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

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S. D. Hove-Musekwa

2009-01-01

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

Cost Effective Community Based Dementia Screening: A Markov Model Simulation

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Erin Saito

2014-01-01

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

In Vivo RNAi-Based Screens: Studies in Model Organisms

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Miki Yamamoto-Hino

2013-11-01

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

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

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

2016-07-01

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

Printer model for dot-on-dot halftone screens

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Balasubramanian, Raja

1995-04-01

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

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

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Lei, Ning; Xiong, Xiaoxiong; Mcintire, Jeff

2017-11-01

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

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

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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

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

DEFF Research Database (Denmark)

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

2011-01-01

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

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

International Nuclear Information System (INIS)

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

2003-01-01

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

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

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

2011-09-12

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

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

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

2018-01-01

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

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

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

2018-05-01

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

Effects of currently used pesticides and their mixtures on the function of thyroid hormone and aryl hydrocarbon receptor in cell culture

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Ghisari, Mandana; Long, Manhai; Tabbo, Agnese; Bonefeld-Jørgensen, Eva Cecilie, E-mail: ebj@mil.au.dk

2015-05-01

Evidence suggest that exposure to pesticides can interfere with the endocrine system by multiple mechanisms. The endocrine disrupting potential of currently used pesticides in Denmark was analyzed as single compounds and in an equimolar mixture of 5 selected pesticides. The pesticides were previously analyzed for effects on the function of estrogen and androgen receptors, the aromatase enzyme and steroidogenesis in vitro. In this study, the effect on thyroid hormone (TH) function and aryl hydrocarbon receptor (AhR) transactivity was assessed using GH3 cell proliferation assay (T-screen) and AhR responsive luciferase reporter gene bioassay, respectively. Thirteen pesticides were analyzed as follows: 2-methyl-4-chlorophenoxyacetic acid, terbuthylazine, iodosulfuron-methyl-sodium, mesosulfuron-methyl, metsulfuron-methyl, chlormequat chloride, bitertanol, propiconazole, prothioconazole, mancozeb and its metabolite ethylene thiourea, cypermethrin, tau-fluvalinate, and malathion (currently banned in DK). In the T-screen, prothioconazole, malathion, tau-fluvalinate, cypermethrin, terbuthylazine and mancozeb significantly stimulated and bitertanol and propiconazole slightly reduced the GH3 cell proliferation. In the presence of triiodothyronine (T3), prothioconazole, tau-fluvalinate, propiconazole, cypermethrin and bitertanol significantly antagonized the T3-induced GH3 cell proliferation. Eleven of the tested pesticides agonized the AhR function, and bitertanol and prothioconazole inhibited the basal AhR activity. Bitertanol, propiconazole, prothioconazole and cypermethrin antagonized the TCDD-induced AhR transactivation at the highest tested concentration. The 5-component mixture had inducing effect but the combined effect could not be predicted due to the presence of bitertanol eliciting inhibitory effect. Upon removal of bitertanol from the mixture, the remaining four pesticides acted additively. In conclusion, our data suggest that pesticides currently used in Denmark

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

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

2012-05-01

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

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

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Siemers Eric R

2010-04-01

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

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

Science.gov (United States)

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

2010-04-30

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

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

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

2018-04-01

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

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

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ZHU Binghua

2017-06-01

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

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

DEFF Research Database (Denmark)

Gorst-Rasmussen, Anders; Scheike, Thomas

2013-01-01

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

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

Science.gov (United States)

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

2018-02-01

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

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

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Fechner Nikolas

2010-03-01

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

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

Science.gov (United States)

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

2010-03-11

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

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

Science.gov (United States)

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

2012-05-01

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

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

Science.gov (United States)

Evanoff, Bradley; Kymes, Steve

2010-06-01

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

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

International Nuclear Information System (INIS)

Wen, X.G.; Zee, A.

1989-01-01

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

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

DEFF Research Database (Denmark)

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

2012-01-01

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

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

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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

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

International Nuclear Information System (INIS)

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

1982-01-01

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

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

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

2016-02-01

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

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

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

1999-02-06

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

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

International Nuclear Information System (INIS)

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

1994-01-01

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

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

Science.gov (United States)

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

2016-11-15

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

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

Science.gov (United States)

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

2016-04-01

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

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

Directory of Open Access Journals (Sweden)

Kitambi SS

2011-09-01

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

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

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

2014-10-19

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

Mathematical Models of the Sinusoidal Screen Family

Directory of Open Access Journals (Sweden)

Tajana Koren

2011-06-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2017-08-01

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

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

Science.gov (United States)

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

2011-01-01

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

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

Science.gov (United States)

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

2018-03-07

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

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

Science.gov (United States)

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

2015-01-01

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

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

Science.gov (United States)

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

2014-12-01

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

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

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Kevin Ten Haaf

2017-04-01

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

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

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

2013-02-01

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

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

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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.

Comparing deep learning models for population screening using chest radiography

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

2018-02-01

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

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

Directory of Open Access Journals (Sweden)

Nikolai Mühlberger

2017-06-01

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

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

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

2018-01-22

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

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

Science.gov (United States)

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

2015-06-01

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

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

Science.gov (United States)

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

2015-09-03

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

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

Science.gov (United States)

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

2015-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-07-01

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

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

DEFF Research Database (Denmark)

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

2014-01-01

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

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

Directory of Open Access Journals (Sweden)

Cristian G. Rodriguez

2016-01-01

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

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

International Nuclear Information System (INIS)

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

2002-01-01

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

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

Science.gov (United States)

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

2012-03-01

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

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

Science.gov (United States)

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

2010-01-01

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

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

Science.gov (United States)

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

2014-07-01

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

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

Science.gov (United States)

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

2015-08-01

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

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

DEFF Research Database (Denmark)

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

2014-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2007-11-01

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

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

International Nuclear Information System (INIS)

Nato, Alejandro Q. Jr.

2003-03-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Nato, Jr, Alejandro Q

2003-03-01

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

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

Science.gov (United States)

Tsunematsu, Miwako; Kakehashi, Masayuki

2015-01-01

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

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

Science.gov (United States)

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

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

Science.gov (United States)

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

2015-10-01

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

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

Directory of Open Access Journals (Sweden)

Wyatt Lawrence A

2005-11-01

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

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

DEFF Research Database (Denmark)

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

2017-01-01

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

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

International Nuclear Information System (INIS)

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

1988-01-01

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

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

Science.gov (United States)

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

2016-02-16

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

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

Science.gov (United States)

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

2017-09-01

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

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

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V. Pogrebnaya Tamara

2017-01-01

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

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

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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.

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

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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.

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

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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.

Primary care colorectal cancer screening correlates with breast cancer screening: implications for colorectal cancer screening improvement interventions.

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Weiss, Jennifer M; Pandhi, Nancy; Kraft, Sally; Potvien, Aaron; Carayon, Pascale; Smith, Maureen A

2018-04-25

National colorectal cancer (CRC) screening rates have plateaued. To optimize interventions targeting those unscreened, a better understanding is needed of how this preventive service fits in with multiple preventive and chronic care needs managed by primary care providers (PCPs). This study examines whether PCP practices of other preventive and chronic care needs correlate with CRC screening. We performed a retrospective cohort study of 90 PCPs and 33,137 CRC screening-eligible patients. Five PCP quality metrics (breast cancer screening, cervical cancer screening, HgbA1c and LDL testing, and blood pressure control) were measured. A baseline correlation test was performed between these metrics and PCP CRC screening rates. Multivariable logistic regression with clustering at the clinic-level estimated odds ratios and 95% confidence intervals for these PCP quality metrics, patient and PCP characteristics, and their relationship to CRC screening. PCP CRC screening rates have a strong correlation with breast cancer screening rates (r = 0.7414, p < 0.001) and a weak correlation with the other quality metrics. In the final adjusted model, the only PCP quality metric that significantly predicted CRC screening was breast cancer screening (OR 1.25; 95% CI 1.11-1.42; p < 0.001). PCP CRC screening rates are highly concordant with breast cancer screening. CRC screening is weakly concordant with cervical cancer screening and chronic disease management metrics. Efforts targeting PCPs to increase CRC screening rates could be bundled with breast cancer screening improvement interventions to increase their impact and success.

Screening important inputs in models with strong interaction properties

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Saltelli, Andrea; Campolongo, Francesca; Cariboni, Jessica

2009-01-01

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

Screening important inputs in models with strong interaction properties

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

2009-07-15

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

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

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Gould, Dinah; Papadopoulos, Irena; Kelly, Daniel

2012-01-01

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

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

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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.

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

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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.

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

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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...

More comprehensive discussion of CRC screening associated with higher screening.

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Mosen, David M; Feldstein, Adrianne C; Perrin, Nancy A; Rosales, A Gabriella; Smith, David H; Liles, Elizabeth G; Schneider, Jennifer L; Meyers, Ronald E; Elston-Lafata, Jennifer

2013-04-01

Examine association of comprehensiveness of colorectal cancer (CRC) screening discussion by primary care physicians (PCPs) with completion of CRC screening. Observational study in Kaiser Permanente Northwest, a group-model health maintenance organization. A total of 883 participants overdue for CRC screening received an automated telephone call (ATC) between April and June 2009 encouraging CRC screening. Between January and March 2010, participants completed a survey on PCPs' discussion of CRC screening and patient beliefs regarding screening. receipt of CRC screening (assessed by electronic medical record [EMR], 9 months after ATC). Primary independent variable: comprehensiveness of CRC screening discussion by PCPs (7-item scale). Secondary independent variables: perceived benefits of screening (4-item scale assessing respondents' agreement with benefits of timely screening) and primary care utilization (EMR; 9 months after ATC). The independent association of variables with CRC screening was assessed with logistic regression. Average scores for comprehensiveness of CRC discussion and perceived benefits were 0.4 (range 0-1) and 4.0 (range 1-5), respectively. A total of 28.2% (n = 249) completed screening, 84% of whom had survey assessments after their screening date. Of screeners, 95.2% completed the fecal immunochemical test. More comprehensive discussion of CRC screening was associated with increased screening (odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.03-2.21). Higher perceived benefits (OR = 1.46, 95% CI = 1.13-1.90) and 1 or more PCP visits (OR = 5.82, 95% CI = 3.87-8.74) were also associated with increased screening. More comprehensive discussion of CRC screening was independently associated with increased CRC screening. Primary care utilization was even more strongly associated with CRC screening, irrespective of discussion of CRC screening.

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

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

2016-02-16

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

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

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

2003-07-01

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

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

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

2016-08-01

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

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

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

2017-07-01

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

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

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

2016-08-01

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

Empirical study of supervised gene screening

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Ma Shuangge

2006-12-01

Full Text Available Abstract Background Microarray studies provide a way of linking variations of phenotypes with their genetic causations. Constructing predictive models using high dimensional microarray measurements usually consists of three steps: (1 unsupervised gene screening; (2 supervised gene screening; and (3 statistical model building. Supervised gene screening based on marginal gene ranking is commonly used to reduce the number of genes in the model building. Various simple statistics, such as t-statistic or signal to noise ratio, have been used to rank genes in the supervised screening. Despite of its extensive usage, statistical study of supervised gene screening remains scarce. Our study is partly motivated by the differences in gene discovery results caused by using different supervised gene screening methods. Results We investigate concordance and reproducibility of supervised gene screening based on eight commonly used marginal statistics. Concordance is assessed by the relative fractions of overlaps between top ranked genes screened using different marginal statistics. We propose a Bootstrap Reproducibility Index, which measures reproducibility of individual genes under the supervised screening. Empirical studies are based on four public microarray data. We consider the cases where the top 20%, 40% and 60% genes are screened. Conclusion From a gene discovery point of view, the effect of supervised gene screening based on different marginal statistics cannot be ignored. Empirical studies show that (1 genes passed different supervised screenings may be considerably different; (2 concordance may vary, depending on the underlying data structure and percentage of selected genes; (3 evaluated with the Bootstrap Reproducibility Index, genes passed supervised screenings are only moderately reproducible; and (4 concordance cannot be improved by supervised screening based on reproducibility.

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

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Philip W. Brownjohn

2017-04-01

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

A Computational model for compressed sensing RNAi cellular screening

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Tan Hua

2012-12-01

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

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

Directory of Open Access Journals (Sweden)

Badawi A

2012-04-01

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

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

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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

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

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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.

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

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

2017-09-27

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

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

Science.gov (United States)

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

2009-12-30

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

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

OpenAIRE

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

2015-01-01

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

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

Science.gov (United States)

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

2011-11-18

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

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

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Periwal Vinita

2011-11-01

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

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

Science.gov (United States)

Roy, Kunal; Mitra, Indrani

2011-07-01

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

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

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

2017-09-01

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

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

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Aymeric Ousset

2018-03-01

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

Screening sensitivity theory

International Nuclear Information System (INIS)

Oblow, E.M.; Perey, F.G.

1984-01-01

A comprehensive rigorous theory is developed for screening sensitivity coefficients in largescale modeling applications. The theory uses Bayesian inference and group theory to establish a probabilistic framework for solving an underdetermined system of linear equations. The underdetermined problem is directly related to statistical screening sensitivity theory as developed in recent years. Several examples of the new approach to screening are worked out in detail and comparisons are made with statistical approaches to the problem. The drawbacks of these latter methods are discussed at some length

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

Science.gov (United States)

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

2016-02-16

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

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

DEFF Research Database (Denmark)

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

2003-01-01

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

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

Science.gov (United States)

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

2017-03-01

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

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

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James Kingsley

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

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

Science.gov (United States)

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

2017-05-01

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

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

International Nuclear Information System (INIS)

Park, Young-Min; Kim, Kwang-Joon

2011-01-01

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

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

DEFF Research Database (Denmark)

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

2015-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1999-12-31

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

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

Science.gov (United States)

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

2015-07-01

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

The cumulative risk of false-positive screening results across screening centres in the Norwegian Breast Cancer Screening Program

Energy Technology Data Exchange (ETDEWEB)

Roman, M., E-mail: Marta.Roman@kreftregisteret.no [Cancer Registry of Norway, Oslo (Norway); Department of Women and Children’s Health, Oslo University Hospital, Oslo (Norway); Skaane, P., E-mail: PERSK@ous-hf.no [Department of Radiology, Oslo University Hospital Ullevaal, University of Oslo, Oslo (Norway); Hofvind, S., E-mail: Solveig.Hofvind@kreftregisteret.no [Cancer Registry of Norway, Oslo (Norway); Oslo and Akershus University College of Applied Sciences, Faculty of Health Science, Oslo (Norway)

2014-09-15

Highlights: • We found variation in early performance measures across screening centres. • Radiologists’ performance may play a key role in the variability. • Potential to improve the effectiveness of breast cancer screening programs. • Continuous surveillance of screening centres and radiologists is essential. - Abstract: Background: Recall for assessment in mammographic screening entails an inevitable number of false-positive screening results. This study aimed to investigate the variation in the cumulative risk of a false positive screening result and the positive predictive value across the screening centres in the Norwegian Breast Cancer Screening Program. Methods: We studied 618,636 women aged 50–69 years who underwent 2,090,575 screening exams (1996–2010. Recall rate, positive predictive value, rate of screen-detected cancer, and the cumulative risk of a false positive screening result, without and with invasive procedures across the screening centres were calculated. Generalized linear models were used to estimate the probability of a false positive screening result and to compute the cumulative false-positive risk for up to ten biennial screening examinations. Results: The cumulative risk of a false-positive screening exam varied from 10.7% (95% CI: 9.4–12.0%) to 41.5% (95% CI: 34.1–48.9%) across screening centres, with a highest to lowest ratio of 3.9 (95% CI: 3.7–4.0). The highest to lowest ratio for the cumulative risk of undergoing an invasive procedure with a benign outcome was 4.3 (95% CI: 4.0–4.6). The positive predictive value of recall varied between 12.0% (95% CI: 11.0–12.9%) and 19.9% (95% CI: 18.3–21.5%), with a highest to lowest ratio of 1.7 (95% CI: 1.5–1.9). Conclusions: A substantial variation in the performance measures across the screening centres in the Norwegian Breast Cancer Screening Program was identified, despite of similar administration, procedures, and quality assurance requirements. Differences in the

The cumulative risk of false-positive screening results across screening centres in the Norwegian Breast Cancer Screening Program

International Nuclear Information System (INIS)

Roman, M.; Skaane, P.; Hofvind, S.

2014-01-01

Highlights: • We found variation in early performance measures across screening centres. • Radiologists’ performance may play a key role in the variability. • Potential to improve the effectiveness of breast cancer screening programs. • Continuous surveillance of screening centres and radiologists is essential. - Abstract: Background: Recall for assessment in mammographic screening entails an inevitable number of false-positive screening results. This study aimed to investigate the variation in the cumulative risk of a false positive screening result and the positive predictive value across the screening centres in the Norwegian Breast Cancer Screening Program. Methods: We studied 618,636 women aged 50–69 years who underwent 2,090,575 screening exams (1996–2010. Recall rate, positive predictive value, rate of screen-detected cancer, and the cumulative risk of a false positive screening result, without and with invasive procedures across the screening centres were calculated. Generalized linear models were used to estimate the probability of a false positive screening result and to compute the cumulative false-positive risk for up to ten biennial screening examinations. Results: The cumulative risk of a false-positive screening exam varied from 10.7% (95% CI: 9.4–12.0%) to 41.5% (95% CI: 34.1–48.9%) across screening centres, with a highest to lowest ratio of 3.9 (95% CI: 3.7–4.0). The highest to lowest ratio for the cumulative risk of undergoing an invasive procedure with a benign outcome was 4.3 (95% CI: 4.0–4.6). The positive predictive value of recall varied between 12.0% (95% CI: 11.0–12.9%) and 19.9% (95% CI: 18.3–21.5%), with a highest to lowest ratio of 1.7 (95% CI: 1.5–1.9). Conclusions: A substantial variation in the performance measures across the screening centres in the Norwegian Breast Cancer Screening Program was identified, despite of similar administration, procedures, and quality assurance requirements. Differences in the

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

Science.gov (United States)

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

2015-01-20

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

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

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Sanjay Basu

2015-05-01

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

Breast Cancer Screening in an Era of Personalized Regimens

Science.gov (United States)

Onega, Tracy; Beaber, Elisabeth F.; Sprague, Brian L.; Barlow, William E.; Haas, Jennifer S.; Tosteson, Anna N.A.; Schnall, Mitchell D.; Armstrong, Katrina; Schapira, Marilyn M.; Geller, Berta; Weaver, Donald L.; Conant, Emily F.

2014-01-01

Breast cancer screening holds a prominent place in public health, health care delivery, policy, and women’s health care decisions. Several factors are driving shifts in how population-based breast cancer screening is approached, including advanced imaging technologies, health system performance measures, health care reform, concern for “overdiagnosis,” and improved understanding of risk. Maximizing benefits while minimizing the harms of screening requires moving from a “1-size-fits-all” guideline paradigm to more personalized strategies. A refined conceptual model for breast cancer screening is needed to align women’s risks and preferences with screening regimens. A conceptual model of personalized breast cancer screening is presented herein that emphasizes key domains and transitions throughout the screening process, as well as multilevel perspectives. The key domains of screening awareness, detection, diagnosis, and treatment and survivorship are conceptualized to function at the level of the patient, provider, facility, health care system, and population/policy arena. Personalized breast cancer screening can be assessed across these domains with both process and outcome measures. Identifying, evaluating, and monitoring process measures in screening is a focus of a National Cancer Institute initiative entitled PROSPR (Population-based Research Optimizing Screening through Personalized Regimens), which will provide generalizable evidence for a risk-based model of breast cancer screening, The model presented builds on prior breast cancer screening models and may serve to identify new measures to optimize benefits-to-harms tradeoffs in population-based screening, which is a timely goal in the era of health care reform. PMID:24830599

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

International Nuclear Information System (INIS)

Wolf, C.

