WorldWideScience

Sample records for stage cox model

  1. Properties of spatial Cox process models

    DEFF Research Database (Denmark)

    Møller, Jesper

    Probabilistic properties of Cox processes of relevance for statistical modelling and inference are studied. Particularly, we study the most important classes of Cox processes, including log Gaussian Cox processes, shot noise Cox processes, and permanent Cox processes. We consider moment properties...... and point process operations such as thinning, displacements, and superpositioning. We also discuss how to simulate specific Cox processes....

  2. Analysis of urinary human chorionic gonadotrophin concentrations in normal and failing pregnancies using longitudinal, Cox proportional hazards and two-stage modelling.

    Science.gov (United States)

    Marriott, Lorrae; Zinaman, Michael; Abrams, Keith R; Crowther, Michael J; Johnson, Sarah

    2017-09-01

    Background Human chorionic gonadotrophin is a marker of early pregnancy. This study sought to determine the possibility of being able to distinguish between healthy and failing pregnancies by utilizing patient-associated risk factors and daily urinary human chorionic gonadotrophin concentrations. Methods Data were from a study that collected daily early morning urine samples from women trying to conceive (n = 1505); 250 of whom became pregnant. Data from 129 women who became pregnant (including 44 miscarriages) were included in these analyses. A longitudinal model was used to profile human chorionic gonadotrophin, a Cox proportional hazards model to assess demographic/menstrual history data on the time to failed pregnancy, and a two-stage model to combine these two models. Results The profile for log human chorionic gonadotrophin concentrations in women suffering miscarriage differs to that of viable pregnancies; rate of human chorionic gonadotrophin rise is slower in those suffering a biochemical loss (loss before six weeks, recognized by a rise and fall of human chorionic gonadotrophin) and tends to plateau at a lower log human chorionic gonadotrophin in women suffering an early miscarriage (loss six weeks or later), compared with viable pregnancies. Maternal age, longest cycle length and time from luteinizing hormone surge to human chorionic gonadotrophin reaching 25 mIU/mL were found to be significantly associated with miscarriage risk. The two-stage model found that for an increase of one day in the time from luteinizing hormone surge to human chorionic gonadotrophin reaching 25 mIU/mL, there is a 30% increase in miscarriage risk (hazard ratio: 1.30; 95% confidence interval: 1.04, 1.62). Conclusion Rise of human chorionic gonadotrophin in early pregnancy could be useful to predict pregnancy viability. Daily tracking of urinary human chorionic gonadotrophin may enable early identification of some pregnancies at risk of miscarriage.

  3. Properties of spatial Cox process models

    DEFF Research Database (Denmark)

    Møller, Jesper

    2005-01-01

    Particularly, we study the most important classes of Cox processes, including log Gaussian Cox processes, shot noise Cox processes, and permanent Cox processes. We consider moment properties and point process operations such as thinning, displacements, and super positioning. We also discuss how...... to simulate specific Cox processes....

  4. Identifying nonproportional covariates in the Cox model

    Czech Academy of Sciences Publication Activity Database

    Kraus, David

    2008-01-01

    Roč. 37, č. 4 (2008), s. 617-625 ISSN 0361-0926 R&D Projects: GA AV ČR(CZ) IAA101120604; GA MŠk(CZ) 1M06047; GA ČR(CZ) GD201/05/H007 Institutional research plan: CEZ:AV0Z10750506 Keywords : Cox model * goodness of fit * proportional hazards assumption * time-varying coefficients Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 0.324, year: 2008

  5. An Additive-Multiplicative Cox-Aalen Regression Model

    DEFF Research Database (Denmark)

    Scheike, Thomas H.; Zhang, Mei-Jie

    2002-01-01

    Aalen model; additive risk model; counting processes; Cox regression; survival analysis; time-varying effects......Aalen model; additive risk model; counting processes; Cox regression; survival analysis; time-varying effects...

  6. Extensions and Applications of the Cox-Aalen Survival Model

    DEFF Research Database (Denmark)

    Scheike, Thomas H.; Zhang, Mei-Jie

    2003-01-01

    Aalen additive risk model; competing risk; counting processes; Cox model; cumulative incidence function; goodness of fit; prediction of survival probability; time-varying effects......Aalen additive risk model; competing risk; counting processes; Cox model; cumulative incidence function; goodness of fit; prediction of survival probability; time-varying effects...

  7. Comparison of Cox and Gray's survival models in severe sepsis

    DEFF Research Database (Denmark)

    Kasal, Jan; Andersen, Zorana Jovanovic; Clermont, Gilles

    2004-01-01

    Although survival is traditionally modeled using Cox proportional hazards modeling, this approach may be inappropriate in sepsis, in which the proportional hazards assumption does not hold. Newer, more flexible models, such as Gray's model, may be more appropriate.......Although survival is traditionally modeled using Cox proportional hazards modeling, this approach may be inappropriate in sepsis, in which the proportional hazards assumption does not hold. Newer, more flexible models, such as Gray's model, may be more appropriate....

  8. Multivariate Product-Shot-noise Cox Point Process Models

    DEFF Research Database (Denmark)

    Jalilian, Abdollah; Guan, Yongtao; Mateu, Jorge

    We introduce a new multivariate product-shot-noise Cox process which is useful for model- ing multi-species spatial point patterns with clustering intra-specific interactions and neutral, negative or positive inter-specific interactions. The auto and cross pair correlation functions of the process...

  9. Cox's regression model for dynamics of grouped unemployment data

    Czech Academy of Sciences Publication Activity Database

    Volf, Petr

    2003-01-01

    Roč. 10, č. 19 (2003), s. 151-162 ISSN 1212-074X R&D Projects: GA ČR GA402/01/0539 Institutional research plan: CEZ:AV0Z1075907 Keywords : mathematical statistics * survival analysis * Cox's model Subject RIV: BB - Applied Statistics, Operational Research

  10. Instrumental variables estimation under a structural Cox model

    DEFF Research Database (Denmark)

    Martinussen, Torben; Nørbo Sørensen, Ditte; Vansteelandt, Stijn

    2017-01-01

    Instrumental variable (IV) analysis is an increasingly popular tool for inferring the effect of an exposure on an outcome, as witnessed by the growing number of IV applications in epidemiology, for instance. The majority of IV analyses of time-to-event endpoints are, however, dominated by heuristic...... and instruments. We propose a novel class of estimators and derive their asymptotic properties. The methodology is illustrated using two real data applications, and using simulated data....... approaches. More rigorous proposals have either sidestepped the Cox model, or considered it within a restrictive context with dichotomous exposure and instrument, amongst other limitations. The aim of this article is to reconsider IV estimation under a structural Cox model, allowing for arbitrary exposure...

  11. Wiener Chaos and the Cox-Ingersoll-Ross model

    OpenAIRE

    Grasselli, M. R.; Hurd, T. R.

    2003-01-01

    In this we paper we recast the Cox--Ingersoll--Ross model of interest rates into the chaotic representation recently introduced by Hughston and Rafailidis. Beginning with the ``squared Gaussian representation'' of the CIR model, we find a simple expression for the fundamental random variable X. By use of techniques from the theory of infinite dimensional Gaussian integration, we derive an explicit formula for the n-th term of the Wiener chaos expansion of the CIR model, for n=0,1,2,.... We th...

  12. Extended cox regression model: The choice of timefunction

    Science.gov (United States)

    Isik, Hatice; Tutkun, Nihal Ata; Karasoy, Durdu

    2017-07-01

    Cox regression model (CRM), which takes into account the effect of censored observations, is one the most applicative and usedmodels in survival analysis to evaluate the effects of covariates. Proportional hazard (PH), requires a constant hazard ratio over time, is the assumptionofCRM. Using extended CRM provides the test of including a time dependent covariate to assess the PH assumption or an alternative model in case of nonproportional hazards. In this study, the different types of real data sets are used to choose the time function and the differences between time functions are analyzed and discussed.

  13. Bootstrapping a change-point Cox model for survival data

    Science.gov (United States)

    Xu, Gongjun; Sen, Bodhisattva; Ying, Zhiliang

    2014-01-01

    This paper investigates the (in)-consistency of various bootstrap methods for making inference on a change-point in time in the Cox model with right censored survival data. A criterion is established for the consistency of any bootstrap method. It is shown that the usual nonparametric bootstrap is inconsistent for the maximum partial likelihood estimation of the change-point. A new model-based bootstrap approach is proposed and its consistency established. Simulation studies are carried out to assess the performance of various bootstrap schemes. PMID:25400719

  14. Box-Cox Mixed Logit Model for Travel Behavior Analysis

    Science.gov (United States)

    Orro, Alfonso; Novales, Margarita; Benitez, Francisco G.

    2010-09-01

    To represent the behavior of travelers when they are deciding how they are going to get to their destination, discrete choice models, based on the random utility theory, have become one of the most widely used tools. The field in which these models were developed was halfway between econometrics and transport engineering, although the latter now constitutes one of their principal areas of application. In the transport field, they have mainly been applied to mode choice, but also to the selection of destination, route, and other important decisions such as the vehicle ownership. In usual practice, the most frequently employed discrete choice models implement a fixed coefficient utility function that is linear in the parameters. The principal aim of this paper is to present the viability of specifying utility functions with random coefficients that are nonlinear in the parameters, in applications of discrete choice models to transport. Nonlinear specifications in the parameters were present in discrete choice theory at its outset, although they have seldom been used in practice until recently. The specification of random coefficients, however, began with the probit and the hedonic models in the 1970s, and, after a period of apparent little practical interest, has burgeoned into a field of intense activity in recent years with the new generation of mixed logit models. In this communication, we present a Box-Cox mixed logit model, original of the authors. It includes the estimation of the Box-Cox exponents in addition to the parameters of the random coefficients distribution. Probability of choose an alternative is an integral that will be calculated by simulation. The estimation of the model is carried out by maximizing the simulated log-likelihood of a sample of observed individual choices between alternatives. The differences between the predictions yielded by models that are inconsistent with real behavior have been studied with simulation experiments.

  15. Diagnostic Measures for the Cox Regression Model with Missing Covariates.

    Science.gov (United States)

    Zhu, Hongtu; Ibrahim, Joseph G; Chen, Ming-Hui

    2015-12-01

    This paper investigates diagnostic measures for assessing the influence of observations and model misspecification in the presence of missing covariate data for the Cox regression model. Our diagnostics include case-deletion measures, conditional martingale residuals, and score residuals. The Q-distance is proposed to examine the effects of deleting individual observations on the estimates of finite-dimensional and infinite-dimensional parameters. Conditional martingale residuals are used to construct goodness of fit statistics for testing possible misspecification of the model assumptions. A resampling method is developed to approximate the p -values of the goodness of fit statistics. Simulation studies are conducted to evaluate our methods, and a real data set is analyzed to illustrate their use.

  16. Ensembling Variable Selectors by Stability Selection for the Cox Model

    Directory of Open Access Journals (Sweden)

    Qing-Yan Yin

    2017-01-01

    Full Text Available As a pivotal tool to build interpretive models, variable selection plays an increasingly important role in high-dimensional data analysis. In recent years, variable selection ensembles (VSEs have gained much interest due to their many advantages. Stability selection (Meinshausen and Bühlmann, 2010, a VSE technique based on subsampling in combination with a base algorithm like lasso, is an effective method to control false discovery rate (FDR and to improve selection accuracy in linear regression models. By adopting lasso as a base learner, we attempt to extend stability selection to handle variable selection problems in a Cox model. According to our experience, it is crucial to set the regularization region Λ in lasso and the parameter λmin properly so that stability selection can work well. To the best of our knowledge, however, there is no literature addressing this problem in an explicit way. Therefore, we first provide a detailed procedure to specify Λ and λmin. Then, some simulated and real-world data with various censoring rates are used to examine how well stability selection performs. It is also compared with several other variable selection approaches. Experimental results demonstrate that it achieves better or competitive performance in comparison with several other popular techniques.

  17. A study of the slope of cox proportional hazard and Weibull models ...

    African Journals Online (AJOL)

    However, when the distributional assumptions for Weibull Model is not satisfied, Cox Proportional Hazard Model will be used, although semi-parametric, because it possessed a similar characteristic of covariates inclusion. The main objective of this research work is to determine if the cox proportional hazard model depend ...

  18. Turbine stage model

    International Nuclear Information System (INIS)

    Kazantsev, A.A.

    2009-01-01

    A model of turbine stage for calculations of NPP turbine department dynamics in real time was developed. The simulation results were compared with manufacturer calculations for NPP low-speed and fast turbines. The comparison results have shown that the model is valid for real time simulation of all modes of turbines operation. The model allows calculating turbine stage parameters with 1% accuracy. It was shown that the developed turbine stage model meets the accuracy requirements if the data of turbine blades setting angles for all turbine stages are available [ru

  19. Model checks for Cox-type regression models based on optimally weighted martingale residuals.

    Science.gov (United States)

    Gandy, Axel; Jensen, Uwe

    2009-12-01

    We introduce directed goodness-of-fit tests for Cox-type regression models in survival analysis. "Directed" means that one may choose against which alternatives the tests are particularly powerful. The tests are based on sums of weighted martingale residuals and their asymptotic distributions.We derive optimal tests against certain competing models which include Cox-type regression models with different covariates and/or a different link function. We report results from several simulation studies and apply our test to a real dataset.

  20. Multi-omics facilitated variable selection in Cox-regression model for cancer prognosis prediction.

    Science.gov (United States)

    Liu, Cong; Wang, Xujun; Genchev, Georgi Z; Lu, Hui

    2017-07-15

    New developments in high-throughput genomic technologies have enabled the measurement of diverse types of omics biomarkers in a cost-efficient and clinically-feasible manner. Developing computational methods and tools for analysis and translation of such genomic data into clinically-relevant information is an ongoing and active area of investigation. For example, several studies have utilized an unsupervised learning framework to cluster patients by integrating omics data. Despite such recent advances, predicting cancer prognosis using integrated omics biomarkers remains a challenge. There is also a shortage of computational tools for predicting cancer prognosis by using supervised learning methods. The current standard approach is to fit a Cox regression model by concatenating the different types of omics data in a linear manner, while penalty could be added for feature selection. A more powerful approach, however, would be to incorporate data by considering relationships among omics datatypes. Here we developed two methods: a SKI-Cox method and a wLASSO-Cox method to incorporate the association among different types of omics data. Both methods fit the Cox proportional hazards model and predict a risk score based on mRNA expression profiles. SKI-Cox borrows the information generated by these additional types of omics data to guide variable selection, while wLASSO-Cox incorporates this information as a penalty factor during model fitting. We show that SKI-Cox and wLASSO-Cox models select more true variables than a LASSO-Cox model in simulation studies. We assess the performance of SKI-Cox and wLASSO-Cox using TCGA glioblastoma multiforme and lung adenocarcinoma data. In each case, mRNA expression, methylation, and copy number variation data are integrated to predict the overall survival time of cancer patients. Our methods achieve better performance in predicting patients' survival in glioblastoma and lung adenocarcinoma. Copyright © 2017. Published by Elsevier

  1. Maximal COX-2 and ppRb expression in neurons occurs during early Braak stages prior to the maximal activation of astrocytes and microglia in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Arendt Thomas

    2005-11-01

    Full Text Available Abstract Neuronal expression of cyclooxygenase-2 (COX-2 and cell cycle proteins is suggested to contribute to neurodegeneration during Alzheimer's disease (AD. The stimulus that induces COX-2 and cell cycle protein expression in AD is still elusive. Activated glia cells are shown to secrete substances that can induce expression of COX-2 and cell cycle proteins in vitro. Using post mortem brain tissue we have investigated whether activation of microglia and astrocytes in AD brain can be correlated with the expression of COX-2 and phosphorylated retinoblastoma protein (ppRb. The highest levels of neuronal COX-2 and ppRb immunoreactivity are observed in the first stages of AD pathology (Braak 0–II, Braak A. No significant difference in COX-2 or ppRb neuronal immunoreactivity is observed between Braak stage 0 and later Braak stages for neurofibrillary changes or amyloid plaques. The mean number of COX-2 or ppRb immunoreactive neurons is significantly decreased in Braak stage C compared to Braak stage A for amyloid deposits. Immunoreactivity for glial markers KP1, CR3/43 and GFAP appears in the later Braak stages and is significantly increased in Braak stage V-VI compared to Braak stage 0 for neurofibrillary changes. In addition, a significant negative correlation is observed between the presence of KP1, CR3/43 and GFAP immunoreactivity and the presence of neuronal immunoreactivity for COX-2 and ppRb. These data show that maximal COX-2 and ppRb immunoreactivity in neurons occurs during early Braak stages prior to the maximal activation of astrocytes and microglia. In contrast to in vitro studies, post mortem data do not support a causal relation between the activation of microglia and astrocytes and the expression of neuronal COX-2 and ppRb in the pathological cascade of AD.

  2. Cox Proportional Hazards Models for Modeling the Time to Onset of Decompression Sickness in Hypobaric Environments

    Science.gov (United States)

    Thompson, Laura A.; Chhikara, Raj S.; Conkin, Johnny

    2003-01-01

    In this paper we fit Cox proportional hazards models to a subset of data from the Hypobaric Decompression Sickness Databank. The data bank contains records on the time to decompression sickness (DCS) and venous gas emboli (VGE) for over 130,000 person-exposures to high altitude in chamber tests. The subset we use contains 1,321 records, with 87% censoring, and has the most recent experimental tests on DCS made available from Johnson Space Center. We build on previous analyses of this data set by considering more expanded models and more detailed model assessments specific to the Cox model. Our model - which is stratified on the quartiles of the final ambient pressure at altitude - includes the final ambient pressure at altitude as a nonlinear continuous predictor, the computed tissue partial pressure of nitrogen at altitude, and whether exercise was done at altitude. We conduct various assessments of our model, many of which are recently developed in the statistical literature, and conclude where the model needs improvement. We consider the addition of frailties to the stratified Cox model, but found that no significant gain was attained above a model that does not include frailties. Finally, we validate some of the models that we fit.

  3. Prediction of Mild Cognitive Impairment Conversion Using a Combination of Independent Component Analysis and the Cox Model.

    Science.gov (United States)

    Liu, Ke; Chen, Kewei; Yao, Li; Guo, Xiaojuan

    2017-01-01

    Mild cognitive impairment (MCI) represents a transitional stage from normal aging to Alzheimer's disease (AD) and corresponds to a higher risk of developing AD. Thus, it is necessary to explore and predict the onset of AD in MCI stage. In this study, we propose a combination of independent component analysis (ICA) and the multivariate Cox proportional hazards regression model to investigate promising risk factors associated with MCI conversion among 126 MCI converters and 108 MCI non-converters from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Using structural magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) data, we extracted brain networks from AD and normal control groups via ICA and then constructed Cox models that included network-based neuroimaging factors for the MCI group. We carried out five separate Cox analyses and the two-modality neuroimaging Cox model identified three significant network-based risk factors with higher prediction performance (accuracy = 73.50%) than those in either single-modality model (accuracy = 68.80%). Additionally, the results of the comprehensive Cox model, including significant neuroimaging factors and clinical variables, demonstrated that MCI individuals with reduced gray matter volume in a temporal lobe-related network of structural MRI [hazard ratio (HR) = 8.29E-05 (95% confidence interval (CI), 5.10E- 07 ~ 0.013)], low glucose metabolism in the posterior default mode network based on FDG-PET [HR = 0.066 (95% CI, 4.63E-03 ~ 0.928)], positive apolipoprotein E ε4-status [HR = 1. 988 (95% CI, 1.531 ~ 2.581)], increased Alzheimer's Disease Assessment Scale-Cognitive Subscale scores [HR = 1.100 (95% CI, 1.059 ~ 1.144)] and Sum of Boxes of Clinical Dementia Rating scores [HR = 1.622 (95% CI, 1.364 ~ 1.930)] were more likely to convert to AD within 36 months after baselines. These significant risk factors in such comprehensive Cox model had the best prediction

  4. Bond and CDS Pricing via the Stochastic Recovery Black-Cox Model

    Directory of Open Access Journals (Sweden)

    Albert Cohen

    2017-04-01

    Full Text Available Building on recent work incorporating recovery risk into structural models by Cohen & Costanzino (2015, we consider the Black-Cox model with an added recovery risk driver. The recovery risk driver arises naturally in the context of imperfect information implicit in the structural framework. This leads to a two-factor structural model we call the Stochastic Recovery Black-Cox model, whereby the asset risk driver At defines the default trigger and the recovery risk driver Rt defines the amount recovered in the event of default. We then price zero-coupon bonds and credit default swaps under the Stochastic Recovery Black-Cox model. Finally, we compare our results with the classic Black-Cox model, give explicit expressions for the recovery risk premium in the Stochastic Recovery Black-Cox model, and detail how the introduction of separate but correlated risk drivers leads to a decoupling of the default and recovery risk premiums in the credit spread. We conclude this work by computing the effect of adding coupons that are paid continuously until default, and price perpetual (consol bonds in our two-factor firm value model, extending calculations in the seminal paper by Leland (1994.

  5. Cyclooxygenase 2 (COX2 and Peroxisome Proliferator-Activated Receptor Gamma (PPARG Are Stage-Dependent Prognostic Markers of Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Stefanie Meyer

    2010-01-01

    TMA-1 contained normal and tumor tissues (n=3448 from 47 organs including skin neoplasms (n=323; TMA-2 88 primary MM, 101 metastases, and 161 benign nevi. Based on a biomodulatory approach combining COX/PPAR-targeting with metronomic low-dose chemotherapy metastases of 36 patients participating in a randomized trial with metastatic (stage IV melanoma were investigated using TMA-3. COX2/PPARG immunoreactivity significantly increased from nevi to primary MM and metastases; COX2 positivity was associated with advanced Clark levels and shorter recurrence-free survival. Patients with PPARG-positive metastases and biomodulatory metronomic chemotherapy alone or combined with COX2/PPARG-targeting showed a significantly prolonged progression-free survival. Regarding primary MM, COX2 expression indicates an increased risk of tumor recurrence. In metastatic MM, PPARG expression may be a predicitive marker for response to biomodulatory stroma-targeted therapy.

  6. Cox proportional hazards models have more statistical power than logistic regression models in cross-sectional genetic association studies

    NARCIS (Netherlands)

    van der Net, Jeroen B.; Janssens, A. Cecile J. W.; Eijkemans, Marinus J. C.; Kastelein, John J. P.; Sijbrands, Eric J. G.; Steyerberg, Ewout W.

    2008-01-01

    Cross-sectional genetic association studies can be analyzed using Cox proportional hazards models with age as time scale, if age at onset of disease is known for the cases and age at data collection is known for the controls. We assessed to what degree and under what conditions Cox proportional

  7. Measures to assess the prognostic ability of the stratified Cox proportional hazards model

    DEFF Research Database (Denmark)

    (Tybjaerg-Hansen, A.) The Fibrinogen Studies Collaboration.The Copenhagen City Heart Study; Tybjærg-Hansen, Anne

    2009-01-01

    Many measures have been proposed to summarize the prognostic ability of the Cox proportional hazards (CPH) survival model, although none is universally accepted for general use. By contrast, little work has been done to summarize the prognostic ability of the stratified CPH model; such measures...

  8. Estimation in the positive stable shared frailty Cox proportional hazards model

    DEFF Research Database (Denmark)

    Martinussen, Torben; Pipper, Christian Bressen

    2005-01-01

    model in situations where the correlated survival data show a decreasing association with time. In this paper, we devise a likelihood based estimation procedure for the positive stable shared frailty Cox model, which is expected to obtain high efficiency. The proposed estimator is provided with large...

  9. a study of the slope of cox proportional hazard and weibull models

    African Journals Online (AJOL)

    Adejumo & Ahmadu

    Keywords: Cox Proportional Hazard Model, Weibull Model,. Slope, Shape parameters, Scale parameter, Survival time. INTRODUCTION. Survival analysis studies the amount of time that it takes before a particular event, such as death, occurrence of a disease, marriage, divorce, occurs. However, the same techniques can ...

  10. A new semi-supervised learning model combined with Cox and SP-AFT models in cancer survival analysis.

    Science.gov (United States)

    Chai, Hua; Li, Zi-Na; Meng, De-Yu; Xia, Liang-Yong; Liang, Yong

    2017-10-12

    Gene selection is an attractive and important task in cancer survival analysis. Most existing supervised learning methods can only use the labeled biological data, while the censored data (weakly labeled data) far more than the labeled data are ignored in model building. Trying to utilize such information in the censored data, a semi-supervised learning framework (Cox-AFT model) combined with Cox proportional hazard (Cox) and accelerated failure time (AFT) model was used in cancer research, which has better performance than the single Cox or AFT model. This method, however, is easily affected by noise. To alleviate this problem, in this paper we combine the Cox-AFT model with self-paced learning (SPL) method to more effectively employ the information in the censored data in a self-learning way. SPL is a kind of reliable and stable learning mechanism, which is recently proposed for simulating the human learning process to help the AFT model automatically identify and include samples of high confidence into training, minimizing interference from high noise. Utilizing the SPL method produces two direct advantages: (1) The utilization of censored data is further promoted; (2) the noise delivered to the model is greatly decreased. The experimental results demonstrate the effectiveness of the proposed model compared to the traditional Cox-AFT model.

  11. Survival prediction based on compound covariate under Cox proportional hazard models.

    Directory of Open Access Journals (Sweden)

    Takeshi Emura

    Full Text Available Survival prediction from a large number of covariates is a current focus of statistical and medical research. In this paper, we study a methodology known as the compound covariate prediction performed under univariate Cox proportional hazard models. We demonstrate via simulations and real data analysis that the compound covariate method generally competes well with ridge regression and Lasso methods, both already well-studied methods for predicting survival outcomes with a large number of covariates. Furthermore, we develop a refinement of the compound covariate method by incorporating likelihood information from multivariate Cox models. The new proposal is an adaptive method that borrows information contained in both the univariate and multivariate Cox regression estimators. We show that the new proposal has a theoretical justification from a statistical large sample theory and is naturally interpreted as a shrinkage-type estimator, a popular class of estimators in statistical literature. Two datasets, the primary biliary cirrhosis of the liver data and the non-small-cell lung cancer data, are used for illustration. The proposed method is implemented in R package "compound.Cox" available in CRAN at http://cran.r-project.org/.

  12. Survival prediction based on compound covariate under Cox proportional hazard models.

    Science.gov (United States)

    Emura, Takeshi; Chen, Yi-Hau; Chen, Hsuan-Yu

    2012-01-01

    Survival prediction from a large number of covariates is a current focus of statistical and medical research. In this paper, we study a methodology known as the compound covariate prediction performed under univariate Cox proportional hazard models. We demonstrate via simulations and real data analysis that the compound covariate method generally competes well with ridge regression and Lasso methods, both already well-studied methods for predicting survival outcomes with a large number of covariates. Furthermore, we develop a refinement of the compound covariate method by incorporating likelihood information from multivariate Cox models. The new proposal is an adaptive method that borrows information contained in both the univariate and multivariate Cox regression estimators. We show that the new proposal has a theoretical justification from a statistical large sample theory and is naturally interpreted as a shrinkage-type estimator, a popular class of estimators in statistical literature. Two datasets, the primary biliary cirrhosis of the liver data and the non-small-cell lung cancer data, are used for illustration. The proposed method is implemented in R package "compound.Cox" available in CRAN at http://cran.r-project.org/.

  13. Comparison of Cox Model Methods in A Low-dimensional Setting with Few Events

    Directory of Open Access Journals (Sweden)

    Francisco M. Ojeda

    2016-08-01

    Full Text Available Prognostic models based on survival data frequently make use of the Cox proportional hazards model. Developing reliable Cox models with few events relative to the number of predictors can be challenging, even in low-dimensional datasets, with a much larger number of observations than variables. In such a setting we examined the performance of methods used to estimate a Cox model, including (i full model using all available predictors and estimated by standard techniques, (ii backward elimination (BE, (iii ridge regression, (iv least absolute shrinkage and selection operator (lasso, and (v elastic net. Based on a prospective cohort of patients with manifest coronary artery disease (CAD, we performed a simulation study to compare the predictive accuracy, calibration, and discrimination of these approaches. Candidate predictors for incident cardiovascular events we used included clinical variables, biomarkers, and a selection of genetic variants associated with CAD. The penalized methods, i.e., ridge, lasso, and elastic net, showed a comparable performance, in terms of predictive accuracy, calibration, and discrimination, and outperformed BE and the full model. Excessive shrinkage was observed in some cases for the penalized methods, mostly on the simulation scenarios having the lowest ratio of a number of events to the number of variables. We conclude that in similar settings, these three penalized methods can be used interchangeably. The full model and backward elimination are not recommended in rare event scenarios.

  14. A simple approach to power and sample size calculations in logistic regression and Cox regression models.

    Science.gov (United States)

    Vaeth, Michael; Skovlund, Eva

    2004-06-15

    For a given regression problem it is possible to identify a suitably defined equivalent two-sample problem such that the power or sample size obtained for the two-sample problem also applies to the regression problem. For a standard linear regression model the equivalent two-sample problem is easily identified, but for generalized linear models and for Cox regression models the situation is more complicated. An approximately equivalent two-sample problem may, however, also be identified here. In particular, we show that for logistic regression and Cox regression models the equivalent two-sample problem is obtained by selecting two equally sized samples for which the parameters differ by a value equal to the slope times twice the standard deviation of the independent variable and further requiring that the overall expected number of events is unchanged. In a simulation study we examine the validity of this approach to power calculations in logistic regression and Cox regression models. Several different covariate distributions are considered for selected values of the overall response probability and a range of alternatives. For the Cox regression model we consider both constant and non-constant hazard rates. The results show that in general the approach is remarkably accurate even in relatively small samples. Some discrepancies are, however, found in small samples with few events and a highly skewed covariate distribution. Comparison with results based on alternative methods for logistic regression models with a single continuous covariate indicates that the proposed method is at least as good as its competitors. The method is easy to implement and therefore provides a simple way to extend the range of problems that can be covered by the usual formulas for power and sample size determination. Copyright 2004 John Wiley & Sons, Ltd.

  15. Network regularised Cox regression and multiplex network models to predict disease comorbidities and survival of cancer.

    Science.gov (United States)

    Xu, Haoming; Moni, Mohammad Ali; Liò, Pietro

    2015-12-01

    In cancer genomics, gene expression levels provide important molecular signatures for all types of cancer, and this could be very useful for predicting the survival of cancer patients. However, the main challenge of gene expression data analysis is high dimensionality, and microarray is characterised by few number of samples with large number of genes. To overcome this problem, a variety of penalised Cox proportional hazard models have been proposed. We introduce a novel network regularised Cox proportional hazard model and a novel multiplex network model to measure the disease comorbidities and to predict survival of the cancer patient. Our methods are applied to analyse seven microarray cancer gene expression datasets: breast cancer, ovarian cancer, lung cancer, liver cancer, renal cancer and osteosarcoma. Firstly, we applied a principal component analysis to reduce the dimensionality of original gene expression data. Secondly, we applied a network regularised Cox regression model on the reduced gene expression datasets. By using normalised mutual information method and multiplex network model, we predict the comorbidities for the liver cancer based on the integration of diverse set of omics and clinical data, and we find the diseasome associations (disease-gene association) among different cancers based on the identified common significant genes. Finally, we evaluated the precision of the approach with respect to the accuracy of survival prediction using ROC curves. We report that colon cancer, liver cancer and renal cancer share the CXCL5 gene, and breast cancer, ovarian cancer and renal cancer share the CCND2 gene. Our methods are useful to predict survival of the patient and disease comorbidities more accurately and helpful for improvement of the care of patients with comorbidity. Software in Matlab and R is available on our GitHub page: https://github.com/ssnhcom/NetworkRegularisedCox.git. Copyright © 2015. Published by Elsevier Ltd.

  16. BFLCRM: A BAYESIAN FUNCTIONAL LINEAR COX REGRESSION MODEL FOR PREDICTING TIME TO CONVERSION TO ALZHEIMER'S DISEASE.

    Science.gov (United States)

    Lee, Eunjee; Zhu, Hongtu; Kong, Dehan; Wang, Yalin; Giovanello, Kelly Sullivan; Ibrahim, Joseph G

    2015-12-01

    The aim of this paper is to develop a Bayesian functional linear Cox regression model (BFLCRM) with both functional and scalar covariates. This new development is motivated by establishing the likelihood of conversion to Alzheimer's disease (AD) in 346 patients with mild cognitive impairment (MCI) enrolled in the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) and the early markers of conversion. These 346 MCI patients were followed over 48 months, with 161 MCI participants progressing to AD at 48 months. The functional linear Cox regression model was used to establish that functional covariates including hippocampus surface morphology and scalar covariates including brain MRI volumes, cognitive performance (ADAS-Cog), and APOE status can accurately predict time to onset of AD. Posterior computation proceeds via an efficient Markov chain Monte Carlo algorithm. A simulation study is performed to evaluate the finite sample performance of BFLCRM.

  17. An application of nonparametric Cox regression model in reliability analysis: A case study

    Czech Academy of Sciences Publication Activity Database

    Volf, Petr

    2004-01-01

    Roč. 40, č. 5 (2004), s. 639-648 ISSN 0023-5954 R&D Projects: GA ČR GA201/02/0049; GA ČR GA402/01/0539 Institutional research plan: CEZ:AV0Z1075907 Keywords : hazard rate * nonparametric regression * Cox model Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 0.224, year: 2004

  18. Accounting for covariate measurement error in a Cox model analysis of recurrence of depression.

    Science.gov (United States)

    Liu, K; Mazumdar, S; Stone, R A; Dew, M A; Houck, P R; Reynolds, C F

    2001-01-01

    When a covariate measured with error is used as a predictor in a survival analysis using the Cox model, the parameter estimate is usually biased. In clinical research, covariates measured without error such as treatment procedure or sex are often used in conjunction with a covariate measured with error. In a randomized clinical trial of two types of treatments, we account for the measurement error in the covariate, log-transformed total rapid eye movement (REM) activity counts, in a Cox model analysis of the time to recurrence of major depression in an elderly population. Regression calibration and two variants of a likelihood-based approach are used to account for measurement error. The likelihood-based approach is extended to account for the correlation between replicate measures of the covariate. Using the replicate data decreases the standard error of the parameter estimate for log(total REM) counts while maintaining the bias reduction of the estimate. We conclude that covariate measurement error and the correlation between replicates can affect results in a Cox model analysis and should be accounted for. In the depression data, these methods render comparable results that have less bias than the results when measurement error is ignored.

  19. Performance of the marginal structural cox model for estimating individual and joined effects of treatments given in combination.

    Science.gov (United States)

    Lusivika-Nzinga, Clovis; Selinger-Leneman, Hana; Grabar, Sophie; Costagliola, Dominique; Carrat, Fabrice

    2017-12-04

    The Marginal Structural Cox Model (Cox-MSM), an alternative approach to handle time-dependent confounder, was introduced for survival analysis and applied to estimate the joint causal effect of two time-dependent nonrandomized treatments on survival among HIV-positive subjects. Nevertheless, Cox-MSM performance in the case of multiple treatments has not been fully explored under different degree of time-dependent confounding for treatments or in case of interaction between treatments. We aimed to evaluate and compare the performance of the marginal structural Cox model (Cox-MSM) to the standard Cox model in estimating the treatment effect in the case of multiple treatments under different scenarios of time-dependent confounding and when an interaction between treatment effects is present. We specified a Cox-MSM with two treatments including an interaction term for situations where an adverse event might be caused by two treatments taken simultaneously but not by each treatment taken alone. We simulated longitudinal data with two treatments and a time-dependent confounder affected by one or the two treatments. To fit the Cox-MSM, we used the inverse probability weighting method. We illustrated the method to evaluate the specific effect of protease inhibitors combined (or not) to other antiretroviral medications on the anal cancer risk in HIV-infected individuals, with CD4 cell count as time-dependent confounder. Overall, Cox-MSM performed better than the standard Cox model. Furthermore, we showed that estimates were unbiased when an interaction term was included in the model. Cox-MSM may be used for accurately estimating causal individual and joined treatment effects from a combination therapy in presence of time-dependent confounding provided that an interaction term is estimated.

  20. Structured Spatio-temporal shot-noise Cox point process models, with a view to modelling forest fires

    DEFF Research Database (Denmark)

    Møller, Jesper; Diaz-Avalos, Carlos

    2010-01-01

    Spatio-temporal Cox point process models with a multiplicative structure for the driving random intensity, incorporating covariate information into temporal and spatial components, and with a residual term modelled by a shot-noise process, are considered. Such models are flexible and tractable...

  1. Structured spatio-temporal shot-noise Cox point process models, with a view to modelling forest fires

    DEFF Research Database (Denmark)

    Møller, Jesper; Diaz-Avalos, Carlos

    Spatio-temporal Cox point process models with a multiplicative structure for the driving random intensity, incorporating covariate information into temporal and spatial components, and with a residual term modelled by a shot-noise process, are considered. Such models are flexible and tractable...

  2. Analysis of a genetically structured variance heterogeneity model using the Box-Cox transformation

    DEFF Research Database (Denmark)

    Yang, Ye; Christensen, Ole Fredslund; Sorensen, Daniel

    2011-01-01

    of the marginal distribution of the data. To investigate how the scale of measurement affects inferences, the genetically structured heterogeneous variance model is extended to accommodate the family of Box–Cox transformations. Litter size data in rabbits and pigs that had previously been analysed...... in the untransformed scale were reanalysed in a scale equal to the mode of the marginal posterior distribution of the Box–Cox parameter. In the rabbit data, the statistical evidence for a genetic component at the level of the environmental variance is considerably weaker than that resulting from an analysis...... in the original metric. In the pig data, the statistical evidence is stronger, but the coefficient of correlation between additive genetic effects affecting mean and variance changes sign, compared to the results in the untransformed scale. The study confirms that inferences on variances can be strongly affected...

  3. [Effects of polydatin on ALT, AST, TNF-alpha, and COX-2 in sepsis model mice].

    Science.gov (United States)

    Li, Xiao-Hui; Wu, Meng-Jiao; Zhang, Li-Na; Zheng, Jia-Jia; Zhang, Li; Wan, Jing-Yuan

    2013-02-01

    To investigate the protective effects of polydatin on sepsis-induced acute liver injury (ALI) in mice, and to preliminarily study its mechanisms. The sepsis model was established using cecal ligation and puncture (CLP).A sham-operation control group was also set up. Polydatin (50, 100, and 300 mg/kg, respectively) was administrated to mice 1 h before CLP. The survival and liver injury were evaluated subsequently per 6 h after CLP. The survived mice were scarified 24 h later. The serum and the liver tissue sample were collected. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by colorimetric method. The content of tumor necrosis factor-alpha (TNF-alpha) was assayed by ELISA. The cyclooxygenase-2 (COX-2) expression in the liver tissue was detected by Western blot. The pathological changes of the hepatic tissue were analyzed by hematoxylin and eosin stain. The mortality of mice reached as high as 50% at 24 h after CLP. The biochemical indices and the pathological changes of the liver tissue showed obvious lesion. The success rate of modeling was 90%. Compared with the sham-operation control group, the serum ALT,AST activity, the TNF-alpha content, and the hepatic COX-2 protein expression markedly increased in the CLP group (P < 0.01). Polydatin improved the sepsis-induced mortality dose-dependently, inhibited increased ALT, AST activity and TNF-alpha, decreased the hepatic COX-2 protein expression, and attenuated the pathological injury of the liver (P < 0.05). Polydatin could effectively protect sepsis-induced ALI, which might be achieved possibly through inhibiting serum TNF-alpha production and hepatic COX-2 expression.

  4. The tariff for fire and theft car insurance: analysis with a Cox model

    Directory of Open Access Journals (Sweden)

    Bruno Scarpa

    2013-05-01

    Full Text Available In this paper we analyze the problem of identification of a tariff for a Fire & Theft Car policy for Insurance Companies. Usually companies obtain this tariff by empirical estimate of the pure rate by evaluating the impact of some personalization variables. In this paper we propose the usage of a semi-parametric Cox model, where the response variable is not the waiting time until an event, but the degree of damage because of theft or fire of a car. The proposed model allows to easily tackle typical problems in data available to the companies, like the presence of franchises, which are treated as censored data.

  5. Segmented relationships to model erosion of regression effect in Cox regression.

    Science.gov (United States)

    Muggeo, Vito M R; Attanasio, Massimo

    2011-08-01

    In this article we propose a parsimonious parameterisation to model the so-called erosion of the covariate effect in the Cox model, namely a covariate effect approaching to zero as the follow-up time increases. The proposed parameterisation is based on the segmented relationship where proper constraints are set to accomodate for the erosion. Relevant hypothesis testing is discussed. The approach is illustrated on two historical datasets in the survival analysis literature, and some simulation studies are presented to show how the proposed framework leads to a test for a global effect with good power as compared with alternative procedures. Finally, possible generalisations are also presented for future research.

  6. Pseudo-partial likelihood estimators for the Cox regression model with missing covariates.

    Science.gov (United States)

    Luo, Xiaodong; Tsai, Wei Yann; Xu, Qiang

    2009-09-01

    By embedding the missing covariate data into a left-truncated and right-censored survival model, we propose a new class of weighted estimating functions for the Cox regression model with missing covariates. The resulting estimators, called the pseudo-partial likelihood estimators, are shown to be consistent and asymptotically normal. A simulation study demonstrates that, compared with the popular inverse-probability weighted estimators, the new estimators perform better when the observation probability is small and improve efficiency of estimating the missing covariate effects. Application to a practical example is reported.

  7. PET imaging of cyclooxygenase-2 (COX-2) in a pre-clinical colorectal cancer model.

    Science.gov (United States)

    Tietz, Ole; Wuest, Melinda; Marshall, Alison; Glubrecht, Darryl; Hamann, Ingrit; Wang, Monica; Bergman, Cody; Way, Jenilee D; Wuest, Frank

    2016-12-01

    Cyclooxygenase-2 (COX-2) is the inducible isoform of the cyclooxygenase enzyme family. COX-2 is involved in tumor development and progression, and frequent overexpression of COX-2 in a variety of human cancers has made COX-2 an important drug target for cancer treatment. Non-invasive imaging of COX-2 expression in cancer would be useful for assessing COX-2-mediated effects on chemoprevention and radiosensitization using COX-2 inhibitors as an emerging class of anti-cancer drugs, especially for colorectal cancer. Herein, we describe the radiopharmacological analysis of [(18)F]Pyricoxib, a novel radiolabeled COX-2 inhibitor, for specific PET imaging of COX-2 in colorectal cancer. Uptake of [(18)F]Pyricoxib was assessed in human colorectal cancer cell lines HCA-7 (COX-2 positive) and HCT-116 (COX-2 negative). Standard COX-2 inhibitors were used to test for specificity of [(18)F]Pyricoxib for COX-2 binding in vitro and in vivo. PET imaging, biodistribution, and radiometabolite analyses were included into radiopharmacological evaluation of [(18)F]Pyricoxib. Radiotracer uptake in COX-2 positive HCA-7 cells was significantly higher than in COX-2 negative HCT-116 cells (P COX-2 inhibitors, celecoxib, rofecoxib, and SC58125, blocked uptake of [(18)F]Pyricoxib in HCA-7 cells in a concentration-dependent manner. The radiotracer was slowly metabolized in mice, with approximately 60 % of intact compound after 2 h post-injection. Selective COX-2-mediated tumor uptake of [(18)F]Pyricoxib in HCA-7 xenografts was confirmed in vivo. Celecoxib (100 mg/kg) selectively blocked tumor uptake by 16 % (PET image analysis; P COX-2 expression in cancer in vivo.

  8. DR Cox

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. D R Cox. Articles written in Resonance – Journal of Science Education. Volume 18 Issue 12 December 2013 pp 1133-1149 Classics. Some Problems Connected with Statistical Inference · D R Cox · More Details Fulltext PDF ...

  9. Cox models with dynamic ridge penalties on time-varying effects of the covariates.

    Science.gov (United States)

    Perperoglou, Aris

    2014-01-15

    Analysis of long-term follow-up survival studies require more sophisticated approaches than the proportional hazards model. To account for the dynamic behaviour of fixed covariates, penalized Cox models can be employed in models with interactions of the covariates and known time functions. In this work, I discuss some of the suggested methods and emphasize on the use of a ridge penalty in survival models. I review different strategies for choosing an optimal penalty weight and argue for the use of the computationally efficient restricted maximum likelihood (REML)-type method. A ridge penalty term can be subtracted from the likelihood when modelling time-varying effects in order to control the behaviour of the time functions. I suggest using flexible time functions such as B-splines and constrain the behaviour of these by adding proper penalties. I present the basic methods and illustrate different penalty weights in two different datasets. Copyright © 2013 John Wiley & Sons, Ltd.

  10. A random effects meta-analysis model with Box-Cox transformation.

    Science.gov (United States)

    Yamaguchi, Yusuke; Maruo, Kazushi; Partlett, Christopher; Riley, Richard D

    2017-07-19

    In a random effects meta-analysis model, true treatment effects for each study are routinely assumed to follow a normal distribution. However, normality is a restrictive assumption and the misspecification of the random effects distribution may result in a misleading estimate of overall mean for the treatment effect, an inappropriate quantification of heterogeneity across studies and a wrongly symmetric prediction interval. We focus on problems caused by an inappropriate normality assumption of the random effects distribution, and propose a novel random effects meta-analysis model where a Box-Cox transformation is applied to the observed treatment effect estimates. The proposed model aims to normalise an overall distribution of observed treatment effect estimates, which is sum of the within-study sampling distributions and the random effects distribution. When sampling distributions are approximately normal, non-normality in the overall distribution will be mainly due to the random effects distribution, especially when the between-study variation is large relative to the within-study variation. The Box-Cox transformation addresses this flexibly according to the observed departure from normality. We use a Bayesian approach for estimating parameters in the proposed model, and suggest summarising the meta-analysis results by an overall median, an interquartile range and a prediction interval. The model can be applied for any kind of variables once the treatment effect estimate is defined from the variable. A simulation study suggested that when the overall distribution of treatment effect estimates are skewed, the overall mean and conventional I 2 from the normal random effects model could be inappropriate summaries, and the proposed model helped reduce this issue. We illustrated the proposed model using two examples, which revealed some important differences on summary results, heterogeneity measures and prediction intervals from the normal random effects model. The

  11. BOX-COX transformation and random regression models for fecal egg count data

    Directory of Open Access Journals (Sweden)

    Marcos Vinicius Silva

    2012-01-01

    Full Text Available Accurate genetic evaluation of livestock is based on appropriate modeling of phenotypic measurements. In ruminants fecal egg count (FEC is commonly used to measure resistance to nematodes. FEC values are not normally distributed and logarithmic transformations have been used to achieve normality before analysis. However, the transformed data are often not normally distributed, especially when data are extremely skewed. A series of repeated FEC measurements may provide information about the population dynamics of a group or individual. A total of 6,375 FEC measures were obtained for 410 animals between 1992 and 2003 from the Beltsville Agricultural Research Center Angus herd. Original data were transformed using an extension of the Box-Cox transformation to approach normality and to estimate (covariance components. We also proposed using random regression models (RRM for genetic and non-genetic studies of FEC. Phenotypes were analyzed using RRM and restricted maximum likelihood. Within the different orders of Legendre polynomials used, those with more parameters (order 4 adjusted FEC data best. Results indicated that the transformation of FEC data utilizing the Box-Cox transformation family was effective in reducing the skewness and kurtosis, and dramatically increased estimates of heritability, and measurements of FEC obtained in the period between 12 and 26 weeks in a 26-week experimental challenge period are genetically correlated.

  12. Statistical power to detect violation of the proportional hazards assumption when using the Cox regression model.

    Science.gov (United States)

    Austin, Peter C

    2018-01-01

    The use of the Cox proportional hazards regression model is widespread. A key assumption of the model is that of proportional hazards. Analysts frequently test the validity of this assumption using statistical significance testing. However, the statistical power of such assessments is frequently unknown. We used Monte Carlo simulations to estimate the statistical power of two different methods for detecting violations of this assumption. When the covariate was binary, we found that a model-based method had greater power than a method based on cumulative sums of martingale residuals. Furthermore, the parametric nature of the distribution of event times had an impact on power when the covariate was binary. Statistical power to detect a strong violation of the proportional hazards assumption was low to moderate even when the number of observed events was high. In many data sets, power to detect a violation of this assumption is likely to be low to modest.

  13. Positional isomerism markedly affects the growth inhibition of colon cancer cells by NOSH-aspirin: COX inhibition and modeling.

    Science.gov (United States)

    Vannini, Federica; Chattopadhyay, Mitali; Kodela, Ravinder; Rao, Praveen P N; Kashfi, Khosrow

    2015-12-01

    We recently reported the synthesis of NOSH-aspirin, a novel hybrid that releases both nitric oxide (NO) and hydrogen sulfide (H2S). In NOSH-aspirin, the two moieties that release NO and H2S are covalently linked at the 1, 2 positions of acetyl salicylic acid, i.e. ortho-NOSH-aspirin (o-NOSH-aspirin). In the present study, we compared the effects of the positional isomers of NOSH-ASA (o-NOSH-aspirin, m-NOSH-aspirin and p-NOSH-aspirin) to that of aspirin on growth of HT-29 and HCT 15 colon cancer cells, belonging to the same histological subtype, but with different expression of cyclooxygenase (COX) enzymes; HT-29 express both COX-1 and COX-2, whereas HCT 15 is COX-null. We also analyzed the effect of these compounds on proliferation and apoptosis in HT-29 cells. Since the parent compound aspirin, inhibits both COX-1 and COX-2, we also evaluated the effects of these compounds on COX-1 and COX-2 enzyme activities and also performed modeling of the interactions between the positional isomers of NOSH-aspirin and COX-1 and COX-2 enzymes. We observed that the three positional isomers of NOSH aspirin inhibited the growth of both colon cancer cell lines with IC50s in the nano-molar range. In particular in HT-29 cells the IC50s for growth inhibition were: o-NOSH-ASA, 0.04±0.011 µM; m-NOSH-ASA, 0.24±0.11 µM; p-NOSH-ASA, 0.46±0.17 µM; and in HCT 15 cells the IC50s for o-NOSH-ASA, m-NOSH-ASA, and p-NOSH-ASA were 0.062 ±0.006 µM, 0.092±0.004 µM, and 0.37±0.04 µM, respectively. The IC50 for aspirin in both cell lines was >5mM at 24h. The reduction of cell growth appeared to be mediated through inhibition of proliferation, and induction of apoptosis. All 3 positional isomers of NOSH-aspirin preferentially inhibited COX-1 over COX-2. These results suggest that the three positional isomers of NOSH-aspirin have the same biological actions, but that o-NOSH-ASA displayed the strongest anti-neoplastic potential. Copyright © 2015 The Authors. Published by Elsevier B.V. All

  14. Nonlinear multiple imputation for continuous covariate within semiparametric Cox model: application to HIV data in Senegal.

    Science.gov (United States)

    Mbougua, Jules Brice Tchatchueng; Laurent, Christian; Ndoye, Ibra; Delaporte, Eric; Gwet, Henri; Molinari, Nicolas

    2013-11-20

    Multiple imputation is commonly used to impute missing covariate in Cox semiparametric regression setting. It is to fill each missing data with more plausible values, via a Gibbs sampling procedure, specifying an imputation model for each missing variable. This imputation method is implemented in several softwares that offer imputation models steered by the shape of the variable to be imputed, but all these imputation models make an assumption of linearity on covariates effect. However, this assumption is not often verified in practice as the covariates can have a nonlinear effect. Such a linear assumption can lead to a misleading conclusion because imputation model should be constructed to reflect the true distributional relationship between the missing values and the observed values. To estimate nonlinear effects of continuous time invariant covariates in imputation model, we propose a method based on B-splines function. To assess the performance of this method, we conducted a simulation study, where we compared the multiple imputation method using Bayesian splines imputation model with multiple imputation using Bayesian linear imputation model in survival analysis setting. We evaluated the proposed method on the motivated data set collected in HIV-infected patients enrolled in an observational cohort study in Senegal, which contains several incomplete variables. We found that our method performs well to estimate hazard ratio compared with the linear imputation methods, when data are missing completely at random, or missing at random. Copyright © 2013 John Wiley & Sons, Ltd.

  15. New Inference Procedures for Semiparametric Varying-Coefficient Partially Linear Cox Models

    Directory of Open Access Journals (Sweden)

    Yunbei Ma

    2014-01-01

    Full Text Available In biomedical research, one major objective is to identify risk factors and study their risk impacts, as this identification can help clinicians to both properly make a decision and increase efficiency of treatments and resource allocation. A two-step penalized-based procedure is proposed to select linear regression coefficients for linear components and to identify significant nonparametric varying-coefficient functions for semiparametric varying-coefficient partially linear Cox models. It is shown that the penalized-based resulting estimators of the linear regression coefficients are asymptotically normal and have oracle properties, and the resulting estimators of the varying-coefficient functions have optimal convergence rates. A simulation study and an empirical example are presented for illustration.

  16. Maximum likelihood estimation for Cox's regression model under nested case-control sampling

    DEFF Research Database (Denmark)

    Scheike, Thomas; Juul, Anders

    2004-01-01

    -like growth factor I was associated with ischemic heart disease. The study was based on a population of 3784 Danes and 231 cases of ischemic heart disease where controls were matched on age and gender. We illustrate the use of the MLE for these data and show how the maximum likelihood framework can be used......Nested case-control sampling is designed to reduce the costs of large cohort studies. It is important to estimate the parameters of interest as efficiently as possible. We present a new maximum likelihood estimator (MLE) for nested case-control sampling in the context of Cox's proportional hazards...... model. The MLE is computed by the EM-algorithm, which is easy to implement in the proportional hazards setting. Standard errors are estimated by a numerical profile likelihood approach based on EM aided differentiation. The work was motivated by a nested case-control study that hypothesized that insulin...

  17. Cox Regression and Parametric Models: Comparison of How They Determine Factors Influencing Survival of Patients with Non-Small Cell Lung Carcinoma

    Science.gov (United States)

    Khaksar, Elahe; Askarishahi, Mohsen; Hekmatimoghaddam, Seyedhossein; Vahedian-Ardakani, Hassanali

    2017-12-29

    Background and objectives: The present study of survival rate of patients with non-small cell carcinoma (NSCLC) compared the efficiency of Cox semi-parametric vs. parametric models in determination of influencing factors. Methods: In this retrospective cohort study, data were gathered from 190 patients with a confirmed diagnosis of NSCLC referred to Shahid Sadoughi and Shohadaye Kargar Hospitals in Yazd, Iran during 2005 to 2014. To identify and compare factors influencing the survival rate, a Cox semi-parametric model was fitted to the data. Data analysis was performed using the R software version R3.3.1, and the significance level was set at 0.05. Results: The average age was 64.5 years. About 40% of patients had stage 4 disease. The median survival was 8 months. After comparing the models, the more efficient was the log-normal distribution (AIC=889.3829), with which disease stage, type of therapy, and age were significant factors. Among the different types of therapy, chemotherapy and radiotherapy yielded higher survival rates, and increased age was associated with lower survival. Conclusion: The most efficient model was a log-normal model. Implementation of optimal therapies at early stages can improve the survival of patients. Creative Commons Attribution License

  18. Multiple imputation of missing covariates for the Cox proportional hazards cure model.

    Science.gov (United States)

    Beesley, Lauren J; Bartlett, Jonathan W; Wolf, Gregory T; Taylor, Jeremy M G

    2016-11-20

    We explore several approaches for imputing partially observed covariates when the outcome of interest is a censored event time and when there is an underlying subset of the population that will never experience the event of interest. We call these subjects 'cured', and we consider the case where the data are modeled using a Cox proportional hazards (CPH) mixture cure model. We study covariate imputation approaches using fully conditional specification. We derive the exact conditional distribution and suggest a sampling scheme for imputing partially observed covariates in the CPH cure model setting. We also propose several approximations to the exact distribution that are simpler and more convenient to use for imputation. A simulation study demonstrates that the proposed imputation approaches outperform existing imputation approaches for survival data without a cure fraction in terms of bias in estimating CPH cure model parameters. We apply our multiple imputation techniques to a study of patients with head and neck cancer. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  19. WebDISCO: a web service for distributed cox model learning without patient-level data sharing.

    Science.gov (United States)

    Lu, Chia-Lun; Wang, Shuang; Ji, Zhanglong; Wu, Yuan; Xiong, Li; Jiang, Xiaoqian; Ohno-Machado, Lucila

    2015-11-01

    The Cox proportional hazards model is a widely used method for analyzing survival data. To achieve sufficient statistical power in a survival analysis, it usually requires a large amount of data. Data sharing across institutions could be a potential workaround for providing this added power. The authors develop a web service for distributed Cox model learning (WebDISCO), which focuses on the proof-of-concept and algorithm development for federated survival analysis. The sensitive patient-level data can be processed locally and only the less-sensitive intermediate statistics are exchanged to build a global Cox model. Mathematical derivation shows that the proposed distributed algorithm is identical to the centralized Cox model. The authors evaluated the proposed framework at the University of California, San Diego (UCSD), Emory, and Duke. The experimental results show that both distributed and centralized models result in near-identical model coefficients with differences in the range [Formula: see text] to [Formula: see text]. The results confirm the mathematical derivation and show that the implementation of the distributed model can achieve the same results as the centralized implementation. The proposed method serves as a proof of concept, in which a publicly available dataset was used to evaluate the performance. The authors do not intend to suggest that this method can resolve policy and engineering issues related to the federated use of institutional data, but they should serve as evidence of the technical feasibility of the proposed approach.Conclusions WebDISCO (Web-based Distributed Cox Regression Model; https://webdisco.ucsd-dbmi.org:8443/cox/) provides a proof-of-concept web service that implements a distributed algorithm to conduct distributed survival analysis without sharing patient level data. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions

  20. Comparison of Cox Model and K-Nearest Neighbor to Estimation of Survival in Kidney Transplant Patients

    Directory of Open Access Journals (Sweden)

    J. Faradmal

    2016-01-01

    Full Text Available Introduction & Objective: Cox model is a common method to estimate survival and validity of the results is dependent on the proportional hazards assumption. K- Nearest neighbor is a nonparametric method for survival probability in heterogeneous communities. The purpose of this study was to compare the performance of k- nearest neighbor method (K-NN with Cox model. Materials & Methods: This retrospective cohort study was conducted in Hamadan Province, on 475 patients who had undergone kidney transplantation from 1994 to 2011. Data were extracted from patients’ medical records using a checklist. The duration of the time between kidney transplantation and rejection was considered as the surviv­al time. Cox model and k- nearest neighbor method were used for Data modeling. The prediction error Brier score was used to compare the performance models. Results: Out of 475 transplantations, 55 episodes of rejection occurred. 5, 10 and 15 year survival rates of transplantation were 91.70 %, 84.90% and 74.50%, respectively. The number of neighborhood optimized using cross validation method was 45. Cumulative Brier score of k-NN algorithm for t=5, 10 and 15 years were 0.003, 0.006 and 0.007, respectively. Cumulative Brier of score Cox model for t=5, 10 and 15 years were 0.036, 0.058 and 0.058, respectively. Prediction error of k-NN algorithm for t=5, 10 and 15 years was less than Cox model that shows that the k-NN method outperforms. Conclusions: The results of this study show that the predictions of KNN has higher accuracy than the Cox model when sample sizes and the number of predictor variables are high. Sci J Hamadan Univ Med Sci . 2016; 22 (4 :300-308

  1. Comparing smoothing techniques in Cox models for exposure-response relationships.

    Science.gov (United States)

    Govindarajulu, Usha S; Spiegelman, Donna; Thurston, Sally W; Ganguli, Bhaswati; Eisen, Ellen A

    2007-09-10

    To allow for non-linear exposure-response relationships, we applied flexible non-parametric smoothing techniques to models of time to lung cancer mortality in two occupational cohorts with skewed exposure distributions. We focused on three different smoothing techniques in Cox models: penalized splines, restricted cubic splines, and fractional polynomials. We compared standard software implementations of these three methods based on their visual representation and criterion for model selection. We propose a measure of the difference between a pair of curves based on the area between them, standardized by the average of the areas under the pair of curves. To capture the variation in the difference over the range of exposure, the area between curves was also calculated at percentiles of exposure and expressed as a percentage of the total difference. The dose-response curves from the three methods were similar in both studies over the denser portion of the exposure range, with the difference between curves up to the 50th percentile less than 1 per cent of the total difference. A comparison of inverse variance weighted areas applied to the data set with a more skewed exposure distribution allowed us to estimate area differences with more precision by reducing the proportion attributed to the upper 1 per cent tail region. Overall, the penalized spline and the restricted cubic spline were closer to each other than either was to the fractional polynomial. (c) 2007 John Wiley & Sons, Ltd.

  2. Fitting Cox Models with Doubly Censored Data Using Spline-Based Sieve Marginal Likelihood

    Science.gov (United States)

    Li, Zhiguo; Owzar, Kouros

    2015-01-01

    In some applications, the failure time of interest is the time from an originating event to a failure event, while both event times are interval censored. We propose fitting Cox proportional hazards models to this type of data using a spline-based sieve maximum marginal likelihood, where the time to the originating event is integrated out in the empirical likelihood function of the failure time of interest. This greatly reduces the complexity of the objective function compared with the fully semiparametric likelihood. The dependence of the time of interest on time to the originating event is induced by including the latter as a covariate in the proportional hazards model for the failure time of interest. The use of splines results in a higher rate of convergence of the estimator of the baseline hazard function compared with the usual nonparametric estimator. The computation of the estimator is facilitated by a multiple imputation approach. Asymptotic theory is established and a simulation study is conducted to assess its finite sample performance. It is also applied to analyzing a real data set on AIDS incubation time. PMID:27239090

  3. Estimating effects of rare haplotypes on failure time using a penalized Cox proportional hazards regression model

    Directory of Open Access Journals (Sweden)

    Tanck Michael WT

    2008-01-01

    Full Text Available Abstract Background This paper describes a likelihood approach to model the relation between failure time and haplotypes in studies with unrelated individuals where haplotype phase is unknown, while dealing with the problem of unstable estimates due to rare haplotypes by considering a penalized log-likelihood. Results The Cox model presented here incorporates the uncertainty related to the unknown phase of multiple heterozygous individuals as weights. Estimation is performed with an EM algorithm. In the E-step the weights are estimated, and in the M-step the parameter estimates are estimated by maximizing the expectation of the joint log-likelihood, and the baseline hazard function and haplotype frequencies are calculated. These steps are iterated until the parameter estimates converge. Two penalty functions are considered, namely the ridge penalty and a difference penalty, which is based on the assumption that similar haplotypes show similar effects. Simulations were conducted to investigate properties of the method, and the association between IL10 haplotypes and risk of target vessel revascularization was investigated in 2653 patients from the GENDER study. Conclusion Results from simulations and real data show that the penalized log-likelihood approach produces valid results, indicating that this method is of interest when studying the association between rare haplotypes and failure time in studies of unrelated individuals.

  4. Neoplasms escape selective COX-2 inhibition in an animal model of breast cancer.

    LENUS (Irish Health Repository)

    Barry, M

    2009-06-01

    Cyclo-oxygenase-2 (COX-2) is up-regulated in malignant tumours rendering it an attractive target for cancer therapeutics. However, whether long-term antagonism maintains its initial efficacy on established tumours is unclear.

  5. Diminished neurogenic femoral artery vasoconstrictor response in a Zucker obese rat model: differential regulation of NOS and COX derivatives.

    Directory of Open Access Journals (Sweden)

    Ana Cristina Martínez

    Full Text Available OBJECTIVE: Peripheral arterial disease is one of the macrovascular complications of type 2 diabetes mellitus. This study addresses femoral artery regulation in a prediabetic model of obese Zucker rats (OZR by examining cross-talk between endothelial and neural factors. METHODS AND RESULTS: Arterial preparations from lean (LZR and OZR were subjected to electrical field stimulation (EFS on basal tone. Nitric oxide synthase (NOS and cyclooxygenase (COX isoform expression patterns were determined by immunohistochemical labelling and Western blotting. Results indicate significantly reduced noradrenergic contractions in preparations from OZR compared with those of LZR. Functional inhibition of endothelial NOS (eNOS indicated a predominant role of this isoform in LZR and its modified activity in OZR. Neural (nNOS and inducible NOS (iNOS were activated and their expression was higher in femoral arteries from OZR. Neurotransmission modulated by large-conductance Ca2+-activated (BKCa or voltage-dependent (KV K+ channels did not seem compromised in the obese animals. Endothelial COX-1 and COX-2 were expressed in LZR and an additional adventitial location of COX-2 was also observed in OZR, explaining the higher COX-2 protein levels detected in this group. Prostanoids derived from both isoforms helped maintain vasoconstriction in LZR while in OZR only COX-2 was active. Superoxide anion inhibition reduced contractions in endothelium-intact arteries from OZR. CONCLUSIONS: Endothelial dysfunction led to reduced neurogenic vasoconstriction in femoral arteries from OZR. In a setting of obesity, NO-dependent nNOS and iNOS dilation activity could be an alternative mechanism to offset COX-2- and reactive oxygen species-mediated vasoconstriction, along with impaired endothelial NO relaxation.

  6. Effects of enriched environment on COX-2, leptin and eicosanoids in a mouse model of breast cancer.

    Directory of Open Access Journals (Sweden)

    Rachida Nachat-Kappes

    Full Text Available Cyclooxygenase-2 (COX-2 and adipokines have been implicated in breast cancer. This study investigated a possible link between COX-2 and adipokines in the development of mammary tumors. A model of environmental enrichment (EE, known to reduce tumor growth was used for a syngeneic murine model of mammary carcinoma. 3-week-old, female C57BL/6 mice were housed in standard environment (SE or EE cages for 9 weeks and transplanted orthotopically with syngeneic EO771 adenocarcinoma cells into the right inguinal mammary fat pad. EE housing influenced mammary gland development with a decrease in COX-2 expressing cells and enhanced side-branching and advanced development of alveolar structures of the mammary gland. Tumor volume and weight were decreased in EE housed mice and were associated with a reduction in COX-2 and Ki67 levels, and an increase in caspase-3 levels. In tumors of SE mice, high COX-2 expression correlated with enhanced leptin detection. Non-tumor-bearing EE mice showed a significant increase in adiponectin levels but no change in those of leptin, F(2-isoprostanes, PGF(2α, IL-6, TNF-α, PAI-1, and MCP-1 levels. Both tumor-bearing groups (SE and EE housing had increased resistin, IL-6, TNF-α, PAI-1 and MCP-1 levels irrespective of the different housing environment demonstrating higher inflammatory response due to the presence of the tumor. This study demonstrates that EE housing influenced normal mammary gland development and inhibited mammary tumor growth resulting in a marked decrease in intratumoral COX-2 activity and an increase in the plasma ratio of adiponectin/leptin levels.

  7. An increased CD25-positive intestinal regulatory T lymphocyte population is dependent upon Cox-2 activity in the Apcmin/+ model.

    Science.gov (United States)

    Faluyi, O O; Fitch, P; Howie, S E M

    2018-01-01

    Only mismatch repair (MMR)-deficient colorectal cancer (CRC) appears to respond well to programmed death (PD)-1 inhibition at the present time. Emerging evidence suggests a role for micro-environmental factors such as CD25 + cells modulating response to PD-1 inhibition. In the Apc Min/+ model of familial adenomatous polyposis (MMR-proficient CRC), increased Cyclooxygenase-2 (Cox-2) expression by cells which include alternatively activated mononuclear phagocytes promotes intestinal tumorigenesis by mechanisms which may include immune suppression. To gain insight into this, we compared regulatory T cell (T reg ) populations between Apc Min/+ and wild-type mice prior to and after the phase of increased intestinal Cox-2-dependent prostaglandin E 2 (PGE 2 ) production. There was no difference in systemic T reg function or numbers between Apc Min/+ and wild-type mice. However, increased numbers of small intestinal CD25 + T regs were observed with increased Cox-2 activity in the absence of any difference in the expression of Tgf-β or Tslp between Apc Min/+ and wild-type mice. Cox-2 inhibitor therapy (Celecoxib) reversed the increase in Apc Min/+ intestinal CD25 + T reg numbers, without decreasing numbers of CD25 + systemic T regs . Forkhead box protein 3 (FoxP3 + ) and Cox-2 + cells were co-localized to the interstitium of adenomas of Apc min/+ mice. These results suggest selective dependence of an 'activated T reg ' phenotype on paracrine Cox-2 activity in Apc Min/+ small intestine. For therapeutic potential, further studies are required to evaluate the relevance of these findings to human cancer as well as the functional significance of CD25 + intestinal T regs in cancer. © 2017 British Society for Immunology.

  8. QSAR Modeling of COX -2 Inhibitory Activity of Some Dihydropyridine and Hydroquinoline Derivatives Using Multiple Linear Regression (MLR) Method.

    Science.gov (United States)

    Akbari, Somaye; Zebardast, Tannaz; Zarghi, Afshin; Hajimahdi, Zahra

    2017-01-01

    COX-2 inhibitory activities of some 1,4-dihydropyridine and 5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives were modeled by quantitative structure-activity relationship (QSAR) using stepwise-multiple linear regression (SW-MLR) method. The built model was robust and predictive with correlation coefficient (R 2 ) of 0.972 and 0.531 for training and test groups, respectively. The quality of the model was evaluated by leave-one-out (LOO) cross validation (LOO correlation coefficient (Q 2 ) of 0.943) and Y-randomization. We also employed a leverage approach for the defining of applicability domain of model. Based on QSAR models results, COX-2 inhibitory activity of selected data set had correlation with BEHm6 (highest eigenvalue n. 6 of Burden matrix/weighted by atomic masses), Mor03u (signal 03/unweighted) and IVDE (Mean information content on the vertex degree equality) descriptors which derived from their structures.

