women aged 50-69 years, the lower sensitivity of mammographic screening in women aged 40-49 years is largely attributed to the lower mammographic tumor detectability and faster tumor growth in the younger women. We used a Monte Carlo simulation model of breast cancer screening by age to estimate the median tumor size detectable on a mammogram and the mean tumor volume doubling time. The estimates were calculated by calibrating the predicted breast cancer incidence rates to the actual rates from the Surveillance, Epidemiology, and End Results (SEER) database and the predicted distributions of screen-detected tumor sizes to the actual distributions obtained from the Breast Cancer Surveillance Consortium (BCSC). The calibrated parameters were used to estimate the relative impact of lower mammographic tumor detectability vs faster tumor volume doubling time on the poorer screening outcomes in younger women compared with older women. Mammography screening outcomes included sensitivity, mean tumor size at detection, lifetime gained, and breast cancer mortality. In addition, the relationship between screening sensitivity and breast cancer mortality was investigated as a function of tumor volume doubling time, mammographic tumor detectability, and screening interval. Lowered mammographic tumor detectability accounted for 79% and faster tumor volume doubling time accounted for 21% of the poorer sensitivity of mammography screening in younger women compared with older women. The relative contributions were similar when the impact of screening was evaluated in terms of mean tumor size at detection, lifetime gained, and breast cancer mortality. Screening sensitivity and breast cancer mortality reduction attributable to screening were almost linearly related when comparing annual or biennial screening with no screening. However, when comparing annual with biennial screening, the greatest reduction in breast cancer mortality attributable to screening did not

  19. Behavioral health screening and intervention for women in Argentina: a preliminary model for the childbearing years

    Directory of Open Access Journals (Sweden)

    Suarez Ordoñez RM

    2015-06-01

    Full Text Available Rocio M Suarez Ordoñez,1 Jorgelina Cesolari,2 Casas Ofelia,2 Ivonne Villavicencio,1 Hendrée E Jones31Research Department, Institute of Cognitive Neuroscience INECO Oroño, 2Neonatology Department, Martin Maternity, Rosario, Santa Fe, Argentina; 3UNC Horizons and Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAAbstract: Untreated behavioral disorders in pregnant women and in women of childbearing age pose physical and psychological safety concerns and are barriers to the well-being of both mother and neonate. The present paper underlines the importance of screening in Argentina for behavioral problems in women of childbearing age, particularly pregnant women and their newborns. Emphasized is the need to formalize this comprehensive screening in a protocol that includes domains of mental disorders, behavioral disorders, education, social environment, employment, desire for maternity, substance use including non-prescription use of prescription medications, eating disorders, suicide risk, interpersonal violence, stress, and trauma. Implementation of such a model would require agreement and cooperation between the public and private health sectors as well as in the development of research for validation of the various screening and interventions tools that would be adopted for general use. Keywords: pregnancy, substance use, assessment, measures

  20. 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

    To assess the budgetary impact of switching from screen-film mammography to full-field digital mammography in a population-based breast cancer screening program. 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. 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. 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.

  1. Budget impact analysis of switching to digital mammography in a population-based breast cancer screening program: a discrete event simulation model.

    Directory of Open Access Journals (Sweden)

    Mercè Comas

    Full Text Available 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.

  2. Impact of an Interdisciplinary Deep Brain Stimulation Screening Model on Post-Surgical Complications in Essential Tremor Patients.

    Directory of Open Access Journals (Sweden)

    Masa-aki Higuchi

    Full Text Available To investigate the relationship of our interdisciplinary screening process on post-operative unintended hospitalizations and quality of life.There are currently no standardized criteria for selection of appropriate Deep Brain Stimulation candidates and little hard data exists to support the use of any singular method.An Essential Tremor cohort was selected from our institutional Deep Brain Stimulation database. The interdisciplinary model utilized seven specialties who pre-operatively screened all potential Deep Brain Stimulation candidates. Concerns for surgery raised by each specialty were documented and classified as none, minor, or major. Charts were reviewed to identify unintended hospitalizations and quality of life measurements at 1 year post-surgery.Eighty-six percent (44/51 of the potential screened candidates were approved for Deep Brain Stimulation. Eight (18% patients had an unintended hospitalization during the follow-up period. Patients with minor or major concerns raised by any specialty service had significantly more unintended hospitalizations when compared to patients without concerns (75% vs. 25%, p < 0.005. The rate of hospitalization revealed a direct relationship to the "level of concern"; ranging from 100% if major concerns, 42% if minor concerns, and 7% if no concerns raised, p = 0.001. Quality of life scores significantly worsened in patients with unintended hospitalizations at 6 (p = 0.046 and 12 months (p = 0.027 when compared to baseline scores. No significant differences in tremor scores between unintended and non-unintended hospitalizations were observed.The number and level of concerns raised during interdisciplinary Deep Brain Stimulation screenings were significantly related to unintended hospitalizations and to a reduced quality of life. The interdisciplinary evaluation may help to stratify risk for these complications. However, data should be interpreted with caution due to the limitations of our study. Further

  3. Evaluating the effectiveness of opportunistic eye screening model for people with diabetes attending diabetes clinic at Mnazi Mmoja Hospital, Zanzibar.

    Science.gov (United States)

    Omar, Fatma J; Sheeladevi, Sethu; Rani, Padmaja Kumari; Ning, Geng; Kabona, George

    2014-06-24

    Diabetes and its related microvascular complications like Diabetic retinopathy are showing an alarming rise in developing countries like Zanzibar. Objective of the present study is to evaluate the impact of integrating eye screening for all subjects attending the diabetes clinic at Mnazi Mmoja Hospital in Zanzibar and to estimate the prevalence of visual impairment and diabetic retinopathy among the subjects. This is a cross sectional study involving 356 randomly selected patients who had attended the diabetes clinic between July and August 2012. All subjects underwent comprehensive eye examination including fundus evaluation after dilatation by a cataract surgeon and an ophthalmologist, independently. Data was collected using the designated questionnaire and analysed using the SPSS software. Blindness and visual impairment was defined as presenting VA eye respectively and DR was graded using the International classification of Diabetic Retinopathy severity grading scale. A total of 356/967 subjects were recruited in a duration of 2 months; 176 (49.4%) were male and the mean age was 52.21 (SD 15.3). Targeted eye screening of diabetics showed that 231/356 (65%) of the subjects had eye problems, including potentially blinding conditions that required immediate intervention in contrast to the existing self reported referral where only 10% of an average of 200 diabetics underwent eye checkup in a year. The prevalence of visual impairment was 20.2%; 95% CI: 16.4-24.7 and blindness in 9.3%; 95% CI: 6.7 -12.7. The prevalence of DR was 28.3% and sight-threatening DR was reported in 9%. Among the DR cases, 30% had sight threatening DR including 28% macular edema, 2% severe NPDR and PDR. Multivariate analysis showed a higher risk for any DR in older subjects >50 years (OR: 2.19; 95% CI: 1.14 - 4.25) and in females (OR: 1.92; 95% CI: 1.07 - 3.44). Opportunistic DR screening model achieved higher yield of identification of visual impairment and DR compared to the yield of 10

  4. ''Statistical treatment of the spectral properties of plasmas in local thermodynamical equilibrium using a screened hydrogenic model''

    International Nuclear Information System (INIS)

    Faussurier, G.

    1996-01-01

    A new screened hydrogenic model is presented. The screening constants depend both on the principal n and orbital l quantum numbers. They have been obtained from numerical fits over a large data base containing ionization potentials and one-electron excitation energies of ions. A rapid and original method to compute the bound-bound and bound-free oscillator strengths is proposed. The discrete spectrum and the series continuum are connected by continuity, and the sum rules are respected. The screened hydrogenic average atom is well-adapted to describe multicharged ion plasmas in local thermodynamic equilibrium (LTE). Using the key principle of statistical mechanics, it is shown first that this model is properly defined and thermodynamically coherent. Secondly, a new method of detailed ionization stage accounting of a LTE plasma is explained. It can be used to reconstruct the distribution of integer charge states in such a plasma from any average atom model. The l -splitting allows one-electron transitions between two subshells with the same principal quantum number n. They may be of great importance when the Rosseland opacity is computed. Though, methods of classical statistical mechanics are required to calculate the distribution of the configurations around the average atom one and so to improve the spectral opacities. The splitting in integer ionic stages can be easily included. The formalism is tested by comparisons with theoretical and experimental results published in the literature. From the photoabsorption spectra encountered, the main results are the correct estimations of both the Rosseland opacity and the detailed charge degrees accounting. (author)

  5. 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.

  6. 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/

  7. Early detection of idiopathic scoliosis – analysis of three screening models

    Science.gov (United States)

    Kowalski, Ireneusz M.; Lewandowski, Roman; Pierożyński, Bogusław; Raistenskis, Juozas; J. Krzych, Łukasz; Kiebzak, Wojciech

    2015-01-01

    Introduction The prevalence of lateral curvatures of the spine ranges from 0.3% to 15.3% in the general population. The aim of the study was to develop and compare three different screening tests for idiopathic scoliosis (IS) with respect to their effectiveness and costs. Material and methods The Delphi method was used to assess the efficacy of each screening algorithm in detecting IS in the population. An economic analysis was also performed. Results Diagnostic Algorithm 1 for IS comprised a screening examination performed by nurses and a general practitioner (GP) with verification by specialists. The unit cost of carrying out diagnostic work-up for IS in Algorithm 1 was €94 per child. The second algorithm involved the use of the moiré computer method, followed by verification by a specialist. The lower unit cost of €86 per child of diagnostic work-up according to Algorithm 2 was due to fewer stages compared to Algorithm 1. The highest effectiveness with the highest costs were found for the third algorithm, with only one stage, a specialist's consultation (cost €153 per child). Conclusions The number of stages in an algorithm does not correlate positively with its efficacy or cost. The recommended scheme is Algorithm 3, where children are examined by rehabilitation specialists or a physiotherapist using a scoliometer and an inclinometer. The use of the apparently most expensive scheme (Algorithm 3) should result in lowering the costs of treatment of established idiopathic scoliosis and, in the long term, prove to be the most cost-effective solution for the health care system. PMID:26528351

  8. 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....

  9. PARAFAC modeling of fluorescence excitation-emission spectra of fish bile for rapid en route screening of PAC exposure

    DEFF Research Database (Denmark)

    Christensen, Jan H.; Tomasi, Giorgio; Strand, Jakob

    2009-01-01

    . The EEMs were decomposed into a four-factor PARAFAC model. The comparison of the PARAFAC factors with the EEMs of PAC metabolites and amino acids suggests that two factors are related to PAC metabolites and two correspond to fluorescent residues of tryptophan and tyrosine in bile proteins. A new......Polycyclic aromatic compound (PAC) metabolites in fish bile can be used as biomarkers for recent environmental exposure to PACs. Here, a novel method for rapid screening of nonhydrolyzed fish bile is presented. The method is based on excitation-emission fluorescence spectroscopy combined...

  10. Induced Pluripotent Stem Cell Technology: A Paradigm Shift in Medical Science for Drug Screening and Disease Modeling.

    Science.gov (United States)

    Nair, Meera; Sandhu, Sardul Singh; Sharma, Anil Kumar

    2017-01-01

    Induced Pluripotent Stem Cell (IPSC) Technology is the most advanced research as it offers an attractive alternative for establishing patient-specific IPSCs to recapitulate phenotypes of not only monogenic diseases (viz. Thalassaemia, Sickle cell anemia, Haemophilia, Tay-Sachs disease), but also late-onset polygenic diseases (viz. Parkinson's disease, Alzheimer's disease, schizophrenia). Over the hindsight, numerous studies of the past and current scientists have led to the production, maturation and understanding of induced pluripotent stem cell technology and its use in basic and clinical research. A systematic search of peer-reviewed scientific literature and clinical trials in public databases were carried out to summarize the evidence on the use of IPSC. Current review sheds light upon the use of patient-derived iPSC models in drug toxicity, screening and discovery which have been derived after referring to more than 200 articles in literature. Furthermore, their use as disease models was also studied signifying the versatility of iPSC lines. Through this review, we describe the advent of iPSC technology, where we comprehensively cover the generation of iPSCs and their characterization along with their prospective applications using IPSC banks in disease modeling and drug screening. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Family psychosocial risk screening guided by the Pediatric Psychosocial Preventative Health Model (PPPHM) using the Psychosocial Assessment Tool (PAT).

    Science.gov (United States)

    Kazak, Anne E; Schneider, Stephanie; Didonato, Stephen; Pai, Ahna L H

    2015-05-01

    Although families of children with cancer and other serious medical conditions have documented psychosocial needs, the systematic identification of needs and delivery of evidence-based care remain challenges. Screening for multifaceted family psychosocial risk is a means by which psychosocial treatment needs for pediatric patients and their families can be identified in an effective and inclusive manner. The Pediatric Psychosocial Preventative Health Model (PPPHM) is a model that can guide systematic assessment of family psychosocial risk. The Psychosocial Assessment Tool (PAT) is a brief parent report screener of psychosocial risk based on the PPPHM that can be used for families of infants through adolescents. The PPPHM and the PAT are described in this paper, along with a summary of data supporting systematic risk assessment. The PPPHM outlines three tiers of family psychosocial risk - Universal (low), Targeted (medium), and Clinical (high). The PAT is a validated measure of psychosocial risk. Scores on the PAT, derived from multiple sites and disease conditions, map on to the PPPHM with indications that one-half to two-thirds of families score at the Universal level of risk based on the PAT. The PAT is a unique screener of psychosocial risk, both in terms of its breadth and underlying model (PPPHM), and its length and format. As an example of a means by which families can be screened early in the treatment process, PAT scores and corresponding PPPHM levels can provide direction for the delivery of evidence-based psychosocial care.