1993-01-01

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

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

Science.gov (United States)

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

2009-01-01

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

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

Czech Academy of Sciences Publication Activity Database

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

2009-01-01

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

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

Science.gov (United States)

Gray, Ewan; Donten, Anna; Karssemeijer, Nico; van Gils, Carla; Evans, D Gareth; Astley, Sue; Payne, Katherine

2017-09-01

To identify the incremental costs and consequences of stratified national breast screening programs (stratified NBSPs) and drivers of relative cost-effectiveness. A decision-analytic model (discrete event simulation) was conceptualized to represent four stratified NBSPs (risk 1, risk 2, masking [supplemental screening for women with higher breast density], and masking and risk 1) compared with the current UK NBSP and no screening. The model assumed a lifetime horizon, the health service perspective to identify costs (£, 2015), and measured consequences in quality-adjusted life-years (QALYs). Multiple data sources were used: systematic reviews of effectiveness and utility, published studies reporting costs, and cohort studies embedded in existing NBSPs. Model parameter uncertainty was assessed using probabilistic sensitivity analysis and one-way sensitivity analysis. The base-case analysis, supported by probabilistic sensitivity analysis, suggested that the risk stratified NBSPs (risk 1 and risk-2) were relatively cost-effective when compared with the current UK NBSP, with incremental cost-effectiveness ratios of £16,689 per QALY and £23,924 per QALY, respectively. Stratified NBSP including masking approaches (supplemental screening for women with higher breast density) was not a cost-effective alternative, with incremental cost-effectiveness ratios of £212,947 per QALY (masking) and £75,254 per QALY (risk 1 and masking). When compared with no screening, all stratified NBSPs could be considered cost-effective. Key drivers of cost-effectiveness were discount rate, natural history model parameters, mammographic sensitivity, and biopsy rates for recalled cases. A key assumption was that the risk model used in the stratification process was perfectly calibrated to the population. This early model-based cost-effectiveness analysis provides indicative evidence for decision makers to understand the key drivers of costs and QALYs for exemplar stratified NBSP. Copyright

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

Science.gov (United States)

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

2009-02-01

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

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

Directory of Open Access Journals (Sweden)

Tu Karen

2005-08-01

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

Do parabens have the ability to interfere with steroidogenesis?

DEFF Research Database (Denmark)

Taxvig, Camilla; Vinggaard, Anne; Hass, Ulla

2008-01-01

The effects of ethyl and butyl paraben on steroidogenesis were evaluated in rats exposed in utero. Pregnant Wistar rats were dosed from gestational day (GD) 7 to GD 21, followed by examination of the dams, and the fetuses. Additionally, both parabens were tested in vitro in the H295R steroidogene......The effects of ethyl and butyl paraben on steroidogenesis were evaluated in rats exposed in utero. Pregnant Wistar rats were dosed from gestational day (GD) 7 to GD 21, followed by examination of the dams, and the fetuses. Additionally, both parabens were tested in vitro in the H295R...... steroidogenesis assay and in the T-screen assay, the later to test for their ability to act as thyroid hormone receptor agonist or antagonist. In the in utero exposure toxicity study, neither ethyl nor butyl paraben showed any treatment-related effects on testosterone production, anogenital distance......, or testicular histopathology. However, butyl paraben caused a significant decrease in the mRNA expression level of estradiol receptor-beta in fetal ovaries, and also significantly decreased the mRNA expression of steroidogenic acute regulatory protein and peripheral benzodiazepine receptor in the adrenal glands...

Cost Analysis of Universal Screening vs. Risk Factor-Based Screening for Methicillin-Resistant Staphylococcus aureus (MRSA.

Directory of Open Access Journals (Sweden)

Virginia R Roth

Full Text Available The literature remains conflicted regarding the most effective way to screen for MRSA. This study was designed to assess costs associated with universal versus risk factor-based screening for the reduction of nosocomial MRSA transmission.The study was conducted at The Ottawa Hospital, a large multi-centre tertiary care facility with approximately 47,000 admissions annually. From January 2006-December 2007, patients underwent risk factor-based screening for MRSA on admission. From January 2008 to August 2009 universal MRSA screening was implemented. A comparison of costs incurred during risk factor-based screening and universal screening was conducted. The model incorporated probabilities relating to the likelihood of being tested and the results of polymerase chain reaction (PCR testing with associated effects in terms of MRSA bacteremia and true positive and negative test results. Inputted costs included laboratory testing, contact precautions and infection control, private room costs, housekeeping, and length of hospital stay. Deterministic sensitivity analyses were conducted.The risk factor-based MRSA screening program screened approximately 30% of admitted patients and cost the hospital over $780 000 annually. The universal screening program screened approximately 83% of admitted patients and cost over $1.94 million dollars, representing an excess cost of $1.16 million per year. The estimated additional cost per patient screened was $17.76.This analysis demonstrated that a universal MRSA screening program was costly from a hospital perspective and was previously known to not be clinically effective at reducing MRSA transmission. These results may be useful to inform future model-based economic analyses of MRSA interventions.

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

Science.gov (United States)

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.

Screening model for nanowire surface-charge sensors in liquid

DEFF Research Database (Denmark)

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

2007-01-01

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

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

Science.gov (United States)

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.

Modeling sequential context effects in diagnostic interpretation of screening mammograms.

Science.gov (United States)

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

2018-07-01

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

Cost-effectiveness analysis of neonatal hearing screening program in china: should universal screening be prioritized?

Directory of Open Access Journals (Sweden)

Huang Li-Hui

2012-04-01

Full Text Available Abstract Background Neonatal hearing screening (NHS has been routinely offered as a vital component of early childhood care in developed countries, whereas such a screening program is still at the pilot or preliminary stage as regards its nationwide implementation in developing countries. To provide significant evidence for health policy making in China, this study aims to determine the cost-effectiveness of NHS program implementation in case of eight provinces of China. Methods A cost-effectiveness model was conducted and all neonates annually born from 2007 to 2009 in eight provinces of China were simulated in this model. The model parameters were estimated from the established databases in the general hospitals or maternal and child health hospitals of these eight provinces, supplemented from the published literature. The model estimated changes in program implementation costs, disability-adjusted life years (DALYs, average cost-effectiveness ratio (ACER, and incremental cost-effectiveness ratio (ICER for universal screening compared to targeted screening in eight provinces. Results and discussion A multivariate sensitivity analysis was performed to determine uncertainty in health effect estimates and cost-effectiveness ratios using a probabilistic modeling technique. Targeted strategy trended to be cost-effective in Guangxi, Jiangxi, Henan, Guangdong, Zhejiang, Hebei, Shandong, and Beijing from the level of 9%, 9%, 8%, 4%, 3%, 7%, 5%, and 2%, respectively; while universal strategy trended to be cost-effective in those provinces from the level of 70%, 70%, 48%, 10%, 8%, 28%, 15%, 4%, respectively. This study showed although there was a huge disparity in the implementation of the NHS program in the surveyed provinces, both universal strategy and targeted strategy showed cost-effectiveness in those relatively developed provinces, while neither of the screening strategy showed cost-effectiveness in those relatively developing provinces. This

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

Science.gov (United States)

Kalliokoski, Tuomo; Ronkko, Toni; Poso, Antti

2008-06-01

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

Science.gov (United States)

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

2016-06-23

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

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

Science.gov (United States)

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

2011-01-04

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

Color screening effect in the quark potential model

International Nuclear Information System (INIS)

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

1993-01-01

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

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

NARCIS (Netherlands)

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

2017-01-01

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

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

Science.gov (United States)

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

2017-09-01

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

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

Science.gov (United States)

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

2017-10-01

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

Breast cancer screening in an era of personalized regimens: a conceptual model and National Cancer Institute initiative for risk-based and preference-based approaches at a population level.

Science.gov (United States)

Onega, Tracy; Beaber, Elisabeth F; Sprague, Brian L; Barlow, William E; Haas, Jennifer S; Tosteson, Anna N A; D Schnall, Mitchell; Armstrong, Katrina; Schapira, Marilyn M; Geller, Berta; Weaver, Donald L; Conant, Emily F

2014-10-01

Breast cancer screening holds a prominent place in public health, health care delivery, policy, and women's health care decisions. Several factors are driving shifts in how population-based breast cancer screening is approached, including advanced imaging technologies, health system performance measures, health care reform, concern for "overdiagnosis," and improved understanding of risk. Maximizing benefits while minimizing the harms of screening requires moving from a "1-size-fits-all" guideline paradigm to more personalized strategies. A refined conceptual model for breast cancer screening is needed to align women's risks and preferences with screening regimens. A conceptual model of personalized breast cancer screening is presented herein that emphasizes key domains and transitions throughout the screening process, as well as multilevel perspectives. The key domains of screening awareness, detection, diagnosis, and treatment and survivorship are conceptualized to function at the level of the patient, provider, facility, health care system, and population/policy arena. Personalized breast cancer screening can be assessed across these domains with both process and outcome measures. Identifying, evaluating, and monitoring process measures in screening is a focus of a National Cancer Institute initiative entitled PROSPR (Population-based Research Optimizing Screening through Personalized Regimens), which will provide generalizable evidence for a risk-based model of breast cancer screening, The model presented builds on prior breast cancer screening models and may serve to identify new measures to optimize benefits-to-harms tradeoffs in population-based screening, which is a timely goal in the era of health care reform. © 2014 American Cancer Society.

Luminescence studies on phosphor screens

International Nuclear Information System (INIS)

Panayiotakis, G.; Nomikos, C.; Bakas, A.; Proimos, B.

1994-01-01

We report our results on x-ray phosphor screens prepared of some new materials focusing attention on their efficiency under fluoroscopy conditions, on optimization conditions and on comparisons among the various materials. All data are presented in absolute values. A theoretical model is presented, that takes into account the granular structure of the screens, permitting the explanation and prediction of the luminescence properties of the screens. (authors)

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

Science.gov (United States)

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

2008-11-01

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

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

Science.gov (United States)

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

2016-01-01

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

Risk Profiling May Improve Lung Cancer Screening

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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

Screening diagnostic program breast cancer

International Nuclear Information System (INIS)

Portnoj, L.M.; Zhakova, I.I.; Budnikova, N.V.; Rukhlyadko, E.D.

1995-01-01

The authors propose their screening program for detection of breast cancer. It includes the entire complex of present-day screening diagnostic methods, starting from an original system for the formation of groups at risk of breast cancer and completed by the direct diagnostic model of detection of the condition, oriented at a differentiated approach to the use of mammographic techniques. The proposed organizational and methodologic screening measures are both economic and diagnostically effective, thus meeting the principal requirements to screening programs. Screening of 8541 risk-groups patients helped detect 867 nodular formations, 244 of which were cancer and 623 benign formations. 8 refs., 3 figs.,

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

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

2016-08-18

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

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

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Fang, Xingang; Bagui, Sikha; Bagui, Subhash

2017-08-01

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

Nuclear clustering and the electron screening puzzle

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Bertulani, C. A.; Spitaleri, C.

2018-01-01

Electron screening changes appreciably the magnitude of astrophysical nuclear reactions within stars. This effect is also observed in laboratory experiments on Earth, where atomic electrons are present in the nuclear targets. Theoretical models were developed over the past 30 years and experimental measurements have been carried out to study electron screening in thermonuclear reactions. None of the theoretical models were able to explain the high values of the experimentally determined screening potentials. We explore the possibility that the "electron screening puzzle" is due to nuclear clusterization and polarization e_ects in the fusion reactions. We will discuss the supporting arguments for this scenario.

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

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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.

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

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David M. Gonzalez

2017-12-01

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

Cost-effectiveness and budget impact analyses of a colorectal cancer screening programme in a high adenoma prevalence scenario using MISCAN-Colon microsimulation model.

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Arrospide, Arantzazu; Idigoras, Isabel; Mar, Javier; de Koning, Harry; van der Meulen, Miriam; Soto-Gordoa, Myriam; Martinez-Llorente, Jose Miguel; Portillo, Isabel; Arana-Arri, Eunate; Ibarrondo, Oliver; Lansdorp-Vogelaar, Iris

2018-04-25

The Basque Colorectal Cancer Screening Programme began in 2009 and the implementation has been complete since 2013. Faecal immunological testing was used for screening in individuals between 50 and 69 years old. Colorectal Cancer in Basque country is characterized by unusual epidemiological features given that Colorectal Cancer incidence is similar to other European countries while adenoma prevalence is higher. The object of our study was to economically evaluate the programme via cost-effectiveness and budget impact analyses with microsimulation models. We applied the Microsimulation Screening Analysis (MISCAN)-Colon model to predict trends in Colorectal Cancer incidence and mortality and to quantify the short- and long-term effects and costs of the Basque Colorectal Cancer Screening Programme. The model was calibrated to the Basque demographics in 2008 and age-specific Colorectal Cancer incidence data in the Basque Cancer Registry from 2005 to 2008 before the screening begun. The model was also calibrated to the high adenoma prevalence observed for the Basque population in a previously published study. The multi-cohort approach used in the model included all the cohorts in the programme during 30 years of implementation, with lifetime follow-up. Unit costs were obtained from the Basque Health Service and both cost-effectiveness analysis and budget impact analysis were carried out. The goodness-of-fit of the model adaptation to observed programme data was evidence of validation. In the cost-effectiveness analysis, the savings from treatment were larger than the added costs due to screening. Thus, the Basque programme was dominant compared to no screening, as life expectancy increased by 29.3 days per person. The savings in the budget analysis appeared 10 years after the complete implementation of the programme. The average annual budget was €73.4 million from year 2023 onwards. This economic evaluation showed a screening intervention with a major health gain

Staged anticonvulsant screening for chronic epilepsy.

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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.

Luminescence studies on phosphor screens

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Panayiotakis, G; Nomikos, C; Bakas, A; Proimos, B [Medical Physics Department, University of Patras, 265 00 Patras, Greece (Greece)

1994-12-31

We report our results on x-ray phosphor screens prepared of some new materials focusing attention on their efficiency under fluoroscopy conditions, on optimization conditions and on comparisons among the various materials. All data are presented in absolute values. A theoretical model is presented, that takes into account the granular structure of the screens, permitting the explanation and prediction of the luminescence properties of the screens. (authors). 12 refs, 3 figs.

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

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

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

Science.gov (United States)

McNab, Walt W.

1997-10-01

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

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

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Tuzcu, Ayla; Bahar, Zuhal; Gözüm, Sebahat

2016-01-01

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

Information-sharing to promote informed choice in prenatal screening in the spirit of the SOGC clinical practice guideline: a proposal for an alternative model.

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Vanstone, Meredith; Kinsella, Elizabeth Anne; Nisker, Jeff

2012-03-01

The 2011 SOGC clinical practice guideline "Prenatal Screening for Fetal Aneuploidy in Singleton Pregnancies" recommends that clinicians offer prenatal screening to all pregnant women and provide counselling in a non-directive manner. Non-directive counselling is intended to facilitate autonomous decision-making and remove the clinician's views regarding a particular course of action. However, recent research in genetic counselling raises concerns that non-directive counselling is neither possible nor desirable, and that it may not be the best way to facilitate informed choice. We propose an alternative model of information-sharing specific to prenatal screening that combines attributes of the models of informative decision-making and shared decision-making. Our proposed model is intended to provide clinicians with a strategy to communicate information about prenatal screening in a way that facilitates a shared deliberative process and autonomous decision-making. Our proposed model may better prepare a pregnant woman to make an informed choice about participating in prenatal screening on the basis of her consideration of the medical information provided by her clinician and her particular circumstances and values.

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

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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.

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

Science.gov (United States)

2008-02-01

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

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

Science.gov (United States)

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

2016-02-29

While the US Preventive Services Task Force has issued recommendations for lung cancer screening, its effectiveness at reducing lung cancer burden may vary at local levels due to regional variations in smoking behaviour. Our objective was to use an existing model to determine the impacts of lung cancer screening alone or in addition to increased smoking cessation in a US region with a relatively high smoking prevalence and lung cancer incidence. Computer-based simulation model. Simulated population of individuals 55 and older based on smoking prevalence and census data from Northeast Pennsylvania. Hypothetical lung cancer control from 2014 to 2050 through (1) screening with CT, (2) intensified smoking cessation or (3) a combination strategy. Primary outcomes were lung cancer mortality rates. Secondary outcomes included number of people eligible for screening and number of radiation-induced lung cancers. Combining lung cancer screening with increased smoking cessation would yield an estimated 8.1% reduction in cumulative lung cancer mortality by 2050. Our model estimated that the number of screening-eligible individuals would progressively decrease over time, indicating declining benefit of a screening-only programme. Lung cancer screening achieved a greater mortality reduction in earlier years, but was later surpassed by smoking cessation. Combining smoking cessation programmes with lung cancer screening would provide the most benefit to a population, especially considering the growing proportion of patients ineligible for screening based on current recommendations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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

Science.gov (United States)

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

2017-06-01

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

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

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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

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

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

2015-12-01

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

Application of ToxCast High-Throughput Screening and ...

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Slide presentation at the SETAC annual meeting on High-Throughput Screening and Modeling Approaches to Identify Steroidogenesis Distruptors Slide presentation at the SETAC annual meeting on High-Throughput Screening and Modeling Approaches to Identify Steroidogenssis Distruptors

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

Directory of Open Access Journals (Sweden)

Andrei Brateanu

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

THE MODEL FOR DIEGETIC ANALYSIS OF SOUNDS IN SCREEN MEDIA

Directory of Open Access Journals (Sweden)

Denikin Anton A.

2013-12-01

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

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

Directory of Open Access Journals (Sweden)

Ortendahl Jesse

2007-10-01

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

SUPER-screening

Energy Technology Data Exchange (ETDEWEB)

Brax, Philippe, E-mail: Philippe.Brax@cea.fr [Institut de Physique Theorique, CEA, IPhT, CNRS, URA 2306, F-91191Gif/Yvette Cedex (France); Davis, Anne-Christine, E-mail: A.C.Davis@damtp.cam.ac.uk [DAMTP, Centre for Mathematical Sciences, University of Cambridge, Wilberforce Road, Cambridge CB3 0WA (United Kingdom); Sakstein, Jeremy, E-mail: J.A.Sakstein@damtp.cam.ac.uk [DAMTP, Centre for Mathematical Sciences, University of Cambridge, Wilberforce Road, Cambridge CB3 0WA (United Kingdom)

2013-02-26

We present a framework for embedding scalar–tensor models of screened modified gravity such as chameleons, symmetrons and environmental dilatons into global supersymmetry. This achieved by secluding the dark sector from both the observable and supersymmetry breaking sectors. We examine the resulting supersymmetric features in a model-independent manner and find that, when the theory follows from an underlying supergravity, the mediation of supersymmetry breaking to the dark sector induces a soft mass for the scalar of order the gravitino mass. This is enough to forbid the construction of supersymmetric symmetrons and ensures that when other screening mechanisms operate, no object in the Universe is unscreened thereby precluding any observable signatures. In view of a possible origin of modified gravity within fundamental physics, we find that only no-scale models can circumvent these features. We also present a novel mechanism where the coupling of the scalar to two other scalars charged under U(1) can dynamically generate a small cosmological constant at late times in the form of a Fayet–Iliopoulos term.

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

International Nuclear Information System (INIS)

Meyer, H.

1983-06-01

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

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

International Nuclear Information System (INIS)

Campolongo, Francesca; Braddock, Roger

1999-01-01

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

Exploiting PubChem for Virtual Screening.

Science.gov (United States)

Xie, Xiang-Qun

2010-12-01

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.

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

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Howard Kirsten

2010-11-01

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

Melanoma screening: Informing public health policy with quantitative modelling.

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Stephen Gilmore

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

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

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

2017-10-01

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

A computer simulation model of the cost-effectiveness of routine Staphylococcus aureus screening and decolonization among lung and heart-lung transplant recipients.

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Clancy, C J; Bartsch, S M; Nguyen, M H; Stuckey, D R; Shields, R K; Lee, B Y

2014-06-01

Our objective was to model the cost-effectiveness and economic value of routine peri-operative Staphylococcus aureus screening and decolonization of lung and heart-lung transplant recipients from hospital and third-party payer perspectives. We used clinical data from 596 lung and heart-lung transplant recipients to develop a model in TreeAge Pro 2009 (Williamsport, MA, USA). Sensitivity analyses varied S. aureus colonization rate (5-15 %), probability of infection if colonized (10-30 %), and decolonization efficacy (25-90 %). Data were collected from the Cardiothoracic Transplant Program at the University of Pittsburgh Medical Center. Consecutive lung and heart-lung transplant recipients from January 2006 to December 2010 were enrolled retrospectively. Baseline rates of S. aureus colonization, infection and decolonization efficacy were 9.6 %, 36.7 %, and 31.9 %, respectively. Screening and decolonization was economically dominant for all scenarios tested, providing more cost savings and health benefits than no screening. Savings per case averted (2012 $US) ranged from $73,567 to $133,157 (hospital perspective) and $10,748 to $16,723 (third party payer perspective), varying with the probability of colonization, infection, and decolonization efficacy. Using our clinical data, screening and decolonization led to cost savings per case averted of $240,602 (hospital perspective) and averted 6.7 S. aureus infections (4.3 MRSA and 2.4 MSSA); 89 patients needed to be screened to prevent one S. aureus infection. Our data support routine S. aureus screening and decolonization of lung and heart-lung transplant patients. The economic value of screening and decolonization was greater than in previous models of other surgical populations.