  9. Comparing of Cox model and parametric models in analysis of effective factors on event time of neuropathy in patients with type 2 diabetes.

    Science.gov (United States)

    Kargarian-Marvasti, Sadegh; Rimaz, Shahnaz; Abolghasemi, Jamileh; Heydari, Iraj

    2017-01-01

    Cox proportional hazard model is the most common method for analyzing the effects of several variables on survival time. However, under certain circumstances, parametric models give more precise estimates to analyze survival data than Cox. The purpose of this study was to investigate the comparative performance of Cox and parametric models in a survival analysis of factors affecting the event time of neuropathy in patients with type 2 diabetes. This study included 371 patients with type 2 diabetes without neuropathy who were registered at Fereydunshahr diabetes clinic. Subjects were followed up for the development of neuropathy between 2006 to March 2016. To investigate the factors influencing the event time of neuropathy, significant variables in univariate model ( P Cox and parametric models ( P Cox and parametric models, ethnicity, high-density lipoprotein and family history of diabetes were identified as predictors of event time of neuropathy ( P Cox and parametric models. According to the results of comparison of survival receiver operating characteristics curves, log-normal model was considered as the most efficient and fitted model.

  10. Comparison of Weibull and Lognormal Cure Models with Cox in the Survival Analysis Of Breast Cancer Patients in Rafsanjan.

    Science.gov (United States)

    Hoseini, Mina; Bahrampour, Abbas; Mirzaee, Moghaddameh

    2017-02-16

    Breast cancer is the most common cancer after lung cancer and the second cause of death. In this study we compared Weibull and Lognormal Cure Models with Cox regression on the survival of breast cancer. A cohort study. The current study retrospective cohort study was conducted on 140 patients referred to Ali Ibn Abitaleb Hospital, Rafsanjan southeastern Iran from 2001 to 2015 suffering from breast cancer. We determined and analyzed the effective survival causes by different models using STATA14. According to AIC, log-normal model was more consistent than Weibull. In the multivariable Lognormal model, the effective factors like smoking, second -hand smoking, drinking herbal tea and the last breast-feeding period were included. In addition, using Cox regression factors of significant were the disease grade, size of tumor and its metastasis (p-valuecancer was studied and the results showed that the effect of pesticides on breast cancer was not in agreement with the models used in this study. Based on different methods for survival analysis, researchers can decide how they can reach a better conclusion. This comparison indicates the result of semi-parametric Cox method is closer to clinical experiences evidences.

  11. Formation of translational risk score based on correlation coefficients as an alternative to Cox regression models for predicting outcome in patients with NSCLC

    Directory of Open Access Journals (Sweden)

    ElAidi Tina

    2011-07-01

    Full Text Available Abstract Background Personalised cancer therapy, such as that used for bronchial carcinoma (BC, requires treatment to be adjusted to the patient's status. Individual risk for progression is estimated from clinical and molecular-biological data using translational score systems. Additional molecular information can improve outcome prediction depending on the marker used and the applied algorithm. Two models, one based on regressions and the other on correlations, were used to investigate the effect of combining various items of prognostic information to produce a comprehensive score. This was carried out using correlation coefficients, with options concerning a more plausible selection of variables for modelling, and this is considered better than classical regression analysis. Methods Clinical data concerning 63 BC patients were used to investigate the expression pattern of five tumour-associated proteins. Significant impact on survival was determined using log-rank tests. Significant variables were integrated into a Cox regression model and a new variable called integrative score of individual risk (ISIR, based on Spearman's correlations, was obtained. Results High tumour stage (TNM was predictive for poor survival, while CD68 and Gas6 protein expression correlated with a favourable outcome. Cox regression model analysis predicted outcome more accurately than using each variable in isolation, and correctly classified 84% of patients as having a clear risk status. Calculation of the integrated score for an individual risk (ISIR, considering tumour size (T, lymph node status (N, metastasis (M, Gas6 and CD68 identified 82% of patients as having a clear risk status. Conclusion Combining protein expression analysis of CD68 and GAS6 with T, N and M, using Cox regression or ISIR, improves prediction. Considering the increasing number of molecular markers, subsequent studies will be required to validate translational algorithms for the prognostic

  12. Causal Mediation Analysis for the Cox Proportional Hazards Model with a Smooth Baseline Hazard Estimator.

    Science.gov (United States)

    Wang, Wei; Albert, Jeffrey M

    2017-08-01

    An important problem within the social, behavioral, and health sciences is how to partition an exposure effect (e.g. treatment or risk factor) among specific pathway effects and to quantify the importance of each pathway. Mediation analysis based on the potential outcomes framework is an important tool to address this problem and we consider the estimation of mediation effects for the proportional hazards model in this paper. We give precise definitions of the total effect, natural indirect effect, and natural direct effect in terms of the survival probability, hazard function, and restricted mean survival time within the standard two-stage mediation framework. To estimate the mediation effects on different scales, we propose a mediation formula approach in which simple parametric models (fractional polynomials or restricted cubic splines) are utilized to approximate the baseline log cumulative hazard function. Simulation study results demonstrate low bias of the mediation effect estimators and close-to-nominal coverage probability of the confidence intervals for a wide range of complex hazard shapes. We apply this method to the Jackson Heart Study data and conduct sensitivity analysis to assess the impact on the mediation effects inference when the no unmeasured mediator-outcome confounding assumption is violated.

  13. Increased COX-2 expression in epithelial and stromal cells of high mammographic density tissues and in a xenograft model of mammographic density.

    Science.gov (United States)

    Chew, G L; Huo, C W; Huang, D; Hill, P; Cawson, J; Frazer, H; Hopper, J L; Haviv, I; Henderson, M A; Britt, K; Thompson, E W

    2015-08-01

    Mammographic density (MD) adjusted for age and body mass index is one of the strongest known risk factors for breast cancer. Given the high attributable risk of MD for breast cancer, chemoprevention with a safe and available agent that reduces MD and breast cancer risk would be beneficial. Cox-2 has been implicated in MD-related breast cancer risk, and was increased in stromal cells in high MD tissues in one study. Our study assessed differential Cox-2 expression in epithelial and stromal cells in paired samples of high and low MD human breast tissue, and in a validated xenograft biochamber model of MD. We also examined the effects of endocrine treatment upon Cox-2 expression in high and low MD tissues in the MD xenograft model. Paired high and low MD human breast tissue samples were immunostained for Cox-2, then assessed for differential expression and staining intensity in epithelial and stromal cells. High and low MD human breast tissues were separately maintained in biochambers in mice treated with Tamoxifen, oestrogen or placebo implants, then assessed for percentage Cox-2 staining in epithelial and stromal cells. Percentage Cox-2 staining was greater for both epithelial (p = 0.01) and stromal cells (p tissues. In high MD biochamber tissues, percentage Cox-2 staining was greater in stromal cells of oestrogen-treated versus placebo-treated tissues (p = 0.05).

  14. Verification of a decision analytic model assumption using real-world practice data: implications for the cost effectiveness of cyclo-oxygenase 2 inhibitors (COX-2s).

    Science.gov (United States)

    Cox, Emily R; Motheral, Brenda; Mager, Doug

    2003-12-01

    To verify the gastroprotective agent (GPA) rate assumption used in cost-effectiveness models for cyclo-oxygenase 2 inhibitors (COX-2s) and to re-estimate model outcomes using GPA rates from actual practice. Prescription and medical claims data obtained from January 1, 1999, through May 31, 2001, from a large preferred provider organization in the Midwest, were used to estimate GPA rates within 3 groups of patients aged at least 18 years who were new to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 therapy: all new NSAID users, new NSAID users with a diagnosis of rheumatoid arthritis (RA) or osteoarthritis (OA), and a matched cohort of new NSAID users. Of the more than 319,000 members with at least 1 day of eligibility, 1900 met the study inclusion criteria for new NSAID users, 289 had a diagnosis of OA or RA, and 1232 were included in the matched cohort. Gastroprotective agent estimates for nonselective NSAID and COX-2 users were consistent across all 3 samples (all new NSAID users, new NSAID users with a diagnosis of OA or RA, and the matched cohort), with COX-2 GPA rates of 22%, 21%, and 20%, and nonselective NSAID GPA rates of 15%, 15%, and 18%, respectively. Re-estimation of the cost-effectiveness model increased the cost per year of life saved for COX-2s from $18,614 to more than $100,000. Contrary to COX-2 cost-effectiveness model assumptions, the rate of GPA use is positive and marginally higher among COX-2 users than among nonselective NSAID users. These findings call into question the use of expert opinion in estimating practice pattern model inputs prior to a product's use in clinical practice. A re-evaluation of COX-2 cost-effectiveness models is warranted.

  15. Effects of nimesulide, a selective COX-2 inhibitor, on cardiovascular function in 2 rat models of diabetes.

    Science.gov (United States)

    Leung, Joanne Y T; Pang, Catherine C Y

    2014-07-01

    Cyclooxygenase-2 (COX-2) has been found to be activated in diabetes. We investigated whether nimesulide (selective COX-2 inhibitor) alters cardiovascular responses to adrenaline in 2 rat models of diabetes. Wistar rats (5-week old) were continuously fed a normal or high-fructose diet (60% of caloric intake). At week 2, half of the rats in each diet regimen were given streptozotocin (STZ) (60 mg/kg, intravenously). At week 6, cardiovascular effects of adrenaline (6 and 16 × 10 mol·kg·min, intravenously) were measured in 4 groups of thiobutabarbital-anesthetized rats (control, fructose, STZ, and fructose-streptozotocin [F-STZ]) before and after the injection of nimesulide (3 mg/kg, intravenously). Both the STZ and F-STZ groups exhibited hyperglycemia and significantly (P < 0.05) reduced left ventricular contractility, mean arterial pressure, arterial and venous resistance, and mean circulatory filling pressure (index of venous tone) responses to adrenaline, relative to the control and fructose groups. Nimesulide did not affect responses in the control and fructose groups but increased the venous and, to a less extent, arterial constriction to adrenaline in both the groups of diabetic rats. The cardiac contractile responses, however, were not altered after nimesulide treatment. The results show that nimesulide partially restored arterial and venous constriction to adrenaline in rats with STZ- and F-STZ-induced diabetes.

  16. Interrelations among SMED Stages: A Causal Model

    Directory of Open Access Journals (Sweden)

    José Roberto Díaz-Reza

    2017-01-01

    Full Text Available Mexico has received a lot of foreign investment that has brought in a wide range of novel production philosophies, such as Single Minute Exchange of Dies (SMED. Despite its popularity and reported effectiveness, Mexican companies often quit SMED implementation as they consider it challenging. This usually happens when organizations are not familiarized enough with each one of the SMED stages or do not know how they are interrelated. In this article the interrelations among the different SMED implementation stages by means of a structural equations model are analyzed. Data for constructing the model were gathered from a survey administered to 250 employees from the Mexican maquiladora industry. The survey assessed the importance of 14 activities belonging to the four SMED stages. The descriptive analyses of these stages were conducted and integrated into a structural equations model as latent variables, to find their level of dependency. The model was constructed using WarpPLS 5 software, and direct, indirect, and total effects among variables are analyzed and validated. Results from the model revealed that Stage 1 of SMED implementation, known as the Identification Stage, has both direct and indirect effects on all the other SMED stages, being the most important stage.

  17. Artificial neural networks versus proportional hazards Cox models to predict 45-year all-cause mortality in the Italian Rural Areas of the Seven Countries Study

    Science.gov (United States)

    2012-01-01

    Background Projection pursuit regression, multilayer feed-forward networks, multivariate adaptive regression splines and trees (including survival trees) have challenged classic multivariable models such as the multiple logistic function, the proportional hazards life table Cox model (Cox), the Poisson’s model, and the Weibull’s life table model to perform multivariable predictions. However, only artificial neural networks (NN) have become popular in medical applications. Results We compared several Cox versus NN models in predicting 45-year all-cause mortality (45-ACM) by 18 risk factors selected a priori: age; father life status; mother life status; family history of cardiovascular diseases; job-related physical activity; cigarette smoking; body mass index (linear and quadratic terms); arm circumference; mean blood pressure; heart rate; forced expiratory volume; serum cholesterol; corneal arcus; diagnoses of cardiovascular diseases, cancer and diabetes; minor ECG abnormalities at rest. Two Italian rural cohorts of the Seven Countries Study, made up of men aged 40 to 59 years, enrolled and first examined in 1960 in Italy. Cox models were estimated by: a) forcing all factors; b) a forward-; and c) a backward-stepwise procedure. Observed cases of deaths and of survivors were computed in decile classes of estimated risk. Forced and stepwise NN were run and compared by C-statistics (ROC analysis) with the Cox models. Out of 1591 men, 1447 died. Model global accuracies were extremely high by all methods (ROCs > 0.810) but there was no clear-cut superiority of any model to predict 45-ACM. The highest ROCs (> 0.838) were observed by NN. There were inter-model variations to select predictive covariates: whereas all models concurred to define the role of 10 covariates (mainly cardiovascular risk factors), family history, heart rate and minor ECG abnormalities were not contributors by Cox models but were so by forced NN. Forced expiratory volume and arm circumference

  18. Artificial neural networks versus proportional hazards Cox models to predict 45-year all-cause mortality in the Italian Rural Areas of the Seven Countries Study

    Directory of Open Access Journals (Sweden)

    Puddu Paolo

    2012-07-01

    Full Text Available Abstract Background Projection pursuit regression, multilayer feed-forward networks, multivariate adaptive regression splines and trees (including survival trees have challenged classic multivariable models such as the multiple logistic function, the proportional hazards life table Cox model (Cox, the Poisson’s model, and the Weibull’s life table model to perform multivariable predictions. However, only artificial neural networks (NN have become popular in medical applications. Results We compared several Cox versus NN models in predicting 45-year all-cause mortality (45-ACM by 18 risk factors selected a priori: age; father life status; mother life status; family history of cardiovascular diseases; job-related physical activity; cigarette smoking; body mass index (linear and quadratic terms; arm circumference; mean blood pressure; heart rate; forced expiratory volume; serum cholesterol; corneal arcus; diagnoses of cardiovascular diseases, cancer and diabetes; minor ECG abnormalities at rest. Two Italian rural cohorts of the Seven Countries Study, made up of men aged 40 to 59 years, enrolled and first examined in 1960 in Italy. Cox models were estimated by: a forcing all factors; b a forward-; and c a backward-stepwise procedure. Observed cases of deaths and of survivors were computed in decile classes of estimated risk. Forced and stepwise NN were run and compared by C-statistics (ROC analysis with the Cox models. Out of 1591 men, 1447 died. Model global accuracies were extremely high by all methods (ROCs > 0.810 but there was no clear-cut superiority of any model to predict 45-ACM. The highest ROCs (> 0.838 were observed by NN. There were inter-model variations to select predictive covariates: whereas all models concurred to define the role of 10 covariates (mainly cardiovascular risk factors, family history, heart rate and minor ECG abnormalities were not contributors by Cox models but were so by forced NN. Forced expiratory volume and arm

  19. Updating prognosis in primary biliary cirrhosis using a time-dependent Cox regression model. PBC1 and PBC2 trial groups

    DEFF Research Database (Denmark)

    Christensen, E; Altman, D G; Neuberger, J

    1993-01-01

    immunoglobulin (Ig)M also indicated a poor prognosis. The survival predicted by the models agreed well with the survival observed in the independent PBC patients. The time-dependent models predicted better than our previously published time-fixed model. CONCLUSIONS: Using the time-dependent Cox models, one can...

  20. Cancer survival analysis using semi-supervised learning method based on Cox and AFT models with L1/2 regularization.

    Science.gov (United States)

    Liang, Yong; Chai, Hua; Liu, Xiao-Ying; Xu, Zong-Ben; Zhang, Hai; Leung, Kwong-Sak

    2016-03-01

    One of the most important objectives of the clinical cancer research is to diagnose cancer more accurately based on the patients' gene expression profiles. Both Cox proportional hazards model (Cox) and accelerated failure time model (AFT) have been widely adopted to the high risk and low risk classification or survival time prediction for the patients' clinical treatment. Nevertheless, two main dilemmas limit the accuracy of these prediction methods. One is that the small sample size and censored data remain a bottleneck for training robust and accurate Cox classification model. In addition to that, similar phenotype tumours and prognoses are actually completely different diseases at the genotype and molecular level. Thus, the utility of the AFT model for the survival time prediction is limited when such biological differences of the diseases have not been previously identified. To try to overcome these two main dilemmas, we proposed a novel semi-supervised learning method based on the Cox and AFT models to accurately predict the treatment risk and the survival time of the patients. Moreover, we adopted the efficient L1/2 regularization approach in the semi-supervised learning method to select the relevant genes, which are significantly associated with the disease. The results of the simulation experiments show that the semi-supervised learning model can significant improve the predictive performance of Cox and AFT models in survival analysis. The proposed procedures have been successfully applied to four real microarray gene expression and artificial evaluation datasets. The advantages of our proposed semi-supervised learning method include: 1) significantly increase the available training samples from censored data; 2) high capability for identifying the survival risk classes of patient in Cox model; 3) high predictive accuracy for patients' survival time in AFT model; 4) strong capability of the relevant biomarker selection. Consequently, our proposed semi

  1. Efficient Estimation of the Cox Model With Auxiliary Subgroup Survival Information.

    Science.gov (United States)

    Huang, Chiung-Yu; Qin, Jing; Tsai, Huei-Ting

    2016-01-01

    With the rapidly increasing availability of data in the public domain, combining information from different sources to infer about associations or differences of interest has become an emerging challenge to researchers. This paper presents a novel approach to improve efficiency in estimating the survival time distribution by synthesizing information from the individual-level data with t -year survival probabilities from external sources such as disease registries. While disease registries provide accurate and reliable overall survival statistics for the disease population, critical pieces of information that influence both choice of treatment and clinical outcomes usually are not available in the registry database. To combine with the published information, we propose to summarize the external survival information via a system of nonlinear population moments and estimate the survival time model using empirical likelihood methods. The proposed approach is more flexible than the conventional meta-analysis in the sense that it can automatically combine survival information for different subgroups and the information may be derived from different studies. Moreover, an extended estimator that allows for a different baseline risk in the aggregate data is also studied. Empirical likelihood ratio tests are proposed to examine whether the auxiliary survival information is consistent with the individual-level data. Simulation studies show that the proposed estimators yield a substantial gain in efficiency over the conventional partial likelihood approach. Two sets of data analysis are conducted to illustrate the methods and theory.

  2. Comparison of Cox Regression and Parametric Models: Application for Assessment of Survival of Pediatric Cases of Acute Leukemia in Southern Iran

    Science.gov (United States)

    Hosseini Teshnizi, Saeed; Taghi Ayatollahi, Seyyed Mohammad

    2017-04-01

    Background: Finding the most appropriate regression model for survival data in cancer casesin order to determine prognosis is an important issue in medical research. Here we compare Cox and parametric regression models regarding survival of children with acute leukemia in southern Iran. Methods: In a retrospective cohort study, information for 197 children with acute leukemia over 6 years was collected through observation and interviews. In order to identify factors affecting their survival, the Cox and parametric (exponential, Weibull, log-logistic, log-normal, Gompertz and generalized gamma) models were fitted to the data. To find the best predictor model, the Akaike’s information criterion (AIC) and the Coxsnell residual were employed. Results: Out of 197 children, 164 (83.3%) had ALL and 33 (16.7%) AML; the mean (± standard deviation) survival time was 52.1±8.10 months. According to both the AIC and the Coxsnell residual, the Cox regression model was the weakest and the log-normal and Weibull models were the best for fitting to data. Based on the log-normal model, age (HR=1.01, p=0.004), residence area (HR=1.60, p=0.038) and WBC (White Blood Cell) (HR=1.57, p=0.014) had significant effects on patient survival. Conclusion: Parametric regression models demonstrate better performance as compared to the Cox model for identifying risk factors for prognosis with acute leukemia data. Just because the assumption of PH (Proportional Hazards) is held for the Cox regression model, we should not ignore parameter models. Creative Commons Attribution License

  3. A Controlled Trial of Chemoprevention Using COX-2 Inhibitors in an Avian Model of Spontaneous Ovarian Carcinogesis

    National Research Council Canada - National Science Library

    Barnes, Mack N

    2007-01-01

    The objective of this study was to determine in a controlled chemoprevention trial the ability of a COX-2 inhibitor to inhibit the development of spontaneously arising genital tract adenocarcinoma in the laying hen (Gall us Domesticus...

  4. Two-Stage Modelling Of Random Phenomena

    Science.gov (United States)

    Barańska, Anna

    2015-12-01

    The main objective of this publication was to present a two-stage algorithm of modelling random phenomena, based on multidimensional function modelling, on the example of modelling the real estate market for the purpose of real estate valuation and estimation of model parameters of foundations vertical displacements. The first stage of the presented algorithm includes a selection of a suitable form of the function model. In the classical algorithms, based on function modelling, prediction of the dependent variable is its value obtained directly from the model. The better the model reflects a relationship between the independent variables and their effect on the dependent variable, the more reliable is the model value. In this paper, an algorithm has been proposed which comprises adjustment of the value obtained from the model with a random correction determined from the residuals of the model for these cases which, in a separate analysis, were considered to be the most similar to the object for which we want to model the dependent variable. The effect of applying the developed quantitative procedures for calculating the corrections and qualitative methods to assess the similarity on the final outcome of the prediction and its accuracy, was examined by statistical methods, mainly using appropriate parametric tests of significance. The idea of the presented algorithm has been designed so as to approximate the value of the dependent variable of the studied phenomenon to its value in reality and, at the same time, to have it "smoothed out" by a well fitted modelling function.

  5. Methodological comparison of marginal structural model, time-varying Cox regression, and propensity score methods : the example of antidepressant use and the risk of hip fracture

    NARCIS (Netherlands)

    Ali, M Sanni; Groenwold, Rolf H H; Belitser, Svetlana V; Souverein, Patrick C; Martín, Elisa; Gatto, Nicolle M; Huerta, Consuelo; Gardarsdottir, Helga; Roes, Kit C B; Hoes, Arno W; de Boer, Antonius; Klungel, Olaf H

    2016-01-01

    BACKGROUND: Observational studies including time-varying treatments are prone to confounding. We compared time-varying Cox regression analysis, propensity score (PS) methods, and marginal structural models (MSMs) in a study of antidepressant [selective serotonin reuptake inhibitors (SSRIs)] use and

  6. Predictive accuracy of novel risk factors and markers: A simulation study of the sensitivity of different performance measures for the Cox proportional hazards regression model

    NARCIS (Netherlands)

    P.C. Austin (Peter); Pencinca, M.J. (Michael J.); E.W. Steyerberg (Ewout)

    2017-01-01

    textabstractPredicting outcomes that occur over time is important in clinical, population health, and health services research. We compared changes in different measures of performance when a novel risk factor or marker was added to an existing Cox proportional hazards regression model. We performed

  7. Pulmonary and Cardiorenal Cyclooxygenase-1 (COX-1, -2 (COX-2, and Microsomal Prostaglandin E Synthase-1 (mPGES-1 and -2 (mPGES-2 Expression in a Hypertension Model

    Directory of Open Access Journals (Sweden)

    Zaher A. Radi

    2007-01-01

    Our work suggests that in hypertensive mice, there are (a significant microanatomic variations in the pulmonary, renal, and cardiac distribution and cellular localization of COX-1, COX-2, mPGES-1, and mPGES-2, and (b no differences in expression between genders.

  8. Do intra-articular hyaluronic acid injections delay total knee replacement in patients with osteoarthritis - A Cox model analysis.

    Science.gov (United States)

    Delbarre, Angélique; Amor, Bernard; Bardoulat, Isabelle; Tetafort, Aymeric; Pelletier-Fleury, Nathalie

    2017-01-01

    This study aimed to describe patients treated for knee osteoarthritis between 2006 and 2013 in France and to compare the delay from diagnosis to total knee replacement between patients who received intra-articular hyaluronic acid injections and those who did not receive the injections. A second objective was to compare direct medical costs for ambulatory care between treatment groups. Patients were selected from a representative sample of the real world administrative claims database using an algorithm developed by experts from the scientific committee of the study. Data were matched with the medico-administrative database for hospital care. A Cox proportional hazards model was stratified for the treatment group and adjusted for available socio-demographic and medical covariates to compare restricted mean survival times at different time points (1, 3, 5 and 7.5 years) between groups. Costs were expressed in 2013 euros. A total of 14,782 patients were treated for knee osteoarthritis (67% women; mean age = 68 years). Among this population, 1,662 patients had total knee replacement (11.2%). At each time point, restricted mean survival time without total knee replacement was significantly higher (p-valueshyaluronic acid group, from +51 to +217 days at 1 and 7.5 years, respectively. For the year preceding total knee replacement, the means for total direct medical costs were similar between groups, €744 vs €805 for treatment and control groups, respectively, (p-value = 0.104). Intra-articular injections accounted for less than 10% of the total costs. This is the first retrospective longitudinal study involving knee osteoarthritis patients using medico-administrative databases in France. The results support the effectiveness of hyaluronic acid injections in delaying total knee replacement and show that patients treated with hyaluronic acid have similar direct medical costs for ambulatory care compared to patients treated with corticosteroids only.

  9. RESEARCH OF EARLY STAGES OF MODELING

    Directory of Open Access Journals (Sweden)

    Andrey Borisovich Nikolaev

    2017-05-01

    Full Text Available In represented article the questions of estimate of accuracy of an average integral characteristics of random process in the course of imitation modeling is considered. For the purposes of analytical treatment of initial stage of modeling a conditionally nonstationary Gaussian process is analyzed as stationary Gaussian process with boundary prehistory. A model of approximant autocorrelation function is recommended. Analytical expression for variance and mathematical expectation of average integral estimation are obtained. Statistical estimation efficiency criterion, the probability of belonging to correct parameter interval is introduced. Dependences of closeness in estimation statistics clearing interval at transient behavior are researched for various types of processes.

  10. Inhibition of COX1/2 alters the host response and reduces ECM scaffold mediated constructive tissue remodeling in a rodent model of skeletal muscle injury.

    Science.gov (United States)

    Dearth, Christopher L; Slivka, Peter F; Stewart, Scott A; Keane, Timothy J; Tay, Justin K; Londono, Ricardo; Goh, Qingnian; Pizza, Francis X; Badylak, Stephen F

    2016-02-01

    Extracellular matrix (ECM) has been used as a biologic scaffold material to both reinforce the surgical repair of soft tissue and serve as an inductive template to promote a constructive tissue remodeling response. Success of such an approach is dependent on macrophage-mediated degradation and remodeling of the biologic scaffold. Macrophage phenotype during these processes is a predictive factor of the eventual remodeling outcome. ECM scaffolds have been shown to promote an anti-inflammatory or M2-like macrophage phenotype in vitro that includes secretion of downstream products of cycolooxygenases 1 and 2 (COX1/2). The present study investigated the effect of a common COX1/2 inhibitor (Aspirin) on macrophage phenotype and tissue remodeling in a rodent model of ECM scaffold treated skeletal muscle injury. Inhibition of COX1/2 reduced the constructive remodeling response by hindering myogenesis and collagen deposition in the defect area. The inhibited response was correlated with a reduction in M2-like macrophages in the defect area. The effects of Aspirin on macrophage phenotype were corroborated using an established in vitro macrophage model which showed a reduction in both ECM induced prostaglandin secretion and expression of a marker of M2-like macrophages (CD206). These results raise questions regarding the common peri-surgical administration of COX1/2 inhibitors when biologic scaffold materials are used to facilitate muscle repair/regeneration. COX1/2 inhibitors such as nonsteroidal anti-inflammatory drugs (NSAIDs) are routinely administered post-surgically for analgesic purposes. While COX1/2 inhibitors are important in pain management, they have also been shown to delay or diminish the healing process, which calls to question their clinical use for treating musculotendinous injuries. The present study aimed to investigate the influence of a common NSAID, Aspirin, on the constructive remodeling response mediated by an ECM scaffold (UBM) in a rat skeletal

  11. Generalised shot noise Cox processes

    DEFF Research Database (Denmark)

    Møller, Jesper; Torrisi, Giovanni Luca

    2005-01-01

    We introduce a class of cox cluster processes called generalised shot noise Cox processes (GSNCPs), which extends the definition of shot noise Cox processes (SNCPs) in two directions: the point process that drives the shot noise is not necessarily Poisson, and the kernel of the shot noise can...... be random. Thereby, a very large class of models for aggregated or clustered point patterns is obtained. Due to the structure of GSNCPs, a number of useful results can be established. We focus first on deriving summary statistics for GSNCPs and, second, on how to simulate such processes. In particular......, results on first- and second-order moment measures, reduced Palm distributions, the J-function, simulation with or without edge effects, and conditional simulation of the intensity function driving a GSNCP are given. Our results are exemplified in important special cases of GSNCPs, and we discuss...

  12. A comparison of breast cancer survival among young, middle-aged, and elderly patients in southern Iran using Cox and empirical Bayesian additive hazard models

    Directory of Open Access Journals (Sweden)

    Samane Nematolahi

    2017-10-01

    Full Text Available OBJECTIVES A survival analysis of breast cancer patients in southern Iran according to age has yet to be conducted. This study aimed to quantify the factors contributing to a poor prognosis, using Cox and empirical Bayesian additive hazard (EBAH models, among young (20-39 years, middle-aged (40-64 years, and elderly (≥ 65 years women. METHODS Data from 1,574 breast cancer patients diagnosed from 2002 to 2012 in the cancer registry of Fars Province (southern Iran were stratified into 3 age groups. The Kaplan-Meier method was used to estimate the overall survival rates. Cox and EBAH models were applied to each age category, and the Akaike information criterion was used to assess the goodness-of-fit of the 2 hazard models. RESULTS As of December 2012, 212 women (13.5% in our study population had died, of whom 43 were young (15.3%, 134 middle-aged (11.8%, and 35 elderly (22.3%. The 5-year survival probability by age category was 0.83 (standard error [SE], 0.03, 0.88 (SE, 0.01, and 0.75 (SE, 0.04, respectively. CONCLUSIONS The Nottingham Prognostic Index was the most effective prognostic factor. The model based on Bayesian methodology performed better with various sample sizes than the Cox model, which is the most widely used method of survival analysis.

  13. One-Stage and Bayesian Two-Stage Optimal Designs for Mixture Models

    OpenAIRE

    Lin, Hefang

    1999-01-01

    In this research, Bayesian two-stage D-D optimal designs for mixture experiments with or without process variables under model uncertainty are developed. A Bayesian optimality criterion is used in the first stage to minimize the determinant of the posterior variances of the parameters. The second stage design is then generated according to an optimality procedure that collaborates with the improved model from first stage data. Our results show that the Bayesian two-stage D-D optimal design...

  14. Do intra-articular hyaluronic acid injections delay total knee replacement in patients with osteoarthritis – A Cox model analysis

    Science.gov (United States)

    Amor, Bernard; Bardoulat, Isabelle; Tetafort, Aymeric; Pelletier-Fleury, Nathalie

    2017-01-01

    Due to the growing worldwide prevalence of knee osteoarthritis, the optimal management of this issue is critical for reducing its burden. Objectives This study aimed to describe patients treated for knee osteoarthritis between 2006 and 2013 in France and to compare the delay from diagnosis to total knee replacement between patients who received intra-articular hyaluronic acid injections and those who did not receive the injections. A second objective was to compare direct medical costs for ambulatory care between treatment groups. Materials and methods Patients were selected from a representative sample of the real world administrative claims database using an algorithm developed by experts from the scientific committee of the study. Data were matched with the medico-administrative database for hospital care. A Cox proportional hazards model was stratified for the treatment group and adjusted for available socio-demographic and medical covariates to compare restricted mean survival times at different time points (1, 3, 5 and 7.5 years) between groups. Costs were expressed in 2013 euros. Results A total of 14,782 patients were treated for knee osteoarthritis (67% women; mean age = 68 years). Among this population, 1,662 patients had total knee replacement (11.2%). At each time point, restricted mean survival time without total knee replacement was significantly higher (p-valueshyaluronic acid group, from +51 to +217 days at 1 and 7.5 years, respectively. For the year preceding total knee replacement, the means for total direct medical costs were similar between groups, €744 vs €805 for treatment and control groups, respectively, (p-value = 0.104). Intra-articular injections accounted for less than 10% of the total costs. Conclusion This is the first retrospective longitudinal study involving knee osteoarthritis patients using medico-administrative databases in France. The results support the effectiveness of hyaluronic acid injections in delaying total knee

  15. Tempol reduces injury area in rat model of spinal cord contusion injury through suppression of iNOS and COX-2 expression.

    Science.gov (United States)

    Quan, Hong-Hua; Kang, Ku-Seong; Sohn, Yoon-Kyung; Li, Ming

    2013-09-01

    The present study focused on the biologic effects of tempol on anti-inflammatory and nitric oxide generation in contusion spinal cord injury (SCI). The animal model of SCI was induced by dropping a 10-g rod (2.0 mm in diameter) at a height of 25 mm. Tempol was injected intraperitoneally a dose of 100 mg/kg at 15 min before SCI. Controls was injected with saline. The contused spinal segments were removed according to time courses, and the expression level of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was analyzed along with the size of irreversibly damaged region. After SCI, the relative amounts of COX-2 and iNOS mRNA were peaked at 8 h after post-injury, and then decreased up to 7 days post-injury, and normal level at 14 days. Expression of COX-2 protein was peaked at 8 h post-injury. With the tempol pre-treatment, the immunoreactivity of COX-2 and nitrotyrosine in paraffin-embedded tissue slices was profoundly decreased. The irreversibly damaged area of the spinal cord was peaked at 3 days after SCI. With tempol pre-treatment, the irreversibly damaged area shows a statistically significant decrease at 3 days after SCI. These evidences indicate that tempol pre-treatment reduces irreversibly damaged area on the contusion SCI in rat. The mechanisms of biologic reactions of tempol might be related to the decreased expressions of COX-2 and iNOS in spinal cord cells, neurons and glia. It is expected that the tempol effect on the SCI is not only antioxidant activity but also anti-inflammatory reaction.

  16. Regulatory activity based risk model identifies survival of stage II and III colorectal carcinoma.

    Science.gov (United States)

    Liu, Gang; Dong, Chuanpeng; Wang, Xing; Hou, Guojun; Zheng, Yu; Xu, Huilin; Zhan, Xiaohui; Liu, Lei

    2017-11-17

    Clinical and pathological indicators are inadequate for prognosis of stage II and III colorectal carcinoma (CRC). In this study, we utilized the activity of regulatory factors, univariate Cox regression and random forest for variable selection and developed a multivariate Cox model to predict the overall survival of Stage II/III colorectal carcinoma in GSE39582 datasets (469 samples). Patients in low-risk group showed a significant longer overall survival and recurrence-free survival time than those in high-risk group. This finding was further validated in five other independent datasets (GSE14333, GSE17536, GSE17537, GSE33113, and GSE37892). Besides, associations between clinicopathological information and risk score were analyzed. A nomogram including risk score was plotted to facilitate the utilization of risk score. The risk score model is also demonstrated to be effective on predicting both overall and recurrence-free survival of chemotherapy received patients. After performing Gene Set Enrichment Analysis (GSEA) between high and low risk groups, we found that several cell-cell interaction KEGG pathways were identified. Funnel plot results showed that there was no publication bias in these datasets. In summary, by utilizing the regulatory activity in stage II and III colorectal carcinoma, the risk score successfully predicts the survival of 1021 stage II/III CRC patients in six independent datasets.

  17. Colloidal Nanocrystals of Wurtzite Zn1-xCoxO (0 ≤ x ≤ 1): Models of Spinodal Decomposition in an Oxide Diluted Magnetic Semiconductor

    Energy Technology Data Exchange (ETDEWEB)

    White, Michael A.; Ochsenbein, Stefan T.; Gamelin, Daniel R.

    2008-11-25

    Magnetic-ion-rich nanoscale inclusions formed by spinodal decomposition have been observed in many diluted magnetic semiconductors and have recently been implicated in the ferromagnetic ordering observed in some of these materials. In this study, colloidal nanocrystals of the ternary alloy wurtzite Zn1-xCoxO, with x ranging from 0.0 (w-ZnO) to 1.0 (w-CoO), have been synthesized as model systems for the proposed spinodal decomposition nanostrucures of ferromagnetic Zn1-xCoxO thin films and powders. As freestanding nanocrystals, these phases do not show any signs of ferromagnetism or superparamagnetism at any value of x. Changes in the electronic absorption and magnetic circular dichroism (MCD) spectra with x are described that should allow optical identification of spinodal decomposition in other Zn1-xCoxO samples. Optical and magneto-optical spectroscopic results are presented for the end member of this series (w-CoO), apparently for the first time, and show this binary oxide to be an indirect gap chargetransfer insulator with Eg ≈ 2.3 eV.

  18. Colloidal Nanocrystals of Wurtzite Zn 1-xCox0 (0 ≤ x ≥ 1) Models of Spinodal Decomposition in an Oxide Diluted Magnetic Semiconductor

    Energy Technology Data Exchange (ETDEWEB)

    White, Michael A.; Ochsenbein, Stefan T.; Gamelin, Daniel R.

    2008-11-25

    Magnetic-ion-rich nanoscale inclusions formed by spinodal decomposition have been observed in many diluted magnetic semiconductors and have recently been implicated in the ferromagnetic ordering observed in some of these materials. In this study, colloidal nanocrystals of the ternary alloy wurtzite Zn1-xCoxO, with x ranging from 0.0 (w-ZnO) to 1.0 (w-CoO), have been synthesized as model systems for the proposed spinodal decomposition nanostrucures of ferromagnetic Zn1-xCoxO thin films and powders. As freestanding nanocrystals, these phases do not show any signs of ferromagnetism or superparamagnetism at any value of x. Changes in the electronic absorption and magnetic circular dichroism (MCD) spectra with x are described that should allow optical identification of spinodal decomposition in other Zn1-xCoxO samples. Optical and magneto-optical spectroscopic results are presented for the end member of this series (w-CoO), apparently for the first time, and show this binary oxide to be an indirect gap chargetransfer insulator with Eg ≈ 2.3 eV.

  19. Stage-by-Stage and Parallel Flow Path Compressor Modeling for a Variable Cycle Engine

    Science.gov (United States)

    Kopasakis, George; Connolly, Joseph W.; Cheng, Larry

    2015-01-01

    This paper covers the development of stage-by-stage and parallel flow path compressor modeling approaches for a Variable Cycle Engine. The stage-by-stage compressor modeling approach is an extension of a technique for lumped volume dynamics and performance characteristic modeling. It was developed to improve the accuracy of axial compressor dynamics over lumped volume dynamics modeling. The stage-by-stage compressor model presented here is formulated into a parallel flow path model that includes both axial and rotational dynamics. This is done to enable the study of compressor and propulsion system dynamic performance under flow distortion conditions. The approaches utilized here are generic and should be applicable for the modeling of any axial flow compressor design.

  20. Stage-specific predictive models for breast cancer survivability.

    Science.gov (United States)

    Kate, Rohit J; Nadig, Ramya

    2017-01-01

    Survivability rates vary widely among various stages of breast cancer. Although machine learning models built in past to predict breast cancer survivability were given stage as one of the features, they were not trained or evaluated separately for each stage. To investigate whether there are differences in performance of machine learning models trained and evaluated across different stages for predicting breast cancer survivability. Using three different machine learning methods we built models to predict breast cancer survivability separately for each stage and compared them with the traditional joint models built for all the stages. We also evaluated the models separately for each stage and together for all the stages. Our results show that the most suitable model to predict survivability for a specific stage is the model trained for that particular stage. In our experiments, using additional examples of other stages during training did not help, in fact, it made it worse in some cases. The most important features for predicting survivability were also found to be different for different stages. By evaluating the models separately on different stages we found that the performance widely varied across them. We also demonstrate that evaluating predictive models for survivability on all the stages together, as was done in the past, is misleading because it overestimates performance. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Generalised shot noise Cox processes

    DEFF Research Database (Denmark)

    Møller, Jesper; Torrisi, Giovanni Luca

    We introduce a new class of Cox cluster processes called generalised shot-noise processes (GSNCPs), which extends the definition of shot noise Cox processes (SNCPs) in two directions: the point process which drives the shot noise is not necessarily Poisson, and the kernel of the shot noise can...... be random. Thereby a very large class of models for aggregated or clustered point patterns is obtained. Due to the structure of GSNCPs, a number of useful results can be established. We focus first on deriving summary statistics for GSNCPs and next on how to make simulation for GSNCPs. Particularly, results...... for first and second order moment measures, reduced Palm distributions, the -function, simulation with or without edge effects, and conditional simulation of the intensity function driving a GSNCP are given. Our results are exemplified for special important cases of GSNCPs, and we discuss the relation...

  2. Decomposition of variance for spatial Cox processes

    DEFF Research Database (Denmark)

    Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

    Spatial Cox point processes is a natural framework for quantifying the various sources of variation governing the spatial distribution of rain forest trees. We introducea general criterion for variance decomposition for spatial Cox processes and apply it to specific Cox process models with additi...... or log linear random intensity functions. We moreover consider a new and flexible class of pair correlation function models given in terms of Mat´ern covariance functions. The proposed methodology is applied to point pattern data sets of locations of tropical rain forest trees....

  3. Decomposition of Variance for Spatial Cox Processes.

    Science.gov (United States)

    Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

    2013-03-01

    Spatial Cox point processes is a natural framework for quantifying the various sources of variation governing the spatial distribution of rain forest trees. We introduce a general criterion for variance decomposition for spatial Cox processes and apply it to specific Cox process models with additive or log linear random intensity functions. We moreover consider a new and flexible class of pair correlation function models given in terms of normal variance mixture covariance functions. The proposed methodology is applied to point pattern data sets of locations of tropical rain forest trees.

  4. Using Swiss Webster mice to model Fetal Alcohol Spectrum Disorders (FASD): An analysis of multilevel time-to-event data through mixed-effects Cox proportional hazards models.

    Science.gov (United States)

    Chi, Peter; Aras, Radha; Martin, Katie; Favero, Carlita

    2016-05-15

    Fetal Alcohol Spectrum Disorders (FASD) collectively describes the constellation of effects resulting from human alcohol consumption during pregnancy. Even with public awareness, the incidence of FASD is estimated to be upwards of 5% in the general population and is becoming a global health problem. The physical, cognitive, and behavioral impairments of FASD are recapitulated in animal models. Recently rodent models utilizing voluntary drinking paradigms have been developed that accurately reflect moderate consumption, which makes up the majority of FASD cases. The range in severity of FASD characteristics reflects the frequency, dose, developmental timing, and individual susceptibility to alcohol exposure. As most rodent models of FASD use C57BL/6 mice, there is a need to expand the stocks of mice studied in order to more fully understand the complex neurobiology of this disorder. To that end, we allowed pregnant Swiss Webster mice to voluntarily drink ethanol via the drinking in the dark (DID) paradigm throughout their gestation period. Ethanol exposure did not alter gestational outcomes as determined by no significant differences in maternal weight gain, maternal liquid consumption, litter size, or pup weight at birth or weaning. Despite seemingly normal gestation, ethanol-exposed offspring exhibit significantly altered timing to achieve developmental milestones (surface righting, cliff aversion, and open field traversal), as analyzed through mixed-effects Cox proportional hazards models. These results confirm Swiss Webster mice as a viable option to study the incidence and causes of ethanol-induced neurobehavioral alterations during development. Future studies in our laboratory will investigate the brain regions and molecules responsible for these behavioral changes. Copyright © 2016. Published by Elsevier B.V.

  5. A two stage data envelopment analysis model with undesirable output

    Science.gov (United States)

    Shariff Adli Aminuddin, Adam; Izzati Jaini, Nur; Mat Kasim, Maznah; Nawawi, Mohd Kamal Mohd

    2017-09-01

    The dependent relationship among the decision making units (DMU) is usually assumed to be non-existent in the development of Data Envelopment Analysis (DEA) model. The dependency can be represented by the multi-stage DEA model, where the outputs from the precedent stage will be the inputs for the latter stage. The multi-stage DEA model evaluate both the efficiency score for each stages and the overall efficiency of the whole process. The existing multi stage DEA models do not focus on the integration with the undesirable output, in which the higher input will generate lower output unlike the normal desirable output. This research attempts to address the inclusion of such undesirable output and investigate the theoretical implication and potential application towards the development of multi-stage DEA model.

  6. Commentary on retirement, identity, and Erikson's developmental stage model.

    Science.gov (United States)

    Osborne, John W

    2009-12-01

    ABSTRACTThe coincidence of retirement and aging, experienced in the later stages of life, can trigger a recurrence of the bipolar tensions of earlier stages described in Erikson's model of personality development. The model provides a means for retirees to understand the ground from which their present identity has developed and how the psychodynamics of previous life stages can be reactivated by the onset of retirement and aging. Stages of the model are illustrated by experiences within the context of retirement. The utility of Erikson's model is suggested as a means of enhancing self-awareness, self-understanding, and adjustment to retirement.

  7. Inhibition of COX-2 expression by topical diclofenac enhanced radiation sensitivity via enhancement of TRAIL in human prostate adenocarcinoma xenograft model

    Science.gov (United States)

    2013-01-01

    Background COX-2 inhibitors have an antitumor potential and have been verified by many researchers. Treatment of cancer cells with external stressors such as irradiation can stimulate the over-expression of COX-2 and possibly confer radiation resistance. In this study, we tested if topical diclofenac, which inhibits both COX-1 and COX-2, administration rendered prostate tumor cells sensitize to the effects of radiation. Methods LNCaP-COX-2 and LNCaP-Neo cells were treated with 0 to 1000 μM diclofenac. Next, a clonogenic assay was performed in which cells were subjected to irradiation (0 to 4 Gy) with or without diclofenac. COX-2 expression and other relevant molecules were measured by real-time PCR and immunohistochemistry after irradiation and diclofenac treatment. In addition, we assessed the tumor volumes of xenograft LNCaP-COX-2 cells treated with topical diclofenac with or without radiation therapy (RT). Results LNCaP-COX-2 and LNCaP-Neo cell lines experienced cytotoxic effects of diclofenac in a dose related manner. Clonogenic assays demonstrated that LNCaP-COX-2 cells were significantly more resistant to RT than LNCaP-Neo cells. Furthermore, the addition of diclofenac sensitized LNCaP-COX-2 not but LNCaP-Neo cells to the cytocidal effects of radiation. In LNCaP-COX-2 cells, diclofenac enhanced radiation-induced apoptosis compared with RT alone. This phenomenon might be attributed to enhancement of RT-induced TRAIL expression as demonstrated by real-time PCR analysis. Lastly, tumor volumes of LNCaP-COX-2 cells xenograft treated with diclofenac or RT alone was >4-fold higher than in mice treated with combined diclofenac and radiation (pdiclofenac enhances the effect of RT on prostate cancer cells that express COX-2. Thus, diclofenac may have potential as radiosensitizer for treatment of prostate cancer. PMID:23289871

  8. Geometric anisotropic spatial point pattern analysis and Cox processes

    DEFF Research Database (Denmark)

    Møller, Jesper; Toftaker, Håkon

    . In particular we study Cox process models with an elliptical pair correlation function, including shot noise Cox processes and log Gaussian Cox processes, and we develop estimation procedures using summary statistics and Bayesian methods. Our methodology is illustrated on real and synthetic datasets of spatial...

  9. A stage-based model of design teaching

    DEFF Research Database (Denmark)

    Beier, Sofie

    2014-01-01

    With a focus on the teaching of design students in higher education, the article will present a teaching approach model that follows the stages of the design process. The model suggests that at the Definition stage, the supervisor can focus on leading the student into a more thorough elaboration...

  10. A Controlled Trial of Chemoprevention Using COX-2 Inhibitors in an Avian Model of Spontaneous Ovarian Carcinogesis

    National Research Council Canada - National Science Library

    Barnes, Mack N; Berry, Wallace D

    2006-01-01

    While a strong rationale for chemoprevention of ovarian carcinoma exists, a mechanism for the comprehensive evaluation of novel compounds is severely impeded by the lack of a validated animal model...

  11. A Controlled Trial of Chemoprevention Using COX-2 Inhibitors in an Avian Model of Spontaneous Ovarian Carcinogenesis

    National Research Council Canada - National Science Library

    Barnes, Mack N; Berry, Wallace D

    2005-01-01

    While a strong rationale for chemoprevention of ovarian carcinoma exists, a mechanism for the comprehensive evaluation of novel compounds is severely impeded by the lack of a validated animal model...

  12. Methodological comparison of marginal structural model, time-varying Cox regression, and propensity score methods: the example of antidepressant use and the risk of hip fracture.

    Science.gov (United States)

    Ali, M Sanni; Groenwold, Rolf H H; Belitser, Svetlana V; Souverein, Patrick C; Martín, Elisa; Gatto, Nicolle M; Huerta, Consuelo; Gardarsdottir, Helga; Roes, Kit C B; Hoes, Arno W; de Boer, Antonius; Klungel, Olaf H

    2016-03-01

    Observational studies including time-varying treatments are prone to confounding. We compared time-varying Cox regression analysis, propensity score (PS) methods, and marginal structural models (MSMs) in a study of antidepressant [selective serotonin reuptake inhibitors (SSRIs)] use and the risk of hip fracture. A cohort of patients with a first prescription for antidepressants (SSRI or tricyclic antidepressants) was extracted from the Dutch Mondriaan and Spanish Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) general practice databases for the period 2001-2009. The net (total) effect of SSRI versus no SSRI on the risk of hip fracture was estimated using time-varying Cox regression, stratification and covariate adjustment using the PS, and MSM. In MSM, censoring was accounted for by inverse probability of censoring weights. The crude hazard ratio (HR) of SSRI use versus no SSRI use on hip fracture was 1.75 (95%CI: 1.12, 2.72) in Mondriaan and 2.09 (1.89, 2.32) in BIFAP. After confounding adjustment using time-varying Cox regression, stratification, and covariate adjustment using the PS, HRs increased in Mondriaan [2.59 (1.63, 4.12), 2.64 (1.63, 4.25), and 2.82 (1.63, 4.25), respectively] and decreased in BIFAP [1.56 (1.40, 1.73), 1.54 (1.39, 1.71), and 1.61 (1.45, 1.78), respectively]. MSMs with stabilized weights yielded HR 2.15 (1.30, 3.55) in Mondriaan and 1.63 (1.28, 2.07) in BIFAP when accounting for censoring and 2.13 (1.32, 3.45) in Mondriaan and 1.66 (1.30, 2.12) in BIFAP without accounting for censoring. In this empirical study, differences between the different methods to control for time-dependent confounding were small. The observed differences in treatment effect estimates between the databases are likely attributable to different confounding information in the datasets, illustrating that adequate information on (time-varying) confounding is crucial to prevent bias. Copyright © 2016 John Wiley & Sons, Ltd.

  13. Predictive models of adjuvant chemotherapy for patients with stage ii colorectal cancer: A retrospective study.

    Science.gov (United States)

    Wei, Bo; Zheng, Xiao-Ming; Lei, Pu-Run; Huang, Yong; Zheng, Zong-Heng; Chen, Tu-Feng; Huang, Jiang-Long; Fang, Jia-Feng; Liang, Cheng-Hua; Wei, Hong-Bo

    2017-09-05

    It remains controversial whether patients with Stage II colorectal cancer would benefit from adjuvant chemotherapy after radical resection. The aim of this study was to establish two mathematical models to identify the suitable patients for adjuvant chemotherapy. The current study comprised of two steps. In the first step, 353 patients with Stage II colorectal cancer who underwent surgical procedures at the Third Affiliated Hospital of Sun Yat-sen University between June 2006 and December 2015 were entered and followed up for 6-120 months. Their clinical data were collected and enrolled into the database. We established two mathematical models by univariate and multivariate Cox regression analysis to identify the target patients; in the second step, 230 patients under the same standard between January 2012 and December 2016 were entered and followed up for 3-62 months to verify the two models' validation. In the first step, totally 340 surgical patients with Stage II colorectal cancer were finally enrolled in this study. Statistical analysis showed that tumor differentiation (TD) (P models: (1) OS risk score = 1.116 × TD + 2.202 × LVI + 3.676 × UPM + 1.438 × LN - 0.493; (2) DFS risk score = 0.789 × TD + 2.074 × LVI + 3.183 × UPM + 1.329 × LN - 0.432. According to the models and cutoff points [(0.07, 1.33) and (-0.04, 1.30), respectively], patients can be divided into three groups: low-risk, moderate-risk, and high-risk. Moreover, the high-risk group patients could benefit from adjuvant chemotherapy. In the second step, totally 221 patients were finally used to verify the models' validation. The results proved that the models were accurate and feasible (Ppredictive models, patients with Stage II colorectal cancer in the high-risk group are strongly recommended for adjuvant chemotherapy, thus facilitating the individualized and precise treatment.

  14. Application of Cox and Parametric Survival Models to Assess Social Determinants of Health Affecting Three-Year Survival of Breast Cancer Patients.

    Science.gov (United States)

    Mohseny, Maryam; Amanpour, Farzaneh; Mosavi-Jarrahi, Alireza; Jafari, Hossein; Moradi-Joo, Mohammad; Davoudi Monfared, Esmat

    2016-01-01

    Breast cancer is one of the most common causes of cancer mortality in Iran. Social determinants of health are among the key factors affecting the pathogenesis of diseases. This cross-sectional study aimed to determine the social determinants of breast cancer survival time with parametric and semi-parametric regression models. It was conducted on male and female patients diagnosed with breast cancer presenting to the Cancer Research Center of Shohada-E-Tajrish Hospital from 2006 to 2010. The Cox proportional hazard model and parametric models including the Weibull, log normal and log-logistic models were applied to determine the social determinants of survival time of breast cancer patients. The Akaike information criterion (AIC) was used to assess the best fit. Statistical analysis was performed with STATA (version 11) software. This study was performed on 797 breast cancer patients, aged 25-93 years with a mean age of 54.7 (±11.9) years. In both semi-parametric and parametric models, the three-year survival was related to level of education and municipal district of residence (P<0.05). The AIC suggested that log normal distribution was the best fit for the three-year survival time of breast cancer patients. Social determinants of health such as level of education and municipal district of residence affect the survival of breast cancer cases. Future studies must focus on the effect of childhood social class on the survival times of cancers, which have hitherto only been paid limited attention.

  15. STAGES OF A STRATEGIC MANAGEMENT MODEL

    Directory of Open Access Journals (Sweden)

    Mihaela – Lavinia CIOBANICA

    2014-06-01

    Full Text Available In the literature dedicated to strategic management there is no unitary vision of the authors regarding the sequence of actions that give content to the respective process and what their stages are. With all existing differences, the visions of different authors nevertheless observe the unitary logic of developing a series of actions. These actions begin with the competitive environment analysis in which the organization operates and with the establishment of its strategic mission and they end with the performance evaluation after the strategy has been applied and, if appropriate, with the reconsidering of this strategy and the making of the necessary corrections to it. Such a basic structure of the process is adopted in most organizations that practice the strategic management. But noticeable differences appear in the degree of the formalization of the process and in the involvement of different managerial levels in the designing and detailing of its components.

  16. General role of the amino and methylsulfamoyl groups in selective cyclooxygenase(COX)-1 inhibition by 1,4-diaryl-1,2,3-triazoles and validation of a predictive pharmacometric PLS model.

    Science.gov (United States)

    Perrone, Maria Grazia; Vitale, Paola; Panella, Andrea; Fortuna, Cosimo G; Scilimati, Antonio

    2015-04-13

    A novel set of 1,4-diaryl-1,2,3-triazoles were projected as a tool to study the effect of both the heteroaromatic triazole as a core ring and a variety of chemical groups with different electronic features, size and shape on the catalytic activity of the two COX isoenzymes. The new triazoles were synthesized in fair to good yields and then evaluated for their inhibitory activity towards COXs arachidonic acid conversion catalysis. Their COXs selectivity was also measured. A predictive pharmacometric Volsurf plus model, experimentally confirmed by the percentage (%) of COXs inhibition at the concentration of 50 μM and IC50 values of the tested compounds, was built by using a number of isoxazoles of known COXs inhibitory activity as a training set. It was found that two compounds {4-(5-methyl-4-phenyl-1H-1,2,3-triazol-1-yl)benzenamine (18) and 4-[1-(4-methoxyphenyl)-5-methyl-1H-1,2,3-triazole-4-yl]benzenamine (19)} bearing an amino group (NH2) are potent and selective COX-1 inhibitors (IC50 = 15 and 3 μM, respectively) and that the presence of a methylsulfamoyl group (SO2CH3) is not a rule to have a Coxib. In fact, 4-(4-methoxyphenyl)-5-methyl-1-[4-(methylsulfonyl)phenyl]-1H-1,2,3-triazole (23) has COX-1 IC50 = 23 μM and was found inactive towards COX-2. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  17. Possibilities Of Opening Up the Stage-Gate Model

    Directory of Open Access Journals (Sweden)

    Biljana Stošić

    2014-12-01

    Full Text Available The paper presents basic elements of the Stage-Gate and Open innovation models, and possible connection of these two, resulting in what is frequently called an “Open Stage-Gate” model. This connection is based on opening up the new product development process and integration of the open innovation principles with the Stage-Gate concept, facilitating the import and export of information and technologies. Having in mind that the Stage Gate has originally been classified as the third generation model of innovation, the paper is dealing with the capabilities for applying the sixth generation Open innovation principles in today’s improved and much more flexible phases and gates of the Stage Gate. Lots of innovative companies are actually using both models in their NPD practice, looking for the most appropriate means of opening up the well-known closed innovation, especially in the domain of ideation through co-creation.

  18. Energy demand in Portuguese manufacturing: a two-stage model

    International Nuclear Information System (INIS)

    Borges, A.M.; Pereira, A.M.

    1992-01-01

    We use a two-stage model of factor demand to estimate the parameters determining energy demand in Portuguese manufacturing. In the first stage, a capital-labor-energy-materials framework is used to analyze the substitutability between energy as a whole and other factors of production. In the second stage, total energy demand is decomposed into oil, coal and electricity demands. The two stages are fully integrated since the energy composite used in the first stage and its price are obtained from the second stage energy sub-model. The estimates obtained indicate that energy demand in manufacturing responds significantly to price changes. In addition, estimation results suggest that there are important substitution possibilities among energy forms and between energy and other factors of production. The role of price changes in energy-demand forecasting, as well as in energy policy in general, is clearly established. (author)

  19. Sample size evaluation for a multiply matched case-control study using the score test from a conditional logistic (discrete Cox PH) regression model.

    Science.gov (United States)

    Lachin, John M

    2008-06-30

    The conditional logistic regression model (Biometrics 1982; 38:661-672) provides a convenient method for the assessment of qualitative or quantitative covariate effects on risk in a study with matched sets, each containing a possibly different number of cases and controls. The conditional logistic likelihood is identical to the stratified Cox proportional hazards model likelihood, with an adjustment for ties (J. R. Stat. Soc. B 1972; 34:187-220). This likelihood also applies to a nested case-control study with multiply matched cases and controls, selected from those at risk at selected event times. Herein the distribution of the score test for the effect of a covariate in the model is used to derive simple equations to describe the power of the test to detect a coefficient theta (log odds ratio or log hazard ratio) or the number of cases (or matched sets) and controls required to provide a desired level of power. Additional expressions are derived for a quantitative covariate as a function of the difference in the assumed mean covariate values among cases and controls and for a qualitative covariate in terms of the difference in the probabilities of exposure for cases and controls. Examples are presented for a nested case-control study and a multiply matched case-control study.

  20. A method for extending stage-discharge relationships using a hydrodynamic model and quantifying the associated uncertainty

    Science.gov (United States)

    Shao, Quanxi; Dutta, Dushmanta; Karim, Fazlul; Petheram, Cuan

    2018-01-01

    Streamflow discharge is a fundamental dataset required to effectively manage water and land resources. However, developing robust stage - discharge relationships called rating curves, from which streamflow discharge is derived, is time consuming and costly, particularly in remote areas and especially at high stage levels. As a result stage - discharge relationships are often heavily extrapolated. Hydrodynamic (HD) models are physically based models used to simulate the flow of water along river channels and over adjacent floodplains. In this paper we demonstrate a method by which a HD model can be used to generate a 'synthetic' stage - discharge relationship at high stages. The method uses a both-side Box-Cox transformation to calibrate the synthetic rating curve such that the regression residuals are as close to the normal distribution as possible. By doing this both-side transformation, the statistical uncertainty in the synthetically derived stage - discharge relationship can be calculated. This enables people trying to make decisions to determine whether the uncertainty in the synthetically generated rating curve at high stage levels is acceptable for their decision. The proposed method is demonstrated in two streamflow gauging stations in north Queensland, Australia.

  1. Relationship between metallothioneins and metals in a natural population of the clam Ruditapes decussatus from Sfax coast: a non-linear model using Box-Cox transformation.

    Science.gov (United States)

    Hamza-Chaffai, A; Amiard, J C; Cosson, R P

    1999-06-01

    Cadmium, copper and zinc were determined concomitantly with metallothionein-like proteins (MTLPs) in the subcellular fractions of Ruditapes decussatus digestive gland. This study covered 4 months and aimed to evaluate the effect of metal pollution and other factors such as sex, size and reproductive state on MTLP levels. Copper concentrations did not vary with month, however Cd and Zn concentrations showed high levels during August. Organisms showing low cadmium concentrations presented the highest cadmium percentages in the soluble fraction (SF) containing MTLPs. However for high cadmium concentrations, the insoluble fraction (IF) was implicated in cadmium association. MTLP levels varied according to the month, the sex and the size of the organisms. A non-linear model based on the Box-Cox transformation, was proposed to describe a positive and a significant relationship between MTLPs and the studied metals. A model including sex and size showed that these two factors affected MTLP levels, but were less important than metals. Males of R. decussatus showed higher significant correlations between MTLP levels and cadmium than females. Moreover, the effect of size and reproductive state on MTLP levels was less perceptible in males than in females. As a result, MTLPs in males of R. decussatus could be proposed as suitable biomarker for detecting metal contamination.

  2. Streamlining environmental product declarations: a stage model

    Science.gov (United States)

    Lefebvre, Elisabeth; Lefebvre, Louis A.; Talbot, Stephane; Le Hen, Gael

    2001-02-01

    General public environmental awareness and education is increasing, therefore stimulating the demand for reliable, objective and comparable information about products' environmental performances. The recently published standard series ISO 14040 and ISO 14025 are normalizing the preparation of Environmental Product Declarations (EPDs) containing comprehensive information relevant to a product's environmental impact during its life cycle. So far, only a few environmentally leading manufacturing organizations have experimented the preparation of EPDs (mostly from Europe), demonstrating its great potential as a marketing weapon. However the preparation of EPDs is a complex process, requiring collection and analysis of massive amounts of information coming from disparate sources (suppliers, sub-contractors, etc.). In a foreseeable future, the streamlining of the EPD preparation process will require product manufacturers to adapt their information systems (ERP, MES, SCADA) in order to make them capable of gathering, and transmitting the appropriate environmental information. It also requires strong functional integration all along the product supply chain in order to ensure that all the information is made available in a standardized and timely manner. The goal of the present paper is two fold: first to propose a transitional model towards green supply chain management and EPD preparation; second to identify key technologies and methodologies allowing to streamline the EPD process and subsequently the transition toward sustainable product development

  3. The Moxie of Kathy Cox

    Science.gov (United States)

    Johns, Stephanie

    2010-01-01

    Kathy Cox, the superintendent of schools for Georgia, believes "excellence is not an accident". She made a name for herself by winning $1 million proving she was smarter than a fifth-grader on a popular television show. This article presents a profile of Cox, her family, her role as school superintendent, and her accomplishments.…

  4. Characterization of the variable cow's age at last calving as a measurement of longevity by using the Kaplan-Meier estimator and the Cox model.

    Science.gov (United States)

    Caetano, S L; Rosa, G J M; Savegnago, R P; Ramos, S B; Bezerra, L A F; Lôbo, R B; de Paz, C C P; Munari, D P

    2013-04-01

    In most studies on beef cattle longevity, only the cows reaching a given number of calvings by a specific age are considered in the analyses. With the aim of evaluating all cows with productive life in herds, taking into consideration the different forms of management on each farm, it was proposed to measure cow longevity from age at last calving (ALC), that is, the most recent calving registered in the files. The objective was to characterize this trait in order to study the longevity of Nellore cattle, using the Kaplan-Meier estimators and the Cox model. The covariables and class effects considered in the models were age at first calving (AFC), year and season of birth of the cow and farm. The variable studied (ALC) was classified as presenting complete information (uncensored = 1) or incomplete information (censored = 0), using the criterion of the difference between the date of each cow's last calving and the date of the latest calving at each farm. If this difference was >36 months, the cow was considered to have failed. If not, this cow was censored, thus indicating that future calving remained possible for this cow. The records of 11 791 animals from 22 farms within the Nellore Breed Genetic Improvement Program ('Nellore Brazil') were used. In the estimation process using the Kaplan-Meier model, the variable of AFC was classified into three age groups. In individual analyses, the log-rank test and the Wilcoxon test in the Kaplan-Meier model showed that all covariables and class effects had significant effects (P 0.05). This analysis indicated that each month added to AFC diminished the risk of the cow's failure in the herd by 2%. Nonetheless, this does not imply that animals with younger AFC had less profitability. Cows with greater numbers of calvings were more precocious than those with fewer calvings.

  5. On spatio-temporal Lévy based Cox processes

    DEFF Research Database (Denmark)

    Prokesova, Michaela; Hellmund, Gunnar; Jensen, Eva Bjørn Vedel

    2006-01-01

    The paper discusses a new class of models for spatio-temporal Cox point processes. In these models, the driving field is defined by means of an integral of a weight function with respect to a Lévy basis. The relations to other Cox process models studied previously are discussed and formulas...

  6. Robust estimation of the expected survival probabilities from high-dimensional Cox models with biomarker-by-treatment interactions in randomized clinical trials

    Directory of Open Access Journals (Sweden)

    Nils Ternès

    2017-05-01

    Full Text Available Abstract Background Thanks to the advances in genomics and targeted treatments, more and more prediction models based on biomarkers are being developed to predict potential benefit from treatments in a randomized clinical trial. Despite the methodological framework for the development and validation of prediction models in a high-dimensional setting is getting more and more established, no clear guidance exists yet on how to estimate expected survival probabilities in a penalized model with biomarker-by-treatment interactions. Methods Based on a parsimonious biomarker selection in a penalized high-dimensional Cox model (lasso or adaptive lasso, we propose a unified framework to: estimate internally the predictive accuracy metrics of the developed model (using double cross-validation; estimate the individual survival probabilities at a given timepoint; construct confidence intervals thereof (analytical or bootstrap; and visualize them graphically (pointwise or smoothed with spline. We compared these strategies through a simulation study covering scenarios with or without biomarker effects. We applied the strategies to a large randomized phase III clinical trial that evaluated the effect of adding trastuzumab to chemotherapy in 1574 early breast cancer patients, for which the expression of 462 genes was measured. Results In our simulations, penalized regression models using the adaptive lasso estimated the survival probability of new patients with low bias and standard error; bootstrapped confidence intervals had empirical coverage probability close to the nominal level across very different scenarios. The double cross-validation performed on the training data set closely mimicked the predictive accuracy of the selected models in external validation data. We also propose a useful visual representation of the expected survival probabilities using splines. In the breast cancer trial, the adaptive lasso penalty selected a prediction model with 4

  7. Stage wise modeling of liquid-extraction column (RDC)

    International Nuclear Information System (INIS)

    Bastani, B.

    2004-01-01

    Stage wise forward mixing model considering coalescence and re dispersion of drops was used to predict the performance of Rotating Disk Liquid Extraction Contactors. Experimental data previously obtained in two RDC columns of 7-62 cm diameter, 73.6 cm height and 21.9 cm diameter,150 cm height were used to evaluate the model predications. Drops-side mass transfer coefficients were predicted applying Hand los-baron drop model and onley's model was used to predict velocities. According to the results obtained the followings could be concluded: (1) If the height of coalescence and re dispersion i.e.:h=h p Q p / Q could be estimated, the stage wise forward mixing with coalescence and re dispersion model will predict the column height and efficiency with the acceptable accuracy, (2) The stage wise modeling predictions are highly dependent on the number of stages used when the number of stages is less than 10 and (3) Application of continuous phase mass transfer axial dispersion coefficients (k c and E c ) obtained from the solute concentration profile along the column height will predict the column performance more accurately than the Calder bank and moo-young (for K c ) and Kumar-Heartland (for E c ) correlations

  8. A kinetic model for the first stage of pygas upgrading

    Directory of Open Access Journals (Sweden)

    J. L. de Medeiros

    2007-03-01

    Full Text Available Pyrolysis gasoline - PYGAS - is an intermediate boiling product of naphtha steam cracking with a high octane number and high aromatic/unsaturated contents. Due to stabilization concerns, PYGAS must be hydrotreated in two stages. The first stage uses a mild trickle-bed conversion for removing extremely reactive species (styrene, dienes and olefins prior to the more severe second stage where sulfured and remaining olefins are hydrogenated in gas phase. This work addresses the reaction network and two-phase kinetic model for the first stage of PYGAS upgrading. Nonlinear estimation was used for model tuning with kinetic data obtained in bench-scale trickle-bed hydrogenation with a commercial Pd/Al2O3 catalyst. On-line sampling experiments were designed to study the influence of variables - temperature and spatial velocity - on the conversion of styrene, dienes and olefins.