  12. A GIS model-based screening of potential contamination of soil and water by pyrethroids in Europe.

    Science.gov (United States)

    Pistocchi, A; Vizcaino, P; Hauck, M

    2009-08-01

    The paper presents a geographic information system (GIS) model-based approach for analysis of potential contamination of soil and water by pyrethroids for the European continent. Pyrethroids are widely used pesticides and their chemical and toxicological characteristics suggest there may be concerns about human health and ecosystems, although so far there is no strong evidence indicating actual risk. However, little monitoring has been conducted and limited experimental information is available. We perform an assessment exercise that demonstrates how accessible information and GIS-based modeling allow to estimate the spatial distribution of chemical concentrations and fluxes at a screening level. The assessment highlights potential hot spots and the main environmental transport pathways, in a quick and simple way. By combining information on pesticide use, crop distribution and landscape and climate parameters we identify potential problem areas to help focusing monitoring campaigns. The approach presented here is simple and fast, and can be applied to virtually all pesticide classes used over a large domain, and is therefore suitable for the screening of large quantities of chemicals, of which the majority has not undergone any systematic environmental monitoring program. The method has been tested through benchmarking with other well-established models. However, further research is needed to evaluate it against experimental observations.

  13. 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.

  14. 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.

  15. 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.

    Science.gov (United States)

    Ousset, Aymeric; Chavez, Pierre-François; Meeus, Joke; Robin, Florent; Schubert, Martin Alexander; Somville, Pascal; Dodou, Kalliopi

    2018-03-07

    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 ( T g 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.

  16. 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

  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; Guelcher, Scott A

    2017-01-01

    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 vs. 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 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 that recapitulate the physical and cellular properties of the tissue microenvironment for investigating mechanisms of disease progression and for screening drugs.

  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. 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.

  20. 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.

  1. 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...

  2. Tele-diabetology to Screen for Diabetes and Associated Complications in Rural India: The Chunampet Rural Diabetes Prevention Project Model.

    Science.gov (United States)

    Mohan, Viswanathan; Prathiba, Vijayaraghavan; Pradeepa, Rajendra

    2014-03-01

    Diabetes, with its acute and long-term complications, has become a major health hazard in developing countries. An estimated 62.4 million people in India have diabetes. With increasing urbanization and industrialization, we can expect huge numbers of people with diabetes in India in the future. Moreover, all diabetes efforts in India are currently focused in urban areas while 70% of India's population actually lives in rural areas. The current statistics demonstrates that urgent interventions are mandatory to curb the epidemic of diabetes and its complications at the grassroots level. This gap in providing diabetes care can be nullified by the use of tele-diabetology. This holds great potential to overcome barriers and improve quality and access to diabetes care to remote, underserved areas of developing counties. The Chunampet Rural Diabetes Prevention Project (CRDPP) has been developed and tested as a successful model for screening and delivering diabetes care to rural areas in developing countries. Using a tele-diabetology mobile van loaded with appropriate equipment, trained technicians, and satellite technology helped us to screen for diabetes and its complications and deliver diabetes care to remote villages in southern India. The Chunampet model can be applied in reaching out to remote areas where specialized diabetes care facilities may not be available. © 2014 Diabetes Technology Society.

  3. 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.

  4. 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.

  5. 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....... In this study, a MOS based on multiple linear regression is proposed: the model screens the most relevant NWP forecast variables and selects the best predictors to fit a regression equation that minimizes the forecast errors, utilizing wind farm power output measurements as input. The performance of the method...... is evaluated in two wind farms, located in different topographical areas and with different NWP grid spacing. Because of the high seasonal variability of NWP forecasts, it was considered appropriate to implement monthly stratified MOS. In both wind farms, the first predictors were always wind speeds (at...

  6. 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.

  7. 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.

  8. Health belief model and practice of breast self-examination and breast cancer screening in Iranian women.

    Science.gov (United States)

    Hajian-Tilaki, Karimollah; Auladi, Sahar

    2014-07-01

    The objective of this study is to determine the role of different health belief model components in practice of breast cancer screening among Iranian women. A cross-sectional study of 500 women aged 18-65 years was conducted in an urban population under the coverage of a health therapeutic system in Babol, northern Iran in 2012. Demographic data and data regarding practice of breast self-examination (BSE), breast clinical examination (BCE), and mammography were collected by interview, and a standard health belief model questionnaire was used to assess women's attitudes in six different domains based on a Likert scale that ranked from 1 to 5. The average score of each item for each domain was calculated. The Wilcoxon rank test and a multiple logistic regression model were used to estimate the odds ratio of each domain for performing breast cancer screening (BSE, BCE, and mammography). The mean age of the women was 31.2 (9.4) years. Overall, the average scores in domains of perceived benefit, self-efficacy, and health motivation were significantly higher among those who performed BSE and BCE, but not for mammography. For the domains of perception of susceptibility, seriousness, and barriers, no significant differences were observed. Higher scores on the scales of perceived benefits, perceived confidence/self-efficacy, and health motivation showed significant positive association with performing BSE [adjusted OR (95 % confidence interval [CI]) 1.73 (1.11, 2.72), 4.01 (2.39, 6.73), and 2.01 (1.30, 3.08), respectively] and BCE [adjusted OR (95 % CI) 1.65 (1.0, 2.95), 2.33 (1.39, 3.91), and 1.58 (1.0, 2.53), respectively], but not for performing mammography. For perceived susceptibility, perceived seriousness, and barriers, no significant association was observed. Positive attitudes toward perceived benefits, perceived confidence/self-efficacy, and health motivation have a strong association with performing BSE and BCE. The impact of health belief model subscales on

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

    OpenAIRE

    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

    2016-01-01

    Objective: 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. Setting: Computer-based simulation m...

  10. 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.

  11. 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.

  12. 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

  13. Screening for angiogenic inhibitors in zebrafish to evaluate a predictive model for developmental vascular toxicity.

    Science.gov (United States)

    Tal, Tamara; Kilty, Claire; Smith, Andrew; LaLone, Carlie; Kennedy, Brendán; Tennant, Alan; McCollum, Catherine W; Bondesson, Maria; Knudsen, Thomas; Padilla, Stephanie; Kleinstreuer, Nicole

    2017-06-01

    Chemically-induced vascular toxicity during embryonic development may cause a wide range of adverse effects. To identify putative vascular disrupting chemicals (pVDCs), a predictive pVDC signature was constructed from 124 U.S. EPA ToxCast high-throughput screening (HTS) assays and used to rank 1060 chemicals for their potential to disrupt vascular development. Thirty-seven compounds were selected for targeted testing in transgenic Tg(kdrl:EGFP) and Tg(fli1:EGFP) zebrafish embryos to identify chemicals that impair developmental angiogenesis. We hypothesized that zebrafish angiogenesis toxicity data would correlate with human cell-based and cell-free in vitro HTS ToxCast data. Univariate statistical associations used to filter HTS data based on correlations with zebrafish angiogenic inhibition in vivo revealed 132 total significant associations, 33 of which were already captured in the pVDC signature, and 689 non-significant assay associations. Correlated assays were enriched in cytokine and extracellular matrix pathways. Taken together, the findings indicate the utility of zebrafish assays to evaluate an HTS-based predictive toxicity signature and also provide an experimental basis for expansion of the pVDC signature with novel HTS assays. Published by Elsevier Inc.

  14. A conservative vapour intrusion screening model of oxygen-limited hydrocarbon vapour biodegradation accounting for building footprint size.

    Science.gov (United States)

    Knight, John H; Davis, Gregory B

    2013-12-01

    Petroleum hydrocarbon vapours pose a reduced risk to indoor air due to biodegradation processes where oxygen is available in the subsurface or below built structures. However, no previous assessment has been available to show the effects of a building footprint (slab size) on oxygen-limited hydrocarbon vapour biodegradation and the potential for oxygen to be present beneath the entire sub-slab region of a building. Here we provide a new, conservative and conceptually simple vapour screening model which links oxygen and hydrocarbon vapour transport and biodegradation in the vicinity and beneath an impervious slab. This defines when vapour risk is insignificant, or conversely when there is potential for vapour to contact the sub-slab of a building. The solution involves complex mathematics to determine the position of an unknown boundary interface between oxygen diffusing in from the ground surface and vapours diffusing upwards from a subsurface vapour source, but the mathematics reduces to a simple relationship between the vapour source concentration and the ratio of the half slab width and depth to the vapour source. Data from known field investigations are shown to be consistent with the model predictions. Examples of 'acceptable' slab sizes for vapour source depths and strengths are given. The predictions are conservative as an estimator of when petroleum hydrocarbon vapours might come in contact with a slab-on-ground building since additional sources of oxygen due to advective flow or diffusion through the slab are ignored. As such the model can be used for screening sites for further investigation. © 2013.

  15. 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

  16. 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

  17. Pre-clinical in vivo models for the screening of bone biomaterials for oral/craniofacial indications: focus on small-animal models.

    Science.gov (United States)

    Stavropoulos, Andreas; Sculean, Anton; Bosshardt, Dieter D; Buser, Daniel; Klinge, Björn

    2015-06-01

    Preclinical in vivo experimental studies are performed for evaluating proof-of-principle concepts, safety and possible unwanted reactions of candidate bone biomaterials before proceeding to clinical testing. Specifically, models involving small animals have been developed for screening bone biomaterials for their potential to enhance bone formation. No single model can completely recreate the anatomic, physiologic, biomechanic and functional environment of the human mouth and jaws. Relevant aspects regarding physiology, anatomy, dimensions and handling are discussed in this paper to elucidate the advantages and disadvantages of small-animal models. Model selection should be based not on the 'expertise' or capacities of the team, but rather on a scientifically solid rationale, and the animal model selected should reflect the question for which an answer is sought. The rationale for using heterotopic or orthotopic testing sites, and intraosseous, periosseous or extraskeletal defect models, is discussed. The paper also discusses the relevance of critical size defect modeling, with focus on calvarial defects in rodents. In addition, the rabbit sinus model and the capsule model in the rat mandible are presented and discussed in detail. All animal experiments should be designed with care and include sample-size and study-power calculations, thus allowing generation of meaningful data. Moreover, animal experiments are subject to ethical approval by the relevant authority. All procedures and the postoperative handling and care, including postoperative analgesics, should follow best practice. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. 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.

  19. 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

  20. 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

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

    Directory of Open Access Journals (Sweden)

    Michael W. Gaultois

    2016-05-01

    Full Text Available 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.

  2. Modelling, screening, and solving of optimisation problems: Application to industrial metal forming processes

    NARCIS (Netherlands)

    Bonte, M.H.A.; van den Boogaard, Antonius H.; Veldman, E.

    2007-01-01

    Coupling Finite Element (FEM) simulations to mathematical optimisation techniques provides a high potential to improve industrial metal forming processes. In order to optimise these processes, all kind of optimisation problems need to be mathematically modelled and subsequently solved using an

  3. Screening and vaccination as determined by the Social Ecological Model and the Theory of Triadic Influence: a systematic review.

    Science.gov (United States)

    Nyambe, Anayawa; Van Hal, Guido; Kampen, Jarl K

    2016-11-17

    Vaccination and screening are forms of primary and secondary prevention methods. These methods are recommended for controlling the spread of a vast number of diseases and conditions. To determine the most effective preventive methods to be used by a society, multi-level models have shown to be more effective than models that focus solely on individual level characteristics. The Social Ecological Model (SEM) and the Theory of Triadic Influence (TTI) are such models. The purpose of this systematic review was to identify main differences and similarities of SEM and TTI regarding screening and vaccination in order to prepare potentially successful prevention programs for practice. A systematic review was conducted. Separate literature searches were performed during January and February 2015 using Medline, Ovid, Proquest, PubMed, University of Antwerp Discovery Service and Web of Science, for articles that apply the SEM and TTI. A Data Extraction Form with mostly closed-end questions was developed to assist with data extraction. Aggregate descriptive statistics were utilized to summarize the general characteristics of the SEM and TTI as documented in the scientific literature. A total of 290 potentially relevant articles referencing the SEM were found. As for the TTI, a total of 131 potentially relevant articles were found. After strict evaluation for inclusion and exclusion criteria, 40 SEM studies and 46 TTI studies were included in the systematic review. The SEM and TTI are theoretical frameworks that share many theoretical concepts and are relevant for several types of health behaviors. However, they differ in the structure of the model, and in how the variables are thought to interact with each other, the TTI being a matrix while the SEM has a ring structure. The main difference consists of the division of the TTI into levels of causation (ultimate, distal and proximal) which are not considered within the levels of the SEM. It was further found that in the articles

  4. 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

  5. A review on animal models for screening potential anti-stress agents.

    Science.gov (United States)

    Jaggi, Amteshwar Singh; Bhatia, Nitish; Kumar, Naresh; Singh, Nirmal; Anand, Preet; Dhawan, Ravi

    2011-12-01

    Stress is a state of threatened homeostasis that produces different physiological as well as pathological changes depending on severity, type and duration of stress. The animal models are pivotal for understanding the pathophysiology of stress-induced behavioral alterations and development of effective therapy for its optimal management. A battery of models has been developed to simulate the clinical pain conditions with diverse etiology. An ideal animal model should be able to reproduce each of the aspects of stress response and should be able to mimic the natural progression of the disease. The present review describes the different types of acute and chronic stress models including immersion in cold water with no escape, cold environment isolation, immobilization/restraint-induced stress, cold-water restraint stress, electric foot shock-induced stress, forced swimming-induced stress, food-deprived activity stress, neonatal isolation-induced stress, predatory stress, day-night light change-induced stress, noise-induced stress, model of post-traumatic stress disorder and chronic unpredictable stress models.