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

Science.gov (United States)

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

2017-11-01

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

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

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Ashleigh R Tuite

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

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

Science.gov (United States)

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

2015-12-28

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

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

Science.gov (United States)

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

2018-04-01

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

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

Science.gov (United States)

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

2008-04-14

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

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

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Zhen Wang

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

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

Science.gov (United States)

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

2014-04-15

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

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

NARCIS (Netherlands)

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

2016-01-01

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

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

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Elizabeth S. Burnside MD, MPH, MS

2017-07-01

Full Text Available Background: There are no publicly available tools designed specifically to assist policy makers to make informed decisions about the optimal ages of breast cancer screening initiation for different populations of US women. Objective: To use three established simulation models to develop a web-based tool called Mammo OUTPuT. Methods: The simulation models use the 1970 US birth cohort and common parameters for incidence, digital screening performance, and treatment effects. Outcomes include breast cancers diagnosed, breast cancer deaths averted, breast cancer mortality reduction, false-positive mammograms, benign biopsies, and overdiagnosis. The Mammo OUTPuT tool displays these outcomes for combinations of age at screening initiation (every year from 40 to 49, annual versus biennial interval, lifetime versus 10-year horizon, and breast density, compared to waiting to start biennial screening at age 50 and continuing to 74. The tool was piloted by decision makers (n = 16 who completed surveys. Results: The tool demonstrates that benefits in the 40s increase linearly with earlier initiation age, without a specific threshold age. Likewise, the harms of screening increase monotonically with earlier ages of initiation in the 40s. The tool also shows users how the balance of benefits and harms varies with breast density. Surveys revealed that 100% of users (16/16 liked the appearance of the site; 94% (15/16 found the tool helpful; and 94% (15/16 would recommend the tool to a colleague. Conclusions: This tool synthesizes a representative subset of the most current CISNET (Cancer Intervention and Surveillance Modeling Network simulation model outcomes to provide policy makers with quantitative data on the benefits and harms of screening women in the 40s. Ultimate decisions will depend on program goals, the population served, and informed judgments about the weight of benefits and harms.

Thermal Analysis of Concrete Storage Cask with Bird Screen Meshes

Energy Technology Data Exchange (ETDEWEB)

Lee, Ju-Chan; Bang, K.S.; Yu, S.H.; Cho, S.S.; Choi, W.S. [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2016-10-15

In this study, a thermal analysis of the cask with bird screen meshes has been performed using a porous media model. The overpack consists of a structural material, a concrete shielding, and a ventilation system. Heat is removed from the cask to the environment by a passive means only. Air inlet and outlet ducts are installed at the bottom and top of the cask for a ventilation system. Bird screen meshes are installed at the air inlet and outlet ducts to inhibit intrusion of debris from the external environment. The presence of this screens introduce an additional resistance to air flow through the ducts. Five types of meshes for bird screen were considered in this study. The bird screen meshes at the inlet and outlet vents reduce the open area for flow by about 44 - 79 %. Flow resistance coefficients for porous media model were deduced from the fluid flow analysis of bird screen meshes. Thermal analyses for the concrete cask have been carried out using a porous media model. The analysis results agreed well with the test results. Therefore, it was shown that the porous media model for the screen mesh was established to estimate the cask temperatures.

Thermal Analysis of Concrete Storage Cask with Bird Screen Meshes

International Nuclear Information System (INIS)

Lee, Ju-Chan; Bang, K.S.; Yu, S.H.; Cho, S.S.; Choi, W.S.

2016-01-01

In this study, a thermal analysis of the cask with bird screen meshes has been performed using a porous media model. The overpack consists of a structural material, a concrete shielding, and a ventilation system. Heat is removed from the cask to the environment by a passive means only. Air inlet and outlet ducts are installed at the bottom and top of the cask for a ventilation system. Bird screen meshes are installed at the air inlet and outlet ducts to inhibit intrusion of debris from the external environment. The presence of this screens introduce an additional resistance to air flow through the ducts. Five types of meshes for bird screen were considered in this study. The bird screen meshes at the inlet and outlet vents reduce the open area for flow by about 44 - 79 %. Flow resistance coefficients for porous media model were deduced from the fluid flow analysis of bird screen meshes. Thermal analyses for the concrete cask have been carried out using a porous media model. The analysis results agreed well with the test results. Therefore, it was shown that the porous media model for the screen mesh was established to estimate the cask temperatures

Observed Screen (Air) and GCM Surface/Screen Temperatures: Implications for Outgoing Longwave Fluxes at the Surface.

Science.gov (United States)

Garratt, J. R.

1995-05-01

There is direct evidence that excess net radiation calculated in general circulation models at continental surfaces [of about 11-17 W m2 (20%-27%) on an annual ~1 is not only due to overestimates in annual incoming shortwave fluxes [of 9-18 W m2 (6%-9%)], but also to underestimates in outgoing longwave fluxes. The bias in the outgoing longwave flux is deduced from a comparison of screen-air temperature observations, available as a global climatology of mean monthly values, and model-calculated surface and screen-air temperatures. An underestimate in the screen temperature computed in general circulation models over continents, of about 3 K on an annual basis, implies an underestimate in the outgoing longwave flux, averaged in six models under study, of 11-15 W m2 (3%-4%). For a set of 22 inland stations studied previously, the residual bias on an annual basis (the residual is the net radiation minus incoming shortwave plus outgoing longwave) varies between 18 and 23 W m2 for the models considered. Additional biases in one or both of the reflected shortwave and incoming longwave components cannot be ruled out.

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

NARCIS (Netherlands)

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

2010-01-01

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

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

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

2014-10-01

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

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

Science.gov (United States)

Hajian, Sepideh; Vakilian, Katayon; Najabadi, Khadijeh Mirzaii; Hosseini, Jalil; Mirzaei, Hamid Reza

2011-01-01

Breast cancer is the most common malignancy in women. Early diagnosis allows efficient treatment and increases survival, but the efficacy of breast self examination (BSE) is not sufficiently well established. The American Cancer Society aims to give women the opportunity to recognize the utility, limitations and adverse effects of breast cancer screening through education models based on psychological theories. With the Health Belief Model, people's health perceptions and attitudes influence their practices, for example with screening. The purpose of this randomized controlled clinical trial was to determine the effect of education based on this model on breast cancer screening in high risk Iranian women. Participants were women with a family history of breast cancer (mother, sister, and daughter). After explanation of the study objectives to participants, they were recruited on obtaining oral consent and each filled out the study questionnaire based on the Health Belief Model. Allocation was into two groups by computerized randomization, control and intervention, receiving education on breast cancer screening. Perceived susceptibility to and seriousness of breast cancer, perceived usefulness of and barriers to BSE, clinical breast examination, and mammography, and self-efficacy in the ability to perform these, were assessed, with comparison of scores for BSE practice before and after education and doing mammography and clinical examination by a physician in intervention and control group. The mean age was 37.8 ± 11.7 (range 19-60). The mean rank in the intervention group significantly differed before and after the education, but except for " perceived threat" and "perceived usefulness of breast self examination", we did not find any significant differences from the control group. After educational sessions, breast self examination and clinical examination practice rates were elevated. Health education based on well known psychological theories for breast cancer

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

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Shikhar Gupta

2014-01-01

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

High-throughput screening of chemicals as functional ...

Science.gov (United States)

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

Heat Flow Measurements on Beam Screens with and without Supports

CERN Document Server

Bozzini, D; Darve, C; Jenninger, B; Kos, N; Willems, D

1999-01-01

The thermal resistance between LHC beam screens and cold bores has been measured on two 10 m long models in the Cryostat Thermal Model (CTM). One beam screen was equipped with stainless steel spring supports and one had no supports and was inserted in a cold bore with reduced diameter. For both beam screens the heat load to the cold bore was well within the LHC budget that is allocated for the beam screen support system.

Machine Learning Approaches Toward Building Predictive Models for Small Molecule Modulators of miRNA and Its Utility in Virtual Screening of Molecular Databases.

Science.gov (United States)

Periwal, Vinita; Scaria, Vinod

2017-01-01

The ubiquitous role of microRNAs (miRNAs) in a number of pathological processes has suggested that they could act as potential drug targets. RNA-binding small molecules offer an attractive means for modulating miRNA function. The availability of bioassay data sets for a variety of biological assays and molecules in public domain provides a new opportunity toward utilizing them to create models and further utilize them for in silico virtual screening approaches to prioritize or assign potential functions for small molecules. Here, we describe a computational strategy based on machine learning for creation of predictive models from high-throughput biological screens for virtual screening of small molecules with the potential to inhibit microRNAs. Such models could be potentially used for computational prioritization of small molecules before performing high-throughput biological assay.

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

NARCIS (Netherlands)

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

2014-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2004-09-15

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

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

OpenAIRE

Veronica, Alderete Maria

2009-01-01

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

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

Science.gov (United States)

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

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

Science.gov (United States)

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

2014-10-21

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

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

Science.gov (United States)

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

2015-01-01

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

Cost-effectiveness of breast cancer screening policies using simulation.

Science.gov (United States)

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.

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

Science.gov (United States)

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

2014-01-01

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

Screens

OpenAIRE

2016-01-01

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

ZNStress: a high-throughput drug screening protocol for identification of compounds modulating neuronal stress in the transgenic mutant sod1G93R zebrafish model of amyotrophic lateral sclerosis.

Science.gov (United States)

McGown, Alexander; Shaw, Dame Pamela J; Ramesh, Tennore

2016-07-26

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease with death on average within 2-3 years of symptom onset. Mutations in superoxide dismutase 1 (SOD1) have been identified to cause ALS. Riluzole, the only neuroprotective drug for ALS provides life extension of only 3 months on average. Thishighlights the need for compound screening in disease models to identify new neuroprotective therapies for this disease. Zebrafish is an emerging model system that is well suited for the study of diseasepathophysiology and also for high throughput (HT) drug screening. The mutant sod1 zebrafish model of ALS mimics the hallmark features of ALS. Using a fluorescence based readout of neuronal stress, we developed a high throughput (HT) screen to identify neuroprotective compounds. Here we show that the zebrafish screen is a robust system that can be used to rapidly screen thousands ofcompounds and also demonstrate that riluzole is capable of reducing neuronal stress in this model system. The screen shows optimal quality control, maintaining a high sensitivity and specificity withoutcompromising throughput. Most importantly, we demonstrate that many compounds previously failed in human clinical trials, showed no stress reducing activity in the zebrafish assay. We conclude that HT drug screening using a mutant sod1 zebrafish is a reliable model system which supplemented with secondary assays would be useful in identifying drugs with potential for neuroprotective efficacy in ALS.

How many "Get Screened" messages does it take? Evidence from colorectal cancer screening promotion in the United States, 2012.

Science.gov (United States)

Cooper, Crystale Purvis; Gelb, Cynthia A; Hawkins, Nikki A

2014-03-01

Colorectal cancer screening has been widely promoted in the United States. We investigated the association between reported exposure to screening information during the past year and screening participation and knowledge. Data from the 2012 HealthStyles Fall survey of U.S. adults were examined using adjusted logistic regression to examine the frequency of exposure to screening information as a predictor of screening participation and knowledge; analyses were limited to participants aged ≥50years with no history of colorectal cancer or polyps (N=1714). Nearly half of the participants (44.9%) reported exposure to colorectal cancer screening information during the previous year. The most common sources of screening information were news reports, advertisements, and health care providers. Screening participation and knowledge consistently increased with the reported frequency of exposure to screening information, and these associations generally persisted when demographic variables were controlled. Compared with unexposed participants, significant gains in screening participation were associated with exposure to screening information 2-3 times (Adj. OR=1.84, p=0.001), 4-9 times (Adj. OR=2.00, p=0.001), and ≥10 times (Adj. OR=3.03, p<0.001) in the adjusted model. Increasing public exposure to screening promotion messages may augment screening participation and knowledge. Published by Elsevier Inc.

Oral cancer screening: serum Raman spectroscopic approach

Science.gov (United States)

Sahu, Aditi K.; Dhoot, Suyash; Singh, Amandeep; Sawant, Sharada S.; Nandakumar, Nikhila; Talathi-Desai, Sneha; Garud, Mandavi; Pagare, Sandeep; Srivastava, Sanjeeva; Nair, Sudhir; Chaturvedi, Pankaj; Murali Krishna, C.

2015-11-01

Serum Raman spectroscopy (RS) has previously shown potential in oral cancer diagnosis and recurrence prediction. To evaluate the potential of serum RS in oral cancer screening, premalignant and cancer-specific detection was explored in the present study using 328 subjects belonging to healthy controls, premalignant, disease controls, and oral cancer groups. Spectra were acquired using a Raman microprobe. Spectral findings suggest changes in amino acids, lipids, protein, DNA, and β-carotene across the groups. A patient-wise approach was employed for data analysis using principal component linear discriminant analysis. In the first step, the classification among premalignant, disease control (nonoral cancer), oral cancer, and normal samples was evaluated in binary classification models. Thereafter, two screening-friendly classification approaches were explored to further evaluate the clinical utility of serum RS: a single four-group model and normal versus abnormal followed by determining the type of abnormality model. Results demonstrate the feasibility of premalignant and specific cancer detection. The normal versus abnormal model yields better sensitivity and specificity rates of 64 and 80% these rates are comparable to standard screening approaches. Prospectively, as the current screening procedure of visual inspection is useful mainly for high-risk populations, serum RS may serve as a useful adjunct for early and specific detection of oral precancers and cancer.

Johnson screen for cooling water intakes

International Nuclear Information System (INIS)

Cook, L.E.

1978-01-01

Johnson surface-water screens provide an alternative to vertical traveling screens for power plant cooling water intakes. In this paper, flow field modeling is discussed, and a series of case studies is presented. The hydraulic information obtained is discussed as it applies to the exclusion of biota and debris from cooling water intake systems

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

Science.gov (United States)

Kéry, Marc

2018-02-01

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

A Cost-Utility Analysis of Prostate Cancer Screening in Australia.

Science.gov (United States)

Keller, Andrew; Gericke, Christian; Whitty, Jennifer A; Yaxley, John; Kua, Boon; Coughlin, Geoff; Gianduzzo, Troy

2017-02-01

The Göteborg randomised population-based prostate cancer screening trial demonstrated that prostate-specific antigen (PSA)-based screening reduces prostate cancer deaths compared with an age-matched control group. Utilising the prostate cancer detection rates from this study, we investigated the clinical and cost effectiveness of a similar PSA-based screening strategy for an Australian population of men aged 50-69 years. A decision model that incorporated Markov processes was developed from a health system perspective. The base-case scenario compared a population-based screening programme with current opportunistic screening practices. Costs, utility values, treatment patterns and background mortality rates were derived from Australian data. All costs were adjusted to reflect July 2015 Australian dollars (A$). An alternative scenario compared systematic with opportunistic screening but with optimisation of active surveillance (AS) uptake in both groups. A discount rate of 5 % for costs and benefits was utilised. Univariate and probabilistic sensitivity analyses were performed to assess the effect of variable uncertainty on model outcomes. Our model very closely replicated the number of deaths from both prostate cancer and background mortality in the Göteborg study. The incremental cost per quality-adjusted life-year (QALY) for PSA screening was A$147,528. However, for years of life gained (LYGs), PSA-based screening (A$45,890/LYG) appeared more favourable. Our alternative scenario with optimised AS improved cost utility to A$45,881/QALY, with screening becoming cost effective at a 92 % AS uptake rate. Both modelled scenarios were most sensitive to the utility of patients before and after intervention, and the discount rate used. PSA-based screening is not cost effective compared with Australia's assumed willingness-to-pay threshold of A$50,000/QALY. It appears more cost effective if LYGs are used as the relevant outcome, and is more cost effective than the

Parameterised post-Newtonian expansion in screened regions

Science.gov (United States)

McManus, Ryan; Lombriser, Lucas; Peñarrubia, Jorge

2017-12-01

The parameterised post-Newtonian (PPN) formalism has enabled stringent tests of static weak-field gravity in a theory-independent manner. Here we incorporate screening mechanisms of modified gravity theories into the framework by introducing an effective gravitational coupling and defining the PPN parameters as functions of position. To determine these functions we develop a general method for efficiently performing the post-Newtonian expansion in screened regimes. For illustration, we derive all the PPN functions for a cubic galileon and a chameleon model. We also analyse the Shapiro time delay effect for these two models and find no deviations from General Relativity insofar as the signal path and the perturbing mass reside in a screened region of space.

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

Science.gov (United States)

Manoharan, Prabu; Chennoju, Kiranmai; Ghoshal, Nanda

2015-07-01

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

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

OpenAIRE

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

2017-01-01

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

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

OpenAIRE

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

2017-01-01

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

Computer Screen Use Detection Using Smart Eyeglasses

Directory of Open Access Journals (Sweden)

Florian Wahl

2017-05-01

Full Text Available Screen use can influence the circadian phase and cause eye strain. Smart eyeglasses with an integrated color light sensor can detect screen use. We present a screen use detection approach based on a light sensor embedded into the bridge of smart eyeglasses. By calculating the light intensity at the user’s eyes for different screens and content types, we found only computer screens to have a significant impact on the circadian phase. Our screen use detection is based on ratios between color channels and used a linear support vector machine to detect screen use. We validated our detection approach in three studies. A test bench was built to detect screen use under different ambient light sources and intensities in a controlled environment. In a lab study, we evaluated recognition performance for different ambient light intensities. By using participant-independent models, we achieved an ROC AUC above 0.9 for ambient light intensities below 200 lx. In a study of typical ADLs, screen use was detected with an average ROC AUC of 0.83 assuming screen use for 30% of the time.

"To Screen or not to Screen": Comparing the Health and Economic Benefits of Early Peanut Introduction Strategies in Five Countries.

Science.gov (United States)

Shaker, Marcus; Stukus, David; Chan, Edmond S; Fleischer, David M; Spergel, Jonathan M; Greenhawt, Matthew

2018-03-30

Early peanut introduction (EPI) in the first year of life is associated with reduced risk of developing peanut allergy in children with either severe eczema and/or egg allergy. However, EPI recommendations differ among countries with formal guidelines. Using simulation and Markov modeling over a 20-year horizon to attempt to explore optimal EPI strategies applied to the US population, we compared high-risk infant specific IgE peanut screening (US/Canadian) with the Australiasian Society for Clinical Immunology and Allergy (Australia/New Zealand) (ASCIA) and the United Kingdom Department of Health (UKDOH) published EPI approaches. Screening peanut skin testing of all children with early onset eczema and/or egg allergy before in-office peanut introduction was dominated by a no-screen approach, in terms of number of cases of peanut allergy prevented, QALY's, and healthcare costs, though screening resulted in a slightly lower rate of allergic reactions to peanut per-patient in high-risk children. Considering costs of peanut allergy in high-risk children, the per-patient cost of early introduction without screening over the model horizon was $6,556.69 (95%CI, $6,512.76-$6,600.62), compared with a cost of $7,576.32 (95%CI, $7,531.38-$7,621.26) for skin test screening prior to introduction. From a US societal perspective, screening prior to introduction cost $654,115,322 and resulted in 3,208 additional peanut allergy diagnoses. Both screening and non-screening approaches dominated deliberately delayed peanut introduction. A no-screening approach for EPI has superior health and economic benefits in terms of number of peanut allergy cases prevented, QALY's, and total health care costs compared to screening and in-office peanut introduction. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Sehrish Iftikhar

2017-11-01

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

QSAR Methods to Screen Endocrine Disruptors

Directory of Open Access Journals (Sweden)

Nicola Porta

2016-08-01

Full Text Available The identification of endocrine disrupting chemicals (EDCs is one of the important goals of environmental chemical hazard screening. We report on in silico methods addressing toxicological studies about EDCs with a special focus on the application of QSAR models for screening purpose. Since Estrogen-like (ER activity has been extensively studied, the majority of the available models are based on ER-related endpoints. Some of these models are here reviewed and described. As example for their application, we screen an assembled dataset of candidate substitutes for some known EDCs belonging to the chemical classes of phthalates, bisphenols and parabens, selected considering their toxicological relevance and broad application, with the general aim of preliminary assessing their ED potential. The goal of the substitution processes is to advance inherently safer chemicals and products, consistent with the principles of green chemistry. Results suggest that the integration of a family of different models accounting for different endpoints can be a convenient way to describe ED as properly as possible and allow also both to increase the confidence of the predictions and to maximize the probability that most active compounds are correctly found.