  9. Dynamic Modelling of the Two-stage Gasification Process

    DEFF Research Database (Denmark)

    Gøbel, Benny; Henriksen, Ulrik B.; Houbak, Niels

    1999-01-01

    A two-stage gasification pilot plant was designed and built as a co-operative project between the Technical University of Denmark and the company REKA.A dynamic, mathematical model of the two-stage pilot plant was developed to serve as a tool for optimising the process and the operating conditions...... of the gasification plant.The model consists of modules corresponding to the different elements in the plant. The modules are coupled together through mass and heat conservation.Results from the model are compared with experimental data obtained during steady and unsteady operation of the pilot plant. A good...

  10. Factors associated with long-stay nursing home admissions among the U.S. elderly population: comparison of logistic regression and the Cox proportional hazards model with policy implications for social work.

    Science.gov (United States)

    Cai, Qian; Salmon, J Warren; Rodgers, Mark E

    2009-01-01

    Two statistical methods were compared to identify key factors associated with long-stay nursing home (LSNH) admission among the U.S. elderly population. Social Work's interest in services to the elderly makes this research critical to the profession. Effectively transitioning the "baby boomer" population into appropriate long-term care will be a great societal challenge. It remains a challenge paramount to the practice of social work. Secondary data analyses using four waves (1995, 1998, 2000, and 2002) of the Health Retirement Study (HRS) coupled with the Assets and Health Dynamics among the Oldest Old (AHEAD) surveys were conducted. Multivariable logistic regression and Cox proportional hazards model were performed and compared. Older age, lower self-perceived health, worse instrumental activities of daily living (IADL), psychiatric problems, and living alone were found significantly associated with increased risk of LSNH admission. In contrast, being female, African American, or Hispanic; owning a home; and having lower level of cognitive impairment reduced the admission risk. Home ownership showed a significant effect in logistic regression, but a marginal effect in the Cox model. The Cox model generally provided more precise parameter estimates than logistic regression. Logistic regression, used frequently in analyses, can provide a good approximation to the Cox model in identifying factors of LSNH admission. However, the Cox model gives more information on how soon the LSNH admission may happen. Our analyses, based on two models, dually identified the factors associated with LSNH admission; therefore, results discussed confidently provide implications for both public and private long-term care policies, as well as improving the assessment capabilities of social work practitioners for development of screening programs among at-risk elderly. Given the predicted surge in this population, significant factors found from this study can be utilized in a strengths

  11. The Analysis, Optimization, and Simulation of a Two-Stage Tandem Queueing Model with Hyperexponential Service Time at Second Stage

    Directory of Open Access Journals (Sweden)

    Vedat Sağlam

    2015-01-01

    Full Text Available The aim of this paper is to analyze a tandem queueing model with two stages. The arrivals to the first stage are Poisson stream and the service time at this stage is exponential. There is no waiting room at first stage. The service time is hyperexponential and no waiting is allowed at second stage. The transition probabilities and loss probabilities of this model are obtained. In addition, the loss probability at second stage is optimized. Performance measures and the variance of the numbers of customers of this tandem queueing model are found. It is seen that the numbers of customers in first stage and second stage are dependent. Finally we have simulated this queueing model. For different values of parameters, exact values, simulated values, and optimal values of obtained performance measures of this model are numerically shown in tables and graphs.

  12. Valuation of Indonesian catastrophic earthquake bonds with generalized extreme value (GEV) distribution and Cox-Ingersoll-Ross (CIR) interest rate model

    Energy Technology Data Exchange (ETDEWEB)

    Gunardi,; Setiawan, Ezra Putranda [Mathematics Department, Gadjah Mada University (Indonesia)

    2015-12-22

    Indonesia is a country with high risk of earthquake, because of its position in the border of earth’s tectonic plate. An earthquake could raise very high amount of damage, loss, and other economic impacts. So, Indonesia needs a mechanism for transferring the risk of earthquake from the government or the (reinsurance) company, as it could collect enough money for implementing the rehabilitation and reconstruction program. One of the mechanisms is by issuing catastrophe bond, ‘act-of-God bond’, or simply CAT bond. A catastrophe bond issued by a special-purpose-vehicle (SPV) company, and then sold to the investor. The revenue from this transaction is joined with the money (premium) from the sponsor company and then invested in other product. If a catastrophe happened before the time-of-maturity, cash flow from the SPV to the investor will discounted or stopped, and the cash flow is paid to the sponsor company to compensate their loss because of this catastrophe event. When we consider the earthquake only, the amount of discounted cash flow could determine based on the earthquake’s magnitude. A case study with Indonesian earthquake magnitude data show that the probability of maximum magnitude can model by generalized extreme value (GEV) distribution. In pricing this catastrophe bond, we assumed stochastic interest rate that following the Cox-Ingersoll-Ross (CIR) interest rate model. We develop formulas for pricing three types of catastrophe bond, namely zero coupon bonds, ‘coupon only at risk’ bond, and ‘principal and coupon at risk’ bond. Relationship between price of the catastrophe bond and CIR model’s parameter, GEV’s parameter, percentage of coupon, and discounted cash flow rule then explained via Monte Carlo simulation.

  13. Valuation of Indonesian catastrophic earthquake bonds with generalized extreme value (GEV) distribution and Cox-Ingersoll-Ross (CIR) interest rate model

    International Nuclear Information System (INIS)

    Gunardi,; Setiawan, Ezra Putranda

    2015-01-01

    Indonesia is a country with high risk of earthquake, because of its position in the border of earth’s tectonic plate. An earthquake could raise very high amount of damage, loss, and other economic impacts. So, Indonesia needs a mechanism for transferring the risk of earthquake from the government or the (reinsurance) company, as it could collect enough money for implementing the rehabilitation and reconstruction program. One of the mechanisms is by issuing catastrophe bond, ‘act-of-God bond’, or simply CAT bond. A catastrophe bond issued by a special-purpose-vehicle (SPV) company, and then sold to the investor. The revenue from this transaction is joined with the money (premium) from the sponsor company and then invested in other product. If a catastrophe happened before the time-of-maturity, cash flow from the SPV to the investor will discounted or stopped, and the cash flow is paid to the sponsor company to compensate their loss because of this catastrophe event. When we consider the earthquake only, the amount of discounted cash flow could determine based on the earthquake’s magnitude. A case study with Indonesian earthquake magnitude data show that the probability of maximum magnitude can model by generalized extreme value (GEV) distribution. In pricing this catastrophe bond, we assumed stochastic interest rate that following the Cox-Ingersoll-Ross (CIR) interest rate model. We develop formulas for pricing three types of catastrophe bond, namely zero coupon bonds, ‘coupon only at risk’ bond, and ‘principal and coupon at risk’ bond. Relationship between price of the catastrophe bond and CIR model’s parameter, GEV’s parameter, percentage of coupon, and discounted cash flow rule then explained via Monte Carlo simulation

  14. Low-dose aspirin, non-steroidal anti-inflammatory drugs, selective COX-2 inhibitors and breast cancer recurrence

    DEFF Research Database (Denmark)

    Cronin-Fenton, Deirdre P; Heide-Jørgensen, Uffe; Ahern, Thomas P

    2016-01-01

    BACKGROUND: Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and selective COX-2 inhibitors may improve outcomes in breast cancer patients. We investigated the association of aspirin, NSAIDs, and use of selective COX-2 inhibitors with breast cancer recurrence. METHODS: We identified incident...... stage I-III Danish breast cancer patients in the Danish Breast Cancer Cooperative Group registry, who were diagnosed during 1996-2008. Prescriptions for aspirin (>99% low-dose aspirin), NSAIDs, and selective COX-2 inhibitors were ascertained from the National Prescription Registry. Follow-up began...... on the date of breast cancer primary surgery and continued until the first of recurrence, death, emigration, or 1 January 2013. We used Cox regression models to compute hazard ratios (HR) and corresponding 95% confidence intervals (95% CI) associating prescriptions with recurrence, adjusting for confounders...

  15. A Comparison of Seven Cox Regression-Based Models to Account for Heterogeneity Across Multiple HIV Treatment Cohorts in Latin America and the Caribbean.

    Science.gov (United States)

    Giganti, Mark J; Luz, Paula M; Caro-Vega, Yanink; Cesar, Carina; Padgett, Denis; Koenig, Serena; Echevarria, Juan; McGowan, Catherine C; Shepherd, Bryan E

    2015-05-01

    Many studies of HIV/AIDS aggregate data from multiple cohorts to improve power and generalizability. There are several analysis approaches to account for cross-cohort heterogeneity; we assessed how different approaches can impact results from an HIV/AIDS study investigating predictors of mortality. Using data from 13,658 HIV-infected patients starting antiretroviral therapy from seven Latin American and Caribbean cohorts, we illustrate the assumptions of seven readily implementable approaches to account for across cohort heterogeneity with Cox proportional hazards models, and we compare hazard ratio estimates across approaches. As a sensitivity analysis, we modify cohort membership to generate specific heterogeneity conditions. Hazard ratio estimates varied slightly between the seven analysis approaches, but differences were not clinically meaningful. Adjusted hazard ratio estimates for the association between AIDS at treatment initiation and death varied from 2.00 to 2.20 across approaches that accounted for heterogeneity; the adjusted hazard ratio was estimated as 1.73 in analyses that ignored across cohort heterogeneity. In sensitivity analyses with more extreme heterogeneity, we noted a slightly greater distinction between approaches. Despite substantial heterogeneity between cohorts, the impact of the specific approach to account for heterogeneity was minimal in our case study. Our results suggest that it is important to account for across cohort heterogeneity in analyses, but that the specific technique for addressing heterogeneity may be less important. Because of their flexibility in accounting for cohort heterogeneity, we prefer stratification or meta-analysis methods, but we encourage investigators to consider their specific study conditions and objectives.

  16. Perioperative Pain Relief by a COX-2 Inhibitor Affects Ileal Repair and Provides a Model for Anastomotic Leakage in the Intestine

    NARCIS (Netherlands)

    van der Vijver, R.J.; Laarhoven, C.J. van; de Man, B.M.; Lomme, R.M.L.M.; Hendriks, T.

    2013-01-01

    The authors examined the potential of the cyclooxygenase 2 (COX-2) inhibitor carprofen to reproducibly induce anastomotic leakage. In experiment 1, an anastomosis was constructed in both ileum and colon of 20 rats, and they were given carprofen (5 mg/kg subcutaneously every 24 hours) or

  17. Early induction of cytokines/cytokine receptors and Cox2, and activation of NF-κB in 4-nitroquinoline 1-oxide-induced murine oral cancer model

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yu-Ching [Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan (China); Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Ho, Heng-Chien; Lee, Miau-Rong [Department of Biochemistry, China Medical University, Taichung 404, Taiwan (China); Lai, Kuang-Chi [Department of Surgery, China Medical University Beigang Hospital, Yunlin 651, Taiwan (China); School of Medicine, China Medical University, Taichung 404, Taiwan (China); Yeh, Chung-Min; Lin, Yueh-Min [Department of Pathology, Changhua Christian Hospital, Changhua 500, Taiwan (China); Ho, Tin-Yun [School of Chinese Medicine, China Medical University, Taichung 404, Taiwan (China); Hsiang, Chien-Yun, E-mail: cyhsiang@mail.cmu.edu.tw [Department of Microbiology, China Medical University, Taichung 404, Taiwan (China); Chung, Jing-Gung, E-mail: jgchung@mail.cmu.edu.tw [Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan (China); Department of Biotechnology, Asia University, Taichung 413, Taiwan (China)

    2012-07-15

    The purpose of this study was to identify the genes induced early in murine oral carcinogenesis. Murine tongue tumors induced by the carcinogen, 4-nitroquinoline 1-oxide (4-NQO), and paired non-tumor tissues were subjected to microarray analysis. Hierarchical clustering of upregulated genes in the tumor tissues revealed an association of induced genes with inflammation. Cytokines/cytokine receptors induced early were subsequently identified, clearly indicating their involvement in oral carcinogenesis. Hierarchical clustering also showed that cytokine-mediated inflammation was possibly linked with Mapk6. Cox2 exhibited the greatest extent (9–18 fold) of induction in the microarray data, and its early induction was observed in a 2 h painting experiment by RT-PCR. MetaCore analysis showed that overexpressed Cox2 may interact with p53 and transcriptionally inhibit expression of several downstream genes. A painting experiment in transgenic mice also demonstrated that NF-κB activates early independently of Cox2 induction. MetaCore analysis revealed the most striking metabolic alterations in tumor tissues, especially in lipid metabolism resulting from the reduction of Pparα and Rxrg. Reduced expression of Mapk12 was noted, and MetaCore analysis established its relationship with decreased efficiency of Pparα phosphorylation. In conclusion, in addition to cytokines/cytokine receptors, the early induction of Cox2 and NF-κB activation is involved in murine oral carcinogenesis.

  18. Two-step two-stage fission gas release model

    International Nuclear Information System (INIS)

    Kim, Yong-soo; Lee, Chan-bock

    2006-01-01

    Based on the recent theoretical model, two-step two-stage model is developed which incorporates two stage diffusion processes, grain lattice and grain boundary diffusion, coupled with the two step burn-up factor in the low and high burn-up regime. FRAPCON-3 code and its in-pile data sets have been used for the benchmarking and validation of this model. Results reveals that its prediction is in better agreement with the experimental measurements than that by any model contained in the FRAPCON-3 code such as ANS 5.4, modified ANS5.4, and Forsberg-Massih model over whole burn-up range up to 70,000 MWd/MTU. (author)

  19. Physiological COX-2 Expression in Breast Epithelium Associates with COX-2 Levels in Ductal Carcinoma in Situ and Invasive Breast Cancer in Young Women

    Science.gov (United States)

    Fornetti, Jaime; Jindal, Sonali; Middleton, Kara A.; Borges, Virginia F.; Schedin, Pepper

    2015-01-01

    Cyclooxygenase-2 (COX-2) overexpression is implicated in increased risk and poorer outcomes in breast cancer in young women. We investigated COX-2 regulation in normal premenopausal breast tissue and its relationship to malignancy in young women. Quantitative COX-2 immunohistochemistry was performed on adjacent normal and breast cancer tissues from 96 premenopausal women with known clinical reproductive histories, and on rat mammary glands with distinct ovarian hormone exposures. COX-2 expression in the normal breast epithelium varied more than 40-fold between women and was associated with COX-2 expression levels in ductal carcinoma in situ and invasive cancer. Normal breast COX-2 expression was independent of known breast cancer prognostic indicators, including tumor stage and clinical subtype, indicating that factors regulating physiological COX-2 expression may be the primary drivers of COX-2 expression in breast cancer. Ovarian hormones, particularly at pregnancy levels, were identified as modulators of COX-2 in normal mammary epithelium. However, serial breast biopsy analysis in nonpregnant premenopausal women suggested relatively stable baseline levels of COX-2 expression, which persisted independent of menstrual cycling. These data provide impetus to investigate how baseline COX-2 expression is regulated in premenopausal breast tissue because COX-2 levels in normal breast epithelium may prove to be an indicator of breast cancer risk in young women, and predict the chemopreventive and therapeutic efficacy of COX-2 inhibitors in this population. PMID:24518566

  20. On A Two-Stage Supply Chain Model In The Manufacturing Industry ...

    African Journals Online (AJOL)

    We model a two-stage supply chain where the upstream stage (stage 2) always meet demand from the downstream stage (stage 1).Demand is stochastic hence shortages will occasionally occur at stage 2. Stage 2 must fill these shortages by expediting using overtime production and/or backordering. We derive optimal ...

  1. [Mechanism of inhibition OF COX-2 and COX-3 in gastrointestinal damage induced by NSAID in rats ].

    Science.gov (United States)

    Laudanno, O M; San Miguel, P; Aramberry, L J; Cesolari, J A

    2003-01-01

    In randomized groups of Wistar rats, the effect inhibitor of selective NASAID over the COX-1, COX-2 and COX-3 the synchronizes inhibition of COX-1 and COX-2, COX-1 and COX-3, COX-2 and COX-3, and COX-1, COX-2 and COX-3 were studied. The conclusions were that the selective inhibition of COX-1, COX-2 and COX-3 no given gastrointestinal damage; the synchronizes inhibition of COX-1 and COX-2 given preferential gastric damage; in contrast the inhibition of COX-2 and COX-3 given massive necrosis preferential in small intestine.

  2. Numerical modelling of the HAB Energy Buoy: Stage 1

    DEFF Research Database (Denmark)

    Kurniawan, Adi

    This report presents the results of the first stage of the project "Numerical modelling of the HAB Energy Buoy". The objectives of this stage are to develop a numerical model of the HAB Energy Buoy, a self-reacting wave energy device consisting of two heaving bodies, and to investigate a number...... and a summary of the main findings is presented. A numerical model of the HAB Energy Buoy has been developed in the frequency domain using two alternative formulations of the equations of motion. The model is capable of predicting the power capture, motion response, and power take-off loads of the device...... configuration are imposed to give a more realistic prediction of the power capture and help ensure a fair comparison. Recommendations with regard to the HAB design are finally suggested....

  3. Predictors of stage transitions in the precaution adoption process model.

    Science.gov (United States)

    de Vet, Emely; de Nooijer, Jascha; Oenema, Anke; de Vries, Nanne K; Brug, Johannes

    2008-01-01

    To explore psychosocial correlates and predictors of stage transitions in the precaution adoption process model (PAPM) for fruit intake. A cohort completed three electronic questionnaires, at baseline (time 0), 35 days later (time 1), and another 32 days later (time 2). Secured Internet Web site. A cohort of 735 adults was formed from a random sample of an existing Internet panel. The mean age was 37.5 years, 51% were women, and 90% were of Dutch origin. Most respondents (48%) had a medium level of education. Precaution adoption process model stage, risk perception, perception of own fruit intake level, attitude, pros, cons, subjective norms, social support, modeling, self-efficacy, and fruit intake (assessed using a food frequency questionnaire). Cross-sectional differences in psychosocial variables and fruit intake across PAPM stages at baseline were analyzed using analysis of variance with Tukey multiple comparisons tests. Predictors of PAPM stage transitions between time 0 and time 1 and between time 1 and time 2 were analyzed using logistic regression analysis. Factors related to attitude and social influences may be important if one is to decide to act, whereas strong self-efficacy may also be required for acting on the decision to act. Although the results should be replicated in a larger and more representative sample, the PAPM seems a good framework for studying fruit intake.

  4. The study on stage financing model of IT project investment.

    Science.gov (United States)

    Chen, Si-hua; Xu, Sheng-hua; Lee, Changhoon; Xiong, Neal N; He, Wei

    2014-01-01

    Stage financing is the basic operation of venture capital investment. In investment, usually venture capitalists use different strategies to obtain the maximum returns. Due to its advantages to reduce the information asymmetry and agency cost, stage financing is widely used by venture capitalists. Although considerable attentions are devoted to stage financing, very little is known about the risk aversion strategies of IT projects. This paper mainly addresses the problem of risk aversion of venture capital investment in IT projects. Based on the analysis of characteristics of venture capital investment of IT projects, this paper introduces a real option pricing model to measure the value brought by the stage financing strategy and design a risk aversion model for IT projects. Because real option pricing method regards investment activity as contingent decision, it helps to make judgment on the management flexibility of IT projects and then make a more reasonable evaluation about the IT programs. Lastly by being applied to a real case, it further illustrates the effectiveness and feasibility of the model.

  5. Salmonella enterica serovar Enteritidis enterocolitis during late stages of gestation induces an adverse pregnancy outcome in the murine model.

    Directory of Open Access Journals (Sweden)

    Mariángeles Noto Llana

    Full Text Available Foodborne diseases caused by Salmonella enterica serovar Enteritidis (S. Enteritidis are a significant health problem. Pregnancy, state of immunological tolerance, is a predisposing condition for the development of infections with intracellular pathogens. Salmonella species can cause pregnancy complications such as chorioamnionitis, transplacental fetal infection, pre term labor, abortions, neonatal and maternal septicemia. However, the specific mechanisms by which Salmonella infections trigger these alterations are not clear. In the present work, using a self-limiting enterocolitis murine model, we show that the ingestion of a low dose of S. Enteritidis at late stages of pregnancy (day 15 of gestation is sufficient to induce massive maternal infection. We found that Salmonella infection leads to 40% of pre term delivery, 33% of abortion and fetal growth restriction. Placental dysfunction during S. Enteritidis enterocolitis was confirmed through cellular infiltration and hypoxia markers (MPO activity and COX-1 and COX-2 expression, respectively. Apoptosis in placental tissue due to Salmonella infection was also evident at day 18 of gestation when investigated by morphometric procedure, DNA fragmentation and Fas/FasL expression. Also, the expression of IFN-γ, TNF-α, IL-17 and IL-10 was up regulated in response to Salmonella not only in placenta, but also in amniotic fluid and maternal serum. Altogether, our results demonstrate that S. Enteritidis enterocolitis during late stages of gestation causes detrimental effect on pregnancy outcome.

  6. Hydrogeological conceptual model development and numerical modelling using CONNECTFLOW, Forsmark modelling stage 2.3

    Energy Technology Data Exchange (ETDEWEB)

    Follin, Sven (SF GeoLogic AB, Taeby (Sweden)); Hartley, Lee; Jackson, Peter; Roberts, David (Serco TAP (United Kingdom)); Marsic, Niko (Kemakta Konsult AB, Stockholm (Sweden))

    2008-05-15

    Three versions of a site descriptive model (SDM) have been completed for the Forsmark area. Version 0 established the state of knowledge prior to the start of the site investigation programme. Version 1.1 was essentially a training exercise and was completed during 2004. Version 1.2 was a preliminary site description and concluded the initial site investigation work (ISI) in June 2005. Three modelling stages are planned for the complete site investigation work (CSI). These are labelled stage 2.1, 2.2 and 2.3, respectively. An important component of each of these stages is to address and continuously try to resolve discipline-specific uncertainties of importance for repository engineering and safety assessment. Stage 2.1 included an updated geological model for Forsmark and aimed to provide a feedback from the modelling working group to the site investigation team to enable completion of the site investigation work. Stage 2.2 described the conceptual understanding and the numerical modelling of the bedrock hydrogeology in the Forsmark area based on data freeze 2.2. The present report describes the modelling based on data freeze 2.3, which is the final data freeze in Forsmark. In comparison, data freeze 2.3 is considerably smaller than data freeze 2.2. Therefore, stage 2.3 deals primarily with model confirmation and uncertainty analysis, e.g. verification of important hypotheses made in stage 2.2 and the role of parameter uncertainty in the numerical modelling. On the whole, the work reported here constitutes an addendum to the work reported in stage 2.2. Two changes were made to the CONNECTFLOW code in stage 2.3. These serve to: 1) improve the representation of the hydraulic properties of the regolith, and 2) improve the conditioning of transmissivity of the deformation zones against single-hole hydraulic tests. The changes to the modelling of the regolith were made to improve the consistency with models made with the MIKE SHE code, which involved the introduction

  7. Experimental model of intracranial arteriovenous shunting in the acute stage.

    Science.gov (United States)

    Numazawa, Shinichi; Sasaki, Tatsuya; Sato, Sonomi; Watanabe, Yoichi; Watanabe, Zenichiro; Kodama, Namio

    2005-06-01

    A model of intracranial arteriovenous (AV) shunting must incorporate local hypoperfusion and simulate the hemodynamics of arteriovenous malformations. In this study, the hemodynamics of an intracranial AV shunt model in the acute stage were clarified. End-to-side anastomoses with a femoral vein graft were performed between a cortical branch of the middle cerebral artery (MCA) and the superior sagittal sinus in anesthetized dogs. Local cerebral blood flow (l-CBF) was measured by laser Doppler blood flowmetry. l-CBF decreased suddenly by 34.2% when the shunt was opened in the ipsilateral MCA territory. Upon re-occlusion, l-CBF immediately equaled or exceeded the pre-opening value and returned to the pre-opening value within the next 15 minutes. Opening the shunt produced little change in l-CBF in the territory of the ipsilateral or contralateral anterior cerebral artery. The decrease in l-CBF was correlated with shunt volume only in the MCA territory. l-CBF manifested a PaCO(2)-dependent increase before shunt opening, but CO(2) reactivity was impaired after opening the shunt only in the MCA territory. This dog model features local hypoperfusion due to intracranial AV shunting and disturbance of CO(2) reactivity in the acute stage. The hemodynamics of this model will be confirmed in the chronic stage.

  8. Modeling heart rate variability including the effect of sleep stages

    Science.gov (United States)

    Soliński, Mateusz; Gierałtowski, Jan; Żebrowski, Jan

    2016-02-01

    We propose a model for heart rate variability (HRV) of a healthy individual during sleep with the assumption that the heart rate variability is predominantly a random process. Autonomic nervous system activity has different properties during different sleep stages, and this affects many physiological systems including the cardiovascular system. Different properties of HRV can be observed during each particular sleep stage. We believe that taking into account the sleep architecture is crucial for modeling the human nighttime HRV. The stochastic model of HRV introduced by Kantelhardt et al. was used as the initial starting point. We studied the statistical properties of sleep in healthy adults, analyzing 30 polysomnographic recordings, which provided realistic information about sleep architecture. Next, we generated synthetic hypnograms and included them in the modeling of nighttime RR interval series. The results of standard HRV linear analysis and of nonlinear analysis (Shannon entropy, Poincaré plots, and multiscale multifractal analysis) show that—in comparison with real data—the HRV signals obtained from our model have very similar properties, in particular including the multifractal characteristics at different time scales. The model described in this paper is discussed in the context of normal sleep. However, its construction is such that it should allow to model heart rate variability in sleep disorders. This possibility is briefly discussed.

  9. Survival analysis II: Cox regression

    NARCIS (Netherlands)

    Stel, Vianda S.; Dekker, Friedo W.; Tripepi, Giovanni; Zoccali, Carmine; Jager, Kitty J.

    2011-01-01

    In contrast to the Kaplan-Meier method, Cox proportional hazards regression can provide an effect estimate by quantifying the difference in survival between patient groups and can adjust for confounding effects of other variables. The purpose of this article is to explain the basic concepts of the

  10. Geology - Background complementary studies. Forsmark modelling stage 2.2

    Energy Technology Data Exchange (ETDEWEB)

    Stephens, Michael B. [Geological Survey of Sweden, Uppsala (Sweden); Skagius, Kristina [Kemakta Konsult AB, Stockholm (Sweden)] (eds.)

    2007-09-15

    During Forsmark model stage 2.2, seven complementary geophysical and geological studies were initiated by the geological modelling team, in direct connection with and as a background support to the deterministic modelling of deformation zones. One of these studies involved a field control on the character of two low magnetic lineaments with NNE and NE trends inside the target volume. The interpretation of these lineaments formed one of the late deliveries to SKB that took place after the data freeze for model stage 2.2 and during the initial stage of the modelling work. Six studies involved a revised processing and analysis of reflection seismic, refraction seismic and selected oriented borehole radar data, all of which had been presented earlier in connection with the site investigation programme. A prime aim of all these studies was to provide a better understanding of the geological significance of indirect geophysical data to the geological modelling team. Such essential interpretative work was lacking in the material acquired in connection with the site investigation programme. The results of these background complementary studies are published together in this report. The titles and authors of the seven background complementary studies are presented below. Summaries of the results of each study, with a focus on the implications for the geological modelling of deformation zones, are presented in the master geological report, SKB-R--07-45. The sections in the master report, where reference is made to each background complementary study and where the summaries are placed, are also provided. The individual reports are listed in the order that they are referred to in the master geological report and as they appear in this report. 1. Scan line fracture mapping and magnetic susceptibility measurements across two low magnetic lineaments with NNE and NE trend, Forsmark. Jesper Petersson, Ulf B. Andersson and Johan Berglund. 2. Integrated interpretation of surface and

  11. Palm distributions for log Gaussian Cox processes

    DEFF Research Database (Denmark)

    Coeurjolly, Jean-Francois; Møller, Jesper; Waagepetersen, Rasmus Plenge

    2017-01-01

    This paper establishes a remarkable result regarding Palm distributions for a log Gaussian Cox process: the reduced Palm distribution for a log Gaussian Cox process is itself a log Gaussian Cox process that only differs from the original log Gaussian Cox process in the intensity function. This new...

  12. Two-stage Bayesian models-application to ZEDB project

    International Nuclear Information System (INIS)

    Bunea, C.; Charitos, T.; Cooke, R.M.; Becker, G.

    2005-01-01

    A well-known mathematical tool to analyze plant specific reliability data for nuclear power facilities is the two-stage Bayesian model. Such two-stage Bayesian models are standard practice nowadays, for example in the German ZEDB project or in the Swedish T-Book, although they may differ in their mathematical models and software implementation. In this paper, we review the mathematical model, its underlying assumptions and supporting arguments. Reasonable conditional assumptions are made to yield tractable and mathematically valid form for the failure rate at plant of interest, given failures and operational times at other plants in the population. The posterior probability of failure rate at plant of interest is sensitive to the choice of hyperprior parameters since the effect of hyperprior distribution will never be dominated by the effect of observation. The methods of Poern and Jeffrey for choosing distributions over hyperparameters are discussed. Furthermore, we will perform verification tasks associated with the theoretical model presented in this paper. The present software implementation produces good agreement with ZEDB results for various prior distributions. The difference between our results and those of ZEDB reflect differences that may arise from numerical implementation, as that would use different step size and truncation bounds

  13. GENERALISED MODEL BASED CONFIDENCE INTERVALS IN TWO STAGE CLUSTER SAMPLING

    Directory of Open Access Journals (Sweden)

    Christopher Ouma Onyango

    2010-09-01

    Full Text Available Chambers and Dorfman (2002 constructed bootstrap confidence intervals in model based estimation for finite population totals assuming that auxiliary values are available throughout a target population and that the auxiliary values are independent. They also assumed that the cluster sizes are known throughout the target population. We now extend to two stage sampling in which the cluster sizes are known only for the sampled clusters, and we therefore predict the unobserved part of the population total. Jan and Elinor (2008 have done similar work, but unlike them, we use a general model, in which the auxiliary values are not necessarily independent. We demonstrate that the asymptotic properties of our proposed estimator and its coverage rates are better than those constructed under the model assisted local polynomial regression model.

  14. Cell-type-specific roles for COX-2 in UVB-induced skin cancer

    Science.gov (United States)

    Herschman, Harvey

    2014-01-01

    In human tumors, and in mouse models, cyclooxygenase-2 (COX-2) levels are frequently correlated with tumor development/burden. In addition to intrinsic tumor cell expression, COX-2 is often present in fibroblasts, myofibroblasts and endothelial cells of the tumor microenvironment, and in infiltrating immune cells. Intrinsic cancer cell COX-2 expression is postulated as only one of many sources for prostanoids required for tumor promotion/progression. Although both COX-2 inhibition and global Cox-2 gene deletion ameliorate ultraviolet B (UVB)-induced SKH-1 mouse skin tumorigenesis, neither manipulation can elucidate the cell type(s) in which COX-2 expression is required for tumorigenesis; both eliminate COX-2 activity in all cells. To address this question, we created Cox-2 flox/flox mice, in which the Cox-2 gene can be eliminated in a cell-type-specific fashion by targeted Cre recombinase expression. Cox-2 deletion in skin epithelial cells of SKH-1 Cox-2 flox/flox;K14Cre + mice resulted, following UVB irradiation, in reduced skin hyperplasia and increased apoptosis. Targeted epithelial cell Cox-2 deletion also resulted in reduced tumor incidence, frequency, size and proliferation rate, altered tumor cell differentiation and reduced tumor vascularization. Moreover, Cox-2 flox/flox;K14Cre + papillomas did not progress to squamous cell carcinomas. In contrast, Cox-2 deletion in SKH-1 Cox-2 flox/flox; LysMCre + myeloid cells had no effect on UVB tumor induction. We conclude that (i) intrinsic epithelial COX-2 activity plays a major role in UVB-induced skin cancer, (ii) macrophage/myeloid COX-2 plays no role in UVB-induced skin cancer and (iii) either there may be another COX-2-dependent prostanoid source(s) that drives UVB skin tumor induction or there may exist a COX-2-independent pathway(s) to UVB-induced skin cancer. PMID:24469308

  15. Geology Forsmark. Site descriptive modelling Forsmark - stage 2.2

    Energy Technology Data Exchange (ETDEWEB)

    Stephens, Michael B. [Geological Survey of Sweden, Uppsala (Sweden); Fox, Aaron; La Pointe, Paul [Golder Associates Inc (United States); Simeonov, Assen [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Isaksson, Hans [GeoVista AB, Luleaa (Sweden); Hermanson, Jan; Oehman, Johan [Golder Associates AB, Stockholm (Sweden)

    2007-10-15

    The geological work during stage 2.2 has involved the development of deterministic models for rock domains (RFM) and deformation zones (ZFM), the identification and deterministic modelling of fracture domains (FFM) inside the candidate volume, i.e. the parts of rock domains that are not affected by deformation zones, and the development of statistical models for fractures and minor deformation zones (geological discrete fracture network modelling or geological DFN modelling). The geological DFN model addresses brittle structures at a scale of less than 1 km, which is the lower cut-off in the deterministic modelling of deformation zones. In order to take account of variability in data resolution, deterministic models for rock domains and deformation zones are presented in both regional and local model volumes, while the geological DFN model is valid within specific fracture domains inside the north-western part of the candidate volume, including the target volume. The geological modelling work has evaluated and made use of: A revised bedrock geological map at the ground surface. Geological and geophysical data from 21 cored boreholes and 33 percussion boreholes. Detailed mapping of fractures and rock units along nine excavations or large surface outcrops. Data bearing on the characterisation (including kinematics) of deformation zones. Complementary geochronological and other rock and fracture analytical data. Lineaments identified on the basis of airborne and high-resolution ground magnetic data. A reprocessing of both surface and borehole reflection seismic data. Seismic refraction data. The outputs of the deterministic modelling work are geometric models in RVS format and detailed property tables for rock domains and deformation zones, and a description of fracture domains. The outputs of the geological DFN modelling process are recommended parameters or statistical distributions that describe fracture set orientations, radius sizes, volumetric intensities

  16. Geology Forsmark. Site descriptive modelling Forsmark - stage 2.2

    International Nuclear Information System (INIS)

    Stephens, Michael B.; Fox, Aaron; La Pointe, Paul; Simeonov, Assen; Isaksson, Hans; Hermanson, Jan; Oehman, Johan

    2007-10-01

    The geological work during stage 2.2 has involved the development of deterministic models for rock domains (RFM) and deformation zones (ZFM), the identification and deterministic modelling of fracture domains (FFM) inside the candidate volume, i.e. the parts of rock domains that are not affected by deformation zones, and the development of statistical models for fractures and minor deformation zones (geological discrete fracture network modelling or geological DFN modelling). The geological DFN model addresses brittle structures at a scale of less than 1 km, which is the lower cut-off in the deterministic modelling of deformation zones. In order to take account of variability in data resolution, deterministic models for rock domains and deformation zones are presented in both regional and local model volumes, while the geological DFN model is valid within specific fracture domains inside the north-western part of the candidate volume, including the target volume. The geological modelling work has evaluated and made use of: A revised bedrock geological map at the ground surface. Geological and geophysical data from 21 cored boreholes and 33 percussion boreholes. Detailed mapping of fractures and rock units along nine excavations or large surface outcrops. Data bearing on the characterisation (including kinematics) of deformation zones. Complementary geochronological and other rock and fracture analytical data. Lineaments identified on the basis of airborne and high-resolution ground magnetic data. A reprocessing of both surface and borehole reflection seismic data. Seismic refraction data. The outputs of the deterministic modelling work are geometric models in RVS format and detailed property tables for rock domains and deformation zones, and a description of fracture domains. The outputs of the geological DFN modelling process are recommended parameters or statistical distributions that describe fracture set orientations, radius sizes, volumetric intensities

  17. Risk model in stage IB1-IIB cervical cancer with positive node after radical hysterectomy

    Directory of Open Access Journals (Sweden)

    Chen Z

    2016-05-01

    Full Text Available Zhilan Chen,1,2,* Kecheng Huang,1,* Zhiyong Lu,1,3 Song Deng,1,4 Jiaqiang Xiong,1 Jia Huang,1 Xiong Li,5 Fangxu Tang,1 Zhihao Wang,6 Haiying Sun,1 Lin Wang,1 Shasha Zhou,1 Xiaoli Wang,1 Yao Jia,1 Ting Hu,1 Juan Gui,7 Dongyi Wan,1 Ding Ma,1 Shuang Li,1 Shixuan Wang11Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Techonology, Wuhan, 2Department of Obstetrics and Gynecology, Wuhan General Hospital of Guangzhou Military Command, Wuhan, 3Hubei Key Laboratory of Embryonic Stem Cell Research, Tai-He Hospital, Hubei University of Medicine, Shiyan, Hubei, 4Department of Obstetrics and Gynecology, University Hospital of Hubei University for Nationalities, Enshi, Hubei, 5Department of Obstetrics and Gynecology, Wuhan Central Hospital, Wuhan, 6Department of Pathology and Pathophysiology, Key Laboratory of Ministry of Education of China for Neurological Disorders, Huazhong University of Science and Techonology, Wuhan, 7Department of Obstetrics and Gynecology, Renmin Hospital, Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workAbstract: The purpose of this study was to identify risk factors in patients with surgically treated node-positive IB1-IIB cervical cancer and to establish a risk model for disease-free survival (DFS and overall survival (OS. A total of 170 patients who underwent radical hysterectomy and bilateral pelvic lymphadenectomy as primary treatment for node-positive International Federation of Gynaecology and Obstetrics (FIGO stage IB1-IIB cervical cancer from January 2002 to December 2008 were retrospectively analyzed. Five published risk models were evaluated in this population. The variables, including common iliac lymph node metastasis and parametrial invasion, were independent predictors of outcome in a multivariate analysis using a Cox regression model. Three distinct prognostic groups (low, intermediate, and high risk

  18. A Dual-Stage Two-Phase Model of Selective Attention

    Science.gov (United States)

    Hubner, Ronald; Steinhauser, Marco; Lehle, Carola

    2010-01-01

    The dual-stage two-phase (DSTP) model is introduced as a formal and general model of selective attention that includes both an early and a late stage of stimulus selection. Whereas at the early stage information is selected by perceptual filters whose selectivity is relatively limited, at the late stage stimuli are selected more efficiently on a…

  19. MCEM algorithm for the log-Gaussian Cox process

    OpenAIRE

    Delmas, Celine; Dubois-Peyrard, Nathalie; Sabbadin, Regis

    2014-01-01

    Log-Gaussian Cox processes are an important class of models for aggregated point patterns. They have been largely used in spatial epidemiology (Diggle et al., 2005), in agronomy (Bourgeois et al., 2012), in forestry (Moller et al.), in ecology (sightings of wild animals) or in environmental sciences (radioactivity counts). A log-Gaussian Cox process is a Poisson process with a stochastic intensity depending on a Gaussian random eld. We consider the case where this Gaussian random eld is ...

  20. Simultaneous confidence bands for Cox regression from semiparametric random censorship.

    Science.gov (United States)

    Mondal, Shoubhik; Subramanian, Sundarraman

    2016-01-01

    Cox regression is combined with semiparametric random censorship models to construct simultaneous confidence bands (SCBs) for subject-specific survival curves. Simulation results are presented to compare the performance of the proposed SCBs with the SCBs that are based only on standard Cox. The new SCBs provide correct empirical coverage and are more informative. The proposed SCBs are illustrated with two real examples. An extension to handle missing censoring indicators is also outlined.

  1. Crocetin Downregulates the Proinflammatory Cytokines in Methylcholanthrene-Induced Rodent Tumor Model and Inhibits COX-2 Expression in Cervical Cancer Cells

    Directory of Open Access Journals (Sweden)

    Bing Chen

    2015-01-01

    Full Text Available The effect of crocetin (C20H24O4 on methylcholanthrene- (MCA- induced uterine cervical cancer in mice was studied in this paper. After the mice were treated orally with crocetin, maleic dialdehyde (MDA, polymorphonuclear cells (PMN, interleukin-1β (IL-1β, and tumor necrosis factor-α (TNF-α were examined by ELISA or immunohistochemistry. The inducible nitric oxide synthase (iNOS activation in HeLa cells was analyzed using fluorescence microscopy for light microscopic examination. The MCA mice showed a significant increase in plasma MDA, PMN, IL-1β, TNF-α, and nitrates levels. At the same time, the mRNA level of COX-2 in HeLa cells was also significantly increased. These changes were attenuated by crocetin supplementation in the MCA mice. Crocetin supplementation in the MCA mice also showed protection against cervical cancer. These results suggest that crocetin may act as a chemopreventive and an anti-inflammatory agent.

  2. Allan Cox 1926”1987

    Science.gov (United States)

    Coe, Rob; Dalrymple, Brent

    More than 1000 friends, students, and colleagues from all over the country filled Stanford Memorial Chapel (Stanford, Calif.) on February 3, 1987, to join in “A Celebration of the Life of Allan Cox.” Allan died early on the morning of January 27 while bicycling, the sport he had come to love the most. Between pieces of his favorite music by Bach and Mozart, Stanford administrators and colleagues spoke in tribute of Allan's unique qualities as friend, scientist, teacher, and dean of the School of Earth Sciences. James Rosse, Vice President and Provost of Stanford University, struck a particularly resonant chord with his personal remarks: "Allan reached out to each person he knew with the warmth and attention that can only come from deep respect and affection for others. I never heard him speak ill of others, and I do not believe he was capable of doing anything that would harm another being. He cared too much to intrude where he was not wanted, but his curiosity about people and the loving care with which he approached them broke down reserve to create remarkable friendships. His enthusiasm and good humor made him a welcome guest in the hearts of the hundreds of students and colleagues who shared the opportunity of knowing Allan Cox as a person."

  3. Matérn thinned Cox processes

    DEFF Research Database (Denmark)

    Andersen, Ina Trolle; Hahn, Ute

    2016-01-01

    and hard core behaviour can be achieved by applying a dependent Matérn thinning to a Cox process. An exact formula for the intensity of a Matérn thinned shot noise Cox process is derived from the Palm distribution. For the more general class of Matérn thinned Cox processes, formulae for the intensity...

  4. Matérn thinned Cox processes

    DEFF Research Database (Denmark)

    Andersen, Ina Trolle; Hahn, Ute

    of clustering and hard core behaviour can be achieved by applying a dependent Matérn thinning to a Cox process. An exact formula for the intensity of a Matérn thinned shot noise Cox process is derived from the Palm distribution. For the more general class of Matérn thinned Cox processes, formulae...

  5. Lévy based Cox point processes

    DEFF Research Database (Denmark)

    Hellmund, Gunnar; Prokesová, Michaela; Jensen, Eva Bjørn Vedel

    2008-01-01

    In this paper we introduce Lévy-driven Cox point processes (LCPs) as Cox point processes with driving intensity function Λ defined by a kernel smoothing of a Lévy basis (an independently scattered, infinitely divisible random measure). We also consider log Lévy-driven Cox point processes (LLCPs...

  6. Transgenic expression of cyclooxygenase-2 (COX2) causes premature aging phenotypes in mice

    Science.gov (United States)

    Feng, Mingxiao; Field, Kevin; Chatzistamou, Ioulia; Shim, Minsub

    2016-01-01

    Cyclooxygenase (COX) is a key enzyme in the biosynthesis of prostanoids, lipid signaling molecules that regulate various physiological processes. COX2, one of the isoforms of COX, is highly inducible in response to a wide variety of cellular and environmental stresses. Increased COX2 expression is thought to play a role in the pathogenesis of many age-related diseases. COX2 expression is also reported to be increased in the tissues of aged humans and mice, which suggests the involvement of COX2 in the aging process. However, it is not clear whether the increased COX2 expression is causal to or a result of aging. We have now addressed this question by creating an inducible COX2 transgenic mouse model. Here we show that post-natal expression of COX2 led to a panel of aging-related phenotypes. The expression of p16, p53, and phospho-H2AX was increased in the tissues of COX2 transgenic mice. Additionally, adult mouse lung fibroblasts from COX2 transgenic mice exhibited increased expression of the senescence-associated β-galactosidase. Our study reveals that the increased COX2 expression has an impact on the aging process and suggests that modulation of COX2 and its downstream signaling may be an approach for intervention of age-related disorders. PMID:27750221

  7. Modelling of the initial stage of the surface discharge development

    International Nuclear Information System (INIS)

    Gibalov, V.; Pietsch, G.

    1998-01-01

    Computer modelling of the initial stage of the surface discharge was performed by solving numerically the coupled continuity, the Poisson and Townsend ionization equations and taking into account the ionization, attachment and detachment processes. The potential distribution at the dielectric surface and at the boundaries which surround the integration region have been calculated with the charge-image method in a 3D approach. In order to eliminate numerical diffusion effects, the solution of the continuity equation was corrected using a flux correction transport routine. At the positive voltage the development of the discharge channel is determined mainly by the shape of the electrode tip. At the negative voltage the following phases of the discharge may be distinguished: the initial phase, the cathode directed streamer phase resulting in the cathode layer formation, and the propagating phase. The physical processes governing each discharge phase are described in detail. (J.U.)

  8. Two-Stage Electricity Demand Modeling Using Machine Learning Algorithms

    Directory of Open Access Journals (Sweden)

    Krzysztof Gajowniczek

    2017-10-01

    Full Text Available Forecasting of electricity demand has become one of the most important areas of research in the electric power industry, as it is a critical component of cost-efficient power system management and planning. In this context, accurate and robust load forecasting is supposed to play a key role in reducing generation costs, and deals with the reliability of the power system. However, due to demand peaks in the power system, forecasts are inaccurate and prone to high numbers of errors. In this paper, our contributions comprise a proposed data-mining scheme for demand modeling through peak detection, as well as the use of this information to feed the forecasting system. For this purpose, we have taken a different approach from that of time series forecasting, representing it as a two-stage pattern recognition problem. We have developed a peak classification model followed by a forecasting model to estimate an aggregated demand volume. We have utilized a set of machine learning algorithms to benefit from both accurate detection of the peaks and precise forecasts, as applied to the Polish power system. The key finding is that the algorithms can detect 96.3% of electricity peaks (load value equal to or above the 99th percentile of the load distribution and deliver accurate forecasts, with mean absolute percentage error (MAPE of 3.10% and resistant mean absolute percentage error (r-MAPE of 2.70% for the 24 h forecasting horizon.

  9. A Multi-Stage Maturity Model for Long-Term IT Outsourcing Relationship Success

    Science.gov (United States)

    Luong, Ming; Stevens, Jeff

    2015-01-01

    The Multi-Stage Maturity Model for Long-Term IT Outsourcing Relationship Success, a theoretical stages-of-growth model, explains long-term success in IT outsourcing relationships. Research showed the IT outsourcing relationship life cycle consists of four distinct, sequential stages: contract, transition, support, and partnership. The model was…

  10. A stage-based model of manatee population dynamics

    Science.gov (United States)

    Runge, M.C.; Langtimm, C.A.; Kendall, W.L.

    2004-01-01

    A stage-structured population model for the Florida manatee (Trichechus manatus latirostris) was developed that explicitly incorporates uncertainty in parameter estimates. The growth rates calculated with this model reflect the status of the regional populations over the most recent 10-yr period. The Northwest and Upper St. Johns River regions have growth rates (8) of 1.037 (95% interval, 1.016?1.056) and 1.062 (1.037?1.081), respectively. The Southwest region has a growth rate of 0.989 (0.946?1.024), suggesting this population has been declining at about 1.1% per year. The estimated growth rate in the Atlantic region is 1.010 (0.988?1.029), but there is some uncertainty about whether adult survival rates have been constant over the last 10 yr; using the mean survival rates from the most recent 5-yr period, the estimated growth rate in this region is 0.970 (0.938?0.998). Elasticity analysis indicates that the most effective management actions should seek to increase adult survival rates. Decomposition of the uncertainty in the growth rates indicates that uncertainty about population status can best be reduced through increased monitoring of adult survival rate.

  11. COX-1 vs. COX-2 as a determinant of basal tone in the internal anal sphincter.

    Science.gov (United States)

    de Godoy, Márcio A F; Rattan, Neeru; Rattan, Satish

    2009-02-01

    Prostanoids, produced endogenously via cyclooxygenases (COXs), have been implicated in the sustained contraction of different smooth muscles. The two major types of COXs are COX-1 and COX-2. The COX subtype involved in the basal state of the internal anal sphincter (IAS) smooth muscle tone is not known. To identify the COX subtype, we examined the effect of COX-1- and COX-2-selective inhibitors, SC-560 and rofecoxib, respectively, on basal tone in the rat IAS. We also determined the effect of selective deletion of COX-1 and COX-2 genes (COX-1(-/-) and COX-2(-/-) mice) on basal tone in murine IAS. Our data show that SC-560 causes significantly more efficacious and potent concentration-dependent decreases in IAS tone than rofecoxib. In support of these data, significantly higher levels of COX-1 than COX-2 mRNA were found in the IAS. In addition, higher levels of COX-1 mRNA and protein were expressed in rat IAS than rectal smooth muscle. In wild-type mice, IAS tone was decreased 41.4 +/- 3.4% (mean +/- SE) by SC-560 (1 x 10(-5) M) and 5.4 +/- 2.2% by rofecoxib (P IAS from wild-type mice and significantly less (0.080 +/- 0.015 mN/mg) in the IAS from COX-1(-/-) mice (P IAS tone.

  12. Model of unplanned smoking initiation of children and adolescents: an integrated stage model of smoking behavior.

    Science.gov (United States)

    Kremers, S P J; Mudde, A N; De Vries, H

    2004-05-01

    Two lines of psychological research have attempted to spell out the stages of adolescent smoking initiation. The first has focused on behavioral stages of smoking initiation, while the second line emphasized motivational stages. A large international sample of European adolescents (N = 10,170, mean age = 13.3 years) was followed longitudinally. Self-reported motivational and behavioral stages of smoking initiation were integrated, leading to the development of the Model of Unplanned Smoking Initiation of Children and Adolescents (MUSICA). The MUSICA postulates that youngsters experiment with smoking while they are in an unmotivated state as regards their plans for smoking regularly in the future. More than 95% of the total population resided in one of the seven stages distinguished by MUSICA. The probability of starting to smoke regularly during the 12 months follow-up period increased with advanced stage assignment at baseline. Unique social cognitive predictors of stage progression from the various stages were identified, but effect sizes of predictors of transitions were small. The integration of motivational and behavioral dimensions improves our understanding of the process of smoking initiation. In contrast to current theories of smoking initiation, adolescent uptake of smoking behavior was found to be an unplanned action.

  13. YAP transcriptionally regulates COX-2 expression and GCCSysm-4 (G-4), a dual YAP/COX-2 inhibitor, overcomes drug resistance in colorectal cancer.

    Science.gov (United States)

    Li, Wei; Cao, Yuanyuan; Xu, Jinling; Wang, Ying; Li, Weijie; Wang, Qian; Hu, Ziwei; Hao, Yaping; Hu, Li; Sun, Yawen; Xu, Guanglin; Ao, Guizhen

    2017-10-16

    Chemotherapy resistance remains a major challenge in cancer treatment. COX-2 (cyclooxygenase 2) is involved in drug resistance and poor prognosis of many neoplastic diseases or cancers. However, investigations identifying new modulators of COX-2 pathway and searching for new chemicals targeting these valid resistant biomarkers are still greatly needed. HCT15, HCT-116, HT-29, COLO205, FHC, IMCE, SW480 cell lines were used to detect the expression of YAP and COX-2. Site-directed mutagenesis, luciferase reporter analysis and ChIP assay were used to test whether YAP activated COX-2 transcription through interaction with TEAD binding sites in the promoter of COX-2. Cell line models exhibiting overexpression or knockdown of some genes were generated using transfection agents. Coimmunoprecipitation was used to detect protein mutual interaction. mRNA and protein levels were measured by qRT-PCR and western blot respectively. Here, we reported that both YAP and COX-2 were overexpressed in colorectal cancer cells. YAP increased COX-2 expression at the level of transcription requiring intact TEAD binding sites in the COX-2 promoter. YAP conferred drug resistance through COX-2 and its related effectors such as MCL, MDR, Survivin. GCCSysm-4 (G-4), a YAP and COX-2 inhibitor, effectively inhibited both YAP and COX-2 activation, induced apoptosis and decreased viability in Taxol-resistant cells. Inhibition of YAP and COX-2 acted synergistically and more efficiently reduced the resistance of CRC cells than either of them alone. Our data provide new mechanisms that YAP is a new upstream regulator of COX-2 pathway and plays an important role in conferring resistance in CRC cells. G-4, targeting YAP-COX-2, may be a novel valuable strategy to combat resistance in CRC.

  14. Cox1 mutation abrogates need for Cox23 in cytochrome c oxidase biogenesis

    Directory of Open Access Journals (Sweden)

    Richard Dela Cruz

    2016-06-01

    Full Text Available Cox23 is a known conserved assembly factor for cytochrome c oxidase, although its role in cytochrome c oxidase (CcO biogenesis remains unresolved. To gain additional insights into its role, we isolated spontaneous suppressors of the respiratory growth defect in cox23∆ yeast cells. We recovered independent colonies that propagated on glycerol/lactate medium for cox23∆ cells at 37°C. We mapped these mutations to the mitochondrial genome and specifically to COX1 yielding an I101F substitution. The I101F Cox1 allele is a gain-of-function mutation enabling yeast to respire in the absence of Cox23. CcO subunit steady-state levels were restored with the I101F Cox1 suppressor mutation and oxygen consumption and CcO activity were likewise restored. Cells harboring the mitochondrial genome encoding I101F Cox1 were used to delete genes for other CcO assembly factors to test the specificity of the Cox1 mutation as a suppressor of cox23∆ cells. The Cox1 mutant allele fails to support respiratory growth in yeast lacking Cox17, Cox19, Coa1, Coa2, Cox14 or Shy1, demonstrating its specific suppressor activity for cox23∆ cells.

  15. A match-mismatch test of a stage model of behaviour change in tobacco smoking

    NARCIS (Netherlands)

    Dijkstra, A; Conijn, B; De Vries, H

    Aims An innovation offered by stage models of behaviour change is that of stage-matched interventions. Match-mismatch studies are the primary test of this idea but also the primary test of the validity of stage models. This study aimed at conducting such a test among tobacco smokers using the Social

  16. Ready or Not: Uses of the Stages of Change Model in Child Welfare

    Science.gov (United States)

    Littell, Julia H.; Girvin, Heather

    2004-01-01

    This article reviews the popular stages of change model, its potential applications in child welfare, and relevant research. Empirical evidence indicates that behavioral change does not occur in a series of stages. The article considers the validity of the stage model, its underlying assumptions, and other conceptualizations of readiness for…

  17. A model of the two-stage Hall thruster discharge

    International Nuclear Information System (INIS)

    Ahedo, E.; Parra, F.I.

    2005-01-01

    The effect of a third, active electrode placed inside the ceramic chamber of a Hall thruster is analyzed. Both electron-collecting and electron-emitting modes are considered. Significant efficiency enhancement with respect to the single-stage operation can be obtained for a good electron-emitting electrode, placed in an intermediate location of the acceleration region, and for an anode-to-electrode (inner-stage) potential significantly larger than the ionization potential. Optimum values of the electrode location and voltage are determined. The performance improvement is due to a reduction of the energy losses to the chamber walls. This is the consequence of lower Joule heating and thus lower electron temperature in the outer stage. When the ionization process is efficient already in the single-stage operation (i) two-stage operation does not affect practically the propellant and voltage utilizations and (ii) thrust efficiency decreases when the intermediate electrode works as an electron collector

  18. Reliability in the Power System Modeled in a Multi- Stage Stochastic Mixed Integer Programming Model

    DEFF Research Database (Denmark)

    Simonsen Nielsen, Michael Pascal

    Contributions from this article are that it takes the characteristics of the power system into account at different stages, which gives a more realistic presentation of the welfare aspects to be gained by an optimal operation/ dispatch of the power system. This article is utilizing a Multi......-Stage Stochastic Mixed Integer Programming Model that handles uncertainty in a flexible and practical way. The method applied relies on state-of-the-art modeling within this field, but the method applied in this article is extended by using decomposition....

  19. An experimentally validated simulation model for a four-stage spray dryer

    DEFF Research Database (Denmark)

    Petersen, Lars Norbert; Poulsen, Niels Kjølstad; Niemann, Hans Henrik

    2017-01-01

    is divided into four consecutive stages: a primary spray drying stage, two heated fluid bed stages, and a cooling fluid bed stage. Each of these stages in the model is assumed ideally mixed and the dynamics are described by mass- and energy balances. These balance equations are coupled with constitutive......In this paper, we develop a dynamic model of an industrial type medium size four-stage spray dryer. The purpose of the model is to enable simulations of the spray dryer at different operating points, such that the model facilitates development and comparison of control strategies. The dryer...... mathematical model is an index-1 differential algebraic equation (DAE) model with 12 states, 9 inputs, 8 disturbances, and 30 parameters. The parameters in the model are identified from well-excited experimental data obtained from the industrialtype spray dryer. The simulated outputs ofthe model are validated...

  20. COX-1 and COX-2 polymorphisms in susceptibility to cerebral palsy in very preterm infants.

    Science.gov (United States)

    Kapitanović Vidak, Helena; Catela Ivković, Tina; Vidak, Zoran; Kapitanović, Sanja

    2017-03-01

    Cerebral palsy (CP) is a nonprogressive motor disorder caused by white matter damage in the developing brain. Recent epidemiological and clinical data suggest intrauterine infection/inflammation as the most common cause of preterm delivery and neonatal complications, including CP. Cyclooxygenases are key enzymes in the conversion of arachidonic acid to prostaglandins. The COX family consists of two isoforms, COX-1 and COX-2. In the brain, COX-2 is constitutively expressed at high levels on pyramidal neurons, while COX-1 is predominantly expressed by microglia and can be upregulated in pathological conditions, such as infection, ischemia and traumatic brain injury. Single nucleotide polymorphisms in the COX-1 and COX-2 gene could have profound effects on COX-1 and COX-2 expression and, directly or indirectly, influence the pathogenesis, development and severity of CP. In this study we investigated the association between single nucleotide polymorphisms of the COX-1 and COX-2 gene and susceptibility to cerebral palsy in very preterm infants. The results of our study showed the association between COX-1 high expression genotype (-842 AA) and COX-1 high expression allele -842A and risk of CP in infants with cystic periventricular leucomalacia (cPVL). Our results support an important role of COX-1 enzyme on microglial activation during neuroinflammation resulting in huge neuroinflammatory response and the proinflammatory mediator overproduction, with the serious white matter damage and CP development as a consequence.

  1. Development of an early-stage toll revenue estimation model.

    Science.gov (United States)

    2012-05-01

    With agencies and states increasingly considering tolls as a means to finance transportation infrastructure, : there is an increasing need to quickly assess the feasibility of potential tolling projects. In the early stages : of a project when an age...

  2. Testing the Box-Cox Parameter for an Integrated Process

    NARCIS (Netherlands)

    J. Huang (Jian); M. Kobayashi (Masahito); M.J. McAleer (Michael)

    2011-01-01

    textabstractThis paper analyses the constant elasticity of volatility (CEV) model suggested by Chan et al. (1992). The CEV model without mean reversion is shown to be the inverse Box-Cox transformation of integrated processes asymptotically. It is demonstrated that the maximum likelihood estimator

  3. A Comparative Study of Cox Regression vs. Log-Logistic ...

    African Journals Online (AJOL)

    Colorectal cancer is common and lethal disease with different incidence rate in different parts of the world which is taken into account as the third cause of cancer-related deaths. In the present study, using non-parametric Cox model and parametric Log-logistic model, factors influencing survival of patients with colorectal ...

  4. Simplifying a physiologically structured population model to a stage-structured biomass model

    NARCIS (Netherlands)

    de Roos, A.M.; Schellekens, T.; van Kooten, T.; van de Wolfshaar, K.E.; Claessen, D.; Persson, L.

    2008-01-01

    We formulate and analyze an archetypal consumer-resource model in terms of ordinary differential equations that consistently translates individual life history processes, in particular food-dependent growth in body size and stage-specific differences between juveniles and adults in resource use and

  5. Regulation of COX and LOX by curcumin.

    Science.gov (United States)

    Rao, Chinthalapally V

    2007-01-01

    Turmeric (Curcuma longa) is extensively used as a household remedy for various diseases. For the last few decades, work has been done to establish the biological activities and pharmacological actions of curcumin, the principle constituent of turmeric. Curcumin has proven to be beneficial in the prevention and treatment of a number of inflammatory diseases due to its anti-inflammatory activity. Arachidonic acid-derived lipid mediators that are intimately involved in inflammation are biosynthesized by pathways dependent on cyclooxygenase (COX) and lipoxygenase (LOX) enzymes. The role of LOX and COX isoforms, particularly COX-2, in the inflammation has been well established. At cellular and molecular levels, curcumin has been shown to regulate a number of signaling pathways, including the eicosanoid pathway involving COX and LOX. A number of studies have been conducted that support curcumin-mediated regulation of COX and LOX pathways, which is an important mechanism by which curcumin prevents a number of disease processes, including the cancer. The specific regulation of 5-LOX and COX-2 by curcumin is not fully established; however, existing evidence indicates that curcumin regulates LOX and COX-2 predominately at the transcriptional level and, to a certain extent, the posttranslational level. Thus, the curcumin-selective transcriptional regulatory action of COX-2, and dual COX/LOX inhibitory potential of this naturally occurring agent provides distinctive advantages over synthetic COX/LOX inhibitors, such as nonsteroidal anti-inflammatory drugs. In this review, we discuss evidence that supports the regulation of COX and LOX enzymes by curcumin as the key mechanism for its beneficial effects in preventing various inflammatory diseases.

  6. Estimating functions for inhomogeneous Cox processes

    DEFF Research Database (Denmark)

    Waagepetersen, Rasmus

    2006-01-01

    Estimation methods are reviewed for inhomogeneous Cox processes with tractable first and second order properties. We illustrate the various suggestions by means of data examples.......Estimation methods are reviewed for inhomogeneous Cox processes with tractable first and second order properties. We illustrate the various suggestions by means of data examples....

  7. HNE as an inducer of COX-2.

    Science.gov (United States)

    Uchida, Koji

    2017-10-01

    Cyclooxygenase-2 (COX-2), an inducible isoform responsible for high levels of prostaglandin (PG) production during inflammation and immune responses, mediate a variety of biological actions involved in vascular pathophysiology. COX-2 is induced by various stimuli, including proinflammatory cytokines, to result in PG synthesis associated with inflammation and carcinogenesis. 4-Hydroxy-2-nonenal (HNE) is one of a group of small molecules that can induce COX-2 expression. The mechanistic studies have revealed that the HNE-induced COX-2 expression results from the stabilization of COX-2 mRNA mediated by the p38 mitogen-activated protein kinase signaling pathway and uniquely requires a serum component, which is eventually identified to be modified low-density lipoproteins (LDLs), such as the oxidized form of LDLs. It has also been shown that HNE-induced COX-2 expression is mechanistically linked to the expression of transcription factor p53 and that the overexpression of COX-2 is associated with down-regulation of a proteasome subunit, leading to the enhanced accumulation of p53 and ubiquitinated proteins and to the enhanced sensitivity toward HNE. Thus, the overall mechanism and pathophysiological role of the COX-2 induction by HNE have become increasingly evident. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Palm distributions for log Gaussian Cox processes

    DEFF Research Database (Denmark)

    Coeurjolly, Jean-Francois; Møller, Jesper; Waagepetersen, Rasmus

    This paper reviews useful results related to Palm distributions of spatial point processes and provides a new result regarding the characterization of Palm distributions for the class of log Gaussian Cox processes. This result is used to study functional summary statistics for a log Gaussian Cox...

  9. Allocatable Fixed Inputs and Two-Stage Aggregation Models of Multioutput Production Decisions

    OpenAIRE

    Barry T. Coyle

    1993-01-01

    Allocation decisions for a fixed input such as land are incorporated into a two-stage aggregation model of multioutput production decisions. The resulting two-stage model is more realistic and is as tractable for empirical research as the standard model.

  10. Evolutionary Stages of e-Tailors and Retailers: Firm Value Determinants Model

    OpenAIRE

    Jae K. Lee; Heegoo Kang; Hoe K. Lee; Han S. Lee

    2002-01-01

    We have studied the evolutionary stages of pure e-tailers, click & mortar (C&M) and brick & mortar (B&M) retailers for three points of time: June 1999, June 2000, and June 2001. To evaluate the dynamic stages of e-tailing business as an innovative venture, we propose four stages: exploration, breakeven, growth, and maturity. The stages are measured by the impact of revenue and income on the firm value, and a regression model is adopted to formulate the model. To empirically examine the stages...

  11. BOX-COX REGRESSION METHOD IN TIME SCALING

    Directory of Open Access Journals (Sweden)

    ATİLLA GÖKTAŞ

    2013-06-01

    Full Text Available Box-Cox regression method with λj, for j = 1, 2, ..., k, power transformation can be used when dependent variable and error term of the linear regression model do not satisfy the continuity and normality assumptions. The situation obtaining the smallest mean square error  when optimum power λj, transformation for j = 1, 2, ..., k, of Y has been discussed. Box-Cox regression method is especially appropriate to adjust existence skewness or heteroscedasticity of error terms for a nonlinear functional relationship between dependent and explanatory variables. In this study, the advantage and disadvantage use of Box-Cox regression method have been discussed in differentiation and differantial analysis of time scale concept.

  12. [p53, p16 E COX-2 expression in esophageal squamous cell carcinoma and histopathological association].

    Science.gov (United States)

    Felin, Izabella Paz Danezi; Grivicich, Ivana; Felin, Carlos Roberto; Regner, Andrea; Rocha, Adriana Brondani da

    2008-01-01

    The esophageal carcinoma represents about 2% of malignant tumors and is the third most common cause of gastrointestinal cancer. The correlation between immunohistochemistry markers, such as p53, p16 and COX-2 proteins and cancer esophageal prognosis has been suggested. To Investigate whether the expression of p53, p16 and COX-2 proteins are associated to tumor staging. For this purpose we proceeded immunohistochemistry assays and TMN in 31 esophageal tumor and normal tissue samples. The p53 nuclear expression was considered positive when it appears in 10.00% or more cells. COX-2 expression was scored according to intensity in three scores (1+, 2+, 3+). On the tumor samples the results presented 48.38% positivity for p53, 16.12% for p16 and 100% with 1+, 2+ or 3+ scores for COX-2. However, when we investigated whether the expression of p53, p16 and COX-2 proteins are related to tumor staging, only COX-2 expression, score 3+, had shown statistical significant association. Therefore, in the present study we could see positive correlation between COX-2 protein and high grade tumor as well as advanced tumor staging in esophageal carcinoma.

  13. Structural neuroimaging across early-stage psychosis: Aberrations in neurobiological trajectories and implications for the staging model.

    Science.gov (United States)

    Bartholomeusz, Cali F; Cropley, Vanessa L; Wannan, Cassandra; Di Biase, Maria; McGorry, Patrick D; Pantelis, Christos

    2017-05-01

    This review critically examines the structural neuroimaging evidence in psychotic illness, with a focus on longitudinal imaging across the first-episode psychosis and ultra-high-risk of psychosis illness stages. A thorough search of the literature involving specifically longitudinal neuroimaging in early illness stages of psychosis was conducted. The evidence supporting abnormalities in brain morphology and altered neurodevelopmental trajectories is discussed in the context of a clinical staging model. In general, grey matter (and, to a lesser extent, white matter) declines across multiple frontal, temporal (especially superior regions), insular and parietal regions during the first episode of psychosis, which has a steeper trajectory than that of age-matched healthy counterparts. Although the ultra-high-risk of psychosis literature is considerably mixed, evidence indicates that certain volumetric structural aberrations predate psychotic illness onset (e.g. prefrontal cortex thinning), while other abnormalities present in ultra-high-risk of psychosis populations are potentially non-psychosis-specific (e.g. hippocampal volume reductions). We highlight the advantages of longitudinal designs, discuss the implications such studies have on clinical staging and provide directions for future research.

  14. Statistical inference for Cox processes

    DEFF Research Database (Denmark)

    Møller, Jesper; Waagepetersen, Rasmus Plenge

    2002-01-01

    Research has generated a number of advances in methods for spatial cluster modelling in recent years, particularly in the area of Bayesian cluster modelling. Along with these advances has come an explosion of interest in the potential applications of this work, especially in epidemiology and genome...... that illuminate the nature and purpose of cluster modelling within different application areas, including astrophysics, epidemiology, ecology, and imaging. The focus then shifts to methods, with discussions on point and object process modelling, perfect sampling of cluster processes, partitioning in space...... and space-time, spatial and spatio-temporal process modelling, nonparametric methods for clustering, and spatio-temporal cluster modelling.   Many figures, some in full color, complement the text, and a single section of references cited makes it easy to locate source material. Leading specialists...

  15. Comment on "Why reduced-form regression models of health effects versus exposures should not replace QRA: livestock production and infant mortality as an example," by Louis Anthony (Tony) Cox, Jr., Risk Analysis 2009, Vol. 29, No. 12.

    Science.gov (United States)

    Sneeringer, Stacy

    2010-04-01

    While a recent paper by Cox in this journal uses as its motivating factor the benefits of quantitative risk assessment, its content is entirely devoted to critiquing Sneeringer's article in the American Journal of Agricultural Economics. Cox's two main critiques of Sneeringer are fundamentally flawed and misrepresent the original article. Cox posits that Sneeringer did A and B, and then argues why A and B are incorrect. However, Sneeringer in fact did C and D; thus critiques of A and B are not applicable to Sneeringer's analysis.

