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

PubMed

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.

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

NASA Astrophysics Data System (ADS)

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.

Colorectal Cancer Deaths Attributable to Nonuse of Screening in the United States

PubMed Central

Meester, Reinier G.S.; Doubeni, Chyke A.; Lansdorp-Vogelaar, Iris; Goede, S.L.; Levin, Theodore R.; Quinn, Virginia P.; van Ballegooijen, Marjolein; Corley, Douglas A.; Zauber, Ann G.

2015-01-01

Purpose Screening is a major contributor to colorectal cancer (CRC) mortality reductions in the U.S., but is underutilized. We estimated the fraction of CRC deaths attributable to nonuse of screening to demonstrate the potential benefits from targeted interventions. Methods The established MISCAN-colon microsimulation model was used to estimate the population attributable fraction (PAF) in people aged ≥50 years. The model incorporates long-term patterns and effects of screening by age and type of screening test. PAF for 2010 was estimated using currently available data on screening uptake; PAF was also projected assuming constant future screening rates to incorporate lagged effects from past increases in screening uptake. We also computed PAF using Levin's formula to gauge how this simpler approach differs from the model-based approach. Results There were an estimated 51,500 CRC deaths in 2010, about 63% (N∼32,200) of which were attributable to non-screening. The PAF decreases slightly to 58% in 2020. Levin's approach yielded a considerably more conservative PAF of 46% (N∼23,600) for 2010. Conclusions The majority of current U.S. CRC deaths are attributable to non-screening. This underscores the potential benefits of increasing screening uptake in the population. Traditional methods of estimating PAF underestimated screening effects compared with model-based approaches. PMID:25721748

Combining structure-based pharmacophore modeling, virtual screening, and in silico ADMET analysis to discover novel tetrahydro-quinoline based pyruvate kinase isozyme M2 activators with antitumor activity

PubMed Central

Chen, Can; Wang, Ting; Wu, Fengbo; Huang, Wei; He, Gu; Ouyang, Liang; Xiang, Mingli; Peng, Cheng; Jiang, Qinglin

2014-01-01

Compared with normal differentiated cells, cancer cells upregulate the expression of pyruvate kinase isozyme M2 (PKM2) to support glycolytic intermediates for anabolic processes, including the synthesis of nucleic acids, amino acids, and lipids. In this study, a combination of the structure-based pharmacophore modeling and a hybrid protocol of virtual screening methods comprised of pharmacophore model-based virtual screening, docking-based virtual screening, and in silico ADMET (absorption, distribution, metabolism, excretion and toxicity) analysis were used to retrieve novel PKM2 activators from commercially available chemical databases. Tetrahydroquinoline derivatives were identified as potential scaffolds of PKM2 activators. Thus, the hybrid virtual screening approach was applied to screen the focused tetrahydroquinoline derivatives embedded in the ZINC database. Six hit compounds were selected from the final hits and experimental studies were then performed. Compound 8 displayed a potent inhibitory effect on human lung cancer cells. Following treatment with Compound 8, cell viability, apoptosis, and reactive oxygen species (ROS) production were examined in A549 cells. Finally, we evaluated the effects of Compound 8 on mice xenograft tumor models in vivo. These results may provide important information for further research on novel PKM2 activators as antitumor agents. PMID:25214764

Analysis of Parametric Adaptive Signal Detection with Applications to Radars and Hyperspectral Imaging

DTIC Science & Technology

2010-02-01

98 8.4.5 Training Screening ............................. .................................................................99 8.5 Experimental...associated with the proposed parametric model. Several im- portant issues are discussed, including model order selection, training screening , and time...parameters associated with the NS-AR model. In addition, we develop model order selection, training screening , and time-series based whitening and

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

PubMed

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.

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

PubMed

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

2006-04-01

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

Characteristics of white LED transmission through a smoke screen

NASA Astrophysics Data System (ADS)

Zheng, Yunfei; Yang, Aiying; Feng, Lihui; Guo, Peng

2018-01-01

The characteristics of white LED transmission through a smoke screen is critical for visible light communication through a smoke screen. Based on the Mie scattering theory, the Monte Carlo transmission model is established. Based on the probability density function, the white LED sampling model is established according to the measured spectrum of a white LED and the distribution angle of the lambert model. The sampling model of smoke screen particle diameter is also established according to its distribution. We simulate numerically the influence the smoke thickness, the smoke concentration and the angle of irradiance of white LED on transmittance of the white LED. We construct a white LED smoke transmission experiment system. The measured result on the light transmittance and the smoke concentration agreed with the simulated result, and demonstrated the validity of simulation model for visible light transmission channel through a smoke screen.

A systematic review on US-based community health navigator (CHN) interventions for cancer screening promotion--comparing community- versus clinic-based navigator models.

PubMed

Hou, Su-I; Roberson, Kiersten

2015-03-01

This study synthesized lessons learned from US-based community and clinic health navigator (CHN) interventions on cancer screening promotion to identify characteristics of models and approaches for addressing cancer disparities. The combination terms "cancer screening" and "community health workers or navigators" or "patient navigators" were used in searching Medline, CINAHL, and PsycInfo. A total of 27 articles published during January 2005∼April 2014 were included. Two CHN models were identified: community-based (15 studies) and clinic/hospital-based (12 studies). While both models used the term "navigators," most community-based programs referred them as community health workers/navigators/advisors, whereas clinic-based programs often called them patient navigators. Most community-based CHN interventions targeted specific racial/ethnic minority or rural groups, while clinic-based programs mostly targeted urban low income or mixed ethnic groups. Most community-based CHN programs outreached members from community networks, while clinic-based programs commonly worked with pre-identified in-service clients. Overall, regardless model type, CHNs had similar roles and responsibilities, and interventions demonstrated effective outcomes. Our review identified characteristics of CHN interventions with attention to different settings. Lessons learned have implication on the dissemination and implementation of CHN interventions for cancer screening promotion across setting and target groups.

Modelling the Costs and Effects of Selective and Universal Hospital Admission Screening for Methicillin-Resistant Staphylococcus aureus

PubMed Central

Hubben, Gijs; Bootsma, Martin; Luteijn, Michiel; Glynn, Diarmuid; Bishai, David

2011-01-01

Background Screening at hospital admission for carriage of methicillin-resistant Staphylococcus aureus (MRSA) has been proposed as a strategy to reduce nosocomial infections. The objective of this study was to determine the long-term costs and health benefits of selective and universal screening for MRSA at hospital admission, using both PCR-based and chromogenic media-based tests in various settings. Methodology/Principal Findings A simulation model of MRSA transmission was used to determine costs and effects over 15 years from a US healthcare perspective. We compared admission screening together with isolation of identified carriers against a baseline policy without screening or isolation. Strategies included selective screening of high risk patients or universal admission screening, with PCR-based or chromogenic media-based tests, in medium (5%) or high nosocomial prevalence (15%) settings. The costs of screening and isolation per averted MRSA infection were lowest using selective chromogenic-based screening in high and medium prevalence settings, at $4,100 and $10,300, respectively. Replacing the chromogenic-based test with a PCR-based test costs $13,000 and $36,200 per additional infection averted, and subsequent extension to universal screening with PCR would cost $131,000 and $232,700 per additional infection averted, in high and medium prevalence settings respectively. Assuming $17,645 benefit per infection averted, the most cost-saving strategies in high and medium prevalence settings were selective screening with PCR and selective screening with chromogenic, respectively. Conclusions/Significance Admission screening costs $4,100–$21,200 per infection averted, depending on strategy and setting. Including financial benefits from averted infections, screening could well be cost saving. PMID:21483492

A cell-based assay for aggregation inhibitors as therapeutics of polyglutamine-repeat disease and validation in Drosophila

NASA Astrophysics Data System (ADS)

Apostol, Barbara L.; Kazantsev, Alexsey; Raffioni, Simona; Illes, Katalin; Pallos, Judit; Bodai, Laszlo; Slepko, Natalia; Bear, James E.; Gertler, Frank B.; Hersch, Steven; Housman, David E.; Marsh, J. Lawrence; Michels Thompson, Leslie

2003-05-01

The formation of polyglutamine-containing aggregates and inclusions are hallmarks of pathogenesis in Huntington's disease that can be recapitulated in model systems. Although the contribution of inclusions to pathogenesis is unclear, cell-based assays can be used to screen for chemical compounds that affect aggregation and may provide therapeutic benefit. We have developed inducible PC12 cell-culture models to screen for loss of visible aggregates. To test the validity of this approach, compounds that inhibit aggregation in the PC12 cell-based screen were tested in a Drosophila model of polyglutamine-repeat disease. The disruption of aggregation in PC12 cells strongly correlates with suppression of neuronal degeneration in Drosophila. Thus, the engineered PC12 cells coupled with the Drosophila model provide a rapid and effective method to screen and validate compounds.

Knowledge based identification of MAO-B selective inhibitors using pharmacophore and structure based virtual screening models.

PubMed

Boppana, Kiran; Dubey, P K; Jagarlapudi, Sarma A R P; Vadivelan, S; Rambabu, G

2009-09-01

Monoamine Oxidase B interaction with known ligands was investigated using combined pharmacophore and structure based modeling approach. The docking results suggested that the pharmacophore and docking models are in good agreement and are used to identify the selective MAO-B inhibitors. The best model, Hypo2 consists of three pharmacophore features, i.e., one hydrogen bond acceptor, one hydrogen bond donor and one ring aromatic. The Hypo2 model was used to screen an in-house database of 80,000 molecules and have resulted in 5500 compounds. Docking studies were performed, subsequently, on the cluster representatives of 530 hits from 5500 compounds. Based on the structural novelty and selectivity index, we have suggested 15 selective MAO-B inhibitors for further synthesis and pharmacological screening.

An Efficient Variable Screening Method for Effective Surrogate Models for Reliability-Based Design Optimization

DTIC Science & Technology

2014-04-01

surrogate model generation is difficult for high -dimensional problems, due to the curse of dimensionality. Variable screening methods have been...a variable screening model was developed for the quasi-molecular treatment of ion-atom collision [16]. In engineering, a confidence interval of...for high -level radioactive waste [18]. Moreover, the design sensitivity method can be extended to the variable screening method because vital

Cost-effectiveness of Population Screening for BRCA Mutations in Ashkenazi Jewish Women Compared With Family History–Based Testing

PubMed Central

Manchanda, Ranjit; Legood, Rosa; Burnell, Matthew; McGuire, Alistair; Raikou, Maria; Loggenberg, Kelly; Wardle, Jane; Sanderson, Saskia; Gessler, Sue; Side, Lucy; Balogun, Nyala; Desai, Rakshit; Kumar, Ajith; Dorkins, Huw; Wallis, Yvonne; Chapman, Cyril; Taylor, Rohan; Jacobs, Chris; Tomlinson, Ian; Beller, Uziel; Menon, Usha

2015-01-01

Background: Population-based testing for BRCA1/2 mutations detects the high proportion of carriers not identified by cancer family history (FH)–based testing. We compared the cost-effectiveness of population-based BRCA testing with the standard FH-based approach in Ashkenazi Jewish (AJ) women. Methods: A decision-analytic model was developed to compare lifetime costs and effects amongst AJ women in the UK of BRCA founder-mutation testing amongst: 1) all women in the population age 30 years or older and 2) just those with a strong FH (≥10% mutation risk). The model assumes that BRCA carriers are offered risk-reducing salpingo-oophorectomy and annual MRI/mammography screening or risk-reducing mastectomy. Model probabilities utilize the Genetic Cancer Prediction through Population Screening trial/published literature to estimate total costs, effects in terms of quality-adjusted life-years (QALYs), cancer incidence, incremental cost-effectiveness ratio (ICER), and population impact. Costs are reported at 2010 prices. Costs/outcomes were discounted at 3.5%. We used deterministic/probabilistic sensitivity analysis (PSA) to evaluate model uncertainty. Results: Compared with FH-based testing, population-screening saved 0.090 more life-years and 0.101 more QALYs resulting in 33 days’ gain in life expectancy. Population screening was found to be cost saving with a baseline-discounted ICER of -£2079/QALY. Population-based screening lowered ovarian and breast cancer incidence by 0.34% and 0.62%. Assuming 71% testing uptake, this leads to 276 fewer ovarian and 508 fewer breast cancer cases. Overall, reduction in treatment costs led to a discounted cost savings of £3.7 million. Deterministic sensitivity analysis and 94% of simulations on PSA (threshold £20000) indicated that population screening is cost-effective, compared with current NHS policy. Conclusion: Population-based screening for BRCA mutations is highly cost-effective compared with an FH-based approach in AJ women age 30 years and older. PMID:25435542

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

PubMed

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.

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

PubMed Central

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 model. Participants Simulated population of individuals 55 and older based on smoking prevalence and census data from Northeast Pennsylvania. Interventions Hypothetical lung cancer control from 2014 to 2050 through (1) screening with CT, (2) intensified smoking cessation or (3) a combination strategy. Primary and secondary outcome measures Primary outcomes were lung cancer mortality rates. Secondary outcomes included number of people eligible for screening and number of radiation-induced lung cancers. Results 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. Conclusions 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. PMID:26928026

Screening for Wilms tumor and hepatoblastoma in children with Beckwith-Wiedemann syndromes: a cost-effective model.

PubMed

McNeil, D E; Brown, M; Ching, A; DeBaun, M R

2001-10-01

We undertook a cost-benefit analysis of screening for Wilms tumor and hepatoblastoma in children with Beckwith-Wiedemann syndrome (BWS), a known cancer predisposition syndrome. The purpose of this analysis was twofold: first, to assess whether screening in children with BWS has the potential to be cost-effective; second, if screening appears to be cost-effective, to determine which parameters would be most important to assess if a screening trial were initiated. We used data from the BWS registry at the National Cancer Institute, the National Wilms Tumor Study (NWTS), and large published series to model events for two hypothetical cohorts of 1,000 infants born with BWS. One hypothetical cohort was screened for cancer until a predetermined age, representing the base case. The other cohort was unscreened. For our base case, we assumed: (a) sonography examinations three times yearly (triannually) from birth until 7 years of age; (b) screening would result in one stage shift downward at diagnosis for Wilms tumor and hepatoblastoma; (c) 100% sensitivity and 95% specificity for detecting clinical stage I Wilms tumor and hepatoblastoma; (d) a 3% discount rate; (e) a false positive result cost of $402. We estimated mortality rates based on published Wilms tumor and hepatoblastoma stage specific survival. Using the base case, screening a child with BWS from birth until 4 years of age results in a cost per life year saved of $9,642 while continuing until 7 years of age results in a cost per life-year saved of $14,740. When variables such as cost of screening examination, discount rate, and effectiveness of screening were varied based on high and low estimates, the incremental cost per life-year saved for screening up until age four remained comparable to acceptable population based cancer screening ranges (< $50,000 per life year saved). Under our model's assumptions, abdominal sonography examinations in children with BWS represent a reasonable strategy for a cancer screening program. A cancer screening trial is warranted to determine if, when, and how often children with BWS should be screened and to determine cost-effectiveness in clinical practice. Published 2001 Wiley-Liss, Inc.

Limitations of basing screening policies on screening trials: The US Preventive Services Task Force and Prostate Cancer Screening.

PubMed

Etzioni, Ruth; Gulati, Roman; Cooperberg, Matt R; Penson, David M; Weiss, Noel S; Thompson, Ian M

2013-04-01

The US Preventive Services Task Force recently recommended against prostate-specific antigen screening for prostate cancer based primarily on evidence from the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. : To examine limitations of basing screening policy on evidence from screening trials. We reviewed published modeling studies that examined population and trial data. The studies (1) project the roles of screening and changes in primary treatment in the US mortality decline; (2) extrapolate the ERSPC mortality reduction to the long-term US setting; (3) estimate overdiagnosis based on US incidence trends; and (4) quantify the impact of control arm screening on PLCO mortality results. Screening plausibly explains 45% and changes in primary treatment can explain 33% of the US prostate cancer mortality decline. Extrapolating the ERSPC results to the long-term US setting implies an absolute mortality reduction at least 5 times greater than that observed in the trial. Approximately 28% of screen-detected cases are overdiagnosed in the United States versus 58% of screen-detected cases suggested by the ERSPC results. Control arm screening can explain the null result in the PLCO trial. Modeling studies indicate that population trends and trial results extended to the long-term population setting are consistent with greater benefit of prostate-specific antigen screening-and more favorable harm-benefit tradeoffs-than has been suggested by empirical trial evidence.

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

Cancer.gov

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

Cell and small animal models for phenotypic drug discovery.

PubMed

Szabo, Mihaly; Svensson Akusjärvi, Sara; Saxena, Ankur; Liu, Jianping; Chandrasekar, Gayathri; Kitambi, Satish S

2017-01-01

The phenotype-based drug discovery (PDD) approach is re-emerging as an alternative platform for drug discovery. This review provides an overview of the various model systems and technical advances in imaging and image analyses that strengthen the PDD platform. In PDD screens, compounds of therapeutic value are identified based on the phenotypic perturbations produced irrespective of target(s) or mechanism of action. In this article, examples of phenotypic changes that can be detected and quantified with relative ease in a cell-based setup are discussed. In addition, a higher order of PDD screening setup using small animal models is also explored. As PDD screens integrate physiology and multiple signaling mechanisms during the screening process, the identified hits have higher biomedical applicability. Taken together, this review highlights the advantages gained by adopting a PDD approach in drug discovery. Such a PDD platform can complement target-based systems that are currently in practice to accelerate drug discovery.

Risk Profiling May Improve Lung Cancer Screening

Cancer.gov

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

Inhibitors of Helicobacter pylori Protease HtrA Found by ‘Virtual Ligand’ Screening Combat Bacterial Invasion of Epithelia

PubMed Central

Schneider, Petra; Hoy, Benjamin; Wessler, Silja; Schneider, Gisbert

2011-01-01

Background The human pathogen Helicobacter pylori (H. pylori) is a main cause for gastric inflammation and cancer. Increasing bacterial resistance against antibiotics demands for innovative strategies for therapeutic intervention. Methodology/Principal Findings We present a method for structure-based virtual screening that is based on the comprehensive prediction of ligand binding sites on a protein model and automated construction of a ligand-receptor interaction map. Pharmacophoric features of the map are clustered and transformed in a correlation vector (‘virtual ligand’) for rapid virtual screening of compound databases. This computer-based technique was validated for 18 different targets of pharmaceutical interest in a retrospective screening experiment. Prospective screening for inhibitory agents was performed for the protease HtrA from the human pathogen H. pylori using a homology model of the target protein. Among 22 tested compounds six block E-cadherin cleavage by HtrA in vitro and result in reduced scattering and wound healing of gastric epithelial cells, thereby preventing bacterial infiltration of the epithelium. Conclusions/Significance This study demonstrates that receptor-based virtual screening with a permissive (‘fuzzy’) pharmacophore model can help identify small bioactive agents for combating bacterial infection. PMID:21483848

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

PubMed

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/

Discovering new PI3Kα inhibitors with a strategy of combining ligand-based and structure-based virtual screening

NASA Astrophysics Data System (ADS)

Yu, Miao; Gu, Qiong; Xu, Jun

2018-02-01

PI3Kα is a promising drug target for cancer chemotherapy. In this paper, we report a strategy of combing ligand-based and structure-based virtual screening to identify new PI3Kα inhibitors. First, naïve Bayesian (NB) learning models and a 3D-QSAR pharmacophore model were built based upon known PI3Kα inhibitors. Then, the SPECS library was screened by the best NB model. This resulted in virtual hits, which were validated by matching the structures against the pharmacophore models. The pharmacophore matched hits were then docked into PI3Kα crystal structures to form ligand-receptor complexes, which are further validated by the Glide-XP program to result in structural validated hits. The structural validated hits were examined by PI3Kα inhibitory assay. With this screening protocol, ten PI3Kα inhibitors with new scaffolds were discovered with IC50 values ranging 0.44-31.25 μM. The binding affinities for the most active compounds 33 and 74 were estimated through molecular dynamics simulations and MM-PBSA analyses.

Scheme for the selection of measurement uncertainty models in blood establishments' screening immunoassays.

PubMed

Pereira, Paulo; Westgard, James O; Encarnação, Pedro; Seghatchian, Jerard; de Sousa, Gracinda

2015-02-01

Blood establishments routinely perform screening immunoassays to assess safety of the blood components. As with any other screening test, results have an inherent uncertainty. In blood establishments the major concern is the chance of false negatives, due to its possible impact on patients' health. This article briefly reviews GUM and diagnostic accuracy models for screening immunoassays, recommending a scheme to support the screening laboratories' staffs on the selection of a model considering the intended use of the screening results (i.e., post-transfusion safety). The discussion is grounded on a "risk-based thinking", risk being considered from the blood donor selection to the screening immunoassays. A combination of GUM and diagnostic accuracy models to evaluate measurement uncertainty in blood establishments is recommended. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Evonik-Mainz Eye Care-Study (EMECS): Development of an Expert System for Glaucoma Risk Detection in a Working Population

PubMed Central

Wahl, Jochen; Barleon, Lorenz; Morfeld, Peter; Lichtmeß, Andrea; Haas-Brähler, Sibylle; Pfeiffer, Norbert

2016-01-01

Purpose To develop an expert system for glaucoma screening in a working population based on a human expert procedure using images of optic nerve head (ONH), visual field (frequency doubling technology, FDT) and intraocular pressure (IOP). Methods 4167 of 13037 (32%) employees between 40 and 65 years of Evonik Industries were screened. An experienced glaucoma expert (JW) assessed papilla parameters and evaluated all individual screening results. His classification into “no glaucoma”, “possible glaucoma” and “probable glaucoma” was defined as “gold standard”. A screening model was developed which was tested versus the gold-standard. This model took into account the assessment of the ONH. Values and relationships of CDR and IOP and the FDT were considered additionally and a glaucoma score was generated. The structure of the screening model was specified a priori whereas values of the parameters were chosen post-hoc to optimize sensitivity and specificity of the algorithm. Simple screening models based on IOP and / or FDT were investigated for comparison. Results 111 persons (2.66%) were classified as glaucoma suspects, thereof 13 (0.31%) as probable and 98 (2.35%) as possible glaucoma suspects by the expert. Re-evaluation by the screening model revealed a sensitivity of 83.8% and a specificity of 99.6% for all glaucoma suspects. The positive predictive value of the model was 80.2%, the negative predictive value 99.6%. Simple screening models showed insufficient diagnostic accuracy. Conclusion Adjustment of ONH and symmetry parameters with respect to excavation and IOP in an expert system produced sufficiently satisfying diagnostic accuracy. This screening model seems to be applicable in such a working population with relatively low age and low glaucoma prevalence. Different experts should validate the model in different populations. PMID:27479301

The Evonik-Mainz Eye Care-Study (EMECS): Development of an Expert System for Glaucoma Risk Detection in a Working Population.

PubMed

Wahl, Jochen; Barleon, Lorenz; Morfeld, Peter; Lichtmeß, Andrea; Haas-Brähler, Sibylle; Pfeiffer, Norbert

2016-01-01

To develop an expert system for glaucoma screening in a working population based on a human expert procedure using images of optic nerve head (ONH), visual field (frequency doubling technology, FDT) and intraocular pressure (IOP). 4167 of 13037 (32%) employees between 40 and 65 years of Evonik Industries were screened. An experienced glaucoma expert (JW) assessed papilla parameters and evaluated all individual screening results. His classification into "no glaucoma", "possible glaucoma" and "probable glaucoma" was defined as "gold standard". A screening model was developed which was tested versus the gold-standard. This model took into account the assessment of the ONH. Values and relationships of CDR and IOP and the FDT were considered additionally and a glaucoma score was generated. The structure of the screening model was specified a priori whereas values of the parameters were chosen post-hoc to optimize sensitivity and specificity of the algorithm. Simple screening models based on IOP and / or FDT were investigated for comparison. 111 persons (2.66%) were classified as glaucoma suspects, thereof 13 (0.31%) as probable and 98 (2.35%) as possible glaucoma suspects by the expert. Re-evaluation by the screening model revealed a sensitivity of 83.8% and a specificity of 99.6% for all glaucoma suspects. The positive predictive value of the model was 80.2%, the negative predictive value 99.6%. Simple screening models showed insufficient diagnostic accuracy. Adjustment of ONH and symmetry parameters with respect to excavation and IOP in an expert system produced sufficiently satisfying diagnostic accuracy. This screening model seems to be applicable in such a working population with relatively low age and low glaucoma prevalence. Different experts should validate the model in different populations.

On the use of hidden Markov models for gaze pattern modeling

NASA Astrophysics Data System (ADS)

Mannaru, Pujitha; Balasingam, Balakumar; Pattipati, Krishna; Sibley, Ciara; Coyne, Joseph

2016-05-01

Some of the conventional metrics derived from gaze patterns (on computer screens) to study visual attention, engagement and fatigue are saccade counts, nearest neighbor index (NNI) and duration of dwells/fixations. Each of these metrics has drawbacks in modeling the behavior of gaze patterns; one such drawback comes from the fact that some portions on the screen are not as important as some other portions on the screen. This is addressed by computing the eye gaze metrics corresponding to important areas of interest (AOI) on the screen. There are some challenges in developing accurate AOI based metrics: firstly, the definition of AOI is always fuzzy; secondly, it is possible that the AOI may change adaptively over time. Hence, there is a need to introduce eye-gaze metrics that are aware of the AOI in the field of view; at the same time, the new metrics should be able to automatically select the AOI based on the nature of the gazes. In this paper, we propose a novel way of computing NNI based on continuous hidden Markov models (HMM) that model the gazes as 2D Gaussian observations (x-y coordinates of the gaze) with the mean at the center of the AOI and covariance that is related to the concentration of gazes. The proposed modeling allows us to accurately compute the NNI metric in the presence of multiple, undefined AOI on the screen in the presence of intermittent casual gazing that is modeled as random gazes on the screen.

Using resource modelling to inform decision making and service planning: the case of colorectal cancer screening in Ireland.

PubMed

Sharp, Linda; Tilson, Lesley; Whyte, Sophie; Ceilleachair, Alan O; Walsh, Cathal; Usher, Cara; Tappenden, Paul; Chilcott, James; Staines, Anthony; Barry, Michael; Comber, Harry

2013-03-19

Organised colorectal cancer screening is likely to be cost-effective, but cost-effectiveness results alone may not help policy makers to make decisions about programme feasibility or service providers to plan programme delivery. For these purposes, estimates of the impact on the health services of actually introducing screening in the target population would be helpful. However, these types of analyses are rarely reported. As an illustration of such an approach, we estimated annual health service resource requirements and health outcomes over the first decade of a population-based colorectal cancer screening programme in Ireland. A Markov state-transition model of colorectal neoplasia natural history was used. Three core screening scenarios were considered: (a) flexible sigmoidoscopy (FSIG) once at age 60, (b) biennial guaiac-based faecal occult blood tests (gFOBT) at 55-74 years, and (c) biennial faecal immunochemical tests (FIT) at 55-74 years. Three alternative FIT roll-out scenarios were also investigated relating to age-restricted screening (55-64 years) and staggered age-based roll-out across the 55-74 age group. Parameter estimates were derived from literature review, existing screening programmes, and expert opinion. Results were expressed in relation to the 2008 population (4.4 million people, of whom 700,800 were aged 55-74). FIT-based screening would deliver the greatest health benefits, averting 164 colorectal cancer cases and 272 deaths in year 10 of the programme. Capacity would be required for 11,095-14,820 diagnostic and surveillance colonoscopies annually, compared to 381-1,053 with FSIG-based, and 967-1,300 with gFOBT-based, screening. With FIT, in year 10, these colonoscopies would result in 62 hospital admissions for abdominal bleeding, 27 bowel perforations and one death. Resource requirements for pathology, diagnostic radiology, radiotherapy and colorectal resection were highest for FIT. Estimates depended on screening uptake. Alternative FIT roll-out scenarios had lower resource requirements. While FIT-based screening would quite quickly generate attractive health outcomes, it has heavy resource requirements. These could impact on the feasibility of a programme based on this screening modality. Staggered age-based roll-out would allow time to increase endoscopy capacity to meet programme requirements. Resource modelling of this type complements conventional cost-effectiveness analyses and can help inform policy making and service planning.

Simulation optimization of PSA-threshold based prostate cancer screening policies

PubMed Central

Zhang, Jingyu; Denton, Brian T.; Shah, Nilay D.; Inman, Brant A.

2013-01-01

We describe a simulation optimization method to design PSA screening policies based on expected quality adjusted life years (QALYs). Our method integrates a simulation model in a genetic algorithm which uses a probabilistic method for selection of the best policy. We present computational results about the efficiency of our algorithm. The best policy generated by our algorithm is compared to previously recommended screening policies. Using the policies determined by our model, we present evidence that patients should be screened more aggressively but for a shorter length of time than previously published guidelines recommend. PMID:22302420

Drug screening using model systems: some basics

PubMed Central

2016-01-01

ABSTRACT 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. PMID:27821602

[Cost-effectiveness analysis of universal screening for thyroid disease in pregnant women in Spain].

PubMed

Donnay Candil, Sergio; Balsa Barro, José Antonio; Álvarez Hernández, Julia; Crespo Palomo, Carlos; Pérez-Alcántara, Ferrán; Polanco Sánchez, Carlos

2015-01-01

To assess the cost-effectiveness of universal screening for thyroid disease in pregnant women in Spain as compared to high risk screening and no screening. A decision-analytic model comparing the incremental cost per quality-adjusted life year (QALY) of universal screening versus high risk screening and versus no screening. was used for the pregnancy and postpartum period. Probabilities from randomized controlled trials were considered for adverse obstetrical outcomes. A Markov model was used to assess the lifetime period after the first postpartum year and account for development of overt hypothyroidism. The main assumptions in the model and use of resources were assessed by local clinical experts. The analysis considered direct healthcare costs only. Universal screening gained .011 QALYs over high risk screening and .014 QALYS over no screening. Total direct costs per patient were €5,786 for universal screening, €5,791 for high risk screening, and €5,781 for no screening. Universal screening was dominant compared to risk-based screening and a very cost-effective alternative as compared to no screening. Use of universal screening instead of high risk screening would result in €2,653,854 annual savings for the Spanish National Health System. Universal screening for thyroid disease in pregnant women in the first trimester is dominant in Spain as compared to risk-based screening, and is cost-effective as compared to no screening (incremental cost-effectiveness ratio of €374 per QALY). Moreover, it allows diagnosing and treating cases of clinical and subclinical hypothyroidism that may not be detected when only high-risk women are screened. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Global Sensitivity Analysis of Environmental Models: Convergence, Robustness and Validation

NASA Astrophysics Data System (ADS)

Sarrazin, Fanny; Pianosi, Francesca; Khorashadi Zadeh, Farkhondeh; Van Griensven, Ann; Wagener, Thorsten

2015-04-01

Global Sensitivity Analysis aims to characterize the impact that variations in model input factors (e.g. the parameters) have on the model output (e.g. simulated streamflow). In sampling-based Global Sensitivity Analysis, the sample size has to be chosen carefully in order to obtain reliable sensitivity estimates while spending computational resources efficiently. Furthermore, insensitive parameters are typically identified through the definition of a screening threshold: the theoretical value of their sensitivity index is zero but in a sampling-base framework they regularly take non-zero values. There is little guidance available for these two steps in environmental modelling though. The objective of the present study is to support modellers in making appropriate choices, regarding both sample size and screening threshold, so that a robust sensitivity analysis can be implemented. We performed sensitivity analysis for the parameters of three hydrological models with increasing level of complexity (Hymod, HBV and SWAT), and tested three widely used sensitivity analysis methods (Elementary Effect Test or method of Morris, Regional Sensitivity Analysis, and Variance-Based Sensitivity Analysis). We defined criteria based on a bootstrap approach to assess three different types of convergence: the convergence of the value of the sensitivity indices, of the ranking (the ordering among the parameters) and of the screening (the identification of the insensitive parameters). We investigated the screening threshold through the definition of a validation procedure. The results showed that full convergence of the value of the sensitivity indices is not necessarily needed to rank or to screen the model input factors. Furthermore, typical values of the sample sizes that are reported in the literature can be well below the sample sizes that actually ensure convergence of ranking and screening.

Prostate-specific antigen-based prostate cancer screening: Past and future.

PubMed

Alberts, Arnout R; Schoots, Ivo G; Roobol, Monique J

2015-06-01

Prostate-specific antigen-based prostate cancer screening remains a controversial topic. Up to now, there is worldwide consensus on the statement that the harms of population-based screening, mainly as a result of overdiagnosis (the detection of clinically insignificant tumors that would have never caused any symptoms), outweigh the benefits. However, worldwide opportunistic screening takes place on a wide scale. The European Randomized Study of Screening for Prostate Cancer showed a reduction in prostate cancer mortality through prostate-specific antigen based-screening. These population-based data need to be individualized in order to avoid screening in those who cannot benefit and start screening in those who will. For now, lacking a more optimal screening approach, screening should only be started after the process of shared decision-making. The focus of future research is the reduction of unnecessary testing and overdiagnosis by further research to better biomarkers and the value of the multiparametric magnetic resonance imaging, potentially combined in already existing prostate-specific antigen-based multivariate risk prediction models. © 2015 The Japanese Urological Association.

Physiologically-based Pharmacokinetic(PBPK) Models Application to Screen Environmental Hazards Related to Adverse Outcome Pathways(AOPs)

EPA Science Inventory

PBPK models are useful in estimating exposure levels based on in vitro to in vivo extrapolation (IVIVE) calculations. Linkage of large sets of chemically screened vitro signature effects to in vivo adverse outcomes using IVIVE is central to the concepts of toxicology in the 21st ...

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

Cancer.gov

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.

Randomized controlled trial of storytelling compared to a personal risk tool intervention on colorectal cancer screening in low-income patients.

PubMed

Larkey, Linda K; McClain, Darya; Roe, Denise J; Hector, Richard D; Lopez, Ana Maria; Sillanpaa, Brian; Gonzalez, Julie

2015-01-01

Screening rates for colorectal cancer (CRC) lag for low-income, minority populations, contributing to poorer survival rates. A model of storytelling as culture-centric health promotion was tested for promoting CRC screening. A two-group parallel randomized controlled trial. Primary care, safety-net clinics. Low-income patients due for CRC screening, ages 50 to 75 years, speaking English or Spanish. Patients were exposed to either a video created from personal stories composited into a drama about "Papa" receiving CRC screening, or an instrument estimating level of personal cancer risk. Patients received a health care provider referral for CRC screening and were followed up for 3 months to document adherence. Behavioral factors related to the narrative model (identification and engagement) and theory of planned behavior. Main effects of the interventions on screening were tested, controlling for attrition factors, and demographic factor associations were assessed. Path analysis with model variables was used to test the direct effects and multiple mediator models. Main effects on CRC screening (roughly half stool-based tests, half colonoscopy) did not indicate significant differences (37% and 42% screened for storytelling and risk-based messages, respectively; n = 539; 33.6% male; 62% Hispanic). Factors positively associated with CRC screening included being female, Hispanic, married or living with a partner, speaking Spanish, having a primary care provider, lower income, and no health insurance. Engagement, working through positive attitudes toward the behavior, predicted CRC screening. A storytelling and a personalized risk-tool intervention achieved similar levels of screening among unscreened/underscreened, low-income patients. Factors usually associated with lower rates of screening (e.g., no insurance, being Hispanic) were related to more adherence. Both interventions' engagement factor facilitated positive attitudes about CRC screening associated with behavior change.

Identification of promising DNA GyrB inhibitors for Tuberculosis using pharmacophore-based virtual screening, molecular docking and molecular dynamics studies.

PubMed

Islam, Md Ataul; Pillay, Tahir S

2017-08-01

In this study, we searched for potential DNA GyrB inhibitors using pharmacophore-based virtual screening followed by molecular docking and molecular dynamics simulation approaches. For this purpose, a set of 248 DNA GyrB inhibitors was collected from the literature and a well-validated pharmacophore model was generated. The best pharmacophore model explained that two each of hydrogen bond acceptors and hydrophobicity regions were critical for inhibition of DNA GyrB. Good statistical results of the pharmacophore model indicated that the model was robust in nature. Virtual screening of molecular databases revealed three molecules as potential antimycobacterial agents. The final screened promising compounds were evaluated in molecular docking and molecular dynamics simulation studies. In the molecular dynamics studies, RMSD and RMSF values undoubtedly explained that the screened compounds formed stable complexes with DNA GyrB. Therefore, it can be concluded that the compounds identified may have potential for the treatment of TB. © 2017 John Wiley & Sons A/S.

The Cost-Effectiveness of School-Based Eating Disorder Screening

PubMed Central

Austin, S. Bryn; LeAnn Noh, H.; Jiang, Yushan; Sonneville, Kendrin R.

2014-01-01

Objectives. We aimed to assess the value of school-based eating disorder (ED) screening for a hypothetical cohort of US public school students. Methods. We used a decision-analytic microsimulation model to model the effectiveness (life-years with ED and quality-adjusted life-years [QALYs]), total direct costs, and cost-effectiveness (cost per QALY gained) of screening relative to current practice. Results. The screening strategy cost $2260 (95% confidence interval [CI] = $1892, $2668) per student and resulted in a per capita gain of 0.25 fewer life-years with ED (95% CI = 0.21, 0.30) and 0.04 QALYs (95% CI = 0.03, 0.05) relative to current practice. The base case cost-effectiveness of the intervention was $9041 per life-year with ED avoided (95% CI = $6617, $12 344) and $56 500 per QALY gained (95% CI = $38 805, $71 250). Conclusions. At willingness-to-pay thresholds of $50 000 and $100 000 per QALY gained, school-based ED screening is 41% and 100% likely to be cost-effective, respectively. The cost-effectiveness of ED screening is comparable to many other accepted pediatric health interventions, including hypertension screening. PMID:25033131

Computationally assisted screening and design of cell-interactive peptides by a cell-based assay using peptide arrays and a fuzzy neural network algorithm.

PubMed

Kaga, Chiaki; Okochi, Mina; Tomita, Yasuyuki; Kato, Ryuji; Honda, Hiroyuki

2008-03-01

We developed a method of effective peptide screening that combines experiments and computational analysis. The method is based on the concept that screening efficiency can be enhanced from even limited data by use of a model derived from computational analysis that serves as a guide to screening and combining the model with subsequent repeated experiments. Here we focus on cell-adhesion peptides as a model application of this peptide-screening strategy. Cell-adhesion peptides were screened by use of a cell-based assay of a peptide array. Starting with the screening data obtained from a limited, random 5-mer library (643 sequences), a rule regarding structural characteristics of cell-adhesion peptides was extracted by fuzzy neural network (FNN) analysis. According to this rule, peptides with unfavored residues in certain positions that led to inefficient binding were eliminated from the random sequences. In the restricted, second random library (273 sequences), the yield of cell-adhesion peptides having an adhesion rate more than 1.5-fold to that of the basal array support was significantly high (31%) compared with the unrestricted random library (20%). In the restricted third library (50 sequences), the yield of cell-adhesion peptides increased to 84%. We conclude that a repeated cycle of experiments screening limited numbers of peptides can be assisted by the rule-extracting feature of FNN.

Perceptions of Colon Cancer Screening by Stage of Screening Test Adoption

PubMed Central

Menon, Usha; Belue, Rhonda; Skinner, Celette Sugg; Rothwell, B. Erin; Champion, Victoria

2011-01-01

Colorectal cancer remains the second leading cause of cancer death in the United States. To fully realize the benefits of early detection of colorectal cancer, screening rates must improve. This study assessed differences in beliefs (from the Health Belief Model) by stage of screening behavior adoption (based on the Transtheoretical Model of Change) as a foundation for intervention development. More people were in the precontemplation stage (not thinking about having the screening test) for fecal occult blood test and sigmoidoscopy versus contemplation (thinking about having the test) or action (adherent with screening). Those in precontemplation stage for fecal occult blood test had lower perceived risk than those in contemplation, lower perceived benefits than those in action, and higher barriers than both those in contemplation and those in action. For sigmoidoscopy stage of readiness, again, precontemplators had lower perceived risk and self-efficacy than contemplators and higher barriers than both contemplators and actors. Given the popularity of the transtheoretical model and the success of stage-based interventions to increase other cancer screening, especially mammography, we should begin to translate such effective interventions to colorectal cancer screening. As such, this study is one of very few to quantify beliefs across stages of colorectal cancer and identify significant differences across stages, laying the foundation for the development and testing of stage-based interventions. PMID:17510580

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

PubMed

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.

Validation of a school-based amblyopia screening protocol in a kindergarten population.

PubMed

Casas-Llera, Pilar; Ortega, Paula; Rubio, Inmaculada; Santos, Verónica; Prieto, María J; Alio, Jorge L

2016-08-04

To validate a school-based amblyopia screening program model by comparing its outcomes to those of a state-of-the-art conventional ophthalmic clinic examination in a kindergarten population of children between the ages of 4 and 5 years. An amblyopia screening protocol, which consisted of visual acuity measurement using Lea charts, ocular alignment test, ocular motility assessment, and stereoacuity with TNO random-dot test, was performed at school in a pediatric 4- to 5-year-old population by qualified healthcare professionals. The outcomes were validated in a selected group by a conventional ophthalmologic examination performed in a fully equipped ophthalmologic center. The ophthalmologic evaluation was used to confirm whether or not children were correctly classified by the screening protocol. The sensitivity and specificity of the test model to detect amblyopia were established. A total of 18,587 4- to 5-year-old children were subjected to the amblyopia screening program during the 2010-2011 school year. A population of 100 children were selected for the ophthalmologic validation screening. A sensitivity of 89.3%, specificity of 93.1%, positive predictive value of 83.3%, negative predictive value of 95.7%, positive likelihood ratio of 12.86, and negative likelihood ratio of 0.12 was obtained for the amblyopia screening validation model. The amblyopia screening protocol model tested in this investigation shows high sensitivity and specificity in detecting high-risk cases of amblyopia compared to the standard ophthalmologic examination. This screening program may be highly relevant for amblyopia screening at schools.

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

Cancer.gov

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

High Throughput Exposure Prioritization of Chemicals Using a Screening-Level Probabilistic SHEDS-Lite Exposure Model

EPA Science Inventory

These novel modeling approaches for screening, evaluating and classifying chemicals based on the potential for biologically-relevant human exposures will inform toxicity testing and prioritization for chemical risk assessment. The new modeling approach is derived from the Stocha...

Cost-effectiveness and budget impact analysis of a population-based screening program for colorectal cancer.

PubMed

Pil, L; Fobelets, M; Putman, K; Trybou, J; Annemans, L

2016-07-01

Colorectal cancer (CRC) is one of the leading causes of cancer mortality in Belgium. In Flanders (Belgium), a population-based screening program with a biennial immunochemical faecal occult blood test (iFOBT) in women and men aged 56-74 has been organised since 2013. This study assessed the cost-effectiveness and budget impact of the colorectal population-based screening program in Flanders (Belgium). A health economic model was conducted, consisting of a decision tree simulating the screening process and a Markov model, with a time horizon of 20years, simulating natural progression. Predicted mortality and incidence, total costs, and quality-adjusted life-years (QALYs) with and without the screening program were calculated in order to determine the incremental cost-effectiveness ratio of CRC screening. Deterministic and probabilistic sensitivity analyses were conducted, taking into account uncertainty of the model parameters. Mortality and incidence were predicted to decrease over 20years. The colorectal screening program in Flanders is found to be cost-effective with an ICER of 1681/QALY (95% CI -1317 to 6601) in males and €4,484/QALY (95% CI -3254 to 18,163). The probability of being cost-effective given a threshold of €35,000/QALY was 100% and 97.3%, respectively. The budget impact analysis showed the extra cost for the health care payer to be limited. This health economic analysis has shown that despite the possible adverse effects of screening and the extra costs for the health care payer and the patient, the population-based screening program for CRC in Flanders is cost-effective and should therefore be maintained. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Parameter screening: the use of a dummy parameter to identify non-influential parameters in a global sensitivity analysis

NASA Astrophysics Data System (ADS)

Khorashadi Zadeh, Farkhondeh; Nossent, Jiri; van Griensven, Ann; Bauwens, Willy

2017-04-01

Parameter estimation is a major concern in hydrological modeling, which may limit the use of complex simulators with a large number of parameters. To support the selection of parameters to include in or exclude from the calibration process, Global Sensitivity Analysis (GSA) is widely applied in modeling practices. Based on the results of GSA, the influential and the non-influential parameters are identified (i.e. parameters screening). Nevertheless, the choice of the screening threshold below which parameters are considered non-influential is a critical issue, which has recently received more attention in GSA literature. In theory, the sensitivity index of a non-influential parameter has a value of zero. However, since numerical approximations, rather than analytical solutions, are utilized in GSA methods to calculate the sensitivity indices, small but non-zero indices may be obtained for the indices of non-influential parameters. In order to assess the threshold that identifies non-influential parameters in GSA methods, we propose to calculate the sensitivity index of a "dummy parameter". This dummy parameter has no influence on the model output, but will have a non-zero sensitivity index, representing the error due to the numerical approximation. Hence, the parameters whose indices are above the sensitivity index of the dummy parameter can be classified as influential, whereas the parameters whose indices are below this index are within the range of the numerical error and should be considered as non-influential. To demonstrated the effectiveness of the proposed "dummy parameter approach", 26 parameters of a Soil and Water Assessment Tool (SWAT) model are selected to be analyzed and screened, using the variance-based Sobol' and moment-independent PAWN methods. The sensitivity index of the dummy parameter is calculated from sampled data, without changing the model equations. Moreover, the calculation does not even require additional model evaluations for the Sobol' method. A formal statistical test validates these parameter screening results. Based on the dummy parameter screening, 11 model parameters are identified as influential. Therefore, it can be denoted that the "dummy parameter approach" can facilitate the parameter screening process and provide guidance for GSA users to define a screening-threshold, with only limited additional resources. Key words: Parameter screening, Global sensitivity analysis, Dummy parameter, Variance-based method, Moment-independent method

Effectiveness Modelling and Economic Evaluation of Primary HPV Screening for Cervical Cancer Prevention in New Zealand

PubMed Central

Lew, Jie-Bin; Simms, Kate; Smith, Megan; Lewis, Hazel; Neal, Harold; Canfell, Karen

2016-01-01

Background New Zealand (NZ) is considering transitioning from 3-yearly cervical cytology screening in women 20–69 years (current practice) to primary HPV screening. We evaluated HPV-based screening in both HPV-unvaccinated women and cohorts offered HPV vaccination in New Zealand (vaccination coverage ~50%). Methods A complex model of HPV transmission, vaccination, cervical screening, and invasive cervical cancer was extensively validated against national population-based datasets. Sixteen potential strategies for HPV screening were considered. Results Most primary HPV strategies were more effective than current practice, for both unvaccinated women and cohorts offered vaccination. The optimal strategy for both groups was 5-yearly HPV screening in women aged 25–69 years with partial genotyping for HPV 16/18 and referral to colposcopy, and cytological triage of other oncogenic types. This is predicted to reduce cervical cancer incidence and mortality by a further 12–16% and to save 4–13% annually in program costs (excluding overheads). The findings are sensitive to assumptions about future adherence to initiating screening at 25 years. Conclusion Primary HPV screening with partial genotyping would be more effective and less costly than the current cytology-based screening program, in both unvaccinated women and cohorts offered vaccination. These findings have been considered in a review of cervical screening in NZ. PMID:27187495

Implementing a Fee-for-Service Cervical Cancer Screening and Treatment Program in Cameroon: Challenges and Opportunities.

PubMed

DeGregorio, Geneva; Manga, Simon; Kiyang, Edith; Manjuh, Florence; Bradford, Leslie; Cholli, Preetam; Wamai, Richard; Ogembo, Rebecca; Sando, Zacharie; Liu, Yuxin; Sheldon, Lisa Kennedy; Nulah, Kathleen; Welty, Thomas; Welty, Edith; Ogembo, Javier Gordon

2017-07-01

Cervical cancer screening is one of the most effective cancer prevention strategies, but most women in Africa have never been screened. In 2007, the Cameroon Baptist Convention Health Services, a large faith-based health care system in Cameroon, initiated the Women's Health Program (WHP) to address this disparity. The WHP provides fee-for-service cervical cancer screening using visual inspection with acetic acid enhanced by digital cervicography (VIA-DC), prioritizing care for women living with HIV/AIDS. They also provide clinical breast examination, family planning (FP) services, and treatment for reproductive tract infection (RTI). Here, we document the strengths and challenges of the WHP screening program and the unique aspects of the WHP model, including a fee-for-service payment system and the provision of other women's health services. We retrospectively reviewed WHP medical records from women who presented for cervical cancer screening from 2007-2014. In 8 years, WHP nurses screened 44,979 women for cervical cancer. The number of women screened increased nearly every year. The WHP is sustained primarily on fees-for-service, with external funding totaling about $20,000 annually. In 2014, of 12,191 women screened for cervical cancer, 99% received clinical breast exams, 19% received FP services, and 4.7% received treatment for RTIs. We document successes, challenges, solutions implemented, and recommendations for optimizing this screening model. The WHP's experience using a fee-for-service model for cervical cancer screening demonstrates that in Cameroon VIA-DC is acceptable, feasible, and scalable and can be nearly self-sustaining. Integrating other women's health services enabled women to address additional health care needs. The Cameroon Baptist Convention Health Services Women's Health Program successfully implemented a nurse-led, fee-for-service cervical cancer screening program using visual inspection with acetic acid-enhanced by digital cervicography in the setting of a large faith-based health care system in Cameroon. It is potentially replicable in many African countries, where faith-based organizations provide a large portion of health care. The cost-recovery model and concept of offering multiple services in a single clinic rather than stand-alone "silo" cervical cancer screening could provide a model for other low-and-middle-income countries planning to roll out a new, or make an existing, cervical cancer screening services accessible, comprehensive, and sustainable. © AlphaMed Press 2017.

Using resource modelling to inform decision making and service planning: the case of colorectal cancer screening in Ireland

PubMed Central

2013-01-01

Background Organised colorectal cancer screening is likely to be cost-effective, but cost-effectiveness results alone may not help policy makers to make decisions about programme feasibility or service providers to plan programme delivery. For these purposes, estimates of the impact on the health services of actually introducing screening in the target population would be helpful. However, these types of analyses are rarely reported. As an illustration of such an approach, we estimated annual health service resource requirements and health outcomes over the first decade of a population-based colorectal cancer screening programme in Ireland. Methods A Markov state-transition model of colorectal neoplasia natural history was used. Three core screening scenarios were considered: (a) flexible sigmoidoscopy (FSIG) once at age 60, (b) biennial guaiac-based faecal occult blood tests (gFOBT) at 55–74 years, and (c) biennial faecal immunochemical tests (FIT) at 55–74 years. Three alternative FIT roll-out scenarios were also investigated relating to age-restricted screening (55–64 years) and staggered age-based roll-out across the 55–74 age group. Parameter estimates were derived from literature review, existing screening programmes, and expert opinion. Results were expressed in relation to the 2008 population (4.4 million people, of whom 700,800 were aged 55–74). Results FIT-based screening would deliver the greatest health benefits, averting 164 colorectal cancer cases and 272 deaths in year 10 of the programme. Capacity would be required for 11,095-14,820 diagnostic and surveillance colonoscopies annually, compared to 381–1,053 with FSIG-based, and 967–1,300 with gFOBT-based, screening. With FIT, in year 10, these colonoscopies would result in 62 hospital admissions for abdominal bleeding, 27 bowel perforations and one death. Resource requirements for pathology, diagnostic radiology, radiotherapy and colorectal resection were highest for FIT. Estimates depended on screening uptake. Alternative FIT roll-out scenarios had lower resource requirements. Conclusions While FIT-based screening would quite quickly generate attractive health outcomes, it has heavy resource requirements. These could impact on the feasibility of a programme based on this screening modality. Staggered age-based roll-out would allow time to increase endoscopy capacity to meet programme requirements. Resource modelling of this type complements conventional cost-effectiveness analyses and can help inform policy making and service planning. PMID:23510135

Effect of vibration on retention characteristics of screen acquisition systems. [for surface tension propellant acquisition

NASA Technical Reports Server (NTRS)

Tegart, J. R.; Aydelott, J. C.

1978-01-01

The design of surface tension propellant acquisition systems using fine-mesh screen must take into account all factors that influence the liquid pressure differentials within the system. One of those factors is spacecraft vibration. Analytical models to predict the effects of vibration have been developed. A test program to verify the analytical models and to allow a comparative evaluation of the parameters influencing the response to vibration was performed. Screen specimens were tested under conditions simulating the operation of an acquisition system, considering the effects of such parameters as screen orientation and configuration, screen support method, screen mesh, liquid flow and liquid properties. An analytical model, based on empirical coefficients, was most successful in predicting the effects of vibration.

Spiritually Based Intervention to Increase Colorectal Cancer Screening among African Americans: Screening and Theory-Based Outcomes from a Randomized Trial

ERIC Educational Resources Information Center

Holt, Cheryl L.; Litaker, Mark S.; Scarinci, Isabel C.; Debnam, Katrina J.; McDavid, Chastity; McNeal, Sandre F.; Eloubeidi, Mohamad A.; Crowther, Martha; Bolland, John; Martin, Michelle Y.

2013-01-01

Colorectal cancer screening has clear benefits in terms of mortality reduction; however, it is still underutilized and especially among medically underserved populations, including African Americans, who also suffer a disproportionate colorectal cancer burden. This study consisted of a theory-driven (health belief model) spiritually based…

Optimization of PSA screening policies: a comparison of the patient and societal perspectives.

PubMed

Zhang, Jingyu; Denton, Brian T; Balasubramanian, Hari; Shah, Nilay D; Inman, Brant A

2012-01-01

To estimate the benefit of PSA-based screening for prostate cancer from the patient and societal perspectives. A partially observable Markov decision process model was used to optimize PSA screening decisions. Age-specific prostate cancer incidence rates and the mortality rates from prostate cancer and competing causes were considered. The model trades off the potential benefit of early detection with the cost of screening and loss of patient quality of life due to screening and treatment. PSA testing and biopsy decisions are made based on the patient's probability of having prostate cancer. Probabilities are inferred based on the patient's complete PSA history using Bayesian updating. The results of all PSA tests and biopsies done in Olmsted County, Minnesota, from 1993 to 2005 (11,872 men and 50,589 PSA test results). Patients' perspective: to maximize expected quality-adjusted life years (QALYs); societal perspective: to maximize the expected monetary value based on societal willingness to pay for QALYs and the cost of PSA testing, prostate biopsies, and treatment. From the patient perspective, the optimal policy recommends stopping PSA testing and biopsy at age 76. From the societal perspective, the stopping age is 71. The expected incremental benefit of optimal screening over the traditional guideline of annual PSA screening with threshold 4.0 ng/mL for biopsy is estimated to be 0.165 QALYs per person from the patient perspective and 0.161 QALYs per person from the societal perspective. PSA screening based on traditional guidelines is found to be worse than no screening at all. PSA testing done with traditional guidelines underperforms and therefore underestimates the potential benefit of screening. Optimal screening guidelines differ significantly depending on the perspective of the decision maker.

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

PubMed

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.

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

PubMed Central

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

2014-01-01

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

Application of multimedia models for screening assessment of long-range transport potential and overall persistence.

PubMed

Klasmeier, Jörg; Matthies, Michael; Macleod, Matthew; Fenner, Kathrin; Scheringer, Martin; Stroebe, Maximilian; Le Gall, Anne Christine; Mckone, Thomas; Van De Meent, Dik; Wania, Frank

2006-01-01

We propose a multimedia model-based methodology to evaluate whether a chemical substance qualifies as POP-like based on overall persistence (Pov) and potential for long-range transport (LRTP). It relies upon screening chemicals against the Pov and LRTP characteristics of selected reference chemicals with well-established environmental fates. Results indicate that chemicals of high and low concern in terms of persistence and long-range transport can be consistently identified by eight contemporary multimedia models using the proposed methodology. Model results for three hypothetical chemicals illustrate that the model-based classification of chemicals according to Pov and LRTP is not always consistent with the single-media half-life approach proposed by the UNEP Stockholm Convention and thatthe models provide additional insight into the likely long-term hazards associated with chemicals in the environment. We suggest this model-based classification method be adopted as a complement to screening against defined half-life criteria at the initial stages of tiered assessments designed to identify POP-like chemicals and to prioritize further environmental fate studies for new and existing chemicals.

Pain, pain intensity and pain disability in high school students are differently associated with physical activity, screening hours and sleep.

PubMed

Silva, Anabela G; Sa-Couto, Pedro; Queirós, Alexandra; Neto, Maritza; Rocha, Nelson P

2017-05-16

Studies exploring the association between physical activity, screen time and sleep and pain usually focus on a limited number of painful body sites. Nevertheless, pain at different body sites is likely to be of different nature. Therefore, this study aims to explore and compare the association between time spent in self-reported physical activity, in screen based activities and sleeping and i) pain presence in the last 7-days for 9 different body sites; ii) pain intensity at 9 different body sites and iii) global disability. Nine hundred sixty nine students completed a questionnaire on pain, time spent in moderate and vigorous physical activity, screen based time watching TV/DVD, playing, using mobile phones and computers and sleeping hours. Univariate and multivariate associations between pain presence, pain intensity and disability and physical activity, screen based time and sleeping hours were investigated. Pain presence: sleeping remained in the multivariable model for the neck, mid back, wrists, knees and ankles/feet (OR 1.17 to 2.11); moderate physical activity remained in the multivariate model for the neck, shoulders, wrists, hips and ankles/feet (OR 1.06 to 1.08); vigorous physical activity remained in the multivariate model for mid back, knees and ankles/feet (OR 1.05 to 1.09) and screen time remained in the multivariate model for the low back (OR = 2.34. Pain intensity: screen time and moderate physical activity remained in the multivariable model for pain intensity at the neck, mid back, low back, shoulder, knees and ankles/feet (Rp 2 0.02 to 0.04) and at the wrists (Rp 2  = 0.04), respectively. Disability showed no association with sleeping, screen time or physical activity. This study suggests both similarities and differences in the patterns of association between time spent in physical activity, sleeping and in screen based activities and pain presence at 8 different body sites. In addition, they also suggest that the factors associated with the presence of pain, pain intensity and pain associated disability are different.

Staged anticonvulsant screening for chronic epilepsy.

PubMed

Berdichevsky, Yevgeny; Saponjian, Yero; Park, Kyung-Il; Roach, Bonnie; Pouliot, Wendy; Lu, Kimberly; Swiercz, Waldemar; Dudek, F Edward; Staley, Kevin J

2016-12-01

Current anticonvulsant screening programs are based on seizures evoked in normal animals. One-third of epileptic patients do not respond to the anticonvulsants discovered with these models. We evaluated a tiered program based on chronic epilepsy and spontaneous seizures, with compounds advancing from high-throughput in vitro models to low-throughput in vivo models. Epileptogenesis in organotypic hippocampal slice cultures was quantified by lactate production and lactate dehydrogenase release into culture media as rapid assays for seizure-like activity and cell death, respectively. Compounds that reduced these biochemical measures were retested with in vitro electrophysiological confirmation (i.e., second stage). The third stage involved crossover testing in the kainate model of chronic epilepsy, with blinded analysis of spontaneous seizures after continuous electrographic recordings. We screened 407 compound-concentration combinations. The cyclooxygenase inhibitor, celecoxib, had no effect on seizures evoked in normal brain tissue but demonstrated robust antiseizure activity in all tested models of chronic epilepsy. The use of organotypic hippocampal cultures, where epileptogenesis occurs on a compressed time scale, and where seizure-like activity and seizure-induced cell death can be easily quantified with biomarker assays, allowed us to circumvent the throughput limitations of in vivo chronic epilepsy models. Ability to rapidly screen compounds in a chronic model of epilepsy allowed us to find an anticonvulsant that would be missed by screening in acute models.

Is diabetes and hypertension screening worthwhile in resource-limited settings? An economic evaluation based on a pilot of a Package of Essential Non-communicable disease interventions in Bhutan.

PubMed

Dukpa, Wangchuk; Teerawattananon, Yot; Rattanavipapong, Waranya; Srinonprasert, Varalak; Tongsri, Watsamon; Kingkaew, Pritaporn; Yothasamut, Jomkwan; Wangchuk, Dorji; Dorji, Tandin; Wangmo, Kinzang

2015-10-01

In response to a lack of cost-effective data on screening and early treatment of diabetes and hypertension in resource-limited settings, a model-based economic evaluation was performed on the World Health Organization (WHO)'s Package of Essential Non-communicable (PEN) disease interventions for primary health care in Bhutan. Both local and international data were applied in the model in order to derive lifetime costs and outcomes resulting from the early treatment of diabetes and hypertension. The results indicate that the current screening option (where people who are overweight, obese or aged 40 years or older who visit primary care facilities are screened for diabetes and hypertension) represents good value for money compared to 'no screening'. The study findings also indicate that expanding opportunistic screening (70% coverage of the target population) to universal screening (where 100% of the target population are screened), is likely to be even more cost-effective. From the sensitivity analysis, the value of the screening options remains the same when disease prevalence varies. Therefore, applying this model to other healthcare settings is warranted, since disease prevalence is one of the major factors in affecting the cost-effectiveness results of screening programs. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2014; all rights reserved.

In silico approaches to identify novel myeloid cell leukemia-1 (Mcl-1) inhibitors for treatment of cancer.

PubMed

Ren, Ji-Xia; Li, Cheng-Ping; Zhou, Xiu-Ling; Cao, Xue-Song; Xie, Yong

2017-08-22

Myeloid cell leukemia-1 (Mcl-1) has been a validated and attractive target for cancer therapy. Over-expression of Mcl-1 in many cancers allows cancer cells to evade apoptosis and contributes to the resistance to current chemotherapeutics. Here, we identified new Mcl-1 inhibitors using a multi-step virtual screening approach. First, based on two different ligand-receptor complexes, 20 pharmacophore models were established by simultaneously using 'Receptor-Ligand Pharmacophore Generation' method and manual build feature method, and then carefully validated by a test database. Then, pharmacophore-based virtual screening (PB-VS) could be performed by using the 20 pharmacophore models. In addition, docking study was used to predict the possible binding poses of compounds, and the docking parameters were optimized before performing docking-based virtual screening (DB-VS). Moreover, a 3D QSAR model was established by applying the 55 aligned Mcl-1 inhibitors. The 55 inhibitors sharing the same scaffold were docked into the Mcl-1 active site before alignment, then the inhibitors with possible binding conformations were aligned. For the training set, the 3D QSAR model gave a correlation coefficient r 2 of 0.996; for the test set, the correlation coefficient r 2 was 0.812. Therefore, the developed 3D QSAR model was a good model, which could be applied for carrying out 3D QSAR-based virtual screening (QSARD-VS). After the above three virtual screening methods orderly filtering, 23 potential inhibitors with novel scaffolds were identified. Furthermore, we have discussed in detail the mapping results of two potent compounds onto pharmacophore models, 3D QSAR model, and the interactions between the compounds and active site residues.

Motivation-based intervention to promote colonoscopy screening: An integration of a fear management model and motivational interviewing

PubMed Central

Pengchit, Watcharaporn; Walters, Scott T.; Simmons, Rebecca G.; Kohlmann, Wendy; Burt, Randall W.; Schwartz, Marc D.; Kinney, Anita Y.

2011-01-01

Colorectal cancer (CRC) screening rates have been low despite effectiveness of screening in reducing CRC mortality. This article outlines the theoretical background and development of an innovative, telephone-based risk communication designed to promote screening among individuals at increased risk for familial CRC. This ongoing intervention integrates the Extended Parallel Process Model of fear management and the motivational interviewing counselling style. Tailoring and implementation intentions are incorporated. The primary outcome is self-reported colonoscopy within nine months following intervention. If proven effective, the remote intervention could be broadly disseminated to individuals at increased familial CRC risk, especially those in geographically underserved areas. PMID:21464114

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

PubMed Central

ten Haaf, Kevin; Tammemägi, Martin C.; Han, Summer S.; Kong, Chung Yin; Plevritis, Sylvia K.; de Koning, Harry J.; Steyerberg, Ewout W.

2017-01-01

Background 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. Methods and findings 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 higher specificity for some models. The PLCOm2012, Bach, and Two-Stage Clonal Expansion incidence models had the best overall performance, with AUCs >0.68 in the NLST and >0.77 in the PLCO. These three models had the highest sensitivity and specificity for predicting 6-y lung cancer incidence in the PLCO chest radiography arm, with sensitivities >79.8% and specificities >62.3%. In contrast, the NLST eligibility criteria yielded a sensitivity of 71.4% and a specificity of 62.2%. Limitations of this study include the lack of identification of optimal risk thresholds, as this requires additional information on the long-term benefits (e.g., life-years gained and mortality reduction) and harms (e.g., overdiagnosis) of risk-based screening strategies using these models. In addition, information on some predictor variables included in the risk prediction models was not available. Conclusions Selection of individuals for lung cancer screening using individual risk is superior to selection criteria based on age and pack-years alone. The benefits, harms, and feasibility of implementing lung cancer screening policies based on risk prediction models should be assessed and compared with those of current recommendations. PMID:28376113

TOWARDS REFINED USE OF TOXICITY DATA IN ...

EPA Pesticide Factsheets

In 2003, an International Life Sciences Institute (ILSI) Working Group examined the potential of statistically based structure-activity relationship (SAR) models for use in screening environmental contaminants for possible developmental toxicants. In 2003, an International Life Sciences Institute (ILSI) Working Group examined the potential of statistically based structure-activity relationship (SAR) models for use in screening environmental contaminants for possible developmental toxicants.

An update on the use of C. elegans for preclinical drug discovery: screening and identifying anti-infective drugs.

PubMed

Kim, Wooseong; Hendricks, Gabriel Lambert; Lee, Kiho; Mylonakis, Eleftherios

2017-06-01

The emergence of antibiotic-resistant and -tolerant bacteria is a major threat to human health. Although efforts for drug discovery are ongoing, conventional bacteria-centered screening strategies have thus far failed to yield new classes of effective antibiotics. Therefore, new paradigms for discovering novel antibiotics are of critical importance. Caenorhabditis elegans, a model organism used for in vivo, offers a promising solution for identification of anti-infective compounds. Areas covered: This review examines the advantages of C. elegans-based high-throughput screening over conventional, bacteria-centered in vitro screens. It discusses major anti-infective compounds identified from large-scale C. elegans-based screens and presents the first clinically-approved drugs, then known bioactive compounds, and finally novel small molecules. Expert opinion: There are clear advantages of using a C. elegans-infection based screening method. A C. elegans-based screen produces an enriched pool of non-toxic, efficacious, potential anti-infectives, covering: conventional antimicrobial agents, immunomodulators, and anti-virulence agents. Although C. elegans-based screens do not denote the mode of action of hit compounds, this can be elucidated in secondary studies by comparing the results to target-based screens, or conducting subsequent target-based screens, including the genetic knock-down of host or bacterial genes.

Promotion and Provision of Colorectal Cancer Screening: A Comparison of Colorectal Cancer Control Program Grantees and Nongrantees, 2011–2012

PubMed Central

Hannon, Peggy A.; Escoffery, Cam; Vu, Thuy; Kohn, Marlana; Vernon, Sally W.; DeGroff, Amy

2014-01-01

Introduction Since 2009, the Centers for Disease Control and Prevention (CDC) has awarded nearly $95 million to 29 states and tribes through the Colorectal Cancer Control Program (CRCCP) to fund 2 program components: 1) providing colorectal cancer (CRC) screening to uninsured and underinsured low-income adults and 2) promoting population-wide CRC screening through evidence-based interventions identified in the Guide to Community Preventive Services (Community Guide). CRCCP is a new model for disseminating and promoting use of evidence-based interventions. If the program proves successful, CDC may adopt the model for future cancer control programs. The objective of our study was to compare the colorectal cancer screening practices of recipients of CRCCP funding (grantees) with those of nonrecipients (nongrantees). Methods We conducted parallel Web-based surveys in 2012 with CRCCP grantees (N = 29) and nongrantees (N = 24) to assess promotion and provision of CRC screening, including the use of evidence-based interventions. Results CRCCP grantees were significantly more likely than nongrantees to use Community Guide-recommended evidence-based interventions (mean, 3.14 interventions vs 1.25 interventions, P < .001) and to use patient navigation services (eg, transportion or language translation services) (72% vs 17%, P < .001) for promoting CRC screening. Both groups were equally likely to use other strategies. CRCCP grantees were significantly more likely to provide CRC screening than were nongrantees (100% versus 50%, P < .001). Conclusion Results suggest that CRCCP funding and support increases use of evidence-based interventions to promote CRC screening, indicating the program’s potential to increase population-wide CRC screening rates. PMID:25275807

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

PubMed

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

2014-04-15

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

3D Pharmacophore-Based Virtual Screening and Docking Approaches toward the Discovery of Novel HPPD Inhibitors.

PubMed

Fu, Ying; Sun, Yi-Na; Yi, Ke-Han; Li, Ming-Qiang; Cao, Hai-Feng; Li, Jia-Zhong; Ye, Fei

2017-06-09

p -Hydroxyphenylpyruvate dioxygenase (HPPD) is not only the useful molecular target in treating life-threatening tyrosinemia type I, but also an important target for chemical herbicides. A combined in silico structure-based pharmacophore and molecular docking-based virtual screening were performed to identify novel potential HPPD inhibitors. The complex-based pharmacophore model (CBP) with 0.721 of ROC used for screening compounds showed remarkable ability to retrieve known active ligands from among decoy molecules. The ChemDiv database was screened using CBP-Hypo2 as a 3D query, and the best-fit hits subjected to molecular docking with two methods of LibDock and CDOCKER in Accelrys Discovery Studio 2.5 (DS 2.5) to discern interactions with key residues at the active site of HPPD. Four compounds with top rankings in the HipHop model and well-known binding model were finally chosen as lead compounds with potential inhibitory effects on the active site of target. The results provided powerful insight into the development of novel HPPD inhibitors herbicides using computational techniques.

A fast boosting-based screening method for large-scale association study in complex traits with genetic heterogeneity.

PubMed

Wang, Lu-Yong; Fasulo, D

2006-01-01

Genome-wide association study for complex diseases will generate massive amount of single nucleotide polymorphisms (SNPs) data. Univariate statistical test (i.e. Fisher exact test) was used to single out non-associated SNPs. However, the disease-susceptible SNPs may have little marginal effects in population and are unlikely to retain after the univariate tests. Also, model-based methods are impractical for large-scale dataset. Moreover, genetic heterogeneity makes the traditional methods harder to identify the genetic causes of diseases. A more recent random forest method provides a more robust method for screening the SNPs in thousands scale. However, for more large-scale data, i.e., Affymetrix Human Mapping 100K GeneChip data, a faster screening method is required to screening SNPs in whole-genome large scale association analysis with genetic heterogeneity. We propose a boosting-based method for rapid screening in large-scale analysis of complex traits in the presence of genetic heterogeneity. It provides a relatively fast and fairly good tool for screening and limiting the candidate SNPs for further more complex computational modeling task.

Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society.

PubMed

Wolf, Andrew M D; Fontham, Elizabeth T H; Church, Timothy R; Flowers, Christopher R; Guerra, Carmen E; LaMonte, Samuel J; Etzioni, Ruth; McKenna, Matthew T; Oeffinger, Kevin C; Shih, Ya-Chen Tina; Walter, Louise C; Andrews, Kimberly S; Brawley, Otis W; Brooks, Durado; Fedewa, Stacey A; Manassaram-Baptiste, Deana; Siegel, Rebecca L; Wender, Richard C; Smith, Robert A

2018-05-30

In the United States, colorectal cancer (CRC) is the fourth most common cancer diagnosed among adults and the second leading cause of death from cancer. For this guideline update, the American Cancer Society (ACS) used an existing systematic evidence review of the CRC screening literature and microsimulation modeling analyses, including a new evaluation of the age to begin screening by race and sex and additional modeling that incorporates changes in US CRC incidence. Screening with any one of multiple options is associated with a significant reduction in CRC incidence through the detection and removal of adenomatous polyps and other precancerous lesions and with a reduction in mortality through incidence reduction and early detection of CRC. Results from modeling analyses identified efficient and model-recommendable strategies that started screening at age 45 years. The ACS Guideline Development Group applied the Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria in developing and rating the recommendations. The ACS recommends that adults aged 45 years and older with an average risk of CRC undergo regular screening with either a high-sensitivity stool-based test or a structural (visual) examination, depending on patient preference and test availability. As a part of the screening process, all positive results on noncolonoscopy screening tests should be followed up with timely colonoscopy. The recommendation to begin screening at age 45 years is a qualified recommendation. The recommendation for regular screening in adults aged 50 years and older is a strong recommendation. The ACS recommends (qualified recommendations) that: 1) average-risk adults in good health with a life expectancy of more than 10 years continue CRC screening through the age of 75 years; 2) clinicians individualize CRC screening decisions for individuals aged 76 through 85 years based on patient preferences, life expectancy, health status, and prior screening history; and 3) clinicians discourage individuals older than 85 years from continuing CRC screening. The options for CRC screening are: fecal immunochemical test annually; high-sensitivity, guaiac-based fecal occult blood test annually; multitarget stool DNA test every 3 years; colonoscopy every 10 years; computed tomography colonography every 5 years; and flexible sigmoidoscopy every 5 years. CA Cancer J Clin 2018;000:000-000. © 2018 American Cancer Society. © 2018 American Cancer Society.

Cost-effectiveness simulation and analysis of colorectal cancer screening in Hong Kong Chinese population: comparison amongst colonoscopy, guaiac and immunologic fecal occult blood testing.

