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Sample records for cox proportional hazards

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

    African Journals Online (AJOL)

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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    African Journals Online (AJOL)

    Adejumo & Ahmadu

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

  4. The Application of Extended Cox Proportional Hazard Method for Estimating Survival Time of Breast Cancer

    Science.gov (United States)

    Husain, Hartina; Astuti Thamrin, Sri; Tahir, Sulaiha; Mukhlisin, Ahmad; Mirna Apriani, M.

    2018-03-01

    Breast cancer is one type of cancer that is the leading cause of death worldwide. This study aims to model the factors that affect the survival time and rate of cure of breast cancer patients. The extended cox model, which is a modification of the proportional hazard cox model in which the proportional hazard assumptions are not met, is used in this study. The maximum likelihood estimation approach is used to estimate the parameters of the model. This method is then applied to medical record data of breast cancer patient in 2011-2016, which is taken from Hasanuddin University Education Hospital. The results obtained indicate that the factors that affect the survival time of breast cancer patients are malignancy and leukocyte levels.

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

    Science.gov (United States)

    Austin, Peter C

    2018-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Takeshi Emura

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    Science.gov (United States)

    Wang, Wei; Albert, Jeffrey M

    2017-08-01

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

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

    Science.gov (United States)

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

    2003-01-01

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

  11. DeepSurv: personalized treatment recommender system using a Cox proportional hazards deep neural network.

    Science.gov (United States)

    Katzman, Jared L; Shaham, Uri; Cloninger, Alexander; Bates, Jonathan; Jiang, Tingting; Kluger, Yuval

    2018-02-26

    Medical practitioners use survival models to explore and understand the relationships between patients' covariates (e.g. clinical and genetic features) and the effectiveness of various treatment options. Standard survival models like the linear Cox proportional hazards model require extensive feature engineering or prior medical knowledge to model treatment interaction at an individual level. While nonlinear survival methods, such as neural networks and survival forests, can inherently model these high-level interaction terms, they have yet to be shown as effective treatment recommender systems. We introduce DeepSurv, a Cox proportional hazards deep neural network and state-of-the-art survival method for modeling interactions between a patient's covariates and treatment effectiveness in order to provide personalized treatment recommendations. We perform a number of experiments training DeepSurv on simulated and real survival data. We demonstrate that DeepSurv performs as well as or better than other state-of-the-art survival models and validate that DeepSurv successfully models increasingly complex relationships between a patient's covariates and their risk of failure. We then show how DeepSurv models the relationship between a patient's features and effectiveness of different treatment options to show how DeepSurv can be used to provide individual treatment recommendations. Finally, we train DeepSurv on real clinical studies to demonstrate how it's personalized treatment recommendations would increase the survival time of a set of patients. The predictive and modeling capabilities of DeepSurv will enable medical researchers to use deep neural networks as a tool in their exploration, understanding, and prediction of the effects of a patient's characteristics on their risk of failure.

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

    Science.gov (United States)

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

    2016-11-20

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

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

    Directory of Open Access Journals (Sweden)

    Tanck Michael WT

    2008-01-01

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

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

    DEFF Research Database (Denmark)

    Martinussen, Torben; Pipper, Christian Bressen

    2005-01-01

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

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

    NARCIS (Netherlands)

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

    2017-01-01

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

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

    Science.gov (United States)

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Puddu Paolo

    2012-07-01

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

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

    Science.gov (United States)

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

    2017-09-01

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

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

    Science.gov (United States)

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

    2016-05-15

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

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

    Science.gov (United States)

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

    2009-01-01

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

  1. Data-driven smooth tests of the proportional hazards assumption

    Czech Academy of Sciences Publication Activity Database

    Kraus, David

    2007-01-01

    Roč. 13, č. 1 (2007), s. 1-16 ISSN 1380-7870 R&D Projects: GA AV ČR(CZ) IAA101120604; GA ČR(CZ) GD201/05/H007 Institutional research plan: CEZ:AV0Z10750506 Keywords : Cox model * Neyman's smooth test * proportional hazards assumption * Schwarz's selection rule Subject RIV: BA - General Mathematics Impact factor: 0.491, year: 2007

  2. Worklife expectancy in a cohort of Danish employees aged 55-65 years - comparing a multi-state Cox proportional hazard approach with conventional multi-state life tables.

    Science.gov (United States)

    Pedersen, Jacob; Bjorner, Jakob Bue

    2017-11-15

    Work life expectancy (WLE) expresses the expected time a person will remain in the labor market until he or she retires. This paper compares a life table approach to estimating WLE to an approach based on multi-state proportional hazards models. The two methods are used to estimate WLE in Danish members and non-members of an early retirement pensioning (ERP) scheme according to levels of health. In 2008, data on self-rated health (SRH) was collected from 5212 employees 55-65 years of age. Data on previous and subsequent long-term sickness absence, unemployment, returning to work, and disability pension was collected from national registers. WLE was estimated from multi-state life tables and through multi-state models. Results from the multi-state model approach agreed with the life table approach but provided narrower confidence intervals for small groups. The shortest WLE was seen for employees with poor SRH and ERP membership while the longest WLE was seen for those with good SRH and no ERP membership. Employees aged 55-56 years with poor SRH but no ERP membership had shorter WLE than employees with good SRH and ERP membership. Relative WLE reversed for the two groups after age 57. At age 55, employees with poor SRH could be expected to spend approximately 12 months on long-term sick leave and 9-10 months unemployed before they retired - regardless of ERP membership. ERP members with poor SRH could be expected to spend 4.6 years working, while non-members could be expected to spend 7.1 years working. WLE estimated through multi-state models provided an effective way to summarize complex data on labor market affiliation. WLE differed noticeably between members and non-members of the ERP scheme. It has been hypothesized that while ERP membership would prompt some employees to retire earlier than they would have done otherwise, this effect would be partly offset by reduced time spent on long-term sick leave or unemployment. Our data showed no indication of

  3. Worklife expectancy in a cohort of Danish employees aged 55–65 years - comparing a multi-state Cox proportional hazard approach with conventional multi-state life tables

    Directory of Open Access Journals (Sweden)

    Jacob Pedersen

    2017-11-01

    Full Text Available Abstract Background Work life expectancy (WLE expresses the expected time a person will remain in the labor market until he or she retires. This paper compares a life table approach to estimating WLE to an approach based on multi-state proportional hazards models. The two methods are used to estimate WLE in Danish members and non-members of an early retirement pensioning (ERP scheme according to levels of health. Methods In 2008, data on self-rated health (SRH was collected from 5212 employees 55–65 years of age. Data on previous and subsequent long-term sickness absence, unemployment, returning to work, and disability pension was collected from national registers. WLE was estimated from multi-state life tables and through multi-state models. Results Results from the multi-state model approach agreed with the life table approach but provided narrower confidence intervals for small groups. The shortest WLE was seen for employees with poor SRH and ERP membership while the longest WLE was seen for those with good SRH and no ERP membership. Employees aged 55–56 years with poor SRH but no ERP membership had shorter WLE than employees with good SRH and ERP membership. Relative WLE reversed for the two groups after age 57. At age 55, employees with poor SRH could be expected to spend approximately 12 months on long-term sick leave and 9–10 months unemployed before they retired – regardless of ERP membership. ERP members with poor SRH could be expected to spend 4.6 years working, while non-members could be expected to spend 7.1 years working. Conclusion WLE estimated through multi-state models provided an effective way to summarize complex data on labor market affiliation. WLE differed noticeably between members and non-members of the ERP scheme. It has been hypothesized that while ERP membership would prompt some employees to retire earlier than they would have done otherwise, this effect would be partly offset by reduced time spent on

  4. Zero Information in the Two-Sample Mixed Proportional Hazards Model

    NARCIS (Netherlands)

    Klaassen, Chris A.J.; Lenstra, Andries J.

    2000-01-01

    The mixed proportional hazards model generalizes the Cox model by incorporating a random effect. In the case of two samples, it is chiefly determined by a triple consisting of a number representing the treatment effect, the integrated base-line hazard, and the distribution of the unobserved random

  5. Goodness-of-fit test for proportional subdistribution hazards model.

    Science.gov (United States)

    Zhou, Bingqing; Fine, Jason; Laird, Glen

    2013-09-30

    This paper concerns using modified weighted Schoenfeld residuals to test the proportionality of subdistribution hazards for the Fine-Gray model, similar to the tests proposed by Grambsch and Therneau for independently censored data. We develop a score test for the time-varying coefficients based on the modified Schoenfeld residuals derived assuming a certain form of non-proportionality. The methods perform well in simulations and a real data analysis of breast cancer data, where the treatment effect exhibits non-proportional hazards. Copyright © 2013 John Wiley & Sons, Ltd.

  6. On estimation methods and test for proportional hazards ...

    African Journals Online (AJOL)

    These methods were described and applied to two datasets, a clinical dataset on breast cancer patients and a dataset on duration of labour before delivery. We also checked for proportional hazards assumptions on some of the covariates used in the analysis. Using Akaike Information Criterion (AIC) for overall model ...

  7. A simple GMM estimator for the semi-parametric mixed proportional hazard model

    OpenAIRE

    Bijwaard, G.E.; Ridder, G.; Woutersen, T.

    2012-01-01

    Ridder and Woutersen (Ridder, G., and T. Woutersen. 2003. “The Singularity of the Efficiency Bound of the Mixed Proportional Hazard Model.” Econometrica 71: 1579–1589) have shown that under a weak condition on the baseline hazard, there exist root-N consistent estimators of the parameters in a semiparametric Mixed Proportional Hazard model with a parametric baseline hazard and unspecified distribution of the unobserved heterogeneity. We extend the linear rank estimator (LRE) of Tsiatis (Tsiat...

  8. A Proportional Hazards Regression Model for the Subdistribution with Covariates-adjusted Censoring Weight for Competing Risks Data

    DEFF Research Database (Denmark)

    He, Peng; Eriksson, Frank; Scheike, Thomas H.

    2016-01-01

    and the covariates are independent. Covariate-dependent censoring sometimes occurs in medical studies. In this paper, we study the proportional hazards regression model for the subdistribution of a competing risk with proper adjustments for covariate-dependent censoring. We consider a covariate-adjusted weight......With competing risks data, one often needs to assess the treatment and covariate effects on the cumulative incidence function. Fine and Gray proposed a proportional hazards regression model for the subdistribution of a competing risk with the assumption that the censoring distribution...... function by fitting the Cox model for the censoring distribution and using the predictive probability for each individual. Our simulation study shows that the covariate-adjusted weight estimator is basically unbiased when the censoring time depends on the covariates, and the covariate-adjusted weight...

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

    DEFF Research Database (Denmark)

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

    2004-01-01

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

  10. A simple GMM estimator for the semi-parametric mixed proportional hazard model

    NARCIS (Netherlands)

    Bijwaard, G.E.; Ridder, G.; Woutersen, T.

    2013-01-01

    Ridder and Woutersen (Ridder, G., and T. Woutersen. 2003. “The Singularity of the Efficiency Bound of the Mixed Proportional Hazard Model.” Econometrica 71: 1579–1589) have shown that under a weak condition on the baseline hazard, there exist root-N consistent estimators of the parameters in a

  11. Survival analysis II: Cox regression

    NARCIS (Netherlands)

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

    2011-01-01

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

  12. ANALYSIS OF MULTIVARIATE FAILURE TIME DATA USING MARGINAL PROPORTIONAL HAZARDS MODEL.

    Science.gov (United States)

    Chen, Ying; Chen, Kani; Ying, Zhiliang

    2010-01-01

    The marginal proportional hazards model is an important tool in the analysis of multivariate failure time data in the presence of censoring. We propose a method of estimation via the linear combinations of martingale residuals. The estimation and inference procedures are easy to implement numerically. The estimation is generally more accurate than the existing pseudo-likelihood approach: the size of efficiency gain can be considerable in some cases, and the maximum relative efficiency in theory is infinite. Consistency and asymptotic normality are established. Empirical evidence in support of the theoretical claims is shown in simulation studies.

  13. Conditional Akaike information under generalized linear and proportional hazards mixed models

    Science.gov (United States)

    Donohue, M. C.; Overholser, R.; Xu, R.; Vaida, F.

    2011-01-01

    We study model selection for clustered data, when the focus is on cluster specific inference. Such data are often modelled using random effects, and conditional Akaike information was proposed in Vaida & Blanchard (2005) and used to derive an information criterion under linear mixed models. Here we extend the approach to generalized linear and proportional hazards mixed models. Outside the normal linear mixed models, exact calculations are not available and we resort to asymptotic approximations. In the presence of nuisance parameters, a profile conditional Akaike information is proposed. Bootstrap methods are considered for their potential advantage in finite samples. Simulations show that the performance of the bootstrap and the analytic criteria are comparable, with bootstrap demonstrating some advantages for larger cluster sizes. The proposed criteria are applied to two cancer datasets to select models when the cluster-specific inference is of interest. PMID:22822261

  14. Proportional hazards model with varying coefficients for length-biased data.

    Science.gov (United States)

    Zhang, Feipeng; Chen, Xuerong; Zhou, Yong

    2014-01-01

    Length-biased data arise in many important applications including epidemiological cohort studies, cancer prevention trials and studies of labor economics. Such data are also often subject to right censoring due to loss of follow-up or the end of study. In this paper, we consider a proportional hazards model with varying coefficients for right-censored and length-biased data, which is used to study the interact effect nonlinearly of covariates with an exposure variable. A local estimating equation method is proposed for the unknown coefficients and the intercept function in the model. The asymptotic properties of the proposed estimators are established by using the martingale theory and kernel smoothing techniques. Our simulation studies demonstrate that the proposed estimators have an excellent finite-sample performance. The Channing House data is analyzed to demonstrate the applications of the proposed method.

  15. Mediation Analysis with Survival Outcomes: Accelerated Failure Time Versus Proportional Hazards Models

    Directory of Open Access Journals (Sweden)

    Lois A Gelfand

    2016-03-01

    Full Text Available Objective: Survival time is an important type of outcome variable in treatment research. Currently, limited guidance is available regarding performing mediation analyses with survival outcomes, which generally do not have normally distributed errors, and contain unobserved (censored events. We present considerations for choosing an approach, using a comparison of semi-parametric proportional hazards (PH and fully parametric accelerated failure time (AFT approaches for illustration.Method: We compare PH and AFT models and procedures in their integration into mediation models and review their ability to produce coefficients that estimate causal effects. Using simulation studies modeling Weibull-distributed survival times, we compare statistical properties of mediation analyses incorporating PH and AFT approaches (employing SAS procedures PHREG and LIFEREG, respectively under varied data conditions, some including censoring. A simulated data set illustrates the findings.Results: AFT models integrate more easily than PH models into mediation models. Furthermore, mediation analyses incorporating LIFEREG produce coefficients that can estimate causal effects, and demonstrate superior statistical properties. Censoring introduces bias in the coefficient estimate representing the treatment effect on outcome – underestimation in LIFEREG, and overestimation in PHREG. With LIFEREG, this bias can be addressed using an alternative estimate obtained from combining other coefficients, whereas this is not possible with PHREG.Conclusions: When Weibull assumptions are not violated, there are compelling advantages to using LIFEREG over PHREG for mediation analyses involving survival-time outcomes. Irrespective of the procedures used, the interpretation of coefficients, effects of censoring on coefficient estimates, and statistical properties should be taken into account when reporting results.

  16. Mediation Analysis with Survival Outcomes: Accelerated Failure Time vs. Proportional Hazards Models

    Science.gov (United States)

    Gelfand, Lois A.; MacKinnon, David P.; DeRubeis, Robert J.; Baraldi, Amanda N.

    2016-01-01

    Objective: Survival time is an important type of outcome variable in treatment research. Currently, limited guidance is available regarding performing mediation analyses with survival outcomes, which generally do not have normally distributed errors, and contain unobserved (censored) events. We present considerations for choosing an approach, using a comparison of semi-parametric proportional hazards (PH) and fully parametric accelerated failure time (AFT) approaches for illustration. Method: We compare PH and AFT models and procedures in their integration into mediation models and review their ability to produce coefficients that estimate causal effects. Using simulation studies modeling Weibull-distributed survival times, we compare statistical properties of mediation analyses incorporating PH and AFT approaches (employing SAS procedures PHREG and LIFEREG, respectively) under varied data conditions, some including censoring. A simulated data set illustrates the findings. Results: AFT models integrate more easily than PH models into mediation models. Furthermore, mediation analyses incorporating LIFEREG produce coefficients that can estimate causal effects, and demonstrate superior statistical properties. Censoring introduces bias in the coefficient estimate representing the treatment effect on outcome—underestimation in LIFEREG, and overestimation in PHREG. With LIFEREG, this bias can be addressed using an alternative estimate obtained from combining other coefficients, whereas this is not possible with PHREG. Conclusions: When Weibull assumptions are not violated, there are compelling advantages to using LIFEREG over PHREG for mediation analyses involving survival-time outcomes. Irrespective of the procedures used, the interpretation of coefficients, effects of censoring on coefficient estimates, and statistical properties should be taken into account when reporting results. PMID:27065906

  17. Parametric bootstrap for testing model fitting in the proportional hazards framework: an application to the survival analysis of Bruna dels Pirineus beef calves.

    Science.gov (United States)

    Casellas, J; Tarrés, J; Piedrafita, J; Varona, L

    2006-10-01

    Given that correct assumptions on the baseline survival function are determinant for the validity of further inferences, specific tools to test the fit of a model to real data become essential in proportional hazards models. In this sense, we have proposed a parametric bootstrap to test the fit of survival models. Monte Carlo simulations are used to generate new data sets from the estimates obtained through the assumed models, and then bootstrap intervals can be established for the survival function along the time space studied. Significant fitting deficiencies are revealed when the real survival function is not included within the bootstrap interval. We tested this procedure in a survival data set of Bruna dels Pirineus beef calves, assuming 4 parametric models (exponential, Weibull, exponential time-dependent, Weibull time-dependent) and the Cox's semiparametric model. Fitting deficiencies were not observed for the Cox's model and the exponential time-dependent model, whereas the Weibull time-dependent model suffered from moderate overestimation at different ages. Thus, the exponential time-dependent model appears to be preferable because of its correct fit for survival data of beef calves and its smaller computational and time requirements. Exponential and Weibull models were completely rejected due to the continuous over- and underestimation of the survival probability reported. Results here highlighted the flexibility of parametric models with time-dependent effects, achieving a fit comparable to nonparametric models.

  18. [Proportional hazards model of birth intervals among marriage cohorts since the 1960s].

    Science.gov (United States)

    Otani, K

    1987-01-01

    With a view to investigating the possibility of an attitudinal change towards the timing of 1st and 2nd births, proportional hazards model analysis of the 1st and 2nd birth intervals and univariate life table analysis were both carried out. Results showed that love matches and conjugal families immediately after marriage are accompanied by a longer 1st birth interval than others, even after controlling for other independent variables. Marriage cohort analysis also shows a net effect on the relative risk of having a 1st birth. Marriage cohorts since the mid-1960s demonstrate a shorter 1st birth interval than the 1961-63 cohort. With regard to the 2nd birth interval, longer 1st birth intervals, arranged marriages, conjugal families immediately following marriage, and higher ages at 1st marriage of women tended to provoke a longer 2nd birth interval. There is no interaction between the 1st birth interval and marriage cohort. Once other independent variables were controlled, with the exception of the marriage cohorts of the early 1970s, the authors found no effect of marriage cohort on the relative risk of having a 2nd birth. This suggests that an attitudinal change towards the timing of births in this period was mainly restricted to that of a 1st birth. Fluctuations in the 2nd birth interval during the 1970-72 marriage cohort were scrutinized in detail. As a result, the authors found that conjugal families after marriage, wives with low educational status, women with husbands in white collar professions, women with white collar fathers, and wives with high age at 1st marriage who married during 1970-72 and had a 1st birth interval during 1972-74 suffered most from the pronounced rise in the 2nd birth interval. This might be due to the relatively high sensitivity to a change in socioeconomic status; the oil crisis occurring around the time of marriage and 1st birth induced a delay in the 2nd birth. The unanimous decrease in the 2nd birth interval among the 1973

  19. Assessing End-Of-Supply Risk of Spare Parts Using the Proportional Hazard Model

    NARCIS (Netherlands)

    X. Li (Xishu); R. Dekker (Rommert); C. Heij (Christiaan); M. Hekimoğlu (Mustafa)

    2016-01-01

    textabstractOperators of long field-life systems like airplanes are faced with hazards in the supply of spare parts. If the original manufacturers or suppliers of parts end their supply, this may have large impacts on operating costs of firms needing these parts. Existing end-of-supply evaluation

  20. The comparison of proportional hazards and accelerated failure time models in analyzing the first birth interval survival data

    Science.gov (United States)

    Faruk, Alfensi

    2018-03-01

    Survival analysis is a branch of statistics, which is focussed on the analysis of time- to-event data. In multivariate survival analysis, the proportional hazards (PH) is the most popular model in order to analyze the effects of several covariates on the survival time. However, the assumption of constant hazards in PH model is not always satisfied by the data. The violation of the PH assumption leads to the misinterpretation of the estimation results and decreasing the power of the related statistical tests. On the other hand, the accelerated failure time (AFT) models do not assume the constant hazards in the survival data as in PH model. The AFT models, moreover, can be used as the alternative to PH model if the constant hazards assumption is violated. The objective of this research was to compare the performance of PH model and the AFT models in analyzing the significant factors affecting the first birth interval (FBI) data in Indonesia. In this work, the discussion was limited to three AFT models which were based on Weibull, exponential, and log-normal distribution. The analysis by using graphical approach and a statistical test showed that the non-proportional hazards exist in the FBI data set. Based on the Akaike information criterion (AIC), the log-normal AFT model was the most appropriate model among the other considered models. Results of the best fitted model (log-normal AFT model) showed that the covariates such as women’s educational level, husband’s educational level, contraceptive knowledge, access to mass media, wealth index, and employment status were among factors affecting the FBI in Indonesia.