  16. Validation of existing prognostic models in patients with early-stage cervical cancer

    NARCIS (Netherlands)

    Biewenga, Petra; van der Velden, Jacobus; Mol, Ben Willem J.; Stalpers, Lukas J. A.; Schilthuis, Marten S.; van der Steeg, Jan Willem; Burger, Matthé P. M.; Buist, Marrije R.

    2009-01-01

    Objective. Models that predict survival and recurrence in patients with early-stage cervical cancer are important tools in patient management, We validated 12 existing prognostic models in an independent population of patients with early-stage cervical cancer. Materials and Methods. We searched the

  17. Analysis of Three-dimension Viscous Flow in the Model Axial Compressor Stage K1002L

    Science.gov (United States)

    Tribunskaia, K.; Kozhukhov, Y. V.

    2017-08-01

    The main investigation subject considered in this paper is axial compressor model stage K1002L. Three simulation models were designed: Scheme 1 - inlet stage model consisting of IGV (Inlet Guide Vane), rotor and diffuser; Scheme 2 - two-stage model: IGV, first-stage rotor, first-stage diffuser, second-stage rotor, EGV (Exit Guide Vane); Scheme 3 - full-round model: IGV, rotor, diffuser. Numerical investigation of the model stage was held for four circumferential velocities at the outer diameter (Uout=125,160,180,210 m/s) within the range of flow coefficient: ϕ = 0.4 - 0.6. The computational domain was created with ANSYS CFX Workbench. According to simulation results, there were constructed aerodynamic characteristic curves of adiabatic efficiency and the adiabatic head coefficient calculated for total parameters were compared with data from the full-scale test received at the Central Boiler and Turbine Institution (CBTI), thus, verification of the calculated data was carried out. Moreover, there were conducted the following studies: comparison of aerodynamic characteristics of the schemes 1, 2; comparison of the sector and full-round models. The analysis and conclusions are supplemented by gas-dynamic method calculation for axial compressor stages.

  18. Toward the understanding of the molecular basis for the inhibition of COX-1 and COX-2 by phenolic compounds present in Uruguayan propolis and grape pomace.

    Science.gov (United States)

    Paulino, Margot; Alvareda, Elena; Iribarne, Federico; Miranda, Pablo; Espinosa, Victoria; Aguilera, Sara; Pardo, Helena

    2016-12-01

    Propolis and grape pomace have significant amounts of phenols which can take part in anti-inflammatory mechanisms. As the cyclooxygenases 1 and 2 (COX-1 and COX-2) are involved in said mechanisms, the possibility for a selective inhibition of COX-2 was analyzed in vitro and in silico. Propolis and grape pomace from Uruguayan species were collected, extracted in hydroalcoholic mixture and analyzed. Based on phenols previously identified, and taking as reference the crystallographic structures of COX-1 and COX-2 in complex with the commercial drug Celecoxib, a molecular docking procedure was devised to adjust 123 phenolic molecular models at the enzyme-binding sites. The most important results of this work are that the extracts have an overall inhibition activity very similar in COX-1 and COX-2, i.e. they do not possess selective inhibition activity for COX-2. Nevertheless, 10 compounds of the phenolic database turned out to be more selective and 94 phenols resulted with similar selectivity than Celecoxib, an outcome that accounts for the overall experimental inhibition measures. Binding site environment observations showed increased polarity in COX-2 as compared with COX-1, suggesting that polarity is the key for selectivity. Accordingly, the screening of molecular contacts pointed to the residues: Arg106, Gln178, Leu338, Ser339, Tyr341, Tyr371, Arg499, Ala502, Val509, and Ser516, which would explain, at the atomic level, the anti-inflammatory effect of the phenolic compounds. Among them, Gln178 and Arg499 appear to be essential for the selective inhibition of COX-2.

  19. A proposed model of psychodynamic psychotherapy linked to Erik Erikson's eight stages of psychosocial development.

    Science.gov (United States)

    Knight, Zelda Gillian

    2017-09-01

    Just as Freud used stages of psychosexual development to ground his model of psychoanalysis, it is possible to do the same with Erik Erikson's stages of development with regards to a model of psychodynamic psychotherapy. This paper proposes an eight-stage model of psychodynamic psychotherapy linked to Erik Erikson's eight stages of psychosocial development. Various suggestions are offered. One such suggestion is that as each of Erikson's developmental stages is triggered by a crisis, in therapy it is triggered by the client's search. The resolution of the search often leads to the development of another search, which implies that the therapy process comprises a series of searches. This idea of a series of searches and resolutions leads to the understanding that identity is developmental and therapy is a space in which a new sense of identity may emerge. The notion of hope is linked to Erikson's stage of Basic Trust and the proposed model of therapy views hope and trust as essential for the therapy process. Two clinical vignettes are offered to illustrate these ideas. Psychotherapy can be approached as an eight-stage process and linked to Erikson's eight stages model of development. Psychotherapy may be viewed as a series of searches and thus as a developmental stage resolution process, which leads to the understanding that identity is ongoing throughout the life span. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Model Development for Atomic Force Microscope Stage Mechanisms

    National Research Council Canada - National Science Library

    Smith, Ralph C; Hatch, Andrew G; De, Tathagata; Salapaka, Murti V; Raye, Julie K; del Rosario, Ricardo C

    2005-01-01

    In this paper, we develop nonlinear constitutive equations and resulting system models quantifying the nonlinear and hysteretic field-displacement relations inherent to lead zirconate titanate (PZT...

  1. The Transtheoretical model for fruit, vegetable and fish consumption: associations between intakes, stages of change and stage transition determinants

    Directory of Open Access Journals (Sweden)

    de Vries Nanne K

    2006-06-01

    Full Text Available Abstract Background Cardiovascular diseases are caused by multiple behavioral factors, including different dietary factors. We examined to what extent fruit, vegetable and fish consumption are related, and whether behavioral determinants vary across these dietary behaviors from a Transtheoretical model perspective. Methods Data were collected among 1142 participants (T0; response rate 46% selected from an Internet panel, who were followed-up one-week later (T1; N = 1055, response rate 92%. Mean age was 35.4 (SD = 11.9 years, 35% was male, and most respondents were of Dutch origin (90%. Of the respondents, 13%, 44% and 43% had a low, medium or high level of education, respectively. Electronic questionnaires assessed fruit, vegetable and fish intake (food frequency questionnaires, stages of change, decisional balance and self-efficacy, for each of these three behaviors. Results Stages of change and (changes in fruit, vegetable and fish intake were only weakly associated; decisional balance and self-efficacy were more strongly associated. Some presumed predictors of stage transitions were similar for fruit, vegetable, and fish intake, i.e., strong pros predicted progress out of precontemplators and low self-efficacy predicted relapse from action/maintenance for all behaviors. However, progress out of contemplation and out of preparation showed different patterns for fruit, vegetable and fish intake. Conclusion The weak associations between intakes and potential determinants for fruit, vegetable, and fish consumption do not warrant an integrated dietary change approach targeting the same determinants for each behavior.

  2. Generating a robust prediction model for stage I lung adenocarcinoma recurrence after surgical resection.

    Science.gov (United States)

    Wu, Yu-Chung; Wei, Nien-Chih; Hung, Jung-Jyh; Yeh, Yi-Chen; Su, Li-Jen; Hsu, Wen-Hu; Chou, Teh-Ying

    2017-10-03

    Lung cancer mortality remains high even after successful resection. Adjuvant treatment benefits stage II and III patients, but not stage I patients, and most studies fail to predict recurrence in stage I patients. Our study included 211 lung adenocarcinoma patients (stages I-IIIA; 81% stage I) who received curative resections at Taipei Veterans General Hospital between January 2001 and December 2012. We generated a prediction model using 153 samples, with validation using an additional 58 clinical outcome-blinded samples. Gene expression profiles were generated using formalin-fixed, paraffin-embedded tissue samples and microarrays. Data analysis was performed using a supervised clustering method. The prediction model generated from mixed stage samples successfully separated patients at high vs. low risk for recurrence. The validation tests hazard ratio (HR = 4.38) was similar to that of the training tests (HR = 4.53), indicating a robust training process. Our prediction model successfully distinguished high- from low-risk stage IA and IB patients, with a difference in 5-year disease-free survival between high- and low-risk patients of 42% for stage IA and 45% for stage IB ( p model for identifying lung adenocarcinoma patients at high risk for recurrence who may benefit from adjuvant therapy. Our prediction performance of the difference in disease free survival between high risk and low risk groups demonstrates more than two fold improvement over earlier published results.

  3. COX-2 expression in ovarian cancer: an updated meta-analysis.

    Science.gov (United States)

    Sun, Haiming; Zhang, Xuelong; Sun, Donglin; Jia, Xueyuan; Xu, Lidan; Qiao, Yuandong; Jin, Yan

    2017-10-20

    The prognostic role of COX-2 expression in ovarian cancer patients has been studied for years, while results remain controversial. Thus we performed a meta-analysis to evaluate the prognostic impact of COX-2 expression on survival of ovarian cancer patients. The databases PubMed, Embase and CNKI were searched. Summary hazard ratio (HR) and 95% confidence intervals (CIs) were calculated to analyze the correlations between COX-2 expression and overall survival (OS), and disease-free survival (DFS). A total of 1,867 patients from 18 studies were enrolled in the final analysis. The results showed that patients with higher COX-2 expression had a poor OS (HR: 1.48; 95% CI: 1.19-1.85) and DFS (HR: 1.81, 95% CI: 1.28-2.55). Subgroup analysis showed that there had significant associations between COX-2 expression and survival rate in most of the subgroups. Furthermore, there were significant associations between COX-2 expression and several clinical parameters such as FIGO stage, histological type and age. These results showed the patients with higher COX-2 expression had a significantly poorer survival rate, COX-2 expression had the potential to be a prognostic marker of ovarian cancer.

  4. Consideration sets, intentions and the inclusion of "don't know" in a two-stage model for voter choice

    NARCIS (Netherlands)

    Paap, R; van Nierop, E; van Heerde, HJ; Wedel, M; Franses, PH; Alsem, KJ

    2005-01-01

    We present a statistical model for voter choice that incorporates a consideration set stage and final vote intention stage. The first stage involves a multivariate probit (MVP) model to describe the probabilities that a candidate or a party gets considered. The second stage of the model is a

  5. Expression of beta-catenin, COX-2 and iNOS in colorectal cancer: relevance of COX-2 adn iNOS inhibitors for treatment in Malaysia.

    Science.gov (United States)

    Hong, Seok Kwan; Gul, Yunus A; Ithnin, Hairuszah; Talib, Arni; Seow, Heng Fong

    2004-01-01

    Promising new pharmacological agents and gene therapy targeting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) could modulate treatment of colorectal cancer in the future. The aim of this study was to elucidate the expression fo beta-catenin and teh presence of COX-2 and iNOS in colorectal cancer specimens in Malaysia. This is a useful prelude to future studies investigating interventions directed towards COX-2 adn iNOS. A cross-section study using retrospective data over a 2-year period (1999-2000) involved 101 archival, formalin-fixed, paraffin-embedded tissue samples of colorectal cancers that were surgically resected in a tertiary referral. COX-2 production was detected in adjacent normal tissue in 34 sample (33.7%) and in tumour tissue in 60 samples (59.4%). More tumours expressed iNOS (82/101, 81.2%) than COX-2. No iNOS expression was detected in adjacent normal tissue. Intense beta-catenin immunoreactivity at the cell-to-cell border. Poorly differentiated tumours had significantly lower total beta-catenin (p = 0.009) and COX-2 scores (p = 0.031). No significant relationships were established between pathological stage and beta-catenin, COX-2 and iNOS scores. the accumulation of beta-catenin does not seem to be sufficient to activate pathways that lead to increased COX-2 and iNOS expression. A high proportion of colorectal cancers were found to express COX-2 and a significant number produced iNOS, suggesting that their inhibitors may be potentially useful as chemotherapeutic agents in the management of colorectal cancer.

  6. Inhibition of bcl-2 and cox-2 Protein Expression after Local Application of a New Carmustine-Loaded Clinoptilolite-Based Delivery System in a Chemically Induced Skin Cancer Model in Mice

    Directory of Open Access Journals (Sweden)

    Cristina Mihaela Ghiciuc

    2017-11-01

    Full Text Available Our research has focused on in vitro and in vivo evaluations of a new Carmustine (BCNU-loaded clinoptilolite-based delivery system. Two clinoptilolite ionic forms—hydrogen form (HCLI and sodium form (NaCLI—were prepared, allowing a loading degree of about 5–6 mg BCNU/g of zeolite matrix due to the dual porous feature of clinoptilolite. Clinoptilolite-based delivery systems released 35.23% of the load in 12 h for the BCNU@HCLI system and only 10.82% for the BCNU@NaCLI system. The BCNU@HCLI system was chosen to develop gel and cream semisolid dosage forms. The cream (C_BCNU@HCLI released 29.6% of the loaded BCNU after 12 h in the Nylon synthetic membrane test and 31.6% in the collagen membrane test, higher by comparison to the gel. The new cream was evaluated in vivo in a chemically induced model of skin cancer in mice. Quantitative immunohistochemistry analysis showed stronger inhibition of B-cell lymphoma-2 (bcl-2 and cyclooxygenase 2 (cox-2 protein expression, known markers for cancer survival and aggressiveness, after the treatment with C_BCNU@HCLI by comparison to all the control treatment types, including an off-label magistral formula commercially available Carmustine cream as reference, bringing evidence that a clinoptilolite-based delivery systems could be used as a cancer drug carriers and controlled release systems (skin-targeted topical delivery systems.

  7. Modelling a Compliant-Based Precise Positioning Stage

    Directory of Open Access Journals (Sweden)

    Giedrius Augustinavičius

    2012-12-01

    Full Text Available The paper presents modelling precise dual axis flexure-based precision positioning systems for micro-positioning applications. The positioning system is featured with monolithic architecture, flexure-based joints and piezo stacks. Its workspace has been evaluated via analytical approaches. Amplification mechanism is optimally designed. The mathematical model of the positioning system has been derived and verified by resorting to finite element analysis (FEA. The established analytical and (FEA models are helpful for optimizing reliable architecture and improving the performance of the positioning system.

  8. Modelling a Compliant-Based Precise Positioning Stage

    Directory of Open Access Journals (Sweden)

    Giedrius Augustinavičius

    2013-02-01

    Full Text Available The paper presents modelling precise dual axis flexure-based precision positioning systems for micro-positioning applications. The positioning system is featured with monolithic architecture, flexure-based joints and piezo stacks. Its workspace has been evaluated via analytical approaches. Amplification mechanism is optimally designed. The mathematical model of the positioning system has been derived and verified by resorting to finite element analysis (FEA. The established analytical and (FEA models are helpful for optimizing reliable architecture and improving the performance of the positioning system.

  9. Differential usage of COX-1 and COX-2 in prostaglandin production by mast cells and basophils.

    Science.gov (United States)

    Bando, Tomoyuki; Fujita, Setsuko; Nagano, Naoko; Yoshikawa, Soichiro; Yamanishi, Yoshinori; Minami, Masashi; Karasuyama, Hajime

    2017-07-01

    Basophils have been erroneously considered as minor relatives of mast cells, due to some phenotypic similarity between them. While recent studies have revealed non-redundant roles for basophils in various immune responses, basophil-derived effector molecules, including lipid mediators, remain poorly characterized, compared to mast cell-derived ones. Here we analyzed and compared eicosanoids produced by mouse basophils and mast cells when stimulated with IgE plus allergens. The production of 5-LOX metabolites such as LTB4 and 5-HETE was detected as early as 0.5 h post-stimulation in both cell types, even though their amounts were much smaller in basophils than in mast cells. In contrast, basophils and mast cells showed distinct time course in the production of COX metabolites, including PGD2, PGE2 and 11-HETE. Their production by mast cells was detected at both 0.5 and 6 h post-stimulation while that by basophils was detectable only at 6 h. Of note, mast cells showed 8-9 times higher levels of COX-1 than did basophils at the resting status. In contrast to unaltered COX-1 expression with or without stimulation, COX-2 expression was up-regulated in both cell types upon activation. Importantly, when activated, basophils expressed 4-5 times higher levels of COX-2 than did mast cells. In accordance with these findings, the late-phase production of the COX metabolites by basophils was completely ablated by COX-2 inhibitor whereas the early-phase production by mast cells was blocked by COX-1 but not COX-2 inhibitor. Thus, the production of COX metabolites is differentially regulated by COX-1 and COX-2 in basophils and mast cells.

  10. Relations of Transtheoretical Model Stage, Self-Efficacy, and Voluntary Physical Activity in African American Preadolescents

    Science.gov (United States)

    Annesi, James J.; Faigenbaum, Avery D.; Westcott, Wayne L.

    2010-01-01

    The transtheoretical model (TTM; Prochaska, DiClemente, & Norcross, 1992) suggests that, at any point, an individual is in one of five stages-of-change related to adopting a behavior. People sequentially advance in stage but may also maintain or even regress, based on personal and environmental factors (Nigg, 2005). A classic study published in…

  11. A developmental model of hierarchical stage structure in objective moral judgements

    NARCIS (Netherlands)

    Boom, J.; Molenaar, P.C.M.

    1989-01-01

    A hierarchical structural model of moral judgment is proposed in which an S is characterized as occupying a particular moral stage. During development, the S's characteristic stage progresses along a latent, ordered dimension in an age-dependent way. Evaluation of prototypic statements

  12. Building performance simulation in the early design stage: An introduction to integrated dynamic models

    DEFF Research Database (Denmark)

    Negendahl, Kristoffer

    2015-01-01

    Designing with building performance simulation feedback in the early design stage has existed since the early days of computational modeling. However, as a consequence of a fragmented building industry building performance simulations (BPSs) in the early design stage are closely related to who is...

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

    Science.gov (United States)

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

  14. The Media Adoption Stage Model of Technology for Art Therapy

    Science.gov (United States)

    Peterson, Brent Christian

    2010-01-01

    This study examined survey data from professional credentialed members of the American Art Therapy Association and 8 follow up interviews to determine how art therapists adopt or reject technology and/or new digital media for therapeutic use with their clients. Using Rogers's (2003) "diffusion of innovation" model, the author identified a…

  15. Thermal properties. Site descriptive modelling Forsmark - stage 2.2

    International Nuclear Information System (INIS)

    Back, Paer-Erik; Wrafter, John; Sundberg, Jan; Rosen, L ars

    2007-09-01

    The lithological data acquired from boreholes and mapping of the rock surface need to be reclassified into thermal rock classes, TRCs. The main reason is to simplify the simulations. The lithological data are used to construct models of the transition between different TRCs, thus describing the spatial statistical structure of each TRC. The result is a set of transition probability models that are used in the simulation of TRCs. The intermediate result of this first stochastic simulation is a number of realisations of the geology, each one equally probable. Based on the thermal data, a spatial statistical thermal model is constructed for each TRC. It consists of a statistical distribution and a variogram for each TRC. These are used in the stochastic simulation of thermal conductivity and the result is a number of equally probable realisations of thermal conductivity for the domain. In the next step, the realisations of TRCs (lithology) and thermal conductivity are merged, i.e. each realisation of geology is filled with simulated thermal conductivity values. The result is a set of realisations of thermal conductivity that considers both the difference in thermal properties between different TRCs, and the variability within each TRC. If the result is desired in a scale different from the simulation scale, i.e. the canister scale, upscaling of the realisations can be performed. The result is a set of equally probable realisations of thermal properties. The presented methodology was applied to rock domain RFM029 and RFM045. The main results are sets of realisations of thermal properties that can be used for further processing, most importantly for statistical analysis and numerical temperature simulations for the design of repository layout (distances between deposition holes). The main conclusions of the thermal modelling are: The choice of scale has a profound influence on the distribution of thermal conductivity values. The variance decreases and the lower tail

  16. Thermal properties. Site descriptive modelling Forsmark - stage 2.2

    Energy Technology Data Exchange (ETDEWEB)

    Back, Paer-Erik; Wrafter, John; Sundberg, Jan [Geo Innova AB (Sweden); Rosen, L ars [Sweco Viak AB (Sweden)

    2007-09-15

    The lithological data acquired from boreholes and mapping of the rock surface need to be reclassified into thermal rock classes, TRCs. The main reason is to simplify the simulations. The lithological data are used to construct models of the transition between different TRCs, thus describing the spatial statistical structure of each TRC. The result is a set of transition probability models that are used in the simulation of TRCs. The intermediate result of this first stochastic simulation is a number of realisations of the geology, each one equally probable. Based on the thermal data, a spatial statistical thermal model is constructed for each TRC. It consists of a statistical distribution and a variogram for each TRC. These are used in the stochastic simulation of thermal conductivity and the result is a number of equally probable realisations of thermal conductivity for the domain. In the next step, the realisations of TRCs (lithology) and thermal conductivity are merged, i.e. each realisation of geology is filled with simulated thermal conductivity values. The result is a set of realisations of thermal conductivity that considers both the difference in thermal properties between different TRCs, and the variability within each TRC. If the result is desired in a scale different from the simulation scale, i.e. the canister scale, upscaling of the realisations can be performed. The result is a set of equally probable realisations of thermal properties. The presented methodology was applied to rock domain RFM029 and RFM045. The main results are sets of realisations of thermal properties that can be used for further processing, most importantly for statistical analysis and numerical temperature simulations for the design of repository layout (distances between deposition holes). The main conclusions of the thermal modelling are: The choice of scale has a profound influence on the distribution of thermal conductivity values. The variance decreases and the lower tail

  17. Distribution of COX-negative mitochondria in myofibers of rats intoxicated with Senna occidentalis seeds.

    Science.gov (United States)

    Calore, N M P; Calore, E E; Sesso, A; Correia, H; Marcondes, M C S L; Vilela de Almeida, L

    2002-04-01

    We have described that administration of seeds or parts of the seed of Senna occidentalis (coffee senna) for long periods, induces histochemical changes in the skeletal muscles of hens and rats that are characteristic of a mitochondrial myopathy--as decrease of SDH and COX activity, with some COX negative fibers. In this experimental model of mitochondrial myopathy, as in many human mitochondrial diseases, there is a random distribution of COX negative fibers. Some fibers are completely COX negative while others are partially negative and others are completely positive. In the present work we have studied the distribution of COX negative mitochondria at transmission electron microscopy in skeletal muscle of rats in this experimental myopathy. In myofibers of intoxicated animals the expression of COX was heterogeneous. The histochemical reaction was observed in the internal membrane (more evident in mitochondrial cristae) of all mitochondria of some myofibers, while it was almost absent in other myofibers. In these myofibers the great part of the mitochondria were negative for COX reaction while other ones had a weak expression of this enzyme (dot or focal expression of COX). Our results indicated that the COX mitochondrial activity is heterogeneously impaired in myofibers of rats intoxicated with S. occidentalis. These abnormalities remember those observed in some types of human mitochondrial myopathies.

  18. Confined mobility in biomembranes modeled by early stage Brownian motion.

    Science.gov (United States)

    Gmachowski, Lech

    2014-08-01

    An equation of motion, derived from the fractal analysis of the Brownian particle trajectory, makes it possible to calculate the time dependence of the mean square displacement for early times, before the Einstein formula becomes valid. The diffusion coefficient increases with the distance travelled which can be restricted by the geometrical conditions. The corresponding diffusion coefficient cannot increase further to achieve a value characteristic for unrestricted environment. Explicit formula is derived for confined diffusivity related to the unrestricted one as dependent on the maximum particle mean square displacement possible normalized by the square of its mean free path. The model describes the lipid and protein diffusion in tubular membranes with different radii, originally fitted by the modified Saffman-Delbrück equation, and the lateral mobility of synthetic model peptides for which the diffusion coefficient is inversely proportional to the radius of the diffusing object and to the thickness of the membrane. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Investigating the performance of directional boundary layer model through staged modeling method

    Science.gov (United States)

    Jeong, Moon-Gyu; Lee, Won-Chan; Yang, Seung-Hune; Jang, Sung-Hoon; Shim, Seong-Bo; Kim, Young-Chang; Suh, Chun-Suk; Choi, Seong-Woon; Kim, Young-Hee

    2011-04-01

    BLM since the feasibility of the BLM has been investigated in many papers[4][5][6]. Instead of fitting the parameters to the wafer critical dimensions (CD) directly, we tried to use the aerial image (AI) from the rigorous simulator with the electromagnetic field (EMF) solver. Usually that kind of method is known as the staged modeling method. To see the advantages of this method we conducted several experiments and observed the results comparing the method of fitting to the wafer CD directly. Through the tests we could observe some remarkable results and confirmed that the staged modeling had better performance in many ways.

  20. Dynamic modeling and simulation of a two-stage series-parallel vibration isolation system

    Directory of Open Access Journals (Sweden)

    Rong Guo

    2016-07-01

    Full Text Available A two-stage series-parallel vibration isolation system is already widely used in various industrial fields. However, when the researchers analyze the vibration characteristics of a mechanical system, the system is usually regarded as a single-stage one composed of two substructures. The dynamic modeling of a two-stage series-parallel vibration isolation system using frequency response function–based substructuring method has not been studied. Therefore, this article presents the source-path-receiver model and the substructure property identification model of such a system. These two models make up the transfer path model of the system. And the model is programmed by MATLAB. To verify the proposed transfer path model, a finite element model simulating a vehicle system, which is a typical two-stage series-parallel vibration isolation system, is developed. The substructure frequency response functions and system level frequency response functions can be obtained by MSC Patran/Nastran and LMS Virtual.lab based on the finite element model. Next, the system level frequency response functions are substituted into the transfer path model to predict the substructural frequency response functions and the system response of the coupled structure can then be further calculated. By comparing the predicted results and exact value, the model proves to be correct. Finally, the random noise is introduced into several relevant system level frequency response functions for error sensitivity analysis. The system level frequency response functions that are most sensitive to the random error are found. Since a two-stage series-parallel system has not been well studied, the proposed transfer path model improves the dynamic theory of the multi-stage vibration isolation system. Moreover, the validation process of the model here actually provides an example for acoustic and vibration transfer path analysis based on the proposed model. And it is worth noting that the

  1. COX-2, VEGF and tumour angiogenesis.

    LENUS (Irish Health Repository)

    Toomey, D P

    2009-06-01

    Epidemiological evidence suggests a protective effective of regular NSAID use against developing cancer. Cyclooxygenase-2, a target of NSAIDs, is upregulated in many cancers and has been associated with increased VEGF production and angiogenesis. Angiogenesis is the formation of new vessels from existing vasculature and as an essential process for tumour development represents an important therapeutic target. Following an extensive review of the literature this article details the current knowledge on the role of COX-2 in tumorigenesis focusing on its relationship to angiogenesis and VEGF production by tumour cells. While COX-2 is clearly detrimental to prognosis and NSAIDs have a beneficial effect, the possibility of COX-2 independent effects being partly or wholly responsible for this benefit cannot be excluded.

  2. A two-phase inspection model for a single component system with three-stage degradation

    International Nuclear Information System (INIS)

    Wang, Huiying; Wang, Wenbin; Peng, Rui

    2017-01-01

    This paper presents a two-phase inspection schedule and an age-based replacement policy for a single plant item contingent on a three-stage degradation process. The two phase inspection schedule can be observed in practice. The three stages are defined as the normal working stage, low-grade defective stage and critical defective stage. When an inspection detects that an item is in the low-grade defective stage, we may delay the preventive replacement action if the time to the age-based replacement is less than or equal to a threshold level. However, if it is above this threshold level, the item will be replaced immediately. If the item is found in the critical defective stage, it is replaced immediately. A hybrid bee colony algorithm is developed to find the optimal solution for the proposed model which has multiple decision variables. A numerical example is conducted to show the efficiency of this algorithm, and simulations are conducted to verify the correctness of the model. - Highlights: • A two-phase inspection model is studied. • The failure process has three stages. • The delayed replacement is considered.

  3. Modelling early stages of relativistic heavy-ion collisions

    Directory of Open Access Journals (Sweden)

    Ruggieri M.

    2016-01-01

    Full Text Available In this study we model early time dynamics of relativistic heavy ion collisions by an initial color-electric field which then decays to a plasma by the Schwinger mechanism. The dynamics of the many particles system produced by the decay is described by relativistic kinetic theory, taking into account the backreaction on the color field by solving self-consistently the kinetic and the field equations. Our main results concern isotropization and thermalization for a 1+1D expanding geometry. In case of small η/s (η/s ≲ 0.3 we find τisotropization ≈ 0.8 fm/c and τthermalization ≈ 1 fm/c in agreement with the common lore of hydrodynamics.

  4. Pregnancy induced changes in Cox-1, Cox-2 and NOSIII vascular and renal expression.

    Science.gov (United States)

    Bobadilla, Rosa A; Bracho, Ismael; Alvarez, Victor M Pérez; Anguiano, Liliana; López, Pedro

    2004-01-01

    In order to establish if there is a mutual regulation between COX and NOS in vascular and renal tissue during pregnancy, we measured the protein expression of COX-1, COX-2 and NOSIII by Western blot comparing the thoracic and abdominal aorta and the renal cortex and medulla of non pregnant and pregnant (21st day) Wistar rats. We found there was no difference in the quantity of protein of any of the two isoforms of COX between the two segments of the aorta of non pregnant animals while an increased expression of both COX-1 And COX-2 was found in the abdominal compared to the thoracic segment of the pregnant rats. An increased expression of NOS III was found in the abdominal segment of the aorta form pregnant rats. No changes were found between pregnant and no pregnant animals in the expression of COX-1 and COX-2 in the renal cortex or medulla while an increased expression of NOS III was found in the cortex from pregnant compared to non pregnant animals. These results suggest the influence of pregnancy is not homogeneous along the aorta and also that a balance between prostaglandins and nitric oxide is responsible of the blunted vascular reactivity during pregnancy in the rat.

  5. Provisional safety analyses for SGT stage 2 -- Models, codes and general modelling approach

    International Nuclear Information System (INIS)

    2014-12-01

    In the framework of the provisional safety analyses for Stage 2 of the Sectoral Plan for Deep Geological Repositories (SGT), deterministic modelling of radionuclide release from the barrier system along the groundwater pathway during the post-closure period of a deep geological repository is carried out. The calculated radionuclide release rates are interpreted as annual effective dose for an individual and assessed against the regulatory protection criterion 1 of 0.1 mSv per year. These steps are referred to as dose calculations. Furthermore, from the results of the dose calculations so-called characteristic dose intervals are determined, which provide input to the safety-related comparison of the geological siting regions in SGT Stage 2. Finally, the results of the dose calculations are also used to illustrate and to evaluate the post-closure performance of the barrier systems under consideration. The principal objective of this report is to describe comprehensively the technical aspects of the dose calculations. These aspects comprise: · the generic conceptual models of radionuclide release from the solid waste forms, of radionuclide transport through the system of engineered and geological barriers, of radionuclide transfer in the biosphere, as well as of the potential radiation exposure of the population, · the mathematical models for the explicitly considered release and transport processes, as well as for the radiation exposure pathways that are included, · the implementation of the mathematical models in numerical codes, including an overview of these codes and the most relevant verification steps, · the general modelling approach when using the codes, in particular the generic assumptions needed to model the near field and the geosphere, along with some numerical details, · a description of the work flow related to the execution of the calculations and of the software tools that are used to facilitate the modelling process, and · an overview of the

  6. Select Dietary Phytochemicals Function as Inhibitors of COX-1 but Not COX-2

    Science.gov (United States)

    Li, Haitao; Zhu, Feng; Sun, Yanwen; Li, Bing; Oi, Naomi; Chen, Hanyong; Lubet, Ronald A.; Bode, Ann M.; Dong, Zigang

    2013-01-01

    Recent clinical trials raised concerns regarding the cardiovascular toxicity of selective cyclooxygenase-2 (COX-2) inhibitors. Many active dietary factors are reported to suppress carcinogenesis by targeting COX-2. A major question was accordingly raised: why has the lifelong use of phytochemicals that likely inhibit COX-2 presumably not been associated with adverse cardiovascular side effects. To answer this question, we selected a library of dietary-derived phytochemicals and evaluated their potential cardiovascular toxicity in human umbilical vein endothelial cells. Our data indicated that the possibility of cardiovascular toxicity of these dietary phytochemicals was low. Further mechanistic studies revealed that the actions of these phytochemicals were similar to aspirin in that they mainly inhibited COX-1 rather than COX-2, especially at low doses. PMID:24098505

  7. Combined activity of COX-1 and COX-2 is increased in non-neoplastic colonic mucosa from colorectal neoplasia patients.

    Science.gov (United States)

    Jensen, Thorbjørn Søren Rønn; Mahmood, Badar; Damm, Morten Bach; Backe, Marie Balslev; Dahllöf, Mattias Salling; Poulsen, Steen Seier; Hansen, Mark Berner; Bindslev, Niels

    2018-02-27

    Cyclooxygenase (COX) activity is increased in endoscopic normal colonic mucosa from patients with colorectal neoplasia (CRN). COX-2 is thought to be the predominant COX isozyme involved in neoplasia. Meanwhile, relative contributions of COX-1 and COX-2 isoforms are unknown. Knowledge about their mutual activity in colonic mucosa is important for diagnostics and targeted therapy for CRN. The aim of this study was to assess the relative function, expression and localization of COX-1 and COX-2 enzymes in colonic non-neoplastic human mucosa and thereby to potentially reveal a mucosal disease predisposition for better treatment. Biopsies were pinched from normal appearing colonic mucosa in patients undergoing endoscopy. Ussing chamber technique was applied for an indirect assessment of epithelial activity, RT-qPCR for expression and immunohistochemistry for localization of COX-1 and COX-2 enzymes in patients without (ctrls) and with a history of CRN (CRN-pts). Combined COX-1 and COX-2 activity was higher in CRN-pts, p = 0.036. COX-2 was primarily localized in absorptive cells, while COX-1 appeared to be restricted to nonenteroendocrine tuft cells of the colonic epithelium. In biopsies from endoscopic normal appearing colonic mucosa, combined activity of COX-1 and COX-2 enzymes is increased in CRN-pts compared with ctrls. This indicates that COX-1 and COX-2 together contribute to an increased proliferation process. Of note, in colonic epithelial cell lining, the COX-1 enzyme seems localized in tuft cells.

  8. Hydrogeological characterisation and modelling of deformation zones and fracture domains, Forsmark modelling stage 2.2

    Energy Technology Data Exchange (ETDEWEB)

    Follin, Sven (SF GeoLogic AB, Taeby (SE)); Leven, Jakob (Swedish Nuclear Fuel and Waste Management Co., Stockholm (SE)); Hartley, Lee; Jackson, Peter; Joyce, Steve; Roberts, David; Swift, Ben (Serco Assurance, Harwell (GB))

    2007-09-15

    The work reported here collates the structural-hydraulic information gathered in 21 cored boreholes and 32 percussion-drilled boreholes belonging to Forsmark site description, modelling stage 2.2. The analyses carried out provide the hydrogeological input descriptions of the bedrock in Forsmark needed by the end users Repository Engineering, Safety Assessment and Environmental Impact Assessment; that is, hydraulic properties of deformation zones and fracture domains. The same information is also needed for constructing 3D groundwater flow models of the Forsmark site and surrounding area. The analyses carried out render the following conceptual model regarding the observed heterogeneity in deformation zone transmissivity: We find the geological division of the deterministically modelled deformation zones into eight categories (sets) useful from a hydrogeological point of view. Seven of the eight categories are steeply dipping, WNW, NW, NNW, NNE, NE, ENE and EW, and on is gently dipping, G. All deformation zones, regardless of orientation (strike and dip), are subjected to a substantial decrease in transmissivity with depth. The data gathered suggest a contrast of c. 20,000 times for the uppermost one kilometre of bedrock, i.e. more than four orders of magnitude. The hydraulic properties below this depth are not investigated. The lateral heterogeneity is also substantial but more irregular in its appearance. For instance, for a given elevation and deformation zone category (orientation), the spatial variability in transmissivity within a particular deformation zone appears to be as large as the variability between all deformation zones. This suggests that the lateral correlation length is shorter than the shortest distance between two adjacent observation points and shorter than the category spacing. The observation that the mean transmissivity of the gently-dipping deformation zones is c. one to two orders of magnitude greater than the mean transmissivities of all

  9. A rat model of early stage osteonecrosis induced by glucocorticoids

    Directory of Open Access Journals (Sweden)

    Kerachian Mohammad

    2011-12-01

    Full Text Available Abstract Background Glucocorticoid (GC-induced osteonecrosis (ON is an important complication of medical therapy. The exact pathomechanisms of ON has not been clearly elucidated. There is a need for a reproducible animal model that better approximates the clinical scenario. Methods To determine the genetic susceptibility of rats to develop GC-induced femoral head ON, we evaluated 5 different inbred strains of rats (Spontaneous Hypertensive Rat, Wistar Kyoto, Wistar Furth, SASCO Fisher and Lewis. Prednisone pellets (dosage of 1.82-2.56 mg/kg/day were implanted subcutaneously for 90. After 90 days, the femurs were resected and examined histologically and radiographically. Pathological and histological examination was performed. Hematoxylin and eosin (H & E staining was used to delineate the femoral head osteonecrosis lesions as well as abnormalities of articular cartilage and growth plate. Results The greatest differences in H & E staining were seen in the Wistar Kyoto and Wistar Furth groups. In these groups 4 out of 5 and 3 out of 5, respectively, steroid-induced rats revealed growth plate disruption with acellular areas. The TUNEL apoptosis staining assay for apoptosis revealed that 4 out of 5 of Wistar Kyoto rats, 5 out of 5 of Wistar Furth, 2 out of 4 of surviving Lewis and 2 out of 2 of the surviving spontaneous hypertensive rats had apoptotic osteocytes in trabeculae, whereas none of the Fisher rats showed apoptotic osteocytes. Conclusions We postulate that Wistar Kyoto, Wistar Furth and spontaneous hypertensive rats may be strains of rats more susceptible to develop ON of the femoral head while Fisher rats were the most resistant.

  10. Expressions and clinical significance of COX-2, VEGF-C, and EFGR in endometrial carcinoma.

    Science.gov (United States)

    Cai, Shengnan; Zhang, Yue-Xiang; Han, Ke; Ding, Yi-Qian

    2017-07-01

    The article is to study the expressions of COX-2, VEGF-C, and EGFR in endometrial carcinoma as well as its clinical significances. Clinical data of 183 patients with endometrial carcinoma who received surgery as initial treatment in the Nanjing Drum Tower Hospital Affiliated to the Nanjing University Medical School and the Nantong Maternal and Child Health Hospital Affiliated to the Nantong University from January 2005 to December 2010 were retrospectively investigated; 152 out of the 183 patients were closely followed up. Expressions of COX-2, VEGF-C, and EGFR proteins in 152 endometrial carcinoma samples were detected by immunohistochemical S-P assay. A 5-year survival rate of 152 patients was 81.56% (124/152). Positive COX-2 expression rate was 67.76% (103/152), and its positive expression was related to FIGO stage, differentiation degree, and myometrial invasion depth of patients (P  0.05). Positive expression rates of VEGF-C and EGFR were 64.47% (98/152) and 82.24% (125/152), respectively, and their positive expression was associated with FIGO stage, differentiation degree, myometrial invasion depth, and lymphatic metastasis (P COX-2 with VEGF-C and of EGFR found that COX-2 was positively correlated with both VEGF-C and EGFR (P  0). Patient prognosis was associated with the FIGO stage, differentiation degree, and myometrial invasion depth of tumors, as well as the presence or absence of lymph node metastasis (P  0.05). COX-2, VEGF-C, and EGFR are of significance for determining the FIGO stage, differentiation degree, and myometrial invasion depth of endometrial carcinoma, of which VEGF-C and EGFR are important in determining whether tumors metastasize to lymph nodes. Combined detection of COX-2, EGFR, and VEGF-C can be used as the indices for early diagnosis, recurrence prediction, and outcome evaluation for patients with endometrial carcinoma.

  11. A Four-Stage Hybrid Model for Hydrological Time Series Forecasting

    Science.gov (United States)

    Di, Chongli; Yang, Xiaohua; Wang, Xiaochao

    2014-01-01

    Hydrological time series forecasting remains a difficult task due to its complicated nonlinear, non-stationary and multi-scale characteristics. To solve this difficulty and improve the prediction accuracy, a novel four-stage hybrid model is proposed for hydrological time series forecasting based on the principle of ‘denoising, decomposition and ensemble’. The proposed model has four stages, i.e., denoising, decomposition, components prediction and ensemble. In the denoising stage, the empirical mode decomposition (EMD) method is utilized to reduce the noises in the hydrological time series. Then, an improved method of EMD, the ensemble empirical mode decomposition (EEMD), is applied to decompose the denoised series into a number of intrinsic mode function (IMF) components and one residual component. Next, the radial basis function neural network (RBFNN) is adopted to predict the trend of all of the components obtained in the decomposition stage. In the final ensemble prediction stage, the forecasting results of all of the IMF and residual components obtained in the third stage are combined to generate the final prediction results, using a linear neural network (LNN) model. For illustration and verification, six hydrological cases with different characteristics are used to test the effectiveness of the proposed model. The proposed hybrid model performs better than conventional single models, the hybrid models without denoising or decomposition and the hybrid models based on other methods, such as the wavelet analysis (WA)-based hybrid models. In addition, the denoising and decomposition strategies decrease the complexity of the series and reduce the difficulties of the forecasting. With its effective denoising and accurate decomposition ability, high prediction precision and wide applicability, the new model is very promising for complex time series forecasting. This new forecast model is an extension of nonlinear prediction models. PMID:25111782

  12. Exploring QSAR with E-state index: selectivity requirements for COX-2 versus COX-1 binding of terphenyl methyl sulfones and sulfonamides.

    Science.gov (United States)

    Chakraborty, Santanu; Sengupta, Chandana; Roy, Kunal

    2004-09-20

    An attempt has been made to explore selectivity requirements for cyclooxygenase-2 (COX-2) versus cyclooxygenase-1 (COX-1) binding of terphenyl methyl sulfones and sulfonamides using electrotopological state (E-state) index and suitable indicator parameters. Multiple linear regression analyses produced statistically acceptable equations: the best relation based on 'all-possible-subsets regression' for COX-1 binding (n=18) showed predicted variance and explained variance of 0.675 and 0.777, respectively, while in case of the best equation for COX-2 binding (n=38), these values rose to 0.842 and 0.874, respectively. For the selectivity relation (n=17), predicted variance and explained variance values were 0.601 and 0.687, respectively. Based on the results of the analyses, three important sites have been suggested: sites A (methylsulfonyl or aminosulfonyl moiety), B (central phenyl ring), and C (terminal phenyl ring containing different substituents). All three sites are important for COX-2 binding while sites B and C are important for COX-1 binding. For COX-2 selectivity, only site C plays an important role. The study shows the utility of E-state index in developing statistically acceptable model having direct physicochemical significance.

  13. Protective effects of levamisole, acetylsalicylic acid, and α-tocopherol against dioxin toxicity measured as the expression of AhR and COX-2 in a chicken embryo model.

    Science.gov (United States)

    Gostomska-Pampuch, Kinga; Ostrowska, Alicja; Kuropka, Piotr; Dobrzyński, Maciej; Ziółkowski, Piotr; Kowalczyk, Artur; Łukaszewicz, Ewa; Gamian, Andrzej; Całkosiński, Ireneusz

    2017-04-01

    Polychlorinated dibenzo-p-dioxins and dibenzofurans (dioxins) are classed as persistent organic pollutants and have adverse effects on multiple functions within the body. Dioxins are known carcinogens, immunotoxins, and teratogens. Dioxins are transformed in vivo, and interactions between the products and the aryl hydrocarbon receptor (AhR) lead to the formation of proinflammatory and toxic metabolites. The aim of this study was to determine whether α-tocopherol (vitamin E), acetylsalicylic acid (ASA), and levamisole can decrease the amount of damage caused by dioxins. Fertile Hubbard Flex commercial line chicken eggs were injected with solutions containing 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or containing TCDD and the test compounds. The chicken embryos and organs were analyzed after 7 and 13 days. The levels at which AhR and cyclooxygenase-2 (COX-2) proteins (which are induced during inflammation) were expressed were evaluated by performing immunohistochemical analyses on embryos treated with TCDD alone or with TCDD and the test compounds. TCDD caused developmental disorders and increased AhR and COX-2 expression in the chicken embryo tissues. Vitamin E, levamisole, ASA, and ASA plus vitamin E inhibited AhR and COX-2 expression in embryos after 7 days and decreased AhR and COX-2 expression in embryos after 13 days. ASA, levamisole, and ASA plus vitamin E weakened the immune response and prevented multiple organ changes. Vitamin E was not fully protective against developmental changes in the embryos.

  14. Log Gaussian Cox processes on the sphere

    DEFF Research Database (Denmark)

    Pacheco, Francisco Andrés Cuevas; Møller, Jesper

    We define and study the existence of log Gaussian Cox processes (LGCPs) for the description of inhomogeneous and aggregated/clustered point patterns on the d-dimensional sphere, with d = 2 of primary interest. Useful theoretical properties of LGCPs are studied and applied for the description of sky...

  15. "Cox orange\\" and \\"Elstar\\" Apple Cultivars

    African Journals Online (AJOL)

    Thinning trials were conducted in the apple orchards of Klein Altendorf experimental station near Bonn, Germany, using 7 year old CV, \\'Cox orange\\' in the year 2001 and 8 year old \\'Elstar\\' apple trees in 2002. The objective was to reduce the number of fruits per tree, yield, improve fruit quality, overcome alternate bearing ...

  16. Integrative health care model for climacteric stage women: design of the intervention.

    Science.gov (United States)

    Doubova, Svetlana V; Espinosa-Alarcón, Patricia; Flores-Hernández, Sergio; Infante, Claudia; Pérez-Cuevas, Ricardo

    2011-02-20

    Climacteric stage women experience significant biological, psychological and social changes. With demographic changes being observed in the growing number of climacteric stage women in Mexico, it is important to improve their knowledge about the climacteric stage and its potential associated problems, encourage their participation in screening programs, and promote the acquisition of healthy lifestyles.At Mexican health care institutions the predominant health care model for climacteric stage women has a biomedical perspective. Medical doctors provide mostly curative services and have limited support from other health professionals. This study aims to design an integrative health care model (IHCM: bio-psycho-social, multidisciplinary and women-centered) applicable in primary care services aimed at climacteric stage women. We present the design, inclusion criteria and detailed description of an IHCM. The IHCM consists of collaborative and coordinated provision of services by a health team, which is involves a family doctor, nurse, psychologist, and the woman herself. The health team promotes the empowerment of women through individual and group counseling on the climacteric stage and health related self-care. The intervention lasts three months followed by a three-month follow-up period to evaluate the effectiveness of the model. The effectiveness of the model will be evaluated through the following aspects: health-related quality of life (HR-QoL), empowerment, self-efficacy and knowledge regarding the climacteric stage and health-related self-care activities, use of screening services, and improvement in lifestyles (regular leisure time physical activity and healthy diet). Participation in preventive activities should be encouraged among women in Mexico. Designing and evaluating the effectiveness of an integrative health care model for women at the climacteric stage, based on the empowerment approach and focus on health-related self-care to improve their HR-QoL is

  17. Pharmacologic inhibition of COX-1 and COX-2 in influenza A viral infection in mice.

    Directory of Open Access Journals (Sweden)

    Michelle A Carey

    Full Text Available BACKGROUND: We previously demonstrated that cyclooxygenase (COX-1 deficiency results in greater morbidity and inflammation, whereas COX-2 deficiency leads to reduced morbidity, inflammation and mortality in influenza infected mice. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effects of COX-1 and COX-2 inhibitors in influenza A viral infection. Mice were given a COX-1 inhibitor (SC-560, a COX-2 inhibitor (celecoxib or no inhibitor beginning 2 weeks prior to influenza A viral infection (200 PFU and throughout the course of the experiment. Body weight and temperature were measured daily as indicators of morbidity. Animals were sacrificed on days 1 and 4 post-infection and bronchoalveolar lavage (BAL fluid was collected or daily mortality was recorded up to 2 weeks post-infection. Treatment with SC-560 significantly increased mortality and was associated with profound hypothermia and greater weight loss compared to celecoxib or control groups. On day 4 of infection, BAL fluid cells were modestly elevated in celecoxib treated mice compared to SC-560 or control groups. Viral titres were similar between treatment groups. Levels of TNF-alpha and G-CSF were significantly attenuated in the SC-560 and celecoxib groups versus control and IL-6 levels were significantly lower in BAL fluid of celecoxib treated mice versus control and versus the SC-560 group. The chemokine KC was significantly lower in SC-560 group versus control. CONCLUSIONS/SIGNIFICANCE: Treatment with a COX-1 inhibitor during influenza A viral infection is detrimental to the host whereas inhibition of COX-2 does not significantly modulate disease severity. COX-1 plays a critical role in controlling the thermoregulatory response to influenza A viral infection in mice.

  18. Stages of Change Model for Participation in Physical Activity during Pregnancy

    Directory of Open Access Journals (Sweden)

    Lene Annette Hagen Haakstad

    2013-01-01

    Full Text Available Background. The transtheoretical model (TTM has been successful in promoting health behavioral change in the general population. However, there is a scant knowledge about physical activity in relation to the TTM during pregnancy. Hence, the aims of the present study were (1 to assess readiness to become or stay physically active according to the TTM and (2 to compare background and health variables across the TTM. Methods. Healthy pregnant women (n=467 were allocated to the study from Oslo University Hospital, Norway. The participants filled in a validated self-administered questionnaire, physical activity pregnancy questionnaire (PAPQ in gestation, weeks 32–36. The questionnaire contained 53 questions with one particular question addressing the TTM and the five stages: (1 precontemplation stage, (2 contemplation stage, (3 preparation stage, (4 action stage, and (5 maintenance stage. Results. More than half of the participants (53% were involved in regular exercise (stages 4-5; however, only six specified that they had recently started an exercise program (stage 4. About 33% reported engaging in some physical activity, but not regularly (stage 3. The results showed that receiving advice from health professionals to exercise during pregnancy increased the likeliness of being in stages 4-5, while higher age, multiparity, pregravid overweight, unhealthy eating habits, pelvic girdle pain, and urinary incontinence were more prevalent with low readiness to change exercise habits (stages 1–3. Conclusion. According to the TTM, more than half of the participants reported to be physically active. Moreover, most of the participants classified as inactive showed a high motivational readiness or intention to increase their physical activity level. Hence, pregnancy may be a window of opportunity for the establishment of long-term physical activity habits.

  19. COX-2 as a determinant of lower disease-free survival for patients affected by ameloblastoma.

    Science.gov (United States)

    Montezuma, Marco Aurélio Petroni; Fonseca, Felipe Paiva; Benites, Bernar Monteiro; Soares, Ciro Dantas; do Amaral-Silva, Gleyson Kleber; de Almeida, Oslei Paes; Soares, Fernando Augusto; Pagano, Rosana Lima; Fregnani, Eduardo Rodrigues

    2018-03-15

    Ameloblastoma is a locally aggressive neoplasm with a poorly understood pathogenesis. Therefore, the aim of this study is to investigate whether COX-2 expression is associated with ameloblastoma microvascular density (MVD) and with tumor aggressiveness. Sixty-three cases of primary ameloblastomas arranged in tissue microarray were submitted to immunohistochemistry against cyclooxigenase-2 (COX-2) and CD34. Clinicopathological parameters regarding sex, age, tumour size, tumour duration, tumour location, treatment, recurrences, radiographic features, vestibular/lingual and basal cortical disruption and follow-up data were obtained from patients' medical records and correlated with the proteins expression. The results on BRAF-V600E expression were obtained from our previous study and correlated with COX-2 and CD34 expressions. Log-rank univariate analysis and multivariate Cox regression model were done to investigate the prognostic potential of the molecular markers. Twenty-eight cases (44.4%) exhibited cytoplasmic positivity for COX-2, predominantly in the columnar peripheral cells, with a mean MVD of 2.2 vessels/mm 2 . COX-2 was significantly associated with recurrences (p COX-2 was significantly associated with a lower 5-year disease-free survival (DFS) rate (p COX-2 expression in ameloblastomas is not associated with MVD, but it is significantly associated with recurrences and with a lower DFS. Copyright © 2018 Elsevier GmbH. All rights reserved.

  20. Radioprotection of intestinal crypt cells by cox-inhibitors

    International Nuclear Information System (INIS)

    Bisnar, Paul O.; Dones, Rosa Angela S.A.; Serna, Paulene-Ver A.; Deocaris, Chester C.; Guttierez, Kalangitan V.; Deocaris, Custer C.

    2006-01-01

    The regulation of tissue homeostasis in the gastrointestinal epithelium after epithelial injury focuses on the prostaglandins(PGs) as its major mediators. The two cyclooxygenase isoforms, cox-1 and cox-2, catalyze synthesis of PGs. Cox-1 is the predominant cyclooxygenase isoform found in the normal intestine. In contrast, cox-2 is present at low levels in normal intestine but is elevated at sites of inflammation, and in adenomas and carcinomas. To study the effects of various commercially-available cox-inhibitors (Ketorolac: cox-1 selective; Celecoxib: cox-2 selective; and Indocid: cox-1/2 non-selective), we determine mouse crypt epithelial cell fate after genotoxic injury with whole-body gamma-ray exposure at 15 Gy. Intestinal tissues of mice treated with cox-2 inhibitors that showed invariable apoptotic event, however, have increased occurrence of regenerating cells. Our results suggest a potential application of cox-2 selective inhibitors as radioprotective agent for normal cells after radiotherapy. (Author)

  1. An Enhanced Preventive Maintenance Optimization Model Based on a Three-Stage Failure Process

    Directory of Open Access Journals (Sweden)

    Ruifeng Yang

    2015-01-01

    Full Text Available Nuclear power plants are highly complex systems and the issues related to their safety are of primary importance. Probabilistic safety assessment is regarded as the most widespread methodology for studying the safety of nuclear power plants. As maintenance is one of the most important factors for affecting the reliability and safety, an enhanced preventive maintenance optimization model based on a three-stage failure process is proposed. Preventive maintenance is still a dominant maintenance policy due to its easy implementation. In order to correspond to the three-color scheme commonly used in practice, the lifetime of system before failure is divided into three stages, namely, normal, minor defective, and severe defective stages. When the minor defective stage is identified, two measures are considered for comparison: one is that halving the inspection interval only when the minor defective stage is identified at the first time; the other one is that if only identifying the minor defective stage, the subsequent inspection interval is halved. Maintenance is implemented immediately once the severe defective stage is identified. Minimizing the expected cost per unit time is our objective function to optimize the inspection interval. Finally, a numerical example is presented to illustrate the effectiveness of the proposed models.

  2. Palaeotemperature reconstructions of the European permafrost zone during Oxygen Isotope Stage 3 compared with climate model results.

    NARCIS (Netherlands)

    van Huissteden, J.; Vandenberghe, J.; Pollard, D.

    2003-01-01

    A palaeotemperature reconstruction based on periglacial phenomena in Europe north of approximately 51 °N, is compared with high-resolution regional climate model simulations of the marine oxygen isotope Stage 3 (Stage 3) palaeoclimate. The experiments represent Stage 3 warm (interstadial), Stage 3

  3. Simulink Model of the Ares I Upper Stage Main Propulsion System

    Science.gov (United States)

    Burchett, Bradley T.

    2008-01-01

    A numerical model of the Ares I upper stage main propulsion system is formulated based on first principles. Equation's are written as non-linear ordinary differential equations. The GASP fortran code is used to compute thermophysical properties of the working fluids. Complicated algebraic constraints are numerically solved. The model is implemented in Simulink and provides a rudimentary simulation of the time history of important pressures and temperatures during re-pressurization, boost and upper stage firing. The model is validated against an existing reliable code, and typical results are shown.

  4. Agil Stage-Gate®: ny model for udviklingsprojekter i mellemstore virksomheder

    DEFF Research Database (Denmark)

    Vedsmand, Tomas; Edwards, Kasper; Hvidt, Nicoline

    Lær at udvikle nye produkter hurtigere og med større træfsikkerhed – ved at arbejde i sprint med agile metoder og træffe de rigtige beslutninger med Stage-Gate® Se også tilhørende: "Værktøjskasse til Agil Stage-Gate®: Ny model for udviklingsprojekter i mellemstore virksomheder" på http://dx.doi.org...

  5. Stability patterns for a size-structured population model and its stage-structured counterpart

    DEFF Research Database (Denmark)

    Zhang, Lai; Pedersen, Michael; Lin, Zhigui

    2015-01-01

    delayed system consisting of a renewal equation for the consumer population birth rate and a delayed differential equation for the resource. Results show that the size- and stage-structured models differ considerably with respect to equilibrium stability, although the two models have completely identical...

  6. Stage-by-Stage and Parallel Flow Path Compressor Modeling for a Variable Cycle Engine, NASA Advanced Air Vehicles Program - Commercial Supersonic Technology Project - AeroServoElasticity

    Science.gov (United States)

    Kopasakis, George; Connolly, Joseph W.; Cheng, Larry

    2015-01-01

    This paper covers the development of stage-by-stage and parallel flow path compressor modeling approaches for a Variable Cycle Engine. The stage-by-stage compressor modeling approach is an extension of a technique for lumped volume dynamics and performance characteristic modeling. It was developed to improve the accuracy of axial compressor dynamics over lumped volume dynamics modeling. The stage-by-stage compressor model presented here is formulated into a parallel flow path model that includes both axial and rotational dynamics. This is done to enable the study of compressor and propulsion system dynamic performance under flow distortion conditions. The approaches utilized here are generic and should be applicable for the modeling of any axial flow compressor design accurate time domain simulations. The objective of this work is as follows. Given the parameters describing the conditions of atmospheric disturbances, and utilizing the derived formulations, directly compute the transfer function poles and zeros describing these disturbances for acoustic velocity, temperature, pressure, and density. Time domain simulations of representative atmospheric turbulence can then be developed by utilizing these computed transfer functions together with the disturbance frequencies of interest.

  7. Why Are There Developmental Stages in Language Learning? A Developmental Robotics Model of Language Development.

    Science.gov (United States)

    Morse, Anthony F; Cangelosi, Angelo

    2017-02-01

    Most theories of learning would predict a gradual acquisition and refinement of skills as learning progresses, and while some highlight exponential growth, this fails to explain why natural cognitive development typically progresses in stages. Models that do span multiple developmental stages typically have parameters to "switch" between stages. We argue that by taking an embodied view, the interaction between learning mechanisms, the resulting behavior of the agent, and the opportunities for learning that the environment provides can account for the stage-wise development of cognitive abilities. We summarize work relevant to this hypothesis and suggest two simple mechanisms that account for some developmental transitions: neural readiness focuses on changes in the neural substrate resulting from ongoing learning, and perceptual readiness focuses on the perceptual requirements for learning new tasks. Previous work has demonstrated these mechanisms in replications of a wide variety of infant language experiments, spanning multiple developmental stages. Here we piece this work together as a single model of ongoing learning with no parameter changes at all. The model, an instance of the Epigenetic Robotics Architecture (Morse et al 2010) embodied on the iCub humanoid robot, exhibits ongoing multi-stage development while learning pre-linguistic and then basic language skills. Copyright © 2016 Cognitive Science Society, Inc.

  8. A two-stage DEA model to evaluate sustainability and energy efficiency of tomato production

    Directory of Open Access Journals (Sweden)

    Hossein Raheli

    2017-12-01

    Full Text Available The aims of this study were to evaluate the sustainability and efficiency of tomato production and to investigate the determinants of inefficiency of tomato farming in Marand region of East Azerbaijan province, Iran. For these purposes, a two-stage methodology was applied, in which for the first time a fractional regression model (FRM was employed in the second stage of analysis, so that, in the first stage a nonparametric Data Envelopment Analysis (DEA was used to analyze the efficiencies of tomato production and in the second stage, farm specific variables such as education level, farmers’ age, total land size and use of manure were used in a fractional regression model to explain how these factors influenced efficiency of tomato farming. The results of the first stage showed that there are considerable differences between efficient and inefficient farmers in the studied area, so that the main differences were in the use of chemical fertilizers, biocides and water for irrigation. Also, the results of second stage revealed that farmers’ age, education level and total land size positively affected efficiency in tomato production. So, better use of land, chemical fertilizers, water for irrigation and improving the farmers’ educational levels through literacy campaign and land consolidation would probably increase the efficiency in the long term. Keywords: Data envelopment analysis, Energy efficiency, Fractional regression model, Tomato

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

    Directory of Open Access Journals (Sweden)

    Siemers Eric R

    2010-04-01

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

  10. A two-stage stochastic rule-based model to determine pre-assembly buffer content

    Science.gov (United States)

    Gunay, Elif Elcin; Kula, Ufuk

    2018-01-01

    This study considers instant decision-making needs of the automobile manufactures for resequencing vehicles before final assembly (FA). We propose a rule-based two-stage stochastic model to determine the number of spare vehicles that should be kept in the pre-assembly buffer to restore the altered sequence due to paint defects and upstream department constraints. First stage of the model decides the spare vehicle quantities, where the second stage model recovers the scrambled sequence respect to pre-defined rules. The problem is solved by sample average approximation (SAA) algorithm. We conduct a numerical study to compare the solutions of heuristic model with optimal ones and provide following insights: (i) as the mismatch between paint entrance and scheduled sequence decreases, the rule-based heuristic model recovers the scrambled sequence as good as the optimal resequencing model, (ii) the rule-based model is more sensitive to the mismatch between the paint entrance and scheduled sequences for recovering the scrambled sequence, (iii) as the defect rate increases, the difference in recovery effectiveness between rule-based heuristic and optimal solutions increases, (iv) as buffer capacity increases, the recovery effectiveness of the optimization model outperforms heuristic model, (v) as expected the rule-based model holds more inventory than the optimization model.

  11. Randomized controlled trials of COX-2 inhibitors

    DEFF Research Database (Denmark)

    Stefansdottir, Gudrun; De Bruin, Marie L; Knol, Mirjam J

    2011-01-01

    BACKGROUND: Naproxen, ibuprofen and diclofenac are frequently used as comparators in randomized controlled trials (RCTs) on the safety and efficacy of cyclooxygenase (COX)-2 inhibitors. Different comparator doses may influence the results of RCTs. It has been hypothesized that RCTs of COX-2...... 1995 and 2009 in which celecoxib or rofecoxib were compared with naproxen, ibuprofen or diclofenac. All articles labelled as RCTs mentioning rofecoxib or celecoxib and one or more of the comparator drugs in the title and/or abstract were included. We extracted information on doses of both non...... dose trends in the case of rofecoxib. CONCLUSIONS: Although the dose trends over time differed for RCTs comparing rofecoxib and celecoxib with diclofenac, ibuprofen or naproxen, the results of our study do not support the hypothesis that dose trends influenced the decision to continue marketing...

  12. Peroxisome Proliferator-Activated Receptor-α Activation Decreases Mean Arterial Pressure, Plasma Interleukin-6, and COX-2 While Increasing Renal CYP4A Expression in an Acute Model of DOCA-Salt Hypertension

    Directory of Open Access Journals (Sweden)

    Dexter L. Lee

    2011-01-01

    Full Text Available Peroxisome proliferator-activated receptor-alpha (PPAR-α activation by fenofibrate reduces blood pressure and sodium retention during DOCA-salt hypertension. PPAR-α activation reduces the expression of inflammatory cytokines, such as interleukin-6 (IL-6. Fenofibrate also induces cytochrome P450 4A (CYP4A and increases 20-hydroxyeicosatetraenoic acid (20-HETE production. This study tested whether the administration of fenofibrate would reduce blood pressure by attenuating plasma IL-6 and renal expression of cyclooxygenase-2 (COX-2, while increasing expression of renal CYP4A during 7 days of DOCA-salt hypertension. We performed uni-nephrectomy on 12–14 week old male Swiss Webster mice and implanted biotelemetry devices in control, DOCA-salt (1.5 mg/g treated mice with or without fenofibrate (500 mg/kg/day in corn oil, intragastrically. Fenofibrate significantly decreased mean arterial pressure and plasma IL-6. In kidney homogenates, fenofibrate increased CYP4A and decreased COX-2 expression. There were no differences in renal cytochrome P450, family 2, subfamily c, polypeptide 23 (CYP2C23 and soluble expoxide hydrolase (sEH expression between the groups. Our results suggest that the blood pressure lowering effect of PPAR-α activation by fenofibrate involves the reduction of plasma IL-6 and COX-2, while increasing CYP4A expression during DOCA-salt hypertension. Our results may also suggest that PPAR-α activation protects the kidney against renal injury via decreased COX-2 expression.

  13. Regulation of Matrix Metalloproteinase-2 Activity by COX-2-PGE2-pAKT Axis Promotes Angiogenesis in Endometriosis

    Science.gov (United States)

    Ray, Amlan K.; DasMahapatra, Pramathes; Swarnakar, Snehasikta

    2016-01-01

    Endometriosis is characterized by the ectopic development of the endometrium which relies on angiogenesis. Although studies have identified the involvement of different matrix metalloproteinases (MMPs) in endometriosis, no study has yet investigated the role of MMP-2 in endometriosis-associated angiogenesis. The present study aims to understand the regulation of MMP-2 activity in endothelial cells and on angiogenesis during progression of ovarian endometriosis. Histological and biochemical data showed increased expressions of vascular endothelial growth factor (VEGF), VEGF receptor-2, cycloxygenase (COX)-2, von Willebrand factor along with angiogenesis during endometriosis progression. Women with endometriosis showed decreased MMP-2 activity in eutopic endometrium as compared to women without endometriosis. However, ectopic ovarian endometrioma showed significantly elevated MMP-2 activity with disease severity. In addition, increased MT1MMP and decreased tissue inhibitors of metalloproteinases (TIMP)-2 expressions were found in the late stages of endometriosis indicating more MMP-2 activation with disease progression. In vitro study using human endothelial cells showed that prostaglandin E2 (PGE2) significantly increased MMP-2 activity as well as tube formation. Inhibition of COX-2 and/or phosphorylated AKT suppressed MMP-2 activity and endothelial tube formation suggesting involvement of PGE2 in regulation of MMP-2 activity during angiogenesis. Moreover, specific inhibition of MMP-2 by chemical inhibitor significantly reduced cellular migration, invasion and tube formation. In ovo assay showed decreased angiogenic branching upon MMP-2 inhibition. Furthermore, a significant reduction of lesion numbers was observed upon inhibition of MMP-2 and COX-2 in mouse model of endometriosis. In conclusion, our study establishes the involvement of MMP-2 activity via COX-2-PGE2-pAKT axis in promoting angiogenesis during endometriosis progression. PMID:27695098

  14. Log-normal censored regression model detecting prognostic factors in gastric cancer: a study of 3018 cases.

    Science.gov (United States)

    Wang, Bin-Bin; Liu, Cai-Gang; Lu, Ping; Latengbaolide, A; Lu, Yang

    2011-06-21

    To investigate the efficiency of Cox proportional hazard model in detecting prognostic factors for gastric cancer. We used the log-normal regression model to evaluate prognostic factors in gastric cancer and compared it with the Cox model. Three thousand and eighteen gastric cancer patients who received a gastrectomy between 1980 and 2004 were retrospectively evaluated. Clinic-pathological factors were included in a log-normal model as well as Cox model. The akaike information criterion (AIC) was employed to compare the efficiency of both models. Univariate analysis indicated that age at diagnosis, past history, cancer location, distant metastasis status, surgical curative degree, combined other organ resection, Borrmann type, Lauren's classification, pT stage, total dissected nodes and pN stage were prognostic factors in both log-normal and Cox models. In the final multivariate model, age at diagnosis, past history, surgical curative degree, Borrmann type, Lauren's classification, pT stage, and pN stage were significant prognostic factors in both log-normal and Cox models. However, cancer location, distant metastasis status, and histology types were found to be significant prognostic factors in log-normal results alone. According to AIC, the log-normal model performed better than the Cox proportional hazard model (AIC value: 2534.72 vs 1693.56). It is suggested that the log-normal regression model can be a useful statistical model to evaluate prognostic factors instead of the Cox proportional hazard model.

  15. Kinetic Energy Losses and Efficiency of an Axial Turbine Stage in Numerical Modeling of Unsteady Flows

    Directory of Open Access Journals (Sweden)

    A. S. Laskin

    2015-01-01

    Full Text Available The article presents the results of numerical investigation of kinetic energy (KE loss and blading efficiency of the single-stage axial turbine under different operating conditions, characterized by the ratio u/C0. The calculations are performed by stationary (Stage method and nonstationary (Transient method methods using ANSYS CFX. The novelty of this work lies in the fact that the numerical simulation of steady and unsteady flows in a turbine stage is conducted, and the results are obtained to determine the loss of KE, both separately by the elements of the flow range and their total values, in the stage efficiency as well. The results obtained are compared with the calculated efficiency according to one-dimensional theory.To solve these problems was selected model of axial turbine stage with D/l = 13, blade profiles of rotor and stator of constant cross-section, similar to tested ones in inverted turbine when = 0.3. The degree of reactivity ρ = 0.27, the rotor speed was varied within the range 1000 ÷ 1800 rev/min.Results obtained allow us to draw the following conclusions:1. The level of averaged coefficients of total KE losses in the range of from 0.48 to 0.75 is from 18% to 21% when calculating by the Stage method and from 21% to 25% by the Transient one.2. The level of averaged coefficients of KE losses with the output speed of in the specified range is from 9% to 13%, and almost the same when in calculating by Stage and Transient methods.3. Levels of averaged coefficients of KE loss in blade tips (relative to the differential enthalpies per stage are changed in the range: from 4% to 3% (Stage and are stored to be equal to 5% (Transient; from 5% to 6% (Stage and from 6% to 8% (Transient.4. Coefficients of KE losses in blade tips GV and RB are higher in calculations of the model stage using the Transient method than the Stage one, respectively, by = 1.5 ÷ 2.5% and = 4 ÷ 5% of the absolute values. These are values to characterize the KE

  16. A two-stage stochastic programming model for the optimal design of distributed energy systems

    International Nuclear Information System (INIS)

    Zhou, Zhe; Zhang, Jianyun; Liu, Pei; Li, Zheng; Georgiadis, Michael C.; Pistikopoulos, Efstratios N.

