Agogo, George O; van der Voet, Hilko; Van't Veer, Pieter; van Eeuwijk, Fred A; Boshuizen, Hendriek C
2016-07-01
Dietary questionnaires are prone to measurement error, which bias the perceived association between dietary intake and risk of disease. Short-term measurements are required to adjust for the bias in the association. For foods that are not consumed daily, the short-term measurements are often characterized by excess zeroes. Via a simulation study, the performance of a two-part calibration model that was developed for a single-replicate study design was assessed by mimicking leafy vegetable intake reports from the multicenter European Prospective Investigation into Cancer and Nutrition (EPIC) study. In part I of the fitted two-part calibration model, a logistic distribution was assumed; in part II, a gamma distribution was assumed. The model was assessed with respect to the magnitude of the correlation between the consumption probability and the consumed amount (hereafter, cross-part correlation), the number and form of covariates in the calibration model, the percentage of zero response values, and the magnitude of the measurement error in the dietary intake. From the simulation study results, transforming the dietary variable in the regression calibration to an appropriate scale was found to be the most important factor for the model performance. Reducing the number of covariates in the model could be beneficial, but was not critical in large-sample studies. The performance was remarkably robust when fitting a one-part rather than a two-part model. The model performance was minimally affected by the cross-part correlation. PMID:27003183
Kautter, John; Pope, Gregory C.
2004-01-01
The authors document the development of the CMS frailty adjustment model, a Medicare payment approach that adjusts payments to a Medicare managed care organization (MCO) according to the functional impairment of its community-residing enrollees. Beginning in 2004, this approach is being applied to certain organizations, such as Program of All-Inclusive Care for the Elderly (PACE), that specialize in providing care to the community-residing frail elderly. In the future, frailty adjustment could be extended to more Medicare managed care organizations. PMID:25372243
External validation of a Cox prognostic model: principles and methods
2013-01-01
Background A prognostic model should not enter clinical practice unless it has been demonstrated that it performs a useful role. External validation denotes evaluation of model performance in a sample independent of that used to develop the model. Unlike for logistic regression models, external validation of Cox models is sparsely treated in the literature. Successful validation of a model means achieving satisfactory discrimination and calibration (prediction accuracy) in the validation sample. Validating Cox models is not straightforward because event probabilities are estimated relative to an unspecified baseline function. Methods We describe statistical approaches to external validation of a published Cox model according to the level of published information, specifically (1) the prognostic index only, (2) the prognostic index together with Kaplan-Meier curves for risk groups, and (3) the first two plus the baseline survival curve (the estimated survival function at the mean prognostic index across the sample). The most challenging task, requiring level 3 information, is assessing calibration, for which we suggest a method of approximating the baseline survival function. Results We apply the methods to two comparable datasets in primary breast cancer, treating one as derivation and the other as validation sample. Results are presented for discrimination and calibration. We demonstrate plots of survival probabilities that can assist model evaluation. Conclusions Our validation methods are applicable to a wide range of prognostic studies and provide researchers with a toolkit for external validation of a published Cox model. PMID:23496923
Prognostic models in coronary artery disease: Cox and network approaches
Mora, Antonio; Sicari, Rosa; Cortigiani, Lauro; Carpeggiani, Clara; Picano, Eugenio; Capobianco, Enrico
2015-01-01
Predictive assessment of the risk of developing cardiovascular diseases is usually provided by computational approaches centred on Cox models. The complex interdependence structure underlying clinical data patterns can limit the performance of Cox analysis and complicate the interpretation of results, thus calling for complementary and integrative methods. Prognostic models are proposed for studying the risk associated with patients with known or suspected coronary artery disease (CAD) undergoing vasodilator stress echocardiography, an established technique for CAD detection and prognostication. In order to complement standard Cox models, network inference is considered a possible solution to quantify the complex relationships between heterogeneous data categories. In particular, a mutual information network is designed to explore the paths linking patient-associated variables to endpoint events, to reveal prognostic factors and to identify the best possible predictors of death. Data from a prospective, multicentre, observational study are available from a previous study, based on 4313 patients (2532 men; 64±11 years) with known (n=1547) or suspected (n=2766) CAD, who underwent high-dose dipyridamole (0.84 mg kg−1 over 6 min) stress echocardiography with coronary flow reserve (CFR) evaluation of left anterior descending (LAD) artery by Doppler. The overall mortality was the only endpoint analysed by Cox models. The estimated connectivity between clinical variables assigns a complementary value to the proposed network approach in relation to the established Cox model, for instance revealing connectivity paths. Depending on the use of multiple metrics, the constraints of regression analysis in measuring the association strength among clinical variables can be relaxed, and identification of communities and prognostic paths can be provided. On the basis of evidence from various model comparisons, we show in this CAD study that there may be characteristic
Prognostic models in coronary artery disease: Cox and network approaches.
Mora, Antonio; Sicari, Rosa; Cortigiani, Lauro; Carpeggiani, Clara; Picano, Eugenio; Capobianco, Enrico
2015-02-01
Predictive assessment of the risk of developing cardiovascular diseases is usually provided by computational approaches centred on Cox models. The complex interdependence structure underlying clinical data patterns can limit the performance of Cox analysis and complicate the interpretation of results, thus calling for complementary and integrative methods. Prognostic models are proposed for studying the risk associated with patients with known or suspected coronary artery disease (CAD) undergoing vasodilator stress echocardiography, an established technique for CAD detection and prognostication. In order to complement standard Cox models, network inference is considered a possible solution to quantify the complex relationships between heterogeneous data categories. In particular, a mutual information network is designed to explore the paths linking patient-associated variables to endpoint events, to reveal prognostic factors and to identify the best possible predictors of death. Data from a prospective, multicentre, observational study are available from a previous study, based on 4313 patients (2532 men; 64±11 years) with known (n=1547) or suspected (n=2766) CAD, who underwent high-dose dipyridamole (0.84 mg kg(-1) over 6 min) stress echocardiography with coronary flow reserve (CFR) evaluation of left anterior descending (LAD) artery by Doppler. The overall mortality was the only endpoint analysed by Cox models. The estimated connectivity between clinical variables assigns a complementary value to the proposed network approach in relation to the established Cox model, for instance revealing connectivity paths. Depending on the use of multiple metrics, the constraints of regression analysis in measuring the association strength among clinical variables can be relaxed, and identification of communities and prognostic paths can be provided. On the basis of evidence from various model comparisons, we show in this CAD study that there may be characteristic
Covariate analysis of survival data: a small-sample study of Cox's model
Johnson, M.E.; Tolley, H.D.; Bryson, M.C.; Goldman, A.S.
1982-09-01
Cox's proportional-hazards model is frequently used to adjust for covariate effects in survival-data analysis. The small-sample performances of the maximum partial likelihood estimators of the regression parameters in a two-covariate hazard function model are evaluated with respect to bias, variance, and power in hypothesis tests. Previous Monte Carlo work on the two-sample problem is reviewed.
Dehesh, Tania; Zare, Najaf; Ayatollahi, Seyyed Mohammad Taghi
2015-01-01
Background. Univariate meta-analysis (UM) procedure, as a technique that provides a single overall result, has become increasingly popular. Neglecting the existence of other concomitant covariates in the models leads to loss of treatment efficiency. Our aim was proposing four new approximation approaches for the covariance matrix of the coefficients, which is not readily available for the multivariate generalized least square (MGLS) method as a multivariate meta-analysis approach. Methods. We evaluated the efficiency of four new approaches including zero correlation (ZC), common correlation (CC), estimated correlation (EC), and multivariate multilevel correlation (MMC) on the estimation bias, mean square error (MSE), and 95% probability coverage of the confidence interval (CI) in the synthesis of Cox proportional hazard models coefficients in a simulation study. Result. Comparing the results of the simulation study on the MSE, bias, and CI of the estimated coefficients indicated that MMC approach was the most accurate procedure compared to EC, CC, and ZC procedures. The precision ranking of the four approaches according to all above settings was MMC ≥ EC ≥ CC ≥ ZC. Conclusion. This study highlights advantages of MGLS meta-analysis on UM approach. The results suggested the use of MMC procedure to overcome the lack of information for having a complete covariance matrix of the coefficients. PMID:26413142
Bootstrapping a change-point Cox model for survival data.
Xu, Gongjun; Sen, Bodhisattva; Ying, Zhiliang
2014-08-20
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
Box-Cox Mixed Logit Model for Travel Behavior Analysis
NASA Astrophysics Data System (ADS)
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.
Cox Regression Models with Functional Covariates for Survival Data
Gellar, Jonathan E.; Colantuoni, Elizabeth; Needham, Dale M.; Crainiceanu, Ciprian M.
2015-01-01
We extend the Cox proportional hazards model to cases when the exposure is a densely sampled functional process, measured at baseline. The fundamental idea is to combine penalized signal regression with methods developed for mixed effects proportional hazards models. The model is fit by maximizing the penalized partial likelihood, with smoothing parameters estimated by a likelihood-based criterion such as AIC or EPIC. The model may be extended to allow for multiple functional predictors, time varying coefficients, and missing or unequally-spaced data. Methods were inspired by and applied to a study of the association between time to death after hospital discharge and daily measures of disease severity collected in the intensive care unit, among survivors of acute respiratory distress syndrome. PMID:26441487
Diagnostic Measures for the Cox Regression Model with Missing Covariates
Zhu, Hongtu; Ibrahim, Joseph G.; Chen, Ming-Hui
2015-01-01
Summary 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. PMID:26903666
Gaussian estimation for discretely observed Cox-Ingersoll-Ross model
NASA Astrophysics Data System (ADS)
Wei, Chao; Shu, Huisheng; Liu, Yurong
2016-07-01
This paper is concerned with the parameter estimation problem for Cox-Ingersoll-Ross model based on discrete observation. First, a new discretized process is built based on the Euler-Maruyama scheme. Then, the parameter estimators are obtained by employing the maximum likelihood method and the explicit expressions of the error of estimation are given. Subsequently, the consistency property of all parameter estimators are proved by applying the law of large numbers for martingales, Holder's inequality, B-D-G inequality and Cauchy-Schwarz inequality. Finally, a numerical simulation example for estimators and the absolute error between estimators and true values is presented to demonstrate the effectiveness of the estimation approach used in this paper.
ERIC Educational Resources Information Center
Chen, Chau-Kuang
2005-01-01
Logistic and Cox regression methods are practical tools used to model the relationships between certain student learning outcomes and their relevant explanatory variables. The logistic regression model fits an S-shaped curve into a binary outcome with data points of zero and one. The Cox regression model allows investigators to study the duration…
Box–Cox Transformation and Random Regression Models for Fecal egg Count Data
da Silva, Marcos Vinícius Gualberto Barbosa; Van Tassell, Curtis P.; Sonstegard, Tad S.; Cobuci, Jaime Araujo; Gasbarre, Louis C.
2012-01-01
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 in an effort to achieve normality before analysis. However, the transformed data are often still 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 6375 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 (co)variance 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. PMID:22303406
Brochhausen, Christoph; Zehbe, Rolf; Gross, Ulrich; Libera, Jeanette; Schubert, Helmut; Nüsing, Rolf M; Klaus, Günter; Kirkpatrick, C James
2008-01-01
Tissue engineering of articular cartilage remains an ongoing challenge. Since tissue regeneration recapitulates ontogenetic processes the growth plate can be regarded as an innovative model to target suitable signalling molecules and growth factors for the tissue engineering of cartilage. In the present study we analysed the expression of cyclooxygenases (COX) in a short-term chondrocyte culture in gelatin-based scaffolds and in articular cartilage of rats and compared it with that in the growth plate. Our results demonstrate the strong cellular expression of COX-1 but only a focal weak expression of COX-2 in the seeded scaffolds. Articular cartilage of rats expresses homogeneously COX-1 and COX-2 with the exception of the apical cell layer. Our findings indicate a functional role of COX in the metabolism of articular chondrocytes. The expression of COX in articular cartilage and in the seeded scaffolds opens interesting perspectives to improve the proliferation and differentiation of chondrocytes in scaffold materials by addition of specific receptor ligands of the COX system. PMID:18198403
NASA Technical Reports Server (NTRS)
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.
Mani, Kalaivani; Dwivedi, Sada Nand; Pandey, Ravindra Mohan
2012-01-01
Objectives In India there has been a decline in overall under-five mortality, with some states still showing very high mortality rates. It is argued that there is family clustering in mortality among children aged <5 years. We explored the effects of programmable (proximate) determinants on under-five mortality by accounting for family-level clustering and adjusting for background variables using Cox frailty model in rural Empowered Action Group states (EAG) in India and compared results with standard models. Methods Analysis included 13,785 live births that occurred five years preceding the National Family Health Survey-3 (2005-06). The Cox frailty model and the traditional Cox proportional hazards models were used. Results The Cox frailty model showed that mother’s age at birth, place of delivery, sex of the baby, composite variable of birth order and birth interval, baby size at birth, and breastfeeding were significant determinants of under-five mortality, after adjusting for the familial frailty effect. The hazard ratio was 1.41 (95% CI=1.14−1.75) for children born to mothers aged 12-19 years compared to mothers aged 20-30 years, 1.42 (95% CI=1.12−1.79) for small-sized than average-sized babies at birth, and 102 (95% CI=81−128) for non-breastfed than breastfed babies. Children had significantly lower mortality risks in the richest than poorest wealth quintile. The familial frailty effect was 2.86 in the rural EAG states. The hazard ratios for the determinants in all the three models were similar except the death of a previous child variable in the Cox frailty model, which had the highest R2 and lowest log-likelihood. Conclusions and Public Health Implications While planning for the child survival program in rural EAG states, parental competence which explains the unobserved familial effect needs to be considered along with significant programmable determinants. The frailty models that provide statistically valid estimates of the covariate effects are
JOINT STRUCTURE SELECTION AND ESTIMATION IN THE TIME-VARYING COEFFICIENT COX MODEL
Xiao, Wei; Lu, Wenbin; Zhang, Hao Helen
2016-01-01
Time-varying coefficient Cox model has been widely studied and popularly used in survival data analysis due to its flexibility for modeling covariate effects. It is of great practical interest to accurately identify the structure of covariate effects in a time-varying coefficient Cox model, i.e. covariates with null effect, constant effect and truly time-varying effect, and estimate the corresponding regression coefficients. Combining the ideas of local polynomial smoothing and group nonnegative garrote, we develop a new penalization approach to achieve such goals. Our method is able to identify the underlying true model structure with probability tending to one and simultaneously estimate the time-varying coefficients consistently. The asymptotic normalities of the resulting estimators are also established. We demonstrate the performance of our method using simulations and an application to the primary biliary cirrhosis data. PMID:27540275
Devarajan, Karthik; Ebrahimi, Nader
2010-01-01
The assumption of proportional hazards (PH) fundamental to the Cox PH model sometimes may not hold in practice. In this paper, we propose a generalization of the Cox PH model in terms of the cumulative hazard function taking a form similar to the Cox PH model, with the extension that the baseline cumulative hazard function is raised to a power function. Our model allows for interaction between covariates and the baseline hazard and it also includes, for the two sample problem, the case of two Weibull distributions and two extreme value distributions differing in both scale and shape parameters. The partial likelihood approach can not be applied here to estimate the model parameters. We use the full likelihood approach via a cubic B-spline approximation for the baseline hazard to estimate the model parameters. A semi-automatic procedure for knot selection based on Akaike’s Information Criterion is developed. We illustrate the applicability of our approach using real-life data. PMID:21076652
Devarajan, Karthik; Ebrahimi, Nader
2011-01-01
The assumption of proportional hazards (PH) fundamental to the Cox PH model sometimes may not hold in practice. In this paper, we propose a generalization of the Cox PH model in terms of the cumulative hazard function taking a form similar to the Cox PH model, with the extension that the baseline cumulative hazard function is raised to a power function. Our model allows for interaction between covariates and the baseline hazard and it also includes, for the two sample problem, the case of two Weibull distributions and two extreme value distributions differing in both scale and shape parameters. The partial likelihood approach can not be applied here to estimate the model parameters. We use the full likelihood approach via a cubic B-spline approximation for the baseline hazard to estimate the model parameters. A semi-automatic procedure for knot selection based on Akaike's Information Criterion is developed. We illustrate the applicability of our approach using real-life data. PMID:21076652
Jackson, Dan; White, Ian R; Seaman, Shaun; Evans, Hannah; Baisley, Kathy; Carpenter, James
2014-11-30
The Cox proportional hazards model is frequently used in medical statistics. The standard methods for fitting this model rely on the assumption of independent censoring. Although this is sometimes plausible, we often wish to explore how robust our inferences are as this untestable assumption is relaxed. We describe how this can be carried out in a way that makes the assumptions accessible to all those involved in a research project. Estimation proceeds via multiple imputation, where censored failure times are imputed under user-specified departures from independent censoring. A novel aspect of our method is the use of bootstrapping to generate proper imputations from the Cox model. We illustrate our approach using data from an HIV-prevention trial and discuss how it can be readily adapted and applied in other settings. PMID:25060703
Jackson, Dan; White, Ian R; Seaman, Shaun; Evans, Hannah; Baisley, Kathy; Carpenter, James
2014-01-01
The Cox proportional hazards model is frequently used in medical statistics. The standard methods for fitting this model rely on the assumption of independent censoring. Although this is sometimes plausible, we often wish to explore how robust our inferences are as this untestable assumption is relaxed. We describe how this can be carried out in a way that makes the assumptions accessible to all those involved in a research project. Estimation proceeds via multiple imputation, where censored failure times are imputed under user-specified departures from independent censoring. A novel aspect of our method is the use of bootstrapping to generate proper imputations from the Cox model. We illustrate our approach using data from an HIV-prevention trial and discuss how it can be readily adapted and applied in other settings. © 2014 The Authors. Statistics in Medicine published by John Wiley & Sons, Ltd. PMID:25060703
ELASTIC NET FOR COX'S PROPORTIONAL HAZARDS MODEL WITH A SOLUTION PATH ALGORITHM.
Wu, Yichao
2012-01-01
For least squares regression, Efron et al. (2004) proposed an efficient solution path algorithm, the least angle regression (LAR). They showed that a slight modification of the LAR leads to the whole LASSO solution path. Both the LAR and LASSO solution paths are piecewise linear. Recently Wu (2011) extended the LAR to generalized linear models and the quasi-likelihood method. In this work we extend the LAR further to handle Cox's proportional hazards model. The goal is to develop a solution path algorithm for the elastic net penalty (Zou and Hastie (2005)) in Cox's proportional hazards model. This goal is achieved in two steps. First we extend the LAR to optimizing the log partial likelihood plus a fixed small ridge term. Then we define a path modification, which leads to the solution path of the elastic net regularized log partial likelihood. Our solution path is exact and piecewise determined by ordinary differential equation systems. PMID:23226932
Comparing Smoothing Techniques for Fitting the Nonlinear Effect of Covariate in Cox Models
Roshani, Daem; Ghaderi, Ebrahim
2016-01-01
Background and Objective: Cox model is a popular model in survival analysis, which assumes linearity of the covariate on the log hazard function, While continuous covariates can affect the hazard through more complicated nonlinear functional forms and therefore, Cox models with continuous covariates are prone to misspecification due to not fitting the correct functional form for continuous covariates. In this study, a smooth nonlinear covariate effect would be approximated by different spline functions. Material and Methods: We applied three flexible nonparametric smoothing techniques for nonlinear covariate effect in the Cox models: penalized splines, restricted cubic splines and natural splines. Akaike information criterion (AIC) and degrees of freedom were used to smoothing parameter selection in penalized splines model. The ability of nonparametric methods was evaluated to recover the true functional form of linear, quadratic and nonlinear functions, using different simulated sample sizes. Data analysis was carried out using R 2.11.0 software and significant levels were considered 0.05. Results: Based on AIC, the penalized spline method had consistently lower mean square error compared to others to selection of smoothed parameter. The same result was obtained with real data. Conclusion: Penalized spline smoothing method, with AIC to smoothing parameter selection, was more accurate in evaluate of relation between covariate and log hazard function than other methods. PMID:27041809
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. PMID:26611766
CG100649, a novel COX-2 inhibitor, inhibits colorectal adenoma and carcinoma growth in mouse models.
Kim, Sun-Hee; Margalit, Ofer; Katoh, Hiroshi; Wang, Dingzhi; Wu, Hong; Xia, Dianren; Holla, Vijaykumar R; Yang, Peiying; DuBois, Raymond N
2014-12-01
Nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 (COX-2) inhibitors (COXIBs) can reduce the risk of developing colorectal cancer (CRC) and are being considered for use as adjuvant therapy for treatment of CRC patients. However, long-term use of most NSAIDs, except aspirin, increases cardiovascular risk, hampering use of these drugs in CRC prevention and possibly for treatment. CG100649 is a new member of the COXIB family, which is proposed to inhibit both COX-2 and carbonic anhydrase-I/-II (CA-I/-II) activity. Using mouse models, we show here that CG100649 inhibits premalignant and malignant colorectal lesions in mouse models, partly through inhibiting tumor cell proliferation. These pre-clinical findings suggest a need for further exploration of CG100649 for CRC prevention and treatment. The long-term safety profile of CG100649, particularly regarding its effect on cardiovascular risk, is yet to be determined. PMID:25085205
Lachin, John M.
2013-01-01
Summary General expressions are described for the evaluation of sample size and power for the K group Mantel-logrank test or the Cox PH model score test. Under an exponential model, the method of Lachin and Foulkes [1] for the 2 group case is extended to the K ≥ 2 group case using the non-centrality parameter of the K – 1 df chi-square test. Similar results are also shown to apply to the K group score test in a Cox PH model. Lachin and Foulkes [1] employed a truncated exponential distribution to provide for a non-linear rate of enrollment. Expressions for the mean time of enrollment and the expected follow-up time in the presence of exponential losses-to-follow-up are presented. When used with the expression for the non-centrality parameter for the test, equations are derived for the evaluation of sample size and power under specific designs with R years of recruitment and T years total duration. Sample size and power are also described for a stratified-adjusted K group test and for the assessment of a group by stratum interaction. Similarly computations are described for a stratified-adjusted analysis of a quantitative covariate and a test of a stratum by covariate interaction in the Cox PH model. PMID:23670965
Default risk modeling beyond the first-passage approximation: extended Black-Cox model.
Katz, Yuri A; Shokhirev, Nikolai V
2010-07-01
We develop a generalization of the Black-Cox structural model of default risk. The extended model captures uncertainty related to firm's ability to avoid default even if company's liabilities momentarily exceeding its assets. Diffusion in a linear potential with the radiation boundary condition is used to mimic a company's default process. The exact solution of the corresponding Fokker-Planck equation allows for derivation of analytical expressions for the cumulative probability of default and the relevant hazard rate. Obtained closed formulas fit well the historical data on global corporate defaults and demonstrate the split behavior of credit spreads for bonds of companies in different categories of speculative-grade ratings with varying time to maturity. Introduction of the finite rate of default at the boundary improves valuation of credit risk for short time horizons, which is the key advantage of the proposed model. We also consider the influence of uncertainty in the initial distance to the default barrier on the outcome of the model and demonstrate that this additional source of incomplete information may be responsible for nonzero credit spreads for bonds with very short time to maturity. PMID:20866698
Default risk modeling beyond the first-passage approximation: Extended Black-Cox model
NASA Astrophysics Data System (ADS)
Katz, Yuri A.; Shokhirev, Nikolai V.
2010-07-01
We develop a generalization of the Black-Cox structural model of default risk. The extended model captures uncertainty related to firm’s ability to avoid default even if company’s liabilities momentarily exceeding its assets. Diffusion in a linear potential with the radiation boundary condition is used to mimic a company’s default process. The exact solution of the corresponding Fokker-Planck equation allows for derivation of analytical expressions for the cumulative probability of default and the relevant hazard rate. Obtained closed formulas fit well the historical data on global corporate defaults and demonstrate the split behavior of credit spreads for bonds of companies in different categories of speculative-grade ratings with varying time to maturity. Introduction of the finite rate of default at the boundary improves valuation of credit risk for short time horizons, which is the key advantage of the proposed model. We also consider the influence of uncertainty in the initial distance to the default barrier on the outcome of the model and demonstrate that this additional source of incomplete information may be responsible for nonzero credit spreads for bonds with very short time to maturity.
Overpaying morbidity adjusters in risk equalization models.
van Kleef, R C; van Vliet, R C J A; van de Ven, W P M M
2016-09-01
Most competitive social health insurance markets include risk equalization to compensate insurers for predictable variation in healthcare expenses. Empirical literature shows that even the most sophisticated risk equalization models-with advanced morbidity adjusters-substantially undercompensate insurers for selected groups of high-risk individuals. In the presence of premium regulation, these undercompensations confront consumers and insurers with incentives for risk selection. An important reason for the undercompensations is that not all information with predictive value regarding healthcare expenses is appropriate for use as a morbidity adjuster. To reduce incentives for selection regarding specific groups we propose overpaying morbidity adjusters that are already included in the risk equalization model. This paper illustrates the idea of overpaying by merging data on morbidity adjusters and healthcare expenses with health survey information, and derives three preconditions for meaningful application. Given these preconditions, we think overpaying may be particularly useful for pharmacy-based cost groups. PMID:26420555
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. PMID:26319435
Inference of median difference based on the Box-Cox model in randomized clinical trials.
Maruo, K; Isogawa, N; Gosho, M
2015-05-10
In randomized clinical trials, many medical and biological measurements are not normally distributed and are often skewed. The Box-Cox transformation is a powerful procedure for comparing two treatment groups for skewed continuous variables in terms of a statistical test. However, it is difficult to directly estimate and interpret the location difference between the two groups on the original scale of the measurement. We propose a helpful method that infers the difference of the treatment effect on the original scale in a more easily interpretable form. We also provide statistical analysis packages that consistently include an estimate of the treatment effect, covariance adjustments, standard errors, and statistical hypothesis tests. The simulation study that focuses on randomized parallel group clinical trials with two treatment groups indicates that the performance of the proposed method is equivalent to or better than that of the existing non-parametric approaches in terms of the type-I error rate and power. We illustrate our method with cluster of differentiation 4 data in an acquired immune deficiency syndrome clinical trial. PMID:25565079
Tanaka, Shinji; Nakamura, Takehiro; Sumitani, Kazunori; Takahashi, Fumio; Konishi, Ryoji; Itano, Toshifumi; Miyamoto, Osamu
2009-09-01
In an attempt to elucidate the involvement of cyclooxygenase (COX) enzymes, particularly COX-1, in epileptogenesis, the localization of COX-1 and COX-2 expression in the mouse kindling model was analyzed by immunohistochemistry. COX-2 was predominantly observed in brain neurons and its concentration in the hippocampus increased with progressing seizures, as reported previously. COX-1 was predominant in microglia and its concentration was also enhanced in the hippocampus and areas around the third ventricle during the progression of seizures. These regions are thought to play an important role in the propagation of limbic seizures. Moreover, the administration of SC-560 (a selective COX-1 inhibitor) or indomethacin (a non-selective COX inhibitor) retarded the progress of seizures. Although the precise function of COX-positive cells in microglia and elsewhere is not clear, our results suggest that COX-1 as well as COX-2 may be involved in epileptogenesis, and that certain COX inhibitors can potentially prevent the occurrence of seizures. PMID:19523994
Theranostic nanoemulsions for macrophage COX-2 inhibition in a murine inflammation model.
Patel, Sravan Kumar; Beaino, Wissam; Anderson, Carolyn J; Janjic, Jelena M
2015-09-01
Targeting macrophages for therapeutic and diagnostic purposes is an attractive approach applicable to multiple diseases. Here, we present a theranostic nanoemulsion platform for simultaneous delivery of an anti-inflammatory drug (celecoxib) to macrophages and monitoring of macrophage migration patterns by optical imaging, as measurement of changes in inflammation. The anti-inflammatory effect of the theranostic nanoemulsions was evaluated in a mouse inflammation model induced with complete Freund's adjuvant (CFA). Nanoemulsions showed greater accumulation in the inflamed vs. control paw, with histology confirming their specific localization in CD68 positive macrophages expressing cyclooxygenase-2 (COX-2) compared to neutrophils. With a single dose administration of the celecoxib-loaded theranostic, we observed a reduction in fluorescence in the paw with time, corresponding to a reduction in macrophage infiltration. Our data strongly suggest that delivery of select agents to infiltrating macrophages can potentially lead to new treatments of inflammatory diseases where macrophage behavior changes are monitored in vivo. PMID:25959685
Sparse estimation of Cox proportional hazards models via approximated information criteria.
Su, Xiaogang; Wijayasinghe, Chalani S; Fan, Juanjuan; Zhang, Ying
2016-09-01
We propose a new sparse estimation method for Cox (1972) proportional hazards models by optimizing an approximated information criterion. The main idea involves approximation of the ℓ0 norm with a continuous or smooth unit dent function. The proposed method bridges the best subset selection and regularization by borrowing strength from both. It mimics the best subset selection using a penalized likelihood approach yet with no need of a tuning parameter. We further reformulate the problem with a reparameterization step so that it reduces to one unconstrained nonconvex yet smooth programming problem, which can be solved efficiently as in computing the maximum partial likelihood estimator (MPLE). Furthermore, the reparameterization tactic yields an additional advantage in terms of circumventing postselection inference. The oracle property of the proposed method is established. Both simulated experiments and empirical examples are provided for assessment and illustration. PMID:26873398
Pain relief model for a COX-2 inhibitor in patients with postoperative dental pain
Rohatagi, Shashank; Kastrissios, Helen; Sasahara, Kunihiro; Truitt, Kenneth; Moberly, James B; Wada, Russell; Salazar, Daniel E
2008-01-01
AIM To develop a pain relief model for a cyclooxygenase (COX)-2 inhibitor, CS-706, that permits prediction of doses for acute pain relief in Japanese and Western populations. METHODS A categorical response model was developed to describe the probability of pain relief (PR) over time for a Phase 2a study. Models were also developed to describe patient's use of rescue medication and onset of pain relief. RESULTS The placebo response was described by a first-order increase in PR that achieved a stable response after 4 h. The effect of CS-706 on PR was described using an Emax model; the plasma concentration of CS-706 producing 50% of the maximum response was estimated to be 87 ng ml−1, the median peak plasma concentration achieved after a 50-mg oral dose. The probability of rescue medication (REMD) decreased over time and was a function of the last observed PR score. This probability was < 16% for patients with a PR score ≥2. The probability of experiencing meaningful PR was 98% in patients who did not require REMD and 47% in those who required REMD. For patients who did not require REMD, the median onset time of meaningful pain relief (TMPR) decreased with increasing doses. In patients who required REMD, there was a saturable decline in TMPR, with the greatest improvement occurring from placebo to 50-mg doses. CONCLUSIONS The set of models developed permitted compilation of multiple dose–response curves for dose selection of CS-706 in Westerners and facilitated scaling of doses to a Japanese population. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Modelling and simulation are being increasingly used to support decision-making in new drug development.Novel modelling methods are required to capture the complexity of multiple end-points for a disease and to address questions such as dose selection in various populations.The focus of this study was to present a novel pain relief model to address such questions. WHAT THIS STUDY ADDS New contributions of this work to the
Using Cox cluster processes to model latent pulse location patterns in hormone concentration data.
Carlson, Nichole E; Grunwald, Gary K; Johnson, Timothy D
2016-04-01
Many hormones, including stress hormones, are intermittently secreted as pulses. The pulsatile location process, describing times when pulses occur, is a regulator of the entire stress system. Characterizing the pulse location process is particularly difficult because the pulse locations are latent; only hormone concentration at sampled times is observed. In addition, for stress hormones the process may change both over the day and relative to common external stimuli. This potentially results in clustering in pulse locations across subjects. Current approaches to characterizing the pulse location process do not capture subject-to-subject clustering in locations. Here we show how a Bayesian Cox cluster process may be adapted as a model of the pulse location process. We show that this novel model of pulse locations is capable of detecting circadian rhythms in pulse locations, clustering of pulse locations between subjects, and identifying exogenous controllers of pulse events. We integrate our pulse location process into a model of hormone concentration, the observed data. A spatial birth-and-death Markov chain Monte Carlo algorithm is used for estimation. We exhibit the strengths of this model on simulated data and adrenocorticotropic and cortisol data collected to study the stress axis in depressed and non-depressed women. PMID:26553914
A nonlinear isobologram model with Box-Cox transformation to both sides for chemical mixtures.