PubMed

Wong, Carlos K H; Lam, Cindy L K; Wan, Y F; Fong, Daniel Y T

2015-10-15

The aim of this study was to evaluate the cost-effectiveness of CRC screening strategies from the healthcare service provider perspective based on Chinese population. A Markov model was constructed to compare the cost-effectiveness of recommended screening strategies including annual/biennial guaiac fecal occult blood testing (G-FOBT), annual/biennial immunologic FOBT (I-FOBT), and colonoscopy every 10 years in Chinese aged 50 year over a 25-year period. External validity of model was tested against data retrieved from published randomized controlled trials of G-FOBT. Recourse use data collected from Chinese subjects among staging of colorectal neoplasm were combined with published unit cost data ($USD in 2009 price values) to estimate a stage-specific cost per patient. Quality-adjusted life-years (QALYs) were quantified based on the stage duration and SF-6D preference-based value of each stage. The cost-effectiveness outcome was the incremental cost-effectiveness ratio (ICER) represented by costs per life-years (LY) and costs per QALYs gained. In base-case scenario, the non-dominated strategies were annual and biennial I-FOBT. Compared with no screening, the ICER presented $20,542/LYs and $3155/QALYs gained for annual I-FOBT, and $19,838/LYs gained and $2976/QALYs gained for biennial I-FOBT. The optimal screening strategy was annual I-FOBT that attained the highest ICER at the threshold of $50,000 per LYs or QALYs gained. The Markov model informed the health policymakers that I-FOBT every year may be the most effective and cost-effective CRC screening strategy among recommended screening strategies, depending on the willingness-to-pay of mass screening for Chinese population. ClinicalTrials.gov Identifier NCT02038283.

GPURFSCREEN: a GPU based virtual screening tool using random forest classifier.

PubMed

Jayaraj, P B; Ajay, Mathias K; Nufail, M; Gopakumar, G; Jaleel, U C A

2016-01-01

In-silico methods are an integral part of modern drug discovery paradigm. Virtual screening, an in-silico method, is used to refine data models and reduce the chemical space on which wet lab experiments need to be performed. Virtual screening of a ligand data model requires large scale computations, making it a highly time consuming task. This process can be speeded up by implementing parallelized algorithms on a Graphical Processing Unit (GPU). Random Forest is a robust classification algorithm that can be employed in the virtual screening. A ligand based virtual screening tool (GPURFSCREEN) that uses random forests on GPU systems has been proposed and evaluated in this paper. This tool produces optimized results at a lower execution time for large bioassay data sets. The quality of results produced by our tool on GPU is same as that on a regular serial environment. Considering the magnitude of data to be screened, the parallelized virtual screening has a significantly lower running time at high throughput. The proposed parallel tool outperforms its serial counterpart by successfully screening billions of molecules in training and prediction phases.

Optimizing colorectal cancer screening by race and sex: Microsimulation analysis II to inform the American Cancer Society colorectal cancer screening guideline.

PubMed

Meester, Reinier G S; Peterse, Elisabeth F P; Knudsen, Amy B; de Weerdt, Anne C; Chen, Jennifer C; Lietz, Anna P; Dwyer, Andrea; Ahnen, Dennis J; Siegel, Rebecca L; Smith, Robert A; Zauber, Ann G; Lansdorp-Vogelaar, Iris

2018-05-30

Colorectal cancer (CRC) risk varies by race and sex. This study, 1 of 2 microsimulation analyses to inform the 2018 American Cancer Society CRC screening guideline, explored the influence of race and sex on optimal CRC screening strategies. Two Cancer Intervention and Surveillance Modeling Network microsimulation models, informed by US incidence data, were used to evaluate a variety of screening methods, ages to start and stop, and intervals for 4 demographic subgroups (black and white males and females) under 2 scenarios for the projected lifetime CRC risk for 40-year-olds: 1) assuming that risk had remained stable since the early screening era and 2) assuming that risk had increased proportionally to observed incidence trends under the age of 40 years. Model-based screening recommendations were based on the predicted level of benefit (life-years gained) and burden (required number of colonoscopies), the incremental burden-to-benefit ratio, and the relative efficiency in comparison with strategies with similar burdens. When lifetime CRC risk was assumed to be stable over time, the models differed in the recommended age to start screening for whites (45 vs 50 years) but consistently recommended screening from the age of 45 years for blacks. When CRC risk was assumed to be increased, the models recommended starting at the age of 45 years, regardless of race and sex. Strategies recommended under both scenarios included colonoscopy every 10 or 15 years, annual fecal immunochemical testing, and computed tomographic colonography every 5 years through the age of 75 years. Microsimulation modeling suggests that CRC screening should be considered from the age of 45 years for blacks and for whites if the lifetime risk has increased proportionally to the incidence for younger adults. Cancer 2018. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Protective Factors Based Model for Screening for Posttraumatic Distress in Adolescents

ERIC Educational Resources Information Center

Pat-Horenczyk, Ruth; Kenan, Avraham Max; Achituv, Michal; Bachar, Eytan

2014-01-01

Background: There is growing application of school-based screening to identify post-traumatic distress in students following exposure to trauma. The consensus method is based on self-report questionnaires that assess posttraumatic symptoms, functional impairment, depression or anxiety. Objective: The current research explored the possibility of…

Breast cancer risk from different mammography screening practices.

PubMed

Bijwaard, Harmen; Brenner, Alina; Dekkers, Fieke; van Dillen, Teun; Land, Charles E; Boice, John D

2010-09-01

Mammography screening is an accepted procedure for early detection of breast tumors among asymptomatic women. Since this procedure involves the use of X rays, it is itself potentially carcinogenic. Although there is general consensus about the benefit of screening for older women, screening practices differ between countries. In this paper radiation risks for these different practices are estimated using a new approach. We model breast cancer induction by ionizing radiation in a cohort of patients exposed to frequent X-ray examinations. The biologically based, mechanistic model provides a better foundation for the extrapolation of risks to different mammography screening practices than empirical models do. The model predicts that the excess relative risk (ERR) doubles when screening starts at age 40 instead of 50 and that a continuation of screening at ages 75 and higher carries little extra risk. The number of induced fatal breast cancers is estimated to be considerably lower than derived from epidemiological studies and from internationally accepted radiation protection risks. The present findings, if used in a risk-benefit analysis for mammography screening, would be more favorable to screening than estimates currently recommended for radiation protection. This has implications for the screening ages that are currently being reconsidered in several countries.

A multivariate cure model for left-censored and right-censored data with application to colorectal cancer screening patterns.

PubMed

Hagar, Yolanda C; Harvey, Danielle J; Beckett, Laurel A

2016-08-30

We develop a multivariate cure survival model to estimate lifetime patterns of colorectal cancer screening. Screening data cover long periods of time, with sparse observations for each person. Some events may occur before the study begins or after the study ends, so the data are both left-censored and right-censored, and some individuals are never screened (the 'cured' population). We propose a multivariate parametric cure model that can be used with left-censored and right-censored data. Our model allows for the estimation of the time to screening as well as the average number of times individuals will be screened. We calculate likelihood functions based on the observations for each subject using a distribution that accounts for within-subject correlation and estimate parameters using Markov chain Monte Carlo methods. We apply our methods to the estimation of lifetime colorectal cancer screening behavior in the SEER-Medicare data set. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

SCREENING MODEL FOR NONAQUEOUS PHASE-LIQUID TRANSPORT IN THE VADOSE ZONE USING GREEN-AMPT AND KINEMATIC WAVE THEORY

EPA Science Inventory

In this paper, a screening model for flow of a nonaqueous phase liquid (NAPL) and associated chemical transport in the vadose zone is developed. he model is based on kinematic approximation of the governing equations for both the NAPL and a partitionable chemical constituent. he ...

Cost-effectiveness of organized versus opportunistic cervical cytology screening in Hong Kong.

PubMed

Kim, Jane J; Leung, Gabriel M; Woo, Pauline P S; Goldie, Sue J

2004-06-01

To assess the cost-effectiveness of alternative cervical cancer screening strategies to inform the design and implementation of a government-sponsored population-based screening programme in Hong Kong. Cost-effectiveness analysis using a computer-based model of cervical carcinogenesis was performed. Strategies included no screening, opportunistic screening (status quo), organized screening using either conventional or liquid-based cytology conducted at different frequencies. The main outcome measures were cancer incidence reduction, years of life saved (YLS), lifetime costs and incremental cost-effectiveness ratios. Data were from local hospitals and laboratories, clinical trials, prospective studies and other published literature. Compared with no screening, a simulation of the current situation of opportunistic screening using cervical cytology produced a nearly 40 per cent reduction in the lifetime risk of cervical cancer. However, with organized screening every 3, 4 and 5 years, corresponding reductions with conventional (and liquid-based) cytology were 90.4 (92.9), 86.8 (90.2) and 83.2 per cent (87.3 per cent) compared with no screening. For all cytology-based screening strategies, opportunistic screening was more costly and less effective than an organized programme of screening every 3, 4 and 5 years. Every 3-, 4- and 5-year screening cost $12,300, $7100 and $800 per YLS, each compared with the next best alternative. Compared with the status quo of opportunistic screening, adopting a policy of organized, mass cervical screening in Hong Kong can substantially increase benefits and reduce costs.

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

NASA Astrophysics Data System (ADS)

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.

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

PubMed

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

2012-05-01

Recent research has identified high hepatitis C virus (HCV) prevalence among older U.S. residents who contracted HCV decades ago and may no longer be recognized as high risk. We assessed the cost-effectiveness of screening 100% of U.S. residents born 1946-1970 over 5 years (birth-cohort screening), compared with current risk-based screening, by projecting costs and outcomes of screening over the remaining lifetime of this birth cohort. A Markov model of the natural history of HCV was developed using data synthesized from surveillance data, published literature, expert opinion, and other secondary sources. We assumed eligible patients were treated with pegylated interferon plus ribavirin, with genotype 1 patients receiving a direct-acting antiviral in combination. The target population is U.S. residents born 1946-1970 with no previous HCV diagnosis. Among the estimated 102 million (1.6 million chronically HCV infected) eligible for screening, birth-cohort screening leads to 84,000 fewer cases of decompensated cirrhosis, 46,000 fewer cases of hepatocellular carcinoma, 10,000 fewer liver transplants, and 78,000 fewer HCV-related deaths. Birth-cohort screening leads to higher overall costs than risk-based screening ($80.4 billion versus $53.7 billion), but yields lower costs related to advanced liver disease ($31.2 billion versus $39.8 billion); birth-cohort screening produces an incremental cost-effectiveness ratio (ICER) of $37,700 per quality-adjusted life year gained versus risk-based screening. Sensitivity analyses showed that reducing the time horizon during which health and economic consequences are evaluated increases the ICER; similarly, decreasing the treatment rates and efficacy increases the ICER. Model results were relatively insensitive to other inputs. Birth-cohort screening for HCV is likely to provide important health benefits by reducing lifetime cases of advanced liver disease and HCV-related deaths and is cost-effective at conventional willingness-to-pay thresholds. Copyright © 2011 American Association for the Study of Liver Diseases.

[HTRF-based high-throughput PGE2 release prohibition model and application in discovering traditional Chinese medicine active ingredients].

PubMed

Bai, Zhi-Ru; Fei, Hong-Qiang; Li, Na; Cao, Liang; Zhang, Chen-Feng; Wang, Tuan-Jie; Ding, Gang; Wang, Zhen-Zhong; Xiao, Wei

2016-02-01

Prostaglandin (PG) E2 is an active substance in pathological and physiological mechanisms, such as inflammation and pain. The in vitro high-throughput assay for screening the inhibitors of reducing PEG2 production is a useful method for finding out antiphlogistic and analgesic candidates. The assay was based on LPS-induced PGE2 production model using a homogeneous time-resolved fluorescence(HTRF) PGE2 testing kit combined with liquid handling automation and detection instruments. The critical steps, including the cell density optimization and IC50 values determination of a positive compound, were taken to verify the stability and sensibility of the assay. Low intra-plate, inter-plate and day-to-day variability were observed in this 384-well, high-throughput format assay. Totally 5 121 samples were selected from the company's traditional Chinese medicine(TCM) material base library and used to screen PGE2 inhibitors. In this model, the cell plating density was 2 000 cells for each well; the average IC₅₀ value for positive compounds was (7.3±0.1) μmol; the Z' factor for test plates was more than 0.5 and averaged at 0.7. Among the 5 121 samples, 228 components exhibited a PGE2 production prohibition rate of more than 50%, and 23 components exhibited more than 80%. This model reached the expected standards in data stability and accuracy, indicating the reliability and authenticity of the screening results. The automated screening system was introduced to make the model fast and efficient, with a average daily screening amount exceeding 14 000 data points and provide a new model for discovering new anti-inflammatory and analgesic drug and quickly screening effective constituents of TCM in the early stage. Copyright© by the Chinese Pharmaceutical Association.

Implementing a Fee‐for‐Service Cervical Cancer Screening and Treatment Program in Cameroon: Challenges and Opportunities

PubMed Central

DeGregorio, Geneva; Manga, Simon; Kiyang, Edith; Manjuh, Florence; Bradford, Leslie; Cholli, Preetam; Wamai, Richard; Ogembo, Rebecca; Sando, Zacharie; Liu, Yuxin; Sheldon, Lisa Kennedy; Nulah, Kathleen; Welty, Thomas; Welty, Edith

2017-01-01

Abstract Background. Cervical cancer screening is one of the most effective cancer prevention strategies, but most women in Africa have never been screened. In 2007, the Cameroon Baptist Convention Health Services, a large faith‐based health care system in Cameroon, initiated the Women's Health Program (WHP) to address this disparity. The WHP provides fee‐for‐service cervical cancer screening using visual inspection with acetic acid enhanced by digital cervicography (VIA‐DC), prioritizing care for women living with HIV/AIDS. They also provide clinical breast examination, family planning (FP) services, and treatment for reproductive tract infection (RTI). Here, we document the strengths and challenges of the WHP screening program and the unique aspects of the WHP model, including a fee‐for‐service payment system and the provision of other women's health services. Methods. We retrospectively reviewed WHP medical records from women who presented for cervical cancer screening from 2007–2014. Results. In 8 years, WHP nurses screened 44,979 women for cervical cancer. The number of women screened increased nearly every year. The WHP is sustained primarily on fees‐for‐service, with external funding totaling about $20,000 annually. In 2014, of 12,191 women screened for cervical cancer, 99% received clinical breast exams, 19% received FP services, and 4.7% received treatment for RTIs. We document successes, challenges, solutions implemented, and recommendations for optimizing this screening model. Conclusion. The WHP's experience using a fee‐for‐service model for cervical cancer screening demonstrates that in Cameroon VIA‐DC is acceptable, feasible, and scalable and can be nearly self‐sustaining. Integrating other women's health services enabled women to address additional health care needs. Implication for Practice. The Cameroon Baptist Convention Health Services Women's Health Program successfully implemented a nurse‐led, fee‐for‐service cervical cancer screening program using visual inspection with acetic acid‐enhanced by digital cervicography in the setting of a large faith‐based health care system in Cameroon. It is potentially replicable in many African countries, where faith‐based organizations provide a large portion of health care. The cost‐recovery model and concept of offering multiple services in a single clinic rather than stand‐alone “silo” cervical cancer screening could provide a model for other low‐and‐middle‐income countries planning to roll out a new, or make an existing, cervical cancer screening services accessible, comprehensive, and sustainable. PMID:28536303

Lung cancer risk prediction to select smokers for screening CT--a model based on the Italian COSMOS trial.

PubMed

Maisonneuve, Patrick; Bagnardi, Vincenzo; Bellomi, Massimo; Spaggiari, Lorenzo; Pelosi, Giuseppe; Rampinelli, Cristiano; Bertolotti, Raffaella; Rotmensz, Nicole; Field, John K; Decensi, Andrea; Veronesi, Giulia

2011-11-01

Screening with low-dose helical computed tomography (CT) has been shown to significantly reduce lung cancer mortality but the optimal target population and time interval to subsequent screening are yet to be defined. We developed two models to stratify individual smokers according to risk of developing lung cancer. We first used the number of lung cancers detected at baseline screening CT in the 5,203 asymptomatic participants of the COSMOS trial to recalibrate the Bach model, which we propose using to select smokers for screening. Next, we incorporated lung nodule characteristics and presence of emphysema identified at baseline CT into the Bach model and proposed the resulting multivariable model to predict lung cancer risk in screened smokers after baseline CT. Age and smoking exposure were the main determinants of lung cancer risk. The recalibrated Bach model accurately predicted lung cancers detected during the first year of screening. Presence of nonsolid nodules (RR = 10.1, 95% CI = 5.57-18.5), nodule size more than 8 mm (RR = 9.89, 95% CI = 5.84-16.8), and emphysema (RR = 2.36, 95% CI = 1.59-3.49) at baseline CT were all significant predictors of subsequent lung cancers. Incorporation of these variables into the Bach model increased the predictive value of the multivariable model (c-index = 0.759, internal validation). The recalibrated Bach model seems suitable for selecting the higher risk population for recruitment for large-scale CT screening. The Bach model incorporating CT findings at baseline screening could help defining the time interval to subsequent screening in individual participants. Further studies are necessary to validate these models.

Lead screening in DBS by solid sampling high-resolution continuum source graphite furnace atomic absorption spectrometry: application to newborns and pregnant women.

PubMed

Rello, Luis; Aramendía, Maite; Belarra, Miguel A; Resano, Martín

2015-01-01

DBS have become a clinical specimen especially adequate for establishing home-based collection protocols. In this work, high-resolution continuum source graphite furnace atomic absorption spectrometry is evaluated for the direct monitoring of Pb in DBS, both as a quantitative tool and a screening method. The development of the screening model is based on the establishment of the unreliability region around the threshold limits, 100 or 50 μg l(-1). More than 500 samples were analyzed to validate the model. The screening method demonstrated high sensitivity (the rate of true positives detected was always higher than 95%), an excellent LOD (1 µg l(-1)) and high throughput (10 min per sample).

Effects of education based on the health belief model on screening behavior in high risk women for breast cancer, Tehran, Iran.

PubMed

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 screening should be extended to the entire populations in developing countries. In addition, we should pay attention to barriers to women undergoing mammography, such as costs, shame and accessibility, and increase the target population awareness and positive attitudes towards benefits of early breast cancer screening.

Screening for thrombophilia in high-risk situations: a meta-analysis and cost-effectiveness analysis.

PubMed

Wu, Olivia; Robertson, Lindsay; Twaddle, Sara; Lowe, Gordon; Clark, Peter; Walker, Isobel; Brenkel, Ivan; Greaves, Mike; Langhorne, Peter; Regan, Lesley; Greer, Ian

2005-10-01

Laboratory testing for the identification of heritable thrombophilia in high-risk patient groups have become common practice; however, indiscriminate testing of all patients is unjustified. The objective of this study was to evaluate the cost-effectiveness of universal and selective history-based thrombophilia screening relative to no screening, from the perspective of the UK National Health Service, in women prior to prescribing combined oral contraceptives and hormone replacement therapy, women during pregnancy and patients prior to major orthopaedic surgery. A decision analysis model was developed, and data from meta-analysis, the literature and two Delphi studies were incorporated in the model. Incremental cost-effectiveness ratios (ICERs) for screening compared with no screening was calculated for each patient group. Of all the patient groups evaluated, universal screening of women prior to prescribing hormone replacement therapy was the most cost-effective (ICER 6824 pounds). In contrast, universal screening of women prior to prescribing combined oral contraceptives was the least cost-effective strategy (ICER 202,402 pounds). Selective thrombophilia screening based on previous personal and/or family history of venous thromboembolism was more cost-effective than universal screening in all the patient groups evaluated.

iScreen: Image-Based High-Content RNAi Screening Analysis Tools.

PubMed

Zhong, Rui; Dong, Xiaonan; Levine, Beth; Xie, Yang; Xiao, Guanghua

2015-09-01

High-throughput RNA interference (RNAi) screening has opened up a path to investigating functional genomics in a genome-wide pattern. However, such studies are often restricted to assays that have a single readout format. Recently, advanced image technologies have been coupled with high-throughput RNAi screening to develop high-content screening, in which one or more cell image(s), instead of a single readout, were generated from each well. This image-based high-content screening technology has led to genome-wide functional annotation in a wider spectrum of biological research studies, as well as in drug and target discovery, so that complex cellular phenotypes can be measured in a multiparametric format. Despite these advances, data analysis and visualization tools are still largely lacking for these types of experiments. Therefore, we developed iScreen (image-Based High-content RNAi Screening Analysis Tool), an R package for the statistical modeling and visualization of image-based high-content RNAi screening. Two case studies were used to demonstrate the capability and efficiency of the iScreen package. iScreen is available for download on CRAN (http://cran.cnr.berkeley.edu/web/packages/iScreen/index.html). The user manual is also available as a supplementary document. © 2014 Society for Laboratory Automation and Screening.

Novel Hybrid Virtual Screening Protocol Based on Molecular Docking and Structure-Based Pharmacophore for Discovery of Methionyl-tRNA Synthetase Inhibitors as Antibacterial Agents

PubMed Central

Liu, Chi; He, Gu; Jiang, Qinglin; Han, Bo; Peng, Cheng

2013-01-01

Methione tRNA synthetase (MetRS) is an essential enzyme involved in protein biosynthesis in all living organisms and is a potential antibacterial target. In the current study, the structure-based pharmacophore (SBP)-guided method has been suggested to generate a comprehensive pharmacophore of MetRS based on fourteen crystal structures of MetRS-inhibitor complexes. In this investigation, a hybrid protocol of a virtual screening method, comprised of pharmacophore model-based virtual screening (PBVS), rigid and flexible docking-based virtual screenings (DBVS), is used for retrieving new MetRS inhibitors from commercially available chemical databases. This hybrid virtual screening approach was then applied to screen the Specs (202,408 compounds) database, a structurally diverse chemical database. Fifteen hit compounds were selected from the final hits and shifted to experimental studies. These results may provide important information for further research of novel MetRS inhibitors as antibacterial agents. PMID:23839093

Comparison of clinical and survival characteristics between prostate cancer patients of PSA-based screening and clinical diagnosis in China.

PubMed

Xu, Libo; Wang, Jinguo; Guo, Baofeng; Zhang, Haixia; Wang, Kaichen; Wang, Ding; Dai, Chang; Zhang, Ling; Zhao, Xuejian

2018-01-02

Prostate-specific antigen (PSA)-based mass screening remains the most controversial topic in prostate cancer. PSA-based mass screening has not been widely used in China yet. The aim of our study was to evaluate the effect of the PSA-based screening in China. The cohort consisted of 1,012 prostate cancer patients. Data were retrospectively collected and clinical characteristics of the cohorts were investigated. Survival was analyzed for prostatic carcinoma of both PSA screened and clinically diagnosed patients according to clinical characteristics and the National Comprehensive Cancer Network (NCCN) risk classification. Cox Proportional Hazards Model analysis was done for risk predictor identification. The median age was 71 years old. Five-year overall and prostate-cancer-specific survival in prostatic adenocarcinoma patients were 77.52% and 79.65%; 10-year survivals were 62.57% and 68.60%, respectively. Survival was significantly poorer in patients with metastases and non-curative management. T staging and Gleason score by NCCN classification effectively stratified prostatic adenocarcinoma patients into different risk groups. T staging was a significant predictor of survival by COX Proportional Hazard Model. PSA screened patients had a significantly higher percentage diagnosed in early stage. PSA screened prostatic adenocarcinoma patients had a better prognosis in both overall and prostate cancer-specific survivals. This Chinese cohort had a lower overall and prostate cancer survival rate than it is reported in western countries. The incidence of early-stage prostate cancer found in PSA-based mass screening was high and there were significant differences in both overall and prostate cancer-specific survival between the PSA-screened and clinically diagnosed patients.

Comparison of clinical and survival characteristics between prostate cancer patients of PSA-based screening and clinical diagnosis in China

PubMed Central

Xu, Libo; Wang, Jinguo; Guo, Baofeng; Zhang, Haixia; Wang, Kaichen; Wang, Ding; Dai, Chang; Zhang, Ling; Zhao, Xuejian

2018-01-01

Prostate-specific antigen (PSA)-based mass screening remains the most controversial topic in prostate cancer. PSA-based mass screening has not been widely used in China yet. The aim of our study was to evaluate the effect of the PSA-based screening in China. The cohort consisted of 1,012 prostate cancer patients. Data were retrospectively collected and clinical characteristics of the cohorts were investigated. Survival was analyzed for prostatic carcinoma of both PSA screened and clinically diagnosed patients according to clinical characteristics and the National Comprehensive Cancer Network (NCCN) risk classification. Cox Proportional Hazards Model analysis was done for risk predictor identification. The median age was 71 years old. Five-year overall and prostate-cancer-specific survival in prostatic adenocarcinoma patients were 77.52% and 79.65%; 10-year survivals were 62.57% and 68.60%, respectively. Survival was significantly poorer in patients with metastases and non-curative management. T staging and Gleason score by NCCN classification effectively stratified prostatic adenocarcinoma patients into different risk groups. T staging was a significant predictor of survival by COX Proportional Hazard Model. PSA screened patients had a significantly higher percentage diagnosed in early stage. PSA screened prostatic adenocarcinoma patients had a better prognosis in both overall and prostate cancer-specific survivals. This Chinese cohort had a lower overall and prostate cancer survival rate than it is reported in western countries. The incidence of early-stage prostate cancer found in PSA-based mass screening was high and there were significant differences in both overall and prostate cancer-specific survival between the PSA-screened and clinically diagnosed patients. PMID:29416625

Predicting the effectiveness of the Finnish population-based colorectal cancer screening programme.

PubMed

Chiu, Sherry Yueh-Hsia; Malila, Nea; Yen, Amy Ming-Fang; Chen, Sam Li-Sheng; Fann, Jean Ching-Yuan; Hakama, Matti

2017-12-01

Objective Because colorectal cancer (CRC) has a long natural history, estimating the effectiveness of CRC screening programmes requires long-term follow-up. As an alternative, we here demonstrate the use of a temporal multi-state natural history model to predict the effectiveness of CRC screening. Methods In the Finnish population-based biennial CRC screening programme using faecal occult blood tests (FOBT), which was conducted in a randomised health services study, we estimated the pre-clinical incidence, the mean sojourn time (MST), and the sensitivity of FOBT using a Markov model to analyse data from 2004 to 2007. These estimates were applied to predict, through simulation, the effects of five rounds of screening on the relative rate of reducing advanced CRC with 6 years of follow-up, and on the reduction in mortality with 10 years of follow-up, in a cohort of 500,000 subjects aged 60 to 69. Results For localised and non-localised CRC, respectively, the MST was 2.06 and 1.36 years and the sensitivity estimates were 65.12% and 73.70%. The predicted relative risk of non-localised CRC and death from CRC in the screened compared with the control population was 0.86 (95% CI: 0.79-0.98) and 0.91 (95% CI: 0.85-1.02), respectively. Conclusion Based on the preliminary results of the Finnish CRC screening programme, our model predicted a 9% reduction in CRC mortality and a 14% reduction in advanced CRC.

The role of area-level deprivation and gender in participation in population-based faecal immunochemical test (FIT) colorectal cancer screening.

PubMed

Clarke, Nicholas; McNamara, Deirdre; Kearney, Patricia M; O'Morain, Colm A; Shearer, Nikki; Sharp, Linda

2016-12-01

This study aimed to investigate the effects of sex and deprivation on participation in a population-based faecal immunochemical test (FIT) colorectal cancer screening programme. The study population included 9785 individuals invited to participate in two rounds of a population-based biennial FIT-based screening programme, in a relatively deprived area of Dublin, Ireland. Explanatory variables included in the analysis were sex, deprivation category of area of residence and age (at end of screening). The primary outcome variable modelled was participation status in both rounds combined (with "participation" defined as having taken part in either or both rounds of screening). Poisson regression with a log link and robust error variance was used to estimate relative risks (RR) for participation. As a sensitivity analysis, data were stratified by screening round. In both the univariable and multivariable models deprivation was strongly associated with participation. Increasing affluence was associated with higher participation; participation was 26% higher in people resident in the most affluent compared to the most deprived areas (multivariable RR=1.26: 95% CI 1.21-1.30). Participation was significantly lower in males (multivariable RR=0.96: 95%CI 0.95-0.97) and generally increased with increasing age (trend per age group, multivariable RR=1.02: 95%CI, 1.01-1.02). No significant interactions between the explanatory variables were found. The effects of deprivation and sex were similar by screening round. Deprivation and male gender are independently associated with lower uptake of population-based FIT colorectal cancer screening, even in a relatively deprived setting. Development of evidence-based interventions to increase uptake in these disadvantaged groups is urgently required. Copyright © 2016. Published by Elsevier Inc.

SCREENING MODEL FOR NONAQUEOUS PHASE LIQUID TRANS- PORT IN THE VADOSE ZONE USING GREEN-AMPT AND KINEMATIC WAVE THEORY

EPA Science Inventory

In this paper, a screening model for flow of a nonaqueous phase liquid (NAPL) and associated chemical transport in the vadose zone is developed. The model is based on kinematic approximation of the governing equations for both the NAPL and a partitionable chemical constituent. Th...

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

PubMed Central

2010-01-01

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. PMID:20433705

Engaging New Migrants in Infectious Disease Screening: A Qualitative Semi-Structured Interview Study of UK Migrant Community Health-Care Leads

PubMed Central

Seedat, Farah; Hargreaves, Sally; Friedland, Jonathan S.

2014-01-01

Migration to Europe - and in particular the UK - has risen dramatically in the past decades, with implications for public health services. Migrants have increased vulnerability to infectious diseases (70% of TB cases and 60% HIV cases are in migrants) and face multiple barriers to healthcare. There is currently considerable debate as to the optimum approach to infectious disease screening in this often hard-to-reach group, and an urgent need for innovative approaches. Little research has focused on the specific experience of new migrants, nor sought their views on ways forward. We undertook a qualitative semi-structured interview study of migrant community health-care leads representing dominant new migrant groups in London, UK, to explore their views around barriers to screening, acceptability of screening, and innovative approaches to screening for four key diseases (HIV, TB, hepatitis B, and hepatitis C). Participants unanimously agreed that current screening models are not perceived to be widely accessible to new migrant communities. Dominant barriers that discourage uptake of screening include disease-related stigma present in their own communities and services being perceived as non-migrant friendly. New migrants are likely to be disproportionately affected by these barriers, with implications for health status. Screening is certainly acceptable to new migrants, however, services need to be developed to become more community-based, proactive, and to work more closely with community organisations; findings that mirror the views of migrants and health-care providers in Europe and internationally. Awareness raising about the benefits of screening within new migrant communities is critical. One innovative approach proposed by participants is a community-based package of health screening combining all key diseases into one general health check-up, to lessen the associated stigma. Further research is needed to develop evidence-based community-focused screening models - drawing on models of best practice from other countries receiving high numbers of migrants. PMID:25330079

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

PubMed

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

2010-04-30

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

The comparative and cost-effectiveness of HPV-based cervical cancer screening algorithms in El Salvador.

PubMed

Campos, Nicole G; Maza, Mauricio; Alfaro, Karla; Gage, Julia C; Castle, Philip E; Felix, Juan C; Cremer, Miriam L; Kim, Jane J

2015-08-15

Cervical cancer is the leading cause of cancer death among women in El Salvador. Utilizing data from the Cervical Cancer Prevention in El Salvador (CAPE) demonstration project, we assessed the health and economic impact of HPV-based screening and two different algorithms for the management of women who test HPV-positive, relative to existing Pap-based screening. We calibrated a mathematical model of cervical cancer to epidemiologic data from El Salvador and compared three screening algorithms for women aged 30-65 years: (i) HPV screening every 5 years followed by referral to colposcopy for HPV-positive women (Colposcopy Management [CM]); (ii) HPV screening every 5 years followed by treatment with cryotherapy for eligible HPV-positive women (Screen and Treat [ST]); and (iii) Pap screening every 2 years followed by referral to colposcopy for Pap-positive women (Pap). Potential harms and complications associated with overtreatment were not assessed. Under base case assumptions of 65% screening coverage, HPV-based screening was more effective than Pap, reducing cancer risk by ∼ 60% (Pap: 50%). ST was the least costly strategy, and cost $2,040 per year of life saved. ST remained the most attractive strategy as visit compliance, costs, coverage, and test performance were varied. We conclude that a screen-and-treat algorithm within an HPV-based screening program is very cost-effective in El Salvador, with a cost-effectiveness ratio below per capita GDP. © 2015 UICC.

Automated image-based phenotypic analysis in zebrafish embryos

PubMed Central

Vogt, Andreas; Cholewinski, Andrzej; Shen, Xiaoqiang; Nelson, Scott; Lazo, John S.; Tsang, Michael; Hukriede, Neil A.

2009-01-01

Presently, the zebrafish is the only vertebrate model compatible with contemporary paradigms of drug discovery. Zebrafish embryos are amenable to automation necessary for high-throughput chemical screens, and optical transparency makes them potentially suited for image-based screening. However, the lack of tools for automated analysis of complex images presents an obstacle to utilizing the zebrafish as a high-throughput screening model. We have developed an automated system for imaging and analyzing zebrafish embryos in multi-well plates regardless of embryo orientation and without user intervention. Images of fluorescent embryos were acquired on a high-content reader and analyzed using an artificial intelligence-based image analysis method termed Cognition Network Technology (CNT). CNT reliably detected transgenic fluorescent embryos (Tg(fli1:EGFP)y1) arrayed in 96-well plates and quantified intersegmental blood vessel development in embryos treated with small molecule inhibitors of anigiogenesis. The results demonstrate it is feasible to adapt image-based high-content screening methodology to measure complex whole organism phenotypes. PMID:19235725

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

PubMed Central

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

2016-01-01

Improved methodologies for modeling cardiac disease phenotypes and accurately screening the efficacy and toxicity of potential therapeutic compounds are actively being sought to advance drug development and improve disease modeling capabilities. To that end, much recent effort has been devoted to the development of novel engineered biomimetic cardiac tissue platforms that accurately recapitulate the structure and function of the human myocardium. Within the field of cardiac engineering, induced pluripotent stem cells (iPSCs) are an exciting tool that offer the potential to advance the current state of the art, as they are derived from somatic cells, enabling the development of personalized medical strategies and patient specific disease models. Here we review different aspects of iPSC-based cardiac engineering technologies. We highlight methods for producing iPSC-derived cardiomyocytes (iPSC-CMs) and discuss their application to compound efficacy/toxicity screening and in vitro modeling of prevalent cardiac diseases. Special attention is paid to the application of micro- and nano-engineering techniques for the development of novel iPSC-CM based platforms and their potential to advance current preclinical screening modalities. PMID:28007615

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

PubMed

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

2015-01-01

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

[Ideas and methods on efficient screening of traditional medicines for anti-osteoporosis activity based on M-Act/Tox integrated evaluation using zebrafish].

PubMed

Wang, Mo; Ling, Jie; Chen, Ying; Song, Jie; Sun, E; Shi, Zi-Qi; Feng, Liang; Jia, Xiao-Bin; Wei, Ying-Jie

2017-11-01

The increasingly apparent liver injury problems of bone strengthening Chinese medicines have brought challenges for clinical application, and it is necessary to consider both effectiveness and safety in screening anti-osteoporosis Chinese medicines. Metabolic transformation is closely related to drug efficacy and toxicity, so it is significant to comprehensively consider metabolism-action/toxicity(M-Act/Tox) for screening anti-osteoporosis Chinese medicines. The current evaluation models and the number of compounds(including metabolites) severely restrict efficient screening in vivo. By referring to previous relevant research and domestic and abroad literature, zebrafish M-Act/Tox integrative method was put forward for efficiently screening anti-osteoporosis herb medicines, which has organically integrated zebrafish metabolism model, osteoporosis model and toxicity evaluation method. This method can break through the bottleneck and blind spots that trace compositions can't achieve efficient and integrated in vivo evaluation, and realize both efficient and comprehensive screening on anti-osteoporosis traditional medicines based on in vivo process taking both safety and effectiveness into account, which is significant to accelerate discovery of effective and safe innovative traditional Chinese medicines for osteoporosis. Copyright© by the Chinese Pharmaceutical Association.

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

PubMed

Evanoff, Bradley; Kymes, Steve

2010-06-01

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

Effect of transient liquid flow on retention characteristics of screen acquisition systems. [design of Space Shuttle feed system

NASA Technical Reports Server (NTRS)

Cady, E. C.

1977-01-01

A design analysis, is developed based on experimental data, to predict the effects of transient flow and pressure surges (caused either by valve or pump operation, or by boiling of liquids in warm lines) on the retention performance of screen acquisition systems. A survey of screen liquid acquisition system applications was performed to determine appropriate system environment and classification. A screen model was developed which assumed that the screen device was a uniformly distributed composite orthotropic structure, and which accounted for liquid inflow/outflow, gas ingestion quality, screen stress, and liquid spill. A series of 177 tests using 13 specimens (5 screen meshes, 4 screen device construction/backup methods, and 2 orientations) with three test fluids (isopropyl alcohol, Freon 114, and LH2) provided data which verified important features of the screen model and resulted in a design tool which could accurately predict the transient startup performance acquisition devices.

What is the most cost-effective population-based cancer screening program for Chinese women?

PubMed

Woo, Pauline P S; Kim, Jane J; Leung, Gabriel M

2007-02-20

To develop a policy-relevant generalized cost-effectiveness (CE) model of population-based cancer screening for Chinese women. Disability-adjusted life-years (DALYs) averted and associated screening and treatment costs under population-based screening using cervical cytology (cervical cancer), mammography (breast cancer), and fecal occult blood testing (FOBT), sigmoidoscopy, FOBT plus sigmoidoscopy, or colonoscopy (colorectal cancer) were estimated, from which average and incremental CE ratios were generated. Probabilistic sensitivity analysis was undertaken to assess stochasticity, parameter uncertainty, and model assumptions. Cervical, breast, and colorectal cancers were together responsible for 13,556 DALYs (in a 1:4:3 ratio, respectively) in Hong Kong's 3.4 million female population annually. All status quo strategies were dominated, thus confirming the suboptimal efficiency of opportunistic screening. Current patterns of screening averted 471 DALYs every year, which could potentially be more than doubled to 1,161 DALYs under the same screening and treatment budgetary threshold of US $50 million with 100% Pap coverage every 4 years and 30% coverage of colonoscopy every 10 years. With higher budgetary caps, biennial mammographic screening starting at age 50 years can be introduced. Our findings have informed how best to achieve allocative efficiency in deploying scarce cancer care dollars but must be coupled with better integrated care planning, improved intersectoral coordination, increased resources, and stronger political will to realize the potential health and economic gains as demonstrated.

Is prostate cancer screening cost-effective? A microsimulation model of prostate-specific antigen-based screening for British Columbia, Canada

PubMed Central

Pataky, Reka; Gulati, Roman; Etzioni, Ruth; Black, Peter; Chi, Kim N.; Coldman, Andrew J.; Pickles, Tom; Tyldesley, Scott; Peacock, Stuart

2015-01-01

Prostate-specific antigen (PSA) screening for prostate cancer may reduce mortality, but it incurs considerable risk of overdiagnosis and potential harm to quality of life. Our objective was to evaluate the cost-effectiveness of PSA screening, with and without adjustment for quality of life, for the British Columbia (BC) population. We adapted an existing natural history model using BC incidence, treatment, cost and mortality patterns. The modeled mortality benefit of screening derives from a stage-shift mechanism, assuming mortality reduction consistent with the European Study of Randomized Screening for Prostate Cancer. The model projected outcomes for 40 year-old men under 14 combinations of screening ages and frequencies. Cost and utility estimates were explored with deterministic sensitivity analysis. The incremental cost-effectiveness of regular screening ranged from $36,300/LYG, for screening every four years from ages 55-69, to $588,300/LYG, for screening every two years from ages 40-74. The marginal benefits of increasing screening frequency to two years or starting screening at age 40 were small and came at significant cost. After utility adjustment, all screening strategies resulted in a loss of QALYs; however, this result was very sensitive to utility estimates. Plausible outcomes under a range of screening strategies inform discussion of prostate cancer screening policy in BC and similar jurisdictions. Screening may be cost-effective but the sensitivity of results to utility values suggests individual preferences for quality versus quantity of life should be a key consideration. PMID:24443367

Cost-effectiveness analysis of population-based screening of hepatocellular carcinoma: Comparing ultrasonography with two-stage screening

PubMed Central

Kuo, Ming-Jeng; Chen, Hsiu-Hsi; Chen, Chi-Ling; Fann, Jean Ching-Yuan; Chen, Sam Li-Sheng; Chiu, Sherry Yueh-Hsia; Lin, Yu-Min; Liao, Chao-Sheng; Chang, Hung-Chuen; Lin, Yueh-Shih; Yen, Amy Ming-Fang

2016-01-01

AIM: To assess the cost-effectiveness of two population-based hepatocellular carcinoma (HCC) screening programs, two-stage biomarker-ultrasound method and mass screening using abdominal ultrasonography (AUS). METHODS: In this study, we applied a Markov decision model with a societal perspective and a lifetime horizon for the general population-based cohorts in an area with high HCC incidence, such as Taiwan. The accuracy of biomarkers and ultrasonography was estimated from published meta-analyses. The costs of surveillance, diagnosis, and treatment were based on a combination of published literature, Medicare payments, and medical expenditure at the National Taiwan University Hospital. The main outcome measure was cost per life-year gained with a 3% annual discount rate. RESULTS: The results show that the mass screening using AUS was associated with an incremental cost-effectiveness ratio of USD39825 per life-year gained, whereas two-stage screening was associated with an incremental cost-effectiveness ratio of USD49733 per life-year gained, as compared with no screening. Screening programs with an initial screening age of 50 years old and biennial screening interval were the most cost-effective. These findings were sensitive to the costs of screening tools and the specificity of biomarker screening. CONCLUSION: Mass screening using AUS is more cost effective than two-stage biomarker-ultrasound screening. The most optimal strategy is an initial screening age at 50 years old with a 2-year inter-screening interval. PMID:27022228

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

EPA Science Inventory

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...

Chip Based Magnetic Imager for Molecular Profiling of Ovarian Cancer Cells

DTIC Science & Technology

2016-12-01

2015) Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis. Cell 160:1246-1260. PMC4380877, PMID:25748654. Acknowledgement of...Weissleder R, Lee H, Zhang F, Sharp PA (2015) Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis. Cell 160:1246-1260. 5. Im H, Shao H...Lett 32(10):1229–1231. 6 of 6 | www.pnas.org/cgi/doi/10.1073/pnas.1501815112 Im et al. Resource Genome-wide CRISPR Screen in a Mouse Model of Tumor

A phase screen model for simulating numerically the propagation of a laser beam in rain

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

Lukin, I P; Rychkov, D S; Falits, A V

2009-09-30

The method based on the generalisation of the phase screen method for a continuous random medium is proposed for simulating numerically the propagation of laser radiation in a turbulent atmosphere with precipitation. In the phase screen model for a discrete component of a heterogeneous 'air-rain droplet' medium, the amplitude screen describing the scattering of an optical field by discrete particles of the medium is replaced by an equivalent phase screen with a spectrum of the correlation function of the effective dielectric constant fluctuations that is similar to the spectrum of a discrete scattering component - water droplets in air. Themore » 'turbulent' phase screen is constructed on the basis of the Kolmogorov model, while the 'rain' screen model utiises the exponential distribution of the number of rain drops with respect to their radii as a function of the rain intensity. Theresults of the numerical simulation are compared with the known theoretical estimates for a large-scale discrete scattering medium. (propagation of laser radiation in matter)« less

Fragment virtual screening based on Bayesian categorization for discovering novel VEGFR-2 scaffolds.

PubMed

Zhang, Yanmin; Jiao, Yu; Xiong, Xiao; Liu, Haichun; Ran, Ting; Xu, Jinxing; Lu, Shuai; Xu, Anyang; Pan, Jing; Qiao, Xin; Shi, Zhihao; Lu, Tao; Chen, Yadong

2015-11-01

The discovery of novel scaffolds against a specific target has long been one of the most significant but challengeable goals in discovering lead compounds. A scaffold that binds in important regions of the active pocket is more favorable as a starting point because scaffolds generally possess greater optimization possibilities. However, due to the lack of sufficient chemical space diversity of the databases and the ineffectiveness of the screening methods, it still remains a great challenge to discover novel active scaffolds. Since the strengths and weaknesses of both fragment-based drug design and traditional virtual screening (VS), we proposed a fragment VS concept based on Bayesian categorization for the discovery of novel scaffolds. This work investigated the proposal through an application on VEGFR-2 target. Firstly, scaffold and structural diversity of chemical space for 10 compound databases were explicitly evaluated. Simultaneously, a robust Bayesian classification model was constructed for screening not only compound databases but also their corresponding fragment databases. Although analysis of the scaffold diversity demonstrated a very unevenly distribution of scaffolds over molecules, results showed that our Bayesian model behaved better in screening fragments than molecules. Through a literature retrospective research, several generated fragments with relatively high Bayesian scores indeed exhibit VEGFR-2 biological activity, which strongly proved the effectiveness of fragment VS based on Bayesian categorization models. This investigation of Bayesian-based fragment VS can further emphasize the necessity for enrichment of compound databases employed in lead discovery by amplifying the diversity of databases with novel structures.

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

PubMed

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

2018-05-15

Lung cancer screening guidelines recommend using individualized risk models to refer ever-smokers for screening. However, different models select different screening populations. The performance of each model in selecting ever-smokers for screening is unknown. To compare the U.S. screening populations selected by 9 lung cancer risk models (the Bach model; the Spitz model; the Liverpool Lung Project [LLP] model; the LLP Incidence Risk Model [LLPi]; the Hoggart model; the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model 2012 [PLCOM2012]; the Pittsburgh Predictor; the Lung Cancer Risk Assessment Tool [LCRAT]; and the Lung Cancer Death Risk Assessment Tool [LCDRAT]) and to examine their predictive performance in 2 cohorts. Population-based prospective studies. United States. Models selected U.S. screening populations by using data from the National Health Interview Survey from 2010 to 2012. Model performance was evaluated using data from 337 388 ever-smokers in the National Institutes of Health-AARP Diet and Health Study and 72 338 ever-smokers in the CPS-II (Cancer Prevention Study II) Nutrition Survey cohort. Model calibration (ratio of model-predicted to observed cases [expected-observed ratio]) and discrimination (area under the curve [AUC]). At a 5-year risk threshold of 2.0%, the models chose U.S. screening populations ranging from 7.6 million to 26 million ever-smokers. These disagreements occurred because, in both validation cohorts, 4 models (the Bach model, PLCOM2012, LCRAT, and LCDRAT) were well-calibrated (expected-observed ratio range, 0.92 to 1.12) and had higher AUCs (range, 0.75 to 0.79) than 5 models that generally overestimated risk (expected-observed ratio range, 0.83 to 3.69) and had lower AUCs (range, 0.62 to 0.75). The 4 best-performing models also had the highest sensitivity at a fixed specificity (and vice versa) and similar discrimination at a fixed risk threshold. These models showed better agreement on size of the screening population (7.6 million to 10.9 million) and achieved consensus on 73% of persons chosen. No consensus on risk thresholds for screening. The 9 lung cancer risk models chose widely differing U.S. screening populations. However, 4 models (the Bach model, PLCOM2012, LCRAT, and LCDRAT) most accurately predicted risk and performed best in selecting ever-smokers for screening. Intramural Research Program of the National Institutes of Health/National Cancer Institute.

Probe molecules (PrM) approach in adverse outcome pathway (AOP) based high throughput screening (HTS): in vivo discovery for developing in vitro target methods

EPA Science Inventory

Efficient and accurate adverse outcome pathway (AOP) based high-throughput screening (HTS) methods use a systems biology based approach to computationally model in vitro cellular and molecular data for rapid chemical prioritization; however, not all HTS assays are grounded by rel...

Evaluation of a Stratified National Breast Screening Program in the United Kingdom: An Early Model-Based Cost-Effectiveness Analysis.

PubMed

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 © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Predicting the stage shift as a result of breast cancer screening in low- and middle-income countries: a proof of concept.

PubMed

Zelle, Sten G; Baltussen, Rob; Otten, Johannes D M; Heijnsdijk, Eveline A M; van Schoor, Guido; Broeders, Mireille J M

2015-03-01

To provide proof of concept for a simple model to estimate the stage shift as a result of breast cancer screening in low- and middle-income countries (LMICs). Stage shift is an essential early detection indicator and an important proxy for the performance and possible further impact of screening programmes. Our model could help LIMCs to choose appropriate control strategies. We assessed our model concept in three steps. First, we calculated the proportional performance rates (i.e. index number Z) based on 16 screening rounds of the Nijmegen Screening Program (384,884 screened women). Second, we used linear regression to assess the association between Z and the amount of stage shift observed in the programme. Third, we hypothesized how Z could be used to estimate the stage shift as a result of breast cancer screening in LMICs. Stage shifts can be estimated by the proportional performance rates (Zs) using linear regression. Zs calculated for each screening round are highly associated with the observed stage shifts in the Nijmegen Screening Program (Pearson's R: 0.798, R square: 0.637). Our model can predict the stage shifts in the Nijmegen Screening Program, and could be applied to settings with different characteristics, although it should not be straightforwardly used to estimate the impact on mortality. Further research should investigate the extrapolation of our model to other settings. As stage shift is an essential screening performance indicator, our model could provide important information on the performance of breast cancer screening programmes that LMICs consider implementing. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Economic Evaluation of Screening Strategies Combined with HPV Vaccination of Preadolescent Girls for the Prevention of Cervical Cancer in Vientiane, Lao PDR

PubMed Central

2016-01-01

Background Several approaches to reduce the incidence of invasive cervical cancers exist. The approach adopted should take into account contextual factors that influence the cost-effectiveness of the available options. Objective To determine the cost-effectiveness of screening strategies combined with a vaccination program for 10-year old girls for cervical cancer prevention in Vientiane, Lao PDR. Methods A population-based dynamic compartment model was constructed. The interventions consisted of a 10-year old girl vaccination program only, or this program combined with screening strategies, i.e., visual inspection with acetic acid (VIA), cytology-based screening, rapid human papillomavirus (HPV) DNA testing, or combined VIA and cytology testing. Simulations were run over 100 years. In base-case scenario analyses, we assumed a 70% vaccination coverage with lifelong protection and a 50% screening coverage. The outcome of interest was the incremental cost per Disability-Adjusted Life Year (DALY) averted. Results In base-case scenarios, compared to the next best strategy, the model predicted that VIA screening of women aged 30–65 years old every three years, combined with vaccination, was the most attractive option, costing 2 544 international dollars (I$) per DALY averted. Meanwhile, rapid HPV DNA testing was predicted to be more attractive than cytology-based screening or its combination with VIA. Among cytology-based screening options, combined VIA with conventional cytology testing was predicted to be the most attractive option. Multi-way sensitivity analyses did not change the results. Compared to rapid HPV DNA testing, VIA had a probability of cost-effectiveness of 73%. Compared to the vaccination only option, the probability that a program consisting of screening women every five years would be cost-effective was around 60% and 80% if the willingness-to-pay threshold is fixed at one and three GDP per capita, respectively. Conclusions A VIA screening program in addition to a girl vaccination program was predicted to be the most attractive option in the health care context of Lao PDR. When compared with other screening methods, VIA was the primary recommended method for combination with vaccination in Lao PDR. PMID:27631732

Economic Evaluation of Screening Strategies Combined with HPV Vaccination of Preadolescent Girls for the Prevention of Cervical Cancer in Vientiane, Lao PDR.

PubMed

Chanthavilay, Phetsavanh; Reinharz, Daniel; Mayxay, Mayfong; Phongsavan, Keokedthong; Marsden, Donald E; Moore, Lynne; White, Lisa J

2016-01-01

Several approaches to reduce the incidence of invasive cervical cancers exist. The approach adopted should take into account contextual factors that influence the cost-effectiveness of the available options. To determine the cost-effectiveness of screening strategies combined with a vaccination program for 10-year old girls for cervical cancer prevention in Vientiane, Lao PDR. A population-based dynamic compartment model was constructed. The interventions consisted of a 10-year old girl vaccination program only, or this program combined with screening strategies, i.e., visual inspection with acetic acid (VIA), cytology-based screening, rapid human papillomavirus (HPV) DNA testing, or combined VIA and cytology testing. Simulations were run over 100 years. In base-case scenario analyses, we assumed a 70% vaccination coverage with lifelong protection and a 50% screening coverage. The outcome of interest was the incremental cost per Disability-Adjusted Life Year (DALY) averted. In base-case scenarios, compared to the next best strategy, the model predicted that VIA screening of women aged 30-65 years old every three years, combined with vaccination, was the most attractive option, costing 2 544 international dollars (I$) per DALY averted. Meanwhile, rapid HPV DNA testing was predicted to be more attractive than cytology-based screening or its combination with VIA. Among cytology-based screening options, combined VIA with conventional cytology testing was predicted to be the most attractive option. Multi-way sensitivity analyses did not change the results. Compared to rapid HPV DNA testing, VIA had a probability of cost-effectiveness of 73%. Compared to the vaccination only option, the probability that a program consisting of screening women every five years would be cost-effective was around 60% and 80% if the willingness-to-pay threshold is fixed at one and three GDP per capita, respectively. A VIA screening program in addition to a girl vaccination program was predicted to be the most attractive option in the health care context of Lao PDR. When compared with other screening methods, VIA was the primary recommended method for combination with vaccination in Lao PDR.

Understanding wax screen-printing: a novel patterning process for microfluidic cloth-based analytical devices.

PubMed

Liu, Min; Zhang, Chunsun; Liu, Feifei

2015-09-03

In this work, we first introduce the fabrication of microfluidic cloth-based analytical devices (μCADs) using a wax screen-printing approach that is suitable for simple, inexpensive, rapid, low-energy-consumption and high-throughput preparation of cloth-based analytical devices. We have carried out a detailed study on the wax screen-printing of μCADs and have obtained some interesting results. Firstly, an analytical model is established for the spreading of molten wax in cloth. Secondly, a new wax screen-printing process has been proposed for fabricating μCADs, where the melting of wax into the cloth is much faster (∼5 s) and the heating temperature is much lower (75 °C). Thirdly, the experimental results show that the patterning effects of the proposed wax screen-printing method depend to a certain extent on types of screens, wax melting temperatures and melting time. Under optimized conditions, the minimum printing width of hydrophobic wax barrier and hydrophilic channel is 100 μm and 1.9 mm, respectively. Importantly, the developed analytical model is also well validated by these experiments. Fourthly, the μCADs fabricated by the presented wax screen-printing method are used to perform a proof-of-concept assay of glucose or protein in artificial urine with rapid high-throughput detection taking place on a 48-chamber cloth-based device and being performed by a visual readout. Overall, the developed cloth-based wax screen-printing and arrayed μCADs should provide a new research direction in the development of advanced sensor arrays for detection of a series of analytes relevant to many diverse applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Pharmacophore Based 3D-QSAR, Virtual Screening and Docking Studies on Novel Series of HDAC Inhibitors with Thiophen Linker as Anticancer Agents.

PubMed

Patel, Preeti; Singh, Avineesh; Patel, Vijay K; Jain, Deepak K; Veerasamy, Ravichandran; Rajak, Harish

2016-01-01

Histone deacetylase (HDAC) inhibitors can reactivate gene expression and inhibit the growth and survival of cancer cells. To identify the important pharmacophoric features and correlate 3Dchemical structure with biological activity using 3D-QSAR and Pharmacophore modeling studies. The pharmacophore hypotheses were developed using e-pharmacophore script and phase module. Pharmacophore hypothesis represents the 3D arrangement of molecular features necessary for activity. A series of 55 compounds with wellassigned HDAC inhibitory activity were used for 3D-QSAR model development. Best 3D-QSAR model, which is a five partial least square (PLS) factor model with good statistics and predictive ability, acquired Q2 (0.7293), R2 (0.9811), cross-validated coefficient rcv 2=0.9807 and R2 pred=0.7147 with low standard deviation (0.0952). Additionally, the selected pharmacophore model DDRRR.419 was used as a 3D query for virtual screening against the ZINC database. In the virtual screening workflow, docking studies (HTVS, SP and XP) were carried out by selecting multiple receptors (PDB ID: 1T69, 1T64, 4LXZ, 4LY1, 3MAX, 2VQQ, 3C10, 1W22). Finally, six compounds were obtained based on high scoring function (dock score -11.2278-10.2222 kcal/mol) and diverse structures. The structure activity correlation was established using virtual screening, docking, energetic based pharmacophore modelling, pharmacophore, atom based 3D QSAR models and their validation. The outcomes of these studies could be further employed for the design of novel HDAC inhibitors for anticancer activity.

Evaluating a De-Centralized Regional Delivery System for Breast Cancer Screening and Patient Navigation for the Rural Underserved.

PubMed

Inrig, Stephen J; Tiro, Jasmin A; Melhado, Trisha V; Argenbright, Keith E; Craddock Lee, Simon J

2014-01-01

Providing breast cancer screening services in rural areas is challenging due to the fractured nature of healthcare delivery systems and complex reimbursement mechanisms that create barriers to access for the under- and uninsured. Interventions that reduce structural barriers to mammography, like patient navigation programs, are effective and recommended, especially for minority and underserved women. Although the literature on rural healthcare is significant, the field lacks studies of adaptive service delivery models and rigorous evaluation of evidence-based programs that facilitate routine screening and appropriate follow-up across large geographic areas. To better understand how to implement a decentralized regional delivery "hub & spoke" model for rural breast cancer screening and patient navigation, we have designed a rigorous, structured, multi-level and mixed-methods evaluation based on Glasgow's RE-AIM model (Reach, Effectiveness, Adoption, Implementation, and Maintenance). The program is comprised of three core components: 1) Outreach to underserved women by partnering with county organizations; 2) Navigation to guide patients through screening and appropriate follow-up; and 3) Centralized Reimbursement to coordinate funding for screening services through a central contract with Medicaid Breast and Cervical Cancer Services (BCCS). Using Glasgow's RE-AIM model, we will: 1) assess which counties have the resources and capacity to implement outreach and/or navigation components, 2) train partners in each county on how to implement components, and 3) monitor process and outcome measures in each county at regular intervals, providing booster training when needed. This evaluation strategy will elucidate how the heterogeneity of rural county infrastructure impacts decentralized service delivery as a navigation program expands. In addition to increasing breast cancer screening access, our model improves and maintains time to diagnostic resolution and facilitates timely referral to local cancer treatment services. We offer this evaluation approach as an exemplar for scientific methods to evaluate the translation of evidence-based federal policy into sustainable health services delivery in a rural setting.

Evaluating a De-Centralized Regional Delivery System for Breast Cancer Screening and Patient Navigation for the Rural Underserved

PubMed Central

Inrig, Stephen J.; Tiro, Jasmin A.; Melhado, Trisha V.; Argenbright, Keith E.; Craddock Lee, Simon J.

2017-01-01

Providing breast cancer screening services in rural areas is challenging due to the fractured nature of healthcare delivery systems and complex reimbursement mechanisms that create barriers to access for the under- and uninsured. Interventions that reduce structural barriers to mammography, like patient navigation programs, are effective and recommended, especially for minority and underserved women. Although the literature on rural healthcare is significant, the field lacks studies of adaptive service delivery models and rigorous evaluation of evidence-based programs that facilitate routine screening and appropriate follow-up across large geographic areas. Objectives To better understand how to implement a decentralized regional delivery “hub & spoke” model for rural breast cancer screening and patient navigation, we have designed a rigorous, structured, multi-level and mixed-methods evaluation based on Glasgow’s RE-AIM model (Reach, Effectiveness, Adoption, Implementation, and Maintenance). Methods and Design The program is comprised of three core components: 1) Outreach to underserved women by partnering with county organizations; 2) Navigation to guide patients through screening and appropriate follow-up; and 3) Centralized Reimbursement to coordinate funding for screening services through a central contract with Medicaid Breast and Cervical Cancer Services (BCCS). Using Glasgow’s RE-AIM model, we will: 1) assess which counties have the resources and capacity to implement outreach and/or navigation components, 2) train partners in each county on how to implement components, and 3) monitor process and outcome measures in each county at regular intervals, providing booster training when needed. Discussion This evaluation strategy will elucidate how the heterogeneity of rural county infrastructure impacts decentralized service delivery as a navigation program expands. In addition to increasing breast cancer screening access, our model improves and maintains time to diagnostic resolution and facilitates timely referral to local cancer treatment services. We offer this evaluation approach as an exemplar for scientific methods to evaluate the translation of evidence-based federal policy into sustainable health services delivery in a rural setting. PMID:28713882

Application of Physiologically-Based Pharmacokinetic/Pharmacodynamic Model for Interpretation of High-throughput Screening Assay for Thyroperoxidase Inhibition

EPA Science Inventory

In vitro based assays are used to identify potential endocrine disrupting chemicals. Thyroperoxidase (TPO), an enzyme essential for thyroid hormone (TH) synthesis, is a target site for disruption of the thyroid axis for which a high-throughput screening (HTPS) assay has recently ...

Cost implications of PSA screening differ by age.

PubMed

Rao, Karthik; Liang, Stella; Cardamone, Michael; Joshu, Corinne E; Marmen, Kyle; Bhavsar, Nrupen; Nelson, William G; Ballentine Carter, H; Albert, Michael C; Platz, Elizabeth A; Pollack, Craig E

2018-05-09

Multiple guidelines seek to alter rates of prostate-specific antigen (PSA)-based prostate cancer screening. The costs borne by payers associated with PSA-based screening for men of different age groups-including the costs of screening and subsequent diagnosis, treatment, and adverse events-remain uncertain. We sought to develop a model of PSA costs that could be used by payers and health care systems to inform cost considerations under a range of different scenarios. We determined the prevalence of PSA screening among men aged 50 and higher using 2013-2014 data from a large, multispecialty group, obtained reimbursed costs associated with screening, diagnosis, and treatment from a commercial health plan, and identified transition probabilities for biopsy, diagnosis, treatment, and complications from the literature to generate a cost model. We estimated annual total costs for groups of men ages 50-54, 55-69, and 70+ years, and varied annual prostate cancer screening prevalence in each group from 5 to 50% and tested hypothetical examples of different test characteristics (e.g., true/false positive rate). Under the baseline screening patterns, costs of the PSA screening represented 10.1% of the total costs; costs of biopsies and associated complications were 23.3% of total costs; and, although only 0.3% of all screen eligible patients were treated, they accounted for 66.7% of total costs. For each 5-percentage point decrease in PSA screening among men aged 70 and older for a single calendar year, total costs associated with prostate cancer screening decreased by 13.8%. For each 5-percentage point decrease in PSA screening among men 50-54 and 55-69 years old, costs were 2.3% and 7.3% lower respectively. With constrained financial resources and with national pressure to decrease use of clinically unnecessary PSA-based prostate cancer screening, there is an opportunity for cost savings, especially by focusing on the downstream costs disproportionately associated with screening men 70 and older.

Microengineering methods for cell-based microarrays and high-throughput drug-screening applications.

PubMed

Xu, Feng; Wu, JinHui; Wang, ShuQi; Durmus, Naside Gozde; Gurkan, Umut Atakan; Demirci, Utkan

2011-09-01

Screening for effective therapeutic agents from millions of drug candidates is costly, time consuming, and often faces concerns due to the extensive use of animals. To improve cost effectiveness, and to minimize animal testing in pharmaceutical research, in vitro monolayer cell microarrays with multiwell plate assays have been developed. Integration of cell microarrays with microfluidic systems has facilitated automated and controlled component loading, significantly reducing the consumption of the candidate compounds and the target cells. Even though these methods significantly increased the throughput compared to conventional in vitro testing systems and in vivo animal models, the cost associated with these platforms remains prohibitively high. Besides, there is a need for three-dimensional (3D) cell-based drug-screening models which can mimic the in vivo microenvironment and the functionality of the native tissues. Here, we present the state-of-the-art microengineering approaches that can be used to develop 3D cell-based drug-screening assays. We highlight the 3D in vitro cell culture systems with live cell-based arrays, microfluidic cell culture systems, and their application to high-throughput drug screening. We conclude that among the emerging microengineering approaches, bioprinting holds great potential to provide repeatable 3D cell-based constructs with high temporal, spatial control and versatility.

Microengineering Methods for Cell Based Microarrays and High-Throughput Drug Screening Applications

PubMed Central

Xu, Feng; Wu, JinHui; Wang, ShuQi; Durmus, Naside Gozde; Gurkan, Umut Atakan; Demirci, Utkan

2011-01-01

Screening for effective therapeutic agents from millions of drug candidates is costly, time-consuming and often face ethical concerns due to extensive use of animals. To improve cost-effectiveness, and to minimize animal testing in pharmaceutical research, in vitro monolayer cell microarrays with multiwell plate assays have been developed. Integration of cell microarrays with microfluidic systems have facilitated automated and controlled component loading, significantly reducing the consumption of the candidate compounds and the target cells. Even though these methods significantly increased the throughput compared to conventional in vitro testing systems and in vivo animal models, the cost associated with these platforms remains prohibitively high. Besides, there is a need for three-dimensional (3D) cell based drug-screening models, which can mimic the in vivo microenvironment and the functionality of the native tissues. Here, we present the state-of-the-art microengineering approaches that can be used to develop 3D cell based drug screening assays. We highlight the 3D in vitro cell culture systems with live cell-based arrays, microfluidic cell culture systems, and their application to high-throughput drug screening. We conclude that among the emerging microengineering approaches, bioprinting holds a great potential to provide repeatable 3D cell based constructs with high temporal, spatial control and versatility. PMID:21725152

Concise review: modeling central nervous system diseases using induced pluripotent stem cells.

PubMed

Zeng, Xianmin; Hunsberger, Joshua G; Simeonov, Anton; Malik, Nasir; Pei, Ying; Rao, Mahendra

2014-12-01

Induced pluripotent stem cells (iPSCs) offer an opportunity to delve into the mechanisms underlying development while also affording the potential to take advantage of a number of naturally occurring mutations that contribute to either disease susceptibility or resistance. Just as with any new field, several models of screening are being explored, and innovators are working on the most efficient methods to overcome the inherent limitations of primary cell screens using iPSCs. In the present review, we provide a background regarding why iPSCs represent a paradigm shift for central nervous system (CNS) disease modeling. We describe the efforts in the field to develop more biologically relevant CNS disease models, which should provide screening assays useful for the pharmaceutical industry. We also provide some examples of successful uses for iPSC-based screens and suggest that additional development could revolutionize the field of drug discovery. The development and implementation of these advanced iPSC-based screens will create a more efficient disease-specific process underpinned by the biological mechanism in a patient- and disease-specific manner rather than by trial-and-error. Moreover, with careful and strategic planning, shared resources can be developed that will enable exponential advances in the field. This will undoubtedly lead to more sensitive and accurate screens for early diagnosis and allow the identification of patient-specific therapies, thus, paving the way to personalized medicine. ©AlphaMed Press.

Cost-effectiveness of orthoptic screening in kindergarten: a decision-analytic model.

PubMed

König, H H; Barry, J C; Leidl, R; Zrenner, E

2000-06-01

The purpose of this study was to analyze the cost-effectiveness of orthoptic screening for amblyopia in kindergarten. A decision-analytic model was used. In this model all kindergarten children in Germany aged 3 years were examined by an orthoptist. Children with positive screening results were referred to an ophthalmologist for diagnosis. The number of newly diagnosed cases of amblyopia, amblyogenic non-obvious strabismus and amblyogenic refractive errors was used as the measure of effectiveness. Direct costs were measured form a third-party payer perspective. Data for model parameters were obtained from the literature and from own measurements in kindergartens. A base analysis was performed using median parameter values. The influence of uncertain parameters was tested in sensitivity analyses. According to the base analysis, the cost of one orthoptic screening test was 7.87 euro. One ophthalmologic examination cost 36.40 euro. The total cost of the screening program in all kindergartens was 3.1 million euro. A total of 4,261 new cases would be detected. The cost-effectiveness ratio was 727 euro per case detected. Sensitivity analysis showed considerable influence of the prevalence rate of target conditions and of the specificity of the orthopic examination on the cost-effectiveness ratio. This analysis provides information which is useful for discussion about the implementation of orthoptic screening and for planning a field study.

Modelling, simulation and verification of the screening process of a swing-bar sieve based on the DEM

NASA Astrophysics Data System (ADS)

Wang, Yang; Yu, Jianqun; Yu, Yajun

2018-05-01

To solve the problems in the DEM simulations of the screening process of a swing-bar sieve, in this paper we propose the real-virtual boundary method to build the geometrical model of the screen deck on a swing-bar sieve. The motion of the swing-bar sieve is modelled by the planer multi-body kinematics. A coupled model of the discrete element method (DEM) with multi-body kinematics (MBK) is presented to simulate the flowing and passing processes of soybean particles on the screen deck. By the comparison of the simulated results with the experimental results of the screening process of the LA-LK laboratory scale swing-bar sieve, the feasibility and validity of the real-virtual boundary method and the coupled DEM-MBK model we proposed in this paper can be verified. This work provides the basis for the optimization design of the swing-bar sieve with circular apertures and complex motion.

Reevaluation of 1999 Health-Based Environmental Screening Levels (HBESLs) for Chemical Warfare Agents

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

Watson, Annetta Paule; Dolislager, Fredrick G

2007-05-01

This report evaluates whether new information and updated scientific models require that changes be made to previously published health-based environmental soil screening levels (HBESLs) and associated environmental fate/breakdown information for chemical warfare agents (USACHPPM 1999). Specifically, the present evaluation describes and compares changes that have been made since 1999 to U.S. Environmental Protection Agency (EPA) risk assessment models, EPA exposure assumptions, as well as to specific chemical warfare agent parameters (e.g., toxicity values). Comparison was made between screening value estimates recalculated with current assumptions and earlier health-based environmental screening levels presented in 1999. The chemical warfare agents evaluated include themore » G-series and VX nerve agents and the vesicants sulfur mustard (agent HD) and Lewisite (agent L). In addition, key degradation products of these agents were also evaluated. Study findings indicate that the combined effect of updates and/or changes to EPA risk models, EPA default exposure parameters, and certain chemical warfare agent toxicity criteria does not result in significant alteration to the USACHPPM (1999) health-based environmental screening level estimates for the G-series and VX nerve agents or the vesicant agents HD and L. Given that EPA's final position on separate Tier 1 screening levels for indoor and outdoor worker screening assessments has not yet been released as of May 2007, the study authors find that the 1999 screening level estimates (see Table ES.1) are still appropriate and protective for screening residential as well as nonresidential sites. As such, risk management decisions made on the basis of USACHPPM (1999) recommendations do not require reconsideration. While the 1999 HBESL values are appropriate for continued use as general screening criteria, the updated '2007' estimates (presented below) that follow the new EPA protocols currently under development are also protective. When EPA finalizes and documents a position on the matter of indoor and outdoor worker screening assessments, site-specific risk assessments should make use of modified models and criteria. Screening values such as those presented in this report may be used to assess soil or other porous media to determine whether chemical warfare agent contamination is present as part of initial site investigations (whether due to intentional or accidental releases) and to determine whether weather/decontamination has adequately mitigated the presence of agent residual to below levels of concern. However, despite the availability of scientifically supported health-based criteria, there are significant resources needs that should be considered during sample planning. In particular, few analytical laboratories are likely to be able to meet these screening levels. Analyses will take time and usually have limited confidence at these concentrations. Therefore, and particularly for the more volatile agents, soil/destructive samples of porous media should be limited and instead enhanced with headspace monitoring and presence-absence wipe sampling.« less

Applying Risk Prediction Models to Optimize Lung Cancer Screening: Current Knowledge, Challenges, and Future Directions.

PubMed

Sakoda, Lori C; Henderson, Louise M; Caverly, Tanner J; Wernli, Karen J; Katki, Hormuzd A

2017-12-01

Risk prediction models may be useful for facilitating effective and high-quality decision-making at critical steps in the lung cancer screening process. This review provides a current overview of published lung cancer risk prediction models and their applications to lung cancer screening and highlights both challenges and strategies for improving their predictive performance and use in clinical practice. Since the 2011 publication of the National Lung Screening Trial results, numerous prediction models have been proposed to estimate the probability of developing or dying from lung cancer or the probability that a pulmonary nodule is malignant. Respective models appear to exhibit high discriminatory accuracy in identifying individuals at highest risk of lung cancer or differentiating malignant from benign pulmonary nodules. However, validation and critical comparison of the performance of these models in independent populations are limited. Little is also known about the extent to which risk prediction models are being applied in clinical practice and influencing decision-making processes and outcomes related to lung cancer screening. Current evidence is insufficient to determine which lung cancer risk prediction models are most clinically useful and how to best implement their use to optimize screening effectiveness and quality. To address these knowledge gaps, future research should be directed toward validating and enhancing existing risk prediction models for lung cancer and evaluating the application of model-based risk calculators and its corresponding impact on screening processes and outcomes.

Pregnant Women's Views on the Feasibility and Acceptability of Web-Based Mental Health E-Screening Versus Paper-Based Screening: A Randomized Controlled Trial.