    2013-01-01

    Highlights: ► The optimal design of distributed energy systems under uncertainty is studied. ► A stochastic model is developed using genetic algorithm and Monte Carlo method. ► The proposed system possesses inherent robustness under uncertainty. ► The inherent robustness is due to energy storage facilities and grid connection. -- Abstract: A distributed energy system is a multi-input and multi-output energy system with substantial energy, economic and environmental benefits. The optimal design of such a complex system under energy demand and supply uncertainty poses significant challenges in terms of both modelling and corresponding solution strategies. This paper proposes a two-stage stochastic programming model for the optimal design of distributed energy systems. A two-stage decomposition based solution strategy is used to solve the optimization problem with genetic algorithm performing the search on the first stage variables and a Monte Carlo method dealing with uncertainty in the second stage. The model is applied to the planning of a distributed energy system in a hotel. Detailed computational results are presented and compared with those generated by a deterministic model. The impacts of demand and supply uncertainty on the optimal design of distributed energy systems are systematically investigated using proposed modelling framework and solution approach.

  17. Questions and Answers for Transplant Candidates about Model for End-Stage Liver Disease (MELD) and Pediatric End-Stage ....

    Science.gov (United States)

    ... 1 patients have acute (sudden and severe onset) liver failure and a life expectancy of hours to a ... younger are placed in categories according to the Pediatric End-stage Liver Disease (PELD) scoring system. Again there is a ...

  18. Intention for Car Use Reduction: Applying a Stage-Based Model.

    Science.gov (United States)

    Olsson, Lars E; Huck, Jana; Friman, Margareta

    2018-01-26

    This study investigates which variables drive intention to reduce car use by modelling a stage of change construct with mechanisms in the Theory of Planned Behavior (TPB) and Norm Activation Model (NAM). Web questionnaires ( n = 794) were collected via 11 workplaces. The socio-demographics, work commute, stage of change, attitudes to sustainable travel modes, social norms, perceived behavioral control, and personal norm were assessed. An initial descriptive analysis revealed that 19% of the employees saw no reason to reduce their car use; 35% would like to reduce their car use but felt it was impossible; 12% were thinking about reducing their car use but were unsure of how or when to do this; 12% had an aim to reduce current car use, and knew which journeys to replace and which modes to use; and 23% try to use modes other than a car for most journeys, and will maintain or reduce their already low car use in the coming months. A series of Ordered Logit Models showed that socio-demographic variables did not explain the stage of change. Instead, personal norms, instrumental and affective attitudes, and perceived behavioral control toward sustainable travel modes were all significant and explained 43% of the variance in stage of change. Furthermore, it was found that the significant relationships were not linear in nature. The analysis also showed an indirect effect of social norms on the stage of change through personal norms. Implications are discussed regarding the design of interventions aimed at influencing a sustainable work commute.

  19. Intention for Car Use Reduction: Applying a Stage-Based Model

    Science.gov (United States)

    2018-01-01

    This study investigates which variables drive intention to reduce car use by modelling a stage of change construct with mechanisms in the Theory of Planned Behavior (TPB) and Norm Activation Model (NAM). Web questionnaires (n = 794) were collected via 11 workplaces. The socio-demographics, work commute, stage of change, attitudes to sustainable travel modes, social norms, perceived behavioral control, and personal norm were assessed. An initial descriptive analysis revealed that 19% of the employees saw no reason to reduce their car use; 35% would like to reduce their car use but felt it was impossible; 12% were thinking about reducing their car use but were unsure of how or when to do this; 12% had an aim to reduce current car use, and knew which journeys to replace and which modes to use; and 23% try to use modes other than a car for most journeys, and will maintain or reduce their already low car use in the coming months. A series of Ordered Logit Models showed that socio-demographic variables did not explain the stage of change. Instead, personal norms, instrumental and affective attitudes, and perceived behavioral control toward sustainable travel modes were all significant and explained 43% of the variance in stage of change. Furthermore, it was found that the significant relationships were not linear in nature. The analysis also showed an indirect effect of social norms on the stage of change through personal norms. Implications are discussed regarding the design of interventions aimed at influencing a sustainable work commute. PMID:29373565

  20. Scrum integration in stage-gate models for collaborative product development

    DEFF Research Database (Denmark)

    Sommer, Anita Friis; Slavensky, Andreas; Nguyen, Vivi Thuy

    2013-01-01

    The relevance of collaborative Product Development (PD) is rising with the decrease of product life cycles combined with growing customer demands. Industrial manufacturers now experience competition in the global market, where differentiation is necessary for survival. Hence, in order...... to differentiate from low-cost competitors and increase PD performance, some industrial manufacturers now seek competitive advantage by experimenting with new ways for collaborative PD. This includes integrating customer-focused agile process models, like Scrum, from the software industry into their existing PD...... models. Thus, instead of replacing traditional stage-gate models agile methods are currently integrated in existing PD models generating hybrid solution for collaborative PD. This paper includes a study of three industrial cases that have successfully integrated Scrum into a stage-gate process model...

  1. A two-stage cascade model of BOLD responses in human visual cortex.

    Directory of Open Access Journals (Sweden)

    Kendrick N Kay

    Full Text Available Visual neuroscientists have discovered fundamental properties of neural representation through careful analysis of responses to controlled stimuli. Typically, different properties are studied and modeled separately. To integrate our knowledge, it is necessary to build general models that begin with an input image and predict responses to a wide range of stimuli. In this study, we develop a model that accepts an arbitrary band-pass grayscale image as input and predicts blood oxygenation level dependent (BOLD responses in early visual cortex as output. The model has a cascade architecture, consisting of two stages of linear and nonlinear operations. The first stage involves well-established computations-local oriented filters and divisive normalization-whereas the second stage involves novel computations-compressive spatial summation (a form of normalization and a variance-like nonlinearity that generates selectivity for second-order contrast. The parameters of the model, which are estimated from BOLD data, vary systematically across visual field maps: compared to primary visual cortex, extrastriate maps generally have larger receptive field size, stronger levels of normalization, and increased selectivity for second-order contrast. Our results provide insight into how stimuli are encoded and transformed in successive stages of visual processing.

  2. The COX-2 inhibitor meloxicam prevents pregnancy when administered as an emergency contraceptive to nonhuman primates.

    Science.gov (United States)

    McCann, Nicole C; Lynch, Terrie J; Kim, Soon Ok; Duffy, Diane M

    2013-12-01

    Cyclooxygenase-2 (COX-2) inhibitors reduce prostaglandin synthesis and disrupt essential reproductive processes. Ultrasound studies in women demonstrated that oral COX-2 inhibitors can delay or prevent follicle collapse associated with ovulation. The goal of this study was to determine if oral administration of a COX-2 inhibitor can inhibit reproductive function with sufficient efficacy to prevent pregnancy in primates. The COX-2 inhibitor meloxicam (or vehicle) was administered orally to proven fertile female cynomolgus macaques using one emergency contraceptive model and three monthly contraceptive models. In the emergency contraceptive model, females were bred with a proven fertile male once 2±1 days before ovulation, returned to the females' home cage, and then received 5 days of meloxicam treatment. In the monthly contraceptive models, females were co-caged for breeding with a proven fertile male for a total of 5 days beginning 2±1 days before ovulation. Animals received meloxicam treatment (1) cycle days 5-22, or (2) every day, or (3) each day of the 5-day breeding period. Female were then assessed for pregnancy. The pregnancy rate with meloxicam administration using the emergency contraception model was 6.5%, significantly lower than the pregnancy rate of 33.3% when vehicle without meloxicam was administered. Pregnancy rates with the three monthly contraceptive models (75%-100%) were not consistent with preventing pregnancy. Oral COX-2 inhibitor administration can prevent pregnancy after a single instance of breeding in primates. While meloxicam may be ineffective for regular contraception, pharmacological inhibition of COX-2 may be an effective method of emergency contraception for women. COX-2 inhibitors can interfere with ovulation, but the contraceptive efficacy of drugs of this class has not been directly tested. This study, conducted in nonhuman primates, is the first to suggest that a COX-2 inhibitor may be effective as an emergency contraceptive.

  3. Dynamic models of staged gasification processes. Documentation of gasification simulator; Dynamiske modeller a f trinopdelte forgasningsprocesser. Dokumentation til forgasser simulator

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-02-15

    In connection with the ERP project 'Dynamic modelling of staged gasification processes' a gasification simulator has been constructed. The simulator consists of: a mathematical model of the gasification process developed at Technical University of Denmark, a user interface programme, IGSS, and a communication interface between the two programmes. (BA)

  4. What makes us think? A three-stage dual-process model of analytic engagement.

    Science.gov (United States)

    Pennycook, Gordon; Fugelsang, Jonathan A; Koehler, Derek J

    2015-08-01

    The distinction between intuitive and analytic thinking is common in psychology. However, while often being quite clear on the characteristics of the two processes ('Type 1' processes are fast, autonomous, intuitive, etc. and 'Type 2' processes are slow, deliberative, analytic, etc.), dual-process theorists have been heavily criticized for being unclear on the factors that determine when an individual will think analytically or rely on their intuition. We address this issue by introducing a three-stage model that elucidates the bottom-up factors that cause individuals to engage Type 2 processing. According to the model, multiple Type 1 processes may be cued by a stimulus (Stage 1), leading to the potential for conflict detection (Stage 2). If successful, conflict detection leads to Type 2 processing (Stage 3), which may take the form of rationalization (i.e., the Type 1 output is verified post hoc) or decoupling (i.e., the Type 1 output is falsified). We tested key aspects of the model using a novel base-rate task where stereotypes and base-rate probabilities cued the same (non-conflict problems) or different (conflict problems) responses about group membership. Our results support two key predictions derived from the model: (1) conflict detection and decoupling are dissociable sources of Type 2 processing and (2) conflict detection sometimes fails. We argue that considering the potential stages of reasoning allows us to distinguish early (conflict detection) and late (decoupling) sources of analytic thought. Errors may occur at both stages and, as a consequence, bias arises from both conflict monitoring and decoupling failures. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Two-stage residual inclusion estimation: addressing endogeneity in health econometric modeling.

    Science.gov (United States)

    Terza, Joseph V; Basu, Anirban; Rathouz, Paul J

    2008-05-01

    The paper focuses on two estimation methods that have been widely used to address endogeneity in empirical research in health economics and health services research-two-stage predictor substitution (2SPS) and two-stage residual inclusion (2SRI). 2SPS is the rote extension (to nonlinear models) of the popular linear two-stage least squares estimator. The 2SRI estimator is similar except that in the second-stage regression, the endogenous variables are not replaced by first-stage predictors. Instead, first-stage residuals are included as additional regressors. In a generic parametric framework, we show that 2SRI is consistent and 2SPS is not. Results from a simulation study and an illustrative example also recommend against 2SPS and favor 2SRI. Our findings are important given that there are many prominent examples of the application of inconsistent 2SPS in the recent literature. This study can be used as a guide by future researchers in health economics who are confronted with endogeneity in their empirical work.

  6. Prediction of Pathological Stage in Patients with Prostate Cancer: A Neuro-Fuzzy Model.

    Directory of Open Access Journals (Sweden)

    Georgina Cosma

    Full Text Available The prediction of cancer staging in prostate cancer is a process for estimating the likelihood that the cancer has spread before treatment is given to the patient. Although important for determining the most suitable treatment and optimal management strategy for patients, staging continues to present significant challenges to clinicians. Clinical test results such as the pre-treatment Prostate-Specific Antigen (PSA level, the biopsy most common tumor pattern (Primary Gleason pattern and the second most common tumor pattern (Secondary Gleason pattern in tissue biopsies, and the clinical T stage can be used by clinicians to predict the pathological stage of cancer. However, not every patient will return abnormal results in all tests. This significantly influences the capacity to effectively predict the stage of prostate cancer. Herein we have developed a neuro-fuzzy computational intelligence model for classifying and predicting the likelihood of a patient having Organ-Confined Disease (OCD or Extra-Prostatic Disease (ED using a prostate cancer patient dataset obtained from The Cancer Genome Atlas (TCGA Research Network. The system input consisted of the following variables: Primary and Secondary Gleason biopsy patterns, PSA levels, age at diagnosis, and clinical T stage. The performance of the neuro-fuzzy system was compared to other computational intelligence based approaches, namely the Artificial Neural Network, Fuzzy C-Means, Support Vector Machine, the Naive Bayes classifiers, and also the AJCC pTNM Staging Nomogram which is commonly used by clinicians. A comparison of the optimal Receiver Operating Characteristic (ROC points that were identified using these approaches, revealed that the neuro-fuzzy system, at its optimal point, returns the largest Area Under the ROC Curve (AUC, with a low number of false positives (FPR = 0.274, TPR = 0.789, AUC = 0.812. The proposed approach is also an improvement over the AJCC pTNM Staging Nomogram (FPR

  7. Prediction of Pathological Stage in Patients with Prostate Cancer: A Neuro-Fuzzy Model

    Science.gov (United States)

    Acampora, Giovanni; Brown, David; Rees, Robert C.

    2016-01-01

    The prediction of cancer staging in prostate cancer is a process for estimating the likelihood that the cancer has spread before treatment is given to the patient. Although important for determining the most suitable treatment and optimal management strategy for patients, staging continues to present significant challenges to clinicians. Clinical test results such as the pre-treatment Prostate-Specific Antigen (PSA) level, the biopsy most common tumor pattern (Primary Gleason pattern) and the second most common tumor pattern (Secondary Gleason pattern) in tissue biopsies, and the clinical T stage can be used by clinicians to predict the pathological stage of cancer. However, not every patient will return abnormal results in all tests. This significantly influences the capacity to effectively predict the stage of prostate cancer. Herein we have developed a neuro-fuzzy computational intelligence model for classifying and predicting the likelihood of a patient having Organ-Confined Disease (OCD) or Extra-Prostatic Disease (ED) using a prostate cancer patient dataset obtained from The Cancer Genome Atlas (TCGA) Research Network. The system input consisted of the following variables: Primary and Secondary Gleason biopsy patterns, PSA levels, age at diagnosis, and clinical T stage. The performance of the neuro-fuzzy system was compared to other computational intelligence based approaches, namely the Artificial Neural Network, Fuzzy C-Means, Support Vector Machine, the Naive Bayes classifiers, and also the AJCC pTNM Staging Nomogram which is commonly used by clinicians. A comparison of the optimal Receiver Operating Characteristic (ROC) points that were identified using these approaches, revealed that the neuro-fuzzy system, at its optimal point, returns the largest Area Under the ROC Curve (AUC), with a low number of false positives (FPR = 0.274, TPR = 0.789, AUC = 0.812). The proposed approach is also an improvement over the AJCC pTNM Staging Nomogram (FPR = 0.032, TPR

  8. Effect of the initial stage of annealing on modeling of enthalpy relaxation in a hyperquenched glass

    DEFF Research Database (Denmark)

    Zhang, Yanfei; Guo, Xiaoju; Yue, Yuanzheng

    2013-01-01

    relaxation in both HQG and AHQG during the initial stage of both the sub-Tg and above-Tg annealing cannot be captured by the existing models. In this Letter we show that the combination of a modified stretched exponential equation [M. Peyron, et al., J. Magn. Reson, Series A 118 (1996) 214] and the recently...

  9. ADM1-based modeling of methane production from acidified sweet sorghum extractin a two stage process

    DEFF Research Database (Denmark)

    Antonopoulou, Georgia; Gavala, Hariklia N.; Skiadas, Ioannis

    2012-01-01

    The present study focused on the application of the Anaerobic Digestion Model 1 οn the methane production from acidified sorghum extract generated from a hydrogen producing bioreactor in a two-stage anaerobic process. The kinetic parameters for hydrogen and volatile fatty acids consumption were e...

  10. Realizing joined-up government : Dynamic capabilities and stage models for transformation

    NARCIS (Netherlands)

    Klievink, B.; Janssen, M.

    2009-01-01

    Joining up remains a high priority on the e-government agenda and requires extensive transformation. Stage models are predictable patterns which exist in the growth of organizations and unfold as discrete time periods that result in discontinuity and can help e-government development towards

  11. Numerical simulation of brain tumor growth model using two-stage ...

    African Journals Online (AJOL)

    In the recent years, the study of glioma growth to be an active field of research Mathematical models that describe the proliferation and diffusion properties of the growth have been developed by many researchers. In this work, the performance analysis of two-stage Gauss-Seidel (TSGS) method to solve the glioma growth ...

  12. Using Five Stage Model to Design of Collaborative Learning Environments in Second Life

    Science.gov (United States)

    Orhan, Sevil; Karaman, M. Kemal

    2014-01-01

    Specifically Second Life (SL) among virtual worlds draws attention of researchers to form collaborative learning environments (Sutcliffe & Alrayes, 2012) since it could be used as a rich platform to simulate a real environment containing many collaborative learning characteristics and interaction tools within itself. Five Stage Model (FSM)…

  13. Violent Victimization and Perpetration during Adolescence: Developmental Stage Dependent Ecological Models

    Science.gov (United States)

    Matjasko, Jennifer L.; Needham, Belinda L.; Grunden, Leslie N.; Farb, Amy Feldman

    2010-01-01

    Using a variant of the ecological-transactional model and developmental theories of delinquency on a nationally representative sample of adolescents, the current study explored the ecological predictors of violent victimization, perpetration, and both for three different developmental stages during adolescence. We examined the relative influence…

  14. Modeling and Nonlinear Control of Electric Power Stage in Hybrid Electric Vehicle

    DEFF Research Database (Denmark)

    Tahri, A.; El Fadil, H.; Guerrero, Josep M.

    2014-01-01

    This paper deals with the problem of modeling and controlling the electric power stage of hybrid electric vehicle. The controlled system consists of a fuel cell (FC) as a main source, a supercapacitor as an auxiliary source, two DC-DC power converters, an inverter and a traction induction motor...

  15. Analysing outsourcing policies in an asset management context : A six-stage model

    NARCIS (Netherlands)

    Schoenmaker, R.; Verlaan, J.G.

    2013-01-01

    Asset managers of civil infrastructure are increasingly outsourcing their maintenance. Whereas maintenance is a cyclic process, decisions to outsource decisions are often project-based, and confusing the discussion on the degree of outsourcing. This paper presents a six-stage model that facilitates

  16. Teriparatide (human PTH1-34) compensates for impaired fracture healing in COX-2 deficient mice.

    Science.gov (United States)

    Yukata, Kiminori; Xie, Chao; Li, Tian-Fang; Brown, Matthew L; Kanchiku, Tsukasa; Zhang, Xinping; Awad, Hani A; Schwarz, Edward M; Beck, Christopher A; Jonason, Jennifer H; O'Keefe, Regis J

    2018-05-01

    Genetic ablation of cyclooxygenase-2 (COX-2) in mice is known to impair fracture healing. To determine if teriparatide (human PTH 1-34 ) can promote healing of Cox-2-deficient fractures, we performed detailed in vivo analyses using a murine stabilized tibia fracture model. Periosteal progenitor cell proliferation as well as bony callus formation was markedly reduced in Cox-2 -/- mice at day 10 post-fracture. Remarkably, intermittent PTH 1-34 administration increased proliferation of periosteal progenitor cells, restored callus formation on day 7, and enhanced bone formation on days 10, 14 and 21 in Cox-2-deficient mice. PTH 1-34 also increased biomechanical torsional properties at days 10 or 14 in all genotypes, consistent with enhanced bony callus formation by radiologic examinations. To determine the effects of intermittent PTH 1-34 for callus remodeling, TRAP staining was performed. Intermittent PTH 1-34 treatment increased the number of TRAP positive cells per total callus area on day 21 in Cox-2 -/- fractures. Taken together, the present findings indicate that intermittent PTH 1-34 treatment could compensate for COX-2 deficiency and improve impaired fracture healing in Cox-2-deficient mice. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Integrative health care model for climacteric stage women: design of the intervention

    Directory of Open Access Journals (Sweden)

    Pérez-Cuevas Ricardo

    2011-02-01

    Full Text Available Abstract Background Climacteric stage women experience significant biological, psychological and social changes. With demographic changes being observed in the growing number of climacteric stage women in Mexico, it is important to improve their knowledge about the climacteric stage and its potential associated problems, encourage their participation in screening programs, and promote the acquisition of healthy lifestyles. At Mexican health care institutions the predominant health care model for climacteric stage women has a biomedical perspective. Medical doctors provide mostly curative services and have limited support from other health professionals. This study aims to design an integrative health care model (IHCM: bio-psycho-social, multidisciplinary and women-centered applicable in primary care services aimed at climacteric stage women. Methods/Design We present the design, inclusion criteria and detailed description of an IHCM. The IHCM consists of collaborative and coordinated provision of services by a health team, which is involves a family doctor, nurse, psychologist, and the woman herself. The health team promotes the empowerment of women through individual and group counseling on the climacteric stage and health related self-care. The intervention lasts three months followed by a three-month follow-up period to evaluate the effectiveness of the model. The effectiveness of the model will be evaluated through the following aspects: health-related quality of life (HR-QoL, empowerment, self-efficacy and knowledge regarding the climacteric stage and health-related self-care activities, use of screening services, and improvement in lifestyles (regular leisure time physical activity and healthy diet. Discussion Participation in preventive activities should be encouraged among women in Mexico. Designing and evaluating the effectiveness of an integrative health care model for women at the climacteric stage, based on the empowerment approach

  18. Travelling wave and convergence in stage-structured reaction-diffusion competitive models with nonlocal delays

    International Nuclear Information System (INIS)

    Xu Rui; Chaplain, M.A.J.; Davidson, F.A.

    2006-01-01

    In this paper, we first investigate a stage-structured competitive model with time delays, harvesting, and nonlocal spatial effect. By using an iterative technique recently developed by Wu and Zou (Wu J, Zou X. Travelling wave fronts of reaction-diffusion systems with delay. J Dynam Differen Equat 2001;13:651-87), sufficient conditions are established for the existence of travelling front solution connecting the two boundary equilibria in the case when there is no positive equilibrium. The travelling wave front corresponds to an invasion by a stronger species which drives the weaker species to extinction. Secondly, we consider a stage-structured competitive model with time delays and nonlocal spatial effect when the domain is finite. We prove the global stability of each of the nonnegative equilibria and demonstrate that the more complex model studied here admits three possible long term behaviors: coexistence, bistability and dominance as is the case for the standard Lotka-Voltera competitive model

  19. Time Delayed Stage-Structured Predator-Prey Model with Birth Pulse and Pest Control Tactics

    OpenAIRE

    Yan, Mei; Li, Yongfeng; Xiang, Zhongyi

    2014-01-01

    Normally, chemical pesticides kill not only pests but also their natural enemies. In order to better control the pests, two-time delayed stage-structured predator-prey models with birth pulse and pest control tactics are proposed and analyzed by using impulsive differential equations in present work. The stability threshold conditions for the mature prey-eradication periodic solutions of two models are derived, respectively. The effects of key parameters including killing efficiency rate, pul...

  20. Dynamics of a Stage Structured Pest Control Model in a Polluted Environment with Pulse Pollution Input

    OpenAIRE

    Liu, Bing; Xu, Ling; Kang, Baolin

    2013-01-01

    By using pollution model and impulsive delay differential equation, we formulate a pest control model with stage structure for natural enemy in a polluted environment by introducing a constant periodic pollutant input and killing pest at different fixed moments and investigate the dynamics of such a system. We assume only that the natural enemies are affected by pollution, and we choose the method to kill the pest without harming natural enemies. Sufficient conditions for global attractivity ...

  1. Model of the nonhydrodynamic stage of a plasma focus (z pinch sausage-type instability)

    International Nuclear Information System (INIS)

    Zueva, N.M.; Imshennik, V.S.; Lokutsievskii, O.V.; Mikhailova, M.S.

    A nonhydrodynamic two-dimensional plasma model convenient for describing a later stage of development of a plasma focus (sausage-type instability) is given. In this model, ions are described by the Vlasov collisionless equation, and electrons are treated in the MHD approximation. More accurately, for electrons, use is made of generalized Ohm's law and the entropy equation, and the condition of quasi-neutrality of the plasma is also adopted

  2. Bifurcation analysis on a delayed SIS epidemic model with stage structure

    Directory of Open Access Journals (Sweden)

    Kejun Zhuang

    2007-05-01

    Full Text Available In this paper, a delayed SIS (Susceptible Infectious Susceptible model with stage structure is investigated. We study the Hopf bifurcations and stability of the model. Applying the normal form theory and the center manifold argument, we derive the explicit formulas determining the properties of the bifurcating periodic solutions. The conditions to guarantee the global existence of periodic solutions are established. Also some numerical simulations for supporting the theoretical are given.

  3. Three Stage Maturity Model in SME’s towards Industry 4.0

    OpenAIRE

    Ganzarain, Jaione; Errasti, Nekane

    2016-01-01

    Purpose: To address the challenges regarding the concept of Industry 4.0 and the diversification methodology and based on the strategic guidance towards Industry 4.0, we propose a process model as a guiding framework for Industry 4.0 collaborative diversification vision, strategy and action building. In this paper we suggest a stage process model to guide and train companies to identify new opportunities for diversification within Industry 4.0. Systematically carrying out the s...

  4. Mechanical and mathematical models of multi-stage horizontal fracturing strings and their application

    Directory of Open Access Journals (Sweden)

    Zhanghua Lian

    2015-03-01

    Full Text Available Multi-stage SRV fracturing in horizontal wells is a new technology developed at home and abroad in recent years to effectively develop shale gas or low-permeability reservoirs, but on the other hand makes the mechanical environment of fracturing strings more complicated at the same time. In view of this, based on the loading features of tubing strings during the multi-stage fracturing of a horizontal well, mechanical models were established for three working cases of multiple packer setting, open differential-pressure sliding sleeve, and open ball-injection sliding sleeve under a hold-down packer. Moreover, mathematical models were respectively built for the above three cases. According to the Lame formula and Von Mises stress calculation formula for the thick-walled cylinder in the theory of elastic mechanics, a mathematical model was also established to calculate the equivalent stress for tubing string safety evaluation when the fracturing string was under the combined action of inner pressure, external squeezing force and axial stress, and another mathematical model was built for the mechanical strength and safety evaluation of multi-stage fracturing strings. In addition, a practical software was developed for the mechanical safety evaluation of horizontal well multi-stage fracturing strings according to the mathematical model developed for the mechanical calculation of the multi-packer string in horizontal wells. The research results were applied and verified in a gas well of Tahe Oilfield in the Tarim Basin with excellent effects, providing a theoretical basis and a simple and reliable technical means for optimal design and safety evaluation of safe operational parameters of multi-stage fracturing strings in horizontal wells.

  5. Women's steps of change and entry into drug abuse treatment. A multidimensional stages of change model.

    Science.gov (United States)

    Brown, V B; Melchior, L A; Panter, A T; Slaughter, R; Huba, G J

    2000-04-01

    The Transtheoretical, or Stages of Change Model, has been applied to the investigation of help-seeking related to a number of addictive behaviors. Overall, the model has shown to be very important in understanding the process of help-seeking. However, substance abuse rarely exists in isolation from other health, mental health, and social problems. The present work extends the original Stages of Change Model by proposing "Steps of Change" as they relate to entry into substance abuse treatment programs for women. Readiness to make life changes in four domains-domestic violence, HIV sexual risk behavior, substance abuse, and mental health-is examined in relation to entry into four substance abuse treatment modalities (12-step, detoxification, outpatient, and residential). The Steps of Change Model hypothesizes that help-seeking behavior of substance-abusing women may reflect a hierarchy of readiness based on the immediacy, or time urgency, of their treatment issues. For example, women in battering relationships may be ready to make changes to reduce their exposure to violence before admitting readiness to seek substance abuse treatment. The Steps of Change Model was examined in a sample of 451 women contacted through a substance abuse treatment-readiness program in Los Angeles, California. A series of logistic regression analyses predict entry into four separate treatment modalities that vary. Results suggest a multidimensional Stages of Change Model that may extend to other populations and to other types of help-seeking behaviors.

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

    Science.gov (United States)

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

    2016-08-01

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

  7. Kidney function and mortality post-liver transplant in the Model for End-Stage Liver Disease era

    Directory of Open Access Journals (Sweden)

    Sethi A

    2011-11-01

    Full Text Available Aastha Sethi1, Michelle M Estrella1, Richard Ugarte2, Mohamed G Atta1 1Johns Hopkins University School of Medicine, Department of Medicine, Baltimore, MD, USA; 2University of Maryland Medical Center, Department of Medicine, Baltimore, MD, USA Abstract: The Model for End-Stage Liver Disease (MELD score incorporates serum creatinine and was introduced to facilitate allocation of orthotopic liver transplantation (LT. The objective is to determine the impact of MELD and kidney function on all-cause mortality. Among LTs performed in a tertiary referral hospital between 1995 and 2009, 419 cases were studied. Cox proportional hazards models were constructed to estimate the hazard ratios (HR and 95% confidence intervals (CI for death. Over mean follow-ups of 8.4 and 3.1 years during the pre-MELD and MELD era, 57 and 63 deaths were observed, respectively. Those transplanted during the MELD era had a higher likelihood of hepatorenal syndrome (8% vs 2%, P < 0.01, lower kidney function (median estimated glomerular filtration rate [eGFR] 77.8 vs 92.6 mL/min/1.73 m2, P < 0.01, and more pretransplantation renal replacement therapy (RRT (5% vs 1%; P < 0.01. All-cause mortality risk was similar in the MELD vs the pre-MELD era (HR: 0.98, 95% CI: 0.58–1.65. The risk of death, however, was nearly 3-fold greater (95% CI: 1.14–6.60 among those requiring pre-transplant RRT. Similarly, eGFR < 60 mL/min/1.73 m2 post-transplant was associated with a 2.5-fold higher mortality (95% CI: 1.48–4.11. The study suggests that MELD implementation had no impact on all-cause mortality post-LT. However, the need for pre-transplant RRT and post-transplant kidney dysfunction was associated with a more than 2-fold greater risk of subsequent death. Keywords: eGFR, mortality, MELD, liver transplant

  8. Isothermal modeling of aerodynamic structure of the swirling flow in a two-stage burner

    Directory of Open Access Journals (Sweden)

    Yusupov Roman

    2017-01-01

    Full Text Available The work deals with the experimental study of the aerodynamic structure of a swirling flow in the isothermal model of two-stage vortex combustion chamber. The main attention is focused on the process of flow mixing of two successively connected tangential swirlers of the first and second stages of the working section. Data on flow visualization are presented for two patterns of flow swirling. Time-averaged profiles of the axial and tangential velocity components are obtained with the help of laser-Doppler anemometer. In the case of flow co-swirling between two stages of the working section, instability of a secondary flow in the form of precessing vortex was distinguished. For the regime with counter flow swirling, effective mixing of the swirl flows was found; this was reflected by formation of the flow with uniform distribution of axial velocity over the cross-section.

  9. Towards a universal barcode of oomycetes--a comparison of the cox1 and cox2 loci.

    Science.gov (United States)

    Choi, Young-Joon; Beakes, Gordon; Glockling, Sally; Kruse, Julia; Nam, Bora; Nigrelli, Lisa; Ploch, Sebastian; Shin, Hyeon-Dong; Shivas, Roger G; Telle, Sabine; Voglmayr, Hermann; Thines, Marco

    2015-11-01

    Oomycetes are a diverse group of eukaryotes in terrestrial, limnic and marine habitats worldwide and include several devastating plant pathogens, for example Phytophthora infestans (potato late blight). The cytochrome c oxidase subunit 2 gene (cox2) has been widely used for identification, taxonomy and phylogeny of various oomycete groups. However, recently the cox1 gene was proposed as a DNA barcode marker instead, together with ITS rDNA. The cox1 locus has been used in some studies of Pythium and Phytophthora, but has rarely been used for other oomycetes, as amplification success of cox1 varies with different lineages and sample ages. To determine which out of cox1 or cox2 is best suited as a universal oomycete barcode, we compared these two genes in terms of (i) PCR efficiency for 31 representative genera, as well as for historic herbarium specimens, and (ii) sequence polymorphism, intra- and interspecific divergence. The primer sets for cox2 successfully amplified all oomycete genera tested, while cox1 failed to amplify three genera. In addition, cox2 exhibited higher PCR efficiency for historic herbarium specimens, providing easier access to barcoding-type material. Sequence data for several historic type specimens exist for cox2, but there are none for cox1. In addition, cox2 yielded higher species identification success, with higher interspecific and lower intraspecific divergences than cox1. Therefore, cox2 is suggested as a partner DNA barcode along with ITS rDNA instead of cox1. The cox2-1 spacer could be a useful marker below species level. Improved protocols and universal primers are presented for all genes to facilitate future barcoding efforts. © 2015 John Wiley & Sons Ltd.

  10. Towards a universal barcode of oomycetes – a comparison of the cox1 and cox2 loci

    Science.gov (United States)

    Choi, Young-Joon; Beakes, Gordon; Glockling, Sally; Kruse, Julia; Nam, Bora; Nigrelli, Lisa; Ploch, Sebastian; Shin, Hyeon-Dong; Shivas, Roger G.; Telle, Sabine; Voglmayr, Hermann; Thines, Marco

    2017-01-01

    Oomycetes are a diverse group of eukaryotes in terrestrial, limnic and marine habitats worldwide and include several devastating plant pathogens, for example Phytophthora infestans (potato late blight). The cytochrome c oxidase subunit 2 gene (cox2) has been widely used for identification, taxonomy and phylogeny of various oomycete groups. However, recently the cox1 gene was proposed as a DNA barcode marker instead, together with ITS rDNA. The cox1 locus has been used in some studies of Pythium and Phytophthora, but has rarely been used for other oomycetes, as amplification success of cox1 varies with different lineages and sample ages. To determine which out of cox1 or cox2 is best suited as a universal oomycete barcode, we compared these two genes in terms of (i) PCR efficiency for 31 representative genera, as well as for historic herbarium specimens, and (ii) sequence polymorphism, intra- and interspecific divergence. The primer sets for cox2 successfully amplified all oomycete genera tested, while cox1 failed to amplify three genera. In addition, cox2 exhibited higher PCR efficiency for historic herbarium specimens, providing easier access to barcoding-type material. Sequence data for several historic type specimens exist for cox2, but there are none for cox1. In addition, cox2 yielded higher species identification success, with higher interspecific and lower intraspecific divergences than cox1. Therefore, cox2 is suggested as a partner DNA barcode along with ITS rDNA instead of cox1. The cox2-1 spacer could be a useful marker below species level. Improved protocols and universal primers are presented for all genes to facilitate future barcoding efforts. PMID:25728598

  11. Incorporating hydraulic/hydromorphologic properties and their stage dependency into hydrologic compartmental models

    Science.gov (United States)

    Gustafsson, A.; Wörman, A.

    2009-04-01

    According to recent studies, the volumetric error of the predicted size of the spring flood in Sweden can be as large as 20%. A significant part of this error originates from simplifications in the spatial and hydrodynamic description of watercourse networks, as well as statistical problems to give proper weight to extreme flows. Possible ways to improve current hydrological modelling practises is by making models more adapted to varying flow conditions as well as by increasing the coupling between model parameters and physical catchment characteristics. This study formulates a methodology based in hydrodynamical/hydraulic theory to investigate how river network characteristics vary with flow stage and how to transfer this information to compartmental hydrologic models such as the HBV/HYPE models. This is particularly important during extreme flows when a significant portion of the water flows outside the normal stream channels. The aim is to combine knowledge about the hydrodynamics and hydro-morphology of watercourse networks to improve the predictions of peak flows. HYPE is a semi-distributed conceptual compartmental hydrological model which is currently being developed at the SMHI as a successor to the HBV model. The model (HYPE) is thought to be better adapted to varying flow conditions by using the dynamical response functions derived by the methodology described here. The distribution of residence times within the watercourse network - and how these depend on flow stage is analysed. This information is then incorporated into the response functions of the HYPE model, i.e. the compartmental model receives a dynamic transformation function relating river discharge to storativity within the sub-catchment. This response function hence reflects the topologic and hydromorphologic characteristics of the watercourse network as well as flow stage. Seven subcatchments in Rönne River basin (1900 km2) are studied to show how this approach can improve the prediction of

  12. A multi-stage 3-D stress field modelling approach exemplified in the Bavarian Molasse Basin

    Science.gov (United States)

    Ziegler, Moritz O.; Heidbach, Oliver; Reinecker, John; Przybycin, Anna M.; Scheck-Wenderoth, Magdalena

    2016-09-01

    The knowledge of the contemporary in situ stress state is a key issue for safe and sustainable subsurface engineering. However, information on the orientation and magnitudes of the stress state is limited and often not available for the areas of interest. Therefore 3-D geomechanical-numerical modelling is used to estimate the in situ stress state and the distance of faults from failure for application in subsurface engineering. The main challenge in this approach is to bridge the gap in scale between the widely scattered data used for calibration of the model and the high resolution in the target area required for the application. We present a multi-stage 3-D geomechanical-numerical approach which provides a state-of-the-art model of the stress field for a reservoir-scale area from widely scattered data records. Therefore, we first use a large-scale regional model which is calibrated by available stress data and provides the full 3-D stress tensor at discrete points in the entire model volume. The modelled stress state is used subsequently for the calibration of a smaller-scale model located within the large-scale model in an area without any observed stress data records. We exemplify this approach with two-stages for the area around Munich in the German Molasse Basin. As an example of application, we estimate the scalar values for slip tendency and fracture potential from the model results as measures for the criticality of fault reactivation in the reservoir-scale model. The modelling results show that variations due to uncertainties in the input data are mainly introduced by the uncertain material properties and missing SHmax magnitude estimates needed for a more reliable model calibration. This leads to the conclusion that at this stage the model's reliability depends only on the amount and quality of available stress information rather than on the modelling technique itself or on local details of the model geometry. Any improvements in modelling and increases

  13. Intention for Car Use Reduction: Applying a Stage-Based Model

    Directory of Open Access Journals (Sweden)

    Lars E. Olsson

    2018-01-01

    Full Text Available This study investigates which variables drive intention to reduce car use by modelling a stage of change construct with mechanisms in the Theory of Planned Behavior (TPB and Norm Activation Model (NAM. Web questionnaires (n = 794 were collected via 11 workplaces. The socio-demographics, work commute, stage of change, attitudes to sustainable travel modes, social norms, perceived behavioral control, and personal norm were assessed. An initial descriptive analysis revealed that 19% of the employees saw no reason to reduce their car use; 35% would like to reduce their car use but felt it was impossible; 12% were thinking about reducing their car use but were unsure of how or when to do this; 12% had an aim to reduce current car use, and knew which journeys to replace and which modes to use; and 23% try to use modes other than a car for most journeys, and will maintain or reduce their already low car use in the coming months. A series of Ordered Logit Models showed that socio-demographic variables did not explain the stage of change. Instead, personal norms, instrumental and affective attitudes, and perceived behavioral control toward sustainable travel modes were all significant and explained 43% of the variance in stage of change. Furthermore, it was found that the significant relationships were not linear in nature. The analysis also showed an indirect effect of social norms on the stage of change through personal norms. Implications are discussed regarding the design of interventions aimed at influencing a sustainable work commute.

  14. Integrating life stages into ecological niche models: a case study on tiger beetles.

    Science.gov (United States)

    Taboada, Angela; von Wehrden, Henrik; Assmann, Thorsten

    2013-01-01

    Detailed understanding of a species' natural history and environmental needs across spatial scales is a primary requisite for effective conservation planning, particularly for species with complex life cycles in which different life stages occupy different niches and respond to the environment at different scales. However, niche models applied to conservation often neglect early life stages and are mostly performed at broad spatial scales. Using the endangered heath tiger beetle (Cicindela sylvatica) as a model species, we relate presence/absence and abundance data of locally dispersing adults and sedentary larvae to abiotic and biotic variables measured in a multiscale approach within the geographic extent relevant to active conservation management. At the scale of hundreds of meters, fine-grained abiotic conditions (i.e., vegetation structure) are fundamental determinants of the occurrence of both life stages, whereas the effect of biotic factors is mostly contained in the abiotic signature. The combination of dense heath vegetation and bare ground areas is thus the first requirement for the species' preservation, provided that accessibility to the suitable habitat is ensured. At a smaller scale (centimetres), the influence of abiotic factors on larval occurrence becomes negligible, suggesting the existence of important additional variables acting within larval proximity. Sustained significant correlations between neighbouring larvae in the models provide an indication of the potential impact of neighbourhood crowding on the larval niche within a few centimetres. Since the species spends the majority of its life cycle in the larval stage, it is essential to consider the hierarchical abiotic and biotic processes affecting the larvae when designing practical conservation guidelines for the species. This underlines the necessity for a more critical evaluation of the consequences of disregarding niche variation between life stages when estimating niches and

  15. Weibull aging models for the single protective channel unavailability analysis by the device of stages

    International Nuclear Information System (INIS)

    Nunes, M.E.C.; Noriega, H.C.; Melo, P.F.F.

    1997-01-01

    Among the features to take into account in the unavailability analysis of protective channels, there is one that plays a dominant role - that of considering the equipment aging. In this sense, the exponential failure model is not adequate, since some transition rates are no more constant. As a consequence, Markovian models cannot be used anymore. As an alternative, one may use the device of stages that allows for transforming a Non Markovian model into an equivalent Markovian one by insertion of a fictitious states set, called stages. For a given time-dependent transition rate, its failure density is analysed as to the best combination of exponential distributions and then the moments of the original distribution and those of the combination are matched to estimate the necessary parameters. In this paper, the aging of the protective channel is supposed to follow Weibull distributions. Typical means and variances for the times to failure are considered and combinations of stages are checked. Initial conditions features are discussed in connection with states that are fictitious and to check the validity of the developed models. Alternative solutions by the discretization of the failure rates are generated. The results obtained agree quite well. (author). 7 refs., 6 figs

  16. Thermodynamic modelling of a two-stage absorption chiller driven at two-temperature levels

    International Nuclear Information System (INIS)

    Figueredo, Gustavo R.; Bourouis, Mahmoud; Coronas, Alberto

    2008-01-01

    The thermodynamic model we develop in this paper considers (i) the external irreversibilities of the endoreversible models; (ii) the irreversibilities due to heat losses; and (iii) the generation of internal entropy due to pressure drops and the temperature and concentration gradients. We considered: (i) external heat losses between the generators of high and intermediate pressures and the ambient and between the ambient and the evaporator; and (ii) internal heat losses from the generators towards the condensers and from the absorber towards the evaporator. This simple but precise model faithfully represents the trend towards efficiency variation at partial loads. We have used the model to analyse the behaviour of a water-LiBr double-stage absorption chiller with 200 kW of cooling power. This machine can operate in summer as a double-stage chiller driven by heat at 170 o C from natural gas, as a single-stage chiller driven by heat at 90 o C from solar energy, or simultaneously in combined mode at both temperatures. It can also operate in winter in 'double-lift' mode for heating with a driving heat at 170 o C from natural gas. We studied the efficiency of the machine at partial loads for several solar fractions and the distribution of the heat transfer areas between the various components of the chiller

  17. COX-2 and p53 in human sinonasal cancer

    DEFF Research Database (Denmark)

    Holmila, Reetta; Cyr, Diane; Luce, Danièle

    2008-01-01

    to development of cancer. Many signals that activate COX-2 also induce tumor suppressor p53, a transcription factor central in cellular stress response. We investigated COX-2 and p53 expressions by immunohistochemistry in 50 SNCs (23 adenocarcinomas, and 27 squamous cell carcinomas (SCC); 48 analyzed for COX-2......The causal role of wood-dust exposure in sinonasal cancer (SNC) has been established in epidemiological studies, but the mechanisms of SNC carcinogenesis are still largely unknown. Increased amounts of COX-2 are found in both premalignant and malignant tissues, and experimental evidence link COX-2...

  18. Monte Carlo Error Analysis Applied to Core Formation: The Single-stage Model Revived

    Science.gov (United States)

    Cottrell, E.; Walter, M. J.

    2009-12-01

    The last decade has witnessed an explosion of studies that scrutinize whether or not the siderophile element budget of the modern mantle can plausibly be explained by metal-silicate equilibration in a deep magma ocean during core formation. The single-stage equilibrium scenario is seductive because experiments that equilibrate metal and silicate can then serve as a proxy for the early earth, and the physical and chemical conditions of core formation can be identified. Recently, models have become more complex as they try to accommodate the proliferation of element partitioning data sets, each of which sets its own limits on the pressure, temperature, and chemistry of equilibration. The ability of single stage models to explain mantle chemistry has subsequently been challenged, resulting in the development of complex multi-stage core formation models. Here we show that the extent to which extant partitioning data are consistent with single-stage core formation depends heavily upon (1) the assumptions made when regressing experimental partitioning data (2) the certainty with which regression coefficients are known and (3) the certainty with which the core/mantle concentration ratios of the siderophile elements are known. We introduce a Monte Carlo algorithm coded in MATLAB that samples parameter space in pressure and oxygen fugacity for a given mantle composition (nbo/t) and liquidus, and returns the number of equilibrium single-stage liquidus “solutions” that are permissible, taking into account the uncertainty in regression parameters and range of acceptable core/mantle ratios. Here we explore the consequences of regression parameter uncertainty and the impact of regression construction on model outcomes. We find that the form of the partition coefficient (Kd with enforced valence state, or D) and the handling of the temperature effect (based on 1-atm free energy data or high P-T experimental observations) critically affects model outcomes. We consider the most

  19. Combination Efficacy of Astragalus membranaceus and Curcuma wenyujin at Different Stages of Tumor Progression in an Imageable Orthotopic Nude Mouse Model of Metastatic Human Ovarian Cancer Expressing Red Fluorescent Protein.

    Science.gov (United States)

    Yin, Gang; Tang, Decai; Dai, Jianguo; Liu, Min; Wu, Mianhua; Sun, Y U; Yang, Zhijian; Hoffman, Robert M; Li, Lin; Zhang, Shuo; Guo, Xiuxia

    2015-06-01

    The present study determined the efficacy of extracts of Astragalus membranaceus (AM) and Curcuma wenyujin (CW), a traditional Chinese medicine herbal mixture, at different tumor stages of an orthotopic nude mouse model of human ovarian cancer expressing red fluorescent protein. The tumor-bearing mice were treated with cisplatinum (CDDP), AM, CW, or a combination of AM and CW in each of three tumor stages, using the same regimen. Group 1 received saline as negative control. Group 2 received CDDP i.p. as positive control with a dose of 2 mg/kg, every three days. Group 3 received AM daily via oral gavage, at a dose of 9120 mg/kg. Group 4 received CW daily via oral gavage, at a dose of 4560 mg/kg. Groups 5, 6 and 7 received combinations of AM and CW daily via oral gavage at low (AM, 2280 mg/kg; CW, 1140 mg/kg), medium (AM, 4560 mg/kg; CW 2280 mg/kg), and high (AM, 9120 mg/kg; CW, 4560 mg/kg) doses. The expression of angiogenesis- and apoptosis-related genes in the tumors were analyzed by immunohistochemistry for matrix metalloproteinase 2 (MMP-2), vascular endothelial growth factor (VEGF) fibroblast growth factor 2 (FGF-2), B-cell lymphoma 2 (Bcl-2) and cyclooxygenase 2 (Cox-2), and by polymerase chain reaction for MMP-2, FGF-2 and Bcl-2. CDDP, AM, and its combination with CW-induced significant growth inhibition of Stage I tumors. Strong efficacy of the combination of AM and CW at high dose was observed. Monotherapy with CDDP, AM, CW, and the combination treatments did not significantly inhibit Stage II and III tumors. The expression of MMP-2, VEGF, FGF-2, and Cox-2 was significantly reduced in Stage I tumors treated with AM, CW, and their combination, suggesting a possible role of these angiogenesis- and apoptosis-related genes in the observed efficacy of the agents tested. This study is the first report on the efficacy of anticancer agents at different stages of ovarian cancer in an orthotopic mouse model. As the tumor progressed, it became treatment

  20. Two-stage stochastic programming model for the regional-scale electricity planning under demand uncertainty

    International Nuclear Information System (INIS)

    Huang, Yun-Hsun; Wu, Jung-Hua; Hsu, Yu-Ju

    2016-01-01

    Traditional electricity supply planning models regard the electricity demand as a deterministic parameter and require the total power output to satisfy the aggregate electricity demand. But in today's world, the electric system planners are facing tremendously complex environments full of uncertainties, where electricity demand is a key source of uncertainty. In addition, electricity demand patterns are considerably different for different regions. This paper developed a multi-region optimization model based on two-stage stochastic programming framework to incorporate the demand uncertainty. Furthermore, the decision tree method and Monte Carlo simulation approach are integrated into the model to simplify electricity demands in the form of nodes and determine the values and probabilities. The proposed model was successfully applied to a real case study (i.e. Taiwan's electricity sector) to show its applicability. Detail simulation results were presented and compared with those generated by a deterministic model. Finally, the long-term electricity development roadmap at a regional level could be provided on the basis of our simulation results. - Highlights: • A multi-region, two-stage stochastic programming model has been developed. • The decision tree and Monte Carlo simulation are integrated into the framework. • Taiwan's electricity sector is used to illustrate the applicability of the model. • The results under deterministic and stochastic cases are shown for comparison. • Optimal portfolios of regional generation technologies can be identified.

  1. Trading stages

    DEFF Research Database (Denmark)

    Steiner, Uli; Tuljapurkar, Shripad; Coulson, Tim

    2012-01-01

    because they are hard to use and interpret, and tools for age and stage structured populations are missing. We present easily interpretable expressions for the sensitivities and elasticities of life expectancy to vital rates in age-stage models, and illustrate their application with two biological......Interest in stage-and age structured models has recently increased because they can describe quantitative traits such as size that are left out of age-only demography. Available methods for the analysis of effects of vital rates on lifespan in stage-structured models have not been widely applied...... examples. Much of our approach relies on trading of time and mortality risk in one stage for time and risk in others. Our approach contributes to the new framework of the study of age- and stage-structured biodemography....

  2. A two-stage fuzzy chance-constrained water management model.

    Science.gov (United States)

    Xu, Jiaxuan; Huang, Guohe; Li, Zoe; Chen, Jiapei

    2017-05-01

    In this study, an inexact two-stage fuzzy gradient chance-constrained programming (ITSFGP) method is developed and applied to the water resources management in the Heshui River Basin, Jiangxi Province, China. The optimization model is established by incorporating interval programming, two-stage stochastic programming, and fuzzy gradient chance-constrained programming within an optimization framework. The hybrid model can address uncertainties represented as fuzzy sets, probability distributions, and interval numbers. It can effectively tackle the interactions between pre-regulated economic targets and the associated environmental penalties attributed to water allocation schemes and reflect the tradeoffs between economic revenues and system-failure risk. Furthermore, uncertainties associated with the decision makers' preferences are considered in decision-making processes. The obtained results can provide decision support for the local sustainable economic development and water resources allocation strategies under multiple uncertainties.

  3. Cancerous Tumour Model Analysis and Constructing schemes of Anti-angiogenesis Therapy at an Early Stage

    Directory of Open Access Journals (Sweden)

    O. Yu. Mukhomorova

    2015-01-01

    Full Text Available Anti-angiogenesis therapy is an alternative and successfully employed method for treatment of cancerous tumour. However, this therapy isn't widely used in medicine because of expensive drugs. It leads naturally to elaboration of such treatment regimens which use minimum amount of drugs.The aim of the paper is to investigate the model of development of illness and elaborate appropriate treatment regimens in the case of early diagnosis of the disease. The given model reflects the therapy at an intermediate stage of the disease treatment. Further treatment is aimed to destroy cancer cells and may be continued by other means, which are not reflected in the model.Analysis of the main properties of the model was carried out with consideration of two types of auxiliary systems. In the first case, the system is considered without control, as a model of tumour development in the absence of medical treatment. The study of the equilibrium point and determination of its type allowed us to describe disease dynamics and to determine tumour size resulting in death. In the second case a model with a constant control was investigated. The study of its equilibrium point showed that continuous control is not sufficient to support satisfactory patient's condition, and it is necessary to elaborate more complex treatment regimens. For this purpose, we used the method of terminal problems consisting in the search for such program control which forces system to a given final state. Selecting the initial and final states is due to medical grounds.As a result, we found two treatment regimens | one-stage treatment regimen and multi-stage one. The properties of each treatment regimen are analyzed and compared. The total amount of used drugs was a criterion for comparing these two treatment regimens. The theoretical conclusions obtained in this work are supported by computer modeling in MATLAB environment.

  4. A Human Life-Stage Physiologically Based Pharmacokinetic and Pharmacodynamic Model for Chlorpyrifos: Development and Validation

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Jordan N.; Hinderliter, Paul M.; Timchalk, Charles; Bartels, M. J.; Poet, Torka S.

    2014-08-01

    Sensitivity to chemicals in animals and humans are known to vary with age. Age-related changes in sensitivity to chlorpyrifos have been reported in animal models. A life-stage physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed to computationally predict disposition of CPF and its metabolites, chlorpyrifos-oxon (the ultimate toxicant) and 3,5,6-trichloro-2-pyridinol (TCPy), as well as B-esterase inhibition by chlorpyrifos-oxon in humans. In this model, age-dependent body weight was calculated from a generalized Gompertz function, and compartments (liver, brain, fat, blood, diaphragm, rapid, and slow) were scaled based on body weight from polynomial functions on a fractional body weight basis. Blood flows among compartments were calculated as a constant flow per compartment volume. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Model simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ≥ 0.55 mg/kg of chlorpyrifos (significantly higher than environmental exposure levels), 6 mo old children are predicted to have higher levels of chlorpyrifos-oxon in blood and higher levels of red blood cell cholinesterase inhibition compared to adults from equivalent oral doses of chlorpyrifos. At lower doses that are more relevant to environmental exposures, the model predicts that adults will have slightly higher levels of chlorpyrifos-oxon in blood and greater cholinesterase inhibition. This model provides a computational framework for age-comparative simulations that can be utilized to predict CPF disposition and biological response over various postnatal life-stages.

  5. The inflammatory effect of infection with Hymenolepis diminuta via the increased expression and activity of COX-1 and COX-2 in the rat jejunum and colon.

    Science.gov (United States)

    Kosik-Bogacka, D I; Baranowska-Bosiacka, I; Kolasa-Wołosiuk, A; Lanocha-Arendarczyk, N; Gutowska, I; Korbecki, J; Namięta, H; Rotter, I

    2016-10-01

    The aim of this study was to determine whether Hymenolepis diminuta may affect the expression and activity of cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2), resulting in the altered levels of their main products - prostaglandins (PGE2) and thromboxane B2 (TXB2). The study used the same experimental model as in our previous studies in which we had observed changes in the transepithelial ion transport, tight junctions and in the indicators of oxidative stress, in both small and large intestines of rats infected with H. diminuta. In this paper, we investigated not only the site of immediate presence of the tapeworm (jejunum), but also a distant site (colon). Inflammation related to H. diminuta infection is associated with the increased expression and activation of cyclooxygenase (COX), enzyme responsible for the synthesis of PGE2 and TXB2, local hormones contributing to the enhanced inflammatory reaction in the jejunum and colon in the infected rats. The increased COX expression and activity is probably caused by the increased levels of free radicals and the weakening of the host's antioxidant defense induced by the presence of the parasite. Our immunohistochemical analysis showed that H. diminuta infection affected not only the intensity of the immunodetection of COX but also the enzyme protein localization within intestinal epithelial cells - from the entire cytoplasm to apical/basal regions of cells, or even to the nucleus. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. A three-stage discrete-time population model: continuous versus seasonal reproduction.

    Science.gov (United States)

    Ackleh, Azmy S; Dib, Youssef M; Jang, Sophia R-J

    2007-10-01

    We consider a three-stage discrete-time population model with density-dependent survivorship and time-dependent reproduction. We provide stability analysis for two types of birth mechanisms: continuous and seasonal. We show that when birth is continuous there exists a unique globally stable interior equilibrium provided that the inherent net reproductive number is greater than unity. If it is less than unity, then extinction is the population's fate. We then analyze the case when birth is a function of period two and show that the unique two-cycle is globally attracting when the inherent net reproductive number is greater than unity, while if it is less than unity the population goes to extinction. The two birth types are then compared. It is shown that for low birth rates the adult average number over a one-year period is always higher when reproduction is continuous. Numerical simulations suggest that this remains true for high birth rates. Thus periodic birth rates of period two are deleterious for the three-stage population model. This is different from the results obtained for a two-stage model discussed by Ackleh and Jang (J. Diff. Equ. Appl., 13, 261-274, 2007), where it was shown that for low birth rates seasonal breeding results in higher adult averages.

  7. Waterhammer Modeling for the Ares I Upper Stage Reaction Control System Cold Flow Development Test Article

    Science.gov (United States)

    Williams, Jonathan H.

    2010-01-01

    The Upper Stage Reaction Control System provides three-axis attitude control for the Ares I launch vehicle during active Upper Stage flight. The system design must accommodate rapid thruster firing to maintain the proper launch trajectory and thus allow for the possibility to pulse multiple thrusters simultaneously. Rapid thruster valve closure creates an increase in static pressure, known as waterhammer, which propagates throughout the propellant system at pressures exceeding nominal design values. A series of development tests conducted in the fall of 2009 at Marshall Space Flight Center were performed using a water-flow test article to better understand fluid performance characteristics of the Upper Stage Reaction Control System. A subset of the tests examined waterhammer along with the subsequent pressure and frequency response in the flight-representative system and provided data to anchor numerical models. This thesis presents a comparison of waterhammer test results with numerical model and analytical results. An overview of the flight system, test article, modeling and analysis are also provided.

  8. Fetal Origins of Life Stage Disease: A Zebrafish Model for the ...

    Science.gov (United States)

    In the U.S., childhood obesity has more than doubled in children and quadrupled in adolescents in the past 30 years, affects 35% of adults, and costs the U.S. healthcare industry >$200 billion annually. The chemical environment in the womb may cause susceptibility to different life-stage and life-long metabolic diseases including obesity. The challenge is to understand if exposures during developmentally sensitive windows impact life-stage disease, such as obesity, by increasing adipose tissue mass. In vitro models lack the integrated systems approach needed to assess adipose development, while mammalian models are impractical in a screen of thousands of chemicals. Therefore, an obesogen screening method was developed to interrogate bioactivity using a full systems approach, in a vertebrate zebrafish model with complete metabolic activity, at a time when the full signaling repertoire is expressed and active, to optimally examine how chemical dose and duration impact life-stage adipose mass. A time-line for adipose depot formation was mapped in zebrafish 6−14 days post fertilization (dpf) using the lipophilic dye, Nile Red, in combination with fluorescent microscopy. Those time points were then used to investigate the impact of embryonic tributyltin chloride (TBT, a known obesogen) exposure (10nM daily renewal, 0−5dpf) on adipose mass. Fluorescent microscopy revealed adipose depots that were larger and appeared 2 days earlier in TBT treated compared to contro

  9. A fractal derivative constitutive model for three stages in granite creep

    Directory of Open Access Journals (Sweden)

    R. Wang

    Full Text Available In this paper, by replacing the Newtonian dashpot with the fractal dashpot and considering damage effect, a new constitutive model is proposed in terms of time fractal derivative to describe the full creep regions of granite. The analytic solutions of the fractal derivative creep constitutive equation are derived via scaling transform. The conventional triaxial compression creep tests are performed on MTS 815 rock mechanics test system to verify the efficiency of the new model. The granite specimen is taken from Beishan site, the most potential area for the China’s high-level radioactive waste repository. It is shown that the proposed fractal model can characterize the creep behavior of granite especially in accelerating stage which the classical models cannot predict. The parametric sensitivity analysis is also conducted to investigate the effects of model parameters on the creep strain of granite. Keywords: Beishan granite, Fractal derivative, Damage evolution, Scaling transformation

  10. A Three-Stage Mechanistic Model for Solidification Cracking During Welding of Steel

    Science.gov (United States)

    Aucott, L.; Huang, D.; Dong, H. B.; Wen, S. W.; Marsden, J.; Rack, A.; Cocks, A. C. F.

    2018-03-01

    A three-stage mechanistic model for solidification cracking during TIG welding of steel is proposed from in situ synchrotron X-ray imaging of solidification cracking and subsequent analysis of fracture surfaces. Stage 1—Nucleation of inter-granular hot cracks: cracks nucleate inter-granularly in sub-surface where maximum volumetric strain is localized and volume fraction of liquid is less than 0.1; the crack nuclei occur at solute-enriched liquid pockets which remain trapped in increasingly impermeable semi-solid skeleton. Stage 2—Coalescence of cracks via inter-granular fracture: as the applied strain increases, cracks coalesce through inter-granular fracture; the coalescence path is preferential to the direction of the heat source and propagates through the grain boundaries to solidifying dendrites. Stage 3—Propagation through inter-dendritic hot tearing: inter-dendritic hot tearing occurs along the boundaries between solidifying columnar dendrites with higher liquid fraction. It is recommended that future solidification cracking criterion shall be based on the application of multiphase mechanics and fracture mechanics to the failure of semi-solid materials.

  11. Chamomile, a novel and selective COX-2 inhibitor with anti-inflammatory activity.

    Science.gov (United States)

    Srivastava, Janmejai K; Pandey, Mitali; Gupta, Sanjay

    2009-11-04

    Inducible cyclooxygenase (COX-2) has been implicated in the process of inflammation and carcinogenesis. Chamomile has long been used in traditional medicine for the treatment of inflammatory diseases. In this study we aimed to investigate whether chamomile interferes with the COX-2 pathway. We used lipopolysaccharide (LPS)-activated RAW 264.7 macrophages as an in vitro model for our studies. Chamomile treatment inhibited the release of LPS-induced prostaglandin E(2) in RAW 264.7 macrophages. This effect was found to be due to inhibition of COX-2 enzyme activity by chamomile. In addition, chamomile caused reduction in LPS-induced COX-2 mRNA and protein expression, without affecting COX-1 expression. The non-steroidal anti-inflammatory drug, sulindac and a specific COX-2 inhibitor, NS398, were shown to act similarly in LPS-activated RAW 264.7 cells. Our data suggest that chamomile works by a mechanism of action similar to that attributed to non-steroidal anti-inflammatory drugs. These findings add a novel aspect to the biological profile of chamomile which might be important for understanding the usefulness of aqueous chamomile extract in the form of tea in preventing inflammation and cancer.

  12. Two-stage estimation in copula models used in family studies

    DEFF Research Database (Denmark)

    Andersen, Elisabeth Anne Wreford

    2005-01-01

    In this paper register based family studies provide the motivation for studying a two-stage estimation procedure in copula models for multivariate failure time data. The asymptotic properties of the estimators in both parametric and semi-parametric models are derived, generalising the approach...... by Shih and Louis (Biometrics vol. 51, pp. 1384-1399, 1995b) and Glidden (Lifetime Data Analysis vol. 6, pp. 141-156, 2000). Because register based family studies often involve very large cohorts a method for analysing a sampled cohort is also derived together with the asymptotic properties...

  13. Simulation model of a single-stage lithium bromide-water absorption cooling unit

    Science.gov (United States)

    Miao, D.

    1978-01-01

    A computer model of a LiBr-H2O single-stage absorption machine was developed. The model, utilizing a given set of design data such as water-flow rates and inlet or outlet temperatures of these flow rates but without knowing the interior characteristics of the machine (heat transfer rates and surface areas), can be used to predict or simulate off-design performance. Results from 130 off-design cases for a given commercial machine agree with the published data within 2 percent.

  14. Development stage and monetization model of micro-blog in China

    Science.gov (United States)

    Xu, Tiansheng; Sun, Liu; Yang, Yiping; Ma, Hui

    2012-01-01

    Micro-blog websites are increasingly attracting the attention of academic and industry researchers. Its market value has been widely concerned and the exploration of its monetization model has entered a substantial stage. In this paper, we describe the history of Micro-blog and propose a comprehensive classification. We then discuss key characteristics based on existing websites mainly in China. A monetization model is concluded according to different features of microblog and the Hype Cycle theory[1]. The paper can be used for future academic research or making strategies for Microblog website practitioners.

  15. How uncertainty in input and parameters influences transport model output: four-stage model case-study

    DEFF Research Database (Denmark)

    Manzo, Stefano; Nielsen, Otto Anker; Prato, Carlo Giacomo

    2015-01-01

    -year model outputs uncertainty. More precisely, this study contributes to the existing literature on the topic by investigating the effects on model outputs uncertainty deriving from the use of (i) different probability distributions in the sampling process, (ii) different assignment algorithms, and (iii...... of coefficient of variation, resulting from stochastic user equilibrium and user equilibrium is, respectively, of 0.425 and 0.468. Finally, network congestion does not show a high effect on model output uncertainty at the network level. However, the final uncertainty of links with higher volume/capacity ratio......If not properly quantified, the uncertainty inherent to transport models makes analyses based on their output highly unreliable. This study investigated uncertainty in four-stage transport models by analysing a Danish case-study: the Næstved model. The model describes the demand of transport...

  16. Clinical significance of COX-2, GLUT-1 and VEGF expressions in endometrial cancer tissues.

    Science.gov (United States)

    Ma, Xiaoping; Hui, Yuzuo; Lin, Li; Wu, Yu; Zhang, Xian; Liu, Peishu

    2015-01-01

    To analyze the clinical significance of COX-2, GLUT-1 and VEGF expressions in endometrial cancer tissues. One hundred and eight tissue samples from the patients with endometrial cancer enrolled in our hospital from August 2011 to July 2014 were selected, including 60 normal tissue samples (normal group), 60 neoplastic tissue samples (neoplastic group) and 60 cancer tissue samples (cancer group). All the samples were subjected to immunohistochemical assay to detect the expressions of COX-2, GLUT-1 and VEGF. The clinical data were also investigated for correlation analysis. The positive rates of COX-2 in normal group, neoplastic group and cancer groups were 3.3%, 21.7% and 55.0% respectively. The positive rates of GLUT-1 in normal group, neoplastic group and cancer groups were 3.3%, 25.0% and 70.0% respectively. The positive rates of VEGF in normal group, neoplastic group and cancer groups were 1.7%, 23.3% and 63.3% respectively. With increasing stage of such cancer, decreasing degree of differentiation and lymphatic metastasis, the positive expression rates of COX-2, GLUT-1 and VEGF proteins were raised significantly (PGLUT-1 (r=0.207, PGLUT-1 and VEGF (r=0.758, PGLUT-1 and VEGF were highly prominent in endometrial cancer, especially in the patients with low degree of differentiation, late stage and metastasis. They functioned synergistically in the onset and progression of this cancer.

  17. A framework for 2-stage global sensitivity analysis of GastroPlus™ compartmental models.

    Science.gov (United States)

    Scherholz, Megerle L; Forder, James; Androulakis, Ioannis P

    2018-04-01

    Parameter sensitivity and uncertainty analysis for physiologically based pharmacokinetic (PBPK) models are becoming an important consideration for regulatory submissions, requiring further evaluation to establish the need for global sensitivity analysis. To demonstrate the benefits of an extensive analysis, global sensitivity was implemented for the GastroPlus™ model, a well-known commercially available platform, using four example drugs: acetaminophen, risperidone, atenolol, and furosemide. The capabilities of GastroPlus were expanded by developing an integrated framework to automate the GastroPlus graphical user interface with AutoIt and for execution of the sensitivity analysis in MATLAB ® . Global sensitivity analysis was performed in two stages using the Morris method to screen over 50 parameters for significant factors followed by quantitative assessment of variability using Sobol's sensitivity analysis. The 2-staged approach significantly reduced computational cost for the larger model without sacrificing interpretation of model behavior, showing that the sensitivity results were well aligned with the biopharmaceutical classification system. Both methods detected nonlinearities and parameter interactions that would have otherwise been missed by local approaches. Future work includes further exploration of how the input domain influences the calculated global sensitivity measures as well as extending the framework to consider a whole-body PBPK model.

  18. Applying the Health Belief Model in Explaining the Stages of Exercise Change in Older Adults

    Directory of Open Access Journals (Sweden)

    Sas-Nowosielski Krzysztof

    2016-12-01

    Full Text Available Introduction. The benefits of physical activity (PA have been so well documented that there is no doubt about the significance of PA for personal and social health. Several theoretical models have been proposed with a view to understanding the phenomenon of PA and other health behaviours. The purpose of this study was to evaluate if and how the variables suggested in the Health Belief Model (HBM determine physical activity stages of change in older adults. Material and methods. A total of 172 students of Universities of the Third Age aged 54 to 75 (mean = 62.89 ± 4.83 years agreed to participate in the study, filling out an anonymous survey measuring their stage of exercise change and determinants of health behaviours proposed by the HBM, including: perceived benefits of physical activity, perceived barriers to physical activity, perceived severity of diseases associated with sedentary lifestyle, perceived susceptibility to these diseases, and self-efficacy. Results. The results only partially support the hypothesis that the HBM predicts intentions and behaviours related to the physical activity of older adults. Only two variables were moderately-to-strongly related to stages of exercise change, namely perceived barriers and self-efficacy. Conclusion. Interventions aimed at informing older adults about the benefits of physical activity and the threats associated with sedentary lifestyle can be expected to have rather a weak influence on their readiness for physical activity.