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

Science.gov (United States)

Janecek, Jirí; Netz, Roland R

2009-02-21

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

Cystic Fibrosis Colorectal Cancer Screening Consensus Recommendations.

Science.gov (United States)

Hadjiliadis, Denis; Khoruts, Alexander; Zauber, Ann G; Hempstead, Sarah E; Maisonneuve, Patrick; Lowenfels, Albert B

2018-02-01

Improved therapy has substantially increased survival of persons with cystic fibrosis (CF). But the risk of colorectal cancer (CRC) in adults with CF is 5-10 times greater compared to the general population, and 25-30 times greater in CF patients after an organ transplantation. To address this risk, the CF Foundation convened a multi-stakeholder task force to develop CRC screening recommendations. The 18-member task force consisted of experts including pulmonologists, gastroenterologists, a social worker, nurse coordinator, surgeon, epidemiologist, statistician, CF adult, and a parent. The committee comprised 3 workgroups: Cancer Risk, Transplant, and Procedure and Preparation. A guidelines specialist at the CF Foundation conducted an evidence synthesis February-March 2016 based on PubMed literature searches. Task force members conducted additional independent searches. A total of 1159 articles were retrieved. After initial screening, the committee read 198 articles in full and analyzed 123 articles to develop recommendation statements. An independent decision analysis evaluating the benefits of screening relative to harms and resources required was conducted by the Department of Public Health at Erasmus Medical Center, Netherlands using the Microsimulation Screening Analysis model from the Cancer Innervation and Surveillance Modeling Network. The task force included recommendation statements in the final guideline only if they reached an 80% acceptance threshold. The task force makes 10 CRC screening recommendations that emphasize shared, individualized decision-making and familiarity with CF-specific gastrointestinal challenges. We recommend colonoscopy as the preferred screening method, initiation of screening at age 40 years, 5-year re-screening and 3-year surveillance intervals (unless shorter interval is indicated by individual findings), and a CF-specific intensive bowel preparation. Organ transplant recipients with CF should initiate CRC screening

Energy saving in greenhouses can be obtained by energy balance-controlled screens

Energy Technology Data Exchange (ETDEWEB)

Andersson, N. E. (Univ. of Aarhus, Faculty of Agricultural Sciences, Dept. of Horticulture, Aarslev (Denmark)), e-mail: niels.andersson@agrsci.dk

2011-03-15

The energy screens in two greenhouses, one clad with double acrylic and one with single glass, were controlled by an energy balance model. The parameters in the model were heat transmission coefficients, air temperature in the greenhouse and outdoors, irradiance and a single constant for the solar energy efficiency. The energy consumption, screen movements and daily light integral were compared with a glass greenhouse in which the energy screens were controlled by irradiance. In the greenhouse with light-controlled screens the set point for opening and closing of the screens was 5 Wm-2. The energy-saving screens controlled by the energy balance model opened later and closed earlier than in the greenhouse with light-controlled screens. When using the energy balance model the energy saving was 14% for the glass greenhouse and 41% for the double acrylic greenhouse compared with the glass greenhouse with light-controlled screens. The air temperature was on average similar in the three greenhouses, but when the screens were controlled by energy balance the daily light integral was approximately 10% lower and the number of hours the screens were closed was prolonged with 35% for the glass-covered greenhouse and 25% for the double acrylic-covered greenhouse compared with the greenhouse with light-controlled screens. Energy peaks in connection with operation of the screens were not reduced. During the experiment Begonia elatior, Dendranthema grandiflora (Chrysanthemum), Hedera helix, Helianthus annuus, Gerbera jamesonii and Kalanchoe blossfeldiana were grown in the greenhouses. There was a trend in prolongation of the production time when the plants were grown in the glass greenhouse with energy balance control of the screens. A lower number of flowers or inflorescences were observed for some of the plant species produced in the greenhouses with energy balance-controlled screens

Cost implications of PSA screening differ by age.

Science.gov (United States)

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

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

Science.gov (United States)

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

2014-11-01

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

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

Science.gov (United States)

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

2014-01-01

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

Depression Screening

Science.gov (United States)

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

Cost-effectiveness of the Norwegian breast cancer screening program.

Science.gov (United States)

van Luijt, P A; Heijnsdijk, E A M; de Koning, H J

2017-02-15

The Norwegian Breast Cancer Screening Programme (NBCSP) has a nation-wide coverage since 2005. All women aged 50-69 years are invited biennially for mammography screening. We evaluated breast cancer mortality reduction and performed a cost-effectiveness analysis, using our microsimulation model, calibrated to most recent data. The microsimulation model allows for the comparison of mortality and costs between a (hypothetical) situation without screening and a situation with screening. Breast cancer incidence in Norway had a steep increase in the early 1990s. We calibrated the model to simulate this increase and included recent costs for screening, diagnosis and treatment of breast cancer and travel and productivity loss. We estimate a 16% breast cancer mortality reduction for a cohort of women, invited to screening, followed over their complete lifetime. Cost-effectiveness is estimated at NOK 112,162 per QALY gained, when taking only direct medical costs into account (the cost of the buses, examinations, and invitations). We used a 3.5% annual discount rate. Cost-effectiveness estimates are substantially below the threshold of NOK 1,926,366 as recommended by the WHO guidelines. For the Norwegian population, which has been gradually exposed to screening, breast cancer mortality reduction for women exposed to screening is increasing and is estimated to rise to ∼30% in 2020 for women aged 55-80 years. The NBCSP is a highly cost-effective measure to reduce breast cancer specific mortality. We estimate a breast cancer specific mortality reduction of 16-30%, at the cost of 112,162 NOK per QALY gained. © 2016 UICC.

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

OpenAIRE

Fayad, Walid

2011-01-01

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

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

Science.gov (United States)

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

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

Science.gov (United States)

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

Quarkonium suppression: Gluonic dissociation vs. colour screening

Indian Academy of Sciences (India)

mechanism comes into play for the initial conditions taken from the self screened parton cascade model in these studies. Keywords. Quark gluon plasma; J ψ; suppression; dissociation; colour screening. PACS No. 12.38.M. 1. Introduction. The last two decades have seen hectic activity towards identifying unique signatures ...

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

Science.gov (United States)

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

2013-01-01

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

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

Science.gov (United States)

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

2016-04-28

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

Benefit, risks and cost-effectiveness of screening for abdominal aortic aneurysm

International Nuclear Information System (INIS)

Schmidt, T.; Muehlberger, N.; Siebert, U.; Chemelli-Steingruber, I.E.; Chemelli, Andreas; Strasak, A.; Kofler, B.

2010-01-01

Purpose: abdominal aortic aneurysms (AAA) cause a considerable number of deaths. A ruptured AAA is associated with a mortality rate of 80%. The purpose of this study was to summarize the current evidence from published health economic models for the long-term effectiveness and cost-effectiveness of screening programs for AAA. Materials and methods: medical, economic and health technology assessment (HTA) databases were systematically searched for cost-effectiveness models up to October 2007. Only models with a lifetime time horizon of evaluating AAA screening in men over 65 years were included in the review. Study data were extracted, standardized and summarized in evidence tables and cost-effectiveness plots. Results: we reviewed 8 cost-effectiveness models published between 1993 and 2007 comparing AAA screening and lack of screening in men over 60. One model yielded a loss of life-years at additional costs. The remaining seven models yielded gains in life expectancy ranging from 0.02 to 0.28LYs. Gains in quality-adjusted life expectancy reported by six of the seven models ranged from 0.015 to 0.059 QALYs. Incremental costs ranged from 96 to 721 Euros. Incremental cost-effectiveness ratios (ICER) ranged from 1443 to 13299 Euros per LY or QALY gained. Conclusion: based on our analysis, the introduction of a screening program to identify AAA will probably gain additional life years and quality of life at acceptable extra costs. The target population for a screening program should be men 65 years and older. (orig.)

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

Science.gov (United States)

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

2009-01-01

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

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

Science.gov (United States)

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

2017-09-01

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

Rapid Screening of Active Components with an Osteoclastic Inhibitory Effect in Herba epimedii Using Quantitative Pattern–Activity Relationships Based on Joint-Action Models

Directory of Open Access Journals (Sweden)

Xiao-Yan Yuan

2017-10-01

Full Text Available Screening of bioactive components is important for modernization and quality control of herbal medicines, while the traditional bioassay-guided phytochemical approach is time-consuming and laborious. The presented study proposes a strategy for rapid screening of active components from herbal medicines. As a case study, the quantitative pattern–activity relationship (QPAR between compounds and the osteoclastic inhibitory effect of Herba epimedii, a widely used herbal medicine in China, were investigated based on joint models. For model construction, standard mixtures data showed that the joint-action models are better than the partial least-squares (PLS model. Then, the Good2bad value, which could reflect components’ importance based on Monte Carlo sampling, was coupled with the joint-action models for screening of active components. A compound (baohuoside I and a component composed of compounds with retention times in the 6.9–7.9 min range were selected by our method. Their inhibition rates were higher than icariin, the key bioactive compound in Herba epimedii, which could inhibit osteoclast differentiation and bone resorption in a previous study. Meanwhile, the half-maximal effective concentration, namely, EC50 value of the selected component was 7.54 μg/mL, much smaller than that of baohuoside I—77 μg/mL—which indicated that there is synergistic action between compounds in the selected component. The results clearly show our proposed method is simple and effective in screening the most-bioactive components and compounds, as well as drug-lead components, from herbal medicines.

Mammography screening: A major issue in medicine.

Science.gov (United States)

Autier, Philippe; Boniol, Mathieu

2018-02-01

change the criteria for the evaluation of cancer screening effectiveness, giving precedence to incidence-based mortality (IBM) and case-control studies. But practically all IBM studies on mammography screening have a strong ecological component in their design. The two IBM studies done in Norway that meet all methodological requirements do not document significant reductions in breast cancer mortality associated with mammography screening. Because of their propensity to exaggerate the health benefits of screening, case-control studies may demonstrate that mammography screening could reduce the risk of death from diseases other than breast cancer. Numerous statistical model approaches have been conducted for estimating the contributions of screening and of patient management to reductions in breast cancer mortality. Unverified assumptions are needed for running these models. For instance, many models assume that if screening had not occurred, the majority of screen-detected asymptomatic cancers would have progressed to symptomatic advanced cancers. This assumption is not grounded in evidence because a large proportion of screen-detected breast cancers represent overdiagnosis and hence non-progressing tumours. The accumulation of population data in well-screened populations diminishes the relevance of model approaches. The comparison of the performance of different screening modalities - e.g. mammography, digital mammography, ultrasonography, magnetic resonance imaging (MRI), three-dimensional tomosynthesis (TDT) - concentrates on detection rates, which is the ability of a technique to detect more cancers than other techniques. However, a greater detection rate tells little about the capacity to prevent interval and advanced cancers and could just reflect additional overdiagnosis. Studies based on the incidence of advanced cancers and on the evaluation of overdiagnosis should be conducted before marketing new breast-imaging technologies. Women at high risk of breast

Approaches to virtual screening and screening library selection.

Science.gov (United States)

Wildman, Scott A

2013-01-01

The ease of access to virtual screening (VS) software in recent years has resulted in a large increase in literature reports. Over 300 publications in the last year report the use of virtual screening techniques to identify new chemical matter or present the development of new virtual screening techniques. The increased use is accompanied by a corresponding increase in misuse and misinterpretation of virtual screening results. This review aims to identify many of the common difficulties associated with virtual screening and allow researchers to better assess the reliability of their virtual screening effort.

[Women's willingness to pay for cancer screening].

Science.gov (United States)

Kwak, Min-Son; Sung, Na-Young; Yang, Jeong Hee; Park, Eun-Cheol; Choi, KuiSon

2006-07-01

The goal of this study is to measure women's willingness to pay for cancer screening and to identify those factors associated with this willingness to pay A population-based telephone survey was performed on 1,562 women (aged 30 years or over) for 2 weeks (9-23th, July, 2004). Data about sociodemographic characteristics, health behaviors, the intention of the cancer screenings and willingness to pay for cancer screening were collected. 1,400 respondents were included in the analysis. The women's willingness to pay for cancer screening and the factors associated with this willingness to pay were evaluated. The results show that 76% of all respondents have a willingness to pay for cancer screening. Among those who are willing to pay, the average and median amount of money for which the respondents are willing to pay are 126,636 (s.d.: 58,414) and 120,000 won, respectively. As the status of education & the income are higher, the average amount that women are willing to pay becomes much more. The amount of money women are willing to pay is the highest during the 'contemplation' stage. Being willing to pay or not is associated with a change of behavior (transtheoretical model), the income, the concern about the cancer risk, the family cancer history, the marital status, the general health exam, age and the place of residence. Income is associated with a greater willingness to pay. Old age was associated with a lower willingness to pay. According to the two-part model, income and TTM are the most important variables associated with the willingness to pay for cancer screening. The cancer screening participation rate is low compared with the willingness to pay for cancer screening. It is thought that we have to consider the participants' behavior that's associated with cancer screening and their willingness to pay in order to organize and manage cancer screening program.

Maximizing gain in high-throughput screening using conformal prediction.

Science.gov (United States)

Svensson, Fredrik; Afzal, Avid M; Norinder, Ulf; Bender, Andreas

2018-02-21

Iterative screening has emerged as a promising approach to increase the efficiency of screening campaigns compared to traditional high throughput approaches. By learning from a subset of the compound library, inferences on what compounds to screen next can be made by predictive models, resulting in more efficient screening. One way to evaluate screening is to consider the cost of screening compared to the gain associated with finding an active compound. In this work, we introduce a conformal predictor coupled with a gain-cost function with the aim to maximise gain in iterative screening. Using this setup we were able to show that by evaluating the predictions on the training data, very accurate predictions on what settings will produce the highest gain on the test data can be made. We evaluate the approach on 12 bioactivity datasets from PubChem training the models using 20% of the data. Depending on the settings of the gain-cost function, the settings generating the maximum gain were accurately identified in 8-10 out of the 12 datasets. Broadly, our approach can predict what strategy generates the highest gain based on the results of the cost-gain evaluation: to screen the compounds predicted to be active, to screen all the remaining data, or not to screen any additional compounds. When the algorithm indicates that the predicted active compounds should be screened, our approach also indicates what confidence level to apply in order to maximize gain. Hence, our approach facilitates decision-making and allocation of the resources where they deliver the most value by indicating in advance the likely outcome of a screening campaign.

Electron screening and its effects on big-bang nucleosynthesis

International Nuclear Information System (INIS)

Wang Biao; Bertulani, C. A.; Balantekin, A. B.

2011-01-01

We study the effects of electron screening on nuclear reaction rates occurring during the big-bang nucleosynthesis epoch. The sensitivity of the predicted elemental abundances on electron screening is studied in detail. It is shown that electron screening does not produce noticeable results in the abundances unless the traditional Debye-Hueckel model for the treatment of electron screening in stellar environments is enhanced by several orders of magnitude. This work rules out electron screening as a relevant ingredient to big-bang nucleosynthesis, confirming a previous study [see Itoh et al., Astrophys. J. 488, 507 (1997)] and ruling out exotic possibilities for the treatment of screening beyond the mean-field theoretical approach.

Long-term evaluation of benefits, harms, and cost-effectiveness of the National Bowel Cancer Screening Program in Australia: a modelling study.

Science.gov (United States)

Lew, Jie-Bin; St John, D James B; Xu, Xiang-Ming; Greuter, Marjolein J E; Caruana, Michael; Cenin, Dayna R; He, Emily; Saville, Marion; Grogan, Paul; Coupé, Veerle M H; Canfell, Karen

2017-07-01

No assessment of the National Bowel Screening Program (NBCSP) in Australia, which considers all downstream benefits, costs, and harms, has been done. We aimed to use a comprehensive natural history model and the most recent information about cancer treatment costs to estimate long-term benefits, costs, and harms of the NBCSP (2 yearly immunochemical faecal occult blood testing screening at age 50-74 years) and evaluate the incremental effect of improved screening participation under different scenarios. In this modelling study, a microsimulation model, Policy1-Bowel, which simulates the development of colorectal cancer via both the conventional adenoma-carcinoma and serrated pathways was used to simulate the NBCSP in 2006-40, taking into account the gradual rollout of NBCSP in 2006-20. The base-case scenario assumed 40% screening participation (currently observed behaviour) and two alternative scenarios assuming 50% and 60% participation by 2020 were modelled. Aggregate year-by-year screening, diagnosis, treatment and surveillance-related costs, resource utilisation (number of screening tests and colonoscopies), and health outcomes (incident colorectal cancer cases and colorectal cancer deaths) were estimated, as was the cost-effectiveness of the NBCSP. With current levels of participation (40%), the NBCSP is expected to prevent 92 200 cancer cases and 59 000 deaths over the period 2015-40; an additional 24 300 and 37 300 cases and 16 800 and 24 800 deaths would be prevented if participation was increased to 50% and 60%, respectively. In 2020, an estimated 101 000 programme-related colonoscopies will be done, associated with about 270 adverse events; an additional 32 500 and 49 800 colonoscopies and 88 and 134 adverse events would occur if participation was increased to 50% and 60%, respectively. The overall number needed to screen (NNS) is 647-788 per death prevented, with 52-59 colonoscopies per death prevented. The programme is cost

Effects of Application of Social Marketing Theory and the Health Belief Model in Promoting Cervical Cancer Screening among Targeted Women in Sisaket Province, Thailand.

Science.gov (United States)

Wichachai, Suparp; Songserm, Nopparat; Akakul, Theerawut; Kuasiri, Chanapong

2016-01-01

Cervical cancer is a major public health problem in Thailand, being ranked second only to breast cancer. Thai women have been reported to have a low rate of cervical cancer screening (27.7% of the 80% goal of WHO). We therefore aimed to apply the social marketing theory and health belief model in promoting cervical cancer screening in Kanthararom District, Sisaket Province. A total of 92 from 974 targeted women aged 3060 years were randomly divided into two groups. The experimental group underwent application of social marketing theory and a health belief model program promoting cervical cancer screening while the control group received normal services. Two research tools were used: (1) application of social marketing theory and health belief model program and (2) questionnaire used to evaluate perceptions of cervical cancer. Descriptive and inferential statistics including paired sample ttest and independent ttest were used to analyze the data. After the program had been used, the mean score of perception of cervical cancer of experimental group was at a higher level (x=4.09; S.D. =0.30), than in the control group (x=3.82; S.D. =0.20) with statistical significance (psocial marketing and the health belief model be used to promote cervical cancer screening in targeted women and it can be promoted as a guideline for other health services, especially in health promotion and disease prevention.

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

International Nuclear Information System (INIS)

1996-01-01

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

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

Science.gov (United States)

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

Risk-Screening Environmental Indicators (RSEI)

Data.gov (United States)

U.S. Environmental Protection Agency — EPA’s Risk-Screening Environmental Indicators (RSEI) is a geographically-based model that helps policy makers and communities explore data on releases of toxic...

Cancer screening in patients infected with HIV.

Science.gov (United States)

Sigel, Keith; Dubrow, Robert; Silverberg, Michael; Crothers, Kristina; Braithwaite, Scott; Justice, Amy

2011-09-01

Non-AIDS-defining cancers are a rising health concern among HIV-infected patients. Cancer screening is now an important component of health maintenance in HIV clinical practice. The decision to screen an HIV-infected patient for cancer should include an assessment of individualized risk for the particular cancer, life expectancy, and the harms and benefits associated with the screening test and its potential outcome. HIV-infected patients are at enhanced risk of several cancers compared to the general population; anal cancer, hepatocellular carcinoma, Hodgkin's lymphoma, and lung cancer all have good evidence demonstrating an enhanced risk in HIV-infected persons. A number of cancer screening interventions have shown benefit for specific cancers in the general population, but data on the application of these tests to HIV-infected persons are limited. Here we review the epidemiology and background literature relating to cancer screening interventions in HIV-infected persons. We then use these data to inform a conceptual model for evaluating HIV-infected patients for cancer screening.