  1. Goodness-of-fit test of the stratified mark-specific proportional hazards model with continuous mark.

    Science.gov (United States)

    Sun, Yanqing; Li, Mei; Gilbert, Peter B

    2016-01-01

    Motivated by the need to assess HIV vaccine efficacy, previous studies proposed an extension of the discrete competing risks proportional hazards model, in which the cause of failure is replaced by a continuous mark only observed at the failure time. However the model assumptions may fail in several ways, and no diagnostic testing procedure for this situation has been proposed. A goodness-of-fit test procedure for the stratified mark-specific proportional hazards model in which the regression parameters depend nonparametrically on the mark and the baseline hazards depends nonparametrically on both time and the mark is proposed. The test statistics are constructed based on the weighted cumulative mark-specific martingale residuals. The critical values of the proposed test statistics are approximated using the Gaussian multiplier method. The performance of the proposed tests are examined extensively in simulations for a variety of the models under the null hypothesis and under different types of alternative models. An analysis of the 'Step' HIV vaccine efficacy trial using the proposed method is presented. The analysis suggests that the HIV vaccine candidate may increase susceptibility to HIV acquisition.

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

    Directory of Open Access Journals (Sweden)

    Samane Nematolahi

    2017-10-01

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

  3. Identifying nonproportional covariates in the Cox model

    Czech Academy of Sciences Publication Activity Database

    Kraus, David

    2008-01-01

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

  4. DR Cox

    Indian Academy of Sciences (India)

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

  5. Shared and unshared exposure measurement error in occupational cohort studies and their effects on statistical inference in proportional hazards models

    Science.gov (United States)

    Laurier, Dominique; Rage, Estelle

    2018-01-01

    Exposure measurement error represents one of the most important sources of uncertainty in epidemiology. When exposure uncertainty is not or only poorly accounted for, it can lead to biased risk estimates and a distortion of the shape of the exposure-response relationship. In occupational cohort studies, the time-dependent nature of exposure and changes in the method of exposure assessment may create complex error structures. When a method of group-level exposure assessment is used, individual worker practices and the imprecision of the instrument used to measure the average exposure for a group of workers may give rise to errors that are shared between workers, within workers or both. In contrast to unshared measurement error, the effects of shared errors remain largely unknown. Moreover, exposure uncertainty and magnitude of exposure are typically highest for the earliest years of exposure. We conduct a simulation study based on exposure data of the French cohort of uranium miners to compare the effects of shared and unshared exposure uncertainty on risk estimation and on the shape of the exposure-response curve in proportional hazards models. Our results indicate that uncertainty components shared within workers cause more bias in risk estimation and a more severe attenuation of the exposure-response relationship than unshared exposure uncertainty or exposure uncertainty shared between individuals. These findings underline the importance of careful characterisation and modeling of exposure uncertainty in observational studies. PMID:29408862

  6. Risk patterns in drug safety study using relative times by accelerated failure time models when proportional hazards assumption is questionable: an illustrative case study of cancer risk of patients on glucose-lowering therapies.

    Science.gov (United States)

    Ng, Edmond S-W; Klungel, Olaf H; Groenwold, Rolf H H; van Staa, Tjeerd-Pieter

    2015-01-01

    Observational drug safety studies may be susceptible to confounding or protopathic bias. This bias may cause a spurious relationship between drug exposure and adverse side effect when none exists and may lead to unwarranted safety alerts. The spurious relationship may manifest itself through substantially different risk levels between exposure groups at the start of follow-up when exposure is deemed too short to have any plausible biological effect of the drug. The restrictive proportional hazards assumption with its arbitrary choice of baseline hazard function renders the commonly used Cox proportional hazards model of limited use for revealing such potential bias. We demonstrate a fully parametric approach using accelerated failure time models with an illustrative safety study of glucose-lowering therapies and show that its results are comparable against other methods that allow time-varying exposure effects. Our approach includes a wide variety of models that are based on the flexible generalized gamma distribution and allows direct comparisons of estimated hazard functions following different exposure-specific distributions of survival times. This approach lends itself to two alternative metrics, namely relative times and difference in times to event, allowing physicians more ways to communicate patient's prognosis without invoking the concept of risks, which some may find hard to grasp. In our illustrative case study, substantial differences in cancer risks at drug initiation followed by a gradual reduction towards null were found. This evidence is compatible with the presence of protopathic bias, in which undiagnosed symptoms of cancer lead to switches in diabetes medication. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Extended cox regression model: The choice of timefunction

    Science.gov (United States)

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

    2017-07-01

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

  8. Proportionality lost - proportionality regained?

    DEFF Research Database (Denmark)

    Werlauff, Erik

    2010-01-01

    In recent years, the European Court of Justice (the ECJ) seems to have accepted restrictions on the freedom of establishment and other basic freedoms, despite the fact that a more thorough proportionality test would have revealed that the restriction in question did not pass the 'rule of reason....... This often cannot be done without thorough knowledge of the particular legal field in which the case is anchored, and the ECJ is often left to flounder somewhat on this, with the result that we are suddenly faced with the Court’s acceptance of a restriction. The difficulty often lies - not in recognising...... result if the proportionality argument had been based on adequate insight. Proportionality-weak decisions are in the article be categorised as: (1) Cases in which the ECJ allows itself to be “talked into” accepting a restriction, and for which the question of proportionality actually has been considered...

  9. Performance of two formal tests based on martingales residuals to check the proportional hazard assumption and the functional form of the prognostic factors in flexible parametric excess hazard models.

    Science.gov (United States)

    Danieli, Coraline; Bossard, Nadine; Roche, Laurent; Belot, Aurelien; Uhry, Zoe; Charvat, Hadrien; Remontet, Laurent

    2017-07-01

    Net survival, the one that would be observed if the disease under study was the only cause of death, is an important, useful, and increasingly used indicator in public health, especially in population-based studies. Estimates of net survival and effects of prognostic factor can be obtained by excess hazard regression modeling. Whereas various diagnostic tools were developed for overall survival analysis, few methods are available to check the assumptions of excess hazard models. We propose here two formal tests to check the proportional hazard assumption and the validity of the functional form of the covariate effects in the context of flexible parametric excess hazard modeling. These tests were adapted from martingale residual-based tests for parametric modeling of overall survival to allow adding to the model a necessary element for net survival analysis: the population mortality hazard. We studied the size and the power of these tests through an extensive simulation study based on complex but realistic data. The new tests showed sizes close to the nominal values and satisfactory powers. The power of the proportionality test was similar or greater than that of other tests already available in the field of net survival. We illustrate the use of these tests with real data from French cancer registries. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Statistical analysis of Caterpillar 793D haul truck engine data and through-life diagnostic information using the proportional hazards model

    Directory of Open Access Journals (Sweden)

    Carstens, W. A.

    2013-08-01

    Full Text Available Physical asset management (PAM is of increasing concern for companies in industry today. A key performance area of PAM is asset care plans (ACPs, which consist of maintenance strategies such as usage based maintenance (UBM and condition based maintenance (CBM. Data obtained from the South African mining industry was modelled using a CBM prognostic model called the proportional hazards model (PHM. Results indicated that the developed model produced estimates that were reasonable representations of reality. These findings provide an exciting basis for the development of future Weibull PHMs that could result in huge maintenance cost savings and reduced failure occurrences.

  11. COX-2 activation is associated with Akt phosphorylation and poor survival in ER-negative, HER2-positive breast cancer

    International Nuclear Information System (INIS)

    Glynn, Sharon A; Ambs, Stefan; Prueitt, Robyn L; Ridnour, Lisa A; Boersma, Brenda J; Dorsey, Tiffany M; Wink, David A; Goodman, Julie E; Yfantis, Harris G; Lee, Dong H

    2010-01-01

    Inducible cyclooxgenase-2 (COX-2) is commonly overexpressed in breast tumors and is a target for cancer therapy. Here, we studied the association of COX-2 with breast cancer survival and how this association is influenced by tumor estrogen and HER2 receptor status and Akt pathway activation. Tumor COX-2, HER2 and estrogen receptor α (ER) expression and phosphorylation of Akt, BAD, and caspase-9 were analyzed immunohistochemically in 248 cases of breast cancer. Spearman's correlation and multivariable logistic regression analyses were used to examine the relationship between COX-2 and tumor characteristics. Kaplan-Meier survival and multivariable Cox proportional hazards regression analyses were used to examine the relationship between COX-2 and disease-specific survival. COX-2 was significantly associated with breast cancer outcome in ER-negative [Hazard ratio (HR) = 2.72; 95% confidence interval (CI), 1.36-5.41; comparing high versus low COX-2] and HER2 overexpressing breast cancer (HR = 2.84; 95% CI, 1.07-7.52). However, the hazard of poor survival associated with increased COX-2 was highest among patients who were both ER-negative and HER2-positive (HR = 5.95; 95% CI, 1.01-34.9). Notably, COX-2 expression in the ER-negative and HER2-positive tumors correlated significantly with increased phosphorylation of Akt and of the two Akt targets, BAD at Ser136 and caspase-9 at Ser196. Up-regulation of COX-2 in ER-negative and HER2-positive breast tumors is associated with Akt pathway activation and is a marker of poor outcome. The findings suggest that COX-2-specific inhibitors and inhibitors of the Akt pathway may act synergistically as anticancer drugs in the ER-negative and HER2-positive breast cancer subtype

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

    Science.gov (United States)

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

    2017-07-15

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

  13. Proportional reasoning

    DEFF Research Database (Denmark)

    Dole, Shelley; Hilton, Annette; Hilton, Geoff

    2015-01-01

    Proportional reasoning is widely acknowledged as a key to success in school mathematics, yet students’ continual difficulties with proportion-related tasks are well documented. This paper draws on a large research study that aimed to support 4th to 9th grade teachers to design and implement tasks...

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

    DEFF Research Database (Denmark)

    Scheike, Thomas; Juul, Anders

    2004-01-01

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

  15. Global Drought Proportional Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Drought Proportional Economic Loss Risk Deciles is a 2.5 minute grid of drought hazard economic loss as proportions of Gross Domestic Product (GDP) per...

  16. Global Earthquake Proportional Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Earthquake Proportional Economic Loss Risk Deciles is a 2.5 minute grid of earthquake hazard economic loss as proportions of Gross Domestic Product (GDP) per...

  17. Global Landslide Proportional Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Landslide Proportional Economic Loss Risk Deciles is a 2.5 minute grid of landslide hazard economic loss as proportions of Gross Domestic Product (GDP) per...

  18. Global Volcano Proportional Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Volcano Proportional Economic Loss Risk Deciles is a 2.5 minute grid of volcano hazard economic loss as proportions of Gross Domestic Product (GDP) per...

  19. Global Flood Proportional Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Flood Proportional Economic Loss Risk Deciles is a 2.5 minute grid of flood hazard economic loss as proportions of Gross Domestic Product (GDP) per analytical...

  20. Global Cyclone Proportional Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Cyclone Proportional Economic Loss Risk Deciles is a 2.5 minute grid of cyclone hazard economic loss as proportions of Gross Domestic Product (GDP) per...

  1. Global Cyclone Proportional Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Cyclone Proportional Economic Loss Risk Deciles is a 2.5 by 2.5 minute grid of cyclone hazard economic loss as proportions of gross domestic product (GDP) per...

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

    Science.gov (United States)

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

    2017-10-12

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

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

    Science.gov (United States)

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

    2015-12-01

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

  4. [Application of SAS macro to evaluated multiplicative and additive interaction in logistic and Cox regression in clinical practices].

    Science.gov (United States)

    Nie, Z Q; Ou, Y Q; Zhuang, J; Qu, Y J; Mai, J Z; Chen, J M; Liu, X Q

    2016-05-01

    Conditional logistic regression analysis and unconditional logistic regression analysis are commonly used in case control study, but Cox proportional hazard model is often used in survival data analysis. Most literature only refer to main effect model, however, generalized linear model differs from general linear model, and the interaction was composed of multiplicative interaction and additive interaction. The former is only statistical significant, but the latter has biological significance. In this paper, macros was written by using SAS 9.4 and the contrast ratio, attributable proportion due to interaction and synergy index were calculated while calculating the items of logistic and Cox regression interactions, and the confidence intervals of Wald, delta and profile likelihood were used to evaluate additive interaction for the reference in big data analysis in clinical epidemiology and in analysis of genetic multiplicative and additive interactions.

  5. Properties of spatial Cox process models

    DEFF Research Database (Denmark)

    Møller, Jesper

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

  6. The Moxie of Kathy Cox

    Science.gov (United States)

    Johns, Stephanie

    2010-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Francisco M. Ojeda

    2016-08-01

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

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

    Science.gov (United States)

    Li, Zhiguo; Owzar, Kouros

    2015-01-01

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

  10. Properties of spatial Cox process models

    DEFF Research Database (Denmark)

    Møller, Jesper

    2005-01-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

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

    Directory of Open Access Journals (Sweden)

    J. Faradmal

    2016-01-01

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

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

    Science.gov (United States)

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

    2003-01-01

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

  14. Generalised shot noise Cox processes

    DEFF Research Database (Denmark)

    Møller, Jesper; Torrisi, Giovanni Luca

    2005-01-01

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

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

    Science.gov (United States)

    Perperoglou, Aris

    2014-01-15

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

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

    Science.gov (United States)

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

    2017-01-01

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

  17. Palm distributions for log Gaussian Cox processes

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  18. Generalised shot noise Cox processes

    DEFF Research Database (Denmark)

    Møller, Jesper; Torrisi, Giovanni Luca

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

  19. The Principle of Proportionality

    DEFF Research Database (Denmark)

    Bennedsen, Morten; Meisner Nielsen, Kasper

    2005-01-01

    Recent policy initiatives within the harmonization of European company laws have promoted a so-called "principle of proportionality" through proposals that regulate mechanisms opposing a proportional distribution of ownership and control. We scrutinize the foundation for these initiatives...... in relationship to the process of harmonization of the European capital markets.JEL classifications: G30, G32, G34 and G38Keywords: Ownership Structure, Dual Class Shares, Pyramids, EU companylaws....

  20. Analysis of error-prone survival data under additive hazards models: measurement error effects and adjustments.

    Science.gov (United States)

    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.

  1. Gas proportional scintillation counter

    International Nuclear Information System (INIS)

    Iguchi, Tetsuo; Nakazawa, Masaharu; Sekiguchi, Akira

    1980-01-01

    As the trial in the first stage of utilizing recoil helium for the measurement of 2 - 14 MeV neutron spectra in the simulated blanket for a nuclear fusion reactor, the He-Xe system gas proportional scintillation counter (GPSC) has been manufactured for trial, giving consideration to the advantages of gas scintillators and further to improve the energy resolution. In GPSC, delayed secondary scintillation pulses are produced, and its amplitude gives the energy resolution the adverse effect. Thus, in order to improve the energy resolution, it is desirable to realize such geometry of proportional counters that the electric field in the vicinity of center wire is sufficiently intense to induce the secondary excitation or ionization. The counters of such construction are called GPSC, in which the actual energy resolution can be improved according to the secondary scintillation pulses without losing the fast primary scintillation pulses useful for fast coincidence technique. The experimental results and the consideration on them are described. As compared with proportional counters, GPSC can give large output pulses even at low voltage, improve the energy resolution greatly as compared with ordinary gas scintillators, and measure the time data by the primary scintillation and the energy data based on the secondary scintillation simultaneously. However, it is likely to be affected by gas impurities more than proportional counters, and inferior in the reproducibility and stability of measurement. (Wakatsuki, Y.)

  2. Allan Cox 1926”1987

    Science.gov (United States)

    Coe, Rob; Dalrymple, Brent

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

  3. Matérn thinned Cox processes

    DEFF Research Database (Denmark)

    Andersen, Ina Trolle; Hahn, Ute

    2016-01-01

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

  4. Matérn thinned Cox processes

    DEFF Research Database (Denmark)

    Andersen, Ina Trolle; Hahn, Ute

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

  5. Lévy based Cox point processes

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

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

    Science.gov (United States)

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

    2009-02-01

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

  8. The divine proportion

    CERN Document Server

    Huntley, H E

    1970-01-01

    Using simple mathematical formulas, most as basic as Pythagoras's theorem and requiring only a very limited knowledge of mathematics, Professor Huntley explores the fascinating relationship between geometry and aesthetics. Poetry, patterns like Pascal's triangle, philosophy, psychology, music, and dozens of simple mathematical figures are enlisted to show that the ""divine proportion"" or ""golden ratio"" is a feature of geometry and analysis which awakes answering echoes in the human psyche. When we judge a work of art aesthetically satisfying, according to his formulation, we are making it c

  9. Treatment versus proportionality

    DEFF Research Database (Denmark)

    Sorensen, David Woodrow Mattson

    2010-01-01

    . This critique, which hinges on proportionality, led to a change in the law on July 1, 2000, after which the length of treatment for non-serious-violent crimes was limited to a maximum of five years. This change was itself criticized by the Council of Medical Forensic Specialists, who argued that time of release...... persons sentenced before and after the July 1, 2000 change in the law. The analysis is based on 1510 persons serving 1554 sentences and utilizes data from the criminal register, the central psychiatric register, the cause of death register, and the population register. The data do not support...

  10. Restrictions and Proportionality

    DEFF Research Database (Denmark)

    Werlauff, Erik

    2009-01-01

    The article discusses three central aspects of the freedoms under European Community law, namely 1) the prohibition against restrictions as an important extension of the prohibition against discrimination, 2) a prohibition against exit restrictions which is just as important as the prohibition...... against host country restrictions, but which is often not recognised to the same extent by national law, and 3) the importance of also identifying and recognising an exit restriction, so that it is possible to achieve the required test of appropriateness and proportionality in relation to the rule...

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

    Directory of Open Access Journals (Sweden)

    Richard Dela Cruz

    2016-06-01

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

  12. Combination COX-2 inhibitor and metformin attenuate rate of joint replacement in osteoarthritis with diabetes: A nationwide, retrospective, matched-cohort study in Taiwan.