  6. Model for High-Throughput Screening of Multitarget Drugs in Chemical Neurosciences: Synthesis, Assay, and Theoretic Study of Rasagiline Carbamates

    Science.gov (United States)

    2013-01-01

    The disappointing results obtained in recent clinical trials renew the interest in experimental/computational techniques for the discovery of neuroprotective drugs. In this context, multitarget or multiplexing QSAR models (mt-QSAR/mx-QSAR) may help to predict neurotoxicity/neuroprotective effects of drugs in multiple assays, on drug targets, and in model organisms. In this work, we study a data set downloaded from CHEMBL; each data point (>8000) contains the values of one out of 37 possible measures of activity, 493 assays, 169 molecular or cellular targets, and 11 different organisms (including human) for a given compound. In this work, we introduce the first mx-QSAR model for neurotoxicity/neuroprotective effects of drugs based on the MARCH-INSIDE (MI) method. First, we used MI to calculate the stochastic spectral moments (structural descriptors) of all compounds. Next, we found a model that classified correctly 2955 out of 3548 total cases in the training and validation series with Accuracy, Sensitivity, and Specificity values > 80%. The model also showed excellent results in Computational-Chemistry simulations of High-Throughput Screening (CCHTS) experiments, with accuracy = 90.6% for 4671 positive cases. Next, we reported the synthesis, characterization, and experimental assays of new rasagiline derivatives. We carried out three different experimental tests: assay (1) in the absence of neurotoxic agents, assay (2) in the presence of glutamate, and assay (3) in the presence of H2O2. Compounds 11 with 27.4%, 8 with 11.6%, and 9 with 15.4% showed the highest neuroprotective effects in assays (1), (2), and (3), respectively. After that, we used the mx-QSAR model to carry out a CCHTS of the new compounds in >400 unique pharmacological tests not carried out experimentally. Consequently, this model may become a promising auxiliary tool for the discovery of new drugs for the treatment of neurodegenerative diseases. PMID:23855599

  7. 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.

    2018-01-01

    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 γB charge pairs. We model intrinsic pK values that would occur hypothetically in the absence of other charges, with use of experimental data on the dependence of pK 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 pK values for isolated γB molecules and we calculate the probabilities of leading proton occupancy configurations, for 4 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 pK values alone and estimate the extents to which γB charge pattern distributions broaden at lower pH and narrow as ionic strength is lowered. These results suggest that for accurate modeling of orientation-dependent γB-γB interactions, consideration of numerous pairs of proton occupancy patterns will be needed. PMID:29346981

  8. Zebrafish as a Screening Model for Testing the Permeability of Blood-Brain Barrier to Small Molecules.

    Science.gov (United States)

    Kim, Seong Soon; Im, So Hee; Yang, Jung Yoon; Lee, Yu-Ri; Kim, Geum Ran; Chae, Jin Sil; Shin, Dae-Seop; Song, Jin Sook; Ahn, Sunjoo; Lee, Byung Hoi; Woo, Jae Chun; Ahn, Jin Hee; Yun, Chang Soo; Kim, Phiho; Kim, Hyoung Rae; Lee, Kyeong-Ryoon; Bae, Myung Ae

    2017-08-01

    The objective of this study was to evaluate the permeability of small molecules into the brain via the blood-brain barrier in zebrafish and to investigate the possibility of using this animal model as a screening tool during the early stages of drug discovery. Fifteen compounds were used to understand the permeation into the brain in zebrafish and mice. The ratio of brain-to-plasma concentration was compared between the two animal models. The partition coefficient (K p,brain ), estimated using the concentration ratio at designated times (0.167, 0.25, 0.5, or 2 h) after oral administrations (per os, p.o), ranged from 0.099 to 5.68 in zebrafish and from 0.080 to 11.8 in mice. A correlation was observed between the K p,brain values obtained from the zebrafish and mice, suggesting that zebrafish can be used to estimate K p,brain to predict drug penetration in humans. Furthermore, in vivo transport experiments to understand the permeability glycoprotein (P-gp) transporter-mediated behavior of loperamide (LPM) in zebrafish were performed. The zebrafish, K p,brain,30min of LPM was determined to be 0.099 ± 0.069 after dosing with LPM alone, which increased to 0.180 ± 0.115 after dosing with LPM and tariquidar (TRQ, an inhibitor of P-gp). In mouse, the K p,brain,30min of LPM was determined to be 0.080 ± 0.004 after dosing with LPM alone and 0.237 ± 0.013 after dosing with LPM and TRQ. These findings indicate that the zebrafish could be used as an effective screening tool during the discovery stages of new drugs to estimate their distribution in the brain.

  9. Cancer Screening

    Directory of Open Access Journals (Sweden)

    Krishna Prasad

    2004-10-01

    Full Text Available Cancer screening is a means to detect cancer early with the goal of decreasing morbidity and mortality. At present, there is a reasonable consensus regarding screening for breast, cervical and colorectal cances and the role of screening is under trial in case of cancers of the lung,  ovaries and prostate. On the other hand, good screening tests are not available for some of the commonest cancers in India like the oral, pharyngeal, esophageal and stomach cancers.

  10. 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.

  11. Full-band Monte Carlo model with screened pseudopotential based phonon scattering rates for a lattice with basis

    Science.gov (United States)

    Nguyen, Phuong Hoa; Hofmann, Karl R.; Paasch, Gernot

    2002-11-01

    In advanced full-band Monte Carlo (MC) models, the Nordheim approximation with a spherical Wigner-Seitz cell for a lattice with two atoms per elementary cell is still common, and in the most detailed work on silicon by Kunikiyo [et al.] [J. Appl. Phys. 74, 297 (1994)], the atomic positions in the cell have been incorrectly introduced in the phonon scattering rates. In this article the correct expressions for the phonon scattering rates based on the screened pseudopotential are formulated for the case of several atoms per unit cell. Furthermore, the simplest wave number dependent approximation is introduced, which contains an average of the cell structure factor and the acoustic and the optical deformation potentials as two parameters to be fitted. While the band structure is determined by the pseudopotential at the reciprocal lattice vectors, the phonon scattering rates are essentially determined by wave numbers below the smallest reciprocal lattice vector. Thus, in the phonon scattering rates, the pseudopotential form factor is modeled by the simple Ashcroft model potential, in contrast to the full band structure, which is calculated using a nonlocal pseudopotential scheme. The parameter in the Ashcroft model potential is determined using a method based on the equilibrium condition. For the screening of the pseudopotential form factor, the Lindhard dielectric function is used. Compared to the Nordheim approximation with a spherical Wigner-Seitz cell, the approximation results in up to 10% lower phonon scattering rates. Examples from a detailed comparison of the influence of the two deformation potentials on the electron and hole drift velocities are presented for Ge and Si at different temperatures. The results are prerequisite for a well-founded choice of the two deformation potentials as fit parameters and they provide an explanation of the differences between the two materials, the origin of the anisotropy of the drift velocities, and the origin of the dent in

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    to limited exposure data there is limited information on chemical use patterns and production and emission quantities. These data gaps require the application of mass balance, statistical and quantitative structure-activity relationship (QSAR) models to predict exposure and exposure potential for humans...... 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......Chemical risk estimation requires quantitative information on exposures and toxicological effects. Quantitative exposure information can include chemical intake rates and (bio)monitoring data; however, such information does not exist for the vast majority of marketed chemicals. In addition...

  13. 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.

  14. 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

  15. 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

  16. Forecasting Human African Trypanosomiasis Prevalences from Population Screening Data Using Continuous Time Models

    NARCIS (Netherlands)

    H. de Vries (Harwin); A.P.M. Wagelmans (Albert); E.C. Hasker (Epco C.); C. Lumbala (Crispin); P. Lutumba (Pascal); S.J. de Vlas (Sake); J. van de Klundert (Joris)

    2016-01-01

    textabstractTo eliminate and eradicate gambiense human African trypanosomiasis (HAT), maximizing the effectiveness of active case finding is of key importance. The progression of the epidemic is largely influenced by the planning of these operations. This paper introduces and analyzes five models

  17. 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.

  18. Modelling physico-chemical properties of (benzo)triazoles, and screening for environmental partitioning.

    Science.gov (United States)

    Bhhatarai, B; Gramatica, P

    2011-01-01

    (Benzo)triazoles are distributed throughout the environment, mainly in water compartments, because of their wide use in industry where they are employed in pharmaceutical, agricultural and deicing products. They are hazardous chemicals that adversely affect humans and other non-target species, and are on the list of substances of very high concern (SVHC) in the new European regulation of chemicals - REACH (Registration, Evaluation, Authorization and Restriction of Chemical substances). Thus there is a vital need for further investigations to understand the behavior of these compounds in biota and the environment. In such a scenario, physico-chemical properties like aqueous solubility, hydrophobicity, vapor pressure and melting point can be useful. However, the limited availability and the high cost of lab testing prevents the acquisition of necessary experimental data that industry must submit for the registration of these chemicals. In such cases a preliminary analysis can be made using Quantitative Structure-Property Relationships (QSPR) models. For such an analysis, we propose Multiple Linear Regression (MLR) models based on theoretical molecular descriptors selected by Genetic Algorithm (GA). Training and prediction sets were prepared a priori by splitting the available experimental data, which were then used to derive statistically robust and predictive (both internally and externally) models. These models, after verification of their structural applicability domain (AD), were used to predict the properties of a total of 351 compounds, including those in the REACH preregistration list. Finally, Principal Component Analysis was applied to the predictions to rank the environmental partitioning properties (relevant for leaching and volatility) of new and untested (benzo)triazoles within the AD of each model. Our study using this approach highlighted compounds dangerous for the aquatic compartment. Similar analyses using predictions obtained by the EPI Suite and

  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. Using logistic regression modeling to predict sexual recidivism: the Minnesota Sex Offender Screening Tool-3 (MnSOST-3).

    Science.gov (United States)

    Duwe, Grant; Freske, Pamela J

    2012-08-01

    This study presents the results from efforts to revise the Minnesota Sex Offender Screening Tool-Revised (MnSOST-R), one of the most widely used sex offender risk-assessment tools. The updated instrument, the MnSOST-3, contains nine individual items, six of which are new. The population for this study consisted of the cross-validation sample for the MnSOST-R (N = 220) and a contemporary sample of 2,315 sex offenders released from Minnesota prisons between 2003 and 2006. To score and select items for the MnSOST-3, we used predicted probabilities generated from a multiple logistic regression model. We used bootstrap resampling to not only refine our selection of predictors but also internally validate the model. The results indicate the MnSOST-3 has a relatively high level of predictive discrimination, as evidenced by an apparent AUC of .821 and an optimism-corrected AUC of .796. The findings show the MnSOST-3 is well calibrated with actual recidivism rates for all but the highest risk offenders. Although estimating a penalized maximum likelihood model did not improve the overall calibration, the results suggest the MnSOST-3 may still be useful in helping identify high-risk offenders whose sexual recidivism risk exceeds 50%. Results from an interrater reliability assessment indicate the instrument, which is scored in a Microsoft Excel application, has an adequate degree of consistency across raters (ICC = .83 for both consistency and absolute agreement).

  1. 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

  2. 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.

  3. Testing of Snorre Field Foam Assisted Water Alternating Gas (FAWAG Performance in New Foam Screening Model

    Directory of Open Access Journals (Sweden)

    Spirov Pavel

    2015-11-01

    Full Text Available Eclipse Functional Foam Model was used in order to provide a guideline for the history matching process (Gas-Oil Ratio (GOR, oil and gas production rates to the Foam Assisted Water Alternating Gas method in the Snorre field, Norway, where the surfactant solution was injected in two slugs to control gas mobility and prevent gas breakthrough. The simulation showed that the first short slug was not efficient while significant GOR decrease and incremental oil production was obtained after the second longer slug in some periods. This study shows that the Eclipse foam model is applicable to the planning of water and gas injections, the testing of various surfactant properties, and the evaluation of the efficiency of the method at the field scale.

  4. QSAR Classification Model for Antibacterial Compounds and Its Use in Virtual Screening

    Science.gov (United States)

    2012-09-26

    Romero -Zaldivar, V.; Castro, E. A. Atom, atom-type, and total nonstochastic and stochastic quadratic fingerprints: a promising approach for modeling...Gimenez, F.; Garcia-March, F. J.; Salabert- Salvador , M. T.; Diaz-Villanueva, W.; Castro-Bleda, M. J.; Villanueva-Pareja, A. Artificial neural networks and...19) Murcia-Soler, M.; Perez-Gimenez, F.; Garcia-March, F. J.; Salabert- Salvador , M. T.; Diaz-Villanueva, W.; Medina-Casamayor, P. Discrimination and

  5. 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.

  6. 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

  7. 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...

  8. 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 ...

  9. Implications of CISNET modeling on number needed to screen and mortality reduction with digital mammography in women 40-49 years old.

    Science.gov (United States)

    Hendrick, R Edward; Helvie, Mark A; Hardesty, Lara A

    2014-12-01

    In this article, we evaluate the implications of recent Cancer Intervention and Surveillance Modeling Network (CISNET) modeling of benefits and harms of screening to women 40-49 years old using annual digital mammography. We show that adding annual digital mammography of women 40-49 years old to biennial screening of women 50-74 years old increases lives saved by 27% and life-years gained by 47%. Annual digital mammography in women 40-49 years old saves 42% more lives and life-years than biennial digital mammography. The number needed to screen to save one life (NNS) with annual digital mammography in women 40-49 years old is 588.

  10. Use of the caco-2 model in the screening of polluting substance toxicity.

    Science.gov (United States)

    Velarde, G; Ait-Aissa, S; Gillet, C; Rogerieux, F; Lambre, C; Vindimian, E; Porcher, J M

    1999-01-01

    The aim of this work was to investigate the oral toxicity of representative chemicals chosen from each class of the list of 132 substances present in industrial effluents after the EEC Directive 76-464. Owing to its characterization as a model of the intestinal epithelium, the CaCo-2 cell line model was chosen. Cytotoxicity was assayed using the tetrazolium blue (MTT) test. For most of the substances, a linear correlation was observed between the octanol/water partition coefficient (log Kw) and the median inhibition concentration (IC(50)). This relationship between lipophilicity and toxicity is the hallmark of a narcotic mechanism of action. However, diethylamine appeared more toxic than the correlation would predict. Other amines were then tested (tert-butylamine, n-butylamine and benzylamine). All of these did not fit into the baseline correlation. The IC(50) were corrected by taking into account only the non-ionized, lipid insoluble, concentration at pH7.3. The amines still did not fit into the correlation, reinforcing the idea of a non-narcotic mechanism. The toxicity of a large number of substances can thus be predicted from their physico-chemical properties only when the substances exert a direct and non-specific effect. The amines appeared more toxic than substances with the same partition coefficient, showing that knowledge of the only lipophilicity is too restrictive to predict toxicity.