Bioprospecting of Thermostable Cellulolytic Enzymes through Modeling and Virtual Screening Method

Directory of Open Access Journals (Sweden)

R. Navanietha Krishnaraj

2017-04-01

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

Consumer preferences for teledermoscopy screening to detect melanoma early.

Science.gov (United States)

Spinks, Jean; Janda, Monika; Soyer, H Peter; Whitty, Jennifer A

2016-01-01

'Store and forward' teledermoscopy is a technology with potential advantages for melanoma screening. Any large-scale implementation of this technology is dependent on consumer acceptance. To investigate preferences for melanoma screening options compared with skin self-examination in adults considered to be at increased risk of developing skin cancer. A discrete choice experiment was completed by 35 consumers, all of whom had prior experience with the use of teledermoscopy, in Queensland, Australia. Participants made 12 choices between screening alternatives described by seven attributes including monetary cost. A mixed logit model was used to estimate the relative weights that consumers place on different aspects of screening, along with the marginal willingness to pay for teledermoscopy as opposed to screening at a clinic. Overall, participants preferred screening/diagnosis by a health professional rather than skin self-examination. Key drivers of screening choice were for results to be reviewed by a dermatologist; a higher detection rate; fewer non-cancerous moles being removed in relation to every skin cancer detected; and less time spent away from usual activities. On average, participants were willing to pay AUD110 to have teledermoscopy with dermatologist review available to them as a screening option. Consumers preferentially value aspects of care that are more feasible with a teledermoscopy screening model, as compared with other skin cancer screening and diagnosis options. This study adds to previous literature in the area which has relied on the use of consumer satisfaction scales to assess the acceptability of teledermoscopy. © The Author(s) 2015.

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

Science.gov (United States)

Harris, Jill; Norton, Amy

2016-01-01

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

Hospitalized Patients with Cirrhosis Should Be Screened for Clostridium difficile Colitis.

Science.gov (United States)

Saab, Sammy; Alper, Theodore; Sernas, Ernesto; Pruthi, Paridhima; Alper, Mikhail A; Sundaram, Vinay

2015-10-01

Clostridium difficile infection (CDI) is an important public health problem in hospitalized patients. Patients with cirrhosis are particularly at risk of increased associated morbidity, mortality, and healthcare utilization from CDI. The aim of this study was to assess the pharmacoeconomic impact of CDI screening on hospitalized patients with cirrhosis. A Markov model was used to compare costs and outcomes of two strategies for the screening of CDI. The first strategy consisted of screening all patients for CDI and treating if detected (screening). In the second strategy, only patients found to have symptomatic CDI were treated (no screening). The probability of underlying CDI prevalence, symptomatic CDI infection, and likelihood of recurrent infection were varied in a sensitivity analysis. The costs of antibiotics and hospitalization were also assessed. Differences in outcome were expressed in ratio of the total costs associated with screening to the total costs associated without screening. The results of our model showed that screening for CDI was consistently associated with improved healthcare outcomes and decreased healthcare utilization across all variables in the one- and two-way sensitivity analyses. Using baseline assumptions, the costs associated with the no screening strategy were 3.54 times that of the screening strategy. Moreover, the mortality for symptomatic CDI was lower in the screening strategy than the no screening strategy. The screening strategy results in less healthcare utilization and improved clinical outcomes. Screening for CDI measures favorably.

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

Science.gov (United States)

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.

Photo screening around the world: Lions Club International Foundation experience.

Science.gov (United States)

Donahue, Sean P; Lorenz, Sylvia; Johnson, Tammy

2008-01-01

To describe the use of photoscreening for preschool vision screening in several diverse locations throughout the world. The MTI photo screener was used to screen pre-verbal children; photographs were interpreted using standard criteria. The Tennessee vision screening program remains successful, screening over 200,000 children during the past 8 years. Similar programs modeled across the United States have screened an additional 500,000 children. A pilot demonstration project in Hong Kong, Beijing, and Brazil screened over 5000 additional children with good success and appropriately low referral rates. Photoscreening can be an appropriate technique for widespread vision screening of preschool children throughout the world.

Screening strategies for atrial fibrillation: a systematic review and cost-effectiveness analysis.

Science.gov (United States)

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

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

KAUST Repository

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

2017-01-01

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

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

KAUST Repository

Hartono, A. D.

2017-10-17

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

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

NARCIS (Netherlands)

Gray, Ewan; Donten, Anna; Karssemeijer, Nico; van Gils, Carla; Evans, D. Gareth R.; Astley, Sue; Payne, Katherine

Objectives: To identify the incremental costs and consequences of stratified national breast screening programs (stratified NBSPs) and drivers of relative cost-effectiveness. Methods: A decision-analytic model (discrete event simulation) was conceptualized to represent four stratified NBSPs (risk 1,

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

NARCIS (Netherlands)

Gray, E.; Donten, A.; Karssemeijer, N.; Gils, C. van; Evans, D.G.; Astley, S.; Payne, K.

2017-01-01

OBJECTIVES: To identify the incremental costs and consequences of stratified national breast screening programs (stratified NBSPs) and drivers of relative cost-effectiveness. METHODS: A decision-analytic model (discrete event simulation) was conceptualized to represent four stratified NBSPs (risk 1,

Pathways of cervical cancer screening among Chinese women

Directory of Open Access Journals (Sweden)

Ma GX

2013-06-01

Full Text Available Grace X Ma,1 Min Qi Wang,2 Xiang S Ma,3 Steven E Shive,4 Yin Tan,5 Jamil I Toubbeh51Department of Public Health, College of Health Professions, Temple University, Philadelphia, PA, 2Department of Public and Community Health, University of Maryland, College Park, MD, 3College of Health Professions and School of Medicine, Temple University, Philadelphia, PA, 4Center for Asian Health, Temple University, and Department of Health, East Stroudsburg University, East Stroudsburg, PA, 5Center for Asian Health, Department of Public Health, College of Health Professions, Temple University, Philadelphia, PA, USABackground: The purpose of this community-based study was to develop a structural equation model for factors contributing to cervical cancer screening among Chinese American women.Methods: A cross-sectional design included a sample of 573 Chinese American women aged 18 years and older. The initial step involved use of confirmatory factor analysis, that included the following variables: access to and satisfaction with health care, and enabling and predisposing cultural and health beliefs. Structural equation model analyses were conducted on factors related to cervical cancer screening.Results: Age, marital status, employment, household income, and having health insurance, but not educational level, were significantly related to cervical screening status. Predisposing and enabling factors were positively associated with cervical cancer screening. The cultural factor was significantly related to the enabling factor or the satisfaction with health care factor.Conclusion: This model highlights the significance of sociocultural factors in relation to cervical cancer screening. These factors were significant, with cultural, predisposing, enabling, and health belief factors and access to and satisfaction with health care reinforcing the need to assist Chinese American women with poor English fluency in translation and awareness of the importance of cervical

South Asian ethnicity, socioeconomic status, and psychological mediators of faecal occult blood colorectal screening participation: A prospective test of a process model.

Science.gov (United States)

Orbell, Sheina; Szczepura, Ala; Weller, David; Gumber, Anil; Hagger, Martin S

2017-12-01

Although ethnicity and socioeconomic status (SES) correlate with health inequality, efforts to explain variance in health behavior attributable to these factors are limited by difficulties in population sampling. We used ethnicity identification software to test effects of psychological beliefs about screening as mediators of ethnicity and SES on faecal occult blood colorectal screening behavior in a no-cost health care context. Adults aged 50-67 years (N = 1,678), of whom 28% were from minority South Asian religiolinguistic ethnic groups (Hindu-Gujarati/Hindi, Muslim-Urdu and Sikh-Punjabi), participated in a prospective survey study. Subsequent screening participation was determined from medical records. Screening nonparticipation in the most deprived SES quintile was 1.6 times that of the least deprived quintile. Nonparticipation was 1.6 times higher in South Asians compared with non-Asians. A process model in which psychological variables mediated effects of ethnicity and SES on uptake was tested using structural equation modeling. Self-efficacy and perceived psychological costs of screening were, respectively, positive and negative direct predictors of uptake. Paths from Hindu, Muslim, and Sikh ethnicity, and SES on uptake were fully mediated by lower self-efficacy and higher perceived psychological costs. Paths from South Asian ethnicity to participation via self-efficacy and psychological costs were direct, and indirect via SES. SES is implicated, but does not fully account for low colorectal screening uptake among South Asians. Targeting increased self-efficacy and reduced perceived psychological costs may minimize health inequality effects. Future research should test independent effects of SES and ethnicity on lower self-efficacy and higher psychological costs. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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

Science.gov (United States)

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

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

Science.gov (United States)

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.

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

Science.gov (United States)

Kitambi, Satish Srinivas; Chandrasekar, Gayathri

2011-01-01

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

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

International Nuclear Information System (INIS)

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

1996-01-01

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

An experimental investigation of head loss through a triangular “V- shaped” screen

Directory of Open Access Journals (Sweden)

Mahmoud Zayed

2018-03-01

Full Text Available Common traditional screens (screens perpendicular and vertical to the flow direction face extensive problems with screen blockage, which can result in adverse hydraulic, environmental, and economic consequences. Experimentally, this paper presents an advanced trash screen concept to reduce traditional screen problems and improve the hydraulic performance of screens. The traditional screen is re-developed using a triangular V shape with circular bars in the flow direction. Triangular V-shaped screen models with different angles, blockage ratios, circular bar designs, and flow discharges were tested in a scaled physical model. The analyses provide promising results. The findings showed that the head loss coefficients were effectively reduced by using the triangular V-shaped screens with circular bars (α < 90° in comparison with the traditional trash screen (α = 90. Additionally, the results indicated that the head loss across the screen increased with increasing flow discharge and blockage ratio. The losses considerably increase by large percentages when the screen becomes blocked by 40%. Low head losses were recorded at low screen angles for the circular bars. A new head loss equation is recommended for triangular screens with circular bars.

Constructing and Validating High-Performance MIEC-SVM Models in Virtual Screening for Kinases: A Better Way for Actives Discovery.

Science.gov (United States)

Sun, Huiyong; Pan, Peichen; Tian, Sheng; Xu, Lei; Kong, Xiaotian; Li, Youyong; Dan Li; Hou, Tingjun

2016-04-22

The MIEC-SVM approach, which combines molecular interaction energy components (MIEC) derived from free energy decomposition and support vector machine (SVM), has been found effective in capturing the energetic patterns of protein-peptide recognition. However, the performance of this approach in identifying small molecule inhibitors of drug targets has not been well assessed and validated by experiments. Thereafter, by combining different model construction protocols, the issues related to developing best MIEC-SVM models were firstly discussed upon three kinase targets (ABL, ALK, and BRAF). As for the investigated targets, the optimized MIEC-SVM models performed much better than the models based on the default SVM parameters and Autodock for the tested datasets. Then, the proposed strategy was utilized to screen the Specs database for discovering potential inhibitors of the ALK kinase. The experimental results showed that the optimized MIEC-SVM model, which identified 7 actives with IC50 < 10 μM from 50 purchased compounds (namely hit rate of 14%, and 4 in nM level) and performed much better than Autodock (3 actives with IC50 < 10 μM from 50 purchased compounds, namely hit rate of 6%, and 2 in nM level), suggesting that the proposed strategy is a powerful tool in structure-based virtual screening.

CLAD DEGRADATION - FEPS SCREENING ARGUMENTS

International Nuclear Information System (INIS)

R. Schreiner

2004-01-01

The purpose of this report is to evaluate and document the screening of the clad degradation features, events, and processes (FEPs) with respect to modeling used to support the Total System Performance Assessment-License Application (TSPA-LA). This report also addresses the effect of certain FEPs on both the cladding and the commercial spent nuclear fuel (CSNF), DOE-owned spent nuclear fuel (DSNF), and defense high-level waste (DHLW) waste forms, as appropriate to address the effects on multiple materials and both components (FEPs 2.1.09.09.0A, 2.1.09.11.0A, 2.1.11.05.0A, 2.1.12.02.0A, and 2.1.12.03.0A). These FEPs are expected to affect the repository performance during the postclosure regulatory period of 10,000 years after permanent closure. Table 1-1 provides the list of cladding FEPs, including their screening decisions (include or exclude). The primary purpose of this report is to identify and document the analysis, screening decision, and TSPA-LA disposition (for included FEPs) or screening argument (for excluded FEPs) for these FEPs related to clad degradation. In some cases, where a FEP covers multiple technical areas and is shared with other FEP reports, this report may provide only a partial technical basis for the screening of the FEP. The full technical basis for shared FEPs is addressed collectively by the sharing FEP reports. The screening decisions and associated TSPA-LA dispositions or screening arguments from all of the FEP reports are cataloged in a project-specific FEPs database

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

Science.gov (United States)

2011-01-01

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

Cost-effectiveness of screening for asymptomatic carotid atherosclerotic disease.

Science.gov (United States)

Derdeyn, C P; Powers, W J

1996-11-01

The value of screening for asymptomatic carotid stenosis has become an important issue with the recently reported beneficial effect of endarterectomy. The purpose of this study is to evaluate the cost-effectiveness of using Doppler ultrasound as a screening tool to select subjects for arteriography and subsequent surgery. A computer model was developed to simulate the cost-effectiveness of screening a cohort of 1000 men during a 20-year period. The primary outcome measure was incremental present-value dollar expenditures for screening and treatment per incremental present-value quality-adjusted life-year (QALY) saved. Estimates of disease prevalence and arteriographic and surgical complication rates were obtained from the literature. Probabilities of stroke and death with surgical and medical treatment were obtained from published clinical trials. Doppler ultrasound sensitivity and specificity were obtained through review of local experience. Estimates of costs were obtained from local Medicare reimbursement data. A one-time screening program of a population with a high prevalence (20%) of > or = 60% stenosis cost $35130 per incremental QALY gained. Decreased surgical benefit or increased annual discount rate was detrimental, resulting in lost QALYs. Annual screening cost $457773 per incremental QALY gained. In a low-prevalence (4%) population, one-time screening cost $52588 per QALY gained, while annual screening was detrimental. The cost-effectiveness of a one-time screening program for an asymptomatic population with a high prevalence of carotid stenosis may be cost-effective. Annual screening is detrimental. The most sensitive variables in this simulation model were long-term stroke risk reduction after surgery and annual discount rate for accumulated costs and QALYs.

Screening for colorectal cancer in Italy: 2011-2012 survey.

Science.gov (United States)

Zorzi, Manuel; Mangone, Lucia; Anghinoni, Emanuela; Baracco, Susanna; Borciani, Elisabetta; Caldarella, Adele; Falcini, Fabio; Fanetti, Anna Clara; Ferretti, Stefano; Giorgi Rossi, Paolo; Michiara, Maria; Randi, Giorgia; Stracci, Fabrizio; Vicentini, Massimo; Zucchetto, Antonella; Zappa, Marco

2015-01-01

The impact of organized screening programmes on colorectal cancer (CRC) can be observed at a population level only several years after the implementation of screening. We compared CRC characteristics by diagnostic modality (screen-detected, non-screen-detected) as an early outcome to monitor screening programme effectiveness. Data on CRCs diagnosed in Italy from 2000 to 2008 were collected by several cancer registries. Linkage with screening datasets made it possible to divide the cases by geographic area, implementation of screening, and modality of diagnosis (screen-detected, non-screen-detected).We compared the main characteristics of the different subgroups of CRCs through multivariate logistic regression models. The study included 23,668 CRCs diagnosed in subjects aged 50-69 years, of which 11.9% were screen-detected (N=2,806), all from the North-Centre of Italy. Among screen-detected CRCs, we observed a higher proportion of males, of cases in the distal colon, and a higher mean age of the patients. Compared with pre-screening cases, screen-detected CRCs showed a better distribution by stage at diagnosis (OR for stage III or IV: 0.40, 95%CI: 0.36-0.44) and grading (OR for poorly differentiated CRCs was 0.86, 95%CI: 0.75-1.00). Screen-detected CRCs have more favourable prognostic characteristics than non-screen-detected cases. A renewed effort to implement screening programmes throughout the entire country is recommended.

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

Directory of Open Access Journals (Sweden)

Abolhassan Naghibi

2016-03-01

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

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

Directory of Open Access Journals (Sweden)

David A Shoham

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

Colon cancer screening

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Screening for colon cancer; Colonoscopy - screening; Sigmoidoscopy - screening; Virtual colonoscopy - screening; Fecal immunochemical test; Stool DNA test; sDNA test; Colorectal cancer - screening; Rectal ...

An experience of qualified preventive screening: shiraz smart screening software.

Science.gov (United States)

Islami Parkoohi, Parisa; Zare, Hashem; Abdollahifard, Gholamreza

2015-01-01

Computerized preventive screening software is a cost effective intervention tool to address non-communicable chronic diseases. Shiraz Smart Screening Software (SSSS) was developed as an innovative tool for qualified screening. It allows simultaneous smart screening of several high-burden chronic diseases and supports reminder notification functionality. The extent in which SSSS affects screening quality is also described. Following software development, preventive screening and annual health examinations of 261 school staff (Medical School of Shiraz, Iran) was carried out in a software-assisted manner. To evaluate the quality of the software-assisted screening, we used quasi-experimental study design and determined coverage, irregular attendance and inappropriateness proportions in relation with the manual and software-assisted screening as well as the corresponding number of requested tests. In manual screening method, 27% of employees were covered (with 94% irregular attendance) while by software-assisted screening, the coverage proportion was 79% (attendance status will clear after the specified time). The frequency of inappropriate screening test requests, before the software implementation, was 41.37% for fasting plasma glucose, 41.37% for lipid profile, 0.84% for occult blood, 0.19% for flexible sigmoidoscopy/colonoscopy, 35.29% for Pap smear, 19.20% for mammography and 11.2% for prostate specific antigen. All of the above were corrected by the software application. In total, 366 manual screening and 334 software-assisted screening tests were requested. SSSS is an innovative tool to improve the quality of preventive screening plans in terms of increased screening coverage, reduction in inappropriateness and the total number of requested tests.

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

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

2017-02-01

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

Prospects for population screening and diagnosis of lung cancer

DEFF Research Database (Denmark)

Field, John K; Oudkerk, Matthijs; Pedersen, Jesper Holst

2013-01-01

Deaths from lung cancer exceed those from any other type of malignancy, with 1·5 million deaths in 2010. Prevention and smoking cessation are still the main methods to reduce the death toll. The US National Lung Screening Trial, which compared CT screening with chest radiograph, yielded a mortality......, and pooled analysis of European CT screening trials, we discuss the main topics that will need consideration. These unresolved issues are risk prediction models to identify patients for CT screening; radiological protocols that use volumetric analysis for indeterminate nodules; options for surgical resection...

Electron screening in molecular fusion reactions

International Nuclear Information System (INIS)

Shoppa, T.D.

1996-01-01

Recent laboratory experiments have measured fusion cross sections at center-of-mass energies low enough for the effects of atomic and molecular electrons to be important. To extract the cross section for bare nuclei from these data (as required for astrophysical applications), it is necessary to understand these screening effects. We study electron screening effects in the low-energy collisions of Z=1 nuclei with hydrogen molecules. Our model is based on a dynamical evolution of the electron wave functions within the TDHF scheme, while the motion of the nuclei is treated classically. We find that at the currently accessible energies the screening effects depend strongly on the molecular orientation. The screening is found to be larger for molecular targets than for atomic targets, due to the reflection symmetry in the latter. The results agree fairly well with data measured for deuteron collisions on molecular deuterium and tritium targets. (orig.)