PubMed

Kingston, Dawn; Austin, Marie-Paule; Veldhuyzen van Zanten, Sander; Harvalik, Paula; Giallo, Rebecca; McDonald, Sarah D; MacQueen, Glenda; Vermeyden, Lydia; Lasiuk, Gerri; Sword, Wendy; Biringer, Anne

2017-04-07

Major international guidelines recommend mental health screening during the perinatal period. However, substantial barriers to screening have been reported by pregnant and postpartum women and perinatal care providers. E-screening offers benefits that may address implementation challenges. The primary objective of this randomized controlled trial was to evaluate the feasibility and acceptability of Web-based mental health e-screening compared with paper-based screening among pregnant women. A secondary objective was to identify factors associated with women's preferences for e-screening and disclosure of mental health concerns. Pregnant women recruited from community and hospital-based antenatal clinics and hospital-based prenatal classes were computer-randomized to a fully automated Web-based e-screening intervention group or a paper-based control group. Women were eligible if they spoke or read English, were willing to be randomized to e-screening, and were willing to participate in a follow-up diagnostic interview. The intervention group completed the Antenatal Psychosocial Health Assessment and the Edinburgh Postnatal Depression Scale on a tablet computer, while controls completed them on paper. All women completed self-report baseline questions and were telephoned 1 week after randomization by a blinded research assistant for a MINI International Neuropsychiatric Interview. Renker and Tonkin's tool of feasibility and acceptability of computerized screening was used to assess the feasibility and acceptability of e-screening compared with paper-based screening. Intention-to-treat analysis was used. To identify factors associated with preference for e-screening and disclosure, variables associated with each outcome at P<.20 were simultaneously entered into final multivariable models to estimate adjusted odds ratios (AORs) and 95% CIs. Of the 675 eligible women approached, 636 agreed to participate (participation rate 94.2%) and were randomized to the intervention (n=305) or control (n=331) groups. There were no significant baseline differences between groups. More women in the e-screening group strongly or somewhat agreed that they would like to use a tablet for answering questions on emotional health (57.9%, 175/302 vs 37.2%, 121/325) and would prefer using a tablet to paper (46.0%, 139/302 vs 29.2%, 95/325), compared with women in the paper-based screening group. There were no differences between groups in women's disclosure of emotional health concerns (94.1%, 284/302 vs 90.2%, 293/325). Women in the e-screening group consistently reported the features of e-screening more favorably than controls (more private or confidential, less impersonal, less time-consuming). In the multivariable models, being in the e-screening group was significantly associated with preferring e-screening (AOR 2.29, 95% CI 1.66-3.17), while no factors were significantly associated with disclosure. The findings suggest that mental health e-screening is feasible and acceptable to pregnant women. Clinicaltrials.gov NCT01899534; https://clinicaltrials.gov/ct2/show/NCT01899534 (Archived by WebCite at http://www.webcitation.org/6ntWg1yWb). ©Dawn Kingston, Marie-Paule Austin, Sander Veldhuyzen van Zanten, Paula Harvalik, Rebecca Giallo, Sarah D McDonald, Glenda MacQueen, Lydia Vermeyden, Gerri Lasiuk, Wendy Sword, Anne Biringer. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 07.04.2017.

Cost-effectiveness of osteoporosis screening strategies for hip fracture prevention in older Chinese people: a decision tree modeling study in the Mr. OS and Ms. OS cohort in Hong Kong.

PubMed

Su, Y; Lai, F T T; Yip, B H K; Leung, J C S; Kwok, T C Y

2018-05-17

Despite the high costs of hip fracture, many governments provide limited support for osteoporosis screening. We demonstrated that osteoporosis screening by dual-energy X-ray absorptiometry (DXA) with or without pre-screening by Fracture Risk Assessment Tool (FRAX) or calcaneal ultrasound are more cost-effective than no screening in Chinese people aged 65 or over in Hong Kong. To examine the cost-effective potential osteoporosis screening strategies for hip fracture prevention in Hong Kong. Decision tree models were constructed to evaluate the cost per quality-adjusted life years (QALYs) of the different osteoporosis screening strategies followed by subsequent 5-year treatment with alendronate compared to no screening (but treat if a hip fracture occurs). The multiple osteoporosis screening strategies were composed of alternative tests and initiation age groups were evaluated with a 10-year horizon, and treatment were assigned if central dual-energy X-ray absorptiometry (DXA) T-score (at either the hip or spine) is - 2.5 or less. Strategies included DXA for all people and pre-screening with the Fracture Risk Assessment Tool (FRAX) at specific thresholds or by calcaneal quantitative ultrasonography (QUS) before taking DXA examination. All the model inputs were based on the Mr. OS and Ms. OS Hong Kong cohort; data are obtained from the Social Welfare Department or the published literature. All of the screening strategies, including the universal screening with DXA and the pre-screening with FRAX or QUS before DXA, were consistently more cost-effective than no screening for people aged 65 years old or over. One-way sensitivity analysis with a more optimistic assumption on treatment adherence or inclusion of other major osteoporotic fractures did not change the results materially. Probabilistic sensitivity analyses showed a dominant role of pre-screening with FRAX followed by subsequent osteoporosis drug treatment in people aged 70 years old or over in Hong Kong. Osteoporosis screening strategies based on DXA with or without pre-screening are more cost-effective compared to no screening for Chinese people aged 65 or over in Hong Kong.

Model-Free Conditional Independence Feature Screening For Ultrahigh Dimensional Data.

PubMed

Wang, Luheng; Liu, Jingyuan; Li, Yong; Li, Runze

2017-03-01

Feature screening plays an important role in ultrahigh dimensional data analysis. This paper is concerned with conditional feature screening when one is interested in detecting the association between the response and ultrahigh dimensional predictors (e.g., genetic makers) given a low-dimensional exposure variable (such as clinical variables or environmental variables). To this end, we first propose a new index to measure conditional independence, and further develop a conditional screening procedure based on the newly proposed index. We systematically study the theoretical property of the proposed procedure and establish the sure screening and ranking consistency properties under some very mild conditions. The newly proposed screening procedure enjoys some appealing properties. (a) It is model-free in that its implementation does not require a specification on the model structure; (b) it is robust to heavy-tailed distributions or outliers in both directions of response and predictors; and (c) it can deal with both feature screening and the conditional screening in a unified way. We study the finite sample performance of the proposed procedure by Monte Carlo simulations and further illustrate the proposed method through two real data examples.

A Model Strategy and Policy for Screening Firefighter Candidates

DTIC Science & Technology

2006-03-01

57 A. INTRODUCTION......................................................................................57 B. STATEGY STATEMENT...of the United States. B. STATEGY STATEMENT The intent of this strategy is to create a model firefighter pre-employment screening process that...provide results that either clearly support the strategy change, clearly refute the need for a strategy change or provide mixed results. Based on

Recruiting African American Men for Cancer Screening Studies: Applying a Culturally Based Model

ERIC Educational Resources Information Center

Abernethy, Alexis D.; Magat, Maricar M.; Houston, Tina R.; Arnold, Harold L., Jr.; Bjorck, Jeffrey P.; Gorsuch, Richard L.

2005-01-01

In a study of psychosocial factors related to prostate cancer screening (PCS) of African American men, researchers achieved significant success in recruitment. Key strategies included addressing specific barriers to PCS for African American men and placing recruitment efforts in a conceptual framework that addressed cultural issues (PEN-3 model).…

Associations between Screen-Based Sedentary Behaviour and Anxiety Symptoms in Mothers with Young Children

PubMed Central

Teychenne, Megan; Hinkley, Trina

2016-01-01

Objectives Anxiety is a serious illness and women (including mothers with young children) are at particular risk. Although physical activity (PA) may reduce anxiety risk, little research has investigated the link between sedentary behaviour and anxiety risk. The aim of this study was to examine the association between screen-based sedentary behaviour and anxiety symptoms, independent of PA, amongst mothers with young children. Methods During 2013–2014, 528 mothers with children aged 2–5 years completed self-report measures of recreational screen-based sedentary behaviour (TV/DVD/video viewing, computer/e-games/hand held device use) and anxiety symptoms (using the Hospital Anxiety and Depression Scale, HADS-A). Linear regression analyses examined the cross-sectional association between screen-based sedentary behaviour and anxiety symptoms. Results In models that adjusted for key demographic and behavioural covariates (including moderate- to vigorous-intensity PA, MVPA), computer/device use (B = 0.212; 95% CI = 0.048, 0.377) and total screen time (B = 0.109; 95% CI = 0.014, 0.205) were positively associated with heightened anxiety symptoms. TV viewing was not associated with anxiety symptoms in either model. Conclusions Higher levels of recreational computer or handheld device use and overall screen time may be linked to higher risk of anxiety symptoms in mothers with young children, independent of MVPA. Further longitudinal and intervention research is required to determine temporal associations. PMID:27191953

Do Men and Women Need to Be Screened Differently with Fecal Immunochemical Testing? A Cost-Effectiveness Analysis.

PubMed

Meulen, Miriam P van der; Kapidzic, Atija; Leerdam, Monique E van; van der Steen, Alex; Kuipers, Ernst J; Spaander, Manon C W; de Koning, Harry J; Hol, Lieke; Lansdorp-Vogelaar, Iris

2017-08-01

Background: Several studies suggest that test characteristics for the fecal immunochemical test (FIT) differ by gender, triggering a debate on whether men and women should be screened differently. We used the microsimulation model MISCAN-Colon to evaluate whether screening stratified by gender is cost-effective. Methods: We estimated gender-specific FIT characteristics based on first-round positivity and detection rates observed in a FIT screening pilot (CORERO-1). Subsequently, we used the model to estimate harms, benefits, and costs of 480 gender-specific FIT screening strategies and compared them with uniform screening. Results: Biennial FIT screening from ages 50 to 75 was less effective in women than men [35.7 vs. 49.0 quality-adjusted life years (QALY) gained, respectively] at higher costs (€42,161 vs. -€5,471, respectively). However, the incremental QALYs gained and costs of annual screening compared with biennial screening were more similar for both genders (8.7 QALYs gained and €26,394 for women vs. 6.7 QALYs gained and €20,863 for men). Considering all evaluated screening strategies, optimal gender-based screening yielded at most 7% more QALYs gained than optimal uniform screening and even resulted in equal costs and QALYs gained from a willingness-to-pay threshold of €1,300. Conclusions: FIT screening is less effective in women, but the incremental cost-effectiveness is similar in men and women. Consequently, screening stratified by gender is not more cost-effective than uniform FIT screening. Impact: Our conclusions support the current policy of uniform FIT screening. Cancer Epidemiol Biomarkers Prev; 26(8); 1328-36. ©2017 AACR . ©2017 American Association for Cancer Research.

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

NASA Astrophysics Data System (ADS)

Iftikhar, Sehrish; Shahid, Ahmad A.; Halim, Sobia A.; Wolters, Pieter J.; Vleeshouwers, Vivianne G. A. A.; Khan, Ajmal; Al-Harrasi, Ahmed; Ahmad, Shahbaz

2017-11-01

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 protocol. 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 new and novel fungicides.

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

PubMed Central

Iftikhar, Sehrish; Shahid, Ahmad A.; Halim, Sobia A.; Wolters, Pieter J.; Vleeshouwers, Vivianne G. A. A.; Khan, Ajmal; Al-Harrasi, Ahmed; Ahmad, Shahbaz

2017-01-01

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. PMID:29204422

A PATO-compliant zebrafish screening database (MODB): management of morpholino knockdown screen information.

PubMed

Knowlton, Michelle N; Li, Tongbin; Ren, Yongliang; Bill, Brent R; Ellis, Lynda Bm; Ekker, Stephen C

2008-01-07

The zebrafish is a powerful model vertebrate amenable to high throughput in vivo genetic analyses. Examples include reverse genetic screens using morpholino knockdown, expression-based screening using enhancer trapping and forward genetic screening using transposon insertional mutagenesis. We have created a database to facilitate web-based distribution of data from such genetic studies. The MOrpholino DataBase is a MySQL relational database with an online, PHP interface. Multiple quality control levels allow differential access to data in raw and finished formats. MODBv1 includes sequence information relating to almost 800 morpholinos and their targets and phenotypic data regarding the dose effect of each morpholino (mortality, toxicity and defects). To improve the searchability of this database, we have incorporated a fixed-vocabulary defect ontology that allows for the organization of morpholino affects based on anatomical structure affected and defect produced. This also allows comparison between species utilizing Phenotypic Attribute Trait Ontology (PATO) designated terminology. MODB is also cross-linked with ZFIN, allowing full searches between the two databases. MODB offers users the ability to retrieve morpholino data by sequence of morpholino or target, name of target, anatomical structure affected and defect produced. MODB data can be used for functional genomic analysis of morpholino design to maximize efficacy and minimize toxicity. MODB also serves as a template for future sequence-based functional genetic screen databases, and it is currently being used as a model for the creation of a mutagenic insertional transposon database.

Lung Cancer Screening May Benefit Those at Highest Risk

Cancer.gov

People at the highest risk for lung cancer, based on a risk model, may be more likely to benefit from screening with low-dose CT, a new analysis suggests. The study authors believe the findings may better define who should undergo lung cancer screening, as this Cancer Currents blog post explains.

Designing a Visual Factors-Based Screen Display Interface: The New Role of the Graphic Technologist.

ERIC Educational Resources Information Center

Faiola, Tony; DeBloois, Michael L.

1988-01-01

Discusses the role of the graphic technologist in preparing computer screen displays for interactive videodisc systems, and suggests screen design guidelines. Topics discussed include the grid system; typography; visual factors research; color; course mobility through branching and software menus; and a model of course integration. (22 references)…

Determinants of individuals' participation in integrated chronic disease screening in Singapore.

PubMed

Venkataraman, Kavita; Wee, Hwee Lin; Ng, Sheryl Hui Xian; Rebello, Salome; Tai, E Shyong; Lee, Jeannette; Tan, Chuen Seng

2016-06-10

A large pool of patients with chronic diseases remains undiagnosed globally and in Singapore. We explored factors associated with participation in a health screening exercise, using revealed preference, that is, actual attendance, to understand why people remain undiagnosed with chronic diseases. A cross-sectional, community-based sample of Singapore residents was invited to participate in home interviews, and subsequently to attend centre-based health screening, between 2004 and 2007. Determinants of health screening participation were identified using logistic regression models based on Andersen's Behavioral Model. Of the 6366 participants who completed health interview, 4092 attended the health screening, while 2274 did not. Older age, Chinese or Indian ethnicity, higher education levels, greater intake of monounsaturated fat, greater transport and leisure-time physical activity were the key predisposing factors associated with greater health screening participation. Greater family cohesion was the key associated enabling factor, while previous diagnosis of dyslipidaemia or musculoskeletal conditions, absence of previously diagnosed diabetes or hypertension and lower perceived physical health were the associated need factors. Our study suggests that ethnicity, education, family cohesion, healthy behaviour patterns and perceived physical health status were key determinants of health screening participation. Enhancing the cultural competence of preventive health services may help increase participation of these groups in screening efforts and reduce the proportions of undiagnosed chronic disease in the community. 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/

Personalized drug discovery: HCA approach optimized for rare diseases at Tel Aviv University.

PubMed

Solmesky, Leonardo J; Weil, Miguel

2014-03-01

The Cell screening facility for personalized medicine (CSFPM) at Tel Aviv University in Israel is devoted to screening small molecules libraries for finding new drugs for rare diseases using human cell based models. The main strategy of the facility is based on smartly reducing the size of the compounds collection in similarity clusters and at the same time keeping high diversity of pharmacophores. This strategy allows parallel screening of several patient derived - cells in a personalized screening approach. The tested compounds are repositioned drugs derived from collections of phase III and FDA approved small molecules. In addition, the facility carries screenings using other chemical libraries and toxicological characterizations of nanomaterials.

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

PubMed

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

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

[Cost effectiveness of mass orthoptic screening in kindergarten for early detection of developmental vision disorders].

PubMed

König, H H; Barry, J C; Leidl, R; Zrenner, E

2000-04-01

Orthoptic screening in the kindergarten is one option to improve early detection of amblyopia in children aged 3 years. The purpose of this study was to analyse the cost-effectiveness of such a screening programme in Germany. Based on data from the literature and own experience gained from orthoptic screening in kindergarten a decision-analytic model was developed. According to the model, all children in kindergarten, aged 3 years, who had not been treated for amblyopia before, were subjected to an orthoptic examination. Non-cooperative children were reexamined in kindergarten after one year. Children with positive test results were examined by an ophthalmologist for diagnosis. Effects were measured by the number of newly diagnosed cases of amblyopia, non-obvious strabismus and amblyogenic refractive errors. Direct costs were estimated from a third-party payer perspective. The influence of uncertain model parameters was tested by sensitivity analysis. In the base analysis the cost per orthoptic screening test was DM 15.39. Examination by an ophthalmologist cost DM 71.20. The total cost of the screening programme in all German kindergartens was DM 6.1 million. With a 1.5% age-specific prevalence of undiagnosed cases, a sensitivity of 95% and a specificity of 98%, a total of 4,261 new cases would be detected. The cost-effectiveness ratio was DM 1,421 per case detected. Sensitivity analysis showed considerable influence of prevalence and specificity on the cost-effectiveness ratio. It was more cost-effective to re-screen non-cooperative children in kindergarten than to have them examined by an ophthalmologist straight-away. The decision-analytic model showed stable results which may serve as a basis for discussion on the implementation of orthoptic screening and for planning a field study.

Study on the millimeter-wave scale absorber based on the Salisbury screen

NASA Astrophysics Data System (ADS)

Yuan, Liming; Dai, Fei; Xu, Yonggang; Zhang, Yuan

2018-03-01

In order to solve the problem on the millimeter-wave scale absorber, the Salisbury screen absorber is employed and designed based on the RL. By optimizing parameters including the sheet resistance of the surface resistive layer, the permittivity and the thickness of the grounded dielectric layer, the RL of the Salisbury screen absorber could be identical with that of the theoretical scale absorber. An example is given to verify the effectiveness of the method, where the Salisbury screen absorber is designed by the proposed method and compared with the theoretical scale absorber. Meanwhile, plate models and tri-corner reflector (TCR) models are constructed according to the designed result and their scattering properties are simulated by FEKO. Results reveal that the deviation between the designed Salisbury screen absorber and the theoretical scale absorber falls within the tolerance of radar Cross section (RCS) measurement. The work in this paper has important theoretical and practical significance in electromagnetic measurement of large scale ratio.

The Use of Economic Evaluation to Inform Newborn Screening Policy Decisions: The Washington State Experience.

PubMed

Grosse, Scott D; Thompson, John D; Ding, Yao; Glass, Michael

2016-06-01

Newborn screening not only saves lives but can also yield net societal economic benefit, in addition to benefits such as improved quality of life to affected individuals and families. Calculations of net economic benefit from newborn screening include the monetary equivalent of avoided deaths and reductions in costs of care for complications associated with late-diagnosed individuals minus the additional costs of screening, diagnosis, and treatment associated with prompt diagnosis. Since 2001 the Washington State Department of Health has successfully implemented an approach to conducting evidence-based economic evaluations of disorders proposed for addition to the state-mandated newborn screening panel. Economic evaluations can inform policy decisions on the expansion of newborn screening panels. This article documents the use of cost-benefit models in Washington State as part of the rule-making process that resulted in the implementation of screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and 4 other metabolic disorders in 2004, cystic fibrosis (CF) in 2006, 15 other metabolic disorders in 2008, and severe combined immune deficiency (SCID) in 2014. We reviewed Washington State Department of Health internal reports and spreadsheet models of expected net societal benefit of adding disorders to the state newborn screening panel. We summarize the assumptions and findings for 2 models (MCAD and CF) and discuss them in relation to findings in the peer-reviewed literature. The MCAD model projected a benefit-cost ratio of 3.4 to 1 based on assumptions of a 20.0 percentage point reduction in infant mortality and a 13.9 percentage point reduction in serious developmental disability. The CF model projected a benefit-cost ratio of 4.0-5.4 to 1 for a discount rate of 3%-4% and a plausible range of 1-2 percentage point reductions in deaths up to age 10 years. The Washington State cost-benefit models of newborn screening were broadly consistent with peer-reviewed literature, and their findings of net benefit appear to be robust to uncertainty in parameters. Public health newborn screening programs can develop their own capacity to project expected costs and benefits of expansion of newborn screening panels, although it would be most efficient if this capacity were shared among programs. © 2016 Milbank Memorial Fund.

The Use of Economic Evaluation to Inform Newborn Screening Policy Decisions: The Washington State Experience

PubMed Central

THOMPSON, JOHN D.; DING, YAO; GLASS, MICHAEL

2016-01-01

Policy Points: Newborn screening not only saves lives but can also yield net societal economic benefit, in addition to benefits such as improved quality of life to affected individuals and families.Calculations of net economic benefit from newborn screening include the monetary equivalent of avoided deaths and reductions in costs of care for complications associated with late‐diagnosed individuals minus the additional costs of screening, diagnosis, and treatment associated with prompt diagnosis.Since 2001 the Washington State Department of Health has successfully implemented an approach to conducting evidence‐based economic evaluations of disorders proposed for addition to the state‐mandated newborn screening panel. Context Economic evaluations can inform policy decisions on the expansion of newborn screening panels. This article documents the use of cost‐benefit models in Washington State as part of the rule‐making process that resulted in the implementation of screening for medium‐chain acyl‐CoA dehydrogenase (MCAD) deficiency and 4 other metabolic disorders in 2004, cystic fibrosis (CF) in 2006, 15 other metabolic disorders in 2008, and severe combined immune deficiency (SCID) in 2014. Methods We reviewed Washington State Department of Health internal reports and spreadsheet models of expected net societal benefit of adding disorders to the state newborn screening panel. We summarize the assumptions and findings for 2 models (MCAD and CF) and discuss them in relation to findings in the peer‐reviewed literature. Findings The MCAD model projected a benefit‐cost ratio of 3.4 to 1 based on assumptions of a 20.0 percentage point reduction in infant mortality and a 13.9 percentage point reduction in serious developmental disability. The CF model projected a benefit‐cost ratio of 4.0‐5.4 to 1 for a discount rate of 3%‐4% and a plausible range of 1‐2 percentage point reductions in deaths up to age 10 years. Conclusions The Washington State cost‐benefit models of newborn screening were broadly consistent with peer‐reviewed literature, and their findings of net benefit appear to be robust to uncertainty in parameters. Public health newborn screening programs can develop their own capacity to project expected costs and benefits of expansion of newborn screening panels, although it would be most efficient if this capacity were shared among programs. PMID:27265561

A Comparison of Parallel and Integrated Models for Implementation of Routine HIV Screening in a Large, Urban Emergency Department.

PubMed

Hankin, Abigail; Freiman, Heather; Copeland, Brittney; Travis, Natasha; Shah, Bijal

2016-01-01

This study compared two approaches for implementation of non-targeted HIV screening in the emergency department (ED): (1) designated HIV counselors screening in parallel with ED care and (2) nurse-based screening integrated into patient triage. A retrospective analysis was performed to compare parallel and integrated screening models using data from the first 12 months of each program. Data for the parallel screening model were extracted from information collected by HIV test counselors and the electronic medical record (EMR). Integrated screening model data were extracted from the EMR and supplemented by data collected by HIV social workers during patient interaction. For both programs, data included demographics, HIV test offer, test acceptance or declination, and test result. A Z-test between two proportions was performed to compare screening frequencies and results. During the first 12 months of parallel screening, approximately 120,000 visits were made to the ED, with 3,816 (3%) HIV tests administered and 65 (2%) new diagnoses of HIV infection. During the first 12 months of integrated screening, 111,738 patients were triaged in the ED, with 16,329 (15%) patients tested and 190 (1%) new diagnoses. Integrated screening resulted in an increased frequency of HIV screening compared with parallel screening (0.15 tests per ED patient visit vs. 0.03 tests per ED patient visit, p<0.001) and an increase in the absolute number of new diagnoses (190 vs. 65), representing a slight decrease in the proportion of new diagnoses (1% vs. 2%, p=0.007). Non-targeted, integrated HIV screening, with test offer and order by ED nurses during patient triage, is feasible and resulted in an increased frequency of HIV screening and a threefold increase in the absolute number of newly identified HIV-positive patients.

Chemical-specific screening criteria for interpretation of biomonitoring data for volatile organic compounds (VOCs)--application of steady-state PBPK model solutions.

PubMed

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 are most appropriately applied to central tendency estimates for such datasets. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Predicting the risk for colorectal cancer with personal characteristics and fecal immunochemical test.

PubMed

Li, Wen; Zhao, Li-Zhong; Ma, Dong-Wang; Wang, De-Zheng; Shi, Lei; Wang, Hong-Lei; Dong, Mo; Zhang, Shu-Yi; Cao, Lei; Zhang, Wei-Hua; Zhang, Xi-Peng; Zhang, Qing-Huai; Yu, Lin; Qin, Hai; Wang, Xi-Mo; Chen, Sam Li-Sheng

2018-05-01

We aimed to predict colorectal cancer (CRC) based on the demographic features and clinical correlates of personal symptoms and signs from Tianjin community-based CRC screening data.A total of 891,199 residents who were aged 60 to 74 and were screened in 2012 were enrolled. The Lasso logistic regression model was used to identify the predictors for CRC. Predictive validity was assessed by the receiver operating characteristic (ROC) curve. Bootstrapping method was also performed to validate this prediction model.CRC was best predicted by a model that included age, sex, education level, occupations, diarrhea, constipation, colon mucosa and bleeding, gallbladder disease, a stressful life event, family history of CRC, and a positive fecal immunochemical test (FIT). The area under curve (AUC) for the questionnaire with a FIT was 84% (95% CI: 82%-86%), followed by 76% (95% CI: 74%-79%) for a FIT alone, and 73% (95% CI: 71%-76%) for the questionnaire alone. With 500 bootstrap replications, the estimated optimism (<0.005) shows good discrimination in validation of prediction model.A risk prediction model for CRC based on a series of symptoms and signs related to enteric diseases in combination with a FIT was developed from first round of screening. The results of the current study are useful for increasing the awareness of high-risk subjects and for individual-risk-guided invitations or strategies to achieve mass screening for CRC.

Does Screen Size Matter for Smartphones? Utilitarian and Hedonic Effects of Screen Size on Smartphone Adoption

PubMed Central

Kim, Ki Joon

2014-01-01

Abstract This study explores the psychological effects of screen size on smartphone adoption by proposing an extended Technology Acceptance Model (TAM) that integrates an empirical comparison between large and small screens with perceived control, affective quality, and the original TAM constructs. A structural equation modeling analysis was conducted on data collected from a between-subjects experiment (N=130) in which users performed a web-based task on a smartphone with either a large (5.3 inches) or a small (3.7 inches) screen. Results show that a large screen, compared to a small screen, is likely to lead to higher smartphone adoption by simultaneously promoting both the utilitarian and hedonic qualities of smartphones, which in turn positively influence perceived ease of use of—and attitude toward—the device respectively. Implications and directions for future research are discussed. PMID:24694112

Does screen size matter for smartphones? Utilitarian and hedonic effects of screen size on smartphone adoption.

PubMed

Kim, Ki Joon; Sundar, S Shyam

2014-07-01

This study explores the psychological effects of screen size on smartphone adoption by proposing an extended Technology Acceptance Model (TAM) that integrates an empirical comparison between large and small screens with perceived control, affective quality, and the original TAM constructs. A structural equation modeling analysis was conducted on data collected from a between-subjects experiment (N=130) in which users performed a web-based task on a smartphone with either a large (5.3 inches) or a small (3.7 inches) screen. Results show that a large screen, compared to a small screen, is likely to lead to higher smartphone adoption by simultaneously promoting both the utilitarian and hedonic qualities of smartphones, which in turn positively influence perceived ease of use of-and attitude toward-the device respectively. Implications and directions for future research are discussed.

The mathematics of a successful deconvolution: a quantitative assessment of mixture-based combinatorial libraries screened against two formylpeptide receptors.

PubMed

Santos, Radleigh G; Appel, Jon R; Giulianotti, Marc A; Edwards, Bruce S; Sklar, Larry A; Houghten, Richard A; Pinilla, Clemencia

2013-05-30

In the past 20 years, synthetic combinatorial methods have fundamentally advanced the ability to synthesize and screen large numbers of compounds for drug discovery and basic research. Mixture-based libraries and positional scanning deconvolution combine two approaches for the rapid identification of specific scaffolds and active ligands. Here we present a quantitative assessment of the screening of 32 positional scanning libraries in the identification of highly specific and selective ligands for two formylpeptide receptors. We also compare and contrast two mixture-based library approaches using a mathematical model to facilitate the selection of active scaffolds and libraries to be pursued for further evaluation. The flexibility demonstrated in the differently formatted mixture-based libraries allows for their screening in a wide range of assays.

Statistical Test for Latent Growth Nonlinearity with Three Time Points. Research Brief 8

ERIC Educational Resources Information Center

Nese, Joseph F. T.

2013-01-01

Curriculum-based measurement (CBM) is a system of assessment used to screen for students at risk for poor learning. CBM benchmark screening assessments are typically administered to all students in the fall, winter, and spring, and these data are frequently used by researchers to model and perhaps explain within-year growth. Modeling growth with…

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

ERIC Educational Resources Information Center

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

2013-01-01

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

Discovery of novel mGluR1 antagonists: a multistep virtual screening approach based on an SVM model and a pharmacophore hypothesis significantly increases the hit rate and enrichment factor.

PubMed

Li, Guo-Bo; Yang, Ling-Ling; Feng, Shan; Zhou, Jian-Ping; Huang, Qi; Xie, Huan-Zhang; Li, Lin-Li; Yang, Sheng-Yong

2011-03-15

Development of glutamate non-competitive antagonists of mGluR1 (Metabotropic glutamate receptor subtype 1) has increasingly attracted much attention in recent years due to their potential therapeutic application for various nervous disorders. Since there is no crystal structure reported for mGluR1, ligand-based virtual screening (VS) methods, typically pharmacophore-based VS (PB-VS), are often used for the discovery of mGluR1 antagonists. Nevertheless, PB-VS usually suffers a lower hit rate and enrichment factor. In this investigation, we established a multistep ligand-based VS approach that is based on a support vector machine (SVM) classification model and a pharmacophore model. Performance evaluation of these methods in virtual screening against a large independent test set, M-MDDR, show that the multistep VS approach significantly increases the hit rate and enrichment factor compared with the individual SB-VS and PB-VS methods. The multistep VS approach was then used to screen several large chemical libraries including PubChem, Specs, and Enamine. Finally a total of 20 compounds were selected from the top ranking compounds, and shifted to the subsequent in vitro and in vivo studies, which results will be reported in the near future. Copyright © 2011 Elsevier Ltd. All rights reserved.

Collective screening tools for early identification of dyslexia

PubMed Central

Andrade, Olga V. C. A.; Andrade, Paulo E.; Capellini, Simone A.

2015-01-01

Current response to intervention models (RTIs) favor a three-tier system. In general, Tier 1 consists of evidence-based, effective reading instruction in the classroom and universal screening of all students at the beginning of the grade level to identify children for early intervention. Non-responders to Tier 1 receive small-group tutoring in Tier 2. Non-responders to Tier 2 are given still more intensive, individual intervention in Tier 3. Limited time, personnel and financial resources derail RTI’s implementation in Brazilian schools because this approach involves procedures that require extra time and extra personnel in all three tiers, including screening tools which normally consist of tasks administered individually. We explored the accuracy of collectively and easily administered screening tools for the early identification of second graders at risk for dyslexia in a two-stage screening model. A first-stage universal screening based on collectively administered curriculum-based measurements was used in 45 7 years old early Portuguese readers from 4 second-grade classrooms at the beginning of the school year and identified an at-risk group of 13 academic low-achievers. Collectively administered tasks based on phonological judgments by matching figures and figures to spoken words [alternative tools for educators (ATE)] and a comprehensive cognitive-linguistic battery of collective and individual assessments were both administered to all children and constituted the second-stage screening. Low-achievement on ATE tasks and on collectively administered writing tasks (scores at the 25th percentile) showed good sensitivity (true positives) and specificity (true negatives) to poor literacy status defined as scores ≤1 SD below the mean on literacy abilities at the end of fifth grade. These results provide implications for the use of a collectively administered screening tool for the early identification of children at risk for dyslexia in a classroom setting. PMID:25667575

Modelling breast cancer tumour growth for a stable disease population.

PubMed

Isheden, Gabriel; Humphreys, Keith

2017-01-01

Statistical models of breast cancer tumour progression have been used to further our knowledge of the natural history of breast cancer, to evaluate mammography screening in terms of mortality, to estimate overdiagnosis, and to estimate the impact of lead-time bias when comparing survival times between screen detected cancers and cancers found outside of screening programs. Multi-state Markov models have been widely used, but several research groups have proposed other modelling frameworks based on specifying an underlying biological continuous tumour growth process. These continuous models offer some advantages over multi-state models and have been used, for example, to quantify screening sensitivity in terms of mammographic density, and to quantify the effect of body size covariates on tumour growth and time to symptomatic detection. As of yet, however, the continuous tumour growth models are not sufficiently developed and require extensive computing to obtain parameter estimates. In this article, we provide a detailed description of the underlying assumptions of the continuous tumour growth model, derive new theoretical results for the model, and show how these results may help the development of this modelling framework. In illustrating the approach, we develop a model for mammography screening sensitivity, using a sample of 1901 post-menopausal women diagnosed with invasive breast cancer.

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

PubMed

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.

ARQiv-HTS, a versatile whole-organism screening platform enabling in vivo drug discovery at high-throughput rates

PubMed Central

White, David T; Eroglu, Arife Unal; Wang, Guohua; Zhang, Liyun; Sengupta, Sumitra; Ding, Ding; Rajpurohit, Surendra K; Walker, Steven L; Ji, Hongkai; Qian, Jiang; Mumm, Jeff S

2017-01-01

The zebrafish has emerged as an important model for whole-organism small-molecule screening. However, most zebrafish-based chemical screens have achieved only mid-throughput rates. Here we describe a versatile whole-organism drug discovery platform that can achieve true high-throughput screening (HTS) capacities. This system combines our automated reporter quantification in vivo (ARQiv) system with customized robotics, and is termed ‘ARQiv-HTS’. We detail the process of establishing and implementing ARQiv-HTS: (i) assay design and optimization, (ii) calculation of sample size and hit criteria, (iii) large-scale egg production, (iv) automated compound titration, (v) dispensing of embryos into microtiter plates, and (vi) reporter quantification. We also outline what we see as best practice strategies for leveraging the power of ARQiv-HTS for zebrafish-based drug discovery, and address technical challenges of applying zebrafish to large-scale chemical screens. Finally, we provide a detailed protocol for a recently completed inaugural ARQiv-HTS effort, which involved the identification of compounds that elevate insulin reporter activity. Compounds that increased the number of insulin-producing pancreatic beta cells represent potential new therapeutics for diabetic patients. For this effort, individual screening sessions took 1 week to conclude, and sessions were performed iteratively approximately every other day to increase throughput. At the conclusion of the screen, more than a half million drug-treated larvae had been evaluated. Beyond this initial example, however, the ARQiv-HTS platform is adaptable to almost any reporter-based assay designed to evaluate the effects of chemical compounds in living small-animal models. ARQiv-HTS thus enables large-scale whole-organism drug discovery for a variety of model species and from numerous disease-oriented perspectives. PMID:27831568

Road screening and distribution route multi-objective robust optimization for hazardous materials based on neural network and genetic algorithm.

PubMed

Ma, Changxi; Hao, Wei; Pan, Fuquan; Xiang, Wang

2018-01-01

Route optimization of hazardous materials transportation is one of the basic steps in ensuring the safety of hazardous materials transportation. The optimization scheme may be a security risk if road screening is not completed before the distribution route is optimized. For road screening issues of hazardous materials transportation, a road screening algorithm of hazardous materials transportation is built based on genetic algorithm and Levenberg-Marquardt neural network (GA-LM-NN) by analyzing 15 attributes data of each road network section. A multi-objective robust optimization model with adjustable robustness is constructed for the hazardous materials transportation problem of single distribution center to minimize transportation risk and time. A multi-objective genetic algorithm is designed to solve the problem according to the characteristics of the model. The algorithm uses an improved strategy to complete the selection operation, applies partial matching cross shift and single ortho swap methods to complete the crossover and mutation operation, and employs an exclusive method to construct Pareto optimal solutions. Studies show that the sets of hazardous materials transportation road can be found quickly through the proposed road screening algorithm based on GA-LM-NN, whereas the distribution route Pareto solutions with different levels of robustness can be found rapidly through the proposed multi-objective robust optimization model and algorithm.

Development and evaluation of nursing user interface screens using multiple methods.

PubMed

Hyun, Sookyung; Johnson, Stephen B; Stetson, Peter D; Bakken, Suzanne

2009-12-01

Building upon the foundation of the Structured Narrative Electronic Health Record (EHR) model, we applied theory-based (combined Technology Acceptance Model and Task-Technology Fit Model) and user-centered methods to explore nurses' perceptions of functional requirements for an electronic nursing documentation system, design user interface screens reflective of the nurses' perspectives, and assess nurses' perceptions of the usability of the prototype user interface screens. The methods resulted in user interface screens that were perceived to be easy to use, potentially useful, and well-matched to nursing documentation tasks associated with Nursing Admission Assessment, Blood Administration, and Nursing Discharge Summary. The methods applied in this research may serve as a guide for others wishing to implement user-centered processes to develop or extend EHR systems. In addition, some of the insights obtained in this study may be informative to the development of safe and efficient user interface screens for nursing document templates in EHRs.

Comparison of Screen Sizes When Using Video Prompting to Teach Adolescents with Autism

ERIC Educational Resources Information Center

Bennett, Kyle D.; Gutierrez, Anibal, Jr.; Loughrey, Tara O.

2016-01-01

Recently, researchers have compared the effectiveness of video-based instruction (VBI), particularly video modeling, when using smaller versus larger screen sizes with positive, but mixed results. Using an adapted alternating treatments design, we compared two different screen sizes (i.e., iPhone 5 versus iPad 2) using video prompting as the VBI…

Fragment-based lead generation: identification of seed fragments by a highly efficient fragment screening technology

NASA Astrophysics Data System (ADS)

Neumann, Lars; Ritscher, Allegra; Müller, Gerhard; Hafenbradl, Doris

2009-08-01

For the detection of the precise and unambiguous binding of fragments to a specific binding site on the target protein, we have developed a novel reporter displacement binding assay technology. The application of this technology for the fragment screening as well as the fragment evolution process with a specific modelling based design strategy is demonstrated for inhibitors of the protein kinase p38alpha. In a fragment screening approach seed fragments were identified which were then used to build compounds from the deep-pocket towards the hinge binding area of the protein kinase p38alpha based on a modelling approach. BIRB796 was used as a blueprint for the alignment of the fragments. The fragment evolution of these deep-pocket binding fragments towards the fully optimized inhibitor BIRB796 included the modulation of the residence time as well as the affinity. The goal of our study was to evaluate the robustness and efficiency of our novel fragment screening technology at high fragment concentrations, compare the screening data with biochemical activity data and to demonstrate the evolution of the hit fragments with fast kinetics, into slow kinetic inhibitors in an in silico approach.

Cost-effectiveness of HPV vaccination in the context of high cervical cancer incidence and low screening coverage.

PubMed

Võrno, Triin; Lutsar, Katrin; Uusküla, Anneli; Padrik, Lee; Raud, Terje; Reile, Rainer; Nahkur, Oliver; Kiivet, Raul-Allan

2017-11-01

Estonia has high cervical cancer incidence and low screening coverage. We modelled the impact of population-based bivalent, quadrivalent or nonavalent HPV vaccination alongside cervical cancer screening. A Markov cohort model of the natural history of HPV infection was used to assess the cost-effectiveness of vaccinating a cohort of 12-year-old girls with bivalent, quadrivalent or nonavalent vaccine in two doses in a national, school-based vaccination programme. The model followed the natural progression of HPV infection into subsequent genital warts (GW); premalignant lesions (CIN1-3); cervical, oropharyngeal, vulvar, vaginal and anal cancer. Vaccine coverage was assumed to be 70%. A time horizon of 88years (up to 100years of age) was used to capture all lifetime vaccination costs and benefits. Costs and utilities were discounted using an annual discount rate of 5%. Vaccination of 12-year-old girls alongside screening compared to screening alone had an incremental cost-effectiveness ratio (ICER) of €14,007 (bivalent), €14,067 (quadrivalent) and €11,633 (nonavalent) per quality-adjusted life-year (QALY) in the base-case scenario and ranged between €5367-21,711, €5142-21,800 and €4563-18,142, respectively, in sensitivity analysis. The results were most sensitive to changes in discount rate, vaccination regimen, vaccine prices and cervical cancer screening coverage. Vaccination of 12-year-old girls alongside current cervical cancer screening can be considered a cost-effective intervention in Estonia. Adding HPV vaccination to the national immunisation schedule is expected to prevent a considerable number of HPV infections, genital warts, premalignant lesions, HPV related cancers and deaths. Although in our model ICERs varied slightly depending on the vaccine used, they generally fell within the same range. Cost-effectiveness of HPV vaccination was found to be most dependent on vaccine cost and duration of vaccine immunity, but not on the type of vaccine used. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of a community cancer education program: the Forsyth County, NC cervical cancer prevention project.

PubMed

Michielutte, R; Dignan, M B; Wells, H B; Young, L D; Jackson, D S; Sharp, P C

1989-01-01

The authors outline the development and implementation of a public health education program for cervical cancer screening among black women in Forsyth County, NC. The educational program includes distributing electronic and printed information media messages, a program of direct education for women, and providing information on current issues in cervical screening to primary-care physicians. Program development was based on social marketing principles, the PRECEDE model, and the communication-behavior change (CBC) model. Since a true experimental design was not feasible, program evaluation is based on several complementary quasi-experimental designs. Analysis of baseline data indicate that the county where the intervention is taking place, and the control county, are similar with respect to both demographic characteristics and the current level of screening activity. Preliminary results indicate that the program has been successful in raising women's level of awareness of cervical cancer and cervical screening.

Cost-utility analysis of screening for diabetic retinopathy in Japan: a probabilistic Markov modeling study.

PubMed

Kawasaki, Ryo; Akune, Yoko; Hiratsuka, Yoshimune; Fukuhara, Shunichi; Yamada, Masakazu

2015-02-01

To evaluate the cost-effectiveness for a screening interval longer than 1 year detecting diabetic retinopathy (DR) through the estimation of incremental costs per quality-adjusted life year (QALY) based on the best available clinical data in Japan. A Markov model with a probabilistic cohort analysis was framed to calculate incremental costs per QALY gained by implementing a screening program detecting DR in Japan. A 1-year cycle length and population size of 50,000 with a 50-year time horizon (age 40-90 years) was used. Best available clinical data from publications and national surveillance data was used, and a model was designed including current diagnosis and management of DR with corresponding visual outcomes. One-way and probabilistic sensitivity analyses were performed considering uncertainties in the parameters. In the base-case analysis, the strategy with a screening program resulted in an incremental cost of 5,147 Japanese yen (¥; US$64.6) and incremental effectiveness of 0.0054 QALYs per person screened. The incremental cost-effectiveness ratio was ¥944,981 (US$11,857) per QALY. The simulation suggested that screening would result in a significant reduction in blindness in people aged 40 years or over (-16%). Sensitivity analyses suggested that in order to achieve both reductions in blindness and cost-effectiveness in Japan, the screening program should screen those aged 53-84 years, at intervals of 3 years or less. An eye screening program in Japan would be cost-effective in detecting DR and preventing blindness from DR, even allowing for the uncertainties in estimates of costs, utility, and current management of DR.

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

PubMed Central

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

Quantitative structure-activity relationship analysis and virtual screening studies for identifying HDAC2 inhibitors from known HDAC bioactive chemical libraries.

PubMed

Pham-The, H; Casañola-Martin, G; Diéguez-Santana, K; Nguyen-Hai, N; Ngoc, N T; Vu-Duc, L; Le-Thi-Thu, H

2017-03-01

Histone deacetylases (HDAC) are emerging as promising targets in cancer, neuronal diseases and immune disorders. Computational modelling approaches have been widely applied for the virtual screening and rational design of novel HDAC inhibitors. In this study, different machine learning (ML) techniques were applied for the development of models that accurately discriminate HDAC2 inhibitors form non-inhibitors. The obtained models showed encouraging results, with the global accuracy in the external set ranging from 0.83 to 0.90. Various aspects related to the comparison of modelling techniques, applicability domain and descriptor interpretations were discussed. Finally, consensus predictions of these models were used for screening HDAC2 inhibitors from four chemical libraries whose bioactivities against HDAC1, HDAC3, HDAC6 and HDAC8 have been known. According to the results of virtual screening assays, structures of some hits with pair-isoform-selective activity (between HDAC2 and other HDACs) were revealed. This study illustrates the power of ML-based QSAR approaches for the screening and discovery of potent, isoform-selective HDACIs.

Hierarchical virtual screening of the dual MMP-2/HDAC-6 inhibitors from natural products based on pharmacophore models and molecular docking.

PubMed

Wang, Yijun; Yang, Limei; Hou, Jiaying; Zou, Qing; Gao, Qi; Yao, Wenhui; Yao, Qizheng; Zhang, Ji

2018-02-12

The dual-target inhibitors tend to improve the response rate in treating tumors, comparing with the single-target inhibitors. Matrix metalloproteinase-2 (MMP-2) and histone deacetylase-6 (HDAC-6) are attractive targets for cancer therapy. In this study, the hierarchical virtual screening of dual MMP-2/HDAC-6 inhibitors from natural products is investigated. The pharmacophore model of MMP-2 inhibitors is built based on ligands, but the pharmacophore model of HDAC-6 inhibitors is built based on the experimental crystal structures of multiple receptor-ligand complexes. The reliability of these two pharmacophore models is validated subsequently. The hierarchical virtual screening, combining these two different pharmacophore models of MMP-2 and HDAC-6 inhibitors with molecular docking, is carried out to identify the dual MMP-2/HDAC-6 inhibitors from a database of natural products. The four potential dual MMP-2/HDAC-6 inhibitors of natural products, STOCK1 N-46177, STOCK1 N-52245, STOCK1 N-55477, and STOCK1 N-69706, are found. The studies of binding modes show that the screened four natural products can simultaneously well bind with the MMP-2 and HDAC-6 active sites by different kinds of interactions, to inhibit the MMP-2 and HDAC-6 activities. In addition, the ADMET properties of screened four natural products are assessed. These found dual MMP-2/HDAC-6 inhibitors of natural products could serve as the lead compounds for designing the new dual MMP-2/HDAC-6 inhibitors having higher biological activities by carrying out structural modifications and optimizations in the future studies.

Multiple receptor-ligand based pharmacophore modeling and molecular docking to screen the selective inhibitors of matrix metalloproteinase-9 from natural products.

PubMed

Gao, Qi; Wang, Yijun; Hou, Jiaying; Yao, Qizheng; Zhang, Ji

2017-07-01

Matrix metalloproteinase-9 (MMP-9) is an attractive target for cancer therapy. In this study, the pharmacophore model of MMP-9 inhibitors is built based on the experimental binding structures of multiple receptor-ligand complexes. It is found that the pharmacophore model consists of six chemical features, including two hydrogen bond acceptors, one hydrogen bond donor, one ring aromatic regions, and two hydrophobic (HY) features. Among them, the two HY features are especially important because they can enter the S1' pocket of MMP-9 which determines the selectivity of MMP-9 inhibitors. The reliability of pharmacophore model is validated based on the two different decoy sets and relevant experimental data. The virtual screening, combining pharmacophore model with molecular docking, is performed to identify the selective MMP-9 inhibitors from a database of natural products. The four novel MMP-9 inhibitors of natural products, NP-000686, NP-001752, NP-014331, and NP-015905, are found; one of them, NP-000686, is used to perform the experiment of in vitro bioassay inhibiting MMP-9, and the IC 50 value was estimated to be only 13.4 µM, showing the strongly inhibitory activity of NP-000686 against MMP-9, which suggests that our screening results should be reliable. The binding modes of screened inhibitors with MMP-9 active sites were discussed. In addition, the ADMET properties and physicochemical properties of screened four compounds were assessed. The found MMP-9 inhibitors of natural products could serve as the lead compounds for designing the new MMP-9 inhibitors by carrying out structural modifications in the future.

Estimating the harms and benefits of prostate cancer screening as used in common practice versus recommended good practice: A microsimulation screening analysis.

PubMed

Carlsson, Sigrid V; de Carvalho, Tiago M; Roobol, Monique J; Hugosson, Jonas; Auvinen, Anssi; Kwiatkowski, Maciej; Villers, Arnauld; Zappa, Marco; Nelen, Vera; Páez, Alvaro; Eastham, James A; Lilja, Hans; de Koning, Harry J; Vickers, Andrew J; Heijnsdijk, Eveline A M

2016-11-15

Prostate-specific antigen (PSA) screening and concomitant treatment can be implemented in several ways. The authors investigated how the net benefit of PSA screening varies between common practice versus "good practice." Microsimulation screening analysis (MISCAN) was used to evaluate the effect on quality-adjusted life-years (QALYs) if 4 recommendations were followed: limited screening in older men, selective biopsy in men with elevated PSA, active surveillance for low-risk tumors, and treatment preferentially delivered at high-volume centers. Outcomes were compared with a base model in which annual screening started at ages 55 to 69 years and were simulated using data from the European Randomized Study of Screening for Prostate Cancer. In terms of QALYs gained compared with no screening, for 1000 screened men who were followed over their lifetime, recommended good practice led to 73 life-years (LYs) and 74 QALYs gained compared with 73 LYs and 56 QALYs for the base model. In contrast, common practice led to 78 LYs gained but only 19 QALYs gained, for a greater than 75% relative reduction in QALYs gained from unadjusted LYs gained. The poor outcomes for common practice were influenced predominantly by the use of aggressive treatment for men with low-risk disease, and PSA testing in older men also strongly reduced potential QALY gains. Commonly used PSA screening and treatment practices are associated with little net benefit. Following a few straightforward clinical recommendations, particularly greater use of active surveillance for low-risk disease and reducing screening in older men, would lead to an almost 4-fold increase in the net benefit of prostate cancer screening. Cancer 2016;122:3386-3393. © 2016 American Cancer Society. © 2016 American Cancer Society.

Chlamydia screening is not cost-effective at low participation rates: evidence from a repeated register-based implementation study in The Netherlands.

PubMed

de Wit, G Ardine; Over, Eelco A B; Schmid, Boris V; van Bergen, Jan E A M; van den Broek, Ingrid V F; van der Sande, Marianne A B; Welte, Robert; Op de Coul, Eline L M; Kretzschmar, Mirjam E

2015-09-01

In three pilot regions of The Netherlands, all 16-29 year olds were invited to participate in three annual rounds of Chlamydia screening. The aim of the present study is to evaluate the cost-effectiveness of repeated Chlamydia screening, based on empirical data. A mathematical model was employed to estimate the influence of repeated screening on prevalence and incidence of Chlamydial infection. A model simulating the natural history of Chlamydia was combined with cost and utility data to estimate the number of major outcomes and quality-adjusted life-years (QALYs) associated with Chlamydia. Six screening scenarios (16-29 years annually; 16-24 years annually; women only; biennial screening; biennial screening women only; screening every five years) were compared with no screening in two sexual networks, representing both lower ('national network') and higher ('urban network') baseline prevalence. Incremental cost-effectiveness ratios (ICERs) for the different screening scenarios were estimated. Uncertainty and sensitivity analyses were performed. In all scenarios and networks, cost per major outcome averted are above €5000. Cost per QALY are at least €50,000. The default scenario as piloted in the Netherlands was least cost-effective, with ICERs of €232,000 in the national and €145,000 in the urban sexual network. Results were robust in sensitivity analyses. It is unlikely that repeated rounds of Chlamydia screening will be cost-effective. Only at high levels of willingness to pay for a QALY (>€50,000) screening may be more cost-effective than no screening. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Fishing anti(lymph)angiogenic drugs with zebrafish.

PubMed

García-Caballero, Melissa; Quesada, Ana R; Medina, Miguel A; Marí-Beffa, Manuel

2018-02-01

Zebrafish, an amenable small teleost fish with a complex mammal-like circulatory system, is being increasingly used for drug screening and toxicity studies. It combines the biological complexity of in vivo models with a higher-throughput screening capability compared with other available animal models. Externally growing, transparent embryos, displaying well-defined blood and lymphatic vessels, allow the inexpensive, rapid, and automatable evaluation of drug candidates that are able to inhibit neovascularisation. Here, we briefly review zebrafish as a model for the screening of anti(lymph)angiogenic drugs, with emphasis on the advantages and limitations of the different zebrafish-based in vivo assays. Copyright © 2017 Elsevier Ltd. All rights reserved.

Creep fatigue life prediction for engine hot section materials (ISOTROPIC)

NASA Technical Reports Server (NTRS)

Nelson, R. S.; Schoendorf, J. F.; Lin, L. S.

1986-01-01

The specific activities summarized include: verification experiments (base program); thermomechanical cycling model; multiaxial stress state model; cumulative loading model; screening of potential environmental and protective coating models; and environmental attack model.

Lung Cancer Risk Models for Screening (R package: lcrisks)

Cancer.gov

In both the absence and presence of screening, the R package lcrisks, calculates individual risks of lung cancer and lung cancer death based on covariates: age, education, sex, race, smoking intensity/duration/quit-years, Body Mass Index, family history of lung-cancer, and self-reported emphysema. In the presence of CT screening akin to the NLST (3 yearly screens, 5 years of follow-up), it uses the covariates to estimate risk of false-positive CT screen as well as the reduction in risk of lung cancer death and increase in risk of lung cancer screening.

Introducing a Model for Optimal Design of Sequential Objective Structured Clinical Examinations

ERIC Educational Resources Information Center

Mortaz Hejri, Sara; Yazdani, Kamran; Labaf, Ali; Norcini, John J.; Jalili, Mohammad

2016-01-01

In a sequential OSCE which has been suggested to reduce testing costs, candidates take a short screening test and who fail the test, are asked to take the full OSCE. In order to introduce an effective and accurate sequential design, we developed a model for designing and evaluating screening OSCEs. Based on two datasets from a 10-station…

Putting newborn hearing screening on the political agenda in Belgium: local initiatives toward a community programme - a qualitative study.

PubMed

Vos, Bénédicte; Lagasse, Raphaël; Levêque, Alain

2014-07-01

The Kingdon model, based on the convergence of three streams (problem, policy, and politics) and the opening of a policy window, analyses the process by which a health issue is placed on the political agenda. We used this model to document the political agenda-setting process of the newborn hearing screening programme in Belgium. A qualitative study based on a document review and on semi-directed interviews was carried out. The interviews were conducted with nine people who had played a role in putting the issue in question on the political agenda, and the documents reviewed included scientific literature and internal reports and publications from the newborn hearing screening programme. The thematic analysis of the data collected was carried out on the basis of the Kingdon model's three streams. The political agenda-setting of this screening programme was based on many factors. The problem stream included factors external to the context under study, such as the technological developments and the contribution of the scientific literature which led to the recommendation to provide newborn hearing screening. The two other streams (policy and politics) covered factors internal to the Belgian context. The fact that it was locally feasible with financial support, the network of doctors convinced of the need for newborn hearing screening, the drafting of various proposals, and the search for financing were all part of the policy stream. The Belgian political context and the policy opportunities concerning preventive medicine were identified as significant factors in the third stream. When these three streams converged, a policy window opened, allowing newborn hearing screening onto the political agenda and enabling the policy decision for its introduction. The advantage of applying the Kingdon model in our approach was the ability to demonstrate the political agenda-setting process, using the three streams. This made it possible to identify the many factors involved in the process. However, the roles of the stakeholders and of the context were somewhat inexplicit in this model.

Adaptive Gaussian mixture models for pre-screening in GPR data

NASA Astrophysics Data System (ADS)

Torrione, Peter; Morton, Kenneth, Jr.; Besaw, Lance E.

2011-06-01

Due to the large amount of data generated by vehicle-mounted ground penetrating radar (GPR) antennae arrays, advanced feature extraction and classification can only be performed on a small subset of data during real-time operation. As a result, most GPR based landmine detection systems implement "pre-screening" algorithms to processes all of the data generated by the antennae array and identify locations with anomalous signatures for more advanced processing. These pre-screening algorithms must be computationally efficient and obtain high probability of detection, but can permit a false alarm rate which might be higher than the total system requirements. Many approaches to prescreening have previously been proposed, including linear prediction coefficients, the LMS algorithm, and CFAR-based approaches. Similar pre-screening techniques have also been developed in the field of video processing to identify anomalous behavior or anomalous objects. One such algorithm, an online k-means approximation to an adaptive Gaussian mixture model (GMM), is particularly well-suited to application for pre-screening in GPR data due to its computational efficiency, non-linear nature, and relevance of the logic underlying the algorithm to GPR processing. In this work we explore the application of an adaptive GMM-based approach for anomaly detection from the video processing literature to pre-screening in GPR data. Results with the ARA Nemesis landmine detection system demonstrate significant pre-screening performance improvements compared to alternative approaches, and indicate that the proposed algorithm is a complimentary technique to existing methods.

Integrating Oral and General Health Screening at Senior Centers for Minority Elders

PubMed Central

Cheng, Bin; Northridge, Mary E.; Kunzel, Carol; Huang, Catherine; Lamster, Ira B.

2013-01-01

Racial/ethnic and socioeconomic disparities regarding untreated oral disease exist for older adults, and poor oral health diminishes quality of life. The ElderSmile program integrated screening for diabetes and hypertension into its community-based oral health activities at senior centers in northern Manhattan. The program found a willingness among minority seniors (aged ≥ 50 years) to be screened for primary care sensitive conditions by dental professionals and a high level of unrecognized disease (7.8% and 24.6% of ElderSmile participants had positive screening results for previously undiagnosed diabetes and hypertension, respectively). Dental professionals may screen for primary care–sensitive conditions and refer patients to health care providers for definitive diagnosis and treatment. The ElderSmile program is a replicable model for community-based oral and general health screening. PMID:23597378

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

PubMed

John, D; Parikh, R

2018-02-01

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

Whole Organism High-Content Screening by Label-Free, Image-Based Bayesian Classification for Parasitic Diseases

PubMed Central

Paveley, Ross A.; Mansour, Nuha R.; Hallyburton, Irene; Bleicher, Leo S.; Benn, Alex E.; Mikic, Ivana; Guidi, Alessandra; Gilbert, Ian H.; Hopkins, Andrew L.; Bickle, Quentin D.

2012-01-01

Sole reliance on one drug, Praziquantel, for treatment and control of schistosomiasis raises concerns about development of widespread resistance, prompting renewed interest in the discovery of new anthelmintics. To discover new leads we designed an automated label-free, high content-based, high throughput screen (HTS) to assess drug-induced effects on in vitro cultured larvae (schistosomula) using bright-field imaging. Automatic image analysis and Bayesian prediction models define morphological damage, hit/non-hit prediction and larval phenotype characterization. Motility was also assessed from time-lapse images. In screening a 10,041 compound library the HTS correctly detected 99.8% of the hits scored visually. A proportion of these larval hits were also active in an adult worm ex-vivo screen and are the subject of ongoing studies. The method allows, for the first time, screening of large compound collections against schistosomes and the methods are adaptable to other whole organism and cell-based screening by morphology and motility phenotyping. PMID:22860151

Research on target information optics communications transmission characteristic and performance in multi-screens testing system

NASA Astrophysics Data System (ADS)

Li, Hanshan

2016-04-01

To enhance the stability and reliability of multi-screens testing system, this paper studies multi-screens target optical information transmission link properties and performance in long-distance, sets up the discrete multi-tone modulation transmission model based on geometric model of laser multi-screens testing system and visible light information communication principle; analyzes the electro-optic and photoelectric conversion function of sender and receiver in target optical information communication system; researches target information transmission performance and transfer function of the generalized visible-light communication channel; found optical information communication transmission link light intensity space distribution model and distribution function; derives the SNR model of information transmission communication system. Through the calculation and experiment analysis, the results show that the transmission error rate increases with the increment of transmission rate in a certain channel modulation depth; when selecting the appropriate transmission rate, the bit error rate reach 0.01.

The Mathematics of a Successful Deconvolution: A Quantitative Assessment of Mixture-Based Combinatorial Libraries Screened Against Two Formylpeptide Receptors

PubMed Central

Santos, Radleigh G.; Appel, Jon R.; Giulianotti, Marc A.; Edwards, Bruce S.; Sklar, Larry A.; Houghten, Richard A.; Pinilla, Clemencia

2014-01-01

In the past 20 years, synthetic combinatorial methods have fundamentally advanced the ability to synthesize and screen large numbers of compounds for drug discovery and basic research. Mixture-based libraries and positional scanning deconvolution combine two approaches for the rapid identification of specific scaffolds and active ligands. Here we present a quantitative assessment of the screening of 32 positional scanning libraries in the identification of highly specific and selective ligands for two formylpeptide receptors. We also compare and contrast two mixture-based library approaches using a mathematical model to facilitate the selection of active scaffolds and libraries to be pursued for further evaluation. The flexibility demonstrated in the differently formatted mixture-based libraries allows for their screening in a wide range of assays. PMID:23722730

Raman spectroscopy-based screening of hepatitis C and associated molecular changes

NASA Astrophysics Data System (ADS)

Bilal, Maria; Bilal, M.; Saleem, M.; Khan, Saranjam; Ullah, Rahat; Fatima, Kiran; Ahmed, M.; Hayat, Abbas; Shahzada, Shaista; Ullah Khan, Ehsan

2017-09-01

This study presents the optical screening of hepatitis C and its associated molecular changes in human blood sera using a partial least-squares regression model based on their Raman spectra. In total, 152 samples were tested through enzyme-linked immunosorbent assay for confirmation. This model utilizes minor spectral variations in the Raman spectra of the positive and control groups. Regression coefficients of this model were analyzed with reference to the variations in concentration of associated molecules in these two groups. It was found that trehalose, chitin, ammonia, and cytokines are positively correlated while lipids, beta structures of proteins, and carbohydrate-binding proteins are negatively correlated with hepatitis C. The regression vector yielded by this model is utilized to predict hepatitis C in unknown samples. This model has been evaluated by a cross-validation method, which yielded a correlation coefficient of 0.91. Moreover, 30 unknown samples were screened for hepatitis C infection using this model to test its performance. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve from these predictions were found to be 93.3%, 100%, 96.7%, and 1, respectively.

Modeling Test and Treatment Strategies for Presymptomatic Alzheimer Disease

PubMed Central

Burke, James F.; Langa, Kenneth M.; Hayward, Rodney A.; Albin, Roger L.

2014-01-01

Objectives In this study, we developed a model of presymptomatic treatment of Alzheimer disease (AD) after a screening diagnostic evaluation and explored the circumstances required for an AD prevention treatment to produce aggregate net population benefit. Methods Monte Carlo simulation methods were used to estimate outcomes in a simulated population derived from data on AD incidence and mortality. A wide variety of treatment parameters were explored. Net population benefit was estimated in aggregated QALYs. Sensitivity analyses were performed by individually varying the primary parameters. Findings In the base-case scenario, treatment effects were uniformly positive, and net benefits increased with increasing age at screening. A highly efficacious treatment (i.e. relative risk 0.6) modeled in the base-case is estimated to save 20 QALYs per 1000 patients screened and 221 QALYs per 1000 patients treated. Conclusions Highly efficacious presymptomatic screen and treat strategies for AD are likely to produce substantial aggregate population benefits that are likely greater than the benefits of aspirin in primary prevention of moderate risk cardiovascular disease (28 QALYS per 1000 patients treated), even in the context of an imperfect treatment delivery environment. PMID:25474698

Cardiovascular Disease Screening By Community Health Workers Can Be Cost-Effective In Low-Resource Countries

PubMed Central

Gaziano, Thomas; Abrahams-Gessel, Shafika; Surka, Sam; Sy, Stephen; Pandya, Ankur; Denman, Catalina A.; Mendoza, Carlos; Puoane, Thandi; Levitt, Naomi S.

2016-01-01

In low-resource settings, a physician is not always available. We recently demonstrated that community health workers—instead of physicians or nurses—can efficiently screen adults for cardiovascular disease in South Africa, Mexico, and Guatemala. In this analysis we sought to determine the health and economic impacts of shifting this screening to community health workers equipped with either a paper-based or a mobile phone–based screening tool. We found that screening by community health workers was very cost-effective or even cost-saving in all three countries, compared to the usual clinic-based screening. The mobile application emerged as the most cost-effective strategy because it could save more lives than the paper tool at minimal extra cost. Our modeling indicated that screening by community health workers, combined with improved treatment rates, would increase the number of deaths averted from 15,000 to 110,000, compared to standard care. Policy makers should promote greater acceptance of community health workers by both national populations and health professionals and should increase their commitment to treating cardiovascular disease and making medications available. PMID:26355056

Accuracy and Cost-Effectiveness of Cervical Cancer Screening by High-Risk HPV DNA Testing of Self-Collected Vaginal Samples

PubMed Central

Balasubramanian, Akhila; Kulasingam, Shalini L.; Baer, Atar; Hughes, James P.; Myers, Evan R.; Mao, Constance; Kiviat, Nancy B.; Koutsky, Laura A.

2010-01-01

Objective Estimate the accuracy and cost-effectiveness of cervical cancer screening strategies based on high-risk HPV DNA testing of self-collected vaginal samples. Materials and Methods A subset of 1,665 women (18-50 years of age) participating in a cervical cancer screening study were screened by liquid-based cytology and by high-risk HPV DNA testing of both self-collected vaginal swab samples and clinician-collected cervical samples. Women with positive/abnormal screening test results and a subset of women with negative screening test results were triaged to colposcopy. Based on individual and combined test results, five screening strategies were defined. Estimates of sensitivity and specificity for cervical intraepithelial neoplasia grade 2 or worse were calculated and a Markov model was used to estimate the incremental cost-effectiveness ratios (ICERs) for each strategy. Results Compared to cytology-based screening, high-risk HPV DNA testing of self-collected vaginal samples was more sensitive (68%, 95%CI=58%-78% versus 85%, 95%CI=76%-94%) but less specific (89%, 95%CI=86%-91% versus 73%, 95%CI=67%-79%). A strategy of high-risk HPV DNA testing of self-collected vaginal samples followed by cytology triage of HPV positive women, was comparably sensitive (75%, 95%CI=64%-86%) and specific (88%, 95%CI=85%-92%) to cytology-based screening. In-home self-collection for high-risk HPV DNA detection followed by in-clinic cytology triage had a slightly lower lifetime cost and a slightly higher quality-adjusted life expectancy than did cytology-based screening (ICER of triennial screening compared to no screening was $9,871/QALY and $12,878/QALY, respectively). Conclusions Triennial screening by high-risk HPV DNA testing of in-home, self-collected vaginal samples followed by in-clinic cytology triage was cost-effective. PMID:20592553

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

PubMed

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.

The potential of imaging techniques as a screening tool for colorectal cancer: a cost-effectiveness analysis.

PubMed

Greuter, Marjolein J E; Berkhof, Johannes; Fijneman, Remond J A; Demirel, Erhan; Lew, Jie-Bin; Meijer, Gerrit A; Stoker, Jaap; Coupé, Veerle M H

2016-07-01

Imaging may be promising for colorectal cancer (CRC) screening, since it has test characteristics comparable with colonoscopy but is less invasive. We aimed to assess the potential of CT colonography (CTC) and MR colonography (MRC) in terms of (cost-effectiveness) using the Adenoma and Serrated pathway to Colorectal CAncer model. We compared several CTC and MRC strategies with 5- or 10-yearly screening intervals with no screening, 10-yearly colonoscopy screening and biennial faecal immunochemical test (FIT) screening. We assumed trial-based participation rates in the base-case analyses and varied the rates in sensitivity analyses. Incremental lifetime costs and health effects were estimated from a healthcare perspective. The health gain of CTC and MRC was similar and ranged from 0.031 to 0.048 life-year gained compared with no screening, for 2-5 screening rounds. Lifetime costs per person for MRC strategies were €60-110 higher than those for CTC strategies with an equal number of screening rounds. All imaging-based strategies were cost-effective compared with no screening. FIT screening was the dominant screening strategy, leading to most LYG and highest cost-savings. Compared with three rounds of colonoscopy screening, CTC with five rounds was found to be cost-effective in an incremental analysis of imaging strategies. Assumptions on screening participation have a major influence on the ordering of strategies in terms of costs and effects. CTC and MRC have potential for CRC screening, compared with no screening and compared with three rounds of 10-yearly colonoscopy screening. When taking FIT screening as the reference, imaging is not cost-effective. Participation is an important driver of effectiveness and cost estimates. This is the first study to assess the cost-effectiveness of MRC screening for CRC.

Carbon monoxide screen for signalized intersections : COSIM, version 4.0 - technical documentation.

DOT National Transportation Integrated Search

2013-06-01

Illinois Carbon Monoxide Screen for Intersection Modeling (COSIM) Version 3.0 is a Windows-based computer : program currently used by the Illinois Department of Transportation (IDOT) to estimate worst-case carbon : monoxide (CO) concentrations near s...

Social-cognitive predictors of low-income parents' restriction of screen time among preschool-aged children.

PubMed

Lampard, Amy M; Jurkowski, Janine M; Davison, Kirsten K

2013-10-01

Parents' rules regarding child television, DVD, video game, and computer use (screen time) have been associated with lower screen use in children. This study aimed to identify modifiable correlates of this behavior by examining social-cognitive predictors of parents' restriction of child screen time. Low-income parents (N = 147) of preschool-aged children (2-6 years) completed self-administered questionnaires examining parent and child screen time, parent restriction of screen time, self-efficacy to restrict screen time, and beliefs about screen time. Structural equation modeling results indicated that greater self-efficacy to restrict screen time (β = .29, p = .016) and greater perceived importance of restricting child screen use (β = .55, p < .001) were associated with greater restriction of child screen use, after controlling for parent screen time. Family-based interventions that consider broader attitudinal factors around child screen time may be necessary to engage parents in restricting screen use.

Cancer literacy as a mediator for cancer screening behaviour in Korean adults.

PubMed

Lee, Hee Yun; Rhee, Taeho Greg; Kim, Nam Keol

2016-09-01

This study investigates the cancer literacy level in Korean adults and examines whether cancer literacy plays a mediating role in the relationship between population characteristics and cancer screening behaviours. We collected data from 585 community-dwelling adults in Korea using self-administered surveys and face-to-face interviews from October to December in 2009. Guided by Andersen's behavioural model, we used a structural equation model to estimate the effect of cancer literacy as a mediator and found that cancer literacy mediated cancer screening behaviour. In the individual path analysis models, cancer literacy played a significant mediating role for the use of eastern medicine, fatalism, health status and the number of chronic diseases. When controlling for other relevant covariates, we found that in the optimal path model, cancer literacy played a mediating role in the relationship between the use of eastern medicine and self-rated health status as well as cancer screening behaviour. Thus, developing community-based cancer education programmes and training clinical practitioners in eastern medicine clinics about the importance of informing their patients about regular cancer screening may be an option to boost cancer literacy and screening behaviour in Korea. © 2015 John Wiley & Sons Ltd.

Effectiveness of a theory-based intervention to increase colorectal cancer screening among Iranian health club members: a randomized trial.

PubMed

Salimzadeh, Hamideh; Eftekhar, Hassan; Majdzadeh, Reza; Montazeri, Ali; Delavari, Alireza

2014-10-01

Colorectal cancer is the third most commonly diagnosed cancer and the fourth leading cause of death in the world. There are few published studies that have used theory-based interventions designed to increase colorectal cancer screening in community lay health organizations. The present study was guided by the theoretical concepts of the preventive health model. Twelve health clubs of a municipal district in Tehran were randomized to two study groups with equal ratio. The control group received usual services throughout the study while the intervention group also received a theory-based educational program on colorectal cancer screening plus a reminder call. Screening behavior, the main outcome, was assessed 4 months after randomization. A total of 360 members aged 50 and older from 12 health clubs completed a baseline survey. Participants in the intervention group reported increased knowledge of colorectal cancer and screening tests at 4 months follow-up (p's < .001). Moreover, exposure to the theory-based intervention significantly improved self-efficacy, perceived susceptibility, efficacy of screening, social support, and intention to be screened for colorectal cancer, from baseline to 4 months follow-up (p's < .001). The screening rate for colorectal cancer was significantly higher in the intervention group compared to the control group (odds ratio = 15.93, 95% CI = 5.57, 45.53). Our theory-based intervention was found to have a significant effect on colorectal cancer screening use as measured by self-report. The findings could have implications for colorectal cancer screening program development and implementation in primary health care settings and through other community organizations.

Patient-completed or symptom-based screening tools for endometriosis: a scoping review.

PubMed

Surrey, Eric; Carter, Cathryn M; Soliman, Ahmed M; Khan, Shahnaz; DiBenedetti, Dana B; Snabes, Michael C

2017-08-01

The objective of this review was to evaluate existing patient-completed screening questionnaires and/or symptom-based predictive models with respect to their potential for use as screening tools for endometriosis in adult women. Validated instruments were of particular interest. We conducted structured searches of PubMed and targeted searches of the gray literature to identify studies reporting on screening instruments used in endometriosis. Studies were screened according to inclusion and exclusion criteria that followed the PICOS (population, intervention, comparison, outcomes, study design) framework. A total of 16 studies were identified, of which 10 described measures for endometriosis in general, 2 described measures for endometriosis at specific sites, and 4 described measures for deep-infiltrating endometriosis. Only 1 study evaluated a questionnaire that was solely patient-completed. Most measures required physician, imaging, or laboratory assessments in addition to patient-completed questionnaires, and several measures relied on complex scoring. Validation for use as a screening tool in adult women with potential endometriosis was lacking in all studies, as most studies focused on diagnosis versus screening. This literature review did not identify any fully validated, symptom-based, patient-reported questionnaires for endometriosis screening in adult women.

Cost effectiveness of mammography screening for Chinese women.