  11. A three-groups model for high-throughput survival screens.

    Science.gov (United States)

    Shaby, Benjamin A; Skibinski, Gaia; Ando, Michael; LaDow, Eva S; Finkbeiner, Steven

    2016-09-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by the progressive deterioration of motor neurons in the cortex and spinal cord. Using an automated robotic microscope platform that enables the longitudinal tracking of thousands of single neurons, we examine the effects a large library of compounds on modulating the survival of primary neurons expressing a mutation known to cause ALS. The goal of our analysis is to identify the few potentially beneficial compounds among the many assayed, the vast majority of which do not extend neuronal survival. This resembles the large-scale simultaneous inference scenario familiar from microarray analysis, but transferred to the survival analysis setting due to the novel experimental setup. We apply a three-component mixture model to censored survival times of thousands of individual neurons subjected to hundreds of different compounds. The shrinkage induced by our model significantly improves performance in simulations relative to performing treatment-wise survival analysis and subsequent multiple testing adjustment. Our analysis identified compounds that provide insight into potential novel therapeutic strategies for ALS. © 2016, The International Biometric Society.

  12. 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

  13. Dissecting electrostatic screening, specific ion binding, and ligand binding in an energetic model for glycine riboswitch folding

    Energy Technology Data Exchange (ETDEWEB)

    Lipfert, Jan; Sim, Adelene Y.L.; Herschlag, Daniel; Doniach, Sebastian (Stanford)

    2010-09-17

    Riboswitches are gene-regulating RNAs that are usually found in the 5{prime}-untranslated regions of messenger RNA. As the sugar-phosphate backbone of RNA is highly negatively charged, the folding and ligand-binding interactions of riboswitches are strongly dependent on the presence of cations. Using small angle X-ray scattering (SAXS) and hydroxyl radical footprinting, we examined the cation dependence of the different folding stages of the glycine-binding riboswitch from Vibrio cholerae. We found that the partial folding of the tandem aptamer of this riboswitch in the absence of glycine is supported by all tested mono- and divalent ions, suggesting that this transition is mediated by nonspecific electrostatic screening. Poisson-Boltzmann calculations using SAXS-derived low-resolution structural models allowed us to perform an energetic dissection of this process. The results showed that a model with a constant favorable contribution to folding that is opposed by an unfavorable electrostatic term that varies with ion concentration and valency provides a reasonable quantitative description of the observed folding behavior. Glycine binding, on the other hand, requires specific divalent ions binding based on the observation that Mg{sup 2+}, Ca{sup 2+}, and Mn{sup 2+} facilitated glycine binding, whereas other divalent cations did not. The results provide a case study of how ion-dependent electrostatic relaxation, specific ion binding, and ligand binding can be coupled to shape the energetic landscape of a riboswitch and can begin to be quantitatively dissected.

  14. 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.

  15. Peripheral arterial disease screening for hemodialysis patients using a fractional-order integrator and transition probability decision-making model.

    Science.gov (United States)

    Wu, Jian-Xing; Li, Chien-Ming; Chen, Guan-Chun; Ho, Yueh-Ren; Lin, Chia-Hung

    2017-04-01

    Atherosclerosis and resultant peripheral arterial disease (PAD) are common complications in patients with type 2 diabetes mellitus or end-stage renal disease and in elderly patients. The prevalence of PAD is higher in patients receiving haemodialysis therapy. For early assessment of arterial occlusion using bilateral photoplethysmography (PPG), such as changes in pulse transit time and pulse shape, bilateral timing differences could be used to identify the risk level of PAD. Hence, the authors propose a discrete fractional-order integrator to calculate the bilateral area under the systolic peak (AUSP). These indices indicated the differences in both rise-timing and amplitudes of PPG signals. The dexter and sinister AUSP ratios were preliminarily used to separate the normal condition from low/high risk of PAD. Then, transition probability-based decision-making model was employed to evaluate the risk levels. The joint probability could be specified as a critical threshold, < 0.81, to identify the true positive for screening low or high risk level of PAD, referring to the patients' health records. In contrast to the bilateral timing differences and traditional methods, the proposed model showed better efficiency in PAD assessments and provided a promising strategy to be implemented in an embedded system.

  16. 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

  17. 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.

  18. Evaluation of primary HPV-DNA testing in relation to visual inspection methods for cervical cancer screening in rural China: an epidemiologic and cost-effectiveness modelling study

    Directory of Open Access Journals (Sweden)

    Kang Yoon-Jung

    2011-06-01

    Full Text Available Abstract Background A new lower-cost rapid-throughput human papillomavirus (HPV test (careHPV, Qiagen, Gaithersburg, USA has been shown to have high sensitivity for the detection of high grade cervical intraepithelial neoplasia. Methods We assessed the outcomes and cost-effectiveness of careHPV screening in rural China, compared to visual inspection with acetic acid, when used alone (VIA or in combination with Lugol's iodine (VIA/VILI. Using data on sexual behaviour, test accuracy, diagnostic practices and costs from studies performed in rural China, we estimated the cost-effectiveness ratio (CER and associated lifetime outcomes for once-lifetime and twice-lifetime screening strategies, and for routine screening at 5-yearly, 10-yearly and IARC-recommended intervals. The optimal age range for once-lifetime screening was also assessed. Results For all strategies, the relative ordering of test technologies in reducing cervical cancer incidence and mortality was VIA (least effective; VIA/VILI; careHPV@1.0 pg/ml and careHPV@0.5 pg/ml (most effective. For once-lifetime strategies, maximum effectiveness was achieved if screening occurred between 35-50 years. Assuming a participation rate of ~70%, once-lifetime screening at age 35 years would reduce cancer mortality by 8% (for VIA to 12% (for careHPV@0.5 over the long term, with a CER of US$557 (for VIA to $959 (for careHPV@1.0 per life year saved (LYS compared to no intervention; referenced to a 2008 GDP per capita in Shanxi Province of $2,975. Correspondingly, regular screening with an age-standardised participation rate of 62% (which has been shown to be achievable in this setting would reduce cervical cancer mortality by 19-28% (for 10-yearly screening to 43-54% (using IARC-recommended intervals, with corresponding CERs ranging from $665 (for 10-yearly VIA to $2,269 (for IARC-recommended intervals using careHPV@1.0 per LYS. Conclusions This modelled analysis suggests that primary careHPV screening

  19. 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).

  20. 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.

  1. Fast Screening Technology for Drug Emergency Management: Predicting Suspicious SNPs for ADR with Information Theory-based Models.

    Science.gov (United States)

    Liang, Zhaohui; Liu, Jun; Huang, Jimmy Xiangji; Zeng, Xing

    2018-01-14

    The genetic polymorphism of Cytochrome P450 (CYP 450) is considered as one of the main causes for adverse drug reactions (ADRs). In order to explore the latent correlations between ADRs and potentially corresponding single-nucleotide polymorphism (SNPs) in CYP450, three algorithms based on information theory are used as the main method to predict the possible relation. The study uses a retrospective case-control study to explore the potential relation of ADRs to specific genomic locations and single-nucleotide polymorphism (SNP). The genomic data collected from 53 healthy volunteers are applied for the analysis, another group of genomic data collected from 30 healthy volunteers excluded from the study are used as the control group. The SNPs respective on five loci of CYP2D6*2,*10,*14 and CYP1A2*1C, *1F are detected by the Applied Biosystem 3130xl. The raw data is processed by ChromasPro to detected the specific alleles on the above loci from each sample. The secondary data are reorganized and processed by R combined with the reports of ADRs from clinical reports. Three information theory based algorithms are implemented for the screening task: JMI, CMIM, and mRMR. If a SNP is selected by more than two algorithms, we are confident to conclude that it is related to the corresponding ADR. The selection results are compared with the control decision tree + LASSO regression model. In the study group where ADRs occur, 10 SNPs are considered relevant to the occurrence of a specific ADR by the combined information theory model. In comparison, only 5 SNPs are considered relevant to a specific ADR by the decision tree + LASSO regression model. In addition, the new method detects more relevant pairs of SNP and ADR which are affected both by SNP and dosage. This implies that the new information theory based model is effective to discover correlations of ADRs and CYP 450 SNPs and is helpful to predict the potential vulnerable genotype for some ADRs. The newly proposed

  2. 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

  3. [MODELS OF CLINICAL IMPLEMENTATION OF CELL FREE FETAL DNA IN THE MATERNAL SERUM SCREENING TEST-ANALYSIS].

    Science.gov (United States)

    Yankova, M; Chaveeva, P; Stratieva, V

    2015-01-01

    Prenatal screening by definition is a way of identifying pregnancies, with a high enough risk to specific fetal damage as to justify the subsequent invasive diagnosis among the seemingly normal pregnancies. [1] The aim of the prenatal screening test is to reach the high diagnostic frequency (DR > 95%), with low false-positive rate (FPR tests (NIPT) are widely adopted and use in clinical practice: 1st Trimester Combined screening (First trimester Combined Screening) and 2nd trimester biochemical screening (Second trimester biochemical screening) and in the last few years through screening Fetal DNA in Maternal serum (cfDNA screening). Since the introduction of the sfDNA test were examined and discussed the results of several ways of application: (1) as a primary screening method without preceding the result of 1st trimester combined screening for chromosomal abnormalities, (2) as a contingent test after 1st trimester combined screening in high risk pregnancies (> 1:100) (3) as a contingent test after 1st trimester combined screening, when the calculated risk is between ( 1:10 to 1:2500). The purpose of the study: to compare the results of different ways of application screening through cfDNA: detection rate (DR) for Tri21, Tri18 and Tri13, procentage of invasive diagnostics and cost-effectiveness ratio of cfDNA test in comparison with the 1st trimester combined screening. To establish the most suitable algorithm for application of cfDNA test. Analyzed were the results of several randomized multi-center clinical studies whose data are processed through a meta-analysis. cfDNA-test has a higher DR for Tri21 for lower FPR, compared to the combined screening in 1st trimester (cfDNA-DR 99%, 1st trimester screening-DR 96% and 0.4%FPR, respectively FPR 5%), but although it is with better results and reduces the incidence of invasive tests, does not justify the significant difference in price-performance ratio. On the other hand cfDNA-test is with a lower detection rate for

  4. The validation of a simulation model incorporating radiation risk for mammography breast cancer screening in women with a hereditary-increased breast cancer risk

    NARCIS (Netherlands)

    Greuter, Marcel J. W.; Jansen-van der Weide, Marijke C.; Jacobi, Cathrien E.; Oosterwijk, Jan C.; Jansen, Liesbeth; Oudkerk, Matthijs; de Bock, Geertruida H.

    Introduction: For women with a BRCA1 or BRCA2 mutation or a strong family history of breast cancer, there is no clear estimation of the risk of tumour induction versus the beneficial effects of mammography screening available. This study aims to validate the Simulation Model on Radiation Risk and

  5. 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,

  6. 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,

  7. 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.

  8. Improvement of paracellular transport in the Caco-2 drug screening model using protein-engineered substrates.

    Science.gov (United States)

    DiMarco, Rebecca L; Hunt, Daniel R; Dewi, Ruby E; Heilshorn, Sarah C

    2017-06-01

    The Caco-2 assay has achieved wide popularity among pharmaceutical companies in the past two decades as an in vitro method for estimation of in vivo oral bioavailability of pharmaceutical compounds during preclinical characterization. Despite its popularity, this assay suffers from a severe underprediction of the transport of drugs which are absorbed paracellularly, that is, which pass through the cell-cell tight junctions of the absorptive cells of the small intestine. Here, we propose that simply replacing the collagen I matrix employed in the standard Caco-2 assay with an engineered matrix, we can control cell morphology and hence regulate the cell-cell junctions that dictate paracellular transport. Specifically, we use a biomimetic engineered extracellular matrix (eECM) that contains modular protein domains derived from two ECM proteins found in the small intestine, fibronectin and elastin. This eECM allows us to independently tune the density of cell-adhesive RGD ligands presented to Caco-2 cells as well as the mechanical stiffness of the eECM. We observe that lower amounts of RGD ligand presentation as well as decreased matrix stiffness results in Caco-2 morphologies that more closely resemble primary small intestinal epithelial cells than Caco-2 cells cultured on collagen. Additionally, these matrices result in Caco-2 monolayers with decreased recruitment of actin to the apical junctional complex and increased expression of claudin-2, a tight junction protein associated with higher paracellular permeability that is highly expressed throughout the small intestine. Consistent with these morphological differences, drugs known to be paracellularly transported in vivo exhibited significantly improved transport rates in this modified Caco-2 model. As expected, permeability of transcellularly transported drugs remained unaffected. Thus, we have demonstrated a method of improving the physiological accuracy of the Caco-2 assay that could be readily adopted by

  9. A touch-screen based paired-associates learning (PAL) task for the rat may provide a translatable pharmacological model of human cognitive impairment.