Decision-analytic modeling to evaluate the long-term effectiveness and cost-effectiveness of HPV-DNA testing in primary cervical cancer screening in Germany

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Krämer, Alexander

2010-01-01

Full Text Available Background: Persistent infections with high-risk types of human papillomavirus (HPV are associated with the development of cervical neoplasia. Compared to cytology HPV testing is more sensitive in detecting high-grade cervical cancer precursors, but with lower specificity. HPV based primary screening for cervical cancer is currently discussed in Germany. Decisions should be based on a systematic evaluation of the long-term effectiveness and cost-effectiveness of HPV based primary screening. Research questions: What is the long-term clinical effectiveness (reduction in lifetime risk of cervical cancer and death due to cervical cancer, life years gained of HPV testing and what is the cost-effectiveness in Euro per life year gained (LYG of including HPV testing in primary cervical cancer screening in the German health care context? How can the screening program be improved with respect to test combination, age at start and end of screening and screening interval and which recommendations should be made for the German health care context? Methods: A previously published and validated decision-analytic model for the German health care context was extended and adapted to the natural history of HPV infection and cervical cancer in order to evaluate different screening strategies that differ by screening interval, and tests, including cytology alone, HPV testing alone or in combination with cytology, and HPV testing with cytology triage for HPV-positive women. German clinical, epidemiological and economic data were used. In the absence of individual data, screening adherence was modelled independently from screening history. Test accuracy data were retrieved from international meta-analyses. Predicted outcomes included reduction in lifetime-risk for cervical cancer cases and deaths, life expectancy, lifetime costs, and discounted incremental cost-effectiveness ratios (ICER. The perspective of the third party payer and 3% annual discount rate were

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

Energy Technology Data Exchange (ETDEWEB)

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

1995-05-01

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

Finite element simulation of impact response of wire mesh screens

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Wang Caizheng

2015-01-01

Full Text Available In this paper, the response of wire mesh screens to low velocity impact with blunt objects is investigated using finite element (FE simulation. The woven wire mesh is modelled with homogeneous shell elements with equivalent smeared mechanical properties. The mechanical behaviour of the woven wire mesh was determined experimentally with tensile tests on steel wire mesh coupons to generate the data for the smeared shell material used in the FE. The effects of impacts with a low mass (4 kg and a large mass (40 kg providing the same impact energy are studied. The joint between the wire mesh screen and the aluminium frame surrounding it is modelled using contact elements with friction between the corresponding elements. Damage to the screen of different types compromising its structural integrity, such as mesh separation and pulling out from the surrounding frame is modelled. The FE simulation is validated with results of impact tests conducted on woven steel wire screen meshes.

Investigating Effects of Screen Layout Elements on Interface and Screen Design Aesthetics

OpenAIRE

Altaboli, Ahamed; Lin, Yingzi

2011-01-01

A recent study suggested the use of the screen layout elements of balance, unity, and sequence as a part of a computational model of interface aesthetics. It is argued that these three elements are the most contributed terms in the model. In the current study, a controlled experiment was designed and conducted to systematically investigate effects of these three elements (balance, unity, and sequence) on the perceived interface aesthetics. Results showed that the three elements have signific...

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

International Nuclear Information System (INIS)

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

2010-01-01

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

Mixed total screening for sulfur isotope

International Nuclear Information System (INIS)

Cui Bin; Zhao Lei; Zhan Zhaoyang; He Zhijun

2003-01-01

The research on modern economic geology indicates that most ore deposits formed with characters of multi-origin, multi-stage and multi-genesis. Quantificational research of Sulfur isotope origin is a difficult problem that puzzles Geochemists all along. So the formation process of an ore deposit can be taken as the mix or the superposition of multi totals, which can be described by the mathematics model of mixed total screening. In the study of mid-down Yangtze River and Dongpo ore field in Hunan province, the authors successfully applied the mathematics model of mixed total screening, quantificationally resolved the problem of Sulfur isotope origin and mineralizing matter origin, and found out the mineralizing mechanism. This is very valuable. (authors)

Promoting cancer screening within the patient centered medical home.

Science.gov (United States)

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.

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

Science.gov (United States)

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

2004-01-01

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

Cervical cancer screening among Lebanese women.

Science.gov (United States)

Bou-Orm, I R; Sakr, R E; Adib, S M

2018-02-01

Cervical cancer is a very common malignancy amongst women worldwide. Pap smear is an effective and inexpensive screening test in asymptomatic women. The aim of this paper was to assess the prevalence of Pap smear screening for cervical cancer among Lebanese women and to determine associated sociodemographic and psychosocial characteristics. This national survey included 2255 women, selected by multi-stage random cluster sampling across Lebanon. A questionnaire about practices and perceptions related to cervical cancer screening was developed based on the "Health Belief Model". The weighted national prevalence of "ever-use" of the Pap smear for screening purposes was 35%. Most important determinants of screening behavior were: residence within Greater Beirut, higher socio-economic status and educational attainment, marriage status, presence of a health coverage, awareness of Pap smear usefulness, knowing someone who had already done it, and a balance between perceived benefits and perceived barriers to Pap smear screening. Regular information campaigns regarding the availability and effectiveness of the test should be devised, targeting in priority the sexually vulnerable women in Lebanon. Moreover, healthcare providers should be encouraged to discuss with their patients the opportunity of obtaining a Pap smear. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Influence of screening on longitudinal-optical phonon scattering in quantum cascade lasers

International Nuclear Information System (INIS)

Ezhov, Ivan; Jirauschek, Christian

2016-01-01

We theoretically investigate the influence of screening on electron-longitudinal optical phonon scattering in quantum cascade lasers. By employing ensemble Monte Carlo simulations, an advanced screening model based on the random-phase approximation is compared to the more elementary Thomas-Fermi and Debye models. For mid-infrared structures, and to a lesser extent also for terahertz designs, the inclusion of screening is shown to affect the simulated current and optical output power. Furthermore, it is demonstrated that by using the electron temperature rather than the lattice temperature, the Debye model can be significantly improved

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

Science.gov (United States)

Ashing-Giwa, K

1999-01-01

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

Alcohol Use Screening

Science.gov (United States)

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

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

Science.gov (United States)

Lanzas, Cristina; Dubberke, Erik R

2014-08-01

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

Final screening round of the NELSON lung cancer screening trial: the effect of a 2.5-year screening interval

NARCIS (Netherlands)

Yousaf-Khan, U.; Aalst, C. van der; Jong, P.A. de; Heuvelmans, M.; Scholten, E.T.; Lammers, J.-W.J.; Ooijen, P. van; Nackaerts, K.; Weenink, C.; Groen, H.; Vliegenthart, R.; Haaf, K. Ten; Oudkerk, M.; Koning, H. de

2016-01-01

In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial

Final screening round of the NELSON lung cancer screening trial : the effect of a 2.5-year screening interval

NARCIS (Netherlands)

Yousaf-Khan, Uraujh; van der Aalst, Carlijn; de Jong, Pim A; Heuvelmans, Marjolein; Scholten, Ernst; Lammers, Jan-Willem; van Ooijen, Peter; Nackaerts, Kristiaan; Weenink, Carla; Groen, Harry; Vliegenthart, Rozemarijn; Ten Haaf, Kevin; Oudkerk, Matthijs; de Koning, Harry

BACKGROUND: In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial

Final screening round of the NELSON lung cancer screening trial : the effect of a 2.5-year screening interval

NARCIS (Netherlands)

Yousaf-Khan, Uraujh; van der Aalst, Carlijn; de Jong, Pim A.; Heuvelmans, Marjolein; Scholten, Ernst; Lammers, Jan-Willem; van Ooijen, Peter; Nackaerts, Kristiaan; Weenink, Carla; Groen, Harry; Vliegenthart, Rozemarijn; Ten Haaf, Kevin; Oudkerk, Matthijs; de Koning, Harry

Background In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial

The Cost-Effectiveness of School-Based Eating Disorder Screening

Science.gov (United States)

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

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

Science.gov (United States)

Ridolfi, Danielle R; Crowther, Janis H

2013-03-01

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

Vasa previa screening strategies: a decision and cost-effectiveness analysis.

Science.gov (United States)

Sinkey, R G; Odibo, A O

2018-05-22

The aim of this study is to perform a decision and cost-effectiveness analysis comparing four screening strategies for the antenatal diagnosis of vasa previa among singleton pregnancies. A decision-analytic model was constructed comparing vasa previa screening strategies. Published probabilities and costs were applied to four transvaginal screening scenarios which occurred at the time of mid-trimester ultrasound: no screening, ultrasound-indicated screening, screening pregnancies conceived by in vitro fertilization (IVF), and universal screening. Ultrasound-indicated screening was defined as performing a transvaginal ultrasound at the time of routine anatomy ultrasound in response to one of the following sonographic findings associated with an increased risk of vasa previa: low-lying placenta, marginal or velamentous cord insertion, or bilobed or succenturiate lobed placenta. The primary outcome was cost per quality adjusted life years (QALY) in U.S. dollars. The analysis was from a healthcare system perspective with a willingness to pay (WTP) threshold of $100,000 per QALY selected. One-way and multivariate sensitivity analyses (Monte-Carlo simulation) were performed. This decision-analytic model demonstrated that screening pregnancies conceived by IVF was the most cost-effective strategy with an incremental cost effectiveness ratio (ICER) of $29,186.50 / QALY. Ultrasound-indicated screening was the second most cost-effective with an ICER of $56,096.77 / QALY. These data were robust to all one-way and multivariate sensitivity analyses performed. Within our baseline assumptions, transvaginal ultrasound screening for vasa previa appears to be most cost-effective when performed among IVF pregnancies. However, both IVF and ultrasound-indicated screening strategies fall within contemporary willingness-to-pay thresholds, suggesting that both strategies may be appropriate to apply in clinical practice. This article is protected by copyright. All rights reserved. This

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

Science.gov (United States)

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

2013-01-01

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

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

Science.gov (United States)

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

2015-11-17

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

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

Science.gov (United States)

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

2016-01-01

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

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

Science.gov (United States)

Aylward, Lesa L; Kirman, Chris R; Blount, Ben C; Hays, Sean M

2010-10-01

The National Health and Nutrition Examination Survey (NHANES) generates population-representative biomonitoring data for many chemicals including volatile organic compounds (VOCs) in blood. However, no health or risk-based screening values are available to evaluate these data from a health safety perspective or to use in prioritizing among chemicals for possible risk management actions. We gathered existing risk assessment-based chronic exposure reference values such as reference doses (RfDs), reference concentrations (RfCs), tolerable daily intakes (TDIs), cancer slope factors, etc. and key pharmacokinetic model parameters for 47 VOCs. Using steady-state solutions to a generic physiologically-based pharmacokinetic (PBPK) model structure, we estimated chemical-specific steady-state venous blood concentrations across chemicals associated with unit oral and inhalation exposure rates and with chronic exposure at the identified exposure reference values. The geometric means of the slopes relating modeled steady-state blood concentrations to steady-state exposure to a unit oral dose or unit inhalation concentration among 38 compounds with available pharmacokinetic parameters were 12.0 microg/L per mg/kg-d (geometric standard deviation [GSD] of 3.2) and 3.2 microg/L per mg/m(3) (GSD=1.7), respectively. Chemical-specific blood concentration screening values based on non-cancer reference values for both oral and inhalation exposure range from 0.0005 to 100 microg/L; blood concentrations associated with cancer risk-specific doses at the 1E-05 risk level ranged from 5E-06 to 6E-02 microg/L. The distribution of modeled steady-state blood concentrations associated with unit exposure levels across VOCs may provide a basis for estimating blood concentration screening values for VOCs that lack chemical-specific pharmacokinetic data. The screening blood concentrations presented here provide a tool for risk assessment-based evaluation of population biomonitoring data for VOCs and

Dynamic screening in solar and stellar nuclear reactions

Energy Technology Data Exchange (ETDEWEB)

Daeppen, W. [Department of Physics and Astronomy, University of Southern California, Los Angeles, CA (United States); Mussack, K. [Los Alamos National Laboratory, XTD-2, Los Alamos, NM (United States)

2012-02-15

In the hot, dense plasma of solar and stellar interiors, Coulomb potentials are screened, resulting in increased nuclear reaction rates. Although Salpeter's approximation for static screening is widely accepted and used in stellar modeling, the question of screening in nuclear reactions was revisited in the 1990s. In particular the issue of dynamic effects was raised by Shaviv and Shaviv, who applied the techniques of molecular dynamics to the conditions in the Sun's core in order to numerically determine the effect of screening. By directly calculating the motion of ions and electrons due to Coulomb interactions, the simulations are used to compute the effect of screening without the mean-field assumption inherent in Salpeter's approximation. In the last few years, the USC group has first reproduced Shaviv and Shaviv's numerical analysis of the screening energy, showing an effect of dynamic screening. When the consequence for the reaction-rate was computed, a rather surprising resulted, which is contrary to that from static screening theory. Our calculations showed that dynamic screening does not significantly change the reaction rate from that of the bare Coulomb potential. If this can be independently confirmed, then the effects of dynamic screening are highly relevant and should be included in stellar nuclear reaction rates (copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

The Potential Cost-Effectiveness of Amblyopia Screening Programs

Science.gov (United States)

Rein, David B.; Wittenborn, John S.; Zhang, Xinzhi; Song, Michael; Saaddine, Jinan B.

2013-01-01

Background To estimate the incremental cost-effectiveness of amblyopia screening at preschool and kindergarten, we compared the costs and benefits of 3 amblyopia screening scenarios to no screening and to each other: (1) acuity/stereopsis (A/S) screening at kindergarten, (2) A/S screening at preschool and kindergarten, and (3) photoscreening at preschool and A/S screening at kindergarten. Methods We programmed a probabilistic microsimulation model of amblyopia natural history and response to treatment with screening costs and outcomes estimated from 2 state programs. We calculated the probability that no screening and each of the 3 interventions were most cost-effective per incremental quality-adjusted life year (QALY) gained and case avoided. Results Assuming a minimal 0.01 utility loss from monocular vision loss, no screening was most cost-effective with a willingness to pay (WTP) of less than $16,000 per QALY gained. A/S screening at kindergarten alone was most cost-effective between a WTP of $17,000 and $21,000. A/S screening at preschool and kindergarten was most cost-effective between a WTP of $22,000 and $75,000, and photoscreening at preschool and A/S screening at kindergarten was most cost-effective at a WTP greater than $75,000. Cost-effectiveness substantially improved when assuming a greater utility loss. All scenarios were cost-effective when assuming a WTP of $10,500 per case of amblyopia cured. Conclusions All 3 screening interventions evaluated are likely to be considered cost-effective relative to many other potential public health programs. The choice of screening option depends on budgetary resources and the value placed on monocular vision loss prevention by funding agencies. PMID:21877675

A deep learning method for early screening of lung cancer

Science.gov (United States)

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.

Prostate Cancer Screening in Jamaica: Results of the Largest National Screening Clinic Prostate Cancer Screening in Jamaica: Results of the Largest National Screening Clinic

International Nuclear Information System (INIS)

Morrison, B. F.; Aiken, W.; Mayhew, R.; Gordon, Y.; Reid, M.

2016-01-01

Prostate cancer is highly prevalent in Jamaica and is the leading cause of cancer-related deaths. Our aim was to evaluate the patterns of screening in the largest organized screening clinic in Jamaica at the Jamaica Cancer Society. A retrospective analysis of all men presenting for screening at the Jamaica Cancer Society from 1995 to 2005 was done. All patients had digital rectal examinations (DRE) and prostate specific antigen (PSA) tests done. Results of prostate biopsies were noted. 1117 men of mean age 59.9 ± 8.2 years presented for screening. The median documented PSA was 1.6 ng/mL (maximum of 5170 ng/mL). Most patients presented for only 1 screen. There was a gradual reduction in the mean age of presentation for screening over the period. Prostate biopsies were requested on 11% of screening visits; however, only 59% of these were done. 5.6% of all persons screened were found to have cancer. Of the cancers diagnosed, Gleason 6 adenocarcinoma was the commonest grade and median PSA was 8.9 ng/mL (range 1.5-1059 ng/mL). Older men tend to screen for prostate cancer in Jamaica. However, compliance with regular maintenance visits and requests for confirmatory biopsies are poor. Screening needs intervention in the Jamaican population.

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

Science.gov (United States)

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

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

Science.gov (United States)

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

2012-11-01

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

Automated Groundwater Screening

International Nuclear Information System (INIS)

Taylor, Glenn A.; Collard, Leonard B.

2005-01-01

The Automated Intruder Analysis has been extended to include an Automated Ground Water Screening option. This option screens 825 radionuclides while rigorously applying the National Council on Radiation Protection (NCRP) methodology. An extension to that methodology is presented to give a more realistic screening factor for those radionuclides which have significant daughters. The extension has the promise of reducing the number of radionuclides which must be tracked by the customer. By combining the Automated Intruder Analysis with the Automated Groundwater Screening a consistent set of assumptions and databases is used. A method is proposed to eliminate trigger values by performing rigorous calculation of the screening factor thereby reducing the number of radionuclides sent to further analysis. Using the same problem definitions as in previous groundwater screenings, the automated groundwater screening found one additional nuclide, Ge-68, which failed the screening. It also found that 18 of the 57 radionuclides contained in NCRP Table 3.1 failed the screening. This report describes the automated groundwater screening computer application

ScreenCube: A 3D Printed System for Rapid and Cost-Effective Chemical Screening in Adult Zebrafish.

Science.gov (United States)

Monstad-Rios, Adrian T; Watson, Claire J; Kwon, Ronald Y

2018-02-01

Phenotype-based small molecule screens in zebrafish embryos and larvae have been successful in accelerating pathway and therapeutic discovery for diverse biological processes. Yet, the application of chemical screens to adult physiologies has been relatively limited due to additional demands on cost, space, and labor associated with screens in adult animals. In this study, we present a 3D printed system and methods for intermittent drug dosing that enable rapid and cost-effective chemical administration in adult zebrafish. Using prefilled screening plates, the system enables dosing of 96 fish in ∼3 min, with a 10-fold reduction in drug quantity compared to that used in previous chemical screens in adult zebrafish. We characterize water quality kinetics during immersion in the system and use these kinetics to rationally design intermittent dosing regimens that result in 100% fish survival. As a demonstration of system fidelity, we show the potential to identify two known chemical inhibitors of adult tail fin regeneration, cyclopamine and dorsomorphin. By developing methods for rapid and cost-effective chemical administration in adult zebrafish, this study expands the potential for small molecule discovery in postembryonic models of development, disease, and regeneration.

Astrophysical tests of gravity: a screening map of the nearby universe

Energy Technology Data Exchange (ETDEWEB)

Cabré, Anna; Vikram, Vinu; Jain, Bhuvnesh [Center for Particle Cosmology, Department of Physics and Astronomy, University of Pennsylvania, 209 South 33rd Street, Philadelphia, PA 19104-6396 (United States); Zhao, Gong-Bo; Koyama, Kazuya, E-mail: annanusca@gmail.com, E-mail: vinu@sas.upenn.edu, E-mail: gong-bo.zhao@port.ac.uk, E-mail: bjain@physics.upenn.edu, E-mail: Kazuya.Koyama@port.ac.uk [Institute of Cosmology and Gravitation, University of Portsmouth, Dennis Sciama Building, Burnaby Road, Portsmouth, PO1 3FX (United Kingdom)

2012-07-01

Astrophysical tests of modified gravity theories in the nearby universe have been emphasized recently by Hui 2009 and Jain 2011. A key element of such tests is the screening mechanism whereby general relativity is restored in massive halos or high density environments like the Milky Way. In chameleon theories of gravity, including all f(R) models, field dwarf galaxies may be unscreened and therefore feel an extra force, as opposed to screened galaxies. The first step to study differences between screened and unscreened galaxies is to create a 3D screening map. We use N-body simulations to test and calibrate simple approximations to determine the level of screening in galaxy catalogs. Sources of systematic errors in the screening map due to observational inaccuracies are modeled and their contamination is estimated. We then apply our methods to create a map out to 200 Mpc in the Sloan Digital Sky Survey footprint using data from the Sloan survey and other sources. In two companion papers this map will be used to carry out new tests of gravity using distance indicators and the disks of dwarf galaxies. We also make our screening map publicly available.

ND and NB systems in quark delocalization color screening model

Energy Technology Data Exchange (ETDEWEB)

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

2017-02-15

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

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

Science.gov (United States)

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

2009-07-17

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

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

NARCIS (Netherlands)

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

2015-01-01

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

Breast cancer screening

Science.gov (United States)

Mammogram - breast cancer screening; Breast exam - breast cancer screening; MRI - breast cancer screening ... is performed to screen women to detect early breast cancer when it is more likely to be cured. ...