Chen, D G; Pounds, J G
1998-01-01
The linear logistical isobologram is a commonly used and powerful graphical and statistical tool for analyzing the combined effects of simple chemical mixtures. In this paper a nonlinear isobologram model is proposed to analyze the joint action of chemical mixtures for quantitative dose-response relationships. This nonlinear isobologram model incorporates two additional new parameters, Ymin and Ymax, to facilitate analysis of response data that are not constrained between 0 and 1, where parameters Ymin and Ymax represent the minimal and the maximal observed toxic response. This nonlinear isobologram model for binary mixtures can be expressed as [formula: see text] In addition, a Box-Cox transformation to both sides is introduced to improve the goodness of fit and to provide a more robust model for achieving homogeneity and normality of the residuals. Finally, a confidence band is proposed for selected isobols, e.g., the median effective dose, to facilitate graphical and statistical analysis of the isobologram. The versatility of this approach is demonstrated using published data describing the toxicity of the binary mixtures of citrinin and ochratoxin as well as a new experimental data from our laboratory for mixtures of mercury and cadmium. PMID:9860894
Measures to assess the prognostic ability of the stratified Cox proportional hazards model.
2009-02-01
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 would be useful in analyses of individual participant data from multiple studies, data from multi-centre studies, and in single study analysis where stratification is used to avoid making assumptions of proportional hazards. We have chosen three measures developed for the unstratified CPH model (Schemper and Henderson's V , Harrell's C-index and Royston and Sauerbrei's D), adapted them for use with the stratified CPH model and demonstrated how their values can be represented over time. Although each of these measures is promising in principle, we found the measure of explained variation V very difficult to apply when data are combined from several studies with differing durations of participant follow-up. The two other measures considered, D and the C-index, were more applicable under such circumstances. We illustrate the methods using individual participant data from several prospective epidemiological studies of chronic disease outcomes. PMID:18833567
Including network knowledge into Cox regression models for biomarker signature discovery.
Fröhlich, Holger
2014-03-01
Discovery of prognostic and diagnostic biomarker gene signatures for diseases, such as cancer, is seen as a major step toward a better personalized medicine. During the last decade various methods have been proposed for that purpose. However, one important obstacle for making gene signatures a standard tool in clinical diagnosis is the typical low reproducibility of these signatures combined with the difficulty to achieve a clear biological interpretation. For that purpose in the last years there has been a growing interest in approaches that try to integrate information from molecular interaction networks. Most of these methods focus on classification problems, that is learn a model from data that discriminates patients into distinct clinical groups. Far less has been published on approaches that predict a patient's event risk. In this paper, we investigate eight methods that integrate network information into multivariable Cox proportional hazard models for risk prediction in breast cancer. We compare the prediction performance of our tested algorithms via cross-validation as well as across different datasets. In addition, we highlight the stability and interpretability of obtained gene signatures. In conclusion, we find GeneRank-based filtering to be a simple, computationally cheap and highly predictive technique to integrate network information into event time prediction models. Signatures derived via this method are highly reproducible. PMID:24430933
Decidual Cox2 inhibition improves fetal and maternal outcomes in a preeclampsia-like mouse model
Woods, Ashley K.; Bartos, Amanda; Heyward, Christa Y.; Lob, Heinrich E.; Isroff, Catherine E.; Butler, Scott D.; Shapiro, Stephanie E.; Dey, Sudhansu K.; Davisson, Robin L.
2016-01-01
Preeclampsia (PE) is a disorder of pregnancy that manifests as late gestational maternal hypertension and proteinuria and can be life-threatening to both the mother and baby. It is believed that abnormal placentation is responsible for the cascade of events leading to the maternal syndrome. Embryo implantation is critical to establishing a healthy pregnancy. Defective implantation can cause adverse “ripple effects,” leading to abnormal decidualization and placentation, retarded fetal development, and poor pregnancy outcomes, such as PE and fetal growth restriction. The precise mechanism(s) of implantation defects that lead to PE remain elusive. BPH/5 mice, which spontaneously develop the cardinal features of PE, show peri-implantation defects including upregulation of Cox2 and IL-15 at the maternal-fetal interface. This was associated with decreased decidual natural killer (dNK) cells, which have important roles in establishing placental perfusion. Interestingly, a single administration of a Cox2 inhibitor (celecoxib) during decidualization restrained Cox2 and IL-15 expression, restored dNK cell numbers, improved fetal growth, and attenuated late gestational hypertension in BPH/5 female mice. This study provides evidence that decidual overexpression of Cox2 and IL-15 may trigger the adverse pregnancy outcomes reflected in the preeclamptic syndrome, underscoring the idea that Cox2 inhibitor treatment is an effective strategy for the prevention of PE-associated fetal and maternal morbidity and mortality. PMID:27159542
Sil, Susmita; Ghosh, Tusharkanti
2016-01-01
The anxiety status is changed along with memory impairments in intracerebroventricular colchicine injected rat model of Alzheimer Disease (cAD) due to neurodegeneration, which has been indicated to be mediated by inflammation. Inducible cox-2, involved in inflammation, may have important role in the colchicine induced alteration of anxiety status. Therefore, the present study was designed to investigate the role of cox-2 on the anxiety behavior (response to novelty in an elevated open field space) of cAD by inhibiting it with three different doses (10, 20, and 30 mg) of etoricoxib (a cox-2 blocker) in two time points (14 and 21 days). The results showed anxiolytic behavior in cAD along with lower serum corticosterone level, both of which were recovered at all the doses of etoricoxib on day 21. On day 14 all of the anxiety parameters showed similar results to that of day 21 at high doses but not at 10 mg/kg body weight. Results indicate that the parameters of anxiety were dependent on neuronal circuitries that were probably sensitive to etoricoxib induced blocking of neurodegeneration. The present study showed that anxiolytic behavior in cADr is predominantly due to cox-2 mediated neuroinflammation induced neurodegeneration in the brain. PMID:26880859
Lee, Eunjee; Zhu, Hongtu; Kong, Dehan; Wang, Yalin; Giovanello, Kelly Sullivan; Ibrahim, Joseph G
2015-01-01
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. PMID:26900412
Grim, Travis W.; Ghosh, Sudeshna; Hsu, Ku-Lung; Cravatt, Benjamin F.; Kinsey, Steven G.; Lichtman, Aron H.
2014-01-01
Common pharmacological treatments of neuropathic and chronic inflammatory pain conditions generally lack efficacy and/or are associated with significant untoward side effects. However, recent preclinical data indicate that combined inhibition of cyclooxygenase (COX) and fatty acid amide hydrolase (FAAH), the primary catabolic enzyme of the endocannabinoid N-arachidonoylethanolamine (anandamide; AEA), produces enhanced antinociceptive effects in a variety of murine models of pain. Accordingly, the primary objective of the present study was to investigate the consequences of co-administration of the COX inhibitor diclofenac and the highly selective FAAH inhibitor PF-3845 in models of neuropathic pain (i.e., chronic constrictive injury of the sciatic nerve (CCI)) and inflammatory pain induced by an intraplantar injection of carrageenan. Here, we report that combined administration of subthreshold doses of these drugs produced enhanced antinociceptive effects in CCI and carrageenan pain models, the latter of which was demonstrated to require both CB1 and CB2 receptors. The combined administration of subthreshold doses of these drugs also increased AEA levels and decreased prostaglandin levels in whole brain. Together, these data add to the growing research that dual blockade of FAAH and COX represents a potential therapeutic strategy for the treatment of neuropathic and inflammatory pain states. PMID:25058512
Bailit, Jennifer L.; Grobman, William A.; Rice, Madeline Murguia; Spong, Catherine Y.; Wapner, Ronald J.; Varner, Michael W.; Thorp, John M.; Leveno, Kenneth J.; Caritis, Steve N.; Shubert, Phillip J.; Tita, Alan T. N.; Saade, George; Sorokin, Yoram; Rouse, Dwight J.; Blackwell, Sean C.; Tolosa, Jorge E.; Van Dorsten, J. Peter
2014-01-01
Objective Regulatory bodies and insurers evaluate hospital quality using obstetrical outcomes, however meaningful comparisons should take pre-existing patient characteristics into account. Furthermore, if risk-adjusted outcomes are consistent within a hospital, fewer measures and resources would be needed to assess obstetrical quality. Our objective was to establish risk-adjusted models for five obstetric outcomes and assess hospital performance across these outcomes. Study Design A cohort study of 115,502 women and their neonates born in 25 hospitals in the United States between March 2008 and February 2011. Hospitals were ranked according to their unadjusted and risk-adjusted frequency of venous thromboembolism, postpartum hemorrhage, peripartum infection, severe perineal laceration, and a composite neonatal adverse outcome. Correlations between hospital risk-adjusted outcome frequencies were assessed. Results Venous thromboembolism occurred too infrequently (0.03%, 95% CI 0.02% – 0.04%) for meaningful assessment. Other outcomes occurred frequently enough for assessment (postpartum hemorrhage 2.29% (95% CI 2.20–2.38), peripartum infection 5.06% (95% CI 4.93–5.19), severe perineal laceration at spontaneous vaginal delivery 2.16% (95% CI 2.06–2.27), neonatal composite 2.73% (95% CI 2.63–2.84)). Although there was high concordance between unadjusted and adjusted hospital rankings, several individual hospitals had an adjusted rank that was substantially different (as much as 12 rank tiers) than their unadjusted rank. None of the correlations between hospital adjusted outcome frequencies was significant. For example, the hospital with the lowest adjusted frequency of peripartum infection had the highest adjusted frequency of severe perineal laceration. Conclusions Evaluations based on a single risk-adjusted outcome cannot be generalized to overall hospital obstetric performance. PMID:23891630
Elghafghuf, Adel; Dufour, Simon; Reyher, Kristen; Dohoo, Ian; Stryhn, Henrik
2014-12-01
Mastitis is a complex disease affecting dairy cows and is considered to be the most costly disease of dairy herds. The hazard of mastitis is a function of many factors, both managerial and environmental, making its control a difficult issue to milk producers. Observational studies of clinical mastitis (CM) often generate datasets with a number of characteristics which influence the analysis of those data: the outcome of interest may be the time to occurrence of a case of mastitis, predictors may change over time (time-dependent predictors), the effects of factors may change over time (time-dependent effects), there are usually multiple hierarchical levels, and datasets may be very large. Analysis of such data often requires expansion of the data into the counting-process format - leading to larger datasets - thus complicating the analysis and requiring excessive computing time. In this study, a nested frailty Cox model with time-dependent predictors and effects was applied to Canadian Bovine Mastitis Research Network data in which 10,831 lactations of 8035 cows from 69 herds were followed through lactation until the first occurrence of CM. The model was fit to the data as a Poisson model with nested normally distributed random effects at the cow and herd levels. Risk factors associated with the hazard of CM during the lactation were identified, such as parity, calving season, herd somatic cell score, pasture access, fore-stripping, and proportion of treated cases of CM in a herd. The analysis showed that most of the predictors had a strong effect early in lactation and also demonstrated substantial variation in the baseline hazard among cows and between herds. A small simulation study for a setting similar to the real data was conducted to evaluate the Poisson maximum likelihood estimation approach with both Gaussian quadrature method and Laplace approximation. Further, the performance of the two methods was compared with the performance of a widely used estimation
Saha, Prosenjit; Mandal, Suvra; Das, Ashes; Das, Sukta
2006-12-01
Swertia chirata, is a bitter plant, used in the Indian system of medicine (Ayurveda) for various human ailments. Our laboratory was the first to report the chemopreventive effect of this plant. The antiproliferative and pro-apoptotic action of amarogentin rich fraction of S. chirata is now demonstrated on a mouse skin carcinogenesis model. Immunohistochemical localization revealed a reduction in proliferating and increase in apoptotic cells in skin lesion following treatment, also reflected in the expression of molecular markers--Cox-II and caspase-3 proteins. It may be possible to calculate relative risk, relative protection and attributable risk from the action of test agents on proliferation and apoptosis. PMID:16517061
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. PMID:24621649
Laakkonen, L; Jobson, R W; Albert, V A
2006-11-01
The evolution of carnivorous plants has been modeled as a selective tradeoff between photosynthetic costs and benefits in nutrient-poor habitats. Although possibly applicable for pitfall and flypaper trappers, more variables may be required for active trapping systems. Bladderwort (utricularia) suction traps react to prey stimuli with an extremely rapid release of elastic instability. Trap setting requires considerable energy to engage an active ion transport process whereby water is pumped out through the thin bladder walls to create negative internal pressure. Accordingly, empirical estimates have shown that respiratory rates in bladders are far greater than in leafy structures. Cytochrome C oxidase (COX) is a multi-subunit enzyme that catalyzes the respiratory reduction of oxygen to water and couples this reaction to translocation of protons, generating a transmembrane electrochemical gradient that is used for the synthesis of adenosine triphosphate (ATP). We have previously demonstrated that two contiguous cysteine residues in helix 3 of COX subunit I (COX I) have evolved under positive Darwinian selection. This motif, absent in approximately 99.9 % of databased COX I proteins from eukaryotes, Archaea, and Bacteria, lies directly at the docking point of COX I helix 3 and cytochrome C. Modeling of bovine COX I suggests the possibility that a vicinal disulfide bridge at this position could cause premature helix termination. The helix 3-4 loop makes crucial contacts with the active site of COX, and we postulate that the C-C motif might cause a conformational change that decouples (or partly decouples) electron transport from proton pumping. Such decoupling would permit bladderworts to optimize power output (which equals energy times rate) during times of need, albeit with a 20 % reduction in overall energy efficiency of the respiratory chain. A new model for the evolution of bladderwort carnivory is proposed that includes respiration as an additional tradeoff
Giganti, Mark J.; Luz, Paula M.; Caro-Vega, Yanink; Cesar, Carina; Padgett, Denis; Koenig, Serena; Echevarria, Juan; McGowan, Catherine C.; Shepherd, Bryan E.
2015-01-01
Abstract 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. PMID:25647087
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. PMID:25647087
Khosravi, Bahareh; Pourahmad, Saeedeh; Bahreini, Amin; Nikeghbalian, Saman; Mehrdad, Goli
2015-01-01
Background: Transplantation is the only treatment for patients with liver failure. Since the therapy imposes high expenses to the patients and community, identification of effective factors on survival of such patients after transplantation is valuable. Objectives: The current study attempted to model the survival of patients (two years old and above) after liver transplantation using neural network and Cox Proportional Hazards (Cox PH) regression models. The event is defined as death due to complications of liver transplantation. Patients and Methods: In a historical cohort study, the clinical findings of 1168 patients who underwent liver transplant surgery (from March 2008 to march 2013) at Shiraz Namazee Hospital Organ Transplantation Center, Shiraz, Southern Iran, were used. To model the one to five years survival of such patients, Cox PH regression model accompanied by three layers feed forward artificial neural network (ANN) method were applied on data separately and their prediction accuracy was compared using the area under the receiver operating characteristic curve (ROC). Furthermore, Kaplan-Meier method was used to estimate the survival probabilities in different years. Results: The estimated survival probability of one to five years for the patients were 91%, 89%, 85%, 84%, and 83%, respectively. The areas under the ROC were 86.4% and 80.7% for ANN and Cox PH models, respectively. In addition, the accuracy of prediction rate for ANN and Cox PH methods was equally 92.73%. Conclusions: The present study detected more accurate results for ANN method compared to those of Cox PH model to analyze the survival of patients with liver transplantation. Furthermore, the order of effective factors in patients’ survival after transplantation was clinically more acceptable. The large dataset with a few missing data was the advantage of this study, the fact which makes the results more reliable. PMID:26500682
Kim, Sungduk; Chen, Ming-Hui; Ibrahim, Joseph G.; Shah, Arvind K.; Lin, Jianxin
2013-01-01
In this paper, we propose a class of Box-Cox transformation regression models with multidimensional random effects for analyzing multivariate responses for individual patient data (IPD) in meta-analysis. Our modeling formulation uses a multivariate normal response meta-analysis model with multivariate random effects, in which each response is allowed to have its own Box-Cox transformation. Prior distributions are specified for the Box-Cox transformation parameters as well as the regression coefficients in this complex model, and the Deviance Information Criterion (DIC) is used to select the best transformation model. Since the model is quite complex, a novel Monte Carlo Markov chain (MCMC) sampling scheme is developed to sample from the joint posterior of the parameters. This model is motivated by a very rich dataset comprising 26 clinical trials involving cholesterol lowering drugs where the goal is to jointly model the three dimensional response consisting of Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Triglycerides (TG) (LDL-C, HDL-C, TG). Since the joint distribution of (LDL-C, HDL-C, TG) is not multivariate normal and in fact quite skewed, a Box-Cox transformation is needed to achieve normality. In the clinical literature, these three variables are usually analyzed univariately: however, a multivariate approach would be more appropriate since these variables are correlated with each other. A detailed analysis of these data is carried out using the proposed methodology. PMID:23580436
Storm Water Management Model Climate Adjustment Tool (SWMM-CAT)
The US EPA’s newest tool, the Stormwater Management Model (SWMM) – Climate Adjustment Tool (CAT) is meant to help municipal stormwater utilities better address potential climate change impacts affecting their operations. SWMM, first released in 1971, models hydrology and hydrauli...
Unified Model for Academic Competence, Social Adjustment, and Psychopathology.
ERIC Educational Resources Information Center
Schaefer, Earl S.; And Others
A unified conceptual model is needed to integrate the extensive research on (1) social competence and adaptive behavior, (2) converging conceptualizations of social adjustment and psychopathology, and (3) emerging concepts and measures of academic competence. To develop such a model, a study was conducted in which teacher ratings were collected on…
NASA Astrophysics Data System (ADS)
Murray, Ross J.; Reason, C. J. C.
2001-07-01
Continuous and finite difference forms of the governing equations are derived for a version of the Bryan-Cox-Semtner ocean general circulation model which has been recast in orthogonal, transversely curvilinear coordinates. The coding closely follows the style of the Geophysical Fluid Dynamics Laboratory modular ocean model No. 1. Curvilinear forms are given for the tracer, internal momentum, and stream function calculations, with the options of horizontal and isopycnal diffusion, eddy-induced transport, nonlinear viscosity, and semiimplicit treatment of the Coriolis force. The model is designed to operate on a rectangular three-dimensional array of points and can accommodate reentrant boundary conditions at both 'northern' and 'east-west' boundaries. Horizontal grid locations are taken as input and need to be supplied by a separate grid generation program. The advantages of using a better behaved and more economical grid in the north polar region are investigated by comparing simulations performed on two curvilinear grids with one performed on a latitude-longitude grid and by comparing filtered and unfiltered latitude-longitude simulations. Resolution of horizontally separated currents in Fram Strait emerges as a key challenge for representing exchanges with the Arctic in global models.
Using Bibliotherapy to Help Children Adjust to Changing Role Models.
ERIC Educational Resources Information Center
Pardeck, John T.; Pardeck, Jean A.
One technique for helping children adjust to changing role models is bibliotherapy--the use of children's books to facilitate identification with and exploration of sex role behavior. Confronted with change in various social systems, particularly the family, children are faced with conflicts concerning their sex role development. The process…
Catastrophe, Chaos, and Complexity Models and Psychosocial Adjustment to Disability.
ERIC Educational Resources Information Center
Parker, Randall M.; Schaller, James; Hansmann, Sandra
2003-01-01
Rehabilitation professionals may unknowingly rely on stereotypes and specious beliefs when dealing with people with disabilities, despite the formulation of theories that suggest new models of the adjustment process. Suggests that Catastrophe, Chaos, and Complexity Theories hold considerable promise in this regard. This article reviews these…
LI, BAOLI; ZHANG, YONGLI; SHI, BINGYIN; CHEN, YAHUI; ZHANG, ZHENGXIANG; LIU, TAO
2013-01-01
This study aimed to determine the effects and mechanisms of gardenia oil on bone density and bone biomechanics in ovariectomized female rats. An ovariectomized rat model was established and the rats were administered various doses of gardenia oil. Rats administered diethylstilbestrol or saline served as the positive and the untreated controls, respectively. All rats received the same surgery, with the exception of the ovariectomy in the sham group. The levels of serum 17β-estradiol, follicle-stimulating hormone, luteinizing hormone, alkaline phosphatase (ALP) and calcium, and the bone material density (BMD), maximum stress and maximum strain were determined. The expression of COX-2 was also determined by immunoblotting and quantitative PCR (qPCR). Gardenia oil increased the serum levels of 17β-estradiol, the BMD, and the maximum stress and maximum strain of bones. The levels of COX-2 protein and COX-2 mRNA were significantly increased in the gardenia oil-treated rats. In conclusion, gardenia oil increases estradiol levels and BMD in an ovariectomized rat model. The effects of gardenia oil are associated with upregulation of the expression of COX-2. PMID:24137227
Lo, Kenneth; Gottardo, Raphael
2012-01-01
Cluster analysis is the automated search for groups of homogeneous observations in a data set. A popular modeling approach for clustering is based on finite normal mixture models, which assume that each cluster is modeled as a multivariate normal distribution. However, the normality assumption that each component is symmetric is often unrealistic. Furthermore, normal mixture models are not robust against outliers; they often require extra components for modeling outliers and/or give a poor representation of the data. To address these issues, we propose a new class of distributions, multivariate t distributions with the Box-Cox transformation, for mixture modeling. This class of distributions generalizes the normal distribution with the more heavy-tailed t distribution, and introduces skewness via the Box-Cox transformation. As a result, this provides a unified framework to simultaneously handle outlier identification and data transformation, two interrelated issues. We describe an Expectation-Maximization algorithm for parameter estimation along with transformation selection. We demonstrate the proposed methodology with three real data sets and simulation studies. Compared with a wealth of approaches including the skew-t mixture model, the proposed t mixture model with the Box-Cox transformation performs favorably in terms of accuracy in the assignment of observations, robustness against model misspecification, and selection of the number of components. PMID:22125375
ERIC Educational Resources Information Center
Pakenham, Kenneth I.; Samios, Christina; Sofronoff, Kate
2005-01-01
The present study examined the applicability of the double ABCX model of family adjustment in explaining maternal adjustment to caring for a child diagnosed with Asperger syndrome. Forty-seven mothers completed questionnaires at a university clinic while their children were participating in an anxiety intervention. The children were aged between…
Vatcheva, KP; Lee, M; McCormick, JB; Rahbar, MH
2016-01-01
Objective To demonstrate the adverse impact of ignoring statistical interactions in regression models used in epidemiologic studies. Study design and setting Based on different scenarios that involved known values for coefficient of the interaction term in Cox regression models we generated 1000 samples of size 600 each. The simulated samples and a real life data set from the Cameron County Hispanic Cohort were used to evaluate the effect of ignoring statistical interactions in these models. Results Compared to correctly specified Cox regression models with interaction terms, misspecified models without interaction terms resulted in up to 8.95 fold bias in estimated regression coefficients. Whereas when data were generated from a perfect additive Cox proportional hazards regression model the inclusion of the interaction between the two covariates resulted in only 2% estimated bias in main effect regression coefficients estimates, but did not alter the main findings of no significant interactions. Conclusions When the effects are synergic, the failure to account for an interaction effect could lead to bias and misinterpretation of the results, and in some instances to incorrect policy decisions. Best practices in regression analysis must include identification of interactions, including for analysis of data from epidemiologic studies.
Ternès, Nils; Rotolo, Federico; Michiels, Stefan
2016-07-10
Correct selection of prognostic biomarkers among multiple candidates is becoming increasingly challenging as the dimensionality of biological data becomes higher. Therefore, minimizing the false discovery rate (FDR) is of primary importance, while a low false negative rate (FNR) is a complementary measure. The lasso is a popular selection method in Cox regression, but its results depend heavily on the penalty parameter λ. Usually, λ is chosen using maximum cross-validated log-likelihood (max-cvl). However, this method has often a very high FDR. We review methods for a more conservative choice of λ. We propose an empirical extension of the cvl by adding a penalization term, which trades off between the goodness-of-fit and the parsimony of the model, leading to the selection of fewer biomarkers and, as we show, to the reduction of the FDR without large increase in FNR. We conducted a simulation study considering null and moderately sparse alternative scenarios and compared our approach with the standard lasso and 10 other competitors: Akaike information criterion (AIC), corrected AIC, Bayesian information criterion (BIC), extended BIC, Hannan and Quinn information criterion (HQIC), risk information criterion (RIC), one-standard-error rule, adaptive lasso, stability selection, and percentile lasso. Our extension achieved the best compromise across all the scenarios between a reduction of the FDR and a limited raise of the FNR, followed by the AIC, the RIC, and the adaptive lasso, which performed well in some settings. We illustrate the methods using gene expression data of 523 breast cancer patients. In conclusion, we propose to apply our extension to the lasso whenever a stringent FDR with a limited FNR is targeted. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26970107
Zavadilová, L; Němcová, E; Stípková, M
2011-08-01
Relationships between conformation traits and functional longevity in Holstein cows were evaluated using survival analysis. Functional longevity was defined as the number of days between the first calving and culling; that is, length of productive life. The data set consisted of 116,369 Holstein cows that first calved from 2003 to 2008. All cows used in the analysis were scored for conformation between d 30 and d 210 of their first lactation. The data included 48% censored records. Analyses were done separately for 20 linear descriptive type traits, 6 composite traits, and height at sacrum measured in centimeters. Cox proportional hazard models were fitted to analyze data. The hazard function was described as the product of a baseline hazard function and the time-independent effects of age at first calving and sire (random), and the time-dependent effects of stage of lactation and lactation number, herd, year and season, herd size, and 305-d milk production. The strongest relationship between a composite trait and functional longevity was for dairy form, followed by udder and final score. Among the descriptive type traits, the strongest relationships with longevity were found for body condition score, angularity, traits related to udder attachment, and udder depth. Foot and leg traits showed substantially lower effect on functional longevity, and the effect of foot angle was minimal. Functional longevity declined with decreased body condition score of cows. Cows with deep udders had significantly lower functional survival compared with cows with shallow udders. In addition, weak central ligament was associated with significant reduction of cow longevity. For dairy form and angularity, cows classified as very good were the worst with respect to longevity, whereas cows classified as poor were the best. An intermediate optimum was evident for rear legs rear view and rear legs set (side view), whereas cows with sickled legs had lower longevity than cows with straighter
Coercively Adjusted Auto Regression Model for Forecasting in Epilepsy EEG
Kim, Sun-Hee; Faloutsos, Christos; Yang, Hyung-Jeong
2013-01-01
Recently, data with complex characteristics such as epilepsy electroencephalography (EEG) time series has emerged. Epilepsy EEG data has special characteristics including nonlinearity, nonnormality, and nonperiodicity. Therefore, it is important to find a suitable forecasting method that covers these special characteristics. In this paper, we propose a coercively adjusted autoregression (CA-AR) method that forecasts future values from a multivariable epilepsy EEG time series. We use the technique of random coefficients, which forcefully adjusts the coefficients with −1 and 1. The fractal dimension is used to determine the order of the CA-AR model. We applied the CA-AR method reflecting special characteristics of data to forecast the future value of epilepsy EEG data. Experimental results show that when compared to previous methods, the proposed method can forecast faster and accurately. PMID:23710252
NASA Astrophysics Data System (ADS)
Freni, Gabriele; Mannina, Giorgio
In urban drainage modelling, uncertainty analysis is of undoubted necessity. However, uncertainty analysis in urban water-quality modelling is still in its infancy and only few studies have been carried out. Therefore, several methodological aspects still need to be experienced and clarified especially regarding water quality modelling. The use of the Bayesian approach for uncertainty analysis has been stimulated by its rigorous theoretical framework and by the possibility of evaluating the impact of new knowledge on the modelling predictions. Nevertheless, the Bayesian approach relies on some restrictive hypotheses that are not present in less formal methods like the Generalised Likelihood Uncertainty Estimation (GLUE). One crucial point in the application of Bayesian method is the formulation of a likelihood function that is conditioned by the hypotheses made regarding model residuals. Statistical transformations, such as the use of Box-Cox equation, are generally used to ensure the homoscedasticity of residuals. However, this practice may affect the reliability of the analysis leading to a wrong uncertainty estimation. The present paper aims to explore the influence of the Box-Cox equation for environmental water quality models. To this end, five cases were considered one of which was the “real” residuals distributions (i.e. drawn from available data). The analysis was applied to the Nocella experimental catchment (Italy) which is an agricultural and semi-urbanised basin where two sewer systems, two wastewater treatment plants and a river reach were monitored during both dry and wet weather periods. The results show that the uncertainty estimation is greatly affected by residual transformation and a wrong assumption may also affect the evaluation of model uncertainty. The use of less formal methods always provide an overestimation of modelling uncertainty with respect to Bayesian method but such effect is reduced if a wrong assumption is made regarding the
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. PMID:25768707
Bayram-Weston, Zubeyde; Olsen, Elliott; Harrison, David J.; Dunnett, Stephen B.; Brooks, Simon P.
2016-01-01
Background The Golgi–Cox stain is an established method for characterising neuron cell morphology. The method highlights neurite processes of stained cells allowing the complexity of dendritic branching to be measured. New methods Conventional rapid Golgi and Golgi–Cox methods all require fresh impregnation in unfixed brain blocks. Here, we describe a modified method that gives high quality staining on brain tissue blocks perfusion-fixed with 4% paraformaldehyde (PFA) and post-fixed by immersion for 24 h. Results Tissue perfused with 4% PFA and post fixed for 24 h remained viable for the modified Golgi–Cox silver impregnation staining of mouse striatum from perfused wild type and zQ175. It was not found necessary to impregnate tissue blocks with Golgi solutions prior to sectioning, as post-sectioned tissues yielded equally good impregnation. Impregnation for 14 days resulted in optimal visualisation of striatal neuron and dendritic morphology. Although no modifications applied to the rapid Golgi method were reliable, the modified Golgi–Cox method yielded consistently reliable high-quality staining. Comparison with existing methods The current method used fixed tissues to reduce damage and preserve cell morphology. The revised method was found to be fast, reliable and cost effective without the need for expensive staining kits and could be performed in any neuroscience lab with limited specialist equipment. Conclusions The present study introduces a robust reproducible and inexpensive staining method for identifying neuronal morphological changes in the post fixed mouse brain, and is suitable for assessing changes in cell morphology in models of neurodegeneration and in response to experimental treatment. PMID:26459195
Decomposition of Variance for Spatial Cox Processes
Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus
2012-01-01
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. PMID:23599558
An interface model for dosage adjustment connects hematotoxicity to pharmacokinetics.
Meille, C; Iliadis, A; Barbolosi, D; Frances, N; Freyer, G
2008-12-01
When modeling is required to describe pharmacokinetics and pharmacodynamics simultaneously, it is difficult to link time-concentration profiles and drug effects. When patients are under chemotherapy, despite the huge amount of blood monitoring numerations, there is a lack of exposure variables to describe hematotoxicity linked with the circulating drug blood levels. We developed an interface model that transforms circulating pharmacokinetic concentrations to adequate exposures, destined to be inputs of the pharmacodynamic process. The model is materialized by a nonlinear differential equation involving three parameters. The relevance of the interface model for dosage adjustment is illustrated by numerous simulations. In particular, the interface model is incorporated into a complex system including pharmacokinetics and neutropenia induced by docetaxel and by cisplatin. Emphasis is placed on the sensitivity of neutropenia with respect to the variations of the drug amount. This complex system including pharmacokinetic, interface, and pharmacodynamic hematotoxicity models is an interesting tool for analysis of hematotoxicity induced by anticancer agents. The model could be a new basis for further improvements aimed at incorporating new experimental features. PMID:19107581
Survival analysis of cervical cancer using stratified Cox regression
NASA Astrophysics Data System (ADS)
Purnami, S. W.; Inayati, K. D.; Sari, N. W. Wulan; Chosuvivatwong, V.; Sriplung, H.