PubMed

Wong, Irene O L; Kuntz, Karen M; Cowling, Benjamin J; Lam, Cindy L K; Leung, Gabriel M

2007-08-15

Although the cost effectiveness of screening mammography in most western developed populations has been accepted, it may not apply to Chinese women, who have a much lower breast cancer incidence. The authors estimated the cost effectiveness of biennial mammography in Hong Kong Chinese women to inform evidence-based screening policies. For the current study, a state-transition Markov model was developed to simulate mammography screening, breast cancer diagnosis, and treatment in a hypothetical cohort of Chinese women. The benefit of mammography was modeled by assuming a stage shift, in which cancers in screened women were more likely to be diagnosed at an earlier disease stage. The authors compared costs, quality-adjusted life years (QALYs) saved, and life years saved (LYS) for 5 screening strategies. Biennial screening resulted in a gain in life expectancy ranging from 4.3 days to 9.4 days compared with no screening at an incremental cost of from US $1,166 to US $2,425 per woman. The least costly, nondominated screening option was screening from ages 40 years to 69 years, with an incremental cost-effectiveness ratio (ICER) of US $61,600 per QALY saved or US $64,400 per LYS compared with no screening. In probabilistic sensitivity analyses, the probability of the ICER being below a threshold of US $50,000 per QALY (LYS) was 15.3% (14.6%). The current results suggested that mammography for Hong Kong Chinese women currently may not be cost effective based on the arbitrary threshold of US $50,000 per QALY. However, clinicians must remain vigilant and periodically should revisit the question of population screening: Disease rates in China have been increasing because of westernization and socioeconomic development.

Cost-effectiveness of annual versus biennial screening mammography for women with high mammographic breast density.

PubMed

Pataky, Reka; Ismail, Zahra; Coldman, Andrew J; Elwood, Mark; Gelmon, Karen; Hedden, Lindsay; Hislop, Greg; Kan, Lisa; McCoy, Bonnie; Olivotto, Ivo A; Peacock, Stuart

2014-12-01

The sensitivity of screening mammography is much lower among women who have dense breast tissue, compared with women who have largely fatty breasts, and they are also at much higher risk of developing the disease. Increasing mammography screening frequency from biennially to annually has been suggested as a policy option to address the elevated risk in this population. The purpose of this study was to assess the cost-effectiveness of annual versus biennial screening mammography among women aged 50-79 with dense breast tissue. A Markov model was constructed based on screening, diagnostic, and treatment pathways for the population-based screening and cancer care programme in British Columbia, Canada. Model probabilities and screening costs were calculated from screening programme data. Costs for breast cancer treatment were calculated from treatment data, and utility values were obtained from the literature. Incremental cost-effectiveness was expressed as cost per quality adjusted life year (QALY), and probabilistic sensitivity analysis was conducted. Compared with biennial screening, annual screening generated an additional 0.0014 QALYs (95% CI: -0.0480-0.0359) at a cost of $819 ($ = Canadian dollars) per patient (95% CI: 506-1185), resulting in an incremental cost effectiveness ratio of $565,912/QALY. Annual screening had a 37.5% probability of being cost-effective at a willingness-to-pay threshold of $100,000/QALY. There is considerable uncertainty about the incremental cost-effectiveness of annual mammography. Further research on the comparative effectiveness of screening strategies for women with high mammographic breast density is warranted, particularly as digital mammography and density measurement become more widespread, before cost-effectiveness can be reevaluated. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

TOWARDS REFINED USE OF TOXICITY DATA IN STATISTICALLY BASED SAR MODELS FOR DEVELOPMENTAL TOXICITY.

EPA Science Inventory

In 2003, an International Life Sciences Institute (ILSI) Working Group examined the potential of statistically based structure-activity relationship (SAR) models for use in screening environmental contaminants for possible developmental toxicants.

Model-based Small Area Estimates of Cancer Risk Factors and Screening Behaviors - Small Area Estimates

Cancer.gov

These model-based estimates use two surveys, the Behavioral Risk Factor Surveillance System (BRFSS) and the National Health Interview Survey (NHIS). The two surveys are combined using novel statistical methodology.

Independence screening for high dimensional nonlinear additive ODE models with applications to dynamic gene regulatory networks.

PubMed

Xue, Hongqi; Wu, Shuang; Wu, Yichao; Ramirez Idarraga, Juan C; Wu, Hulin

2018-05-02

Mechanism-driven low-dimensional ordinary differential equation (ODE) models are often used to model viral dynamics at cellular levels and epidemics of infectious diseases. However, low-dimensional mechanism-based ODE models are limited for modeling infectious diseases at molecular levels such as transcriptomic or proteomic levels, which is critical to understand pathogenesis of diseases. Although linear ODE models have been proposed for gene regulatory networks (GRNs), nonlinear regulations are common in GRNs. The reconstruction of large-scale nonlinear networks from time-course gene expression data remains an unresolved issue. Here, we use high-dimensional nonlinear additive ODEs to model GRNs and propose a 4-step procedure to efficiently perform variable selection for nonlinear ODEs. To tackle the challenge of high dimensionality, we couple the 2-stage smoothing-based estimation method for ODEs and a nonlinear independence screening method to perform variable selection for the nonlinear ODE models. We have shown that our method possesses the sure screening property and it can handle problems with non-polynomial dimensionality. Numerical performance of the proposed method is illustrated with simulated data and a real data example for identifying the dynamic GRN of Saccharomyces cerevisiae. Copyright © 2018 John Wiley & Sons, Ltd.

[Vis-NIR spectroscopic pattern recognition combined with SG smoothing applied to breed screening of transgenic sugarcane].

PubMed

Liu, Gui-Song; Guo, Hao-Song; Pan, Tao; Wang, Ji-Hua; Cao, Gan

2014-10-01

Based on Savitzky-Golay (SG) smoothing screening, principal component analysis (PCA) combined with separately supervised linear discriminant analysis (LDA) and unsupervised hierarchical clustering analysis (HCA) were used for non-destructive visible and near-infrared (Vis-NIR) detection for breed screening of transgenic sugarcane. A random and stability-dependent framework of calibration, prediction, and validation was proposed. A total of 456 samples of sugarcane leaves planting in the elongating stage were collected from the field, which was composed of 306 transgenic (positive) samples containing Bt and Bar gene and 150 non-transgenic (negative) samples. A total of 156 samples (negative 50 and positive 106) were randomly selected as the validation set; the remaining samples (negative 100 and positive 200, a total of 300 samples) were used as the modeling set, and then the modeling set was subdivided into calibration (negative 50 and positive 100, a total of 150 samples) and prediction sets (negative 50 and positive 100, a total of 150 samples) for 50 times. The number of SG smoothing points was ex- panded, while some modes of higher derivative were removed because of small absolute value, and a total of 264 smoothing modes were used for screening. The pairwise combinations of first three principal components were used, and then the optimal combination of principal components was selected according to the model effect. Based on all divisions of calibration and prediction sets and all SG smoothing modes, the SG-PCA-LDA and SG-PCA-HCA models were established, the model parameters were optimized based on the average prediction effect for all divisions to produce modeling stability. Finally, the model validation was performed by validation set. With SG smoothing, the modeling accuracy and stability of PCA-LDA, PCA-HCA were signif- icantly improved. For the optimal SG-PCA-LDA model, the recognition rate of positive and negative validation samples were 94.3%, 96.0%; and were 92.5%, 98.0% for the optimal SG-PCA-LDA model, respectively. Vis-NIR spectro- scopic pattern recognition combined with SG smoothing could be used for accurate recognition of transgenic sugarcane leaves, and provided a convenient screening method for transgenic sugarcane breeding.

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

PubMed

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.

Application of QSAR and shape pharmacophore modeling approaches for targeted chemical library design.

PubMed

Ebalunode, Jerry O; Zheng, Weifan; Tropsha, Alexander

2011-01-01

Optimization of chemical library composition affords more efficient identification of hits from biological screening experiments. The optimization could be achieved through rational selection of reagents used in combinatorial library synthesis. However, with a rapid advent of parallel synthesis methods and availability of millions of compounds synthesized by many vendors, it may be more efficient to design targeted libraries by means of virtual screening of commercial compound collections. This chapter reviews the application of advanced cheminformatics approaches such as quantitative structure-activity relationships (QSAR) and pharmacophore modeling (both ligand and structure based) for virtual screening. Both approaches rely on empirical SAR data to build models; thus, the emphasis is placed on achieving models of the highest rigor and external predictive power. We present several examples of successful applications of both approaches for virtual screening to illustrate their utility. We suggest that the expert use of both QSAR and pharmacophore models, either independently or in combination, enables users to achieve targeted libraries enriched with experimentally confirmed hit compounds.

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

NASA Astrophysics Data System (ADS)

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.

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

PubMed Central

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

2015-01-01

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

Free Energy-Based Virtual Screening and Optimization of RNase H Inhibitors of HIV-1 Reverse Transcriptase.

PubMed

Zhang, Baofeng; D'Erasmo, Michael P; Murelli, Ryan P; Gallicchio, Emilio

2016-09-30

We report the results of a binding free energy-based virtual screening campaign of a library of 77 α-hydroxytropolone derivatives against the challenging RNase H active site of the reverse transcriptase (RT) enzyme of human immunodeficiency virus-1. Multiple protonation states, rotamer states, and binding modalities of each compound were individually evaluated. The work involved more than 300 individual absolute alchemical binding free energy parallel molecular dynamics calculations and over 1 million CPU hours on national computing clusters and a local campus computational grid. The thermodynamic and structural measures obtained in this work rationalize a series of characteristics of this system useful for guiding future synthetic and biochemical efforts. The free energy model identified key ligand-dependent entropic and conformational reorganization processes difficult to capture using standard docking and scoring approaches. Binding free energy-based optimization of the lead compounds emerging from the virtual screen has yielded four compounds with very favorable binding properties, which will be the subject of further experimental investigations. This work is one of the few reported applications of advanced-binding free energy models to large-scale virtual screening and optimization projects. It further demonstrates that, with suitable algorithms and automation, advanced-binding free energy models can have a useful role in early-stage drug-discovery programs.

Novel high-resolution computed tomography-based radiomic classifier for screen-identified pulmonary nodules in the National Lung Screening Trial.

PubMed

Peikert, Tobias; Duan, Fenghai; Rajagopalan, Srinivasan; Karwoski, Ronald A; Clay, Ryan; Robb, Richard A; Qin, Ziling; Sicks, JoRean; Bartholmai, Brian J; Maldonado, Fabien

2018-01-01

Optimization of the clinical management of screen-detected lung nodules is needed to avoid unnecessary diagnostic interventions. Herein we demonstrate the potential value of a novel radiomics-based approach for the classification of screen-detected indeterminate nodules. Independent quantitative variables assessing various radiologic nodule features such as sphericity, flatness, elongation, spiculation, lobulation and curvature were developed from the NLST dataset using 726 indeterminate nodules (all ≥ 7 mm, benign, n = 318 and malignant, n = 408). Multivariate analysis was performed using least absolute shrinkage and selection operator (LASSO) method for variable selection and regularization in order to enhance the prediction accuracy and interpretability of the multivariate model. The bootstrapping method was then applied for the internal validation and the optimism-corrected AUC was reported for the final model. Eight of the originally considered 57 quantitative radiologic features were selected by LASSO multivariate modeling. These 8 features include variables capturing Location: vertical location (Offset carina centroid z), Size: volume estimate (Minimum enclosing brick), Shape: flatness, Density: texture analysis (Score Indicative of Lesion/Lung Aggression/Abnormality (SILA) texture), and surface characteristics: surface complexity (Maximum shape index and Average shape index), and estimates of surface curvature (Average positive mean curvature and Minimum mean curvature), all with P<0.01. The optimism-corrected AUC for these 8 features is 0.939. Our novel radiomic LDCT-based approach for indeterminate screen-detected nodule characterization appears extremely promising however independent external validation is needed.

Virtual screening and optimization of Type II inhibitors of JAK2 from a natural product library.

PubMed

Ma, Dik-Lung; Chan, Daniel Shiu-Hin; Wei, Guo; Zhong, Hai-Jing; Yang, Hui; Leung, Lai To; Gullen, Elizabeth A; Chiu, Pauline; Cheng, Yung-Chi; Leung, Chung-Hang

2014-11-21

Amentoflavone has been identified as a JAK2 inhibitor by structure-based virtual screening of a natural product library. In silico optimization using the DOLPHIN model yielded analogues with enhanced potency against JAK2 activity and HCV activity in cellulo. Molecular modeling and kinetic experiments suggested that the analogues may function as Type II inhibitors of JAK2.

Cost-effectiveness of population-based screening for colorectal cancer: a comparison of guaiac-based faecal occult blood testing, faecal immunochemical testing and flexible sigmoidoscopy

PubMed Central

Sharp, L; Tilson, L; Whyte, S; O'Ceilleachair, A; Walsh, C; Usher, C; Tappenden, P; Chilcott, J; Staines, A; Barry, M; Comber, H

2012-01-01

Background: Several colorectal cancer-screening tests are available, but it is uncertain which provides the best balance of risks and benefits within a screening programme. We evaluated cost-effectiveness of a population-based screening programme in Ireland based on (i) biennial guaiac-based faecal occult blood testing (gFOBT) at ages 55–74, with reflex faecal immunochemical testing (FIT); (ii) biennial FIT at ages 55–74; and (iii) once-only flexible sigmoidoscopy (FSIG) at age 60. Methods: A state-transition model was used to estimate costs and outcomes for each screening scenario vs no screening. A third party payer perspective was adopted. Probabilistic sensitivity analyses were undertaken. Results: All scenarios would be considered highly cost-effective compared with no screening. The lowest incremental cost-effectiveness ratio (ICER vs no screening €589 per quality-adjusted life-year (QALY) gained) was found for FSIG, followed by FIT (€1696) and gFOBT (€4428); gFOBT was dominated. Compared with FSIG, FIT was associated with greater gains in QALYs and reductions in lifetime cancer incidence and mortality, but was more costly, required considerably more colonoscopies and resulted in more complications. Results were robust to variations in parameter estimates. Conclusion: Population-based screening based on FIT is expected to result in greater health gains than a policy of gFOBT (with reflex FIT) or once-only FSIG, but would require significantly more colonoscopy resources and result in more individuals experiencing adverse effects. Weighing these advantages and disadvantages presents a considerable challenge to policy makers. PMID:22343624

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

PubMed

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

2015-10-01

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

Prediction of lung cancer incidence on the low-dose computed tomography arm of the National Lung Screening Trial: A dynamic Bayesian network

PubMed Central

Petousis, Panayiotis; Han, Simon X.; Aberle, Denise; Bui, Alex A.T.

2016-01-01

Introduction Identifying high-risk lung cancer individuals at an early disease stage is the most effective way of improving survival. The landmark National Lung Screening Trial (NLST) demonstrated the utility of low-dose computed tomography (LDCT) imaging to reduce mortality (relative to x-ray screening). As a result of the NLST and other studies, imaging-based lung cancer screening programs are now being implemented. However, LDCT interpretation results in a high number of false positives. A set of dynamic Bayesian networks (DBN) were designed and evaluated to provide insight into how longitudinal data can be used to help inform lung cancer screening decisions. Methods The LDCT arm of the NLST dataset was used to build and explore five DBNs for high-risk individuals. Three of these DBNs were built using a backward construction process, and two using structure learning methods. All models employ demographic, smoking status, cancer history, family lung cancer history, exposure risk factors, comorbidities related to lung cancer, and LDCT screening outcome information. Given the uncertainty arising from lung cancer screening, a cancer state-space model based on lung cancer staging was utilized to characterize the cancer status of an individual over time. The models were evaluated on balanced training and test sets of cancer and non-cancer cases to deal with data imbalance and overfitting. Results Results were comparable to expert decisions. The average area under the curve (AUC) of the receiver operating characteristic (ROC) for the three intervention points of the NLST trial was higher than 0.75 for all models. Evaluation of the models on the complete LDCT arm of the NLST dataset (N = 25, 486) demonstrated satisfactory generalization. Consensus of predictions over similar cases is reported in concordance statistics between the models’ and the physicians’ predictions. The models’ predictive ability with respect to missing data was also evaluated with the sample of cases that missed the second screening exam of the trial (N = 417). The DBNs outperformed comparison models such as logistic regression and naïve Bayes. Conclusion The lung cancer screening DBNs demonstrated high discrimination and predictive power with the majority of cancer and non-cancer cases. PMID:27664507

Understanding the Low Level of Cervical Cancer Screening in Masaka Uganda Using the ASE Model: A Community-Based Survey.

PubMed

Twinomujuni, Cyprian; Nuwaha, Fred; Babirye, Juliet Ndimwibo

2015-01-01

Cervical cancer is one of the leading causes of cancer deaths among women globally and its impact is mostly felt in developing countries like Uganda where its prevalence is higher and utilization of cancer screening services is low. This study aimed to identify factors associated with intention to screen for cervical cancer among women of reproductive age in Masaka Uganda using the attitude, social influence and self efficacy (ASE) model. A descriptive community based survey was conducted among 416 women. A semi-structured interviewer administered questionnaire was used to collect data. Unadjusted and adjusted prevalence ratios (PR) were computed using a generalized linear model with Poisson family and a log link using STATA 12. Only 7% (29/416) of our study respondents had ever screened for cervical cancer although a higher proportion (63%, 262/416) reported intention to screen for cervical cancer. The intention to screen for cervical cancer was higher among those who said they were at risk of developing cervical cancer (Adjusted prevalence ratio [PR] 2.0, 95% CI 1.60-2.58), those who said they would refer other women for screening (Adjusted PR 1.4, 95% CI 1.06-1.88) and higher among those who were unafraid of being diagnosed with cervical cancer (Adjusted PR 1.6, 95% CI 1.36-1.93). Those who reported discussions on cervical cancer with health care providers (Adjusted PR 1.2, 95% CI 1.05-1.44), those living with a sexual partner (Adjusted PR 1.4, 95% CI 1.11-1.68), and those who were formally employed (Adjusted PR 1.2, 95% CI 1.03-1.35) more frequently reported intention to screen for cervical cancer. In conclusion, health education to increase risk perception, improve women's attitudes towards screening for cervical cancer and address the fears held by the women would increase intention to screen for cervical cancer. Interventions should also target increased discussions with health workers.

Using Collaborative Simulation Modeling to Develop a Web-Based Tool to Support Policy-Level Decision Making About Breast Cancer Screening Initiation Age

PubMed Central

Burnside, Elizabeth S.; Lee, Sandra J.; Bennette, Carrie; Near, Aimee M.; Alagoz, Oguzhan; Huang, Hui; van den Broek, Jeroen J.; Kim, Joo Yeon; Ergun, Mehmet A.; van Ravesteyn, Nicolien T.; Stout, Natasha K.; de Koning, Harry J.; Mandelblatt, Jeanne S.

2017-01-01

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. PMID:29376135

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

PubMed Central

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 earlier in the course of infection. PMID:21625489

Immobilized enzyme reactors in HPLC and its application in inhibitor screening: A review

PubMed Central

Fang, Si-Meng; Wang, Hai-Na; Zhao, Zhong-Xi; Wang, Wei-Hong

2011-01-01

This paper sets out to summarize the literatures based on immobilized enzyme bio-chromatography and its application in inhibitors screening in the last decade. In order to screen enzyme inhibitors from a mass of compounds in preliminary screening, multi-pore materials with good biocompatibility are used for the supports of immobilizing enzymes, and then the immobilized enzyme reactor applied as the immobilized enzyme stationary phase in HPLC. Therefore, a technology platform of high throughput screening is gradually established to screen the enzyme inhibitors as new anti-tumor drugs. Here, we briefly summarize the selective methods of supports, immobilization techniques, co-immobilized enzymes system and the screening model. PMID:29403726

Screening Chemicals for Estrogen Receptor Bioactivity Using a Computational Model.

PubMed

Browne, Patience; Judson, Richard S; Casey, Warren M; Kleinstreuer, Nicole C; Thomas, Russell S

2015-07-21

The U.S. Environmental Protection Agency (EPA) is considering high-throughput and computational methods to evaluate the endocrine bioactivity of environmental chemicals. Here we describe a multistep, performance-based validation of new methods and demonstrate that these new tools are sufficiently robust to be used in the Endocrine Disruptor Screening Program (EDSP). Results from 18 estrogen receptor (ER) ToxCast high-throughput screening assays were integrated into a computational model that can discriminate bioactivity from assay-specific interference and cytotoxicity. Model scores range from 0 (no activity) to 1 (bioactivity of 17β-estradiol). ToxCast ER model performance was evaluated for reference chemicals, as well as results of EDSP Tier 1 screening assays in current practice. The ToxCast ER model accuracy was 86% to 93% when compared to reference chemicals and predicted results of EDSP Tier 1 guideline and other uterotrophic studies with 84% to 100% accuracy. The performance of high-throughput assays and ToxCast ER model predictions demonstrates that these methods correctly identify active and inactive reference chemicals, provide a measure of relative ER bioactivity, and rapidly identify chemicals with potential endocrine bioactivities for additional screening and testing. EPA is accepting ToxCast ER model data for 1812 chemicals as alternatives for EDSP Tier 1 ER binding, ER transactivation, and uterotrophic assays.

Integration of Life-Stage Physiologically Based Pharmacokinetic Models with Adverse Outcome Pathways and Environmental Exposure Models to Screen for Environmental Hazards

EPA Science Inventory

A Life-stage Physiologically-Based Pharmacokinetic (PBPK) model was developed to include descriptions of several life-stage events such as pregnancy, fetal development, the neonate and child growth. The overall modeling strategy was used for in vitro to in vivo (IVIVE) extrapolat...

Estimation of sojourn time in chronic disease screening without data on interval cases.

PubMed

Chen, T H; Kuo, H S; Yen, M F; Lai, M S; Tabar, L; Duffy, S W

2000-03-01

Estimation of the sojourn time on the preclinical detectable period in disease screening or transition rates for the natural history of chronic disease usually rely on interval cases (diagnosed between screens). However, to ascertain such cases might be difficult in developing countries due to incomplete registration systems and difficulties in follow-up. To overcome this problem, we propose three Markov models to estimate parameters without using interval cases. A three-state Markov model, a five-state Markov model related to regional lymph node spread, and a five-state Markov model pertaining to tumor size are applied to data on breast cancer screening in female relatives of breast cancer cases in Taiwan. Results based on a three-state Markov model give mean sojourn time (MST) 1.90 (95% CI: 1.18-4.86) years for this high-risk group. Validation of these models on the basis of data on breast cancer screening in the age groups 50-59 and 60-69 years from the Swedish Two-County Trial shows the estimates from a three-state Markov model that does not use interval cases are very close to those from previous Markov models taking interval cancers into account. For the five-state Markov model, a reparameterized procedure using auxiliary information on clinically detected cancers is performed to estimate relevant parameters. A good fit of internal and external validation demonstrates the feasibility of using these models to estimate parameters that have previously required interval cancers. This method can be applied to other screening data in which there are no data on interval cases.

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

PubMed

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.

Cost-Effectiveness Analysis of Screening for and Managing Identified Hypertension for Cardiovascular Disease Prevention in Vietnam

PubMed Central

Nguyen, Thi-Phuong-Lan; Wright, E. Pamela; Nguyen, Thanh-Trung; Schuiling-Veninga, C. C. M.; Bijlsma, M. J.; Nguyen, Thi-Bach-Yen; Postma, M. J.

2016-01-01

Objective To inform development of guidelines for hypertension management in Vietnam, we evaluated the cost-effectiveness of different strategies on screening for hypertension in preventing cardiovascular disease (CVD). Methods A decision tree was combined with a Markov model to measure incremental cost-effectiveness of different approaches to hypertension screening. Values used as input parameters for the model were taken from different sources. Various screening intervals (one-off, annually, biannually) and starting ages to screen (35, 45 or 55 years) and coverage of treatment were analysed. We ran both a ten-year and a lifetime horizon. Input parameters for the models were extracted from local and regional data. Probabilistic sensitivity analysis was used to evaluate parameter uncertainty. A threshold of three times GDP per capita was applied. Results Cost per quality adjusted life year (QALY) gained varied in different screening scenarios. In a ten-year horizon, the cost-effectiveness of screening for hypertension ranged from cost saving to Int$ 758,695 per QALY gained. For screening of men starting at 55 years, all screening scenarios gave a high probability of being cost-effective. For screening of females starting at 55 years, the probability of favourable cost-effectiveness was 90% with one-off screening. In a lifetime horizon, cost per QALY gained was lower than the threshold of Int$ 15,883 in all screening scenarios among males. Similar results were found in females when starting screening at 55 years. Starting screening in females at 45 years had a high probability of being cost-effective if screening biannually was combined with increasing coverage of treatment by 20% or even if sole biannual screening was considered. Conclusion From a health economic perspective, integrating screening for hypertension into routine medical examination and related coverage by health insurance could be recommended. Screening for hypertension has a high probability of being cost-effective in preventing CVD. An adequate screening strategy can best be selected based on age, sex and screening interval. PMID:27192051

Cost-Effectiveness of Screening Individuals With Cystic Fibrosis for Colorectal Cancer.

PubMed

Gini, Andrea; Zauber, Ann G; Cenin, Dayna R; Omidvari, Amir-Houshang; Hempstead, Sarah E; Fink, Aliza K; Lowenfels, Albert B; Lansdorp-Vogelaar, Iris

2017-12-27

Individuals with cystic fibrosis are at increased risk of colorectal cancer (CRC) compared to the general population, and risk is higher among those who received an organ transplant. We performed a cost-effectiveness analysis to determine optimal CRC screening strategies for patients with cystic fibrosis. We adjusted the existing Microsimulation Screening Analysis-Colon microsimulation model to reflect increased CRC risk and lower life expectancy in patients with cystic fibrosis. Modeling was performed separately for individuals who never received an organ transplant and patients who had received an organ transplant. We modeled 76 colonoscopy screening strategies that varied the age range and screening interval. The optimal screening strategy was determined based on a willingness to pay threshold of $100,000 per life-year gained. Sensitivity and supplementary analyses were performed, including fecal immunochemical test (FIT) as an alternative test, earlier ages of transplantation, and increased rates of colonoscopy complications, to assess whether optimal screening strategies would change. Colonoscopy every 5 years, starting at age 40 years, was the optimal colonoscopy strategy for patients with cystic fibrosis who never received an organ transplant; this strategy prevented 79% of deaths from CRC. Among patients with cystic fibrosis who had received an organ transplant, optimal colonoscopy screening should start at an age of 30 or 35 years, depending on the patient's age at time of transplantation. Annual FIT screening was predicted to be cost-effective for patients with cystic fibrosis. However, the level of accuracy of the FIT in population is not clear. Using a Microsimulation Screening Analysis-Colon microsimulation model, we found screening of patients with cystic fibrosis for CRC to be cost-effective. Due to the higher risk in these patients for CRC, screening should start at an earlier age with a shorter screening interval. The findings of this study (especially those on FIT screening) may be limited by restricted evidence available for patients with cystic fibrosis. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Cost Effectiveness of Screening Individuals With Cystic Fibrosis for Colorectal Cancer.

PubMed

Gini, Andrea; Zauber, Ann G; Cenin, Dayna R; Omidvari, Amir-Houshang; Hempstead, Sarah E; Fink, Aliza K; Lowenfels, Albert B; Lansdorp-Vogelaar, Iris

2018-02-01

Individuals with cystic fibrosis are at increased risk of colorectal cancer (CRC) compared with the general population, and risk is higher among those who received an organ transplant. We performed a cost-effectiveness analysis to determine optimal CRC screening strategies for patients with cystic fibrosis. We adjusted the existing Microsimulation Screening Analysis-Colon model to reflect increased CRC risk and lower life expectancy in patients with cystic fibrosis. Modeling was performed separately for individuals who never received an organ transplant and patients who had received an organ transplant. We modeled 76 colonoscopy screening strategies that varied the age range and screening interval. The optimal screening strategy was determined based on a willingness to pay threshold of $100,000 per life-year gained. Sensitivity and supplementary analyses were performed, including fecal immunochemical test (FIT) as an alternative test, earlier ages of transplantation, and increased rates of colonoscopy complications, to assess if optimal screening strategies would change. Colonoscopy every 5 years, starting at an age of 40 years, was the optimal colonoscopy strategy for patients with cystic fibrosis who never received an organ transplant; this strategy prevented 79% of deaths from CRC. Among patients with cystic fibrosis who had received an organ transplant, optimal colonoscopy screening should start at an age of 30 or 35 years, depending on the patient's age at time of transplantation. Annual FIT screening was predicted to be cost-effective for patients with cystic fibrosis. However, the level of accuracy of the FIT in this population is not clear. Using a Microsimulation Screening Analysis-Colon model, we found screening of patients with cystic fibrosis for CRC to be cost effective. Because of the higher risk of CRC in these patients, screening should start at an earlier age with a shorter screening interval. The findings of this study (especially those on FIT screening) may be limited by restricted evidence available for patients with cystic fibrosis. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Estimating the Effect of Targeted Screening Strategies: An Application to Colonoscopy and Colorectal Cancer.

PubMed

Thomas, Duncan C

2017-07-01

Screening behavior depends on previous screening history and family members' behaviors, which can act as both confounders and intermediate variables on a causal pathway from screening to disease risk. Conventional analyses that adjust for these variables can lead to incorrect inferences about the causal effect of screening if high-risk individuals are more likely to be screened. Analyzing the data in a manner that treats screening as randomized conditional on covariates allows causal parameters to be estimated; inverse probability weighting based on propensity of exposure scores is one such method considered here. I simulated family data under plausible models for the underlying disease process and for screening behavior to assess the performance of alternative methods of analysis and whether a targeted screening approach based on individuals' risk factors would lead to a greater reduction in cancer incidence in the population than a uniform screening policy. Simulation results indicate that there can be a substantial underestimation of the effect of screening on subsequent cancer risk when using conventional analysis approaches, which is avoided by using inverse probability weighting. A large case-control study of colonoscopy and colorectal cancer from Germany shows a strong protective effect of screening, but inverse probability weighting makes this effect even stronger. Targeted screening approaches based on either fixed risk factors or family history yield somewhat greater reductions in cancer incidence with fewer screens needed to prevent one cancer than population-wide approaches, but the differences may not be large enough to justify the additional effort required. See video abstract at, http://links.lww.com/EDE/B207.

Cost-effectiveness of computed tomography colonography in colorectal cancer screening: a systematic review.

PubMed

Hanly, Paul; Skally, Mairead; Fenlon, Helen; Sharp, Linda

2012-10-01

The European Code Against Cancer recommends individuals aged ≥ 50 should participate in colorectal cancer screening. CT-colonography (CTC) is one of several screening tests available. We systematically reviewed evidence on, and identified key factors influencing, cost-effectiveness of CTC screening. PubMed, Medline, and the Cochrane library were searched for cost-effectiveness or cost-utility analyses of CTC-based screening, published in English, January 1999 to July 2010. Data was abstracted on setting, model type and horizon, screening scenario(s), comparator(s), participants, uptake, CTC performance and cost, effectiveness, ICERs, and whether extra-colonic findings and medical complications were considered. Sixteen studies were identified from the United States (n = 11), Canada (n = 2), and France, Italy, and the United Kingdom (1 each). Markov state-transition (n = 14) or microsimulation (n = 2) models were used. Eleven considered direct medical costs only; five included indirect costs. Fourteen compared CTC with no screening; fourteen compared CTC with colonoscopy-based screening; fewer compared CTC with sigmoidoscopy (8) or fecal tests (4). Outcomes assessed were life-years gained/saved (13), QALYs (2), or both (1). Three considered extra-colonic findings; seven considered complications. CTC appeared cost-effective versus no screening and, in general, flexible sigmoidoscopy and fecal occult blood testing. Results were mixed comparing CTC to colonoscopy. Parameters most influencing cost-effectiveness included: CTC costs, screening uptake, threshold for polyp referral, and extra-colonic findings. Evidence on cost-effectiveness of CTC screening is heterogeneous, due largely to between-study differences in comparators and parameter values. Future studies should: compare CTC with currently favored tests, especially fecal immunochemical tests; consider extra-colonic findings; and conduct comprehensive sensitivity analyses.

Impact of comorbidity on colorectal cancer screening cost-effectiveness study in diabetic populations.

PubMed

Dinh, Tuan A; Alperin, Peter; Walter, Louise C; Smith, Robert

2012-06-01

Although comorbidity has been shown to affect the benefits and risks of colorectal cancer (CRC) screening, it has not been accounted for in prior cost-effectiveness analyses of CRC screening. To evaluate the impact of diagnosis of diabetes mellitus, a highly prevalent comorbidity in U.S. adults aged 50 and older, on health and economic outcomes of CRC screening. Cost-effectiveness analysis using an integrated modeling framework. Derived from basic and epidemiologic studies, clinical trials, cancer registries, and a colonoscopy database. U.S. 50-year-old population. Lifetime. Costs are based on Medicare reimbursement rates. Colonoscopy screening at ten-year intervals, beginning at age 50, and discontinued after age 50, 60, 70, 80 or death. Health outcomes and cost effectiveness. Diabetes diagnosis significantly affects cost-effectiveness of CRC screening. For the same CRC screening strategy, a person without diabetes at age 50 gained on average 0.07-0.13 life years more than a person diagnosed with diabetes at age 50 or younger. For a population of 1,000 patients diagnosed with diabetes at baseline, increasing stop age from 70 years to 80 years increased quality-adjusted life years (QALYs) gained by 0.3, with an incremental cost-effectiveness ratio of $206,671/QALY. The corresponding figures for 1,000 patients without diabetes are 2.3 QALYs and $46,957/QALY. Cost-effectiveness results are sensitive to cost of colonoscopy and adherence to colonoscopy screening. Results depend on accuracy of model assumptions. Benefits of CRC screening differ substantially for patients with and without diabetes. Screening for CRC in patients diagnosed with diabetes at age 50 or younger is not cost-effective beyond age 70. Screening recommendations should be individualized based on the presence of comorbidities.

Cost-Effectiveness of Patient Navigation to Increase Adherence with Screening Colonoscopy Among Minority Individuals

PubMed Central

Ladabaum, Uri; Mannalithara, Ajitha; Jandorf, Lina; Itzkowitz, Steven H.

2015-01-01

Background Colorectal cancer (CRC) screening is underutilized by minority populations. Patient navigation increases adherence with screening colonoscopy. We estimated the cost-effectiveness of navigation for screening colonoscopy from the perspective of a payer seeking to improve population health. Methods We informed our validated model of CRC screening with inputs from navigation studies in New York City (population 43% African American, 49% Hispanic, 4% White, 4% Other; base case screening 40% without and 65% with navigation, navigation costs $29/colonoscopy completer, $21/non-completer, $3/non-navigated). We compared: 1) navigation vs. no navigation for one-time screening colonoscopy in unscreened persons age ≥50; 2) programs of colonoscopy with vs. without navigation, vs. fecal occult blood testing (FOBT) or immunochemical testing (FIT) for ages 50-80. Results In the base case: 1) one-time navigation gained quality-adjusted life-years (QALYs) and decreased costs; 2) longitudinal navigation cost $9,800/QALY gained vs. no navigation, and assuming comparable uptake rates, it cost $118,700/QALY gained vs. FOBT, but was less effective and more costly than FIT. Results were most dependent on screening participation rates and navigation costs: 1) assuming a 5% increase in screening uptake with navigation and navigation cost of $150/completer, one-time navigation cost $26,400/QALY gained; 2) longitudinal navigation with 75% colonoscopy uptake cost <$25,000/QALY gained vs. FIT when FIT uptake was <50%. Probabilistic sensitivity analyses did not alter the conclusions. Conclusions Navigation for screening colonoscopy appears to be cost-effective, and one-time navigation may be cost-saving. In emerging healthcare models that reward outcomes, payers should consider covering the costs of navigation for screening colonoscopy. PMID:25492455

Quantitative estimates of the impact of sensitivity and specificity in mammographic screening in Germany.

PubMed Central

Warmerdam, P G; de Koning, H J; Boer, R; Beemsterboer, P M; Dierks, M L; Swart, E; Robra, B P

1997-01-01

STUDY OBJECTIVE: To estimate quantitatively the impact of the quality of mammographic screening (in terms of sensitivity and specificity) on the effects and costs of nationwide breast cancer screening. DESIGN: Three plausible "quality" scenarios for a biennial breast cancer screening programme for women aged 50-69 in Germany were analysed in terms of costs and effects using the Microsimulation Screening Analysis model on breast cancer screening and the natural history of breast cancer. Firstly, sensitivity and specificity in the expected situation (or "baseline" scenario) were estimated from a model based analysis of empirical data from 35,000 screening examinations in two German pilot projects. In the second "high quality" scenario, these properties were based on the more favourable diagnostic results from breast cancer screening projects and the nationwide programme in The Netherlands. Thirdly, a worst case, "low quality" hypothetical scenario with a 25% lower sensitivity than that experienced in The Netherlands was analysed. SETTING: The epidemiological and social situation in Germany in relation to mass screening for breast cancer. RESULTS: In the "baseline" scenario, an 11% reduction in breast cancer mortality was expected in the total German female population, ie 2100 breast cancer deaths would be prevented per year. It was estimated that the "high quality" scenario, based on Dutch experience, would lead to the prevention of an additional 200 deaths per year and would also cut the number of false positive biopsy results by half. The cost per life year gained varied from Deutsche mark (DM) 15,000 on the "high quality" scenario to DM 21,000 in the "low quality" setting. CONCLUSIONS: Up to 20% of the total costs of a screening programme can be spent on quality improvement in order to achieve a substantially higher reduction in mortality and reduce undesirable side effects while retaining the same cost effectiveness ratio as that estimated from the German data. PMID:9196649

Decision Support and the Effectiveness of Web-based Delivery and Information Tailoring for Bowel Cancer Screening: An Exploratory Study

PubMed Central

Wilson, Carlene J; Zajac, Ian T; Hart, Elizabeth; McGillivray, Jane A

2012-01-01

Background Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females throughout the developed world. Population screening using fecal occult blood tests (FOBTs) facilitates early detection and greater chance of survival, but participation rates are low. We developed a Web-based decision tool to provide information tailored to an individual’s decision stage for CRC screening and attitude toward screening utilizing the Preventive Health Model (PHM) and Precaution Adoption Process Model (PAPM) as theoretical frameworks for screening behavior. We describe the practical steps employed in the tool’s design and the subsequent conduct of an exploratory study. Objective To design a decision tool for CRC screening and conduct an exploratory study among average-risk men and women to (1) test the impact of message type (tailored vs non-tailored) and message delivery modality (Web-based vs paper-based) on attitudes toward screening and screening uptake, and (2) investigate the acceptability of the decision tool and relevance of materials. Methods Participants (n = 100), recruited from a population sample of men and women aged 50-76 residing in urban Adelaide, Australia, were randomly assigned to a control group or one of 4 interventions: (1) Web-based and tailored information, (2) paper-based and tailored information, (3) Web-based and non-tailored (generic) information, or (4) paper-based and non-tailored information. Participation was augmented by snowball recruitment (n = 19). Questionnaires based on PHM variables were administered pre- and post-intervention. Participants were given the opportunity to request an FOBT. Following the intervention, participants discussed the acceptability of the tool. Results Full data were available for 87.4% (104/119) of participants. Post-intervention, perceived susceptibility scores for individuals receiving tailored information increased from mean 10.6 (SD 2.1) to mean 11.8 (SD 2.2). Scores on self-efficacy increased in the tailored group from mean 11.7 (SD 2.0) to mean 12.6 (SD 1.8). There were significant time x modality x message effects for social influence and salience and coherence, reflecting an increase in these scores for tailored Web-based participants only; social influence scores increased from mean 11.7 (SD 2.6) to mean 14.9 (SD 2.3), and salience and coherence scores increased from mean 16.0 (SD 2.2) to mean 17.7 (SD 2.1). There was no greater influence of modality or message type on movement toward a decision to screen or screening uptake, indicating that neither tailored messages nor a Web modality had superior effect. Overall, participants regarded tailored messages positively, but thought that the Web tool lacked “media richness.” Conclusions This exploratory study confirms that tailoring on PHM predictors of CRC screening has the potential to positively address attitudes toward screening. However, tailoring on these variables did not result in significantly increased screening uptake. Future research should consider other possible psychosocial influences. Mode of delivery did not affect outcomes, but as a delivery medium, the Web has economic and logistical advantages over paper. PMID:23611950

Inefficiencies and high-value improvements in U.S. cervical cancer screening practice: A cost-effectiveness analysis

PubMed Central

Kim, Jane J.; Campos, Nicole G.; Sy, Stephen; Burger, Emily A.; Cuzick, Jack; Castle, Philip E.; Hunt, William C.; Waxman, Alan; Wheeler, Cosette M.

2016-01-01

Background Studies suggest that cervical cancer screening practice in the United States is inefficient. The cost and health implications of non-compliance in the screening process compared to recommended guidelines are uncertain. Objective To estimate the benefits, costs, and cost-effectiveness of current cervical cancer screening practice and assess the value of screening improvements. Design Model-based cost-effectiveness analysis. Data Sources New Mexico HPV Pap Registry; medical literature. Target Population Cohort of women eligible for routine screening. Time Horizon Lifetime. Perspective Societal. Interventions Current cervical cancer screening practice; improved compliance to guidelines-based screening interval, triage testing, diagnostic referrals, and precancer treatment referrals. Outcome Measures Reductions in lifetime cervical cancer risk, quality-adjusted life-years (QALYs), lifetime costs, incremental cost-effectiveness ratios (ICERs), incremental net monetary benefits (INMBs Results of Base-Case Analysis Current screening practice was associated with lower health benefit and was not cost-effective relative to guidelines-based strategies. Improvements in the screening process were associated with higher QALYs and small changes in costs. Perfect c4mpliance to a 3-yearly screening interval and to colposcopy/biopsy referrals were associated with the highest INMBs ($759 and $741, respectively, at a willingness-to-pay threshold of $100,000 per QALY gained); together, the INMB increased to $1,645. Results of Sensitivity Analysis Current screening practice was inefficient in 100% of simulations. The rank ordering of screening improvements according to INMBs was stable over a range of screening inputs and willingness-to-pay thresholds. Limitations The impact of HPV vaccination was not considered. Conclusions The added health benefit of improving compliance to guidelines, especially the 3-yearly interval for cytology screening and diagnostic follow-up, may justify additional investments in interventions to improve U.S. cervical cancer screening practice. Funding Source U.S. National Cancer Institute. PMID:26414147

Cost-effectiveness of WHO-Recommended Algorithms for TB Case Finding at Ethiopian HIV Clinics.

PubMed

Adelman, Max W; McFarland, Deborah A; Tsegaye, Mulugeta; Aseffa, Abraham; Kempker, Russell R; Blumberg, Henry M

2018-01-01

The World Health Organization (WHO) recommends active tuberculosis (TB) case finding and a rapid molecular diagnostic test (Xpert MTB/RIF) to detect TB among people living with HIV (PLHIV) in high-burden settings. Information on the cost-effectiveness of these recommended strategies is crucial for their implementation. We conducted a model-based cost-effectiveness analysis comparing 2 algorithms for TB screening and diagnosis at Ethiopian HIV clinics: (1) WHO-recommended symptom screen combined with Xpert for PLHIV with a positive symptom screen and (2) current recommended practice algorithm (CRPA; based on symptom screening, smear microscopy, and clinical TB diagnosis). Our primary outcome was US$ per disability-adjusted life-year (DALY) averted. Secondary outcomes were additional true-positive diagnoses, and false-negative and false-positive diagnoses averted. Compared with CRPA, combining a WHO-recommended symptom screen with Xpert was highly cost-effective (incremental cost of $5 per DALY averted). Among a cohort of 15 000 PLHIV with a TB prevalence of 6% (900 TB cases), this algorithm detected 8 more true-positive cases than CRPA, and averted 2045 false-positive and 8 false-negative diagnoses compared with CRPA. The WHO-recommended algorithm was marginally costlier ($240 000) than CRPA ($239 000). In sensitivity analysis, the symptom screen/Xpert algorithm was dominated at low Xpert sensitivity (66%). In this model-based analysis, combining a WHO-recommended symptom screen with Xpert for TB diagnosis among PLHIV was highly cost-effective ($5 per DALY averted) and more sensitive than CRPA in a high-burden, resource-limited setting.

Longitudinal evaluation of physician payment reform and team-based care for chronic disease management and prevention.

PubMed

Kiran, Tara; Kopp, Alexander; Moineddin, Rahim; Glazier, Richard H

2015-11-17

We evaluated a large-scale transition of primary care physicians to blended capitation models and team-based care in Ontario, Canada, to understand the effect of each type of reform on the management and prevention of chronic disease. We used population-based administrative data to assess monitoring of diabetes mellitus and screening for cervical, breast and colorectal cancer among patients belonging to team-based capitation, non-team-based capitation or enhanced fee-for-service medical homes as of Mar. 31, 2011 (n = 10 675 480). We used Poisson regression models to examine these associations for 2011. We then used a fitted nonlinear model to compare changes in outcomes between 2001 and 2011 by type of medical home. In 2011, patients in a team-based capitation setting were more likely than those in an enhanced fee-for-service setting to receive diabetes monitoring (39.7% v. 31.6%, adjusted relative risk [RR] 1.22, 95% confidence interval [CI] 1.18 to 1.25), mammography (76.6% v. 71.5%, adjusted RR 1.06, 95% CI 1.06 to 1.07) and colorectal cancer screening (63.0% v. 60.9%, adjusted RR 1.03, 95% CI 1.02 to 1.04). Over time, patients in medical homes with team-based capitation experienced the greatest improvement in diabetes monitoring (absolute difference in improvement 10.6% [95% CI 7.9% to 13.2%] compared with enhanced fee for service; 6.4% [95% CI 3.8% to 9.1%] compared with non-team-based capitation) and cervical cancer screening (absolute difference in improvement 7.0% [95% CI 5.5% to 8.5%] compared with enhanced fee for service; 5.3% [95% CI 3.8% to 6.8%] compared with non-team-based capitation). For breast and colorectal cancer screening, there were no significant differences in change over time between different types of medical homes. The shift to capitation payment and the addition of team-based care in Ontario were associated with moderate improvements in processes related to diabetes care, but the effects on cancer screening were less clear. © 2015 Canadian Medical Association or its licensors.

Modeling the Dynamics of High-Grade Serous Ovarian Cancer Progression for Transvaginal Ultrasound-Based Screening and Early Detection

PubMed Central

Lee, Jung-Min; Levy, Doron

2016-01-01

High-grade serous ovarian cancer (HGSOC) represents the majority of ovarian cancers and accounts for the largest proportion of deaths from the disease. A timely detection of low volume HGSOC should be the goal of any screening studies. However, numerous transvaginal ultrasound (TVU) detection-based population studies aimed at detecting low-volume disease have not yielded reduced mortality rates. A quantitative invalidation of TVU as an effective HGSOC screening strategy is a necessary next step. Herein, we propose a mathematical model for a quantitative explanation on the reported failure of TVU-based screening to improve HGSOC low-volume detectability and overall survival.We develop a novel in silico mathematical assessment of the efficacy of a unimodal TVU monitoring regimen as a strategy aimed at detecting low-volume HGSOC in cancer-positive cases, defined as cases for which the inception of the first malignant cell has already occurred. Our findings show that the median window of opportunity interval length for TVU monitoring and HGSOC detection is approximately 1.76 years. This does not translate into reduced mortality levels or improved detection accuracy in an in silico cohort across multiple TVU monitoring frequencies or detection sensitivities. We demonstrate that even a semiannual, unimodal TVU monitoring protocol is expected to miss detectable HGSOC. Lastly, we find that circa 50% of the simulated HGSOC growth curves never reach the baseline detectability threshold, and that on average, 5–7 infrequent, rate-limiting stochastic changes in the growth parameters are associated with reaching HGSOC detectability and mortality thresholds respectively. Focusing on a malignancy poorly studied in the mathematical oncology community, our model captures the dynamic, temporal evolution of HGSOC progression. Our mathematical model is consistent with recent case reports and prospective TVU screening population studies, and provides support to the empirical recommendation against frequent HGSOC screening. PMID:27257824

A Nonlinear Regression Model Estimating Single Source Concentrations of Primary and Secondarily Formed 2.5

EPA Science Inventory

Various approaches and tools exist to estimate local and regional PM_2.5 impacts from a single emissions source, ranging from simple screening techniques to Gaussian based dispersion models and complex grid-based Eulerian photochemical transport models. These approache...

Identifying Structural Alerts Based on Zebrafish Developmental Morphological Toxicity (TDS)

EPA Science Inventory

Zebrafish constitute a powerful alternative animal model for chemical hazard evaluation. To provide an in vivo complement to high-throughput screening data from the ToxCast program, zebrafish developmental toxicity screens were conducted on the ToxCast Phase I (Padilla et al., 20...

AOPs and Biomarkers: Bridging High Throughput Screening and Regulatory Decision Making

EPA Science Inventory

As high throughput screening (HTS) plays a larger role in toxicity testing, camputational toxicology has emerged as a critical component in interpreting the large volume of data produced. Computational models designed to quantify potential adverse effects based on HTS data will b...

Using handgrip strength to screen for diabetes in developing countries.

PubMed

Eckman, Molly; Gigliotti, Christopher; Sutermaster, Staci; Butler, Peter J; Mehta, Khanjan

2016-01-01

Lack of access to healthcare in the developing world has created a need for locally-based primary and pre-primary healthcare systems. Many regions of the world have adopted Community Health Worker (CHW) programmes, but volunteers in these programmes lack the tools and resources to screen for disease. Because of its simplicity of operation, handgrip strength (HGS) measurements have the potential to be an affordable and effective screening tool for conditions that cause muscle weakness in this context. In the study described in this report, translators were used to collect data on age, gender, height, weight, blood pressure, HGS and key demographic data. HGS was significantly lower for diabetics than patients without diabetes. A simple binary logistic model was created that used HGS, age, blood pressure and BMI to predict a patient's probability of having diabetes. This study develops a predictive model for diabetes using HGS and other basic health measurements and shows that HGS-based screening is a viable method of early detection of diabetes.

Identification of novel antitubulin agents by using a virtual screening approach based on a 7-point pharmacophore model of the tubulin colchi-site.

PubMed

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.

Pharmacophore Models and Pharmacophore-Based Virtual Screening: Concepts and Applications Exemplified on Hydroxysteroid Dehydrogenases.

PubMed

Kaserer, Teresa; Beck, Katharina R; Akram, Muhammad; Odermatt, Alex; Schuster, Daniela

2015-12-19

Computational methods are well-established tools in the drug discovery process and can be employed for a variety of tasks. Common applications include lead identification and scaffold hopping, as well as lead optimization by structure-activity relationship analysis and selectivity profiling. In addition, compound-target interactions associated with potentially harmful effects can be identified and investigated. This review focuses on pharmacophore-based virtual screening campaigns specifically addressing the target class of hydroxysteroid dehydrogenases. Many members of this enzyme family are associated with specific pathological conditions, and pharmacological modulation of their activity may represent promising therapeutic strategies. On the other hand, unintended interference with their biological functions, e.g., upon inhibition by xenobiotics, can disrupt steroid hormone-mediated effects, thereby contributing to the development and progression of major diseases. Besides a general introduction to pharmacophore modeling and pharmacophore-based virtual screening, exemplary case studies from the field of short-chain dehydrogenase/reductase (SDR) research are presented. These success stories highlight the suitability of pharmacophore modeling for the various application fields and suggest its application also in futures studies.

Enhancing HIV Testing and Treatment among Men Who Have Sex with Men in China: A Pilot Model with Two-Rapid Tests, Single Blood Draw Session, and Intensified Case Management in Six Cities in 2013.

PubMed

Zhang, Dapeng; Lu, Hongyan; Zhuang, Minghua; Wu, Guohui; Yan, Hongjing; Xu, Jun; Wei, Xiaoli; Li, Chengmei; Meng, Sining; Fu, Xiaojing; Qi, Jinlei; Wang, Peng; Luo, Mei; Dai, Min; Yip, Ray; Sun, Jiangping; Wu, Zunyou

2016-01-01

To explore models to improve HIV testing, linkage to care and treatment among men who have sex with men (MSM) in cooperation with community-based organizations (CBOs) in China. We introduced a new model for HIV testing services targeting MSM in six cities in 2013.These models introduced provision of rapid HIV testing by CBO staff and streamlined processes for HIV screening, confirmation of initial reactive screening results, and linkage to care among diagnosed people. We monitored attrition along each step of the continuum of care from screening to treatment and compared program performance between 2012 and 2013. According to the providers of two rapid tests (HIV screening), four different services delivery models were examined in 2013: Model A = first screen at CDC, second at CDC (Model A = CDC+CDC), Model B = first and second screens at CBOs (Model B = CBO+CBO), Model C = first screen at CBO, second at Hospital (Model C = CBO+Hosp), and Model D = first screen at CBO, second at CDC (Model D = CBO+CDC). Logistic regressions were performed to assess advantages of different screening models of case finding and case management. Compared to 2012, the number of HIV screening tests performed for MSM increased 35.8% in 2013 (72,577 in 2013 vs. 53,455 in 2012). We observed a 5.6% increase in proportion of cases screened reactive receiving HIV confirmatory tests (93.9% in 2013 vs. 89.2% in 2012, χ2 = 48.52, p<0.001) and 65% reduction in loss to CD4 cell count tests (15% in 2013 vs. 43% in 2012, χ2 = 628.85, p<0.001). Regarding linkage to care and treatment, the 2013 pilot showed that the Model D had the highest rate of loss between screening reactive and confirmatory test among the four models, with 18.1% fewer receiving a second screening test and a further 5.9% loss among those receiving HIV confirmatory tests. The Model B and the Model C showed lower losses (0.8% and 1.3%) for newly diagnosed HIV positives receiving CD4 cell count tests, and higher rates of HIV positives referred to designated ART hospitals (88.0% and 93.3%) than the Model A and Model D (4.6% and 5.7% for CD4 cell count test, and 68.9% and 64.4% for referring to designated ART hospitals). The proportion of cases where the screening test was reactive that were commenced on ART was highest in Model C; 52.8% of cases commenced on ART compared to 38.9%, 34.2% and 21.1% in Models A, B and D respectively. Using Model A as a reference group, the multivariate logistic regression results also showed the advantages of Models B, C and D, which increased CD4 cell count test, referral to designated ART hospitals and initiation of ART, when controlling for program city and other factors. This study has demonstrated that involvement of CBOs in HIV rapid testing provision, streamlining testing and care procedures and early hospital case management can improve testing, linkage to, and retention in care and treatment among MSM in China.

DNA from fecal immunochemical test can replace stool for detection of colonic lesions using a microbiota-based model.

PubMed

Baxter, Nielson T; Koumpouras, Charles C; Rogers, Mary A M; Ruffin, Mack T; Schloss, Patrick D

2016-11-14

There is a significant demand for colorectal cancer (CRC) screening methods that are noninvasive, inexpensive, and capable of accurately detecting early stage tumors. It has been shown that models based on the gut microbiota can complement the fecal occult blood test and fecal immunochemical test (FIT). However, a barrier to microbiota-based screening is the need to collect and store a patient's stool sample. Using stool samples collected from 404 patients, we tested whether the residual buffer containing resuspended feces in FIT cartridges could be used in place of intact stool samples. We found that the bacterial DNA isolated from FIT cartridges largely recapitulated the community structure and membership of patients' stool microbiota and that the abundance of bacteria associated with CRC were conserved. We also found that models for detecting CRC that were generated using bacterial abundances from FIT cartridges were equally predictive as models generated using bacterial abundances from stool. These findings demonstrate the potential for using residual buffer from FIT cartridges in place of stool for microbiota-based screening for CRC. This may reduce the need to collect and process separate stool samples and may facilitate combining FIT and microbiota-based biomarkers into a single test. Additionally, FIT cartridges could constitute a novel data source for studying the role of the microbiome in cancer and other diseases.

Performance and Cost-Effectiveness of Computed Tomography Lung Cancer Screening Scenarios in a Population-Based Setting: A Microsimulation Modeling Analysis in Ontario, Canada.

PubMed

Ten Haaf, Kevin; Tammemägi, Martin C; Bondy, Susan J; van der Aalst, Carlijn M; Gu, Sumei; McGregor, S Elizabeth; Nicholas, Garth; de Koning, Harry J; Paszat, Lawrence F

2017-02-01

The National Lung Screening Trial (NLST) results indicate that computed tomography (CT) lung cancer screening for current and former smokers with three annual screens can be cost-effective in a trial setting. However, the cost-effectiveness in a population-based setting with >3 screening rounds is uncertain. Therefore, the objective of this study was to estimate the cost-effectiveness of lung cancer screening in a population-based setting in Ontario, Canada, and evaluate the effects of screening eligibility criteria. This study used microsimulation modeling informed by various data sources, including the Ontario Health Insurance Plan (OHIP), Ontario Cancer Registry, smoking behavior surveys, and the NLST. Persons, born between 1940 and 1969, were examined from a third-party health care payer perspective across a lifetime horizon. Starting in 2015, 576 CT screening scenarios were examined, varying by age to start and end screening, smoking eligibility criteria, and screening interval. Among the examined outcome measures were lung cancer deaths averted, life-years gained, percentage ever screened, costs (in 2015 Canadian dollars), and overdiagnosis. The results of the base-case analysis indicated that annual screening was more cost-effective than biennial screening. Scenarios with eligibility criteria that required as few as 20 pack-years were dominated by scenarios that required higher numbers of accumulated pack-years. In general, scenarios that applied stringent smoking eligibility criteria (i.e., requiring higher levels of accumulated smoking exposure) were more cost-effective than scenarios with less stringent smoking eligibility criteria, with modest differences in life-years gained. Annual screening between ages 55-75 for persons who smoked ≥40 pack-years and who currently smoke or quit ≤10 y ago yielded an incremental cost-effectiveness ratio of $41,136 Canadian dollars ($33,825 in May 1, 2015, United States dollars) per life-year gained (compared to annual screening between ages 60-75 for persons who smoked ≥40 pack-years and who currently smoke or quit ≤10 y ago), which was considered optimal at a cost-effectiveness threshold of $50,000 Canadian dollars ($41,114 May 1, 2015, US dollars). If 50% lower or higher attributable costs were assumed, the incremental cost-effectiveness ratio of this scenario was estimated to be $38,240 ($31,444 May 1, 2015, US dollars) or $48,525 ($39,901 May 1, 2015, US dollars), respectively. If 50% lower or higher costs for CT examinations were assumed, the incremental cost-effectiveness ratio of this scenario was estimated to be $28,630 ($23,542 May 1, 2015, US dollars) or $73,507 ($60,443 May 1, 2015, US dollars), respectively. This scenario would screen 9.56% (499,261 individuals) of the total population (ever- and never-smokers) at least once, which would require 4,788,523 CT examinations, and reduce lung cancer mortality in the total population by 9.05% (preventing 13,108 lung cancer deaths), while 12.53% of screen-detected cancers would be overdiagnosed (4,282 overdiagnosed cases). Sensitivity analyses indicated that the overall results were most sensitive to variations in CT examination costs. Quality of life was not incorporated in the analyses, and assumptions for follow-up procedures were based on data from the NLST, which may not be generalizable to a population-based setting. Lung cancer screening with stringent smoking eligibility criteria can be cost-effective in a population-based setting.

Data Sources for the Model-based Small Area Estimates of Cancer-Related Knowledge - Small Area Estimates

Cancer.gov

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

Nonbleeding adenomas: Evidence of systematic false-negative fecal immunochemical test results and their implications for screening effectiveness-A modeling study.

PubMed

van der Meulen, Miriam P; Lansdorp-Vogelaar, Iris; van Heijningen, Else-Mariëtte B; Kuipers, Ernst J; van Ballegooijen, Marjolein

2016-06-01

If some adenomas do not bleed over several years, they will cause systematic false-negative fecal immunochemical test (FIT) results. The long-term effectiveness of FIT screening has been estimated without accounting for such systematic false-negativity. There are now data with which to evaluate this issue. The authors developed one microsimulation model (MISCAN [MIcrosimulation SCreening ANalysis]-Colon) without systematic false-negative FIT results and one model that allowed a percentage of adenomas to be systematically missed in successive FIT screening rounds. Both variants were adjusted to reproduce the first-round findings of the Dutch CORERO FIT screening trial. The authors then compared simulated detection rates in the second screening round with those observed, and adjusted the simulated percentage of systematically missed adenomas to those data. Finally, the authors calculated the impact of systematic false-negative FIT results on the effectiveness of repeated FIT screening. The model without systematic false-negativity simulated higher detection rates in the second screening round than observed. These observed rates could be reproduced when assuming that FIT systematically missed 26% of advanced and 73% of nonadvanced adenomas. To reduce the false-positive rate in the second round to the observed level, the authors also had to assume that 30% of false-positive findings were systematically false-positive. Systematic false-negative FIT testing limits the long-term reduction of biennial FIT screening in the incidence of colorectal cancer (35.6% vs 40.9%) and its mortality (55.2% vs 59.0%) in participants. The results of the current study provide convincing evidence based on the combination of real-life and modeling data that a percentage of adenomas are systematically missed by repeat FIT screening. This impairs the efficacy of FIT screening. Cancer 2016;122:1680-8. © 2016 American Cancer Society. © 2016 American Cancer Society.

Navy Fuel Composition and Screening Tool (FCAST) v2.8

DTIC Science & Technology

2016-05-10

allowed us to develop partial least squares (PLS) models based on gas chromatography–mass spectrometry (GC-MS) data that predict fuel properties. The...Chemometric property modeling Partial least squares PLS Compositional profiler Naval Air Systems Command Air-4.4.5 Patuxent River Naval Air Station Patuxent...Cumulative predicted residual error sum of squares DiEGME Diethylene glycol monomethyl ether FCAST Fuel Composition and Screening Tool FFP Fit for

Impact of fecal immunochemical test-based screening programs on proximal and distal colorectal cancer surgery rates: A natural multiple-baseline experiment.

PubMed

Fedeli, Ugo; Zorzi, Manuel; Urso, Emanuele D L; Gennaro, Nicola; Dei Tos, Angelo P; Saugo, Mario

2015-11-15

Colorectal cancer (CRC) screening programs based on the fecal immunochemical test (FIT) were found to reduce overall CRC surgery rates, but to the authors' knowledge data by subsite are lacking. The objective of the current study was to assess the impact of FIT-based screening on proximal and distal CRC surgical resection rates. The Veneto region in Italy can be subdivided into 3 areas with staggered introduction of FIT-based screening programs: early (2002-2004), intermediate (2005-2007), and late (2008-2009) areas. Time series of proximal and distal CRC surgery were investigated in the 3 populations between 2001 and 2012 by Joinpoint regression analysis and segmented Poisson regression models. The impact of screening was similar in the study populations. Rates of distal CRC surgical resection were stable before screening, increased at the time of screening implementation (rate ratio [RR], 1.25; 95% confidence interval [95% CI], 1.14-1.37), and thereafter declined by 10% annually (RR, 0.90; 95% CI, 0.88-0.92). Rates of proximal CRC surgical resection increased by 4% annually before screening (RR, 1.04; 95% CI, 1.03-1.05) but, after a peak at the time of screening initiation, the trend was reversed. The percentage represented by proximal CRC surgery rose from 28% in 2001 to 41% in 2012. In this natural multiple-baseline experiment, consistent findings across each time series demonstrated that FIT-based screening programs have an impact both on proximal and distal CRC surgery rates. However, underlying preexisting epidemiological trends are leading to a rapidly increasing percentage of proximal CRC. © 2015 American Cancer Society.

Applying under-sampling techniques and cost-sensitive learning methods on risk assessment of breast cancer.

PubMed

Hsu, Jia-Lien; Hung, Ping-Cheng; Lin, Hung-Yen; Hsieh, Chung-Ho

2015-04-01

Breast cancer is one of the most common cause of cancer mortality. Early detection through mammography screening could significantly reduce mortality from breast cancer. However, most of screening methods may consume large amount of resources. We propose a computational model, which is solely based on personal health information, for breast cancer risk assessment. Our model can be served as a pre-screening program in the low-cost setting. In our study, the data set, consisting of 3976 records, is collected from Taipei City Hospital starting from 2008.1.1 to 2008.12.31. Based on the dataset, we first apply the sampling techniques and dimension reduction method to preprocess the testing data. Then, we construct various kinds of classifiers (including basic classifiers, ensemble methods, and cost-sensitive methods) to predict the risk. The cost-sensitive method with random forest classifier is able to achieve recall (or sensitivity) as 100 %. At the recall of 100 %, the precision (positive predictive value, PPV), and specificity of cost-sensitive method with random forest classifier was 2.9 % and 14.87 %, respectively. In our study, we build a breast cancer risk assessment model by using the data mining techniques. Our model has the potential to be served as an assisting tool in the breast cancer screening.

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

PubMed

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

2017-02-01

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

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

PubMed

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

2014-07-01

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

Putting newborn hearing screening on the political agenda in Belgium: local initiatives toward a community programme – a qualitative study

PubMed Central

2014-01-01

Background The Kingdon model, based on the convergence of three streams (problem, policy, and politics) and the opening of a policy window, analyses the process by which a health issue is placed on the political agenda. We used this model to document the political agenda-setting process of the newborn hearing screening programme in Belgium. Methods A qualitative study based on a document review and on semi-directed interviews was carried out. The interviews were conducted with nine people who had played a role in putting the issue in question on the political agenda, and the documents reviewed included scientific literature and internal reports and publications from the newborn hearing screening programme. The thematic analysis of the data collected was carried out on the basis of the Kingdon model’s three streams. Results The political agenda-setting of this screening programme was based on many factors. The problem stream included factors external to the context under study, such as the technological developments and the contribution of the scientific literature which led to the recommendation to provide newborn hearing screening. The two other streams (policy and politics) covered factors internal to the Belgian context. The fact that it was locally feasible with financial support, the network of doctors convinced of the need for newborn hearing screening, the drafting of various proposals, and the search for financing were all part of the policy stream. The Belgian political context and the policy opportunities concerning preventive medicine were identified as significant factors in the third stream. When these three streams converged, a policy window opened, allowing newborn hearing screening onto the political agenda and enabling the policy decision for its introduction. Conclusions The advantage of applying the Kingdon model in our approach was the ability to demonstrate the political agenda-setting process, using the three streams. This made it possible to identify the many factors involved in the process. However, the roles of the stakeholders and of the context were somewhat inexplicit in this model. PMID:24986647

Ligand efficiency based approach for efficient virtual screening of compound libraries.

PubMed

Ke, Yi-Yu; Coumar, Mohane Selvaraj; Shiao, Hui-Yi; Wang, Wen-Chieh; Chen, Chieh-Wen; Song, Jen-Shin; Chen, Chun-Hwa; Lin, Wen-Hsing; Wu, Szu-Huei; Hsu, John T A; Chang, Chung-Ming; Hsieh, Hsing-Pang

2014-08-18

Here we report for the first time the use of fit quality (FQ), a ligand efficiency (LE) based measure for virtual screening (VS) of compound libraries. The LE based VS protocol was used to screen an in-house database of 125,000 compounds to identify aurora kinase A inhibitors. First, 20 known aurora kinase inhibitors were docked to aurora kinase A crystal structure (PDB ID: 2W1C); and the conformations of docked ligand were used to create a pharmacophore (PH) model. The PH model was used to screen the database compounds, and rank (PH rank) them based on the predicted IC50 values. Next, LE_Scale, a weight-dependant LE function, was derived from 294 known aurora kinase inhibitors. Using the fit quality (FQ = LE/LE_Scale) score derived from the LE_Scale function, the database compounds were reranked (PH_FQ rank) and the top 151 (0.12% of database) compounds were assessed for aurora kinase A inhibition biochemically. This VS protocol led to the identification of 7 novel hits, with compound 5 showing aurora kinase A IC50 = 1.29 μM. Furthermore, testing of 5 against a panel of 31 kinase reveals that it is selective toward aurora kinase A & B, with <50% inhibition for other kinases at 10 μM concentrations and is a suitable candidate for further development. Incorporation of FQ score in the VS protocol not only helped identify a novel aurora kinase inhibitor, 5, but also increased the hit rate of the VS protocol by improving the enrichment factor (EF) for FQ based screening (EF = 828), compared to PH based screening (EF = 237) alone. The LE based VS protocol disclosed here could be applied to other targets for hit identification in an efficient manner. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

A Systematic Strategy for Screening and Application of Specific Biomarkers in Hepatotoxicity Using Metabolomics Combined With ROC Curves and SVMs.

PubMed

Li, Yubo; Wang, Lei; Ju, Liang; Deng, Haoyue; Zhang, Zhenzhu; Hou, Zhiguo; Xie, Jiabin; Wang, Yuming; Zhang, Yanjun

2016-04-01

Current studies that evaluate toxicity based on metabolomics have primarily focused on the screening of biomarkers while largely neglecting further verification and biomarker applications. For this reason, we used drug-induced hepatotoxicity as an example to establish a systematic strategy for screening specific biomarkers and applied these biomarkers to evaluate whether the drugs have potential hepatotoxicity toxicity. Carbon tetrachloride (5 ml/kg), acetaminophen (1500 mg/kg), and atorvastatin (5 mg/kg) are established as rat hepatotoxicity models. Fifteen common biomarkers were screened by multivariate statistical analysis and integration analysis-based metabolomics data. The receiver operating characteristic curve was used to evaluate the sensitivity and specificity of the biomarkers. We obtained 10 specific biomarker candidates with an area under the curve greater than 0.7. Then, a support vector machine model was established by extracting specific biomarker candidate data from the hepatotoxic drugs and nonhepatotoxic drugs; the accuracy of the model was 94.90% (92.86% sensitivity and 92.59% specificity) and the results demonstrated that those ten biomarkers are specific. 6 drugs were used to predict the hepatotoxicity by the support vector machines model; the prediction results were consistent with the biochemical and histopathological results, demonstrating that the model was reliable. Thus, this support vector machine model can be applied to discriminate the between the hepatic or nonhepatic toxicity of drugs. This approach not only presents a new strategy for screening-specific biomarkers with greater diagnostic significance but also provides a new evaluation pattern for hepatotoxicity, and it will be a highly useful tool in toxicity estimation and disease diagnoses. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Cardiovascular Disease Screening By Community Health Workers Can Be Cost-Effective In Low-Resource Countries.

PubMed

Gaziano, Thomas; Abrahams-Gessel, Shafika; Surka, Sam; Sy, Stephen; Pandya, Ankur; Denman, Catalina A; Mendoza, Carlos; Puoane, Thandi; Levitt, Naomi S

2015-09-01

In low-resource settings, a physician is not always available. We recently demonstrated that community health workers-instead of physicians or nurses-can efficiently screen adults for cardiovascular disease in South Africa, Mexico, and Guatemala. In this analysis we sought to determine the health and economic impacts of shifting this screening to community health workers equipped with either a paper-based or a mobile phone-based screening tool. We found that screening by community health workers was very cost-effective or even cost-saving in all three countries, compared to the usual clinic-based screening. The mobile application emerged as the most cost-effective strategy because it could save more lives than the paper tool at minimal extra cost. Our modeling indicated that screening by community health workers, combined with improved treatment rates, would increase the number of deaths averted from 15,000 to 110,000, compared to standard care. Policy makers should promote greater acceptance of community health workers by both national populations and health professionals and should increase their commitment to treating cardiovascular disease and making medications available. Project HOPE—The People-to-People Health Foundation, Inc.

High-Throughput Screening by Nuclear Magnetic Resonance (HTS by NMR) for the Identification of PPIs Antagonists.

PubMed

Wu, Bainan; Barile, Elisa; De, Surya K; Wei, Jun; Purves, Angela; Pellecchia, Maurizio

2015-01-01

In recent years the ever so complex field of drug discovery has embraced novel design strategies based on biophysical fragment screening (fragment-based drug design; FBDD) using nuclear magnetic resonance spectroscopy (NMR) and/or structure-guided approaches, most often using X-ray crystallography and computer modeling. Experience from recent years unveiled that these methods are more effective and less prone to artifacts compared to biochemical high-throughput screening (HTS) of large collection of compounds in designing protein inhibitors. Hence these strategies are increasingly becoming the most utilized in the modern pharmaceutical industry. Nonetheless, there is still an impending need to develop innovative and effective strategies to tackle other more challenging targets such as those involving protein-protein interactions (PPIs). While HTS strategies notoriously fail to identify viable hits against such targets, few successful examples of PPIs antagonists derived by FBDD strategies exist. Recently, we reported on a new strategy that combines some of the basic principles of fragment-based screening with combinatorial chemistry and NMR-based screening. The approach, termed HTS by NMR, combines the advantages of combinatorial chemistry and NMR-based screening to rapidly and unambiguously identify bona fide inhibitors of PPIs. This review will reiterate the critical aspects of the approach with examples of possible applications.

High-throughput screening by Nuclear Magnetic Resonance (HTS by NMR) for the identification of PPIs antagonists

PubMed Central

Wu, Bainan; Barile, Elisa; De, Surya K.; Wei, Jun; Purves, Angela; Pellecchia, Maurizio

2015-01-01

In recent years the ever so complex field of drug discovery has embraced novel design strategies based on biophysical fragment screening (fragment-based drug design; FBDD) using nuclear magnetic resonance spectroscopy (NMR) and/or structure-guided approaches, most often using X-ray crystallography and computer modeling. Experience from recent years unveiled that these methods are more effective and less prone to artifacts compared to biochemical high-throughput screening (HTS) of large collection of compounds in designing protein inhibitors. Hence these strategies are increasingly becoming the most utilized in the modern pharmaceutical industry. Nonetheless, there is still an impending need to develop innovative and effective strategies to tackle other more challenging targets such as those involving protein-protein interactions (PPIs). While HTS strategies notoriously fail to identify viable hits against such targets, few successful examples of PPIs antagonists derived by FBDD strategies exist. Recently, we reported on a new strategy that combines some of the basic principles of fragment-based screening with combinatorial chemistry and NMR-based screening. The approach, termed HTS by NMR, combines the advantages of combinatorial chemistry and NMR-based screening to rapidly and unambiguously identify bona fide inhibitors of PPIs. This review will reiterate the critical aspects of the approach with examples of possible applications. PMID:25986689

Cost-effectiveness of breast cancer screening policies using simulation.