Screening of the hearing of newborns - Update

Directory of Open Access Journals (Sweden)

von Voß, Hubertus

2006-11-01

Full Text Available Introduction: Permanent congenital bilateral hearing loss (CHL of moderate or greater degree (≥40 dB HL is a rare disease, with a prevalence of about 1 to 3 per 1000 births. However, it is one of the most frequent congenital diseases. Reliance on physician observation and parental recognition has not been successful in the past in detecting significant hearing loss in the first year of life. With this strategy significant hearing losses have been detected in the second year of life. With two objective technologies based on physiologic response to sound, otoacoustic emissions (OAE and auditory brainstem response (ABR hearing screening in the first days of life is made possible. Objectives: The objective of this health technology assessment report is to update the evaluation on clinical effectiveness and cost-effectiveness of newborn hearing screening programs. Universal newborn hearing screening (UHNS (i, selective screening of high risk newborns (ii, and the absence of a systematic screening program are compared for age at identification and age at hearing aid fitting of children with hearing loss. Secondly the potential benefits of early intervention are analysed. Costs and cost-effectiveness of newborn hearing screening programs are determined. This report is intended to make a contribution to the decision making whether and under which conditions a newborn hearing screening program should be reimbursed by the statutory sickness funds in Germany. Methods: This health technology assessment report updates a former health technology assessment (Kunze et al. 2004 [1]. A systematic review of the literature was conducted, based on a documented search and selection of the literature using predefined inclusion and exclusion criteria and a documented extraction and appraisal of the included studies. To assess the cost-effectiveness of the different screening strategies in Germany the decision analytic Markov state model which had been developed in

[Methodology of Screening New Antibiotics: Present Status and Prospects].

Science.gov (United States)

Trenin, A S

2015-01-01

Due to extensive distribution of pathogen resistance to available pharmaceuticals and serious problems in the treatment of various infections and tumor diseases, the necessity of new antibiotics is urgent. The basic methodological approaches to chemical synthesis of antibiotics and screening of new antibiotics among natural products, mainly among microbial secondary metabolites, are considered in the review. Since the natural compounds are very much diverse, screening of such substances gives a good opportunity to discover antibiotics of various chemical structure and mechanism of action. Such an approach followed by chemical or biological transformation, is capable of providing the health care with new effective pharmaceuticals. The review is mainly concentrated on screening of natural products and methodological problems, such as: isolation of microbial producers from the habitats, cultivation of microorganisms producing appropriate substances, isolation and chemical characterization of microbial metabolites, identification of the biological activity of the metabolites. The main attention is paid to the problems of microbial secondary metabolism and design of new models for screening biologically active compounds. The last achievements in the field of antibiotics and most perspective approaches to future investigations are discussed. The main methodological approach to isolation and cultivation of the producers remains actual and needs constant improvement. The increase of the screening efficiency can be achieved by more rapid chemical identification of antibiotics and design of new screening models based on the biological activity detection.

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

Science.gov (United States)

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.

Charge degeneracy removal in the screened hydrogen atom

International Nuclear Information System (INIS)

Penna, Andre L A; Diniz, Joao B; Oliveira, Fernando A

2009-01-01

We derive an analytical model for the states of the screened hydrogen atom by using a new charge degeneracy removal approach. Starting from the nonzero Thomas-Fermi parameter q, we show that screening effect is due to breaks of the charge degeneracy in each quantum level of the hydrogen atom. The charge degeneracy removal reparametrizes the atomic system through the effective nuclear charge α n,l and the appearance of a dual charge γ n,l for each quantum level. In this approach, we show that the screening of a quantum state depends hierarchically on the screening from all previous quantum states with the same angular quantum numbers. The excited state energies E n,l (q) are analytically found taking into account the contribution of this new charge degeneracy for each quantum level. Finally, we also have estimated accurate critical screening parameters q* n,l for the bound-unbound transition.

Breast, prostate, and thyroid cancer screening tests and overdiagnosis.

Science.gov (United States)

Jung, Minsoo

The purpose of this study was to examine overdiagnosis and overtreatment related to cancer screening and to review relevant reports and studies. A comprehensive search of peer-reviewed and gray literature was conducted for relevant studies published between January 2000 and December 2015 reporting breast, prostate, and thyroid cancer screening tests and overdiagnosis. This study revealed no dichotomy on where screening would lower risk or cause overdiagnosis and overtreatment. Many screening tests did both, that is, at population level, there were both benefit (decreased disease-specific mortality) and harm (overdiagnosis and overtreatment). Therefore, we need to consider a balanced argument with citations for the potential benefits of screening along with the harms associated with screening. Although the benefits and harms can only be tested through randomized trials, important data from cohort studies, diagnostic accuracy studies, and modeling work can help define the extent of benefits and harms in the population. The health care cycle that prompt patients to undergo periodic screening tests is self-reinforcing. In most developed countries, screening test recommendations encourage periodic testing. Therefore, patients are continuing their screening. It is necessary for patients to become wise consumers of screening tests and make decisions with their physicians regarding further testing and treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

COVARIANCE ASSISTED SCREENING AND ESTIMATION.

Science.gov (United States)

Ke, By Tracy; Jin, Jiashun; Fan, Jianqing

2014-11-01

Consider a linear model Y = X β + z , where X = X n,p and z ~ N (0, I n ). The vector β is unknown and it is of interest to separate its nonzero coordinates from the zero ones (i.e., variable selection). Motivated by examples in long-memory time series (Fan and Yao, 2003) and the change-point problem (Bhattacharya, 1994), we are primarily interested in the case where the Gram matrix G = X ' X is non-sparse but sparsifiable by a finite order linear filter. We focus on the regime where signals are both rare and weak so that successful variable selection is very challenging but is still possible. We approach this problem by a new procedure called the Covariance Assisted Screening and Estimation (CASE). CASE first uses a linear filtering to reduce the original setting to a new regression model where the corresponding Gram (covariance) matrix is sparse. The new covariance matrix induces a sparse graph, which guides us to conduct multivariate screening without visiting all the submodels. By interacting with the signal sparsity, the graph enables us to decompose the original problem into many separated small-size subproblems (if only we know where they are!). Linear filtering also induces a so-called problem of information leakage , which can be overcome by the newly introduced patching technique. Together, these give rise to CASE, which is a two-stage Screen and Clean (Fan and Song, 2010; Wasserman and Roeder, 2009) procedure, where we first identify candidates of these submodels by patching and screening , and then re-examine each candidate to remove false positives. For any procedure β̂ for variable selection, we measure the performance by the minimax Hamming distance between the sign vectors of β̂ and β. We show that in a broad class of situations where the Gram matrix is non-sparse but sparsifiable, CASE achieves the optimal rate of convergence. The results are successfully applied to long-memory time series and the change-point model.

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

Science.gov (United States)

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

2013-08-26

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

78 FR 76860 - Contraband Screening for Criminal Justice Applications

Science.gov (United States)

2013-12-19

... for the detection of contraband. Screening technology is widely used by criminal justice practitioners...: 1. Model Number and Name of the screening system/device. 2. Technology used by the system/device for... container or bag), Plastic, Wood, Ceramic, Powder (in a small packet), and/or Paper (e.g., folded currency...

Lung Cancer Screening May Benefit Those at Highest Risk

Science.gov (United States)

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.

RBC Antibody Screen

Science.gov (United States)

... C Cystic Fibrosis (CF) Gene Mutations Testing Cytomegalovirus (CMV) Tests D-dimer Dengue Fever Testing Des-gamma- ... Index of Screening Recommendations Not Listed? Not Listed? Newborn Screening Screening Tests for Infants Screening Tests for ...

Predicted impact of extending the screening interval for diabetic retinopathy: the Scottish Diabetic Retinopathy Screening programme.

Science.gov (United States)

Looker, H C; Nyangoma, S O; Cromie, D T; Olson, J A; Leese, G P; Philip, S; Black, M W; Doig, J; Lee, N; Briggs, A; Hothersall, E J; Morris, A D; Lindsay, R S; McKnight, J A; Pearson, D W M; Sattar, N A; Wild, S H; McKeigue, P; Colhoun, H M

2013-08-01

The aim of our study was to identify subgroups of patients attending the Scottish Diabetic Retinopathy Screening (DRS) programme who might safely move from annual to two yearly retinopathy screening. This was a retrospective cohort study of screening data from the DRS programme collected between 2005 and 2011 for people aged ≥12 years with type 1 or type 2 diabetes in Scotland. We used hidden Markov models to calculate the probabilities of transitions to referable diabetic retinopathy (referable background or proliferative retinopathy) or referable maculopathy. The study included 155,114 individuals with no referable diabetic retinopathy or maculopathy at their first DRS examination and with one or more further DRS examinations. There were 11,275 incident cases of referable diabetic eye disease (9,204 referable maculopathy, 2,071 referable background or proliferative retinopathy). The observed transitions to referable background or proliferative retinopathy were lower for people with no visible retinopathy vs mild background retinopathy at their prior examination (respectively, 1.2% vs 8.1% for type 1 diabetes and 0.6% vs 5.1% for type 2 diabetes). The lowest probability for transitioning to referable background or proliferative retinopathy was among people with two consecutive screens showing no visible retinopathy, where the probability was <0.3% for type 1 and <0.2% for type 2 diabetes at 2 years. Transition rates to referable diabetic eye disease were lowest among people with type 2 diabetes and two consecutive screens showing no visible retinopathy. If such people had been offered two yearly screening the DRS service would have needed to screen 40% fewer people in 2009.

The influence of the negative-positive ratio and screening database size on the performance of machine learning-based virtual screening.

Science.gov (United States)

Kurczab, Rafał; Bojarski, Andrzej J

2017-01-01

The machine learning-based virtual screening of molecular databases is a commonly used approach to identify hits. However, many aspects associated with training predictive models can influence the final performance and, consequently, the number of hits found. Thus, we performed a systematic study of the simultaneous influence of the proportion of negatives to positives in the testing set, the size of screening databases and the type of molecular representations on the effectiveness of classification. The results obtained for eight protein targets, five machine learning algorithms (SMO, Naïve Bayes, Ibk, J48 and Random Forest), two types of molecular fingerprints (MACCS and CDK FP) and eight screening databases with different numbers of molecules confirmed our previous findings that increases in the ratio of negative to positive training instances greatly influenced most of the investigated parameters of the ML methods in simulated virtual screening experiments. However, the performance of screening was shown to also be highly dependent on the molecular library dimension. Generally, with the increasing size of the screened database, the optimal training ratio also increased, and this ratio can be rationalized using the proposed cost-effectiveness threshold approach. To increase the performance of machine learning-based virtual screening, the training set should be constructed in a way that considers the size of the screening database.

Collective screening tools for early identification of dyslexia

Directory of Open Access Journals (Sweden)

Olga Valéria Campana Dos Anjos Andrade

2015-01-01

Full Text Available Current response to intervention models (RTI 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. Nonresponders to Tier 1 receive small-group tutoring in Tier 2. Nonresponders 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 seven 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

Collective screening tools for early identification of dyslexia

Science.gov (United States)

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

ESR/ERS white paper on lung cancer screening

Energy Technology Data Exchange (ETDEWEB)

Kauczor, Hans-Ulrich; Stackelberg, Oyunbileg von [University Hospital Heidelberg, Dept of Diagnostic and Interventional Radiology, Heidelberg (Germany); Member of the German Lung Research Center, Translational Lung Research Center, Heidelberg (Germany); Bonomo, Lorenzo [A. Gemelli University Hospital, Institute of Radiology, Rome (Italy); Gaga, Mina [Athens Chest Hospital, 7th Resp. Med. Dept and Asthma Center, Athens (Greece); Nackaerts, Kristiaan [KU Leuven-University of Leuven, University Hospitals Leuven, Department of Respiratory Diseases/Respiratory Oncology Unit, Leuven (Belgium); Peled, Nir [Tel Aviv University, Davidoff Cancer Center, Rabin Medical Center, Tel Aviv (Israel); Prokop, Mathias [Radboud University Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen (Netherlands); Remy-Jardin, Martine [Department of Thoracic Imaging, Hospital Calmette (EA 2694), CHRU et Universite de Lille, Lille (France); Sculier, Jean-Paul [Universite Libre de Bruxelles, Thoracic oncology, Institut Jules Bordet, Brussels (Belgium); Collaboration: on behalf of the European Society of Radiology (ESR) and the European Respiratory Society (ERS)

2015-09-15

Lung cancer is the most frequently fatal cancer, with poor survival once the disease is advanced. Annual low-dose computed tomography has shown a survival benefit in screening individuals at high risk for lung cancer. Based on the available evidence, the European Society of Radiology and the European Respiratory Society recommend lung cancer screening in comprehensive, quality-assured, longitudinal programmes within a clinical trial or in routine clinical practice at certified multidisciplinary medical centres. Minimum requirements include: standardised operating procedures for low-dose image acquisition, computer-assisted nodule evaluation, and positive screening results and their management; inclusion/exclusion criteria; expectation management; and smoking cessation programmes. Further refinements are recommended to increase quality, outcome and cost-effectiveness of lung cancer screening: inclusion of risk models, reduction of effective radiation dose, computer-assisted volumetric measurements and assessment of comorbidities (chronic obstructive pulmonary disease and vascular calcification). All these requirements should be adjusted to the regional infrastructure and healthcare system, in order to exactly define eligibility using a risk model, nodule management and a quality assurance plan. The establishment of a central registry, including a biobank and an image bank, and preferably on a European level, is strongly encouraged. (orig.)

ESR/ERS white paper on lung cancer screening

International Nuclear Information System (INIS)

Kauczor, Hans-Ulrich; Stackelberg, Oyunbileg von; Bonomo, Lorenzo; Gaga, Mina; Nackaerts, Kristiaan; Peled, Nir; Prokop, Mathias; Remy-Jardin, Martine; Sculier, Jean-Paul

2015-01-01

Lung cancer is the most frequently fatal cancer, with poor survival once the disease is advanced. Annual low-dose computed tomography has shown a survival benefit in screening individuals at high risk for lung cancer. Based on the available evidence, the European Society of Radiology and the European Respiratory Society recommend lung cancer screening in comprehensive, quality-assured, longitudinal programmes within a clinical trial or in routine clinical practice at certified multidisciplinary medical centres. Minimum requirements include: standardised operating procedures for low-dose image acquisition, computer-assisted nodule evaluation, and positive screening results and their management; inclusion/exclusion criteria; expectation management; and smoking cessation programmes. Further refinements are recommended to increase quality, outcome and cost-effectiveness of lung cancer screening: inclusion of risk models, reduction of effective radiation dose, computer-assisted volumetric measurements and assessment of comorbidities (chronic obstructive pulmonary disease and vascular calcification). All these requirements should be adjusted to the regional infrastructure and healthcare system, in order to exactly define eligibility using a risk model, nodule management and a quality assurance plan. The establishment of a central registry, including a biobank and an image bank, and preferably on a European level, is strongly encouraged. (orig.)

Evaluation of the effect of an audit and feedback reporting tool on screening participation: The Primary Care Screening Activity Report (PCSAR).

Science.gov (United States)

Jonah, Leigh; Pefoyo, Anna Kone; Lee, Alex; Hader, Joanne; Strasberg, Suzanne; Kupets, Rachel; Chiarelli, Anna M; Tinmouth, Jill

2017-03-01

Participation in cancer screening is critical to its effectiveness in reducing the burden of cancer. The Primary Care Screening Activity Report (PCSAR), an electronic report, was developed as an innovative audit and feedback tool to increase screening participation in Ontario's cancer screening programs. This study aims to assess its impact on patient screening participation. This study used a retrospective cohort design to evaluate the effectiveness of the 2014 PCSAR on screening participation in Ontario's three screening programs (breast, cervix and colorectal). The 3 cohorts comprised all participants eligible for each of the programs enrolled with a primary care physician in Ontario. Two exposures were evaluated for each cohort: enrollment with a physician who was registered to receive the PCSAR and enrollment with a registered physician who also logged into the PCSAR. Logistic regression modelling was used to assess the magnitude of the effect of PCSAR on participation, adjusting for participant and physician characteristics. Across all three screening programs, 63% of eligible physicians registered to receive the PCSAR and 38% of those registered logged-in to view it. Patients of physicians who registered were significantly more likely to participate in screening, with odds ratios ranging from 1.06 [1.04;1.09] to 1.15 [1.12;1.19]. The adjusted odds ratios associated with PCSAR log-in were 1.07 [1.03;1.12] to 1.18 [1.14;1.22] across all screening programs. Implementation of the PCSAR was associated with a small increase in screening participation. The PCSAR appears to be modestly effective in assisting primary care physicians in optimizing cancer screening participation among their patients. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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.

Staged anticonvulsant screening for chronic epilepsy

OpenAIRE

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

2016-01-01

Abstract Objective: 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. Methods: Epileptogenesis in organotypic hippocampal slice cultures was quantified by lactate production and l...

The shape dependence of chameleon screening

Science.gov (United States)

Burrage, Clare; Copeland, Edmund J.; Moss, Adam; Stevenson, James A.

2018-01-01

Chameleon scalar fields can screen their associated fifth forces from detection by changing their mass with the local density. These models are an archetypal example of a screening mechanism, and have become an important target for both cosmological surveys and terrestrial experiments. In particular there has been much recent interest in searching for chameleon fifth forces in the laboratory. It is known that the chameleon force is less screened around non-spherical sources, but only the field profiles around a few simple shapes are known analytically. In this work we introduce a numerical code that solves for the chameleon field around arbitrary shapes with azimuthal symmetry placed in a spherical vacuum chamber. We find that deviations from spherical symmetry can increase the chameleon acceleration experienced by a test particle, and that the least screened objects are those which minimize some internal dimension. For the shapes considered in this work, keeping the mass, density and background environment fixed, the accelerations due to the source varied by a factor of ~ 3.

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

Science.gov (United States)

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.

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

DEFF Research Database (Denmark)

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

2015-01-01

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

Is mammography screening history a predictor of future breast cancer risk?

DEFF Research Database (Denmark)

Andersen, Sune Bangsbøll; Törnberg, Sven; Kilpeläinen, Sini

2015-01-01

Inspired by the model by Walter and Day for risk of cervical cancer following negative screens, one might hypothesize that women in a mammography screening programme with a certain number of negative screens had a lower remaining breast cancer risk than that of women in general. We studied whether...... number of negative screens was a predictor for a low remaining breast cancer risk in women participating in the mammography screening programmes in Stockholm, Copenhagen and Funen. Data were collected from the mammography screening programmes in Stockholm, Sweden (1989-2012), Copenhagen, Denmark (1991......-2009) and Funen, Denmark (1993-2009), and linked to the respective cancer registries. We calculated cumulative hazard rates for breast cancer in women in cohorts defined by age at entry and number of negative screens for the maximum follow-up period in each screening centre. For all centres and cohorts...

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

Science.gov (United States)

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

2017-05-15

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

Youth Justice staff attitudes towards screening for self-harm.

Science.gov (United States)

Knowles, Sarah E; Townsend, Ellen; Anderson, Martin P

2012-09-01

Young offenders are recognised as a high-risk group for suicidal behaviour. It is essential that the screening used to identify those at risk and refer them to mental health services is effective, especially in community settings where service utilisation is low. Staff attitudes towards screening for suicide and self-harm are likely to influence how a young offender engages with the screening process. Our study is the first to explore community youth justice staff attitudes towards, and perceptions of, screening for self-harmful behaviour. Eight semi-structured interviews were conducted at an English Youth Offending Team in June 2006 with staff who had used the suicide screening tool with young offenders. Data were analysed using Interpretative Phenomenological Analysis. Staff attitudes towards working within the screening system varied along two dimensions. The first 'active/passive' dimension related to perceived confidence in dealing with self-harm. The second 'positive/negative' dimension related to perceptions of the benefits of screening and the effectiveness of mental health provision for young offenders. Results indicate that barriers to effective screening must be tackled at both individual and organisational levels. The model of attitudes presented here could be used to increase understanding of how staff can be supported to engage effectively with the screening system. © 2012 Blackwell Publishing Ltd.