2016-04-01
Cervical cancer is one of the mostly widely cancer cause of the women death in the world including Indonesia. Most cervical cancer patients come to the hospital already in an advanced stadium. As a result, the treatment of cervical cancer becomes more difficult and even can increase the death's risk. One of parameter that can be used to assess successfully of treatment is the probability of survival. This study raises the issue of cervical cancer survival patients at Dr. Soetomo Hospital using stratified Cox regression based on six factors such as age, stadium, treatment initiation, companion disease, complication, and anemia. Stratified Cox model is used because there is one independent variable that does not satisfy the proportional hazards assumption that is stadium. The results of the stratified Cox model show that the complication variable is significant factor which influent survival probability of cervical cancer patient. The obtained hazard ratio is 7.35. It means that cervical cancer patient who has complication is at risk of dying 7.35 times greater than patient who did not has complication. While the adjusted survival curves showed that stadium IV had the lowest probability of survival.
Wong, May C M; Lam, K F; Lo, Edward C M
2006-02-15
In some controlled clinical trials in dental research, multiple failure time data from the same patient are frequently observed that result in clustered multiple failure time. Moreover, the treatments are often delivered by more than one operator and thus the multiple failure times are clustered according to a multilevel structure when the operator effects are assumed to be random. In practice, it is often too expensive or even impossible to monitor the study subjects continuously, but they are examined periodically at some regular pre-scheduled visits. Hence, discrete or grouped clustered failure time data are collected. The aim of this paper is to illustrate the use of the Monte Carlo Markov chain (MCMC) approach and non-informative prior in a Bayesian framework to mimic the maximum likelihood (ML) estimation in a frequentist approach in multilevel modelling of clustered grouped survival data. A three-level model with additive variance components model for the random effects is considered in this paper. Both the grouped proportional hazards model and the dynamic logistic regression model are used. The approximate intra-cluster correlation of the log failure times can be estimated when the grouped proportional hazards model is used. The statistical package WinBUGS is adopted to estimate the parameter of interest based on the MCMC method. The models and method are applied to a data set obtained from a prospective clinical study on a cohort of Chinese school children that atraumatic restorative treatment (ART) restorations were placed on permanent teeth with carious lesions. Altogether 284 ART restorations were placed by five dentists and clinical status of the ART restorations was evaluated annually for 6 years after placement, thus clustered grouped failure times of the restorations were recorded. Results based on the grouped proportional hazards model revealed that clustering effect among the log failure times of the different restorations from the same child was
Disaster Hits Home: A Model of Displaced Family Adjustment after Hurricane Katrina
ERIC Educational Resources Information Center
Peek, Lori; Morrissey, Bridget; Marlatt, Holly
2011-01-01
The authors explored individual and family adjustment processes among parents (n = 30) and children (n = 55) who were displaced to Colorado after Hurricane Katrina. Drawing on in-depth interviews with 23 families, this article offers an inductive model of displaced family adjustment. Four stages of family adjustment are presented in the model: (a)…
ERIC Educational Resources Information Center
Tay, Louis; Drasgow, Fritz
2012-01-01
Two Monte Carlo simulation studies investigated the effectiveness of the mean adjusted X[superscript 2]/df statistic proposed by Drasgow and colleagues and, because of problems with the method, a new approach for assessing the goodness of fit of an item response theory model was developed. It has been previously recommended that mean adjusted…
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. PMID:26765502
Validity of the Néel-Arrhenius model for highly anisotropic CoxFe3-xO4 nanoparticles
NASA Astrophysics Data System (ADS)
Torres, T. E.; Lima, E.; Mayoral, A.; Ibarra, A.; Marquina, C.; Ibarra, M. R.; Goya, G. F.
2015-11-01
We report a systematic study on the structural and magnetic properties of CoxFe3-xO4 magnetic nanoparticles with sizes between 5 and 25 nm, prepared by thermal decomposition of Fe(acac)3 and Co(acac)2. The large magneto-crystalline anisotropy of the synthesized particles resulted in high blocking temperatures (42 K < TB < 345 K for 5 < d < 13 nm) and large coercive fields (HC ≈ 1600 kA/m for T = 5 K). The smallest particles (⟨d⟩=5 nm) revealed the existence of a magnetically hard, spin-disordered surface. The thermal dependence of static and dynamic magnetic properties of the whole series of samples could be explained within the Neel-Arrhenius relaxation framework by including the thermal dependence of the magnetocrystalline anisotropy constant K1(T), without the need of ad-hoc corrections. This approach, using the empirical Brükhatov-Kirensky relation, provided K1(0) values very similar to the bulk material from either static or dynamic magnetic measurements, as well as realistic values for the response times (τ0 ≈ 10-10s). Deviations from the bulk anisotropy values found for the smallest particles could be qualitatively explained based on Zener's relation between K1(T) and M(T).
Cyclooxygenase-2 (COX-2) expression in canine intracranial meningiomas.
Rossmeisl, J H; Robertson, J L; Zimmerman, K L; Higgins, M A; Geiger, D A
2009-09-01
Meningiomas are the most common canine intracranial tumour. Neurologic disability and death from treatment failure remain problematic despite current surgical and radiotherapeutic treatments for canine intracranial meningiomas. Cyclooxygenase-2 (COX-2) over-expression has been demonstrated in multiple canine malignancies, and COX-2 inhibitory treatment strategies have been shown to have both preventative and therapeutic effects in spontaneous and experimental models of cancer. The purpose of this study was to evaluate COX-2 expression in canine intracranial meningiomas. Immunohistochemical and Western blot (WB) analyses showed COX-2 expression in multiple tissues of the normal canine brain, and 87% (21/24) of intracranial meningiomas studied were immunoreactive to COX-2. No significant associations between COX-2 immunoreactivity and tumour grade were identified. Further studies are required to elucidate the physiologic roles of constitutive COX-2 expression in the central nervous system as well as its participation in meningioma tumourigenesis. PMID:19691646
Meadows, Cheyney; Rajala-Schultz, Päivi J; Frazer, Grant S; Meiring, Richard W; Hoblet, Kent H
2006-12-18
An observational study was conducted in order to assess the impact of a contract breeding program on the reproductive performance in a selected group of Ohio dairies using event-time analysis. The contract breeding program was offered by a breeding co-operative and featured tail chalking and daily evaluation of cows for insemination by co-operative technicians. Dairy employees no longer handled estrus detection activities. Between early 2002 and mid-2004, test-day records related to production and reproduction were obtained for 16,453 lactations representing 11,398 cows in a non-random sample of 31 dairies identified as well-managed client herds of the breeding co-operative. Of the 31 herds, 15 were using the contract breeding at the start of the data acquisition period, having started in the previous 2 years. The remaining 16 herds managed their own breeding program and used the co-operative for semen purchase. Cox proportional hazards modeling techniques were used to estimate the association of the contract breeding, as well as the effect of other significant predictors, with the hazard of pregnancy. Two separate Cox models were developed and compared: one that only considered fixed covariates and a second that included both fixed and time-varying covariates. Estimates of effects were expressed as the hazard ratio (HR) for pregnancy. Results of the fixed covariates model indicated that, controlling for breed, herd size, use of ovulation synchronization protocols in the herd, whether somatic cell score exceeded 4.5 prior to pregnancy or censoring, parity, calving season, and maximum test-day milk prior to pregnancy or censoring, the contract breeding program was associated with an increased hazard of pregnancy (HR=1.315; 95% CI 1.261-1.371). The results of the time-varying covariates model, which controlled for breed, herd size, use of ovulation synchronization protocols, somatic cell score above 4.5, parity, calving season, and testing season also found that the
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) on ALC. In the analysis considering all covariables and class effects, using the Wald test in the Cox model, only the season of birth of the cow was not significant for ALC (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
Mahdi, Chanif; Nurdiana, Nurdiana; Kikuchi, Takheshi; Fatchiyah, Fatchiyah
2014-01-01
To understand the structural features that dictate the selectivity of the two isoforms of the prostaglandin H2 synthase (PGHS/COX), the three-dimensional (3D) structure of COX-1/COX-2 was assessed by means of binding energy calculation of virtual molecular dynamic with using ligand alpha-Patchouli alcohol isomers. Molecular interaction studies with COX-1 and COX-2 were done using the molecular docking tools by Hex 8.0. Interactions were further visualized by using Discovery Studio Client 3.5 software tool. The binding energy of molecular interaction was calculated by AMBER12 and Virtual Molecular Dynamic 1.9.1 software. The analysis of the alpha-Patchouli alcohol isomer compounds showed that all alpha-Patchouli alcohol isomers were suggested as inhibitor of COX-1 and COX-2. Collectively, the scoring binding energy calculation (with PBSA Model Solvent) of alpha-Patchouli alcohol isomer compounds (CID442384, CID6432585, CID3080622, CID10955174, and CID56928117) was suggested as candidate for a selective COX-1 inhibitor and CID521903 as nonselective COX-1/COX-2. PMID:25484897
Raharjo, Sentot Joko; Mahdi, Chanif; Nurdiana, Nurdiana; Kikuchi, Takheshi; Fatchiyah, Fatchiyah
2014-01-01
To understand the structural features that dictate the selectivity of the two isoforms of the prostaglandin H2 synthase (PGHS/COX), the three-dimensional (3D) structure of COX-1/COX-2 was assessed by means of binding energy calculation of virtual molecular dynamic with using ligand alpha-Patchouli alcohol isomers. Molecular interaction studies with COX-1 and COX-2 were done using the molecular docking tools by Hex 8.0. Interactions were further visualized by using Discovery Studio Client 3.5 software tool. The binding energy of molecular interaction was calculated by AMBER12 and Virtual Molecular Dynamic 1.9.1 software. The analysis of the alpha-Patchouli alcohol isomer compounds showed that all alpha-Patchouli alcohol isomers were suggested as inhibitor of COX-1 and COX-2. Collectively, the scoring binding energy calculation (with PBSA Model Solvent) of alpha-Patchouli alcohol isomer compounds (CID442384, CID6432585, CID3080622, CID10955174, and CID56928117) was suggested as candidate for a selective COX-1 inhibitor and CID521903 as nonselective COX-1/COX-2. PMID:25484897
ERIC Educational Resources Information Center
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. Although she…
Covariate-Adjusted Linear Mixed Effects Model with an Application to Longitudinal Data
Nguyen, Danh V.; Şentürk, Damla; Carroll, Raymond J.
2009-01-01
Linear mixed effects (LME) models are useful for longitudinal data/repeated measurements. We propose a new class of covariate-adjusted LME models for longitudinal data that nonparametrically adjusts for a normalizing covariate. The proposed approach involves fitting a parametric LME model to the data after adjusting for the nonparametric effects of a baseline confounding covariate. In particular, the effect of the observable covariate on the response and predictors of the LME model is modeled nonparametrically via smooth unknown functions. In addition to covariate-adjusted estimation of fixed/population parameters and random effects, an estimation procedure for the variance components is also developed. Numerical properties of the proposed estimators are investigated with simulation studies. The consistency and convergence rates of the proposed estimators are also established. An application to a longitudinal data set on calcium absorption, accounting for baseline distortion from body mass index, illustrates the proposed methodology. PMID:19266053
Bourens, Myriam; Boulet, Aren; Leary, Scot C.; Barrientos, Antoni
2014-01-01
Cytochrome c oxidase (CIV) deficiency is one of the most common respiratory chain defects in patients presenting with mitochondrial encephalocardiomyopathies. CIV biogenesis is complicated by the dual genetic origin of its structural subunits, and assembly of a functional holoenzyme complex requires a large number of nucleus-encoded assembly factors. In general, the functions of these assembly factors remain poorly understood, and mechanistic investigations of human CIV biogenesis have been limited by the availability of model cell lines. Here, we have used small interference RNA and transcription activator-like effector nucleases (TALENs) technology to create knockdown and knockout human cell lines, respectively, to study the function of the CIV assembly factor COX20 (FAM36A). These cell lines exhibit a severe, isolated CIV deficiency due to instability of COX2, a mitochondrion-encoded CIV subunit. Mitochondria lacking COX20 accumulate CIV subassemblies containing COX1 and COX4, similar to those detected in fibroblasts from patients carrying mutations in the COX2 copper chaperones SCO1 and SCO2. These results imply that in the absence of COX20, COX2 is inefficiently incorporated into early CIV subassemblies. Immunoprecipitation assays using a stable COX20 knockout cell line expressing functional COX20-FLAG allowed us to identify an interaction between COX20 and newly synthesized COX2. Additionally, we show that SCO1 and SCO2 act on COX20-bound COX2. We propose that COX20 acts as a chaperone in the early steps of COX2 maturation, stabilizing the newly synthesized protein and presenting COX2 to its metallochaperone module, which in turn facilitates the incorporation of mature COX2 into the CIV assembly line. PMID:24403053
A New Climate Adjustment Tool: An update to EPA’s Storm Water Management Model
The US EPA’s newest tool, the Stormwater Management Model (SWMM) – Climate Adjustment Tool (CAT) is meant to help municipal stormwater utilities better address potential climate change impacts affecting their operations.
Procedures for adjusting regional regression models of urban-runoff quality using local data
Hoos, Anne B.; Lizarraga, Joy S.
1996-01-01
Statistical operations termed model-adjustment procedures can be used to incorporate local data into existing regression modes to improve the predication of urban-runoff quality. Each procedure is a form of regression analysis in which the local data base is used as a calibration data set; the resulting adjusted regression models can then be used to predict storm-runoff quality at unmonitored sites. Statistical tests of the calibration data set guide selection among proposed procedures.
NASA Astrophysics Data System (ADS)
Gunardi, Setiawan, Ezra Putranda
2015-12-01
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.
Modeling of an Adjustable Beam Solid State Light Project
NASA Technical Reports Server (NTRS)
Clark, Toni
2015-01-01
This proposal is for the development of a computational model of a prototype variable beam light source using optical modeling software, Zemax Optics Studio. The variable beam light source would be designed to generate flood, spot, and directional beam patterns, while maintaining the same average power usage. The optical model would demonstrate the possibility of such a light source and its ability to address several issues: commonality of design, human task variability, and light source design process improvements. An adaptive lighting solution that utilizes the same electronics footprint and power constraints while addressing variability of lighting needed for the range of exploration tasks can save costs and allow for the development of common avionics for lighting controls.
Yan, Ying; Yi, Grace Y
2016-07-01
Covariate measurement error occurs commonly in survival analysis. Under the proportional hazards model, measurement error effects have been well studied, and various inference methods have been developed to correct for error effects under such a model. In contrast, error-contaminated survival data under the additive hazards model have received relatively less attention. In this paper, we investigate this problem by exploring measurement error effects on parameter estimation and the change of the hazard function. New insights of measurement error effects are revealed, as opposed to well-documented results for the Cox proportional hazards model. We propose a class of bias correction estimators that embraces certain existing estimators as special cases. In addition, we exploit the regression calibration method to reduce measurement error effects. Theoretical results for the developed methods are established, and numerical assessments are conducted to illustrate the finite sample performance of our methods. PMID:26328545
Circumplex and Spherical Models for Child School Adjustment and Competence.
ERIC Educational Resources Information Center
Schaefer, Earl S.; Edgerton, Marianna
The goal of this study is to broaden the scope of a conceptual model for child behavior by analyzing constructs relevant to cognition, conation, and affect. Two samples were drawn from school populations. For the first sample, 28 teachers from 8 rural, suburban, and urban schools rated 193 kindergarten children. Each teacher rated up to eight…
A General Linear Model Approach to Adjusting the Cumulative GPA.
ERIC Educational Resources Information Center
Young, John W.
A general linear model (GLM), using least-squares techniques, was used to develop a criterion measure to replace freshman year grade point average (GPA) in college admission predictive validity studies. Problems with the use of GPA include those associated with the combination of grades from different courses and disciplines into a single measure,…
Cell-type-specific roles for COX-2 in UVB-induced skin cancer
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
Gunardi,; Setiawan, Ezra Putranda
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.
Tsai, Chen-An; Lee, Kuan-Ting; Liu, Jen-pei
2016-01-01
A key feature of precision medicine is that it takes individual variability at the genetic or molecular level into account in determining the best treatment for patients diagnosed with diseases detected by recently developed novel biotechnologies. The enrichment design is an efficient design that enrolls only the patients testing positive for specific molecular targets and randomly assigns them for the targeted treatment or the concurrent control. However there is no diagnostic device with perfect accuracy and precision for detecting molecular targets. In particular, the positive predictive value (PPV) can be quite low for rare diseases with low prevalence. Under the enrichment design, some patients testing positive for specific molecular targets may not have the molecular targets. The efficacy of the targeted therapy may be underestimated in the patients that actually do have the molecular targets. To address the loss of efficiency due to misclassification error, we apply the discrete mixture modeling for time-to-event data proposed by Eng and Hanlon [8] to develop an inferential procedure, based on the Cox proportional hazard model, for treatment effects of the targeted treatment effect for the true-positive patients with the molecular targets. Our proposed procedure incorporates both inaccuracy of diagnostic devices and uncertainty of estimated accuracy measures. We employed the expectation-maximization algorithm in conjunction with the bootstrap technique for estimation of the hazard ratio and its estimated variance. We report the results of simulation studies which empirically investigated the performance of the proposed method. Our proposed method is illustrated by a numerical example. PMID:27120450
Development of a charge adjustment model for cardiac catheterization.
Brennan, Andrew; Gauvreau, Kimberlee; Connor, Jean; O'Connell, Cheryl; David, Sthuthi; Almodovar, Melvin; DiNardo, James; Banka, Puja; Mayer, John E; Marshall, Audrey C; Bergersen, Lisa
2015-02-01
A methodology that would allow for comparison of charges across institutions has not been developed for catheterization in congenital heart disease. A single institution catheterization database with prospectively collected case characteristics was linked to hospital charges related and limited to an episode of care in the catheterization laboratory for fiscal years 2008-2010. Catheterization charge categories (CCC) were developed to group types of catheterization procedures using a combination of empiric data and expert consensus. A multivariable model with outcome charges was created using CCC and additional patient and procedural characteristics. In 3 fiscal years, 3,839 cases were available for analysis. Forty catheterization procedure types were categorized into 7 CCC yielding a grouper variable with an R (2) explanatory value of 72.6%. In the final CCC, the largest proportion of cases was in CCC 2 (34%), which included diagnostic cases without intervention. Biopsy cases were isolated in CCC 1 (12%), and percutaneous pulmonary valve placement alone made up CCC 7 (2%). The final model included CCC, number of interventions, and cardiac diagnosis (R (2) = 74.2%). Additionally, current financial metrics such as APR-DRG severity of illness and case mix index demonstrated a lack of correlation with CCC. We have developed a catheterization procedure type financial grouper that accounts for the diverse case population encountered in catheterization for congenital heart disease. CCC and our multivariable model could be used to understand financial characteristics of a population at a single point in time, longitudinally, and to compare populations. PMID:25113520
Comparison of the Properties of Regression and Categorical Risk-Adjustment Models
Averill, Richard F.; Muldoon, John H.; Hughes, John S.
2016-01-01
Clinical risk-adjustment, the ability to standardize the comparison of individuals with different health needs, is based upon 2 main alternative approaches: regression models and clinical categorical models. In this article, we examine the impact of the differences in the way these models are constructed on end user applications. PMID:26945302
ERIC Educational Resources Information Center
Olejnik, Stephen; Mills, Jamie; Keselman, Harvey
2000-01-01
Evaluated the use of Mallow's C(p) and Wherry's adjusted R squared (R. Wherry, 1931) statistics to select a final model from a pool of model solutions using computer generated data. Neither statistic identified the underlying regression model any better than, and usually less well than, the stepwise selection method, which itself was poor for…
Khan, Azmat Ali; Alanazi, Amer M; Jabeen, Mumtaz; Hassan, Iftekhar; Bhat, Mashooq Ahmad
2016-07-01
The present approach enumerates the effectiveness of tuftsin tagged nano-liposome for the cytosolic transport of 2,6-di-isopropylphenol-linolenic acid conjugate against liver cancer in mice. Initially, the conjugate in its free form was examined for anticancer potential on HepG2 liver cancer cells. Induction of apoptosis and suppression of migration and adhesion of HepG2 cells confirmed the effectiveness of conjugate as an anticancer agent. After this, role of the conjugate entrapped in a nano-carrier was evaluated in animal model. The nano-formulation comprising of conjugate bearing tuftsin tagged liposome was firsly characterized and then its therapeutic effect was determined. The nano-formulation had 100-130nm size nanoparticles and showed sustained release of the conjugate in the surrounding milieu. The nano-formulation distinctly reduced the expression of COX-2, an important molecule that is vastly expressed in hepatocellular carcinoma. The utilization of in-house engineered nano-formulation was also successful in significantly up-regulating Bax and down-regulating bcl-2 gene expression eventually helping in better survival of treated mice. Histopathological analysis also revealed positive recovery of the general architecture and the violent death of cancer cells by apoptosis at tumor specific site. The site specific delivery of conjugate entrapped in tuftsin tagged liposomes was highly safe as well as efficaceous. Nano-formulation based approach showed a visible chemotherapeutic effect on liver cancer progression in experimental mice thereby making it a potential candidate for treatment of liver cancer in clinical settings. PMID:27261618
Milly, P.C.D.; Dunne, K.A.
2011-01-01
Hydrologic models often are applied to adjust projections of hydroclimatic change that come from climate models. Such adjustment includes climate-bias correction, spatial refinement ("downscaling"), and consideration of the roles of hydrologic processes that were neglected in the climate model. Described herein is a quantitative analysis of the effects of hydrologic adjustment on the projections of runoff change associated with projected twenty-first-century climate change. In a case study including three climate models and 10 river basins in the contiguous United States, the authors find that relative (i.e., fractional or percentage) runoff change computed with hydrologic adjustment more often than not was less positive (or, equivalently, more negative) than what was projected by the climate models. The dominant contributor to this decrease in runoff was a ubiquitous change in runoff (median 211%) caused by the hydrologic model's apparent amplification of the climate-model-implied growth in potential evapotranspiration. Analysis suggests that the hydrologic model, on the basis of the empirical, temperature-based modified Jensen-Haise formula, calculates a change in potential evapotranspiration that is typically 3 times the change implied by the climate models, which explicitly track surface energy budgets. In comparison with the amplification of potential evapotranspiration, central tendencies of other contributions from hydrologic adjustment (spatial refinement, climate-bias adjustment, and process refinement) were relatively small. The authors' findings highlight the need for caution when projecting changes in potential evapotranspiration for use in hydrologic models or drought indices to evaluate climatechange impacts on water. Copyright ?? 2011, Paper 15-001; 35,952 words, 3 Figures, 0 Animations, 1 Tables.
Liu, Yu-Ching; Ho, Heng-Chien; Lee, Miau-Rong; Lai, Kuang-Chi; Yeh, Chung-Min; Lin, Yueh-Min; Ho, Tin-Yun; Hsiang, Chien-Yun; Chung, Jing-Gung
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.
Ghatak, Shibnath; Vyas, Alok; Misra, Suniti; O'Brien, Paul; Zambre, Ajit; Fresco, Victor M; Markwald, Roger R; Swamy, K Venkateshwara; Afrasiabi, Zahra; Choudhury, Amitava; Khetmalas, Madhukar; Padhye, Subhash
2014-01-01
Although dual inhibition of Cyclooxygenase-2 (COX-2) and 5-Lipoxygenase (5-LOX) enzymes is highly effective than targeting COX or LOX alone, there are only a few reports of examining such compounds in case of colorectal cancers (CRC). In the present work we report that the novel di-tert-butyl phenol-based dual inhibitors DTPSAL, DTPBHZ, DTPINH, and DTPNHZ exhibit significant cytotoxicity against human CRC cell lines. Molecular docking studies revealed a good fit of these compounds in the COX-2 and 5-LOX protein cavities. The inhibitors show significant inhibition of COX-2 and 5-LOX activities and are effective against a panel of human colon cancer cell lines including HCA-7, HT-29, SW480 and intestinal Apc10.1 cells as well as the hyaluronan synthase-2 (Has2) enzyme over-expressing colon cancer cells, through inhibition of the Hyaluronan/CD44v6 cell survival pathway. Western blot analysis and qRT-PCR analyses indicated that the di-tert-butyl phenol-based dual inhibitors reduce the expression of COX-2, 5-LOX, and CD44v6 in human colon cancer HCA-7 cells, while the combination of CD44v6shRNA and DTPSAL has an additional inhibitory effect on CD44v6 mRNA expression. The synergistic inhibitory effect of Celecoxib and Licofelone on CD44v6 mRNA expression suggests that the present dual inhibitors down-regulate cyclooxygenase and lipoxygenase enzymes through CD44v6. The compounds also exhibited enhanced antiproliferative potency compared to standard dual COX/LOX inhibitor, viz. Licofelone. Importantly, the HA/CD44v6 antagonist CD44v6shRNA in combination with synthetic compounds had a sensitizing effect on the cancer cells which enhanced their antiproliferative potency, a finding which is crucial for the anti-proliferative potency of the novel synthetic di-tert-butyl phenol based dual COX-LOX inhibitors in colon cancer cells. PMID:24295787
Milly, Paul C.; Dunne, Krista A.
2011-01-01
Hydrologic models often are applied to adjust projections of hydroclimatic change that come from climate models. Such adjustment includes climate-bias correction, spatial refinement ("downscaling"), and consideration of the roles of hydrologic processes that were neglected in the climate model. Described herein is a quantitative analysis of the effects of hydrologic adjustment on the projections of runoff change associated with projected twenty-first-century climate change. In a case study including three climate models and 10 river basins in the contiguous United States, the authors find that relative (i.e., fractional or percentage) runoff change computed with hydrologic adjustment more often than not was less positive (or, equivalently, more negative) than what was projected by the climate models. The dominant contributor to this decrease in runoff was a ubiquitous change in runoff (median -11%) caused by the hydrologic model’s apparent amplification of the climate-model-implied growth in potential evapotranspiration. Analysis suggests that the hydrologic model, on the basis of the empirical, temperature-based modified Jensen–Haise formula, calculates a change in potential evapotranspiration that is typically 3 times the change implied by the climate models, which explicitly track surface energy budgets. In comparison with the amplification of potential evapotranspiration, central tendencies of other contributions from hydrologic adjustment (spatial refinement, climate-bias adjustment, and process refinement) were relatively small. The authors’ findings highlight the need for caution when projecting changes in potential evapotranspiration for use in hydrologic models or drought indices to evaluate climate-change impacts on water.
Block adjustment of Chang'E-1 images based on rational function model
NASA Astrophysics Data System (ADS)
Liu, Bin; Liu, Yiliang; Di, Kaichang; Sun, Xiliang
2014-05-01
Chang'E-1(CE-1) is the first lunar orbiter of China's lunar exploration program. The CCD camera carried by CE-1 has acquired stereo images covering the entire lunar surface. Block adjustment and 3D mapping using CE-1 images are of great importance for morphological and other scientific research of the Moon. Traditional block adjustment based on rigorous sensor model is complicated due to a large number of parameters and possible correlations among them. To tackle this problem, this paper presents a block adjustment method using Rational Function Model (RFM). The RFM parameters are generated based on rigorous sensor model using virtual grid of control points. Afterwards, the RFM based block adjustment solves the refinement parameters through a least squares solution. Experimental results using CE-1 images located in Sinus Irdium show that the RFM can fit the rigorous sensor model with a high precision of 1% pixel level. Through the RFM-based block adjustment, the back-projection residuals in image space can be reduced from around 1.5 pixels to sub-pixel., indicating that RFM can replace rigorous sensor model for geometric processing of lunar images.
Partial least squares Cox regression for genome-wide data.
Nygård, Ståle; Borgan, Ornulf; Lingjaerde, Ole Christian; Størvold, Hege Leite
2008-06-01
Most methods for survival prediction from high-dimensional genomic data combine the Cox proportional hazards model with some technique of dimension reduction, such as partial least squares regression (PLS). Applying PLS to the Cox model is not entirely straightforward, and multiple approaches have been proposed. The method of Park etal. (Bioinformatics 18(Suppl. 1):S120-S127, 2002) uses a reformulation of the Cox likelihood to a Poisson type likelihood, thereby enabling estimation by iteratively reweighted partial least squares for generalized linear models. We propose a modification of the method of Park et al. (2002) such that estimates of the baseline hazard and the gene effects are obtained in separate steps. The resulting method has several advantages over the method of Park et al. (2002) and other existing Cox PLS approaches, as it allows for estimation of survival probabilities for new patients, enables a less memory-demanding estimation procedure, and allows for incorporation of lower-dimensional non-genomic variables like disease grade and tumor thickness. We also propose to combine our Cox PLS method with an initial gene selection step in which genes are ordered by their Cox score and only the highest-ranking k% of the genes are retained, obtaining a so-called supervised partial least squares regression method. In simulations, both the unsupervised and the supervised version outperform other Cox PLS methods. PMID:18188699
Richardson, David B.; Laurier, Dominique; Schubauer-Berigan, Mary K.; Tchetgen, Eric Tchetgen; Cole, Stephen R.
2014-01-01
Workers' smoking histories are not measured in many occupational cohort studies. Here we discuss the use of negative control outcomes to detect and adjust for confounding in analyses that lack information on smoking. We clarify the assumptions necessary to detect confounding by smoking and the additional assumptions necessary to indirectly adjust for such bias. We illustrate these methods using data from 2 studies of radiation and lung cancer: the Colorado Plateau cohort study (1950–2005) of underground uranium miners (in which smoking was measured) and a French cohort study (1950–2004) of nuclear industry workers (in which smoking was unmeasured). A cause-specific relative hazards model is proposed for estimation of indirectly adjusted associations. Among the miners, the proposed method suggests no confounding by smoking of the association between radon and lung cancer—a conclusion supported by adjustment for measured smoking. Among the nuclear workers, the proposed method suggests substantial confounding by smoking of the association between radiation and lung cancer. Indirect adjustment for confounding by smoking resulted in an 18% decrease in the adjusted estimated hazard ratio, yet this cannot be verified because smoking was unmeasured. Assumptions underlying this method are described, and a cause-specific proportional hazards model that allows easy implementation using standard software is presented. PMID:25245043
Attar-Schwartz, Shalhevet
2015-09-01
Warm and emotionally close relationships with parents and grandparents have been found in previous studies to be linked with better adolescent adjustment. The present study, informed by Family Systems Theory and Intergenerational Solidarity Theory, uses a moderated mediation model analyzing the contribution of the dynamics of these intergenerational relationships to adolescent adjustment. Specifically, it examines the mediating role of emotional closeness to the closest grandparent in the relationship between emotional closeness to a parent (the offspring of the closest grandparent) and adolescent adjustment difficulties. The model also examines the moderating role of emotional closeness to parents in the relationship between emotional closeness to grandparents and adjustment difficulties. The study was based on a sample of 1,405 Jewish Israeli secondary school students (ages 12-18) who completed a structured questionnaire. It was found that emotional closeness to the closest grandparent was more strongly associated with reduced adjustment difficulties among adolescents with higher levels of emotional closeness to their parents. In addition, adolescent adjustment and emotional closeness to parents was partially mediated by emotional closeness to grandparents. Examining the family conditions under which adolescents' relationships with grandparents is stronger and more beneficial for them can help elucidate variations in grandparent-grandchild ties and expand our understanding of the mechanisms that shape child outcomes. PMID:26237053
Modeling Quality-Adjusted Life Expectancy Loss Resulting from Tobacco Use in the United States
ERIC Educational Resources Information Center
Kaplan, Robert M.; Anderson, John P.; Kaplan, Cameron M.
2007-01-01
Purpose: To describe the development of a model for estimating the effects of tobacco use upon Quality Adjusted Life Years (QALYs) and to estimate the impact of tobacco use on health outcomes for the United States (US) population using the model. Method: We obtained estimates of tobacco consumption from 6 years of the National Health Interview…
Evaluation of the Stress Adjustment and Adaptation Model among Families Reporting Economic Pressure
ERIC Educational Resources Information Center
Vandsburger, Etty; Biggerstaff, Marilyn A.
2004-01-01
This research evaluates the Stress Adjustment and Adaptation Model (double ABCX model) examining the effects resiliency resources on family functioning when families experience economic pressure. Families (N = 128) with incomes at or below the poverty line from a rural area of a southern state completed measures of perceived economic pressure,…
A Model of Divorce Adjustment for Use in Family Service Agencies.
ERIC Educational Resources Information Center
Faust, Ruth Griffith
1987-01-01
Presents a combined educationally and therapeutically oriented model of treatment to (1) control and lessen disruptive experiences associated with divorce; (2) enable individuals to improve their skill in coping with adjustment reactions to divorce; and (3) modify the pressures and response of single parenthood. Describes the model's four-session…
ERIC Educational Resources Information Center
Nettles, Saundra Murray; Caughy, Margaret O'Brien; O'Campo, Patricia J.