    Science.gov (United States)

    Talpos, John C; Aerts, Nancy; Fellini, Laetitia; Steckler, Thomas

    2014-07-01

    The use of touch-screen equipped operant boxes is an increasingly popular approach for modeling human cognition in the rodent. However little data is currently available describing the effects of pharmacological manipulations on touch-screen based tasks. Owing to the relationship between performance on visual-spatial paired associates learning (PAL) with schizophrenia and Alzheimer's disease one task of specific interest is the touch-screen PAL task developed for rodents (J. Talpos et al., 2009). The goal of this study was to profile a range of the commonly used pharmacological models of schizophrenia and Alzheimer's disease to investigate the sensitivity of PAL to these models of disease. Male Lister hooded rats were trained on PAL until stable performance was obtained. The effects of PCP, ketamine, amphetamine, LSD, scopolamine, and biperiden (recently proposed as an alternative to scopolamine) were then tested on animals performing the PAL task. While all compounds influenced responding during PAL, only PCP and amphetamine impaired performance with minimal changes in secondary measures (response latencies, trials completed). Surprisingly ketamine did not cause a change in percent correct despite being an NMDA antagonist, indicating that not all NMDA antagonists are equal in the touch-screen platform. This finding is in agreement with existing literature showing differential effects of NMDA antagonists on a wide variety of behavioral assays include tasks of attention, memory, and cognitive flexibility (Gilmour et al., 2009; Dix et al., 2010; Smith et al., 2011). Moreover biperiden showed no benefit when compared to scopolamine, highlighting the current lack of an effective pharmacological model of cholinergic dysfunction in the touch-screen platform. These data demonstrate that performance on PAL can be disrupted by common pharmacological disease models, suggesting that PAL may have the sensitivity to serve as a translational test for the study of cognition in

  10. 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.

  11. Screening for supra-additive effects of cytotoxic drugs and gamma irradiation in an in vitro model for hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lambert, B. [Ghent Univ. Hosptial, Nuclear Medicine Div., Ghent (Belgium)]. E-mail: bieke.lambert@Ugent.be; De Ridder, L. [Ghent Univ., Dept. of Histology, Anatomy, and Embryology, Ghent (Belgium); Slegers, G. [Ghent Univ., Dept. of Radiopharmacy, Ghent (Belgium); De Gelder, V. [Ghent Univ., Dept. of Medical Physics, Ghent (Belgium); Dierckx, R.A. [Ghent Univ. Hosptial, Nuclear Medicine Div., Ghent (Belgium); Thierens, H. [Ghent Univ., Dept. of Medical Physics, Ghent (Belgium)

    2004-02-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. A wide variety of treatment modalities is available for palliative therapy of HCC, although there is no strong evidence that these treatments can have a significant impact on survival. The aim of this work was to screen cytotoxic drugs relevant in the treatment of HCC for enhancement of the effect of irradiation in an in vitro model. As the majority of patients presenting with HCC suffer reduced liver function, attention was paid to low-dose effects of the cytotoxic drugs tested. To reflect this situation in vivo, multicellular tumor aggregates or 'spheroids' of HepG2 cells were cultured and exposed to gamma irradiation alone or in combination with cisplatin for 4 h, gemcitabin for 4 or 24 h, or 5-fluorouracil for 4 h. In one experiment, the spheroids were cultured for 4 weeks in multiwell plates that allowed adhesion. Measurement of two-dimensional spheroid outgrowth was made every week for each spheroid. This kind of growth depends on the proliferation and motility of the cells that form the spheroid. In a second experiment, toxicity was evaluated by comparative growth curves by means of a three-dimensional growth assay and by histology. Supra-additive effects lasting for 4 weeks were observed for all drugs tested in combination with a gamma irradiation of 10 Gy. (author)

  12. Antipsoriatic activity of ethanolic extract of Woodfordia fruticosa (L.) Kurz flowers in a novel in vivo screening model.

    Science.gov (United States)

    Srivastava, Amit Kumar; Nagar, Hemant Kumar; Chandel, Harinarayan Singh; Ranawat, Mahendra Singh

    2016-01-01

    The aim of this study was to investigate the antipsoriatic activity of ethanolic extract of Woodfordia fruticosa flowers (EEWF) using a novel in vivo screening model. For induction of psoriasis, 0.1 ml of prepared complete Freund's adjuvant (CFA) and formaldehyde mixture (1:10 ratio) was topically applied for 7 days on the dorsum surface of the skin of Swiss albino mice. Psoriasis severity index (PSI) was evaluated by phenotypic (redness, erythema, and scales) and histological features (epidermal thickness). Therapeutic effect of 0.05% and 0.1% (w/w) ointments of EEWF was evaluated after the induction of psoriasis. Ointments of EEWF flowers were applied once daily for 3 weeks, and antipsoriatic activity was evaluated by scoring the PSI and histological examination. We observed the phenotypic and histological features and found a progressive reduction ( P < 0.05) in the severity of psoriatic lesions (redness, erythema, and scales) from day 7 to 21 st day and decreased epidermal thickness in animals treated with 0.05% and 0.1% (w/w) ointments of EEWF. The results showed that 0.05% and 0.1% (w/w) ointments of EEWF have dose-dependent beneficial effects in CFA and formaldehyde-induced psoriasis. The present investigation revealed that W. fruticosa flowers possess potent antipsoriatic activity and can be used for psoriasis treatment.

  13. Overall performance optimization of a spiral pipe type heater by fluid- structure interaction modeling and partitioning screening method

    Directory of Open Access Journals (Sweden)

    Lei Guo

    2018-03-01

    Full Text Available A spiral pipe type heater is applied to the natural gas transportation system to inhibit gas hydrate, but fracture failure often happens at the joint of a coil pipe and a gathering pipe. To understand the mechanical behavior of the spiral pipe heater, a mechanical model of the coil pipe acted by the gas fluid is constructed, and the mechanical characteristics of the fracture point are obtained by numerical calculation. Then, the relation between angle parameters and the axial force, shear force, bending moment as well as stress of the structure is gotten. Comparison calculations of heat exchange before and after structural adjustment are done to get the optimized structure parameters of better mechanical properties and high heating rate. From this study, it is found that although the mechanical properties are improved, when increasing an angle parameter, the heat transfer performance is decreased. A coordination method is used for resolving the contradiction between heat transfer performance and mechanical properties to get an overall performance optimization. The provided partitioning screening method can improve the heating efficiency and mechanical properties of the heater obviously and conveniently.

  14. Baker yeast-induced fever in young rats: characterization and validation of an animal model for antipyretics screening.

    Science.gov (United States)

    Tomazetti, Jorgete; Avila, Daiana Silva; Ferreira, Ana Paula Oliveira; Martins, Juliana Saibt; Souza, Fabiane Rosa; Royer, Carine; Rubin, Maribel Antonello; Oliveira, Marlí Redin; Bonacorso, Hélio Gauze; Martins, Marcos Antônio Pinto; Zanatta, Nilo; Mello, Carlos Fernando

    2005-08-30

    In this study we describe a low-cost and reliable method for inducing fever in young male rats (28-30 days of age, 75-90 g), which seems suitable for the screening of new antipyretics. The effects of temperature measuring procedure-induced stress on the basal rectal temperature and on Baker yeast-induced hyperthermia was assessed. Rectal temperature (T) was recorded every hour for 12 h (07:00-19:00 h) with a lubricated thermistor probe. The animals were injected intraperitoneally with baker yeast (0.25, 0.135, 0.05 g/kg) or the equivalent volume of saline at 7:00 h. The administration of 0.135 g/kg baker yeast induced a sustained increase in rectal temperature for 4 h. Classical (dipyrone and acetaminophen) and novel (MPCA and FPCA) antipyretics, at doses that had no effect per se, reverted baker yeast-induced fever. The method presented induces a clear-cut fever, which is reverted by antipyretics commonly used in human beings and selected novel antipyretics in small animals. The method also allows antipyretic evaluation with low amount of drugs, due to the use of small animals and to the small variability of the pyretic response, which ultimately causes a significant reduction in the number of animals necessary for antipyretic evaluation. Therefore, this study describes an animal model of fever that is not only advantageous from the economical and technical point of view, but that also bears ethical concerns.

  15. Information needs and preferences of low and high literacy consumers for decisions about colorectal cancer screening: utilizing a linguistic model

    Science.gov (United States)

    Smith, Sian K; Trevena, Lyndal; Nutbeam, Don; Barratt, Alexandra; McCaffery, Kirsten J

    2008-01-01

    Abstract Context  The use of written decision aids (DAs) in clinical practice has proliferated. However, few DAs have been developed for low literacy users, despite this group having low knowledge about healthcare and lacking involvement in health decisions. Objective  To explore the information needs and understanding of adults with varying literacy in relation to colorectal cancer screening, and to consider their responses to two versions of a decision aid. Participants  Thirty‐three men and women aged 45–74 years were recruited from Adult Basic Education classes (n = 17) and University Continuing Education programs (n = 16). Methods  We used qualitative methods (in‐depth, semi‐structured interviews) to compare and contrast the views of adults with lower and higher literacy levels, to gain a better understanding of how people with lower literacy value and interpret specific DA content and components; and determine whether needs and preferences are specific to lower literacy groups or generic across the broad literacy spectrum. Results  Regardless of literacy perspective, participants’ interpretations of the DA were shaped by their prior knowledge and expectations, as well as their values and preferences. This influenced perceptions of the DAs role in supporting informed decision making. A linguistic theoretical model was applied to interpret the findings. This facilitated considerations beyond the traditional focus on the readability of materials. Conclusion  Decision aids developers may find it useful to apply alternative approaches (linguistic) when creating DAs for consumers of varying literacy. PMID:18494957

  16. Effects of Group Counseling Based on Health Belief Model on Cervical Cancer Screening Beliefs and Performance of Rural Women in Kaboudrahang, Iran

    Science.gov (United States)

    Parsa, Parisa; Sharifi, Fatemeh; Shobeiri, Fatemeh; Karami, Manoocher

    2017-06-25

    Objective: Pap smear test is an appropriate screening method for early diagnosis of cervical cancer and reduction of mortality. This study targeted effects of group counseling based on the Health Belief Model on cervical cancer screening practices of Iranian rural women. Method: This quasi-experimental study was conducted on 80 rural women under coverage of the health care centers in rural areas in the city of Kabudrahang, Iran, in 2015. The data collection tool was a researcher-made questionnaire covering demographic information, Health Belief Model (HBM) constructs and screening performance. Data were collected using a multi-stage sampling method. Group counseling was conducted based on the Health Belief Model and the GATHER steps in three sessions for the intervention group. Counseling included an introduction to cervical cancer, disease symptoms, warning signs and prevention approaches. Pap smear testing in both intervention and control groups was evaluated two months after the group counseling. Results: Before the intervention, there was no significant difference between both groups in the HBM constructs and performance. After the intervention, a significant difference was seen in the perceived susceptibility (Pbeliefs of rural women regarding cervical cancer screening and increase their performance. Creative Commons Attribution License

  17. 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).

  18. An over expression APP model for anti-Alzheimer disease drug screening created by zinc finger nuclease technology.

    Directory of Open Access Journals (Sweden)

    Xiaojing Zhang

    Full Text Available Zinc Finger Nucleases (ZFNs, famous for their ability to precisely and efficiently modify specific genomic loci, have been employed in numerous transgenic model organism and cell constructions. Here we employ the ZFNs technology, with homologous recombination (HR, to construct sequence-specific Amyloid Precursor Protein (APP knock-in cells. With the use of ZFNs, we established APP knock in cell lines with gene-modification efficiencies of about 7%. We electroporated DNA fragment containing the promoter and the protein coding regions of the zinc finger nucleases into cells, instead of the plasmids, to avoid problems associated with off target homologous recombination, and adopted a pair of mutated FokI cleavage domains to reduce the toxic effects of the ZFNs on cell growth. Since over-expression of APP, or a subdomain of it, might lead to an immediately lethal effect, we used the Cre-LoxP System to regulate APP expression. Our genetically transformed cell lines, w5c1 and s12c8, showed detectable APP and Amyloid β (Aβ production. The Swedish double mutation in the APP coding sequence enhanced APP and Aβ abundance. What is more, the activity of the three key secretases in Aβ formation could be modulated, indicating that these transgenic cells have potential for drug screening to modify amyloid metabolism in cells. Our transformed cells could readily be propagated in culture and should provide an excellent experimental medium for elucidating aspects of the molecular pathogenesis of Alzheimer's disease, especially those concerning the amyloidogenic pathways involving mutations in the APP coding sequence. The cellular models may also serve as a tool for deriving potentially useful therapeutic agents.

  19. 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

  20. 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...

  1. 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

  2. Competing-risks model in screening for pre-eclampsia in twin pregnancy by maternal characteristics and medical history.