PubMed

Gocgun, Y; Banjevic, D; Taghipour, S; Montgomery, N; Harvey, B J; Jardine, A K S; Miller, A B

2015-08-01

In this paper, we study breast cancer screening policies using computer simulation. We developed a multi-state Markov model for breast cancer progression, considering both the screening and treatment stages of breast cancer. The parameters of our model were estimated through data from the Canadian National Breast Cancer Screening Study as well as data in the relevant literature. Using computer simulation, we evaluated various screening policies to study the impact of mammography screening for age-based subpopulations in Canada. We also performed sensitivity analysis to examine the impact of certain parameters on number of deaths and total costs. The analysis comparing screening policies reveals that a policy in which women belonging to the 40-49 age group are not screened, whereas those belonging to the 50-59 and 60-69 age groups are screened once every 5 years, outperforms others with respect to cost per life saved. Our analysis also indicates that increasing the screening frequencies for the 50-59 and 60-69 age groups decrease mortality, and that the average number of deaths generally decreases with an increase in screening frequency. We found that screening annually for all age groups is associated with the highest costs per life saved. Our analysis thus reveals that cost per life saved increases with an increase in screening frequency. Copyright © 2015 Elsevier Ltd. All rights reserved.

QUANTITATIVE IN VITRO MEASUREMENT OF CELLULAR PROCESSES CRITICAL TO THE DEVELOPMENT OF NEURAL CONNECTIVITY USING HCA.

EPA Science Inventory

New methods are needed to screen thousands of environmental chemicals for toxicity, including developmental neurotoxicity. In vitro, cell-based assays that model key cellular events have been proposed for high throughput screening of chemicals for developmental neurotoxicity. Whi...

ASSESSMENT OF SYNAPSE FORMATION IN RAT PRIMARY NEURAL CELL CULTURE USING HIGH CONTENT MICROSCOPY.

EPA Science Inventory

Cell-based assays can model neurodevelopmental processes including neurite growth and synaptogenesis, and may be useful for screening and evaluation of large numbers of chemicals for developmental neurotoxicity. This work describes the use of high content screening (HCS) to dete...

A web-based screening tool for near-port air quality assessments

EPA Science Inventory

The Community model for near-PORT applications (C-PORT) is a screening tool with an intended purpose of calculating differences in annual averaged concentration patterns and relative contributions of various source categories over the spatial domain within about 10 km of the port...

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

PubMed

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

2015-01-20

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

Holistic computational structure screening of more than 12,000 candidates for solid lithium-ion conductor materials

NASA Astrophysics Data System (ADS)

Sendek, Austin D.; Yang, Qian; Cubuk, Ekin D.; Duerloo, Karel-Alexander N.; Cui, Yi; Reed, Evan J.

We present a new type of large-scale computational screening approach for identifying promising candidate materials for solid state electrolytes for lithium ion batteries that is capable of screening all known lithium containing solids. To predict the likelihood of a candidate material exhibiting high lithium ion conductivity, we leverage machine learning techniques to train an ionic conductivity classification model using logistic regression based on experimental measurements reported in the literature. This model, which is built on easily calculable atomistic descriptors, provides new insight into the structure-property relationship for superionic behavior in solids and is approximately one million times faster to evaluate than DFT-based approaches to calculating diffusion coefficients or migration barriers. We couple this model with several other technologically motivated heuristics to reduce the list of candidate materials from the more than 12,000 known lithium containing solids to 21 structures that show promise as electrolytes, few of which have been examined experimentally. Our screening utilizes structures and electronic information contained in the Materials Project database. This work is supported by an Office of Technology Licensing Fellowship through the Stanford Graduate Fellowship Program and a seed Grant from the TomKat Center for Sustainable Energy at Stanford.

Interprofessional Peer-Assisted Learning as a Model of Instruction in Doctor of Audiology Programs.

PubMed

Serpanos, Yula C; Senzer, Deborah; Gordon, Daryl M

2017-09-18

This study reports on interprofessional peer-assisted learning (PAL) as a model of instruction in the preparation of doctoral audiology students. Ten Doctor of Audiology (AuD) students provided training in audiologic screening for 53 graduate speech-language pathology students in 9 individual PAL sessions. Pre- and post-surveys assessed the peer teaching experience for AuD students in 5 areas of their confidence in audiologic screening: knowledge, skill, making a referral based on outcomes, teaching, and supervising. Pre- and post-learning outcomes in audiologic screening for the speech-language pathology student trainees determined the effectiveness of training by their AuD student peers. Survey outcomes revealed significant (p < .001) improvement in the overall confidence of AuD student peer instructors. Speech-language pathology students trained by their AuD peers exhibited significant (p = .003) improvements in their knowledge and skill and making outcome-based referrals in audiologic screening, supporting the effectiveness of the PAL paradigm. In addition to meeting required accreditation and professional certification competency standards, the PAL instructional model offers an innovative curricular approach in interprofessional education and in the teaching and supervisory preparation of students in doctoral audiology programs.

Model-based analysis of costs and outcomes of non-invasive prenatal testing for Down's syndrome using cell free fetal DNA in the UK National Health Service.

PubMed

Morris, Stephen; Karlsen, Saffron; Chung, Nancy; Hill, Melissa; Chitty, Lyn S

2014-01-01

Non-invasive prenatal testing (NIPT) for Down's syndrome (DS) using cell free fetal DNA in maternal blood has the potential to dramatically alter the way prenatal screening and diagnosis is delivered. Before NIPT can be implemented into routine practice, information is required on its costs and benefits. We investigated the costs and outcomes of NIPT for DS as contingent testing and as first-line testing compared with the current DS screening programme in the UK National Health Service. We used a pre-existing model to evaluate the costs and outcomes associated with NIPT compared with the current DS screening programme. The analysis was based on a hypothetical screening population of 10,000 pregnant women. Model inputs were taken from published sources. The main outcome measures were number of DS cases detected, number of procedure-related miscarriages and total cost. At a screening risk cut-off of 1∶150 NIPT as contingent testing detects slightly fewer DS cases, has fewer procedure-related miscarriages, and costs the same as current DS screening (around UK£280,000) at a cost of £500 per NIPT. As first-line testing NIPT detects more DS cases, has fewer procedure-related miscarriages, and is more expensive than current screening at a cost of £50 per NIPT. When NIPT uptake increases, NIPT detects more DS cases with a small increase in procedure-related miscarriages and costs. NIPT is currently available in the private sector in the UK at a price of £400-£900. If the NHS cost was at the lower end of this range then at a screening risk cut-off of 1∶150 NIPT as contingent testing would be cost neutral or cost saving compared with current DS screening. As first-line testing NIPT is likely to produce more favourable outcomes but at greater cost. Further research is needed to evaluate NIPT under real world conditions.

Cost-Effectiveness/Cost-Benefit Analysis of Newborn Screening for Severe Combined Immune Deficiency in Washington State.

PubMed

Ding, Yao; Thompson, John D; Kobrynski, Lisa; Ojodu, Jelili; Zarbalian, Guisou; Grosse, Scott D

2016-05-01

To evaluate the expected cost-effectiveness and net benefit of the recent implementation of newborn screening (NBS) for severe combined immunodeficiency (SCID) in Washington State. We constructed a decision analysis model to estimate the costs and benefits of NBS in an annual birth cohort of 86 600 infants based on projections of avoided infant deaths. Point estimates and ranges for input variables, including the birth prevalence of SCID, proportion detected asymptomatically without screening through family history, screening test characteristics, survival rates, and costs of screening, diagnosis, and treatment were derived from published estimates, expert opinion, and the Washington NBS program. We estimated treatment costs stratified by age of identification and SCID type (with or without adenosine deaminase deficiency). Economic benefit was estimated using values of $4.2 and $9.0 million per death averted. We performed sensitivity analyses to evaluate the influence of key variables on the incremental cost-effectiveness ratio (ICER) of net direct cost per life-year saved. Our model predicts an additional 1.19 newborn infants with SCID detected preclinically through screening, in addition to those who would have been detected early through family history, and 0.40 deaths averted annually. Our base-case model suggests an ICER of $35 311 per life-year saved, and a benefit-cost ratio of either 5.31 or 2.71. Sensitivity analyses found ICER values <$100 000 and positive net benefit for plausible assumptions on all variables. Our model suggests that NBS for SCID in Washington is likely to be cost-effective and to show positive net economic benefit. Published by Elsevier Inc.

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

PubMed

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.

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

PubMed

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

2014-01-29

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

Prediction of Chlamydia trachomatis infection to facilitate selective screening on population and individual level: a cross-sectional study of a population-based screening programme.

PubMed

van Klaveren, David; Götz, Hannelore M; Op de Coul, Eline Lm; Steyerberg, Ewout W; Vergouwe, Yvonne

2016-09-01

To develop prediction models for Chlamydia trachomatis (Ct) infection with different levels of detail in information, that is, from readily available data in registries and from additional questionnaires. All inhabitants of Rotterdam and Amsterdam aged 16-29 were invited yearly from 2008 until 2011 for home-based testing. Their registry data included gender, age, ethnicity and neighbourhood-level socioeconomic status (SES). Participants were asked to fill in a questionnaire on education, sexually transmitted infection history, symptoms, partner information and sexual behaviour. We developed prediction models for Ct infection using first-time participant data-including registry variables only and with additional questionnaire variables-by multilevel logistic regression analysis to account for clustering within neighbourhoods. We assessed the discriminative ability by the area under the receiver operating characteristic curve (AUC). Four per cent (3540/80 385) of the participants was infected. The strongest registry predictors for Ct infection were young age (especially for women) and Surinamese, Antillean or sub-Saharan African ethnicity. Neighbourhood-level SES was of minor importance. Strong questionnaire predictors were low to intermediate education level, ethnicity of the partner (non-Dutch) and having sex with casual partners. When using a prediction model including questionnaire risk factors (AUC 0.74, 95% CI 0.736 to 0.752) for selective screening, 48% of the participating population needed to be screened to find 80% (95% CI 78.4% to 81.0%) of Ct infections. The model with registry risk factors only (AUC 0.67, 95% CI 0.656 to 0.675) required 60% to be screened to find 78% (95% CI 76.6% to 79.4%) of Ct infections. A registry-based prediction model can facilitate selective Ct screening at population level, with further refinement at the individual level by including questionnaire risk factors. 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/

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

PubMed

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

2018-01-22

Risk stratification of screened populations could help improve colorectal cancer (CRC) screening. Use of the modified Asia-Pacific Colorectal Screening (APCS) score has been proposed in the Asia-Pacific region. This study was performed to build a new useful scoring model for CRC screening. Data were reviewed from 5218 asymptomatic Japanese individuals who underwent their first screening colonoscopy. Multivariate logistic regression was used to investigate risk factors for advanced colorectal neoplasia (ACN), and a new scoring model for the prediction of ACN was developed based on the results. The discriminatory capability of the new model and the modified APCS score were assessed and compared. Internal validation was also performed. ACN was detected in 225 participants. An 8-point scoring model for the prediction of ACN was developed using five independent risk factors for ACN (male sex, higher age, presence of two or more first-degree relatives with CRC, body mass index of > 22.5 kg/m 2 , and smoking history of > 18.5 pack-years). The prevalence of ACN was 1.6% (34/2172), 5.3% (127/2419), and 10.2% (64/627) in participants with scores of < 3, ≥ 3 to < 5, and ≥ 5, respectively. The c-statistic of the scoring model was 0.70 (95% confidence interval, 0.67-0.73) in both the development and internal validation sets, and this value was higher than that of the modified APCS score [0.68 (95% confidence interval, 0.65-0.71), P = 0.03]. We built a new simple scoring model for prediction of ACN in a Japanese population that could stratify the screened population into low-, moderate-, and high-risk groups.

Agent-Based Computational Modeling to Examine How Individual Cell Morphology Affects Dosimetry

EPA Science Inventory

Cell-based models utilizing high-content screening (HCS) data have applications for predictive toxicology. Evaluating concentration-dependent effects on cell fate and state response is a fundamental utilization of HCS data.Although HCS assays may capture quantitative readouts at ...

Protection motivation theory in predicting intention to receive cervical cancer screening in rural Chinese women.

PubMed

Bai, Yang; Liu, Qing; Chen, Xinguang; Gao, Yanduo; Gong, Huiyun; Tan, Xiaodong; Zhang, Min; Tuo, Jiyu; Zhang, Yuling; Xiang, Qunying; Deng, Fenghua; Liu, Guiling

2018-02-01

Despite the significance of cervical cancer screening, motivating more women to participate remains a challenge in resource-limited settings. In this study, we tested the protection motivation theory (PMT) in predicting screening intentions. Participants were women from Wufeng, a typical rural county in China. Participants (n = 3000) with no cervical cancer history were recruited from 10 randomly selected villages. As mediating variables, 6 PMT constructs (Perceived Risk, Fear Arousal, Perceived Severity, Response Efficacy, Response Cost, and Self-Efficacy) were measured using the standardized questionnaire. Structural equation modeling (SEM) method was employed to test PMT-based prediction models. Of the total sample, 57.77% believed that regular screening may reduce cervical cancer risk, and 45.26% agreed that women should be screened regularly. Our data fit the PMT model well (GFI = 0.95, AGFI = 0.93, CFI = 0.90, RMSEA = 0.06, SRMR = 0.04, Chi-square/df = 2.47). Knowledge of screening was directly and positively associated with screening intention. Age, annual income, and awareness of and prior experience with screening were significantly associated with screening intention by enhancing cervical cancer risk perception and by reducing response cost (P<0.05 for both). PMT can be used as guidance to investigate cervical cancer screening intentions among rural women in China with focus on cancer knowledge, some demographic factors, and awareness of and previous experience with screening. These findings, if verified with longitudinal data, can be used for intervention program development. Copyright © 2017 John Wiley & Sons, Ltd.

Using the Theory of Planned Behavior to Understand Cervical Cancer Screening Among Latinas.

PubMed

Roncancio, Angelica M; Ward, Kristy K; Sanchez, Ingrid A; Cano, Miguel A; Byrd, Theresa L; Vernon, Sally W; Fernandez-Esquer, Maria Eugenia; Fernandez, Maria E

2015-10-01

To reduce the high incidence of cervical cancer among Latinas in the United States it is important to understand factors that predict screening behavior. The aim of this study was to test the utility of theory of planned behavior in predicting cervical cancer screening among a group of Latinas. A sample of Latinas (N = 614) completed a baseline survey about Pap test attitudes subjective norms, perceived behavioral control, and intention to be screened for cervical cancer. At 6 months postbaseline, cervical cancer screening behavior was assessed. Structural equation modeling was used to test the theory. Model fit statistics indicated good model fit: χ(2)(48) = 54.32, p = .246; comparative fit index = .992; root mean square error of approximation = .015; weighted root mean square residual = .687. Subjective norms (p = .005) and perceived behavioral control (p < .0001) were positively associated with intention to be screened for cervical cancer, and the intention to be screened predicted actual cervical cancer screening (p < .0001). The proportion of variance (R2) in intention accounted for by the predictors was .276 and the R2 in cervical cancer screening accounted for was .130. This study provides support for the use of the theory of planned behavior in predicting cervical cancer screening among Latinas. This knowledge can be used to inform the development of a theory of planned behavior-based intervention to increase cervical cancer screening among Latinas and reduce the high incidence of cervical cancer in this group of women. © 2015 Society for Public Health Education.

Optimal use of colonoscopy and fecal immunochemical test for population-based colorectal cancer screening: a cost-effectiveness analysis using Japanese data.

PubMed

Sekiguchi, Masau; Igarashi, Ataru; Matsuda, Takahisa; Matsumoto, Minori; Sakamoto, Taku; Nakajima, Takeshi; Kakugawa, Yasuo; Yamamoto, Seiichiro; Saito, Hiroshi; Saito, Yutaka

2016-02-01

There have been few cost-effectiveness analyses of population-based colorectal cancer screening in Japan, and there is no consensus on the optimal use of total colonoscopy and the fecal immunochemical test for colorectal cancer screening with regard to cost-effectiveness and total colonoscopy workload. The present study aimed to examine the cost-effectiveness of colorectal cancer screening using Japanese data to identify the optimal use of total colonoscopy and fecal immunochemical test. We developed a Markov model to assess the cost-effectiveness of colorectal cancer screening offered to an average-risk population aged 40 years or over. The cost, quality-adjusted life-years and number of total colonoscopy procedures required were evaluated for three screening strategies: (i) a fecal immunochemical test-based strategy; (ii) a total colonoscopy-based strategy; (iii) a strategy of adding population-wide total colonoscopy at 50 years to a fecal immunochemical test-based strategy. All three strategies dominated no screening. Among the three, Strategy 1 was dominated by Strategy 3, and the incremental cost per quality-adjusted life-years gained for Strategy 2 against Strategies 1 and 3 were JPY 293 616 and JPY 781 342, respectively. Within the Japanese threshold (JPY 5-6 million per QALY gained), Strategy 2 was the most cost-effective, followed by Strategy 3; however, Strategy 2 required more than double the number of total colonoscopy procedures than the other strategies. The total colonoscopy-based strategy could be the most cost-effective for population-based colorectal cancer screening in Japan. However, it requires more total colonoscopy procedures than the other strategies. Depending on total colonoscopy capacity, the strategy of adding total colonoscopy for individuals at a specified age to a fecal immunochemical test-based screening may be an optimal solution. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

AutoClickChem: click chemistry in silico.

PubMed

Durrant, Jacob D; McCammon, J Andrew

2012-01-01

Academic researchers and many in industry often lack the financial resources available to scientists working in "big pharma." High costs include those associated with high-throughput screening and chemical synthesis. In order to address these challenges, many researchers have in part turned to alternate methodologies. Virtual screening, for example, often substitutes for high-throughput screening, and click chemistry ensures that chemical synthesis is fast, cheap, and comparatively easy. Though both in silico screening and click chemistry seek to make drug discovery more feasible, it is not yet routine to couple these two methodologies. We here present a novel computer algorithm, called AutoClickChem, capable of performing many click-chemistry reactions in silico. AutoClickChem can be used to produce large combinatorial libraries of compound models for use in virtual screens. As the compounds of these libraries are constructed according to the reactions of click chemistry, they can be easily synthesized for subsequent testing in biochemical assays. Additionally, in silico modeling of click-chemistry products may prove useful in rational drug design and drug optimization. AutoClickChem is based on the pymolecule toolbox, a framework that may facilitate the development of future python-based programs that require the manipulation of molecular models. Both the pymolecule toolbox and AutoClickChem are released under the GNU General Public License version 3 and are available for download from http://autoclickchem.ucsd.edu.

AutoClickChem: Click Chemistry in Silico

PubMed Central

Durrant, Jacob D.; McCammon, J. Andrew

2012-01-01

Academic researchers and many in industry often lack the financial resources available to scientists working in “big pharma.” High costs include those associated with high-throughput screening and chemical synthesis. In order to address these challenges, many researchers have in part turned to alternate methodologies. Virtual screening, for example, often substitutes for high-throughput screening, and click chemistry ensures that chemical synthesis is fast, cheap, and comparatively easy. Though both in silico screening and click chemistry seek to make drug discovery more feasible, it is not yet routine to couple these two methodologies. We here present a novel computer algorithm, called AutoClickChem, capable of performing many click-chemistry reactions in silico. AutoClickChem can be used to produce large combinatorial libraries of compound models for use in virtual screens. As the compounds of these libraries are constructed according to the reactions of click chemistry, they can be easily synthesized for subsequent testing in biochemical assays. Additionally, in silico modeling of click-chemistry products may prove useful in rational drug design and drug optimization. AutoClickChem is based on the pymolecule toolbox, a framework that may facilitate the development of future python-based programs that require the manipulation of molecular models. Both the pymolecule toolbox and AutoClickChem are released under the GNU General Public License version 3 and are available for download from http://autoclickchem.ucsd.edu. PMID:22438795

A ranking method for the concurrent learning of compounds with various activity profiles.

PubMed

Dörr, Alexander; Rosenbaum, Lars; Zell, Andreas

2015-01-01

In this study, we present a SVM-based ranking algorithm for the concurrent learning of compounds with different activity profiles and their varying prioritization. To this end, a specific labeling of each compound was elaborated in order to infer virtual screening models against multiple targets. We compared the method with several state-of-the-art SVM classification techniques that are capable of inferring multi-target screening models on three chemical data sets (cytochrome P450s, dehydrogenases, and a trypsin-like protease data set) containing three different biological targets each. The experiments show that ranking-based algorithms show an increased performance for single- and multi-target virtual screening. Moreover, compounds that do not completely fulfill the desired activity profile are still ranked higher than decoys or compounds with an entirely undesired profile, compared to other multi-target SVM methods. SVM-based ranking methods constitute a valuable approach for virtual screening in multi-target drug design. The utilization of such methods is most helpful when dealing with compounds with various activity profiles and the finding of many ligands with an already perfectly matching activity profile is not to be expected.

Penman-Monteith approaches for estimating crop evapotranspiration in screenhouses--a case study with table-grape.

PubMed

Pirkner, Moran; Dicken, Uri; Tanny, Josef

2014-07-01

In arid and semi-arid regions many crops are grown under screens or in screenhouses to protect them from excessive radiation, strong winds, hailstorms and insects, and to reduce crop water requirements. Screens modify the crop microclimate, which means that it is necessary to accurately estimate crop water use under screens in order to improve the irrigation management and thereby increase water-use efficiency. The goal of the present study was to develop a set of calibrated relationships between inside and outside climatic variables, which would enable growers to predict crop water use under screens, based on standard external meteorological measurements and evapotranspiration (ET) models. Experiments were carried out in the Jordan Valley region of eastern Israel in a table-grape vineyard that was covered with a transparent screen providing 10% shading. An eddy covariance system was deployed in the middle of the vineyard and meteorological variables were measured inside and outside the screenhouse. Two ET models were evaluated: a classical Penman-Monteith model (PM) and a Penman-Monteith model modified for screenhouse conditions by the inclusion of an additional boundary-layer resistance (PMsc). Energy-balance closure analysis, presented as a linear relation between half-hourly values of available and consumed energy (1,344 data points), yielded the regression Y=1.05X-9.93 (W m(-2)), in which Y=sum of latent and sensible heat fluxes, and X=net radiation minus soil heat flux, with R2=0.81. To compensate for overestimation of the eddy fluxes, ET was corrected by forcing the energy balance closure. Average daily ET under the screen was 5.4±0.54 mm day(-1), in general agreement with the model estimates and the applied irrigation. The results showed that measured ET under the screen was, on average, 34% lower than that estimated outside, indicating significant potential water saving through screening irrigated vineyards. The PM model was somewhat more accurate than the PMsc for estimating ET under the screen. A model sensitivity analysis illustrates how changes in certain climatic conditions or screen properties would affect evapotranspiration.

Screen time and young children: Promoting health and development in a digital world.

PubMed

2017-11-01

The digital landscape is evolving more quickly than research on the effects of screen media on the development, learning and family life of young children. This statement examines the potential benefits and risks of screen media in children younger than 5 years, focusing on developmental, psychosocial and physical health. Evidence-based guidance to optimize and support children's early media experiences involves four principles: minimizing, mitigating, mindfully using and modelling healthy use of screens. Knowing how young children learn and develop informs best practice strategies for health care providers.

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

PubMed

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

2017-10-01

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

Resources Required for Cervical Cancer Prevention in Low- and Middle-Income Countries.

PubMed

Campos, Nicole G; Sharma, Monisha; Clark, Andrew; Kim, Jane J; Resch, Stephen C

2016-01-01

Cervical cancer is the fourth leading cause of cancer death in women, with 85% of cases and deaths occurring in developing countries. While organized screening programs have reduced cervical cancer incidence in high-income countries through detection and treatment of precancerous lesions, the implementation of organized screening has not been effective in low-resource settings due to lack of infrastructure and limited budgets. Our objective was to estimate the cost of comprehensive primary and secondary cervical cancer prevention in low- and middle-income countries. We performed a modeling analysis to estimate 1) for girls aged 10 years, the cost of 2-dose human papillomavirus (HPV) vaccination; and 2) for women aged 30 to 49 years, the cost of cervical cancer screening (with visual inspection with acetic acid (VIA), HPV testing, or cytology) and preventive treatment in 102 low- and middle-income countries from 2015 to 2024. We used an Excel-based costing and service utilization model to estimate financial costs (2013 US$) based on prevalence of HPV, prevalence of precancerous lesions, and screening test performance. Where epidemiologic data were unavailable, we extrapolated from settings with data using an individual-based microsimulation model of cervical carcinogenesis (calibrated to 20 settings) and multivariate regression. Total HPV vaccination costs ranged from US$8.6 billion to US$24.2 billion for all scenarios considered (immediate, 5-year, or 10-year roll-out; price per dose US$4.55-US$70 by country income level). The total cost of screening and preventive treatment ranged from US$5.1 billion (10-year roll-out, screening once at age 35 years) to US$42.3 billion (immediate roll-out, high intensity screening). Limitations of this analysis include the assumption of standardized protocols by country income level that did not account for the potential presence of multiple screening modalities or management strategies within a country, and extrapolation of cost and epidemiologic data to settings where data were limited. The estimated cost of comprehensive cervical cancer prevention with 2-dose HPV vaccination of 10-year-old girls and screening of women aged 30 to 49 years ranges from US$13.7 billion to US$66.5 billion, depending on speed of roll-out, vaccine price per dose, and screening test and frequency. Findings demonstrate the substantial impact of vaccine price in middle-income countries that are not eligible for assistance from Gavi, the Vaccine Alliance. Replacing routine cytology with HPV-based screening may reduce total costs. Data on the health impact and relative cost-effectiveness of strategies are needed to determine the best value for public health dollars.

Resources Required for Cervical Cancer Prevention in Low- and Middle-Income Countries

PubMed Central

Campos, Nicole G.; Sharma, Monisha; Clark, Andrew; Kim, Jane J.; Resch, Stephen C.

2016-01-01

Background Cervical cancer is the fourth leading cause of cancer death in women, with 85% of cases and deaths occurring in developing countries. While organized screening programs have reduced cervical cancer incidence in high-income countries through detection and treatment of precancerous lesions, the implementation of organized screening has not been effective in low-resource settings due to lack of infrastructure and limited budgets. Our objective was to estimate the cost of comprehensive primary and secondary cervical cancer prevention in low- and middle-income countries. Methods and Findings We performed a modeling analysis to estimate 1) for girls aged 10 years, the cost of 2-dose human papillomavirus (HPV) vaccination; and 2) for women aged 30 to 49 years, the cost of cervical cancer screening (with visual inspection with acetic acid (VIA), HPV testing, or cytology) and preventive treatment in 102 low- and middle-income countries from 2015 to 2024. We used an Excel-based costing and service utilization model to estimate financial costs (2013 US$) based on prevalence of HPV, prevalence of precancerous lesions, and screening test performance. Where epidemiologic data were unavailable, we extrapolated from settings with data using an individual-based microsimulation model of cervical carcinogenesis (calibrated to 20 settings) and multivariate regression. Total HPV vaccination costs ranged from US$8.6 billion to US$24.2 billion for all scenarios considered (immediate, 5-year, or 10-year roll-out; price per dose US$4.55-US$70 by country income level). The total cost of screening and preventive treatment ranged from US$5.1 billion (10-year roll-out, screening once at age 35 years) to US$42.3 billion (immediate roll-out, high intensity screening). Limitations of this analysis include the assumption of standardized protocols by country income level that did not account for the potential presence of multiple screening modalities or management strategies within a country, and extrapolation of cost and epidemiologic data to settings where data were limited. Conclusions The estimated cost of comprehensive cervical cancer prevention with 2-dose HPV vaccination of 10-year-old girls and screening of women aged 30 to 49 years ranges from US$13.7 billion to US$66.5 billion, depending on speed of roll-out, vaccine price per dose, and screening test and frequency. Findings demonstrate the substantial impact of vaccine price in middle-income countries that are not eligible for assistance from Gavi, the Vaccine Alliance. Replacing routine cytology with HPV-based screening may reduce total costs. Data on the health impact and relative cost-effectiveness of strategies are needed to determine the best value for public health dollars. PMID:27711124

In silico study of in vitro GPCR assays by QSAR modeling

EPA Science Inventory

The U.S. EPA is screening thousands of chemicals of environmental interest in hundreds of in vitro high-throughput screening (HTS) assays (the ToxCast program). One goal is to prioritize chemicals for more detailed analyses based on activity in molecular initiating events (MIE) o...

Model stream channel testing of a UV-transparent polymer-based passive sampler for ultra-low-cost water screening applications

EPA Science Inventory

Passive samplers are increasingly being considered for analyses of waters for screening applications, to monitor for the presence of unwanted chemical compounds. Passive samplers typically work by accumulating and concentrating chemicals from the surrounding water over time, all...

Using Radiation Risk Models in Cancer Screening Simulations: Important Assumptions and Effects on Outcome Projections

PubMed Central

Lee, Janie M.; McMahon, Pamela M.; Lowry, Kathryn P.; Omer, Zehra B.; Eisenberg, Jonathan D.; Pandharipande, Pari V.; Gazelle, G. Scott

2012-01-01

Purpose: To evaluate the effect of incorporating radiation risk into microsimulation (first-order Monte Carlo) models for breast and lung cancer screening to illustrate effects of including radiation risk on patient outcome projections. Materials and Methods: All data used in this study were derived from publicly available or deidentified human subject data. Institutional review board approval was not required. The challenges of incorporating radiation risk into simulation models are illustrated with two cancer screening models (Breast Cancer Model and Lung Cancer Policy Model) adapted to include radiation exposure effects from mammography and chest computed tomography (CT), respectively. The primary outcome projected by the breast model was life expectancy (LE) for BRCA1 mutation carriers. Digital mammographic screening beginning at ages 25, 30, 35, and 40 years was evaluated in the context of screenings with false-positive results and radiation exposure effects. The primary outcome of the lung model was lung cancer–specific mortality reduction due to annual screening, comparing two diagnostic CT protocols for lung nodule evaluation. The Metropolis-Hastings algorithm was used to estimate the mean values of the results with 95% uncertainty intervals (UIs). Results: Without radiation exposure effects, the breast model indicated that annual digital mammography starting at age 25 years maximized LE (72.03 years; 95% UI: 72.01 years, 72.05 years) and had the highest number of screenings with false-positive results (2.0 per woman). When radiation effects were included, annual digital mammography beginning at age 30 years maximized LE (71.90 years; 95% UI: 71.87 years, 71.94 years) with a lower number of screenings with false-positive results (1.4 per woman). For annual chest CT screening of 50-year-old females with no follow-up for nodules smaller than 4 mm in diameter, the lung model predicted lung cancer–specific mortality reduction of 21.50% (95% UI: 20.90%, 22.10%) without radiation risk and 17.75% (95% UI: 16.97%, 18.41%) with radiation risk. Conclusion: Because including radiation exposure risk can influence long-term projections from simulation models, it is important to include these risks when conducting modeling-based assessments of diagnostic imaging. © RSNA, 2012 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11110352/-/DC1 PMID:22357897

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

PubMed

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

2015-08-01

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

Quantum probability ranking principle for ligand-based virtual screening.

PubMed

Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

2017-04-01

Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.

Quantum probability ranking principle for ligand-based virtual screening

NASA Astrophysics Data System (ADS)

Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

2017-04-01

Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.

A deep learning method for early screening of lung cancer

NASA Astrophysics Data System (ADS)

Zhang, Kunpeng; Jiang, Huiqin; Ma, Ling; Gao, Jianbo; Yang, Xiaopeng

2018-04-01

Lung cancer is the leading cause of cancer-related deaths among men. In this paper, we propose a pulmonary nodule detection method for early screening of lung cancer based on the improved AlexNet model. In order to maintain the same image quality as the existing B/S architecture PACS system, we convert the original CT image into JPEG format image by analyzing the DICOM file firstly. Secondly, in view of the large size and complex background of CT chest images, we design the convolution neural network on basis of AlexNet model and sparse convolution structure. At last we train our models on the software named DIGITS which is provided by NVIDIA. The main contribution of this paper is to apply the convolutional neural network for the early screening of lung cancer and improve the screening accuracy by combining the AlexNet model with the sparse convolution structure. We make a series of experiments on the chest CT images using the proposed method, of which the sensitivity and specificity indicates that the method presented in this paper can effectively improve the accuracy of early screening of lung cancer and it has certain clinical significance at the same time.

The Pittsburgh Cervical Cancer Screening Model: a risk assessment tool.

PubMed

Austin, R Marshall; Onisko, Agnieszka; Druzdzel, Marek J

2010-05-01

Evaluation of cervical cancer screening has grown increasingly complex with the introduction of human papillomavirus (HPV) vaccination and newer screening technologies approved by the US Food and Drug Administration. To create a unique Pittsburgh Cervical Cancer Screening Model (PCCSM) that quantifies risk for histopathologic cervical precancer (cervical intraepithelial neoplasia [CIN] 2, CIN3, and adenocarcinoma in situ) and cervical cancer in an environment predominantly using newer screening technologies. The PCCSM is a dynamic Bayesian network consisting of 19 variables available in the laboratory information system, including patient history data (most recent HPV vaccination data), Papanicolaou test results, high-risk HPV results, procedure data, and histopathologic results. The model's graphic structure was based on the published literature. Results from 375 441 patient records from 2005 through 2008 were used to build and train the model. Additional data from 45 930 patients were used to test the model. The PCCSM compares risk quantitatively over time for histopathologically verifiable CIN2, CIN3, adenocarcinoma in situ, and cervical cancer in screened patients for each current cytology result category and for each HPV result. For each current cytology result, HPV test results affect risk; however, the degree of cytologic abnormality remains the largest positive predictor of risk. Prior history also alters the CIN2, CIN3, adenocarcinoma in situ, and cervical cancer risk for patients with common current cytology and HPV test results. The PCCSM can also generate negative risk projections, estimating the likelihood of the absence of histopathologic CIN2, CIN3, adenocarcinoma in situ, and cervical cancer in screened patients. The PCCSM is a dynamic Bayesian network that computes quantitative cervical disease risk estimates for patients undergoing cervical screening. Continuously updatable with current system data, the PCCSM provides a new tool to monitor cervical disease risk in the evolving postvaccination era.

Persuasive Interventions for Controversial Cancer Screening Recommendations: Testing a Novel Approach to Help Patients Make Evidence-Based Decisions

PubMed Central

Saver, Barry G.; Mazor, Kathleen M.; Luckmann, Roger; Cutrona, Sarah L.; Hayes, Marcela; Gorodetsky, Tatyana; Esparza, Nancy; Bacigalupe, Gonzalo

2017-01-01

PURPOSE We wanted to evaluate novel decision aids designed to help patients trust and accept the controversial, evidence-based, US Preventive Services Task Force recommendations about prostate cancer screening (from 2012) and mammography screening for women aged 40 to 49 years (from 2009). METHODS We created recorded vignettes of physician-patient discussions about prostate cancer screening and mammography, accompanied by illustrative slides, based on principles derived from preceding qualitative work and behavioral science literature. We conducted a randomized crossover study with repeated measures with 27 men aged 50 to 74 years and 35 women aged 40 to 49 years. All participants saw a video intervention and a more traditional, paper-based decision aid intervention in random order. At entry and after seeing each intervention, they were surveyed about screening intentions, perceptions of benefits and harm, and decisional conflict. RESULTS Changes in screening intentions were analyzed without regard to order of intervention after an initial analyses showed no evidence of an order effect. At baseline, 69% of men and 86% of women reported wanting screening, with 31% and 6%, respectively, unsure. Mean change on a 3-point, yes, unsure, no scale was −0.93 (P = <.001) for men and −0.50 (P = <.001) for women after seeing the video interventions vs 0.0 and −0.06 (P = .75) after seeing the print interventions. At the study end, 33% of men and 49% of women wanted screening, and 11% and 20%, respectively, were unsure. CONCLUSIONS Our novel, persuasive video interventions significantly changed the screening intentions of substantial proportions of viewers. Our approach needs further testing but may provide a model for helping patients to consider and accept evidence-based, counterintuitive recommendations. PMID:28376460

A systematic approach to prioritize drug targets using machine learning, a molecular descriptor-based classification model, and high-throughput screening of plant derived molecules: a case study in oral cancer.

PubMed

Randhawa, Vinay; Kumar Singh, Anil; Acharya, Vishal

2015-12-01

Systems-biology inspired identification of drug targets and machine learning-based screening of small molecules which modulate their activity have the potential to revolutionize modern drug discovery by complementing conventional methods. To utilize the effectiveness of such pipelines, we first analyzed the dysregulated gene pairs between control and tumor samples and then implemented an ensemble-based feature selection approach to prioritize targets in oral squamous cell carcinoma (OSCC) for therapeutic exploration. Based on the structural information of known inhibitors of CXCR4-one of the best targets identified in this study-a feature selection was implemented for the identification of optimal structural features (molecular descriptor) based on which a classification model was generated. Furthermore, the CXCR4-centered descriptor-based classification model was finally utilized to screen a repository of plant derived small-molecules to obtain potential inhibitors. The application of our methodology may assist effective selection of the best targets which may have previously been overlooked, that in turn will lead to the development of new oral cancer medications. The small molecules identified in this study can be ideal candidates for trials as potential novel anti-oral cancer agents. Importantly, distinct steps of this whole study may provide reference for the analysis of other complex human diseases.

Bedside ROP screening and telemedicine interpretation integrated to a neonatal transport system: Economic aspects and return on investment analysis.

PubMed

Kovács, Gábor; Somogyvári, Zsolt; Maka, Erika; Nagyjánosi, László

Peter Cerny Ambulance Service - Premature Eye Rescue Program (PCA-PERP) uses digital retinal imaging (DRI) with remote interpretation in bedside ROP screening, which has advantages over binocular indirect ophthalmoscopy (BIO) in screening of premature newborns. We aimed to demonstrate that PCA-PERP provides good value for the money and to model the cost ramifications of a similar newly launched system. As DRI was demonstrated to have high diagnostic performance, only the costs of bedside DRI-based screening were compared to those of traditional transport and BIO-based screening (cost-minimization analysis). The total costs of investment and maintenance were analyzed with micro-costing method. A ten-year analysis time-horizon and service provider's perspective were applied. From the launch of PCA-PERP up to the end of 2014, 3722 bedside examinations were performed in the PCA covered central region of Hungary. From 2009 to 2014, PCA-PERP saved 92,248km and 3633 staff working hours, with an annual nominal cost-savings ranging from 17,435 to 35,140 Euro. The net present value was 127,847 Euro at the end of 2014, with a payback period of 4.1years and an internal rate of return of 20.8%. Our model presented the NPVs of different scenarios with different initial investments, annual number of transports and average transport distances. PCA-PERP as bedside screening with remote interpretation, when compared to a transport-based screening with BIO, produced better cost-savings from the perspective of the service provider and provided a return on initial investment within five years after the project initiation. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2017-06-01

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

Combining Computational Methods for Hit to Lead Optimization in Mycobacterium tuberculosis Drug Discovery

PubMed Central

Ekins, Sean; Freundlich, Joel S.; Hobrath, Judith V.; White, E. Lucile; Reynolds, Robert C

2013-01-01

Purpose Tuberculosis treatments need to be shorter and overcome drug resistance. Our previous large scale phenotypic high-throughput screening against Mycobacterium tuberculosis (Mtb) has identified 737 active compounds and thousands that are inactive. We have used this data for building computational models as an approach to minimize the number of compounds tested. Methods A cheminformatics clustering approach followed by Bayesian machine learning models (based on publicly available Mtb screening data) was used to illustrate that application of these models for screening set selections can enrich the hit rate. Results In order to explore chemical diversity around active cluster scaffolds of the dose-response hits obtained from our previous Mtb screens a set of 1924 commercially available molecules have been selected and evaluated for antitubercular activity and cytotoxicity using Vero, THP-1 and HepG2 cell lines with 4.3%, 4.2% and 2.7% hit rates, respectively. We demonstrate that models incorporating antitubercular and cytotoxicity data in Vero cells can significantly enrich the selection of non-toxic actives compared to random selection. Across all cell lines, the Molecular Libraries Small Molecule Repository (MLSMR) and cytotoxicity model identified ~10% of the hits in the top 1% screened (>10 fold enrichment). We also showed that seven out of nine Mtb active compounds from different academic published studies and eight out of eleven Mtb active compounds from a pharmaceutical screen (GSK) would have been identified by these Bayesian models. Conclusion Combining clustering and Bayesian models represents a useful strategy for compound prioritization and hit-to lead optimization of antitubercular agents. PMID:24132686

Cost-effectiveness of an HPV self-collection campaign in Uganda: comparing models for delivery of cervical cancer screening in a low-income setting

PubMed Central

Campos, Nicole G; Tsu, Vivien; Jeronimo, Jose; Njama-Meya, Denise; Mvundura, Mercy; Kim, Jane J

2017-01-01

Abstract 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. Demonstration projects will be needed to confirm the validity of our logistical, costing and compliance assumptions. PMID:28369405

Cost-effectiveness of an HPV self-collection campaign in Uganda: comparing models for delivery of cervical cancer screening in a low-income setting.

PubMed

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. Demonstration projects will be needed to confirm the validity of our logistical, costing and compliance assumptions. © The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

High-throughput screening of chemicals as functional ...

EPA Pesticide Factsheets

Identifying chemicals that provide a specific function within a product, yet have minimal impact on the human body or environment, is the goal of most formulation chemists and engineers practicing green chemistry. We present a methodology to identify potential chemical functional substitutes from large libraries of chemicals using machine learning based models. We collect and analyze publicly available information on the function of chemicals in consumer products or industrial processes to identify a suite of harmonized function categories suitable for modeling. We use structural and physicochemical descriptors for these chemicals to build 41 quantitative structure–use relationship (QSUR) models for harmonized function categories using random forest classification. We apply these models to screen a library of nearly 6400 chemicals with available structure information for potential functional substitutes. Using our Functional Use database (FUse), we could identify uses for 3121 chemicals; 4412 predicted functional uses had a probability of 80% or greater. We demonstrate the potential application of the models to high-throughput (HT) screening for “candidate alternatives” by merging the valid functional substitute classifications with hazard metrics developed from HT screening assays for bioactivity. A descriptor set could be obtained for 6356 Tox21 chemicals that have undergone a battery of HT in vitro bioactivity screening assays. By applying QSURs, we wer

A chemical family-based strategy for uncovering hidden bioactive molecules and multicomponent interactions in herbal medicines.

PubMed

Song, Hui-Peng; Wu, Si-Qi; Hao, Haiping; Chen, Jun; Lu, Jun; Xu, Xiaojun; Li, Ping; Yang, Hua

2016-03-30

Two concepts involving natural products were proposed and demonstrated in this paper. (1) Natural product libraries (e.g. herbal extract) are not perfect for bioactivity screening because of the vast complexity of compound compositions, and thus a library reconstruction procedure is necessary before screening. (2) The traditional mode of "screening single compound" could be improved to "screening single compound, drug combination and multicomponent interaction" due to the fact that herbal medicines work by integrative effects of multi-components rather than single effective constituents. Based on the two concepts, we established a novel strategy aiming to make screening easier and deeper. Using thrombin as the model enzyme, we firstly uncovered the minor lead compounds, potential drug combinations and multicomponent interactions in an herbal medicine of Dan-Qi pair, showing a significant advantage over previous methods. This strategy was expected to be a new and promising mode for investigation of herbal medicines.

Discovery of Antibiotics-derived Polymers for Gene Delivery using Combinatorial Synthesis and Cheminformatics Modeling

PubMed Central

Potta, Thrimoorthy; Zhen, Zhuo; Grandhi, Taraka Sai Pavan; Christensen, Matthew D.; Ramos, James; Breneman, Curt M.; Rege, Kaushal

2014-01-01

We describe the combinatorial synthesis and cheminformatics modeling of aminoglycoside antibiotics-derived polymers for transgene delivery and expression. Fifty-six polymers were synthesized by polymerizing aminoglycosides with diglycidyl ether cross-linkers. Parallel screening resulted in identification of several lead polymers that resulted in high transgene expression levels in cells. The role of polymer physicochemical properties in determining efficacy of transgene expression was investigated using Quantitative Structure-Activity Relationship (QSAR) cheminformatics models based on Support Vector Regression (SVR) and ‘building block’ polymer structures. The QSAR model exhibited high predictive ability, and investigation of descriptors in the model, using molecular visualization and correlation plots, indicated that physicochemical attributes related to both, aminoglycosides and diglycidyl ethers facilitated transgene expression. This work synergistically combines combinatorial synthesis and parallel screening with cheminformatics-based QSAR models for discovery and physicochemical elucidation of effective antibiotics-derived polymers for transgene delivery in medicine and biotechnology. PMID:24331709

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

PubMed

Spyrakis, Francesca; Cavasotto, Claudio N

2015-10-01

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

Model-Free Feature Screening for Ultrahigh Dimensional Discriminant Analysis

PubMed Central

Cui, Hengjian; Li, Runze

2014-01-01

This work is concerned with marginal sure independence feature screening for ultra-high dimensional discriminant analysis. The response variable is categorical in discriminant analysis. This enables us to use conditional distribution function to construct a new index for feature screening. In this paper, we propose a marginal feature screening procedure based on empirical conditional distribution function. We establish the sure screening and ranking consistency properties for the proposed procedure without assuming any moment condition on the predictors. The proposed procedure enjoys several appealing merits. First, it is model-free in that its implementation does not require specification of a regression model. Second, it is robust to heavy-tailed distributions of predictors and the presence of potential outliers. Third, it allows the categorical response having a diverging number of classes in the order of O(nκ) with some κ ≥ 0. We assess the finite sample property of the proposed procedure by Monte Carlo simulation studies and numerical comparison. We further illustrate the proposed methodology by empirical analyses of two real-life data sets. PMID:26392643

Vibration characteristics of an inclined flip-flow screen panel in banana flip-flow screens

NASA Astrophysics Data System (ADS)

Xiong, Xiaoyan; Niu, Linkai; Gu, Chengxiang; Wang, Yinhua

2017-12-01

A banana flip-flow screen is an effective solution for the screening of high-viscosity, high-water and fine materials. As one of the key components, the vibration characteristics of the inclined flip-flow screen panel largely affects the screen performance and the processing capacity. In this paper, a mathematical model for the vibration characteristic of the inclined flip-flow screen panel is proposed based on Catenary theory. The reasonability of Catenary theory in analyzing the vibration characteristic of flip-flow screen panels is verified by a published experiment. Moreover, the effects of the rotation speed of exciters, the incline angle, the slack length and the characteristics of the screen on the vertical deflection, the vertical velocity and the vertical acceleration of the screen panel are investigated parametrically. The results show that the rotation speed of exciters, the incline angle, the slack length and the characteristics of the screen have significant effects on the vibrations of an inclined flip-flow screen panel, and these parameters should be optimized.

"Plate cherry picking": a novel semi-sequential screening paradigm for cheaper, faster, information-rich compound selection.

PubMed

Crisman, Thomas J; Jenkins, Jeremy L; Parker, Christian N; Hill, W Adam G; Bender, Andreas; Deng, Zhan; Nettles, James H; Davies, John W; Glick, Meir

2007-04-01

This work describes a novel semi-sequential technique for in silico enhancement of high-throughput screening (HTS) experiments now employed at Novartis. It is used in situations in which the size of the screen is limited by the readout (e.g., high-content screens) or the amount of reagents or tools (proteins or cells) available. By performing computational chemical diversity selection on a per plate basis (instead of a per compound basis), 25% of the 1,000,000-compound screening was optimized for general initial HTS. Statistical models are then generated from target-specific primary results (percentage inhibition data) to drive the cherry picking and testing from the entire collection. Using retrospective analysis of 11 HTS campaigns, the authors show that this method would have captured on average two thirds of the active compounds (IC(50) < 10 microM) and three fourths of the active Murcko scaffolds while decreasing screening expenditure by nearly 75%. This result is true for a wide variety of targets, including G-protein-coupled receptors, chemokine receptors, kinases, metalloproteinases, pathway screens, and protein-protein interactions. Unlike time-consuming "classic" sequential approaches that require multiple iterations of cherry picking, testing, and building statistical models, here individual compounds are cherry picked just once, based directly on primary screening data. Strikingly, the authors demonstrate that models built from primary data are as robust as models built from IC(50) data. This is true for all HTS campaigns analyzed, which represent a wide variety of target classes and assay types.

Screen-based sedentary behaviours among a nationally representative sample of youth: are Canadian kids couch potatoes?

PubMed

Leatherdale, S T; Ahmed, R

2011-09-01

To determine the percentage of Canadian youth meeting screen-time guidelines and to identify characteristics associated with different screen-time behaviours. Using nationally representative data collected from the 2008/2009 Youth Smoking Survey (YSS), we analyzed three screen-time behaviours, cigarette smoking, weekly spending money, self esteem, region and grade by sex, and conducted four logistic regression models to examine factors associated with more than 2 hours a day of sedentary screen time. Of 51 922 Canadian youth in grades 6 to 12, 50.9% spent more than 2 hours per day in screen-based behaviours. The average daily screen time was 7.8 (± 2.3) hours. Males and current smokers were more likely to report over 2 hours per day watching TV and videos or playing video games, whereas students in higher grades and those with weekly spending money were more likely to report playing or surfing on a computer. Youth with higher self-esteem were less likely to report spending over 2 hours per day in each of the three screen-time behaviours examined. Developing a better understanding of the factors associated with more hours of screen time is required to develop and target interventions that reduce screen-time behaviours.

Computer-aided system of evaluation for population-based all-in-one service screening (CASE-PASS): from study design to outcome analysis with bias adjustment.

PubMed

Chen, Li-Sheng; Yen, Amy Ming-Fang; Duffy, Stephen W; Tabar, Laszlo; Lin, Wen-Chou; Chen, Hsiu-Hsi

2010-10-01

Population-based routine service screening has gained popularity following an era of randomized controlled trials. The evaluation of these service screening programs is subject to study design, data availability, and the precise data analysis for adjusting bias. We developed a computer-aided system that allows the evaluation of population-based service screening to unify these aspects and facilitate and guide the program assessor to efficiently perform an evaluation. This system underpins two experimental designs: the posttest-only non-equivalent design and the one-group pretest-posttest design and demonstrates the type of data required at both the population and individual levels. Three major analyses were developed that included a cumulative mortality analysis, survival analysis with lead-time adjustment, and self-selection bias adjustment. We used SAS AF software to develop a graphic interface system with a pull-down menu style. We demonstrate the application of this system with data obtained from a Swedish population-based service screen and a population-based randomized controlled trial for the screening of breast, colorectal, and prostate cancer, and one service screening program for cervical cancer with Pap smears. The system provided automated descriptive results based on the various sources of available data and cumulative mortality curves corresponding to the study designs. The comparison of cumulative survival between clinically and screen-detected cases without a lead-time adjustment are also demonstrated. The intention-to-treat and noncompliance analysis with self-selection bias adjustments are also shown to assess the effectiveness of the population-based service screening program. Model validation was composed of a comparison between our adjusted self-selection bias estimates and the empirical results on effectiveness reported in the literature. We demonstrate a computer-aided system allowing the evaluation of population-based service screening programs with an adjustment for self-selection and lead-time bias. This is achieved by providing a tutorial guide from the study design to the data analysis, with bias adjustment. Copyright © 2010 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2016-01-01

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. PMID:25601192

Web-based depression screening and psychiatric consultation for college students: a feasibility and acceptability study.

PubMed

Williams, Aya; Larocca, Rachel; Chang, Trina; Trinh, Nhi-Ha; Fava, Maurizio; Kvedar, Joseph; Yeung, Albert

2014-01-01

Background. A steady rise in the prevalence of depression among college students has negatively affected student quality of life. This study investigates the feasibility and acceptability of a Web-based model, including Skype, to screen and provide psychiatric consultation to depressed college students. Methods. Students completed the 9-item Patient Health Questionnaire (PHQ-9) online; those who screened positive (PHQ-9 ≥ 10) or endorsed any level of suicidal ideation were offered Web-based psychiatric consultation using Skype. After the consultation, students filled out a 7-item satisfaction questionnaire to report on the acceptability of this Web-based method. Results. A total of 972 students consented to the online depression screening and 285 screened positive. Of those, 69 students consented and 17 students successfully completed the psychiatric consultation via Skype. Thirteen (76.4%) students found the interview useful in helping them understand their depression. Fifteen (88.2%) students thought that psychologists and psychiatrists could successfully see patients via videoconferencing. Conclusions. Current online technologies can provide depression screening and psychiatric consultation to college students; those who participated reported a positive experience. Future studies will need to address the low levels of participation among college students and attract students who are underserved, as well as use a videoconferencing platform that adequately protects data confidentiality.

Web-Based Depression Screening and Psychiatric Consultation for College Students: A Feasibility and Acceptability Study

PubMed Central

Williams, Aya; LaRocca, Rachel; Chang, Trina; Trinh, Nhi-Ha; Fava, Maurizio

2014-01-01

Background. A steady rise in the prevalence of depression among college students has negatively affected student quality of life. This study investigates the feasibility and acceptability of a Web-based model, including Skype, to screen and provide psychiatric consultation to depressed college students. Methods. Students completed the 9-item Patient Health Questionnaire (PHQ-9) online; those who screened positive (PHQ-9 ≥ 10) or endorsed any level of suicidal ideation were offered Web-based psychiatric consultation using Skype. After the consultation, students filled out a 7-item satisfaction questionnaire to report on the acceptability of this Web-based method. Results. A total of 972 students consented to the online depression screening and 285 screened positive. Of those, 69 students consented and 17 students successfully completed the psychiatric consultation via Skype. Thirteen (76.4%) students found the interview useful in helping them understand their depression. Fifteen (88.2%) students thought that psychologists and psychiatrists could successfully see patients via videoconferencing. Conclusions. Current online technologies can provide depression screening and psychiatric consultation to college students; those who participated reported a positive experience. Future studies will need to address the low levels of participation among college students and attract students who are underserved, as well as use a videoconferencing platform that adequately protects data confidentiality. PMID:24799895

Illustrating economic evaluation of diagnostic technologies: comparing Helicobacter pylori screening strategies in prevention of gastric cancer in Canada.

PubMed

Xie, Feng; O'Reilly, Daria; Ferrusi, Ilia L; Blackhouse, Gord; Bowen, James M; Tarride, Jean-Eric; Goeree, Ron

2009-05-01

The aim of this paper is to present an economic evaluation of diagnostic technologies using Helicobacter pylori screening strategies for the prevention of gastric cancer as an illustration. A Markov model was constructed to compare the lifetime cost and effectiveness of 4 potential strategies: no screening, the serology test by enzyme-linked immunosorbent assay (ELISA), the stool antigen test (SAT), and the (13)C-urea breath test (UBT) for the detection of H. pylori among a hypothetical cohort of 10,000 Canadian men aged 35 years. Special parameter consideration included the sensitivity and specificity of each screening strategy, which determined the model structure and treatment regimen. The primary outcome measured was the incremental cost-effectiveness ratio between the screening strategies and the no-screening strategy. Base-case analysis and probabilistic sensitivity analysis were performed using the point estimates of the parameters and Monte Carlo simulations, respectively. Compared with the no-screening strategy in the base-case analysis, the incremental cost-effectiveness ratio was $33,000 per quality-adjusted life-year (QALY) for the ELISA, $29,800 per QALY for the SAT, and $50,400 per QALY for the UBT. The probabilistic sensitivity analysis revealed that the no-screening strategy was more cost effective if the willingness to pay (WTP) was <$20,000 per QALY, while the SAT had the highest probability of being cost effective if the WTP was >$30,000 per QALY. Both the ELISA and the UBT were not cost-effective strategies over a wide range of WTP values. Although the UBT had the highest sensitivity and specificity, either no screening or the SAT could be the most cost-effective strategy depending on the WTP threshold values from an economic perspective. This highlights the importance of economic evaluations of diagnostic technologies.

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

PubMed Central

Tsunematsu, Miwako; Kakehashi, Masayuki

2015-01-01

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

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

PubMed

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

2009-02-01

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

Automated Protocol for Large-Scale Modeling of Gene Expression Data.

PubMed

Hall, Michelle Lynn; Calkins, David; Sherman, Woody

2016-11-28

With the continued rise of phenotypic- and genotypic-based screening projects, computational methods to analyze, process, and ultimately make predictions in this field take on growing importance. Here we show how automated machine learning workflows can produce models that are predictive of differential gene expression as a function of a compound structure using data from A673 cells as a proof of principle. In particular, we present predictive models with an average accuracy of greater than 70% across a highly diverse ∼1000 gene expression profile. In contrast to the usual in silico design paradigm, where one interrogates a particular target-based response, this work opens the opportunity for virtual screening and lead optimization for desired multitarget gene expression profiles.

Novel approaches for targeting the adenosine A2A receptor.

PubMed

Yuan, Gengyang; Gedeon, Nicholas G; Jankins, Tanner C; Jones, Graham B

2015-01-01

The adenosine A2A receptor (A2AR) represents a drug target for a wide spectrum of diseases. Approaches for targeting this membrane-bound protein have been greatly advanced by new stabilization techniques. The resulting X-ray crystal structures and subsequent analyses provide deep insight to the A2AR from both static and dynamic perspectives. Application of this, along with other biophysical methods combined with fragment-based drug design (FBDD), has become a standard approach in targeting A2AR. Complementarities of in silico screening based- and biophysical screening assisted- FBDD are likely to feature in future approaches in identifying novel ligands against this key receptor. This review describes evolution of the above approaches for targeting A2AR and highlights key modulators identified. It includes a review of: adenosine receptor structures, homology modeling, X-ray structural analysis, rational drug design, biophysical methods, FBDD and in silico screening. As a drug target, the A2AR is attractive as its function plays a role in a wide spectrum of diseases including oncologic, inflammatory, Parkinson's and cardiovascular diseases. Although traditional approaches such as high-throughput screening and homology model-based virtual screening (VS) have played a role in targeting A2AR, numerous shortcomings have generally restricted their applications to specific ligand families. Using stabilization methods for crystallization, X-ray structures of A2AR have greatly accelerated drug discovery and influenced development of biophysical-in silico hybrid screening methods. Application of these new methods to other ARs and G-protein-coupled receptors is anticipated in the future.

Measuring quality of adolescent preventive services of health plan enrollees and school-based health center users.

PubMed

Klein, Jonathan D; Handwerker, Lisa; Sesselberg, Tracy S; Sutter, Erika; Flanagan, Erinn; Gawronski, Beth

2007-08-01

To evaluate whether quality of care provided to adolescents enrolled in a community-based managed care plan was better for those who also received some care at school-based health centers (SBHCs). The Young Adult Health Care Survey (YAHCS) was administered to 374 adolescents (commercially insured, Medicaid-insured, and SBHC users) to assess risk behaviors, provision of preventive screening and counseling, and quality of care. SBHC users were most likely to report that their provider told them their discussions were confidential, and that they received screening/counseling on sexually transmitted diseases (STDs), HIV/AIDS, condom use, and birth control. Commercially insured adolescents were least likely to report discussion of sexual health issues. SBHC users had the highest mean YAHCS quality measure scores for screening/counseling on pregnancy/STDs, diet and exercise, and helpfulness of counseling provided; Medicaid-insured teens had the lowest scores on four of seven measures. Regression models controlled for demographics, use of screener, and site of care showed that use of a screener had a significant impact on six of seven quality measure models. Younger age predicted screening for risk behaviors; being female, African-American, and an SBHC user predicted screening on pregnancy/STDs. SBHCs may increase adolescents' access to confidential care, and SBHC providers may be more likely than those in other settings to screen and counsel patients about sexual health. Overall quality of preventive care reported by commercially insured adolescents may be better in some health content areas and worse in others compared with care reported by Medicaid-insured youth and SBHC users.

Medical students, clinical preventive services, and shared decision-making.

PubMed

Keefe, Carole W; Thompson, Margaret E; Noel, Mary Margaret

2002-11-01

Improving access to preventive care requires addressing patient, provider, and systems barriers. Patients often lack knowledge or are skeptical about the importance of prevention. Physicians feel that they have too little time, are not trained to deliver preventive services, and are concerned about the effectiveness of prevention. We have implemented an educational module in the required family practice clerkship (1) to enhance medical student learning about common clinical preventive services and (2) to teach students how to inform and involve patients in shared decision making about those services. Students are asked to examine available evidence-based information for preventive screening services. They are encouraged to look at the recommendations of various organizations and use such resources as reports from the U.S. Preventive Services Task Force to determine recommendations they want to be knowledgeable about in talking with their patients. For learning shared decision making, students are trained to use a model adapted from Braddock and colleagues(1) to discuss specific screening services and to engage patients in the process of making informed decisions about what is best for their own health. The shared decision making is presented and modeled by faculty, discussed in small groups, and students practice using Web-based cases and simulations. The students are evaluated using formative and summative performance-based assessments as they interact with simulated patients about (1) screening for high blood cholesterol and other lipid abnormalities, (2) screening for colorectal cancer, (3) screening for prostate cancer, and (4) screening for breast cancer. The final student evaluation is a ten-minute, videotaped discussion with a simulated patient about screening for colorectal cancer that is graded against a checklist that focuses primarily on the elements of shared decision making. Our medical students appear quite willing to accept shared decision making as a skill that they should have in working with patients, and this was the primary focus of the newly implemented module. However, we have learned that students need to deepen their understanding of screening services in order to help patients understand the associated benefits and risks. The final videotaped interaction with a simulated patient about colorectal cancer screening has been very helpful in making it more obvious to faculty what students believe and know about screening for colorectal cancer. As the students are asked to discuss clinical issues with patients and discuss the pros and cons of screening tests as part of the shared decision-making process, their thinking becomes transparent and it is evident where curricular changes and enhancements are required. We have found that an explicit model that allows students to demonstrate a process for shared decision making is a good introductory tool. We think it would be helpful to provide students with more formative feedback. We would like to develop faculty development programs around shared decision making so that more of our clinical faculty would model such a process with patients. Performance-based assessments are resource-intensive, but they appear to be worth the added effort in terms of enhanced skills development and a more comprehensive appraisal of student learning.

Model-based error diffusion for high fidelity lenticular screening.

PubMed

Lau, Daniel; Smith, Trebor

2006-04-17

Digital halftoning is the process of converting a continuous-tone image into an arrangement of black and white dots for binary display devices such as digital ink-jet and electrophotographic printers. As printers are achieving print resolutions exceeding 1,200 dots per inch, it is becoming increasingly important for halftoning algorithms to consider the variations and interactions in the size and shape of printed dots between neighboring pixels. In the case of lenticular screening where statistically independent images are spatially multiplexed together, ignoring these variations and interactions, such as dot overlap, will result in poor lenticular image quality. To this end, we describe our use of model-based error-diffusion for the lenticular screening problem where statistical independence between component images is achieved by restricting the diffusion of error to only those pixels of the same component image where, in order to avoid instabilities, the proposed approach involves a novel error-clipping procedure.

Recommendations From the International Colorectal Cancer Screening Network on the Evaluation of the Cost of Screening Programs.

PubMed

Subramanian, Sujha; Tangka, Florence K L; Hoover, Sonja; Nadel, Marion; Smith, Robert; Atkin, Wendy; Patnick, Julietta

2016-01-01

Worldwide, colorectal cancer is the fourth leading cause of death from cancer and the incidence is projected to increase. Many countries are exploring the introduction of organized screening programs, but there is limited information on the resources required and guidance for cost-effective implementation. To facilitate the generating of the economics evidence base for program implementation, we collected and analyzed detailed program cost data from 5 European members of the International Colorectal Cancer Screening Network. The cost per person screened estimates, often used to compare across programs as an overall measure, varied significantly across the programs. In addition, there were substantial differences in the programmatic and clinical cost incurred, even when the same type of screening test was used. Based on these findings, several recommendations are provided to enhance the underlying methodology and validity of the comparative economic assessments. The recommendations include the need for detailed activity-based cost information, the use of a comprehensive set of effectiveness measures to adequately capture differences between programs, and the incorporation of data from multiple programs in cost-effectiveness models to increase generalizability. Economic evaluation of real-world colorectal cancer-screening programs is essential to derive valuable insights to improve program operations and ensure optimal use of available resources.

Readability, suitability, and health content assessment of web-based patient education materials on colorectal cancer screening.

PubMed

Tian, Chenlu; Champlin, Sara; Mackert, Michael; Lazard, Allison; Agrawal, Deepak

2014-08-01

Colorectal cancer (CRC) screening rates in the Unites States are still below target level. Web-based patient education materials are used by patients and providers to provide supplemental information on CRC screening. Low literacy levels and patient perceptions are significant barriers to screening. There are little data on the quality of these online materials from a health literacy standpoint or whether they address patients' perceptions. To evaluate the readability, suitability, and health content of web-based patient education materials on colon cancer screening. Descriptive study. Web-based patient materials. Twelve reputable and popular online patient education materials were evaluated. Readability was measured by using the Flesch-Kincaid Reading Grade Level, and suitability was determined by the Suitability Assessment of Materials, a scale that considers characteristics such as content, graphics, layout/typography, and learning stimulation. Health content was evaluated within the framework of the Health Belief Model, a behavioral model that relates patients' perceptions of susceptibility to disease, severity, and benefits and barriers to their medical decisions. Each material was scored independently by 3 reviewers. Flesch-Kincaid Reading Grade Level score, Suitability Assessment of Materials score, health content score. Readability for 10 of 12 materials surpassed the maximum recommended sixth-grade reading level. Five were 10th grade level and above. Only 1 of 12 materials received a superior suitability score; 3 materials received inadequate scores. Health content analysis revealed that only 50% of the resources discussed CRC risk in the general population and <25% specifically addressed patients at high risk, such as African Americans, smokers, patients with diabetes, and obese patients. For perceived barriers to screening, only 8.3% of resources discussed embarrassment, 25% discussed pain with colonoscopy, 25% addressed cost of colonoscopy, and none specifically mentioned the need to get colonoscopy when no symptoms are present. No material discussed the social benefits of screening. Descriptive design. Most online patient education materials for CRC screening are written beyond the recommended sixth-grade reading level, with suboptimal suitability. Health content is lacking in addressing key perceived risks, barriers, and benefits to CRC screening. Developing more appropriate and targeted patient education resources on CRC may improve patient understanding and promote screening. Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Development of predictive pharmacophore model for in silico screening, and 3D QSAR CoMFA and CoMSIA studies for lead optimization, for designing of potent tumor necrosis factor alpha converting enzyme inhibitors

NASA Astrophysics Data System (ADS)

Murumkar, Prashant Revan; Zambre, Vishal Prakash; Yadav, Mange Ram

2010-02-01

A chemical feature-based pharmacophore model was developed for Tumor Necrosis Factor-α converting enzyme (TACE) inhibitors. A five point pharmacophore model having two hydrogen bond acceptors (A), one hydrogen bond donor (D) and two aromatic rings (R) with discrete geometries as pharmacophoric features was developed. The pharmacophore model so generated was then utilized for in silico screening of a database. The pharmacophore model so developed was validated by using four compounds having proven TACE inhibitory activity which were grafted into the database. These compounds mapped well onto the five listed pharmacophoric features. This validated pharmacophore model was also used for alignment of molecules in CoMFA and CoMSIA analysis. The contour maps of the CoMFA/CoMSIA models were utilized to provide structural insight for activity improvement of potential novel TACE inhibitors. The pharmacophore model so developed could be used for in silico screening of any commercial/in house database for identification of TACE inhibiting lead compounds, and the leads so identified could be optimized using the developed CoMSIA model. The present work highlights the tremendous potential of the two mutually complementary ligand-based drug designing techniques (i.e. pharmacophore mapping and 3D-QSAR analysis) using TACE inhibitors as prototype biologically active molecules.

Impact of the National Breast and Cervical Cancer Early Detection Program on cervical cancer mortality among uninsured low-income women in the U.S., 1991-2007.

PubMed

Ekwueme, Donatus U; Uzunangelov, Vladislav J; Hoerger, Thomas J; Miller, Jacqueline W; Saraiya, Mona; Benard, Vicki B; Hall, Ingrid J; Royalty, Janet; Li, Chunyu; Myers, Evan R

2014-09-01

The benefits of the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) on cervical cancer screening for participating uninsured low-income women have never been measured. To estimate the benefits in life-years (LYs) gained; quality-adjusted life-years (QALYs) gained; and deaths averted. A cervical cancer simulation model was constructed based on an existing cohort model. The model was applied to NBCCEDP participants aged 18-64 years. Screening habits for uninsured low-income women were estimated using National Health Interview Survey data from 1990 to 2005 and NBCCEDP data from 1991 to 2007. The study was conducted during 2011-2012 and covered all 68 NBCCEDP grantees in 50 states, the District of Columbia, five U.S. territories, and 12 tribal organizations. Separate simulations were performed for the following three scenarios: (1) women who received NBCCEDP (Program) screening; (2) women who received screening without the program (No Program); and (3) women who received no screening (No Screening). Among 1.8 million women screened in 1991-2007, the Program added 10,369 LYs gained compared to No Program, and 101,509 LYs gained compared to No Screening. The Program prevented 325 women from dying of cervical cancer relative to No Program, and 3,829 relative to No Screening. During this time period, the Program accounted for 15,589 QALYs gained when compared with No Program, and 121,529 QALYs gained when compared with No Screening. These estimates suggest that NBCCEDP cervical cancer screening has reduced mortality among medically underserved low-income women who participated in the program. Published by Elsevier Inc.

A Collaborative Model for Community-Based Health Care Screening of Homeless Adolescents.

ERIC Educational Resources Information Center

Busen, Nancy H.; Beech, Bettina

1997-01-01

A multidisciplinary team from community organizations serving the homeless and from universities collaborated in screening 150 homeless adolescents for psychosocial and physical risks. The population had a history of physical, sexual, and substance abuse as well as high rates of HIV and hepatitis B. Case management by advanced practice nurses was…

Health economics of screening for gynaecological cancers.

PubMed

Kulasingam, Shalini; Havrilesky, Laura

2012-04-01

In this chapter, we summarise findings from recent cost-effectiveness analyses of screening for cervical cancer and ovarian cancer. We begin with a brief summary of key issues that affect the cost-effectiveness of screening, including disease burden, and availability and type of screening tests. For cervical cancer, we discuss the potential effect of human papilloma virus vaccines on screening. Outstanding epidemiological and cost-effectiveness issues are included. For cervical cancer, this includes incorporating the long-term effect of treatment (including adverse birth outcomes in treated women who are of reproductive age) into cost-effectiveness models using newly available trial data to identify the best strategy for incorporating human papilloma virus tests. A second issue is the need for additional data on human papilloma virus vaccines, such as effectiveness of reduced cancer incidence and mortality, effectiveness in previously exposed women and coverage. Definitive data on these parameters will allow us to update model-based analyses to include more realistic estimates, and also potentially dramatically alter our approach to screening. For ovarian cancer, outstanding issues include confirming within the context of a trial that screening is effective for reducing mortality and incorporating tests with high specificity into screening into screening algorithms for ovarian cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.

Primary HPV testing versus cytology-based cervical screening in women in Australia vaccinated for HPV and unvaccinated: effectiveness and economic assessment for the National Cervical Screening Program.

PubMed

Lew, Jie-Bin; Simms, Kate T; Smith, Megan A; Hall, Michaela; Kang, Yoon-Jung; Xu, Xiang Ming; Caruana, Michael; Velentzis, Louiza Sofia; Bessell, Tracey; Saville, Marion; Hammond, Ian; Canfell, Karen

2017-02-01

Australia's National Cervical Screening Program currently recommends cytological screening every 2 years for women aged 18-69 years. Human papillomavirus (HPV) vaccination was implemented in 2007 with high population coverage, and falls in high-grade lesions in young women have been reported extensively. This decline prompted a major review of the National Cervical Screening Program and new clinical management guidelines, for which we undertook this analysis. We did effectiveness modelling and an economic assessment of potential new screening strategies, using a model of HPV transmission, vaccination, natural history, and cervical screening. First, we evaluated 132 screening strategies, including those based on cytology and primary HPV testing. Second, after a recommendation was made to adopt primary HPV screening with partial genotyping and direct referral to colposcopy of women positive for HPV16/18, we evaluated the final effect of HPV screening after incorporating new clinical guidelines for women positive for HPV. Both evaluations considered both unvaccinated and vaccinated cohorts. Strategies entailing HPV testing every 5 years and either partial genotyping for HPV16/18 or cytological co-testing were the most effective. One of the most effective and cost-effective strategies comprised primary HPV screening with referral of women positive for oncogenic HPV16/18 direct to colposcopy, with reflex cytological triage for women with other oncogenic types and direct referral for those in this group with high-grade cytological findings. After incorporating detailed clinical guidelines recommendations, this strategy is predicted to reduce cervical cancer incidence and mortality by 31% and 36%, respectively, in unvaccinated cohorts, and by 24% and 29%, respectively, in cohorts offered vaccination. Furthermore, this strategy is predicted to reduce costs by up to 19% for unvaccinated cohorts and 26% for cohorts offered vaccination, compared with the current programme. Primary HPV screening every 5 years with partial genotyping is predicted to be substantially more effective and potentially cost-saving compared with the current cytology-based screening programme undertaken every 2 years. These findings underpin the decision to transition to primary HPV screening with partial genotyping in the Australian National Cervical Screening Program, which will occur in May, 2017. Department of Health, Australia. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license. Published by Elsevier Ltd.. All rights reserved.