2008-01-01
Examining recent research on neighborhood influences on child development, this review focuses on social influences on school adjustment in the early elementary years. A model to guide community research and intervention is presented. The components of the model of integrated processes are neighborhoods and their effects on academic outcomes and…
Risk adjustment of Medicare capitation payments using the CMS-HCC model.
Pope, Gregory C; Kautter, John; Ellis, Randall P; Ash, Arlene S; Ayanian, John Z; Lezzoni, Lisa I; Ingber, Melvin J; Levy, Jesse M; Robst, John
2004-01-01
This article describes the CMS hierarchical condition categories (HCC) model implemented in 2004 to adjust Medicare capitation payments to private health care plans for the health expenditure risk of their enrollees. We explain the model's principles, elements, organization, calibration, and performance. Modifications to reduce plan data reporting burden and adaptations for disabled, institutionalized, newly enrolled, and secondary payer subpopulations are discussed. PMID:15493448
Community Influences on Adjustment in First Grade: An Examination of an Integrated Process Model
ERIC Educational Resources Information Center
Caughy, Margaret O'Brien; Nettles, Saundra M.; O'Campo, Patricia J.
2007-01-01
We examined the impact of neighborhood characteristics both directly and indirectly as mediated by parent coaching and the parent/child affective relationship on behavioral and school adjustment in a sample of urban dwelling first graders. We used structural equations modeling to assess model fit and estimate direct, indirect, and total effects of…
Lipid Adjustment for Chemical Exposures: Accounting for Concomitant Variables
Li, Daniel; Longnecker, Matthew P.; Dunson, David B.
2013-01-01
Background Some environmental chemical exposures are lipophilic and need to be adjusted by serum lipid levels before data analyses. There are currently various strategies that attempt to account for this problem, but all have their drawbacks. To address such concerns, we propose a new method that uses Box-Cox transformations and a simple Bayesian hierarchical model to adjust for lipophilic chemical exposures. Methods We compared our Box-Cox method to existing methods. We ran simulation studies in which increasing levels of lipid-adjusted chemical exposure did and did not increase the odds of having a disease, and we looked at both single-exposure and multiple-exposures cases. We also analyzed an epidemiology dataset that examined the effects of various chemical exposures on the risk of birth defects. Results Compared with existing methods, our Box-Cox method produced unbiased estimates, good coverage, similar power, and lower type-I error rates. This was the case in both single- and multiple-exposure simulation studies. Results from analysis of the birth-defect data differed from results using existing methods. Conclusion Our Box-Cox method is a novel and intuitive way to account for the lipophilic nature of certain chemical exposures. It addresses some of the problems with existing methods, is easily extendable to multiple exposures, and can be used in any analyses that involve concomitant variables. PMID:24051893
Contact angle adjustment in equation-of-state-based pseudopotential model
NASA Astrophysics Data System (ADS)
Hu, Anjie; Li, Longjian; Uddin, Rizwan; Liu, Dong
2016-05-01
The single component pseudopotential lattice Boltzmann model has been widely applied in multiphase simulation due to its simplicity and stability. In many studies, it has been claimed that this model can be stable for density ratios larger than 1000. However, the application of the model is still limited to small density ratios when the contact angle is considered. The reason is that the original contact angle adjustment method influences the stability of the model. Moreover, simulation results in the present work show that, by applying the original contact angle adjustment method, the density distribution near the wall is artificially changed, and the contact angle is dependent on the surface tension. Hence, it is very inconvenient to apply this method with a fixed contact angle, and the accuracy of the model cannot be guaranteed. To solve these problems, a contact angle adjustment method based on the geometry analysis is proposed and numerically compared with the original method. Simulation results show that, with our contact angle adjustment method, the stability of the model is highly improved when the density ratio is relatively large, and it is independent of the surface tension.
Huang, Lam O.; Infante-Rivard, Claire; Labbe, Aurélie
2016-01-01
Transmission of the two parental alleles to offspring deviating from the Mendelian ratio is termed Transmission Ratio Distortion (TRD), occurs throughout gametic and embryonic development. TRD has been well-studied in animals, but remains largely unknown in humans. The Transmission Disequilibrium Test (TDT) was first proposed to test for association and linkage in case-trios (affected offspring and parents); adjusting for TRD using control-trios was recommended. However, the TDT does not provide risk parameter estimates for different genetic models. A loglinear model was later proposed to provide child and maternal relative risk (RR) estimates of disease, assuming Mendelian transmission. Results from our simulation study showed that case-trios RR estimates using this model are biased in the presence of TRD; power and Type 1 error are compromised. We propose an extended loglinear model adjusting for TRD. Under this extended model, RR estimates, power and Type 1 error are correctly restored. We applied this model to an intrauterine growth restriction dataset, and showed consistent results with a previous approach that adjusted for TRD using control-trios. Our findings suggested the need to adjust for TRD in avoiding spurious results. Documenting TRD in the population is therefore essential for the correct interpretation of genetic association studies.
Cummings, E. Mark; Merrilees, Christine E.; Schermerhorn, Alice C.; Goeke-Morey, Marcie C.; Shirlow, Peter; Cairns, Ed
2013-01-01
Relations between political violence and child adjustment are matters of international concern. Past research demonstrates the significance of community, family and child psychological processes in child adjustment, supporting study of inter-relations between multiple social ecological factors and child adjustment in contexts of political violence. Testing a social ecological model, 300 mothers and their children (M= 12.28 years, SD = 1.77) from Catholic and Protestant working class neighborhoods in Belfast, Northern Ireland completed measures of community discord, family relations, and children’s regulatory processes (i.e., emotional security) and outcomes. Historical political violence in neighborhoods based on objective records (i.e., politically motivated deaths) were related to family members’ reports of current sectarian and non-sectarian antisocial behavior. Interparental conflict and parental monitoring and children’s emotional security about both the community and family contributed to explanatory pathways for relations between sectarian antisocial behavior in communities and children’s adjustment problems. The discussion evaluates support for social ecological models for relations between political violence and child adjustment and its implications for understanding relations in other parts of the world. PMID:20423550
Cummings, E Mark; Merrilees, Christine E; Schermerhorn, Alice C; Goeke-Morey, Marcie C; Shirlow, Peter; Cairns, Ed
2010-05-01
Relations between political violence and child adjustment are matters of international concern. Past research demonstrates the significance of community, family, and child psychological processes in child adjustment, supporting study of interrelations between multiple social ecological factors and child adjustment in contexts of political violence. Testing a social ecological model, 300 mothers and their children (M = 12.28 years, SD = 1.77) from Catholic and Protestant working class neighborhoods in Belfast, Northern Ireland, completed measures of community discord, family relations, and children's regulatory processes (i.e., emotional security) and outcomes. Historical political violence in neighborhoods based on objective records (i.e., politically motivated deaths) were related to family members' reports of current sectarian antisocial behavior and nonsectarian antisocial behavior. Interparental conflict and parental monitoring and children's emotional security about both the community and family contributed to explanatory pathways for relations between sectarian antisocial behavior in communities and children's adjustment problems. The discussion evaluates support for social ecological models for relations between political violence and child adjustment and its implications for understanding relations in other parts of the world. PMID:20423550
ERIC Educational Resources Information Center
Bernard, Lori L.; Guarnaccia, Charles A.
2003-01-01
Purpose: Caregiver bereavement adjustment literature suggests opposite models of impact of role strain on bereavement adjustment after care-recipient death--a Complicated Grief Model and a Relief Model. This study tests these competing models for husband and adult-daughter caregivers of breast cancer hospice patients. Design and Methods: This…
Kiang, Lisa; Witkow, Melissa R; Thompson, Taylor L
2016-07-01
The model minority image is a common and pervasive stereotype that Asian American adolescents must navigate. Using multiwave data from 159 adolescents from Asian American backgrounds (mean age at initial recruitment = 15.03, SD = .92; 60 % female; 74 % US-born), the current study targeted unexplored aspects of the model minority experience in conjunction with more traditionally measured experiences of negative discrimination. When examining normative changes, perceptions of model minority stereotyping increased over the high school years while perceptions of discrimination decreased. Both experiences were not associated with each other, suggesting independent forms of social interactions. Model minority stereotyping generally promoted academic and socioemotional adjustment, whereas discrimination hindered outcomes. Moreover, in terms of academic adjustment, the model minority stereotype appears to protect against the detrimental effect of discrimination. Implications of the complex duality of adolescents' social interactions are discussed. PMID:26251100
A Four-Part Model of Autonomy during Emerging Adulthood: Associations with Adjustment
ERIC Educational Resources Information Center
Lamborn, Susie D.; Groh, Kelly
2009-01-01
We found support for a four-part model of autonomy that links connectedness, separation, detachment, and agency to adjustment during emerging adulthood. Based on self-report surveys of 285 American college students, expected associations among the autonomy variables were found. In addition, agency, as measured by self-reliance, predicted lower…
A Threshold Model of Social Support, Adjustment, and Distress after Breast Cancer Treatment
ERIC Educational Resources Information Center
Mallinckrodt, Brent; Armer, Jane M.; Heppner, P. Paul
2012-01-01
This study examined a threshold model that proposes that social support exhibits a curvilinear association with adjustment and distress, such that support in excess of a critical threshold level has decreasing incremental benefits. Women diagnosed with a first occurrence of breast cancer (N = 154) completed survey measures of perceived support…
Simultaneous confidence bands for Cox regression from semiparametric random censorship.
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. PMID:25691289
NASA Astrophysics Data System (ADS)
Naipal, V.; Reick, C.; Pongratz, J.; Van Oost, K.
2015-03-01
Large uncertainties exist in estimated rates and the extent of soil erosion by surface runoff on a global scale, and this limits our understanding of the global impact that soil erosion might have on agriculture and climate. The Revised Universal Soil Loss Equation (RUSLE) model is due to its simple structure and empirical basis a frequently used tool in estimating average annual soil erosion rates at regional to global scales. However, large spatial scale applications often rely on coarse data input, which is not compatible with the local scale at which the model is parameterized. This study aimed at providing the first steps in improving the global applicability of the RUSLE model in order to derive more accurate global soil erosion rates. We adjusted the topographical and rainfall erosivity factors of the RUSLE model and compared the resulting soil erosion rates to extensive empirical databases on soil erosion from the USA and Europe. Adjusting the topographical factor required scaling of slope according to the fractal method, which resulted in improved topographical detail in a coarse resolution global digital elevation model. Applying the linear multiple regression method to adjust rainfall erosivity for various climate zones resulted in values that are in good comparison with high resolution erosivity data for different regions. However, this method needs to be extended to tropical climates, for which erosivity is biased due to the lack of high resolution erosivity data. After applying the adjusted and the unadjusted versions of the RUSLE model on a global scale we find that the adjusted RUSLE model not only shows a global higher mean soil erosion rate but also more variability in the soil erosion rates. Comparison to empirical datasets of the USA and Europe shows that the adjusted RUSLE model is able to decrease the very high erosion rates in hilly regions that are observed in the unadjusted RUSLE model results. Although there are still some regional
An improved bundle adjustment model and algorithm with novel block matrix partition method
NASA Astrophysics Data System (ADS)
Xia, Zemin; Li, Zhongwei; Zhong, Kai
2014-11-01
Sparse bundle adjustment is widely applied in computer vision and photogrammetry. However, existing implementation is based on the model of n 3D points projecting onto m different camera imaging planes at m positions, which can't be applied to commonly monocular, binocular or trinocular imaging systems. A novel design and implementation of bundle adjustment algorithm is proposed in this paper, which is based on n 3D points projecting onto the same camera imaging plane at m positions .To improve the performance of the algorithm, a novel sparse block matrix partition method is proposed. Experiments show that the improved bundle adjustment is effective, robust and has a better tolerance to pixel coordinates error.
NASA Astrophysics Data System (ADS)
Naipal, V.; Reick, C.; Pongratz, J.; Van Oost, K.
2015-09-01
Large uncertainties exist in estimated rates and the extent of soil erosion by surface runoff on a global scale. This limits our understanding of the global impact that soil erosion might have on agriculture and climate. The Revised Universal Soil Loss Equation (RUSLE) model is, due to its simple structure and empirical basis, a frequently used tool in estimating average annual soil erosion rates at regional to global scales. However, large spatial-scale applications often rely on coarse data input, which is not compatible with the local scale on which the model is parameterized. Our study aims at providing the first steps in improving the global applicability of the RUSLE model in order to derive more accurate global soil erosion rates. We adjusted the topographical and rainfall erosivity factors of the RUSLE model and compared the resulting erosion rates to extensive empirical databases from the USA and Europe. By scaling the slope according to the fractal method to adjust the topographical factor, we managed to improve the topographical detail in a coarse resolution global digital elevation model. Applying the linear multiple regression method to adjust rainfall erosivity for various climate zones resulted in values that compared well to high resolution erosivity data for different regions. However, this method needs to be extended to tropical climates, for which erosivity is biased due to the lack of high resolution erosivity data. After applying the adjusted and the unadjusted versions of the RUSLE model on a global scale we find that the adjusted version shows a global higher mean erosion rate and more variability in the erosion rates. Comparison to empirical data sets of the USA and Europe shows that the adjusted RUSLE model is able to decrease the very high erosion rates in hilly regions that are observed in the unadjusted RUSLE model results. Although there are still some regional differences with the empirical databases, the results indicate that the
Medeiros, Stephen; Hagen, Scott; Weishampel, John; Angelo, James
2015-03-25
Digital elevation models (DEMs) derived from airborne lidar are traditionally unreliable in coastal salt marshes due to the inability of the laser to penetrate the dense grasses and reach the underlying soil. To that end, we present a novel processing methodology that uses ASTER Band 2 (visible red), an interferometric SAR (IfSAR) digital surface model, and lidar-derived canopy height to classify biomass density using both a three-class scheme (high, medium and low) and a two-class scheme (high and low). Elevation adjustments associated with these classes using both median and quartile approaches were applied to adjust lidar-derived elevation values closer to true bare earth elevation. The performance of the method was tested on 229 elevation points in the lower Apalachicola River Marsh. The two-class quartile-based adjusted DEM produced the best results, reducing the RMS error in elevation from 0.65 m to 0.40 m, a 38% improvement. The raw mean errors for the lidar DEM and the adjusted DEM were 0.61 ± 0.24 m and 0.32 ± 0.24 m, respectively, thereby reducing the high bias by approximately 49%.
Medeiros, Stephen; Hagen, Scott; Weishampel, John; Angelo, James
2015-03-25
Digital elevation models (DEMs) derived from airborne lidar are traditionally unreliable in coastal salt marshes due to the inability of the laser to penetrate the dense grasses and reach the underlying soil. To that end, we present a novel processing methodology that uses ASTER Band 2 (visible red), an interferometric SAR (IfSAR) digital surface model, and lidar-derived canopy height to classify biomass density using both a three-class scheme (high, medium and low) and a two-class scheme (high and low). Elevation adjustments associated with these classes using both median and quartile approaches were applied to adjust lidar-derived elevation values closer tomore » true bare earth elevation. The performance of the method was tested on 229 elevation points in the lower Apalachicola River Marsh. The two-class quartile-based adjusted DEM produced the best results, reducing the RMS error in elevation from 0.65 m to 0.40 m, a 38% improvement. The raw mean errors for the lidar DEM and the adjusted DEM were 0.61 ± 0.24 m and 0.32 ± 0.24 m, respectively, thereby reducing the high bias by approximately 49%.« less
An appraisal-based coping model of attachment and adjustment to arthritis.
Sirois, Fuschia M; Gick, Mary L
2016-05-01
Guided by pain-related attachment models and coping theory, we used structural equation modeling to test an appraisal-based coping model of how insecure attachment was linked to arthritis adjustment in a sample of 365 people with arthritis. The structural equation modeling analyses revealed indirect and direct associations of anxious and avoidant attachment with greater appraisals of disease-related threat, less perceived social support to deal with this threat, and less coping efficacy. There was evidence of reappraisal processes for avoidant but not anxious attachment. Findings highlight the importance of considering attachment style when assessing how people cope with the daily challenges of arthritis. PMID:24984717
Cassidy, Adam R
2016-01-01
The objective of this study was to establish latent executive function (EF) and psychosocial adjustment factor structure, to examine associations between EF and psychosocial adjustment, and to explore potential development differences in EF-psychosocial adjustment associations in healthy children and adolescents. Using data from the multisite National Institutes of Health (NIH) magnetic resonance imaging (MRI) Study of Normal Brain Development, the current investigation examined latent associations between theoretically and empirically derived EF factors and emotional and behavioral adjustment measures in a large, nationally representative sample of children and adolescents (7-18 years old; N = 352). Confirmatory factor analysis (CFA) was the primary method of data analysis. CFA results revealed that, in the whole sample, the proposed five-factor model (Working Memory, Shifting, Verbal Fluency, Externalizing, and Internalizing) provided a close fit to the data, χ(2)(66) = 114.48, p < .001; RMSEA = .046; NNFI = .973; CFI = .980. Significant negative associations were demonstrated between Externalizing and both Working Memory and Verbal Fluency (p < .01) factors. A series of increasingly restrictive tests led to the rejection of the hypothesis of invariance, thereby precluding formal statistical examination of age-related differences in latent EF-psychosocial adjustment associations. Findings indicate that childhood EF skills are best conceptualized as a constellation of interconnected yet distinguishable cognitive self-regulatory skills. Individual differences in certain domains of EF track meaningfully and in expected directions with emotional and behavioral adjustment indices. Externalizing behaviors, in particular, are associated with latent Working Memory and Verbal Fluency factors. PMID:25569593
Kautter, John; Pope, Gregory C; Ingber, Melvin; Freeman, Sara; Patterson, Lindsey; Cohen, Michael; Keenan, Patricia
2014-01-01
Beginning in 2014, individuals and small businesses are able to purchase private health insurance through competitive Marketplaces. The Affordable Care Act (ACA) provides for a program of risk adjustment in the individual and small group markets in 2014 as Marketplaces are implemented and new market reforms take effect. The purpose of risk adjustment is to lessen or eliminate the influence of risk selection on the premiums that plans charge. The risk adjustment methodology includes the risk adjustment model and the risk transfer formula. This article is the second of three in this issue of the Review that describe the Department of Health and Human Services (HHS) risk adjustment methodology and focuses on the risk adjustment model. In our first companion article, we discuss the key issues and choices in developing the methodology. In this article, we present the risk adjustment model, which is named the HHS-Hierarchical Condition Categories (HHS-HCC) risk adjustment model. We first summarize the HHS-HCC diagnostic classification, which is the key element of the risk adjustment model. Then the data and methods, results, and evaluation of the risk adjustment model are presented. Fifteen separate models are developed. For each age group (adult, child, and infant), a model is developed for each cost sharing level (platinum, gold, silver, and bronze metal levels, as well as catastrophic plans). Evaluation of the risk adjustment models shows good predictive accuracy, both for individuals and for groups. Lastly, this article provides examples of how the model output is used to calculate risk scores, which are an input into the risk transfer formula. Our third companion paper describes the risk transfer formula. PMID:25360387
Kautter, John; Pope, Gregory C; Ingber, Melvin; Freeman, Sara; Patterson, Lindsey; Cohen, Michael; Keenan, Patricia
2014-01-01
Beginning in 2014, individuals and small businesses are able to purchase private health insurance through competitive Marketplaces. The Affordable Care Act (ACA) provides for a program of risk adjustment in the individual and small group markets in 2014 as Marketplaces are implemented and new market reforms take effect. The purpose of risk adjustment is to lessen or eliminate the influence of risk selection on the premiums that plans charge. The risk adjustment methodology includes the risk adjustment model and the risk transfer formula. This article is the second of three in this issue of the Review that describe the Department of Health and Human Services (HHS) risk adjustment methodology and focuses on the risk adjustment model. In our first companion article, we discuss the key issues and choices in developing the methodology. In this article, we present the risk adjustment model, which is named the HHS-Hierarchical Condition Categories (HHS-HCC) risk adjustment model. We first summarize the HHS-HCC diagnostic classification, which is the key element of the risk adjustment model. Then the data and methods, results, and evaluation of the risk adjustment model are presented. Fifteen separate models are developed. For each age group (adult, child, and infant), a model is developed for each cost sharing level (platinum, gold, silver, and bronze metal levels, as well as catastrophic plans). Evaluation of the risk adjustment models shows good predictive accuracy, both for individuals and for groups. Lastly, this article provides examples of how the model output is used to calculate risk scores, which are an input into the risk transfer formula. Our third companion paper describes the risk transfer formula. PMID:25360387
Lithium-ion Open Circuit Voltage (OCV) curve modelling and its ageing adjustment
NASA Astrophysics Data System (ADS)
Lavigne, L.; Sabatier, J.; Francisco, J. Mbala; Guillemard, F.; Noury, A.
2016-08-01
This paper is a contribution to lithium-ion batteries modelling taking into account aging effects. It first analyses the impact of aging on electrode stoichiometry and then on lithium-ion cell Open Circuit Voltage (OCV) curve. Through some hypotheses and an appropriate definition of the cell state of charge, it shows that each electrode equilibrium potential, but also the whole cell equilibrium potential can be modelled by a polynomial that requires only one adjustment parameter during aging. An adjustment algorithm, based on the idea that for two fixed OCVs, the state of charge between these two equilibrium states is unique for a given aging level, is then proposed. Its efficiency is evaluated on a battery pack constituted of four cells.
Parra, Edwin Roger; Lin, Flavia; Martins, Vanessa; Rangel, Maristela Peres; Capelozzi, Vera Luiza
2013-01-01
OBJECTIVE: To study the expression of COX-1 and COX-2 in the remodeled lung in systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF) patients, correlating that expression with patient survival. METHODS: We examined open lung biopsy specimens from 24 SSc patients and 30 IPF patients, using normal lung tissue as a control. The histological patterns included fibrotic nonspecific interstitial pneumonia (NSIP) in SSc patients and usual interstitial pneumonia (UIP) in IPF patients. We used immunohistochemistry and histomorphometry to evaluate the expression of COX-1 and COX-2 in alveolar septa, vessels, and bronchioles. We then correlated that expression with pulmonary function test results and evaluated its impact on patient survival. RESULTS: The expression of COX-1 and COX-2 in alveolar septa was significantly higher in IPF-UIP and SSc-NSIP lung tissue than in the control tissue. No difference was found between IPF-UIP and SSc-NSIP tissue regarding COX-1 and COX-2 expression. Multivariate analysis based on the Cox regression model showed that the factors associated with a low risk of death were younger age, high DLCO/alveolar volume, IPF, and high COX-1 expression in alveolar septa, whereas those associated with a high risk of death were advanced age, low DLCO/alveolar volume, SSc (with NSIP), and low COX-1 expression in alveolar septa. CONCLUSIONS: Our findings suggest that strategies aimed at preventing low COX-1 synthesis will have a greater impact on SSc, whereas those aimed at preventing high COX-2 synthesis will have a greater impact on IPF. However, prospective randomized clinical trials are needed in order to confirm that. PMID:24473763
Akasaka, Hironari; So, Shui-Ping; Ruan, Ke-He
2015-06-16
In vascular inflammation, prostaglandin E2 (PGE₂) is largely biosynthesized by microsomal PGE₂ synthase-1 (mPGES-1), competing with other downstream eicosanoid-synthesizing enzymes, such as PGIS, a synthase of a vascular protector prostacyclin (PGI₂), to isomerize the cyclooxygenase (COX)-2-derived prostaglandin H2 (PGH₂). In this study, we found that a majority of the product from the cells co-expressing human COX-2, mPGES-1, and PGIS was PGE₂. We hypothesize that the molecular and cellular mechanisms are related to the post-translational endoplasmic reticulum (ER) arrangement of those enzymes. A set of fusion enzymes, COX-2-linker [10 amino acids (aa)]-PGIS and COX-2-linker (22 amino acids)-PGIS, were created as "The Bioruler", in which the 10 and 22 amino acids are defined linkers with known helical structures and distances (14.4 and 30.8 Å, respectively). Our experiments have shown that the efficiency of PGI₂ biosynthesis was reduced when the separation distance increased from 10 to 22 amino acids. When COX-2-10aa-PGIS (with a 14.4 Å separation) was co-expressed with mPGES-1 on the ER membrane, a major product was PGE₂, but not PGI₂. However, expression of COX-2-10aa-PGIS and mPGES-1 on a separated ER with a distance of ≫30.8 Å reduced the level of PGE₂ production. These data indicated that the mPGES-1 is "complex-likely" colocalized with COX-2 within a distance of 14.4 Å. In addition, the cells co-expressing COX-1-10aa-PGIS and mPGES-1 produced PGI₂ mainly, but not PGE₂. This indicates that mPGES-1 is expressed much farther from COX-1. These findings have led to proposed models showing the different post-translational ER organization between COX-2 and COX-1 with respect to the topological arrangement of the mPGES-1 during vascular inflammation. PMID:25988363
ERIC Educational Resources Information Center
Siman-Tov, Ayelet; Kaniel, Shlomo
2011-01-01
The research validates a multivariate model that predicts parental adjustment to coping successfully with an autistic child. The model comprises four elements: parental stress, parental resources, parental adjustment and the child's autism symptoms. 176 parents of children aged between 6 to 16 diagnosed with PDD answered several questionnaires…
Li, Li; Brumback, Babette A; Weppelmann, Thomas A; Morris, J Glenn; Ali, Afsar
2016-08-15
Motivated by an investigation of the effect of surface water temperature on the presence of Vibrio cholerae in water samples collected from different fixed surface water monitoring sites in Haiti in different months, we investigated methods to adjust for unmeasured confounding due to either of the two crossed factors site and month. In the process, we extended previous methods that adjust for unmeasured confounding due to one nesting factor (such as site, which nests the water samples from different months) to the case of two crossed factors. First, we developed a conditional pseudolikelihood estimator that eliminates fixed effects for the levels of each of the crossed factors from the estimating equation. Using the theory of U-Statistics for independent but non-identically distributed vectors, we show that our estimator is consistent and asymptotically normal, but that its variance depends on the nuisance parameters and thus cannot be easily estimated. Consequently, we apply our estimator in conjunction with a permutation test, and we investigate use of the pigeonhole bootstrap and the jackknife for constructing confidence intervals. We also incorporate our estimator into a diagnostic test for a logistic mixed model with crossed random effects and no unmeasured confounding. For comparison, we investigate between-within models extended to two crossed factors. These generalized linear mixed models include covariate means for each level of each factor in order to adjust for the unmeasured confounding. We conduct simulation studies, and we apply the methods to the Haitian data. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26892025
NASA Astrophysics Data System (ADS)
Müller, Marc F.; Thompson, Sally E.
2013-10-01
Estimating precipitation over large spatial areas remains a challenging problem for hydrologists. Sparse ground-based gauge networks do not provide a robust basis for interpolation, and the reliability of remote sensing products, although improving, is still imperfect. Current techniques to estimate precipitation rely on combining these different kinds of measurements to correct the bias in the satellite observations. We propose a novel procedure that, unlike existing techniques, (i) allows correcting the possibly confounding effects of different sources of errors in satellite estimates, (ii) explicitly accounts for the spatial heterogeneity of the biases and (iii) allows the use of non overlapping historical observations. The proposed method spatially aggregates and interpolates gauge data at the satellite grid resolution by focusing on parameters that describe the frequency and intensity of the rainfall observed at the gauges. The resulting gridded parameters can then be used to adjust the probability density function of satellite rainfall observations at each grid cell, accounting for spatial heterogeneity. Unlike alternate methods, we explicitly adjust biases on rainfall frequency in addition to its intensity. Adjusted rainfall distributions can then readily be applied as input in stochastic rainfall generators or frequency domain hydrological models. Finally, we also provide a procedure to use them to correct remotely sensed rainfall time series. We apply the method to adjust the distributions of daily rainfall observed by the TRMM satellite in Nepal, which exemplifies the challenges associated with a sparse gauge network and large biases due to complex topography. In a cross-validation analysis on daily rainfall from TRMM 3B42 v6, we find that using a small subset of the available gauges, the proposed method outperforms local rainfall estimations using the complete network of available gauges to directly interpolate local rainfall or correct TRMM by adjusting
Biologically Inspired Visual Model With Preliminary Cognition and Active Attention Adjustment.
Qiao, Hong; Xi, Xuanyang; Li, Yinlin; Wu, Wei; Li, Fengfu
2015-11-01
Recently, many computational models have been proposed to simulate visual cognition process. For example, the hierarchical Max-Pooling (HMAX) model was proposed according to the hierarchical and bottom-up structure of V1 to V4 in the ventral pathway of primate visual cortex, which could achieve position- and scale-tolerant recognition. In our previous work, we have introduced memory and association into the HMAX model to simulate visual cognition process. In this paper, we improve our theoretical framework by mimicking a more elaborate structure and function of the primate visual cortex. We will mainly focus on the new formation of memory and association in visual processing under different circumstances as well as preliminary cognition and active adjustment in the inferior temporal cortex, which are absent in the HMAX model. The main contributions of this paper are: 1) in the memory and association part, we apply deep convolutional neural networks to extract various episodic features of the objects since people use different features for object recognition. Moreover, to achieve a fast and robust recognition in the retrieval and association process, different types of features are stored in separated clusters and the feature binding of the same object is stimulated in a loop discharge manner and 2) in the preliminary cognition and active adjustment part, we introduce preliminary cognition to classify different types of objects since distinct neural circuits in a human brain are used for identification of various types of objects. Furthermore, active cognition adjustment of occlusion and orientation is implemented to the model to mimic the top-down effect in human cognition process. Finally, our model is evaluated on two face databases CAS-PEAL-R1 and AR. The results demonstrate that our model exhibits its efficiency on visual recognition process with much lower memory storage requirement and a better performance compared with the traditional purely computational
NASA Astrophysics Data System (ADS)
Brix, H.; Menemenlis, D.; Hill, C.; Dutkiewicz, S.; Jahn, O.; Wang, D.; Bowman, K.; Zhang, H.
2015-11-01
The NASA Carbon Monitoring System (CMS) Flux Project aims to attribute changes in the atmospheric accumulation of carbon dioxide to spatially resolved fluxes by utilizing the full suite of NASA data, models, and assimilation capabilities. For the oceanic part of this project, we introduce ECCO2-Darwin, a new ocean biogeochemistry general circulation model based on combining the following pre-existing components: (i) a full-depth, eddying, global-ocean configuration of the Massachusetts Institute of Technology general circulation model (MITgcm), (ii) an adjoint-method-based estimate of ocean circulation from the Estimating the Circulation and Climate of the Ocean, Phase II (ECCO2) project, (iii) the MIT ecosystem model "Darwin", and (iv) a marine carbon chemistry model. Air-sea gas exchange coefficients and initial conditions of dissolved inorganic carbon, alkalinity, and oxygen are adjusted using a Green's Functions approach in order to optimize modeled air-sea CO2 fluxes. Data constraints include observations of carbon dioxide partial pressure (pCO2) for 2009-2010, global air-sea CO2 flux estimates, and the seasonal cycle of the Takahashi et al. (2009) Atlas. The model sensitivity experiments (or Green's Functions) include simulations that start from different initial conditions as well as experiments that perturb air-sea gas exchange parameters and the ratio of particulate inorganic to organic carbon. The Green's Functions approach yields a linear combination of these sensitivity experiments that minimizes model-data differences. The resulting initial conditions and gas exchange coefficients are then used to integrate the ECCO2-Darwin model forward. Despite the small number (six) of control parameters, the adjusted simulation is significantly closer to the data constraints (37% cost function reduction, i.e., reduction in the model-data difference, relative to the baseline simulation) and to independent observations (e.g., alkalinity). The adjusted air-sea gas
A finite element model updating technique for adjustment of parameters near boundaries
NASA Astrophysics Data System (ADS)
Gwinn, Allen Fort, Jr.