    Science.gov (United States)

    Lu, Chieh-Hua; Chung, Chi-Hsiang; Lee, Chien-Hsing; Hsieh, Chang-Hsun; Hung, Yi-Jen; Lin, Fu-Huang; Tsao, Chang-Huei; Hsieh, Po-Shiuan; Chien, Wu-Chien

    2018-01-01

    Osteoarthritis (OA) is the most common form of arthritis associated with an increased prevalence of type 2 diabetes mellitus (T2DM), however their impact on decreasing joint replacement surgery has yet to be elucidated. This study aimed to investigate if the combination of COX-2 inhibitor and metformin therapy in OA with T2DM were associated with lower the rate of joint replacement surgery than COX-2 inhibitor alone. In total, 968 subjects with OA and T2DM under COX-2 inhibitor and metformin therapy (case group) between 1 January to 31 December 2000 were selected from the National Health Insurance Research Database of Taiwan, along with 1936 patients were the 1:2 gender-, age-, and index year-controls matched without metformin therapy (control group) in this study. Cox proportional hazards analysis was used to compare the rate of receiving joint replacement surgery during 10 years of follow-up. At the end of follow-up, 438 of all enrolled subjects (15.08%) had received the joint replacement surgery, including 124 in the case group (12.81%) and 314 in the control group (16.22%). The case group tended to be associated with lower rate of receiving the joint replacement surgery at the end of follow-up than the control group (p = 0.003). Cox proportional hazards regression (HR) analysis revealed that study subjects under combination therapy with metformin had lower rate of joint replacement surgery (adjusted HR 0.742 (95% CI = 0.601-0.915, p = 0.005)). In the subgroups, study subjects in the combination metformin therapy who were female, good adherence (>80%), lived in the highest urbanization levels of residence, treatment in the hospital center and lower monthly insurance premiums were associated with a lower risk of joint replacement surgery than those without. Patients who have OA and T2DM receiving combination COX-2 inhibitors and metformin therapy associated with lower joint replacement surgery rates than those without and this may be attributable to combination

  13. Constant Proportion Portfolio Insurance

    DEFF Research Database (Denmark)

    Jessen, Cathrine

    2014-01-01

    Portfolio insurance, as practiced in 1987, consisted of trading between an underlying stock portfolio and cash, using option theory to place a floor on the value of the position, as if it included a protective put. Constant Proportion Portfolio Insurance (CPPI) is an option-free variation...... on the theme, originally proposed by Fischer Black. In CPPI, a financial institution guarantees a floor value for the “insured” portfolio and adjusts the stock/bond mix to produce a leveraged exposure to the risky assets, which depends on how far the portfolio value is above the floor. Plain-vanilla portfolio...... insurance largely died with the crash of 1987, but CPPI is still going strong. In the frictionless markets of finance theory, the issuer’s strategy to hedge its liability under the contract is clear, but in the real world with transactions costs and stochastic jump risk, the optimal strategy is less obvious...

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

    Science.gov (United States)

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

    2017-03-01

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

  15. Regulation of COX and LOX by curcumin.

    Science.gov (United States)

    Rao, Chinthalapally V

    2007-01-01

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

  16. High proportions of PD-1and PD-L1leukocytes in classical Hodgkin lymphoma microenvironment are associated with inferior outcome

    DEFF Research Database (Denmark)

    Hollander, Peter; Kamper, Peter; Smedby, Karin Ekstrom

    2017-01-01

    . Our aim was to investigate the prognostic impact of PD-1, programmed death-ligand 1 (PD-L1), and PD-L2 in the tumor microenvironment in diagnostic biopsies of patients with cHL. Patients from Denmark and Sweden, diagnosed between 1990 and 2007 and ages 15 to 86 years, were included. Tissue microarray...... samples were available from 387 patients. Immunohistochemistry was used to detect PD-1, PD-L1, and PD-L2, and the proportions of positive cells were calculated. Event-free survival (EFS; time to treatment failure) and overall survival (OS) were analyzed using Cox proportional hazards regression. High.......15-10.37). This is the first study to show a correlation after multivariate analysis between inferior outcome in cHL and a high proportion of both PD-1+and PD-L1+leukocytes in the tumor microenvironment....

  17. Incidence proportion of and risk factors for AIDS patients diagnosed with HIV dementia, central nervous system toxoplasmosis, and cryptococcal meningitis.

    Science.gov (United States)

    Wang, F; So, Y; Vittinghoff, E; Malani, H; Reingold, A; Lewis, E; Giordano, J; Janssen, R

    1995-01-01

    We undertook this study to determine the incidence proportion of and risk factors for AIDS patients diagnosed with human immunodeficiency virus (HIV) dementia, central nervous system (CNS) toxoplasmosis, and cryptococcal meningitis. A historical cohort of 487 consecutive inpatients with AIDS treated by San Francisco General Hospital inpatient and outpatient services entered the study. We abstracted all available records for demographic information, diagnoses, and dates of death and estimated the incidence proportion of AIDS patients diagnosed with major CNS complications using the Kaplan-Meier method. We used the Cox proportional hazards model to analyze the effect of demographic factors on the hazard (risk per unit time) of diagnosis with these CNS conditions. The estimated incidence proportion of patients diagnosed with HIV dementia within 1 and 2 years of AIDS diagnosis increased from 0.10 to 0.18. Corresponding proportions were 0.10 and 0.19 for CNS toxoplasmosis and 0.10 and 0.14 for cryptococcal meningitis. Only HIV dementia was independently associated with increasing age at AIDS diagnosis (relative hazard [RH] of 2.75 for ages 41-50 [95% confidence interval, 1.08-6.98]; RH of 4.73 for ages > 50 [95% confidence interval, 1.41-15.87]) and with injection drug use (RH of 2.03; 95% confidence interval, 1.19-3.47). HIV dementia, CNS toxoplasmosis, and cryptococcal meningitis are about equally common complications in patients with AIDS, but only HIV dementia is associated with increasing age at AIDS diagnosis and injection drug use.

  18. Estimating functions for inhomogeneous Cox processes

    DEFF Research Database (Denmark)

    Waagepetersen, Rasmus

    2006-01-01

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

  19. HNE as an inducer of COX-2.

    Science.gov (United States)

    Uchida, Koji

    2017-10-01

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

  20. Palm distributions for log Gaussian Cox processes

    DEFF Research Database (Denmark)

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

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

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

    Science.gov (United States)

    Hosseini Teshnizi, Saeed; Taghi Ayatollahi, Seyyed Mohammad

    2017-04-01

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

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

    Science.gov (United States)

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

    2017-10-20

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

  3. Decomposition of variance for spatial Cox processes

    DEFF Research Database (Denmark)

    Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

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

  4. Decomposition of Variance for Spatial Cox Processes.

    Science.gov (United States)

    Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

    2013-03-01

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

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

    Science.gov (United States)

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

    2004-01-01

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

  6. Visual Manipulatives for Proportional Reasoning.

    Science.gov (United States)

    Moore, Joyce L.; Schwartz, Daniel L.

    The use of a visual representation in learning about proportional relations was studied, examining students' understandings of the invariance of a multiplicative relation on both sides of a proportion equation and the invariance of the structural relations that exist in different semantic types of proportion problems. Subjects were 49 high-ability…

  7. Flexible parametric modelling of cause-specific hazards to estimate cumulative incidence functions

    Science.gov (United States)

    2013-01-01

    Background Competing risks are a common occurrence in survival analysis. They arise when a patient is at risk of more than one mutually exclusive event, such as death from different causes, and the occurrence of one of these may prevent any other event from ever happening. Methods There are two main approaches to modelling competing risks: the first is to model the cause-specific hazards and transform these to the cumulative incidence function; the second is to model directly on a transformation of the cumulative incidence function. We focus on the first approach in this paper. This paper advocates the use of the flexible parametric survival model in this competing risk framework. Results An illustrative example on the survival of breast cancer patients has shown that the flexible parametric proportional hazards model has almost perfect agreement with the Cox proportional hazards model. However, the large epidemiological data set used here shows clear evidence of non-proportional hazards. The flexible parametric model is able to adequately account for these through the incorporation of time-dependent effects. Conclusion A key advantage of using this approach is that smooth estimates of both the cause-specific hazard rates and the cumulative incidence functions can be obtained. It is also relatively easy to incorporate time-dependent effects which are commonly seen in epidemiological studies. PMID:23384310

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

    Science.gov (United States)

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

    2017-07-01

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

  9. Introduction: Two Kinds of Proportion

    Directory of Open Access Journals (Sweden)

    Matthew A Cohen

    2014-06-01

    Full Text Available The subject of architectural proportional systems in the history of architecture, the topic of this special collection of essays in 'Architectural Histories', has long been characterized by a fundamental ambiguity: the word and concept of proportion simultaneously signify two unrelated and in some ways opposite meanings. Proportion can refer to ratios, or it can refer to architectural beauty. In this introduction to the papers that follow, Matthew A. Cohen proposes a simple clarification of this ambiguity as a framework for continued discussion of this subject: that whenever scholars use the word proportion, they specify whether they intend ‘proportion-as-ratio’ or ‘proportion-as-beauty’. The frequent blending of these meanings today, Cohen argues, is a survival of attitudes toward proportional systems in architecture that were prevalent as long ago as the early Renaissance. Cohen proposes an alternative to Rudolf Wittkower's paradigmatic ‘break-away’ theory of the history of proportional systems, according to which virtually everyone accepted proportional systems as sources of universal beauty in architecture until the mid-eighteenth century, and after that time virtually everyone believed that beauty and proportional systems were matters of individual preference. Rather than a long period respectful of tradition followed by a long period skeptical of it, Cohen argues, based in part on a new interpretation of Claude Perrault’s 1683 codification of the notion of positive beauty, that architects and others have always had access to two parallel strands of thought pertaining to proportional systems: a skeptical-pragmatic strand and a respectful-metaphysical strand. This new historical and historiographical interpretation of the problem of architectural proportional systems, and the new vocabulary with which to discuss it critically presented herein, helps to separate aesthetic from historical considerations.

  10. COX-2, VEGF and tumour angiogenesis.

    LENUS (Irish Health Repository)

    Toomey, D P

    2009-06-01

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

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

    Science.gov (United States)

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

    2004-01-01

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

  12. Proportioning of light weight concrete

    DEFF Research Database (Denmark)

    Palmus, Lars

    1996-01-01

    Development of a method to determine the proportions of the raw materials in light weight concrete made with leight expanded clay aggregate. The method is based on composite theory......Development of a method to determine the proportions of the raw materials in light weight concrete made with leight expanded clay aggregate. The method is based on composite theory...

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2018-02-27

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

  15. Log Gaussian Cox processes on the sphere

    DEFF Research Database (Denmark)

    Pacheco, Francisco Andrés Cuevas; Møller, Jesper

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

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

    African Journals Online (AJOL)

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

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

    Directory of Open Access Journals (Sweden)

    Michelle A Carey

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

  18. Proportional counter end effects eliminator

    International Nuclear Information System (INIS)

    Meekins, J.F.

    1976-01-01

    An improved gas-filled proportional counter which includes a resistor network connected between the anode and cathode at the ends of the counter in order to eliminate ''end effects'' is described. 3 Claims, 2 Drawing Figures

  19. Electronics for proportional drift tubes

    International Nuclear Information System (INIS)

    Fremont, G.; Friend, B.; Mess, K.H.; Schmidt-Parzefall, W.; Tarle, J.C.; Verweij, H.; CERN-Hamburg-Amsterdam-Rome-Moscow Collaboration); Geske, K.; Riege, H.; Schuett, J.; CERN-Hamburg-Amsterdam-Rome-Moscow Collaboration); Semenov, Y.; CERN-Hamburg-Amsterdam-Rome-Moscow Collaboration)

    1980-01-01

    An electronic system for the read-out of a large number of proportional drift tubes (16,000) has been designed. This system measures deposited charge and drift-time of the charge of a particle traversing a proportional drift tube. A second event can be accepted during the read-out of the system. Up to 40 typical events can be collected and buffered before a data transfer to a computer is necessary. (orig.)

  20. Radioprotection of intestinal crypt cells by cox-inhibitors

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  1. Analogical proportions: another logical view

    Science.gov (United States)

    Prade, Henri; Richard, Gilles

    This paper investigates the logical formalization of a restricted form of analogical reasoning based on analogical proportions, i.e. statements of the form a is to b as c is to d. Starting from a naive set theoretic interpretation, we highlight the existence of two noticeable companion proportions: one states that a is to b the converse of what c is to d (reverse analogy), while the other called paralogical proportion expresses that what a and b have in common, c and d have it also. We identify the characteristic postulates of the three types of proportions and examine their consequences from an abstract viewpoint. We further study the properties of the set theoretic interpretation and of the Boolean logic interpretation, and we provide another light on the understanding of the role of permutations in the modeling of the three types of proportions. Finally, we address the use of these proportions as a basis for inference in a propositional setting, and relate it to more general schemes of analogical reasoning. The differences between analogy, reverse-analogy, and paralogy is still emphasized in a three-valued setting, which is also briefly presented.

  2. Randomized controlled trials of COX-2 inhibitors

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  3. Development of multiwire proportional chambers

    CERN Document Server

    Charpak, G

    1969-01-01

    It has happened quite often in the history of science that theoreticians, confronted with some major difficulty, have successfully gone back thirty years to look at ideas that had then been thrown overboard. But it is rare that experimentalists go back thirty years to look again at equipment which had become out-dated. This is what Charpak and his colleagues did to emerge with the 'multiwire proportional chamber' which has several new features making it a very useful addition to the armoury of particle detectors. In the 1930s, ion-chambers, Geiger- Muller counters and proportional counters, were vital pieces of equipment in nuclear physics research. Other types of detectors have since largely replaced them but now the proportional counter, in new array, is making a comeback.

  4. Bayesian Inference on Proportional Elections

    Science.gov (United States)

    Brunello, Gabriel Hideki Vatanabe; Nakano, Eduardo Yoshio

    2015-01-01

    Polls for majoritarian voting systems usually show estimates of the percentage of votes for each candidate. However, proportional vote systems do not necessarily guarantee the candidate with the most percentage of votes will be elected. Thus, traditional methods used in majoritarian elections cannot be applied on proportional elections. In this context, the purpose of this paper was to perform a Bayesian inference on proportional elections considering the Brazilian system of seats distribution. More specifically, a methodology to answer the probability that a given party will have representation on the chamber of deputies was developed. Inferences were made on a Bayesian scenario using the Monte Carlo simulation technique, and the developed methodology was applied on data from the Brazilian elections for Members of the Legislative Assembly and Federal Chamber of Deputies in 2010. A performance rate was also presented to evaluate the efficiency of the methodology. Calculations and simulations were carried out using the free R statistical software. PMID:25786259

  5. The escape gated proportional counter

    International Nuclear Information System (INIS)

    Bibbo, G.; Sanford, P.W.

    1981-01-01

    Proportional counters, designed to detect hard X-rays, are generally filled with Xe or Kr or a mixture of Xe and Kr. In a large multichamber proportional counter the K-fluorescent radiation of these gases, which escapes the cell of origin, but is absorbed in other cells of the counter, provides an additional signal. A coincidence technique, which makes use of this signal to reduce the charged particle background and to correct the energy spectrum for the escape peak, has been evaluated. The detector has an improved energy resolution over that of the conventional proportional counter and preliminary results indicate that a reduction in the background by a factor of about 1000 can be obtained. Its combined properties of very efficient background reduction and improved energy resolution make this type of instrument most suitable for spectroscopic studies of astronomical X-ray sources in the energy range of 15-100 keV. (orig.)

  6. Bayesian inference on proportional elections.

    Directory of Open Access Journals (Sweden)

    Gabriel Hideki Vatanabe Brunello

    Full Text Available Polls for majoritarian voting systems usually show estimates of the percentage of votes for each candidate. However, proportional vote systems do not necessarily guarantee the candidate with the most percentage of votes will be elected. Thus, traditional methods used in majoritarian elections cannot be applied on proportional elections. In this context, the purpose of this paper was to perform a Bayesian inference on proportional elections considering the Brazilian system of seats distribution. More specifically, a methodology to answer the probability that a given party will have representation on the chamber of deputies was developed. Inferences were made on a Bayesian scenario using the Monte Carlo simulation technique, and the developed methodology was applied on data from the Brazilian elections for Members of the Legislative Assembly and Federal Chamber of Deputies in 2010. A performance rate was also presented to evaluate the efficiency of the methodology. Calculations and simulations were carried out using the free R statistical software.

  7. Saving Money Using Proportional Reasoning

    Science.gov (United States)

    de la Cruz, Jessica A.; Garney, Sandra

    2016-01-01

    It is beneficial for students to discover intuitive strategies, as opposed to the teacher presenting strategies to them. Certain proportional reasoning tasks are more likely to elicit intuitive strategies than other tasks. The strategies that students are apt to use when approaching a task, as well as the likelihood of a student's success or…

  8. Social Justice and Proportional Reasoning

    Science.gov (United States)

    Simic-Muller, Ksenija

    2015-01-01

    Ratio and proportional reasoning tasks abound that have connections to real-world situations. Examples in this article demonstrate how textbook tasks can easily be transformed into authentic real-world problems that shed light on issues of equity and fairness, such as population growth and crime rates. A few ideas are presented on how teachers can…

  9. Factors Determining Disease Duration in Alzheimer’s Disease: A Postmortem Study of 103 Cases Using the Kaplan-Meier Estimator and Cox Regression

    Directory of Open Access Journals (Sweden)

    R. A. Armstrong

    2014-01-01

    Full Text Available Factors associated with duration of dementia in a consecutive series of 103 Alzheimer’s disease (AD cases were studied using the Kaplan-Meier estimator and Cox regression analysis (proportional hazard model. Mean disease duration was 7.1 years (range: 6 weeks–30 years, standard deviation = 5.18; 25% of cases died within four years, 50% within 6.9 years, and 75% within 10 years. Familial AD cases (FAD had a longer duration than sporadic cases (SAD, especially cases linked to presenilin (PSEN genes. No significant differences in duration were associated with age, sex, or apolipoprotein E (Apo E genotype. Duration was reduced in cases with arterial hypertension. Cox regression analysis suggested longer duration was associated with an earlier disease onset and increased senile plaque (SP and neurofibrillary tangle (NFT pathology in the orbital gyrus (OrG, CA1 sector of the hippocampus, and nucleus basalis of Meynert (NBM. The data suggest shorter disease duration in SAD and in cases with hypertensive comorbidity. In addition, degree of neuropathology did not influence survival, but spread of SP/NFT pathology into the frontal lobe, hippocampus, and basal forebrain was associated with longer disease duration.

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

    Science.gov (United States)

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

    2015-05-01

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

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

    Czech Academy of Sciences Publication Activity Database

    Volf, Petr

    2004-01-01

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

  12. Disease proportions attributable to environment

    Directory of Open Access Journals (Sweden)

    Vineis Paolo

    2007-11-01

    Full Text Available Abstract Population disease proportions attributable to various causal agents are popular as they present a simplified view of the contribution of each agent to the disease load. However they are only summary figures that may be easily misinterpreted or over-interpreted even when the causal link between an exposure and an effect is well established. This commentary discusses several issues surrounding the estimation of attributable proportions, particularly with reference to environmental causes of cancers, and critically examines two recently published papers. These issues encompass potential biases as well as the very definition of environment and of environmental agent. The latter aspect is not just a semantic question but carries implications for the focus of preventive actions, whether centred on the material and social environment or on single individuals.

  13. Metacarpal proportions in Australopithecus africanus.

    Science.gov (United States)

    Green, David J; Gordon, Adam D

    2008-05-01

    Recent work has shown that, despite being craniodentally more derived, Australopithecus africanus had more apelike limb-size proportions than A. afarensis. Here, we test whether the A. africanus hand, as judged by metacarpal shaft and articular proportions, was similarly apelike. More specifically, did A. africanus have a short and narrow first metacarpal (MC1) relative to the other metacarpals? Proportions of both MC breadth and length were considered: the geometric mean (GM) of articular and midshaft measurements of MC1 breadth was compared to those of MC2-4, and MC1 length was compared to MC3 length individually and also to the GM of MC2 and 3 lengths. To compare the extant hominoid sample with an incomplete A. africanus fossil record (11 attributed metacarpals), a resampling procedure imposed sampling constraints on the comparative groups that produced composite intrahand ratios. Resampled ratios in the extant sample are not significantly different from actual ratios based on associated elements, demonstrating the methodological appropriateness of this technique. Australopithecus africanus metacarpals do not differ significantly from the great apes in the comparison of breadth ratios but are significantly greater than chimpanzees and orangutans in both measures of relative length. Conversely, A. africanus has a significantly smaller breadth ratio than modern humans, but does not significantly differ from this group in either measure of relative length. We conclude that the first metacarpals of A. africanus are more apelike in relative breadth while also being more humanlike in relative length, a finding consistent with previous work on A. afarensis hand proportions. This configuration would have likely promoted a high degree of manipulative dexterity, but the relatively slender, apelike first metacarpal suggests that A. africanus did not place the same mechanical demands on the thumb as more recent, stone-tool-producing hominins.