Development and application of hybrid structure based method for efficient screening of ligands binding to G-protein coupled receptors

NASA Astrophysics Data System (ADS)

Kortagere, Sandhya; Welsh, William J.

2006-12-01

G-protein coupled receptors (GPCRs) comprise a large superfamily of proteins that are targets for nearly 50% of drugs in clinical use today. In the past, the use of structure-based drug design strategies to develop better drug candidates has been severely hampered due to the absence of the receptor's three-dimensional structure. However, with recent advances in molecular modeling techniques and better computing power, atomic level details of these receptors can be derived from computationally derived molecular models. Using information from these models coupled with experimental evidence, it has become feasible to build receptor pharmacophores. In this study, we demonstrate the use of the Hybrid Structure Based (HSB) method that can be used effectively to screen and identify prospective ligands that bind to GPCRs. Essentially; this multi-step method combines ligand-based methods for building enriched libraries of small molecules and structure-based methods for screening molecules against the GPCR target. The HSB method was validated to identify retinal and its analogues from a random dataset of ˜300,000 molecules. The results from this study showed that the 9 top-ranking molecules are indeed analogues of retinal. The method was also tested to identify analogues of dopamine binding to the dopamine D2 receptor. Six of the ten top-ranking molecules are known analogues of dopamine including a prodrug, while the other thirty-four molecules are currently being tested for their activity against all dopamine receptors. The results from both these test cases have proved that the HSB method provides a realistic solution to bridge the gap between the ever-increasing demand for new drugs to treat psychiatric disorders and the lack of efficient screening methods for GPCRs.

Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement.

PubMed

Grossman, David C; Curry, Susan J; Owens, Douglas K; Bibbins-Domingo, Kirsten; Caughey, Aaron B; Davidson, Karina W; Doubeni, Chyke A; Ebell, Mark; Epling, John W; Kemper, Alex R; Krist, Alex H; Kubik, Martha; Landefeld, C Seth; Mangione, Carol M; Silverstein, Michael; Simon, Melissa A; Siu, Albert L; Tseng, Chien-Wen

2018-05-08

In the United States, the lifetime risk of being diagnosed with prostate cancer is approximately 13%, and the lifetime risk of dying of prostate cancer is 2.5%. The median age of death from prostate cancer is 80 years. Many men with prostate cancer never experience symptoms and, without screening, would never know they have the disease. African American men and men with a family history of prostate cancer have an increased risk of prostate cancer compared with other men. To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on prostate-specific antigen (PSA)-based screening for prostate cancer. The USPSTF reviewed the evidence on the benefits and harms of PSA-based screening for prostate cancer and subsequent treatment of screen-detected prostate cancer. The USPSTF also commissioned a review of existing decision analysis models and the overdiagnosis rate of PSA-based screening. The reviews also examined the benefits and harms of PSA-based screening in patient subpopulations at higher risk of prostate cancer, including older men, African American men, and men with a family history of prostate cancer. Adequate evidence from randomized clinical trials shows that PSA-based screening programs in men aged 55 to 69 years may prevent approximately 1.3 deaths from prostate cancer over approximately 13 years per 1000 men screened. Screening programs may also prevent approximately 3 cases of metastatic prostate cancer per 1000 men screened. Potential harms of screening include frequent false-positive results and psychological harms. Harms of prostate cancer treatment include erectile dysfunction, urinary incontinence, and bowel symptoms. About 1 in 5 men who undergo radical prostatectomy develop long-term urinary incontinence, and 2 in 3 men will experience long-term erectile dysfunction. Adequate evidence shows that the harms of screening in men older than 70 years are at least moderate and greater than in younger men because of increased risk of false-positive results, diagnostic harms from biopsies, and harms from treatment. The USPSTF concludes with moderate certainty that the net benefit of PSA-based screening for prostate cancer in men aged 55 to 69 years is small for some men. How each man weighs specific benefits and harms will determine whether the overall net benefit is small. The USPSTF concludes with moderate certainty that the potential benefits of PSA-based screening for prostate cancer in men 70 years and older do not outweigh the expected harms. For men aged 55 to 69 years, the decision to undergo periodic PSA-based screening for prostate cancer should be an individual one and should include discussion of the potential benefits and harms of screening with their clinician. Screening offers a small potential benefit of reducing the chance of death from prostate cancer in some men. However, many men will experience potential harms of screening, including false-positive results that require additional testing and possible prostate biopsy; overdiagnosis and overtreatment; and treatment complications, such as incontinence and erectile dysfunction. In determining whether this service is appropriate in individual cases, patients and clinicians should consider the balance of benefits and harms on the basis of family history, race/ethnicity, comorbid medical conditions, patient values about the benefits and harms of screening and treatment-specific outcomes, and other health needs. Clinicians should not screen men who do not express a preference for screening. (C recommendation) The USPSTF recommends against PSA-based screening for prostate cancer in men 70 years and older. (D recommendation).

A Model for Maternal Depression

PubMed Central

Connelly, Cynthia D.; Baker-Ericzen, Mary J.; Hazen, Andrea L.; Landsverk, John

2010-01-01

Abstract With the awareness of maternal depression as a prevalent public health issue and its important link to child physical and mental health, attention has turned to how healthcare providers can respond effectively. Intimate partner violence (IPV) and the use of alcohol, tobacco, and other drugs are strongly related to depression, particularly for low-income women. The American College of Obstetricians and Gynecologists (ACOG) recommends psychosocial screening of pregnant women at least once per trimester, yet screening is uncommonly done. Research suggests that a collaborative care approach improves identification, outcomes, and cost-effectiveness of care. This article presents The Perinatal Mental Health Model, a community-based model that developed screening and referral partnerships for use in community obstetric settings in order to specifically address the psychosocial needs of culturally diverse, low-income mothers. PMID:20718624

Potential impact of legislation mandating breast density notification: benefits, harms, and cost effectiveness of supplemental ultrasound screening

PubMed Central

Sprague, Brian L.; Stout, Natasha K.; Schechter, Clyde; van Ravesteyn, Nicolien T.; Cevik, Mucahit; Alagoz, Oguzhan; Lee, Christoph I.; van den Broek, Jeroen J.; Miglioretti, Diana L.; Mandelblatt, Jeanne S.; de Koning, Harry J.; Kerlikowske, Karla; Lehman, Constance D.; Tosteson, Anna N. A.

2014-01-01

Background At least nineteen states have laws that require telling women with dense breasts and a negative screening mammogram to consider supplemental screening. The most readily available supplemental screening modality is ultrasound, yet little is known about its effectiveness. Objective To evaluate the benefits, harms, and cost-effectiveness of supplemental ultrasound screening for women with dense breasts. Design Comparative modeling with 3 validated simulation models. Data Sources Surveillance, Epidemiology, and End Results Program; Breast Cancer Surveillance Consortium; the medical literature. Target Population A contemporary cohort of women eligible for routine screening. Time Horizon Lifetime. Perspective Payer. Interventions Supplemental ultrasound screening for women with dense breasts following a negative screening mammogram. Outcome Measures Breast cancer deaths averted, quality-adjusted life years (QALYs) gained, false positive ultrasound biopsy recommendations, costs, costs per QALY gained. Results of Base-Case Analysis Supplemental ultrasound screening after a negative mammogram for women aged 50–74 with heterogeneously or extremely dense breasts averted 0.36 additional breast cancer deaths (range across models: 0.14–0.75), gained 1.7 QALYs (0.9–4.7), and resulted in 354 false-positive ultrasound biopsy recommendations (345–421) per 1000 women with dense breasts compared with biennial screening by mammography alone. The cost-effectiveness ratio was $325,000 per QALY gained ($112,000-$766,000). Restricting supplemental ultrasound screening to women with extremely dense breasts cost $246,000 per QALY gained ($74,000-$535,000). Results of Sensitivity Analysis The conclusions were not sensitive to ultrasound performance characteristics, screening frequency, or starting age. Limitations Provider costs for coordinating supplemental ultrasound were not considered. Conclusions Supplemental ultrasound screening for women with dense breasts undergoing screening mammography would substantially increase costs while producing relatively small benefits in breast cancer deaths averted and QALYs gained. Primary Funding Source National Institutes of Health PMID:25486550

Postnatal Growth and Retinopathy of Prematurity Study: Rationale, Design, and Subject Characteristics.

PubMed

Binenbaum, Gil; Tomlinson, Lauren A

2017-02-01

Postnatal-growth-based predictive models demonstrate strong potential for improving the low specificity of retinopathy of prematurity (ROP) screening. Prior studies are limited by inadequate sample size. We sought to study a sufficiently large cohort of at-risk infants to enable development of a model with highly precise estimates of sensitivity for severe ROP. The Postnatal Growth and ROP (G-ROP) Study was a multicenter retrospective cohort study of infants at 30 North American hospitals during 2006-2012. A total of 65 G-ROP-certified abstractors submitted data to a secure, web-based database. Data included ROP examination findings, treatments, complications, daily weight measurements, daily oxygen supplementation, maternal/infant demographics, medical comorbidities, surgical events, and weekly nutrition. Data quality was monitored with system validation rules, data audits, and discrepancy algorithms. Of 11,261 screened infants, 8334 were enrolled, and 2927 had insufficient data due to transfer, discharge, or death. Of the enrolled infants, 90% (7483) had a known ROP outcome and were included in the study. Median birth weight was 1070 g (range 310-3000g) and mean gestational age 28 weeks (range 22-35 weeks). Severe ROP (Early Treatment of Retinopathy type 1 or 2) developed in 931 infants (12.5%). Successful incorporation of a predictive model into ROP screening requires confidence that it will capture cases of severe ROP. This dataset provides power to estimate sensitivity with half-confidence interval width of less than 0.5%, determined by the high number of severe ROP cases. The G-ROP Study represents a large, diverse cohort of at-risk infants undergoing ROP screening. It will facilitate evaluation of growth-based algorithms to improve efficiency of ROP screening.

Screening tool to evaluate the vulnerability of down-gradient receptors to groundwater contaminants from uncapped landfills

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

Baker, Ronald J.; Reilly, Timothy J.; Lopez, Anthony

2015-09-15

Highlights: • A spreadsheet-based risk screening tool for groundwater affected by landfills is presented. • Domenico solute transport equations are used to estimate downgradient contaminant concentrations. • Landfills are categorized as presenting high, moderate or low risks. • Analysis of parameter sensitivity and examples of the method’s application are given. • The method has value to regulators and those considering redeveloping closed landfills. - Abstract: A screening tool for quantifying levels of concern for contaminants detected in monitoring wells on or near landfills to down-gradient receptors (streams, wetlands and residential lots) was developed and evaluated. The tool uses Quick Domenicomore » Multi-scenario (QDM), a spreadsheet implementation of Domenico-based solute transport, to estimate concentrations of contaminants reaching receptors under steady-state conditions from a constant-strength source. Unlike most other available Domenico-based model applications, QDM calculates the time for down-gradient contaminant concentrations to approach steady state and appropriate dispersivity values, and allows for up to fifty simulations on a single spreadsheet. Sensitivity of QDM solutions to critical model parameters was quantified. The screening tool uses QDM results to categorize landfills as having high, moderate and low levels of concern, based on contaminant concentrations reaching receptors relative to regulatory concentrations. The application of this tool was demonstrated by assessing levels of concern (as defined by the New Jersey Pinelands Commission) for thirty closed, uncapped landfills in the New Jersey Pinelands National Reserve, using historic water-quality data from monitoring wells on and near landfills and hydraulic parameters from regional flow models. Twelve of these landfills are categorized as having high levels of concern, indicating a need for further assessment. This tool is not a replacement for conventional numerically-based transport model or other available Domenico-based applications, but is suitable for quickly assessing the level of concern posed by a landfill or other contaminant point source before expensive and lengthy monitoring or remediation measures are taken. In addition to quantifying the level of concern using historic groundwater-monitoring data, the tool allows for archiving model scenarios and adding refinements as new data become available.« less

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

PubMed Central

Mirtz, Timothy A; Thompson, Mark A; Greene, Leon; Wyatt, Lawrence A; Akagi, Cynthia G

2005-01-01

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 school/community health planners may influence clinical health promotion practices. PMID:16318632

GeauxDock: Accelerating Structure-Based Virtual Screening with Heterogeneous Computing

PubMed Central

Fang, Ye; Ding, Yun; Feinstein, Wei P.; Koppelman, David M.; Moreno, Juana; Jarrell, Mark; Ramanujam, J.; Brylinski, Michal

2016-01-01

Computational modeling of drug binding to proteins is an integral component of direct drug design. Particularly, structure-based virtual screening is often used to perform large-scale modeling of putative associations between small organic molecules and their pharmacologically relevant protein targets. Because of a large number of drug candidates to be evaluated, an accurate and fast docking engine is a critical element of virtual screening. Consequently, highly optimized docking codes are of paramount importance for the effectiveness of virtual screening methods. In this communication, we describe the implementation, tuning and performance characteristics of GeauxDock, a recently developed molecular docking program. GeauxDock is built upon the Monte Carlo algorithm and features a novel scoring function combining physics-based energy terms with statistical and knowledge-based potentials. Developed specifically for heterogeneous computing platforms, the current version of GeauxDock can be deployed on modern, multi-core Central Processing Units (CPUs) as well as massively parallel accelerators, Intel Xeon Phi and NVIDIA Graphics Processing Unit (GPU). First, we carried out a thorough performance tuning of the high-level framework and the docking kernel to produce a fast serial code, which was then ported to shared-memory multi-core CPUs yielding a near-ideal scaling. Further, using Xeon Phi gives 1.9× performance improvement over a dual 10-core Xeon CPU, whereas the best GPU accelerator, GeForce GTX 980, achieves a speedup as high as 3.5×. On that account, GeauxDock can take advantage of modern heterogeneous architectures to considerably accelerate structure-based virtual screening applications. GeauxDock is open-sourced and publicly available at www.brylinski.org/geauxdock and https://figshare.com/articles/geauxdock_tar_gz/3205249. PMID:27420300

GeauxDock: Accelerating Structure-Based Virtual Screening with Heterogeneous Computing.

PubMed

Fang, Ye; Ding, Yun; Feinstein, Wei P; Koppelman, David M; Moreno, Juana; Jarrell, Mark; Ramanujam, J; Brylinski, Michal

2016-01-01

Computational modeling of drug binding to proteins is an integral component of direct drug design. Particularly, structure-based virtual screening is often used to perform large-scale modeling of putative associations between small organic molecules and their pharmacologically relevant protein targets. Because of a large number of drug candidates to be evaluated, an accurate and fast docking engine is a critical element of virtual screening. Consequently, highly optimized docking codes are of paramount importance for the effectiveness of virtual screening methods. In this communication, we describe the implementation, tuning and performance characteristics of GeauxDock, a recently developed molecular docking program. GeauxDock is built upon the Monte Carlo algorithm and features a novel scoring function combining physics-based energy terms with statistical and knowledge-based potentials. Developed specifically for heterogeneous computing platforms, the current version of GeauxDock can be deployed on modern, multi-core Central Processing Units (CPUs) as well as massively parallel accelerators, Intel Xeon Phi and NVIDIA Graphics Processing Unit (GPU). First, we carried out a thorough performance tuning of the high-level framework and the docking kernel to produce a fast serial code, which was then ported to shared-memory multi-core CPUs yielding a near-ideal scaling. Further, using Xeon Phi gives 1.9× performance improvement over a dual 10-core Xeon CPU, whereas the best GPU accelerator, GeForce GTX 980, achieves a speedup as high as 3.5×. On that account, GeauxDock can take advantage of modern heterogeneous architectures to considerably accelerate structure-based virtual screening applications. GeauxDock is open-sourced and publicly available at www.brylinski.org/geauxdock and https://figshare.com/articles/geauxdock_tar_gz/3205249.

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

PubMed

Arnold, Matthias

2017-12-02

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

Electronic screen use and mental well-being of 10-12-year-old children.

PubMed

Yang, Fei; Helgason, Asgeir R; Sigfusdottir, Inga Dora; Kristjansson, Alfgeir Logi

2013-06-01

Today's children spend a great deal of time viewing electronic screen material, but the consequences of such behaviors, if any, are unknown. This study sought to identify (i) the magnitude of total daily electronic screen time and (ii) the relations between electronic screen use and mental well-being indicators, in a sample of 10-12-year-old children. We analysed cross-sectional, population-based data of 10-12-year-old children from the 2007 Youth in Iceland school survey (n = 10,829, response rate: 81.7%, boys: 50.5%). Logistic regression models with odds ratios and 95% confidence intervals were conducted to assess the odds of each selected mental well-being indicator, depending on the number of daily hours spent on each electronic screen-based activity. All analyses were conducted separately for boys and girls and adjusted for family structure. The prevalence of self-reported screen use of 4 hours per day or more ranges from 2.8% to 6.6% among boys and from 1.0% to 3.8% among girls. All five screen-based activities were significantly associated with all seven well-being indicators (P < 0.001) with symptoms being more common with increased time spent on screen use. This study is the first of its kind to demonstrate a dose-response relationship between electronic screen use and mental well-being in 10-12-year-old children. Further research is needed to assess the validity and potential implications of these findings.

Women's attitude towards routine human platelet antigen-screening in pregnancy.

PubMed

Winkelhorst, Dian; Loeff, Rosanne M; van den Akker-Van Marle, M Elske; de Haas, Masja; Oepkes, Dick

2017-08-01

Fetal and neonatal alloimmune thrombocytopenia is a potentially life-threatening disease with excellent preventative treatment available for subsequent pregnancies. To prevent index cases, the effectiveness of a population-based screening program has been suggested repeatedly. Therefore, we aimed to evaluate women's attitude towards possible future human platelet antigen-screening in pregnancy. We performed a cross-sectional questionnaire study among healthy pregnant women receiving prenatal care in one of seven participating midwifery practices. Attitude was assessed using a questionnaire based on the validated Multidimensional Measurement of Informed Choice model, containing questions assessing knowledge, attitude and intention to participate. A total of 143 of the 220 women (65%) completed and returned the questionnaire. A positive attitude towards human platelet antigen-screening was expressed by 91% of participants, of which 94% was based on sufficient knowledge. Attitude was more likely to be negatively influenced by the opinion that screening can be frightening. Informed choices were made in 87% and occurred significantly less in women from non-European origin, 89% in European women vs. 60% in non-European women (p = 0.03). Pregnant women in the Netherlands expressed a positive attitude towards human platelet antigen-screening in pregnancy. We therefore expect a high rate of informed uptake when human platelet antigen-screening is implemented. In future counseling on human platelet antigen-screening, ethnicity and possible anxiety associated with a screening test need to be specifically addressed. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Patient-centered medical home implementation and use of preventive services: the role of practice socioeconomic context.

PubMed

Markovitz, Amanda R; Alexander, Jeffrey A; Lantz, Paula M; Paustian, Michael L

2015-04-01

The patient-centered medical home (PCMH) model of primary care is being implemented in a wide variety of socioeconomic contexts, yet there has been little research on whether its effects differ by context. Clinical preventive service use, including cancer screening, is an important outcome to assess the effectiveness of the PCMH within and across socioeconomic contexts. To determine whether the relationship between the PCMH and cancer screening is conditional on the socioeconomic context in which a primary care physician practice operates. A longitudinal study spanning July 1, 2009, through June 30, 2012, using data from the Blue Cross Blue Shield of Michigan Physician Group Incentive Program was conducted. Michigan nonpediatric primary care physician practices that participated in the Physician Group Incentive Program (5452 practice-years) were included. Sample size and outlier exclusion criteria were applied to each outcome. We examined the interaction between practices' PCMH implementation scores and their socioeconomic context. The implementation of a PCMH was self-reported by the practice's affiliated physician organizations and was measured as a continuous score ranging from 0 to 1. Socioeconomic context was calculated using a market-based approach based on zip code characteristics of the practice's patients and by combining multiple measures using principal components analysis. Breast, cervical, and colorectal cancer screening rates for practices' Blue Cross Blue Shield of Michigan patients. The implementation of a PCMH was associated with higher breast, cervical, and colorectal cancer screening rates across most market socioeconomic contexts. In multivariable models, the PCMH was associated with a higher rate of screening for breast cancer (5.4%; 95% CI, 1.5% to 9.3%), cervical cancer (4.2%; 95% CI, 1.4% to 6.9%), and colorectal cancer (7.0%; 95% CI, 3.6% to 10.5%) in the lowest socioeconomic group but nonsignificant differences in screening for breast cancer (2.6%; 95% CI, -0.1% to 5.3%) and cervical cancer (-0.5%; 95% CI, -2.7% to 1.7%) and a higher rate of colorectal cancer (4.5%; 95% CI, 1.8% to 7.3%) screening in the highest socioeconomic group. Because PCMH implementation was associated with larger increases in screening in lower socioeconomic practice settings, models suggest reduced disparities in screening rates across these contexts. For example, the model-predicted disparity in breast cancer screening rates between the highest and lowest socioeconomic contexts was 6% (77.9% vs 72.2%) among practices with no PCMH implementation and 3% (80.3% vs. 77.0%) among practices with full PCMH implementation. In our study, the PCMH model was associated with improved cancer screening rates across contexts but may be especially relevant for practices in lower socioeconomic areas.

Health economic evaluation of plasma oxysterol screening in the diagnosis of Niemann-Pick Type C disease among intellectually disabled using discrete event simulation.

PubMed

van Karnebeek, Clara D M; Mohammadi, Tima; Tsao, Nicole; Sinclair, Graham; Sirrs, Sandra; Stockler, Sylvia; Marra, Carlo

2015-02-01

Recently a less invasive method of screening and diagnosing Niemann-Pick C (NP-C) disease has emerged. This approach involves the use of a metabolic screening test (oxysterol assay) instead of the current practice of clinical assessment of patients suspected of NP-C (review of medical history, family history and clinical examination for the signs and symptoms). Our objective is to compare costs and outcomes of plasma oxysterol screening versus current practice in diagnosis of NP-C disease among intellectually disabled (ID) patients using decision-analytic methods. A discrete event simulation model was conducted to follow ID patients through the diagnosis and treatment of NP-C, forecast the costs and effectiveness for a cohort of ID patients and compare the outcomes and costs in two different arms of the model: plasma oxysterol screening and routine diagnosis procedure (anno 2013) over 5 years of follow up. Data from published sources and clinical trials were used in simulation model. Unit costs and quality-adjusted life-years (QALYs) were discounted at a 3% annual rate in the base case analysis. Deterministic and probabilistic sensitivity analyses were conducted. The outcomes of the base case model showed that using plasma oxysterol screening for diagnosis of NP-C disease among ID patients is a dominant strategy. It would result in lower total cost and would slightly improve patients' quality of life. The average amount of cost saving was $3642 CAD and the incremental QALYs per each individual ID patient in oxysterol screening arm versus current practice of diagnosis NP-C was 0.0022 QALYs. Results of sensitivity analysis demonstrated robustness of the outcomes over the wide range of changes in model inputs. Whilst acknowledging the limitations of this study, we conclude that screening ID children and adolescents with oxysterol tests compared to current practice for the diagnosis of NP-C is a dominant strategy with clinical and economic benefits. The less costly, more sensitive and specific oxysterol test has potential to save costs to the healthcare system while improving patients' quality of life and may be considered as a routine tool in the NP-C diagnosis armamentarium for ID. Further research is needed to elucidate its effectiveness in patients presenting characteristics other than ID in childhood and adolescence. Copyright © 2014 Elsevier Inc. All rights reserved.

Spatially resolving density-dependent screening around a single charged atom in graphene

NASA Astrophysics Data System (ADS)

Wong, Dillon; Corsetti, Fabiano; Wang, Yang; Brar, Victor W.; Tsai, Hsin-Zon; Wu, Qiong; Kawakami, Roland K.; Zettl, Alex; Mostofi, Arash A.; Lischner, Johannes; Crommie, Michael F.

2017-05-01

Electrons in two-dimensional graphene sheets behave as interacting chiral Dirac fermions and have unique screening properties due to their symmetry and reduced dimensionality. By using a combination of scanning tunneling spectroscopy measurements and theoretical modeling we have characterized how graphene's massless charge carriers screen individual charged calcium atoms. A backgated graphene device configuration has allowed us to directly visualize how the screening length for this system can be tuned with carrier density. Our results provide insight into electron-impurity and electron-electron interactions in a relativistic setting with important consequences for other graphene-based electronic devices.

Applying operations research to optimize a novel population management system for cancer screening.

PubMed

Zai, Adrian H; Kim, Seokjin; Kamis, Arnold; Hung, Ken; Ronquillo, Jeremiah G; Chueh, Henry C; Atlas, Steven J

2014-02-01

To optimize a new visit-independent, population-based cancer screening system (TopCare) by using operations research techniques to simulate changes in patient outreach staffing levels (delegates, navigators), modifications to user workflow within the information technology (IT) system, and changes in cancer screening recommendations. TopCare was modeled as a multiserver, multiphase queueing system. Simulation experiments implemented the queueing network model following a next-event time-advance mechanism, in which systematic adjustments were made to staffing levels, IT workflow settings, and cancer screening frequency in order to assess their impact on overdue screenings per patient. TopCare reduced the average number of overdue screenings per patient from 1.17 at inception to 0.86 during simulation to 0.23 at steady state. Increases in the workforce improved the effectiveness of TopCare. In particular, increasing the delegate or navigator staff level by one person improved screening completion rates by 1.3% or 12.2%, respectively. In contrast, changes in the amount of time a patient entry stays on delegate and navigator lists had little impact on overdue screenings. Finally, lengthening the screening interval increased efficiency within TopCare by decreasing overdue screenings at the patient level, resulting in a smaller number of overdue patients needing delegates for screening and a higher fraction of screenings completed by delegates. Simulating the impact of changes in staffing, system parameters, and clinical inputs on the effectiveness and efficiency of care can inform the allocation of limited resources in population management.

Screening Magnetic Resonance Imaging-Based Prediction Model for Assessing Immediate Therapeutic Response to Magnetic Resonance Imaging-Guided High-Intensity Focused Ultrasound Ablation of Uterine Fibroids.

PubMed

Kim, Young-sun; Lim, Hyo Keun; Park, Min Jung; Rhim, Hyunchul; Jung, Sin-Ho; Sohn, Insuk; Kim, Tae-Joong; Keserci, Bilgin

2016-01-01

The aim of this study was to fit and validate screening magnetic resonance imaging (MRI)-based prediction models for assessing immediate therapeutic responses of uterine fibroids to MRI-guided high-intensity focused ultrasound (MR-HIFU) ablation. Informed consent from all subjects was obtained for our institutional review board-approved study. A total of 240 symptomatic uterine fibroids (mean diameter, 6.9 cm) in 152 women (mean age, 43.3 years) treated with MR-HIFU ablation were retrospectively analyzed (160 fibroids for training, 80 fibroids for validation). Screening MRI parameters (subcutaneous fat thickness [mm], x1; relative peak enhancement [%] in semiquantitative perfusion MRI, x2; T2 signal intensity ratio of fibroid to skeletal muscle, x3) were used to fit prediction models with regard to ablation efficiency (nonperfused volume/treatment cell volume, y1) and ablation quality (grade 1-5, poor to excellent, y2), respectively, using the generalized estimating equation method. Cutoff values for achievement of treatment intent (efficiency >1.0; quality grade 4/5) were determined based on receiver operating characteristic curve analysis. Prediction performances were validated by calculating positive and negative predictive values. Generalized estimating equation analyses yielded models of y1 = 2.2637 - 0.0415x1 - 0.0011x2 - 0.0772x3 and y2 = 6.8148 - 0.1070x1 - 0.0050x2 - 0.2163x3. Cutoff values were 1.312 for ablation efficiency (area under the curve, 0.7236; sensitivity, 0.6882; specificity, 0.6866) and 4.019 for ablation quality (0.8794; 0.7156; 0.9020). Positive and negative predictive values were 0.917 and 0.500 for ablation efficiency and 0.978 and 0.600 for ablation quality, respectively. Screening MRI-based prediction models for assessing immediate therapeutic responses of uterine fibroids to MR-HIFU ablation were fitted and validated, which may reduce the risk of unsuccessful treatment.

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

DTIC Science & Technology

2008-02-01

West Society of Toxicology in Breckenridge, CO in September 2007: “Identification of Curcumin Analogs Toxic against Prostate Cancer Cells Through...quantitative structure-activity relationship ( QSAR ) and ligand-based virtual screening (LBVS) to explore the possibility of improving their efficacy...Student in my laboratory has presented part of this data at the 25th Annual Meeting of the Mountain West Society of Toxicology in Breckenridge, CO in

Φ-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays.

PubMed

Guyon, Laurent; Lajaunie, Christian; Fer, Frédéric; Bhajun, Ricky; Sulpice, Eric; Pinna, Guillaume; Campalans, Anna; Radicella, J Pablo; Rouillier, Philippe; Mary, Mélissa; Combe, Stéphanie; Obeid, Patricia; Vert, Jean-Philippe; Gidrol, Xavier

2015-09-18

Phenotypic screening monitors phenotypic changes induced by perturbations, including those generated by drugs or RNA interference. Currently-used methods for scoring screen hits have proven to be problematic, particularly when applied to physiologically relevant conditions such as low cell numbers or inefficient transfection. Here, we describe the Φ-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens. Φ-score performance was assessed with simulations, a validation experiment and its application to gene identification in a large-scale RNAi screen. Using robust statistics and a variance model, we demonstrated that the Φ-score showed better sensitivity, selectivity and reproducibility compared to classical approaches. The improved performance of the Φ-score paves the way for cell-based screening of primary cells, which are often difficult to obtain from patients in sufficient numbers. We also describe a dedicated merging procedure to pool scores from small interfering RNAs targeting the same gene so as to provide improved visualization and hit selection.

Φ-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays

PubMed Central

Guyon, Laurent; Lajaunie, Christian; fer, Frédéric; bhajun, Ricky; sulpice, Eric; pinna, Guillaume; campalans, Anna; radicella, J. Pablo; rouillier, Philippe; mary, Mélissa; combe, Stéphanie; obeid, Patricia; vert, Jean-Philippe; gidrol, Xavier

2015-01-01

Phenotypic screening monitors phenotypic changes induced by perturbations, including those generated by drugs or RNA interference. Currently-used methods for scoring screen hits have proven to be problematic, particularly when applied to physiologically relevant conditions such as low cell numbers or inefficient transfection. Here, we describe the Φ-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens. Φ-score performance was assessed with simulations, a validation experiment and its application to gene identification in a large-scale RNAi screen. Using robust statistics and a variance model, we demonstrated that the Φ-score showed better sensitivity, selectivity and reproducibility compared to classical approaches. The improved performance of the Φ-score paves the way for cell-based screening of primary cells, which are often difficult to obtain from patients in sufficient numbers. We also describe a dedicated merging procedure to pool scores from small interfering RNAs targeting the same gene so as to provide improved visualization and hit selection. PMID:26382112

Development and applicability of a ready-to-use PCR system for GMO screening.

PubMed

Rosa, Sabrina F; Gatto, Francesco; Angers-Loustau, Alexandre; Petrillo, Mauro; Kreysa, Joachim; Querci, Maddalena

2016-06-15

With the growing number of GMOs introduced to the market, testing laboratories have seen their workload increase significantly. Ready-to-use multi-target PCR-based detection systems, such as pre-spotted plates (PSP), reduce analysis time while increasing capacity. This paper describes the development and applicability to GMO testing of a screening strategy involving a PSP and its associated web-based Decision Support System. The screening PSP was developed to detect all GMOs authorized in the EU in one single PCR experiment, through the combination of 16 validated assays. The screening strategy was successfully challenged in a wide inter-laboratory study on real-life food/feed samples. The positive outcome of this study could result in the adoption of a PSP screening strategy across the EU; a step that would increase harmonization and quality of GMO testing in the EU. Furthermore, this system could represent a model for other official control areas where high-throughput DNA-based detection systems are needed. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Small molecule correctors of F508del-CFTR discovered by structure-based virtual screening

NASA Astrophysics Data System (ADS)

Kalid, Ori; Mense, Martin; Fischman, Sharon; Shitrit, Alina; Bihler, Hermann; Ben-Zeev, Efrat; Schutz, Nili; Pedemonte, Nicoletta; Thomas, Philip J.; Bridges, Robert J.; Wetmore, Diana R.; Marantz, Yael; Senderowitz, Hanoch

2010-12-01

Folding correctors of F508del-CFTR were discovered by in silico structure-based screening utilizing homology models of CFTR. The intracellular segment of CFTR was modeled and three cavities were identified at inter-domain interfaces: (1) Interface between the two Nucleotide Binding Domains (NBDs); (2) Interface between NBD1 and Intracellular Loop (ICL) 4, in the region of the F508 deletion; (3) multi-domain interface between NBD1:2:ICL1:2:4. We hypothesized that compounds binding at these interfaces may improve the stability of the protein, potentially affecting the folding yield or surface stability. In silico structure-based screening was performed at the putative binding-sites and a total of 496 candidate compounds from all three sites were tested in functional assays. A total of 15 compounds, representing diverse chemotypes, were identified as F508del folding correctors. This corresponds to a 3% hit rate, tenfold higher than hit rates obtained in corresponding high-throughput screening campaigns. The same binding sites also yielded potentiators and, most notably, compounds with a dual corrector-potentiator activity (dual-acting). Compounds harboring both activity types may prove to be better leads for the development of CF therapeutics than either pure correctors or pure potentiators. To the best of our knowledge this is the first report of structure-based discovery of CFTR modulators.

Parents' preferences for services for children with hearing loss: a conjoint analysis study.

PubMed

Fitzpatrick, Elizabeth; Coyle, Douglas E; Durieux-Smith, Andrée; Graham, Ian D; Angus, Douglas E; Gaboury, Isabelle

2007-12-01

Early identification of permanent childhood hearing loss through universal newborn hearing screening is rapidly becoming a standard of care. However, it is well recognized that hearing screening must be embedded within a comprehensive system of rehabilitation and parent support services. This study was undertaken with parents of young children with permanent hearing loss to examine their preferences for characteristics associated with intervention services. A secondary goal was to explore whether preferences may differ according to patient subgroups. Conjoint analysis, a preference-based economic technique, was used to investigate parents' strength of preferences. A cross-sectional survey that consisted of hypothetical clinic scenarios was developed based on information from qualitative interviews with parents. The questionnaire was administered to parents receiving intervention services in the province of Ontario, Canada, shortly after the implementation of a universal hearing screening program. The sample was recruited from three different clinical programs. A total of 48 of 75 respondents completed the questionnaire, a response rate of 64%. The participants varied by screening status of the child (25 screened, 23 not screened), type of device (23 hearing aids, 25 cochlear implants), and region. All five characteristics of care that were selected for inclusion in the survey were found to be statistically significant attributes of services: coordinated services, access to parent support, access to information, frequency of services, and location of services. Parents showed a preference for clinic-based rather than home-based services. Preferences toward once a week therapy services rather than services two to three times weekly were also found. In particular, parents valued service models that consisted of well-coordinated care with access to support from other parents. Differences in respondents according to hearing screening status (screened or unscreened), type of hearing device (hearing aid or cochlear implant), or region (Ottawa or Toronto) did not seem to affect parents' preferences for attributes of care. Conjoint analysis is a useful technique for quantifying parents' preferences for care. The values expressed by parents provide insights into the aspects of a service model that should receive consideration in the development of programs for young children with hearing loss and their families.

Feasible economic strategies to improve screening compliance for colorectal cancer in Korea

PubMed Central

Park, Sang Min; Yun, Young Ho; Kwon, Soonman

2005-01-01

AIM: While colorectal cancer (CRC) is an ideal target for population screening, physician and patient attitudes contribute to low levels of screening uptake. This study was carried out to find feasible economic strategies to improve the CRC screening compliance in Korea. METHODS: The natural history of a simulated cohort of 50-year-old Korean in the general population was modeled with CRC screening until the age of 80 years. Cases of positive results were worked up with colonoscopy. After polypectomy, colonoscopy was repeated every 3 years. Baseline screening compliance without insurance coverage by the national health insurance (NHI) was assumed to be 30%. If NHI covered the CRC screening or the reimbursement of screening to physicians increased, the compliance was assumed to increase. We evaluated 16 different CRC screening strategies based on Markov model. RESULTS: When the NHI did not cover the screening and compliance was 30%, non-dominated strategies were colonoscopy every 5 years (COL5) and colonoscopy every 3 years (COL3). In all scenarios of various compliance rates with raised coverage of the NHI and increased reimbursement of colonoscopy, COL10, COL5 and COL3 were non-dominated strategies, and COL10 had lower or minimal incremental medical cost and financial burden on the NHI than the strategy of no screening. These results were stable with sensitivity analyses. CONCLUSION: Economic strategies for promoting screening compliance can be accompanied by expanding insurance coverage by the NHI and by increasing reimbursement for CRC screening to providers. COL10 was a cost-effective and cost saving screening strategy for CRC in Korea. PMID:15786532

Optical photon transport in powdered-phosphor scintillators. Part II. Calculation of single-scattering transport parameters

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

Poludniowski, Gavin G.; Evans, Philip M.

2013-04-15

Purpose: Monte Carlo methods based on the Boltzmann transport equation (BTE) have previously been used to model light transport in powdered-phosphor scintillator screens. Physically motivated guesses or, alternatively, the complexities of Mie theory have been used by some authors to provide the necessary inputs of transport parameters. The purpose of Part II of this work is to: (i) validate predictions of modulation transform function (MTF) using the BTE and calculated values of transport parameters, against experimental data published for two Gd{sub 2}O{sub 2}S:Tb screens; (ii) investigate the impact of size-distribution and emission spectrum on Mie predictions of transport parameters; (iii)more » suggest simpler and novel geometrical optics-based models for these parameters and compare to the predictions of Mie theory. A computer code package called phsphr is made available that allows the MTF predictions for the screens modeled to be reproduced and novel screens to be simulated. Methods: The transport parameters of interest are the scattering efficiency (Q{sub sct}), absorption efficiency (Q{sub abs}), and the scatter anisotropy (g). Calculations of these parameters are made using the analytic method of Mie theory, for spherical grains of radii 0.1-5.0 {mu}m. The sensitivity of the transport parameters to emission wavelength is investigated using an emission spectrum representative of that of Gd{sub 2}O{sub 2}S:Tb. The impact of a grain-size distribution in the screen on the parameters is investigated using a Gaussian size-distribution ({sigma}= 1%, 5%, or 10% of mean radius). Two simple and novel alternative models to Mie theory are suggested: a geometrical optics and diffraction model (GODM) and an extension of this (GODM+). Comparisons to measured MTF are made for two commercial screens: Lanex Fast Back and Lanex Fast Front (Eastman Kodak Company, Inc.). Results: The Mie theory predictions of transport parameters were shown to be highly sensitive to both grain size and emission wavelength. For a phosphor screen structure with a distribution in grain sizes and a spectrum of emission, only the average trend of Mie theory is likely to be important. This average behavior is well predicted by the more sophisticated of the geometrical optics models (GODM+) and in approximate agreement for the simplest (GODM). The root-mean-square differences obtained between predicted MTF and experimental measurements, using all three models (GODM, GODM+, Mie), were within 0.03 for both Lanex screens in all cases. This is excellent agreement in view of the uncertainties in screen composition and optical properties. Conclusions: If Mie theory is used for calculating transport parameters for light scattering and absorption in powdered-phosphor screens, care should be taken to average out the fine-structure in the parameter predictions. However, for visible emission wavelengths ({lambda} < 1.0 {mu}m) and grain radii (a > 0.5 {mu}m), geometrical optics models for transport parameters are an alternative to Mie theory. These geometrical optics models are simpler and lead to no substantial loss in accuracy.« less

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

PubMed Central

Chavez, Pierre-François; Meeus, Joke; Robin, Florent; Schubert, Martin Alexander; Somville, Pascal

2018-01-01

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. PMID:29518936

Identification of effective screening strategies for cardiovascular disease prevention in a developing country: using cardiovascular risk-estimation and risk-reduction tools for policy recommendations.

PubMed

Selvarajah, Sharmini; Haniff, Jamaiyah; Kaur, Gurpreet; Guat Hiong, Tee; Bujang, Adam; Chee Cheong, Kee; Bots, Michiel L

2013-02-25

Recent increases in cardiovascular risk-factor prevalences have led to new national policy recommendations of universal screening for primary prevention of cardiovascular disease in Malaysia. This study assessed whether the current national policy recommendation of universal screening was optimal, by comparing the effectiveness and impact of various cardiovascular screening strategies. Data from a national population based survey of 24 270 participants aged 30 to 74 was used. Five screening strategies were modelled for the overall population and by gender; universal and targeted screening (four age cut-off points). Screening strategies were assessed based on the ability to detect high cardiovascular risk populations (effectiveness), incremental effectiveness, impact on cardiovascular event prevention and cost of screening. 26.7% (95% confidence limits 25.7, 27.7) were at high cardiovascular risk, men 34.7% (33.6, 35.8) and women 18.9% (17.8, 20). Universal screening identified all those at high-risk and resulted in one high-risk individual detected for every 3.7 people screened, with an estimated cost of USD60. However, universal screening resulted in screening an additional 7169 persons, with an incremental cost of USD115,033 for detection of one additional high-risk individual in comparison to targeted screening of those aged ≥35 years. The cost, incremental cost and impact of detection of high-risk individuals were more for women than men for all screening strategies. The impact of screening women aged ≥45 years was similar to universal screening in men. Targeted gender- and age-specific screening strategies would ensure more optimal utilisation of scarce resources compared to the current policy recommendations of universal screening.

Identification of effective screening strategies for cardiovascular disease prevention in a developing country: using cardiovascular risk-estimation and risk-reduction tools for policy recommendations

PubMed Central

2013-01-01

Background Recent increases in cardiovascular risk-factor prevalences have led to new national policy recommendations of universal screening for primary prevention of cardiovascular disease in Malaysia. This study assessed whether the current national policy recommendation of universal screening was optimal, by comparing the effectiveness and impact of various cardiovascular screening strategies. Methods Data from a national population based survey of 24 270 participants aged 30 to 74 was used. Five screening strategies were modelled for the overall population and by gender; universal and targeted screening (four age cut-off points). Screening strategies were assessed based on the ability to detect high cardiovascular risk populations (effectiveness), incremental effectiveness, impact on cardiovascular event prevention and cost of screening. Results 26.7% (95% confidence limits 25.7, 27.7) were at high cardiovascular risk, men 34.7% (33.6, 35.8) and women 18.9% (17.8, 20). Universal screening identified all those at high-risk and resulted in one high-risk individual detected for every 3.7 people screened, with an estimated cost of USD60. However, universal screening resulted in screening an additional 7169 persons, with an incremental cost of USD115,033 for detection of one additional high-risk individual in comparison to targeted screening of those aged ≥35 years. The cost, incremental cost and impact of detection of high-risk individuals were more for women than men for all screening strategies. The impact of screening women aged ≥45 years was similar to universal screening in men. Conclusions Targeted gender- and age-specific screening strategies would ensure more optimal utilisation of scarce resources compared to the current policy recommendations of universal screening. PMID:23442728

Public health genomics and personalized prevention: lessons from the COGS project.

PubMed

Pashayan, N; Hall, A; Chowdhury, S; Dent, T; Pharoah, P D P; Burton, H

2013-11-01

Using the principles of public health genomics, we examined the opportunities and challenges of implementing personalized prevention programmes for cancer at the population level. Our model-based estimates indicate that polygenic risk stratification can potentially improve the effectiveness and cost-effectiveness of screening programmes. However, compared with 'one-size-fits-all' screening programmes, personalized screening adds further layers of complexity to the organization of screening services and raises ethical, legal and social challenges. Before polygenic inheritance is translated into population screening strategy, evidence from empirical research and engagement with and education of the public and the health professionals are needed. © 2013 The Association for the Publication of the Journal of Internal Medicine.

Public stated preferences and predicted uptake for genome-based colorectal cancer screening

PubMed Central

2014-01-01

Background Emerging developments in nanomedicine allow the development of genome-based technologies for non-invasive and individualised screening for diseases such as colorectal cancer. The main objective of this study was to measure user preferences for colorectal cancer screening using a nanopill. Methods A discrete choice experiment was used to estimate the preferences for five competing diagnostic techniques including the nanopill and iFOBT. Alternative screening scenarios were described using five attributes namely: preparation involved, sensitivity, specificity, complication rate and testing frequency. Fourteen random and two fixed choice tasks, each consisting of three alternatives, were offered to 2225 individuals. Data were analysed using the McFadden conditional logit model. Results Thirteen hundred and fifty-six respondents completed the questionnaire. The most important attributes (and preferred levels) were the screening technique (nanopill), sensitivity (100%) and preparation (no preparation). Stated screening uptake for the nanopill was 79%, compared to 76% for iFOBT. In the case of screening with the nanopill, the percentage of people preferring not to be screened would be reduced from 19.2% (iFOBT) to 16.7%. Conclusions Although the expected benefits of nanotechnology based colorectal cancer screening are improved screening uptake, assuming more accurate test results and less preparation involved, the relative preference of the nanopill is only slightly higher than the iFOBT. Estimating user preferences during the development of diagnostic technologies could be used to identify relative performance, including perceived benefits and harms compared to competitors allowing for significant changes to be made throughout the process of development. PMID:24642027

Performer-centric Interface Design.

ERIC Educational Resources Information Center

McGraw, Karen L.

1995-01-01

Describes performer-centric interface design and explains a model-based approach for conducting performer-centric analysis and design. Highlights include design methodology, including cognitive task analysis; creating task scenarios; creating the presentation model; creating storyboards; proof of concept screens; object models and icons;…

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

PubMed Central

Hardouin, Jean-Benoit; Grall-Bronnec, Marie; Challet-Bouju, Gaëlle

2017-01-01

Introduction 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. Methods and analysis 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. Ethics and dissemination 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. Trial registration number NCT02415296. PMID:28515192

Validation and cost-effectiveness of a home-based screening system for amblyopia.

PubMed

Lan, Weizhong; Zhao, Feng; Li, Zhen; Zeng, Junwen; Liu, Wenyan; Lu, Jinhua; Zheng, Dehui; Lin, Lixia; Ge, Jian; Yang, Zhikuan

2012-06-01

To investigate the cost-effectiveness of a novel home-based screening system for amblyopia and amblyogenic risk factors. Evaluation of diagnostic test or technology. Two thousand four hundred forty-two preschoolers 3 to 6 years of age from 10 kindergartens randomly selected from Guangzhou participated in the study in 2009. Preschoolers were assessed for amblyopia and amblyogenic risk factors by their parents using the home-based screening system and were re-evaluated by professionals who conducted a comprehensive eye examination. Sensitivity, specificity, positive predictive value, negative predictive value, and the cost-benefit of the home-based screening system were calculated by comparing the results from the home-assessed model and those from the professional evaluation. Three thousand three hundred children were invited to participate in the study, and 2308 (1216 boys and 1092 girls) completed all of the procedures. Twenty-four amblyopes were found by professional examinations. Fifteen of these amblyopes had not been diagnosed previously, and 12 of them were detected by the home-assessment model. The sensitivity, specificity, positive predictive value, and negative predictive value were 80.0%, 94.1%, 8.2%, and 99.9%, respectively. Professional examinations cost an average of US $1131.00 per case of amblyopia detected, whereas the cost was only US $266.00 per case for the home-based method. For amblyogenic factors, 50, 87, and 96 children were classified into grade I, II, or III according to the professional examinations. The corresponding numbers in the home-based system were 23, 29, and 15, respectively. Accordingly, the true positive rates were 46.0%, 33.3%, and 15.6% for each grade. The home-based amblyopia screening system was found to be a simple, effective, and cost-beneficial method for amblyopia screening and amblyogenic risk factors. The approach offers a practical option for developing areas with large populations. The author(s) have no proprietary or commercial interest in any materials discussed in this article. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Entertainment education for prostate cancer screening: a randomized trial among primary care patients with low health literacy.

PubMed

Volk, Robert J; Jibaja-Weiss, Maria L; Hawley, Sarah T; Kneuper, Suzanne; Spann, Stephen J; Miles, Brian J; Hyman, David J

2008-12-01

To evaluate an entertainment-based patient decision aid for prostate cancer screening among patients with low or high health literacy. Male primary care patients from two clinical sites, one characterized as serving patients with low health literacy (n=149) and the second as serving patients with high health literacy (n=301), were randomized to receive an entertainment-based decision aid for prostate cancer screening or an audiobooklet-control aid with the same learner content but without the entertainment features. Postintervention and 2-week follow-up assessments were conducted. Patients at the low-literacy site were more engaged with the entertainment-based aid than patients at the high-literacy site. Overall, knowledge improved for all patients. Among patients at the low-literacy site, the entertainment-based aid was associated with lower decisional conflict and greater self-advocacy (i.e., mastering and obtaining information about screening) when compared to patients given the audiobooklet. No differences between the aids were observed for patients at the high-literacy site. Entertainment education may be an effective strategy for promoting informed decision making about prostate cancer screening among patients with lower health literacy. As barriers to implementing computer-based patient decision support programs decrease, alternative models for delivering these programs should be explored.

Cost-effectiveness of a patient navigation program to improve cervical cancer screening.

PubMed

Li, Yan; Carlson, Erin; Villarreal, Roberto; Meraz, Leah; Pagán, José A

2017-07-01

To assess the cost-effectiveness of a community-based patient navigation program to improve cervical cancer screening among Hispanic women 18 or older in San Antonio, Texas. We used a microsimulation model of cervical cancer to project the long-term cost-effectiveness of a community-based patient navigation program compared with current practice. We used program data from 2012 to 2015 and published data from the existing literature as model input. Taking a societal perspective, we estimated the lifetime costs, life expectancy, and quality-adjusted life-years and conducted 2-way sensitivity analyses to account for parameter uncertainty. The patient navigation program resulted in a per-capita gain of 0.2 years of life expectancy. The program was highly cost-effective relative to no intervention (incremental cost-effectiveness ratio of $748). The program costs would have to increase up to 10 times from $311 for it not to be cost-effective. The 3-year community-based patient navigation program effectively increased cervical cancer screening uptake and adherence and improved the cost-effectiveness of the screening program for Hispanic women 18 years or older in San Antonio, Texas. Future research is needed to translate and disseminate the patient navigation program to other socioeconomic and demographic groups to test its robustness and design.

A three-dimensional refractive index model for simulation of optical wave propagation in atmospheric turbulence

NASA Astrophysics Data System (ADS)

Paramonov, P. V.; Vorontsov, A. M.; Kunitsyn, V. E.

2015-10-01

Numerical modeling of optical wave propagation in atmospheric turbulence is traditionally performed with using the so-called "split"-operator method, when the influence of the propagation medium's refractive index inhomogeneities is accounted for only within a system of infinitely narrow layers (phase screens) where phase is distorted. Commonly, under certain assumptions, such phase screens are considered as mutually statistically uncorrelated. However, in several important applications including laser target tracking, remote sensing, and atmospheric imaging, accurate optical field propagation modeling assumes upper limitations on interscreen spacing. The latter situation can be observed, for instance, in the presence of large-scale turbulent inhomogeneities or in deep turbulence conditions, where interscreen distances become comparable with turbulence outer scale and, hence, corresponding phase screens cannot be statistically uncorrelated. In this paper, we discuss correlated phase screens. The statistical characteristics of screens are calculated based on a representation of turbulent fluctuations of three-dimensional (3D) refractive index random field as a set of sequentially correlated 3D layers displaced in the wave propagation direction. The statistical characteristics of refractive index fluctuations are described in terms of the von Karman power spectrum density. In the representation of these 3D layers by corresponding phase screens, the geometrical optics approximation is used.

Cost-effectiveness of Chlamydia antibody tests in subfertile women.

PubMed

Fiddelers, A A A; Land, J A; Voss, G; Kessels, A G H; Severens, J L

2005-02-01

For the evaluation of tubal function, Chlamydia antibody testing (CAT) has been introduced as a screening test. We compared six CAT screening strategies (five CAT tests and one combination of tests), with respect to their cost-effectiveness, by using IVF pregnancy rate as outcome measure. A decision analytic model was developed based on a source population of 1715 subfertile women. The model incorporates hysterosalpingography (HSG), laparoscopy and IVF. To calculate IVF pregnancy rates, costs, effects, cost-effectiveness and incremental costs per effect of the six different CAT screening strategies were determined. pELISA Medac turned out to be the most cost-effective CAT screening strategy (15 075 per IVF pregnancy), followed by MIF Anilabsystems (15 108). A combination of tests (pELISA Medac and MIF Anilabsystems; 15 127) did not improve the cost-effectiveness of the single strategies. Sensitivity analyses showed that the results are robust for changes in the baseline values of the model parameters. Only small differences were found between the screening strategies regarding the cost-effectiveness, although pELISA Medac was the most cost-effective strategy. Before introducing a particular CAT test into clinical practice, one should consider the effects and consequences of the entire screening strategy, instead of only the diagnostic accuracy of the test used.

Polygenic susceptibility to testicular cancer: implications for personalised health care.

PubMed

Litchfield, Kevin; Mitchell, Jonathan S; Shipley, Janet; Huddart, Robert; Rajpert-De Meyts, Ewa; Skakkebæk, Niels E; Houlston, Richard S; Turnbull, Clare

2015-11-17

The increasing incidence of testicular germ cell tumour (TGCT) combined with its strong heritable basis suggests that stratified screening for the early detection of TGCT may be clinically useful. We modelled the efficiency of such a personalised screening approach, based on genetic risk profiling in combination with other diagnostic tools. We compared the number of cases potentially detectable in the population under a number of screening models. The polygenic risk scoring (PRS) model was assumed to have a log-normal relative risk distribution across the 19 currently known TGCT susceptibility variants. The diagnostic performance of testicular biopsy and non-invasive semen analysis was also assessed, within a simulated combined screening programme. The area under the curve for the TGCT PRS model was 0.72 with individuals in the top 1% of the PRS having a nine-fold increased TGCT risk compared with the population median. Results from population-screening simulations only achieved a maximal positive predictive value (PPV) of 60%, highlighting broader clinical factors that challenge such strategies, not least the rare nature of TGCT. In terms of future improvements, heritability estimates suggest that a significant number of additional genetic risk factors for TGCT remain to be discovered, identification of which would potentially yield improvement of the PPV to 80-90%. While personalised screening models may offer enhanced TGCT risk discrimination, presently the case for population-level testing is not compelling. However, future advances, such as more routine generation of whole genome data is likely to alter the landscape. More targeted screening programs may plausibly then offer clinical benefit, particularly given the significant survivorship issues associated with the successful treatment of TGCT.

Spiritually based intervention to increase colorectal cancer screening among African Americans: screening and theory-based outcomes from a randomized trial.

PubMed

Holt, Cheryl L; Litaker, Mark S; Scarinci, Isabel C; Debnam, Katrina J; McDavid, Chastity; McNeal, Sandre F; Eloubeidi, Mohamad A; Crowther, Martha; Bolland, John; Martin, Michelle Y

2013-08-01

Colorectal cancer screening has clear benefits in terms of mortality reduction; however, it is still underutilized and especially among medically underserved populations, including African Americans, who also suffer a disproportionate colorectal cancer burden. This study consisted of a theory-driven (health belief model) spiritually based intervention aimed at increasing screening among African Americans through a community health advisor-led educational series in 16 churches. Using a randomized design, churches were assigned to receive either the spiritually based intervention or a nonspiritual comparison, which was the same in every way except that it did not contain spiritual/religious content and themes. Trained and certified peer community health advisors in each church led a series of two group educational sessions on colorectal cancer and screening. Study enrollees completed a baseline, 1-month, and 12-month follow-up survey at their churches. The interventions had significant pre-post impact on awareness of all four screening modalities, and self-report receipt of fecal occult blood test, flexible sigmoidoscopy, and colonoscopy. There were no significant study group differences in study outcomes, with the exception of fecal occult blood test utilization, whereas those in the nonspiritual intervention reported significantly greater pre-post change. Both of these community-engaged, theory-driven, culturally relevant approaches to increasing colorectal cancer awareness and screening appeared to have an impact on study outcomes. Although adding spiritual/religious themes to the intervention was appealing to the audience, it may not result in increased intervention efficacy.

Hit Generation in TB Drug Discovery: From Genome to Granuloma

PubMed Central

2018-01-01

Current tuberculosis (TB) drug development efforts are not sufficient to end the global TB epidemic. Recent efforts have focused on the development of whole-cell screening assays because biochemical, target-based inhibitor screens during the last two decades have not delivered new TB drugs. Mycobacterium tuberculosis (Mtb), the causative agent of TB, encounters diverse microenvironments and can be found in a variety of metabolic states in the human host. Due to the complexity and heterogeneity of Mtb infection, no single model can fully recapitulate the in vivo conditions in which Mtb is found in TB patients, and there is no single “standard” screening condition to generate hit compounds for TB drug development. However, current screening assays have become more sophisticated as researchers attempt to mirror the complexity of TB disease in the laboratory. In this review, we describe efforts using surrogates and engineered strains of Mtb to focus screens on specific targets. We explain model culture systems ranging from carbon starvation to hypoxia, and combinations thereof, designed to represent the microenvironment which Mtb encounters in the human body. We outline ongoing efforts to model Mtb infection in the lung granuloma. We assess these different models, their ability to generate hit compounds, and needs for further TB drug development, to provide direction for future TB drug discovery. PMID:29384369

Cost effectiveness of fecal DNA screening for colorectal cancer: a systematic review and quality appraisal of the literature.

PubMed

Skally, Mairead; Hanly, Paul; Sharp, Linda

2013-06-01

Fecal DNA (fDNA) testing is a noninvasive potential alternative to current colorectal cancer screening tests. We conducted a systematic review and quality assessment of studies of cost-effectiveness of fDNA as a colorectal cancer screening tool (compared with no screening and other screening modalities), and identified key variables that impinged on cost-effectiveness. We searched MEDLINE, Embase, and the Centre for Reviews and Dissemination for cost-effectiveness studies of fDNA-based screening, published in English by September 2011. Studies that undertook an economic evaluation of fDNA, using either a cost-effectiveness or cost-utility analysis, compared with other relevant screening modalities and/or no screening were included. Additional inclusion criteria related to the presentation of data pertaining to model variables including time horizon, costs, fDNA performance characteristics, screening uptake, and comparators. A total of 369 articles were initially identified for review. After removing duplicates and applying inclusion and exclusion criteria, seven articles were included in the final review. Data was abstracted on key descriptor variables including screening scenarios, time horizon, costs, test performance characteristics, screening uptake, comparators, and incremental cost-effectiveness ratios. Quality assessment was undertaken using a standard checklist for economic evaluations. Studies cited by cost-effectiveness articles as the source of data on fDNA test performance characteristics were also reviewed. Seven cost-effectiveness studies were included, from the USA (4), Canada (1), Israel (1), and Taiwan (1). Markov models (5), a partially observable Markov decision process model (1) and MISCAN and SimCRC (1) microsimulation models were used. All studies took a third-party payer perspective and one included, in addition, a societal perspective. Comparator screening tests, screening intervals, and specific fDNA tests varied between studies. fDNA sensitivity and specificity parameters were derived from 12 research studies and one meta-analysis. Outcomes assessed were life-years gained and quality-adjusted life-years gained. fDNA was cost-effective when compared with no screening in six studies. Compared with other screening modalities, fDNA was not considered cost-effective in any of the base-case analyses: in five studies it was dominated by all alternatives considered. Sensitivity analyses identified cost, compliance, and test parameters as key influential parameters. In general, poor presentation of "study design" and "data collection" details lowered the quality of included articles. Although the literature searches were designed for high sensitivity, the possibility cannot be excluded that some eligible studies may have been missed. Reports (such as Health Technology Assessments produced by government agencies) and other forms of grey literature were excluded because they are difficult to identify systematically and/or may not report methods and results in sufficient detail for assessment. On the basis of the available (albeit limited) evidence, while fDNA is cost-effective when compared with no screening, it is currently dominated by most of the other available screening options. Cost and test performance appear to be the main influences on cost-effectiveness.

PROGRESS TOWARDS DEVELOPMENT OF AN AMPHIBIAN-BASED THYROID SCREENING ASSAY USING XENOPUS LAEVIS: ORGANISMAL AND THYROIDAL RESPONSES TO THE MODEL COMPOUNDS 6-PROPYLTHIOURACIL, METHIMAZOLE, AND THYROXINE.

EPA Science Inventory

The data presented in this manuscript specifically addresses the development and standardization needs associated with an amphibian thyroid axis screening assay. A protocol for an amphibian growth and reproduction test has been requested by the Office of Science Council and Polic...

Reasons Given by High School Students for Refusing Sexually Transmitted Disease Screening

ERIC Educational Resources Information Center

Sanders, Ladatra S.; Nsuami, Malanda; Cropley, Lorelei D.; Taylor, Stephanie N.

2007-01-01

Objective: To determine reasons given by high school students for refusing to participate in a school-based noninvasive chlamydia and gonorrhea screening that was offered at no cost to students, using the health belief model as theoretical framework. Design: Cross-sectional survey. Setting: Public high schools in a southern urban United States…

Perceived Neighborhood Quality and Cancer Screening Behavior: Evidence from the Survey of the Health of Wisconsin.

PubMed

Beyer, Kirsten M M; Malecki, Kristen M; Hoormann, Kelly A; Szabo, Aniko; Nattinger, Ann B

2016-02-01

Socioeconomic disparities in colorectal and breast cancer screening persist, partially accounting for disparities in cancer outcomes. Some neighborhood characteristics--particularly area level socioeconomic factors--have been linked to cancer screening behavior, but few studies have examined the relationship between perceived neighborhood quality and screening behavior, which may provide more insight into the ways in which neighborhood environments shape cancer related behaviors. This study examines the relationship between several aspects of the perceived neighborhood environment and breast and colorectal cancer screening behavior among a population-based sample of Wisconsin residents. A sub-goal was to compare the relevance of different perceived neighborhood factors for different screening tests. This is a cross-sectional study of 2008-2012 data from the Survey of the Health of Wisconsin, a population-based annual survey of Wisconsin residents. An average risk sample of Black, Hispanic and White women age 50 and older (n = 1265) were selected. Survey regression analyses examined predictors of screening, as well as adherence to screening guidelines. Models controlled for individual socio-demographic information and insurance status. Perceptions of social and physical disorder, including fear of crime and visible garbage, were associated with screening rates. Findings emphasize the particular importance of these factors for colorectal cancer screening, indicating the necessity of improving screening rates in areas characterized by social disorganization, crime, and physical disorder. Additional work should be done to further investigate the pathways that explain the linkage between neighborhood conditions, perceived neighborhood risks and cancer screening behavior.

Risk stratification in cervical cancer screening by complete screening history: Applying bioinformatics to a general screening population.

PubMed

Baltzer, Nicholas; Sundström, Karin; Nygård, Jan F; Dillner, Joakim; Komorowski, Jan

2017-07-01

Women screened for cervical cancer in Sweden are currently treated under a one-size-fits-all programme, which has been successful in reducing the incidence of cervical cancer but does not use all of the participants' available medical information. This study aimed to use women's complete cervical screening histories to identify diagnostic patterns that may indicate an increased risk of developing cervical cancer. A nationwide case-control study was performed where cervical cancer screening data from 125,476 women with a maximum follow-up of 10 years were evaluated for patterns of SNOMED diagnoses. The cancer development risk was estimated for a number of different screening history patterns and expressed as Odds Ratios (OR), with a history of 4 benign cervical tests as reference, using logistic regression. The overall performance of the model was moderate (64% accuracy, 71% area under curve) with 61-62% of the study population showing no specific patterns associated with risk. However, predictions for high-risk groups as defined by screening history patterns were highly discriminatory with ORs ranging from 8 to 36. The model for computing risk performed consistently across different screening history lengths, and several patterns predicted cancer outcomes. The results show the presence of risk-increasing and risk-decreasing factors in the screening history. Thus it is feasible to identify subgroups based on their complete screening histories. Several high-risk subgroups identified might benefit from an increased screening density. Some low-risk subgroups identified could likely have a moderately reduced screening density without additional risk. © 2017 UICC.

Prediction of prostate cancer in unscreened men: external validation of a risk calculator.

PubMed

van Vugt, Heidi A; Roobol, Monique J; Kranse, Ries; Määttänen, Liisa; Finne, Patrik; Hugosson, Jonas; Bangma, Chris H; Schröder, Fritz H; Steyerberg, Ewout W

2011-04-01

Prediction models need external validation to assess their value beyond the setting where the model was derived from. To assess the external validity of the European Randomized study of Screening for Prostate Cancer (ERSPC) risk calculator (www.prostatecancer-riskcalculator.com) for the probability of having a positive prostate biopsy (P(posb)). The ERSPC risk calculator was based on data of the initial screening round of the ERSPC section Rotterdam and validated in 1825 and 531 men biopsied at the initial screening round in the Finnish and Swedish sections of the ERSPC respectively. P(posb) was calculated using serum prostate specific antigen (PSA), outcome of digital rectal examination (DRE), transrectal ultrasound and ultrasound assessed prostate volume. The external validity was assessed for the presence of cancer at biopsy by calibration (agreement between observed and predicted outcomes), discrimination (separation of those with and without cancer), and decision curves (for clinical usefulness). Prostate cancer was detected in 469 men (26%) of the Finnish cohort and in 124 men (23%) of the Swedish cohort. Systematic miscalibration was present in both cohorts (mean predicted probability 34% versus 26% observed, and 29% versus 23% observed, both p<0.001). The areas under the curves were 0.76 and 0.78, and substantially lower for the model with PSA only (0.64 and 0.68 respectively). The model proved clinically useful for any decision threshold compared with a model with PSA only, PSA and DRE, or biopsying all men. A limitation is that the model is based on sextant biopsies results. The ERSPC risk calculator discriminated well between those with and without prostate cancer among initially screened men, but overestimated the risk of a positive biopsy. Further research is necessary to assess the performance and applicability of the ERSPC risk calculator when a clinical setting is considered rather than a screening setting. Copyright © 2010 Elsevier Ltd. All rights reserved.

Multi-modality image registration for effective thermographic fever screening

NASA Astrophysics Data System (ADS)

Dwith, C. Y. N.; Ghassemi, Pejhman; Pfefer, Joshua; Casamento, Jon; Wang, Quanzeng

2017-02-01

Fever screening based on infrared thermographs (IRTs) is a viable mass screening approach during infectious disease pandemics, such as Ebola and Severe Acute Respiratory Syndrome (SARS), for temperature monitoring in public places like hospitals and airports. IRTs have been found to be powerful, quick and non-invasive methods for detecting elevated temperatures. Moreover, regions medially adjacent to the inner canthi (called the canthi regions in this paper) are preferred sites for fever screening. Accurate localization of the canthi regions can be achieved through multi-modality registration of infrared (IR) and white-light images. Here we propose a registration method through a coarse-fine registration strategy using different registration models based on landmarks and edge detection on eye contours. We have evaluated the registration accuracy to be within +/- 2.7 mm, which enables accurate localization of the canthi regions.

Screening for heat transport by groundwater in closed geothermal systems.

PubMed

Ferguson, Grant

2015-01-01

Heat transfer due to groundwater flow can significantly affect closed geothermal systems. Here, a screening method is developed, based on Peclet numbers for these systems and Darcy's law. Conduction-only conditions should not be expected where specific discharges exceed 10(-8)  m/s. Constraints on hydraulic gradients allow for preliminary screening for advection based on rock or soil types. Identification of materials with very low hydraulic conductivity, such as shale and intact igneous and metamorphic rock, allow for analysis with considering conduction only. Variability in known hydraulic conductivity allows for the possibility of advection in most other rocks and soil types. Further screening relies on refinement of estimates of hydraulic gradients and hydraulic conductivity through site investigations and modeling until the presence or absence of conduction can be confirmed. © 2014, National Ground Water Association.

Selecting a mix of prevention strategies against cervical cancer for maximum efficiency with an optimization program.

PubMed

Demarteau, Nadia; Breuer, Thomas; Standaert, Baudouin

2012-04-01

Screening and vaccination against human papillomavirus (HPV) can protect against cervical cancer. Neither alone can provide 100% protection. Consequently it raises the important question about the most efficient combination of screening at specified time intervals and vaccination to prevent cervical cancer. Our objective was to identify the mix of cervical cancer prevention strategies (screening and/or vaccination against HPV) that achieves maximum reduction in cancer cases within a fixed budget. We assessed the optimal mix of strategies for the prevention of cervical cancer using an optimization program. The evaluation used two models. One was a Markov cohort model used as the evaluation model to estimate the costs and outcomes of 52 different prevention strategies. The other was an optimization model in which the results of each prevention strategy of the previous model were entered as input data. The latter model determined the combination of the different prevention options to minimize cervical cancer under budget, screening coverage and vaccination coverage constraints. We applied the model in two countries with different healthcare organizations, epidemiology, screening practices, resource settings and treatment costs: the UK and Brazil. 100,000 women aged 12 years and above across the whole population over a 1-year period at steady state were included. The intervention was papanicolaou (Pap) smear screening programmes and/or vaccination against HPV with the bivalent HPV 16/18 vaccine (Cervarix® [Cervarix is a registered trademark of the GlaxoSmithKline group of companies]). The main outcome measures were optimal distribution of the population between different interventions (screening, vaccination, screening plus vaccination and no screening or vaccination) with the resulting number of cervical cancer and associated costs. In the base-case analysis (= same budget as today), the optimal prevention strategy would be, after introducing vaccination with a coverage rate of 80% in girls aged 12 years and retaining screening coverage at pre-vaccination levels (65% in the UK, 50% in Brazil), to increase the screening interval to 6 years (from 3) in the UK and to 5 years (from 3) in Brazil. This would result in a reduction of cervical cancer by 41% in the UK and by 54% in Brazil from pre-vaccination levels with no budget increase. Sensitivity analysis shows that vaccination alone at 80% coverage with no screening would achieve a cervical cancer reduction rate of 20% in the UK and 43% in Brazil compared with the pre-vaccination situation with a budget reduction of 30% and 14%, respectively. In both countries, the sharp reduction in cervical cancer is seen when the vaccine coverage rate exceeds the maximum screening coverage rate, or when screening coverage rate exceeds the maximum vaccine coverage rate, while maintaining the budget. As with any model, there are limitations to the value of predictions depending upon the assumptions made in each model. Spending the same budget that was used for screening and treatment of cervical cancer in the pre-vaccination era, results of the optimization program show that it would be possible to substantially reduce the number of cases by implementing an optimal combination of HPV vaccination (80% coverage) and screening at pre-vaccination coverage (65% UK, 50% Brazil) while extending the screening interval to every 6 years in the UK and 5 years in Brazil.

Promoting community awareness of the need for colorectal cancer screening: a pilot study.

PubMed

Greenwald, Beverly

2006-01-01

The purpose of this pilot study was to determine if a community education program based on the Health Belief Model effectively promotes awareness of the need for colorectal cancer (CRC) prevention and screening. An education program was given to 20 employees of an accounting firm in a midwestern city. A survey evaluated the participants' beliefs about CRC, before and after the presentation. The results support a significant increase in the belief that CRC is preventable, and in 5 of 6 screening factors from the Health Belief Model. Participants were encouraged to share what they learned and reported that they anticipate sharing with at least 31 others. A screening questionnaire was distributed as a "cue to action" to discuss CRC screening with their physicians. Participants' intention to discuss CRC with their physicians also increased. The actual effectiveness will be evaluated with 11 participants who volunteered for a 1-year follow-up study. This community education concept had several advantages, including simultaneous access to many participants who share personal testimonials and who invite peers to become screened. The program was effective in increasing awareness of the need for CRC prevention and screening, even beyond those in attendance. The results of the 1-year follow-up study may provide more insight to what education factors promote screening most effectively.

Analysis of the diffraction effects for a multi-view autostereoscopic three-dimensional display system based on shutter parallax barriers with full resolution

NASA Astrophysics Data System (ADS)

Meng, Yang; Yu, Zhongyuan; Jia, Fangda; Zhang, Chunyu; Wang, Ye; Liu, Yumin; Ye, Han; Chen, Laurence Lujun

2017-10-01

A multi-view autostereoscopic three-dimensional (3D) system is built by using a 2D display screen and a customized parallax-barrier shutter (PBS) screen. The shutter screen is controlled dynamically by address driving matrix circuit and it is placed in front of the display screen at a certain location. The system could achieve densest viewpoints due to its specially optical and geometric design which is based on concept of "eye space". The resolution of 3D imaging is not reduced compared to 2D mode by using limited time division multiplexing technology. The diffraction effects may play an important role in 3D display imaging quality, especially when applied to small screen, such as iPhone screen etc. For small screen, diffraction effects may contribute crosstalk between binocular views, image brightness uniformity etc. Therefore, diffraction effects are analyzed and considered in a one-dimensional shutter screen model of the 3D display, in which the numerical simulation of light from display pixels on display screen through parallax barrier slits to each viewing zone in eye space, is performed. The simulation results provide guidance for criteria screen size over which the impact of diffraction effects are ignorable, and below which diffraction effects must be taken into account. Finally, the simulation results are compared to the corresponding experimental measurements and observation with discussion.

Trainable structure-activity relationship model for virtual screening of CYP3A4 inhibition.