Even though there have been many advances in research related to methods of updating finite element models based on measured normal mode vibration characteristics, there is yet to be a widely accepted method that works reliably with a wide range of problems. This dissertation focuses on the specific class of problems having to do with changes in stiffness near the clamped boundary of plate structures. This class of problems is especially important as it relates to the performance of turbine engine blades, where a change in stiffness at the base of the blade can be indicative of structural damage. The method that is presented herein is a new technique for resolving the differences between the physical structure and the finite element model. It is a semi-iterative technique that incorporates a "physical expansion" of the measured eigenvectors along with appropriate scaling of these expanded eigenvectors into an iterative loop that uses the Engel's model modification method to then calculate adjusted stiffness parameters for the finite element model. Three example problems are presented that use eigenvalues and mass normalized eigenvectors that have been calculated from experimentally obtained accelerometer readings. The test articles that were used were all thin plates with one edge fully clamped. They each had a cantilevered length of 8.5 inches and a width of 4 inches. The three plates differed from one another in thickness from 0.100 inches to 0.188 inches. These dimensions were selected in order to approximate a gas turbine engine blade. The semi-iterative modification technique is shown to do an excellent job of calculating the necessary adjustments to the finite element model so that the analytically determined eigenvalues and eigenvectors for the adjusted model match the corresponding values from the experimental data with good agreement. Furthermore, the semi-iterative method is quite robust. For the examples presented here, the method consistently converged
Interfacial free energy adjustable phase field crystal model for homogeneous nucleation.
Guo, Can; Wang, Jincheng; Wang, Zhijun; Li, Junjie; Guo, Yaolin; Huang, Yunhao
2016-05-18
To describe the homogeneous nucleation process, an interfacial free energy adjustable phase-field crystal model (IPFC) was proposed by reconstructing the energy functional of the original phase field crystal (PFC) methodology. Compared with the original PFC model, the additional interface term in the IPFC model effectively can adjust the magnitude of the interfacial free energy, but does not affect the equilibrium phase diagram and the interfacial energy anisotropy. The IPFC model overcame the limitation that the interfacial free energy of the original PFC model is much less than the theoretical results. Using the IPFC model, we investigated some basic issues in homogeneous nucleation. From the viewpoint of simulation, we proceeded with an in situ observation of the process of cluster fluctuation and obtained quite similar snapshots to colloidal crystallization experiments. We also counted the size distribution of crystal-like clusters and the nucleation rate. Our simulations show that the size distribution is independent of the evolution time, and the nucleation rate remains constant after a period of relaxation, which are consistent with experimental observations. The linear relation between logarithmic nucleation rate and reciprocal driving force also conforms to the steady state nucleation theory. PMID:27117814
Adjusting for Network Size and Composition Effects in Exponential-Family Random Graph Models.
Krivitsky, Pavel N; Handcock, Mark S; Morris, Martina
2011-07-01
Exponential-family random graph models (ERGMs) provide a principled way to model and simulate features common in human social networks, such as propensities for homophily and friend-of-a-friend triad closure. We show that, without adjustment, ERGMs preserve density as network size increases. Density invariance is often not appropriate for social networks. We suggest a simple modification based on an offset which instead preserves the mean degree and accommodates changes in network composition asymptotically. We demonstrate that this approach allows ERGMs to be applied to the important situation of egocentrically sampled data. We analyze data from the National Health and Social Life Survey (NHSLS). PMID:21691424
Remote Sensing-based Methodologies for Snow Model Adjustments in Operational Streamflow Prediction
NASA Astrophysics Data System (ADS)
Bender, S.; Miller, W. P.; Bernard, B.; Stokes, M.; Oaida, C. M.; Painter, T. H.
2015-12-01
Water management agencies rely on hydrologic forecasts issued by operational agencies such as NOAA's Colorado Basin River Forecast Center (CBRFC). The CBRFC has partnered with the Jet Propulsion Laboratory (JPL) under funding from NASA to incorporate research-oriented, remotely-sensed snow data into CBRFC operations and to improve the accuracy of CBRFC forecasts. The partnership has yielded valuable analysis of snow surface albedo as represented in JPL's MODIS Dust Radiative Forcing in Snow (MODDRFS) data, across the CBRFC's area of responsibility. When dust layers within a snowpack emerge, reducing the snow surface albedo, the snowmelt rate may accelerate. The CBRFC operational snow model (SNOW17) is a temperature-index model that lacks explicit representation of snowpack surface albedo. CBRFC forecasters monitor MODDRFS data for emerging dust layers and may manually adjust SNOW17 melt rates. A technique was needed for efficient and objective incorporation of the MODDRFS data into SNOW17. Initial development focused in Colorado, where dust-on-snow events frequently occur. CBRFC forecasters used retrospective JPL-CBRFC analysis and developed a quantitative relationship between MODDRFS data and mean areal temperature (MAT) data. The relationship was used to generate adjusted, MODDRFS-informed input for SNOW17. Impacts of the MODDRFS-SNOW17 MAT adjustment method on snowmelt-driven streamflow prediction varied spatially and with characteristics of the dust deposition events. The largest improvements occurred in southwestern Colorado, in years with intense dust deposition events. Application of the method in other regions of Colorado and in "low dust" years resulted in minimal impact. The MODDRFS-SNOW17 MAT technique will be implemented in CBRFC operations in late 2015, prior to spring 2016 runoff. Collaborative investigation of remote sensing-based adjustment methods for the CBRFC operational hydrologic forecasting environment will continue over the next several years.
NASA Astrophysics Data System (ADS)
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."
“A model of mother-child Adjustment in Arab Muslim Immigrants to the US”
Hough, Edythe s; Templin, Thomas N; Kulwicki, Anahid; Ramaswamy, Vidya; Katz, Anne
2009-01-01
We examined the mother-child adjustment and child behavior problems in Arab Muslim immigrant families residing in the U.S.A. The sample of 635 mother-child dyads was comprised of mothers who emigrated from 1989 or later and had at least one early adolescent child between the ages of 11 to 15 years old who was also willing to participate. Arabic speaking research assistants collected the data from the mothers and children using established measures of maternal and child stressors, coping, and social support; maternal distress; parent-child relationship; and child behavior problems. A structural equation model (SEM) was specified a priori with 17 predicted pathways. With a few exceptions, the final SEM model was highly consistent with the proposed model and had a good fit to the data. The model accounted for 67% of the variance in child behavior problems. Child stressors, mother-child relationship, and maternal stressors were the causal variables that contributed the most to child behavior problems. The model also accounted for 27% of the variance in mother-child relationship. Child active coping, child gender, mother’s education, and maternal distress were all predictive of the mother-child relationship. Mother-child relationship also mediated the effects of maternal distress and child active coping on child behavior problems. These findings indicate that immigrant mothers contribute greatly to adolescent adjustment, both as a source of risk and protection. These findings also suggest that intervening with immigrant mothers to reduce their stress and strengthening the parent-child relationship are two important areas for promoting adolescent adjustment. PMID:19758737
A spatial model of bird abundance as adjusted for detection probability
Gorresen, P.M.; Mcmillan, G.P.; Camp, R.J.; Pratt, T.K.
2009-01-01
Modeling the spatial distribution of animals can be complicated by spatial and temporal effects (i.e. spatial autocorrelation and trends in abundance over time) and other factors such as imperfect detection probabilities and observation-related nuisance variables. Recent advances in modeling have demonstrated various approaches that handle most of these factors but which require a degree of sampling effort (e.g. replication) not available to many field studies. We present a two-step approach that addresses these challenges to spatially model species abundance. Habitat, spatial and temporal variables were handled with a Bayesian approach which facilitated modeling hierarchically structured data. Predicted abundance was subsequently adjusted to account for imperfect detection and the area effectively sampled for each species. We provide examples of our modeling approach for two endemic Hawaiian nectarivorous honeycreepers: 'i'iwi Vestiaria coccinea and 'apapane Himatione sanguinea. ?? 2009 Ecography.
Biochemistry of cyclooxygenase (COX)-2 inhibitors and molecular pathology of COX-2 in neoplasia.
Fosslien, E
2000-10-01
Several types of human tumors overexpress cyclooxygenase (COX) -2 but not COX-1, and gene knockout transfection experiments demonstrate a central role of COX-2 in experimental tumorigenesis. COX-2 produces prostaglandins that inhibit apoptosis and stimulate angiogenesis and invasiveness. Selective COX-2 inhibitors reduce prostaglandin synthesis, restore apoptosis, and inhibit cancer cell proliferation. In animal studies they limit carcinogen-induced tumorigenesis. In contrast, aspirin-like nonselective NSAIDs such as sulindac and indomethacin inhibit not only the enzymatic action of the highly inducible, proinflammatory COX-2 but the constitutively expressed, cytoprotective COX-1 as well. Consequently, nonselective NSAIDs can cause platelet dysfunction, gastrointestinal ulceration, and kidney damage. For that reason, selective inhibition of COX-2 to treat neoplastic proliferation is preferable to nonselective inhibition. Selective COX-2 inhibitors, such as meloxicam, celecoxib (SC-58635), and rofecoxib (MK-0966), are NSAIDs that have been modified chemically to preferentially inhibit COX-2 but not COX-1. For instance, meloxicam inhibits the growth of cultured colon cancer cells (HCA-7 and Moser-S) that express COX-2 but has no effect on HCT-116 tumor cells that do not express COX-2. NS-398 induces apoptosis in COX-2 expressing LNCaP prostate cancer cells and, surprisingly, in colon cancer S/KS cells that does not express COX-2. This effect may due to induction of apoptosis through uncoupling of oxidative phosphorylation and down-regulation of Bcl-2, as has been demonstrated for some nonselective NSAIDs, for instance, flurbiprofen. COX-2 mRNA and COX-2 protein is constitutively expressed in the kidney, brain, spinal cord, and ductus deferens, and in the uterus during implantation. In addition, COX-2 is constitutively and dominantly expressed in the pancreatic islet cells. These findings might somewhat limit the use of presently available selective COX-2 inhibitors
Observational Constraint of Aerosol Effects on the CMIP5 Inter-model Spread of Adjusted Forcings
NASA Astrophysics Data System (ADS)
Chen, J.; Wennberg, P. O.; Jiang, J. H.; Su, H.; Bordoni, S.
2013-12-01
The simulated global-mean temperature (GMT) change over the past 150 years is quite consistent across CMIP5 climate models and also consistent with the observations. However, the predicted future GMT under the identical CO2 forcing is divergent. This paradox is partly due to the errors in the predicted GMT produced by historical greenhouse gas (GHG) forcing being compensated by the parameterization of aerosol cloud radiative forcing. Historical increases in anthropogenic aerosols exert an overall (but highly uncertain) cooling effect in the climate system, which partially offsets the warming due to well mixed greenhouse gases (WMGHGs). Because aerosol concentrations are predicted to eventually decrease in future scenarios, climate change becomes dominated by warming due to the WMGHG. This change in the relative importance of forcing by aerosol versus WMGHG makes apparent the substantial differences in prediction of climate by WMGHG forcing. Here we investigate the role of aerosols in the context of adjusted forcing changes in the historical runs and the effect of aerosols on the cloud feedback. Our preliminary results suggest that models which are more sensitive to the increase in concentration of CO2 have a larger aerosol radiative cooling effect. By comparing the historicalMisc runs and historicalGHG runs, we find that aerosols exert a potential impact on the cloud adjusted forcings, especially shortwave cloud adjusted forcings. We use the CLIPSO, MISR and CERES data as the benchmark to evaluate the present aerosol simulations. Using satellite observations to assess the relative reliability of the different model responses and to constrain the simulated aerosol radiative forcing will contribute significantly to reducing the across model spread in future climate simulations and identifying some missing physical processes.
Glacial isostatic adjustment using GNSS permanent stations and GIA modelling tools
NASA Astrophysics Data System (ADS)
Kollo, Karin; Spada, Giorgio; Vermeer, Martin
2013-04-01
Glacial Isostatic Adjustment (GIA) affects the Earth's mantle in areas which were once ice covered and the process is still ongoing. In this contribution we focus on GIA processes in Fennoscandian and North American uplift regions. In this contribution we use horizontal and vertical uplift rates from Global Navigation Satellite System (GNSS) permanent stations. For Fennoscandia the BIFROST dataset (Lidberg, 2010) and North America the dataset from Sella, 2007 were used respectively. We perform GIA modelling with the SELEN program (Spada and Stocchi, 2007) and we vary ice model parameters in space in order to find ice model which suits best with uplift values obtained from GNSS time series analysis. In the GIA modelling, the ice models ICE-5G (Peltier, 2004) and the ice model denoted as ANU05 ((Fleming and Lambeck, 2004) and references therein) were used. As reference, the velocity field from GNSS permanent station time series was used for both target areas. Firstly the sensitivity to the harmonic degree was tested in order to reduce the computation time. In the test, nominal viscosity values and pre-defined lithosphere thicknesses models were used, varying maximum harmonic degree values. Main criteria for choosing the suitable harmonic degree was chi-square fit - if the error measure does not differ more than 10%, then one might use as well lower harmonic degree value. From this test, maximum harmonic degree of 72 was chosen to perform calculations, as the larger value did not significantly modify the results obtained, as well the computational time for observations was kept reasonable. Secondly the GIA computations were performed to find the model, which could fit with highest probability to the GNSS-based velocity field in the target areas. In order to find best fitting Earth viscosity parameters, different viscosity profiles for the Earth models were tested and their impact on horizontal and vertical velocity rates from GIA modelling was studied. For every
Elizur, Y; Ziv, M
2001-01-01
While heterosexist family undermining has been demonstrated to be a developmental risk factor in the life of persons with same-gender orientation, the issue of protective family factors is both controversial and relatively neglected. In this study of Israeli gay males (N = 114), we focused on the interrelations of family support, family acceptance and family knowledge of gay orientation, and gay male identity formation, and their effects on mental health and self-esteem. A path model was proposed based on the hypotheses that family support, family acceptance, family knowledge, and gay identity formation have an impact on psychological adjustment, and that family support has an effect on gay identity formation that is mediated by family acceptance. The assessment of gay identity formation was based on an established stage model that was streamlined for cross-cultural practice by defining three basic processes of same-gender identity formation: self-definition, self-acceptance, and disclosure (Elizur & Mintzer, 2001). The testing of our conceptual path model demonstrated an excellent fit with the data. An alternative model that hypothesized effects of gay male identity on family acceptance and family knowledge did not fit the data. Interpreting these results, we propose that the main effect of family support/acceptance on gay identity is related to the process of disclosure, and that both general family support and family acceptance of same-gender orientation play a significant role in the psychological adjustment of gay men. PMID:11444052
Principal Component Analysis of breast DCE-MRI Adjusted with a Model Based Method
Eyal, Erez.; Badikhi, Daria; Furman-Haran, Edna; Kelcz, Fredrick; Kirshenbaum, Kevin J.; Degani, Hadassa
2010-01-01
Purpose To investigate a fast, objective and standardized method for analyzing breast DCE-MRI applying principal component analysis (PCA) adjusted with a model based method. Materials and Methods 3D gradient-echo dynamic contrast-enhanced breast images of 31 malignant and 38 benign lesions, recorded on a 1.5 Tesla scanner were retrospectively analyzed by PCA and by the model based three-time-point (3TP) method. Results Intensity scaled (IS) and enhancement scaled (ES) datasets were reduced by PCA yielding a 1st IS-eigenvector that captured the signal variation between fat and fibroglandular tissue; two IS-eigenvectors and the two first ES-eigenvectors that captured contrast-enhanced changes, whereas the remaining eigenvectors captured predominantly noise changes. Rotation of the two contrast related eigenvectors led to a high congruence between the projection coefficients and the 3TP parameters. The ES-eigenvectors and the rotation angle were highly reproducible across malignant lesions enabling calculation of a general rotated eigenvector base. ROC curve analysis of the projection coefficients of the two eigenvectors indicated high sensitivity of the 1st rotated eigenvector to detect lesions (AUC>0.97) and of the 2nd rotated eigenvector to differentiate malignancy from benignancy (AUC=0.87). Conclusion PCA adjusted with a model-based method provided a fast and objective computer-aided diagnostic tool for breast DCE-MRI. PMID:19856419
Hirozawa, Anne M; Montez-Rath, Maria E; Johnson, Elizabeth C; Solnit, Stephen A; Drennan, Michael J; Katz, Mitchell H; Marx, Rani
2016-01-01
We compared prospective risk adjustment models for adjusting patient panels at the San Francisco Department of Public Health. We used 4 statistical models (linear regression, two-part model, zero-inflated Poisson, and zero-inflated negative binomial) and 4 subsets of predictor variables (age/gender categories, chronic diagnoses, homelessness, and a loss to follow-up indicator) to predict primary care visit frequency. Predicted visit frequency was then used to calculate patient weights and adjusted panel sizes. The two-part model using all predictor variables performed best (R = 0.20). This model, designed specifically for safety net patients, may prove useful for panel adjustment in other public health settings. PMID:27576054
Regional Differences in the Neuronal Expression of Cyclooxygenase-2 (COX-2) in the Newborn Pig Brain
Oláh, Orsolya; Németh, István; Tóth-Szűki, Valéria; Bari, Ferenc; Domoki, Ferenc
2012-01-01
Cyclooxygenase (COX)-2 is the major constitutively expressed COX isoform in the newborn brain. COX-2 derived prostanoids and reactive oxygen species appear to play a major role in the mechanism of perinatal hypoxic-ischemic injury in the newborn piglet, an accepted animal model of the human term neonate. The study aimed to quantitatively determine COX-2 immunopositive neurons in different brain regions in piglets under normoxic conditions (n=15), and 4 hours after 10 min asphyxia (n=11). Asphyxia did not induce significant changes in neuronal COX-2 expression of any studied brain areas. In contrast, there was a marked regional difference in all experimental groups. Thus, significant difference was observed between fronto-parietal and temporo-occipital regions: 59±4% and 67±3% versus 41±2%* and 31±3%* respectively (mean±SEM, data are pooled from all subjects, n=26, *p<0.05, vs. fronto-parietal region). In the hippocampus, COX-2 immunopositivity was rare (highest expression in CA1 region: 14±2%). The studied subcortical areas showed negligible COX-2 staining. Our findings suggest that asphyxia does not significantly alter the pattern of neuronal COX-2 expression in the early reventilation period. Furthermore, based on the striking differences observed in cortical neuronal COX-2 distribution, the contribution of COX-2 mediated neuronal injury after asphyxia may also show region-specific differences. PMID:22829712
Ku80 cooperates with CBP to promote COX-2 expression and tumor growth
Qin, Yu; Xuan, Yang; Jia, Yunlu; Hu, Wenxian; Yu, Wendan; Dai, Meng; Li, Zhenglin; Yi, Canhui; Zhao, Shilei; Li, Mei; Du, Sha; Cheng, Wei; Xiao, Xiangsheng; Chen, Yiming; Wu, Taihua; Meng, Songshu; Yuan, Yuhui; Liu, Quentin; Huang, Wenlin; Guo, Wei; Wang, Shusen; Deng, Wuguo
2015-01-01
Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Overexpression of Ku80 was associated with poor prognosis in patients with lung cancers. We conclude that Ku80 promotes COX-2 expression and tumor growth and is a potential therapeutic target in lung cancer. PMID:25797267
Goeritz, Marie L.; Marder, Eve
2014-01-01
We describe a new technique to fit conductance-based neuron models to intracellular voltage traces from isolated biological neurons. The biological neurons are recorded in current-clamp with pink (1/f) noise injected to perturb the activity of the neuron. The new algorithm finds a set of parameters that allows a multicompartmental model neuron to match the recorded voltage trace. Attempting to match a recorded voltage trace directly has a well-known problem: mismatch in the timing of action potentials between biological and model neuron is inevitable and results in poor phenomenological match between the model and data. Our approach avoids this by applying a weak control adjustment to the model to promote alignment during the fitting procedure. This approach is closely related to the control theoretic concept of a Luenberger observer. We tested this approach on synthetic data and on data recorded from an anterior gastric receptor neuron from the stomatogastric ganglion of the crab Cancer borealis. To test the flexibility of this approach, the synthetic data were constructed with conductance models that were different from the ones used in the fitting model. For both synthetic and biological data, the resultant models had good spike-timing accuracy. PMID:25008414
Obtaining diverse behaviors in a climate model without the use of flux adjustment
NASA Astrophysics Data System (ADS)
Yamazaki, K.; Rowlands, D. J.; Williamson, D.; Allen, M.
2011-12-01
Efforts have been made in past research to attain a wide range of atmosphere and ocean model behaviors by perturbing the model physics of Global Climate Models. However, obtaining a large spread of behaviors of the ocean model has so far been unsuccessful. In an ongoing project within RAPID-WATCH, physical parameters of HadCM3 have been perturbed within plausible ranges across the Latin-hypercube to generate a 10,000 member ensemble, which have been running on the distributed computing platform of climateprediction.net. In this work we resample and run a second, 20,000 member ensemble of model variants that have been identified not to drift significantly away from a realistic initial base state, a key step since we are not using flux adjustment. To this end, they are conditioned on the diagnosed fluxes from the first ensemble by statistical methods to sample regions of parameter space that are predicted to exhibit low top-of-atmosphere (TOA) flux imbalance. Specifically, we constrain the distribution of outgoing longwave radiation (OLR) and reflected shortwave radiation (RSR) by laying an uncertainty ellipse at the 99% significance level, using the error analysis from Tett et al. (2011), over the standard configuration. In addition, parameters are sampled to generate a wide spread in estimated climate sensitivities, informed by results from a separate, coupled atmosphere-thermodynamic ocean coupled model ensemble. The results from the conditioned ensemble show that its members have successfully attained the distribution of OLR and RSR very similar to those predicted, while exhibiting a wide range of behaviors in both the atmosphere and the ocean. The spread of estimated effective climate sensitivity with the balanced TOA fluxes shows that the range of sensitivities of the conditioned ensemble is substantially smaller than that obtained with flux adjustment, but still as large or larger than the range in an ensemble of opportunity. This confirms that flux adjustment
Modeling fluvial incision and transient landscape evolution: Influence of dynamic channel adjustment
NASA Astrophysics Data System (ADS)
Attal, M.; Tucker, G. E.; Whittaker, A. C.; Cowie, P. A.; Roberts, G. P.
2008-09-01
Channel geometry exerts a fundamental control on fluvial processes. Recent work has shown that bedrock channel width depends on a number of parameters, including channel slope, and is not solely a function of drainage area as is commonly assumed. The present work represents the first attempt to investigate the consequences of dynamic, gradient-sensitive channel adjustment for drainage-basin evolution. We use the Channel-Hillslope Integrated Landscape Development (CHILD) model to analyze the response of a catchment to a given tectonic perturbation, using, as a template, the topography of a well-documented catchment in the footwall of an active normal fault in the Apennines (Italy) that is known to be undergoing a transient response to tectonic forcing. We show that the observed transient response can be reproduced to first order with a simple detachment-limited fluvial incision law. Transient landscape is characterized by gentler gradients and a shorter response time when dynamic channel adjustment is allowed. The differences in predicted channel geometry between the static case (width dependent solely on upstream area) and dynamic case (width dependent on both drainage area and channel slope) lead to contrasting landscape morphologies when integrated at the scale of a whole catchment, particularly in presence of strong tilting and/or pronounced slip-rate acceleration. Our results emphasize the importance of channel width in controlling fluvial processes and landscape evolution. They stress the need for using a dynamic hydraulic scaling law when modeling landscape evolution, particularly when the relative uplift field is nonuniform.
Watanabe, K I; Ohama, T
2001-01-01
In the unicellular green alga, Chlamydomonas reinhardtii, cytochrome oxidase subunit 2 (cox2) and 3 (cox3) genes are missing from the mitochondrial genome. We isolated and sequenced a BAC clone that carries the whole cox3 gene and its corresponding cDNA. Almost the entire cox2 gene and its cDNA were also determined. Comparison of the genomic and the corresponding cDNA sequences revealed that the cox3 gene contains as many as nine spliceosomal introns and that cox2 bears six introns. Putative mitochondria targeting signals were predicted at each N terminal of the cox genes. These spliceosomal introns were typical GT-AG-type introns, which are very common not only in Chlamydomonas nuclear genes but also in diverse eukaryotic taxa. We found no particular distinguishing features in the cox introns. Comparative analysis of these genes with the various mitochondrial genes showed that 8 of the 15 introns were interrupting the conserved mature protein coding segments, while the other 7 introns were located in the N-terminal target peptide regions. Phylogenetic analysis of the evolutionary position of C. reinhardtii in Chlorophyta was carried out and the existence of the cox2 and cox3 genes in the mitochondrial genome was superimposed in the tree. This analysis clearly shows that these cox genes were relocated during the evolution of Chlorophyceae. It is apparent that long before the estimated period of relocation of these mitochondrial genes, the cytosol had lost the splicing ability for group II introns. Therefore, at least eight introns located in the mature protein coding region cannot be the direct descendant of group II introns. Here, we conclude that the presence of these introns is due to the invasion of spliceosomal introns, which occurred during the evolution of Chlorophyceae. This finding provides concrete evidence supporting the "intron-late" model, which rests largely on the mobility of spliceosomal introns. PMID:11675593
(R)-Profens Are Substrate-Selective Inhibitors of Endocannabinoid Oxygenation by COX-2
Duggan, Kelsey C.; Hermanson, Daniel J.; Musee, Joel; Prusakiewicz, Jeffery J.; Scheib, Jami L.; Carter, Bruce D.; Banerjee, Surajit; Oates, J.A.; Marnett, Lawrence J.
2012-01-01
Cyclooxygenase-2 (COX-2) catalyzes the oxygenation of arachidonic acid and the endocannabinoids, 2-arachidonoylglycerol and arachidonoylethanolamide. Evaluation of a series of COX-2 inhibitors revealed that many weak, competitive inhibitors of arachidonic acid oxygenation are potent inhibitors of endocannabinoid oxygenation. (R)-Enantiomers of ibuprofen, naproxen, and flurbiprofen, which are considered to be inactive as COX-2 inhibitors, are potent “substrate-selective inhibitors” of endocannabinoid oxygenation. Crystal structures of the COX-2-(R)-naproxen and COX-2-(R)-flurbiprofen complexes verified this unexpected binding and defined the orientation of the (R)-enantiomers relative to (S)-enantiomers. (R)-Profens selectively inhibited endocannabinoid oxygenation by lipopolysaccharide-stimulated dorsal root ganglion cells. Substrate-selective inhibition provides novel tools for investigating the role of COX-2 in endocannabinoid oxygenation and a possible explanation for the ability of (R)-profens to maintain endocannabinoid tone in models of neuropathic pain. PMID:22053353
Tosteson, Tor D.; Morden, Nancy E.; Stukel, Therese A.; O'Malley, A. James
2014-01-01
The estimation of treatment effects is one of the primary goals of statistics in medicine. Estimation based on observational studies is subject to confounding. Statistical methods for controlling bias due to confounding include regression adjustment, propensity scores and inverse probability weighted estimators. These methods require that all confounders are recorded in the data. The method of instrumental variables (IVs) can eliminate bias in observational studies even in the absence of information on confounders. We propose a method for integrating IVs within the framework of Cox's proportional hazards model and demonstrate the conditions under which it recovers the causal effect of treatment. The methodology is based on the approximate orthogonality of an instrument with unobserved confounders among those at risk. We derive an estimator as the solution to an estimating equation that resembles the score equation of the partial likelihood in much the same way as the traditional IV estimator resembles the normal equations. To justify this IV estimator for a Cox model we perform simulations to evaluate its operating characteristics. Finally, we apply the estimator to an observational study of the effect of coronary catheterization on survival. PMID:25506259
Shen, S; Ohodnicki, PR; Kernion, SJ; McHenry, ME
2012-11-15
Composition dependence of resistivity is studied in amorphous (Fe100-xCox)(89-y)Zr7B4Cuy (0 <= x <= 50, y = 0, 1) alloys. The two-current model proposed by Mott for crystalline materials is extended to a disordered amorphous system where s-d scattering is dominant in electron conduction. A rigid-band assumption is made due to the small atomic number difference between Fe and Co. Band structures with a constant density of states (DOS), parabolic distributed DOS, and Gaussian distributed DOS were investigated to fit experimental data. The Gaussian distributed DOS was found to simulate the resistivity maximum and magnetic moment maximum in the Fe-rich region. The basic concepts presented here can potentially provide insight into the optimization of FeCo-based HITPERM alloys for applications at increased frequencies. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4765673
A model of the western Laurentide Ice Sheet, using observations of glacial isostatic adjustment
NASA Astrophysics Data System (ADS)
Gowan, Evan J.; Tregoning, Paul; Purcell, Anthony; Montillet, Jean-Philippe; McClusky, Simon
2016-05-01
We present the results of a new numerical model of the late glacial western Laurentide Ice Sheet, constrained by observations of glacial isostatic adjustment (GIA), including relative sea level indicators, uplift rates from permanent GPS stations, contemporary differential lake level change, and postglacial tilt of glacial lake level indicators. The later two datasets have been underutilized in previous GIA based ice sheet reconstructions. The ice sheet model, called NAICE, is constructed using simple ice physics on the basis of changing margin location and basal shear stress conditions in order to produce ice volumes required to match GIA. The model matches the majority of the observations, while maintaining a relatively realistic ice sheet geometry. Our model has a peak volume at 18,000 yr BP, with a dome located just east of Great Slave Lake with peak thickness of 4000 m, and surface elevation of 3500 m. The modelled ice volume loss between 16,000 and 14,000 yr BP amounts to about 7.5 m of sea level equivalent, which is consistent with the hypothesis that a large portion of Meltwater Pulse 1A was sourced from this part of the ice sheet. The southern part of the ice sheet was thin and had a low elevation profile. This model provides an accurate representation of ice thickness and paleo-topography, and can be used to assess present day uplift and infer past climate.
Procedures for adjusting regional regression models of urban-runoff quality using local data
Hoos, A.B.; Sisolak, J.K.
1993-01-01
Statistical operations termed model-adjustment procedures (MAP?s) can be used to incorporate local data into existing regression models to improve the prediction of urban-runoff quality. Each MAP is a form of regression analysis in which the local data base is used as a calibration data set. Regression coefficients are determined from the local data base, and the resulting `adjusted? regression models can then be used to predict storm-runoff quality at unmonitored sites. The response variable in the regression analyses is the observed load or mean concentration of a constituent in storm runoff for a single storm. The set of explanatory variables used in the regression analyses is different for each MAP, but always includes the predicted value of load or mean concentration from a regional regression model. The four MAP?s examined in this study were: single-factor regression against the regional model prediction, P, (termed MAP-lF-P), regression against P,, (termed MAP-R-P), regression against P, and additional local variables (termed MAP-R-P+nV), and a weighted combination of P, and a local-regression prediction (termed MAP-W). The procedures were tested by means of split-sample analysis, using data from three cities included in the Nationwide Urban Runoff Program: Denver, Colorado; Bellevue, Washington; and Knoxville, Tennessee. The MAP that provided the greatest predictive accuracy for the verification data set differed among the three test data bases and among model types (MAP-W for Denver and Knoxville, MAP-lF-P and MAP-R-P for Bellevue load models, and MAP-R-P+nV for Bellevue concentration models) and, in many cases, was not clearly indicated by the values of standard error of estimate for the calibration data set. A scheme to guide MAP selection, based on exploratory data analysis of the calibration data set, is presented and tested. The MAP?s were tested for sensitivity to the size of a calibration data set. As expected, predictive accuracy of all MAP?s for
MACRO FOR ESTIMATING THE BOX-COX POWER TRANSFORMATION
In their classic paper, Box and Cox (1964) demonstrated how a dependent variable could be transformed to satisfy simultaneously, assumptions implicit in the analysis of linear models. For the class of analyses in which the response of interest is positive and where no transformat...
de Araújo Júnior, Raimundo Fernandes; Souza, Tatiana Oliveira; de Medeiros, Caroline Addison Xavier; de Souza, Lélia Batista; Freitas, Maria de Lourdes; de Lucena, Hévio Freitas; do Socorro Costa Feitosa Alves, Maria; de Araújo, Aurigena Antunes
2013-01-01
Periodontal diseases are initiated primarily by Gram-negative, tooth-associated microbial biofilms that elicit a host response that causes osseous and soft tissue destruction. Carvedilol is a β-blocker used as a multifunctional neurohormonal antagonist that has been shown to act not only as an anti-oxidant but also as an anti-inflammatory drug. This study evaluated whether Carvedilol exerted a protective role against ligature-induced periodontitis in a rat model and defined how Carvedilol affected metalloproteinases and RANKL/RANK/OPG expression in the context of bone remodeling. Rats were randomly divided into 5 groups (n = 10/group): (1) non-ligated (NL), (2) ligature-only (LO), and (3) ligature plus Carvedilol (1, 5 or 10 mg/kg daily for 10 days). Periodontal tissue was analyzed for histopathlogy and using immunohistochemical analysis characterized the expression profiles of MMP-2, MMP-9, COX-2, and RANKL/RANK/OPG and determined the presence of IL-1β, IL-10 and TNF-α, myeloperoxidase (MPO), malonaldehyde (MDA) and, glutathione (GSH). MPO activity in the group with periodontal disease was significantly increased compared to the control group (p<0.05). Rats treated with 10 mg/kg Carvedilol presented with significantly reduced MPO and MDA concentrations (p<0.05) in addition to presenting with reduced levels of the pro-inflammatory cytokines IL-1 β and TNF-α (p<0.05). IL-10 levels in Carvedilol-treated rats remained unaltered. Immunohistochemical analysis demonstrated reduced expression of MMP-2, MMP-9, RANK, RANKL, COX-2, and OPG in rats treated with 10 mg/kg Carvedilol. This study demonstrated that Carvedilol affected bone formation/destruction and anti-inflammatory activity in a rat model of periodontitis. PMID:23843954
Adjusting Satellite Rainfall Error in Mountainous Areas for Flood Modeling Applications
NASA Astrophysics Data System (ADS)
Zhang, X.; Anagnostou, E. N.; Astitha, M.; Vergara, H. J.; Gourley, J. J.; Hong, Y.