  14. An Additive-Multiplicative Cox-Aalen Regression Model

    DEFF Research Database (Denmark)

    Scheike, Thomas H.; Zhang, Mei-Jie

    2002-01-01

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

  15. Complete hazard ranking to analyze right-censored data: An ALS survival study.

    Directory of Open Access Journals (Sweden)

    Zhengnan Huang

    2017-12-01

    Full Text Available Survival analysis represents an important outcome measure in clinical research and clinical trials; further, survival ranking may offer additional advantages in clinical trials. In this study, we developed GuanRank, a non-parametric ranking-based technique to transform patients' survival data into a linear space of hazard ranks. The transformation enables the utilization of machine learning base-learners including Gaussian process regression, Lasso, and random forest on survival data. The method was submitted to the DREAM Amyotrophic Lateral Sclerosis (ALS Stratification Challenge. Ranked first place, the model gave more accurate ranking predictions on the PRO-ACT ALS dataset in comparison to Cox proportional hazard model. By utilizing right-censored data in its training process, the method demonstrated its state-of-the-art predictive power in ALS survival ranking. Its feature selection identified multiple important factors, some of which conflicts with previous studies.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  17. Hazardous Drugs

    Science.gov (United States)

    ... and hazardous drugs in the workplace. Pharmacy . OSHA Hospital eTool. Reviews safety and health topics related to hazardous drugs including drug handling, administration, storage, and disposal. OSHA has identified worker exposure ...

  18. Geometric anisotropic spatial point pattern analysis and Cox processes

    DEFF Research Database (Denmark)

    Møller, Jesper; Toftaker, Håkon

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

  19. Photodetectors for scintillator proportionality measurement

    Energy Technology Data Exchange (ETDEWEB)

    Moses, William W. [Lawrence Berkeley National Laboratory (United States)], E-mail: wwmoses@lbl.gov; Choong, Woon-Seng [Lawrence Berkeley National Laboratory (United States); Hull, Giulia; Payne, Steve; Cherepy, Nerine; Valentine, John D. [Lawrence Livermore National Laboratory (United States)

    2009-10-21

    We evaluate photodetectors for use in a Compton Coincidence apparatus designed for measuring scintillator proportionality. There are many requirements placed on the photodetector in these systems, including active area, linearity, and the ability to accurately measure low light levels (which implies high quantum efficiency and high signal-to-noise ratio). Through a combination of measurement and Monte Carlo simulation, we evaluate a number of potential photodetectors, especially photomultiplier tubes and hybrid photodetectors. Of these, we find that the most promising devices available are photomultiplier tubes with high ({approx}50%) quantum efficiency, although hybrid photodetectors with high quantum efficiency would be preferable.

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

    Science.gov (United States)

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

    2015-11-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  2. COX-2 and p53 in human sinonasal cancer

    DEFF Research Database (Denmark)

    Holmila, Reetta; Cyr, Diane; Luce, Danièle

    2008-01-01

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

  3. Constant Proportion Debt Obligations (CPDOs)

    DEFF Research Database (Denmark)

    Cont, Rama; Jessen, Cathrine

    2012-01-01

    be made arbitrarily small—and thus the credit rating arbitrarily high—by increasing leverage, but the ratings obtained strongly depend on assumptions on the credit environment (high spread or low spread). More importantly, CPDO loss distributions are found to exhibit a wide range of tail risk measures......Constant Proportion Debt Obligations (CPDOs) are structured credit derivatives that generate high coupon payments by dynamically leveraging a position in an underlying portfolio of investment-grade index default swaps. CPDO coupons and principal notes received high initial credit ratings from...... the major rating agencies, based on complex models for the joint transition of ratings and spreads for all names in the underlying portfolio. We propose a parsimonious model for analysing the performance of CPDO strategies using a top-down approach that captures the essential risk factors of the CPDO. Our...

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

    Science.gov (United States)

    Lachin, John M

    2008-06-30

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

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

    DEFF Research Database (Denmark)

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

    2001-01-01

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

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

    Science.gov (United States)

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

    2009-12-15

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

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

    Science.gov (United States)

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

    2010-01-01

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

  8. Reproductive Hazards

    Science.gov (United States)

    ... and the ability to have children. Something that affects reproductive health is called a reproductive hazard. Examples include: Radiation Metals such as lead and mercury Chemicals such as pesticides Cigarettes Some viruses Alcohol For men, a reproductive hazard can affect the ...

  9. COMPUTERS HAZARDS

    Directory of Open Access Journals (Sweden)

    Andrzej Augustynek

    2007-01-01

    Full Text Available In June 2006, over 12.6 million Polish users of the Web registered. On the average, each of them spent 21 hours and 37 minutes monthly browsing the Web. That is why the problems of the psychological aspects of computer utilization have become an urgent research subject. The results of research into the development of Polish information society carried out in AGH University of Science and Technology, under the leadership of Leslaw H. Haber, in the period from 2000 until present time, indicate the emergence dynamic changes in the ways of computer utilization and their circumstances. One of the interesting regularities has been the inverse proportional relation between the level of computer skills and the frequency of the Web utilization.It has been found that in 2005, compared to 2000, the following changes occurred:- A significant drop in the number of students who never used computers and the Web;- Remarkable increase in computer knowledge and skills (particularly pronounced in the case of first years student- Decreasing gap in computer skills between students of the first and the third year; between male and female students;- Declining popularity of computer games.It has been demonstrated also that the hazard of computer screen addiction was the highest in he case of unemployed youth outside school system. As much as 12% of this group of young people were addicted to computer. A lot of leisure time that these youths enjoyed inducted them to excessive utilization of the Web. Polish housewives are another population group in risk of addiction to the Web. The duration of long Web charts carried out by younger and younger youths has been another matter of concern. Since the phenomenon of computer addiction is relatively new, no specific therapy methods has been developed. In general, the applied therapy in relation to computer addition syndrome is similar to the techniques applied in the cases of alcohol or gambling addiction. Individual and group

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

    Science.gov (United States)

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

    2007-12-01

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

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

    LENUS (Irish Health Repository)

    Khan, M

    2012-04-01

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

  12. The higher proportion of men with psoriasis treated with biologics may be explained by more severe disease in men.

    Directory of Open Access Journals (Sweden)

    David Hägg

    Full Text Available OBJECTIVES: Moderate to severe psoriasis, once regarded as merely a skin disease, is today seen as an inflammatory systemic disease. The sex ratio of the prevalence of psoriasis is balanced. In recent years several reports have documented that men receive more systemic or UV treatment than women, and different hypotheses were made. In PsoReg, the national registry for systemic treatment of psoriasis in Sweden, we have, like other European registries, observed a predominance of men (59%, especially of men treated with biologics (63%. Biologics are a relatively new group of very effective but high-priced drugs. The objective of this study was to analyse if women are discriminated by not having the same access to the high-priced biologics. DESIGN: Population based cohort study using data from a nationwide quality register of psoriasis patients. POPULATION: 2294 patients with moderate to severe psoriasis receiving systemic treatment from a specialist in dermatology. MAIN OUTCOME MEASURES: Time to initiation of biologic treatment. A multiple Cox proportional hazard's regression was performed, with time to initiating a biologic treatment as the outcome in order to assess the independent role of the patient's sex in initiating such therapy. The psoriasis severity was defined as a time-varying variable. RESULTS: Men had more severe psoriasis than women according to the Psoriasis Area and Severity Index (PASI, regardless of age at enrolment, and throughout the study period. The analysis in the multiple Cox regression show that age, psoriasis severity and psoriasis arthropathy were relevant factors for initiating biologic therapy, whereas sex is not. CONCLUSIONS: Although as many women as men are believed to suffer from psoriasis, men seem to be more severely affected by psoriasis. The asymmetry in allocation of biologic therapy thereby probably reflects the differing disease activity between the sexes, and is not a discrimination against women per se.

  13. ''Hazardous'' terminology

    International Nuclear Information System (INIS)

    Powers, J.

    1991-01-01

    A number of terms (e.g., ''hazardous chemicals,'' ''hazardous materials,'' ''hazardous waste,'' and similar nomenclature) refer to substances that are subject to regulation under one or more federal environmental laws. State laws and regulations also provide additional, similar, or identical terminology that may be confused with the federally defined terms. Many of these terms appear synonymous, and it easy to use them interchangeably. However, in a regulatory context, inappropriate use of narrowly defined terms can lead to confusion about the substances referred to, the statutory provisions that apply, and the regulatory requirements for compliance under the applicable federal statutes. This information Brief provides regulatory definitions, a brief discussion of compliance requirements, and references for the precise terminology that should be used when referring to ''hazardous'' substances regulated under federal environmental laws. A companion CERCLA Information Brief (EH-231-004/0191) addresses ''toxic'' nomenclature

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

    DEFF Research Database (Denmark)

    Scheike, Thomas H.; Zhang, Mei-Jie

    2003-01-01

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

  15. On spatio-temporal Lévy based Cox processes

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  16. COX-1 inhibitory effect of medicinal plants of Ghana

    DEFF Research Database (Denmark)

    Larsen, Birgitte HV; Soelberg, Jens; Jäger, Anna

    2015-01-01

    Plants used to treat inflammatory ailments, pain, fever and infections in Ghana, were tested for COX-1 inhibitory activity. Ethanolic extracts of 17 species were tested in a COX-1 assay. The extracts of Gardenia ternifolia, Thonningia sanguinea, Triumfetta rhomboidea, and the root of Zanthoxylum ...

  17. COX-2 is associated with periodontitis in Europeans

    NARCIS (Netherlands)

    Schaefer, A.S.; Richter, G.M.; Nothnagel, M.; Laine, M.L.; Noack, B.; Glas, J.; Schrezenmeir, J.; Groessner-Schreiber, B.; Jepsen, S.; Loos, B.G.; Schreiber, S.

    2010-01-01

    COX-2 plays an important role in periodontitis by mediating inflammatory reactions in periodontal tissues, and the COX-2 polymorphisms rs20417 and rs689466 have been reported to be associated with periodontitis in populations of Taiwanese and Chinese ethnicity. To test whether these variants were

  18. Welding hazards

    International Nuclear Information System (INIS)

    Khan, M.A.

    1992-01-01

    Welding technology is advancing rapidly in the developed countries and has converted into a science. Welding involving the use of electricity include resistance welding. Welding shops are opened in residential area, which was causing safety hazards, particularly the teenagers and children who eagerly see the welding arc with their naked eyes. There are radiation hazards from ultra violet rays which irritate the skin, eye irritation. Welding arc light of such intensity could damage the eyes. (Orig./A.B.)

  19. Global Multihazard Proportional Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Multihazard Proportional Economic Loss Risks is a 2.5 minute grid of a multihazard-based economic loss risk as a proportion of the economic productivity of...

  20. Cognitive and Metacognitive Aspects of Proportional Reasoning

    Science.gov (United States)

    Modestou, Modestina; Gagatsis, Athanasios

    2010-01-01

    In this study we attempt to propose a new model of proportional reasoning based both on bibliographical and research data. This is impelled with the help of three written tests involving analogical, proportional, and non-proportional situations that were administered to pupils from grade 7 to 9. The results suggest the existence of a…

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

    Science.gov (United States)

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

    2017-01-01

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

  2. Hazardous Chemicals

    Centers for Disease Control (CDC) Podcasts

    2007-04-10

    Chemicals are a part of our daily lives, providing many products and modern conveniences. With more than three decades of experience, The Centers for Disease Control and Prevention (CDC) has been in the forefront of efforts to protect and assess people's exposure to environmental and hazardous chemicals. This report provides information about hazardous chemicals and useful tips on how to protect you and your family from harmful exposure.  Created: 4/10/2007 by CDC National Center for Environmental Health.   Date Released: 4/13/2007.

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

    Science.gov (United States)

    Vaeth, Michael; Skovlund, Eva

    2004-06-15

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

  4. Antitumor effects of celecoxib in COX-2 expressing and non-expressing canine melanoma cell lines.

    Science.gov (United States)

    Seo, Kyoung-Won; Coh, Ye-Rin; Rebhun, Robert B; Ahn, Jin-Ok; Han, Sei-Myung; Lee, Hee-Woo; Youn, Hwa-Young

    2014-06-01

    Cyclooxygenase-2 (COX-2) is a potential target for chemoprevention and cancer therapy. Celecoxib, a selective COX-2 inhibitor, inhibits cell growth of various types of human cancer including malignant melanoma. In dogs, oral malignant melanoma represents the most common oral tumor and is often a fatal disease. Therefore, there is a desperate need to develop additional therapeutic strategies. The purpose of this study was to investigate the anticancer effects of celecoxib on canine malignant melanoma cell lines that express varying levels of COX-2. Celecoxib induced a significant anti-proliferative effect in both LMeC and CMeC-1 cells. In the CMeC cells, treatment of 50 μM celecoxib caused an increase in cells in the G0/G1 and a decreased proportion of cells in G-2 phase. In the LMeC cells, 50 μM of celecoxib led to an increase in the percentage of cells in the sub-G1 phase and a significant activation of caspase-3 when compared to CMeC-1 cells. In conclusion, these results demonstrate that celecoxib exhibits antitumor effects on canine melanoma LMeC and CMeC-1 cells by induction of G1-S cell cycle arrest and apoptosis. Our data suggest that celecoxib might be effective as a chemotherapeutic agent against canine malignant melanoma. Copyright © 2014. Published by Elsevier Ltd.

  5. MCEM algorithm for the log-Gaussian Cox process

    OpenAIRE

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

    2014-01-01

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

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

    Science.gov (United States)

    Mondal, Shoubhik; Subramanian, Sundarraman

    2016-01-01

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

  7. Thiazoles and Thiazolidinones as COX/LOX Inhibitors.

    Science.gov (United States)

    Liaras, Konstantinos; Fesatidou, Maria; Geronikaki, Athina

    2018-03-18

    Inflammation is a natural process that is connected to various conditions and disorders such as arthritis, psoriasis, cancer, infections, asthma, etc. Based on the fact that cyclooxygenase isoenzymes (COX-1, COX-2) are responsible for the production of prostaglandins that play an important role in inflammation, traditional treatment approaches include administration of non-steroidal anti-inflammatory drugs (NSAIDs), which act as selective or non-selective COX inhibitors. Almost all of them present a number of unwanted, often serious, side effects as a consequence of interference with the arachidonic acid cascade. In search for new drugs to avoid side effects, while maintaining high potency over inflammation, scientists turned their interest to the synthesis of dual COX/LOX inhibitors, which could provide numerous therapeutic advantages in terms of anti-inflammatory activity, improved gastric protection and safer cardiovascular profile compared to conventional NSAIDs. Τhiazole and thiazolidinone moieties can be found in numerous biologically active compounds of natural origin, as well as synthetic molecules that possess a wide range of pharmacological activities. This review focuses on the biological activity of several thiazole and thiazolidinone derivatives as COX-1/COX-2 and LOX inhibitors.

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

    Science.gov (United States)

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

    2016-01-01

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

  9. Determinant Factors in Graft Rejection Using Cox Regression, among the Recipients of Second Renal Transplant in Imam Khomeini Hospital in Urmia, 1988-2000

    Directory of Open Access Journals (Sweden)

    Rahim Tahmasebi

    2010-09-01

    Full Text Available Background: The objective of this study was to evaluate graft survival among the recipients of second renal transplant in Imam Khomeini centre hospital in Urmia. Methods: The study population consisted of 50 patients receiving renal grafts for the second time between 1988 and 2008 in Imam Khomeini centre hospital in Urmia. Two survival outcomes, first and second graft survival, were analyzed. Graft survival was defined from date of transplant until its rejection. For the purpose of graft survival analysis, graft failure was defined as return to dialysis, and death due to the functioning graft. Data were collected through individual patient questionnaires. Demographic and clinical factors, transfusion history, type of immunosuppressive drugs, levels of serum creatinine, triglyceride, cholesterol, and LDL at 3 and 6 months after transplantation were collected. Cox-proportional hazard model and Kaplan-Meier were used to data analysis. Results: First graft survival at 1, 2, 3, and 5 years was 74%, 66%, 53%, and 41%, respectively. Second graft survival at 1, 2, 3, and 5 years was 81%, 74%, 70%, and 61%, respectively. Causes of graft loss in first renal transplantation were 6% sever acute graft rejection, 12% acute graft rejection and 82% chronic graft rejection. In the multivariate analysis, only serum creatinine, blood pressure, and immunosuppressive drugs predicted first graft loss and serum creatinine, immunosuppressive drugs, and related donor family predicted second graft rejection. Conclusion: The serum creatinine and immunosuppressive drugs including cyclosporine, cellcept, and prednisolone are the most influential factors on graft survival.

  10. A comparison of Cox and logistic regression for use in genome-wide association studies of cohort and case-cohort design.

    Science.gov (United States)

    Staley, James R; Jones, Edmund; Kaptoge, Stephen; Butterworth, Adam S; Sweeting, Michael J; Wood, Angela M; Howson, Joanna M M

    2017-06-01

    Logistic regression is often used instead of Cox regression to analyse genome-wide association studies (GWAS) of single-nucleotide polymorphisms (SNPs) and disease outcomes with cohort and case-cohort designs, as it is less computationally expensive. Although Cox and logistic regression models have been compared previously in cohort studies, this work does not completely cover the GWAS setting nor extend to the case-cohort study design. Here, we evaluated Cox and logistic regression applied to cohort and case-cohort genetic association studies using simulated data and genetic data from the EPIC-CVD study. In the cohort setting, there was a modest improvement in power to detect SNP-disease associations using Cox regression compared with logistic regression, which increased as the disease incidence increased. In contrast, logistic regression had more power than (Prentice weighted) Cox regression in the case-cohort setting. Logistic regression yielded inflated effect estimates (assuming the hazard ratio is the underlying measure of association) for both study designs, especially for SNPs with greater effect on disease. Given logistic regression is substantially more computationally efficient than Cox regression in both settings, we propose a two-step approach to GWAS in cohort and case-cohort studies. First to analyse all SNPs with logistic regression to identify associated variants below a pre-defined P-value threshold, and second to fit Cox regression (appropriately weighted in case-cohort studies) to those identified SNPs to ensure accurate estimation of association with disease.

  11. Radioactive hazards

    International Nuclear Information System (INIS)

    Gill, J.R.

    1980-01-01

    The use of radioactive substances in hospital laboratories is discussed and the attendant hazards and necessary precautions examined. The new legislation under the Health and Safety at Work Act which, it is proposed, will replace existing legal requirements in the field of health and safety at work by a system of regulations and approved codes of practice designed to maintain or improve the standards of health, safety and welfare already established, is considered with particular reference to protection against ionising radiations. (UK)

  12. Salt supplementation ameliorates developmental kidney defects in COX-2-/- mice.

    Science.gov (United States)

    Slattery, Patrick; Frölich, Stefanie; Goren, Itamar; Nüsing, Rolf M

    2017-06-01

    Deficiency of cyclooxygenase-2 (COX-2) activity in the early postnatal period causes impairment of kidney development leading to kidney insufficiency. We hypothesize that impaired NaCl reabsorption during the first days of life is a substantial cause for nephrogenic defects observed in COX-2 -/- mice and that salt supplementation corrects these defects. Daily injections of NaCl (0.8 mg·g -1 ·day -1 ) for the first 10 days after birth ameliorated impaired kidney development in COX-2 -/- pups resulting in an increase in glomerular size and fewer immature superficial glomeruli. However, impaired renal subcortical growth was not corrected. Increasing renal tubular flow by volume load or injections of KCl did not relieve the renal histomorphological damage. Administration of torsemide and spironolactone also affected nephrogenesis resulting in diminished glomeruli and cortical thinning. Treatment of COX-2 -/- pups with NaCl/DOCA caused a stronger mitigation of glomerular size and induced a slight but significant growth of cortical tissue mass. After birth, renal mRNA expression of NHE3, NKCC2, ROMK, NCCT, ENaC, and Na + /K + -ATPase increased relative to postnatal day 2 in wild-type mice. However, in COX-2 -/- mice, a significantly lower expression was observed for NCCT, whereas NaCl/DOCA treatment significantly increased NHE3 and ROMK expression. Long-term effects of postnatal NaCl/DOCA injections indicate improved kidney function with normalization of pathologically enhanced creatinine and urea plasma levels; also, albumin excretion was observed. In summary, we present evidence that salt supplementation during the COX-2-dependent time frame of nephrogenesis partly reverses renal morphological defects in COX-2 -/- mice and improves kidney function. Copyright © 2017 the American Physiological Society.