    Science.gov (United States)

    Francisco, C; Wright, D; Benkő, Z; Syngelaki, A; Nicolaides, K H

    2017-10-01

    A survival-time regression model for gestational age at delivery with pre-eclampsia (PE) in singleton pregnancy, using maternal demographic characteristics and medical history, was reported previously. The objective of this study was to extend this model to dichorionic (DC) and monochorionic (MC) twin pregnancy. The study population included 1789 DC and 430 MC twin pregnancies and 93 297 singleton pregnancies. A survival-time model for gestational age at delivery with PE was developed from variables of maternal characteristics and medical history. The risk of PE with delivery pregnancies was determined and compared with that in singleton pregnancies. In singleton pregnancies comprising women of Caucasian racial origin, mean weight of 69 kg at 12 weeks' gestation, mean height of 164 cm, nulliparous, with spontaneous conception, no family history of PE and no history of diabetes mellitus, systemic lupus erythematosus or antiphospholipid syndrome, the mean of the Gaussian distribution of gestational age at delivery with PE was 55 weeks. In DC twins with PE, mean gestational age at delivery was shifted to the left by 8.2 (95% CI, 7.2-9.1) weeks and in MC twins it was shifted to the left by 10.0 (95% CI, 8.5-11.4) weeks. The risk of delivery with PE occurring at, or before, a specified gestational age is given by the area under the fitted distribution curve. For a reference population with the above characteristics, the estimated risk of PE history has been developed for estimation of patient-specific risks for PE in DC and MC twin pregnancy. Such estimation of the a-priori risk for PE 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 screening for the disease. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

  3. Model for Risk-Based Screening of Diabetic Retinopathy in People With Newly-Diagnosed Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Chatziralli, Irini; Sergentanis, Theodoros N; Crosby-Nwaobi, Roxanne; Winkley, Kirsty; Eleftheriadis, Haralabos; Ismail, Khalida; Amiel, Stephanie A; Sivaprasad, Sobha

    2017-05-01

    The purpose of this study was to evaluate the role of inflammatory/lipid markers and potential risk factors for diabetic retinopathy (DR) development in newly diagnosed patients with type 2 diabetes mellitus (T2DM). Participants in this study were 1062 patients with newly diagnosed T2DM. Demographic and clinical data of patients were collected. Assessment of DR status was performed using digital two-field photography. In addition, HbA1c (%), lipid profile, and urinary albumin were measured at recruitment. The following inflammatory markers were also measured: serum C-reactive protein, white blood cells, platelet, adiponectin, IL-4, IL-6, IL-10, vascular endothelial growth factor, tumor necrosis factor-α (TNF-α), IL-1b, IL-1 receptor antagonist (IL-1RA), and monocyte chemotactic protein-1. Univariate and multivariate analyses of the association of various potential risk factors and DR were conducted. Univariate analysis showed that male sex, any cardiovascular event, and HbA1c were positively associated with DR, while IL-1RA, IL-1b, IL-6, and TNF-α were significantly negatively associated with presence of DR in the cohort. Risk factors that remained significantly associated with DR presence at the multivariate analysis were male sex, any cardiovascular event, HbA1c, and IL-1RA. Our study demonstrated that HbA1c levels, male sex, and previous cardiovascular events were risk factors for presence of DR in people with newly diagnosed T2DM, while IL-1RA seemed to have a protective role. The prevalence of DR in our population was 20.2%, reflecting current practice. Our findings may contribute to future risk-based modelling of screening for DR.

  4. 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.

  5. Airport Screening

    Science.gov (United States)

    ... travel continues, especially given the ongoing threat of terrorism. The technology used in screening people and their ... can be found on the Radiation Terms and Definitions page on the Health Physics Society website at ...

  6. Toxicology screen

    Science.gov (United States)

    ... the type and approximate amount of legal and illegal drugs a person has taken. How the Test is ... prescription medicines that have not been prescribed, and illegal drugs have not been detected. A blood toxicology screen ...

  7. Streptococcal screen

    Science.gov (United States)

    A streptococcal screen is a test to detect group A streptococcus. This bacteria is the most common cause of ... throat swab. The swab is tested to identify group A streptococcus. It takes about 7 minutes to get the ...

  8. Large-scale microfluidics providing high-resolution and high-throughput screening of Caenorhabditis elegans poly-glutamine aggregation model

    Science.gov (United States)

    Mondal, Sudip; Hegarty, Evan; Martin, Chris; Gökçe, Sertan Kutal; Ghorashian, Navid; Ben-Yakar, Adela

    2016-10-01

    Next generation drug screening could benefit greatly from in vivo studies, using small animal models such as Caenorhabditis elegans for hit identification and lead optimization. Current in vivo assays can operate either at low throughput with high resolution or with low resolution at high throughput. To enable both high-throughput and high-resolution imaging of C. elegans, we developed an automated microfluidic platform. This platform can image 15 z-stacks of ~4,000 C. elegans from 96 different populations using a large-scale chip with a micron resolution in 16 min. Using this platform, we screened ~100,000 animals of the poly-glutamine aggregation model on 25 chips. We tested the efficacy of ~1,000 FDA-approved drugs in improving the aggregation phenotype of the model and identified four confirmed hits. This robust platform now enables high-content screening of various C. elegans disease models at the speed and cost of in vitro cell-based assays.

  9. From Omics to Drug Metabolism and High Content Screen of Natural Product in Zebrafish: A New Model for Discovery of Neuroactive Compound

    Directory of Open Access Journals (Sweden)

    Ming Wai Hung

    2012-01-01

    Full Text Available The zebrafish (Danio rerio has recently become a common model in the fields of genetics, environmental science, toxicology, and especially drug screening. Zebrafish has emerged as a biomedically relevant model for in vivo high content drug screening and the simultaneous determination of multiple efficacy parameters, including behaviour, selectivity, and toxicity in the content of the whole organism. A zebrafish behavioural assay has been demonstrated as a novel, rapid, and high-throughput approach to the discovery of neuroactive, psychoactive, and memory-modulating compounds. Recent studies found a functional similarity of drug metabolism systems in zebrafish and mammals, providing a clue with why some compounds are active in zebrafish in vivo but not in vitro, as well as providing grounds for the rationales supporting the use of a zebrafish screen to identify prodrugs. Here, we discuss the advantages of the zebrafish model for evaluating drug metabolism and the mode of pharmacological action with the emerging omics approaches. Why this model is suitable for identifying lead compounds from natural products for therapy of disorders with multifactorial etiopathogenesis and imbalance of angiogenesis, such as Parkinson's disease, epilepsy, cardiotoxicity, cerebral hemorrhage, dyslipidemia, and hyperlipidemia, is addressed.

  10. Evidence for the credibility of health economic models for health policy decision-making: a systematic literature review of screening for abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Søgaard, Rikke; Lindholt, Jes S.

    2012-01-01

    OBJECTIVE: To investigate whether the credibility of health economic models of screening for abdominal aortic aneurysms for health policy decision-making has improved since 2005 when a systematic review by Campbell et al. concluded that reporting standards were poor and there was divergence between...... benefited from general advances in health economic modelling and some improvements in reporting were noted. However, the low level of agreement between studies in model structures and assumptions, and difficulty in justifying these (convergent validity), remain a threat to the credibility of health economic...

  11. 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.

  12. Evaluation of the colorectal cancer screening Programme in the Basque Country (Spain and its effectiveness based on the Miscan-colon model

    Directory of Open Access Journals (Sweden)

    I. Idigoras

    2017-08-01

    Full Text Available Abstract The population-based Basque Colorectal Cancer (CRC Screening Programme started in 2009 with a biennial immunochemical quantitative test (FIT biennial and colonoscopy under sedation in positive cases. The population target of 586,700 residents was from 50 to 69 years old and the total coverage was reached at the beginning of 2014. The aim of our study was to determine possible scenarios in terms of incidence, mortality and reduction of Life-years-Lost (L-y-L in the medium and long term of CRC. Methods Invitations were sent out by the Programme from 2009 to 2014, with combined organizational strategies. Simulation was done by MISCAN-colon (Microsimulation Screening Analysis over 30 years comparing the results of screening vs no-screening, taking the population-based Cancer Registry into account. Lifetime population and real data from the Programme were used from 2008 to 2012. The model was run differentially for men and women. Results 924,416 invitations were sent out from 2009 to 2014. The average participation rate was 68.4%, CRC detection rate was 3.4% and the Advanced Adenoma detection rate was 24.0‰, with differences observed in sex and age. Future scenarios showed a higher decrease of incidence (17.2% vs 14.7%, mortality (28.1% vs 22.4% and L-y-L (22.6% vs 18.4% in men than women in 2030. Conclusions The Basque Country CRC Programme results are aligned to its strategy and comparable to other programmes. MISCAN model was found to be a useful tool to predict the benefits of the programme in the future. The effectiveness of the Programme has not been formally established as case control studies are required to determine long term benefits from the screening strategy.

  13. Evaluation of the colorectal cancer screening Programme in the Basque Country (Spain) and its effectiveness based on the Miscan-colon model.

    Science.gov (United States)

    Idigoras, I; Arrospide, A; Portillo, I; Arana-Arri, E; Martínez-Indart, L; Mar, J; de Koning, H J; Lastra, R; Soto-Gordoa, M; van der Meulen, M; Lansdorp-Vogelaar, I

    2017-08-01

    The population-based Basque Colorectal Cancer (CRC) Screening Programme started in 2009 with a biennial immunochemical quantitative test (FIT) biennial and colonoscopy under sedation in positive cases. The population target of 586,700 residents was from 50 to 69 years old and the total coverage was reached at the beginning of 2014. The aim of our study was to determine possible scenarios in terms of incidence, mortality and reduction of Life-years-Lost (L-y-L) in the medium and long term of CRC. Invitations were sent out by the Programme from 2009 to 2014, with combined organizational strategies. Simulation was done by MISCAN-colon (Microsimulation Screening Analysis) over 30 years comparing the results of screening vs no-screening, taking the population-based Cancer Registry into account. Lifetime population and real data from the Programme were used from 2008 to 2012. The model was run differentially for men and women. 924,416 invitations were sent out from 2009 to 2014. The average participation rate was 68.4%, CRC detection rate was 3.4% and the Advanced Adenoma detection rate was 24.0‰, with differences observed in sex and age. Future scenarios showed a higher decrease of incidence (17.2% vs 14.7%), mortality (28.1% vs 22.4%) and L-y-L (22.6% vs 18.4%) in men than women in 2030. The Basque Country CRC Programme results are aligned to its strategy and comparable to other programmes. MISCAN model was found to be a useful tool to predict the benefits of the programme in the future. The effectiveness of the Programme has not been formally established as case control studies are required to determine long term benefits from the screening strategy.

  14. 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

  15. Primary hepatocytes from Arctic char (Salvelinus alpinus) as a relevant Arctic in vitro model for screening contaminants and environmental extracts.

    Science.gov (United States)

    Petersen, Karina; Hultman, Maria T; Tollefsen, Knut Erik

    2017-06-01

    Contaminants find their way to the Arctic through long-range atmospheric transport, transport via ocean currents, and through increased anthropogenic activity. Some of the typical pollutants reaching the Arctic (PAHs, PCBs) are known to induce cytochrome P450 1a (CYP1A) protein expression and ethoxyresorufin-O-deethylase (EROD) activity through the aryl hydrocarbon receptor (AhR). In addition, some endocrine disrupting chemicals (EDCs) such as estrogen mimics (xenoestrogens) have been documented in Arctic areas and they may interfere with natural sexual development and reproduction. In vitro assays that are capable of detecting effects of such pollutants, covering multiple endpoints, are generally based on mammalian or temperate species and there are currently no well-characterized cell-based in vitro assays for effect assessment from Arctic fish species. The present study aimed to develop a high-throughput and multi-endpoint in vitro assay from Arctic char (Salvelinus alpinus) to provide a non-animal (alternative) testing method for an ecologically relevant Arctic species. A method for isolation and exposure of primary hepatocytes from Arctic char for studying the toxic effects and mode of action (MoA) of pollutants was applied and validated. The multi-versatility of the bioassay was assessed by classical biomarker responses such as cell viability (membrane integrity and metabolic activity), phase I detoxification (CYP1A protein expression, EROD activity) and estrogen receptor (ER) mediated vitellogenin (Vtg) protein expression using a selection of model compounds, environmental pollutants and an environmental extract containing a complex mixture of pollutants. Primary hepatocytes from Arctic char were successfully isolated and culture conditions optimized to identify the most optimal assay conditions for covering multiple endpoints. The hepatocytes responded with concentration-dependent responses to all of the model compounds, most of the environmental pollutants

  16. 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

  17. 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

  18. Strongly screening electron capture for nuclides 52, 53, 59, 60Fe by the Shell-Model Monte Carlo method in pre-supernovae

    Science.gov (United States)

    Liu, Jing-Jing; Peng, Qiu-He; Liu, Dong-Mei

    2017-09-01

    The death of massive stars due to supernova explosions is a key ingredient in stellar evolution and stellar population synthesis. Electron capture (EC) plays a vital role in supernova explosions. Using the Shell-Model Monte Carlo method, based on the nuclear random phase approximation and linear response theory model for electrons, we study the strong screening EC rates of 52, 53, 59, 60Fe in pre-supernovae. The results show that the screening rates can decrease by about 18.66%. Our results may become a good foundation for future investigation of the evolution of late-type stars, supernova explosion mechanisms and numerical simulations. Supported by National Natural Science Foundation of China (11565020), Counterpart Foundation of Sanya (2016PT43), Special Foundation of Science and Technology Cooperation for Advanced Academy and Regional of Sanya (2016YD28), Scientific Research Staring Foundation for 515 Talented Project of Hainan Tropical Ocean University (RHDRC201701) and Natural Science Foundation of Hainan Province (114012)

  19. 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

  20. Use of risk projection models to estimate mortality and incidence from radiation-induced breast cancer in screening programs

    Energy Technology Data Exchange (ETDEWEB)

    Ramos, M [Chemical and Nuclear Engineering Department, Polytechnic University of Valencia, Camino de Vera s/n 46022 Valencia (Spain); Ferrer, S [Chemical and Nuclear Engineering Department, Polytechnic University of Valencia, Camino de Vera s/n 46022 Valencia (Spain); Villaescusa, J I [Radiation Protection Service, Hospital Universitario La Fe, Avda Campanar, 21 46009 Valencia (Spain); Verdu, G [Chemical and Nuclear Engineering Department, Polytechnic University of Valencia, Camino de Vera s/n 46022 Valencia (Spain); Salas, M D [Public Health General Direction, Conselleria de Sanitat de Valencia, C/Micer Masco, 31 46021 Valencia (Spain); Cuevas, M D [Assistential Service General Direction, Conselleria de Sanitat de Valencia, C/Micer Masco, 31 46021 Valencia (Spain)

    2005-02-07

    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{sup -6}, 6 x 10{sup -4}] versus the natural rate of dying from breast cancer in the Valencian Community which is 9.2 x 10{sup -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.

  1. 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

  2. Beliefs and behaviors of breast cancer screening in women referring to health care centers in northwest Iran according to the champion health belief model scale.