  19. Structured model of bacterial growth and tests with activated sludge in a one-stage and two-stage chemostat

    NARCIS (Netherlands)

    Harder, A.

    1979-01-01

    A kinetic model for a growing culture of micro-organisms was developed that correlated the biochemical structure of cells with quantitative physiological behaviour. The three-compartment model was adequate for simulation of continuous, batch and transient experiments with activated sludge fed on

  20. Variant outcomes of liver transplantation for hepatitis C virus patients in different age categories: impact of the model for end-stage liver disease score.

    Science.gov (United States)

    Hu, Zhenhua; Zhou, Jie; Li, Zhiwei; Xiang, Jie; Zhang, Qijun; Yan, Sheng; Wu, Jian; Zhang, Min; Wang, Weilin; Zheng, Shusen

    2017-04-01

    Whether the introduction of model for end-stage liver disease (MELD) has an effect on transplant outcome for different age categories remain unclear. We analyzed 49,762 adult hepatitis C virus (HCV) candidates through 1 January 1995 to 31 December 2012 from the Scientific Registry of Transplant Recipients. Patients were divided into four age categories (18-34, 35-49, 60-64, ≥65 years) in the pre-MELD era and MELD era, respectively. Waiting list dropouts have decreased in the MELD era for all categories. A reduced trend in survival was observed for 18-34 years patients in the MELD era compared with the pre-MELD era, with 5-year intention-to-treat, overall and graft survival of 56.5%, 57.9%, 56.3% vs. 56.4%, 69.7%, 64.4% (P = 0.604, 0.034, and 0.071, respectively). For other age categories, survival rates were all superior in the MELD era. Cox-regression analysis showed values of hazard ratio for age increased with advanced age (all >1) in the pre-MELD era compared with the reference group (18-34 years), while these hazard ratios were liver allocation may adversely affect survival of specific HCV patients. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  1. Global Bifurcation Analysis of a Population Model with Stage Structure and Beverton-Holt Saturation Function

    Science.gov (United States)

    Fan, Li; Tang, Sanyi

    In the present paper, we perform a complete bifurcation analysis of a two-stage population model, in which the per capita birth rate and stage transition rate from juveniles to adults are density dependent and take the general Beverton-Holt functions. Our study reveals a rich bifurcation structure including codimension-one bifurcations such as saddle-node, Hopf, homoclinic bifurcations, and codimension-two bifurcations such as Bogdanov-Takens (BT), Bautin bifurcations, etc. Moreover, by employing the polynomial analysis and approximation techniques, the existences of equilibria, Hopf and BT bifurcations as well as the formulas for calculating their bifurcation sets have been provided. Finally, the complete bifurcation diagrams and associate phase portraits are obtained not only analytically but also confirmed and extended numerically.

  2. Application of the health promotion model to predict stages of exercise behaviour in Iranian adolescents.

    Science.gov (United States)

    Taymoori, P; Niknami, S; Berry, T; Ghofranipour, F; Kazemnejad, A

    2009-01-01

    A cluster random sample of 1073 students in the Islamic Republic of Iran (mean age 14.37 years) completed a self-report questionnaire consisting of an exercise measure, selected constructs of Pender's health promotion model and an assessment of stages of behaviour change in exercise. In multivariate discriminant analysis, exercise self-efficacy, perceived barriers to exercise, perceived benefits of exercise and exercise behaviour were significant predictors of the stage of exercise behaviour change for both female and male adolescents. The findings support the importance of self-efficacy for engaging in physical activity for both sexes of Iranian adolescents. The barriers faced by Iranian girls should be considered in interventions to increase physical activity rates.

  3. Design model for bending vibrations of single-stage tunnel fan rotor

    Science.gov (United States)

    Krasyuk, AM; Kosykh, PV

    2018-03-01

    Using of one-mass model of tunnel fan rotor is justified for estimation calculation of the natural bending vibrations frequency during the design stage. It’s shown that the evaluative computation of the main axial tunnel fan at the early design stage yields the acceptable accuracy. It is shown that after completion of the design, the mass of the stepped-type shaft differs from the mass of the calculated uniform-diameter shaft no more than by 40%. Inclusion of this additional mass in the estimation calculation makes it possible to improve the calculation accuracy. The region of the dimensionless rotor design parameters at which the relative difference of frequency in the evaluative and verification calculations is not higher than 5 % is determined.

  4. Integrating Growth Stage Deficit Irrigation into a Process Based Crop Model

    Science.gov (United States)

    Lopez, Jose R.; Winter, Jonathan M.; Elliott, Joshua; Ruane, Alex C.; Porter, Cheryl; Hoogenboom, Gerrit

    2017-01-01

    Current rates of agricultural water use are unsustainable in many regions, creating an urgent need to identify improved irrigation strategies for water limited areas. Crop models can be used to quantify plant water requirements, predict the impact of water shortages on yield, and calculate water productivity (WP) to link water availability and crop yields for economic analyses. Many simulations of crop growth and development, especially in regional and global assessments, rely on automatic irrigation algorithms to estimate irrigation dates and amounts. However, these algorithms are not well suited for water limited regions because they have simplistic irrigation rules, such as a single soil-moisture based threshold, and assume unlimited water. To address this constraint, a new modeling framework to simulate agricultural production in water limited areas was developed. The framework consists of a new automatic irrigation algorithm for the simulation of growth stage based deficit irrigation under limited seasonal water availability; and optimization of growth stage specific parameters. The new automatic irrigation algorithm was used to simulate maize and soybean in Gainesville, Florida, and first used to evaluate the sensitivity of maize and soybean simulations to irrigation at different growth stages and then to test the hypothesis that water productivity calculated using simplistic irrigation rules underestimates WP. In the first experiment, the effect of irrigating at specific growth stages on yield and irrigation water use efficiency (IWUE) in maize and soybean was evaluated. In the reproductive stages, IWUE tended to be higher than in the vegetative stages (e.g. IWUE was 18% higher than the well watered treatment when irrigating only during R3 in soybean), and when rainfall events were less frequent. In the second experiment, water productivity (WP) was significantly greater with optimized irrigation schedules compared to non-optimized irrigation schedules in

  5. Inhibition of both COX-1 and COX-2 and resulting decrease in the level of prostaglandins E2 is responsible for non-steroidal anti-inflammatory drug (NSAID)-dependent exacerbation of colitis.

    Science.gov (United States)

    Tanaka, Ken-Ichiro; Suemasu, Shintaro; Ishihara, Tomoaki; Tasaka, Yuichi; Arai, Yasuhiro; Mizushima, Tohru

    2009-01-28

    A number of clinical studies have shown that non-steroidal anti-inflammatory drugs (NSAIDs) exacerbate inflammatory bowel disease; however the molecular mechanism whereby this occurs remains unclear. NSAIDs inhibit cyclooxygenase (COX), which has subtypes COX-1 and COX-2. In this study, we have examined the effect of various types of NSAIDs on the development of dextran sulfate sodium (DSS)-induced colitis, an animal model of inflammatory bowel disease. The DSS-induced colitis was worsened by administration of non-selective NSAIDs but not by COX-1 or COX-2 selective inhibitors. However, administration of a combination of both COX-1- and COX-2-selective inhibitors exacerbated the colitis. The intestinal level of PGE(2) dramatically decreased in response to administration of COX-1- and COX-2-selective inhibitors, and exogenously administered PGE(2) suppressed the exacerbation of colitis by NSAIDs. The expression of mucin proteins, which protect the intestinal mucosa, was suppressed by non-selective NSAIDs and this expression was restored by PGE(2), both in vivo and in vitro. Intestinal mucosal cell growth was inhibited by non-selective NSAIDs and this cell growth was restored by PGE(2), both in vivo and in vitro. This study provides evidence that inhibition of both COX-1 and COX-2 and the resulting dramatic decrease in the intestinal level of PGE(2) is responsible for NSAID-dependent exacerbation of DSS-induced colitis. Furthermore, expression of mucin proteins and intestinal mucosal cell growth seems to be involved in this exacerbation and its suppression by PGE(2).

  6. A two-stage storage routing model for green roof runoff detention.

    Science.gov (United States)

    Vesuviano, Gianni; Sonnenwald, Fred; Stovin, Virginia

    2014-01-01

    Green roofs have been adopted in urban drainage systems to control the total quantity and volumetric flow rate of runoff. Modern green roof designs are multi-layered, their main components being vegetation, substrate and, in almost all cases, a separate drainage layer. Most current hydrological models of green roofs combine the modelling of the separate layers into a single process; these models have limited predictive capability for roofs not sharing the same design. An adaptable, generic, two-stage model for a system consisting of a granular substrate over a hard plastic 'egg box'-style drainage layer and fibrous protection mat is presented. The substrate and drainage layer/protection mat are modelled separately by previously verified sub-models. Controlled storm events are applied to a green roof system in a rainfall simulator. The time-series modelled runoff is compared to the monitored runoff for each storm event. The modelled runoff profiles are accurate (mean Rt(2) = 0.971), but further characterization of the substrate component is required for the model to be generically applicable to other roof configurations with different substrate.

  7. Population balance modelling and multi-stage optimal control of a pulsed spray fluidized bed granulation.

    Science.gov (United States)

    Liu, Huolong; Li, Mingzhong

    2014-07-01

    In this work, one-dimensional population balance models (PBMs) have been developed to model a pulsed top-spray fluidized bed granulation. The developed PBMs have linked the key binder solution spray operating factors of the binder spray rate, atomizing air pressure and pulsed frequency of spray with the granule properties to predict granule growth behaviour in the pulsed spray fluidized bed granulation process at different operating conditions with accuracy. A multi-stage open optimal control strategy based on the developed PBMs was proposed to reduce the model mismatch, in which through adjusting the trajectory of the evolution of the granule size distribution at predefined sample intervals, to determine the optimal operating variables related to the binder spray including the spray rate of binding liquid, atomizing air pressure and pulsed frequency of spray. The effectiveness of the proposed modelling and multi-stage open optimal control strategies has been validated by experimental and simulation tests. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Modeling Remote I/O versus Staging Tradeoff in Multi-Data Center Computing

    International Nuclear Information System (INIS)

    Suslu, Ibrahim H

    2014-01-01

    In multi-data center computing, data to be processed is not always local to the computation. This is a major challenge especially for data-intensive Cloud computing applications, since large amount of data would need to be either moved the local sites (staging) or accessed remotely over the network (remote I/O). Cloud application developers generally chose between staging and remote I/O intuitively without making any scientific comparison specific to their application data access patterns since there is no generic model available that they can use. In this paper, we propose a generic model for the Cloud application developers which would help them to choose the most appropriate data access mechanism for their specific application workloads. We define the parameters that potentially affect the end-to-end performance of the multi-data center Cloud applications which need to access large datasets over the network. To test and validate our models, we implemented a series of synthetic benchmark applications to simulate the most common data access patterns encountered in Cloud applications. We show that our model provides promising results in different settings with different parameters, such as network bandwidth, server and client capabilities, and data access ratio

  9. Acute upregulation of COX-2 by renal artery stenosis

    DEFF Research Database (Denmark)

    Mann, Birgitte; Hartner, A; Jensen, B L

    2001-01-01

    This study aimed to characterize the influence of acute renal artery stenosis on cyclooxygenase-2 (COX-2) and renin expression in the juxtaglomerular apparatus. For this purpose, male Sprague-Dawley rats received a left renal artery clip, and COX-2 mRNA, COX-2 immunoreactivity, plasma renin...... activity, and renin mRNA levels were determined. COX-2 mRNA and COX-2 immunoreactivity in the macula densa region in the clipped kidneys increased as early as 6 h after clipping and reached a maximal expression 1-2 days after clipping. Although values for plasma renin activity were elevated markedly at all...... time points examined, remaining renin mRNA levels were unchanged after 6 h and then increased to reach a maximum value 1-2 days after clipping. In the contralateral intact kidney, renin mRNA and COX-2 immunoreactivity decreased to approximately 50% of their normal values. To investigate a possible...

  10. COX, LOX and platelet aggregation inhibitory properties of Lauraceae neolignans.

    Science.gov (United States)

    Coy, Ericsson David; Cuca, Luis Enrique; Sefkow, Michael

    2009-12-15

    The anti-inflammatory potential of 26 neolignans (14 of the bicyclooctane-type and 12 of the benzofuran-type), isolated from three Lauraceae species (Pleurothyrium cinereum, Ocotea macrophylla and Nectandra amazonum), was evaluated in vitro through inhibition of COX-1, COX-2, 5-LOX and agonist-induced aggregation of rabbit platelets. Benzofuran neolignans were found to be selective COX-2 inhibitors, whereas bicyclooctane neolignans inhibit selectively the PAF-action as well as COX-1 and 5-LOX. The neolignan 9-nor-7,8-dehydro-isolicarin B 15 and cinerin C 7 were found to be the most potent COX-2 inhibitor and PAF-antagonist, respectively. Nectamazin C 10 exhibited dual 5-LOX/COX-2 inhibition.

  11. Molecular basis of cyclooxygenase enzymes (COXs) selective inhibition

    Science.gov (United States)

    Limongelli, Vittorio; Bonomi, Massimiliano; Marinelli, Luciana; Gervasio, Francesco Luigi; Cavalli, Andrea; Novellino, Ettore; Parrinello, Michele

    2010-01-01

    The widely used nonsteroidal anti-inflammatory drugs block the cyclooxygenase enzymes (COXs) and are clinically used for the treatment of inflammation, pain, and cancers. A selective inhibition of the different isoforms, particularly COX-2, is desirable, and consequently a deeper understanding of the molecular basis of selective inhibition is of great demand. Using an advanced computational technique we have simulated the full dissociation process of a highly potent and selective inhibitor, SC-558, in both COX-1 and COX-2. We have found a previously unreported alternative binding mode in COX-2 explaining the time-dependent inhibition exhibited by this class of inhibitors and consequently their long residence time inside this isoform. Our metadynamics-based approach allows us to illuminate the highly dynamical character of the ligand/protein recognition process, thus explaining a wealth of experimental data and paving the way to an innovative strategy for designing new COX inhibitors with tuned selectivity. PMID:20215464

  12. An examination of adaptive cellular protective mechanisms using a multi-stage carcinogenesis model

    International Nuclear Information System (INIS)

    Schollnberger, H.; Stewart, R. D.; Mitchel, R. E. J.; Hofmann, W.

    2004-01-01

    A multi-stage cancer model that describes the putative rate-limiting steps in carcinogenesis was developed and used to investigate the potential impact on lung cancer incidence of the hormesis mechanisms suggested by Feinendegen and Pollycove. In this deterministic cancer model, radiation and endogenous processes damage the DNA of target cells in the lung. Some fraction of the misrepaired our unrepaired DNA damage induces genomic instability and, ultimately, leads to the accumulation of malignant cells. The model accounts for cell birth and death processes. Ita also includes a rate of malignant transformation and a lag period for tumour formation. Cellular defence mechanisms are incorporated into the model by postulating dose and dose rate dependent radical scavenging. The accuracy of DNA damage repair also depends on dose and dose rate. Sensitivity studies were conducted to identify critical model inputs and to help define the shapes of the cumulative lung cancer incidence curves that may arise when dose and dose rate dependent cellular defence mechanisms are incorporated into a multi-stage cancer model. For lung cancer, both linear no-threshold (LNT) and non-LNT shaped responses can be obtained. The reported studied clearly show that it is critical to know whether or not and to what extent multiply damaged DNA sites are formed by endogenous processes. Model inputs that give rise to U-shaped responses are consistent with an effective cumulative lung cancer incidence threshold that may be as high as 300 mGy (4 mGy per year for 75 years). (Author) 11 refs

  13. Comparing stochastic differential equations and agent-based modelling and simulation for early-stage cancer.

    Science.gov (United States)

    Figueredo, Grazziela P; Siebers, Peer-Olaf; Owen, Markus R; Reps, Jenna; Aickelin, Uwe

    2014-01-01

    There is great potential to be explored regarding the use of agent-based modelling and simulation as an alternative paradigm to investigate early-stage cancer interactions with the immune system. It does not suffer from some limitations of ordinary differential equation models, such as the lack of stochasticity, representation of individual behaviours rather than aggregates and individual memory. In this paper we investigate the potential contribution of agent-based modelling and simulation when contrasted with stochastic versions of ODE models using early-stage cancer examples. We seek answers to the following questions: (1) Does this new stochastic formulation produce similar results to the agent-based version? (2) Can these methods be used interchangeably? (3) Do agent-based models outcomes reveal any benefit when compared to the Gillespie results? To answer these research questions we investigate three well-established mathematical models describing interactions between tumour cells and immune elements. These case studies were re-conceptualised under an agent-based perspective and also converted to the Gillespie algorithm formulation. Our interest in this work, therefore, is to establish a methodological discussion regarding the usability of different simulation approaches, rather than provide further biological insights into the investigated case studies. Our results show that it is possible to obtain equivalent models that implement the same mechanisms; however, the incapacity of the Gillespie algorithm to retain individual memory of past events affects the similarity of some results. Furthermore, the emergent behaviour of ABMS produces extra patters of behaviour in the system, which was not obtained by the Gillespie algorithm.

  14. Development of PBPK models for PFOA and PFOS for human pregnancy and lactation life stages.

    Science.gov (United States)

    Loccisano, Anne E; Longnecker, Matthew P; Campbell, Jerry L; Andersen, Melvin E; Clewell, Harvey J

    2013-01-01

    Perfluoroalkyl acid carboxylates and sulfonates (PFAA) have many consumer and industrial applications. Developmental toxicity studies in animals have raised concern about potential reproductive/developmental effects of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS); however, in humans conflicting results have been reported for associations between maternal PFAA levels and these outcomes. Risk assessments and interpretation of available human data during gestation and lactation are hindered due to lack of a framework for understanding and estimating maternal, fetal, and neonatal pharmacokinetics (PK). Physiologically based pharmacokinetic (PBPK) models were developed for PFOA and PFOS for the gestation and lactation life stages in humans to understand how the physiological changes associated with development affect pharmacokinetics of these compounds in the mother, fetus, and infant. These models were derived from PBPK models for PFOA/PFOS that were previously developed for adult humans and rats during gestation and lactation and from existing human pregnancy and lactation models developed for other chemicals. The models simulated PFOA and PFOS concentrations in fetal, infant, and maternal plasma and milk, were compared to available data in humans, and also were used to estimate maternal exposure. The models reported here identified several research needs, which include (1) the identification of transporters involved in renal resorption to explain the multiyear half-lives of these compounds in humans, (2) factors affecting clearance of PFOA/PFOS during gestation and lactation, and (3) data to estimate clearance of PFOA/PFOS in infants. These models may help address concerns regarding possible adverse health effects due to PFOA/PFOS exposure in the fetus and infant and may be useful in comparing pharmacokinetics across life stages.

  15. COX-1 and -2 activity of rose hip.

    Science.gov (United States)

    Jäger, A K; Eldeen, I M S; van Staden, J

    2007-12-01

    The objective of this study was to investigate whether the clinically observed efficacy of rose hip in the treatment of osteoarthritis is due to inhibition of cyclooxygenase-1 and -2. Water, methanol, dichloromethane and hexane extracts of rose hip were tested for in vitro COX-1 and 2 activity. The organic solvent extracts showed good inhibition of both COX-1 and 2. The methanol extract was most active in both assays with IC(50) values of 12 microg/mL for COX-1 and 19 microg/mL for COX-2. The clinically observed effect might be due to inhibition of cyclooxygenase. Copyright (c) 2007 John Wiley & Sons, Ltd.

  16. Cox-2 inhibitors and the risk of cardiovascular thrombotic events.

    LENUS (Irish Health Repository)

    Khan, M

    2012-04-01

    In 1971, Vane showed that the analgesic action of traditional NSAIDs relies on inhibition of the cyclo-oxygenase (COX) enzyme, which in turn results in reduced synthesis of proalgesic prostaglandins. Two decades later COX was shown to exist as two distinct isoforms. The constitutive isoform COX-1, supports the beneficial homeostatic functions whereas the inducible isoform, COX-2 becomes up regulated by inflammatory mediators and its products cause many of the symptoms of inflammatory diseases such as rheumatoid and osteoarthritis. Despite the benefits of NSAIDs for acute and chronic pain one of the most clinically significant and well characterized adverse effect is on GI mucosa. The search for NSAIDs with less gastrointestinal toxicity led to the introduction of the selective cyclo-oxygenase-2 (COX-2) inhibitors. The COX-2 selective (COX-1 sparing) inhibitors are associated with reduced GI mucosal damage as demonstrated in several trials. In light of the overwhelming and sometimes contradictory information for patients and physicians regarding the safety of COX-2 agents this article will summarize the available evidence regarding cardiovascular (CV) safety data and contemporary recommendations for prescribing of COX-2-selective NSAIDs.

  17. Modeling Humans as Reinforcement Learners: How to Predict Human Behavior in Multi-Stage Games

    Science.gov (United States)

    Lee, Ritchie; Wolpert, David H.; Backhaus, Scott; Bent, Russell; Bono, James; Tracey, Brendan

    2011-01-01

    This paper introduces a novel framework for modeling interacting humans in a multi-stage game environment by combining concepts from game theory and reinforcement learning. The proposed model has the following desirable characteristics: (1) Bounded rational players, (2) strategic (i.e., players account for one anothers reward functions), and (3) is computationally feasible even on moderately large real-world systems. To do this we extend level-K reasoning to policy space to, for the first time, be able to handle multiple time steps. This allows us to decompose the problem into a series of smaller ones where we can apply standard reinforcement learning algorithms. We investigate these ideas in a cyber-battle scenario over a smart power grid and discuss the relationship between the behavior predicted by our model and what one might expect of real human defenders and attackers.

  18. Mathematical modeling of the heat treatment and combustion of a coal particle. III. Volatile escape stage

    Science.gov (United States)

    Enkhjargal, Kh.; Salomatov, V. V.

    2011-05-01

    The present paper is a continuation of previous publications of the authors in this journal in which two phases of the multistage process of combustion of a coal particle were considered in detail with the help of mathematical modeling: its radiation-convection heating and drying. In the present work, the escape dynamics of volatiles is investigated. The physico-mathematical model of the thermodestruction of an individual coal particle with a dominant influence of endothermal effects has been formulated. Approximate-analytical solutions of this model that are of paramount importance for detailed analysis of the influence of the physical and regime parameters on the escape dynamics of volatiles have been found. The results obtained form the basis for engineering calculations of the volatile escape stage and can be used successfully in the search for effective regimes of burning of various solid fuels, in particular, Shivé-Ovoos coal of Mongolia.

  19. Evaluation of a prognostic model for risk of relapse in stage I seminoma surveillance

    DEFF Research Database (Denmark)

    Chung, Peter; Daugaard, Gedske; Tyldesley, Scott

    2015-01-01

    of 3 cm) was a predictor for relapse, HR 1.87 (95% CI 1.15, 3.06), whereas rete testis invasion HR 1.36, (95% CI 0.81, 2.28) was not statistically significant. The 3-year relapse risk based on the primary tumor size alone increased from 9% for 1 cm primary tumor to 26% for 8 cm tumor. A clinically...... useful, highly discriminating prognostic model remains elusive in stage I seminoma surveillance as we were unable to validate the previously developed model. However, primary tumor size retained prognostic importance and a scale of relapse risk based on the unit increment of tumor size was developed...... analyzed. Variables including age and pathology of the primary tumor: small vessel invasion, tumor size, and invasion of rete testis were analyzed. Specifically median tumor size and rete testis invasion was tested to evaluate the performance of the published model. Median follow-up was 3.85 years (0...

  20. A transition-constrained discrete hidden Markov model for automatic sleep staging

    Directory of Open Access Journals (Sweden)

    Pan Shing-Tai

    2012-08-01

    Full Text Available Abstract Background Approximately one-third of the human lifespan is spent sleeping. To diagnose sleep problems, all-night polysomnographic (PSG recordings including electroencephalograms (EEGs, electrooculograms (EOGs and electromyograms (EMGs, are usually acquired from the patient and scored by a well-trained expert according to Rechtschaffen & Kales (R&K rules. Visual sleep scoring is a time-consuming and subjective process. Therefore, the development of an automatic sleep scoring method is desirable. Method The EEG, EOG and EMG signals from twenty subjects were measured. In addition to selecting sleep characteristics based on the 1968 R&K rules, features utilized in other research were collected. Thirteen features were utilized including temporal and spectrum analyses of the EEG, EOG and EMG signals, and a total of 158 hours of sleep data were recorded. Ten subjects were used to train the Discrete Hidden Markov Model (DHMM, and the remaining ten were tested by the trained DHMM for recognition. Furthermore, the 2-fold cross validation was performed during this experiment. Results Overall agreement between the expert and the results presented is 85.29%. With the exception of S1, the sensitivities of each stage were more than 81%. The most accurate stage was SWS (94.9%, and the least-accurately classified stage was S1 ( Conclusion The results of the experiments demonstrate that the proposed method significantly enhances the recognition rate when compared with prior studies.

  1. Modeling two-stage bunch compression with wakefields: Macroscopic properties and microbunching instability

    Directory of Open Access Journals (Sweden)

    R. A. Bosch

    2008-09-01

    Full Text Available In a two-stage compression and acceleration system, where each stage compresses a chirped bunch in a magnetic chicane, wakefields affect high-current bunches. The longitudinal wakes affect the macroscopic energy and current profiles of the compressed bunch and cause microbunching at short wavelengths. For macroscopic wavelengths, impedance formulas and tracking simulations show that the wakefields can be dominated by the resistive impedance of coherent edge radiation. For this case, we calculate the minimum initial bunch length that can be compressed without producing an upright tail in phase space and associated current spike. Formulas are also obtained for the jitter in the bunch arrival time downstream of the compressors that results from the bunch-to-bunch variation of current, energy, and chirp. Microbunching may occur at short wavelengths where the longitudinal space-charge wakes dominate or at longer wavelengths dominated by edge radiation. We model this range of wavelengths with frequency-dependent impedance before and after each stage of compression. The growth of current and energy modulations is described by analytic gain formulas that agree with simulations.

  2. Lack of miRNA misregulation at early pathological stages in Drosophila neurodegenerative disease models

    Directory of Open Access Journals (Sweden)

    Anita eReinhardt

    2012-10-01

    Full Text Available Late onset neurodegenerative diseases represent a major public health concern as the population in many countries ages. Both frequent diseases such as Alzheimer disease (AD, 14% incidence for 80-84 year old Europeans or Parkinson disease (PD, 1.4% prevalence for > 55 years old share, with other low-incidence neurodegenerative pathologies such as spinocerebellar ataxias (SCAs, 0.01% prevalence and frontotemporal lobar degeneration (FTLD, 0.02% prevalence, a lack of efficient treatment in spite of important research efforts. Besides significant progress, studies with animal models have revealed unexpected complexities in the degenerative process, emphasizing a need to better understand the underlying pathological mechanisms. Recently, microRNAs, a class of small regulatory non-coding RNAs, have been implicated in some neurodegenerative diseases. The current data supporting a role of miRNAs in PD, tauopathies, dominant ataxias and FTLD will first be discussed to emphasize the different levels of the pathological processes which may be affected by miRNAs. To investigate a potential involvement of miRNA dysregulation in the early stages of these neurodegenerative diseases we have used Drosophila models for 7 diseases (PD, 3 FTLD, 3 dominant ataxias that recapitulate many features of the human diseases. We performed deep sequencing of head small RNAs after 3 days of pathological protein expression in the fly head neurons. We found no evidence for a statistically significant difference in miRNA expression in this early stage of the pathological process. In addition, we could not identify small non coding CAG repeat RNAs (sCAG in polyQ disease models. Thus our data suggest that transcriptional deregulation of miRNAs or sCAG is unlikely to play a significant role in the initial stages of neurodegenerative diseases.

  3. Proteomics-based systems biology modeling of bovine germinal vesicle stage oocyte and cumulus cell interaction.

    Directory of Open Access Journals (Sweden)

    Divyaswetha Peddinti

    Full Text Available BACKGROUND: Oocytes are the female gametes which establish the program of life after fertilization. Interactions between oocyte and the surrounding cumulus cells at germinal vesicle (GV stage are considered essential for proper maturation or 'programming' of oocytes, which is crucial for normal fertilization and embryonic development. However, despite its importance, little is known about the molecular events and pathways involved in this bidirectional communication. METHODOLOGY/PRINCIPAL FINDINGS: We used differential detergent fractionation multidimensional protein identification technology (DDF-Mud PIT on bovine GV oocyte and cumulus cells and identified 811 and 1247 proteins in GV oocyte and cumulus cells, respectively; 371 proteins were significantly differentially expressed between each cell type. Systems biology modeling, which included Gene Ontology (GO and canonical genetic pathway analysis, showed that cumulus cells have higher expression of proteins involved in cell communication, generation of precursor metabolites and energy, as well as transport than GV oocytes. Our data also suggests a hypothesis that oocytes may depend on the presence of cumulus cells to generate specific cellular signals to coordinate their growth and maturation. CONCLUSIONS/SIGNIFICANCE: Systems biology modeling of bovine oocytes and cumulus cells in the context of GO and protein interaction networks identified the signaling pathways associated with the proteins involved in cell-to-cell signaling biological process that may have implications in oocyte competence and maturation. This first comprehensive systems biology modeling of bovine oocytes and cumulus cell proteomes not only provides a foundation for signaling and cell physiology at the GV stage of oocyte development, but are also valuable for comparative studies of other stages of oocyte development at the molecular level.

  4. Statistical geological discrete fracture network model. Forsmark modelling stage 2.2

    International Nuclear Information System (INIS)

    Fox, Aaron; La Pointe, Paul; Simeonov, Assen; Hermanson, Jan; Oehman, Johan

    2007-11-01

    The Swedish Nuclear Fuel and Waste Management Company (SKB) is performing site characterization at two different locations, Forsmark and Laxemar, in order to locate a site for a final geologic repository for spent nuclear fuel. The program is built upon the development of Site Descriptive Models (SDMs) at specific timed data freezes. Each SDM is formed from discipline-specific reports from across the scientific spectrum. This report describes the methods, analyses, and conclusions of the geological modeling team with respect to a geological and statistical model of fractures and minor deformation zones (henceforth referred to as the geological DFN), version 2.2, at the Forsmark site. The geological DFN builds upon the work of other geological modelers, including the deformation zone (DZ), rock domain (RD), and fracture domain (FD) models. The geological DFN is a statistical model for stochastically simulating rock fractures and minor deformation zones as a scale of less than 1,000 m (the lower cut-off of the DZ models). The geological DFN is valid within four specific fracture domains inside the local model region, and encompassing the candidate volume at Forsmark: FFM01, FFM02, FFM03, and FFM06. The models are build using data from detailed surface outcrop maps and the cored borehole record at Forsmark. The conceptual model for the Forsmark 2.2 geological revolves around the concept of orientation sets; for each fracture domain, other model parameters such as size and intensity are tied to the orientation sets. Two classes of orientation sets were described; Global sets, which are encountered everywhere in the model region, and Local sets, which represent highly localized stress environments. Orientation sets were described in terms of their general cardinal direction (NE, NW, etc). Two alternatives are presented for fracture size modeling: - the tectonic continuum approach (TCM, TCMF) described by coupled size-intensity scaling following power law distributions

  5. Statistical geological discrete fracture network model. Forsmark modelling stage 2.2

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Aaron; La Pointe, Paul [Golder Associates Inc (United States); Simeonov, Assen [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Hermanson, Jan; Oehman, Johan [Golder Associates AB, Stockholm (Sweden)

    2007-11-15

    The Swedish Nuclear Fuel and Waste Management Company (SKB) is performing site characterization at two different locations, Forsmark and Laxemar, in order to locate a site for a final geologic repository for spent nuclear fuel. The program is built upon the development of Site Descriptive Models (SDMs) at specific timed data freezes. Each SDM is formed from discipline-specific reports from across the scientific spectrum. This report describes the methods, analyses, and conclusions of the geological modeling team with respect to a geological and statistical model of fractures and minor deformation zones (henceforth referred to as the geological DFN), version 2.2, at the Forsmark site. The geological DFN builds upon the work of other geological modelers, including the deformation zone (DZ), rock domain (RD), and fracture domain (FD) models. The geological DFN is a statistical model for stochastically simulating rock fractures and minor deformation zones as a scale of less than 1,000 m (the lower cut-off of the DZ models). The geological DFN is valid within four specific fracture domains inside the local model region, and encompassing the candidate volume at Forsmark: FFM01, FFM02, FFM03, and FFM06. The models are build using data from detailed surface outcrop maps and the cored borehole record at Forsmark. The conceptual model for the Forsmark 2.2 geological revolves around the concept of orientation sets; for each fracture domain, other model parameters such as size and intensity are tied to the orientation sets. Two classes of orientation sets were described; Global sets, which are encountered everywhere in the model region, and Local sets, which represent highly localized stress environments. Orientation sets were described in terms of their general cardinal direction (NE, NW, etc). Two alternatives are presented for fracture size modeling: - the tectonic continuum approach (TCM, TCMF) described by coupled size-intensity scaling following power law distributions

  6. A two-stage value chain model for vegetable marketing chain efficiency evaluation: A transaction cost approach

    OpenAIRE

    Lu Hualiang

    2006-01-01

    We applied a two-stage value chain model to investigate the effects of input application and occasional transaction costs on vegetable marketing chain efficiencies with a farm household-level data set. In the first stage, the production efficiencies with the combination of resource endowments, capital and managerial inputs, and production techniques were evaluated; then at the second stage, the marketing technical efficiencies were determined under the marketing value of the vegetables for th...

  7. Modeling the fine fragmentation following the triggering stage of a vapor explosion

    International Nuclear Information System (INIS)

    Darbord, I.

    1997-01-01

    In the frame of PWR severe accidents, where the core melt, this thesis studies one of the stages of an FCI (fuel coolant interaction) or vapor explosion. An FCI is a rapid evaporation of a coolant when it comes into contact with a hot liquid. More precisely, the subject of this study is the triggering stage of the FCI, when a fuel drop of diameter around one centimeter breaks up into many fragments, diameter of which is around a hundred micrometers. The model describes the cyclic collapse and growth of a vapor bubble around the fuel droplet and its fragmentation. The main features of the model are: - the destabilization of the film or the vapor bubble due to the growth of Rayleigh-Taylor instabilities (those form coolant jets that contact the fuel surface); - The mechanisms of fragmentation, following the contacts (in the case of entrapment of a certain amount of coolant in the fuel, the entrapped coolant evaporates violently after it has been heated to the homogeneous nucleation temperature); - the transient heat transfer from the fragments to the coolant and the elevated vapor production, which leads to an important expansion of the bubble (about this point, the cooling of the fragments has been described by a transient heat transfer coefficient linked to nucleate boiling). The results of the model show good agreement with experimental data. (Author)

  8. Modelling and Control of the Multi-Stage Cable Pulley-Driven Flexible-Joint Robot

    Directory of Open Access Journals (Sweden)

    Phongsaen Pitakwatchara

    2014-07-01

    Full Text Available This work is concerned with the task space impedance control of a robot driven through a multi-stage nonlinear flexible transmission system. Specifically, a two degrees-of-freedom cable pulley-driven flexible-joint robot is considered. Realistic modelling of the system is developed within the bond graph modelling framework. The model captures the nonlinear compliance behaviour of the multi-stage cable pulley transmission system, the spring effect of the augmented counterbalancing mechanism, the major loss throughout the system elements, and the typical inertial dynamics of the robot. Next, a task space impedance controller based on limited information about the angle and the current of the motors is designed. The motor current is used to infer the transmitted torque, by which the motor inertia may be modulated. The motor angle is employed to estimate the stationary distal robot link angle and the robot joint velocity. They are used in the controller to generate the desired damping force and to shape the potential energy of the flexible joint robot system to the desired configuration. Simulation and experimental results of the controlled system signify the competency of the proposed control law.

  9. Analysis of multi-species point patterns using multivariate log Gaussian Cox processes

    DEFF Research Database (Denmark)

    Waagepetersen, Rasmus; Guan, Yongtao; Jalilian, Abdollah

    Multivariate log Gaussian Cox processes are flexible models for multivariate point patterns. However, they have so far only been applied in bivariate cases. In this paper we move beyond the bivariate case in order to model multi-species point patterns of tree locations. In particular we address...

  10. Traffic jam and discontinuity induced by slowdown in two-stage optimal-velocity model

    Science.gov (United States)

    Tanaka, Katsunori; Nagai, Ryoichi; Nagatani, Takashi

    2006-10-01

    We study the traffic states and jams induced by a slowdown of vehicles in a single-lane highway. The two-stage optimal velocity model is used in which the optimal velocity function has two turning points. The fundamental (flow-density) diagrams are calculated. At low density, the flow (current) increases linearly with density, while it saturates at some values of intermediate density. When the flow saturates, the discontinuous front (stationary shock wave) appears before or within the section of slowdown. The values of saturated flow are determined by the extreme values of theoretical current curves. The relationship between the densities is derived before and after the discontinuity.

  11. Dynamic modeling of a three-stage low-temperature ethanol reformer for fuel cell application

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, Vanesa M.; Serra, Maria [Institut de Robotica i Informatica Industrial (CSIC-UPC), Llorens i Artigas 4-6, 08028 Barcelona (Spain); Lopez, Eduardo; Llorca, Jordi [Institut de Tecniques Energetiques, Universitat Politecnica de Catalunya, Diagonal 647, ed. ETSEIB, 08028 Barcelona (Spain)

    2009-07-01

    A low-temperature ethanol reformer based on a cobalt catalyst for the production of hydrogen has been designed aiming the feed of a fuel cell for an autonomous low-scale power production unit. The reformer comprises three stages: ethanol dehydrogenation to acetaldehyde and hydrogen over SnO{sub 2} followed by acetaldehyde steam reforming over Co(Fe)/ZnO catalyst and water gas shift reaction. Kinetic data have been obtained under different experimental conditions and a dynamic model has been developed for a tubular reformer loaded with catalytic monoliths for the production of the hydrogen required to feed a 1 kW PEMFC. (author)

  12. Non-Asymptotic Oracle Inequalities for the High-Dimensional Cox Regression via Lasso.

    Science.gov (United States)

    Kong, Shengchun; Nan, Bin

    2014-01-01

    We consider finite sample properties of the regularized high-dimensional Cox regression via lasso. Existing literature focuses on linear models or generalized linear models with Lipschitz loss functions, where the empirical risk functions are the summations of independent and identically distributed (iid) losses. The summands in the negative log partial likelihood function for censored survival data, however, are neither iid nor Lipschitz.We first approximate the negative log partial likelihood function by a sum of iid non-Lipschitz terms, then derive the non-asymptotic oracle inequalities for the lasso penalized Cox regression using pointwise arguments to tackle the difficulties caused by lacking iid Lipschitz losses.

  13. Mathematical modelling of the maternal cardiovascular system in the three stages of pregnancy.

    Science.gov (United States)

    Corsini, Chiara; Cervi, Elena; Migliavacca, Francesco; Schievano, Silvia; Hsia, Tain-Yen; Pennati, Giancarlo

    2017-09-01

    In this study, a mathematical model of the female circulation during pregnancy is presented in order to investigate the hemodynamic response to the cardiovascular changes associated with each trimester of pregnancy. First, a preliminary lumped parameter model of the circulation of a non-pregnant female was developed, including the heart, the systemic circulation with a specific block for the uterine district and the pulmonary circulation. The model was first tested at rest; then heart rate and vascular resistances were individually varied to verify the correct response to parameter alterations characterising pregnancy. In order to simulate hemodynamics during pregnancy at each trimester, the main changes applied to the model consisted in reducing vascular resistances, and simultaneously increasing heart rate and ventricular wall volumes. Overall, reasonable agreement was found between model outputs and in vivo data, with the trends of the cardiac hemodynamic quantities suggesting correct response of the heart model throughout pregnancy. Results were reported for uterine hemodynamics, with flow tracings resembling typical Doppler velocity waveforms at each stage, including pulsatility indexes. Such a model may be used to explore the changes that happen during pregnancy in female with cardiovascular diseases. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  14. Chemical analysis of simulated high level waste glasses to support stage III sulfate solubility modeling

    Energy Technology Data Exchange (ETDEWEB)

    Fox, K. M. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2016-03-17

    The U.S. Department of Energy (DOE), Office of Environmental Management (EM) is sponsoring an international, collaborative project to develop a fundamental model for sulfate solubility in nuclear waste glass. The solubility of sulfate has a significant impact on the achievable waste loading for nuclear waste forms within the DOE complex. These wastes can contain relatively high concentrations of sulfate, which has low solubility in borosilicate glass. This is a significant issue for low-activity waste (LAW) glass and is projected to have a major impact on the Hanford Tank Waste Treatment and Immobilization Plant (WTP). Sulfate solubility has also been a limiting factor for recent high level waste (HLW) sludge processed at the Savannah River Site (SRS) Defense Waste Processing Facility (DWPF). The low solubility of sulfate in glass, along with melter and off-gas corrosion constraints, dictate that the waste be blended with lower sulfate concentration waste sources or washed to remove sulfate prior to vitrification. The development of enhanced borosilicate glass compositions with improved sulfate solubility will allow for higher waste loadings and accelerate mission completion.The objective of the current scope being pursued by SHU is to mature the sulfate solubility model to the point where it can be used to guide glass composition development for DWPF and WTP, allowing for enhanced waste loadings and waste throughput at these facilities. A series of targeted glass compositions was selected to resolve data gaps in the model and is identified as Stage III. SHU fabricated these glasses and sent samples to SRNL for chemical composition analysis. SHU will use the resulting data to enhance the sulfate solubility model and resolve any deficiencies. In this report, SRNL provides chemical analyses for the Stage III, simulated HLW glasses fabricated by SHU in support of the sulfate solubility model development.

  15. Three stage maturity model in SME’s toward industry 4.0

    Energy Technology Data Exchange (ETDEWEB)

    Ganzarain, J.; Errasti, N.

    2016-07-01

    To address the challenges regarding the concept of Industry 4.0 and the diversification methodology and based on the strategic guidance towards Industry 4.0, we propose a process model as a guiding framework for Industry 4.0 collaborative diversification vision, strategy and action building. In this paper we suggest a stage process model to guide and train companies to identify new opportunities for diversification within Industry 4.0. Systematically carrying out the stages will take a company to their individual specific vision and collaborative vision between different companies in the Industry 4.0 scenario. Design/methodology/approach: This new collaborative diversification methodology involves industry within the pilot program; from the diversification and capacity assessment analysis of the companys profile, skills and technologies that dominates, to identify the diversification opportunity map and its business modeling within the Industry 4.0 paradigm. Findings: The application of maturity models to the Industry 4.0 may help organizations to integrate this methodology into their culture. Results show a real need for guided support in developing a company-specific Industry 4.0 vision and specific project planning. Originality/value: Industry 4.0 promotes a vision where recent developments in information technology are expected to enable entirely new forms of cooperative engineering and manufacturing. The vision of industry 4.0 describes a whole new approach to business operations, and especially the production industries. To address the challenges regarding the concept of Industry 4.0 and the diversification methodology discussed above, and based on the strategic guidance towards Industry 4.0, we propose a unique process model as a guiding framework for Industry 4.0 collaborative diversification vision, strategy and action building.

  16. Three stage maturity model in SME’s toward industry 4.0

    International Nuclear Information System (INIS)

    Ganzarain, J.; Errasti, N.

    2016-01-01

    To address the challenges regarding the concept of Industry 4.0 and the diversification methodology and based on the strategic guidance towards Industry 4.0, we propose a process model as a guiding framework for Industry 4.0 collaborative diversification vision, strategy and action building. In this paper we suggest a stage process model to guide and train companies to identify new opportunities for diversification within Industry 4.0. Systematically carrying out the stages will take a company to their individual specific vision and collaborative vision between different companies in the Industry 4.0 scenario. Design/methodology/approach: This new collaborative diversification methodology involves industry within the pilot program; from the diversification and capacity assessment analysis of the companys profile, skills and technologies that dominates, to identify the diversification opportunity map and its business modeling within the Industry 4.0 paradigm. Findings: The application of maturity models to the Industry 4.0 may help organizations to integrate this methodology into their culture. Results show a real need for guided support in developing a company-specific Industry 4.0 vision and specific project planning. Originality/value: Industry 4.0 promotes a vision where recent developments in information technology are expected to enable entirely new forms of cooperative engineering and manufacturing. The vision of industry 4.0 describes a whole new approach to business operations, and especially the production industries. To address the challenges regarding the concept of Industry 4.0 and the diversification methodology discussed above, and based on the strategic guidance towards Industry 4.0, we propose a unique process model as a guiding framework for Industry 4.0 collaborative diversification vision, strategy and action building.

  17. Applying the Stages of Change model to Type 2 diabetes care in Trinidad: a randomised trial.

    Science.gov (United States)

    Partapsingh, V A; Maharaj, R G; Rawlins, J M

    2011-10-11

    To improve glycaemic control among Type 2 diabetics using patient-physician consultations guided by the Stages of Change (SOC) model. A randomised trial was conducted. After ensuring concealment of allocation, Type 2 diabetics were randomly assigned to receive the intervention or the control. The intervention consisted of identifying each patient's Stage of Change for managing their diabetes by diet, exercise and medications, and applying personalised, stage-specific care during the patient-physician consultations based on the SOC model. Patients in the control group received routine care. The variables of interest were effect on glycaemic control (measured by the difference in HbA1c levels) and patients' readiness to change (measured by identifying patients' SOC for managing their diabetes by diet, exercise and medications). Participants were primarily over age 50, male and Indo-Trinidadian. Most had received only a primary school education and over 65% had a monthly income of $320 USD/month or less. Sixty-one Type 2 diabetics participated in each arm. Three patients were lost to follow-up in the intervention arm. After 48 weeks, there was an overall increase in HbA1c of 0.52% (SE 0.17) and 1.09% (SE 0.18) for both the intervention and control groups respectively. There was a relative reduction in HbA1c of 0.57% (95% CI 0.07, 1.07) with the intervention group compared to the control (p = 0.025). For exercise and diet there was an overall tendency for participants in the intervention arm to move to a more favourable SOC, but little change was noted with regards medication use. The result suggests a tendency to a worsening of glycaemic control in this population despite adopting more favourable SOC for diet and exercise. We hypothesized that harsh social conditions prevailing at the time of the study overrode the clinical intervention.

  18. Validated Competing Event Model for the Stage I-II Endometrial Cancer Population

    Energy Technology Data Exchange (ETDEWEB)

    Carmona, Ruben; Gulaya, Sachin; Murphy, James D. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Rose, Brent S. [Harvard Radiation Oncology Program, Harvard Medical School, Boston, Massachusetts (United States); Wu, John; Noticewala, Sonal [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); McHale, Michael T. [Department of Reproductive Medicine, Division of Gynecologic Oncology, University of California San Diego, La Jolla, California (United States); Yashar, Catheryn M. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Vaida, Florin [Department of Family and Preventive Medicine, Biostatistics and Bioinformatics, University of California San Diego Medical Center, San Diego, California (United States); Mell, Loren K., E-mail: lmell@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)

    2014-07-15

    Purpose/Objectives(s): Early-stage endometrial cancer patients are at higher risk of noncancer mortality than of cancer mortality. Competing event models incorporating comorbidity could help identify women most likely to benefit from treatment intensification. Methods and Materials: 67,397 women with stage I-II endometrioid adenocarcinoma after total hysterectomy diagnosed from 1988 to 2009 were identified in Surveillance, Epidemiology, and End Results (SEER) and linked SEER-Medicare databases. Using demographic and clinical information, including comorbidity, we sought to develop and validate a risk score to predict the incidence of competing mortality. Results: In the validation cohort, increasing competing mortality risk score was associated with increased risk of noncancer mortality (subdistribution hazard ratio [SDHR], 1.92; 95% confidence interval [CI], 1.60-2.30) and decreased risk of endometrial cancer mortality (SDHR, 0.61; 95% CI, 0.55-0.78). Controlling for other variables, Charlson Comorbidity Index (CCI) = 1 (SDHR, 1.62; 95% CI, 1.45-1.82) and CCI >1 (SDHR, 3.31; 95% CI, 2.74-4.01) were associated with increased risk of noncancer mortality. The 10-year cumulative incidences of competing mortality within low-, medium-, and high-risk strata were 27.3% (95% CI, 25.2%-29.4%), 34.6% (95% CI, 32.5%-36.7%), and 50.3% (95% CI, 48.2%-52.6%), respectively. With increasing competing mortality risk score, we observed a significant decline in omega (ω), indicating a diminishing likelihood of benefit from treatment intensification. Conclusion: Comorbidity and other factors influence the risk of competing mortality among patients with early-stage endometrial cancer. Competing event models could improve our ability to identify patients likely to benefit from treatment intensification.

  19. CONVERGENT SYNTHESIS AND EVALUATION OF 18F-LABELED AZULENIC COX2 PROBES FOR CANCER IMAGING

    Directory of Open Access Journals (Sweden)

    Donald D. Nolting

    2013-01-01

    Full Text Available The overall objectives of this research are to (i develop azulene-based PET probes and (ii image COX2 as a potential biomarker of breast cancer. Several lines of research have demonstrated that COX2 is overexpressed in breast cancer and that its presence correlates with poor prognoses. While other studies have reported that COX2 inhibition can be modulated and used beneficially as a chemopreventive strategy in cancer, no viable mechanism for achieving that approach has yet been developed. This shortfall could be circumvented through in vivo imaging of COX2 activity, particularly using sensitive imaging techniques such as PET. Toward that goal, our laboratory focuses on the development of novel 18F-labled COX2 probes. We began the synthesis of the probes by transforming tropolone into a lactone, which was subjected to an [8+2] cycloaddition reaction to yield 2-methylazulene as the core ring of the probe. After exploring numerous synthetic routes, the final target molecule and precursor PET compounds were prepared successfully using convergent synthesis. Conventional 18F labeling methods caused precursor decomposition, which prompted us to hypothesize that the acidic protons of the methylene moiety between the azulene and thiazole rings were readily abstracted by a strong base such as potassium carbonate. Ultimately, this caused the precursors to disintegrate. This observation was supported after successfully using an 18F labeling strategy that employed a much milder phosphate buffer. The 18F-labeled COX2 probe was tested in a breast cancer xenograft mouse model. The data obtained via successive whole-body PET/CT scans indicated probe accumulation and retention in the tumor. Overall, the probe was stable in vivo and no defluorination was observed. A biodistribution study and Western blot analysis corroborate with the imaging data. In conclusion, this novel COX2 PET probe was shown to be a promising agent for cancer imaging and deserves further

  20. A tri-stage cluster identification model for accurate analysis of seismic catalogs

    Directory of Open Access Journals (Sweden)

    S. J. Nanda

    2013-02-01

    Full Text Available In this paper we propose a tri-stage cluster identification model that is a combination of a simple single iteration distance algorithm and an iterative K-means algorithm. In this study of earthquake seismicity, the model considers event location, time and magnitude information from earthquake catalog data to efficiently classify events as either background or mainshock and aftershock sequences. Tests on a synthetic seismicity catalog demonstrate the efficiency of the proposed model in terms of accuracy percentage (94.81% for background and 89.46% for aftershocks. The close agreement between lambda and cumulative plots for the ideal synthetic catalog and that generated by the proposed model also supports the accuracy of the proposed technique. There is flexibility in the model design to allow for proper selection of location and magnitude ranges, depending upon the nature of the mainshocks present in the catalog. The effectiveness of the proposed model also is evaluated by the classification of events in three historic catalogs: California, Japan and Indonesia. As expected, for both synthetic and historic catalog analysis it is observed that the density of events classified as background is almost uniform throughout the region, whereas the density of aftershock events are higher near the mainshocks.

  1. Two-Stage Hidden Markov Model in Gesture Recognition for Human Robot Interaction

    Directory of Open Access Journals (Sweden)

    Nhan Nguyen-Duc-Thanh

    2012-07-01

    Full Text Available Hidden Markov Model (HMM is very rich in mathematical structure and hence can form the theoretical basis for use in a wide range of applications including gesture representation. Most research in this field, however, uses only HMM for recognizing simple gestures, while HMM can definitely be applied for whole gesture meaning recognition. This is very effectively applicable in Human-Robot Interaction (HRI. In this paper, we introduce an approach for HRI in which not only the human can naturally control the robot by hand gesture, but also the robot can recognize what kind of task it is executing. The main idea behind this method is the 2-stages Hidden Markov Model. The 1st HMM is to recognize the prime command-like gestures. Based on the sequence of prime gestures that are recognized from the 1st stage and which represent the whole action, the 2nd HMM plays a role in task recognition. Another contribution of this paper is that we use the output Mixed Gaussian distribution in HMM to improve the recognition rate. In the experiment, we also complete a comparison of the different number of hidden states and mixture components to obtain the optimal one, and compare to other methods to evaluate this performance.

  2. Time Delayed Stage-Structured Predator-Prey Model with Birth Pulse and Pest Control Tactics

    Directory of Open Access Journals (Sweden)

    Mei Yan

    2014-01-01

    Full Text Available Normally, chemical pesticides kill not only pests but also their natural enemies. In order to better control the pests, two-time delayed stage-structured predator-prey models with birth pulse and pest control tactics are proposed and analyzed by using impulsive differential equations in present work. The stability threshold conditions for the mature prey-eradication periodic solutions of two models are derived, respectively. The effects of key parameters including killing efficiency rate, pulse period, the maximum birth effort per unit of time of natural enemy, and maturation time of prey on the threshold values are discussed in more detail. By comparing the two threshold values of mature prey-extinction, we provide the fact that the second control tactic is more effective than the first control method.

  3. Delimitation of the user in the creation stages, modeling and prototyping of the clothing product

    Directory of Open Access Journals (Sweden)

    Elen Makara

    2016-12-01

    Full Text Available Because of complaints of clothes that do not fit well and bother, or even the difficulty of acquiring a suitable outfit for an occasion, to the clothing industry may be failing to consider the user in developing their products. The aim of this paper was to determine whether the steps for creating, modeling and prototyping of garment products the user is being considered, as for a design project is right to consider it at all stages of development. For this a literature review and interviews with professionals was held. With the results we can see the difficulty that professionals have to define the public to create the pieces. We also found that most professionals understand the importance of measures table however end up adjusting the empirically, and the realization of prototype testing many choose models that does not match the reality of the public company

  4. THE IMPLEMENTATION OF THE 5E MODEL STAGES TO BUILD STUDENTS’ VOCABULARY

    Directory of Open Access Journals (Sweden)

    Muhammad Rochman

    2015-12-01

    Full Text Available There are stages of human to learn something. In early ages, they will learn simplest things to the complicated ones. A learning process of human is started with and introductory and it tries to connect with their prior knowledge to the new one. Children begin to curious about what they want to know and start to make some questions about what they want to know. In the process of finding the answers of their own questions, they will interact with others and try to share the knowledge in this process. The result of this study illustrates that the implementation of the 5E model in teaching vocabulary that can enhance the students’ vocabulary achievement and successfully encourages them to actively and enthusiastically take part in the teaching-learning process of vocabulary through group task. Keywords: implementation, vocabulary, vocabulary course, and 5E model

  5. COX-1 inhibitory effect of medicinal plants of Ghana

    DEFF Research Database (Denmark)

    Larsen, Birgitte HV; Soelberg, Jens; Jäger, Anna

    2015-01-01

    Plants used to treat inflammatory ailments, pain, fever and infections in Ghana, were tested for COX-1 inhibitory activity. Ethanolic extracts of 17 species were tested in a COX-1 assay. The extracts of Gardenia ternifolia, Thonningia sanguinea, Triumfetta rhomboidea, and the root of Zanthoxylum ...

  6. COX-2 is associated with periodontitis in Europeans

    NARCIS (Netherlands)

    Schaefer, A.S.; Richter, G.M.; Nothnagel, M.; Laine, M.L.; Noack, B.; Glas, J.; Schrezenmeir, J.; Groessner-Schreiber, B.; Jepsen, S.; Loos, B.G.; Schreiber, S.

    2010-01-01

    COX-2 plays an important role in periodontitis by mediating inflammatory reactions in periodontal tissues, and the COX-2 polymorphisms rs20417 and rs689466 have been reported to be associated with periodontitis in populations of Taiwanese and Chinese ethnicity. To test whether these variants were

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

    Science.gov (United States)

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

  8. The genealogical decomposition of a matrix population model with applications to the aggregation of stages.

    Science.gov (United States)

    Bienvenu, François; Akçay, Erol; Legendre, Stéphane; McCandlish, David M

    2017-06-01

    Matrix projection models are a central tool in many areas of population biology. In most applications, one starts from the projection matrix to quantify the asymptotic growth rate of the population (the dominant eigenvalue), the stable stage distribution, and the reproductive values (the dominant right and left eigenvectors, respectively). Any primitive projection matrix also has an associated ergodic Markov chain that contains information about the genealogy of the population. In this paper, we show that these facts can be used to specify any matrix population model as a triple consisting of the ergodic Markov matrix, the dominant eigenvalue and one of the corresponding eigenvectors. This decomposition of the projection matrix separates properties associated with lineages from those associated with individuals. It also clarifies the relationships between many quantities commonly used to describe such models, including the relationship between eigenvalue sensitivities and elasticities. We illustrate the utility of such a decomposition by introducing a new method for aggregating classes in a matrix population model to produce a simpler model with a smaller number of classes. Unlike the standard method, our method has the advantage of preserving reproductive values and elasticities. It also has conceptually satisfying properties such as commuting with changes of units. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. INHOMOGENEITY IN SPATIAL COX POINT PROCESSES – LOCATION DEPENDENT THINNING IS NOT THE ONLY OPTION

    Directory of Open Access Journals (Sweden)

    Michaela Prokešová

    2010-11-01

    Full Text Available In the literature on point processes the by far most popular option for introducing inhomogeneity into a point process model is the location dependent thinning (resulting in a second-order intensity-reweighted stationary point process. This produces a very tractable model and there are several fast estimation procedures available. Nevertheless, this model dilutes the interaction (or the geometrical structure of the original homogeneous model in a special way. When concerning the Markov point processes several alternative inhomogeneous models were suggested and investigated in the literature. But it is not so for the Cox point processes, the canonical models for clustered point patterns. In the contribution we discuss several other options how to define inhomogeneous Cox point process models that result in point patterns with different types of geometric structure. We further investigate the possible parameter estimation procedures for such models.

  10. Værktøjskasse til Agil Stage-Gate®: Ny model for udviklingsprojekter i mellemstore virksomheder

    DEFF Research Database (Denmark)

    Vedsmand, Tomas; Edwards, Kasper; Hvidt, Nicoline

    Denne værktøjskasse er et tillæg for guiden Agil Stage-Gate: Ny model for udviklingsprojekter i mellemstore virksomheder. (http://dx.doi.org/10.11581/DTU:00000028)......Denne værktøjskasse er et tillæg for guiden Agil Stage-Gate: Ny model for udviklingsprojekter i mellemstore virksomheder. (http://dx.doi.org/10.11581/DTU:00000028)...

  11. A transition-constrained discrete hidden Markov model for automatic sleep staging.

    Science.gov (United States)

    Pan, Shing-Tai; Kuo, Chih-En; Zeng, Jian-Hong; Liang, Sheng-Fu

    2012-08-21

    Approximately one-third of the human lifespan is spent sleeping. To diagnose sleep problems, all-night polysomnographic (PSG) recordings including electroencephalograms (EEGs), electrooculograms (EOGs) and electromyograms (EMGs), are usually acquired from the patient and scored by a well-trained expert according to Rechtschaffen & Kales (R&K) rules. Visual sleep scoring is a time-consuming and subjective process. Therefore, the development of an automatic sleep scoring method is desirable. The EEG, EOG and EMG signals from twenty subjects were measured. In addition to selecting sleep characteristics based on the 1968 R&K rules, features utilized in other research were collected. Thirteen features were utilized including temporal and spectrum analyses of the EEG, EOG and EMG signals, and a total of 158  hours of sleep data were recorded. Ten subjects were used to train the Discrete Hidden Markov Model (DHMM), and the remaining ten were tested by the trained DHMM for recognition. Furthermore, the 2-fold cross validation was performed during this experiment. Overall agreement between the expert and the results presented is 85.29%. With the exception of S1, the sensitivities of each stage were more than 81%. The most accurate stage was SWS (94.9%), and the least-accurately classified stage was S1 (<34%). In the majority of cases, S1 was classified as Wake (21%), S2 (33%) or REM sleep (12%), consistent with previous studies. However, the total time of S1 in the 20 all-night sleep recordings was less than 4%. The results of the experiments demonstrate that the proposed method significantly enhances the recognition rate when compared with prior studies.

  12. Market splitting in Germany – New evidence from a three-stage numerical model of Europe

    International Nuclear Information System (INIS)

    Trepper, Katrin; Bucksteeg, Michael; Weber, Christoph

    2015-01-01

    With the sharp increase in redispatch measures seen during recent years, the importance of an efficient congestion management has increased, particularly in Germany. As the current market design, with a single bidding area, ignores the physical constraints of the transmission grid, there is an ongoing discussion about introducing price zones. Against this background, we develop a three-stage approach to model redispatch and market splitting for Germany while considering interactions with interconnected countries. We identify an increasing spatial imbalance between generation and load and delays in grid extension as being the main drivers for the increase of modeled redispatch volumes from 2012 to 2020. We show that market splitting reduces imminent congestion although results are sensitive to the zonal delimitation and corresponding net transfer capacities. The overall welfare effect is negligible, but price differences between the bidding areas investigated, i.e. one Northern and Southern price zone, result in considerable distributional effects. While consumers in Northern Germany would benefit – producer rents and in particular the value of wind energy would decrease – the opposite is true for Southern Germany. We conclude that market splitting constitutes a solution to reduce redispatch measures as long as transmission grid expansion is further delayed. - Highlights: • A three-stage approach to model redispatch and zonal pricing is proposed. • Energy transition will lead to a tripling of congestion in Germany until 2020. • Market splitting in Germany substantially reduces redispatch measures. • Overall welfare gain is negligible, but considerable distributional effects occur. • The beneficial effects of market splitting depend strongly on its design.

  13. Mathematical Model of the One-stage Magneto-optical Sensor Based on Faraday Effect

    Science.gov (United States)

    Babaev, O. G.; Paranin, V. D.; Sinitsin, L. I.

    2018-01-01

    The aim of this work is to refine a model of magneto-optical sensors based on Faraday’s longitudinal magneto-optical effect. The tasks of the study include computer modeling and analysis of the transfer characteristic of a single-stage magneto-optical sensor for various polarization of the input beam and non-ideal optical components. The proposed mathematical model and software make it possible to take into account the non-ideal characteristics of film polaroids observed in operation in the near infrared region and at increased temperatures. On the basis of the results of the model analysis it was found that the dependence of normalized transmission T(γ2) has periodic nature. Choosing the angle (γ 2-γ 1) makes it possible to shift the initial operation point and change the sensitivity dT/dγ 2. The influence of the input beam polarization increases with the increase of polaroid parameter deviation from ideal and shows itself as reduction of modulation depth and angular shift of the sensor conversion response.

  14. A Risk-Based Interval Two-Stage Programming Model for Agricultural System Management under Uncertainty

    Directory of Open Access Journals (Sweden)

    Ye Xu

    2016-01-01

    Full Text Available Nonpoint source (NPS pollution caused by agricultural activities is main reason that water quality in watershed becomes worse, even leading to deterioration. Moreover, pollution control is accompanied with revenue’s fall for agricultural system. How to design and generate a cost-effective and environmentally friendly agricultural production pattern is a critical issue for local managers. In this study, a risk-based interval two-stage programming model (RBITSP was developed. Compared to general ITSP model, significant contribution made by RBITSP model was that it emphasized importance of financial risk under various probabilistic levels, rather than only being concentrated on expected economic benefit, where risk is expressed as the probability of not meeting target profit under each individual scenario realization. This way effectively avoided solutions’ inaccuracy caused by traditional expected objective function and generated a variety of solutions through adjusting weight coefficients, which reflected trade-off between system economy and reliability. A case study of agricultural production management with the Tai Lake watershed was used to demonstrate superiority of proposed model. Obtained results could be a base for designing land-structure adjustment patterns and farmland retirement schemes and realizing balance of system benefit, system-failure risk, and water-body protection.

  15. One- and two-stage Arrhenius models for pharmaceutical shelf life prediction.

    Science.gov (United States)

    Fan, Zhewen; Zhang, Lanju

    2015-01-01

    One of the most challenging aspects of the pharmaceutical development is the demonstration and estimation of chemical stability. It is imperative that pharmaceutical products be stable for two or more years. Long-term stability studies are required to support such shelf life claim at registration. However, during drug development to facilitate formulation and dosage form selection, an accelerated stability study with stressed storage condition is preferred to quickly obtain a good prediction of shelf life under ambient storage conditions. Such a prediction typically uses Arrhenius equation that describes relationship between degradation rate and temperature (and humidity). Existing methods usually rely on the assumption of normality of the errors. In addition, shelf life projection is usually based on confidence band of a regression line. However, the coverage probability of a method is often overlooked or under-reported. In this paper, we introduce two nonparametric bootstrap procedures for shelf life estimation based on accelerated stability testing, and compare them with a one-stage nonlinear Arrhenius prediction model. Our simulation results demonstrate that one-stage nonlinear Arrhenius method has significant lower coverage than nominal levels. Our bootstrap method gave better coverage and led to a shelf life prediction closer to that based on long-term stability data.

  16. Modeling bacterial attachment to surfaces as an early stage of biofilm development.

    Science.gov (United States)

    El Moustaid, Fadoua; Eladdadi, Amina; Uys, Lafras

    2013-06-01

    Biofilms are present in all natural, medical and industrial surroundings where bacteria live. Biofilm formation is a key factor in the growth and transport of both beneficial and harmful bacteria. While much is known about the later stages of biofilm formation, less is known about its initiation which is an important first step in the biofilm formation. In this paper, we develop a non-linear system of partial differential equations of Keller-Segel type model in one-dimensional space, which couples the dynamics of bacterial movement to that of the sensing molecules. In this case, bacteria perform a biased random walk towards the sensing molecules. We derive the boundary conditions of the adhesion of bacteria to a surface using zero-Dirichlet boundary conditions, while the equation describing sensing molecules at the interface needed particular conditions to be set. The numerical results show the profile of bacteria within the space and the time evolution of the density within the free-space and on the surface. Testing different parameter values indicate that significant amount of sensing molecules present on the surface leads to a faster bacterial movement toward the surface which is the first step of biofilm initiation. Our work gives rise to results that agree with the biological description of the early stages of biofilm formation.

  17. Utility of Modeling End-Stage Liver Disease in Children with Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    Hamid Reza Kianifar

    2014-01-01

    Full Text Available Introduction: Chronic liver diseases consist of wide spectrum disorders that may be complicated by cirrhosis and therefore need to transplantation. The pediatric end-stage liver disease (PELD score and model of end-stage liver disease (MELD score has been used as predictors of mortality chronic liver diseases listed for liver transplantation. The aim of this study is evaluation of relation between PELDMELD score and evidence of cirrhosis in children with choronic liver disease.   Materials and Method: This cross-sectional study conducted on 106 patients of chronic liver disease referred to Ghaem Haspital, Mashhad University of Medical Science, Iran during 24 months period (2010-2013. PELD and MELD score were calculated for all patients. Clincal and patholoogical findings of cirrhosis were recorded.   Results: Mean age of patients was 68/3 ± 41.8 months. Mean PELDMELD score was -1/59± 9/64. There was significant correlation between PELDMELD score and clinical icter, spelenomegaly, evidence of hepatopulminary syndrome, esophageal varices, evidence of cirrhosis in tissue specimences.   Conclusion: PELDMELD score appear to be benefit for detection of cirrhotic children among paients with choronic liver disease.

  18. TCDD Induced Pericardial Edema and Relative COX-2 Expression in Medaka (Oryzias Latipes) Embryos

    Science.gov (United States)

    Dong, Wu; Matsumura, Fumio; Kullman, Seth W.

    2010-01-01

    Exposure to dioxin and other aryl hydrocarbon receptor (AhR) ligands results in multiple, specific developmental cardiovascular phenotypes including pericardial edema and circulatory failure in small aquarium fish models. Although phenotypes are well described, mechanistic underpinnings for such toxicities remain elusive. Here we suggest that AhR activation results in stimulation of inflammation and “eicosanoid” pathways, which contribute to the observed developmental, cardiovascular phenotypes. We demonstrate that medaka embryos exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.05–1 ppb) during early development result in a dose-related increase in the prevalence of pericardial edema and that this phenotype correlates with an increase in cyclooxygenase-2 (COX-2) gene expression. Those individuals exhibiting the edema phenotype had significantly greater COX-2 mRNA than their nonedematous cohort. Selective pharmacological inhibition of COX-2, with NS-398, and genetic knock down of COX-2 with a translation initiation morpholino significantly attenuated prevalence and severity of edema phenotype. Subsequently, exposures of medaka embryos to arachidonic acid (AA) resulted in recapitulation of the pericardial edema phenotype and significantly increased COX-2 expression only in those individuals exhibiting the edema phenotype compared with their nonedematous cohort. AA exposure does not result in significant induction of cytochrome P450 1A expression, suggesting that pericardial edema can be induced independent of AhR/aryl hydrocarbon receptor nuclear translocator/dioxin response element interactions. Results from this study demonstrate that developmental exposure to TCDD results in an induction of inflammatory mediators including COX-2, which contribute to the onset, and progression of heart dysmorphogenesis in the medaka model. PMID:20801906

  19. Effect of Ginkgo biloba extract on the expressions of Cox-2 and GST ...

    African Journals Online (AJOL)

    2014-03-01

    Mar 1, 2014 ... Its underlying biological mechanism remains unclear and no well-documented drug and ... Objectives: To explore the effect of EGb on expressions of cyclooxygenase-2 (Cox-2) and glutathione S-transferase Pi. (GST-Pi) in the ..... in an animal model of Parkinson's disease: Therapeutic perspectives. Nutri-.