  13. Mix Proportion Design of Asphalt Concrete

    Science.gov (United States)

    Wu, Xianhu; Gao, Lingling; Du, Shoujun

    2017-12-01

    Based on the gradation of AC and SMA, this paper designs a new type of anti slide mixture with two types of advantages. Chapter introduces the material selection, ratio of ore mixture ratio design calculation, and determine the optimal asphalt content test and proportioning design of asphalt concrete mix. This paper introduces the new technology of mix proportion.

  14. Relating arithmetical techniques of proportion to geometry

    DEFF Research Database (Denmark)

    Wijayanti, Dyana

    2015-01-01

    The purpose of this study is to investigate how textbooks introduce and treat the theme of proportion in geometry (similarity) and arithmetic (ratio and proportion), and how these themes are linked to each other in the books. To pursue this aim, we use the anthropological theory of the didactic...

  15. Large-Scale Analysis of Art Proportions

    DEFF Research Database (Denmark)

    Jensen, Karl Kristoffer

    2014-01-01

    ) and with majority of images having a proportion larger than one, but less than e.g. the golden ratio. Furthermore, more images have the inversed proportion, meaning that portrait paintings are more common than landscape paintings. The inverse is true for photographs, i.e. more landscape than portrait format......While literature often tries to impute mathematical constants into art, this large-scale study (11 databases of paintings and photos, around 200.000 items) shows a different truth. The analysis, consisting of the width/height proportions, shows a value of rarely if ever one (square...

  16. BOX-COX REGRESSION METHOD IN TIME SCALING

    Directory of Open Access Journals (Sweden)

    ATİLLA GÖKTAŞ

    2013-06-01

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

  17. Changes in osteoarthritis management by general practitioners in the COX2-inhibitor era-concomitant gastroprotective therapy.

    Science.gov (United States)

    Bouée, Stéphane; Charlemagne, Agnès; Fagnani, Francis; Le Jeunne, Philippe; Sermet, Catherine; Naudin, Florence; Lancry, Pierre-Jean

    2004-05-01

    Two selective COX2 inhibitors, rofecoxib and celecoxib, were introduced on the French market in 2000. We evaluated their use in the treatment of osteoarthritis by general practitioners, with special attention to concomitant prescription of gastroprotective agents. The Thales Epidemiology Observatory is a medical database compiled by a representative sample of 1000 general practitioners in France. We examined the data collected during the year before and the year after the introduction of rofecoxib and celecoxib on the French market (November 1999-October 2001). During each of the 2 years of the study period, about 200,000 visits for 70,000 patients were entered into the database. COX2 inhibitors were prescribed at a rapidly increasing rate during the second year, when they accounted for 38% of the prescription volume for nonsteroidal antiinflammatory drugs (NSAIDs) and 25% of prescribed medication costs. In some patients, COX2 inhibitors were substituted for nonselective NSAIDs, and in others they were used as first-line NSAID therapy. On average over the 2-year study period, 22.1% of prescriptions for conventional NSAIDs included a prescription for a gastroprotective agent; this proportion increased from 18.6% in November 1999 to 24.8% in October 2001. Among prescriptions for COX2 inhibitors, 17.5% included a gastroprotective agent. General practitioners have been prompt to use COX2 inhibitors in the treatment of osteoarthritis. However, they have not decreased their use of concomitant gastroprotective treatment. Thus, they seem aware that proof of a lower long-term risk of gastrointestinal toxicity with COX2 inhibitors is lacking, and that elderly patients such as those with osteoarthritis are at high risk for gastrointestinal side effects of NSAIDs. Copyright 2003 Elsevier SAS

  18. Tsunami hazard

    International Nuclear Information System (INIS)

    2013-01-01

    Tohoku Earthquake Tsunami on 11 March, 2011 has led the Fukushima Daiichi nuclear power plant to a serious accident, which highlighted a variety of technical issues such as a very low design tsunami height and insufficient preparations in case a tsunami exceeding the design tsunami height. Lessons such as to take measures to be able to maintain the important safety features of the facility for tsunamis exceeding design height and to implement risk management utilizing Probabilistic Safety Assessment are shown. In order to implement the safety assessment on nuclear power plants across Japan accordingly to the back-fit rule, Nuclear Regulatory Commission will promulgate/execute the New Safety Design Criteria in July 2013. JNES has positioned the 'enhancement of probabilistic tsunami hazard assessment' as highest priority issue and implemented in order to support technically the Nuclear Regulatory Authority in formulating the new Safety Design Criteria. Findings of the research had reflected in the 'Technical Review Guidelines for Assessing Design Tsunami Height based on tsunami hazards'. (author)

  19. Proportional neutron counters for reactor engineering

    International Nuclear Information System (INIS)

    Artem'eva, I.V.; Zasadych, Yu.B.; Malyshev, E.K.

    1986-01-01

    Proportional neutron counters, designed for measuring the neutron flux density at nuclear reactors; position sensitive proportional neutron counters and recoil proton proportional counters, used at research reactors and accelerators are considered. Modern level of proportional neutron counters is described and trends in development of that field of engineering are determined. Specifications of detectors for industrial application are presented. The main trend in reactor detector development is the increase of service life, radiation resistance and thermal resistance. A particular place among the counters is occupied by position sensitive detectors, which appear to be the most rapidly developing detector type. Their further development and application sphere expansion depend on the production technology improvement, the development and lowering the price of the measuring electronic equipment

  20. Bayesian analysis of log Gaussian Cox processes for disease mapping

    DEFF Research Database (Denmark)

    Benes, Viktor; Bodlák, Karel; Møller, Jesper

    We consider a data set of locations where people in Central Bohemia have been infected by tick-borne encephalitis, and where population census data and covariates concerning vegetation and altitude are available. The aims are to estimate the risk map of the disease and to study the dependence...... of the risk on the covariates. Instead of using the common area level approaches we consider a Bayesian analysis for a log Gaussian Cox point process with covariates. Posterior characteristics for a discretized version of the log Gaussian Cox process are computed using markov chain Monte Carlo methods...

  1. Hazardous Air Pollutants

    Science.gov (United States)

    ... Protection Agency Search Search Contact Us Share Hazardous Air Pollutants Hazardous air pollutants are those known to ... of industrial facilities in two phases . About Hazardous Air Pollutants What are Hazardous Air Pollutants? Health and ...

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

    Science.gov (United States)

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

    2015-01-01

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

  3. Deficiency in either COX-1 or COX-2 genes does not affect amyloid beta protein burden in amyloid precursor protein transgenic mice.

    Science.gov (United States)

    Park, Sun Ah; Chevallier, Nathalie; Tejwani, Karishma; Hung, Mary M; Maruyama, Hiroko; Golde, Todd E; Koo, Edward H

    2016-09-09

    Epidemiologic studies indicate that chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a lower risk for developing Alzheimer's disease (AD). Because the primary mode of action of NSAIDs is to inhibit cyclooxygenase (COX) activity, it has been proposed that perturbed activity of COX-1 or COX-2 contributes to AD pathogenesis. To test the role of COX-1 or COX-2 in amyloid deposition and amyloid-associated inflammatory changes, we examined amyloid precursor protein (APP) transgenic mice in the context of either COX-1 or COX-2 deficiency. Our studies showed that loss of either COX-1 or COX-2 gene did not alter amyloid burden in brains of the APP transgenic mice. However, one marker of microglial activation (CD45) was decreased in brains of COX-1 deficient/APP animals and showed a strong trend in reduction in COX-2 deficient/APP animals. These results suggest that COX activity and amyloid deposition in brain are likely independent processes. Further, if NSAIDs do causally reduce the risks of AD, then our findings indicate that the mechanisms are likely not due primarily to their inhibition on COX or γ-secretase modulation activity, the latter reported recently after acute dosing of ibuprofen in humans and nonhuman primates. Copyright © 2016. Published by Elsevier Inc.

  4. Electrostatic hazards

    CERN Document Server

    Luttgens, Günter; Luttgens, Gnter; Luttgens, G Nter

    1997-01-01

    In the US, UK and Europe there is in excess of one notifiable dust or electrostatic explosion every day of the year. This clearly makes the hazards associated with the handling of materials subject to either cause or react to electrostatic discharge of vital importance to anyone associated with their handling or industrial bulk use. This book provides a comprehensive guide to the dangers of static electricity and how to avoid them. It will prove invaluable to safety managers and professionals, as well as all personnel involved in the activities concerned, in the chemical, agricultural, pharmaceutical and petrochemical process industries. The book makes extended use of case studies to illustrate the principles being expounded, thereby making it far more open, accessible and attractive to the practitioner in industry than the highly theoretical texts which are also available. The authors have many years' experience in the area behind them, including the professional teaching of the content provided here. Günte...

  5. Proportion congruency effects: Instructions may be enough

    Directory of Open Access Journals (Sweden)

    Olga eEntel

    2014-10-01

    Full Text Available Learning takes time, namely, one needs to be exposed to contingency relations between stimulus dimensions in order to learn, whereas intentional control can be recruited through task demands. Therefore showing that control can be recruited as a function of experimental instructions alone, that is, adapting the processing according to the instructions before the exposure to the task, can be taken as evidence for existence of control recruitment in the absence of learning. This was done by manipulating the information given at the outset of the experiment. In the first experiment, we manipulated list-level congruency proportion. Half of the participants were informed that most of the stimuli would be congruent, whereas the other half were informed that most of the stimuli would be incongruent. This held true for the stimuli in the second part of each experiment. In the first part, however, the proportion of the two stimulus types was equal. A proportion congruent effect was found in both parts of the experiment, but it was larger in the second part. In our second experiment, we manipulated the proportion of the stimuli within participants by applying an item-specific design. This was done by presenting some color words most often in their congruent color, and other color words in incongruent colors. Participants were informed about the exact word-color pairings in advance. Similar to Experiment 1, this held true only for the second experimental part. In contrast to our first experiment, informing participants in advance did not result in an item-specific proportion effect, which was observed only in the second part. Thus our results support the hypothesis that instructions may be enough to trigger list-level control, yet learning does contribute to the proportion congruent effect under such conditions. The item-level proportion effect is apparently caused by learning or at least it is moderated by it.

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

    DEFF Research Database (Denmark)

    Jalilian, Abdollah; Guan, Yongtao; Mateu, Jorge

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

  7. Immunohistochemical Expression of COX-2 in Uterine Serous Carcinoma Tissue

    Directory of Open Access Journals (Sweden)

    Joseph Menczer

    2016-03-01

    Material and methods. Cox-2 expression assessment by immunohistochemistry was performed on deparaffinized sections of paraffin-embedded tissue blocks of consecutive available USC uterine specimens of patients diagnosed from 2000 to 2014. Staining of more than 10% of the cells was considered positive. Staining intensity was graded on a 0 and ndash;3 scale. A scoring index was calculated by multiplying the intensity grade by the percentage of stained cells and considered low when it was equal to 1 or less and high when it was more than 1. Clinicopathological data were retrospectively abstracted from the records of the study group patients Results. The study comprised uterine specimens of 31 USC patients. Positive immunohistochemical staining was observed in 25 (80.6% USC specimens and a high score in 6 (19.4% of them. No association between immunohistochemical staining parameters and clinicopathological prognostic factors was observed. Conclusion. Although our findings should be verified in larger series, it seems that in view of the lack of association between immunohistochemical Cox-2 staining parameters in USC tissue and clinicopathological prognostic factors, this aggressive tumor is not a candidate for the use of selective Cox-2 inhibitors. Key words: Cox-2 expression, uterine carcinosarcoma, clinicopathological prognostic factors [J Interdiscipl Histopathol 2016; 4(1.000: 9-12

  8. Convergence of posteriors for discretized log Gaussian Cox processes

    DEFF Research Database (Denmark)

    Waagepetersen, Rasmus Plenge

    2004-01-01

    In Markov chain Monte Carlo posterior computation for log Gaussian Cox processes (LGCPs) a discretization of the continuously indexed Gaussian field is required. It is demonstrated that approximate posterior expectations computed from discretized LGCPs converge to the exact posterior expectations...... when the cell sizes of the discretization tends to zero. The effect of discretization is studied in a data example....

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

    Volf, Petr

    2003-01-01

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

  11. CoX zeolites and their exchange with deuterium

    International Nuclear Information System (INIS)

    Novakova, J.; Kubelkova, L.; Jiru, P.

    1976-01-01

    An analysis of the gaseous phase using a mass spectrometer and analysis of the solid phase using an infrared spectrophotometer was made to investigate the deuterium exchange with hydrogen mostly bound in hydroxyl groups of zeolites CoX(21 and 47%) and NaX. It was found that with the increasing amount of cobalt ions the number of exchangeable hydrogens of the zeolite increases; the respective types of the hydrogen are discussed with respect to the particular dehydration temperatures. The rate of the D 2 +OH exchange is substantially faster with the CoX than with the NaX zeolite, and exhibits a decrease with increasing dehydration. On the other hand, the rate of D 2 +H 2 exchange without zeolite hydrogen incorporation, catalyzed by CoX zeolites, increases with increasing dehydration. The increased activation of gaseous hydrogen molecules is related to the presence in the zeolite of cobalt ions whose properties change during dehydration with the change in their environment. Hydroxyl groups of the CoX zeolites are not equivalent during the exchange; the hydroxyl hydrogens of the 3740 cm -1 band are exchanged more slowly than are the other hydrogens. (author)

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

    African Journals Online (AJOL)

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

  13. Intravenous glutamine enhances COX-2 activity giving cardioprotection.

    LENUS (Irish Health Repository)

    McGuinness, Jonathan

    2009-03-01

    Preconditioning, a highly evolutionary conserved endogenous protective response, provides the most powerful form of anti-infarct protection known. We investigated whether acute intravenous glutamine, through an effect on cyclooxygenase (COX)-2 and heat shock protein (HSP) 72, might induce preconditioning.

  14. Progress in studying scintillator proportionality: Phenomenological model

    Energy Technology Data Exchange (ETDEWEB)

    Bizarri, Gregory; Cherepy, Nerine; Choong, Woon-Seng; Hull, Giulia; Moses, William; Payne, Sephen; Singh, Jai; Valentine, John; Vasilev, Andrey; Williams, Richard

    2009-04-30

    We present a model to describe the origin of non-proportional dependence of scintillator light yield on the energy of an ionizing particle. The non-proportionality is discussed in terms of energy relaxation channels and their linear and non-linear dependences on the deposited energy. In this approach, the scintillation response is described as a function of the deposited energy deposition and the kinetic rates of each relaxation channel. This mathematical framework allows both a qualitative interpretation and a quantitative fitting representation of scintillation non-proportionality response as function of kinetic rates. This method was successfully applied to thallium doped sodium iodide measured with SLYNCI, a new facility using the Compton coincidence technique. Finally, attention is given to the physical meaning of the dominant relaxation channels, and to the potential causes responsible for the scintillation non-proportionality. We find that thallium doped sodium iodide behaves as if non-proportionality is due to competition between radiative recombinations and non-radiative Auger processes.

  15. Butane gas-flow proportional counter

    International Nuclear Information System (INIS)

    Han Jingquan; Ren Wei; Ma Liping

    2000-01-01

    It is experimentally proved that the butane can be used as an operating gas of the proportional counter. The operating performances of the counter with the butane are quite similar to that with the methane. A KX-50 butane flow proportional counter is described and its plateau characteristic is determined. For this counter, the plateau length, the slope of the plateau, the background count rate is 600 V, 1.7% per 100 V, 0.02s -1 for 239 Pu α source and about 500 V, 1.8% per 100 V, 3s -1 for 90 Sr- 90 Y source, respectively

  16. Canine Conjectures: Using Data for Proportional Reasoning

    Science.gov (United States)

    Westenskow, Arla; Moyer-Packenham, Patricia S.

    2011-01-01

    No person, place, or thing can capture the attention of a class of sixth graders like "man's best friend." To prompt students' interest in a series of lessons on proportional relationships, the authors brought in a unique teaching aid--a dog. A family dog was used to supply the measurements for scatter plots and variables so that students could…

  17. Obtaining a Proportional Allocation by Deleting Items

    NARCIS (Netherlands)

    Dorn, B.; de Haan, R.; Schlotter, I.; Röthe, J.

    2017-01-01

    We consider the following control problem on fair allocation of indivisible goods. Given a set I of items and a set of agents, each having strict linear preference over the items, we ask for a minimum subset of the items whose deletion guarantees the existence of a proportional allocation in the

  18. Proportional green time scheduling for traffic lights

    NARCIS (Netherlands)

    P. Kovacs; Le, T. (Tung); R. Núñez Queija (Rudesindo); Vu, H. (Hai); N. Walton

    2016-01-01

    textabstractWe consider the decentralized scheduling of a large number of urban traffic lights. We investigate factors determining system performance, in particular, the length of the traffic light cycle and the proportion of green time allocated to each junction. We study the effect of the length

  19. LTR design of proportional-integral observers

    DEFF Research Database (Denmark)

    Niemann, Hans Henrik; Stoustrup, Jakob; Shafai, B.

    1995-01-01

    This paper applies the proportional-integral (PI) observer in connection with loop transfer recovery (LTR) design for continuous-time systems. We show that a PI observer makes it possible to obtain time recovery, i.e., exact recovery for t -+ -, under mild conditions. Based on an extension...

  20. Adaptive bayesian analysis for binomial proportions

    CSIR Research Space (South Africa)

    Das, Sonali

    2008-10-01

    Full Text Available The authors consider the problem of statistical inference of binomial proportions for non-matched, correlated samples, under the Bayesian framework. Such inference can arise when the same group is observed at a different number of times with the aim...

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

    Science.gov (United States)

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

    2017-01-01

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

  2. Introduction of β-d-mannuronic acid (M2000) as a novel NSAID with immunosuppressive property based on COX-1/COX-2 activity and gene expression.

    Science.gov (United States)

    Mirshafiey, Abbas; Taeb, Mahsa; Mortazavi-Jahromi, Seyed Shahabeddin; Jafarnezhad-Ansariha, Fahimeh; Rehm, Bernd H A; Esposito, Emanuela; Cuzzocrea, Salvatore; Matsuo, Hidenori

    2017-10-01

    The NSAIDs which inhibit the cyclooxygenase (COX) enzymes are among medications widely used to treat pain and inflammation. These drugs cause digestive complications resulting in inhibition of the COX-1 enzyme, while the inhibition of the COX-2 enzyme has therapeutic effects. Therefore research focuses on the production of medications that specifically inhibit the COX-2 enzyme. This study aimed to study the effects of β-d-mannuronic (M2000) acid on the gene expression and activity of COX-1/COX-2 enzymes in order to introduce a novel NSAID for treating inflammatory diseases. The mRNA expression levels of COXs were analyzed with qRT-PCR. Prostaglandin E 2 (PGE 2 ) concentration in culture media was determined using ELISA method. Our results indicated that the M2000 at low and high dose could significantly reduce the gene expression level of COX-2 compared to the LPS group (pCOX-1 compared to the LPS group. Moreover, it was noticed that this drug strongly and significantly reduced the activity of COX-1/COX-2 enzymes at the three concentrations of 5, 50 and 500 mMol/ml compared to the LPS and arachidonic acid groups (pCOX-1/COX-2 enzymes, with suppressing the gene expression of COX-2 specifically. Therefore, based on gene expression findings this drug might be categorized and introduced as a novel NSAID with selective COX-2 inhibitory effect. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  3. Instrumental variables estimation under a structural Cox model

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  4. COX-2 Protects against Atherosclerosis Independently of Local Vascular Prostacyclin: Identification of COX-2 Associated Pathways Implicate Rgl1 and Lymphocyte Networks

    Science.gov (United States)

    Kirkby, Nicholas S.; Lundberg, Martina H.; Wright, William R.; Warner, Timothy D.; Paul-Clark, Mark J.; Mitchell, Jane A.