PubMed

Didziapetris, Remigijus; Dapkunas, Justas; Sazonovas, Andrius; Japertas, Pranas

2010-11-01

A new structure-activity relationship model predicting the probability for a compound to inhibit human cytochrome P450 3A4 has been developed using data for >800 compounds from various literature sources and tested on PubChem screening data. Novel GALAS (Global, Adjusted Locally According to Similarity) modeling methodology has been used, which is a combination of baseline global QSAR model and local similarity based corrections. GALAS modeling method allows forecasting the reliability of prediction thus defining the model applicability domain. For compounds within this domain the statistical results of the final model approach the data consistency between experimental data from literature and PubChem datasets with the overall accuracy of 89%. However, the original model is applicable only for less than a half of PubChem database. Since the similarity correction procedure of GALAS modeling method allows straightforward model training, the possibility to expand the applicability domain has been investigated. Experimental data from PubChem dataset served as an example of in-house high-throughput screening data. The model successfully adapted itself to both data classified using the same and different IC₅₀ threshold compared with the training set. In addition, adjustment of the CYP3A4 inhibition model to compounds with a novel chemical scaffold has been demonstrated. The reported GALAS model is proposed as a useful tool for virtual screening of compounds for possible drug-drug interactions even prior to the actual synthesis.

Screening tool to evaluate the vulnerability of down-gradient receptors to groundwater contaminants from uncapped landfills

USGS Publications Warehouse

Baker, Ronald J.; Reilly, Timothy J.; Lopez, Anthony R.; Romanok, Kristin M.; Wengrowski, Edward W

2015-01-01

A screening tool for quantifying levels of concern for contaminants detected in monitoring wells on or near landfills to down-gradient receptors (streams, wetlands and residential lots) was developed and evaluated. The tool uses Quick Domenico Multi-scenario (QDM), a spreadsheet implementation of Domenico-based solute transport, to estimate concentrations of contaminants reaching receptors under steady-state conditions from a constant-strength source. Unlike most other available Domenico-based model applications, QDM calculates the time for down-gradient contaminant concentrations to approach steady state and appropriate dispersivity values, and allows for up to fifty simulations on a single spreadsheet. Sensitivity of QDM solutions to critical model parameters was quantified. The screening tool uses QDM results to categorize landfills as having high, moderate and low levels of concern, based on contaminant concentrations reaching receptors relative to regulatory concentrations. The application of this tool was demonstrated by assessing levels of concern (as defined by the New Jersey Pinelands Commission) for thirty closed, uncapped landfills in the New Jersey Pinelands National Reserve, using historic water-quality data from monitoring wells on and near landfills and hydraulic parameters from regional flow models. Twelve of these landfills are categorized as having high levels of concern, indicating a need for further assessment. This tool is not a replacement for conventional numerically-based transport model or other available Domenico-based applications, but is suitable for quickly assessing the level of concern posed by a landfill or other contaminant point source before expensive and lengthy monitoring or remediation measures are taken. In addition to quantifying the level of concern using historic groundwater-monitoring data, the tool allows for archiving model scenarios and adding refinements as new data become available.

Strategy for Identifying Repurposed Drugs for the Treatment of Cerebral Cavernous Malformation

PubMed Central

Gibson, Christopher C.; Zhu, Weiquan; Davis, Chadwick T.; Bowman-Kirigin, Jay A.; Chan, Aubrey C.; Ling, Jing; Walker, Ashley E.; Goitre, Luca; Monache, Simona Delle; Retta, Saverio Francesco; Shiu, Yan-Ting E.; Grossmann, Allie H.; Thomas, Kirk R.; Donato, Anthony J.; Lesniewski, Lisa A.; Whitehead, Kevin J.; Li, Dean Y.

2014-01-01

Background Cerebral cavernous malformation (CCM) is a hemorrhagic stroke disease affecting up to 0.5% of North Americans with no approved non-surgical treatment. A subset of patients have a hereditary form of the disease due primarily to loss-of-function mutations in KRIT1, CCM2, or PDCD10. We sought to identify known drugs that could be repurposed to treat CCM. Methods and Results We developed an unbiased screening platform based on both cellular and animal models of loss-of-function of CCM2. Our discovery strategy consisted of four steps: an automated immunofluorescence and machine-learning-based primary screen of structural phenotypes in human endothelial cells deficient in CCM2; a secondary screen of functional changes in endothelial stability in these same cells; a rapid in vivo tertiary screen of dermal microvascular leak in mice lacking endothelial Ccm2; and finally a quaternary screen of CCM lesion burden in these same mice. We screened 2,100 known drugs and bioactive compounds, and identified two candidates for further study, cholecalciferol (Vitamin D3) and tempol (a scavenger of superoxide). Each drug decreased lesion burden in a mouse model of CCM vascular disease by approximately 50%. Conclusions By identifying known drugs as potential therapeutics for CCM, we have decreased the time, cost, and risk of bringing treatments to patients. Each drug also prompts additional exploration of biomarkers of CCM disease. We further suggest that the structure-function screening platform presented here may be adapted and scaled to facilitate drug discovery for diverse loss-of-function genetic vascular disease. PMID:25486933

Cardiac Screening Prior to Stimulant Treatment of ADHD: A Survey of US-Based Pediatricians

PubMed Central

Rodday, Angie Mae; Saunders, Tully S.; Cohen, Joshua T.; Wong, John B.; Parsons, Susan K.

2012-01-01

OBJECTIVES: To determine pediatricians’ attitudes, barriers, and practices regarding cardiac screening before initiating treatment with stimulants for attention-deficit/hyperactivity disorder. METHODS: A survey of 1600 randomly selected, practicing US pediatricians with American Academy of Pediatrics membership was conducted. Multivariate models were created for 3 screening practices: (1) performing an in-depth cardiac history and physical (H & P) examination, (2) discussing potential stimulant-related cardiac risks, and (3) ordering an electrocardiogram (ECG). RESULTS: Of 817 respondents (51%), 525 (64%) met eligibility criteria. Regarding attitudes, pediatricians agreed that both the risk for sudden cardiac death (SCD) (24%) and legal liability (30%) were sufficiently high to warrant cardiac assessment; 75% agreed that physicians were responsible for informing families about SCD risk. When identifying cardiac disorders, few (18%) recognized performing an in-depth cardiac H & P as a barrier; in contrast, 71% recognized interpreting a pediatric ECG as a barrier. When asked about cardiac screening practices before initiating stimulant treatment for a recent patient, 93% completed a routine H & P, 48% completed an in-depth cardiac H & P, and 15% ordered an ECG. Almost half (46%) reported discussing stimulant-related cardiac risks. Multivariate modeling indicated that ≥1 of these screening practices were associated with physicians’ attitudes about SCD risk, legal liability, their responsibility to inform about risk, their ability to perform an in-depth cardiac H & P, and family concerns about risk. CONCLUSIONS: Variable pediatrician attitudes and cardiac screening practices reflect the limited evidence base and conflicting guidelines regarding cardiac screening. Barriers to identifying cardiac disorders influence practice. PMID:22250023

Value Analysis of Digital Breast Tomosynthesis for Breast Cancer Screening in a US Medicaid Population.

PubMed

Miller, Jeffrey D; Bonafede, Machaon M; Herschorn, Sally D; Pohlman, Scott K; Troeger, Kathleen A; Fajardo, Laurie L

2017-04-01

Better understanding regarding the clinical-economic value of digital breast tomosynthesis (DBT) for breast cancer screening for Medicaid enrollees is needed to help inform sound, value-based decision making. The objective of this study was to conduct a clinical-economic value analysis of DBT for breast cancer screening among women enrolled in Medicaid to assess the potential clinical benefits, associated expenditures, and net budget impact of DBT. Two annual screening mammography scenarios were evaluated with an economic model: (1) full-field digital mammography and (2) combined full-field digital mammography and DBT. The model focused on two main drivers of DBT value: (1) capacity for DBT to reduce the number of women recalled for additional follow-up imaging and diagnostic services and (2) capacity of DBT to facilitate earlier diagnosis of cancer at earlier stages, when treatment costs are lower. Model analysis results showed that the use of DBT as a mammographic screening modality by Medicaid enrollees potentially reduces the need for follow-up diagnostic services and improves the detection of invasive cancers, allowing earlier, less costly treatment. With the modest incremental reimbursement of $37 for DBT expected for a typical Medicaid claim, annual cost savings from DBT predicted by the model amounts to $8.14 per patient, potentially translating into more than $12,000 savings per year for an average-sized Medicaid plan and as much as $207,000 savings per year for a typical state Medicaid program. Wider adoption of DBT presents an opportunity to deliver value-based care to Medicaid programs and to help address disparities and barriers to accessing preventive care by some of the nation's most vulnerable citizens. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Cost-Effectiveness of Osteoporosis Screening Strategies for Men

PubMed Central

Nayak, Smita; Greenspan, Susan L.

2016-01-01

Osteoporosis affects many men, with significant morbidity and mortality. However, the best osteoporosis screening strategies for men are unknown. We developed an individual-level state-transition cost-effectiveness model with a lifetime time horizon to identify the cost-effectiveness of different osteoporosis screening strategies for U.S. men involving various screening tests (dual-energy x-ray absorptiometry (DXA); the Osteoporosis Self-Assessment Tool (OST); or a fracture risk assessment strategy using age, femoral neck bone mineral density (BMD), and Vertebral Fracture Assessment (VFA)); screening initiation ages (50, 60, 70, or 80); and repeat screening intervals (5 years or 10 years). In base-case analysis, no screening was a less effective option than all other strategies evaluated; furthermore, no screening was more expensive than all strategies that involved screening with DXA or the OST risk assessment instrument, and thus no screening was “dominated” by screening with DXA or OST at all evaluated screening initiation ages and repeat screening intervals. Screening strategies that most frequently appeared as most cost-effective in base-case analysis and one-way sensitivity analyses when assuming willingness-to-pay of $50,000/QALY or $100,000/QALY included screening initiation at age 50 with the fracture risk assessment strategy and repeat screening every 10 years; screening initiation at age 50 with fracture risk assessment and repeat screening every 5 years; and screening initiation at age 50 with DXA and repeat screening every 5 years. In conclusion, expansion of osteoporosis screening for U.S. men to initiate routine screening at age 50 or 60 would be expected to be effective and of good value for improving health outcomes. A fracture risk assessment strategy using variables of age, femoral neck BMD, and VFA is likely to be the most effective of the evaluated strategies within accepted cost-effectiveness parameters. DXA and OST are also reasonable screening options, albeit likely slightly less effective than the evaluated fracture risk assessment strategy. PMID:26751984

Cost-effectiveness of prostate cancer screening: a simulation study based on ERSPC data.

PubMed

Heijnsdijk, E A M; de Carvalho, T M; Auvinen, A; Zappa, M; Nelen, V; Kwiatkowski, M; Villers, A; Páez, A; Moss, S M; Tammela, T L J; Recker, F; Denis, L; Carlsson, S V; Wever, E M; Bangma, C H; Schröder, F H; Roobol, M J; Hugosson, J; de Koning, H J

2015-01-01

The results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial showed a statistically significant 29% prostate cancer mortality reduction for the men screened in the intervention arm and a 23% negative impact on the life-years gained because of quality of life. However, alternative prostate-specific antigen (PSA) screening strategies for the population may exist, optimizing the effects on mortality reduction, quality of life, overdiagnosis, and costs. Based on data of the ERSPC trial, we predicted the numbers of prostate cancers diagnosed, prostate cancer deaths averted, life-years and quality-adjusted life-years (QALY) gained, and cost-effectiveness of 68 screening strategies starting at age 55 years, with a PSA threshold of 3, using microsimulation modeling. The screening strategies varied by age to stop screening and screening interval (one to 14 years or once in a lifetime screens), and therefore number of tests. Screening at short intervals of three years or less was more cost-effective than using longer intervals. Screening at ages 55 to 59 years with two-year intervals had an incremental cost-effectiveness ratio of $73000 per QALY gained and was considered optimal. With this strategy, lifetime prostate cancer mortality reduction was predicted as 13%, and 33% of the screen-detected cancers were overdiagnosed. When better quality of life for the post-treatment period could be achieved, an older age of 65 to 72 years for ending screening was obtained. Prostate cancer screening can be cost-effective when it is limited to two or three screens between ages 55 to 59 years. Screening above age 63 years is less cost-effective because of loss of QALYs because of overdiagnosis. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Optimizing screening for tuberculosis and hepatitis B prior to starting tumor necrosis factor-α inhibitors in Crohn's disease.

PubMed

van der Have, Mike; Oldenburg, Bas; Fidder, Herma H; Belderbos, Tim D G; Siersema, Peter D; van Oijen, Martijn G H

2014-03-01

Treatment with tumor necrosis factor-α (TNF-α) inhibitors in patients with Crohn's disease (CD) is associated with potentially serious infections, including tuberculosis (TB) and hepatitis B virus (HBV). We assessed the cost-effectiveness of extensive TB screening and HBV screening prior to initiating TNF-α inhibitors in CD. We constructed two Markov models: (1) comparing tuberculin skin test (TST) combined with chest X-ray (conventional TB screening) versus TST and chest X-ray followed by the interferon-gamma release assay (extensive TB screening) in diagnosing TB; and (2) HBV screening versus no HBV screening. Our base-case included an adult CD patient starting with infliximab treatment. Input parameters were extracted from the literature. Direct medical costs were assessed and discounted following a third-party payer perspective. The main outcome was the incremental cost-effectiveness ratio (ICER). Sensitivity and Monte Carlo analyses were performed over wide ranges of probability and cost estimates. At base-case, the ICERs of extensive screening and HBV screening were €64,340 and €75,760 respectively to gain one quality-adjusted life year. Sensitivity analyses concluded that extensive TB screening was a cost-effective strategy if the latent TB prevalence is more than 12 % or if the false positivity rate of TST is more than 20 %. HBV screening became cost-effective if HBV reactivation or HBV-related mortality is higher than 37 and 62 %, respectively. Extensive TB screening and HBV screening are not cost-effective compared with conventional TB screening and no HBV screening, respectively. However, when targeted at high-risk patient groups, these screening strategies are likely to become cost-effective.

A review on PARP1 inhibitors: Pharmacophore modeling, virtual and biological screening studies to identify novel PARP1 inhibitors.

PubMed

Singh, Sardar Shamshair; Sarma, Jagarlapudi A R P; Narasu, Lakshmi; Dayam, Raveendra; Xu, Shili; Neamati, Nouri

2014-01-01

A tremendous research on Poly (ADP-ribose) polymerase (PARP) pertaining to cancer and ischemia is in very rapid progress. PARP's are a specific class of enzymes that repairs the damaged DNA. Recent findings suggest also that PARP-1 is the most abundantly expressed nuclear enzyme which involves in various therapeutic areas like inflammation, stroke, cardiac ischemia, cancer and diabetes. The current review describes the overview on clinical candidates of PARP1 and its current status in clinical trials. This paper also covers identification of potent PARP1 inhibitors using structure and ligand based pharmacophore models. Finally 36 potential hits were identified from the virtual screening of pharmacophore models and screened for PARP1 activity. 15 actives were identified as potent PARP1 inhibitors and further optimization of these analogues are in progress.

Economic evaluation of long-term impacts of universal newborn hearing screening.

PubMed

Chiou, Shu-Ti; Lung, Hou-Ling; Chen, Li-Sheng; Yen, Amy Ming-Fang; Fann, Jean Ching-Yuan; Chiu, Sherry Yueh-Hsia; Chen, Hsiu-Hsi

2017-01-01

Little is known about the long-term efficacious and economic impacts of universal newborn hearing screening (UNHS). An analytical Markov decision model was framed with two screening strategies: UNHS with transient evoked otoacoustic emission (TEOAE) test and automatic acoustic brainstem response (aABR) test against no screening. By estimating intervention and long-term costs on treatment and productivity losses and the utility of life years determined by the status of hearing loss, we computed base-case estimates of the incremental cost-utility ratios (ICURs). The scattered plot of ICUR and acceptability curve was used to assess the economic results of aABR versus TEOAE or both versus no screening. A hypothetical cohort of 200,000 Taiwanese newborns. TEOAE and aABR dominated over no screening strategy (ICUR = $-4800.89 and $-4111.23, indicating less cost and more utility). Given $20,000 of willingness to pay (WTP), the probability of being cost-effective of aABR against TEOAE was up to 90%. UNHS for hearing loss with aABR is the most economic option and supported by economically evidence-based evaluation from societal perspective.

Robust Microplate-Based Methods for Culturing and in Vivo Phenotypic Screening of Chlamydomonas reinhardtii

PubMed Central

Haire, Timothy C.; Bell, Cody; Cutshaw, Kirstin; Swiger, Brendan; Winkelmann, Kurt; Palmer, Andrew G.

2018-01-01

Chlamydomonas reinhardtii (Cr), a unicellular alga, is routinely utilized to study photosynthetic biochemistry, ciliary motility, and cellular reproduction. Its minimal culture requirements, unicellular morphology, and ease of transformation have made it a popular model system. Despite its relatively slow doubling time, compared with many bacteria, it is an ideal eukaryotic system for microplate-based studies utilizing either, or both, absorbance as well as fluorescence assays. Such microplate assays are powerful tools for researchers in the areas of toxicology, pharmacology, chemical genetics, biotechnology, and more. However, while microplate-based assays are valuable tools for screening biological systems, these methodologies can significantly alter the conditions in which the organisms are cultured and their subsequent physiology or morphology. Herein we describe a novel method for the microplate culture and in vivo phenotypic analysis of growth, viability, and photosynthetic pigments of C. reinhardtii. We evaluated the utility of our assay by screening silver nanoparticles for their effects on growth and viability. These methods are amenable to a wide assortment of studies and present a significant advancement in the methodologies available for research involving this model organism. PMID:29623083

Robust Microplate-Based Methods for Culturing and in Vivo Phenotypic Screening of Chlamydomonas reinhardtii.

PubMed

Haire, Timothy C; Bell, Cody; Cutshaw, Kirstin; Swiger, Brendan; Winkelmann, Kurt; Palmer, Andrew G

2018-01-01

Chlamydomonas reinhardtii (Cr), a unicellular alga, is routinely utilized to study photosynthetic biochemistry, ciliary motility, and cellular reproduction. Its minimal culture requirements, unicellular morphology, and ease of transformation have made it a popular model system. Despite its relatively slow doubling time, compared with many bacteria, it is an ideal eukaryotic system for microplate-based studies utilizing either, or both, absorbance as well as fluorescence assays. Such microplate assays are powerful tools for researchers in the areas of toxicology, pharmacology, chemical genetics, biotechnology, and more. However, while microplate-based assays are valuable tools for screening biological systems, these methodologies can significantly alter the conditions in which the organisms are cultured and their subsequent physiology or morphology. Herein we describe a novel method for the microplate culture and in vivo phenotypic analysis of growth, viability, and photosynthetic pigments of C. reinhardtii . We evaluated the utility of our assay by screening silver nanoparticles for their effects on growth and viability. These methods are amenable to a wide assortment of studies and present a significant advancement in the methodologies available for research involving this model organism.

Discrete Fourier Transform-Based Multivariate Image Analysis: Application to Modeling of Aromatase Inhibitory Activity.

PubMed

Barigye, Stephen J; Freitas, Matheus P; Ausina, Priscila; Zancan, Patricia; Sola-Penna, Mauro; Castillo-Garit, Juan A

2018-02-12

We recently generalized the formerly alignment-dependent multivariate image analysis applied to quantitative structure-activity relationships (MIA-QSAR) method through the application of the discrete Fourier transform (DFT), allowing for its application to noncongruent and structurally diverse chemical compound data sets. Here we report the first practical application of this method in the screening of molecular entities of therapeutic interest, with human aromatase inhibitory activity as the case study. We developed an ensemble classification model based on the two-dimensional (2D) DFT MIA-QSAR descriptors, with which we screened the NCI Diversity Set V (1593 compounds) and obtained 34 chemical compounds with possible aromatase inhibitory activity. These compounds were docked into the aromatase active site, and the 10 most promising compounds were selected for in vitro experimental validation. Of these compounds, 7419 (nonsteroidal) and 89 201 (steroidal) demonstrated satisfactory antiproliferative and aromatase inhibitory activities. The obtained results suggest that the 2D-DFT MIA-QSAR method may be useful in ligand-based virtual screening of new molecular entities of therapeutic utility.

Synergism of virtual screening and medicinal chemistry: identification and optimization of allosteric antagonists of metabotropic glutamate receptor 1.

PubMed

Noeske, Tobias; Trifanova, Dina; Kauss, Valerjans; Renner, Steffen; Parsons, Christopher G; Schneider, Gisbert; Weil, Tanja

2009-08-01

We report the identification of novel potent and selective metabotropic glutamate receptor 1 (mGluR1) antagonists by virtual screening and subsequent hit optimization. For ligand-based virtual screening, molecules were represented by a topological pharmacophore descriptor (CATS-2D) and clustered by a self-organizing map (SOM). The most promising compounds were tested in mGluR1 functional and binding assays. We identified a potent chemotype exhibiting selective antagonistic activity at mGluR1 (functional IC(50)=0.74+/-0.29 microM). Hit optimization yielded lead structure 16 with an affinity of K(i)=0.024+/-0.001 microM and greater than 1000-fold selectivity for mGluR1 versus mGluR5. Homology-based receptor modelling suggests a binding site compatible with previously reported mutation studies. Our study demonstrates the usefulness of ligand-based virtual screening for scaffold-hopping and rapid lead structure identification in early drug discovery projects.

Interprofessional collaborative practice incorporating training for alcohol and drug use screening for healthcare providers in rural areas.

PubMed

Puskar, Kathy; Mitchell, Ann M; Albrecht, Susan A; Frank, Linda R; Kane, Irene; Hagle, Holly; Lindsay, Dawn; Lee, Heeyoung; Fioravanti, Marie; Talcott, Kimberly S

2016-07-01

Interprofessional collaborative practice expands resources in rural and underserved communities. This article explores the impact of an online education programme on the perceptions of healthcare providers about interprofessional care within alcohol and drug use screening for rural residents. Nurses, behavioural health counsellors, and public health professionals participated in an evidence-based practice (screening, brief intervention, and referral to treatment-SBIRT) model that targets individuals who use alcohol and other drugs in a risky manner. SBIRT is recommended by the United States Preventive Services Task Force as a universal, evidence-based screening tool. Online modules, case simulation practice, and interprofessional dialogues are used to deliver practice-based learning experiences. A quasi-experimental method with pre-tests and post-tests was utilised. Results indicate increased perceptions of professional competence, need for cooperation, actual cooperation, and role values pre-to-post training. Implications suggest that online interprofessional education is useful but the added component of professional dialogues regarding patient cases offers promise in promoting collaborative practice.

Experiential Education at a University-based Wellness Center

PubMed Central

Berdine, Hildegarde

2007-01-01

Objectives To enhance students' learning and confidence in their abilities to provide wellness screenings and disease counseling. Design An experiential rotation was implemented in January 2004 within the Center for Pharmacy Care, a pharmacist-coordinated, University-based wellness center that offers preventive health screenings, risk assessments, patient education, medication and lifestyle counseling, educational seminars, and referral for common health conditions, such as hypertension, diabetes and osteoporosis. Assessment A brief survey instrument consisting of both open-ended questions and ratings of perceived abilities and confidence to provide screening and counseling was administered to students prior to and upon completion of the experience. Results of the survey indicate that the experience significantly enhanced students' preparedness and confidence to conduct community-based wellness screenings. Conclusion Students gained confidence in implementing and conducting wellness programs and became motivated to incorporate such programs into their future practice. This experience can serve as a teaching model for other programs to achieve student conpetencies in helath promotion and disease prevention. PMID:17619649

Screening Tool for Early Postnatal Prediction of Retinopathy of Prematurity in Preterm Newborns (STEP-ROP).

PubMed

Ricard, Caroline A; Dammann, Christiane E L; Dammann, Olaf

2017-01-01

Retinopathy of prematurity (ROP) is a disorder of the preterm newborn characterized by neurovascular disruption in the immature retina that may cause visual impairment and blindness. To develop a clinical screening tool for early postnatal prediction of ROP in preterm newborns based on risk information available within the first 48 h of postnatal life. Using data submitted to the Vermont Oxford Network (VON) between 1995 and 2015, we created logistic regression models based on infants born <28 completed weeks gestational age. We developed a model with 60% of the data and identified birth weight, gestational age, respiratory distress syndrome, non-Hispanic ethnicity, and multiple gestation as predictors of ROP. We tested the model in the remaining 40%, performed tenfold cross-validation, and tested the score in ELGAN study data. Of the 1,052 newborns in the VON database, 627 recorded an ROP status. Forty percent had no ROP, 40% had mild ROP (stages 1 and 2), and 20% had severe ROP (stages 3-5). We created a weighted score to predict any ROP based on the multivariable regression model. A cutoff score of 5 had the best sensitivity (95%, 95% CI 93-97), while maintaining a strong positive predictive value (63%, 95% CI 57-68). When applied to the ELGAN data, sensitivity was lower (72%, 95% CI 69-75), but PPV was higher (80%, 95% CI 77-83). STEP-ROP is a promising screening tool. It is easy to calculate, does not rely on extensive postnatal data collection, and can be calculated early after birth. Early ROP screening may help physicians limit patient exposure to additional risk factors, and may be useful for risk stratification in clinical trials aimed at reducing ROP. © 2017 S. Karger AG, Basel.

Pharmacophore modeling, docking, and principal component analysis based clustering: combined computer-assisted approaches to identify new inhibitors of the human rhinovirus coat protein.

PubMed

Steindl, Theodora M; Crump, Carolyn E; Hayden, Frederick G; Langer, Thierry

2005-10-06

The development and application of a sophisticated virtual screening and selection protocol to identify potential, novel inhibitors of the human rhinovirus coat protein employing various computer-assisted strategies are described. A large commercially available database of compounds was screened using a highly selective, structure-based pharmacophore model generated with the program Catalyst. A docking study and a principal component analysis were carried out within the software package Cerius and served to validate and further refine the obtained results. These combined efforts led to the selection of six candidate structures, for which in vitro anti-rhinoviral activity could be shown in a biological assay.

Coformer screening using thermal analysis based on binary phase diagrams.

PubMed

Yamashita, Hiroyuki; Hirakura, Yutaka; Yuda, Masamichi; Terada, Katsuhide

2014-08-01

The advent of cocrystals has demonstrated a growing need for efficient and comprehensive coformer screening in search of better development forms, including salt forms. Here, we investigated a coformer screening system for salts and cocrystals based on binary phase diagrams using thermal analysis and examined the effectiveness of the method. Indomethacin and tenoxicam were used as models of active pharmaceutical ingredients (APIs). Physical mixtures of an API and 42 kinds of coformers were analyzed using Differential Scanning Calorimetry (DSC) and X-ray DSC. We also conducted coformer screening using a conventional slurry method and compared these results with those from the thermal analysis method and previous studies. Compared with the slurry method, the thermal analysis method was a high-performance screening system, particularly for APIs with low solubility and/or propensity to form solvates. However, this method faced hurdles for screening coformers combined with an API in the presence of kinetic hindrance for salt or cocrystal formation during heating or if there is degradation near the metastable eutectic temperature. The thermal analysis and slurry methods are considered complementary to each other for coformer screening. Feasibility of the thermal analysis method in drug discovery practice is ensured given its small scale and high throughput.

Development and validation of the assessment of health literacy in breast and cervical cancer screening.

PubMed

Han, Hae-Ra; Huh, Boyun; Kim, Miyong T; Kim, Jiyun; Nguyen, Tam

2014-01-01

For many people limited health literacy is a major barrier to effective preventive health behavior such as cancer screening, yet a comprehensive health literacy measure that is specific to breast and cervical cancer screening is not readily available. The purpose of this article is to describe the development and testing of a new instrument to measure health literacy in the context of breast and cervical cancer screening, the Assessment of Health Literacy in Cancer Screening (AHL-C). The AHL-C is based on Baker's conceptualization of health literacy and modeled from the two most popular health literacy tests, the Rapid Estimate of Adult Literacy in Medicine and the Test of Functional Health Literacy in Adults. The AHL-C consists of four subscales; print literacy, numeracy, comprehension, and familiarity. We used baseline data from 560 Korean American immigrant women who participated in a community-based randomized trial designed to test the effect of a health literacy-focused intervention to promote breast and cervical cancer screening. Rigorous psychometric testing supports that the AHL-C is reliable, valid, and significantly correlated with theoretically selected variables. Future research is needed to test the utility of the AHL-C in predicting cancer screening outcomes.

An in vitro approach for lipolysis measurement using high-resolution mass spectrometry and partial least squares based analysis.

PubMed

Chang, Wen-Qi; Zhou, Jian-Liang; Li, Yi; Shi, Zi-Qi; Wang, Li; Yang, Jie; Li, Ping; Liu, Li-Fang; Xin, Gui-Zhong

2017-01-15

The elevation of free fatty acids (FFAs) has been regarded as a universal metabolic signature of excessive adipocyte lipolysis. Nowadays, in vitro lipolysis assay is generally essential for drug screening prior to the animal study. Here, we present a novel in vitro approach for lipolysis measurement combining UHPLC-Orbitrap and partial least squares (PLS) based analysis. Firstly, the calibration matrix was constructed by serial proportions of mixed samples (blended with control and model samples). Then, lipidome profiling was performed by UHPLC-Orbitrap, and 403 variables were extracted and aligned as dataset. Owing to the high resolution of Orbitrap analyzer and open source lipid identification software, 28 FFAs were further screened and identified. Based on the relative intensity of the screened FFAs, PLS regression model was constructed for lipolysis measurement. After leave-one-out cross-validation, ten principal components have been designated to build the final PLS model with excellent performances (RMSECV, 0.0268; RMSEC, 0.0173; R 2 , 0.9977). In addition, the high predictive accuracy (R 2  = 0.9907 and RMSEP = 0.0345) of the trained PLS model was also demonstrated using test samples. Finally, taking curcumin as a model compound, its antilipolytic effect on palmitic acid-induced lipolysis was successfully predicted as 31.78% by the proposed approach. Besides, supplementary evidences of curcumin induced modification in FFAs compositions as well as lipidome were given by PLS extended methods. Different from general biological assays, high resolution MS-based method provide more sophisticated information included in biological events. Thus, the novel biological evaluation model proposed here showed promising perspectives for drug evaluation or disease diagnosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Screening strategies for atrial fibrillation: a systematic review and cost-effectiveness analysis.

PubMed

Welton, Nicky J; McAleenan, Alexandra; Thom, Howard Hz; Davies, Philippa; Hollingworth, Will; Higgins, Julian Pt; Okoli, George; Sterne, Jonathan Ac; Feder, Gene; Eaton, Diane; Hingorani, Aroon; Fawsitt, Christopher; Lobban, Trudie; Bryden, Peter; Richards, Alison; Sofat, Reecha

2017-05-01

Atrial fibrillation (AF) is a common cardiac arrhythmia that increases the risk of thromboembolic events. Anticoagulation therapy to prevent AF-related stroke has been shown to be cost-effective. A national screening programme for AF may prevent AF-related events, but would involve a substantial investment of NHS resources. To conduct a systematic review of the diagnostic test accuracy (DTA) of screening tests for AF, update a systematic review of comparative studies evaluating screening strategies for AF, develop an economic model to compare the cost-effectiveness of different screening strategies and review observational studies of AF screening to provide inputs to the model. Systematic review, meta-analysis and cost-effectiveness analysis. Primary care. Adults. Screening strategies, defined by screening test, age at initial and final screens, screening interval and format of screening {systematic opportunistic screening [individuals offered screening if they consult with their general practitioner (GP)] or systematic population screening (when all eligible individuals are invited to screening)}. Sensitivity, specificity and diagnostic odds ratios; the odds ratio of detecting new AF cases compared with no screening; and the mean incremental net benefit compared with no screening. Two reviewers screened the search results, extracted data and assessed the risk of bias. A DTA meta-analysis was perfomed, and a decision tree and Markov model was used to evaluate the cost-effectiveness of the screening strategies. Diagnostic test accuracy depended on the screening test and how it was interpreted. In general, the screening tests identified in our review had high sensitivity (> 0.9). Systematic population and systematic opportunistic screening strategies were found to be similarly effective, with an estimated 170 individuals needed to be screened to detect one additional AF case compared with no screening. Systematic opportunistic screening was more likely to be cost-effective than systematic population screening, as long as the uptake of opportunistic screening observed in randomised controlled trials translates to practice. Modified blood pressure monitors, photoplethysmography or nurse pulse palpation were more likely to be cost-effective than other screening tests. A screening strategy with an initial screening age of 65 years and repeated screens every 5 years until age 80 years was likely to be cost-effective, provided that compliance with treatment does not decline with increasing age. A national screening programme for AF is likely to represent a cost-effective use of resources. Systematic opportunistic screening is more likely to be cost-effective than systematic population screening. Nurse pulse palpation or modified blood pressure monitors would be appropriate screening tests, with confirmation by diagnostic 12-lead electrocardiography interpreted by a trained GP, with referral to a specialist in the case of an unclear diagnosis. Implementation strategies to operationalise uptake of systematic opportunistic screening in primary care should accompany any screening recommendations. Many inputs for the economic model relied on a single trial [the Screening for Atrial Fibrillation in the Elderly (SAFE) study] and DTA results were based on a few studies at high risk of bias/of low applicability. Comparative studies measuring long-term outcomes of screening strategies and DTA studies for new, emerging technologies and to replicate the results for photoplethysmography and GP interpretation of 12-lead electrocardiography in a screening population. This study is registered as PROSPERO CRD42014013739. The National Institute for Health Research Health Technology Assessment programme.

Biosensor-based small molecule fragment screening with biolayer interferometry

NASA Astrophysics Data System (ADS)

Wartchow, Charles A.; Podlaski, Frank; Li, Shirley; Rowan, Karen; Zhang, Xiaolei; Mark, David; Huang, Kuo-Sen

2011-07-01

Biosensor-based fragment screening is a valuable tool in the drug discovery process. This method is advantageous over many biochemical methods because primary hits can be distinguished from non-specific or non-ideal interactions by examining binding profiles and responses, resulting in reduced false-positive rates. Biolayer interferometry (BLI), a technique that measures changes in an interference pattern generated from visible light reflected from an optical layer and a biolayer containing proteins of interest, is a relatively new method for monitoring small molecule interactions. The BLI format is based on a disposable sensor that is immersed in 96-well or 384-well plates. BLI has been validated for small molecule detection and fragment screening with model systems and well-characterized targets where affinity constants and binding profiles are generally similar to those obtained with surface plasmon resonsance (SPR). Screens with challenging targets involved in protein-protein interactions including BCL-2, JNK1, and eIF4E were performed with a fragment library of 6,500 compounds, and hit rates were compared for these targets. For eIF4E, a protein containing a PPI site and a nucleotide binding site, results from a BLI fragment screen were compared to results obtained in biochemical HTS screens. Overlapping hits were observed for the PPI site, and hits unique to the BLI screen were identified. Hit assessments with SPR and BLI are described.

Sensitive fluorimetric assays for α-glucosidase activity and inhibitor screening based on β-cyclodextrin-coated quantum dots.

PubMed

Liu, Si-Yao; Wang, Huan; He, Tian; Qi, Liang; Zhang, Zhi-Qi

2016-02-01

A fluorescence method was established for a α-glucosidase activity assay and inhibitor screening based on β-cyclodextrin-coated quantum dots. p-Nitrophenol, the hydrolysis product of the α-glucosidase reaction, could quench the fluorescence of β-cyclodextrin-coated quantum dots via an electron transfer process, leading to fluorescence turn-off, whereas the fluorescence of the system turned on in the presence of α-glucosidase inhibitors. Taking advantage of the excellent properties of quantum dots, this method provided a very simple, rapid and sensitive screening method for α-glucosidase inhibitors. Two α-glucosidase inhibitors, 2,4,6-tribromophenol and acarbose, were used to evaluate the feasibility of this screening model, and IC50 values of 24 μM and 0.55 mM were obtained respectively, which were lower than those previously reported. The method may have potential application in screening α-glucosidase inhibitors. Copyright © 2015 John Wiley & Sons, Ltd.

Newborn screening healthcare information system based on service-oriented architecture.

PubMed

Hsieh, Sung-Huai; Hsieh, Sheau-Ling; Chien, Yin-Hsiu; Weng, Yung-Ching; Hsu, Kai-Ping; Chen, Chi-Huang; Tu, Chien-Ming; Wang, Zhenyu; Lai, Feipei

2010-08-01

In this paper, we established a newborn screening system under the HL7/Web Services frameworks. We rebuilt the NTUH Newborn Screening Laboratory's original standalone architecture, having various heterogeneous systems operating individually, and restructured it into a Service-Oriented Architecture (SOA), distributed platform for further integrity and enhancements of sample collections, testing, diagnoses, evaluations, treatments or follow-up services, screening database management, as well as collaboration, communication among hospitals; decision supports and improving screening accuracy over the Taiwan neonatal systems are also addressed. In addition, the new system not only integrates the newborn screening procedures among phlebotomy clinics, referral hospitals, as well as the newborn screening center in Taiwan, but also introduces new models of screening procedures for the associated, medical practitioners. Furthermore, it reduces the burden of manual operations, especially the reporting services, those were heavily dependent upon previously. The new system can accelerate the whole procedures effectively and efficiently. It improves the accuracy and the reliability of the screening by ensuring the quality control during the processing as well.

Enhancing Ear and Hearing Health Access for Children With Technology and Connectivity.

PubMed

Swanepoel, De Wet

2017-10-12

Technology and connectivity advances are demonstrating increasing potential to improve access of service delivery to persons with hearing loss. This article demonstrates use cases from community-based hearing screening and automated diagnosis of ear disease. This brief report reviews recent evidence for school- and home-based hearing testing in underserved communities using smartphone technologies paired with calibrated headphones. Another area of potential impact facilitated by technology and connectivity is the use of feature extraction algorithms to facilitate automated diagnosis of most common ear conditions from video-otoscopic images. Smartphone hearing screening using calibrated headphones demonstrated equivalent sensitivity and specificity for school-based hearing screening. Automating test sequences with a forced-choice response paradigm allowed persons with minimal training to offer screening in underserved communities. The automated image analysis and diagnosis system for ear disease demonstrated an overall accuracy of 80.6%, which is up to par and exceeds accuracy rates previously reported for general practitioners and pediatricians. The emergence of these tools that capitalize on technology and connectivity advances enables affordable and accessible models of service delivery for community-based ear and hearing care.

Is a Perceived Activity-Friendly Environment Associated with More Physical Activity and Fewer Screen-Based Activities in Adolescents?

PubMed

Kopcakova, Jaroslava; Dankulincova Veselska, Zuzana; Madarasova Geckova, Andrea; Bucksch, Jens; Nalecz, Hanna; Sigmundova, Dagmar; van Dijk, Jitse P; Reijneveld, Sijmen A

2017-01-03

Background: The aim of this study is to explore if perception of an activity-friendly environment is associated with more physical activity and fewer screen-based activities among adolescents. Methods: We collected self-reported data in 2014 via the Health Behavior in School-aged Children cross-sectional study from four European countries ( n = 13,800, mean age = 14.4, 49.4% boys). We explored the association of perceived environment (e.g., "There are other children nearby home to go out and play with") with physical activity and screen-based activities using a binary logistic regression model adjusted for age, gender, family affluence and country. Results: An environment perceived as activity-friendly was associated with higher odds that adolescents meet recommendations for physical activity (odds ratio (OR) for one standard deviation (SD) change = 1.11, 95% confidence interval (CI) 1.05-1.18) and lower odds for excessive screen-based activities (OR for 1 SD better = 0.93, 95% CI 0.88-0.98). Conclusions: Investment into an activity-friendly environment may support the promotion of active life styles in adolescence.

Development of a Salmonella screening tool for consumer complaint-based foodborne illness surveillance systems.

PubMed

Li, John; Maclehose, Rich; Smith, Kirk; Kaehler, Dawn; Hedberg, Craig

2011-01-01

Foodborne illness surveillance based on consumer complaints detects outbreaks by finding common exposures among callers, but this process is often difficult. Laboratory testing of ill callers could also help identify potential outbreaks. However, collection of stool samples from all callers is not feasible. Methods to help screen calls for etiology are needed to increase the efficiency of complaint surveillance systems and increase the likelihood of detecting foodborne outbreaks caused by Salmonella. Data from the Minnesota Department of Health foodborne illness surveillance database (2000 to 2008) were analyzed. Complaints with identified etiologies were examined to create a predictive model for Salmonella. Bootstrap methods were used to internally validate the model. Seventy-one percent of complaints in the foodborne illness database with known etiologies were due to norovirus. The predictive model had a good discriminatory ability to identify Salmonella calls. Three cutoffs for the predictive model were tested: one that maximized sensitivity, one that maximized specificity, and one that maximized predictive ability, providing sensitivities and specificities of 32 and 96%, 100 and 54%, and 89 and 72%, respectively. Development of a predictive model for Salmonella could help screen calls for etiology. The cutoff that provided the best predictive ability for Salmonella corresponded to a caller reporting diarrhea and fever with no vomiting, and five or fewer people ill. Screening calls for etiology would help identify complaints for further follow-up and result in identifying Salmonella cases that would otherwise go unconfirmed; in turn, this could lead to the identification of more outbreaks.

Intention to undergo colonoscopy screening among relatives of colorectal cancer cases: a theory-based model.

PubMed

Boonyasiriwat, Watcharaporn; Hung, Man; Hon, Shirley D; Tang, Philip; Pappas, Lisa M; Burt, Randall W; Schwartz, Marc D; Stroup, Antoinette M; Kinney, Anita Y

2014-06-01

It is recommended that persons having familial risk of colorectal cancer begin regular colonoscopy screening at an earlier age than those in the general population. However, many individuals at increased risk do not adhere to these screening recommendations. The goal of this study was to examine cognitive, affective, social, and behavioral motivators of colonoscopy intention among individuals at increased risk of familial colorectal cancer. Relatives of colorectal cancer cases (N = 481) eligible for colonoscopy screening completed a survey assessing constructs from several theoretical frameworks including fear appeal theories. Structural equation modeling indicated that perceived colorectal cancer risk, past colonoscopy, fear of colorectal cancer, support from family and friends, and health-care provider recommendation were determinants of colonoscopy intention. Future interventions to promote colonoscopy in this increased risk population should target the factors we identified as motivators. (ClinicalTrials.gov number NCT01274143).

Niche-based screening identifies small-molecule inhibitors of leukemia stem cells.

PubMed

Hartwell, Kimberly A; Miller, Peter G; Mukherjee, Siddhartha; Kahn, Alissa R; Stewart, Alison L; Logan, David J; Negri, Joseph M; Duvet, Mildred; Järås, Marcus; Puram, Rishi; Dancik, Vlado; Al-Shahrour, Fatima; Kindler, Thomas; Tothova, Zuzana; Chattopadhyay, Shrikanta; Hasaka, Thomas; Narayan, Rajiv; Dai, Mingji; Huang, Christina; Shterental, Sebastian; Chu, Lisa P; Haydu, J Erika; Shieh, Jae Hung; Steensma, David P; Munoz, Benito; Bittker, Joshua A; Shamji, Alykhan F; Clemons, Paul A; Tolliday, Nicola J; Carpenter, Anne E; Gilliland, D Gary; Stern, Andrew M; Moore, Malcolm A S; Scadden, David T; Schreiber, Stuart L; Ebert, Benjamin L; Golub, Todd R

2013-12-01

Efforts to develop more effective therapies for acute leukemia may benefit from high-throughput screening systems that reflect the complex physiology of the disease, including leukemia stem cells (LSCs) and supportive interactions with the bone marrow microenvironment. The therapeutic targeting of LSCs is challenging because LSCs are highly similar to normal hematopoietic stem and progenitor cells (HSPCs) and are protected by stromal cells in vivo. We screened 14,718 compounds in a leukemia-stroma co-culture system for inhibition of cobblestone formation, a cellular behavior associated with stem-cell function. Among those compounds that inhibited malignant cells but spared HSPCs was the cholesterol-lowering drug lovastatin. Lovastatin showed anti-LSC activity in vitro and in an in vivo bone marrow transplantation model. Mechanistic studies demonstrated that the effect was on target, via inhibition of HMG-CoA reductase. These results illustrate the power of merging physiologically relevant models with high-throughput screening.

Niche-based screening identifies small-molecule inhibitors of leukemia stem cells

PubMed Central

Mukherjee, Siddhartha; Kahn, Alissa R; Stewart, Alison L; Logan, David J; Negri, Joseph M; Duvet, Mildred; Järås, Marcus; Puram, Rishi; Dancik, Vlado; Al-Shahrour, Fatima; Kindler, Thomas; Tothova, Zuzana; Chattopadhyay, Shrikanta; Hasaka, Thomas; Narayan, Rajiv; Dai, Mingji; Huang, Christina; Shterental, Sebastian; Chu, Lisa P; Haydu, J Erika; Shieh, Jae Hung; Steensma, David P; Munoz, Benito; Bittker, Joshua A; Shamji, Alykhan F; Clemons, Paul A; Tolliday, Nicola J; Carpenter, Anne E; Gilliland, D Gary; Stern, Andrew M; Moore, Malcolm A S; Scadden, David T; Schreiber, Stuart L; Ebert, Benjamin L; Golub, Todd R

2014-01-01

Efforts to develop more effective therapies for acute leukemia may benefit from high-throughput screening systems that reflect the complex physiology of the disease, including leukemia stem cells (LSCs) and supportive interactions with the bone-marrow microenvironment. The therapeutic targeting of LSCs is challenging because LSCs are highly similar to normal hematopoietic stem and progenitor cells (HSPCs) and are protected by stromal cells in vivo. We screened 14,718 compounds in a leukemia-stroma co-culture system for inhibition of cobblestone formation, a cellular behavior associated with stem-cell function. Among those that inhibited malignant cells but spared HSPCs was the cholesterol-lowering drug lovastatin. Lovastatin showed anti-LSC activity in vitro and in an in vivo bone marrow transplantation model. Mechanistic studies demonstrated that the effect was on-target, via inhibition of HMGCoA reductase. These results illustrate the power of merging physiologically-relevant models with high-throughput screening. PMID:24161946

Strongly screening corrections to antineutrino energy loss by β --decay of nuclides 53Fe, 54Fe, 55Fe, and 56Fe in supernova

NASA Astrophysics Data System (ADS)

Liu, Jing-Jing; Liu, Dong-Mei

2018-06-01

Based on the p-f shell-model, we discuss and calculate β--decay half-lives of neutron-rich nuclei, with a consideration of shell and pair effects, the decay energy, and the nucleon numbers. According to the linear response theory model, we study the effect of electron screening on the electron energy, beta-decay threshold energy, and the antineutrino energy loss rate by β--decay of some iron isotopes. We find that the electron screening antineutrino energy loss rates increase by about two orders of magnitude due to the shell effects and the pairing effect. Beta-decay rates with Q-value corrections due to strong electron screening are higher than those without the Q-value corrections by more than two orders of magnitude. Our conclusions may be helpful for the research on numerical simulations of the cooling of stars.

MODELS AND METHODS FOR PETROLEUM HYDROCARBON RISK ASSESSMENT: ONSITE, LUSTRISK, AND HSSM

EPA Science Inventory

U.S. EPA has developed three tiers of models for analysis of fuel releases from underground storage tank (UST) systems: 1) OnSite; 2) LUSTRisk, and 3) the Hydrocarbon Spill Screening Model (HSSM). The tiered approach to modeling allows users to select a model based upon the amoun...

Promoting cancer screening within the patient centered medical home.

PubMed

Sarfaty, Mona; Wender, Richard; Smith, Robert

2011-01-01

While consensus has grown that primary care is the essential access point in a high-performing health care system, the current model of primary care underperforms in both chronic disease management and prevention. The Patient Centered Medical Home model (PCMH) is at the center of efforts to reinvent primary care practice, and is regarded as the most promising approach to addressing the burden of chronic disease, improving health outcomes, and reducing health spending. However, the potential for the medical home to improve the delivery of cancer screening (and preventive services in general) has received limited attention in both conceptualization and practice. Medical home demonstrations to date have included few evidence-based preventive services in their outcome measures, and few have evaluated the effect of different payment models. Decreasing use of hospitals and emergency rooms and an emphasis on improving chronic care represent improvements in effective delivery of healthcare, but leave opportunities for reducing the burden of cancer untouched. Data confirm that what does or does not happen in the primary care setting has a substantial impact on cancer outcomes. Insofar as cancer is the leading cause of death before age 80, the PCMH model must prioritize adherence to cancer screening according to recommended guidelines, and systems, financial incentives, and reimbursements must be aligned to achieve that goal. This article explores capacities that are needed in the medical home model to facilitate the integration of cancer screening and other preventive services. These capacities include improved patient access and communication, health risk assessments, periodic preventive health exams, use of registries that store cancer risk information and screening history, ability to track and follow up on tests and referrals, feedback on performance, and payment models that reward cancer screening. Copyright © 2011 American Cancer Society, Inc.

Liquid-based cervical cytology using ThinPrep technology: weighing the pros and cons in a cost-effectiveness analysis.

PubMed

de Bekker-Grob, Esther W; de Kok, Inge M C M; Bulten, Johan; van Rosmalen, Joost; Vedder, Judith E M; Arbyn, Marc; Klinkhamer, Paul J J M; Siebers, Albertus G; van Ballegooijen, Marjolein

2012-08-01

Cervical cancer screening with liquid-based cytology (LBC) has been developed as an alternative to the conventional Papanicolaou (CP) smear. Cost-effectiveness is one of the issues when evaluating LBC. Based on the results of a Dutch randomised controlled trial, we conducted cost-effectiveness threshold analyses to investigate under what circumstances manually screened ThinPrep LBC is cost-effective for screening. The MISCAN-Cervix microsimulation model and data from the Dutch NETHCON trial (including 89,784 women) were used to estimate the costs and (quality-adjusted) life years ((QA)LYs) gained for EU screening schedules, varying cost-effectiveness threshold values. Screening strategies were primary cytological screening with LBC or CP, and triage with human papillomavirus (HPV) testing. Threshold analyses showed that screening with LBC as a primary test can be cost-effective if LBC is less than 3.2 more costly per test than CP, if the sensitivity of LBC is at least 3-5 % points higher than CP, if the quality of life for women in triage follow-up is only 0.39, or if the rate of inadequate CP smears is at least 16.2 %. Regarding test characteristics and costs of LBC and CP, only under certain conditions will a change from CP to manually screened ThinPrep LBC be cost-effective. If none of these conditions are met, implementation of manually screened ThinPrep LBC seems warranted only if there are advantages other than cost-effectiveness. Further research is needed to establish whether other LBC systems will be more favorable with regard to cost-effectiveness.

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

PubMed

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

2016-06-01

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

Cost and effects of different admission screening strategies to control the spread of methicillin-resistant Staphylococcus aureus.

PubMed

Gurieva, Tanya; Bootsma, Martin C J; Bonten, Marc J M

2013-01-01

Nosocomial infection rates due to antibiotic-resistant bacteriae, e.g., methicillin-resistant Staphylococcus aureus (MRSA) remain high in most countries. Screening for MRSA carriage followed by barrier precautions for documented carriers (so-called screen and isolate (S&I)) has been successful in some, but not all settings. Moreover, different strategies have been proposed, but comparative studies determining their relative effects and costs are not available. We, therefore, used a mathematical model to evaluate the effect and costs of different S&I strategies and to identify the critical parameters for this outcome. The dynamic stochastic simulation model consists of 3 hospitals with general wards and intensive care units (ICUs) and incorporates readmission of carriers of MRSA. Patient flow between ICUs and wards was based on real observations. Baseline prevalence of MRSA was set at 20% in ICUs and hospital-wide at 5%; ranges of costs and infection rates were based on published data. Four S&I strategies were compared to a do-nothing scenario: S&I of previously documented carriers ("flagged" patients); S&I of flagged patients and ICU admissions; S&I of flagged and group of "frequent" patients; S&I of all hospital admissions (universal screening). Evaluated levels of efficacy of S&I were 10%, 25%, 50% and 100%. Our model predicts that S&I of flagged and S&I of flagged and ICU patients are the most cost-saving strategies with fastest return of investment. For low isolation efficacy universal screening and S&I of flagged and "frequent" patients may never become cost-saving. Universal screening is predicted to prevent hardly more infections than S&I of flagged and "frequent" patients, albeit at higher costs. Whether an intervention becomes cost-saving within 10 years critically depends on costs per infection in ICU, costs of screening and isolation efficacy.

Cost and Effects of Different Admission Screening Strategies to Control the Spread of Methicillin-resistant Staphylococcus aureus

PubMed Central

Gurieva, Tanya; Bootsma, Martin C. J.; Bonten, Marc J. M.

2013-01-01

Nosocomial infection rates due to antibiotic-resistant bacteriae, e.g., methicillin-resistant Staphylococcus aureus (MRSA) remain high in most countries. Screening for MRSA carriage followed by barrier precautions for documented carriers (so-called screen and isolate (S&I)) has been successful in some, but not all settings. Moreover, different strategies have been proposed, but comparative studies determining their relative effects and costs are not available. We, therefore, used a mathematical model to evaluate the effect and costs of different S&I strategies and to identify the critical parameters for this outcome. The dynamic stochastic simulation model consists of 3 hospitals with general wards and intensive care units (ICUs) and incorporates readmission of carriers of MRSA. Patient flow between ICUs and wards was based on real observations. Baseline prevalence of MRSA was set at 20% in ICUs and hospital-wide at 5%; ranges of costs and infection rates were based on published data. Four S&I strategies were compared to a do-nothing scenario: S&I of previously documented carriers (“flagged” patients); S&I of flagged patients and ICU admissions; S&I of flagged and group of “frequent” patients; S&I of all hospital admissions (universal screening). Evaluated levels of efficacy of S&I were 10%, 25%, 50% and 100%. Our model predicts that S&I of flagged and S&I of flagged and ICU patients are the most cost-saving strategies with fastest return of investment. For low isolation efficacy universal screening and S&I of flagged and “frequent” patients may never become cost-saving. Universal screening is predicted to prevent hardly more infections than S&I of flagged and “frequent” patients, albeit at higher costs. Whether an intervention becomes cost-saving within 10 years critically depends on costs per infection in ICU, costs of screening and isolation efficacy. PMID:23436984

Cost-effectiveness of the faecal immunochemical test at a range of positivity thresholds compared with the guaiac faecal occult blood test in the NHS Bowel Cancer Screening Programme in England

PubMed Central

Halloran, Stephen

2017-01-01

Objectives Through the National Health Service (NHS) Bowel Cancer Screening Programme (BCSP), men and women in England aged between 60 and 74 years are invited for colorectal cancer (CRC) screening every 2 years using the guaiac faecal occult blood test (gFOBT). The aim of this analysis was to estimate the cost–utility of the faecal immunochemical test for haemoglobin (FIT) compared with gFOBT for a cohort beginning screening aged 60 years at a range of FIT positivity thresholds. Design We constructed a cohort-based Markov state transition model of CRC disease progression and screening. Screening uptake, detection, adverse event, mortality and cost data were taken from BCSP data and national sources, including a recent large pilot study of FIT screening in the BCSP. Results Our results suggest that FIT is cost-effective compared with gFOBT at all thresholds, resulting in cost savings and quality-adjusted life years (QALYs) gained over a lifetime time horizon. FIT was cost-saving (p<0.001) and resulted in QALY gains of 0.014 (95% CI 0.012 to 0.017) at the base case threshold of 180 µg Hb/g faeces. Greater health gains and cost savings were achieved as the FIT threshold was decreased due to savings in cancer management costs. However, at lower thresholds, FIT was also associated with more colonoscopies (increasing from 32 additional colonoscopies per 1000 people invited for screening for FIT 180 µg Hb/g faeces to 421 additional colonoscopies per 1000 people invited for screening for FIT 20 µg Hb/g faeces over a 40-year time horizon). Parameter uncertainty had limited impact on the conclusions. Conclusions This is the first published economic analysis of FIT screening in England using data directly comparing FIT with gFOBT in the NHS BSCP. These results for a cohort starting screening aged 60 years suggest that FIT is highly cost-effective at all thresholds considered. Further modelling is needed to estimate economic outcomes for screening across all age cohorts simultaneously. PMID:29079605

Molecular testing for Lynch syndrome in people with colorectal cancer: systematic reviews and economic evaluation.

PubMed

Snowsill, Tristan; Coelho, Helen; Huxley, Nicola; Jones-Hughes, Tracey; Briscoe, Simon; Frayling, Ian M; Hyde, Chris

2017-09-01

Inherited mutations in deoxyribonucleic acid (DNA) mismatch repair (MMR) genes lead to an increased risk of colorectal cancer (CRC), gynaecological cancers and other cancers, known as Lynch syndrome (LS). Risk-reducing interventions can be offered to individuals with known LS-causing mutations. The mutations can be identified by comprehensive testing of the MMR genes, but this would be prohibitively expensive in the general population. Tumour-based tests - microsatellite instability (MSI) and MMR immunohistochemistry (IHC) - are used in CRC patients to identify individuals at high risk of LS for genetic testing. MLH1 (MutL homologue 1) promoter methylation and BRAF V600E testing can be conducted on tumour material to rule out certain sporadic cancers. To investigate whether testing for LS in CRC patients using MSI or IHC (with or without MLH1 promoter methylation testing and BRAF V600E testing) is clinically effective (in terms of identifying Lynch syndrome and improving outcomes for patients) and represents a cost-effective use of NHS resources. Systematic reviews were conducted of the published literature on diagnostic test accuracy studies of MSI and/or IHC testing for LS, end-to-end studies of screening for LS in CRC patients and economic evaluations of screening for LS in CRC patients. A model-based economic evaluation was conducted to extrapolate long-term outcomes from the results of the diagnostic test accuracy review. The model was extended from a model previously developed by the authors. Ten studies were identified that evaluated the diagnostic test accuracy of MSI and/or IHC testing for identifying LS in CRC patients. For MSI testing, sensitivity ranged from 66.7% to 100.0% and specificity ranged from 61.1% to 92.5%. For IHC, sensitivity ranged from 80.8% to 100.0% and specificity ranged from 80.5% to 91.9%. When tumours showing low levels of MSI were treated as a positive result, the sensitivity of MSI testing increased but specificity fell. No end-to-end studies of screening for LS in CRC patients were identified. Nine economic evaluations of screening for LS in CRC were identified. None of the included studies fully matched the decision problem and hence a new economic evaluation was required. The base-case results in the economic evaluation suggest that screening for LS in CRC patients using IHC, BRAF V600E and MLH1 promoter methylation testing would be cost-effective at a threshold of £20,000 per quality-adjusted life-year (QALY). The incremental cost-effectiveness ratio for this strategy was £11,008 per QALY compared with no screening. Screening without tumour tests is not predicted to be cost-effective. Most of the diagnostic test accuracy studies identified were rated as having a risk of bias or were conducted in unrepresentative samples. There was no direct evidence that screening improves long-term outcomes. No probabilistic sensitivity analysis was conducted. Systematic review evidence suggests that MSI- and IHC-based testing can be used to identify LS in CRC patients, although there was heterogeneity in the methods used in the studies identified and the results of the studies. There was no high-quality empirical evidence that screening improves long-term outcomes and so an evidence linkage approach using modelling was necessary. Key determinants of whether or not screening is cost-effective are the accuracy of tumour-based tests, CRC risk without surveillance, the number of relatives identified for cascade testing, colonoscopic surveillance effectiveness and the acceptance of genetic testing. Future work should investigate screening for more causes of hereditary CRC and screening for LS in endometrial cancer patients. This study is registered as PROSPERO CRD42016033879. The National Institute for Health Research Health Technology Assessment programme.

Applying operations research to optimize a novel population management system for cancer screening

PubMed Central

Zai, Adrian H; Kim, Seokjin; Kamis, Arnold; Hung, Ken; Ronquillo, Jeremiah G; Chueh, Henry C; Atlas, Steven J

2014-01-01

Objective To optimize a new visit-independent, population-based cancer screening system (TopCare) by using operations research techniques to simulate changes in patient outreach staffing levels (delegates, navigators), modifications to user workflow within the information technology (IT) system, and changes in cancer screening recommendations. Materials and methods TopCare was modeled as a multiserver, multiphase queueing system. Simulation experiments implemented the queueing network model following a next-event time-advance mechanism, in which systematic adjustments were made to staffing levels, IT workflow settings, and cancer screening frequency in order to assess their impact on overdue screenings per patient. Results TopCare reduced the average number of overdue screenings per patient from 1.17 at inception to 0.86 during simulation to 0.23 at steady state. Increases in the workforce improved the effectiveness of TopCare. In particular, increasing the delegate or navigator staff level by one person improved screening completion rates by 1.3% or 12.2%, respectively. In contrast, changes in the amount of time a patient entry stays on delegate and navigator lists had little impact on overdue screenings. Finally, lengthening the screening interval increased efficiency within TopCare by decreasing overdue screenings at the patient level, resulting in a smaller number of overdue patients needing delegates for screening and a higher fraction of screenings completed by delegates. Conclusions Simulating the impact of changes in staffing, system parameters, and clinical inputs on the effectiveness and efficiency of care can inform the allocation of limited resources in population management. PMID:24043318

Digital watermarking opportunities enabled by mobile media proliferation

NASA Astrophysics Data System (ADS)

Modro, Sierra; Sharma, Ravi K.

2009-02-01

Consumer usages of mobile devices and electronic media are changing. Mobile devices now include increased computational capabilities, mobile broadband access, better integrated sensors, and higher resolution screens. These enhanced features are driving increased consumption of media such as images, maps, e-books, audio, video, and games. As users become more accustomed to using mobile devices for media, opportunities arise for new digital watermarking usage models. For example, transient media, like images being displayed on screens, could be watermarked to provide a link between mobile devices. Applications based on these emerging usage models utilizing watermarking can provide richer user experiences and drive increased media consumption. We describe the enabling factors and highlight a few of the usage models and new opportunities. We also outline how the new opportunities are driving further innovation in watermarking technologies. We discuss challenges in market adoption of applications based on these usage models.

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

PubMed

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

2014-11-01

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

Nurse's Desk: food bank-based outreach and screening to decrease unmet referral needs.

PubMed

Larsson, Laura S; Kuster, Emilie

2013-01-01

The Nurse's Desk health screening project used the Intervention Wheel model to conduct outreach, screening, education, and referral for food bank clients (n = 506). Blood glucose, blood pressure, health care utilization, and unmet referral needs were assessed. Screening results identified 318 clients (62.8%) with 1 or more unmet referral needs, including 6 clients (3.16%) with capillary blood glucose more than 199 mg/dL and 132 (31.9%) with hypertension. Clients had higher-than-average systolic and diastolic blood pressures and undiagnosed diabetes than in the general population. A client-approved method for tracking completed referrals is needed for this potentially high-risk population.

Pharmacophore-Map-Pick: A Method to Generate Pharmacophore Models for All Human GPCRs.

PubMed

Dai, Shao-Xing; Li, Gong-Hua; Gao, Yue-Dong; Huang, Jing-Fei

2016-02-01

GPCR-based drug discovery is hindered by a lack of effective screening methods for most GPCRs that have neither ligands nor high-quality structures. With the aim to identify lead molecules for these GPCRs, we developed a new method called Pharmacophore-Map-Pick to generate pharmacophore models for all human GPCRs. The model of ADRB2 generated using this method not only predicts the binding mode of ADRB2-ligands correctly but also performs well in virtual screening. Findings also demonstrate that this method is powerful for generating high-quality pharmacophore models. The average enrichment for the pharmacophore models of the 15 targets in different GPCR families reached 15-fold at 0.5 % false-positive rate. Therefore, the pharmacophore models can be applied in virtual screening directly with no requirement for any ligand information or shape constraints. A total of 2386 pharmacophore models for 819 different GPCRs (99 % coverage (819/825)) were generated and are available at http://bsb.kiz.ac.cn/GPCRPMD. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Improving a complex finite-difference ground water flow model through the use of an analytic element screening model

USGS Publications Warehouse

Hunt, R.J.; Anderson, M.P.; Kelson, V.A.

1998-01-01

This paper demonstrates that analytic element models have potential as powerful screening tools that can facilitate or improve calibration of more complicated finite-difference and finite-element models. We demonstrate how a two-dimensional analytic element model was used to identify errors in a complex three-dimensional finite-difference model caused by incorrect specification of boundary conditions. An improved finite-difference model was developed using boundary conditions developed from a far-field analytic element model. Calibration of a revised finite-difference model was achieved using fewer zones of hydraulic conductivity and lake bed conductance than the original finite-difference model. Calibration statistics were also improved in that simulated base-flows were much closer to measured values. The improved calibration is due mainly to improved specification of the boundary conditions made possible by first solving the far-field problem with an analytic element model.This paper demonstrates that analytic element models have potential as powerful screening tools that can facilitate or improve calibration of more complicated finite-difference and finite-element models. We demonstrate how a two-dimensional analytic element model was used to identify errors in a complex three-dimensional finite-difference model caused by incorrect specification of boundary conditions. An improved finite-difference model was developed using boundary conditions developed from a far-field analytic element model. Calibration of a revised finite-difference model was achieved using fewer zones of hydraulic conductivity and lake bed conductance than the original finite-difference model. Calibration statistics were also improved in that simulated base-flows were much closer to measured values. The improved calibration is due mainly to improved specification of the boundary conditions made possible by first solving the far-field problem with an analytic element model.

Cocrystal screening of hydroxybenzamides with benzoic acid derivatives: a comparative study of thermal and solution-based methods.

PubMed

Manin, Alex N; Voronin, Alexander P; Drozd, Ksenia V; Manin, Nikolay G; Bauer-Brandl, Annette; Perlovich, German L

2014-12-18

The main problem occurring at the early stages of cocrystal search is the choice of an effective screening technique. Among the most popular techniques of obtaining cocrystals are crystallization from solution, crystallization from melt and solvent-drop grinding. This paper represents a comparative analysis of the following screening techniques: DSC cocrystal screening method, thermal microscopy and saturation temperature method. The efficiency of different techniques of cocrystal screening was checked in 18 systems. Benzamide and benzoic acid derivatives were chosen as model systems due to their ability to form acid-amide supramolecular heterosynthon. The screening has confirmed the formation of 6 new cocrystals. The screening by the saturation temperature method has the highest screen-out rate but the smallest range of application. DSC screening has a satisfactory accuracy and allows screening over a short time. Thermal microscopy is most efficient as an additional technique used to interpret ambiguous DSC screening results. The study also included an analysis of the influence of solvent type and component solubility on cocrystal formation. Copyright © 2014 Elsevier B.V. All rights reserved.

Classifying the Indication for Colonoscopy Procedures: A Comparison of NLP Approaches in a Diverse National Healthcare System.

PubMed

Patterson, Olga V; Forbush, Tyler B; Saini, Sameer D; Moser, Stephanie E; DuVall, Scott L

2015-01-01

In order to measure the level of utilization of colonoscopy procedures, identifying the primary indication for the procedure is required. Colonoscopies may be utilized not only for screening, but also for diagnostic or therapeutic purposes. To determine whether a colonoscopy was performed for screening, we created a natural language processing system to identify colonoscopy reports in the electronic medical record system and extract indications for the procedure. A rule-based model and three machine-learning models were created using 2,000 manually annotated clinical notes of patients cared for in the Department of Veterans Affairs. Performance of the models was measured and compared. Analysis of the models on a test set of 1,000 documents indicates that the rule-based system performance stays fairly constant as evaluated on training and testing sets. However, the machine learning model without feature selection showed significant decrease in performance. Therefore, rule-based classification system appears to be more robust than a machine-learning system in cases when no feature selection is performed.

Cost-effectiveness of national mandatory screening of all admissions to English National Health Service hospitals for meticillin-resistant Staphylococcus aureus: a mathematical modelling study.

PubMed

Robotham, Julie V; Deeny, Sarah R; Fuller, Chris; Hopkins, Susan; Cookson, Barry; Stone, Sheldon

2016-03-01

In December, 2010, National Health Service (NHS) England introduced national mandatory screening of all admissions for meticillin-resistant Staphylococcus aureus (MRSA). We aimed to assess the effectiveness and cost-effectiveness of this policy, from a regional or national health-care decision makers' perspective, compared with alternative screening strategies. We used an individual-based dynamic transmission model parameterised with national MRSA audit data to assess the effectiveness and cost-effectiveness of admission screening of patients in English NHS hospitals compared with five alternative strategies (including no screening, checklist-activated screening, and high-risk specialty-based screening), accompanied by patient isolation and decolonisation, over a 5 year time horizon. We evaluated strategies for different NHS hospital types (acute, teaching, and specialist), MRSA prevalence, and transmission potentials using probabilistic sensitivity analyses. Compared with no screening, mean cost per quality-adjusted life-year (QALY) of screening all admissions was £89,000-148,000 (range £68,000-222,000), and this strategy was consistently more costly and less effective than alternatives for all hospital types. At a £30,000/QALY willingness-to-pay threshold and current prevalence, only the no-screening strategy was cost effective. The next best strategies were, in acute and teaching hospitals, targeting of high-risk specialty admissions (30-40% chance of cost-effectiveness; mean incremental cost-effectiveness ratios [ICERs] £45,200 [range £35,300-61,400] and £48,000/QALY [£34,600-74,800], respectively) and, in specialist hospitals, screening these patients plus risk-factor-based screening of low-risk specialties (a roughly 20% chance of cost-effectiveness; mean ICER £62,600/QALY [£48,000-89,400]). As prevalence and transmission increased, targeting of high-risk specialties became the optimum strategy at the NHS willingness-to-pay threshold (£30,000/QALY). Switching from screening all admissions to only high-risk specialty admissions resulted in a mean reduction in total costs per year (not considering uncertainty) of £2·7 million per acute hospital, £2·9 million per teaching, and £474,000 per specialist hospital for a minimum rise in infections (about one infection per year per hospital). Our results show that screening all admissions for MRSA is unlikely to be cost effective in England at the current NHS willingness-to-pay threshold, and our findings informed modified guidance to NHS England in 2014. Screening admissions to high-risk specialties is likely to represent better resource use in terms of cost per QALY gained. UK Department of Health. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Spatial Distribution of Hepatitis C Virus Infections and Associated Determinants--An Application of a Geographically Weighted Poisson Regression for Evidence-Based Screening Interventions in Hotspots.

PubMed

Kauhl, Boris; Heil, Jeanne; Hoebe, Christian J P A; Schweikart, Jürgen; Krafft, Thomas; Dukers-Muijrers, Nicole H T M

2015-01-01

Hepatitis C Virus (HCV) infections are a major cause for liver diseases. A large proportion of these infections remain hidden to care due to its mostly asymptomatic nature. Population-based screening and screening targeted on behavioural risk groups had not proven to be effective in revealing these hidden infections. Therefore, more practically applicable approaches to target screenings are necessary. Geographic Information Systems (GIS) and spatial epidemiological methods may provide a more feasible basis for screening interventions through the identification of hotspots as well as demographic and socio-economic determinants. Analysed data included all HCV tests (n = 23,800) performed in the southern area of the Netherlands between 2002-2008. HCV positivity was defined as a positive immunoblot or polymerase chain reaction test. Population data were matched to the geocoded HCV test data. The spatial scan statistic was applied to detect areas with elevated HCV risk. We applied global regression models to determine associations between population-based determinants and HCV risk. Geographically weighted Poisson regression models were then constructed to determine local differences of the association between HCV risk and population-based determinants. HCV prevalence varied geographically and clustered in urban areas. The main population at risk were middle-aged males, non-western immigrants and divorced persons. Socio-economic determinants consisted of one-person households, persons with low income and mean property value. However, the association between HCV risk and demographic as well as socio-economic determinants displayed strong regional and intra-urban differences. The detection of local hotspots in our study may serve as a basis for prioritization of areas for future targeted interventions. Demographic and socio-economic determinants associated with HCV risk show regional differences underlining that a one-size-fits-all approach even within small geographic areas may not be appropriate. Future screening interventions need to consider the spatially varying association between HCV risk and associated demographic and socio-economic determinants.

Optogenetic stimulation of multiwell MEA plates for neural and cardiac applications

NASA Astrophysics Data System (ADS)

Clements, Isaac P.; Millard, Daniel C.; Nicolini, Anthony M.; Preyer, Amanda J.; Grier, Robert; Heckerling, Andrew; Blum, Richard A.; Tyler, Phillip; McSweeney, K. M.; Lu, Yi-Fan; Hall, Diana; Ross, James D.

2016-03-01

Microelectrode array (MEA) technology enables advanced drug screening and "disease-in-a-dish" modeling by measuring the electrical activity of cultured networks of neural or cardiac cells. Recent developments in human stem cell technologies, advancements in genetic models, and regulatory initiatives for drug screening have increased the demand for MEA-based assays. In response, Axion Biosystems previously developed a multiwell MEA platform, providing up to 96 MEA culture wells arrayed into a standard microplate format. Multiwell MEA-based assays would be further enhanced by optogenetic stimulation, which enables selective excitation and inhibition of targeted cell types. This capability for selective control over cell culture states would allow finer pacing and probing of cell networks for more reliable and complete characterization of complex network dynamics. Here we describe a system for independent optogenetic stimulation of each well of a 48-well MEA plate. The system enables finely graded control of light delivery during simultaneous recording of network activity in each well. Using human induced pluripotent stem cell (hiPSC) derived cardiomyocytes and rodent primary neuronal cultures, we demonstrate high channel-count light-based excitation and suppression in several proof-of-concept experimental models. Our findings demonstrate advantages of combining multiwell optical stimulation and MEA recording for applications including cardiac safety screening, neural toxicity assessment, and advanced characterization of complex neuronal diseases.

Impact of age cutoffs on a lynch syndrome screening program.