  20. A Three-Stage Supply Chain Investment Model under Asymmetric Information

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    investments to tier-1 and possibly tier-2 suppliers leads to relatively poor performance due to under-investments. The superior arrangement is the centralized conditional model, where the OEM forces coordination among upstream suppliers by offering conditional financing. We close the paper with an analogy......Specific supply-chain investments are vital in achieving faster lead-time performance and more competitive costs. In practice, such as in the highly leveraged telecom sector, the coordinating original equipment manufacturers (OEM) often delegate the upstream coordination of suppliers to contract...... coordinator (say an OEM) to either control or delegate the investment decision of some shared resource (say dedicated machines, information or product standards, etc) to a contract manufacturer (CM) or to an upstream supplier in a three-stage supply chain. The analysis derives closed-form results...

  1. The relative efficiency of Iranian’s rural traffic police: a three-stage DEA model

    Directory of Open Access Journals (Sweden)

    Habibollah Rahimi

    2017-10-01

    Full Text Available Abstract Background Road traffic Injuries (RTIs as a health problem imposes governments to implement different interventions. Target achievement in this issue required effective and efficient measures. Efficiency evaluation of traffic police as one of the responsible administrators is necessary for resource management. Therefore, this study conducted to measure Iran’s rural traffic police efficiency. Methods This was an ecological study. To obtain pure efficiency score, three-stage DEA model was conducted with seven inputs and three output variables. At the first stage, crude efficiency score was measured with BCC-O model. Next, to extract the effects of socioeconomic, demographic, traffic count and road infrastructure as the environmental variables and statistical noise, the Stochastic Frontier Analysis (SFA model was applied and the output values were modified according to similar environment and statistical noise conditions. Then, the pure efficiency score was measured using modified outputs and BCC-O model. Results In total, the efficiency score of 198 police stations from 24 provinces of 31 provinces were measured. The annual means (standard deviation of damage, injury and fatal accidents were 247.7 (258.4, 184.9 (176.9, and 28.7 (19.5, respectively. Input averages were 5.9 (3.0 patrol teams, 0.5% (0.2 manpower proportions, 7.5 (2.9 patrol cars, 0.5 (1.3 motorcycles, 77,279.1 (46,794.7 penalties, 90.9 (2.8 cultural and educational activity score, 0.7 (2.4 speed cameras. The SFA model showed non-significant differences between police station performances and the most differences attributed to the environmental and random error. One-way main road, by road, traffic count and the number of household owning motorcycle had significant positive relations with inefficiency score. The length of freeway/highway and literacy rate variables had negative relations, significantly. Pure efficiency score was with mean of 0.95 and SD of 0.09. Conclusions

  2. The relative efficiency of Iranian's rural traffic police: a three-stage DEA model.

    Science.gov (United States)

    Rahimi, Habibollah; Soori, Hamid; Nazari, Seyed Saeed Hashemi; Motevalian, Seyed Abbas; Azar, Adel; Momeni, Eskandar; Javartani, Mehdi

    2017-10-13

    Road traffic Injuries (RTIs) as a health problem imposes governments to implement different interventions. Target achievement in this issue required effective and efficient measures. Efficiency evaluation of traffic police as one of the responsible administrators is necessary for resource management. Therefore, this study conducted to measure Iran's rural traffic police efficiency. This was an ecological study. To obtain pure efficiency score, three-stage DEA model was conducted with seven inputs and three output variables. At the first stage, crude efficiency score was measured with BCC-O model. Next, to extract the effects of socioeconomic, demographic, traffic count and road infrastructure as the environmental variables and statistical noise, the Stochastic Frontier Analysis (SFA) model was applied and the output values were modified according to similar environment and statistical noise conditions. Then, the pure efficiency score was measured using modified outputs and BCC-O model. In total, the efficiency score of 198 police stations from 24 provinces of 31 provinces were measured. The annual means (standard deviation) of damage, injury and fatal accidents were 247.7 (258.4), 184.9 (176.9), and 28.7 (19.5), respectively. Input averages were 5.9 (3.0) patrol teams, 0.5% (0.2) manpower proportions, 7.5 (2.9) patrol cars, 0.5 (1.3) motorcycles, 77,279.1 (46,794.7) penalties, 90.9 (2.8) cultural and educational activity score, 0.7 (2.4) speed cameras. The SFA model showed non-significant differences between police station performances and the most differences attributed to the environmental and random error. One-way main road, by road, traffic count and the number of household owning motorcycle had significant positive relations with inefficiency score. The length of freeway/highway and literacy rate variables had negative relations, significantly. Pure efficiency score was with mean of 0.95 and SD of 0.09. Iran's traffic police has potential opportunity to reduce

  3. Multi-stage IT project evaluation: The flexibility value obtained by implementing and resolving Berk, Green and Naik (2004) model

    Science.gov (United States)

    Abid, Fathi; Guermazi, Dorra

    2009-11-01

    In this paper, we evaluate a multi-stage information technology investment project, by implementing and resolving Berk, Green and Naik's (2004) model, which takes into account specific features of IT projects and considers the real option to suspend investment at each stage. We present a particular case of the model where the project value is the solution of an optimal control problem with a single state variable. In this case, the model is more intuitive and tractable. The case study confirms the practical potential of the model and highlights the importance of the real-option approach compared to classical discounted cash flow techniques in the valuation of IT projects.

  4. Sensitivity of Calanus spp. copepods to environmental changes in the North Sea using life-stage structured models

    DEFF Research Database (Denmark)

    Maar, Marie; Møller, Eva Friis; Gürkan, Zeren

    2013-01-01

    . finmarchicus in this region. The aim of this study is to use life-stage structured models of the two Calanus species embedded in a 3D coupled hydrodynamic-biogeochemical model to investigate how the biogeography of C. finmarchicus and C. helgolandicus is modified by changes in ± 2°C sea water temperatures......, overwintering and oceanic inflow in the North Sea. Life-stage structured models are validated against CPR data and vertical distributions north of the Dogger Bank in the North Sea for the reference year 2005. The model shows that 1) ± 2°C changes from the current level mainly influence the seasonal patterns...

  5. Two-Stage orders sequencing system for mixed-model assembly

    Science.gov (United States)

    Zemczak, M.; Skolud, B.; Krenczyk, D.

    2015-11-01

    In the paper, the authors focus on the NP-hard problem of orders sequencing, formulated similarly to Car Sequencing Problem (CSP). The object of the research is the assembly line in an automotive industry company, on which few different models of products, each in a certain number of versions, are assembled on the shared resources, set in a line. Such production type is usually determined as a mixed-model production, and arose from the necessity of manufacturing customized products on the basis of very specific orders from single clients. The producers are nowadays obliged to provide each client the possibility to determine a huge amount of the features of the product they are willing to buy, as the competition in the automotive market is large. Due to the previously mentioned nature of the problem (NP-hard), in the given time period only satisfactory solutions are sought, as the optimal solution method has not yet been found. Most of the researchers that implemented inaccurate methods (e.g. evolutionary algorithms) to solving sequencing problems dropped the research after testing phase, as they were not able to obtain reproducible results, and met problems while determining the quality of the received solutions. Therefore a new approach to solving the problem, presented in this paper as a sequencing system is being developed. The sequencing system consists of a set of determined rules, implemented into computer environment. The system itself works in two stages. First of them is connected with the determination of a place in the storage buffer to which certain production orders should be sent. In the second stage of functioning, precise sets of sequences are determined and evaluated for certain parts of the storage buffer under certain criteria.

  6. Properties of type IV plaster considering variation in the mold/model position during setting stage

    Directory of Open Access Journals (Sweden)

    Tarcisio José de Arruda Paes Junior

    2010-04-01

    Full Text Available Objective: To assess the influence of the position of the mold during the setting stage of type IV stone plaster Durone (Dentsply Ind. Com., Rio de Janeiro, Brazil, on the following properties: surface hardness and roughness. Methods: For the roughness test, two groups (n=6 in the form of pellets were prepared. In the first group, the surface of the base of the device was turned down during the plaster setting stage (N, in the second group this position was inverted, which has been described as an act of capsize it (E. For analysis, a roughness meter with reading precision of 0.01 μm was used. With regard to the hardness analysis, two groups with conical-shaped samples were obtained. The plasters were left to set under the same conditions of the mold/model position described for the previous experiment. Hardness measurement was performed in a durometer with a spherical penetrating tip for Rockwell readout. Three measurements were performed for each test specimen in both tests. Results: The hardness (N - 39.8, standard deviation = 3.3, E - 30.8, standard deviation = 5.6 and roughness data (N - 0.67, standard deviation = 0.17, E - 0.74, standard deviation = 0.13 submitted to the Student’s-t test (5% showed no statistically significant differences for the roughness test (0.489, but showed statistically significant differences for the hardness test (0.014. Conclusion: The variation in the mold/model position influenced the final characteristics of the specimens in terms of hardness, since those obtained with the capsize technique showed lower surface hardness, whereas for roughness these differences were not statistically significant.

  7. Statistical modeling of CTV motion and deformation for IMRT of early-stage rectal cancer.

    Science.gov (United States)

    Bondar, Luiza; Intven, Martijn; Burbach, J P Maarten; Budiarto, Eka; Kleijnen, Jean-Paul; Philippens, Marielle; van Asselen, Bram; Seravalli, Enrica; Reerink, Onne; Raaymakers, Bas

    2014-11-01

    To derive and validate a statistical model of motion and deformation for the clinical target volume (CTV) of early-stage rectal cancer patients. For 16 patients, 4 to 5 magnetic resonance images (MRI) were acquired before each fraction was administered. The CTV was delineated on each MRI. Using a leave-one-out methodology, we constructed a population-based principal component analysis (PCA) model of the CTV motion and deformation of 15 patients, and we tested the model on the left-out patient. The modeling error was calculated as the amount of the CTV motion-deformation of the left-out-patient that could not be explained by the PCA model. Next, the PCA model was used to construct a PCA target volume (PCA-TV) by accumulating motion-deformations simulated by the model. A PCA planning target volume (PTV) was generated by expanding the PCA-TV by uniform margins. The PCA-PTV was compared with uniform and nonuniform CTV-to-PTV margins. To allow comparison, geometric margins were determined to ensure adequate coverage, and the volume difference between the PTV and the daily CTV (CTV-to-PTV volume) was calculated. The modeling error ranged from 0.9 ± 0.5 to 2.9 ± 2.1 mm, corresponding to a reduction of the CTV motion-deformation between 6% and 60% (average, 23% ± 11%). The reduction correlated with the magnitude of the CTV motion-deformation (P<.001, R=0.66). The PCA-TV and the CTV required 2-mm and 7-mm uniform margins, respectively. The nonuniform CTV-to-PTV margins were 4 mm in the left, right, inferior, superior, and posterior directions and 8 mm in the anterior direction. Compared to uniform and nonuniform CTV-to-PTV margins, the PCA-based PTV significantly decreased (P<.001) the average CTV-to-PTV volume by 128 ± 20 mL (49% ± 4%) and by 35 ± 6 mL (20% ± 3.5%), respectively. The CTV motion-deformation of a new patient can be explained by a population-based PCA model. A PCA model-generated PTV significantly improved sparing of organs at risk compared to uniform

  8. Design of formative assessment model for professional behavior using stages of change theory.

    Science.gov (United States)

    Hashemi, Akram; Mirzazadeh, Azim; Shirazi, Mandana; Asghari, Fariba

    2016-01-01

    Background: Professionalism is a core competency of physicians. This study was conducted to design a model for formative assessment of professional commitment in medical students according to stages of change theory. Methods: In this qualitative study, data were collected through literature review & focus group interviews in the Tehran University of Medical Sciences in 2013 and analyzed using content analysis approach. Results: Review of the literature and results of focus group interviews led to design a formative assessment model of professional commitment in three phases, including pre-contemplation, contemplation, and readiness for behavior change that each one has interventional and assessment components. In the second phase of the study, experts' opinion collected in two main categories: the educational environment (factors related to students, students' assessment and educational program); and administrative problems (factors related to subcultures, policymakers or managers and budget). Moreover, there was a section of recommendations for each category related to curriculum, professors, students, assessments, making culture, the staff and reinforcing administrative factors. Conclusion: This type of framework analysis made it possible to develop a conceptual model that could be effective on forming the professional commitment and behavioral change in medical students.

  9. A Two-Stage Queue Model to Optimize Layout of Urban Drainage System considering Extreme Rainstorms

    Directory of Open Access Journals (Sweden)

    Xinhua He

    2017-01-01

    Full Text Available Extreme rainstorm is a main factor to cause urban floods when urban drainage system cannot discharge stormwater successfully. This paper investigates distribution feature of rainstorms and draining process of urban drainage systems and uses a two-stage single-counter queue method M/M/1→M/D/1 to model urban drainage system. The model emphasizes randomness of extreme rainstorms, fuzziness of draining process, and construction and operation cost of drainage system. Its two objectives are total cost of construction and operation and overall sojourn time of stormwater. An improved genetic algorithm is redesigned to solve this complex nondeterministic problem, which incorporates with stochastic and fuzzy characteristics in whole drainage process. A numerical example in Shanghai illustrates how to implement the model, and comparisons with alternative algorithms show its performance in computational flexibility and efficiency. Discussions on sensitivity of four main parameters, that is, quantity of pump stations, drainage pipe diameter, rainstorm precipitation intensity, and confidence levels, are also presented to provide guidance for designing urban drainage system.

  10. Compliance modeling of planar flexure-based mechanisms and its application to micro-motion stages

    Directory of Open Access Journals (Sweden)

    Yunsong Du

    2016-07-01

    Full Text Available This article presents the compliance modeling method of flexure-based mechanisms. The relationship between deformations and loads of the flexure members and the end effector is analyzed according to the zero virtual work principle. Using the matrix method, concise compliance equations for flexure serial and parallel structures are derived in conjunction with consideration of the compliance calculation errors of flexure hinges. Finally, relationships between the output compliances and geometrical parameters of a 3-revolute-revolute-revolute micro-motion stage are discussed. To validate the proposed compliance modeling method, the output compliances calculated by the empirical and theoretical compliance equations are subsequently compared with values derived from finite element analysis (FEA. The comparisons indicate that the results obtained from the empirical compliance equations are in good agreement with those derived from FEA, whereas the errors calculated by the theoretical equations are much larger, which demonstrate the accuracy of the empirical compliance equations and validate the proposed compliance modeling method.

  11. Formation of Behavioural Finance as the Natural Stage of the Human Model Evolution in Economics

    Directory of Open Access Journals (Sweden)

    Viktor Pavlovich Ivanitsky

    2017-09-01

    Full Text Available The paper presents the background analysis of the formation of human model in economics. in the conditions of the constantly performing development of the economic science until the neoclassic paradigm and its modifications. Among them is behavioural finance, which presents a special interest for modern researchers. The evolution of the model of making economically significant decisions in inter-temporal and essential dimensions is the subject matter of the research. We have shown that the concept of the economic human model itself is the multidimensional one. In parallel with the processes of economical, social and political changes and economic science development, the economic human model was becoming more complex and relevant for each period of time. In this regard, we followed the stages of defining the concept of “subject rationality”. The study determines the significant traits implemented by researchers to create a full and consistent human model. We demonstrate the gradual development of economists’ idea of different types of the motivation of economic agents. Along with the financial factors of motivation, the scientists begin to take into account non-financial ones. This approach can help researchers get more “humanistic” view at the economic human. The modern concept of the economic human with attention to its implicit restrictions is formed through the complication of requirements to the rationality and its components crystallization. In the paper, we characterize contribution of the domestic scientists to the development of new directions of economic theory. The research describes the role of different regional economic scientific schools in the process of the formation of the Russian behavioural finance school

  12. Spleen dynamic contrast-enhanced magnetic resonance imaging as a new method for staging liver fibrosis in a piglet model.

    Directory of Open Access Journals (Sweden)

    Li Zhou

    Full Text Available OBJECTIVE: To explore spleen hemodynamic alteration in liver fibrosis with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI, and to determine how to stage liver fibrosis with spleen DCE-MRI parameters. MATERIALS AND METHODS: Sixteen piglets were prospectively used to model liver fibrosis staged by liver biopsy, and underwent spleen DCE-MRI on 0, 5th, 9th, 16th and 21st weekend after modeling this disease. DCE-MRI parameters including time to peak (TTP, positive enhancement integral (PEI, maximum slope of increase (MSI and maximum slope of decrease (MSD of spleen were measured, and statistically analyzed to stage this disease. RESULTS: Spearman's rank correlation tests showed that TTP tended to increase with increasing stages of liver fibrosis (r = 0.647, P0.05, and decreased from stage 2 to 4 (P0.05. Mann-Whitney tests demonstrated that TTP and PEI could classify fibrosis between stage 0 and 1-4, between 0-1 and 2-4, between 0-2 and 3-4, or between 0-3 and 4 (all P<0.01. MSD could discriminate between 0-2 and 3-4 (P = 0.006, or between 0-3 and 4 (P = 0.012. MSI could not differentiate between any two stages. Receiver operating characteristic analysis illustrated that area under receiver operating characteristic curve (AUC of TTP was larger than of PEI for classifying stage ≥1 and ≥2 (AUC = 0.851 and 0.783, respectively. PEI could best classify stage ≥3 and 4 (AUC = 0.903 and 0.96, respectively. CONCLUSION: Spleen DCE-MRI has potential to monitor spleen hemodynamic alteration and classify liver fibrosis stages.

  13. Stage-dependent alterations of progenitor cell proliferation and neurogenesis in an animal model of Wernicke-Korsakoff syndrome

    Science.gov (United States)

    Vetreno, Ryan P.; Klintsova, Anna; Savage, Lisa M.

    2011-01-01

    Alcohol-induced Wernicke-Korsakoff syndrome (WKS) culminates in bilateral diencephalic lesion and severe amnesia. Using the pyrithiamine-induced thiamine deficiency (PTD) animal paradigm of WKS, our laboratory has demonstrated hippocampal dysfunction in the absence of gross anatomical pathology. Extensive literature has revealed reduced hippocampal neurogenesis following a neuropathological insult, which might contribute to hippocampus-based learning and memory impairments. Thus, the current investigation was conducted to determine whether PTD treatment altered hippocampal neurogenesis in a stage-dependent fashion. Male Sprague-Dawley rats were assigned to one of 4 stages of thiamine deficiency based on behavioral symptoms: pre-symptomatic stage, ataxic stage, early post-opisthotonus stage, or the late post-opisthotonus stage. The S-phase mitotic marker 5′-bromo-2′-deoxyuridine (BrdU) was administered at the conclusion of each stage following thiamine restoration and subjects were perfused 24-hours or 28-days after BrdU to assess cellular proliferation or neurogenesis and survival, respectively. Dorsal hippocampal sections were immunostained for BrdU (proliferating cell marker), NeuN (neurons), GFAP (astrocytes), Iba-1 (microglia), and O4 (oligodendrocytes). The PTD treatment increased progenitor cell proliferation and survival during the early post-opisthotonus stage. However, levels of neurogenesis were reduced during this stage as well as the late post-opisthotonus stage where there was also an increase in astrocytogenesis. The diminished numbers of newly generated neurons (BrdU/NeuN co-localization) was paralleled by increased BrdU cells that did not co-localize with any of the phenotypic markers during these later stages. These data demonstrate that long-term alterations in neurogenesis and gliogenesis might contribute to the observed hippocampal dysfunction in the PTD model and human WKS. PMID:21440532

  14. Expressão das proteínas p53 e Cox-2 em adenocarcinoma intestinal e mucosa adjacente Expression of p53 and Cox-2 proteins in intestinal adenocarcinoma and adjacent mucosa

    Directory of Open Access Journals (Sweden)

    Carlos Roberto Felin

    2008-03-01

    Full Text Available Este estudo teve como objetivo verificar se existe associação entre o estadiamento do tumor e a expressão das proteínas p53 e Ciclooxigenase-2 (Cox-2 em adenocarcinoma de intestino. Foi realizado um estudo retrospectivo de 40 blocos de parafina contendo amostras obtidas de ressecção cirúrgica de tecido intestinal anteriormente diagnosticado como adenocarcinoma de intestino humano. O material foi coletado no período entre 1998 e 2003 no Hospital Universitário de Santa Maria, RS, Brasil. Como controle, foram utilizadas amostras de áreas não tumorais de mucosa adjacente, referentes a cada caso (n = 40. Utilizamos a imuno-histoquímica para analisar este material quanto à expressão das proteínas p53 e Cox-2. A expressão das proteínas p53 e Cox-2 foi significativamente maior em tecido tumoral quando comparada com mucosa adjacente. Detectamos positividade total para Cox-2 (100%, e parcial (70% para p53 em tecido tumoral. Foi verificada associação significativa entre expressão da proteína p53 e estadiamento segundo Astler-Coller, mas não com a classificação TNM. Quanto à proteína Cox-2, não foi observada associação significativa com estadiamento do tumor de intestino. Os achados sugerem que existe uma tendência entre a expressão da proteína p53 e Cox-2 com o estadiamento do tumor, sendo necessária comprovação com estudos futuros.The objective of this study is to establish a possible association between staging and the expression of p53 and cyclooxygenase-2 (Cox-2 proteins in intestinal adenocarcinoma. A retrospective study of 40 embedded paraffins with surgical specimens of intestinal Adenocarcinoma was performed. The samples were collected during 1998 and 2003 at Hospital Universitário de Santa Maria, RS, Brasil. Samples of non-tumoral tissues (n = 40 were used as a negative control. The expression of p53 and Cox-2 was immunohistochemically studied. The expression of p53 and Cox-2 proteins was significantly higher in

  15. Liver dysfunction assessed by model for end-stage liver disease excluding INR (MELD-XI scoring system predicts adverse prognosis in heart failure.

    Directory of Open Access Journals (Sweden)

    Satoshi Abe

    Full Text Available AIMS: Liver dysfunction due to heart failure (HF is often referred to as cardiac or congestive hepatopathy. The composite Model for End-Stage Liver Disease excluding INR (MELD-XI is a robust scoring system of liver function, and a high score is associated with poor prognosis in advanced HF patients with a heart transplantation and/or ventricular assist device. However, the impact of MELD-XI on the prognosis of HF patients in general remains unclear. METHODS AND RESULTS: We retrospectively analyzed 562 patients who were admitted to our hospital for the treatment of decompensated HF. A MELD-XI score was graded, and patients were divided into two groups based on the median value of MELD-XI score: Group L (MELD-XI <10, n = 289 and Group H (MELD-XI ≥10, n = 273. We compared all-cause mortality and echocardiographic findings between the two groups. In the follow-up period (mean 471 days, 104 deaths (62 cardiac deaths and 42 non-cardiac deaths were observed. The event (cardiac death, non-cardiac death, all-cause death-free rate was significantly higher in group L than in group H (logrank P<0.05, respectively. In the Cox proportional hazard analysis, a high MELD-XI score was found to be an independent predictor of cardiac deaths and all-cause mortality in HF patients. Regarding echocardiographic parameters, right atrial and ventricular areas, inferior vena cava diameter, and systolic pulmonary artery pressure were higher in group H than in group L (P<0.05, respectively. CONCLUSIONS: The MELD-XI scoring system, a marker of liver function, can identify high-risk patients with right heart volume overload, higher pulmonary arterial pressure and multiple organ failure associated with HF.

  16. Two-stage collaborative global optimization design model of the CHPG microgrid

    Science.gov (United States)

    Liao, Qingfen; Xu, Yeyan; Tang, Fei; Peng, Sicheng; Yang, Zheng

    2017-06-01

    With the continuous developing of technology and reducing of investment costs, renewable energy proportion in the power grid is becoming higher and higher because of the clean and environmental characteristics, which may need more larger-capacity energy storage devices, increasing the cost. A two-stage collaborative global optimization design model of the combined-heat-power-and-gas (abbreviated as CHPG) microgrid is proposed in this paper, to minimize the cost by using virtual storage without extending the existing storage system. P2G technology is used as virtual multi-energy storage in CHPG, which can coordinate the operation of electric energy network and natural gas network at the same time. Demand response is also one kind of good virtual storage, including economic guide for the DGs and heat pumps in demand side and priority scheduling of controllable loads. Two kinds of storage will coordinate to smooth the high-frequency fluctuations and low-frequency fluctuations of renewable energy respectively, and achieve a lower-cost operation scheme simultaneously. Finally, the feasibility and superiority of proposed design model is proved in a simulation of a CHPG microgrid.

  17. Dynamics of gastropod infection by first-stage larvae of protostrongylid nematodes--a model.

    Science.gov (United States)

    Rezác, P; Kindlmann, P; Dostálková, I; Holasová, E

    1993-12-01

    For the description of the dynamics of snail infection by the 1st-stage larvae of protostrongylid nematodes, Skorping (1988) used the miracidia-snail model (Anderson, 1978). Here it is shown that, in contrast to miracidia, in protostrongylids the instantaneous rate of infection, alpha, is strongly dependent on the experimental design (factors like host size and size of the experimental arena). With respect to this, Anderson's model is modified by incorporation of the experimental design. The parameter alpha in its new sense as the rate of penetration (probability that the infective larva will penetrate into the host during a time unit) is shown to remain dependent, although much less so, on the experimental design. Only the inclusion of the assumed effect of mucus, which decreases the rate of penetration, yields a parameter alpha 0 (the initial rate of penetration), which is completely independent of the design of the experiment, is species-specific, and also gives the best fit to the empirical data. As the above-mentioned factors can strongly influence the value of the instantaneous rate of infection in the laboratory experiments, alpha 0 is more suitable as a measure of either the larval infectivity for the snail or snail susceptibility to infection by the protostrongylid larvae.

  18. Simulation of the Two Stages Stretch-Blow Molding Process: Infrared Heating and Blowing Modeling

    International Nuclear Information System (INIS)

    Bordival, M.; Schmidt, F. M.; Le Maoult, Y.; Velay, V.

    2007-01-01

    In the Stretch-Blow Molding (SBM) process, the temperature distribution of the reheated perform affects drastically the blowing kinematic, the bottle thickness distribution, as well as the orientation induced by stretching. Consequently, mechanical and optical properties of the final bottle are closely related to heating conditions. In order to predict the 3D temperature distribution of a rotating preform, numerical software using control-volume method has been developed. Since PET behaves like a semi-transparent medium, the radiative flux absorption was computed using Beer Lambert law. In a second step, 2D axi-symmetric simulations of the SBM have been developed using the finite element package ABAQUS registered . Temperature profiles through the preform wall thickness and along its length were computed and applied as initial condition. Air pressure inside the preform was not considered as an input variable, but was automatically computed using a thermodynamic model. The heat transfer coefficient applied between the mold and the polymer was also measured. Finally, the G'sell law was used for modeling PET behavior. For both heating and blowing stage simulations, a good agreement has been observed with experimental measurements. This work is part of the European project ''APT P ACK'' (Advanced knowledge of Polymer deformation for Tomorrow's PACKaging)

  19. An early-stage design model for estimating ship evacuation patterns using the ship-centric Markov decision process

    NARCIS (Netherlands)

    Kana, A.A.; Droste, K.

    2017-01-01

    An early-stage design model is presented that estimates personnel locations on board a vessel during times of evacuation. This model takes into account various levels of uncertainty and pain that individuals may feel while heading toward safety, while simultaneously not requiring highly detailed

  20. Re-thinking stages of cognitive development: an appraisal of connectionist models on the balance scale task

    NARCIS (Netherlands)

    Quinlan, P.T.; van der Maas, H.L.J.; Jansen, B.R.J.; Booij, O.; Rendell, M.

    2007-01-01

    The present paper re-appraises connectionist attempts to explain how human cognitive development appears to progress through a series of sequential stages. Models of performance on the Piagetian balance scale task are the focus of attention. Limitations of these models are discussed and replications

  1. Tracking cognitive processing stages with MEG : A spatio-temporal model of associative recognition in the brain

    NARCIS (Netherlands)

    Borst, Jelmer P; Ghuman, Avniel S; Anderson, John R

    2016-01-01

    In this study, we investigated the cognitive processing stages underlying associative recognition using MEG. Over the last four decades, a model of associative recognition has been developed in the ACT-R cognitive architecture. This model was first exclusively based on behavior, but was later

  2. An idealized model for tree-grass coexistence in savannas : The role of life stage structure and fire disturbances

    NARCIS (Netherlands)

    Baudena, Mara|info:eu-repo/dai/nl/340303867; D'Andrea, Fabio; Provenzale, A.

    2010-01-01

    1. We discuss a simple implicit-space model for the competition of trees and grasses in an idealized savanna environment. The model represents patch occupancy dynamics within the habitat and introduces life stage structure in the tree population, namely adults and seedlings. A tree can be

  3. Characterisation of cyclooxygenase 1 and 2 expression in mouse resident peritoneal macrophages in vitro; interactions of non steroidal anti-inflammatory drugs with COX2.

    Science.gov (United States)

    Tordjman, C; Coge, F; Andre, N; Rique, H; Spedding, M; Bonnet, J

    1995-05-17

    Resident peritoneal macrophages exposed to inflammatory stimuli (zymosan, lipopolysaccharide (LPS)) represent a widely used model for studying arachidonic acid metabolism and for screening of prostaglandin (PG) synthesis inhibitors. In the present study, cyclooxygenase 1 (COX1) was shown constitutively expressed in mouse adherent and non-adherent macrophages whereas expression of COX2 was observed only in adherent cells, even when cultured in minimal conditions (Ca-, Mg- and serum-free medium). The COX2 expression was amplified by arachidonic acid cascade stimulating agents (Ca, Mg, zymosan) and by LPS in a time-dependant manner; PGE2 by itself amplified LPS-induced COX2 expression. In well-defined experimental conditions of COX2 expression (LPS-stimulated adherent macrophages), we studied specific interactions of some representative anti-inflammatory drugs with COX2 enzymatic activity and expression. By contrast with dexamethasone, which reduced PGE2 release together with a strong reduction of COX2 expression (protein and mRNA), non steroidal anti-inflammatory drugs (NSAIDs) reduced PGE2 synthesis without any effect at the COX2 mRNA level. This reduction of PGE2 production by NSAIDs resulted from either an exclusive enzymatic inhibition (aspirin, NS398, 6-Methoxy naphtyl acetic acid) or an enzymatic inhibition associated with a slight decrease of COX2 protein level (indomethacin). For paracetamol and salicylic acid, two weak inhibitors of COX enzymatic activity, reduction of PGE2 synthesis appeared to be related to reduced level of COX2. These findings show that the macrophage can be used as a cellular model to study specifically COX1 and COX2. In this cell type, COX2 expression is dependent on adhesion, enhanced by stimulation of arachidonic acid metabolism, and auto amplified by PGE2. Furthermore, the results indicate that known NSAIDs differ in their interaction with cyclooxygenase, being able to inhibit either COX2 enzymatic activity, and/or COX2 expression

  4. Thiazoles and Thiazolidinones as COX/LOX Inhibitors.

    Science.gov (United States)

    Liaras, Konstantinos; Fesatidou, Maria; Geronikaki, Athina

    2018-03-18

    Inflammation is a natural process that is connected to various conditions and disorders such as arthritis, psoriasis, cancer, infections, asthma, etc. Based on the fact that cyclooxygenase isoenzymes (COX-1, COX-2) are responsible for the production of prostaglandins that play an important role in inflammation, traditional treatment approaches include administration of non-steroidal anti-inflammatory drugs (NSAIDs), which act as selective or non-selective COX inhibitors. Almost all of them present a number of unwanted, often serious, side effects as a consequence of interference with the arachidonic acid cascade. In search for new drugs to avoid side effects, while maintaining high potency over inflammation, scientists turned their interest to the synthesis of dual COX/LOX inhibitors, which could provide numerous therapeutic advantages in terms of anti-inflammatory activity, improved gastric protection and safer cardiovascular profile compared to conventional NSAIDs. Τhiazole and thiazolidinone moieties can be found in numerous biologically active compounds of natural origin, as well as synthetic molecules that possess a wide range of pharmacological activities. This review focuses on the biological activity of several thiazole and thiazolidinone derivatives as COX-1/COX-2 and LOX inhibitors.

  5. Decomposition of variance for spatial Cox processes

    DEFF Research Database (Denmark)

    Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

    2013-01-01

    with additive or log linear random intensity functions. We moreover consider a new and flexible class of pair correlation function models given in terms of normal variance mixture covariance functions. The proposed methodology is applied to point pattern data sets of locations of tropical rain forest trees....

  6. Decomposition of variance for spatial Cox processes

    DEFF Research Database (Denmark)

    Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

    with additive or log linear random intensity functions. We moreover consider a new and flexible class of pair correlation function models given in terms of Matérn covariance functions. The proposed methodology is applied to point pattern data sets of locations of tropical rain forest trees....

  7. Two-stage model of development of heterogeneous uranium-lead systems in zircon

    International Nuclear Information System (INIS)

    Mel'nikov, N.N.; Zevchenkov, O.A.

    1985-01-01

    Behaviour of isotope systems of multiphase zircons at their two-stage distortion is considered. The results of calculations testify to the fact that linear correlations on the diagram with concordance can be explained including two-stage discovery of U-Pb systems of cogenetic zircons if zircon is considered physically heterogeneous and losing in its different part different ratios of accumulated radiogenic lead. ''Metamorphism ages'' obtained by these two-stage opening zircons are intermediate, and they not have geochronological significance while ''crystallization ages'' remain rather close to real ones. Two-stage opening zircons in some cases can be diagnosed by discordance of their crystal component

  8. Validity and reliability of an application review process using dedicated reviewers in one stage of a multi-stage admissions model.

    Science.gov (United States)

    Zeeman, Jacqueline M; McLaughlin, Jacqueline E; Cox, Wendy C

    2017-11-01

    With increased emphasis placed on non-academic skills in the workplace, a need exists to identify an admissions process that evaluates these skills. This study assessed the validity and reliability of an application review process involving three dedicated application reviewers in a multi-stage admissions model. A multi-stage admissions model was utilized during the 2014-2015 admissions cycle. After advancing through the academic review, each application was independently reviewed by two dedicated application reviewers utilizing a six-construct rubric (written communication, extracurricular and community service activities, leadership experience, pharmacy career appreciation, research experience, and resiliency). Rubric scores were extrapolated to a three-tier ranking to select candidates for on-site interviews. Kappa statistics were used to assess interrater reliability. A three-facet Many-Facet Rasch Model (MFRM) determined reviewer severity, candidate suitability, and rubric construct difficulty. The kappa statistic for candidates' tier rank score (n = 388 candidates) was 0.692 with a perfect agreement frequency of 84.3%. There was substantial interrater reliability between reviewers for the tier ranking (kappa: 0.654-0.710). Highest construct agreement occurred in written communication (kappa: 0.924-0.984). A three-facet MFRM analysis explained 36.9% of variance in the ratings, with 0.06% reflecting application reviewer scoring patterns (i.e., severity or leniency), 22.8% reflecting candidate suitability, and 14.1% reflecting construct difficulty. Utilization of dedicated application reviewers and a defined tiered rubric provided a valid and reliable method to effectively evaluate candidates during the application review process. These analyses provide insight into opportunities for improving the application review process among schools and colleges of pharmacy. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. The Application of Extended Cox Proportional Hazard Method for Estimating Survival Time of Breast Cancer

    Science.gov (United States)

    Husain, Hartina; Astuti Thamrin, Sri; Tahir, Sulaiha; Mukhlisin, Ahmad; Mirna Apriani, M.

    2018-03-01

    Breast cancer is one type of cancer that is the leading cause of death worldwide. This study aims to model the factors that affect the survival time and rate of cure of breast cancer patients. The extended cox model, which is a modification of the proportional hazard cox model in which the proportional hazard assumptions are not met, is used in this study. The maximum likelihood estimation approach is used to estimate the parameters of the model. This method is then applied to medical record data of breast cancer patient in 2011-2016, which is taken from Hasanuddin University Education Hospital. The results obtained indicate that the factors that affect the survival time of breast cancer patients are malignancy and leukocyte levels.

  10. Modelling the enigmatic Late Pliocene Glacial Event - Marine Isotope Stage M2

    Science.gov (United States)

    Dolan, Aisling M.; Haywood, Alan M.; Hunter, Stephen J.; Tindall, Julia C.; Dowsett, Harry J.; Hill, Daniel J.; Pickering, Steven J.

    2015-01-01

    The Pliocene Epoch (5.2 to 2.58 Ma) has often been targeted to investigate the nature of warm climates. However, climate records for the Pliocene exhibit significant variability and show intervals that apparently experienced a cooler than modern climate. Marine Isotope Stage (MIS) M2 (~ 3.3 Ma) is a globally recognisable cooling event that disturbs an otherwise relatively (compared to present-day) warm background climate state. It remains unclear whether this event corresponds to significant ice sheet build-up in the Northern and Southern Hemisphere. Estimates of sea level for this interval vary, and range from modern values to estimates of 65 m sea level fall with respect to present day. Here we implement plausible M2 ice sheet configurations into a coupled atmosphere–ocean climate model to test the hypothesis that larger-than-modern ice sheet configurations may have existed at M2. Climate model results are compared with proxy climate data available for M2 to assess the plausibility of each ice sheet configuration. Whilst the outcomes of our data/model comparisons are not in all cases straight forward to interpret, there is little indication that results from model simulations in which significant ice masses have been prescribed in the Northern Hemisphere are incompatible with proxy data from the North Atlantic, Northeast Arctic Russia, North Africa and the Southern Ocean. Therefore, our model results do not preclude the possibility of the existence of larger ice masses during M2 in the Northern or Southern Hemisphere. Specifically they are not able to discount the possibility of significant ice masses in the Northern Hemisphere during the M2 event, consistent with a global sea-level fall of between 40 m and 60 m. This study highlights the general need for more focused and coordinated data generation in the future to improve the coverage and consistency in proxy records for M2, which will allow these and future M2 sensitivity tests to be interrogated

  11. A two-stage method for microcalcification cluster segmentation in mammography by deformable models

    International Nuclear Information System (INIS)

    Arikidis, N.; Kazantzi, A.; Skiadopoulos, S.; Karahaliou, A.; Costaridou, L.; Vassiou, K.

    2015-01-01

    Purpose: Segmentation of microcalcification (MC) clusters in x-ray mammography is a difficult task for radiologists. Accurate segmentation is prerequisite for quantitative image analysis of MC clusters and subsequent feature extraction and classification in computer-aided diagnosis schemes. Methods: In this study, a two-stage semiautomated segmentation method of MC clusters is investigated. The first stage is targeted to accurate and time efficient segmentation of the majority of the particles of a MC cluster, by means of a level set method. The second stage is targeted to shape refinement of selected individual MCs, by means of an active contour model. Both methods are applied in the framework of a rich scale-space representation, provided by the wavelet transform at integer scales. Segmentation reliability of the proposed method in terms of inter and intraobserver agreements was evaluated in a case sample of 80 MC clusters originating from the digital database for screening mammography, corresponding to 4 morphology types (punctate: 22, fine linear branching: 16, pleomorphic: 18, and amorphous: 24) of MC clusters, assessing radiologists’ segmentations quantitatively by two distance metrics (Hausdorff distance—HDIST cluster , average of minimum distance—AMINDIST cluster ) and the area overlap measure (AOM cluster ). The effect of the proposed segmentation method on MC cluster characterization accuracy was evaluated in a case sample of 162 pleomorphic MC clusters (72 malignant and 90 benign). Ten MC cluster features, targeted to capture morphologic properties of individual MCs in a cluster (area, major length, perimeter, compactness, and spread), were extracted and a correlation-based feature selection method yielded a feature subset to feed in a support vector machine classifier. Classification performance of the MC cluster features was estimated by means of the area under receiver operating characteristic curve (Az ± Standard Error) utilizing tenfold cross

  12. A two-stage method for microcalcification cluster segmentation in mammography by deformable models

    Energy Technology Data Exchange (ETDEWEB)

    Arikidis, N.; Kazantzi, A.; Skiadopoulos, S.; Karahaliou, A.; Costaridou, L., E-mail: costarid@upatras.gr [Department of Medical Physics, School of Medicine, University of Patras, Patras 26504 (Greece); Vassiou, K. [Department of Anatomy, School of Medicine, University of Thessaly, Larissa 41500 (Greece)

    2015-10-15

    Purpose: Segmentation of microcalcification (MC) clusters in x-ray mammography is a difficult task for radiologists. Accurate segmentation is prerequisite for quantitative image analysis of MC clusters and subsequent feature extraction and classification in computer-aided diagnosis schemes. Methods: In this study, a two-stage semiautomated segmentation method of MC clusters is investigated. The first stage is targeted to accurate and time efficient segmentation of the majority of the particles of a MC cluster, by means of a level set method. The second stage is targeted to shape refinement of selected individual MCs, by means of an active contour model. Both methods are applied in the framework of a rich scale-space representation, provided by the wavelet transform at integer scales. Segmentation reliability of the proposed method in terms of inter and intraobserver agreements was evaluated in a case sample of 80 MC clusters originating from the digital database for screening mammography, corresponding to 4 morphology types (punctate: 22, fine linear branching: 16, pleomorphic: 18, and amorphous: 24) of MC clusters, assessing radiologists’ segmentations quantitatively by two distance metrics (Hausdorff distance—HDIST{sub cluster}, average of minimum distance—AMINDIST{sub cluster}) and the area overlap measure (AOM{sub cluster}). The effect of the proposed segmentation method on MC cluster characterization accuracy was evaluated in a case sample of 162 pleomorphic MC clusters (72 malignant and 90 benign). Ten MC cluster features, targeted to capture morphologic properties of individual MCs in a cluster (area, major length, perimeter, compactness, and spread), were extracted and a correlation-based feature selection method yielded a feature subset to feed in a support vector machine classifier. Classification performance of the MC cluster features was estimated by means of the area under receiver operating characteristic curve (Az ± Standard Error) utilizing

  13. Mathematical modeling of a continuous alcoholic fermentation process in a two-stage tower reactor cascade with flocculating yeast recycle.

    Science.gov (United States)

    de Oliveira, Samuel Conceição; de Castro, Heizir Ferreira; Visconti, Alexandre Eliseu Stourdze; Giudici, Reinaldo

    2015-03-01

    Experiments of continuous alcoholic fermentation of sugarcane juice with flocculating yeast recycle were conducted in a system of two 0.22-L tower bioreactors in series, operated at a range of dilution rates (D 1 = D 2 = 0.27-0.95 h(-1)), constant recycle ratio (α = F R /F = 4.0) and a sugar concentration in the feed stream (S 0) around 150 g/L. The data obtained in these experimental conditions were used to adjust the parameters of a mathematical model previously developed for the single-stage process. This model considers each of the tower bioreactors as a perfectly mixed continuous reactor and the kinetics of cell growth and product formation takes into account the limitation by substrate and the inhibition by ethanol and biomass, as well as the substrate consumption for cellular maintenance. The model predictions agreed satisfactorily with the measurements taken in both stages of the cascade. The major differences with respect to the kinetic parameters previously estimated for a single-stage system were observed for the maximum specific growth rate, for the inhibition constants of cell growth and for the specific rate of substrate consumption for cell maintenance. Mathematical models were validated and used to simulate alternative operating conditions as well as to analyze the performance of the two-stage process against that of the single-stage process.

  14. Training pharmacists in the stage-of-change model of smoking cessation and motivational interviewing: A randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Pasquale Caponnetto

    2017-10-01

    Full Text Available This study evaluated the effect of training pharmacists in the stage-of-change model for smoking cessation and motivational interviewing on smoking cessation outcomes. A training based on the stage-of-change model for smoking cessation and motivational interviewing was introduced to pharmacists. Pharmacists were randomly assigned to the intervention or control group. The control group attended a 3-hour training session, whereas the intervention group also attended a further 6-hour training session. At week 24, 12.2 percent of the smokers quit smoking in the intervention group, whereas 1.6 percent of the smokers quit smoking in the control group. The findings of this study showed that training pharmacists, in the stage-of-change model for smoking cessation and motivational interviewing, improves smoking reduction and cessation rates.

  15. Evaluation of carcinogenic potential of diuron in a rat mammary two-stage carcinogenesis model.

    Science.gov (United States)

    Grassi, Tony Fernando; Rodrigues, Maria Aparecida Marchesan; de Camargo, João Lauro Viana; Barbisan, Luís Fernando

    2011-04-01

    This study aimed to evaluate the carcinogenic potential of the herbicide Diuron in a two-stage rat medium-term mammary carcinogenesis model initiated by 7,12-dimethylbenz(a)anthracene (DMBA). Female seven-week-old Sprague-Dawley (SD) rats were allocated to six groups: groups G1 to G4 received intragastrically (i.g.) a single 50 mg/kg dose of DMBA; groups G5 and G6 received single administration of canola oil (vehicle of DMBA). Groups G1 and G5 received a basal diet, and groups G2, G3, G4, and G6 were fed the basal diet with the addition of Diuron at 250, 1250, 2500, and 2500 ppm, respectively. After twenty-five weeks, the animals were euthanized and mammary tumors were histologically confirmed and quantified. Tumor samples were also processed for immunohistochemical evaluation of the expressions of proliferating cell nuclear antigen (PCNA), cleaved caspase-3, estrogen receptor-α (ER-α), p63, bcl-2, and bak. Diuron treatment did not increase the incidence or multiplicity of mammary tumors (groups G2 to G4 versus Group G1). Also, exposure to Diuron did not alter tumor growth (cell proliferation and apoptosis indexes) or immunoreactivity to ER-α, p63 (myoephitelial marker), or bcl-2 and bak (apoptosis regulatory proteins). These findings indicate that Diuron does not have a promoting potential on mammary carcinogenesis in female SD rats initiated with DMBA.

  16. Parametric Modeling Investigation of a Radially-Staged Low-Emission Aviation Combustor

    Science.gov (United States)

    Heath, Christopher M.

    2016-01-01

    Aviation gas-turbine combustion demands high efficiency, wide operability and minimal trace gas emissions. Performance critical design parameters include injector geometry, combustor layout, fuel-air mixing and engine cycle conditions. The present investigation explores these factors and their impact on a radially staged low-emission aviation combustor sized for a next-generation 24,000-lbf-thrust engine. By coupling multi-fidelity computational tools, a design exploration was performed using a parameterized annular combustor sector at projected 100% takeoff power conditions. Design objectives included nitrogen oxide emission indices and overall combustor pressure loss. From the design space, an optimal configuration was selected and simulated at 7.1, 30 and 85% part-power operation, corresponding to landing-takeoff cycle idle, approach and climb segments. All results were obtained by solution of the steady-state Reynolds-averaged Navier-Stokes equations. Species concentrations were solved directly using a reduced 19-step reaction mechanism for Jet-A. Turbulence closure was obtained using a nonlinear K-epsilon model. This research demonstrates revolutionary combustor design exploration enabled by multi-fidelity physics-based simulation.

  17. Large animal model of functional tricuspid regurgitation in pacing induced end-stage heart failure.

    Science.gov (United States)

    Malinowski, Marcin; Proudfoot, Alistair G; Langholz, David; Eberhart, Lenora; Brown, Michael; Schubert, Hans; Wodarek, Jeremy; Timek, Tomasz A

    2017-06-01

    Functional tricuspid regurgitation (FTR) is common in patients with advanced heart failure and frequently complicates left ventricular assist device implantation yet remains poorly understood. We set out to establish large animal model of FTR that could serve as a research platform to investigate the pathogenesis of FTR associated with end-stage heart failure. : Through right thoracotomy, ten adult sheep underwent implantation of pacemaker with epicardial LV lead, five sonomicrometry crystals on the right ventricle, and left and right ventricular telemetry pressure sensors during a beating heart off-pump procedure. After 5 ± 1 days of recovery, baseline haemodynamic, echocardiographic and sonomicrometry data were collected. Animals were paced thereafter at a rate of 220-240 beats/min until the development of heart failure and concomitant tricuspid regurgitation. : Three animals died during early recovery period and one during the pacing phase. Six surviving animals were paced for a mean of 14 ± 5 days. Cardiac function was significantly depressed compared to baseline, with LV ejection fraction falling from 69 ± 2% to 22 ± 4% ( P  heart failure patients presenting for mechanical support. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  18. Optimal pulse fishing policy in stage-structured models with birth pulses

    International Nuclear Information System (INIS)

    Gao Shujing; Chen Lansun; Sun Lihua

    2005-01-01

    In this paper, we propose exploited models with stage structure for the dynamics in a fish population for which periodic birth pulse and pulse fishing occur at different fixed time. Using the stroboscopic map, we obtain an exact cycle of system, and obtain the threshold conditions for its stability. Bifurcation diagrams are constructed with the birth rate (or pulse fishing time or harvesting effort) as the bifurcation parameter, and these are observed to display complex dynamic behaviors, including chaotic bands with period windows, period-doubling, multi-period-halving and incomplete period-doubling bifurcation, pitch-fork and tangent bifurcation, non-unique dynamics (meaning that several attractors or attractor and chaos coexist) and attractor crisis. This suggests that birth pulse and pulse fishing provide a natural period or cyclicity that make the dynamical behaviors more complex. Moreover, we show that the pulse fishing has a strong impact on the persistence of the fish population, on the volume of mature fish stock and on the maximum annual-sustainable yield. An interesting result is obtained that, after the birth pulse, the population can sustain much higher harvesting effort if the mature fish is removed as early as possible

  19. The Discovery of Processing Stages: Analyzing EEG data with Hidden Semi-Markov Models

    NARCIS (Netherlands)

    Borst, Jelmer; Anderson, John R.

    2015-01-01

    In this paper we propose a new method for identifying processing stages in human information processing. Since the 1860s scientists have used different methods to identify processing stages, usually based on reaction time (RT) differences between conditions. To overcome the limitations of RT-based

  20. Rock Mechanics Forsmark. Site descriptive modelling Forsmark stage 2.2

    Energy Technology Data Exchange (ETDEWEB)

    Glamheden, Rune; Fredriksson, Anders (Golder Associates AB (SE)); Roeshoff, Kennert; Karlsson, Johan (Berg Bygg Konsult AB (SE)); Hakami, Hossein (Itasca Geomekanik AB (SE)); Christiansson, Rolf (Swedish Nuclear Fuel and Waste Management Co., Stockholm (SE))

    2007-12-15

    The Swedish Nuclear Fuel and Waste Management Company (SKB) is undertaking site characterisation at two different locations, Forsmark and Laxemar/Simpevarp, with the objective of siting a geological repository for spent nuclear fuel. The characterisation of a site is an integrated work carried out by several disciplines including geology, rock mechanics, thermal properties, hydrogeology, hydrogeochemistry and surface systems. This report presents the rock mechanics model of the Forsmark site up to stage 2.2. The scope of work has included compilation and analysis of primary data of intact rock and fractures, estimation of the rock mass mechanical properties and estimation of the in situ state of stress at the Forsmark site. The laboratory results on intact rock and fractures in the target volume demonstrate a good quality rock mass that is strong, stiff and relatively homogeneous. The homogeneity is also supported by the lithological and the hydrogeological models. The properties of the rock mass have been initially estimated by two separate modelling approaches, one empirical and one theoretical. An overall final estimate of the rock mass properties were achieved by integrating the results from the two models via a process termed 'Harmonization'. Both the tensile tests, carried out perpendicular and parallel to the foliation, and the theoretical analyses of the rock mass properties in directions parallel and perpendicular to the major principal stress, result in parameter values almost independent of direction. This indicates that the rock mass in the target volume is isotropic. The rock mass quality in the target volume appears to be of high and uniform quality. Those portions with reduced rock mass quality that do exist are mainly related to sections with increased fracture frequency. Such sections are associated with deformation zones according to the geological description. The results of adjacent rock domains and fracture domains of the target

  1. An adaptive two-stage analog/regression model for probabilistic prediction of small-scale precipitation in France

    Science.gov (United States)

    Chardon, Jérémy; Hingray, Benoit; Favre, Anne-Catherine

    2018-01-01

    Statistical downscaling models (SDMs) are often used to produce local weather scenarios from large-scale atmospheric information. SDMs include transfer functions which are based on a statistical link identified from observations between local weather and a set of large-scale predictors. As physical processes driving surface weather vary in time, the most relevant predictors and the regression link are likely to vary in time too. This is well known for precipitation for instance and the link is thus often estimated after some seasonal stratification of the data. In this study, we present a two-stage analog/regression model where the regression link is estimated from atmospheric analogs of the current prediction day. Atmospheric analogs are identified from fields of geopotential heights at 1000 and 500 hPa. For the regression stage, two generalized linear models are further used to model the probability of precipitation occurrence and the distribution of non-zero precipitation amounts, respectively. The two-stage model is evaluated for the probabilistic prediction of small-scale precipitation over France. It noticeably improves the skill of the prediction for both precipitation occurrence and amount. As the analog days vary from one prediction day to another, the atmospheric predictors selected in the regression stage and the value of the corresponding regression coefficients can vary from one prediction day to another. The model allows thus for a day-to-day adaptive and tailored downscaling. It can also reveal specific predictors for peculiar and non-frequent weather configurations.

  2. A staged model of communication effects: evidence from an entertainment-education radio soap opera in Tanzania.

    Science.gov (United States)

    Vaughan, P W; Rogers, E M

    2000-01-01

    The authors draw on (1) the hierarchy-of-effects (HOE) model, (2) the stages-of-change (SOC) model, (3) social learning theory (SLT), and (4) the diffusion of innovations (DOI) to synthesize a staged model through which communication messages have effects on individual behavior change by stimulating (1) involvement with media characters and role modeling of their actions, and (2) interpersonal communication. Data from a field experiment in Tanzania on the effects of an entertainment-education radio soap opera, Twende na Wakati (Let's Go With the Times), on the adoption of family planning, are analyzed in light of a six-staged model of communication effects. It is found that (1) the model provides a useful framework for understanding the effects of an entertainment-education program, and (2) the radio soap opera promoted progress through the stages for family planning adoption in the treatment area in three of the four years of broadcast, and in the comparison area after broadcasts of the radio program began there.

  3. Designing a crisis management model in Iran’s archival centers: Pre-crisis stage

    Directory of Open Access Journals (Sweden)

    Maryam Nakhoda

    2018-03-01

    Full Text Available The purpose of this research is to design a crisis management model in the archival centers of Iran during the pre-crisis phase. The present study was conducted with a qualitative approach using the Grounded theory method. The necessary data was collected using semi-structured interviews. Data saturation was a major factor in determining the sample size. The research population included 20 crisis management specialists and managers of archives in Iran and the data analysis was performed in three stages: open, axial, and selective coding. The paradigmatic model derived from the findings of the research includes the sections of the causal conditions, strategies, intervening conditions and the underlying conditions and their outcomes. The causal conditions are located in two categories of internal crises such as biological crises and lack of proper management, and external crises such as natural disasters, fires and human-made crises. Intervener conditions and backgrounds include cat-egories such as lack of specialist staff training, lack of appropriate environmental conditions and management mechanisms, archival building and human resources issues. To prevent and mitigate the effects of the crisis in archives, some strategies are required such as modern education for resil-ience, teaching how to use documents, standardizing buildings and equipment (non-use of steel skeletons in building archives, use of concrete skeletons Armed or metal, as well as the use of walls and doors and floors of anti-fire covers in the building of archives and the establishment of multi-layer protective systems for the protection of documents.

  4. Salt supplementation ameliorates developmental kidney defects in COX-2-/- mice.

    Science.gov (United States)

    Slattery, Patrick; Frölich, Stefanie; Goren, Itamar; Nüsing, Rolf M

    2017-06-01

    Deficiency of cyclooxygenase-2 (COX-2) activity in the early postnatal period causes impairment of kidney development leading to kidney insufficiency. We hypothesize that impaired NaCl reabsorption during the first days of life is a substantial cause for nephrogenic defects observed in COX-2 -/- mice and that salt supplementation corrects these defects. Daily injections of NaCl (0.8 mg·g -1 ·day -1 ) for the first 10 days after birth ameliorated impaired kidney development in COX-2 -/- pups resulting in an increase in glomerular size and fewer immature superficial glomeruli. However, impaired renal subcortical growth was not corrected. Increasing renal tubular flow by volume load or injections of KCl did not relieve the renal histomorphological damage. Administration of torsemide and spironolactone also affected nephrogenesis resulting in diminished glomeruli and cortical thinning. Treatment of COX-2 -/- pups with NaCl/DOCA caused a stronger mitigation of glomerular size and induced a slight but significant growth of cortical tissue mass. After birth, renal mRNA expression of NHE3, NKCC2, ROMK, NCCT, ENaC, and Na + /K + -ATPase increased relative to postnatal day 2 in wild-type mice. However, in COX-2 -/- mice, a significantly lower expression was observed for NCCT, whereas NaCl/DOCA treatment significantly increased NHE3 and ROMK expression. Long-term effects of postnatal NaCl/DOCA injections indicate improved kidney function with normalization of pathologically enhanced creatinine and urea plasma levels; also, albumin excretion was observed. In summary, we present evidence that salt supplementation during the COX-2-dependent time frame of nephrogenesis partly reverses renal morphological defects in COX-2 -/- mice and improves kidney function. Copyright © 2017 the American Physiological Society.

  5. 4-Stage Online Presence Model: Model for Module Design and Delivery Using Web 2.0 Technologies to Facilitate Critical Thinking Skills

    Science.gov (United States)

    Goh, WeiWei; Dexter, Barbara; Self, Richard

    2014-01-01

    The main purpose of this paper is to present a conceptual model for the use of web 2.0 online technologies in order to develop and enhance students' critical thinking skills at higher education level. Wiki is chosen as the main focus in this paper. The model integrates Salmon's 5-stage model (Salmon, 2002) with Garrison's Community of Inquiry…

  6. Eye Movement Deficits Are Consistent with a Staging Model of pTDP-43 Pathology in Amyotrophic Lateral Sclerosis.

    Directory of Open Access Journals (Sweden)

    Martin Gorges

    Full Text Available The neuropathological process underlying amyotrophic lateral sclerosis (ALS can be traced as a four-stage progression scheme of sequential corticofugal axonal spread. The examination of eye movement control gains deep insights into brain network pathology and provides the opportunity to detect both disturbance of the brainstem oculomotor circuitry as well as executive deficits of oculomotor function associated with higher brain networks.To study systematically oculomotor characteristics in ALS and its underlying network pathology in order to determine whether eye movement deterioration can be categorized within a staging system of oculomotor decline that corresponds to the neuropathological model.Sixty-eight ALS patients and 31 controls underwent video-oculographic, clinical and neuropsychological assessments.Oculomotor examinations revealed increased anti- and delayed saccades' errors, gaze-palsy and a cerebellary type of smooth pursuit disturbance. The oculomotor disturbances occurred in a sequential manner: Stage 1, only executive control of eye movements was affected. Stage 2 indicates disturbed executive control plus 'genuine' oculomotor dysfunctions such as gaze-paly. We found high correlations (p<0.001 between the oculomotor stages and both, the clinical presentation as assessed by the ALS Functional Rating Scale (ALSFRS score, and cognitive scores from the Edinburgh Cognitive and Behavioral ALS Screen (ECAS.Dysfunction of eye movement control in ALS can be characterized by a two-staged sequential pattern comprising executive deficits in Stage 1 and additional impaired infratentorial oculomotor control pathways in Stage 2. This pattern parallels the neuropathological staging of ALS and may serve as a technical marker of the neuropathological spreading.

  7. Impact of two-stage turbocharging architectures on pumping losses of automotive engines based on an analytical model

    International Nuclear Information System (INIS)

    Galindo, J.; Serrano, J.R.; Climent, H.; Varnier, O.

    2010-01-01

    Present work presents an analytical study of two-stage turbocharging configuration performance. The aim of this work is to understand the influence of different two-stage-architecture parameters to optimize the use of exhaust manifold gases energy and to aid decision making process. An analytical model giving the relationship between global compression ratio and global expansion ratio is developed as a function of basic engine and turbocharging system parameters. Having an analytical solution, the influence of different variables, such as expansion ratio between HP and LP turbine, intercooler efficiency, turbochargers efficiency, cooling fluid temperature and exhaust temperature are studied independently. Engine simulations with proposed analytical model have been performed to analyze the influence of these different parameters on brake thermal efficiency and pumping mean effective pressure. The results obtained show the overall performance of the two-stage system for the whole operative range and characterize the optimum control of the elements for each operative condition. The model was also used to compare single-stage and two-stage architectures performance for the same engine operative conditions. Benefits and limits in terms of breathing capabilities and brake thermal efficiency of each type of system have been presented and analyzed.

  8. An inexact mixed risk-aversion two-stage stochastic programming model for water resources management under uncertainty.

    Science.gov (United States)

    Li, W; Wang, B; Xie, Y L; Huang, G H; Liu, L

    2015-02-01

    Uncertainties exist in the water resources system, while traditional two-stage stochastic programming is risk-neutral and compares the random variables (e.g., total benefit) to identify the best decisions. To deal with the risk issues, a risk-aversion inexact two-stage stochastic programming model is developed for water resources management under uncertainty. The model was a hybrid methodology of interval-parameter programming, conditional value-at-risk measure, and a general two-stage stochastic programming framework. The method extends on the traditional two-stage stochastic programming method by enabling uncertainties presented as probability density functions and discrete intervals to be effectively incorporated within the optimization framework. It could not only provide information on the benefits of the allocation plan to the decision makers but also measure the extreme expected loss on the second-stage penalty cost. The developed model was applied to a hypothetical case of water resources management. Results showed that that could help managers generate feasible and balanced risk-aversion allocation plans, and analyze the trade-offs between system stability and economy.

  9. Bedrock geology Forsmark. Modelling stage 2.3. Implications for and verification of the deterministic geological models based on complementary data

    Energy Technology Data Exchange (ETDEWEB)

    Stephens, Michael B. (Geological Survey of Sweden, Uppsala (Sweden)); Simeonov, Assen (Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden)); Isaksson, Hans (GeoVista AB, Luleaa (Sweden))

    2008-12-15

    The Swedish Nuclear Fuel and Waste Management Company is in the process of completing site descriptive modelling at two locations in Sweden, with the objective to site a deep geological repository for spent nuclear fuel. At Forsmark, the results of the stage 2.2 geological modelling formed the input for downstream users. Since complementary ground and borehole geological and geophysical data, acquired after model stage 2.2, were not planned to be included in the deterministic rock domain, fracture domain and deformation zone models supplied to the users, it was deemed necessary to evaluate the implications of these stage 2.3 data for the stage 2.2 deterministic geological models and, if possible, to make use of these data to verify the models. This report presents the results of the analysis of the complementary stage 2.3 geological and geophysical data. Model verification from borehole data has been implemented in the form of a prediction-outcome test. The stage 2.3 geological and geophysical data at Forsmark mostly provide information on the bedrock outside the target volume. Additional high-resolution ground magnetic data and the data from the boreholes KFM02B, KFM11A, KFM12A and HFM33 to HFM37 can be included in this category. Other data complement older information of identical character, both inside and outside this volume. These include the character and kinematics of deformation zones and fracture mineralogy. In general terms, it can be stated that all these new data either confirm the geological modelling work completed during stage 2.2 or are in good agreement with the data that were used in this work. In particular, although the new high-resolution ground magnetic data modify slightly the position and trace length of some stage 2.2 deformation zones at the ground surface, no new or modified deformation zones with a trace length longer than 3,000 m at the ground surface have emerged. It is also apparent that the revision of fracture orientation data

  10. Bedrock geology Forsmark. Modelling stage 2.3. Implications for and verification of the deterministic geological models based on complementary data

    International Nuclear Information System (INIS)

    Stephens, Michael B.; Simeonov, Assen; Isaksson, Hans

    2008-12-01

    The Swedish Nuclear Fuel and Waste Management Company is in the process of completing site descriptive modelling at two locations in Sweden, with the objective to site a deep geological repository for spent nuclear fuel. At Forsmark, the results of the stage 2.2 geological modelling formed the input for downstream users. Since complementary ground and borehole geological and geophysical data, acquired after model stage 2.2, were not planned to be included in the deterministic rock domain, fracture domain and deformation zone models supplied to the users, it was deemed necessary to evaluate the implications of these stage 2.3 data for the stage 2.2 deterministic geological models and, if possible, to make use of these data to verify the models. This report presents the results of the analysis of the complementary stage 2.3 geological and geophysical data. Model verification from borehole data has been implemented in the form of a prediction-outcome test. The stage 2.3 geological and geophysical data at Forsmark mostly provide information on the bedrock outside the target volume. Additional high-resolution ground magnetic data and the data from the boreholes KFM02B, KFM11A, KFM12A and HFM33 to HFM37 can be included in this category. Other data complement older information of identical character, both inside and outside this volume. These include the character and kinematics of deformation zones and fracture mineralogy. In general terms, it can be stated that all these new data either confirm the geological modelling work completed during stage 2.2 or are in good agreement with the data that were used in this work. In particular, although the new high-resolution ground magnetic data modify slightly the position and trace length of some stage 2.2 deformation zones at the ground surface, no new or modified deformation zones with a trace length longer than 3,000 m at the ground surface have emerged. It is also apparent that the revision of fracture orientation data

  11. Illicit drug use and abuse/dependence: modeling of two-stage variables using the CCC approach.

    Science.gov (United States)

    Agrawal, A; Neale, M C; Jacobson, K C; Prescott, C A; Kendler, K S

    2005-06-01

    Drug use and abuse/dependence are stages of a complex drug habit. Most genetically informative models that are fit to twin data examine drug use and abuse/dependence independent of each other. This poses an interesting question: for a multistage process, how can we partition the factors influencing each stage specifically from the factors that are common to both stages? We used a causal-common-contingent (CCC) model to partition the common and specific influences on drug use and abuse/dependence. Data on use and abuse/dependence of cannabis, cocaine, sedatives, stimulants and any illicit drug was obtained from male and female twin pairs. CCC models were tested individually for each sex and in a sex-equal model. Our results suggest that there is evidence for additive genetic, shared environmental and unique environmental influences that are common to illicit drug use and abuse/dependence. Furthermore, we found substantial evidence for factors that were specific to abuse/dependence. Finally, sexes could be equated for all illicit drugs. The findings of this study emphasize the need for models that can partition the sources of individual differences into common and stage-specific influences.

  12. Stages of Dairy Products Consumption Change by Medical Students: The Trans Theoretical Model

    Directory of Open Access Journals (Sweden)

    N. Kholdi

    2013-02-01

    Full Text Available Background and Objective: In spite of the reverse relationship between Dairy products consumption and chronic diseases, the university students do not consume enough amounts of dairy products. Success interventions for changing dairy consumption patterns need to determine its stages of change. Determining medical students’ readiness to change the dairy consumption pattern through stages of change was the aim of this study. Methods: For this descriptive analytical cross-sectional study, 404 medical students were selected by random clustered sampling. The food frequency and stages of change questionnaires were used to get data. The relationship between age, sex, body mass index, settlement situation, marriage situation and educational STATUS with dairy consumption stages of change were analyzed by chi-2, Kruskal-wallis, Spearman correlation and logistic regression. Results: Less than 50% of students (40% females and 46% males consumed enough servings of dairy products daily. The servings of dairy consumption had not relation with sex, marriage or settlement status, age and body mass index. The least number of students (12.6% were in precontemplation and 26% in contemplation, 18.8% in preparation, and 24.8 and 17.8% in action and maintenance stages. While there was relationship between educational status and stages of change, such a relation had not been found between other variables and stages of change. The percent of internship students in action and maintenance stages were greater than students in medical basic sciences (OR=1.7. Conclusion: Regards to students’ inadequate amount and inappropriate kind of dairy products consumption and readiness to change dairy consumption in about half of students, it seems necessary to apply appropriate intervention strategies on the basis of stages of change to correct dairy consumption patterns.

  13. Construction of a pathological risk model of occult lymph node metastases for prognostication by semi-automated image analysis of tumor budding in early-stage oral squamous cell carcinoma.

    Science.gov (United States)

    Pedersen, Nicklas Juel; Jensen, David Hebbelstrup; Lelkaitis, Giedrius; Kiss, Katalin; Charabi, Birgitte; Specht, Lena; von Buchwald, Christian

    2017-03-14

    It is challenging to identify at diagnosis those patients with early oral squamous cell carcinoma (OSCC), who have a poor prognosis and those that have a high risk of harboring occult lymph node metastases. The aim of this study was to develop a standardized and objective digital scoring method to evaluate the predictive value of tumor budding. We developed a semi-automated image-analysis algorithm, Digital Tumor Bud Count (DTBC), to evaluate tumor budding. The algorithm was tested in 222 consecutive patients with early-stage OSCC and major endpoints were overall (OS) and progression free survival (PFS). We subsequently constructed and cross-validated a binary logistic regression model and evaluated its clinical utility by decision curve analysis. A high DTBC was an independent predictor of both poor OS and PFS in a multivariate Cox regression model. The logistic regression model was able to identify patients with occult lymph node metastases with an area under the curve (AUC) of 0.83 (95% CI: 0.78-0.89, P <0.001) and a 10-fold cross-validated AUC of 0.79. Compared to other known histopathological risk factors, the DTBC had a higher diagnostic accuracy. The proposed, novel risk model could be used as a guide to identify patients who would benefit from an up-front neck dissection.