    2014-01-01

    Cyxlo-oxygenase (COX)-2 inhibitors, including traditional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with increased cardiovascular side effects, including myocardial infarction. We and others have shown that COX-1 and not COX-2 drives vascular prostacyclin in the healthy cardiovascular system, re-opening the question of how COX-2 might regulate cardiovascular health. In diseased, atherosclerotic vessels, the relative contribution of COX-2 to prostacyclin formation is not clear. Here we have used apoE−/−/COX-2−/− mice to show that, whilst COX-2 profoundly limits atherosclerosis, this protection is independent of local prostacyclin release. These data further illustrate the need to look for new explanations, targets and pathways to define the COX/NSAID/cardiovascular risk axis. Gene expression profiles in tissues from apoE−/−/COX-2−/− mice showed increased lymphocyte pathways that were validated by showing increased T-lymphocytes in plaques and elevated plasma Th1-type cytokines. In addition, we identified a novel target gene, rgl1, whose expression was strongly reduced by COX-2 deletion across all examined tissues. This study is the first to demonstrate that COX-2 protects vessels against atherosclerotic lesions independently of local vascular prostacyclin and uses systems biology approaches to identify new mechanisms relevant to development of next generation NSAIDs. PMID:24887395

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

    Science.gov (United States)

    Herschman, Harvey

    2014-01-01

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

  6. COX-2 Inhibitors for Cancer Treatment in Dogs

    Directory of Open Access Journals (Sweden)

    Andrigo Barboza De Nardi*, Talita Mariana Morata Raposo1, Rafael Ricardo Huppes1, Carlos Roberto Daleck2 and Renée Laufer Amorim3

    2011-10-01

    Full Text Available Cancer is one of the main causes of death in canines and felines, and this fact is probably related to the increase in the longevity of these species. The longer the animals live, the higher the exposure to carcinogenic agents will be. With the high incidence of cancer in companion animals, new studies are currently being performed with the aim of finding therapeutic options which make the complete inhibition of the development of neoplasms in animals possible in the future. The correlation of cyclooxygenase-2 (COX-2 whith the development of cancer opens the way for the use of new therapeutic approaches. This relationship has been suggested based on various studies which established an association between the chronic use of nonsteroidal anti-inflammatory drugs (NSAID and a decrease in the incidence of colon carcinoma. As cancer progresses, COX-2 participates in the arachidonic acid metabolism by synthesizing prostaglandins which can mediate various mechanisms related to cancer development such as: increase in angiogenesis, inhibition of apoptosis, suppression of the immune response, acquisition of greater invasion capacity and metastasis. Accordingly, overexpression of this enzyme in tumors has been associated with the most aggressive, poor-prognosis cancer types, especially carcinomas. Therefore, treatments which use COX-2 inhibitors such as coxibs, whether administered as single agents or in combination with conventional antineoplastic chemotherapy, are an alternative for extending the survival of our cancer patients.

  7. Pulse triggering mechanism of air proportional counters

    International Nuclear Information System (INIS)

    Aoyama, T.; Mori, T.; Watanabe, T.

    1983-01-01

    This paper describes the pulse triggering mechanism of a cylindrical proportional counter filled with air at atmospheric pressure for the incidence of β-rays. Experimental results indicate that primary electrons created distantly from the anode wire by a β-ray are transformed into negative ions, which then detach electrons close to the anode wire and generate electron avalanches thus triggering pulses, while electrons created near the anode wire by a β-ray directly trigger a pulse. Since a negative ion pulse is triggered by a single electron detached from a negative ion, multiple pulses are generated by a large number of ions produced by the incidence of a single β-ray. It is therefore necessary not to count pulses triggered by negative ions but to count those by primary electrons alone when use is made of air proportional counters for the detection of β-rays. (orig.)

  8. Vaccination coverage and immunization timeliness among children aged 12-23 months in Senegal: a Kaplan-Meier and Cox regression analysis approach.

    Science.gov (United States)

    Mbengue, Mouhamed Abdou Salam; Mboup, Aminata; Ly, Indou Deme; Faye, Adama; Camara, Fatou Bintou Niang; Thiam, Moussa; Ndiaye, Birahim Pierre; Dieye, Tandakha Ndiaye; Mboup, Souleymane

    2017-01-01

    Expanded programme on immunizations in resource-limited settings currently measure vaccination coverage defined as the proportion of children aged 12-23 months that have completed their vaccination. However, this indicator does not address the important question of when the scheduled vaccines were administered. We assessed the determinants of timely immunization to help the national EPI program manage vaccine-preventable diseases and impact positively on child survival in Senegal. Vaccination data were obtained from the Demographic and Health Survey (DHS) carried out across the 14 regions in the country. Children were aged between 12-23 months. The assessment of vaccination coverage was done with the health card and/or by the mother's recall of the vaccination act. For each vaccine, an assessment of delay in age-appropriate vaccination was done following WHO recommendations. Additionally, Kaplan-Meier survival function was used to estimate the proportion vaccinated by age and cox-proportional hazards models were used to examine risk factors for delays. A total of 2444 living children between 12-23 months of age were included in the analysis. The country vaccination was below the WHO recommended coverage level and, there was a gap in timeliness of children immunization. While BCG vaccine uptake was over 95%, coverage decreased with increasing number of Pentavalent vaccine doses (Penta 1: 95.6%, Penta 2: 93.5%: Penta 3: 89.2%). Median delay for BCG was 1.7 weeks. For polio at birth, the median delay was 5 days; all other vaccine doses had median delays of 2-4 weeks. For Penta 1 and Penta 3, 23.5% and 15.7% were given late respectively. A quarter of measles vaccines were not administered or were scheduled after the recommended age. Vaccinations that were not administered within the recommended age ranges were associated with mothers' poor education level, multiple siblings, low socio-economic status and living in rural areas. A significant delay in receipt of infant

  9. Vaccination coverage and immunization timeliness among children aged 12-23 months in Senegal: a Kaplan-Meier and Cox regression analysis approach

    Science.gov (United States)

    Mbengue, Mouhamed Abdou Salam; Mboup, Aminata; Ly, Indou Deme; Faye, Adama; Camara, Fatou Bintou Niang; Thiam, Moussa; Ndiaye, Birahim Pierre; Dieye, Tandakha Ndiaye; Mboup, Souleymane

    2017-01-01

    Introduction Expanded programme on immunizations in resource-limited settings currently measure vaccination coverage defined as the proportion of children aged 12-23 months that have completed their vaccination. However, this indicator does not address the important question of when the scheduled vaccines were administered. We assessed the determinants of timely immunization to help the national EPI program manage vaccine-preventable diseases and impact positively on child survival in Senegal. Methods Vaccination data were obtained from the Demographic and Health Survey (DHS) carried out across the 14 regions in the country. Children were aged between 12-23 months. The assessment of vaccination coverage was done with the health card and/or by the mother’s recall of the vaccination act. For each vaccine, an assessment of delay in age-appropriate vaccination was done following WHO recommendations. Additionally, Kaplan-Meier survival function was used to estimate the proportion vaccinated by age and cox-proportional hazards models were used to examine risk factors for delays. Results A total of 2444 living children between 12–23 months of age were included in the analysis. The country vaccination was below the WHO recommended coverage level and, there was a gap in timeliness of children immunization. While BCG vaccine uptake was over 95%, coverage decreased with increasing number of Pentavalent vaccine doses (Penta 1: 95.6%, Penta 2: 93.5%: Penta 3: 89.2%). Median delay for BCG was 1.7 weeks. For polio at birth, the median delay was 5 days; all other vaccine doses had median delays of 2-4 weeks. For Penta 1 and Penta 3, 23.5% and 15.7% were given late respectively. A quarter of measles vaccines were not administered or were scheduled after the recommended age. Vaccinations that were not administered within the recommended age ranges were associated with mothers’ poor education level, multiple siblings, low socio-economic status and living in rural areas

  10. General methods for analyzing bounded proportion data

    OpenAIRE

    Hossain, Abu

    2017-01-01

    This thesis introduces two general classes of models for analyzing proportion response variable when the response variable Y can take values between zero and one, inclusive of zero and/or one. The models are inflated GAMLSS model and generalized Tobit GAMLSS model. The inflated GAMLSS model extends the flexibility of beta inflated models by allowing the distribution on (0,1) of the continuous component of the dependent variable to come from any explicit or transformed (i.e. logit or truncated...

  11. Cylindrical geometry for proportional and drift chambers

    International Nuclear Information System (INIS)

    Sadoulet, B.

    1975-06-01

    For experiments performed around storage rings such as e + e - rings or the ISR pp rings, cylindrical wire chambers are very attractive. They surround the beam pipe completely without any dead region in the azimuth, and fit well with the geometry of events where particles are more or less spherically produced. Unfortunately, cylindrical proportional or drift chambers are difficult to make. Problems are discussed and two approaches to fabricating the cathodes are discussed. (WHK)

  12. 2 π gaseous flux proportional detector

    International Nuclear Information System (INIS)

    Guevara, E.A.; Costello, E.D.; Di Carlo, R.O.

    1986-01-01

    A counting system has been developed in order to measure carbon-14 samples obtained in the course of a study of a plasmapheresis treatment for diabetic children. The system is based on the use of a 2π gaseous flux proportional detector especially designed for the stated purpose. The detector is described and experiment results are given, determining the characteristic parameters which set up the working conditions. (Author) [es

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

    Science.gov (United States)

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

    2017-10-16

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

  14. Is the Proportion of Carbohydrate Intake Associated with the Incidence of Diabetes Complications?—An Analysis of the Japan Diabetes Complications Study

    Directory of Open Access Journals (Sweden)

    Chika Horikawa

    2017-02-01

    Full Text Available The appropriate proportions of macronutritional intake have been controversial in medical nutritional therapy for diabetes, and evidence of the effects of carbohydrate consumption on diabetes complications in prospective settings is sparse. We investigated the relationships between proportions of carbohydrate intake as the % of total energy and diabetes complications in a nationwide cohort of Japanese patients with type 2 diabetes aged 40–70 years with hemoglobin A1c ≥6.5%. The analysis was of 1516 responders to a baseline dietary survey assessed by the Food Frequency Questionnaire based on food groups. Primary outcomes were times to overt nephropathy, diabetic retinopathy, and cardiovascular disease (CVD after 8 years. Hazard ratios (HRs for proportions of carbohydrate intake were estimated by Cox regression adjusted for confounders. High carbohydrate intake was significantly related to higher intakes of grain, fruits, and sweets/snacks and lower intakes of soybean and soy products, vegetables, seaweed, meat and processed meat, fish and processed fish, eggs, milk and dairy products, oil, and alcoholic beverages. During the eight-year follow-up, there were 81, 275, and 129 events of overt nephropathy, diabetic retinopathy, and CVD, respectively. After adjustment for confounders, HRs for complications in patients with carbohydrate intake in the second or third tertiles (51.0%–56.4% and ≥56.5%, respectively compared with carbohydrate intake in the first tertile (<50.9%, referent were analyzed. No significant associations were shown in the second and third tertiles relative to first tertile (overt nephropathy: 1.05 (95% Confidence Interval, 0.54–2.06 and 0.98 (0.40–2.44; diabetic retinopathy: 1.30 (0.90–1.88 and 1.30 (0.78–2.15; and CVD: 0.95 (0.55–1.63 and 1.37 (0.69–2.72. By exploring potentially nonlinear relationships, trends for the incidence of diabetes complications according to proportions of carbohydrate intake were not

  15. Hazard classification methodology

    International Nuclear Information System (INIS)

    Brereton, S.J.

    1996-01-01

    This document outlines the hazard classification methodology used to determine the hazard classification of the NIF LTAB, OAB, and the support facilities on the basis of radionuclides and chemicals. The hazard classification determines the safety analysis requirements for a facility

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

    Science.gov (United States)

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

    2016-12-01

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

  17. Acquisition and processing of proportional chamber data

    International Nuclear Information System (INIS)

    Kozhevnikov, Yu.A.

    1987-01-01

    A data acquisition unit for proportional chambers is described which can select data belonging to individual groups of simultaneously triggered adjacent channels (clusters) and encodes them into a format suitable for further processing. The unit is built as a standard CAMAC module of double width, was designed to operate with hardware reading significant data only, and can serve up to 8192 detection channels. The unit can be tested independently and can operate with an external storage without connection to the crate bus. Two types of errors associated with data reception are detected and diagnosed in the course of data acquisition

  18. Recent advances in gas scintillation proportional counters

    International Nuclear Information System (INIS)

    Palmer, H.E.

    1975-01-01

    Various geometrical configurations for gas scintillation proportional counters have been investigated in order to determine which is best for use in a large volume, high efficiency counter for measuring low energy gamma and x-rays. A xenon filled counter having a rod anode inside a cylindrical cathode appears to provide the best configuration for providing a uniform field and the best resolution over the total volume of the counter. The details of construction and operating characteristics of various shaped counters are described. (U.S.)

  19. High pressure BF3 proportional counter

    International Nuclear Information System (INIS)

    Mihara, Masaru; Gotoh, Eiichiro; Kodama, Masahiro

    1978-01-01

    Plateau and pulse characteristics of high pressure BF 3 proportional counter were investigated in terms of counter geometry and gas pressure, in order to develop a small-sized and high-sensitive one. Description is given of the construction of improved gas filling equipment with filling procedure. A tentative brass counter, 67 mm in cathode diameter, 40 micron in anode diameter, filled to 1.2 kg/cm 2 revealed characteristics of 150 volts plateau range, the slope of which being 3% per 100 volts at the operation voltage of around 3.3 kV, and 103% full width at half-maximum in the pulse height distribution. (auth.)

  20. Designing an optimally proportional inorganic scintillator

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Jai, E-mail: jai.singh@cdu.edu.au [School of Engineering and IT, B-Purple-12, Faculty of EHSE, Charles Darwin University, NT 0909 (Australia); Koblov, Alexander [School of Engineering and IT, B-Purple-12, Faculty of EHSE, Charles Darwin University, NT 0909 (Australia)

    2012-09-01

    The nonproportionality observed in the light yield of inorganic scintillators is studied theoretically as a function of the rates of bimolecular and Auger quenching processes occurring within the electron track initiated by a gamma- or X-ray photon incident on a scintillator. Assuming a cylindrical track, the influence of the track radius and concentration of excitations created within the track on the scintillator light yield is also studied. Analysing the calculated light yield a guideline for inventing an optimally proportional scintillator with optimal energy resolution is presented.

  1. The Arabidopsis COX11 homolog is essential for cytochrome c oxidase activity

    Directory of Open Access Journals (Sweden)

    Ivan eRadin

    2015-12-01

    Full Text Available Members of the ubiquitous COX11 (cytochrome c oxidase 11 protein family are involved in copper delivery to the COX complex. In this work, we characterize the Arabidopsis thaliana COX11 homolog (encoded by locus At1g02410. Western blot analyses and confocal microscopy identified Arabidopsis COX11 as an integral mitochondrial protein. Despite sharing high sequence and structural similarities, the Arabidopsis COX11 is not able to functionally replace the Saccharomyces cerevisiae COX11 homolog. Nevertheless, further analysis confirmed the hypothesis that Arabidopsis COX11 is essential for COX activity. Disturbance of COX11 expression through knockdown (KD or overexpression (OE affected COX activity. In KD lines, the activity was reduced by ~50%, resulting in root growth inhibition, smaller rosettes and leaf curling. In OE lines, the reduction was less pronounced (~80% of the wild type, still resulting in root growth inhibition. Additionally, pollen germination was impaired in COX11 KD and OE plants. This effect on pollen germination can only partially be attributed to COX deficiency and may indicate a possible auxiliary role of COX11 in ROS metabolism. In agreement with its role in energy production, the COX11 promoter is highly active in cells and tissues with high-energy demand for example shoot and root meristems or vascular tissues of source and sink organs. In COX11 KD lines, the expression of the plasma-membrane copper transporter COPT2 and of several copper chaperones was upregulated, indicative of a retrograde signaling pathway pertinent to copper homeostasis. Based on our data, we postulate that COX11 is a mitochondrial chaperone, which plays an important role for plant growth and pollen germination as essential COX complex assembly factor.

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

    Science.gov (United States)

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

    2016-01-01

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

  3. Energy Proportionality for Disk Storage Using Replication

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jinoh; Rotem, Doron

    2010-09-09

    Energy saving has become a crucial concern in datacenters as several reports predict that the anticipated energy costs over a three year period will exceed hardware acquisition. In particular, saving energy for storage is of major importance as storage devices (and cooling them off) may contribute over 25 percent of the total energy consumed in a datacenter. Recent work introduced the concept of energy proportionality and argued that it is a more relevant metric than just energy saving as it takes into account the tradeoff between energy consumption and performance. In this paper, we present a novel approach, called FREP (Fractional Replication for Energy Proportionality), for energy management in large datacenters. FREP includes areplication strategy and basic functions to enable flexible energy management. Specifically, our method provides performance guarantees by adaptively controlling the power states of a group of disks based on observed and predicted workloads. Our experiments, using a set of real and synthetic traces, show that FREP dramatically reduces energy requirements with a minimal response time penalty.

  4. Amplifier Design for Proportional Ionization Chambers

    Energy Technology Data Exchange (ETDEWEB)

    Baker, W. H.

    1950-08-24

    This paper presents the requirements of a nuclear amplifier of short resolving time, designed to accept pulses of widely varying amplitudes. Data are given which show that a proportional ionization chamber loaded with a 1,000-ohm resistor develops pulses of 0.5 microsecond duration and several volts amplitude. Results indicate that seven basic requirements are imposed on the amplifier when counting soft beta and gamma radiation in the presence of alpha particles, without absorbers. It should, (1) have a fast recovery time, (2) have a relatively good low frequency response, (3) accept pulses of widely varying heights without developing spurious pulsed, (4) have a limiting output stage, (5) preserve the inherently short rise time of the chamber, (6) minimize pulse integration, and (7) have sufficient gain to detect the weak pulses well below the chamber voltage at which continuous discharge takes place. The results obtained with an amplifier which meets these requirements is described. A formula is derived which indicates that redesign of the proportional ionization chamber might eliminate the need for an amplifier. This may be possible if the radioactive particles are collimated parallel to the collecting electrode.

  5. Proportional-Integral-Resonant AC Current Controller

    Directory of Open Access Journals (Sweden)

    STOJIC, D.

    2017-02-01

    Full Text Available In this paper an improved stationary-frame AC current controller based on the proportional-integral-resonant control action (PIR is proposed. Namely, the novel two-parameter PIR controller is applied in the stationary-frame AC current control, accompanied by the corresponding parameter-tuning procedure. In this way, the proportional-resonant (PR controller, common in the stationary-frame AC current control, is extended by the integral (I action in order to enable the AC current DC component tracking, and, also, to enable the DC disturbance compensation, caused by the voltage source inverter (VSI nonidealities and by nonlinear loads. The proposed controller parameter-tuning procedure is based on the three-phase back-EMF-type load, which corresponds to a wide range of AC power converter applications, such as AC motor drives, uninterruptible power supplies, and active filters. While the PIR controllers commonly have three parameters, the novel controller has two. Also, the provided parameter-tuning procedure needs only one parameter to be tuned in relation to the load and power converter model parameters, since the second controller parameter is directly derived from the required controller bandwidth value. The dynamic performance of the proposed controller is verified by means of simulation and experimental runs.

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

    Science.gov (United States)

    Xu, Gongjun; Sen, Bodhisattva; Ying, Zhiliang

    2014-01-01

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

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

    OpenAIRE

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

    2003-01-01

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

  8. Hazard reduction in nanotechnology

    NARCIS (Netherlands)

    Reijnders, L.

    2008-01-01

    The release of hazardous substances is a matter of concern for nanotechnology. This may include some nanoparticles, reactants, by-products, and solvents. The use of low-hazard solvents may reduce the hazards from nanoparticle production and nanomaterial processing. The hazards of inorganic

  9. LC-MS/MS confirms that COX-1 drives vascular prostacyclin whilst gene expression pattern reveals non-vascular sites of COX-2 expression.

    Directory of Open Access Journals (Sweden)

    Nicholas S Kirkby

    Full Text Available There are two schools of thought regarding the cyclooxygenase (COX isoform active in the vasculature. Using urinary prostacyclin markers some groups have proposed that vascular COX-2 drives prostacyclin release. In contrast, we and others have found that COX-1, not COX-2, is responsible for vascular prostacyclin production. Our experiments have relied on immunoassays to detect the prostacyclin breakdown product, 6-keto-PGF1α and antibodies to detect COX-2 protein. Whilst these are standard approaches, used by many laboratories, antibody-based techniques are inherently indirect and have been criticized as limiting the conclusions that can be drawn. To address this question, we measured production of prostanoids, including 6-keto-PGF1α, by isolated vessels and in the circulation in vivo using liquid chromatography tandem mass spectrometry and found values essentially identical to those obtained by immunoassay. In addition, we determined expression from the Cox2 gene using a knockin reporter mouse in which luciferase activity reflects Cox2 gene expression. Using this we confirm the aorta to be essentially devoid of Cox2 driven expression. In contrast, thymus, renal medulla, and regions of the brain and gut expressed substantial levels of luciferase activity, which correlated well with COX-2-dependent prostanoid production. These data are consistent with the conclusion that COX-1 drives vascular prostacyclin release and puts the sparse expression of Cox2 in the vasculature in the context of the rest of the body. In doing so, we have identified the thymus, gut, brain and other tissues as target organs for consideration in developing a new understanding of how COX-2 protects the cardiovascular system.