PubMed

Gudgeon, James M; Belnap, Thomas W; Williams, Janet L; Williams, Marc S

2013-07-01

To determine the impact of applying an age cutoff to tumor-based Lynch syndrome (LS) screening, specifically focusing on changes in relative effectiveness, efficiency, and cost. The project was undertaken to answer questions about implementation of the LS screening program in an integrated health care delivery system. Clinical data extracted from an internal cancer registry, previous modeling efforts, published literature, and gray data were used to populate decision models designed to answer questions about the impact of age cutoffs in LS screening. Patients with colorectal cancer (CRC) were stratified at 10-year intervals from ages 50 to 80 years and compared with no age cutoff. Outcomes are reported for a cohort of 325 patients screened and includes total cost to screen, LS cases present in the cutoff category, number of LS cases expected to be identified by screening, cost per LS case detected, and total number and percentage of LS cases missed. Applying an age cutoff to an LS screening program has considerable potential for decreasing total screening costs and increasing efficiency, but at a loss of effectiveness. Imposing an age cutoff of 50 years reduces the cost of the screening program to 16% of a program with no age cutoff, but at the expense of missing more than half of the cases. Failure to identify LS cases is magnified by a cascade effect in family members. The results of this analysis influenced the final policy in our system.

Global sensitivity analysis for urban water quality modelling: Terminology, convergence and comparison of different methods

NASA Astrophysics Data System (ADS)

Vanrolleghem, Peter A.; Mannina, Giorgio; Cosenza, Alida; Neumann, Marc B.

2015-03-01

Sensitivity analysis represents an important step in improving the understanding and use of environmental models. Indeed, by means of global sensitivity analysis (GSA), modellers may identify both important (factor prioritisation) and non-influential (factor fixing) model factors. No general rule has yet been defined for verifying the convergence of the GSA methods. In order to fill this gap this paper presents a convergence analysis of three widely used GSA methods (SRC, Extended FAST and Morris screening) for an urban drainage stormwater quality-quantity model. After the convergence was achieved the results of each method were compared. In particular, a discussion on peculiarities, applicability, and reliability of the three methods is presented. Moreover, a graphical Venn diagram based classification scheme and a precise terminology for better identifying important, interacting and non-influential factors for each method is proposed. In terms of convergence, it was shown that sensitivity indices related to factors of the quantity model achieve convergence faster. Results for the Morris screening method deviated considerably from the other methods. Factors related to the quality model require a much higher number of simulations than the number suggested in literature for achieving convergence with this method. In fact, the results have shown that the term "screening" is improperly used as the method may exclude important factors from further analysis. Moreover, for the presented application the convergence analysis shows more stable sensitivity coefficients for the Extended-FAST method compared to SRC and Morris screening. Substantial agreement in terms of factor fixing was found between the Morris screening and Extended FAST methods. In general, the water quality related factors exhibited more important interactions than factors related to water quantity. Furthermore, in contrast to water quantity model outputs, water quality model outputs were found to be characterised by high non-linearity.

Evaluation of the Microsoft Kinect for screening ACL injury.

PubMed

Stone, Erik E; Butler, Michael; McRuer, Aaron; Gray, Aaron; Marks, Jeffrey; Skubic, Marjorie

2013-01-01

A study was conducted to evaluate the use of the skeletal model generated by the Microsoft Kinect SDK in capturing four biomechanical measures during the Drop Vertical Jump test. These measures, which include: knee valgus motion from initial contact to peak flexion, frontal plane knee angle at initial contact, frontal plane knee angle at peak flexion, and knee-to-ankle separation ratio at peak flexion, have proven to be useful in screening for future knee anterior cruciate ligament (ACL) injuries among female athletes. A marker-based Vicon motion capture system was used for ground truth. Results indicate that the Kinect skeletal model likely has acceptable accuracy for use as part of a screening tool to identify elevated risk for ACL injury.

Cost-effectiveness of prenatal screening strategies for congenital heart disease.

PubMed

Pinto, N M; Nelson, R; Puchalski, M; Metz, T D; Smith, K J

2014-07-01

The economic implications of strategies to improve prenatal screening for congenital heart disease (CHD) in low-risk mothers have not been explored. The aim was to perform a cost-effectiveness analysis of different screening methods. We constructed a decision analytic model of CHD prenatal screening strategies (four-chamber screen (4C), 4C + outflow, nuchal translucency (NT) or fetal echocardiography) populated with probabilities from the literature. The model included whether initial screens were interpreted by a maternal-fetal medicine (MFM) specialist and different referral strategies if they were read by a non-MFM specialist. The primary outcome was the incremental cost per defect detected. Costs were obtained from Medicare National Fee estimates. A probabilistic sensitivity analysis was undertaken on model variables commensurate with their degree of uncertainty. In base-case analysis, 4C + outflow referred to an MFM specialist was the least costly strategy per defect detected. The 4C screen and the NT screen were dominated by other strategies (i.e. were more costly and less effective). Fetal echocardiography was the most effective, but most costly. On simulation of 10 000 low-risk pregnancies, 4C + outflow screen referred to an MFM specialist remained the least costly per defect detected. For an additional $580 per defect detected, referral to cardiology after a 4C + outflow was the most cost-effective for the majority of iterations, increasing CHD detection by 13 percentage points. The addition of examination of the outflow tracts to second-trimester ultrasound increases detection of CHD in the most cost-effective manner. Strategies to improve outflow-tract imaging and to refer with the most efficiency may be the best way to improve detection at a population level. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

Vision Algorithms Catch Defects in Screen Displays

NASA Technical Reports Server (NTRS)

2014-01-01

Andrew Watson, a senior scientist at Ames Research Center, developed a tool called the Spatial Standard Observer (SSO), which models human vision for use in robotic applications. Redmond, Washington-based Radiant Zemax LLC licensed the technology from NASA and combined it with its imaging colorimeter system, creating a powerful tool that high-volume manufacturers of flat-panel displays use to catch defects in screens.

Exploiting PubChem for Virtual Screening

PubMed Central

Xie, Xiang-Qun

2011-01-01

Importance of the field PubChem is a public molecular information repository, a scientific showcase of the NIH Roadmap Initiative. The PubChem database holds over 27 million records of unique chemical structures of compounds (CID) derived from nearly 70 million substance depositions (SID), and contains more than 449,000 bioassay records with over thousands of in vitro biochemical and cell-based screening bioassays established, with targeting more than 7000 proteins and genes linking to over 1.8 million of substances. Areas covered in this review This review builds on recent PubChem-related computational chemistry research reported by other authors while providing readers with an overview of the PubChem database, focusing on its increasing role in cheminformatics, virtual screening and toxicity prediction modeling. What the reader will gain These publicly available datasets in PubChem provide great opportunities for scientists to perform cheminformatics and virtual screening research for computer-aided drug design. However, the high volume and complexity of the datasets, in particular the bioassay-associated false positives/negatives and highly imbalanced datasets in PubChem, also creates major challenges. Several approaches regarding the modeling of PubChem datasets and development of virtual screening models for bioactivity and toxicity predictions are also reviewed. Take home message Novel data-mining cheminformatics tools and virtual screening algorithms are being developed and used to retrieve, annotate and analyze the large-scale and highly complex PubChem biological screening data for drug design. PMID:21691435

Costs of cervical cancer screening and treatment using visual inspection with acetic acid (VIA) and cryotherapy in Ghana: the importance of scale

PubMed Central

Quentin, Wilm; Adu-Sarkodie, Yaw; Terris-Prestholt, Fern; Legood, Rosa; Opoku, Baafuor K; Mayaud, Philippe

2011-01-01

Objectives To estimate the incremental costs of visual inspection with acetic acid (VIA) and cryotherapy at cervical cancer screening facilities in Ghana; to explore determinants of costs through modelling; and to estimate national scale-up and annual programme costs. Methods Resource-use data were collected at four out of six active VIA screening centres, and unit costs were ascertained to estimate the costs per woman of VIA and cryotherapy. Modelling and sensitivity analysis were used to explore the influence of observed differences between screening facilities on estimated costs and to calculate national costs. Results Incremental economic costs per woman screened with VIA ranged from 4.93 US$ to 14.75 US$, and costs of cryotherapy were between 47.26 US$ and 84.48 US$ at surveyed facilities. Under base case assumptions, our model estimated the costs of VIA to be 6.12 US$ per woman and those of cryotherapy to be 27.96 US$. Sensitivity analysis showed that the number of women screened per provider and treated per facility was the most important determinants of costs. National annual programme costs were estimated to be between 0.6 and 4.0 million US$ depending on assumed coverage and adopted screening strategy. Conclusion When choosing between different cervical cancer prevention strategies, the feasibility of increasing uptake to achieve economies of scale should be a major concern. PMID:21214692

Costs of cervical cancer screening and treatment using visual inspection with acetic acid (VIA) and cryotherapy in Ghana: the importance of scale.

PubMed

Quentin, Wilm; Adu-Sarkodie, Yaw; Terris-Prestholt, Fern; Legood, Rosa; Opoku, Baafuor K; Mayaud, Philippe

2011-03-01

To estimate the incremental costs of visual inspection with acetic acid (VIA) and cryotherapy at cervical cancer screening facilities in Ghana; to explore determinants of costs through modelling; and to estimate national scale-up and annual programme costs. Resource-use data were collected at four out of six active VIA screening centres, and unit costs were ascertained to estimate the costs per woman of VIA and cryotherapy. Modelling and sensitivity analysis were used to explore the influence of observed differences between screening facilities on estimated costs and to calculate national costs. Incremental economic costs per woman screened with VIA ranged from 4.93 US$ to 14.75 US$, and costs of cryotherapy were between 47.26 US$ and 84.48 US$ at surveyed facilities. Under base case assumptions, our model estimated the costs of VIA to be 6.12 US$ per woman and those of cryotherapy to be 27.96 US$. Sensitivity analysis showed that the number of women screened per provider and treated per facility was the most important determinants of costs. National annual programme costs were estimated to be between 0.6 and 4.0 million US$ depending on assumed coverage and adopted screening strategy.   When choosing between different cervical cancer prevention strategies, the feasibility of increasing uptake to achieve economies of scale should be a major concern. © 2011 Blackwell Publishing Ltd.

Generic Degraded Congiguration Probability Analysis for DOE Codisposal Waste Package

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

S.F.A. Deng; M. Saglam; L.J. Gratton

2001-05-23

In accordance with the technical work plan, ''Technical Work Plan For: Department of Energy Spent Nuclear Fuel Work Packages'' (CRWMS M&O 2000c), this Analysis/Model Report (AMR) is developed for the purpose of screening out degraded configurations for U.S. Department of Energy (DOE) spent nuclear fuel (SNF) types. It performs the degraded configuration parameter and probability evaluations of the overall methodology specified in the ''Disposal Criticality Analysis Methodology Topical Report'' (YMP 2000, Section 3) to qualifying configurations. Degradation analyses are performed to assess realizable parameter ranges and physical regimes for configurations. Probability calculations are then performed for configurations characterized by k{submore » eff} in excess of the Critical Limit (CL). The scope of this document is to develop a generic set of screening criteria or models to screen out degraded configurations having potential for exceeding a criticality limit. The developed screening criteria include arguments based on physical/chemical processes and probability calculations and apply to DOE SNF types when codisposed with the high-level waste (HLW) glass inside a waste package. The degradation takes place inside the waste package and is long after repository licensing has expired. The emphasis of this AMR is on degraded configuration screening and the probability analysis is one of the approaches used for screening. The intended use of the model is to apply the developed screening criteria to each DOE SNF type following the completion of the degraded mode criticality analysis internal to the waste package.« less

An adaptive algorithm for the detection of microcalcifications in simulated low-dose mammography.

PubMed

Treiber, O; Wanninger, F; Führ, H; Panzer, W; Regulla, D; Winkler, G

2003-02-21

This paper uses the task of microcalcification detection as a benchmark problem to assess the potential for dose reduction in x-ray mammography. We present the results of a newly developed algorithm for detection of microcalcifications as a case study for a typical commercial film-screen system (Kodak Min-R 2000/2190). The first part of the paper deals with the simulation of dose reduction for film-screen mammography based on a physical model of the imaging process. Use of a more sensitive film-screen system is expected to result in additional smoothing of the image. We introduce two different models of that behaviour, called moderate and strong smoothing. We then present an adaptive, model-based microcalcification detection algorithm. Comparing detection results with ground-truth images obtained under the supervision of an expert radiologist allows us to establish the soundness of the detection algorithm. We measure the performance on the dose-reduced images in order to assess the loss of information due to dose reduction. It turns out that the smoothing behaviour has a strong influence on detection rates. For moderate smoothing. a dose reduction by 25% has no serious influence on the detection results. whereas a dose reduction by 50% already entails a marked deterioration of the performance. Strong smoothing generally leads to an unacceptable loss of image quality. The test results emphasize the impact of the more sensitive film-screen system and its characteristics on the problem of assessing the potential for dose reduction in film-screen mammography. The general approach presented in the paper can be adapted to fully digital mammography.

An adaptive algorithm for the detection of microcalcifications in simulated low-dose mammography

NASA Astrophysics Data System (ADS)

Treiber, O.; Wanninger, F.; Führ, H.; Panzer, W.; Regulla, D.; Winkler, G.

2003-02-01

This paper uses the task of microcalcification detection as a benchmark problem to assess the potential for dose reduction in x-ray mammography. We present the results of a newly developed algorithm for detection of microcalcifications as a case study for a typical commercial film-screen system (Kodak Min-R 2000/2190). The first part of the paper deals with the simulation of dose reduction for film-screen mammography based on a physical model of the imaging process. Use of a more sensitive film-screen system is expected to result in additional smoothing of the image. We introduce two different models of that behaviour, called moderate and strong smoothing. We then present an adaptive, model-based microcalcification detection algorithm. Comparing detection results with ground-truth images obtained under the supervision of an expert radiologist allows us to establish the soundness of the detection algorithm. We measure the performance on the dose-reduced images in order to assess the loss of information due to dose reduction. It turns out that the smoothing behaviour has a strong influence on detection rates. For moderate smoothing, a dose reduction by 25% has no serious influence on the detection results, whereas a dose reduction by 50% already entails a marked deterioration of the performance. Strong smoothing generally leads to an unacceptable loss of image quality. The test results emphasize the impact of the more sensitive film-screen system and its characteristics on the problem of assessing the potential for dose reduction in film-screen mammography. The general approach presented in the paper can be adapted to fully digital mammography.

Economic evaluation of DNA ploidy analysis vs liquid-based cytology for cervical screening.

PubMed

Nghiem, V T; Davies, K R; Beck, J R; Follen, M; MacAulay, C; Guillaud, M; Cantor, S B

2015-06-09

DNA ploidy analysis involves automated quantification of chromosomal aneuploidy, a potential marker of progression toward cervical carcinoma. We evaluated the cost-effectiveness of this method for cervical screening, comparing five ploidy strategies (using different numbers of aneuploid cells as cut points) with liquid-based Papanicolaou smear and no screening. A state-transition Markov model simulated the natural history of HPV infection and possible progression into cervical neoplasia in a cohort of 12-year-old females. The analysis evaluated cost in 2012 US$ and effectiveness in quality-adjusted life-years (QALYs) from a health-system perspective throughout a lifetime horizon in the US setting. We calculated incremental cost-effectiveness ratios (ICERs) to determine the best strategy. The robustness of optimal choices was examined in deterministic and probabilistic sensitivity analyses. In the base-case analysis, the ploidy 4 cell strategy was cost-effective, yielding an increase of 0.032 QALY and an ICER of $18 264/QALY compared to no screening. For most scenarios in the deterministic sensitivity analysis, the ploidy 4 cell strategy was the only cost-effective strategy. Cost-effectiveness acceptability curves showed that this strategy was more likely to be cost-effective than the Papanicolaou smear. Compared to the liquid-based Papanicolaou smear, screening with a DNA ploidy strategy appeared less costly and comparably effective.

Incorporating Virtual Reactions into a Logic-based Ligand-based Virtual Screening Method to Discover New Leads

PubMed Central

Reynolds, Christopher R; Muggleton, Stephen H; Sternberg, Michael J E

2015-01-01

The use of virtual screening has become increasingly central to the drug development pipeline, with ligand-based virtual screening used to screen databases of compounds to predict their bioactivity against a target. These databases can only represent a small fraction of chemical space, and this paper describes a method of exploring synthetic space by applying virtual reactions to promising compounds within a database, and generating focussed libraries of predicted derivatives. A ligand-based virtual screening tool Investigational Novel Drug Discovery by Example (INDDEx) is used as the basis for a system of virtual reactions. The use of virtual reactions is estimated to open up a potential space of 1.21×1012 potential molecules. A de novo design algorithm known as Partial Logical-Rule Reactant Selection (PLoRRS) is introduced and incorporated into the INDDEx methodology. PLoRRS uses logical rules from the INDDEx model to select reactants for the de novo generation of potentially active products. The PLoRRS method is found to increase significantly the likelihood of retrieving molecules similar to known actives with a p-value of 0.016. Case studies demonstrate that the virtual reactions produce molecules highly similar to known actives, including known blockbuster drugs. PMID:26583052

Constructing and Validating High-Performance MIEC-SVM Models in Virtual Screening for Kinases: A Better Way for Actives Discovery

PubMed Central

Sun, Huiyong; Pan, Peichen; Tian, Sheng; Xu, Lei; Kong, Xiaotian; Li, Youyong; Dan Li; Hou, Tingjun

2016-01-01

The MIEC-SVM approach, which combines molecular interaction energy components (MIEC) derived from free energy decomposition and support vector machine (SVM), has been found effective in capturing the energetic patterns of protein-peptide recognition. However, the performance of this approach in identifying small molecule inhibitors of drug targets has not been well assessed and validated by experiments. Thereafter, by combining different model construction protocols, the issues related to developing best MIEC-SVM models were firstly discussed upon three kinase targets (ABL, ALK, and BRAF). As for the investigated targets, the optimized MIEC-SVM models performed much better than the models based on the default SVM parameters and Autodock for the tested datasets. Then, the proposed strategy was utilized to screen the Specs database for discovering potential inhibitors of the ALK kinase. The experimental results showed that the optimized MIEC-SVM model, which identified 7 actives with IC50 < 10 μM from 50 purchased compounds (namely hit rate of 14%, and 4 in nM level) and performed much better than Autodock (3 actives with IC50 < 10 μM from 50 purchased compounds, namely hit rate of 6%, and 2 in nM level), suggesting that the proposed strategy is a powerful tool in structure-based virtual screening. PMID:27102549

Constructing and Validating High-Performance MIEC-SVM Models in Virtual Screening for Kinases: A Better Way for Actives Discovery.

PubMed

Sun, Huiyong; Pan, Peichen; Tian, Sheng; Xu, Lei; Kong, Xiaotian; Li, Youyong; Dan Li; Hou, Tingjun

2016-04-22

The MIEC-SVM approach, which combines molecular interaction energy components (MIEC) derived from free energy decomposition and support vector machine (SVM), has been found effective in capturing the energetic patterns of protein-peptide recognition. However, the performance of this approach in identifying small molecule inhibitors of drug targets has not been well assessed and validated by experiments. Thereafter, by combining different model construction protocols, the issues related to developing best MIEC-SVM models were firstly discussed upon three kinase targets (ABL, ALK, and BRAF). As for the investigated targets, the optimized MIEC-SVM models performed much better than the models based on the default SVM parameters and Autodock for the tested datasets. Then, the proposed strategy was utilized to screen the Specs database for discovering potential inhibitors of the ALK kinase. The experimental results showed that the optimized MIEC-SVM model, which identified 7 actives with IC50 < 10 μM from 50 purchased compounds (namely hit rate of 14%, and 4 in nM level) and performed much better than Autodock (3 actives with IC50 < 10 μM from 50 purchased compounds, namely hit rate of 6%, and 2 in nM level), suggesting that the proposed strategy is a powerful tool in structure-based virtual screening.

A prediction model based on an artificial intelligence system for moderate to severe obstructive sleep apnea.

PubMed

Sun, Lei Ming; Chiu, Hung-Wen; Chuang, Chih Yuan; Liu, Li

2011-09-01

Obstructive sleep apnea (OSA) is a major concern in modern medicine; however, it is difficult to diagnose. Screening questionnaires such as the Berlin questionnaire, Rome questionnaire, and BASH'IM score are used to identify patients with OSA. However, the sensitivity and specificity of these tools are not satisfactory. We aim to introduce an artificial intelligence method to screen moderate to severe OSA patients (apnea-hypopnea index ≧15). One hundred twenty patients were asked to complete a newly developed questionnaire before undergoing an overnight polysomnography (PSG) study. One hundred ten validated questionnaires were enrolled in this study. Genetic algorithm (GA) was used to build the five best models based on these questionnaires. The same data were analyzed with logistic regression (LR) for comparison. The sensitivity of the GA models varied from 81.8% to 88.0%, with a specificity of 95% to 97%. On the other hand, the sensitivity and specificity of the LR model were 55.6% and 57.9%, respectively. GA provides a good solution to build models for screening moderate to severe OSA patients, who require PSG evaluation and medical intervention. The questionnaire did not require any special biochemistry data and was easily self-administered. The sensitivity and specificity of the GA models are satisfactory and may improve when more patients are recruited.

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

NASA Astrophysics Data System (ADS)

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

2017-10-01

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

Metadata Standard and Data Exchange Specifications to Describe, Model, and Integrate Complex and Diverse High-Throughput Screening Data from the Library of Integrated Network-based Cellular Signatures (LINCS).

PubMed

Vempati, Uma D; Chung, Caty; Mader, Chris; Koleti, Amar; Datar, Nakul; Vidović, Dušica; Wrobel, David; Erickson, Sean; Muhlich, Jeremy L; Berriz, Gabriel; Benes, Cyril H; Subramanian, Aravind; Pillai, Ajay; Shamu, Caroline E; Schürer, Stephan C

2014-06-01

The National Institutes of Health Library of Integrated Network-based Cellular Signatures (LINCS) program is generating extensive multidimensional data sets, including biochemical, genome-wide transcriptional, and phenotypic cellular response signatures to a variety of small-molecule and genetic perturbations with the goal of creating a sustainable, widely applicable, and readily accessible systems biology knowledge resource. Integration and analysis of diverse LINCS data sets depend on the availability of sufficient metadata to describe the assays and screening results and on their syntactic, structural, and semantic consistency. Here we report metadata specifications for the most important molecular and cellular components and recommend them for adoption beyond the LINCS project. We focus on the minimum required information to model LINCS assays and results based on a number of use cases, and we recommend controlled terminologies and ontologies to annotate assays with syntactic consistency and semantic integrity. We also report specifications for a simple annotation format (SAF) to describe assays and screening results based on our metadata specifications with explicit controlled vocabularies. SAF specifically serves to programmatically access and exchange LINCS data as a prerequisite for a distributed information management infrastructure. We applied the metadata specifications to annotate large numbers of LINCS cell lines, proteins, and small molecules. The resources generated and presented here are freely available. © 2014 Society for Laboratory Automation and Screening.

An in vivo multiplexed small molecule screening platform

PubMed Central

Yang, Dian; Ogasawara, Daisuke; Dix, Melissa M.; Rogers, Zoë N.; Chuang, Chen-Hua; McFarland, Christopher D.; Chiou, Shin-Heng; Brown, J. Mark; Cravatt, Benjamin F.; Bogyo, Matthew; Winslow, Monte M.

2016-01-01

Phenotype-based small molecule screening is a powerful method to identify regulators of cellular function. However, such screens are generally performed in vitro using conditions that do not necessarily model complex physiological conditions or disease states. Here, we use molecular cell barcoding to enable direct in vivo phenotypic screening of libraries of small molecules. The multiplexed nature of this approach allows rapid in vivo analysis of hundreds to thousands of compounds. Using this platform, we screened >700 covalent inhibitors directed towards hydrolases for their effect on pancreatic cancer metastatic seeding. We identified multiple hits and confirmed the relevant target of one compound as the lipase ABHD6. Pharmacological and genetic studies confirmed the role of this enzyme as a regulator of metastatic fitness. Our results highlight the applicability of this multiplexed screening platform for investigating complex processes in vivo. PMID:27617390

Discovery of novel drugs for promising targets.

PubMed

Martell, Robert E; Brooks, David G; Wang, Yan; Wilcoxen, Keith

2013-09-01

Once a promising drug target is identified, the steps to actually discover and optimize a drug are diverse and challenging. The goal of this study was to provide a road map to navigate drug discovery. Review general steps for drug discovery and provide illustrating references. A number of approaches are available to enhance and accelerate target identification and validation. Consideration of a variety of potential mechanisms of action of potential drugs can guide discovery efforts. The hit to lead stage may involve techniques such as high-throughput screening, fragment-based screening, and structure-based design, with informatics playing an ever-increasing role. Biologically relevant screening models are discussed, including cell lines, 3-dimensional culture, and in vivo screening. The process of enabling human studies for an investigational drug is also discussed. Drug discovery is a complex process that has significantly evolved in recent years. © 2013 Elsevier HS Journals, Inc. All rights reserved.

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

PubMed

Shoham, David A; Tong, Liping; Lamberson, Peter J; Auchincloss, Amy H; Zhang, Jun; Dugas, Lara; Kaufman, Jay S; Cooper, Richard S; Luke, Amy

2012-01-01

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.

Development of a Screening Model for Design and Costing of an Innovative Tailored Granular Activated Carbon Technology to Treat Perchlorate-Contaminated Water

DTIC Science & Technology

2007-03-01

column experiments were used to obtain model parameters . Cost data used in the model were based on conventional GAC installations, as modified to...43 Calculation of Parameters ...66 Determination of Parameter Values

Increasing Cervical Cancer Screening Coverage: A Randomised, Community-Based Clinical Trial.

PubMed

Acera, Amelia; Manresa, Josep Maria; Rodriguez, Diego; Rodriguez, Ana; Bonet, Josep Maria; Trapero-Bertran, Marta; Hidalgo, Pablo; Sànchez, Norman; de Sanjosé, Silvia

2017-01-01

Opportunistic cervical cancer screening can lead to suboptimal screening coverage. Coverage could be increased after a personalised invitation to the target population. We present a community randomized intervention study with three strategies aiming to increase screening coverage. The CRICERVA study is a community-based clinical trial to improve coverage of population-based screening in the Cerdanyola SAP area in Barcelona.A total of 32,858 women residing in the study area, aged 30 to 70 years were evaluated. A total of 15,965 women were identified as having no registration of a cervical cytology in the last 3.5 years within the Public Health data base system. Eligible women were assigned to one of four community randomized intervention groups (IGs): (1) (IG1 N = 4197) personalised invitation letter, (2) (IG2 N = 3601) personalised invitation letter + informative leaflet, (3) (IG3 N = 6088) personalised invitation letter + informative leaflet + personalised phone call and (4) (Control N = 2079) based on spontaneous demand of cervical cancer screening as officially recommended. To evaluate screening coverage, we used heterogeneity tests to compare impact of the interventions and mixed logistic regression models to assess the age effect. We refer a "rescue" visit as the screening visit resulting from the study invitation. Among the 13,886 women in the IGs, 2,862 were evaluated as having an adequate screening history after the initial contact; 4,263 were lost to follow-up and 5,341 were identified as having insufficient screening and thus being eligible for a rescue visit. All intervention strategies significantly increased participation to screening compared to the control group. Coverage after the intervention reached 84.1% while the control group reached 64.8%. The final impact of our study was an increase of 20% in the three IGs and of 9% in the control group (p<0.001). Within the intervention arms, age was an important determinant of rescue visits showing a statistical interaction with the coverage attained in the IGs. Within the intervention groups, final screening coverage was significantly higher in IG3 (84.4%) (p<0.001). However, the differences were more substantial in the age groups 50-59 and those 60+. The highest impact of the IG3 intervention was observed among women 60+ y.o with 32.0% of them being rescued for screening. The lowest impact of the interventions was in younger women. The study confirms that using individual contact methods and assigning a fixed screening date notably increases participation in screening. The response to the invitation is strongly dependent on age. ClinicalTrials.gov NCT01373723.

Universal Versus Targeted Screening for Lynch Syndrome: Comparing Ascertainment and Costs Based on Clinical Experience.

PubMed

Erten, Mujde Z; Fernandez, Luca P; Ng, Hank K; McKinnon, Wendy C; Heald, Brandie; Koliba, Christopher J; Greenblatt, Marc S

2016-10-01

Strategies to screen colorectal cancers (CRCs) for Lynch syndrome are evolving rapidly; the optimal strategy remains uncertain. We compared targeted versus universal screening of CRCs for Lynch syndrome. In 2010-2011, we employed targeted screening (age < 60 and/or Bethesda criteria). From 2012 to 2014, we screened all CRCs. Immunohistochemistry for the four mismatch repair proteins was done in all cases, followed by other diagnostic studies as indicated. We modeled the diagnostic costs of detecting Lynch syndrome and estimated the 5-year costs of preventing CRC by colonoscopy screening, using a system dynamics model. Using targeted screening, 51/175 (29 %) cancers fit criteria and were tested by immunohistochemistry; 15/51 (29 %, or 8.6 % of all CRCs) showed suspicious loss of ≥1 mismatch repair protein. Germline mismatch repair gene mutations were found in 4/4 cases sequenced (11 suspected cases did not have germline testing). Using universal screening, 17/292 (5.8 %) screened cancers had abnormal immunohistochemistry suspicious for Lynch syndrome. Germline mismatch repair mutations were found in only 3/10 cases sequenced (7 suspected cases did not have germline testing). The mean cost to identify Lynch syndrome probands was ~$23,333/case for targeted screening and ~$175,916/case for universal screening at our institution. Estimated costs to identify and screen probands and relatives were: targeted, $9798/case and universal, $38,452/case. In real-world Lynch syndrome management, incomplete clinical follow-up was the major barrier to do genetic testing. Targeted screening costs 2- to 7.5-fold less than universal and rarely misses Lynch syndrome cases. Future changes in testing costs will likely change the optimal algorithm.

Structure Based Virtual Screening Studies to Identify Novel Potential Compounds for GPR142 and Their Relative Dynamic Analysis for Study of Type 2 Diabetes

NASA Astrophysics Data System (ADS)

Kaushik, Aman C.; Kumar, Sanjay; Wei, Dong Q.; Sahi, Shakti

2018-02-01

GPR142 (G protein receptor 142) is a novel orphan GPCR (G protein coupled receptor) belonging to ‘Class A’ of GPCR family and expressed in beta cells of pancreas. In this study, we reported the structure based virtual screening to identify the hit compounds which can be developed as leads for potential agonists. The results were validated through induced fit docking, pharmacophore modeling and system biology approaches. Since, there is no solved crystal structure of GPR142, we attempted to predict the 3D structure followed by validation and then identification of active site using threading and ab initio methods. Also, structure based virtual screening was performed against a total of 1171519 compounds from different libraries and only top 20 best hit compounds were screened and analyzed. Moreover, the biochemical pathway of GPR142 complex with screened compound2 was also designed and compared with experimental data. Interestingly, compound2 showed an increase in insulin production via Gq mediated signaling pathway suggesting the possible role of novel GPR142 agonists in therapy against type 2 diabetes.

Perceived Neighborhood Quality and Cancer Screening Behavior: Evidence from the Survey of the Health of Wisconsin

PubMed Central

Beyer, Kirsten M. M.; Malecki, Kristen M.; Hoormann, Kelly A.; Szabo, Aniko; Nattinger, Ann B.

2016-01-01

Socioeconomic disparities in colorectal and breast cancer screening persist, partially accounting for disparities in cancer outcomes. Some neighborhood characteristics – particularly area level socioeconomic factors – have been linked to cancer screening behavior, but few studies have examined the relationship between perceived neighborhood quality and screening behavior, which may provide more insight into the ways in which neighborhood environments shape cancer related behaviors. This study examines the relationship between several aspects of the perceived neighborhood environment and breast and colorectal cancer screening behavior among a population-based sample of Wisconsin residents. A sub-goal was to compare the relevance of different perceived neighborhood factors for different screening tests. This is a cross-sectional study of 2008–2012 data from the Survey of the Health of Wisconsin (SHOW), a population-based annual survey of Wisconsin residents. An average risk sample of Black, Hispanic and White women age 50 and older (n=1265) were selected. Survey regression analyses examined predictors of screening, as well as adherence to screening guidelines. Models controlled for individual socio-demographic information and insurance status. Perceptions of social and physical disorder, including fear of crime and visible garbage, were associated with screening rates. Findings emphasize the particular importance of these factors for colorectal cancer screening, indicating the necessity of improving screening rates in areas characterized by social disorganization, crime, and physical disorder. Additional work should be done to further investigate the pathways that explain the linkage between neighborhood conditions, perceived neighborhood risks and cancer screening behavior. PMID:26275881

Enhanced maternal and child health nurse care for women experiencing intimate partner/family violence: protocol for MOVE, a cluster randomised trial of screening and referral in primary health care

PubMed Central

2012-01-01

Background Intimate partner violence (IPV) can result in significant harm to women and families and is especially prevalent when women are pregnant or recent mothers. Maternal and child health nurses (MCHN) in Victoria, Australia are community-based nurse/midwives who see over 95% of all mothers with newborns. MCHN are in an ideal position to identify and support women experiencing IPV, or refer them to specialist family violence services. Evidence for IPV screening in primary health care is inconclusive to date. The Victorian government recently required nurses to screen all mothers when babies are four weeks old, offering an opportunity to examine the effectiveness of MCHN IPV screening practices. This protocol describes the development and design of MOVE, a study to examine IPV screening effectiveness and the sustainability of screening practice. Methods/design MOVE is a cluster randomised trial of a good practice model of MCHN IPV screening involving eight maternal and child health nurse teams in Melbourne, Victoria. Normalisation Process Theory (NPT) was incorporated into the design, implementation and evaluation of the MOVE trial to enhance and evaluate sustainability. Using NPT, the development stage combined participatory action research with intervention nurse teams and a systematic review of nurse IPV studies to develop an intervention model incorporating consensus guidelines, clinical pathway and strategies for individual nurses, their teams and family violence services. Following twelve months’ implementation, primary outcomes assessed include IPV inquiry, IPV disclosure by women and referral using data from MCHN routine data collection and a survey to all women giving birth in the previous eight months. IPV will be measured using the Composite Abuse Scale. Process and impact evaluation data (online surveys and key stakeholders interviews) will highlight NPT concepts to enhance sustainability of IPV identification and referral. Data will be collected again in two years. Discussion MOVE will be the first randomised trial to determine IPV screening effectiveness in a community based nurse setting and the first to examine sustainability of an IPV screening intervention. It will further inform the debate about the effectiveness of IPV screening and describe IPV prevalence in a community based post-partum and early infant population. Trial registration ACTRN12609000424202 PMID:22994910

Entertainment Education for Prostate Cancer Screening: A Randomized Trial among Primary Care Patients with Low Health Literacy

PubMed Central

Volk, Robert J.; Jibaja-Weiss, Maria L.; Hawley, Sarah T.; Kneuper, Suzanne; Spann, Stephen J.; Miles, Brian J.; Hyman, David J.

2008-01-01

Objective To evaluate an entertainment-based patient decision aid for prostate cancer screening among patients with low or high health literacy. Methods Male primary care patients from two clinical sites, one characterized as serving patients with low health literacy (n=149) and the second as serving patients with high health literacy (n=301), were randomized to receive an entertainment-based decision aid for prostate cancer screening or an audiobooklet-control aid with the same learner content but without the entertainment features. Postintervention and 2-week follow-up assessments were conducted. Results Patients at the low-literacy site were more engaged with the entertainment-based aid than patients at the high-literacy site. Overall, knowledge improved for all patients. Among patients at the low-literacy site, the entertainment-based aid was associated with lower decisional conflict and greater self-advocacy (i.e., mastering and obtaining information about screening) when compared to patients given the audiobooklet. No differences between the aids were observed for patients at the high-literacy site. Conclusions Entertainment education may be an effective strategy for promoting informed decision making about prostate cancer screening among patients with lower health literacy. Practice Implications As barriers to implementing computer-based patient decision support programs decrease, alternative models for delivering these programs should be explored. PMID:18760888

Identification of Patients at Risk for Hereditary Colorectal Cancer

PubMed Central

Mishra, Nitin; Hall, Jason

2012-01-01

Diagnosis of hereditary colorectal cancer syndromes requires clinical suspicion and knowledge of such syndromes. Lynch syndrome is the most common cause of hereditary colorectal cancer. Other less common causes include familial adenomatous polyposis (FAP), Peutz-Jeghers syndrome (PJS), juvenile polyposis syndrome, and others. There have been a growing number of clinical and molecular tools used to screen and test at risk individuals. Screening tools include diagnostic clinical criteria, family history, genetic prediction models, and tumor testing. Patients who are high risk based on screening should be referred for genetic testing. PMID:23730221

Evaluation of a Screening System for Obesogenic Compounds: Screening of Endocrine Disrupting Compounds and Evaluation of the PPAR Dependency of the Effect

PubMed Central

Pereira-Fernandes, Anna; Demaegdt, Heidi; Vandermeiren, Karine; Hectors, Tine L. M.; Jorens, Philippe G.; Blust, Ronny; Vanparys, Caroline

2013-01-01

Recently the environmental obesogen hypothesis has been formulated, proposing a role for endocrine disrupting compounds (EDCs) in the development of obesity. To evaluate this hypothesis, a screening system for obesogenic compounds is urgently needed. In this study, we suggest a standardised protocol for obesogen screening based on the 3T3-L1 cell line, a well-characterised adipogenesis model, and direct fluorescent measurement using Nile red lipid staining technique. In a first phase, we characterised the assay using the acknowledged obesogens rosiglitazone and tributyltin. Based on the obtained dose-response curves for these model compounds, a lipid accumulation threshold value was calculated to ensure the biological relevance and reliability of statistically significant effects. This threshold based method was combined with the well described strictly standardized mean difference (SSMD) method for classification of non-, weak- or strong obesogenic compounds. In the next step, a range of EDCs, used in personal and household care products (parabens, musks, phthalates and alkylphenol compounds), were tested to further evaluate the obesogenicity screening assay for its discriminative power and sensitivity. Additionally, the peroxisome proliferator activated receptor γ (PPARγ) dependency of the positive compounds was evaluated using PPARγ activation and antagonist experiments. Our results showed the adipogenic potential of all tested parabens, several musks and phthalate compounds and bisphenol A (BPA). PPARγ activation was associated with adipogenesis for parabens, phthalates and BPA, however not required for obesogenic effects induced by Tonalide, indicating the role of other obesogenic mechanisms for this compound. PMID:24155963

Thermal Testing and Analysis of an Efficient High-Temperature Multi-Screen Internal Insulation

NASA Technical Reports Server (NTRS)

Weiland, Stefan; Handrick, Karin; Daryabeigi, Kamran

2007-01-01

Conventional multi-layer insulations exhibit excellent insulation performance but they are limited to the temperature range to which their components reflective foils and spacer materials are compatible. For high temperature applications, the internal multi-screen insulation IMI has been developed that utilizes unique ceramic material technology to produce reflective screens with high temperature stability. For analytical insulation sizing a parametric material model is developed that includes the main contributors for heat flow which are radiation and conduction. The adaptation of model-parameters based on effective steady-state thermal conductivity measurements performed at NASA Langley Research Center (LaRC) allows for extrapolation to arbitrary stack configurations and temperature ranges beyond the ones that were covered in the conductivity measurements. Experimental validation of the parametric material model was performed during the thermal qualification test of the X-38 Chin-panel, where test results and predictions showed a good agreement.

Evaluating a stage model in predicting monolingual spanish-speaking Latinas' cervical cancer screening practices: the role of psychosocial and cultural predictors.

PubMed

Arredondo, Elva Maria; Pollak, Kathryn; Costanzo, Philip R

2008-12-01

The goals of this study are to evaluate (a) the effectiveness of a stage model in predicting Latinas' self-report of obtaining a Pap test and (b) the unique role of psychosocial/cultural factors in predicting progress toward behavior change. One-on-one structured interviews with monolingual Spanish-speaking Latinas (n=190) were conducted. Most participants (85%) intended to obtain a Pap smear within 1 year; therefore, staging women based on intention was not possible. Moreover, results from the polychotomous hierarchical logistic regression suggest that psychosocial and cultural factors were independent predictors of Pap test history. A stage model may not be appropriate for predicting Pap test screening among Latinas. Results suggest that unique cultural, psychosocial, and demographic factors may inhibit cervical cancer screening practices. Clinicians may need to tailor messages on these cultural and psychosocial factors to increase Pap testing among Latinas.

Does cholesterol screening result in negative labeling effects? Results of the Massachusetts Model Systems for Blood Cholesterol Screening Project.

PubMed

Havas, S; Reisman, J; Hsu, L; Koumjian, L

1991-01-01

Several previous studies that looked at the effects of labeling individuals as hypertensive found increases in psychosocial distress, diminished feelings of well-being, or absenteeism. Other studies found no such effects. Thus far, similar studies relating to labeling for high blood cholesterol levels have not been published. The Massachusetts Model Systems for Blood Cholesterol Screening Project investigated whether labeling effects occurred as a result of the community-based screening, education, and referral programs it conducted in Worcester and Lowell. Nine questions concerning perceptions of physical and psychological well-being were asked on a questionnaire given to screening participants. The same questions were asked as part of a follow-up questionnaire given to all individuals identified as having high blood cholesterol levels at one of the screenings. Comparison of the baseline and follow-up results did not demonstrate significant overall negative effects among any age, sex, racial, income, or educational groups. On the contrary, responses to many of the questions revealed small but statistically significant improvements in perceptions of physical and psychological well-being. The absence of negative labeling effects may be attributable to the positive, supportive approach to participant counseling taken by the project.

Predictive Accuracy of the Liverpool Lung Project Risk Model for Stratifying Patients for Computed Tomography Screening for Lung Cancer

PubMed Central

Raji, Olaide Y.; Duffy, Stephen W.; Agbaje, Olorunshola F.; Baker, Stuart G.; Christiani, David C.; Cassidy, Adrian; Field, John K.

2013-01-01

Background External validation of existing lung cancer risk prediction models is limited. Using such models in clinical practice to guide the referral of patients for computed tomography (CT) screening for lung cancer depends on external validation and evidence of predicted clinical benefit. Objective To evaluate the discrimination of the Liverpool Lung Project (LLP) risk model and demonstrate its predicted benefit for stratifying patients for CT screening by using data from 3 independent studies from Europe and North America. Design Case–control and prospective cohort study. Setting Europe and North America. Patients Participants in the European Early Lung Cancer (EUELC) and Harvard case–control studies and the LLP population-based prospective cohort (LLPC) study. Measurements 5-year absolute risks for lung cancer predicted by the LLP model. Results The LLP risk model had good discrimination in both the Harvard (area under the receiver-operating characteristic curve [AUC], 0.76 [95% CI, 0.75 to 0.78]) and the LLPC (AUC, 0.82 [CI, 0.80 to 0.85]) studies and modest discrimination in the EUELC (AUC, 0.67 [CI, 0.64 to 0.69]) study. The decision utility analysis, which incorporates the harms and benefit of using a risk model to make clinical decisions, indicates that the LLP risk model performed better than smoking duration or family history alone in stratifying high-risk patients for lung cancer CT screening. Limitations The model cannot assess whether including other risk factors, such as lung function or genetic markers, would improve accuracy. Lack of information on asbestos exposure in the LLPC limited the ability to validate the complete LLP risk model. Conclusion Validation of the LLP risk model in 3 independent external data sets demonstrated good discrimination and evidence of predicted benefits for stratifying patients for lung cancer CT screening. Further studies are needed to prospectively evaluate model performance and evaluate the optimal population risk thresholds for initiating lung cancer screening. Primary Funding Source Roy Castle Lung Cancer Foundation. PMID:22910935

Role of the source to building lateral separation distance in petroleum vapor intrusion.

PubMed

Verginelli, Iason; Capobianco, Oriana; Baciocchi, Renato

2016-06-01

The adoption of source to building separation distances to screen sites that need further field investigation is becoming a common practice for the evaluation of the vapor intrusion pathway at sites contaminated by petroleum hydrocarbons. Namely, for the source to building vertical distance, the screening criteria for petroleum vapor intrusion have been deeply investigated in the recent literature and fully addressed in the recent guidelines issued by ITRC and U.S.EPA. Conversely, due to the lack of field and modeling studies, the source to building lateral distance received relatively low attention. To address this issue, in this work we present a steady-state vapor intrusion analytical model incorporating a piecewise first-order aerobic biodegradation limited by oxygen availability that accounts for lateral source to building separation. The developed model can be used to evaluate the role and relevance of lateral vapor attenuation as well as to provide a site-specific assessment of the lateral screening distances needed to attenuate vapor concentrations to risk-based values. The simulation outcomes showed to be consistent with field data and 3-D numerical modeling results reported in previous studies and, for shallow sources, with the screening criteria recommended by U.S.EPA for the vertical separation distance. Indeed, although petroleum vapors can cover maximum lateral distances up to 25-30m, as highlighted by the comparison of model outputs with field evidences of vapor migration in the subsurface, simulation results by this new model indicated that, regardless of the source concentration and depth, 6m and 7m lateral distances are sufficient to attenuate petroleum vapors below risk-based values for groundwater and soil sources, respectively. However, for deep sources (>5m) and for low to moderate source concentrations (benzene concentrations lower than 5mg/L in groundwater and 0.5mg/kg in soil) the above criteria were found extremely conservative as the model results indicated that for such scenarios the lateral screening distance may be set equal to zero. Copyright © 2016 Elsevier B.V. All rights reserved.

Using Weighted Entropy to Rank Chemicals in Quantitative High Throughput Screening Experiments

PubMed Central

Shockley, Keith R.

2014-01-01

Quantitative high throughput screening (qHTS) experiments can simultaneously produce concentration-response profiles for thousands of chemicals. In a typical qHTS study, a large chemical library is subjected to a primary screen in order to identify candidate hits for secondary screening, validation studies or prediction modeling. Different algorithms, usually based on the Hill equation logistic model, have been used to classify compounds as active or inactive (or inconclusive). However, observed concentration-response activity relationships may not adequately fit a sigmoidal curve. Furthermore, it is unclear how to prioritize chemicals for follow-up studies given the large uncertainties that often accompany parameter estimates from nonlinear models. Weighted Shannon entropy can address these concerns by ranking compounds according to profile-specific statistics derived from estimates of the probability mass distribution of response at the tested concentration levels. This strategy can be used to rank all tested chemicals in the absence of a pre-specified model structure or the approach can complement existing activity call algorithms by ranking the returned candidate hits. The weighted entropy approach was evaluated here using data simulated from the Hill equation model. The procedure was then applied to a chemical genomics profiling data set interrogating compounds for androgen receptor agonist activity. PMID:24056003

Comparison of slope instability screening tools following a large storm event and application to forest management and policy

NASA Astrophysics Data System (ADS)

Whittaker, Kara A.; McShane, Dan

2012-04-01

The objective of this study was to assess and compare the ability of two slope instability screening tools developed by the Washington State Department of Natural Resources (WDNR) to assess landslide risks associated with forestry activities. HAZONE is based on a semi-quantitative method that incorporates the landslide frequency rate and landslide area rate for delivery of mapped landforms. SLPSTAB is a GIS-based model of inherent landform characteristics that utilizes slope geometry derived from DEMs and climatic data. Utilization of slope instability screening tools by geologists, land managers, and regulatory agencies can reduce the frequency and magnitude of landslides. Aquatic habitats are negatively impacted by elevated rates and magnitudes of landslides associated with forest management practices due to high sediment loads and alteration of stream channels and morphology. In 2007 a large storm with heavy rainfall impacted southwestern Washington State trigging over 2500 landslides. This storm event and accompanying landslides provides an opportunity to assess the slope stability screening tools developed by WDNR. Landslide density (up to 6.5 landslides per km2) from the storm was highest in the areas designated by the screening tools as high hazard areas, and both of the screening tools were equal in their ability to predict landslide locations. Landslides that initiated in low hazard areas may have resulted from a variety of site-specific factors that deviated from assumed model values, from the inadequate identification of potentially unstable landforms due to low resolution DEMs, or from the inadequate implementation of the state Forest Practices Rules. We suggest that slope instability screening tools can be better utilized by forest management planners and regulators to meet policy goals regarding minimizing landslide rates and impacts to sensitive aquatic species.

Screening for gastric cancer and surveillance of premalignant lesions: a systematic review of cost-effectiveness studies.

PubMed

Areia, Miguel; Carvalho, Rita; Cadime, Ana Teresa; Rocha Gonçalves, Francisco; Dinis-Ribeiro, Mário

2013-10-01

Cost-effectiveness studies are highly dependent on the models, settings, and variables used and should be based on systematic reviews. We systematically reviewed cost-effectiveness studies that address screening for gastric cancer and/or surveillance of precancerous conditions and lesions. A systematic review of cost-effectiveness studies was performed by conducting a sensitive search in seven databases (PubMed, Scopus, Web of Science, Current Contents Connect, Centre for Reviews and Dissemination, Academic Search Complete, and CINAHL Plus), independently evaluated by two investigators. Articles were evaluated for type of study, perspective, model, intervention, incremental cost-effectiveness ratio, clinical or cost variables, and quality, according to published guidelines. From 2395 abstracts, 23 articles were included: 19 concerning population screening and 4 on following up premalignant lesions. Studies on Helicobacter pylori screening concluded that serology was cost-effective, depending on cancer incidence and endoscopy cost (incremental cost-effectiveness ratio: 6264-25,881), and eradication after endoscopic resection was also cost-effective (dominant) based on one study. Studies on imaging screening concluded that endoscopy was more cost-effective than no screening (incremental cost-effectiveness ratio: 3376-26,836). Articles on follow-up of premalignant lesions reported conflicting results (incremental cost-effectiveness ratio: 1868-72,519 for intestinal metaplasia; 18,600-39,800 for dysplasia). Quality assessment revealed a unanimous lack of a detailed systematic review and fulfillment of a median number of 23 items (20-26) of 35 possible ones. The available evidence shows that Helicobacter pylori serology or endoscopic population screening is cost-effective, while endoscopic surveillance of premalignant gastric lesions presents conflicting results. Better implementation of published guidelines and accomplishment of systematic detailed reviews are needed. © 2013 John Wiley & Sons Ltd.

A Risk Prediction Index for Advanced Colorectal Neoplasia at Screening Colonoscopy.

PubMed

Schroy, Paul C; Wong, John B; O'Brien, Michael J; Chen, Clara A; Griffith, John L

2015-07-01

Eliciting patient preferences within the context of shared decision making has been advocated for colorectal cancer screening. Risk stratification for advanced colorectal neoplasia (ACN) might facilitate more effective shared decision making when selecting an appropriate screening option. Our objective was to develop and validate a clinical index for estimating the probability of ACN at screening colonoscopy. We conducted a cross-sectional analysis of 3,543 asymptomatic, mostly average-risk patients 50-79 years of age undergoing screening colonoscopy at two urban safety net hospitals. Predictors of ACN were identified using multiple logistic regression. Model performance was internally validated using bootstrapping methods. The final index consisted of five independent predictors of risk (age, smoking, alcohol intake, height, and a combined sex/race/ethnicity variable). Smoking was the strongest predictor (net reclassification improvement (NRI), 8.4%) and height the weakest (NRI, 1.5%). Using a simplified weighted scoring system based on 0.5 increments of the adjusted odds ratio, the risk of ACN ranged from 3.2% (95% confidence interval (CI), 2.6-3.9) for the low-risk group (score ≤2) to 8.6% (95% CI, 7.4-9.7) for the intermediate/high-risk group (score 3-11). The model had moderate to good overall discrimination (C-statistic, 0.69; 95% CI, 0.66-0.72) and good calibration (P=0.73-0.93). A simple 5-item risk index based on readily available clinical data accurately stratifies average-risk patients into low- and intermediate/high-risk categories for ACN at screening colonoscopy. Uptake into clinical practice could facilitate more effective shared decision-making for CRC screening, particularly in situations where patient and provider test preferences differ.

Drug Discovery in Fish, Flies, and Worms

PubMed Central

Strange, Kevin

2016-01-01

Abstract Nonmammalian model organisms such as the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the zebrafish Danio rerio provide numerous experimental advantages for drug discovery including genetic and molecular tractability, amenability to high-throughput screening methods and reduced experimental costs and increased experimental throughput compared to traditional mammalian models. An interdisciplinary approach that strategically combines the study of nonmammalian and mammalian animal models with diverse experimental tools has and will continue to provide deep molecular and genetic understanding of human disease and will significantly enhance the discovery and application of new therapies to treat those diseases. This review will provide an overview of C. elegans, Drosophila, and zebrafish biology and husbandry and will discuss how these models are being used for phenotype-based drug screening and for identification of drug targets and mechanisms of action. The review will also describe how these and other nonmammalian model organisms are uniquely suited for the discovery of drug-based regenerative medicine therapies. PMID:28053067

A school-based public health model to reduce oral health disparities.

PubMed

Dudovitz, Rebecca N; Valiente, Jonathan E; Espinosa, Gloria; Yepes, Claudia; Padilla, Cesar; Puffer, Maryjane; Slavkin, Harold C; Chung, Paul J

2018-12-01

Although dental decay is preventable, it remains the most common pediatric chronic disease. We describe a public health approach to implementing a scalable and sustainable school-based oral health program for low-income urban children. The Los Angeles Trust for Children's Health, a nonprofit affiliated with the Los Angeles Unified School District, applied a public health model and developed a broad-based community-coalition to a) establish a District Oral Health Nurse position to coordinate oral health services, and b) implement a universal school-based oral health screening and fluoride varnishing program, with referral to a dental home. Key informant interviews and focus groups informed program development. Parent surveys assessed preventative oral health behaviors and access to oral health services. Results from screening exams, program costs and rates of reimbursement were recorded. From 2012 to 2015, six elementary schools and three dental provider groups participated. Four hundred ninety-one parents received oral health education and 89 served as community oral health volunteers; 3,399 screenings and fluoride applications were performed on 2,776 children. Sixty-six percent of children had active dental disease, 27 percent had visible tooth decay, and 6 percent required emergent care. Of the 623 students who participated for two consecutive years, 56 percent had fewer or no visible caries at follow-up, while only 17 percent had additional disease. Annual program cost was $69.57 per child. Using a broad based, oral health coalition, a school-based universal screening and fluoride varnishing program can improve the oral health of children with a high burden of untreated dental diseases. © 2017 American Association of Public Health Dentistry.

Financial Incentives and Cervical Cancer Screening Participation in Ontario's Primary Care Practice Models.

PubMed

Pendrith, Ciara; Thind, Amardeep; Zaric, Gregory S; Sarma, Sisira

2016-08-01

The primary objective of this paper is to compare cervical cancer screening rates of family physicians in Ontario's two dominant reformed practice models, Family Health Group (FHG) and Family Health Organization (FHO), and traditional fee-for-service (FFS) model. Both reformed models formally enrol patients and offer extensive pay-for-performance incentives; however, they differ by remuneration for core services (FHG is FFS; FHO is capitated). The secondary objective is to estimate the average and marginal costs of screening in each model. Using administrative data on 7,298 family physicians and their 2,083,633 female patients aged 35-69 eligible for cervical cancer screening in 2011, we assessed screening rates after adjusting for patient and physician characteristics. Predicted screening rates, fees and bonus payments were used to estimate the average and marginal costs of cervical cancer screening. Adjusted screening rates were highest in the FHG (81.9%), followed by the FHO (79.6%), and then the traditional FFS model (74.2%). The cost of a cervical cancer screening was $18.30 in the FFS model. The estimated average cost of screening in the FHGs and FHOs were $29.71 and $35.02, respectively, while the corresponding marginal costs were $33.05 and $39.06. We found significant differences in cervical cancer screening rates across Ontario's primary care practice models. Cervical screening rates were significantly higher in practice models eligible for incentives (FHGs and FHOs) than the traditional FFS model. However, the average and marginal cost of screening were lowest in the traditional FFS model and highest in the FHOs. Copyright © 2016 Longwoods Publishing.

Metabolomics-based prediction models of yeast strains for screening of metabolites contributing to ethanol stress tolerance

NASA Astrophysics Data System (ADS)

Hashim, Z.; Fukusaki, E.

2016-06-01

The increased demand for clean, sustainable and renewable energy resources has driven the development of various microbial systems to produce biofuels. One of such systems is the ethanol-producing yeast. Although yeast produces ethanol naturally using its native pathways, production yield is low and requires improvement for commercial biofuel production. Moreover, ethanol is toxic to yeast and thus ethanol tolerance should be improved to further enhance ethanol production. In this study, we employed metabolomics-based strategy using 30 single-gene deleted yeast strains to construct multivariate models for ethanol tolerance and screen metabolites that relate to ethanol sensitivity/tolerance. The information obtained from this study can be used as an input for strain improvement via metabolic engineering.

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

PubMed

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.

The Long-Term Effectiveness and Cost Effectiveness of Organized versus Opportunistic Screening for Breast Cancer in Austria.

PubMed

Schiller-Fruehwirth, Irmgard; Jahn, Beate; Einzinger, Patrick; Zauner, Günther; Urach, Christoph; Siebert, Uwe

2017-09-01

In 2014, Austrian health authorities implemented an organized breast cancer screening program. Until then, there has been a long-standing tradition of opportunistic screening. To evaluate the cost-effectiveness of organized screening compared with opportunistic screening, as well as to identify factors influencing the clinical and economic outcomes. We developed and validated an individual-level state-transition model and assessed the health outcomes and costs of organized and opportunistic screening for 40-year-old asymptomatic women. The base-case analysis compared a scenario involving organized biennial screening with a scenario reflecting opportunistic screening practice for an average-risk woman aged 45 to 69 years. We applied an annual discount rate of 3% and estimated the incremental cost-effectiveness ratio in terms of the cost (2012 euros) per life-year gained (LYG) from a health care perspective. Deterministic and probabilistic sensitivity analyses were performed to assess uncertainty. Compared with opportunistic screening, an organized program yielded on average additional 0.0118 undiscounted life-years (i.e., 4.3 days) and cost savings of €41 per woman. In the base-case analysis, the incremental cost-effectiveness ratio of organized screening was approximately €20,000 per LYG compared with no screening. Assuming a willingness-to-pay threshold of €50,000 per LYG, there was a 70% probability that organized screening would be considered cost-effective. The attendance rate, but not the test accuracy of mammography, was an influential factor for the cost-effectiveness. The decision to adopt organized screening is likely an efficient use of limited health care resources in Austria. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

A randomized comparison of print and web communication on colorectal cancer screening.

PubMed

Weinberg, David S; Keenan, Eileen; Ruth, Karen; Devarajan, Karthik; Rodoletz, Michelle; Bieber, Eric J

2013-01-28

New methods to enhance colorectal cancer (CRC) screening rates are needed. The web offers novel possibilities to educate patients and to improve health behaviors, such as cancer screening. Evidence supports the efficacy of health communications that are targeted and tailored to improve the uptake of recommendations. We identified unscreened women at average risk for CRC from the scheduling databases of obstetrics and gynecology practices in 2 large health care systems. Participants consented to a randomized controlled trial that compared CRC screening uptake after receipt of CRC screening information delivered via the web or in print form. Participants could also be assigned to a control (usual care) group. Women in the interventional arms received tailored information in a high- or low-monitoring Cognitive Social Information Processing model-defined attentional style. The primary outcome was CRC screening participation at 4 months. A total of 904 women were randomized to the interventional or control group. At 4 months, CRC screening uptake was not significantly different in the web (12.2%), print (12.0%), or control (12.9%) group. Attentional style had no effect on screening uptake for any group. Some baseline participant factors were associated with greater screening, including higher income (P = .03), stage of change (P < .001), and physician recommendation to screen (P < .001). A web-based educational intervention was no more effective than a print-based one or control (no educational intervention) in increasing CRC screening rates in women at average risk of CRC. Risk messages tailored to attentional style had no effect on screening uptake. In average-risk populations, use of the Internet for health communication without additional enhancement is unlikely to improve screening participation. clinicaltrials.gov Identifier: NCT00459030.

Screening and clustering of sparse regressions with finite non-Gaussian mixtures.

PubMed

Zhang, Jian

2017-06-01

This article proposes a method to address the problem that can arise when covariates in a regression setting are not Gaussian, which may give rise to approximately mixture-distributed errors, or when a true mixture of regressions produced the data. The method begins with non-Gaussian mixture-based marginal variable screening, followed by fitting a full but relatively smaller mixture regression model to the selected data with help of a new penalization scheme. Under certain regularity conditions, the new screening procedure is shown to possess a sure screening property even when the population is heterogeneous. We further prove that there exists an elbow point in the associated scree plot which results in a consistent estimator of the set of active covariates in the model. By simulations, we demonstrate that the new procedure can substantially improve the performance of the existing procedures in the content of variable screening and data clustering. By applying the proposed procedure to motif data analysis in molecular biology, we demonstrate that the new method holds promise in practice. © 2016, The International Biometric Society.

Cost Effectiveness of Age-Specific Screening Intervals for People With Family Histories of Colorectal Cancer.

PubMed

Naber, Steffie K; Kuntz, Karen M; Henrikson, Nora B; Williams, Marc S; Calonge, Ned; Goddard, Katrina A B; Zallen, Doris T; Ganiats, Theodore G; Webber, Elizabeth M; Janssens, A Cecile J W; van Ballegooijen, Marjolein; Zauber, Ann G; Lansdorp-Vogelaar, Iris

2018-01-01

Relative risk of colorectal cancer (CRC) decreases with age among individuals with a family history of CRC. However, no screening recommendations specify less frequent screening with increasing age. We aimed to determine whether such a refinement would be cost effective. We determined the relative risk for CRC for individuals based on age and number of affected first-degree relatives (FDRs) using data from publications. For each number of affected FDRs, we used the Microsimulation Screening Analysis model to estimate costs and effects of colonoscopy screening strategies with different age ranges and intervals. Screening was then optimized sequentially, starting with the youngest age group, and allowing the interval of screening to change at certain ages. Strategies with an incremental cost effectiveness ratio below $100,000 per quality-adjusted life year were considered cost effective. For people with 1 affected FDR (92% of those with a family history), screening every 3 years beginning at an age of 40 years is most cost effective. If no adenomas are found, the screening interval can gradually be extended to 5 and 7 years, at ages 45 and 55 years, respectively. From a cost-effectiveness perspective, individuals with more affected FDRs should start screening earlier and at shorter intervals. However, frequency can be reduced if no abnormalities are found. Using a microsimulation model, we found that for individuals with a family history of CRC, it is cost effective to gradually increase the screening interval if several subsequent screening colonoscopies have negative results and no new cases of CRC are found in family members. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Sedentary Screen Time and Left Ventricular Structure and Function: the CARDIA Study

PubMed Central

Gibbs, Bethany Barone; Reis, Jared P.; Schelbert, Erik B.; Craft, Lynette L.; Sidney, Steve; Lima, Joao; Lewis, Cora E.

2013-01-01

Sedentary screen time (watching TV or using a computer) predicts cardiovascular outcomes independently from moderate and vigorous physical activity and could impact left ventricular structure and function through the adverse consequences of sedentary behavior. Purpose To determine whether sedentary screen time is associated with measures of left ventricular structure and function. Methods The Coronary Artery Risk Development in Young Adults (CARDIA) Study measured screen time by questionnaire and left ventricular structure and function by echocardiography in 2,854 black and white participants, aged 43–55 years, in 2010–2011. Generalized linear models evaluated cross-sectional trends for echocardiography measures across higher categories of screen time and adjusting for demographics, smoking, alcohol, and physical activity. Further models adjusted for potential intermediate factors (blood pressure, antihypertensive medication use, diabetes, and body mass index (BMI). Results The relationship between screen time and left ventricular mass(LVM) differed in blacks vs. whites. Among whites, higher screen time was associated with larger LVM (P<0.001), after adjustment for height, demographics, and lifestyle variables. Associations between screen time and LVM persisted when adjusting for blood pressure, antihypertensive medication use, and diabetes (P=0.008) but not with additional adjustment for BMI (P=0.503). Similar relationships were observed for screen time with LVM indexed to height2.7, relative wall thickness, and mass-to-volume ratio. Screen time was not associated with left ventricular structure among blacks or left ventricular function in either race group. Conclusions Sedentary screen time is associated with greater LVM in white adults and this relationship was largely explained by higher overall adiposity. The lack of association in blacks supports a potential qualitative difference in the cardiovascular consequences of sedentary screen-based behavior. PMID:23863618

Automatic non-proliferative diabetic retinopathy screening system based on color fundus image.

PubMed

Xiao, Zhitao; Zhang, Xinpeng; Geng, Lei; Zhang, Fang; Wu, Jun; Tong, Jun; Ogunbona, Philip O; Shan, Chunyan

2017-10-26

Non-proliferative diabetic retinopathy is the early stage of diabetic retinopathy. Automatic detection of non-proliferative diabetic retinopathy is significant for clinical diagnosis, early screening and course progression of patients. This paper introduces the design and implementation of an automatic system for screening non-proliferative diabetic retinopathy based on color fundus images. Firstly, the fundus structures, including blood vessels, optic disc and macula, are extracted and located, respectively. In particular, a new optic disc localization method using parabolic fitting is proposed based on the physiological structure characteristics of optic disc and blood vessels. Then, early lesions, such as microaneurysms, hemorrhages and hard exudates, are detected based on their respective characteristics. An equivalent optical model simulating human eyes is designed based on the anatomical structure of retina. Main structures and early lesions are reconstructed in the 3D space for better visualization. Finally, the severity of each image is evaluated based on the international criteria of diabetic retinopathy. The system has been tested on public databases and images from hospitals. Experimental results demonstrate that the proposed system achieves high accuracy for main structures and early lesions detection. The results of severity classification for non-proliferative diabetic retinopathy are also accurate and suitable. Our system can assist ophthalmologists for clinical diagnosis, automatic screening and course progression of patients.

Discovery of novel Pim-1 kinase inhibitors by a hierarchical multistage virtual screening approach based on SVM model, pharmacophore, and molecular docking.

PubMed

Ren, Ji-Xia; Li, Lin-Li; Zheng, Ren-Lin; Xie, Huan-Zhang; Cao, Zhi-Xing; Feng, Shan; Pan, You-Li; Chen, Xin; Wei, Yu-Quan; Yang, Sheng-Yong

2011-06-27

In this investigation, we describe the discovery of novel potent Pim-1 inhibitors by employing a proposed hierarchical multistage virtual screening (VS) approach, which is based on support vector machine-based (SVM-based VS or SB-VS), pharmacophore-based VS (PB-VS), and docking-based VS (DB-VS) methods. In this approach, the three VS methods are applied in an increasing order of complexity so that the first filter (SB-VS) is fast and simple, while successive ones (PB-VS and DB-VS) are more time-consuming but are applied only to a small subset of the entire database. Evaluation of this approach indicates that it can be used to screen a large chemical library rapidly with a high hit rate and a high enrichment factor. This approach was then applied to screen several large chemical libraries, including PubChem, Specs, and Enamine as well as an in-house database. From the final hits, 47 compounds were selected for further in vitro Pim-1 inhibitory assay, and 15 compounds show nanomolar level or low micromolar inhibition potency against Pim-1. In particular, four of them were found to have new scaffolds which have potential for the chemical development of Pim-1 inhibitors.

Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers.

PubMed

Otto, Nicola; Opatz, Till

2012-01-01

In the search for new ligands for the Ullmann diaryl ether synthesis, permitting the coupling of electron-rich aryl bromides at relatively low temperatures, 56 structurally diverse multidentate ligands were screened in a model system that uses copper iodide in acetonitrile with potassium phosphate as the base. The ligands differed largely in their performance, but no privileged structural class could be identified.

Quality-of-life effects of prostate-specific antigen screening

PubMed Central

Heijnsdijk, EAM; Wever, EM; Auvinen, A; Hugosson, J; Ciatto, S; Nelen, V; Kwiatkowski, M; Villers, A; Páez, A; Moss, SM; Zappa, M; Tammela, TLJ; Mäkinen, T; Carlsson, S; Korfage, IJ; Essink-Bot, ML; Otto, SJ; Draisma, G; Bangma, CH; Roobol, MJ; Schröder, FH; de Koning, HJ

2016-01-01

Background The European Randomized Study of Screening for Prostate Cancer (ERSPC) reported a 29% prostate cancer mortality reduction among screened men after 11 years. However, it is uncertain to what extent harms from overdiagnosis and treatment on quality of life counterbalance this benefit. Methods Based on ERSPC follow-up data, we used micro-simulation modeling (MISCAN) to predict the number of prostate cancers, treatments, deaths and quality-adjusted life-years (QALYs) gained following the introduction of screening. Various screening strategies, efficacies, and quality of life assumptions were modeled. Results Per 1,000 men of all ages followed for their entire lifespan we predicted for annual screening from age 55–69 years: 9 fewer deaths due to prostate cancer (28% reduction), 14 fewer men receiving palliative therapy (35% reduction), and 73 life-years gained (average 8.4 years per prostate cancer death avoided). QALYs gained were 56 (range: −21, 97), a reduction of 23% from unadjusted life-years gained. The number needed to screen (NNS) was 98 and number needed to detect (NND) 5. Also inviting men aged 70–74 resulted in more life-years (82) but similar QALYs (56). Conclusions Although NNS and NND are more favorable than previously calculated, the benefit of PSA screening is diminished by loss of QALYs, that is dependent primarily on post-diagnosis long-term effects. Longer follow-up data from both the ERSPC and quality of life are essential before making universal recommendations regarding screening. PMID:22894572

Recommendations for Methicillin-Resistant Staphylococcus aureus Prevention in Adult ICUs: A Cost-Effectiveness Analysis.

PubMed

Whittington, Melanie D; Atherly, Adam J; Curtis, Donna J; Lindrooth, Richard C; Bradley, Cathy J; Campbell, Jonathan D

2017-08-01

Patients in the ICU are at the greatest risk of contracting healthcare-associated infections like methicillin-resistant Staphylococcus aureus. This study calculates the cost-effectiveness of methicillin-resistant S aureus prevention strategies and recommends specific strategies based on screening test implementation. A cost-effectiveness analysis using a Markov model from the hospital perspective was conducted to determine if the implementation costs of methicillin-resistant S aureus prevention strategies are justified by associated reductions in methicillin-resistant S aureus infections and improvements in quality-adjusted life years. Univariate and probabilistic sensitivity analyses determined the influence of input variation on the cost-effectiveness. ICU. Hypothetical cohort of adults admitted to the ICU. Three prevention strategies were evaluated, including universal decolonization, targeted decolonization, and screening and isolation. Because prevention strategies have a screening component, the screening test in the model was varied to reflect commonly used screening test categories, including conventional culture, chromogenic agar, and polymerase chain reaction. Universal and targeted decolonization are less costly and more effective than screening and isolation. This is consistent for all screening tests. When compared with targeted decolonization, universal decolonization is cost-saving to cost-effective, with maximum cost savings occurring when a hospital uses more expensive screening tests like polymerase chain reaction. Results were robust to sensitivity analyses. As compared with screening and isolation, the current standard practice in ICUs, targeted decolonization, and universal decolonization are less costly and more effective. This supports updating the standard practice to a decolonization approach.

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

NASA Astrophysics Data System (ADS)

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 structure based docking and scoring approaches in identifying promising hits by virtual screening of molecular libraries.

Estimates of over-diagnosis of breast cancer due to population-based mammography screening in South Australia after adjustment for lead time effects.

PubMed

Beckmann, Kerri; Duffy, Stephen W; Lynch, John; Hiller, Janet; Farshid, Gelareh; Roder, David

2015-09-01

To estimate over-diagnosis due to population-based mammography screening using a lead time adjustment approach, with lead time measures based on symptomatic cancers only. Women aged 40-84 in 1989-2009 in South Australia eligible for mammography screening. Numbers of observed and expected breast cancer cases were compared, after adjustment for lead time. Lead time effects were modelled using age-specific estimates of lead time (derived from interval cancer rates and predicted background incidence, using maximum likelihood methods) and screening sensitivity, projected background breast cancer incidence rates (in the absence of screening), and proportions screened, by age and calendar year. Lead time estimates were 12, 26, 43 and 53 months, for women aged 40-49, 50-59, 60-69 and 70-79 respectively. Background incidence rates were estimated to have increased by 0.9% and 1.2% per year for invasive and all breast cancer. Over-diagnosis among women aged 40-84 was estimated at 7.9% (0.1-12.0%) for invasive cases and 12.0% (5.7-15.4%) when including ductal carcinoma in-situ (DCIS). We estimated 8% over-diagnosis for invasive breast cancer and 12% inclusive of DCIS cancers due to mammography screening among women aged 40-84. These estimates may overstate the extent of over-diagnosis if the increasing prevalence of breast cancer risk factors has led to higher background incidence than projected. © The Author(s) 2015.

Cervical cancer screening in Bulgaria--past and present experience.

PubMed

Valerianova, Zdravka; Panayotova, Yulia; Amati, Camilla; Baili, Paolo

2010-01-01

In Bulgaria the previously (1970-1985) existing population based cervical cancer screening was replaced in the early 1990s with an opportunistic model due to political and socioeconomic reasons. As a result, in the last 20 years, cervical cancer incidence and mortality rates steady increased. The objective of the EUROCHIP project in Bulgaria was to evaluate the readiness of the health system as well as health providers' attitudes to implementation in the country of a population based screening program for cervical cancer. Using a structured questionnaire, a convenience sample of medical specialists representing different actors involved in cervical cancer prevention, treatment, financing and policy were interviewed. The majority of interviewed practitioners worried that organization and implementation of an effective population-based cervical cancer screening program is not possible in the current unstable health system. A nostalgic attitude to the cervical cancer screening, performed in the past and pessimistic view on the capability of the current health system to cope are strong. As main barriers to implementation of an effective program were pointed financial and organizational ones. Motivation for gynecologists to perform smear test should include better information, organization and payment. Medical specialists in Bulgaria are aware of the alarming rates of cervical cancer incidence and mortality in the country. However, due to the insufficient communication and interaction between policy makers and front-line health care staff, they do not have enough information on the ongoing programs. Absence of health policy regarding screening is considered as main barrier for implementation of an effective screening program.