    Science.gov (United States)

    Fouladi, Nasrin; Pourfarzi, Farhad; Mazaheri, Effat; Asl, Hossein Alimohammadi; Rezaie, Minoo; Amani, Fiouz; Nejad, Masumeh Rostam

    2013-01-01

    Breast cancer is the most common cancer in women. All ages are susceptible and more than 90% of the patients can be cured with early diagnosis. Breast self-examination (BSE) and mammography can be useful for this aim. In this study we examined the components of the Champion health belief model to identify if they could predict the intentions of women to perform such screening. A total of 380 women aged 30 and above who had referred to health-care centers were assessed for use of breast cancer screening over the past year with a modified health belief model questionnaire. Logistic regression was applied to identify leading independent predictors. In this study 27% of the women performed BSE in the last year but only 6.8% of them used mammography as a way of screening. There were significant differences regarding all components of the model except for perceived severity between women that underwent BSE. over the past year and those that did not. Findings were similar for mammography. Regression analysis revealed that intentions to perform BSE were predicted by perceived self-efficacy and perceived barriers to BSE while intentions to perform mammography were predicted by perceived barriers. This study indicated that self-efficacy can support performance of BSE while perceived barriers are important for not performing both BSE and mammography. Thus we must educate women to increase their self-efficacy and decrease their perceived barriers.

  3. Investigating ER-Associated Degradation with RNAi Screening - and Searching for Model Proteins to Do It with

    DEFF Research Database (Denmark)

    Jensen, Njal Winther

    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...... to possess the required properties. RNAi screening was then performed to identify proteins of the ERAD machinery that was needed for the successful degradation of a HA-tagged version of the ATP13A2 mutant (HA-ATP13A2). After a validation phase, one of the identified proteins, Sec61α was verified as being...

  4. Evaluation of OASIS QSAR Models Using ToxCast™ in Vitro Estrogen and Androgen Receptor Binding Data and Application in an Integrated Endocrine Screening Approach

    Science.gov (United States)

    Bhhatarai, Barun; Wilson, Daniel M.; Price, Paul S.; Marty, Sue; Parks, Amanda K.; Carney, Edward

    2016-01-01

    Background: Integrative testing strategies (ITSs) for potential endocrine activity can use tiered in silico and in vitro models. Each component of an ITS should be thoroughly assessed. Objectives: We used the data from three in vitro ToxCast™ binding assays to assess OASIS, a quantitative structure-activity relationship (QSAR) platform covering both estrogen receptor (ER) and androgen receptor (AR) binding. For stronger binders (described here as AC50 QSAR predictions of ER or AR binding to the results from 18 ER and 10 AR transactivation assays, 72 ER-binding reference compounds, and the in vivo uterotrophic assay. Methods: NovaScreen binding assay data for ER (human, bovine, and mouse) and AR (human, chimpanzee, and rat) were used to assess the sensitivity, specificity, concordance, and applicability domain of two OASIS QSAR models. The binding strength relative to the QSAR-predicted binding strength was examined for the ER data. The relationship of QSAR predictions of binding to transactivation- and pathway-based assays, as well as to in vivo uterotrophic responses, was examined. Results: The QSAR models had both high sensitivity (> 75%) and specificity (> 86%) for ER as well as both high sensitivity (92–100%) and specificity (70–81%) for AR. For compounds within the domains of the ER and AR QSAR models that bound with AC50 QSAR models accurately predicted the binding for the parent compounds. The parent compounds were active in all transactivation assays where metabolism was incorporated and, except for those compounds known to require metabolism to manifest activity, all assay platforms where metabolism was not incorporated. Compounds in-domain and predicted to bind by the ER QSAR model that were positive in ToxCast™ ER binding at AC50 QSAR models had high sensitivity and specificity when compounds were in-domain of the models. Based on this research, we recommend a tiered screening approach wherein a) QSAR is used to identify compounds in-domain of

  5. 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

  6. 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.

  7. 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,…

  8. Screening of different stress factors and development of growth/no growth models for Zygosaccharomyces rouxii in modified Sabouraud medium, mimicking intermediate moisture foods (IMF).

    Science.gov (United States)

    Vermeulen, A; Daelman, J; Van Steenkiste, J; Devlieghere, F

    2012-12-01

    The microbial stability of intermediate moisture foods (IMF) is linked with the possible growth of osmophilic yeast and xerophilic moulds. As most of these products have a long shelf life the assessment of the microbial stability is often an important hurdle in product innovation. In this study a screening of several Zygosaccharomyces rouxii strains towards individual stress factors was performed and growth/no growth models were developed, incorporating a(w), pH, acetic acid and ethanol concentrations. These stress factors are important for sweet IMF such as chocolate fillings, ganache, marzipan, etc. A comparison was made between a logistic regression model with and without the incorporation of time as an explanatory variable. Next to the model development, a screening of the effect of chemical preservatives (sorbate and benzoate) was performed, in combination with relevant stress factors within the experimental design of the model. The results of the study showed that the influence of the investigated environmental stress factors on the growth/no growth boundary of Z. rouxii is the most significant in the first 30-40 days of incubation. Incorporating time as an explanatory variable in the model had the advantage that the growth/no growth boundary could be predicted at each time between 0 and 60 days of incubation at 22 °C. However, the growth/no growth boundary enlarged significantly leading to a less accurate prediction on the growth probability of Z. rouxii. The developed models can be a useful tool for product developers of sweet IMF. Screening with chemical preservatives revealed that benzoic acid was much less active towards Z. rouxii than sorbic acid or a mixture of both acids. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. 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)

  10. High-content screening technology combined with a human granuloma model as a new approach to evaluate the activities of drugs against Mycobacterium tuberculosis.

    Science.gov (United States)

    Silva-Miranda, Mayra; Ekaza, Euloge; Breiman, Adrien; Asehnoune, Karim; Barros-Aguirre, David; Pethe, Kevin; Ewann, Fanny; Brodin, Priscille; Ballell-Pages, Lluís; Altare, Frédéric

    2015-01-01

    Tuberculosis remains a major health problem due to the emergence of drug-resistant strains of Mycobacterium tuberculosis. Some models have provided valuable information about drug resistance and efficacy; however, the translation of these results into effective human treatments has mostly proven unsuccessful. In this study, we adapted high-content screening (HCS) technology to investigate the activities of antitubercular compounds in the context of an in vitro granuloma model. We observed significant shifts in the MIC50s between the activities of the compounds under extracellular and granuloma conditions. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. 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.

  12. 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 ...

  13. Marginal public health gain of screening for colorectal cancer: modelling study, based on WHO and national databases in the Nordic countries

    DEFF Research Database (Denmark)

    Sigurdsson, J.A.; Getz, L.; Sjonell, G.

    2013-01-01

    was modelled among people 55-74 years in accordance with the 2011 Cochrane review of biannual screening, using the faecal occult blood test (FOBT) for 10 years, resulting in 15% relative risk reduction in CRC deaths among all those invited [intention-to-treat; relative risk 0.85; confidence interval (CI) 0...... calculated mean mortality for the period 2005-2009. Results Invitation to a CRC screening programme for 10 years could influence 0.5-0.9% (95%CI 0.4-1.2) of all deaths in the age group 65-74 years. Among the remaining 99% of premature deaths, around 50% were caused by lung cancer, other lung diseases...

  14. Impact of replacing cytology with human papillomavirus testing for cervical cancer screening on the prevalence ofTrichomonas vaginalis: a modelling study.

    Science.gov (United States)

    Hui, Ben B; Reulein, Caitlin P; Guy, Rebecca J; Donovan, Basil; Hocking, Jane S; Law, Matthew G; Regan, David G

    2018-01-11

    Trichomonas vaginalis (TV) is the most common curable STI worldwide and is associated with increased risk of HIV acquisition and serious reproductive morbidities. The prevalence of TV infection is very low in Australian cities, and this is thought to be at least partly due to incidental detection and treatment of TV in women participating in the cervical cytology screening programme. In 2017, the national cervical screening programme will transition to a new model based on testing for high-risk (HR) human papillomavirus (HPV), with a reduced frequency and commencement at an older age. We model the potential impact of this transition on TV prevalence in Australia. A mathematical model was developed to describe the transmission of TV in the general population and used to evaluate scenarios that capture the switch from cytology-based screening to HR HPV testing. Under these scenarios, individuals with asymptomatic TV who test negative for HR HPV will remain undiagnosed and untreated. We estimate the change in TV prevalence expected to occur due to the switch from cytology to HR HPV testing and changes to the frequency and age at commencement of screening. Our results suggest that with the transition to HR HPV testing, TV prevalence may increase from the current ~0.4% to 2.8% within 20 years if TV testing coverage is not increased and HR HPV prevalence does not decline further. If HR HPV prevalence continues to decline at its current rate with ongoing vaccination, TV prevalence is predicted to increase to 3.0% within this time frame. Our modelling suggests that in a setting like Australia, where TV can be detected incidentally through cytology-based cervical screening, a transition to HPV testing is likely to result in increasing TV prevalence over time unless additional measures are implemented to increase TV testing and treatment. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial

  15. Developing and validating predictive decision tree models from mining chemical structural fingerprints and high–throughput screening data in PubChem

    Directory of Open Access Journals (Sweden)

    Bryant Stephen H

    2008-09-01

    Full Text Available Abstract Background Recent advances in high-throughput screening (HTS techniques and readily available compound libraries generated using combinatorial chemistry or derived from natural products enable the testing of millions of compounds in a matter of days. Due to the amount of information produced by HTS assays, it is a very challenging task to mine the HTS data for potential interest in drug development research. Computational approaches for the analysis of HTS results face great challenges due to the large quantity of information and significant amounts of erroneous data produced. Results In this study, Decision Trees (DT based models were developed to discriminate compound bioactivities by using their chemical structure fingerprints provided in the PubChem system http://pubchem.ncbi.nlm.nih.gov. The DT models were examined for filtering biological activity data contained in four assays deposited in the PubChem Bioassay Database including assays tested for 5HT1a agonists, antagonists, and HIV-1 RT-RNase H inhibitors. The 10-fold Cross Validation (CV sensitivity, specificity and Matthews Correlation Coefficient (MCC for the models are 57.2~80.5%, 97.3~99.0%, 0.4~0.5 respectively. A further evaluation was also performed for DT models built for two independent bioassays, where inhibitors for the same HIV RNase target were screened using different compound libraries, this experiment yields enrichment factor of 4.4 and 9.7. Conclusion Our results suggest that the designed DT models can be used as a virtual screening technique as well as a complement to traditional approaches for hits selection.

  16. Developing and validating predictive decision tree models from mining chemical structural fingerprints and high-throughput screening data in PubChem.

    Science.gov (United States)

    Han, Lianyi; Wang, Yanli; Bryant, Stephen H

    2008-09-25

    Recent advances in high-throughput screening (HTS) techniques and readily available compound libraries generated using combinatorial chemistry or derived from natural products enable the testing of millions of compounds in a matter of days. Due to the amount of information produced by HTS assays, it is a very challenging task to mine the HTS data for potential interest in drug development research. Computational approaches for the analysis of HTS results face great challenges due to the large quantity of information and significant amounts of erroneous data produced. In this study, Decision Trees (DT) based models were developed to discriminate compound bioactivities by using their chemical structure fingerprints provided in the PubChem system http://pubchem.ncbi.nlm.nih.gov. The DT models were examined for filtering biological activity data contained in four assays deposited in the PubChem Bioassay Database including assays tested for 5HT1a agonists, antagonists, and HIV-1 RT-RNase H inhibitors. The 10-fold Cross Validation (CV) sensitivity, specificity and Matthews Correlation Coefficient (MCC) for the models are 57.2 approximately 80.5%, 97.3 approximately 99.0%, 0.4 approximately 0.5 respectively. A further evaluation was also performed for DT models built for two independent bioassays, where inhibitors for the same HIV RNase target were screened using different compound libraries, this experiment yields enrichment factor of 4.4 and 9.7. Our results suggest that the designed DT models can be used as a virtual screening technique as well as a complement to traditional approaches for hits selection.

  17. 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)

  18. A model of integrated lung and focused heart ultrasound as a new screening examination in infants at risk of respiratory or hemodynamic compromise

    Directory of Open Access Journals (Sweden)

    Yasser Elsayed

    2017-02-01

    Full Text Available Objective: This was a feasibility study to determine whether an edu­cational program conducted over 2 days followed by 25 performed studies under supervision equips physicians with the skills to accurately interpret and perform integrated lung ultrasound (LUS and focused heart ultrasound (FHUS as a screening exam in infants at risk of respiratory or hemodynamic compromise.Methods: We conducted a training course over 2 days (total of 16 hours to teach fellows how to interpret a pre-designed model of LUS and FHUS, as a screening exam for infants at risk of respiratory or hemodynamic compromise. Then trainees performed 25 cases with different neonatal lung and functional heart issues. The screening model included only the basic views required to evaluate common lung parenchymal and functional neonatal heart conditions in sick infants. The accuracy of interpretation during the course was assessed by Kappa.Results: The inter-rater agreement between all trainees and instructor improved on the second day of the course to Kappa 0.86 (95% CI: 0.72-0.97 for LUS views and 0.78 (95% CI: 0.69-0.91 for FHUS views. The inter-rater agreement between trainees themselves improved from Kappa 0.64 (95% CI: 0.47-0.81 for LUS on day one to 0.89 (95% CI: 0.81-0.96 on day two. And from 0.58 (95% CI: 0.44-0.73 on day one to 0.75 (95% CI: 0.68-0.84 on day two.Conclusion: Bedside screening, using integrated LUS and FHUS can be a useful adjunct to clinical examination in infants at risk of respiratory or hemodynamic compromise.

  19. 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.

  20. 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 ...

  1. 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

  2. Migration modeling to estimate exposure to chemicals in food packaging for application in highthroughput risk-based screening and Life Cycle Assessment

    DEFF Research Database (Denmark)

    Ernstoff, Alexi; Jolliet, O.; Huang, L.