2014-12-01
This study aims to investigate the use of high-resolution Numerical Weather Prediction (NWP) for evaluating biases of satellite rainfall estimates of flood-inducing storms in mountainous areas and associated improvements in flood modeling. Satellite-retrieved precipitation has been considered as a feasible data source for global-scale flood modeling, given that satellite has the spatial coverage advantage over in situ (rain gauges and radar) observations particularly over mountainous areas. However, orographically induced heavy precipitation events tend to be underestimated and spatially smoothed by satellite products, which error propagates non-linearly in flood simulations.We apply a recently developed retrieval error and resolution effect correction method (Zhang et al. 2013*) on the NOAA Climate Prediction Center morphing technique (CMORPH) product based on NWP analysis (or forecasting in the case of real-time satellite products). The NWP rainfall is derived from the Weather Research and Forecasting Model (WRF) set up with high spatial resolution (1-2 km) and explicit treatment of precipitation microphysics.In this study we will show results on NWP-adjusted CMORPH rain rates based on tropical cyclones and a convective precipitation event measured during NASA's IPHEX experiment in the South Appalachian region. We will use hydrologic simulations over different basins in the region to evaluate propagation of bias correction in flood simulations. We show that the adjustment reduced the underestimation of high rain rates thus moderating the strong rainfall magnitude dependence of CMORPH rainfall bias, which results in significant improvement in flood peak simulations. Further study over Blue Nile Basin (western Ethiopia) will be investigated and included in the presentation. *Zhang, X. et al. 2013: Using NWP Simulations in Satellite Rainfall Estimation of Heavy Precipitation Events over Mountainous Areas. J. Hydrometeor, 14, 1844-1858.
The effects of the Cox maze procedure on atrial function
Voeller, Rochus K.; Zierer, Andreas; Lall, Shelly C.; Sakamoto, Shun–ichiro; Chang, Nai–Lun; Schuessler, Richard B.; Moon, Marc R.; Damiano, Ralph J.
2010-01-01
Objective The effects of the Cox maze procedure on atrial function remain poorly defined. The purpose of this study was to investigate the effects of a modified Cox maze procedure on left and right atrial function in a porcine model. Methods After cardiac magnetic resonance imaging, 6 pigs underwent pericardiotomy (sham group), and 6 pigs underwent a modified Cox maze procedure (maze group) with bipolar radiofrequency ablation. The maze group had preablation and immediate postablation left and right atrial pressure–volume relations measured with conductance catheters. All pigs survived for 30 days. Magnetic resonance imaging was then repeated for both groups, and conductance catheter measurements were repeated for the right atrium in the maze group. Results Both groups had significantly higher left atrial volumes postoperatively. Magnetic resonance imaging–derived reservoir and booster pump functional parameters were reduced postoperatively for both groups, but there was no difference in these parameters between the groups. The maze group had significantly higher reduction in the medial and lateral left atrial wall contraction postoperatively. There was no change in immediate left atrial elastance or in the early and 30-day right atrial elastance after the Cox maze procedure. Although the initial left atrial stiffness increased after ablation, right atrial diastolic stiffness did not change initially or at 30 days. Conclusions Performing a pericardiotomy alone had a significant effect on atrial function that can be quantified by means of magnetic resonance imaging. The effects of the Cox maze procedure on left atrial function could only be detected by analyzing segmental wall motion. Understanding the precise physiologic effects of the Cox maze procedure on atrial function will help in developing less-damaging lesion sets for the surgical treatment of atrial fibrillation. PMID:19026812
Stark, David T.; Bazan, Nicolas G.
2011-01-01
Stimulation of synaptic NMDA receptors (NMDARs) induces neuroprotection, while extrasynaptic NMDARs promote excitotoxic cell death. Neuronal expression of cyclooxygenase-2 (COX-2) is enhanced by synaptic NMDARs, and although this enzyme mediates neuronal functions, COX-2 is also regarded as a key modulator of neuroinflammation and is thought to exacerbate excitotoxicity via overproduction of prostaglandins. This raises an apparent paradox: synaptic NMDARs are pro-survival yet are essential for robust neuronal COX-2 expression. We hypothesized that stimulation of extrasynaptic NMDARs converts COX-2 signaling from a physiological to a potentially pathological process. We combined HPLC-ESI-MS/MS-based mediator lipidomics and unbiased image analysis in mouse dissociated and organotypic cortical cultures to uncover that synaptic and extrasynaptic NMDARs differentially modulate neuronal COX-2 expression and activity. We show that synaptic NMDARs enhance neuronal COX-2 expression, while sustained synaptic stimulation limits COX-2 activity by suppressing cellular levels of the primary COX-2 substrate, arachidonic acid (AA). In contrast, extrasynaptic NMDARs suppress COX-2 expression while activating phospholipase A2 (PLA2), which enhances AA levels by hydrolysis of membrane phospholipids. Thus, sequential activation of synaptic then extrasynaptic NMDARs maximizes COX-2-dependent prostaglandin synthesis. We also show that excitotoxic events only drive induction of COX-2 expression through abnormal synaptic network excitability. Finally, we show that non-enzymatic lipid peroxidation of arachidonic and other polyunsaturated fatty acids is a function of network activity history. A new paradigm emerges from our results suggesting that pathological COX-2 signaling associated with models of stroke, epilepsy, and neurodegeneration requires specific spatio-temporal NMDAR stimulation. PMID:21957234
Lehmann, E. D.; Deutsch, T.
1992-01-01
Joe Daniels is a 41 year old, 76kg male, insulin-treated diabetic patient who was diagnosed as being diabetic in 1972, at the age of 22. Joe recently found that he was having hypoglycaemic symptoms. Using self-monitoring blood glucose equipment glycaemic levels below 3.0 mmol/l were recorded at least once a week while hyperglycaemic readings (> 16 mmol/l) were observed 2-3 times per week. Joe came into hospital to have his glycaemic control improved as doctors were concerned about the risks of him suffering a serious hypoglycaemic attack. Using some of the data collected by Joe while in hospital we will demonstrate how a computer model of glucose-insulin interaction in type I diabetes can be used interactively to teach diabetic patients about their diabetes and educate them to adjust their own insulin injections and diet. PMID:1482868
de Araújo Júnior, Raimundo Fernandes; da Silva Reinaldo, Maria Patrícia Oliveira; Brito, Gerly Anne de Castro; Cavalcanti, Pedro de França; Freire, Marco Aurélio de Moura; de Medeiros, Caroline Addison Xavier; de Araújo, Aurigena Antunes
2014-01-01
Methotrexate (MTX) is a pro-oxidant compound that depletes dihydrofolate pools and is widely used in the treatment of leukaemia and other malignancies. The efficacy of methotrexate is often limited by mucositis and intestinal injury, which are major causes of morbidity in children and adults. The aim of this study was to evaluate the effect of olmesartan (OLM), an angiotensin II receptor antagonist, on an Intestinal Mucositis Model (IMM) induced by MTX in Wistar rats. IMM was induced via intraperitoneal (i.p.) administration of MTX (7 mg/kg) for three consecutive days. The animals were pre-treated with oral OLM at 0.5, 1 or 5 mg/kg or with vehicle 30 min prior to exposure to MTX. Small intestinal homogenates were assayed for levels of the IL-1β, IL-10 and TNF-α cytokines, malondialdehyde and myeloperoxidase activity. Additionally, immunohistochemical analyses of MMP-2, MMP-9, COX-2, RANK/RANKL and SOCS-1 and confocal microscopy analysis of SOCS-1 expression were performed. Treatment with MTX + OLM (5 mg/kg) resulted in a reduction of mucosal inflammatory infiltration, ulcerations, vasodilatation and haemorrhagic areas (p<0.05) as well as reduced concentrations of MPO (p<0.001) and the pro-inflammatory cytokines IL-1β (p<0.001) and TNF-a (p<0.01), and increase anti-inflammatory cytocine IL-10 (p<0.05). Additionally, the combined treatment reduced expression of MMP-2, MMP-9, COX-2, RANK and RANKL(p<0.05) and increased cytoplasmic expression of SOCS-1 (p<0.05). Our findings confirm the involvement of OLM in reducing the inflammatory response through increased immunosuppressive signalling in an IMM. We also suggest that the beneficial effect of olmesartan treatment is specifically exerted during the damage through blocking inflammatory cytocines. PMID:25531650
COX7AR is a Stress-inducible Mitochondrial COX Subunit that Promotes Breast Cancer Malignancy.
Zhang, Kezhong; Wang, Guohui; Zhang, Xuebao; Hüttemann, Philipp P; Qiu, Yining; Liu, Jenney; Mitchell, Allison; Lee, Icksoo; Zhang, Chao; Lee, Jin-Sook; Pecina, Petr; Wu, Guojun; Yang, Zeng-Quan; Hüttemann, Maik; Grossman, Lawrence I
2016-01-01
Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, plays a key role in regulating mitochondrial energy production and cell survival. COX subunit VIIa polypeptide 2-like protein (COX7AR) is a novel COX subunit that was recently found to be involved in mitochondrial supercomplex assembly and mitochondrial respiration activity. Here, we report that COX7AR is expressed in high energy-demanding tissues, such as brain, heart, liver, and aggressive forms of human breast cancer cells. Under cellular stress that stimulates energy metabolism, COX7AR is induced and incorporated into the mitochondrial COX complex. Functionally, COX7AR promotes cellular energy production in human mammary epithelial cells. Gain- and loss-of-function analysis demonstrates that COX7AR is required for human breast cancer cells to maintain higher rates of proliferation, clone formation, and invasion. In summary, our study revealed that COX7AR is a stress-inducible mitochondrial COX subunit that facilitates human breast cancer malignancy. These findings have important implications in the understanding and treatment of human breast cancer and the diseases associated with mitochondrial energy metabolism. PMID:27550821
COX7AR is a Stress-inducible Mitochondrial COX Subunit that Promotes Breast Cancer Malignancy
Zhang, Kezhong; Wang, Guohui; Zhang, Xuebao; Hüttemann, Philipp P.; Qiu, Yining; Liu, Jenney; Mitchell, Allison; Lee, Icksoo; Zhang, Chao; Lee, Jin-sook; Pecina, Petr; Wu, Guojun; Yang, Zeng-quan; Hüttemann, Maik; Grossman, Lawrence I.
2016-01-01
Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, plays a key role in regulating mitochondrial energy production and cell survival. COX subunit VIIa polypeptide 2-like protein (COX7AR) is a novel COX subunit that was recently found to be involved in mitochondrial supercomplex assembly and mitochondrial respiration activity. Here, we report that COX7AR is expressed in high energy-demanding tissues, such as brain, heart, liver, and aggressive forms of human breast cancer cells. Under cellular stress that stimulates energy metabolism, COX7AR is induced and incorporated into the mitochondrial COX complex. Functionally, COX7AR promotes cellular energy production in human mammary epithelial cells. Gain- and loss-of-function analysis demonstrates that COX7AR is required for human breast cancer cells to maintain higher rates of proliferation, clone formation, and invasion. In summary, our study revealed that COX7AR is a stress-inducible mitochondrial COX subunit that facilitates human breast cancer malignancy. These findings have important implications in the understanding and treatment of human breast cancer and the diseases associated with mitochondrial energy metabolism. PMID:27550821
UPDATING THE FREIGHT TRUCK STOCK ADJUSTMENT MODEL: 1997 VEHICLE INVENTORY AND USE SURVEY DATA
Davis, S.C.
2000-11-16
The Energy Information Administration's (EIA's) National Energy Modeling System (NEMS) Freight Truck Stock Adjustment Model (FTSAM) was created in 1995 relying heavily on input data from the 1992 Economic Census, Truck Inventory and Use Survey (TIUS). The FTSAM is part of the NEMS Transportation Sector Model, which provides baseline energy projections and analyzes the impacts of various technology scenarios on consumption, efficiency, and carbon emissions. The base data for the FTSAM can be updated every five years as new Economic Census information is released. Because of expertise in using the TIUS database, Oak Ridge National Laboratory (ORNL) was asked to assist the EIA when the new Economic Census data were available. ORNL provided the necessary base data from the 1997 Vehicle Inventory and Use Survey (VIUS) and other sources to update the FTSAM. The next Economic Census will be in the year 2002. When those data become available, the EIA will again want to update the FTSAM using the VIUS. This report, which details the methodology of estimating and extracting data from the 1997 VIUS Microdata File, should be used as a guide for generating the data from the next VIUS so that the new data will be as compatible as possible with the data in the model.
Punamäki, R L; Qouta, S; el Sarraj, E
1997-08-01
The relations between traumatic events, perceived parenting styles, children's resources, political activity, and psychological adjustment were examined among 108 Palestinian boys and girls of 11-12 years of age. The results showed that exposure to traumatic events increased psychological adjustment problems directly and via 2 mediating paths. First, the more traumatic events children had experienced, the more negative parenting they experienced. And, the poorer they perceived parenting, the more they suffered from high neuroticism and low self-esteem. Second, the more traumatic events children had experienced, the more political activity they showed, and the more active they were, the more they suffered from psychological adjustment problems. Good perceived parenting protected children's psychological adjustment by making them less vulnerable in two ways. First, traumatic events decreased their intellectual, creative, and cognitive resources, and a lack of resources predicted many psychological adjustment problems in a model excluding perceived parenting. Second, political activity increased psychological adjustment problems in the same model, but not in the model including good parenting. PMID:9306648
The Trauma Outcome Process Assessment Model: A Structural Equation Model Examination of Adjustment
ERIC Educational Resources Information Center
Borja, Susan E.; Callahan, Jennifer L.
2009-01-01
This investigation sought to operationalize a comprehensive theoretical model, the Trauma Outcome Process Assessment, and test it empirically with structural equation modeling. The Trauma Outcome Process Assessment reflects a robust body of research and incorporates known ecological factors (e.g., family dynamics, social support) to explain…
A new glacial isostatic adjustment model of the Innuitian Ice Sheet, Arctic Canada
NASA Astrophysics Data System (ADS)
Simon, K. M.; James, T. S.; Dyke, A. S.
2015-07-01
A reconstruction of the Innuitian Ice Sheet (IIS) is developed that incorporates first-order constraints on its spatial extent and history as suggested by regional glacial geology studies. Glacial isostatic adjustment modelling of this ice sheet provides relative sea-level predictions that are in good agreement with measurements of post-glacial sea-level change at 18 locations. The results indicate peak thicknesses of the Innuitian Ice Sheet of approximately 1600 m, up to 400 m thicker than the minimum peak thicknesses estimated from glacial geology studies, but between approximately 1000 to 1500 m thinner than the peak thicknesses present in previous GIA models. The thickness history of the best-fit Innuitian Ice Sheet model developed here, termed SJD15, differs from the ICE-5G reconstruction and provides an improved fit to sea-level measurements from the lowland sector of the ice sheet. Both models provide a similar fit to relative sea-level measurements from the alpine sector. The vertical crustal motion predictions of the best-fit IIS model are in general agreement with limited GPS observations, after correction for a significant elastic crustal response to present-day ice mass change. The new model provides approximately 2.7 m equivalent contribution to global sea-level rise, an increase of +0.6 m compared to the Innuitian portion of ICE-5G. SJD15 is qualitatively more similar to the recent ICE-6G ice sheet reconstruction, which appears to also include more spatially extensive ice cover in the Innuitian region than ICE-5G.
NASA Astrophysics Data System (ADS)
Yang, M. F.
In this research we present a stylized model to find the optimal strategy for integrated vendor-buyer inventory model with fuzzy annual demand and fuzzy adjustable production rate. This model with such consideration is based on the total cost optimization under a common stock strategy. However, the supposition of known annual demand and adjustable production rate in most related publications may not be realistic. This paper proposes the triangular fuzzy number of annual demand and adjustable production rate and then employs the signed distance, to find the estimation of the common total cost in the fuzzy sense and derives the corresponding optimal buyer`s quantity consequently and the integer number of lots in which the items are delivered from the vendor to the purchaser. A numerical example is provided and the results of fuzzy and crisp models are compared.
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. PMID:20345577
NASA Astrophysics Data System (ADS)
Root, Bart; Tarasov, Lev; van der Wal, Wouter
2014-05-01
The global ice budget is still under discussion because the observed 120-130 m eustatic sea level equivalent since the Last Glacial Maximum (LGM) can not be explained by the current knowledge of land-ice melt after the LGM. One possible location for the missing ice is the Barents Sea Region, which was completely covered with ice during the LGM. This is deduced from relative sea level observations on Svalbard, Novaya Zemlya and the North coast of Scandinavia. However, there are no observations in the middle of the Barents Sea that capture the post-glacial uplift. With increased precision and longer time series of monthly gravity observations of the GRACE satellite mission it is possible to constrain Glacial Isostatic Adjustment in the center of the Barents Sea. This study investigates the extra constraint provided by GRACE data for modeling the past ice geometry in the Barents Sea. We use CSR release 5 data from February 2003 to July 2013. The GRACE data is corrected for the past 10 years of secular decline of glacier ice on Svalbard, Novaya Zemlya and Frans Joseph Land. With numerical GIA models for a radially symmetric Earth, we model the expected gravity changes and compare these with the GRACE observations after smoothing with a 250 km Gaussian filter. The comparisons show that for the viscosity profile VM5a, ICE-5G has too strong a gravity signal compared to GRACE. The regional calibrated ice sheet model (GLAC) of Tarasov appears to fit the amplitude of the GRACE signal. However, the GRACE data are very sensitive to the ice-melt correction, especially for Novaya Zemlya. Furthermore, the ice mass should be more concentrated to the middle of the Barents Sea. Alternative viscosity models confirm these conclusions.
Four-dimensional data assimilation applied to photochemical air quality modeling is used to suggest adjustments to the emissions inventory of the Atlanta, Georgia metropolitan area. In this approach, a three-dimensional air quality model, coupled with direct sensitivity analys...
Sales, Brian C; McGuire, Michael A; Sefat, A. S.; Mandrus, David
2010-01-01
A simple two band model is used to describe the magnitude and temperature dependence of the magnetic susceptibility, Hall coefficient, resistivity and Seebeck data from undoped and Co doped BaFe2As2. Overlapping rigid parabolic electron and hole bands are considered as a model of the electronic structure of the FeAs-based semimetals. The model has only three parameters: the electron and hole effective masses and the position of the valence band maximum with respect to the conduction band minimum. The model is able to reproduce in a semiquantitative fashion the magnitude and temperature dependence of many of the normal state magnetic and transport data from the FeAs-type materials, including the ubiquitous increase in the magnetic susceptibility with increasing temperature.
A Class of Elementary Particle Models Without Any Adjustable Real Parameters
NASA Astrophysics Data System (ADS)
't Hooft, Gerard
2011-12-01
Conventional particle theories such as the Standard Model have a number of freely adjustable coupling constants and mass parameters, depending on the symmetry algebra of the local gauge group and the representations chosen for the spinor and scalar fields. There seems to be no physical principle to determine these parameters as long as they stay within certain domains dictated by the renormalization group. Here however, reasons are given to demand that, when gravity is coupled to the system, local conformal invariance should be a spontaneously broken exact symmetry. The argument has to do with the requirement that black holes obey a complementarity principle relating ingoing observers to outside observers, or equivalently, initial states to final states. This condition fixes all parameters, including masses and the cosmological constant. We suspect that only examples can be found where these are all of order one in Planck units, but the values depend on the algebra chosen. This paper combines findings reported in two previous preprints (G. 't Hooft in arXiv:1009.0669 [gr-qc], 2010; arXiv:1011.0061 [gr-qc], 2010) and puts these in a clearer perspective by shifting the emphasis towards the implications for particle models.
Testing the compatibility of constraints for parameters of a geodetic adjustment model
NASA Astrophysics Data System (ADS)
Lehmann, Rüdiger; Neitzel, Frank
2013-06-01
Geodetic adjustment models are often set up in a way that the model parameters need to fulfil certain constraints. The normalized Lagrange multipliers have been used as a measure of the strength of constraint in such a way that if one of them exceeds in magnitude a certain threshold then the corresponding constraint is likely to be incompatible with the observations and the rest of the constraints. We show that these and similar measures can be deduced as test statistics of a likelihood ratio test of the statistical hypothesis that some constraints are incompatible in the same sense. This has been done before only for special constraints (Teunissen in Optimization and Design of Geodetic Networks, pp. 526-547, 1985). We start from the simplest case, that the full set of constraints is to be tested, and arrive at the advanced case, that each constraint is to be tested individually. Every test is worked out both for a known as well as for an unknown prior variance factor. The corresponding distributions under null and alternative hypotheses are derived. The theory is illustrated by the example of a double levelled line.
Kendall, W.L.; Hines, J.E.; Nichols, J.D.
2003-01-01
Matrix population models are important tools for research and management of populations. Estimating the parameters of these models is an important step in applying them to real populations. Multistate capture-recapture methods have provided a useful means for estimating survival and parameters of transition between locations or life history states but have mostly relied on the assumption that the state occupied by each detected animal is known with certainty. Nevertheless, in some cases animals can be misclassified. Using multiple capture sessions within each period of interest, we developed a method that adjusts estimates of transition probabilities for bias due to misclassification. We applied this method to 10 years of sighting data for a population of Florida manatees (Trichechus manatus latirostris) in order to estimate the annual probability of transition from nonbreeding to breeding status. Some sighted females were unequivocally classified as breeders because they were clearly accompanied by a first-year calf. The remainder were classified, sometimes erroneously, as nonbreeders because an attendant first-year calf was not observed or was classified as more than one year old. We estimated a conditional breeding probability of 0.31 + 0.04 (estimate + 1 SE) when we ignored misclassification bias, and 0.61 + 0.09 when we accounted for misclassification.
Soares, Ana Paula; Guisande, M Adelina; Diniz, António M; Almeida, Leandro S
2006-05-01
This article presents a model of interaction of personal and contextual variables in the prediction of academic performance and psychosocial development of Portuguese college students. The sample consists of 560 first-year college students of the University of Minho. The path analysis results suggest that initial expectations of the students' involvement in academic life constituted an effective predictor of their involvement during their first year; as well as the social climate of the classroom influenced their involvement, well-being and levels of satisfaction obtained. However, these relationships were not strong enough to influence the criterion variables integrated in the model (academic performance and psychosocial development). Academic performance was predicted by the high school grades and college entrance examination scores, and the level of psychosocial development was determined by the level of development showed at the time they entered college. Though more research is needed, these results point to the importance of students' pre-college characteristics when we are considering the quality of their college adjustment process. PMID:17296040
Cyclooxygenase (COX) Inhibitors and the Newborn Kidney
Smith, Francine G.; Wade, Andrew W.; Lewis, Megan L.; Qi, Wei
2012-01-01
This review summarizes our current understanding of the role of cyclo-oxygenase inhibitors (COXI) in influencing the structural development as well as the function of the developing kidney. COXI administered either during pregnancy or after birth can influence kidney development including nephronogenesis, and can decrease renal perfusion and ultrafiltration potentially leading to acute kidney injury in the newborn period. To date, which COX isoform (COX-1 or COX-2) plays a more important role in during fetal development and influences kidney function early in life is not known, though evidence points to a predominant role for COX-2. Clinical implications of the use of COXI in pregnancy and in the newborn infant are also evaluated herein, with specific reference to the potential effects of COXI on nephronogenesis as well as newborn kidney function. PMID:24281306
Enhancing multiple-point geostatistical modeling: 1. Graph theory and pattern adjustment
NASA Astrophysics Data System (ADS)
Tahmasebi, Pejman; Sahimi, Muhammad
2016-03-01
In recent years, higher-order geostatistical methods have been used for modeling of a wide variety of large-scale porous media, such as groundwater aquifers and oil reservoirs. Their popularity stems from their ability to account for qualitative data and the great flexibility that they offer for conditioning the models to hard (quantitative) data, which endow them with the capability for generating realistic realizations of porous formations with very complex channels, as well as features that are mainly a barrier to fluid flow. One group of such models consists of pattern-based methods that use a set of data points for generating stochastic realizations by which the large-scale structure and highly-connected features are reproduced accurately. The cross correlation-based simulation (CCSIM) algorithm, proposed previously by the authors, is a member of this group that has been shown to be capable of simulating multimillion cell models in a matter of a few CPU seconds. The method is, however, sensitive to pattern's specifications, such as boundaries and the number of replicates. In this paper the original CCSIM algorithm is reconsidered and two significant improvements are proposed for accurately reproducing large-scale patterns of heterogeneities in porous media. First, an effective boundary-correction method based on the graph theory is presented by which one identifies the optimal cutting path/surface for removing the patchiness and discontinuities in the realization of a porous medium. Next, a new pattern adjustment method is proposed that automatically transfers the features in a pattern to one that seamlessly matches the surrounding patterns. The original CCSIM algorithm is then combined with the two methods and is tested using various complex two- and three-dimensional examples. It should, however, be emphasized that the methods that we propose in this paper are applicable to other pattern-based geostatistical simulation methods.
COX-2 gene dosage-dependent defects in kidney development.
Slattery, Patrick; Frölich, Stefanie; Schreiber, Yannik; Nüsing, Rolf M
2016-05-15
Deletion of cyclooxygenase (COX)-2 causes impairment of kidney development, including hypothrophic glomeruli and cortical thinning. A critical role for COX-2 is seen 4-8 days postnatally. The present study was aimed at answering whether different COX-2 gene dosage and partial pharmacological COX-2 inhibition impairs kidney development. We studied kidney development in COX-2(+/+), COX-2(+/-), and COX-2(-/-) mice as well as in C57Bl6 mice treated postnatally with low (5 mg·kg(-1)·day(-1)) and high (10 mg·kg(-1)·day(-1)) doses of the selective COX-2 inhibitor SC-236. COX-2(+/-) mice exhibit impaired kidney development leading to reduced glomerular size but, in contrast to COX-2(-/-) mice, only marginal cortical thinning. Moreover, in COX-2(+/-) and COX-2(-/-) kidneys, juxtamedullary glomeruli, which develop in the very early stages of nephrogenesis, also showed a size reduction. In COX-2(+/-) kidneys at the age of 8 days, we observed significantly less expression of COX-2 mRNA and protein and less PGE2 and PGI2 synthetic activity compared with COX-2(+/+) kidneys. The renal defects in COX-2(-/-) and COX-2(+/-) kidneys could be mimicked by high and low doses of SC-236, respectively. In aged COX-2(+/-) kidneys, glomerulosclerosis was observed; however, in contrast to COX-2(-/-) kidneys, periglomerular fibrosis was absent. COX-2(+/-) mice showed signs of kidney insufficiency, demonstrated by enhanced serum creatinine levels, quite similar to COX-2(-/-) mice, but, in contrast, serum urea remained at the control level. In summary, function of both COX-2 gene alleles is absolutely necessary to ensure physiological development of the mouse kidney. Loss of one copy of the COX-2 gene or partial COX-2 inhibition is associated with distinct renal damage and reduced kidney function. PMID:26984955
Reversible Suppression of Cyclooxygenase 2 (COX-2) Expression In Vivo by Inducible RNA Interference
Zaiss, Anne K.; Zuber, Johannes; Chu, Chun; Machado, Hidevaldo B.; Jiao, Jing; Catapang, Arthur B.; Ishikawa, Tomo-o; Gil, Jose S.; Lowe, Scott W.; Herschman, Harvey R.
2014-01-01
Prostaglandin-endoperoxide synthase 2 (PTGS2), also known as cyclooxygenase 2 (COX-2), plays a critical role in many normal physiological functions and modulates a variety of pathological conditions. The ability to turn endogenous COX-2 on and off in a reversible fashion, at specific times and in specific cell types, would be a powerful tool in determining its role in many contexts. To achieve this goal, we took advantage of a recently developed RNA interference system in mice. An shRNA targeting the Cox2 mRNA 3′untranslated region was inserted into a microRNA expression cassette, under the control of a tetracycline response element (TRE) promoter. Transgenic mice containing the COX-2-shRNA were crossed with mice encoding a CAG promoter-driven reverse tetracycline transactivator, which activates the TRE promoter in the presence of tetracycline/doxycycline. To facilitate testing the system, we generated a knockin reporter mouse in which the firefly luciferase gene replaces the Cox2 coding region. Cox2 promoter activation in cultured cells from triple transgenic mice containing the luciferase allele, the shRNA and the transactivator transgene resulted in robust luciferase and COX-2 expression that was reversibly down-regulated by doxycycline administration. In vivo, using a skin inflammation-model, both luciferase and COX-2 expression were inhibited over 80% in mice that received doxycycline in their diet, leading to a significant reduction of infiltrating leukocytes. In summary, using inducible RNA interference to target COX-2 expression, we demonstrate potent, reversible Cox2 gene silencing in vivo. This system should provide a valuable tool to analyze cell type-specific roles for COX-2. PMID:24988319
Genetic Deletion of COX-2 Diminishes VEGF Production in Mouse Retinal Müller Cells
Yanni, Susan E.; McCollum, Gary W.; Penn, John S.
2010-01-01
Non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit COX activity, reduce the production of retinal VEGF and neovascularization in relevant models of ocular disease. We hypothesized that COX-2 mediates VEGF production in retinal Müller cells, one of its primary sources in retinal neovascular disease. The purpose of this study was to determine the role of COX-2 and its products in VEGF expression and secretion. These studies have more clearly defined the role of COX-2 and COX-2-derived prostanoids in retinal angiogenesis. Müller cells derived from wild-type and COX-2 null mice were exposed to hypoxia for 0–24 hours. COX-2 protein and activity were assessed by western blot analysis and GC-MS, respectively. VEGF production was assessed by ELISA. Wild-type mouse Müller cells were treated with vehicle (0.1% DMSO), 10 µM PGE2, or PGE2 + 5 µM H-89 (a PKA inhibitor), for 12 hours. VEGF production was assessed by ELISA. Hypoxia significantly increased COX-2 protein (p ≤ 0.05) and activity (p ≤ 0.05), and VEGF production (p ≤ 0.0003). COX-2 null Müller cells produced significantly less VEGF in response to hypoxia (p ≤ 0.05). Of the prostanoids, PGE2 was significantly increased by hypoxia (p ≤ 0.02). Exogenous PGE2 significantly increased VEGF production by Müller cells (p ≤ 0.0039), and this effect was inhibited by H-89 (p ≤ 0.055). These data demonstrate that hypoxia induces COX-2, prostanoid production, and VEGF synthesis in Müller cells, and that VEGF production is at least partially COX-2-dependent. Our study suggests that PGE2, signaling through the EP2 and/or EP4 receptor and PKA, mediates the VEGF response of Müller cells. PMID:20398651
Glacial isostatic adjustment in Fennoscandia from GRACE data and comparison with geodynamical models
NASA Astrophysics Data System (ADS)
Steffen, Holger; Denker, Heiner; Müller, Jürgen
2008-10-01
The Earth's gravity field observed by the Gravity Recovery and Climate Experiment (GRACE) satellite mission shows variations due to the integral effect of mass variations in the atmosphere, hydrosphere and geosphere. Several institutions, such as the GeoForschungsZentrum (GFZ) Potsdam, the University of Texas at Austin, Center for Space Research (CSR) and the Jet Propulsion Laboratory (JPL), Pasadena, provide GRACE monthly solutions, which differ slightly due to the application of different reduction models and centre-specific processing schemes. The GRACE data are used to investigate the mass variations in Fennoscandia, an area which is strongly influenced by glacial isostatic adjustment (GIA). Hence the focus is set on the computation of secular trends. Different filters (e.g. isotropic and non-isotropic filters) are discussed for the removal of high frequency noise to permit the extraction of the GIA signal. The resulting GRACE based mass variations are compared to global hydrology models (WGHM, LaDWorld) in order to (a) separate possible hydrological signals and (b) validate the hydrology models with regard to long period and secular components. In addition, a pattern matching algorithm is applied to localise the uplift centre, and finally the GRACE signal is compared with the results from a geodynamical modelling. The GRACE data clearly show temporal gravity variations in Fennoscandia. The secular variations are in good agreement with former studies and other independent data. The uplift centre is located over the Bothnian Bay, and the whole uplift area comprises the Scandinavian Peninsula and Finland. The secular variations derived from the GFZ, CSR and JPL monthly solutions differ up to 20%, which is not statistically significant, and the largest signal of about 1.2 μGal/year is obtained from the GFZ solution. Besides the GIA signal, two peaks with positive trend values of about 0.8 μGal/year exist in central eastern Europe, which are not GIA-induced, and
NASA Astrophysics Data System (ADS)
Menna, F.; Nocerino, E.; Troisi, S.; Remondino, F.