  10. Proportional representation apportionment methods and their applications

    CERN Document Server

    Pukelsheim, Friedrich

    2017-01-01

    The book offers an in-depth study of the translation of vote counts into seat numbers in proportional representation systems  – an approach guided by practical needs. It also provides plenty of empirical instances illustrating the results. It analyzes in detail the 2014 elections to the European Parliament in the 28 member states, as well as the 2009 and 2013 elections to the German Bundestag. This second edition is a complete revision and expanded version of the first edition published in 2014, and many empirical election results that serve as examples have been updated. Further, a final chapter has been added assembling biographical sketches and authoritative quotes from individuals who pioneered the development of apportionment methodology. The mathematical exposition and the interrelations with political science and constitutional jurisprudence make this an apt resource for interdisciplinary courses and seminars on electoral systems and apportionment methods.

  11. Differential effects of selective cyclooxygenase (COX)-1 and COX-2 inhibitors on anorexic response and prostaglandin generation in various tissues induced by zymosan.

    Science.gov (United States)

    Naoi, Kazuhisa; Kogure, Suguru; Saito, Masataka; Hamazaki, Tomohito; Watanabe, Shiro

    2006-07-01

    We have shown that anorexic response is induced by intraperitoneal injection of zymosan in mice, although the role of prostaglandins in this response is relatively unknown as compared with lipopolysaccharide (LPS)-induced anorexic response. Indomethacin (0.5 and 2.0 mg/kg), a non-selective cyclooxygenase (COX) inhibitor, as well as meloxicam (0.5 mg/kg), a selective COX-2 inhibitor, but not FR122047 (2.0 mg/kg), a selective COX-1 inhibitor, attenuated zymosan-induced anorexia. Zymosan injection elevated COX-2 expression in brain and liver but not in small intestine and colon. Meloxicam (0.5 mg/kg) and FR122047 treatment (2.0 mg/kg) similarly suppressed the generation of brain prostaglandin E(2) (PGE(2)) and peritoneal prostacyclin (PGI(2)) upon zymosan injection. PGE(2) generation in liver upon zymosan injection was suppressed by meloxicam (0.5 mg/kg) but not by FR122047 treatment (2.0 mg/kg). Our observations suggest that COX-2 plays an important role in zymosan-induced anorexia, which is a similar feature in LPS-induced anorexic response. However, non-selective inhibition by selective COX-1 and COX-2 inhibitors of brain PGE(2) generation upon zymosan injection does not support the role of COX-2 expressed in brain in zymosan-induced anorexic response. PGE(2) generation in liver may account for peripheral role of COX-2 in zymosan-induced anorexic response.

  12. A duplicated coxI gene is associated with cytoplasmic male sterility ...

    Indian Academy of Sciences (India)

    The new CMS line is comparable to euplasmic lines for almost all characters, except for flowers which bear slender, needle-like anthers with aborted pollen. Detailed Southern analysis revealed two copies of coxI gene in the CMS line. One copy, coxI-1 is similar to the coxI gene of B. juncea, whereas the second copy, coxI-2 ...

  13. COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

    International Nuclear Information System (INIS)

    Asting, Annika Gustafsson; Carén, Helena; Andersson, Marianne; Lönnroth, Christina; Lagerstedt, Kristina; Lundholm, Kent

    2011-01-01

    Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4) showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3) were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue

  14. COX-2 Forms Regulatory Loop with YAP to Promote Proliferation and Tumorigenesis of Hepatocellular Carcinoma Cells.

    Science.gov (United States)

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

    2018-04-01

    COX-2 and YAP are shown to be highly associated with hepatocellular carcinoma (HCC) and frequently upregulated during tumor formation. However, despite their importance, whether there is a mutual interaction between COX-2 and YAP and how they regulate each other are not clear. In this paper, we showed that COX-2 overexpression in HCC cell lines resulted in increased levels of YAP mRNA, protein, and its target genes. COX-2 promoted proliferation of HCC cell lines, and knockdown of YAP antagonized this effect. In addition, our results indicated that EP2 and Wnt/β-Catenin mediate the transcriptional induction of YAP by COX-2. On the other hand, YAP increased COX-2 expression at the level of transcription requiring intact TEAD binding sites in the COX-2 promoter. Collectively, these findings indicated that COX-2 is not only a stimulus of YAP but also a target of Hippo-YAP pathway, thus forming a positive feedback circuit, COX-2-PGE 2 -EP2-Gαs-β-catenin-YAP-COX-2. In a further study, we showed that inhibition of YAP and COX-2 acted synergistically and more efficiently reduced the growth of HCC cells and tumor formation than either of them alone, suggesting that dual governing of YAP and COX-2 may lead to the discovery of promising therapeutic strategies for HCC patients via blocking this positive feedback loop. Copyright © 2018. Published by Elsevier Inc.

  15. Neoadjuvant selective COX-2 inhibition down-regulates important oncogenic pathways in patients with esophageal adenocarcinoma

    NARCIS (Netherlands)

    Tuynman, Jurriaan B.; Buskens, Christianne J.; Kemper, Kristel; ten Kate, Fiebo J. W.; Offerhaus, G. Johan A.; Richel, Dirk J.; van Lanschot, J. Jan B.

    2005-01-01

    OBJECTIVES: To evaluate the effects of neoadjuvant therapy with the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib in vitro and in patients with esophageal adenocarcinoma on COX-2 and MET expression. SUMMARY BACKGROUND DATA: High COX-2 and/or MET expression levels are negative prognostic

  16. Secretory phospholipase A(2) induces delayed neuronal COX-2 expression compared with glutamate

    DEFF Research Database (Denmark)

    Kolko, Miriam; Nielsen, Marianne; Bazan, Nicolas G

    2002-01-01

    and immunohistochemistry. An up-regulation of COX-2, c-fos, and c-jun, but not COX-1, was observed around the lesion as well as in the neocortex 4 hr after the injection. Hippocampal up-regulation of COX-2 was seen in dentate gyrus 8 hr after injection. When glutamate was injected, up-regulation of the early...

  17. COX-2 Forms Regulatory Loop with YAP to Promote Proliferation and Tumorigenesis of Hepatocellular Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Guanglin Xu

    2018-04-01

    Full Text Available COX-2 and YAP are shown to be highly associated with hepatocellular carcinoma (HCC and frequently upregulated during tumor formation. However, despite their importance, whether there is a mutual interaction between COX-2 and YAP and how they regulate each other are not clear. In this paper, we showed that COX-2 overexpression in HCC cell lines resulted in increased levels of YAP mRNA, protein, and its target genes. COX-2 promoted proliferation of HCC cell lines, and knockdown of YAP antagonized this effect. In addition, our results indicated that EP2 and Wnt/β-Catenin mediate the transcriptional induction of YAP by COX-2. On the other hand, YAP increased COX-2 expression at the level of transcription requiring intact TEAD binding sites in the COX-2 promoter. Collectively, these findings indicated that COX-2 is not only a stimulus of YAP but also a target of Hippo-YAP pathway, thus forming a positive feedback circuit, COX-2-PGE2-EP2-Gαs-β-catenin-YAP-COX-2. In a further study, we showed that inhibition of YAP and COX-2 acted synergistically and more efficiently reduced the growth of HCC cells and tumor formation than either of them alone, suggesting that dual governing of YAP and COX-2 may lead to the discovery of promising therapeutic strategies for HCC patients via blocking this positive feedback loop.

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

    Science.gov (United States)

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

    2016-12-01

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

  19. Efficacy and safety of COX-2 inhibitors for advanced non-small-cell lung cancer with chemotherapy: a meta-analysis.

    Science.gov (United States)

    Dai, Ping; Li, Jing; Ma, Xiao-Ping; Huang, Jian; Meng, Juan-Juan; Gong, Ping

    2018-01-01

    The study of cyclooxygenase-2 (COX-2) inhibitors is now mired in controversy. We performed a meta-analysis to assess the efficacy and safety profile of COX-2 inhibitors in patients with advanced non-small-cell lung cancer (NSCLC). A literature search of PubMed, EMBASE, the Cochrane Central databases, and ClinicalTrials.gov, up until March 26, 2017, identified relevant randomized controlled trials. Data analysis was performed using Stata 12.0. Six eligible trials (1,794 patients) were selected from the 407 studies that were identified initially. A significant difference, favoring COX-2 inhibitors plus chemotherapy over chemotherapy alone, was observed in the overall response rate (relative risk [RR] =1.25, 95% confidence interval [CI]: 1.06-1.48). Further, we conducted two subgroup analyses according to the type of COX-2 inhibitors (celecoxib, rofecoxib, or apricoxib) and treatment line (first or second chemotherapy). The first-line treatment includes: NP (changchun red bean + cisplatin or carboplatin), GP (double fluorine cytidine + cisplatin or carboplatin), or TP (paclitaxel + cisplatin or carboplatin, docetaxel + cisplatin or carboplatin). The second-line treatment includes two internationally recognized compounds, one is docetaxel and the other is the pemetrexed, both of which are individually selected. In subgroup analysis, significantly increased overall response rate (ORR) results were found for rofecoxib plus chemotherapy (RR =1.56, 95% CI: 1.08-2.25) and COX-2 inhibitor given with first-line chemotherapy (RR =1.27, 95% CI: 1.07-1.50). However, there was no difference between COX-2 inhibitors plus chemotherapy and chemotherapy alone in overall survival (hazard ratio [HR] =1.04, 95% CI: 0.91-1.18), progression-free survival (HR =0.97, 95% CI: 0.86-1.10), and 1-year survival rate (RR =1.03, 95% CI: 0.89-1.20). Toxicity did not differ significantly between COX-2 inhibitors plus chemotherapy and chemotherapy alone with the exception of leukopenia (RR =1.21, 95

  20. Southern Dietary Pattern is Associated With Hazard of Acute Coronary Heart Disease in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

    Science.gov (United States)

    Shikany, James M; Safford, Monika M; Newby, P K; Durant, Raegan W; Brown, Todd M; Judd, Suzanne E

    2015-09-01

    The association of overall diet, as characterized by dietary patterns, with risk of incident acute coronary heart disease (CHD) has not been studied extensively in samples including sociodemographic and regional diversity. We used data from 17 418 participants in Reasons for Geographic and Racial Differences in Stroke (REGARDS), a national, population-based, longitudinal study of white and black adults aged ≥45 years, enrolled from 2003 to 2007. We derived dietary patterns with factor analysis and used Cox proportional hazards regression to examine hazard of incident acute CHD events - nonfatal myocardial infarction and acute CHD death - associated with quartiles of consumption of each pattern, adjusted for various levels of covariates. Five primary dietary patterns emerged: Convenience, Plant-based, Sweets, Southern, and Alcohol and Salad. A total of 536 acute CHD events occurred over a median (interquartile range) 5.8 (2.1) years of follow-up. After adjustment for sociodemographics, lifestyle factors, and energy intake, highest consumers of the Southern pattern (characterized by added fats, fried food, eggs, organ and processed meats, and sugar-sweetened beverages) experienced a 56% higher hazard of acute CHD (comparing quartile 4 with quartile 1: hazard ratio, 1.56; 95% confidence interval, 1.17-2.08; P for trend across quartiles=0.003). Adding anthropometric and medical history variables to the model attenuated the association somewhat (hazard ratio, 1.37; 95% confidence interval, 1.01-1.85; P=0.036). A dietary pattern characteristic of the southern United States was associated with greater hazard of CHD in this sample of white and black adults in diverse regions of the United States. © 2015 American Heart Association, Inc.

  1. Search Region of Origin Honey Bee A. mellifera in Indonesia Region Using Mitochondrial DNA intergenic cox1/cox2

    Directory of Open Access Journals (Sweden)

    Mohamad Rusdi Hidayat

    2011-12-01

    Full Text Available Apis mellifera is a favourite honey bee for the beekeepers throughout many countries. This species comprise of 24 subspecies. Based on phylogeography and morphometric evidences, these subspecies have been grouped into four lineage; namely the African (A, Western and Northern Europe (M, Southeastern Europe (C, and Near Eastern (O. Apis mellifera have been imported to Indonesia since 1972, and mostly from Australia. However, until recently there are no data about the A. mellifera subspecies and the origin. Therefore the objective of this research is to determine the lineage of A. mellifera in Indonesia based on mtDNA intergenic region between cox1/cox2 genes. In this region there are two DNA fragments, P and Q fragnant, that can be used to determine the A. mellifera lineage. The methodology used consist of samples collection, DNA isolation, DNA amplification, DNA restriction using DraI enzyme, DNA sequencing, and DNA alignment using Clustal X and MEGA spftwares. DNA fragment amplified by using E2 and H1 primer revealed a 863 bp. Digestion of the region with the DraI restriction enzyme revealed one haplotype, which consist of five DNA fragments. Based on DNA sequences and DNA alignment, A. mellifera in Indonesia was homologue with the C lineage. Its subspecies is A. m. ligustica that lived natively in Italy, they were imported to Indonesia from Australia

  2. Calibration of proportional counters in microdosimetry

    International Nuclear Information System (INIS)

    Varma, M.N.

    1982-01-01

    Many microdosimetric spectra for low LET as well as high LET radiations are measured using commercially available (similar to EG and G) Rossi proportional counters. This paper discusses the corrections to be applied to data when calibration of the counter is made using one type of radiation, and then the counter is used in a different radiation field. The principal correction factor is due to differences in W-value of the radiation used for calibration and the radiation for which microdosimetric measurements are made. Both propane and methane base tissue-equivalent (TE) gases are used in these counters. When calibrating the detectors, it is important to use the correct stopping power value for that gas. Deviations in y-bar/sub F/ and y-bar/sub D/ are calculated for 60 Co using different extrapolation procedures from 0.15 keV/μm to zero event size. These deviations can be as large as 30%. Advantages of reporting microdosimetric parameters such as y-bar/sub F/ and y-bar/sub D/ above a certain minimum cut-off are discussed

  3. Evaluation of craniofacial proportions: A pilot study.

    Science.gov (United States)

    Sadeghian, Saied; Motamedi, Ali Mohammad Kalantar; Haerian, Alireza; Rafiei, Elahe

    2015-01-01

    Regarding the need for determining the cephalometric norms for each population and the advantages of proportional analyses, we evaluated the variables of McNamara and Schwartz analyses and their relation in a pilot study on 6-17 years old Iranian students and provided formulas, which show these relations. In this descriptive-analytical study, a tatal of cephalometric radiographs from the archive documents of Orthodontic Department of Isfahan Dental School was selected and traced. The variables of McNamara and Schwartz analyses were investigated. The data were analyzed by t-test and linear regression and Spearman correlation coefficient tests using SPSS 12 software, and the significance was set at 0.05. Then, a formula was suggested for predicting the relation between the jaws, cranium and face. The variables measured in this study were significantly different between the genders (P < 0.05), except for Co-Gn (P = 0.055), and they were higher in boys. All variables significantly increased (P < 0.05) with age from 6 to 17 years. The formulas presented in this study can be used for calculating the amount of PNS-APmax, Go-APmax and the Co-Gn, anterior nasal spine-menton in the Iranian population. Within the limitation of this study, the formula presented in this study might be considered to predict the relation between jaw dimensions and cranial base and facial dimensions in the Iranian population.

  4. Proportional counter measurements in neutron therapy beams

    International Nuclear Information System (INIS)

    Menzel, H.G.

    1984-01-01

    Dosimetry for clinical neutron therapy requires a characterization of radiation quality in addition to the specification of absorbed dose. Generally, a very simple approach has been adopted which consists in separating total absorbed dose into neutron and photon fractions. This is explained by the requirement of clinical dosimetry to apply methods suitable for routine measurements, by the lack of generally accepted improved alternatives, and by the fact that radiation quality is only one of several problems in neutron therapy not sufficiently solved. Spectra measured with low-pressure tissue-equivalent proportional counters (experimental microdosimetry) provide a detailed description of the physical properties of the radiation field at neutron therapy facilities. These descriptions are suitable for explaining the influence of different parameters (collimation, field size, phantom) on radiation quality. Although the physical properties of the radiation field as described by the measured microdosimetric distributions and quantities are not the only properties relevant for radiation effects, in general there are reasons to believe that they provide a suitable radiation quality characterization for the limited range of applications in neutron therapy. (author)

  5. Exact tests for Hardy-Weinberg proportions.

    Science.gov (United States)

    Engels, William R

    2009-12-01

    Exact conditional tests are often required to evaluate statistically whether a sample of diploids comes from a population with Hardy-Weinberg proportions or to confirm the accuracy of genotype assignments. This requirement is especially common when the sample includes multiple alleles and sparse data, thus rendering asymptotic methods, such as the common chi(2)-test, unreliable. Such an exact test can be performed using the likelihood ratio as its test statistic rather than the more commonly used probability test. Conceptual advantages in using the likelihood ratio are discussed. A substantially improved algorithm is described to permit the performance of a full-enumeration exact test on sample sizes that are too large for previous methods. An improved Monte Carlo algorithm is also proposed for samples that preclude full enumeration. These algorithms are about two orders of magnitude faster than those currently in use. Finally, methods are derived to compute the number of possible samples with a given set of allele counts, a useful quantity for evaluating the feasibility of the full enumeration procedure. Software implementing these methods, ExactoHW, is provided.

  6. Validation of models with proportional bias

    Directory of Open Access Journals (Sweden)

    Salvador Medina-Peralta

    2017-01-01

    Full Text Available Objective. This paper presents extensions to Freese’s statistical method for model-validation when proportional bias (PB is present in the predictions. The method is illustrated with data from a model that simulates grassland growth. Materials and methods. The extensions to validate models with PB were: the maximum anticipated error for the original proposal, hypothesis testing, and the maximum anticipated error for the alternative proposal, and the confidence interval for a quantile of error distribution. Results. The tested model had PB, which once removed, and with a confidence level of 95%, the magnitude of error does not surpass 1225.564 kg ha-1. Therefore, the validated model can be used to predict grassland growth. However, it would require a fit of its structure based on the presence of PB. Conclusions. The extensions presented to validate models with PB are applied without modification in the model structure. Once PB is corrected, the confidence interval for the quantile 1-α of the error distribution enables a higher bound for the magnitude of the prediction error and it can be used to evaluate the evolution of the model for a system prediction.

  7. Expression and Activity of COX-1 and COX-2 in Acanthamoeba sp.-Infected Lungs According to the Host Immunological Status.

    Science.gov (United States)

    Łanocha-Arendarczyk, Natalia; Baranowska-Bosiacka, Irena; Kot, Karolina; Gutowska, Izabela; Kolasa-Wołosiuk, Agnieszka; Chlubek, Dariusz; Kosik-Bogacka, Danuta

    2018-01-02

    Little is known about the pathomechanism of pulmonary infections caused by Acanthamoeba sp. Therefore, the aim of this study was to determine whether Acanthamoeba sp. may affect the expression and activity of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), resulting in the altered levels of their main products, prostaglandins (PGE₂) and thromboxane B₂ (TXB₂), in lungs of immunocompetent or immunosuppressed hosts. Acanthamoeba sp. induced a strong expression of COX-1 and COX-2 proteins in the lungs of immunocompetent mice, which, however, did not result in significant differences in the expression of PGE₂ and TXB₂. Our immunohistochemical analysis showed that immunosuppression induced by glucocorticoids in Acanthamoeba sp.-infected mice caused a decrease in COX-1 and COX-2 (not at the beginning of infection) in lung tissue. These results suggest that similar to COX-2, COX-1 is an important mediator of the pathophysiology in experimental pulmonary acanthamoebiasis. We suggest that the signaling pathways important for Acanthamoeba sp. induction of lung infection might interact with each other and depend on the host immune status.