ToxCast Workflow: High-throughput screening assay data processing, analysis and management (SOT)

Science.gov (United States)

US EPA’s ToxCast program is generating data in high-throughput screening (HTS) and high-content screening (HCS) assays for thousands of environmental chemicals, for use in developing predictive toxicity models. Currently the ToxCast screening program includes over 1800 unique c...

Uncertainty Quantification in High Throughput Screening ...

Science.gov (United States)

Using uncertainty quantification, we aim to improve the quality of modeling data from high throughput screening assays for use in risk assessment. ToxCast is a large-scale screening program that analyzes thousands of chemicals using over 800 assays representing hundreds of biochemical and cellular processes, including endocrine disruption, cytotoxicity, and zebrafish development. Over 2.6 million concentration response curves are fit to models to extract parameters related to potency and efficacy. Models built on ToxCast results are being used to rank and prioritize the toxicological risk of tested chemicals and to predict the toxicity of tens of thousands of chemicals not yet tested in vivo. However, the data size also presents challenges. When fitting the data, the choice of models, model selection strategy, and hit call criteria must reflect the need for computational efficiency and robustness, requiring hard and somewhat arbitrary cutoffs. When coupled with unavoidable noise in the experimental concentration response data, these hard cutoffs cause uncertainty in model parameters and the hit call itself. The uncertainty will then propagate through all of the models built on the data. Left unquantified, this uncertainty makes it difficult to fully interpret the data for risk assessment. We used bootstrap resampling methods to quantify the uncertainty in fitting models to the concentration response data. Bootstrap resampling determines confidence intervals for

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

International Nuclear Information System (INIS)

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

2005-01-01

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

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

Science.gov (United States)

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

2014-11-06

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

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

Directory of Open Access Journals (Sweden)

Faye M. Drawnel

2014-11-01

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

Plasma screening effects on the energies of hydrogen atom

International Nuclear Information System (INIS)

Soylu, A.

2012-01-01

A more general exponential cosine screened Coulomb potential is used for the first time to investigate the screening effects on the hydrogen atom in plasmas. This potential is examined for four different cases that correspond to four different type potentials when the different parameters are used in the potential within the framework of the well-known asymptotic iteration method. By solving the corresponding the radial Schrödinger equation with the screened and exponential cosine screened Coulomb potentials and comparing the obtained energy eigenvalues with the results of other studies, the applicability of the method to this kind of plasma physics problem is shown. The energy values of more general exponential cosine screened Coulomb potential are presented for various parameters in the potential. One of the advantages of the present potential is that it exhibits stronger screening effect than that of the exponential cosine screened Coulomb potential and it is also reduced to screened Coulomb and exponential cosine screened Coulomb as well as Coulomb potentials for special values of parameters. The parameters in the potential would be useful to model screening effects which cause an increase or decrease in the energy values of hydrogen atom in both Debye and quantum plasmas and in this manner this potential would be useful for the investigations of the atomic structure and collisions in plasmas.

Predictors of participation in prostate cancer screening at worksites.

Science.gov (United States)

Weinrich, S P; Greiner, E; Reis-Starr, C; Yoon, S; Weinrich, M

1998-01-01

Unfortunately, African American men have a higher incidence of and a higher mortality rate for prostate cancer than White men but are less likely to participate in prostate cancer screening. This correlational survey research identifies predictors for participation in a free prostate cancer screening in 179 men, 64% of whom are African American. Each man was invited to see his personal physician for a free prostate cancer screening following a prostate cancer educational program given at his worksite. Forty-seven percent of the African American men went to their personal physician following the educational program and received a digital rectal examination (DRE) and a prostate specific antigen (PSA) screening. In the original cohort of educational program attendees, only 16% of the African Americans had obtained a DRE in the previous 12 months. However, 44% subsequently did participate in free DRE screening. Similarly, only 6% of the African American men had received a PSA screening in the previous 12 months, yet 42% obtained a PSA screening after the educational program, a sevenfold increase. Implications for allocating limited resources for education and screening to the high-risk group of African American men are discussed. This study's model of a prostate cancer educational program at worksites followed by attendees visiting their personal physician for screening could be replicated throughout the United States to increase African American men's participation in prostate cancer screening.

Prenatal screening and genetics

DEFF Research Database (Denmark)

Alderson, P; Aro, A R; Dragonas, T

2001-01-01

Although the term 'genetic screening' has been used for decades, this paper discusses how, in its most precise meaning, genetic screening has not yet been widely introduced. 'Prenatal screening' is often confused with 'genetic screening'. As we show, these terms have different meanings, and we...... examine definitions of the relevant concepts in order to illustrate this point. The concepts are i) prenatal, ii) genetic screening, iii) screening, scanning and testing, iv) maternal and foetal tests, v) test techniques and vi) genetic conditions. So far, prenatal screening has little connection...... with precisely defined genetics. There are benefits but also disadvantages in overstating current links between them in the term genetic screening. Policy making and professional and public understandings about screening could be clarified if the distinct meanings of prenatal screening and genetic screening were...

Methicillin-resistant Staphylococcus aureus screening as a patient safety initiative: using patients' experiences to improve the quality of screening practices.

Science.gov (United States)

Currie, Kay; Knussen, Christina; Price, Lesley; Reilly, Jacqui

2014-01-01

To explore the patient experience and acceptability of methicillin-resistant Staphylococcus aureus screening of inpatient admissions to acute hospital settings. Prevention of healthcare-associated infections such as methicillin-resistant Staphylococcus aureus is a major patient safety concern internationally. Screening of patients for methicillin-resistant Staphylococcus aureus colonisation is becoming a routine aspect of hospital admission; however, evidence of the patient experience and acceptability of methicillin-resistant Staphylococcus aureus screening is limited. A mixed-methods study set in six acute care hospitals in three Scottish regions. Data collection involved postdischarge self-report survey of patients who had been screened (n = 54) and qualitative patient interviews (n = 10). Theoretical constructs derived from the Health Belief Model and Theory of Planned Behaviour used in analysis. Findings indicated that methicillin-resistant Staphylococcus aureus screening was broadly acceptable to patients. The experience of screening did not appear to be problematic; responses demonstrate that screening provided reassurance and generated confidence that health organisations were tackling healthcare-associated infections. Patients were less positive regarding the provision of information, the possibility of refusing a screen and the consequences of a positive test result. Furthermore, there were indications that patients wanted to be told the results of the screen and strong support for screening of hospital staff. Analysis of constructs from our theoretical frameworks provides evidence that attitudes were largely positive; responses indicate a belief in the beneficial impact of methicillin-resistant Staphylococcus aureus screening for patients and the wider community. However, it is important that health professionals continually assess the patient experience of 'routine' aspects of health care such as MRSA screening. The findings from this study suggest that

SCREENING CHEMICALS FOR ESTROGEN RECEPTOR BIOACTIVITY USING A COMPUTATIONAL MODEL

Science.gov (United States)

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

Participant selection for lung cancer screening by risk modelling (the Pan-Canadian Early Detection of Lung Cancer [PanCan] study): a single-arm, prospective study.

Science.gov (United States)

Tammemagi, Martin C; Schmidt, Heidi; Martel, Simon; McWilliams, Annette; Goffin, John R; Johnston, Michael R; Nicholas, Garth; Tremblay, Alain; Bhatia, Rick; Liu, Geoffrey; Soghrati, Kam; Yasufuku, Kazuhiro; Hwang, David M; Laberge, Francis; Gingras, Michel; Pasian, Sergio; Couture, Christian; Mayo, John R; Nasute Fauerbach, Paola V; Atkar-Khattra, Sukhinder; Peacock, Stuart J; Cressman, Sonya; Ionescu, Diana; English, John C; Finley, Richard J; Yee, John; Puksa, Serge; Stewart, Lori; Tsai, Scott; Haider, Ehsan; Boylan, Colm; Cutz, Jean-Claude; Manos, Daria; Xu, Zhaolin; Goss, Glenwood D; Seely, Jean M; Amjadi, Kayvan; Sekhon, Harmanjatinder S; Burrowes, Paul; MacEachern, Paul; Urbanski, Stefan; Sin, Don D; Tan, Wan C; Leighl, Natasha B; Shepherd, Frances A; Evans, William K; Tsao, Ming-Sound; Lam, Stephen

2017-11-01

Results from retrospective studies indicate that selecting individuals for low-dose CT lung cancer screening on the basis of a highly predictive risk model is superior to using criteria similar to those used in the National Lung Screening Trial (NLST; age, pack-year, and smoking quit-time). We designed the Pan-Canadian Early Detection of Lung Cancer (PanCan) study to assess the efficacy of a risk prediction model to select candidates for lung cancer screening, with the aim of determining whether this approach could better detect patients with early, potentially curable, lung cancer. We did this single-arm, prospective study in eight centres across Canada. We recruited participants aged 50-75 years, who had smoked at some point in their life (ever-smokers), and who did not have a self-reported history of lung cancer. Participants had at least a 2% 6-year risk of lung cancer as estimated by the PanCan model, a precursor to the validated PLCOm2012 model. Risk variables in the model were age, smoking duration, pack-years, family history of lung cancer, education level, body-mass index, chest x-ray in the past 3 years, and history of chronic obstructive pulmonary disease. Individuals were screened with low-dose CT at baseline (T0), and at 1 (T1) and 4 (T4) years post-baseline. The primary outcome of the study was incidence of lung cancer. This study is registered with ClinicalTrials.gov, number NCT00751660. 7059 queries came into the study coordinating centre and were screened for PanCan risk. 15 were duplicates, so 7044 participants were considered for enrolment. Between Sept 24, 2008, and Dec 17, 2010, we recruited and enrolled 2537 eligible ever-smokers. After a median follow-up of 5·5 years (IQR 3·2-6·1), 172 lung cancers were diagnosed in 164 individuals (cumulative incidence 0·065 [95% CI 0·055-0·075], incidence rate 138·1 per 10 000 person-years [117·8-160·9]). There were ten interval lung cancers (6% of lung cancers and 6% of individuals with cancer

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

Science.gov (United States)

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

2017-11-01

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

3D mosquito screens to create window double screen traps for mosquito control.

Science.gov (United States)

Khattab, Ayman; Jylhä, Kaisa; Hakala, Tomi; Aalto, Mikko; Malima, Robert; Kisinza, William; Honkala, Markku; Nousiainen, Pertti; Meri, Seppo

2017-08-29

Mosquitoes are vectors for many diseases such as malaria. Insecticide-treated bed nets and indoor residual spraying of insecticides are the principal malaria vector control tools used to prevent malaria in the tropics. Other interventions aim at reducing man-vector contact. For example, house screening provides additive or synergistic effects to other implemented measures. We used commercial screen materials made of polyester, polyethylene or polypropylene to design novel mosquito screens that provide remarkable additional benefits to those commonly used in house screening. The novel design is based on a double screen setup made of a screen with 3D geometric structures parallel to a commercial mosquito screen creating a trap between the two screens. Owing to the design of the 3D screen, mosquitoes can penetrate the 3D screen from one side but cannot return through the other side, making it a unidirectional mosquito screen. Therefore, the mosquitoes are trapped inside the double screen system. The permissiveness of both sides of the 3D screens for mosquitoes to pass through was tested in a wind tunnel using the insectary strain of Anopheles stephensi. Among twenty-five tested 3D screen designs, three designs from the cone, prism, or cylinder design groups were the most efficient in acting as unidirectional mosquito screens. The three cone-, prism-, and cylinder-based screens allowed, on average, 92, 75 and 64% of Anopheles stephensi mosquitoes released into the wind tunnel to penetrate the permissive side and 0, 0 and 6% of mosquitoes to escape through the non-permissive side, respectively. A cone-based 3D screen fulfilled the study objective. It allowed capturing 92% of mosquitoes within the double screen setup inside the wind tunnel and blocked 100% from escaping. Thus, the cone-based screen effectively acted as a unidirectional mosquito screen. This 3D screen-based trap design could therefore be used in house screening as a means of avoiding infective bites and

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

Directory of Open Access Journals (Sweden)

Cemal Cagatay Bilgin

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

Steroidogenesis in vitro : towards relevant models for endocrine disruptor screening

NARCIS (Netherlands)

Roelofs, M.J.E.

2016-01-01

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

Variations in screening outcome among pairs of screening radiologists at non-blinded double reading of screening mammograms: a population-based study

NARCIS (Netherlands)

Klompenhouwer, E. G.; Duijm, L. E. M.; Voogd, A. C.; den Heeten, G. J.; Nederend, J.; Jansen, F. H.; Broeders, M. J. M.

2014-01-01

Substantial inter-observer variability in screening mammography interpretation has been reported at single reading. However, screening results of pairs of screening radiologists have not yet been published. We determined variations in screening performances among pairs of screening radiologists at

Newborn screening healthcare information system based on service-oriented architecture.

Science.gov (United States)

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.

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

Science.gov (United States)

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

2013-11-01

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

Overdiagnosis, sojourn time, and sensitivity in the Copenhagen mammography screening program

DEFF Research Database (Denmark)

Olsen, Anne Helene; Agbaje, Olorunsola F; Myles, Jonathan P

2006-01-01

models to the screening data, including preclinical incidence of progressive cancers and nonprogressive (i.e., overdiagnosed) cancers. We estimated mean sojourn time as 2.7 years (95% confidence interval [CI] 2.2-3.1) and screening test sensitivity as 100% (95% CI 99.8-100). Overdiagnosis was estimated...... to be 7.8% (95% CI 0.3-26.5) at the first screen and 0.5% (95% CI 0.02-2.1) at the second screen. This corresponds to 4.8% of all cancers diagnosed among participants during the first two invitation rounds and following intervals. A modest overdiagnosis was estimated for the Copenhagen screening program...

Clad Degradation - FEPs Screening Arguments

International Nuclear Information System (INIS)

E. Siegmann

2004-01-01

The purpose of this report is to document the screening of the cladding degradation features, events, and processes (FEPs) for commercial spent nuclear fuel (CSNF). This report also addresses the effect of some FEPs on both the cladding and the CSNF, DSNF, and HLW waste forms where it was considered appropriate to address the effects on both materials together. This report summarizes the work of others to screen clad degradation FEPs in a manner consistent with, and used in, the Total System Performance Assessment-License Application (TSPA-LA). This document was prepared according to ''Technical Work Plan for Waste Form Degradation Modeling, Testing, and Analyses in Support of LA'' (BSC 2004a [DIRS 167796])

Long-term evaluation of benefits, harms, and cost-effectiveness of the National Bowel Cancer Screening Program in Australia: A modelling study

NARCIS (Netherlands)

Lew, J.-B. (Jie-Bin); St John, D.J.B. (D James B); X.-M. Xu (Xiang-Ming); M.J.W. Greuter (Marcel); Caruana, M. (Michael); D.R. Cenin (Dayna R.); He, E. (Emily); Saville, M. (Marion); Grogan, P. (Paul); V.M.H. Coupé (Veerle); K. Canfell (Karen)

2017-01-01

textabstractBackground: No assessment of the National Bowel Screening Program (NBCSP) in Australia, which considers all downstream benefits, costs, and harms, has been done. We aimed to use a comprehensive natural history model and the most recent information about cancer treatment costs to estimate

Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

Directory of Open Access Journals (Sweden)

Millard M

2017-10-01

Full Text Available Marie Millard,1,2 Ilya Yakavets,1–3 Vladimir Zorin,3,4 Aigul Kulmukhamedova,1,2,5 Sophie Marchal,1,2 Lina Bezdetnaya1,2 1Centre de Recherche en Automatique de Nancy, Centre National de la Recherche Scientifique UMR 7039, Université de Lorraine, 2Research Department, Institut de Cancérologie de Lorraine, Vandœuvre-lès-Nancy, France; 3Laboratory of Biophysics and Biotechnology, 4International Sakharov Environmental Institute, Belarusian State University, Minsk, Belarus; 5Department of Radiology, Medical Company Sunkar, Almaty, Kazakhstan Abstract: The increasing number of publications on the subject shows that nanomedicine is an attractive field for investigations aiming to considerably improve anticancer chemotherapy. Based on selective tumor targeting while sparing healthy tissue, carrier-mediated drug delivery has been expected to provide significant benefits to patients. However, despite reduced systemic toxicity, most nanodrugs approved for clinical use have been less effective than previously anticipated. The gap between experimental results and clinical outcomes demonstrates the necessity to perform comprehensive drug screening by using powerful preclinical models. In this context, in vitro three-dimensional models can provide key information on drug behavior inside the tumor tissue. The multicellular tumor spheroid (MCTS model closely mimics a small avascular tumor with the presence of proliferative cells surrounding quiescent cells and a necrotic core. Oxygen, pH and nutrient gradients are similar to those of solid tumor. Furthermore, extracellular matrix (ECM components and stromal cells can be embedded in the most sophisticated spheroid design. All these elements together with the physicochemical properties of nanoparticles (NPs play a key role in drug transport, and therefore, the MCTS model is appropriate to assess the ability of NP to penetrate the tumor tissue. This review presents recent developments in MCTS models for a

Cancer screening guidelines.

Science.gov (United States)

Zoorob, R; Anderson, R; Cefalu, C; Sidani, M

2001-03-15

Numerous medical organizations have developed cancer screening guidelines. Faced with the broad, and sometimes conflicting, range of recommendations for cancer screening, family physicians must determine the most reasonable and up-to-date method of screening. Major medical organizations have generally achieved consensus on screening guidelines for breast, cervical and colorectal cancer. For breast cancer screening in women ages 50 to 70, clinical breast examination and mammography are generally recommended every one or two years, depending on the medical organization. For cervical cancer screening, most organizations recommend a Papanicolaou test and pelvic examination at least every three years in patients between 20 and 65 years of age. Annual fecal occult blood testing along with flexible sigmoidoscopy at five-year to 10-year intervals is the standard recommendation for colorectal cancer screening in patients older than 50 years. Screening for prostate cancer remains a matter of debate. Some organizations recommend digital rectal examination and a serum prostate-specific antigen test for men older than 50 years, while others do not. In the absence of compelling evidence to indicate a high risk of endometrial cancer, lung cancer, oral cancer and ovarian cancer, almost no medical organizations have developed cancer screening guidelines for these types of cancer.

Comparison of cumulative false-positive risk of screening mammography in the United States and Denmark

DEFF Research Database (Denmark)

Jacobsen, Katja Kemp

2015-01-01

INTRODUCTION: In the United States (US), about one-half of women screened with annual mammography have at least one false-positive test after ten screens. The estimate for European women screened ten times biennially is much lower. We evaluate to what extent screening interval, mammogram type......=400,204), between 1991-2012 and 1993-2013, respectively. Model-based cumulative false-positive risks were computed for the entire sample, using two statistical methods (Hubbard Njor) previously used to estimate false-positive risks in the US and Europe. RESULTS: Empirical cumulative risk of at least...... one false-positive test after eight (annual or biennial) screens was 41.9% in BCSC, 16.1% in Copenhagen, and 7.4% in Funen. Variation in screening interval and mammogram type did not explain the differences by country. Using the Hubbard method, the model-based cumulative risks after eight screens...

Optimal screening and donor management in a public stool bank.

Science.gov (United States)

Kazerouni, Abbas; Burgess, James; Burns, Laura J; Wein, Lawrence M

2015-12-17

Fecal microbiota transplantation is an effective treatment for recurrent Clostridium difficile infection and is being investigated as a treatment for other microbiota-associated diseases. To facilitate these activities, an international public stool bank has been created, which screens donors and processes stools in a standardized manner. The goal of this research is to use mathematical modeling and analysis to optimize screening and donor management at the stool bank. Compared to the current policy of screening active donors every 60 days before releasing their quarantined stools for sale, costs can be reduced by 10.3 % by increasing the screening frequency to every 36 days. In addition, the stool production rate varies widely across donors, and using donor-specific screening, where higher producers are screened more frequently, also reduces costs, as does introducing an interim (i.e., between consecutive regular tests) stool test for just rotavirus and C. difficile. We also derive a donor release (i.e., into the system) policy that allows the supply to approximately match an exponentially increasing deterministic demand. More frequent screening, interim screening for rotavirus and C. difficile, and donor-specific screening, where higher stool producers are screened more frequently, are all cost-reducing measures. If screening costs decrease in the future (e.g., as a result of bringing screening in house), a bottleneck for implementing some of these recommendations may be the reluctance of donors to undergo serum screening more frequently than monthly.