  14. Coconut water of different maturity stages ameliorates inflammatory processes in model of inflammation

    Science.gov (United States)

    Rao, Sadia Saleem; Najam, Rahila

    2016-01-01

    Aim: Coconut water is a natural beverage that is a part of daily diet of many people. This study was designed to explore the anti-inflammatory activity of coconut water of different maturation stages (young and mature) with rat paw edema model of inflammation using plethysmometer. Methodology: For this study, albino rats were selected and divided into four equal groups (10 rats in each group). Group 1 was set as control and administered distilled water 1 ml orally; Groups 2 and 3 were treated with young and mature coconut water, respectively, at 4 ml/100 g dose orally. Group 4 was treated with the standard drug (ibuprofen) at 400 mg/70 kg. 0.1 ml of 1% w/v acetic acid was administered in the subplantar tissue of rat paw 30 min after oral treatments of groups. Plethysmometer was used to measure rat paw edema. Results: Results revealed that both coconut water possess significant anti-inflammatory activity (P coconut water was 20.22%, 35.13%, 42.52%, and 36% at 1, 2, 3, and 4 h of acetic acid administration, respectively. However, maximum percent inhibition (42.52%) was observed in the second phase of the inflammatory process. On the other hand, percent inhibition by mature coconut water was 18.80%, 25.94%, 24.13%, and 18.66% at 1, 2, 3, and 4 h of acetic acid administration, respectively. However, maximum percent inhibition (25.94%) was observed in the first phase of the inflammatory process. Conclusions: This study strongly suggests the use of young coconut water for potent anti-inflammatory effect and mature coconut water for moderate anti-inflammatory effect. PMID:27366350

  15. Statistical dictionaries for hypothetical in silico model of the early-stage intermediate in protein folding

    Science.gov (United States)

    Kalinowska, Barbara; Fabian, Piotr; Stąpor, Katarzyna; Roterman, Irena

    2015-07-01

    The polypeptide chain folding process appears to be a multi-stage phenomenon. The scientific community has recently devoted much attention to early stages of this process, with numerous attempts at simulating them—either experimentally or in silico. This paper presents a comparative analysis of the predicted and observed results of folding simulations. The proposed technique, based on statistical dictionaries, yields a global accuracy of 57 %—a marked improvement over older approaches (with an accuracy of approximately 46 %).

  16. Combination therapy of PKCζ and COX-2 inhibitors synergistically suppress melanoma metastasis.

    Science.gov (United States)

    Zhou, Ping; Qin, Jiaqi; Li, Yuan; Li, Guoxia; Wang, Yinsong; Zhang, Ning; Chen, Peng; Li, Chunyu

    2017-09-02

    Metastatic malignant melanoma is one of the most aggressive malignancies and its treatment remains challenging. Recent studies demonstrate that the melanoma metastasis has correlations with the heightened activations of protein kinase C ζ (PKCζ) and cyclooxygenase-2 (COX-2) signaling pathways. Targeted inhibitions for PKCζ and COX-2 have been considered as the promising strategies for the treatment of melanoma metastasis. Thus, the PKCζ inhibitor J-4 and COX-2 inhibitor Celecoxib were combined to treat melanoma metastasis in this study. The Transwell assay, Wound-healing assay and Adhesion assay were used to evaluate the inhibition of combined therapy of J-4 and Celecoxib on melanoma cells invasion, migration and adhesion in vitro, respectively. The impaired actin polymerization was observed by confocal microscope and inactivated signal pathways about PKCζ and COX-2 were confirmed by the Western blotting assay. The B16-F10/C57BL mouse melanoma model was used to test the inhibition of combined therapy of J-4 and Celecoxib on melanoma metastasis in vivo. The in vitro results showed that the combination of J-4 and Celecoxib exerted synergistic inhibitory effects on the migration, invasion and adhesion of melanoma B16-F10 and A375 cells with combination index less than 1. The actin polymerization and phosphorylation of Cofilin required in cell migration were severely impaired, which is due to the inactivation of PKCζ related signal pathways and the decrease of COX-2. The combined inhibition of PKCζ and COX-2 induced Mesenchymal-Epithelial Transition (MET) in melanoma cells with the expression of E-Cadherin increasing and Vimentin decreasing. The secretion of MMP-2/MMP-9 also significantly decreased after the combination treatment. In C57BL/6 mice intravenously injected with B16-F10 cells (5 × 10 4 cells/mouse), co-treatment of J-4 and Celecoxib also severely suppressed melanoma lung metastasis. The body weight monitoring and HE staining results indicated the

  17. Sildenafil (Viagra® Prevents Cox-1/ TXA2 Pathway-Mediated Vascular Hypercontractility in ApoE-/- Mice

    Directory of Open Access Journals (Sweden)

    Marcos A.S. Leal

    2017-12-01

    Full Text Available Background/Aims: The atherosclerotic apolipoprotein E-deficient (apoE-/- mouse exhibits impaired vasodilation and enhanced vasoconstriction responsiveness. The objectives of this study were: a to determine the relative contribution of cyclooxygenases (Cox-1 and Cox-2, thromboxane A2 (TXA2 and endothelin-1 (ET-1 to enhancing vascular hyperresponsiveness in this model of atherosclerosis and b to investigate the beneficial effects of the phosphodiesterase 5 inhibitor sildenafil on this endothelial dysfunction. Methods: Adult male apoE-/- mice were treated with sildenafil (40 mg/kg/day, for 3 weeks and compared with non-treated ApoE-/- and wild-type mice. The beneficial effects of sildenafil on vascular contractile response to phenylephrine (PE in aortic rings were evaluated before and after incubation with Cox-1 (SC-560 or Cox-2 (NS-398 inhibitors or the TP antagonist SQ-29548, and on contractile responsiveness to ET-1. Results: ApoE-/- mice exhibited enhanced vasoconstriction to PE (Rmax ∼35%, p<0.01, which was prevented by treatment with sildenafil. The enhanced PE-induced contractions were abolished by both Cox-1 inhibition and TP antagonist, but were not modified by Cox-2 inhibition. Aortic rings from ApoE-/- mice also exhibited enhanced contractions to ET-1 (Rmax ∼30%, p<0.01, which were attenuated in sildenafil-treated ApoE-/- mice. In addition, we observed augmented levels of vascular proinflammatory cytokines in ApoE-/- mice, which were partially corrected by treatment with sildenafil (IL-6, IL-10/IL-6 ratio and MCP-1. Conclusion: The present data show that the Cox-1/TXA2 pathway prevails over the Cox-2 isoform in the mediation of vascular hypercontractility observed in apoE-/-mice. The results also show a beneficial effect of sildenafil on this endothelial dysfunction and on the proinflammatory cytokines in atherosclerotic animals, opening new perspectives for the treatment of other endothelium-related cardiovascular abnormalities.

  18. Simultaneous silencing of TGF-β1 and COX-2 reduces human skin hypertrophic scar through activation of fibroblast apoptosis.

    Science.gov (United States)

    Zhou, Jia; Zhao, Yixuan; Simonenko, Vera; Xu, John J; Liu, Kai; Wang, Deling; Shi, Jingli; Zhong, Tianyi; Zhang, Lixia; Zeng, Lun; Huang, Bin; Tang, Shenggao; Lu, Alan Y; Mixson, A James; Sun, Yangbai; Lu, Patrick Y; Li, Qingfeng

    2017-10-06

    Excessive skin scars due to elective operations or trauma represent a challenging clinical problem. Pathophysiology of hypertrophic scars entails a prolonged inflammatory and proliferative phase of wound healing. Over expression of TGF-β1 and COX-2 play key regulatory roles of the aberrant fibrogenic responses and proinflammatory mediators. When we silenced TGF-β1 and COX-2 expression simultaneously in primary human fibroblasts, a marked increase in the apoptotic cell population occurred in contrast to those only treated with either TGF-β1 or COX-2 siRNA alone. Furthermore, using human hypertrophic scar and skin graft implant models in mice, we observed significant size reductions of the implanted tissues following intra-scar administration of TGF-β1/COX-2 specific siRNA combination packaged with Histidine Lysine Polymer (HKP). Gene expression analyses of those treated tissues revealed silencing of the target gene along with down regulations of pro-fibrotic factors such as α-SMA, hydroxyproline acid, Collagen 1 and Collagen 3. Using TUNEL assay detection, we found that the human fibroblasts in the implanted tissues treated with the TGF-β1/COX-2 siRNAs combination exhibited significant apoptotic activity. Therefore we conclude that a synergistic effect of the TGF-β1/COX-2siRNAs combination contributed to the size reductions of the hypertrophic scar implants, through activation of fibroblast apoptosis and re-balancing between scar tissue deposition and degradation.

  19. Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation.

    Directory of Open Access Journals (Sweden)

    Lisa Y Pang

    Full Text Available Osteosarcoma is the most common primary bone tumour of both children and dogs. It is an aggressive tumour in both species with a rapid clinical course leading ultimately to metastasis. In dogs and children distant metastasis occurs in >80% of individuals treated by surgery alone. Both canine and human osteosarcoma has been shown to contain a sub-population of cancer stem cells (CSCs, which may drive tumour growth, recurrence and metastasis, suggesting that naturally occurring canine osteosarcoma could act as a preclinical model for the human disease. Here we report the successful isolation of CSCs from primary canine osteosarcoma, as well as established cell lines. We show that these cells can form tumourspheres, and demonstrate relative resistance to chemotherapy. We demonstrate similar results for the human osteosarcma cell lines, U2OS and SAOS2. Utilizing the Affymetrix canine microarray, we are able to definitively show that there are significant differences in global gene expression profiles of isolated osteosarcoma stem cells and the daughter adherent cells. We identified 13,221 significant differences (p = 0.05, and significantly, COX-2 was expressed 141-fold more in CSC spheres than daughter adherent cells. To study the role of COX-2 expression in CSCs we utilized the COX-2 inhibitors meloxicam and mavacoxib. We found that COX-2 inhibition had no effect on CSC growth, or resistance to chemotherapy. However inhibition of COX-2 in daughter cells prevented sphere formation, indicating a potential significant role for COX-2 in tumour initiation.

  20. CD36 deficiency leads to choroidal involution via COX2 down-regulation in rodents.

    Directory of Open Access Journals (Sweden)

    Marianne Houssier

    2008-02-01

    Full Text Available BACKGROUND: In the Western world, a major cause of blindness is age-related macular degeneration (AMD. Recent research in angiogenesis has furthered the understanding of choroidal neovascularization, which occurs in the "wet" form of AMD. In contrast, very little is known about the mechanisms of the predominant, "dry" form of AMD, which is characterized by retinal atrophy and choroidal involution. The aim of this study is to elucidate the possible implication of the scavenger receptor CD36 in retinal degeneration and choroidal involution, the cardinal features of the dry form of AMD. METHODS AND FINDINGS: We here show that deficiency of CD36, which participates in outer segment (OS phagocytosis by the retinal pigment epithelium (RPE in vitro, leads to significant progressive age-related photoreceptor degeneration evaluated histologically at different ages in two rodent models of CD36 invalidation in vivo (Spontaneous hypertensive rats (SHR and CD36-/- mice. Furthermore, these animals developed significant age related choroidal involution reflected in a 100%-300% increase in the avascular area of the choriocapillaries measured on vascular corrosion casts of aged animals. We also show that proangiogenic COX2 expression in RPE is stimulated by CD36 activating antibody and that CD36-deficient RPE cells from SHR rats fail to induce COX2 and subsequent vascular endothelial growth factor (VEGF expression upon OS or antibody stimulation in vitro. CD36-/- mice express reduced levels of COX2 and VEGF in vivo, and COX2-/- mice develop progressive choroidal degeneration similar to what is seen in CD36 deficiency. CONCLUSIONS: CD36 deficiency leads to choroidal involution via COX2 down-regulation in the RPE. These results show a novel molecular mechanism of choroidal degeneration, a key feature of dry AMD. These findings unveil a pathogenic process, to our knowledge previously undescribed, with important implications for the development of new therapies.

  1. Research on Operation Strategy for Bundled Wind-thermal Generation Power Systems Based on Two-Stage Optimization Model

    Science.gov (United States)

    Sun, Congcong; Wang, Zhijie; Liu, Sanming; Jiang, Xiuchen; Sheng, Gehao; Liu, Tianyu

    2017-05-01

    Wind power has the advantages of being clean and non-polluting and the development of bundled wind-thermal generation power systems (BWTGSs) is one of the important means to improve wind power accommodation rate and implement “clean alternative” on generation side. A two-stage optimization strategy for BWTGSs considering wind speed forecasting results and load characteristics is proposed. By taking short-term wind speed forecasting results of generation side and load characteristics of demand side into account, a two-stage optimization model for BWTGSs is formulated. By using the environmental benefit index of BWTGSs as the objective function, supply-demand balance and generator operation as the constraints, the first-stage optimization model is developed with the chance-constrained programming theory. By using the operation cost for BWTGSs as the objective function, the second-stage optimization model is developed with the greedy algorithm. The improved PSO algorithm is employed to solve the model and numerical test verifies the effectiveness of the proposed strategy.

  2. Optimization of material flow in the nuclear fuel cycle using a cyclic multi-stage production-to-inventory model

    International Nuclear Information System (INIS)

    DePorter, E.L.

    1977-01-01

    The nuclear fuel cycle is modelled as a cyclic, multi-stage production-to-inventory system. The objective is to meet a known deterministic demand for energy while minimizing acquisition, production, and inventory holding costs for all stages of the fuel cycle. The model allows for cyclic flow (feedback) of materials, material flow conversion factors at each stage, production lag times at each stage, and for escalating costs of uranium ore. It does not allow shortages to occur in inventories. The model is optimized by the application of the calculus of variations and specifically through recently developed theorems on the solution of functionals constrained by inequalities. The solution is a set of optimal cumulative production trajectories which define the stagewise production rates. Analysis of these production rates reveals the optimal nuclear fuel cycle costs and that inventories (stockpiles) occur in uranium fields, enriched uranium hexafluoride, and fabricated fuel assemblies. An analysis of the sensitivity of the model to variation in three important parameters is performed

  3. Tumor Control Probability Modeling for Stereotactic Body Radiation Therapy of Early-Stage Lung Cancer Using Multiple Bio-physical Models

    Science.gov (United States)

    Liu, Feng; Tai, An; Lee, Percy; Biswas, Tithi; Ding, George X.; El Naqa, Isaam; Grimm, Jimm; Jackson, Andrew; Kong, Feng-Ming (Spring); LaCouture, Tamara; Loo, Billy; Miften, Moyed; Solberg, Timothy; Li, X Allen

    2017-01-01

    Purpose To analyze pooled clinical data using different radiobiological models and to understand the relationship between biologically effective dose (BED) and tumor control probability (TCP) for stereotactic body radiotherapy (SBRT) of early-stage non-small cell lung cancer (NSCLC). Method and Materials The clinical data of 1-, 2-, 3-, and 5-year actuarial or Kaplan-Meier TCP from 46 selected studies were collected for SBRT of NSCLC in the literature. The TCP data were separated for Stage T1 and T2 tumors if possible, otherwise collected for combined stages. BED was calculated at isocenters using six radiobiological models. For each model, the independent model parameters were determined from a fit to the TCP data using the least chi-square (χ2) method with either one set of parameters regardless of tumor stages or two sets for T1 and T2 tumors separately. Results The fits to the clinic data yield consistent results of large α/β ratios of about 20 Gy for all models investigated. The regrowth model that accounts for the tumor repopulation and heterogeneity leads to a better fit to the data, compared to other 5 models where the fits were indistinguishable between the models. The models based on the fitting parameters predict that the T2 tumors require about additional 1 Gy physical dose at isocenters per fraction (≤5 fractions) to achieve the optimal TCP when compared to the T1 tumors. Conclusion This systematic analysis of a large set of published clinical data using different radiobiological models shows that local TCP for SBRT of early-stage NSCLC has strong dependence on BED with large α/β ratios of about 20 Gy. The six models predict that a BED (calculated with α/β of 20) of 90 Gy is sufficient to achieve TCP ≥ 95%. Among the models considered, the regrowth model leads to a better fit to the clinical data. PMID:27871671

  4. Simplified model for end-stage liver disease score predicts mortality for tricuspid valve surgery†

    Science.gov (United States)

    Tsuda, Kazumasa; Koide, Masaaki; Kunii, Yoshifumi; Watanabe, Kazumasa; Miyairi, Satoshi; Ohashi, Yuko; Harada, Takashi

    2013-01-01

    OBJECTIVES The model for end-stage liver disease score (MELD = 3.8*LN[total bilirubin] + 9.6*LN[creatinine] + 11.2*[PT-INR] + 6.4) predicts mortality for tricuspid valve surgery. However, the MELD is problematic in patients undergoing warfarin therapy, as warfarin affects the international normalized ratio (INR). This study aimed to determine whether a simplified MELD score that does not require the INR for calculation could predict mortality for patients undergoing tricuspid valve surgery. Simplified MELD METHODS A total of 172 patients (male: 66, female: 106; mean age, 63.8 ± 10.3 years) who underwent tricuspid replacement (n = 18) or repair (n = 154) from January 1991 to July 2011 at a single centre were included. Of them, 168 patients in whom the simplified MELD score could be calculated were retrospectively analysed. The relationship between in-hospital mortality and perioperative variables was assessed by univariate and multivariate analysis. RESULTS The rate of in-hospital mortality was 6.4%. The mean admission simplified MELD score for the patients who died was significantly higher than for those surviving beyond discharge (11.3 ± 4.1 vs 5.8 ± 4.0; P = 0.001). By multivariate analysis, independent risk factors for in-hospital mortality included higher simplified MELD score (P = 0.001) and tricuspid valve replacement (P = 0.023). In-hospital mortality and morbidity increased along with increasing simplified MELD score. Scores 14 were associated with mortalities of 0, 2.0, 8.3 and 66.7%, respectively. The incidence of serious complications (multiple organ failure, P = 0.005; prolonged ventilation, P = 0.01; need for haemodialysis; P = 0.002) was also significantly higher in patients with simplified MELD score ≥7. CONCLUSIONS The simplified MELD score predicts mortality in patients undergoing tricuspid valve surgery. This model requires only total bilirubin and creatinine and is therefore applicable in patients undergoing warfarin therapy. PMID:23403770

  5. Bayesian analysis of log Gaussian Cox processes for disease mapping

    DEFF Research Database (Denmark)

    Benes, Viktor; Bodlák, Karel; Møller, Jesper

    We consider a data set of locations where people in Central Bohemia have been infected by tick-borne encephalitis, and where population census data and covariates concerning vegetation and altitude are available. The aims are to estimate the risk map of the disease and to study the dependence...... of the risk on the covariates. Instead of using the common area level approaches we consider a Bayesian analysis for a log Gaussian Cox point process with covariates. Posterior characteristics for a discretized version of the log Gaussian Cox process are computed using markov chain Monte Carlo methods...

  6. A Model to Predict the Use of Surgical Resection for Advanced-Stage Non-Small Cell Lung Cancer Patients.

    Science.gov (United States)

    David, Elizabeth A; Andersen, Stina W; Beckett, Laurel A; Melnikow, Joy; Kelly, Karen; Cooke, David T; Brown, Lisa M; Canter, Robert J

    2017-11-01

    For advanced-stage non-small cell lung cancer, chemotherapy and chemoradiotherapy are the primary treatments. Although surgical intervention in these patients is associated with improved survival, the effect of selection bias is poorly defined. Our objective was to characterize selection bias and identify potential surgical candidates by constructing a Surgical Selection Score (SSS). Patients with clinical stage IIIA, IIIB, or IV non-small cell lung cancer were identified in the National Cancer Data Base from 1998 to 2012. Logistic regression was used to develop the SSS based on clinical characteristics. Estimated area under the receiver operating characteristic curve was used to assess discrimination performance of the SSS. Kaplan-Meier analysis was used to compare patients with similar SSSs. We identified 300,572 patients with stage IIIA, IIIB, or IV non-small cell lung cancer without missing data; 6% (18,701) underwent surgical intervention. The surgical cohort was 57% stage IIIA (n = 10,650), 19% stage IIIB (n = 3,483), and 24% stage IV (n = 4,568). The areas under the receiver operating characteristic curve from the best-fit logistic regression model in the training and validation sets were not significantly different, at 0.83 (95% confidence interval, 0.82 to 0.83) and 0.83 (95% confidence interval, 0.82 to 0.83). The range of SSS is 43 to 1,141. As expected, SSS was a good predictor of survival. Within each quartile of SSS, patients in the surgical group had significantly longer survival than nonsurgical patients (p < 0.001). A prediction model for selection of patients for surgical intervention was created. Once validated and prospectively tested, this model may be used to identify patients who may benefit from surgical intervention. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  7. Hourly cooling load forecasting using time-indexed ARX models with two-stage weighted least squares regression

    International Nuclear Information System (INIS)

    Guo, Yin; Nazarian, Ehsan; Ko, Jeonghan; Rajurkar, Kamlakar

    2014-01-01

    Highlights: • Developed hourly-indexed ARX models for robust cooling-load forecasting. • Proposed a two-stage weighted least-squares regression approach. • Considered the effect of outliers as well as trend of cooling load and weather patterns. • Included higher order terms and day type patterns in the forecasting models. • Demonstrated better accuracy compared with some ARX and ANN models. - Abstract: This paper presents a robust hourly cooling-load forecasting method based on time-indexed autoregressive with exogenous inputs (ARX) models, in which the coefficients are estimated through a two-stage weighted least squares regression. The prediction method includes a combination of two separate time-indexed ARX models to improve prediction accuracy of the cooling load over different forecasting periods. The two-stage weighted least-squares regression approach in this study is robust to outliers and suitable for fast and adaptive coefficient estimation. The proposed method is tested on a large-scale central cooling system in an academic institution. The numerical case studies show the proposed prediction method performs better than some ANN and ARX forecasting models for the given test data set

  8. Deficiency in either COX-1 or COX-2 genes does not affect amyloid beta protein burden in amyloid precursor protein transgenic mice.

    Science.gov (United States)

    Park, Sun Ah; Chevallier, Nathalie; Tejwani, Karishma; Hung, Mary M; Maruyama, Hiroko; Golde, Todd E; Koo, Edward H

    2016-09-09

    Epidemiologic studies indicate that chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a lower risk for developing Alzheimer's disease (AD). Because the primary mode of action of NSAIDs is to inhibit cyclooxygenase (COX) activity, it has been proposed that perturbed activity of COX-1 or COX-2 contributes to AD pathogenesis. To test the role of COX-1 or COX-2 in amyloid deposition and amyloid-associated inflammatory changes, we examined amyloid precursor protein (APP) transgenic mice in the context of either COX-1 or COX-2 deficiency. Our studies showed that loss of either COX-1 or COX-2 gene did not alter amyloid burden in brains of the APP transgenic mice. However, one marker of microglial activation (CD45) was decreased in brains of COX-1 deficient/APP animals and showed a strong trend in reduction in COX-2 deficient/APP animals. These results suggest that COX activity and amyloid deposition in brain are likely independent processes. Further, if NSAIDs do causally reduce the risks of AD, then our findings indicate that the mechanisms are likely not due primarily to their inhibition on COX or γ-secretase modulation activity, the latter reported recently after acute dosing of ibuprofen in humans and nonhuman primates. Copyright © 2016. Published by Elsevier Inc.

  9. Hydrological and thermal effects of hydropeaking on early life stages of salmonids: A modelling approach for implementing mitigation strategies.

    Science.gov (United States)

    Casas-Mulet, Roser; Saltveit, Svein Jakob; Alfredsen, Knut Tore

    2016-12-15

    Alterations in hydrological and thermal regimes can potentially affect salmonid early life stages development and survival. The dewatering of salmon spawning redds due to hydropeaking can lead to mortality in early life stages, with higher impact on the alevins as they have lower tolerance to dewatering than the eggs. Flow-related mitigation measures can reduce early life stage mortality. We present a set of modelling tools to assess impacts and mitigation options to minimise the risk of mortality in early life stages in hydropeaking rivers. We successfully modelled long-term hydrological and thermal alterations and consequences for development rates. We estimated the risk of early life stages mortality and assessed the cost-effectiveness of implementing three release-related mitigation options (A,B,C). The economic cost of mitigation was low and ranged between 0.7% and 2.6% of the annual hydropower production. Options reducing the flow during spawning (B and C) in addition to only release minimum flows during development (A) were considered more effective for egg and alevin survival. Options B and C were however constraint by water availability in the system for certain years, and therefore only option A was always feasible. The set of modelling tools used in this study were satisfactory and their applications can be useful especially in systems where little field data is available. Targeted measures built on well-informed modelling tools can be tested on their effectiveness to mitigate dewatering effects vs. the hydropower system capacity to release or conserve water for power production. Environmental flow releases targeting specific ecological objectives can provide better cost-effective options than conventional operational rules complying with general legislation. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Multiple recent horizontal transfers of the cox1 intron in Solanaceae and extended co-conversion of flanking exons.

    Science.gov (United States)

    Sanchez-Puerta, Maria V; Abbona, Cinthia C; Zhuo, Shi; Tepe, Eric J; Bohs, Lynn; Olmstead, Richard G; Palmer, Jeffrey D

    2011-09-27

    -conversion suggests that other cox1 conversions may be longer than realized but obscured by the exceptional conservation of plant mitochondrial sequences. Our findings provide further support for the rampant-transfer model of cox1 intron evolution and recommend the Solanaceae as a model system for the experimental analysis of cox1 intron transfer in plants.

  11. Bootstrap-based methods for estimating standard errors in Cox's regression analyses of clustered event times.

    Science.gov (United States)

    Xiao, Yongling; Abrahamowicz, Michal

    2010-03-30

    We propose two bootstrap-based methods to correct the standard errors (SEs) from Cox's model for within-cluster correlation of right-censored event times. The cluster-bootstrap method resamples, with replacement, only the clusters, whereas the two-step bootstrap method resamples (i) the clusters, and (ii) individuals within each selected cluster, with replacement. In simulations, we evaluate both methods and compare them with the existing robust variance estimator and the shared gamma frailty model, which are available in statistical software packages. We simulate clustered event time data, with latent cluster-level random effects, which are ignored in the conventional Cox's model. For cluster-level covariates, both proposed bootstrap methods yield accurate SEs, and type I error rates, and acceptable coverage rates, regardless of the true random effects distribution, and avoid serious variance under-estimation by conventional Cox-based standard errors. However, the two-step bootstrap method over-estimates the variance for individual-level covariates. We also apply the proposed bootstrap methods to obtain confidence bands around flexible estimates of time-dependent effects in a real-life analysis of cluster event times.

  12. Standardizing acute toxicity data for use in ecotoxicology models: influence of test type, life stage, and concentration reporting.

    Science.gov (United States)

    Raimondo, Sandy; Vivian, Deborah N; Barron, Mace G

    2009-10-01

    Ecotoxicological models generally have large data requirements and are frequently based on existing information from diverse sources. Standardizing data for toxicological models may be necessary to reduce extraneous variation and to ensure models reflect intrinsic relationships. However, the extent to which data standardization is necessary remains unclear, particularly when data transformations are used in model development. An extensive acute toxicity database was compiled for aquatic species to comprehensively assess the variation associated with acute toxicity test type (e.g., flow-through, static), reporting concentrations as nominal or measured, and organism life stage. Three approaches were used to assess the influence of these factors on log-transformed acute toxicity: toxicity ratios, log-linear models of factor groups, and comparison of interspecies correlation estimation (ICE) models developed using either standardized test types or reported concentration type. In general, median ratios were generally less than 2.0, the slopes of log-linear models were approximately one for well-represented comparisons, and ICE models developed using data from standardized test types or reported concentrations did not differ substantially. These results indicate that standardizing test data by acute test type, reported concentration type, or life stage may not be critical for developing ecotoxicological models using large datasets of log-transformed values.

  13. An adaptive two-stage analog/regression model for probabilistic prediction of small-scale precipitation in France

    Directory of Open Access Journals (Sweden)

    J. Chardon

    2018-01-01

    Full Text Available Statistical downscaling models (SDMs are often used to produce local weather scenarios from large-scale atmospheric information. SDMs include transfer functions which are based on a statistical link identified from observations between local weather and a set of large-scale predictors. As physical processes driving surface weather vary in time, the most relevant predictors and the regression link are likely to vary in time too. This is well known for precipitation for instance and the link is thus often estimated after some seasonal stratification of the data. In this study, we present a two-stage analog/regression model where the regression link is estimated from atmospheric analogs of the current prediction day. Atmospheric analogs are identified from fields of geopotential heights at 1000 and 500 hPa. For the regression stage, two generalized linear models are further used to model the probability of precipitation occurrence and the distribution of non-zero precipitation amounts, respectively. The two-stage model is evaluated for the probabilistic prediction of small-scale precipitation over France. It noticeably improves the skill of the prediction for both precipitation occurrence and amount. As the analog days vary from one prediction day to another, the atmospheric predictors selected in the regression stage and the value of the corresponding regression coefficients can vary from one prediction day to another. The model allows thus for a day-to-day adaptive and tailored downscaling. It can also reveal specific predictors for peculiar and non-frequent weather configurations.

  14. Fractional Models Simulating Non-Fickian Behavior in Four-Stage Single-Well Push-Pull Tests

    Science.gov (United States)

    Chen, Kewei; Zhan, Hongbin; Yang, Qiang

    2017-11-01

    Four-stage single-well push-pull (SWPP) tracer tests, including injection, chasing, resting, and pumping, were conducted in a fractured aquifer at Newark basin. An anomalous transport phenomenon observed in the SWPP tests is the linear decline of breakthrough curves (BTCs) at late time with slope of -1.8 in log-log plots. A time-dependent fractional model is developed to interpret the anomalous transport behavior. This model considers a time-dependent power law memory function and a time-dependent fractional advection-dispersion operator. The fractional advection-dispersion equations (fADE) are solved in a radial coordinate system using the implicit Euler method. A semi-analytical solution of the first-order rate-limited mobile-immobile model (FORMIM) is derived for comparison. It is found that both the nonlocal transport in time and space can produce the long-tailed BTC. A smaller time-fractional or space-fractional index leads to a lower peak concentration and a larger late-time slope. The mass distribution of the fractional-in-space (FS) model exhibits power law decline at the leading plume edge. Early breakthrough during pumping is not observed because the mobile mass at the start of pumping is nonzero and more concentrated near the wellbore. The capacity ratio is an important factor that affects the peak concentration. A larger capacity ratio leads to greater peak concentration. A smaller time-fractional index in the injection, chasing, or resting stage will move the BTC downward and the slope of the late time BTC is determined by the space-fractional index over all stages and the time-fractional index in the pumping stage. The capability of the existing models to recover the BTC of the SWPP test is discussed and some guidelines for how to choose the appropriate model to interpret the SWPP test data are proposed.

  15. Comparative effectiveness of one-stage versus two-stage basilic vein transposition arteriovenous fistulas.

    Science.gov (United States)

    Ghaffarian, Amir A; Griffin, Claire L; Kraiss, Larry W; Sarfati, Mark R; Brooke, Benjamin S

    2018-02-01

    Basilic vein transposition (BVT) fistulas may be performed as either a one-stage or two-stage operation, although there is debate as to which technique is superior. This study was designed to evaluate the comparative clinical efficacy and cost-effectiveness of one-stage vs two-stage BVT. We identified all patients at a single large academic hospital who had undergone creation of either a one-stage or two-stage BVT between January 2007 and January 2015. Data evaluated included patient demographics, comorbidities, medication use, reasons for abandonment, and interventions performed to maintain patency. Costs were derived from the literature, and effectiveness was expressed in quality-adjusted life-years (QALYs). We analyzed primary and secondary functional patency outcomes as well as survival during follow-up between one-stage and two-stage BVT procedures using multivariate Cox proportional hazards models and Kaplan-Meier analysis with log-rank tests. The incremental cost-effectiveness ratio was used to determine cost savings. We identified 131 patients in whom 57 (44%) one-stage BVT and 74 (56%) two-stage BVT fistulas were created among 8 different vascular surgeons during the study period that each performed both procedures. There was no significant difference in the mean age, male gender, white race, diabetes, coronary disease, or medication profile among patients undergoing one- vs two-stage BVT. After fistula transposition, the median follow-up time was 8.3 months (interquartile range, 3-21 months). Primary patency rates of one-stage BVT were 56% at 12-month follow-up, whereas primary patency rates of two-stage BVT were 72% at 12-month follow-up. Patients undergoing two-stage BVT also had significantly higher rates of secondary functional patency at 12 months (57% for one-stage BVT vs 80% for two-stage BVT) and 24 months (44% for one-stage BVT vs 73% for two-stage BVT) of follow-up (P < .001 using log-rank test). However, there was no significant difference

  16. Immunohistochemical Expression of COX-2 in Uterine Serous Carcinoma Tissue

    Directory of Open Access Journals (Sweden)

    Joseph Menczer

    2016-03-01

    Material and methods. Cox-2 expression assessment by immunohistochemistry was performed on deparaffinized sections of paraffin-embedded tissue blocks of consecutive available USC uterine specimens of patients diagnosed from 2000 to 2014. Staining of more than 10% of the cells was considered positive. Staining intensity was graded on a 0 and ndash;3 scale. A scoring index was calculated by multiplying the intensity grade by the percentage of stained cells and considered low when it was equal to 1 or less and high when it was more than 1. Clinicopathological data were retrospectively abstracted from the records of the study group patients Results. The study comprised uterine specimens of 31 USC patients. Positive immunohistochemical staining was observed in 25 (80.6% USC specimens and a high score in 6 (19.4% of them. No association between immunohistochemical staining parameters and clinicopathological prognostic factors was observed. Conclusion. Although our findings should be verified in larger series, it seems that in view of the lack of association between immunohistochemical Cox-2 staining parameters in USC tissue and clinicopathological prognostic factors, this aggressive tumor is not a candidate for the use of selective Cox-2 inhibitors. Key words: Cox-2 expression, uterine carcinosarcoma, clinicopathological prognostic factors [J Interdiscipl Histopathol 2016; 4(1.000: 9-12

  17. Convergence of posteriors for discretized log Gaussian Cox processes

    DEFF Research Database (Denmark)

    Waagepetersen, Rasmus Plenge

    2004-01-01

    In Markov chain Monte Carlo posterior computation for log Gaussian Cox processes (LGCPs) a discretization of the continuously indexed Gaussian field is required. It is demonstrated that approximate posterior expectations computed from discretized LGCPs converge to the exact posterior expectations...... when the cell sizes of the discretization tends to zero. The effect of discretization is studied in a data example....

  18. CoX zeolites and their exchange with deuterium

    International Nuclear Information System (INIS)

    Novakova, J.; Kubelkova, L.; Jiru, P.

    1976-01-01

    An analysis of the gaseous phase using a mass spectrometer and analysis of the solid phase using an infrared spectrophotometer was made to investigate the deuterium exchange with hydrogen mostly bound in hydroxyl groups of zeolites CoX(21 and 47%) and NaX. It was found that with the increasing amount of cobalt ions the number of exchangeable hydrogens of the zeolite increases; the respective types of the hydrogen are discussed with respect to the particular dehydration temperatures. The rate of the D 2 +OH exchange is substantially faster with the CoX than with the NaX zeolite, and exhibits a decrease with increasing dehydration. On the other hand, the rate of D 2 +H 2 exchange without zeolite hydrogen incorporation, catalyzed by CoX zeolites, increases with increasing dehydration. The increased activation of gaseous hydrogen molecules is related to the presence in the zeolite of cobalt ions whose properties change during dehydration with the change in their environment. Hydroxyl groups of the CoX zeolites are not equivalent during the exchange; the hydroxyl hydrogens of the 3740 cm -1 band are exchanged more slowly than are the other hydrogens. (author)

  19. Intravenous glutamine enhances COX-2 activity giving cardioprotection.

    LENUS (Irish Health Repository)

    McGuinness, Jonathan

    2009-03-01

    Preconditioning, a highly evolutionary conserved endogenous protective response, provides the most powerful form of anti-infarct protection known. We investigated whether acute intravenous glutamine, through an effect on cyclooxygenase (COX)-2 and heat shock protein (HSP) 72, might induce preconditioning.

  20. Monitoring the censored lognormal reliability data in a three-stage process using AFT model

    Science.gov (United States)

    Goodarzi, Azam; Amiri, Amirhossein; Asadzadeh, Shervin

    2017-09-01

    Improving the product reliability is the main concern in both manufacturing and service processes which is obtained by monitoring the reliability-related quality characteristics. Nowadays, products or services are the result of processes with dependent stages referred to as multistage processes. In these processes, the quality characteristic in each stage is affected by the quality characteristic in the previous stages known as cascade property. Two regression-adjusted control schemes are applied to monitor the output quality variables of interest. Moreover, censoring is among the main limitations while monitoring the reliability-related quality characteristics, causing not to record the real values of some observations. Hence, the right censored observations are used to extend monitoring schemes under both the fixed- and variable-competing risks. In this paper, the accelerated failure time (AFT) is used to relate the reliability-related quality characteristic with lognormal distribution to the incoming variables. Then, two cause-selecting control charts are developed to monitor outgoing quality variables when censoring happens in each reliability-related stage. The performance of the control charts is evaluated and compared through extensive simulation studies under the censored and non-censored scenarios.

  1. A Theoretical Model for the Four-Stage Music-Industry Internship Program.

    Science.gov (United States)

    Schenbeck, Lyn

    1996-01-01

    Describes student development through experiential learning in a four-stage internship within a college music-industry curriculum, and uses the Steinaker-Bell experiential taxonomy to show how embedding a multistage internship throughout the curriculum, rather than at the end, greatly enhances learning. Suggests ways in which the multistage…

  2. Terminal-stage prognostic analysis in candidemia.

    Science.gov (United States)

    Takuma, Takahiro; Shoji, Hisashi; Niki, Yoshihito

    2015-05-01

    Candidemia has an extremely high mortality rate but is not always the direct cause of death. Therefore, determining the effect of candidemia on death is extremely difficult. We investigated prognostic factors in patients with culture-proven candidemia at 2 Japanese university teaching hospitals from April 2009 through May 2013. To examine the effects of comorbid conditions, the Charlson comorbidity index was determined, and patients were subjectively classified into 3 clinical prognostic stages (terminal [death expected within 1 month], semiterminal [death expected within 6 months], and nonterminal [expected to live more than 6 months]). The Cox proportional hazard model was used for univariate and multivariate analyses of factors possibly affecting survival. On univariate analysis, factors identified as associated with an increased mortality rate were: admission to an internal medicine department, Candida glabrata, immunosuppression, hypotension, hypoxemia, and a terminal prognostic stage. Factors associated with a decreased mortality rate were: serum albumin, endophthalmitis investigation, and nonterminal prognostic stage. The mortality rate was significantly related to the prognostic stage on multivariate analysis (P candidemia. More important than candidemia in causing the deaths of patients with candidemia were the patients' background and comorbidity status. Therefore, rigorous methods should be used when investigating causes of death in terminally ill patients with candidemia. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  3. THE 7 STAGE MODEL FOR FACILITATING MORAL CASE DELIBERATION IN HEALTH-CARE INSTITUTIONS: A PRACTICAL ILLUSTRATION OF A META-MODEL.

    Science.gov (United States)

    de Bree, Menno; Veening, Eite

    2016-01-01

    During a moral case deliberation-session, health care professionals come together in order to reflect on a moral issue they have to deal with. Since the whole process of sorting facts out, identifying moral issues, formulating and weighing arguments et cetera, can be quite complex, there should always be a well-trained facilitator present, who safeguards the flow of the session. In order to train and to assess the quality of these facilitators, we developed the so-called 7 stage model of moral case deliberation. This model is a meta-model, describing all the stages and all the activities that take place during each mcd-session--regardless of variables like the type of case that is being discussed, the number of participants, or the reflection method that is being applied. These 7 stages are: introduction, case selection, method selection, factual exploration, analysis, conclusion and rounding off. The model makes it possible to describe all the tasks facilitators at least have to perform in order to steer their group through theses stages in a fruitful and efficient way. It also makes it possible to identify the minimum generic competencies each facilitator should master, in order to perform these tasks successfully. In this paper, we introduce the model (to our knowledge, the first of its kind), discuss some of the most important theoretical backgrounds, provide a theoretical justification, and above all, give a practical illustration of how the model can be applied when facilitating an mcd-session.

  4. Harvesting policy for a delayed stage-structured Holling II predator-prey model with impulsive stocking prey

    International Nuclear Information System (INIS)

    Jiao Jianjun; Meng Xinzhu; Chen Lansun

    2009-01-01

    A predator-prey model with a stage structure for the predator, which improves the assumption that each individual predator has the same ability to capture prey, is proposed by Wang et al. [Wang W, Mulone G, Salemi F, Salone V. Permanence and stability of a stage-structured predator-prey model. J Math Anal Appl 2001;262:499-528]. It is assumed that immature individuals and mature individuals of the predator are divided by a fixed age and that immature predators do not have the ability to attack prey. We do economic management behavior for Wang model [Wang et al., 2001] by continuous harvesting on predator and impulsive stocking on prey. Then, a delayed stage-structured Holling type II predator-prey model with impulsive stocking prey and continuous harvesting predator is established. It is also assumed that the predating products of the predator is only to increase its bearing ability. We obtain the sufficient conditions of the global attractivity of predator-extinction boundary periodic solution and the permanence of the system. Our results show that the behavior of impulsive stocking prey plays an important role for the permanence of the system, and provide tactical basis for the biological resource management. Further, the numerical analysis is also inserted to illuminate the dynamics of the system.

  5. Can metabolic tumor parameters on primary staging18F-FDG PET/CT aid in risk stratification of primary central nervous system lymphomas for patient management as a prognostic model?

    Science.gov (United States)

    Okuyucu, K; Alagoz, E; Ince, S; Ozaydin, S; Arslan, N

    Primary central nervous system (CNS) lymphoma is an aggressive and fatal extranodal non-Hodgkin lymphoma jailed in CNS at initial diagnosis. Its prognosis is poor and the disease has a fatal outcome when compared with systemic non-Hodgkin lymphoma. A few baseline risk stratification scoring systems have been suggested to estimate the prognosis mainly based on serum lactate dehydrogenase level,age, Karnofsky performance score, involvement of deep brain structures and cerebrospinal fluid protein concentration. 18 F-FDG PET/CT has a high prognostic value with respect to overall survival and disease-free survival in many cancers and lymphomas. We aimed to investigate metabolic tumor indexes on primary staging 18 F-FDG PET/CT as prognostic markers in primary CNS lymphoma. Fourteen patients with primary CNS diffuse large B-cell lymphoma (stage i) were enrolled in this retrospective cohort study. Primary staging 18 F-FDG PET/CT was performed and quantitative parameters like maximum standardized uptake value, average standardized uptake value, metabolic tumor volume and total lesion glycolysis (TLG) were calculated for all patients before the treatment. Cox regression models were performed to determine their relation with survival time. In the evaluation of all potential risk factors impacting recurrence/metastases (age, sex, serum lactate dehydrogenase, involvement of deep brain structures, maximum standardized uptake value, average standardized uptake value, metabolic tumor volume, and TLG) with univariate analysis, TLG remained statistically significant (P=.02). Metabolic tumor parameters are useful in prognosis estimation of primary CNS lymphomas, especially TLG, which is the most important one and may play a role in patient management. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  6. Enhancing the Predicting Accuracy of the Water Stage Using a Physical-Based Model and an Artificial Neural Network-Genetic Algorithm in a River System

    Directory of Open Access Journals (Sweden)

    Wen-Cheng Liu

    2014-06-01

    Full Text Available Accurate simulations of river stages during typhoon events are critically important for flood control and are necessary for disaster prevention and water resources management in Taiwan. This study applies two artificial neural network (ANN models, including the back propagation neural network (BPNN and genetic algorithm neural network (GANN techniques, to improve predictions from a one-dimensional flood routing hydrodynamic model regarding the water stages during typhoon events in the Danshuei River system in northern Taiwan. The hydrodynamic model is driven by freshwater discharges at the upstream boundary conditions and by the water levels at the downstream boundary condition. The model provides a sound physical basis for simulating water stages along the river. The simulated results of the hydrodynamic model show that the model cannot reproduce the water stages at different stations during typhoon events for the model calibration and verification phases. The BPNN and GANN models can improve the simulated water stages compared with the performance of the hydrodynamic model. The GANN model satisfactorily predicts water stages during the training and verification phases and exhibits the lowest values of mean absolute error, root-mean-square error and peak error compared with the simulated results at different stations using the hydrodynamic model and the BPNN model. Comparison of the simulated results shows that the GANN model can be successfully applied to predict the water stages of the Danshuei River system during typhoon events.

  7. Synthesis, anti-inflammatory screening, molecular docking, and COX-1,2/-5-LOX inhibition profile of some novel quinoline derivatives.

    Science.gov (United States)

    Chaaban, Ibrahim; Rizk, Ola H; Ibrahim, Tamer M; Henen, Shery S; El-Khawass, El-Sayeda M; Bayad, Aida E; El-Ashmawy, Ibrahim M; Nematalla, Hisham A

    2018-03-20

    New quinoline compounds comprising pyrazole scaffold through different amide linkages were synthesized. The synthesized compounds were evaluated for their anti-inflammatory activity. Eight compounds (5c, 11b,c, 12c, 14a,b, 20a and 21a) were found to exhibit promising anti-inflammatory profiles in acute and sub-acute inflammatory models. They were screened for their ulcerogenic activity and none of them showed significant ulcerogenic activity comparable to the reference drug celecoxib and are well tolerated by experimental animals with high safety margin (ALD 50  > 0.3 g/kg). Compounds 5c, 11b,c, 12c, 14a,b, 20a and 21a showed significant in vitro LOX inhibitory activity higher than that of zileuton. In vitro COX-1/COX-2 inhibition study revealed that compounds 12c, 14a,b and 20a showed higher selectivity towards COX-2 than COX-1. Among the tested compounds, 12c, 14a and 14b showed the highest inhibitory activity against COX-2 with an IC 50 values of 0.1, 0.11 and 0.11 μM respectively. The docking experiments attempted to postulate the binding mode for the most active compounds in the binding site of COX-2 enzymes and confirmed the high selectivity binding towards COX-2 enzyme over COX-1. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Correlations of IGF-1R and COX-2 Expressions with Ras and BRAF Genetic Mutations, Clinicopathological Features and Prognosis of Colorectal Cancer Patients.

    Science.gov (United States)

    Jin, Mei; Long, Zi-Wen; Yang, Jing; Lin, Xiang

    2018-01-01

    This case-control study aims to investigate the correlations of insulin-like growth factor receptor 1 (IGF-1R) and cyclooxygenase 2 (COX-2) expressions with Ras and BRAF genetic mutations, clinicopathological features and prognosis of colorectal cancer (CRC) patients. A total of 213 CRC patients (case group) and 200 healthy individuals (control group) were selected from our hospital. Ras (K-Ras/N-Ras) and BRAF genetic mutations were detected by direct sequencing. The positive expression rates of IGF-IR and COX-2 in CRC and normal tissues were detected using immunohistochemistry. RT-qPCR and Western blotting were applied to detect the mRNA and protein expressions of IGF-IR and COX-2 in CRC tissues and normal tissues. Total mutation rate of N-Ras, BRAF and K-Ras in case group were 5.2%, 12.2% and 47.4%, respectively. The expressions of IGF-IR and COX-2 were higher in CRC tissues with Ras and BRAF mutations than in those without. CRC tissues with Ras mutation showed higher COX-2 expression than those with BRAF mutation. IGF-IR and COX-2 expressions were correlated to infiltration degree, lymphatic metastasis (in CRC tissues with and without Ras and BRAF mutations), and Dukes stages (only in CRC tissues with Ras and BRAF mutations). CRC patients with negative expressions of IGF-IR and COX-2 had significantly higher accumulative survival rate and longer mean survival duration than those with positive expressions of IGF-IR and COX-2. These findings indicate that IGF-1R and COX-2 expressions may be associated with Ras and BRAF genetic mutations, clinicopathological feature and prognosis of CRC patients.

  9. Relationships between transtheoretical model stages of change, decisional balance, self-efficacy, and physical activity level among Nigerian market vendors.

    Science.gov (United States)

    Maruf, Fatai Adesina; Ibikunle, Peter Olanrewaju; Raji, Najim Olanrewaju

    2014-01-01

    This study explored decisional balance, self-efficacy, and physical activity (PA) level in relation to stages of change (SoC) for PA among Nigerian vendors. The study explored associations among decisional balance, self-efficacy, and PA level, and examined differences, by stage, in decisional balance, self-efficacy, and PA level. Cross-sectional survey. Outdoor markets located in Eke Amobi, Nkwo, and Okpuno Egbu in Nnewi, southeastern Nigeria. Participants were 499 market vendors (98 males and 401 females). Self-efficacy, perceived barrier and benefit, PA level, and SoC for PA. Spearman rank-order and partial correlations; analysis of variance by gender with Bonferroni post hoc adjustment. Self-efficacy (r = 0.69; p = 0.000), perceived benefit (r = .12; p = .007), and perceived barrier (r = -.11; p = .017) for PA were related to the SoC. Adjusting for age, gender, and marital status, only self-efficacy (r = .48; p = .000) remained correlated with the SoC. In males, significant differences in perceived barrier (p = .003) and benefit (p = .003) lay between stages of contemplation and preparation and between stages of precontemplation and contemplation for self-efficacy (p = .006). In females, there were significance differences in self-efficacy across stages of precontemplation and contemplation (p = .000) and preparation and action (p = .007). When designing PA interventions, age, gender, and marital status should be considered in explaining the relationships between outcome constructs of transtheoretical model (TTM) and SoC in vendors. It is also important to note that the stages at which outcome constructs of TTM change during PA interventions vary in males and females.

  10. Mathematical modeling of the heat treatment and combustion of a coal particle. IV. Ignition stage

    Science.gov (United States)

    Enkhjargal, Kh.; Salomatov, V. V.

    2011-07-01

    The present paper is the continuation of the previous publications of the present authors in the Journal of Engineering Physics under the general title in which three sequential stages of the thermal preparation of a carbon particle for combustion are considered: heating, drying, and the yield of volatiles. The present paper is devoted to a detailed investigation of the stage of ignition of a carbon particle under the conditions of external radiative-convective supply that most adequately reflects the furnace medium. The characteristics of thermal ignition of a carbon matrix were studied with the aid of the adiabatic method. Such parameters as time and the heating temperature, the time of induction, the total time and the temperature of ignition of a carbon particle, the scale temperature, etc. have been found. The degree of dependence of the time of ignition on the initial temperature of the particle, the temperature of the external medium, heat transfer coefficient, and other inlet data has been analyzed.

  11. Modelling of an air-cooled two-stage Rankine cycle for electricity production

    International Nuclear Information System (INIS)

    Liu, Bo

    2014-01-01

    This work considers a two stage Rankine cycle architecture slightly different from a standard Rankine cycle for electricity generation. Instead of expanding the steam to extremely low pressure, the vapor leaves the turbine at a higher pressure then having a much smaller specific volume. It is thus possible to greatly reduce the size of the steam turbine. The remaining energy is recovered by a bottoming cycle using a working fluid which has a much higher density than the water steam. Thus, the turbines and heat exchangers are more compact; the turbine exhaust velocity loss is lower. This configuration enables to largely reduce the global size of the steam water turbine and facilitate the use of a dry cooling system. The main advantage of such an air cooled two stage Rankine cycle is the possibility to choose the installation site of a large or medium power plant without the need of a large and constantly available water source; in addition, as compared to water cooled cycles, the risk regarding future operations is reduced (climate conditions may affect water availability or temperature, and imply changes in the water supply regulatory rules). The concept has been investigated by EDF R and D. A 22 MW prototype was developed in the 1970's using ammonia as the working fluid of the bottoming cycle for its high density and high latent heat. However, this fluid is toxic. In order to search more suitable working fluids for the two stage Rankine cycle application and to identify the optimal cycle configuration, we have established a working fluid selection methodology. Some potential candidates have been identified. We have evaluated the performances of the two stage Rankine cycles operating with different working fluids in both design and off design conditions. For the most acceptable working fluids, components of the cycle have been sized. The power plant concept can then be evaluated on a life cycle cost basis. (author)

  12. Modelling quality of fresh-cut tomato based on stage of maturity and storage conditions

    OpenAIRE

    Moreira Lana, M.

    2005-01-01

    Fresh-cut or minimally processed vegetables are those which have been trimmed and/or peeled and/or cut into 100% usable product and still maintain freshness. Contrary to other processing methods (freezing, canning and drying for example) the minimal processing operations reduce the shelf life in relation to the raw material (intact product).In this thesis the changes in quality of tomato fruits after cutting into transversal slices were analysed and quantified in relation to the stage of matu...

  13. Two-stage Lagrangian modeling of ignition processes in ignition quality tester and constant volume combustion chambers

    KAUST Repository

    Alfazazi, Adamu

    2016-08-10

    The ignition characteristics of isooctane and n-heptane in an ignition quality tester (IQT) were simulated using a two-stage Lagrangian (TSL) model, which is a zero-dimensional (0-D) reactor network method. The TSL model was also used to simulate the ignition delay of n-dodecane and n-heptane in a constant volume combustion chamber (CVCC), which is archived in the engine combustion network (ECN) library (http://www.ca.sandia.gov/ecn). A detailed chemical kinetic model for gasoline surrogates from the Lawrence Livermore National Laboratory (LLNL) was utilized for the simulation of n-heptane and isooctane. Additional simulations were performed using an optimized gasoline surrogate mechanism from RWTH Aachen University. Validations of the simulated data were also performed with experimental results from an IQT at KAUST. For simulation of n-dodecane in the CVCC, two n-dodecane kinetic models from the literature were utilized. The primary aim of this study is to test the ability of TSL to replicate ignition timings in the IQT and the CVCC. The agreement between the model and the experiment is acceptable except for isooctane in the IQT and n-heptane and n-dodecane in the CVCC. The ability of the simulations to replicate observable trends in ignition delay times with regard to changes in ambient temperature and pressure allows the model to provide insights into the reactions contributing towards ignition. Thus, the TSL model was further employed to investigate the physical and chemical processes responsible for controlling the overall ignition under various conditions. The effects of exothermicity, ambient pressure, and ambient oxygen concentration on first stage ignition were also studied. Increasing ambient pressure and oxygen concentration was found to shorten the overall ignition delay time, but does not affect the timing of the first stage ignition. Additionally, the temperature at the end of the first stage ignition was found to increase at higher ambient pressure

  14. A two-stage flow-based intrusion detection model for next-generation networks.

    Science.gov (United States)

    Umer, Muhammad Fahad; Sher, Muhammad; Bi, Yaxin

    2018-01-01

    The next-generation network provides state-of-the-art access-independent services over converged mobile and fixed networks. Security in the converged network environment is a major challenge. Traditional packet and protocol-based intrusion detection techniques cannot be used in next-generation networks due to slow throughput, low accuracy and their inability to inspect encrypted payload. An alternative solution for protection of next-generation networks is to use network flow records for detection of malicious activity in the network traffic. The network flow records are independent of access networks and user applications. In this paper, we propose a two-stage flow-based intrusion detection system for next-generation networks. The first stage uses an enhanced unsupervised one-class support vector machine which separates malicious flows from normal network traffic. The second stage uses a self-organizing map which automatically groups malicious flows into different alert clusters. We validated the proposed approach on two flow-based datasets and obtained promising results.

  15. Introduction of β-d-mannuronic acid (M2000) as a novel NSAID with immunosuppressive property based on COX-1/COX-2 activity and gene expression.

    Science.gov (United States)

    Mirshafiey, Abbas; Taeb, Mahsa; Mortazavi-Jahromi, Seyed Shahabeddin; Jafarnezhad-Ansariha, Fahimeh; Rehm, Bernd H A; Esposito, Emanuela; Cuzzocrea, Salvatore; Matsuo, Hidenori

    2017-10-01

    The NSAIDs which inhibit the cyclooxygenase (COX) enzymes are among medications widely used to treat pain and inflammation. These drugs cause digestive complications resulting in inhibition of the COX-1 enzyme, while the inhibition of the COX-2 enzyme has therapeutic effects. Therefore research focuses on the production of medications that specifically inhibit the COX-2 enzyme. This study aimed to study the effects of β-d-mannuronic (M2000) acid on the gene expression and activity of COX-1/COX-2 enzymes in order to introduce a novel NSAID for treating inflammatory diseases. The mRNA expression levels of COXs were analyzed with qRT-PCR. Prostaglandin E 2 (PGE 2 ) concentration in culture media was determined using ELISA method. Our results indicated that the M2000 at low and high dose could significantly reduce the gene expression level of COX-2 compared to the LPS group (pCOX-1 compared to the LPS group. Moreover, it was noticed that this drug strongly and significantly reduced the activity of COX-1/COX-2 enzymes at the three concentrations of 5, 50 and 500 mMol/ml compared to the LPS and arachidonic acid groups (pCOX-1/COX-2 enzymes, with suppressing the gene expression of COX-2 specifically. Therefore, based on gene expression findings this drug might be categorized and introduced as a novel NSAID with selective COX-2 inhibitory effect. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  16. A Predictive Model of Multi-Stage Production Planning for Fixed Time Orders

    Directory of Open Access Journals (Sweden)

    Kozłowski Edward

    2014-09-01

    Full Text Available The traditional production planning model based upon a deterministic approach is well described in the literature. Due to the uncertain nature of manufacturing processes, such model can however incorrectly represent actual situations on the shop floor. This study develops a mathematical modeling framework for generating production plans in a multistage manufacturing process. The devised model takes into account the stochastic model for predicting the occurrence of faulty products. The aim of the control model is to determine the number of products which should be manufactured in each planning period to minimize both manufacturing costs and potential financial penalties for failing to fulfill the order completely.

  17. A Measure of Common Variables Associated with Career Stages as Perceived by Principals and Teachers: Validation of a Model for Career Development.

    Science.gov (United States)

    DeMoulin, Donald F.; Guyton, John W.

    This pilot study sought to establish validity of a teacher career development model based on results from previous research which had isolated a series of career stages and several characteristics of each stage. The model was constructed to identify characteristics associated with effective and ineffective transfer of knowledge from teacher to…

  18. A reliability model of the Angra 1 power system by the device of stages optimized by genetic algorithms

    International Nuclear Information System (INIS)

    Crossetti, Patricia Guimaraes

    2006-01-01

    This thesis proposes a probabilistic model to perform the reliability analysis of nuclear power plant systems under aging. This work analyses the Angra 1 power system. Systems subject to aging consist of components whose failure rates are not all constant, thus generating Non-Markovian models. Genetic algorithms were used for optimizing the application of the device of stages. Two approaches were used in the optimization, MCEF and MCEV. The results obtained for the Angra 1 power system show that the probability of a station blackout is negligible. (author)

  19. The Application of CPA to Calculations of the Mean Magnetic Moment in the Gd1-xNi, Gd1-xFe, Gd1xCox, and Y1-xCox Intermetallic Compounds

    DEFF Research Database (Denmark)

    Szpunar, B.; Kozarzewski, B.

    1977-01-01

    with a narrow d-band is considered. The magnetic moment of the alloy at zero temperature is calculated within the molecular field and Hartree-Fock approximations. Disorder is treated in the coherent potential approximation. Results are in good agreement with the experimental data obtained for the crystalline......Calculations are made of the mean magnetic moment per atom of the transition metal and the rare-earth metal in the intermetallic compounds, Gd1-x,Nix, Gd1-x Fex, Gd1-x Cox, and Y1-x Cox. A simple model of the disordered alloy consisting of spins localized on the rare-earth atoms and interacting...

  20. Food Polyphenols Fail to Cause a Biologically Relevant Reduction of COX-2 Activity.

    Directory of Open Access Journals (Sweden)

    Ina Willenberg

    Full Text Available Epidemiologic studies show a correlation between the dietary intake of food polyphenols and beneficial health effects. Several in vitro studies indicate that the anti-inflammatory potential of polyphenols is, at least in part, mediated by a modulation of the enzymes of the arachidonic acid cascade, such as the prostaglandin forming cyclooxygenases (COXs. Evidence that this mode of action can be transferred to the situation in vivo is scarce. This study characterized effects of a subset of polyphenols on COX-2 expression and activity in vitro and compared the potency with known drugs. Next, the in vivo relevance of the observed in vitro effects was tested. Enzyme assays and incubations of polyphenols with the cancer cell line HCA-7 and lipopolysaccharide (LPS stimulated primary monocytes support the hypothesis that polyphenols can effect COX-2 expression and activity in vitro. The effects were most pronounced in the monocyte assay for wogonin, apigenin, resveratrol and genistein with IC50 values of 1.5 μM, 2.6 μM, 2.8 μM and 7.4 μM. However, these values are 100- to 1000-fold higher in comparison to those of the known pharmaceuticals celecoxib, indomethacin and dexamethasone. In an animal model of LPS induced sepsis, pretreatment with polyphenols (i. p. 100 mg/kg bw did not result in decreased plasma or tissue prostaglandin levels, whereas the positive control celecoxib effectively attenuated LPS induced prostaglandin formation. These data suggest that despite the moderate potency in vitro, an effect of polyphenols on COX-2 during acute inflammation is unlikely, even if a high dose of polyphenols is ingested.

  1. COX-2 Protects against Atherosclerosis Independently of Local Vascular Prostacyclin: Identification of COX-2 Associated Pathways Implicate Rgl1 and Lymphocyte Networks

    Science.gov (United States)

    Kirkby, Nicholas S.; Lundberg, Martina H.; Wright, William R.; Warner, Timothy D.; Paul-Clark, Mark J.; Mitchell, Jane A.

    2014-01-01

    Cyxlo-oxygenase (COX)-2 inhibitors, including traditional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with increased cardiovascular side effects, including myocardial infarction. We and others have shown that COX-1 and not COX-2 drives vascular prostacyclin in the healthy cardiovascular system, re-opening the question of how COX-2 might regulate cardiovascular health. In diseased, atherosclerotic vessels, the relative contribution of COX-2 to prostacyclin formation is not clear. Here we have used apoE−/−/COX-2−/− mice to show that, whilst COX-2 profoundly limits atherosclerosis, this protection is independent of local prostacyclin release. These data further illustrate the need to look for new explanations, targets and pathways to define the COX/NSAID/cardiovascular risk axis. Gene expression profiles in tissues from apoE−/−/COX-2−/− mice showed increased lymphocyte pathways that were validated by showing increased T-lymphocytes in plaques and elevated plasma Th1-type cytokines. In addition, we identified a novel target gene, rgl1, whose expression was strongly reduced by COX-2 deletion across all examined tissues. This study is the first to demonstrate that COX-2 protects vessels against atherosclerotic lesions independently of local vascular prostacyclin and uses systems biology approaches to identify new mechanisms relevant to development of next generation NSAIDs. PMID:24887395

  2. Stage-structured matrix models for organisms with non-geometric development times

    Science.gov (United States)

    Andrew Birt; Richard M. Feldman; David M. Cairns; Robert N. Coulson; Maria Tchakerian; Weimin Xi; James M. Guldin

    2009-01-01

    Matrix models have been used to model population growth of organisms for many decades. They are popular because of both their conceptual simplicity and their computational efficiency. For some types of organisms they are relatively accurate in predicting population growth; however, for others the matrix approach does not adequately model...

  3. COX-2 Inhibitors for Cancer Treatment in Dogs

    Directory of Open Access Journals (Sweden)

    Andrigo Barboza De Nardi*, Talita Mariana Morata Raposo1, Rafael Ricardo Huppes1, Carlos Roberto Daleck2 and Renée Laufer Amorim3

    2011-10-01

    Full Text Available Cancer is one of the main causes of death in canines and felines, and this fact is probably related to the increase in the longevity of these species. The longer the animals live, the higher the exposure to carcinogenic agents will be. With the high incidence of cancer in companion animals, new studies are currently being performed with the aim of finding therapeutic options which make the complete inhibition of the development of neoplasms in animals possible in the future. The correlation of cyclooxygenase-2 (COX-2 whith the development of cancer opens the way for the use of new therapeutic approaches. This relationship has been suggested based on various studies which established an association between the chronic use of nonsteroidal anti-inflammatory drugs (NSAID and a decrease in the incidence of colon carcinoma. As cancer progresses, COX-2 participates in the arachidonic acid metabolism by synthesizing prostaglandins which can mediate various mechanisms related to cancer development such as: increase in angiogenesis, inhibition of apoptosis, suppression of the immune response, acquisition of greater invasion capacity and metastasis. Accordingly, overexpression of this enzyme in tumors has been associated with the most aggressive, poor-prognosis cancer types, especially carcinomas. Therefore, treatments which use COX-2 inhibitors such as coxibs, whether administered as single agents or in combination with conventional antineoplastic chemotherapy, are an alternative for extending the survival of our cancer patients.

  4. Estimating radiation-induced cancer risk using MVK two-stage model for carcinogenesis

    International Nuclear Information System (INIS)

    Kai, M.; Kusama, T.; Aoki, Y.

    1993-01-01

    Based on the carcinogenesis model as proposed by Moolgavkar et al., time-dependent relative risk models were derived for projecting the time variation in excess relative risk. If it is assumed that each process is described by time-independent linear dose-response relationship, the time variation in excess relative risk is influenced by the parameter related with the promotion process. The risk model based carcinogenesis theory would play a marked role in estimating radiation-induced cancer risk in constructing a projection model or transfer model

  5. Two-stage Bayesian model to evaluate the effect of air pollution on chronic respiratory diseases using drug prescriptions.

    Science.gov (United States)

    Blangiardo, Marta; Finazzi, Francesco; Cameletti, Michela

    2016-08-01

    Exposure to high levels of air pollutant concentration is known to be associated with respiratory problems which can translate into higher morbidity and mortality rates. The link between air pollution and population health has mainly been assessed considering air quality and hospitalisation or mortality data. However, this approach limits the analysis to individuals characterised by severe conditions. In this paper we evaluate the link between air pollution and respiratory diseases using general practice drug prescriptions for chronic respiratory diseases, which allow to draw conclusions based on the general population. We propose a two-stage statistical approach: in the first stage we specify a space-time model to estimate the monthly NO2 concentration integrating several data sources characterised by different spatio-temporal resolution; in the second stage we link the concentration to the β2-agonists prescribed monthly by general practices in England and we model the prescription rates through a small area approach. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Mathematical modeling of the heat treatment and combustion of a coal particle. V. Burn-up stage

    Science.gov (United States)

    Enkhjargal, Kh.; Salomatov, V. V.

    2011-07-01

    The present material is a sequel of the previous publications of the authors in this journal under a common title in which by means of mathematical modeling the sequential stages of the process of combustion of coal fuels have been obtained: heating, drying, escape of volatiles, and ignition. Mathematical models of the final stage of combustion of an individual particle — the burn-up stage — have been formulated. On the basis of the solution methods for nonlinear boundary-value problems developed by us, approximate-analytic formulas for two characteristic regimes, burn-up simultaneously with the evaporation of the remaining moisture and burn-up of the completely dried coke residue, have been obtained. The previous history of the physical and chemical phenomena in the general burning pattern is taken into account. The influence of the ash shell on the duration of combustion has been extimated. Comparison of calculations by the obtained dependences with the results of other authors has been made. It showed an accuracy sufficient for engineering applications.

  7. A manufacturing quality assessment model based-on two stages interval type-2 fuzzy logic

    Science.gov (United States)

    Purnomo, Muhammad Ridwan Andi; Helmi Shintya Dewi, Intan

    2016-01-01

    This paper presents the development of an assessment models for manufacturing quality using Interval Type-2 Fuzzy Logic (IT2-FL). The proposed model is developed based on one of building block in sustainable supply chain management (SSCM), which is benefit of SCM, and focuses more on quality. The proposed model can be used to predict the quality level of production chain in a company. The quality of production will affect to the quality of product. Practically, quality of production is unique for every type of production system. Hence, experts opinion will play major role in developing the assessment model. The model will become more complicated when the data contains ambiguity and uncertainty. In this study, IT2-FL is used to model the ambiguity and uncertainty. A case study taken from a company in Yogyakarta shows that the proposed manufacturing quality assessment model can work well in determining the quality level of production.

  8. Dynamic modelling of a one-stage spur gear system and vibration-based tooth crack detection analysis

    Science.gov (United States)

    Mohammed, Omar D.; Rantatalo, Matti; Aidanpää, Jan-Olov

    2015-03-01

    For the purpose of simulation and vibration-based condition monitoring of a geared system, it is important to model the system with an appropriate number of degrees of freedom (DOF). In earlier papers several models were suggested and it is therefore of interest to evaluate their limitations. In the present study a 12 DOF gear dynamic model including a gyroscopic effect was developed and the equations of motions were derived. A one-stage reduction gear was modelled using three different dynamic models (with 6, 8 and 8 reduced to 6 DOF), as well as the developed model (with 12 DOF), which is referred as the fourth model in this paper. The time-varying mesh stiffness was calculated, and dynamic simulation was then performed for different crack sizes. Time domain scalar indicators (the RMS, kurtosis and the crest factor) were applied for fault detection analysis. The results of the first model show a clearly visible difference from those of the other studied models, which were made more realistic by including two more DOF to describe the motor and load. Both the symmetric and the asymmetric disc cases were studied using the fourth model. In the case of disc symmetry, the results of the obtained response are close to those obtained from both the second and third models. Furthermore, the second model showed a slight influence from inter-tooth friction, and therefore the third model is adequate for simulating the pinion's y-displacement in the case of the symmetric disc. In the case of the asymmetric disc, the results deviate from those obtained in the symmetric case. Therefore, for simulating the pinion's y-displacement, the fourth