2015-04-01
The surveying and 3D modelling of objects that extend both below and above the water level, such as ships, harbour structures, offshore platforms, are still an open issue. Commonly, a combined and simultaneous survey is the adopted solution, with acoustic/optical sensors respectively in underwater and in air (most common) or optical/optical sensors both below and above the water level. In both cases, the system must be calibrated and a ship is to be used and properly equipped with also a navigation system for the alignment of sequential 3D point clouds. Such a system is usually highly expensive and has been proved to work with still structures. On the other hand for free floating objects it does not provide a very practical solution. In this contribution, a flexible, low-cost alternative for surveying floating objects is presented. The method is essentially based on photogrammetry, employed for surveying and modelling both the emerged and submerged parts of the object. Special targets, named Orientation Devices, are specifically designed and adopted for the successive alignment of the two photogrammetric models (underwater and in air). A typical scenario where the proposed procedure can be particularly suitable and effective is the case of a ship after an accident whose damaged part is underwater and necessitate to be measured (Figure 1). The details of the mathematical procedure are provided in the paper, together with a critical explanation of the results obtained from the adoption of the method for the survey of a small pleasure boat in floating condition.
An assessment of the ICE6G_C(VM5a) glacial isostatic adjustment model
NASA Astrophysics Data System (ADS)
Purcell, A.; Tregoning, P.; Dehecq, A.
2016-05-01
The recent release of the next-generation global ice history model, ICE6G_C(VM5a), is likely to be of interest to a wide range of disciplines including oceanography (sea level studies), space gravity (mass balance studies), glaciology, and, of course, geodynamics (Earth rheology studies). In this paper we make an assessment of some aspects of the ICE6G_C(VM5a) model and show that the published present-day radial uplift rates are too high along the eastern side of the Antarctic Peninsula (by ˜8.6 mm/yr) and beneath the Ross Ice Shelf (by ˜5 mm/yr). Furthermore, the published spherical harmonic coefficients—which are meant to represent the dimensionless present-day changes due to glacial isostatic adjustment (GIA)—contain excessive power for degree ≥90, do not agree with physical expectations and do not represent accurately the ICE6G_C(VM5a) model. We show that the excessive power in the high-degree terms produces erroneous uplift rates when the empirical relationship of Purcell et al. (2011) is applied, but when correct Stokes coefficients are used, the empirical relationship produces excellent agreement with the fully rigorous computation of the radial velocity field, subject to the caveats first noted by Purcell et al. (2011). Using the Australian National University (ANU) groups CALSEA software package, we recompute the present-day GIA signal for the ice thickness history and Earth rheology used by Peltier et al. (2015) and provide dimensionless Stokes coefficients that can be used to correct satellite altimetry observations for GIA over oceans and by the space gravity community to separate GIA and present-day mass balance change signals. We denote the new data sets as ICE6G_ANU.
Modeling Fluvial Incision and Transient Landscape Evolution: Influence of Dynamic Channel Adjustment
NASA Astrophysics Data System (ADS)
Attal, M.; Tucker, G. E.; Cowie, P. A.; Whittaker, A. C.; Roberts, G. P.
2007-12-01
Channel geometry exerts a fundamental control on fluvial processes. Recent work has shown that bedrock channel width (W) depends on a number of parameters, including channel slope, and is not only a function of drainage area (A) as is commonly assumed. The present work represents the first attempt to investigate the consequences, for landscape evolution, of using a static expression of channel width (W ~ A0.5) versus a relationship that allows channels to dynamically adjust to changes in slope. We consider different models for the evolution of the channel geometry, including constant width-to-depth ratio (after Finnegan et al., Geology, v. 33, no. 3, 2005), and width-to-depth ratio varying as a function of slope (after Whittaker et al., Geology, v. 35, no. 2, 2007). We use the Channel-Hillslope Integrated Landscape Development (CHILD) model to analyze the response of a catchment to a given tectonic disturbance. The topography of a catchment in the footwall of an active normal fault in the Apennines (Italy) is used as a template for the study. We show that, for this catchment, the transient response can be fairly well reproduced using a simple detachment-limited fluvial incision law. We also show that, depending on the relationship used to express channel width, initial steady-state topographies differ, as do transient channel width, slope, and the response time of the fluvial system. These differences lead to contrasting landscape morphologies when integrated at the scale of a whole catchment. Our results emphasize the importance of channel width in controlling fluvial processes and landscape evolution. They stress the need for using a dynamic hydraulic scaling law when modeling landscape evolution, particularly when the uplift field is non-uniform.
Viscum album-Mediated COX-2 Inhibition Implicates Destabilization of COX-2 mRNA
Saha, Chaitrali; Hegde, Pushpa; Friboulet, Alain; Bayry, Jagadeesh; Kaveri, Srinivas V.
2015-01-01
Extensive use of Viscum album (VA) preparations in the complementary therapy of cancer and in several other human pathologies has led to an increasing number of cellular and molecular approaches to explore the mechanisms of action of VA. We have recently demonstrated that, VA preparations exert a potent anti-inflammatory effect by selectively down-regulating the COX-2-mediated cytokine-induced secretion of prostaglandin E2 (PGE2), one of the important molecular signatures of inflammatory reactions. In this study, we observed a significant down-regulation of COX-2 protein expression in VA-treated A549 cells however COX-2 mRNA levels were unaltered. Therefore, we hypothesized that VA induces destabilisation of COX-2 mRNA, thereby depleting the available functional COX-2 mRNA for the protein synthesis and for the subsequent secretion of PGE2. To address this question, we analyzed the molecular degradation of COX-2 protein and its corresponding mRNA in A549 cell line. Using cyclohexamide pulse chase experiment, we demonstrate that, COX-2 protein degradation is not affected by the treatment with VA whereas experiments on transcriptional blockade with actinomycin D, revealed a marked reduction in the half life of COX-2 mRNA due to its rapid degradation in the cells treated with VA compared to that in IL-1β-stimulated cells. These results thus demonstrate that VA-mediated inhibition of PGE2 implicates destabilization of COX-2 mRNA. PMID:25664986
Glacial isostatic adjustment on 3-D Earth models: a finite-volume formulation
NASA Astrophysics Data System (ADS)
Latychev, Konstantin; Mitrovica, Jerry X.; Tromp, Jeroen; Tamisiea, Mark E.; Komatitsch, Dimitri; Christara, Christina C.
2005-05-01
We describe and present results from a finite-volume (FV) parallel computer code for forward modelling the Maxwell viscoelastic response of a 3-D, self-gravitating, elastically compressible Earth to an arbitrary surface load. We implement a conservative, control volume discretization of the governing equations using a tetrahedral grid in Cartesian geometry and a low-order, linear interpolation. The basic starting grid honours all major radial discontinuities in the Preliminary Reference Earth Model (PREM), and the models are permitted arbitrary spatial variations in viscosity and elastic parameters. These variations may be either continuous or discontinuous at a set of grid nodes forming a 3-D surface within the (regional or global) modelling domain. In the second part of the paper, we adopt the FV methodology and a spherically symmetric Earth model to generate a suite of predictions sampling a broad class of glacial isostatic adjustment (GIA) data types (3-D crustal motions, long-wavelength gravity anomalies). These calculations, based on either a simple disc load history or a global Late Pleistocene ice load reconstruction (ICE-3G), are benchmarked against predictions generated using the traditional normal-mode approach to GIA. The detailed comparison provides a guide for future analyses (e.g. what grid resolution is required to obtain a specific accuracy?) and it indicates that discrepancies in predictions of 3-D crustal velocities less than 0.1 mm yr-1 are generally obtainable for global grids with ~3 × 106 nodes; however, grids of higher resolution are required to predict large-amplitude (>1 cm yr-1) radial velocities in zones of peak post-glacial uplift (e.g. James bay) to the same level of absolute accuracy. We conclude the paper with a first application of the new formulation to a 3-D problem. Specifically, we consider the impact of mantle viscosity heterogeneity on predictions of present-day 3-D crustal motions in North America. In these tests, the
Assessment of an adjustment factor to model radar range dependent error
NASA Astrophysics Data System (ADS)
Sebastianelli, S.; Russo, F.; Napolitano, F.; Baldini, L.
2012-09-01
Quantitative radar precipitation estimates are affected by errors determined by many causes such as radar miscalibration, range degradation, attenuation, ground clutter, variability of Z-R relation, variability of drop size distribution, vertical air motion, anomalous propagation and beam-blocking. Range degradation (including beam broadening and sampling of precipitation at an increasing altitude)and signal attenuation, determine a range dependent behavior of error. The aim of this work is to model the range-dependent error through an adjustment factor derived from the G/R ratio trend against the range, where G and R are the corresponding rain gauge and radar rainfall amounts computed at each rain gauge location. Since range degradation and signal attenuation effects are negligible close to the radar, resultsshowthatwithin 40 km from radar the overall range error is independent of the distance from Polar 55C and no range-correction is needed. Nevertheless, up to this distance, the G/R ratiocan showa concave trend with the range, which is due to the melting layer interception by the radar beam during stratiform events.
Comparison of Two Foreign Body Retrieval Devices with Adjustable Loops in a Swine Model
Konya, Andras
2006-12-15
The purpose of the study was to compare two similar foreign body retrieval devices, the Texan{sup TM} (TX) and the Texan LONGhorn{sup TM} (TX-LG), in a swine model. Both devices feature a {<=}30-mm adjustable loop. Capture times and total procedure times for retrieving foreign bodies from the infrarenal aorta, inferior vena cava, and stomach were compared. All attempts with both devices (TX, n = 15; TX-LG, n = 14) were successful. Foreign bodies in the vasculature were captured quickly using both devices (mean {+-} SD, 88 {+-} 106 sec for TX vs 67 {+-} 42 sec for TX-LG) with no significant difference between them. The TX-LG, however, allowed significantly better capture times than the TX in the stomach (p = 0.022), Overall, capture times for the TX-LG were significantly better than for the TX (p = 0.029). There was no significant difference between the total procedure times in any anatomic region. TX-LG performed significantly better than the TX in the stomach and therefore overall. The better torque control and maneuverability of TX-LG resulted in better performance in large anatomic spaces.
COX-2 inhibitors: a novel strategy in the management of breast cancer.
Regulski, Miłosz; Regulska, Katarzyna; Prukała, Wiesław; Piotrowska, Hanna; Stanisz, Beata; Murias, Marek
2016-04-01
Cyclooxygenase-2 (COX-2) inhibitors are common anti-inflammatory drugs with pleiotropic, endogenous actions that could be useful in the management of breast cancer. Here, we provide a complete understanding of the biochemistry of COX-2 and discuss the various molecular mechanisms behind its increased expression in breast cancer. We also analyze the possible mechanisms responsible for the anticancer effect of COX-2 inhibitors and provide an overview of the available preclinical and clinical data on the use of COX-2 inhibitors in breast cancer. Finally, we describe a mathematical model of the relation between the structure and biological potency of promising new COX-2 inhibitors (trans-stilbenes) using a 2D quantitative structure-activity relationship (QSAR) technique. PMID:26723915
Praticò, D; Tillmann, C; Zhang, Z B; Li, H; FitzGerald, G A
2001-03-13
The cyclooxygenase (COX) product, prostacyclin (PGI(2)), inhibits platelet activation and vascular smooth-muscle cell migration and proliferation. Biochemically selective inhibition of COX-2 reduces PGI(2) biosynthesis substantially in humans. Because deletion of the PGI(2) receptor accelerates atherogenesis in the fat-fed low density lipoprotein receptor knockout mouse, we wished to determine whether selective inhibition of COX-2 would accelerate atherogenesis in this model. To address this hypothesis, we used dosing with nimesulide, which inhibited COX-2 ex vivo, depressed urinary 2,3 dinor 6-keto PGF(1alpha) by approximately 60% but had no effect on thromboxane formation by platelets, which only express COX-1. By contrast, the isoform nonspecific inhibitor, indomethacin, suppressed platelet function and thromboxane formation ex vivo and in vivo, coincident with effects on PGI(2) biosynthesis indistinguishable from nimesulide. Indomethacin reduced the extent of atherosclerosis by 55 +/- 4%, whereas nimesulide failed to increase the rate of atherogenesis. Despite their divergent effects on atherogenesis, both drugs depressed two indices of systemic inflammation, soluble intracellular adhesion molecule-1, and monocyte chemoattractant protein-1 to a similar but incomplete degree. Neither drug altered serum lipids and the marked increase in vascular expression of COX-2 during atherogenesis. Accelerated progression of atherosclerosis is unlikely during chronic intake of specific COX-2 inhibitors. Furthermore, evidence that COX-1-derived prostanoids contribute to atherogenesis suggests that controlled evaluation of the effects of nonsteroidal anti-inflammatory drugs and/or aspirin on plaque progression in humans is timely. PMID:11248083
Glacial isostatic adjustment model with composite 3-D Earth rheology for Fennoscandia
NASA Astrophysics Data System (ADS)
van der Wal, Wouter; Barnhoorn, Auke; Stocchi, Paolo; Gradmann, Sofie; Wu, Patrick; Drury, Martyn; Vermeersen, Bert
2013-07-01
Models for glacial isostatic adjustment (GIA) can provide constraints on rheology of the mantle if past ice thickness variations are assumed to be known. The Pleistocene ice loading histories that are used to obtain such constraints are based on an a priori 1-D mantle viscosity profile that assumes a single deformation mechanism for mantle rocks. Such a simplified viscosity profile makes it hard to compare the inferred mantle rheology to inferences from seismology and laboratory experiments. It is unknown what constraints GIA observations can provide on more realistic mantle rheology with an ice history that is not based on an a priori mantle viscosity profile. This paper investigates a model for GIA with a new ice history for Fennoscandia that is constrained by palaeoclimate proxies and glacial sediments. Diffusion and dislocation creep flow law data are taken from a compilation of laboratory measurements on olivine. Upper-mantle temperature data sets down to 400 km depth are derived from surface heatflow measurements, a petrochemical model for Fennoscandia and seismic velocity anomalies. Creep parameters below 400 km are taken from an earlier study and are only varying with depth. The olivine grain size and water content (a wet state, or a dry state) are used as free parameters. The solid Earth response is computed with a global spherical 3-D finite-element model for an incompressible, self-gravitating Earth. We compare predictions to sea level data and GPS uplift rates in Fennoscandia. The objective is to see if the mantle rheology and the ice model is consistent with GIA observations. We also test if the inclusion of dislocation creep gives any improvements over predictions with diffusion creep only, and whether the laterally varying temperatures result in an improved fit compared to a widely used 1-D viscosity profile (VM2). We find that sea level data can be explained with our ice model and with information on mantle rheology from laboratory experiments
NASA Astrophysics Data System (ADS)
Addor, Nans; Rohrer, Marco; Furrer, Reinhard; Seibert, Jan
2016-03-01
Bias adjustment methods usually do not account for the origins of biases in climate models and instead perform empirical adjustments. Biases in the synoptic circulation are for instance often overlooked when postprocessing regional climate model (RCM) simulations driven by general circulation models (GCMs). Yet considering atmospheric circulation helps to establish links between the synoptic and the regional scale, and thereby provides insights into the physical processes leading to RCM biases. Here we investigate how synoptic circulation biases impact regional climate simulations and influence our ability to mitigate biases in precipitation and temperature using quantile mapping. We considered 20 GCM-RCM combinations from the ENSEMBLES project and characterized the dominant atmospheric flow over the Alpine domain using circulation types. We report in particular a systematic overestimation of the frequency of westerly flow in winter. We show that it contributes to the generalized overestimation of winter precipitation over Switzerland, and this wet regional bias can be reduced by improving the simulation of synoptic circulation. We also demonstrate that statistical bias adjustment relying on quantile mapping is sensitive to circulation biases, which leads to residual errors in the postprocessed time series. Overall, decomposing GCM-RCM time series using circulation types reveals connections missed by analyses relying on monthly or seasonal values. Our results underscore the necessity to better diagnose process misrepresentation in climate models to progress with bias adjustment and impact modeling.
An assessment of the ICE6G_C (VM5A) glacial isostatic adjustment model
NASA Astrophysics Data System (ADS)
Purcell, Anthony; Tregoning, Paul; Dehecq, Amaury
2016-04-01
The recent release of the next-generation global ice history model, ICE6G_C(VM5a) [Peltier et al., 2015, Argus et al. 2014] is likely to be of interest to a wide range of disciplines including oceanography (sea level studies), space gravity (mass balance studies), glaciology and, of course, geodynamics (Earth rheology studies). In this presentation I will assess some aspects of the ICE6G_C(VM5a) model and the accompanying published data sets. I will demonstrate that the published present-day radial uplift rates are too high along the eastern side of the Antarctic Peninsula (by ˜8.6 mm/yr) and beneath the Ross Ice Shelf (by ˜5 mm/yr). Further, the published spherical harmonic coefficients - which are meant to represent the dimensionless present-day changes due to glacial isostatic adjustment (GIA) - will be shown to contain excessive power for degree ≥ 90, to be physically implausible and to not represent accurately the ICE6G_C(VM5a) model. The excessive power in the high degree terms produces erroneous uplift rates when the empirical relationship of Purcell et al. [2011] is applied but, when correct Stokes' coefficients are used, the empirical relationship will be shown to produce excellent agreement with the fully rigorous computation of the radial velocity field, subject to the caveats first noted by Purcell et al. [2011]. Finally, a global radial velocity field for the present-day GIA signal, and corresponding Stoke's coefficients will be presented for the ICE6GC ice model history using the VM5a rheology model. These results have been obtained using the ANU group's CALSEA software package and can be used to correct satellite altimetry observations for GIA over oceans and by the space gravity community to separate GIA and present-day mass balance change signals without any of the shortcomings of the previously published data-sets. We denote the new data sets ICE6G_ANU.
Bazzazian, S; Besharat, M A
2012-01-01
The aim of this study was to develop and test a model of adjustment to type I diabetes. Three hundred young adults (172 females and 128 males) with type I diabetes were asked to complete the Adult Attachment Inventory (AAI), the Brief Illness Perception Questionnaire (Brief IPQ), Task-oriented subscale of the Coping Inventory for Stressful Situations (CISS), D-39, and well-being subscale of the Mental Health Inventory (MHI). HbA1c was obtained from laboratory examination. Results from structural equation analysis partly supported the hypothesized model. Secure and avoidant attachment styles were found to have effects on illness perception, ambivalent attachment style did not have significant effect on illness perception. Three attachment styles had significant effect on task-oriented coping strategy. Avoidant attachment had negative direct effect on adjustment too. Regression effects of illness perception and task-oriented coping strategy on adjustment were positive. Therefore, positive illness perception and more usage of task-oriented coping strategy predict better adjustment to diabetes. So, the results confirmed the theoretical bases and empirical evidence of effectiveness of attachment styles in adjustment to chronic disease and can be helpful in devising preventive policies, determining high-risk maladjusted patients, and planning special psychological treatment. PMID:21678193
Mortality Prediction in ICUs Using A Novel Time-Slicing Cox Regression Method
Wang, Yuan; Chen, Wenlin; Heard, Kevin; Kollef, Marin H.; Bailey, Thomas C.; Cui, Zhicheng; He, Yujie; Lu, Chenyang; Chen, Yixin
2015-01-01
Over the last few decades, machine learning and data mining have been increasingly used for clinical prediction in ICUs. However, there is still a huge gap in making full use of the time-series data generated from ICUs. Aiming at filling this gap, we propose a novel approach entitled Time Slicing Cox regression (TS-Cox), which extends the classical Cox regression into a classification method on multi-dimensional time-series. Unlike traditional classifiers such as logistic regression and support vector machines, our model not only incorporates the discriminative features derived from the time-series, but also naturally exploits the temporal orders of these features based on a Cox-like function. Empirical evaluation on MIMIC-II database demonstrates the efficacy of the TS-Cox model. Our TS-Cox model outperforms all other baseline models by a good margin in terms of AUC_PR, sensitivity and PPV, which indicates that TS-Cox may be a promising tool for mortality prediction in ICUs. PMID:26958269
NASA Astrophysics Data System (ADS)
Belousov, V. I.; Ezhela, V. V.; Kuyanov, Yu. V.; Tkachenko, N. P.
2015-12-01
The experience of using the dynamic atlas of the experimental data and mathematical models of their description in the problems of adjusting parametric models of observable values depending on kinematic variables is presented. The functional possibilities of an image of a large number of experimental data and the models describing them are shown by examples of data and models of observable values determined by the amplitudes of elastic scattering of hadrons. The Internet implementation of an interactive tool DaMoScope and its interface with the experimental data and codes of adjusted parametric models with the parameters of the best description of data are schematically shown. The DaMoScope codes are freely available.
Belousov, V. I.; Ezhela, V. V.; Kuyanov, Yu. V. Tkachenko, N. P.
2015-12-15
The experience of using the dynamic atlas of the experimental data and mathematical models of their description in the problems of adjusting parametric models of observable values depending on kinematic variables is presented. The functional possibilities of an image of a large number of experimental data and the models describing them are shown by examples of data and models of observable values determined by the amplitudes of elastic scattering of hadrons. The Internet implementation of an interactive tool DaMoScope and its interface with the experimental data and codes of adjusted parametric models with the parameters of the best description of data are schematically shown. The DaMoScope codes are freely available.
ERIC Educational Resources Information Center
Rulison, Kelly L.; Gest, Scott D.; Loken, Eric; Welsh, Janet A.
2010-01-01
The association between affiliating with aggressive peers and behavioral, social and psychological adjustment was examined. Students initially in 3rd, 4th, and 5th grade (N = 427) were followed biannually through 7th grade. Students' peer-nominated groups were identified. Multilevel modeling was used to examine the independent contributions of…
The Effectiveness of the Strength-Centered Career Adjustment Model for Dual-Career Women in Taiwan
ERIC Educational Resources Information Center
Wang, Yu-Chen; Tien, Hsiu-Lan Shelley
2011-01-01
The authors investigated the effectiveness of a Strength-Centered Career Adjustment Model for dual-career women (N = 28). Fourteen women in the experimental group received strength-centered career counseling for 6 to 8 sessions; the 14 women in the control group received test services in 1 to 2 sessions. All participants completed the Personal…
ERIC Educational Resources Information Center
Hawkins, Amy L.; Haskett, Mary E.
2014-01-01
Background: Abused children's internal working models (IWM) of relationships are known to relate to their socioemotional adjustment, but mechanisms through which negative representations increase vulnerability to maladjustment have not been explored. We sought to expand the understanding of individual differences in IWM of abused children and…
Hoos, Anne B.; Patel, Anant R.
1996-01-01
Model-adjustment procedures were applied to the combined data bases of storm-runoff quality for Chattanooga, Knoxville, and Nashville, Tennessee, to improve predictive accuracy for storm-runoff quality for urban watersheds in these three cities and throughout Middle and East Tennessee. Data for 45 storms at 15 different sites (five sites in each city) constitute the data base. Comparison of observed values of storm-runoff load and event-mean concentration to the predicted values from the regional regression models for 10 constituents shows prediction errors, as large as 806,000 percent. Model-adjustment procedures, which combine the regional model predictions with local data, are applied to improve predictive accuracy. Standard error of estimate after model adjustment ranges from 67 to 322 percent. Calibration results may be biased due to sampling error in the Tennessee data base. The relatively large values of standard error of estimate for some of the constituent models, although representing significant reduction (at least 50 percent) in prediction error compared to estimation with unadjusted regional models, may be unacceptable for some applications. The user may wish to collect additional local data for these constituents and repeat the analysis, or calibrate an independent local regression model.
Select Dietary Phytochemicals Function as Inhibitors of COX-1 but Not COX-2
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
Data Assimilation and Adjusted Spherical Harmonic Model of VTEC Map over Thailand
NASA Astrophysics Data System (ADS)
Klinngam, Somjai; Maruyama, Takashi; Tsugawa, Takuya; Ishii, Mamoru; Supnithi, Pornchai; Chiablaem, Athiwat
2016-07-01
The global navigation satellite system (GNSS) and high frequency (HF) communication are vulnerable to the ionospheric irregularities, especially when the signal travels through the low-latitude region and around the magnetic equator known as equatorial ionization anomaly (EIA) region. In order to study the ionospheric effects to the communications performance in this region, the regional map of the observed total electron content (TEC) can show the characteristic and irregularities of the ionosphere. In this work, we develop the two-dimensional (2D) map of vertical TEC (VTEC) over Thailand using the adjusted spherical harmonic model (ASHM) and the data assimilation technique. We calculate the VTEC from the receiver independent exchange (RINEX) files recorded by the dual-frequency global positioning system (GPS) receivers on July 8th, 2012 (quiet day) at 12 stations around Thailand: 0° to 25°E and 95°N to 110°N. These stations are managed by Department of Public Works and Town & Country Planning (DPT), Thailand, and the South East Asia Low-latitude ionospheric Network (SEALION) project operated by National Institute of Information and Communications Technology (NICT), Japan, and King Mongkut's Institute of Technology Ladkrabang (KMITL). We compute the median observed VTEC (OBS-VTEC) in the grids with the spatial resolution of 2.5°x5° in latitude and longitude and time resolution of 2 hours. We assimilate the OBS-VTEC with the estimated VTEC from the International Reference Ionosphere model (IRI-VTEC) as well as the ionosphere map exchange (IONEX) files provided by the International GNSS Service (IGS-VTEC). The results show that the estimation of the 15-degree ASHM can be improved when both of IRI-VTEC and IGS-VTEC are weighted by the latitude-dependent factors before assimilating with the OBS-VTEC. However, the IRI-VTEC assimilation can improve the ASHM estimation more than the IGS-VTEC assimilation. Acknowledgment: This work is partially funded by the
Huang, Jian; Zhang, Di; Xie, Fuqiang; Lin, Degui
2015-01-01
Increasing evidence suggests that cancer stem cells (CSCs) are responsible for tumor initiation and maintenance. Additionally, it is becoming apparent that cyclooxygenase (COX) signaling is associated with canine mammary tumor development. The goals of the present study were to investigate COX-2 expression patterns and their effect on CSC-mediated tumor initiation in primary canine mammary tissues and tumorsphere models using immunohistochemistry. Patterns of COX-2, CD44, octamer-binding transcription factor (Oct)-3/4, and epidermal growth factor receptor (EGFR) expression were examined in malignant mammary tumor (MMT) samples and analyzed in terms of clinicopathological characteristics. COX-2 and Oct-3/4 expression was higher in MMTs compared to other histological samples with heterogeneous patterns. In MMTs, COX-2 expression correlated with tumor malignancy features. Significant associations between COX-2, CD44, and EGFR were observed in low-differentiated MMTs. Comparative analysis showed that the levels of COX-2, CD44, and Oct-3/4 expression varied significantly among TSs of three histological grades. Enhanced COX-2 staining was consistently observed in TSs. Similar levels of staining intensity were found for CD44 and Oct-3/4, but EGFR expression was weak. Our findings indicate the potential role of COX-2 in CSC-mediated tumor initiation, and suggest that COX-2 inhibition may help treat canine mammary tumors by targeting CSCs. PMID:26124697
Vázquez-Acevedo, Miriam; Rubalcava-Gracia, Diana; González-Halphen, Diego
2014-11-01
The cox3 gene, encoding subunit III of cytochrome c oxidase (Cox3) is in mitochondrial genomes except in chlorophycean algae, where it is localized in the nucleus. Therefore, algae like Chlamydomonas reinhardtii, Polytomella sp. and Volvox carteri, synthesize the Cox3 polypeptide in the cytosol, import it into mitochondria, and integrate it into the cytochrome c oxidase complex. In this work, we followed the in vitro internalization of the Cox3 precursor by isolated, import-competent mitochondria of Polytomella sp. In this colorless alga, the precursor Cox3 protein is synthesized with a long, cleavable, N-terminal mitochondrial targeting sequence (MTS) of 98 residues. In an import time course, a transient Cox3 intermediate was identified, suggesting that the long MTS is processed more than once. The first processing step is sensitive to the metalo-protease inhibitor 1,10-ortophenantroline, suggesting that it is probably carried out by the matrix-located Mitochondrial Processing Protease. Cox3 is readily imported through an energy-dependent import pathway and integrated into the inner mitochondrial membrane, becoming resistant to carbonate extraction. Furthermore, the imported Cox3 protein was assembled into cytochrome c oxidase, as judged by the presence of a labeled band co-migrating with complex IV in Blue Native Electrophoresis. A model for the biogenesis of Cox3 in chlorophycean algae is proposed. This is the first time that the in vitro mitochondrial import of a cytosol-synthesized Cox3 subunit is described. PMID:24561572
Association Between COX-2 Polymorphisms and Lung Cancer Risk
Wang, Weiwei; Fan, Xinyun; Zhang, Yong; Yang, Yi; Yang, Siyuan; Li, Gaofeng
2015-01-01
Background Multiple relevant risk factors for lung cancer have been reported in different populations, but results of previous studies were not consistent. Therefore, a meta-analysis is necessary to summarize these outcomes and reach a relatively comprehensive conclusion. Material/Methods STATA 12.0 software was used for all statistical of the relationship between COX-2 polymorphisms and lung cancer risk. Inter-study heterogeneity was examined with the Q statistic (significance level at P<0.1). The publication bias among studies in the meta-analysis was analyzed with Begg’s funnel plot and Egger’s test. Hardy-Weinberg equilibrium was tested in all controls of the studies. Results COX-2 rs20417 polymorphism had a significant association with reduced risk of lung cancer under homozygous and recessive models, and similar results were observed in white and population-based subgroups under 2 and 3 contrasts, respectively. Additionally, rs2066826 polymorphism manifested a strong correlation with increased risk of lung cancer under 5 genetic models. Conclusions In COX-2 gene, rs20417 may have a certain relationship with reduced risk of lung cancer, while rs2066826 may increase the risk of lung cancer. PMID:26624903
Conger, R D; Patterson, G R; Ge, X
1995-02-01
In this study of parental stress and adolescent adjustment, experiences of negative life events during the recent past were used to generate a measure of acute stress. In addition, multiple indicators based on reports from various informants were used to estimate latent constructs for parental depression, discipline practices, and adolescent adjustment. Employing 2 independent samples of families from 2 different regions of the country (rural Iowa and a medium-sized city in Oregon), structural equation models were used to test the hypothesis that in intact families acute stress experienced by parents is linked to boys' adjustment (average age equaled 11.8 years in the Oregon sample, 12.7 years in the Iowa sample) through 2 different causal mechanisms. The findings showed that parental stress was related to adjustment through stress-related parental depression that is, in turn, correlated with disrupted discipline practices. Poor discipline appears to provide the direct link with developmental outcomes. The structural equation model (SEM) used to test the proposed mediational process was consistent with the data for mothers and boys from both the Oregon and the Iowa samples. The similarity in results was less clear for fathers and boys. Implications of these results for future replication studies are discussed. PMID:7497831
Telzer, Eva H; Yuen, Cynthia; Gonzales, Nancy; Fuligni, Andrew J
2016-07-01
The acculturation gap-distress model purports that immigrant children acculturate faster than do their parents, resulting in an acculturation gap that leads to family and youth maladjustment. However, empirical support for the acculturation gap-distress model has been inconclusive. In the current study, 428 Mexican-American adolescents (50.2 % female) and their primary caregivers independently completed questionnaires assessing their levels of American and Mexican cultural orientation, family functioning, and youth adjustment. Contrary to the acculturation gap-distress model, acculturation gaps were not associated with poorer family or youth functioning. Rather, adolescents with higher levels of Mexican cultural orientations showed positive outcomes, regardless of their parents' orientations to either American or Mexican cultures. Findings suggest that youths' heritage cultural maintenance may be most important for their adjustment. PMID:26759225
A Key Challenge in Global HRM: Adding New Insights to Existing Expatriate Spouse Adjustment Models
ERIC Educational Resources Information Center
Gupta, Ritu; Banerjee, Pratyush; Gaur, Jighyasu
2012-01-01
This study is an attempt to strengthen the existing knowledge about factors affecting the adjustment process of the trailing expatriate spouse and the subsequent impact of any maladjustment or expatriate failure. We conducted a qualitative enquiry using grounded theory methodology with 26 Indian spouses who had to deal with their partner's…
ERIC Educational Resources Information Center
Donaldson, Tarryn; Earl, Joanne K.; Muratore, Alexa M.