    2017-01-01

    and risk prioritization and screening. To fulfill the need for a migration model flexibly suitable for such tools, we develop an accurate and rapid (high-throughput) approach. The developed model estimates the fraction of an organic chemical migrating from polymeric packaging into food for user-defined...... instantaneously estimates migration from packaging into food for user-defined scenarios, and has improved performance over common model simplifications. The common practice of setting the package-food partition coefficient = 1 for specific "worst-case" scenarios is insufficient to predict the equilibrium......Specialty software and simplified models are often used to estimate "worst-case" migration of potentially toxic chemicals from packaging into food. Current approaches, however, cannot efficiently and accurately provide estimates of migration for emerging applications, e.g. in Life Cycle Assessment...

  3. [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.

  4. A translation inhibitor identified in a Drosophila screen enhances the effect of ionizing radiation and taxol in mammalian models of cancer

    Directory of Open Access Journals (Sweden)

    Mara Gladstone

    2012-05-01

    We described previously a screening protocol in Drosophila melanogaster that allows us to identify small molecules that increase the killing effect of ionizing radiation in vivo in a multicellular context. The ability of this screen to identify agents that enhance the effect of radiation in human cancer models has been validated in published proof-of-concept studies. Here we describe an agent, identified by screening through two National Cancer Institute (NCI small molecule libraries in Drosophila, that increases the effect of radiation. This agent, Bouvardin (NSC 259968, inhibits the elongation step of protein synthesis. We find that Bouvardin enhances the killing effect of X-rays in both Drosophila larvae and in human cancer cells. More detailed analysis showed that Bouvardin also increases the effect of radiation in clonogenic assays and in human cancer xenografts in mice. Finally, we present data that Bouvardin can also increase the efficacy of taxol. Regulation of translation is important to cancer biology. Current therapies target every aspect of cancer cell proliferation from growth factor signaling to cell division, with the exception of translation elongation. Our identification of Bouvardin as an enhancer of radio- and chemo-therapeutic agents suggests that targeting this niche has the potential to improve existing cancer therapies.

  5. 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

  6. 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.

  7. Cervical screening: default and compliance.

    Science.gov (United States)

    Martin, J; Main, P J

    1992-04-01

    Health visitors could play a key role in educating at risk women about the benefits of cervical screening. Jane Martin and Peter J Main examine some of the models which outline barriers to screening uptake and consider which will help the health visitor to increase the knowledge and understanding of at risk clients.

  8. 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.

  9. 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.

  10. 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...

  11. AB003. Validation of a two-stage screening model to predict moderate to severe obstructive sleep apnea in chronic tetraplegia

    Science.gov (United States)

    Graco, Marnie; Cross, Susan; Thiyagarajan, Chinnaya; Shafazand, Shirin; Ayas, Najib; Schembri, Rachel; Booker, Lauren; Nicholls, Carmel; Burns, Patricia; Nash, Mark; Green, Sally; Berlowitz, David J.

    2018-01-01

    Background Prevalence of obstructive sleep apnea (OSA) in people with chronic spinal cord injury (SCI) is estimated at between 28% and 77%. Current guidelines recommend polysomnography (PSG) for all people with SCI and symptoms of OSA. However, PSG is a resource intensive and frequently inaccessible test, especially in SCI. A two-stage model of questionnaire followed by overnight oximetry has been found to accurately detect moderate to severe OSA in the able-bodied. To determine whether a similar two-stage model can detect moderate to severe OSA in chronic tetraplegia. Methods An existing dataset of 78 people with tetraplegia was examined to determine predictors of OSA for inclusion in a new questionnaire. Cut-offs for the model were estimated with receiver operating characteristics (ROC) curve analysis. Model accuracy was evaluated prospectively in 100 participants with chronic, traumatic tetraplegia across four international SCI units. Results Multivariate analysis identified injury completeness, age, sleepiness, self-reported snoring and apneas for the new questionnaire [ROC area under curve (AUC) 0.87 (95% CI: 0.79–0.95)]. Oxygen desaturation index was also highly predictive [0.93 (0.87–0.98)]. The two-stage model had a sensitivity and specificity of 83% (66–93%) and 88% (75–94%) in the development group (n=78), and 77% (65–87%) and 81% (68–90%) in the validation group (n=100). Conclusions The two-stage screening model provides an accurate and translatable alternative to full PSG for identifying moderate to severe OSA in people with chronic tetraplegia. Implementation of this screening model could substantially increase the detection of OSA in tetraplegia and improve access to treatments.

  12. 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.

  13. 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.

  14. Prenatal Genetic Screening Tests

    Science.gov (United States)

    ... FAQs Prenatal Genetic Screening Tests Page Navigation ▼ ACOG Pregnancy Book Prenatal Genetic Screening Tests Patient Education FAQs Prenatal Genetic Screening Tests Patient Education Pamphlets - ...

  15. 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

  16. 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

    ; 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. Conclusions: High risk discrimination was validated in the DLCST cohort, mainly determined by nodule size. Age and family history of lung cancer were......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...... 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...

  17. Per-residue energy decomposition pharmacophore model to enhance virtual screening in drug discovery: a study for identification of reverse transcriptase inhibitors as potential anti-HIV agents

    Directory of Open Access Journals (Sweden)

    Cele FN

    2016-04-01

    Full Text Available Favourite N Cele, Muthusamy Ramesh, Mahmoud ES Soliman Molecular Modelling and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa Abstract: A novel virtual screening approach is implemented herein, which is a further improvement of our previously published “target-bound pharmacophore modeling approach”. The generated pharmacophore library is based only on highly contributing amino acid residues, instead of arbitrary pharmacophores, which are most commonly used in the conventional approaches in literature. Highly contributing amino acid residues were distinguished based on free binding energy contributions obtained from calculation from molecular dynamic (MD simulations. To the best of our knowledge; this is the first attempt in the literature using such an approach; previous approaches have relied on the docking score to generate energy-based pharmacophore models. However, docking scores are reportedly unreliable. Thus, we present a model for a per-residue energy decomposition, constructed from MD simulation ensembles generating a more trustworthy pharmacophore model, which can be applied in drug discovery workflow. This work is aimed at introducing a more rational approach to the field of drug design, rather than comparing the validity of this approach against those previously reported. We recommend additional computational and experimental work to further validate this approach. This approach was used to screen for potential reverse transcriptase inhibitors using the pharmacophoric features of compound GSK952. The complex was subjected to docking, thereafter, MD simulation confirmed the stability of the system. Experimentally determined inhibitors with known HIV-reverse transcriptase inhibitory activity were used to validate the protocol. Two potential hits (ZINC46849657 and ZINC54359621 showed a significant potential with regard to free binding energy. Reported results obtained from

  18. In silico exploration of c-KIT inhibitors by pharmaco-informatics methodology: pharmacophore modeling, 3D QSAR, docking studies, and virtual screening.

    Science.gov (United States)

    Chaudhari, Prashant; Bari, Sanjay

    2016-02-01

    c-KIT is a component of the platelet-derived growth factor receptor family, classified as type-III receptor tyrosine kinase. c-KIT has been reported to be involved in, small cell lung cancer, other malignant human cancers, and inflammatory and autoimmune diseases associated with mast cells. Available c-KIT inhibitors suffer from tribulations of growing resistance or cardiac toxicity. A combined in silico pharmacophore and structure-based virtual screening was performed to identify novel potential c-KIT inhibitors. In the present study, five molecules from the ZINC database were retrieved as new potential c-KIT inhibitors, using Schrödinger's Maestro 9.0 molecular modeling suite. An atom-featured 3D QSAR model was built using previously reported c-KIT inhibitors containing the indolin-2-one scaffold. The developed 3D QSAR model ADHRR.24 was found to be significant (R2 = 0.9378, Q2 = 0.7832) and instituted to be sufficiently robust with good predictive accuracy, as confirmed through external validation approaches, Y-randomization and GH approach [GH score 0.84 and Enrichment factor (E) 4.964]. The present QSAR model was further validated for the OECD principle 3, in that the applicability domain was calculated using a "standardization approach." Molecular docking of the QSAR dataset molecules and final ZINC hits were performed on the c-KIT receptor (PDB ID: 3G0E). Docking interactions were in agreement with the developed 3D QSAR model. Model ADHRR.24 was explored for ligand-based virtual screening followed by in silico ADME prediction studies. Five molecules from the ZINC database were obtained as potential c-KIT inhibitors with high in -silico predicted activity and strong key binding interactions with the c-KIT receptor.

  19. Pharmacophore modeling and structure-based virtual screening to identify potent inhibitors targeting LuxP of Vibrio harveyi.

    Science.gov (United States)

    Rajamanikandan, Sundaraj; Srinivasan, Pappu

    2016-12-01

    The main aim of the study is to identify molecules that can disrupt quorum sensing (QS) system of Vibrio harveyi and therefore perhaps the production of toxins. Recently, a novel class of dioxazaborocane derivatives has been found to block AI-2 QS by targeting LuxPQ, but the mechanism of protein inhibition is still unclear. In order to investigate the possible binding modes, all the derivatives were docked into the binding site of LuxP using induced fit docking (IFD). The computed binding affinity is in good agreement with the experimental data. Resultant protein-ligand complexes were simulated using Desmond module and the result revealed better binding of ligands in the binding site of LuxP. Both pharmacophore- and structure-based virtual screening was performed to identify novel hits against LuxP. A filtering protocol, including lipinski filters, number of rotatable bonds and three levels of docking precisions were used for the selection of hits with specific properties. The virtual screening results were then combined and analyzed, which retrieved six hits with significant Glide score, binding affinity toward LuxP. The pharmacokinetic properties of the retrieved hits are in the acceptable range. Enrichment calculation was performed to validate the final hits, to discriminate the active compounds from the inactive compounds. The identified hits could serve as a base for further drug development against LuxP of Vibrio harveyi.

  20. Cost-effectiveness of Chagas disease screening in Latin American migrants at primary health-care centres in Europe: a Markov model analysis.

    Science.gov (United States)

    Requena-Méndez, Ana; Bussion, Sheila; Aldasoro, Edelweiss; Jackson, Yves; Angheben, Andrea; Moore, David; Pinazo, Maria-Jesús; Gascón, Joaquim; Muñoz, Jose; Sicuri, Elisa

    2017-04-01

    Chagas disease is currently prevalent in European countries hosting large communities from Latin America. Whether asymptomatic individuals at risk of Chagas disease living in Europe should be screened and treated accordingly is unclear. We performed an economic evaluation of systematic Chagas disease screening of the Latin American population attending primary care centres in Europe. We constructed a decision tree model that compared the test option (screening of asymptomatic individuals, treatment, and follow-up of positive cases) with the no-test option (screening, treating, and follow-up of symptomatic individuals). The decision tree included a Markov model with five states, related to the chronic stage of the disease: indeterminate, cardiomyopathy, gastrointestinal, response to treatment, and death. The model started with a target population of 100 000 individuals, of which 4·2% (95% CI 2·2-6·8) were estimated to be infected by Trypanosoma cruzi. The primary outcome was the incremental cost-effectiveness ratio (ICER) between test and no-test options. Deterministic and probabilistic analyses (Monte Carlo simulations) were performed. In the deterministic analysis, total costs referred to 100 000 individuals in the test and no-test option were €30 903 406 and €6 597 403 respectively, with a difference of €24 306 003. The respective number of quality-adjusted life-years (QALYs) gained in the test and no-test option were 61 820·82 and 57 354·42. The ICER was €5442. In the probabilistic analysis, total costs for the test and no-test option were €32 163 649 (95% CI 31 263 705-33 063 593) and €6 904 764 (6 703 258-7 106 270), respectively. The respective number of QALYs gained was 64 634·35 (95% CI 62 809·6-66 459·1) and 59 875·73 (58 191·18-61 560·28). The difference in QALYs gained between the test and no test options was 4758·62 (95% CI 4618·42-4898·82). The incremental cost

  1. 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

  2. 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

  3. Differentiation of AmpC beta-lactamase binders vs. decoys using classification kNN QSAR modeling and application of the QSAR classifier to virtual screening

    Science.gov (United States)

    Hsieh, Jui-Hua; Wang, Xiang S.; Teotico, Denise; Golbraikh, Alexander; Tropsha, Alexander

    2008-09-01

    The use of inaccurate scoring functions in docking algorithms may result in the selection of compounds with high predicted binding affinity that nevertheless are known experimentally not to bind to the target receptor. Such falsely predicted binders have been termed `binding decoys'. We posed a question as to whether true binders and decoys could be distinguished based only on their structural chemical descriptors using approaches commonly used in ligand based drug design. We have applied the k-Nearest Neighbor ( kNN) classification QSAR approach to a dataset of compounds characterized as binders or binding decoys of AmpC beta-lactamase. Models were subjected to rigorous internal and external validation as part of our standard workflow and a special QSAR modeling scheme was employed that took into account the imbalanced ratio of inhibitors to non-binders (1:4) in this dataset. 342 predictive models were obtained with correct classification rate (CCR) for both training and test sets as high as 0.90 or higher. The prediction accuracy was as high as 100% (CCR = 1.00) for the external validation set composed of 10 compounds (5 true binders and 5 decoys) selected randomly from the original dataset. For an additional external set of 50 known non-binders, we have achieved the CCR of 0.87 using very conservative model applicability domain threshold. The validated binary kNN QSAR models were further employed for mining the NCGC AmpC screening dataset (69653 compounds). The consensus prediction of 64 compounds identified as screening hits in the AmpC PubChem assay disagreed with their annotation in PubChem but was in agreement with the results of secondary assays. At the same time, 15 compounds were identified as potential binders contrary to their annotation in PubChem. Five of them were tested experimentally and showed inhibitory activities in millimolar range with the highest binding constant Ki of 135 μM. Our studies suggest that validated QSAR models could complement

  4. 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 pipelin