2010-01-01
Extending earlier research, this study explores individual (e.g. demographic and health characteristics), psychosocial (e.g. mastery and planning) and organizational factors (e.g. conditions of workforce exit) influencing retirement adjustment. Survey data were collected from 570 semi-retired and retired men and women aged 45 years and older.…
ERIC Educational Resources Information Center
Wong, Jessica Y.; Earl, Joanne K.
2009-01-01
This cross-sectional study examines three predictors of retirement adjustment: individual (demographic and health), psychosocial (work centrality), and organizational (conditions of workforce exit). It also examines the effect of work centrality on post-retirement activity levels. Survey data was collected from 394 retirees (aged 45-93 years).…
ERIC Educational Resources Information Center
Ray, Corey E.; Elliott, Stephen N.
2006-01-01
This study examined the hypothesized relationship between social adjustment, as measured by perceived social support, self-concept, and social skills, and performance on academic achievement tests. Participants included 27 teachers and 77 fourth- and eighth-grade students with diverse academic and behavior competencies. Teachers were asked to…
Divorce Stress and Adjustment Model: Locus of Control and Demographic Predictors.
ERIC Educational Resources Information Center
Barnet, Helen Smith
This study depicts the divorce process over three time periods: predivorce decision phase, divorce proper, and postdivorce. Research has suggested that persons with a more internal locus of control experience less intense and shorter intervals of stress during the divorce proper and better postdivorce adjustment than do persons with a more…
ERIC Educational Resources Information Center
Sonderegger, Robi; Barrett, Paula M.; Creed, Peter A.
2004-01-01
Building on previous cultural adjustment profile work by Sonderegger and Barrett (2004), the aim of this study was to propose an organised structure for a number of single risk factors that have been linked to acculturative-stress in young migrants. In recognising that divergent situational characteristics (e.g., school level, gender, residential…
ERIC Educational Resources Information Center
Asberg, Kia K.; Bowers, Clint; Renk, Kimberly; McKinney, Cliff
2008-01-01
Today's society puts constant demands on the time and resources of all individuals, with the resulting stress promoting a decline in psychological adjustment. Emerging adults are not exempt from this experience, with an alarming number reporting excessive levels of stress and stress-related problems. As a result, the present study addresses the…
Barks, C.S.
1995-01-01
Storm-runoff water-quality data were used to verify and, when appropriate, adjust regional regression models previously developed to estimate urban storm- runoff loads and mean concentrations in Little Rock, Arkansas. Data collected at 5 representative sites during 22 storms from June 1992 through January 1994 compose the Little Rock data base. Comparison of observed values (0) of storm-runoff loads and mean concentrations to the predicted values (Pu) from the regional regression models for nine constituents (chemical oxygen demand, suspended solids, total nitrogen, total ammonia plus organic nitrogen as nitrogen, total phosphorus, dissolved phosphorus, total recoverable copper, total recoverable lead, and total recoverable zinc) shows large prediction errors ranging from 63 to several thousand percent. Prediction errors for six of the regional regression models are less than 100 percent, and can be considered reasonable for water-quality models. Differences between 0 and Pu are due to variability in the Little Rock data base and error in the regional models. Where applicable, a model adjustment procedure (termed MAP-R-P) based upon regression with 0 against Pu was applied to improve predictive accuracy. For 11 of the 18 regional water-quality models, 0 and Pu are significantly correlated, that is much of the variation in 0 is explained by the regional models. Five of these 11 regional models consistently overestimate O; therefore, MAP-R-P can be used to provide a better estimate. For the remaining seven regional models, 0 and Pu are not significanfly correlated, thus neither the unadjusted regional models nor the MAP-R-P is appropriate. A simple estimator, such as the mean of the observed values may be used if the regression models are not appropriate. Standard error of estimate of the adjusted models ranges from 48 to 130 percent. Calibration results may be biased due to the limited data set sizes in the Little Rock data base. The relatively large values of
Barrientos, Antoni; Gouget, Karine; Horn, Darryl; Soto, Ileana C.; Fontanesi, Flavia
2008-01-01
Eukaryotic cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. COX is a multimeric enzyme formed by subunits of dual genetic origin whose assembly is intricate and highly regulated. In addition to the structural subunits, a large number of accessory factors are required to build the holoenzyme. The function of these factors is required in all stages of the assembly process. They are relevant to human health because devastating human disorders have been associated with mutations in nuclear genes encoding conserved COX assembly factors. The study of yeast strains and human cell lines from patients carrying mutations in structural subunits and COX assembly factors has been invaluable to attain the current state of knowledge, even if still fragmentary, of the COX assembly process. After the identification of the genes involved, the isolation and characterization of genetic and metabolic suppressors of COX assembly defects, reviewed here, have become a profitable strategy to gain insight into their functions and the pathways in which they operate. Additionally, they have the potential to provide useful information for devising therapeutic approaches to combat human disorders associated with COX deficiency. PMID:18522805
Cerella, Claudia; Sobolewski, Cyril; Chateauvieux, Sébastien; Henry, Estelle; Schnekenburger, Michael; Ghelfi, Jenny; Dicato, Mario; Diederich, Marc
2011-11-15
Enzymatic inhibitors of pro-inflammatory cyclooxygenase-2 (COX-2) possess multiple anti-cancer effects, including chemosensitization. These effects are not always linked to the inhibition of the COX-2 enzyme. Here we analyze the effects of three COX-2 enzyme inhibitors (nimesulide, NS-398 and celecoxib) on apoptosis in different hematopoietic cancer models. Surprisingly, COX-2 inhibitors strongly prevent apoptosis induced by a panel of chemotherapeutic agents. We selected U937 cells as a model of sensitive cells for further studies. Here, we provide evidence that the protective effect is COX-independent. No suppression of the low basal prostaglandin (PG)E(2) production may be observed upon treatment by COX-2 inhibitors. Besides, the non-active celecoxib analog 2,5-dimethyl-celecoxib is able to protect from apoptosis as well. We demonstrate early prevention of the stress-induced apoptotic signaling, prior to Bax/Bak activation. This preventive effect fits with an impairment of the ability of chemotherapeutic agents to trigger apoptogenic stress. Accordingly, etoposide-induced DNA damage is strongly attenuated in the presence of COX-2 inhibitors. In contrast, COX-2 inhibitors do not exert any anti-apoptotic activity when cells are challenged with physiological stimuli (anti-Fas, TNFα or Trail) or with hydrogen peroxide, which do not require internalization and/or are not targeted by chemoresistance proteins. Altogether, our findings show a differential off-target anti-apoptotic effect of COX-2 inhibitors on intrinsic vs. extrinsic apoptosis at the very early steps of intracellular signaling, prior to commitment. The results imply that an exacerbation of the chemoresistance phenomena may be implicated. PMID:21745461
Oxidative switches in functioning of mammalian copper chaperone Cox17
Voronova, Anastassia; Meyer-Klaucke, Wolfram; Meyer, Thomas; Rompel, Annette; Krebs, Bernt; Kazantseva, Jekaterina; Sillard, Rannar; Palumaa, Peep
2007-01-01
Cox17, a copper chaperone for cytochrome-c oxidase, is an essential and highly conserved protein in eukaryotic organisms. Yeast and mammalian Cox17 share six conserved cysteine residues, which are involved in complex redox reactions as well as in metal binding and transfer. Mammalian Cox17 exists in three oxidative states, each characterized by distinct metal-binding properties: fully reduced mammalian Cox170S–S binds co-operatively to four Cu+; Cox172S–S, with two disulfide bridges, binds to one of either Cu+ or Zn2+; and Cox173S–S, with three disulfide bridges, does not bind to any metal ions. The Em (midpoint redox potential) values for two redox couples of Cox17, Cox173S–S↔Cox172S–S (Em1) and Cox172S–S↔Cox170S–S (Em2), were determined to be −197 mV and −340 mV respectively. The data indicate that an equilibrium exists in the cytosol between Cox170S-S and Cox172S–S, which is slightly shifted towards Cox170S-S. In the IMS (mitochondrial intermembrane space), the equilibrium is shifted towards Cox172S–S, enabling retention of Cox172S–S in the IMS and leading to the formation of a biologically competent form of the Cox17 protein, Cox172S–S, capable of copper transfer to the copper chaperone Sco1. XAS (X-ray absorption spectroscopy) determined that Cu4Cox17 contains a Cu4S6-type copper–thiolate cluster, which may provide safe storage of an excess of copper ions. PMID:17672825
Martelli, A; Testai, L; Anzini, M; Cappelli, A; Di Capua, A; Biava, M; Poce, G; Consalvi, S; Giordani, A; Caselli, G; Rovati, L; Ghelardini, C; Patrignani, P; Sautebin, L; Breschi, M C; Calderone, V
2013-12-01
Selective cyclooxygenase 2 (COX2) inhibitors (COXIBs) are effective anti-inflammatory and analgesic drugs with improved gastrointestinal (GI) safety compared to nonselective nonsteroidal anti-inflammatory drugs known as traditional (tNSAIDs). However, their use is associated with a cardiovascular (CV) hazard (i.e. increased incidence of thrombotic events and hypertension) due to the inhibition of COX2-dependent vascular prostacyclin. Aiming to design COX2-selective inhibitors with improved CV safety, new NO-releasing COXIBs (NO-COXIBs) have been developed. In these hybrid drugs, the NO-mediated CV effects are expected to compensate for the COXIB-mediated inhibition of prostacyclin. This study evaluates the potential CV beneficial effects of VA694, a promising NO-COXIB, the anti-inflammatory effects of which have been previously characterized in several in vitro and in vivo experimental models. When incubated in hepatic homogenate, VA694 acted as a slow NO-donor. Moreover, it caused NO-mediated relaxant effects in the vascular smooth muscle. The chronic oral administration of VA694 to young spontaneously hypertensive rats (SHRs) significantly slowed down the age-related development of hypertension and was associated with increased plasma levels of nitrates, stable end-metabolites of NO. Furthermore, a significant improvement of coronary flow and a significant reduction of endothelial dysfunction were observed in SHRs submitted to chronic administration of VA694. In conclusion, VA694 is a promising COX2-inhibiting hybrid drug, showing NO releasing properties which may mitigate the CV deleterious effects associated with the COX2-inhibition. PMID:24083950
NASA Astrophysics Data System (ADS)
Cotroneo, Vincenzo; Davis, William N.; Reid, Paul B.; Schwartz, Daniel A.; Trolier-McKinstry, Susan; Wilke, Rudeger H. T.
2011-09-01
The present generation of X-ray telescopes emphasizes either high image quality (e.g. Chandra with sub-arc second resolution) or large effective area (e.g. XMM-Newton), while future observatories under consideration (e.g. Athena, AXSIO) aim to greatly enhance the effective area, while maintaining moderate (~10 arc-seconds) image quality. To go beyond the limits of present and planned missions, the use of thin adjustable optics for the control of low-order figure error is needed to obtain the high image quality of precisely figured mirrors along with the large effective area of thin mirrors. The adjustable mirror prototypes under study at Smithsonian Astrophysical Observatory are based on two different principles and designs: 1) thin film lead-zirconate-titanate (PZT) piezoelectric actuators directly deposited on the mirror back surface, with the strain direction parallel to the glass surface (for sub-arc-second angular resolution and large effective area), and 2) conventional leadmagnesium- niobate (PMN) electrostrictive actuators with their strain direction perpendicular to the mirror surface (for 3-5 arc second resolution and moderate effective area). We have built and operated flat test mirrors of these adjustable optics. We present the comparison between theoretical influence functions as obtained by finite element analysis and the measured influence functions obtained from the two test configurations.
Shapiro, Y; Moran, D; Epstein, Y; Stroschein, L; Pandolf, K B
1995-05-01
Under outdoor conditions this model was over estimating sweat loss response in shaded (low solar radiation) environments, and underestimating the response when solar radiation was high (open field areas). The present study was conducted in order to adjust the model to be applicable under outdoor environmental conditions. Four groups of fit acclimated subjects participated in the study. They were exposed to three climatic conditions (30 degrees, 65% rh; 31 degrees C, 40% rh; and 40 degrees C, 20% rh) and three levels of metabolic rate (100, 300 and 450 W) in shaded and sunny areas while wearing shorts, cotton fatigues (BDUs) or protective garments. The original predictive equation for sweat loss was adjusted for the outdoor conditions by evaluating separately the radiative heat exchange, short-wave absorption in the body and long-wave emission from the body to the atmosphere and integrating them in the required evaporation component (Ereq) of the model, as follows: Hr = 1.5SL0.6/I(T) (watt) H1 = 0.047Me.th/I(T) (watt), where SL is solar radiation (W.m-2), Me.th is the Stephan Boltzman constant, and I(T) is the effective clothing insulation coefficient. This adjustment revealed a high correlation between the measured and expected values of sweat loss (r = 0.99, p < 0.0001). PMID:7737107
NKG201xGIA - first results for a new model of glacial isostatic adjustment in Fennoscandia
NASA Astrophysics Data System (ADS)
Steffen, Holger; Barletta, Valentina; Kollo, Karin; Milne, Glenn A.; Nordman, Maaria; Olsson, Per-Anders; Simpson, Matthew J. R.; Tarasov, Lev; Ågren, Jonas
2016-04-01
Glacial isostatic adjustment (GIA) is a dominant process in northern Europe, which is observed with several geodetic and geophysical methods. The observed land uplift due to this process amounts to about 1 cm/year in the northern Gulf of Bothnia. GIA affects the establishment and maintenance of reliable geodetic and gravimetric reference networks in the Nordic countries. To support a high level of accuracy in the determination of position, adequate corrections have to be applied with dedicated models. Currently, there are efforts within a Nordic Geodetic Commission (NKG) activity towards a model of glacial isostatic adjustment for Fennoscandia. The new model, NKG201xGIA, to be developed in the near future will complement the forthcoming empirical NKG land uplift model, which will substitute the currently used empirical land uplift model NKG2005LU (Ågren & Svensson, 2007). Together, the models will be a reference for vertical and horizontal motion, gravity and geoid change and more. NKG201xGIA will also provide uncertainty estimates for each field. Following former investigations, the GIA model is based on a combination of an ice and an earth model. The selected reference ice model, GLAC, for Fennoscandia, the Barents/Kara seas and the British Isles is provided by Lev Tarasov and co-workers. Tests of different ice and earth models will be performed based on the expertise of each involved modeler. This includes studies on high resolution ice sheets, different rheologies, lateral variations in lithosphere and mantle viscosity and more. This will also be done in co-operation with scientists outside NKG who help in the development and testing of the model. References Ågren, J., Svensson, R. (2007): Postglacial Land Uplift Model and System Definition for the New Swedish Height System RH 2000. Reports in Geodesy and Geographical Information Systems Rapportserie, LMV-Rapport 4, Lantmäteriet, Gävle.
Kleinman, Lawrence C; Norton, Edward C
2009-01-01
Objective To develop and validate a general method (called regression risk analysis) to estimate adjusted risk measures from logistic and other nonlinear multiple regression models. We show how to estimate standard errors for these estimates. These measures could supplant various approximations (e.g., adjusted odds ratio [AOR]) that may diverge, especially when outcomes are common. Study Design Regression risk analysis estimates were compared with internal standards as well as with Mantel–Haenszel estimates, Poisson and log-binomial regressions, and a widely used (but flawed) equation to calculate adjusted risk ratios (ARR) from AOR. Data Collection Data sets produced using Monte Carlo simulations. Principal Findings Regression risk analysis accurately estimates ARR and differences directly from multiple regression models, even when confounders are continuous, distributions are skewed, outcomes are common, and effect size is large. It is statistically sound and intuitive, and has properties favoring it over other methods in many cases. Conclusions Regression risk analysis should be the new standard for presenting findings from multiple regression analysis of dichotomous outcomes for cross-sectional, cohort, and population-based case–control studies, particularly when outcomes are common or effect size is large. PMID:18793213
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, Va: American Psychiatric Publishing. 2013. Powell AD. Grief, bereavement, and adjustment disorders. In: Stern TA, Rosenbaum ...
Golgi-Cox Staining Step by Step
Zaqout, Sami; Kaindl, Angela M.
2016-01-01
Golgi staining remains a key method to study neuronal morphology in vivo. Since most protocols delineating modifications of the original staining method lack details on critical steps, establishing this method in a laboratory can be time-consuming and frustrating. Here, we describe the Golgi-Cox staining in such detail that should turn the staining into an easily feasible method for all scientists working in the neuroscience field. PMID:27065817
McKinney, Cliff; Renk, Kimberly
2008-06-01
Although parent-adolescent interactions have been examined, relevant variables have not been integrated into a multivariate model. As a result, this study examined a multivariate model of parent-late adolescent gender dyads in an attempt to capture important predictors in late adolescents' important and unique transition to adulthood. The sample for this study consisted of 151 male and 324 female late adolescents, who reported on their mothers' and fathers' parenting style, their family environment, their mothers' and fathers' expectations for them, the conflict that they experience with their mothers and fathers, and their own adjustment. Overall, the variables had significant relationships with one another. Further, the male-father, male-mother, and female-father structural equation models that were examined suggested that parenting style has an indirect relationship with late adolescents' adjustment through characteristics of the family environment and the conflict that is experienced in families; such findings were not evident for the female-mother model. Thus, the examination of parent-late adolescent interactions should occur in the context of the gender of parents and their late adolescents. PMID:17710537
Towards a universal barcode of oomycetes--a comparison of the cox1 and cox2 loci.
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. PMID:25728598
Meta-analysis of cyclooxygenase-2 (COX-2) 765G>C polymorphism and Alzheimer's disease.
Su, Jianhua; Wen, Shihong; Zhu, Jinlong; Liu, Ruiping; Yang, Jinsong
2016-09-01
The cyclooxygenase-2 (COX-2) 765G>C polymorphism has been extensively investigated for association with Alzheimer's disease (AD). However, results of different studies have been inconsistent. The aim of the present meta-analysis was to evaluate the association between the 765G>C polymorphism of the COX-2 gene and susceptibility to AD. We searched all related subjects in PubMed, Embase, SinoMed, and China Knowledge Resource Integrated Database and identified seven studies that reported a relationship between the COX-2 765G>C polymorphism and AD. A total of 1260 cases and 1112 controls were included in the seven studies. Our data suggest that the COX-2 765G>C polymorphism may decrease the risk of AD in five genetic models. As a result, this meta-analysis suggests the 765G>C polymorphism of the COX-2 gene may be a protective factor for AD. As our sample size was limited, large-scale, well-designed studies are necessary to validate the association between the COX-2 765G>C polymorphism and AD. PMID:27443496
Ziadinov, I.; Mathis, A.; Trachsel, D.; Rysmukhambetova, A.; Abdyjaparov, T. A.; Kuttubaev, O. T.; Deplazes, P.; Torgerson, P. R.
2008-01-01
Echinococcosis is a major emerging zoonosis in central Asia. A cross-sectional study of dogs in four villages in rural Kyrgyzstan was undertaken to investigate the epidemiology and transmission of Echinococcus spp. A total of 466 dogs were examined by arecoline purgation for the presence of Echinococcus granulosus and Echinococcus multilocularis. In addition, a faecal sample from each dog was examined for taeniid eggs. Any taeniid eggs found were investigated using PCR techniques (multiplex and single target PCR) to improve the diagnostic sensitivity by confirming the presence of Echinococcus spp. and to identify E. granulosus strains. A total of 83 (18%) dogs had either E. granulosus adults in purge material and/or E. granulosus eggs in their faeces as confirmed by PCR. Three genotypes of E. granulosus: G1, G4 and the G6/7 complex were shown to be present in these dogs through subsequent sequence analysis. Purge analysis combined with PCR identified 50 dogs that were infected with adult E. multilocularis and/or had E. multilocularis eggs in their faeces (11%). Bayesian techniques were employed to estimate the true prevalence, the diagnostic sensitivity and specificity of the procedures used and the transmission parameters. The sensitivity of arecoline purgation for the detection of echinococcosis in dogs was rather low, with a value of 38% (Credible intervals (CIs) 27–50%) for E. granulosus and 21% (CIs 11–34%) for E. multilocularis. The specificity of arecoline purgation was assumed to be 100%. The sensitivity of coproscopy followed by PCR of the isolated eggs was calculated as 78% (CIs 57–87%) for E. granulosus and 50% (CIs 29–72%) for E. multilocularis with specificity of 93% (CIs 88–96%) and 100% (CIs 97–100), respectively. The 93% specificity of the coprological-PCR for E. granulosus could suggest coprophagia rather than true infections. After adjusting for the sensitivity of the diagnostic procedures, the estimated true prevalence of infection of
Bao, J Y
1991-04-01
The commonly used microforceps have a much greater opening distance and spring resistance than needed. A piece of plastic ring or rubber band can be used to adjust the opening distance and reduce most of the spring resistance, making the user feel more comfortable and less fatigued. PMID:2051437
Dynamic Modeling of Adjustable-Speed Pumped Storage Hydropower Plant: Preprint
Muljadi, E.; Singh, M.; Gevorgian, V.; Mohanpurkar, M.; Havsapian, R.; Koritarov, V.
2015-04-06
Hydropower is the largest producer of renewable energy in the U.S. More than 60% of the total renewable generation comes from hydropower. There is also approximately 22 GW of pumped storage hydropower (PSH). Conventional PSH uses a synchronous generator, and thus the rotational speed is constant at synchronous speed. This work details a hydrodynamic model and generator/power converter dynamic model. The optimization of the hydrodynamic model is executed by the hydro-turbine controller, and the electrical output real/reactive power is controlled by the power converter. All essential controllers to perform grid-interface functions and provide ancillary services are included in the model.
Kalra, Jaspreet; Kumar, Puneet; Majeed, Abu Bakar Abdul; Prakash, Atish
2016-01-01
Several lines of evidence indicate that beta amyloid (β-A) production, neurofibrillary tangles and neuroinflammation are interrelated in the pathogenesis of Alzheimer's disease (AD). AD is associated with enhanced β-A production and accumulation resulting in neuroinflammation probably via activation of lipoxygenase (LOX) and cyclooxygenase (COX) pathways. Therefore, the present study was designed to investigate the role of LOX and COX inhibitors (zafirlukast and valdecoxib) in amyloidogenesis in β-A1-42 oligomer induced experimental AD in rats. The behavioral activities were assessed using actophotometer, novel object recognition test (ORT), Morris water maze (MWM) followed by biochemical assessments, determination of proinflammatory cytokines and mediators (TNF-α, IL-1β and PGE2), β-A1-42 levels and histopathological analysis. ICV administration of β-A1-42 oligomer produced significant impairment in memory consolidation. In addition to this significant increase in mito-oxidative stress, neuroinflammatory markers, acetylcholinesterase (AChE) toxicity, β-A1-42 level, neuronal cell death and neuroinflammation are more profound in β-A1-42 oligomer treated AD rats. Administration of zafirlukast (15 and 30mg/kg), and valdecoxib (5 and 10mg/kg) significantly improved the behavioral performances and showed significant reversal of mito-oxidative damage declining the neuroinflammation in β-A1-42 oligomer treated rats. Furthermore, more profound effects were observed at the sub-therapeutic dose combination of zafirlukast (15mg/kg) and valdecoxib (5mg/kg). The results of the present study indicate that protective effects of zafirlukast and valdecoxib are achieved through the blockade of release of LOX and COX metabolites therefore, representing a new therapeutic target for treating AD and other neurodegenerative disorders. PMID:27106205
ERIC Educational Resources Information Center
Fanti, Kostas A.; Henrich, Christopher C.; Brookmeyer, Kathryn A.; Kuperminc, Gabriel P.
2008-01-01
The present study includes externalizing problems, internalizing problems, mother-adolescent relationship quality, and father-adolescent relationship quality in the same structural equation model and tests the longitudinal reciprocal association among all four variables over a 1-year period. A transactional model in which adolescents'…
Covariate Measurement Error Adjustment for Multilevel Models with Application to Educational Data
ERIC Educational Resources Information Center
Battauz, Michela; Bellio, Ruggero; Gori, Enrico
2011-01-01
This article proposes a multilevel model for the assessment of school effectiveness where the intake achievement is a predictor and the response variable is the achievement in the subsequent periods. The achievement is a latent variable that can be estimated on the basis of an item response theory model and hence subject to measurement error.…
A self-adjusting flow dependent formulation for the classical Smagorinsky model coefficient
NASA Astrophysics Data System (ADS)
Ghorbaniasl, G.; Agnihotri, V.; Lacor, C.
2013-05-01
In this paper, we propose an efficient formula for estimating the model coefficient of a Smagorinsky model based subgrid scale eddy viscosity. The method allows vanishing eddy viscosity through a vanishing model coefficient in regions where the eddy viscosity should be zero. The advantage of this method is that the coefficient of the subgrid scale model is a function of the flow solution, including the translational and the rotational velocity field contributions. Furthermore, the value of model coefficient is optimized without using the dynamic procedure thereby saving significantly on computational cost. In addition, the method guarantees the model coefficient to be always positive with low fluctuation in space and time. For validation purposes, three test cases are chosen: (i) a fully developed channel flow at {mathopRenolimits} _tau = 180, 395, (ii) a fully developed flow through a rectangular duct of square cross section at {mathopRenolimits} _tau = 300, and (iii) a smooth subcritical flow past a stationary circular cylinder, at a Reynolds number of {mathopRenolimits} = 3900, where the wake is fully turbulent but the cylinder boundary layers remain laminar. A main outcome is the good behavior of the proposed model as compared to reference data. We have also applied the proposed method to a CT-based simplified human upper airway model, where the flow is transient.
Frykholm, Karolin; Berntsson, Ronnie Per-Arne; Claesson, Magnus; de Battice, Laura; Odegrip, Richard; Stenmark, Pål; Westerlund, Fredrik
2016-01-01
The Cox protein from bacteriophage P2 forms oligomeric filaments and it has been proposed that DNA can be wound up around these filaments, similar to how histones condense DNA. We here use fluorescence microscopy to study single DNA–Cox complexes in nanofluidic channels and compare how the Cox homologs from phages P2 and WΦ affect DNA. By measuring the extension of nanoconfined DNA in absence and presence of Cox we show that the protein compacts DNA and that the binding is highly cooperative, in agreement with the model of a Cox filament around which DNA is wrapped. Furthermore, comparing microscopy images for the wild-type P2 Cox protein and two mutants allows us to discriminate between compaction due to filament formation and compaction by monomeric Cox. P2 and WΦ Cox have similar effects on the physical properties of DNA and the subtle, but significant, differences in DNA binding are due to differences in binding affinity rather than binding mode. The presented work highlights the use of single DNA molecule studies to confirm structural predictions from X-ray crystallography. It also shows how a small protein by oligomerization can have great impact on the organization of DNA and thereby fulfill multiple regulatory functions. PMID:27131370
Frykholm, Karolin; Berntsson, Ronnie Per-Arne; Claesson, Magnus; de Battice, Laura; Odegrip, Richard; Stenmark, Pål; Westerlund, Fredrik
2016-09-01
The Cox protein from bacteriophage P2 forms oligomeric filaments and it has been proposed that DNA can be wound up around these filaments, similar to how histones condense DNA. We here use fluorescence microscopy to study single DNA-Cox complexes in nanofluidic channels and compare how the Cox homologs from phages P2 and WΦ affect DNA. By measuring the extension of nanoconfined DNA in absence and presence of Cox we show that the protein compacts DNA and that the binding is highly cooperative, in agreement with the model of a Cox filament around which DNA is wrapped. Furthermore, comparing microscopy images for the wild-type P2 Cox protein and two mutants allows us to discriminate between compaction due to filament formation and compaction by monomeric Cox. P2 and WΦ Cox have similar effects on the physical properties of DNA and the subtle, but significant, differences in DNA binding are due to differences in binding affinity rather than binding mode. The presented work highlights the use of single DNA molecule studies to confirm structural predictions from X-ray crystallography. It also shows how a small protein by oligomerization can have great impact on the organization of DNA and thereby fulfill multiple regulatory functions. PMID:27131370
NASA Astrophysics Data System (ADS)
Willis, M. J.; Wilson, T. J.; James, T. S.; Mazzotti, S.; Bevis, M. G.; Kendrick, E. C.; Brown, A. K.
2010-12-01
The IJ05 Antarctic ice sheet history is employed to drive a suite of approximately one thousand two-layered, laterally-homogeneous spherical Earth models and generate predictions of Antarctic crustal uplift due to glacial isostatic adjustment (GIA). GPS data collected between 1996 and 2010 on the flanks of the West Antarctic Rift System are used to produce bedrock uplift rates that are compared with the model predictions. The models that display the best fit to the data have softer, weaker upper-mantle viscosities than those published in many previous studies. A low viscosity upper-mantle is in agreement with seismic tomography that indicates that the upper mantle beneath much of West Antarctica has slower than average seismic shear-wave velocities. Best fit models further feature thin elastic lithospheres, a situation that is also corroborated by recent airborne gravity and seismic investigations. The best fit GIA models are used to generate crustal uplift rates and gravity changes that are larger than previously published models used to correct GRACE observations and infer Antarctic ice mass balance.The new models, which are the first GPS-constrained GIA corrections for GRACE in Antarctica, increases the ice-mass loss estimate for West Antarctica.
In vivo correction of COX deficiency by activation of the AMPK/PGC-1α axis.
Viscomi, Carlo; Bottani, Emanuela; Civiletto, Gabriele; Cerutti, Raffaele; Moggio, Maurizio; Fagiolari, Gigliola; Schon, Eric A; Lamperti, Costanza; Zeviani, Massimo
2011-07-01
Increased mitochondrial biogenesis by activation of PPAR- or AMPK/PGC-1α-dependent homeostatic pathways has been proposed as a treatment for mitochondrial disease. We tested this hypothesis on three recombinant mouse models characterized by defective cytochrome c-oxidase (COX) activity: a knockout (KO) mouse for Surf1, a knockout/knockin mouse for Sco2, and a muscle-restricted KO mouse for Cox15. First, we demonstrated that double-recombinant animals overexpressing PGC-1α in skeletal muscle on a Surf1 KO background showed robust induction of mitochondrial biogenesis and increase of mitochondrial respiratory chain activities, including COX. No such effect was obtained by treating both Surf1(-/-) and Cox15(-/-) mice with the pan-PPAR agonist bezafibrate, which instead showed adverse effects in either model. Contrariwise, treatment with the AMPK agonist AICAR led to partial correction of COX deficiency in all three models, and, importantly, significant motor improvement up to normal in the Sco2(KO/KI) mouse. These results open new perspectives for therapy of mitochondrial disease. PMID:21723506