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

    Science.gov (United States)

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

    2015-12-01

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

  9. COX-2 disruption leads to increased central vasopressin stores and impaired urine concentrating ability in mice

    DEFF Research Database (Denmark)

    Nørregaard, Rikke; Madsen, Kirsten; Hansen, Pernille B L

    2011-01-01

    RNA and peptide level, AVP plasma concentration, and AVP-regulated renal transport protein abundances were measured. In male COX-2(-/-), basal urine output and water intake were elevated while urine osmolality was decreased compared with WT. Water deprivation resulted in lower urine osmolality, higher plasma......-outer medulla), AQP3 (all regions), and UT-A1 (inner medulla) protein abundances were elevated in COX-2(-/-) at baseline and further increased after WD. COX-2(-/-) mice had elevated plasma urea and creatinine and accumulation of small subcapsular glomeruli. In conclusion, hypothalamic COX-2 activity......It was hypothesized that cyclooxygenase-2 (COX-2) activity promotes urine concentrating ability through stimulation of vasopressin (AVP) release after water deprivation (WD). COX-2-deficient (COX-2(-/-), C57BL/6) and wild-type (WT) mice were water deprived for 24 h, and water balance, central AVP m...

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

    Science.gov (United States)

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

    2010-09-01

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

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

    Science.gov (United States)

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

    2013-11-20

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

  12. Hepatic ischemia and reperfusion injury in the absence of myeloid cell-derived COX-2 in mice.

    Directory of Open Access Journals (Sweden)

    Sergio Duarte

    Full Text Available Cyclooxygenase-2 (COX-2 is a mediator of hepatic ischemia and reperfusion injury (IRI. While both global COX-2 deletion and pharmacologic COX-2 inhibition ameliorate liver IRI, the clinical use of COX-2 inhibitors has been linked to increased risks of heart attack and stroke. Therefore, a better understanding of the role of COX-2 in different cell types may lead to improved therapeutic strategies for hepatic IRI. Macrophages of myeloid origin are currently considered to be important sources of the COX-2 in damaged livers. Here, we used a Cox-2flox conditional knockout mouse (COX-2-M/-M to examine the function of COX-2 expression in myeloid cells during liver IRI. COX-2-M/-M mice and their WT control littermates were subjected to partial liver ischemia followed by reperfusion. COX-2-M/-M macrophages did not express COX-2 upon lipopolysaccharide stimulation and COX-2-M/-M livers showed reduced levels of COX-2 protein post-IRI. Nevertheless, selective deletion of myeloid cell-derived COX-2 failed to ameliorate liver IRI; serum transaminases and histology were comparable in both COX-2-M/-M and WT mice. COX-2-M/-M livers, like WT livers, developed extensive necrosis, vascular congestion, leukocyte infiltration and matrix metalloproteinase-9 (MMP-9 expression post-reperfusion. In addition, myeloid COX-2 deletion led to a transient increase in IL-6 levels after hepatic reperfusion, when compared to controls. Administration of celecoxib, a selective COX-2 inhibitor, resulted in significantly improved liver function and histology in both COX-2-M/-M and WT mice post-reperfusion, providing evidence that COX-2-mediated liver IRI is caused by COX-2 derived from a source(s other than myeloid cells. In conclusion, these results support the view that myeloid COX-2, including myeloid-macrophage COX-2, is not responsible for the hepatic IRI phenotype.

  13. RASAM Hazard Identification

    OpenAIRE

    2002-01-01

    Interactive Media Element This media helps students refine their understanding of the various types of hazards; mishaps, hazards, causal factors. Last modified: 5/18/2009 SW4582 Weapon Systems Software Safety

  14. Hazard Analysis Database Report

    CERN Document Server

    Grams, W H

    2000-01-01

    The Hazard Analysis Database was developed in conjunction with the hazard analysis activities conducted in accordance with DOE-STD-3009-94, Preparation Guide for U S . Department of Energy Nonreactor Nuclear Facility Safety Analysis Reports, for HNF-SD-WM-SAR-067, Tank Farms Final Safety Analysis Report (FSAR). The FSAR is part of the approved Authorization Basis (AB) for the River Protection Project (RPP). This document describes, identifies, and defines the contents and structure of the Tank Farms FSAR Hazard Analysis Database and documents the configuration control changes made to the database. The Hazard Analysis Database contains the collection of information generated during the initial hazard evaluations and the subsequent hazard and accident analysis activities. The Hazard Analysis Database supports the preparation of Chapters 3 ,4 , and 5 of the Tank Farms FSAR and the Unreviewed Safety Question (USQ) process and consists of two major, interrelated data sets: (1) Hazard Analysis Database: Data from t...

  15. Handling Hazardous Materials.

    Science.gov (United States)

    Piper, James; Piverotto, John

    1990-01-01

    Describes a 16-hour course in hazard communication for vocational instructors, which teaches the proper use, storage, and disposal of hazardous materials in the laboratory as well as techniques for teaching safety. (SK)

  16. Global Landslide Hazard Distribution

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Landslide Hazard Distribution is a 2.5 minute grid of global landslide and snow avalanche hazards based upon work of the Norwegian Geotechnical Institute...

  17. Hazard function theory for nonstationary natural hazards

    Science.gov (United States)

    Read, Laura K.; Vogel, Richard M.

    2016-04-01

    Impact from natural hazards is a shared global problem that causes tremendous loss of life and property, economic cost, and damage to the environment. Increasingly, many natural processes show evidence of nonstationary behavior including wind speeds, landslides, wildfires, precipitation, streamflow, sea levels, and earthquakes. Traditional probabilistic analysis of natural hazards based on peaks over threshold (POT) generally assumes stationarity in the magnitudes and arrivals of events, i.e., that the probability of exceedance of some critical event is constant through time. Given increasing evidence of trends in natural hazards, new methods are needed to characterize their probabilistic behavior. The well-developed field of hazard function analysis (HFA) is ideally suited to this problem because its primary goal is to describe changes in the exceedance probability of an event over time. HFA is widely used in medicine, manufacturing, actuarial statistics, reliability engineering, economics, and elsewhere. HFA provides a rich theory to relate the natural hazard event series (X) with its failure time series (T), enabling computation of corresponding average return periods, risk, and reliabilities associated with nonstationary event series. This work investigates the suitability of HFA to characterize nonstationary natural hazards whose POT magnitudes are assumed to follow the widely applied generalized Pareto model. We derive the hazard function for this case and demonstrate how metrics such as reliability and average return period are impacted by nonstationarity and discuss the implications for planning and design. Our theoretical analysis linking hazard random variable X with corresponding failure time series T should have application to a wide class of natural hazards with opportunities for future extensions.

  18. Modern management of paediatric burns | Cox | Continuing Medical ...

    African Journals Online (AJOL)

    Burns in children differ in multiple aspects from those in adults; the extent and depth of the burn injury are often more severe, the child's body proportions differ, resulting in greater evaporative water and heat loss, and fluid requirements are therefore generally greater. Importantly, many childhood burns are preventable.

  19. [Dexketoprofene, selective cox-1 inhibitor nsaids, without gastrointestinal injury in rats].

    Science.gov (United States)

    Laudanno, O M; Piombo, Gabriela; Cesolari, J A M; Godoy, Alicia; Rocaspana, Adriana; Aramberry, L

    2002-05-01

    Dexketoprofene (De) NSAID was studied as a selective COX-1 inhibitor in comparison with Ketorolac (Ke), a mainly COX-1 inhibitor. De and Ke were administered to different groups of animals in a dose-dependent manner, i.e., 3-15 and 25 mgs/kg. The gastrointestinal mucosa damage was macroscopically and microscopically quantified at 24 hs, as well as leukocyte infiltration (LI) and neosinophilia. Similarly, Indomethacin (Indo) damage (COX-1-COX-2), with 25 mgs/kg. Dose was compared. On the other hand, De and Ke at inhibitory selective COX-1 dose (3 mg/kg) plus Celecoxib, selective COX-2 inhibitor, yielding no gastrointestinal damage, with decreased LI and without neutrophilia, the same as Ke (n.s.). Similarly De at higher dose (2.5 mgs/kg), produced minimal gastrointestinal lesions, showing a preferential COX-1 inhibitor behavior. Ke and Indo produced important gastrointestinal necrotic and erosive lesions with remarkable LI and neutrophilia (p < 0.001). On the other hand, COX-1 De dose plus Celecoxib produced evident gastrointestinal lesions, increased LI and neutrophilia, the same as Indo, pointing out that the gastrointestinal damage is due to COX-1 and COX-2 inhibition.

  20. High-Dimensional Additive Hazards Regression for Oral Squamous Cell Carcinoma Using Microarray Data: A Comparative Study

    Directory of Open Access Journals (Sweden)

    Omid Hamidi

    2014-01-01

    Full Text Available Microarray technology results in high-dimensional and low-sample size data sets. Therefore, fitting sparse models is substantial because only a small number of influential genes can reliably be identified. A number of variable selection approaches have been proposed for high-dimensional time-to-event data based on Cox proportional hazards where censoring is present. The present study applied three sparse variable selection techniques of Lasso, smoothly clipped absolute deviation and the smooth integration of counting, and absolute deviation for gene expression survival time data using the additive risk model which is adopted when the absolute effects of multiple predictors on the hazard function are of interest. The performances of used techniques were evaluated by time dependent ROC curve and bootstrap .632+ prediction error curves. The selected genes by all methods were highly significant (P<0.001. The Lasso showed maximum median of area under ROC curve over time (0.95 and smoothly clipped absolute deviation showed the lowest prediction error (0.105. It was observed that the selected genes by all methods improved the prediction of purely clinical model indicating the valuable information containing in the microarray features. So it was concluded that used approaches can satisfactorily predict survival based on selected gene expression measurements.

  1. Evolution of nonsteroidal anti-inflammatory drugs (NSAIDs): cyclooxygenase (COX) inhibition and beyond.

    Science.gov (United States)

    Rao, Praveen; Knaus, Edward E

    2008-09-20

    NSAIDs constitute an important class of drugs with therapeutic applications that have spanned several centuries. Treatment of inflammatory conditions such as rheumatoid arthritis (RA) and osteoarthritis (OA) starting from the classic drug aspirin to the recent rise and fall of selective COX-2 inhibitors has provided an enthralling evolution. Efforts to discover an ultimate magic bullet to treat inflammation continues to be an important drug design challenge. This review traces the origins of NSAIDs, their mechanism of action at the molecular level such as cyclooxygenase (COX) inhibition, development of selective COX-2 inhibitors, their adverse cardiovascular effects, and some recent developments targeted to the design of effective anti-inflammatory agents with reduced side effects. Literature data is presented describing important discoveries pertaining to the sequential development of classical NSAIDs and then selective COX-2 inhibitors, their mechanism of action, the structural basis for COX inhibition, and recent discoveries. A brief history of the development of NSAIDs and the market withdrawal of selective COX-2 inhibitors is explained, followed by the description of prostaglandin biosynthesis, COX isoforms, structure and function. The structural basis for COX-1 and COX-2 inhibition is described along with methods used to evaluate COX-1/COX-2 inhibition. This is followed by a section that encompasses the major chemical classes of selective COX-2 inhibitors. The final section describes briefly some of the recent advances toward developing effective anti-inflammatory agents such as nitric oxide donor NO-NSAIDs, dual COX/LOX inhibitors and anti-TNF therapy. A great deal of progress has been made toward developing novel anti-inflammatory agents. In spite of the tremendous advances in the last decade, the design and development of a safe, effective and economical therapy for treating inflammatory conditions still presents a major challenge.

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

    Science.gov (United States)

    Chakraborty, Santanu; Sengupta, Chandana; Roy, Kunal

    2004-09-20

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

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

    Science.gov (United States)

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

    2007-09-10

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

  4. Hazardous Waste: Learn the Basics of Hazardous Waste

    Science.gov (United States)

    ... Page Contact Us to ask a question, provide feedback, or report a problem. Hazardous Waste Hazardous Waste Home Learn the Basics of Hazardous Waste Hazardous Waste Management Generation Identification Definition of Solid Waste Exclusions Characterization Delistings Transportation Land ...

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

    Directory of Open Access Journals (Sweden)

    Qing-Yan Yin

    2017-01-01

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

  6. Factors associated with methadone treatment duration: a Cox regression analysis.

    Directory of Open Access Journals (Sweden)

    Chao-Kuang Lin

    Full Text Available This study examined retention rates and associated predictors of methadone maintenance treatment (MMT duration among 128 newly admitted patients in Taiwan. A semi-structured questionnaire was used to obtain demographic and drug use history. Daily records of methadone taken and test results for HIV, HCV, and morphine toxicology were taken from a computerized medical registry. Cox regression analyses were performed to examine factors associated with MMT duration. MMT retention rates were 80.5%, 68.8%, 53.9%, and 41.4% for 3, 6, 12, and 18 months, respectively. Excluding 38 patients incarcerated during the study period, retention rates were 81.1%, 73.3%, 61.1%, and 48.9% for 3 months, 6 months, 12 months, and 18 months, respectively. No participant seroconverted to HIV and 1 died during the 18-months follow-up. Results showed that being female, imprisonment, a longer distance from house to clinic, having a lower methadone dose after 30 days, being HCV positive, and in the New Taipei city program predicted early patient dropout. The findings suggest favorable MMT outcomes of HIV seroincidence and mortality. Results indicate that the need to minimize travel distance and to provide programs that meet women's requirements justify expansion of MMT clinics in Taiwan.

  7. Population death sequences and Cox processes driven by interacting Feller diffusions

    CERN Document Server

    Wei Gang; Feng Jian Feng

    2002-01-01

    We carry out a complete study on the relationship between Cox processes driven by interacting Feller diffusions and death sequences of immigration-emigration linked population networks. It is first proved that the Cox process driven by a Feller diffusion is equivalent to the death sequence of a birth and death process. The conclusion is then generalized to the case of Cox processes driven by interacting Feller diffusions and death sequences of interacting populations.

  8. Population death sequences and Cox processes driven by interacting Feller diffusions

    International Nuclear Information System (INIS)

    Wei Gang; Clifford, Peter; Feng Jianfeng

    2002-01-01

    We carry out a complete study on the relationship between Cox processes driven by interacting Feller diffusions and death sequences of immigration-emigration linked population networks. It is first proved that the Cox process driven by a Feller diffusion is equivalent to the death sequence of a birth and death process. The conclusion is then generalized to the case of Cox processes driven by interacting Feller diffusions and death sequences of interacting populations

  9. Hazard Analysis Database Report

    Energy Technology Data Exchange (ETDEWEB)

    GAULT, G.W.

    1999-10-13

    The Hazard Analysis Database was developed in conjunction with the hazard analysis activities conducted in accordance with DOE-STD-3009-94, Preparation Guide for US Department of Energy Nonreactor Nuclear Facility Safety Analysis Reports, for the Tank Waste Remediation System (TWRS) Final Safety Analysis Report (FSAR). The FSAR is part of the approved TWRS Authorization Basis (AB). This document describes, identifies, and defines the contents and structure of the TWRS FSAR Hazard Analysis Database and documents the configuration control changes made to the database. The TWRS Hazard Analysis Database contains the collection of information generated during the initial hazard evaluations and the subsequent hazard and accident analysis activities. The database supports the preparation of Chapters 3,4, and 5 of the TWRS FSAR and the USQ process and consists of two major, interrelated data sets: (1) Hazard Evaluation Database--Data from the results of the hazard evaluations; and (2) Hazard Topography Database--Data from the system familiarization and hazard identification.

  10. COX Inhibition Profile and Molecular Docking Studies of Some 2-(Trimethoxyphenyl)-Thiazoles.

    Science.gov (United States)

    Oniga, Smaranda Dafina; Pacureanu, Liliana; Stoica, Cristina Ioana; Palage, Mariana Doina; Crăciun, Alexandra; Rusu, Laurentiu Răzvan; Crisan, Elena-Luminita; Araniciu, Cătălin

    2017-09-09

    Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used therapeutic agents that exhibit frequent and sometimes severe adverse effects, including gastrointestinal ulcerations and cardiovascular disorders. In an effort to obtain safer NSAIDs, we assessed the direct cyclooxygenase (COX) inhibition activity and we investigated the potential COX binding mode of some previously reported 2-(trimethoxyphenyl)-thiazoles. The in vitro COX inhibition assays were performed against ovine COX-1 and human recombinant COX-2. Molecular docking studies were performed to explain the possible interactions between the inhibitors and both COX isoforms binding pockets. Four of the tested compounds proved to be good inhibitors of both COX isoforms, but only compound A3 showed a good COX-2 selectivity index, similar to meloxicam. The plausible binding mode of compound A3 revealed hydrogen bond interactions with binding site key residues including Arg120, Tyr355, Ser530, Met522 and Trp387, whereas hydrophobic contacts were detected with Leu352, Val349, Leu359, Phe518, Gly526, and Ala527. Computationally predicted pharmacokinetic profile revealed A3 as lead candidate. The present data prove that the investigated compounds inhibit COX and thus confirm the previously reported in vivo anti-inflammatory screening results suggesting that A3 is a suitable candidate for further development as a NSAID.

  11. COX-2 and PPAR-γ confer cannabidiol-induced apoptosis of human lung cancer cells.

    Science.gov (United States)

    Ramer, Robert; Heinemann, Katharina; Merkord, Jutta; Rohde, Helga; Salamon, Achim; Linnebacher, Michael; Hinz, Burkhard

    2013-01-01

    The antitumorigenic mechanism of cannabidiol is still controversial. This study investigates the role of COX-2 and PPAR-γ in cannabidiol's proapoptotic and tumor-regressive action. In lung cancer cell lines (A549, H460) and primary cells from a patient with lung cancer, cannabidiol elicited decreased viability associated with apoptosis. Apoptotic cell death by cannabidiol was suppressed by NS-398 (COX-2 inhibitor), GW9662 (PPAR-γ antagonist), and siRNA targeting COX-2 and PPAR-γ. Cannabidiol-induced apoptosis was paralleled by upregulation of COX-2 and PPAR-γ mRNA and protein expression with a maximum induction of COX-2 mRNA after 8 hours and continuous increases of PPAR-γ mRNA when compared with vehicle. In response to cannabidiol, tumor cell lines exhibited increased levels of COX-2-dependent prostaglandins (PG) among which PGD(2) and 15-deoxy-Δ(12,14)-PGJ(2) (15d-PGJ(2)) caused a translocation of PPAR-γ to the nucleus and induced a PPAR-γ-dependent apoptotic cell death. Moreover, in A549-xenografted nude mice, cannabidiol caused upregulation of COX-2 and PPAR-γ in tumor tissue and tumor regression that was reversible by GW9662. Together, our data show a novel proapoptotic mechanism of cannabidiol involving initial upregulation of COX-2 and PPAR-γ and a subsequent nuclear translocation of PPAR-γ by COX-2-dependent PGs.

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

    Science.gov (United States)

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

    2002-04-01

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

  13. Identification of N-Acetyldopamine Dimers from the Dung Beetle Catharsius molossus and Their COX-1 and COX-2 Inhibitory Activities

    Directory of Open Access Journals (Sweden)

    Juan Lu

    2015-08-01

    Full Text Available Recent studies focusing on identifying the biological agents of Catharsius molossus have led to the identification of three new N-acetyldopamine dimers molossusamide A–C (1-3 and two known compounds 4 and 5. The structures of the new compounds were identified by comprehensive spectroscopic evidences. Compound 4 was found to have inhibitory effects towards COX-1 and COX-2.

  14. Genomic and lipidomic analyses differentiate the compensatory roles of two COX isoforms during systemic inflammation in mice.

    Science.gov (United States)

    Li, Xinzhi; Mazaleuskaya, Liudmila L; Ballantyne, Laurel L; Meng, Hu; FitzGerald, Garret A; Funk, Colin D

    2018-01-01

    Both cyclooxygenase (COX)-1 and COX-2, encoded by Ptgs1 and Ptgs2 , function coordinately during inflammation. But the relative contributions and compensations of COX-1 and COX-2 to inflammatory responses remain unanswered. We used three engineered mouse lines where the Ptgs1 and Ptgs2 genes substitute for one another to discriminate the distinct roles and interchangeability of COX isoforms during systemic inflammation. In macrophages, kidneys, and lungs, "flipped" Ptgs genes generate a "reversed" COX expression pattern, where the knock-in COX-2 is expressed constitutively and the knock-in COX-1 is lipopolysaccharide inducible. A panel of eicosanoids detected in serum and kidney demonstrates that prostaglandin (PG) biosynthesis requires native COX-1 and cannot be rescued by the knock-in COX-2. Our data further reveal preferential compensation of COX isoforms for prostanoid production in macrophages and throughout the body, as reflected by urinary PG metabolites. NanoString analysis indicates that inflammatory networks can be maintained by isoform substitution in inflamed macrophages. However, COX-1>COX-2 macrophages show reduced activation of inflammatory signaling pathways, indicating that COX-1 may be replaced by COX-2 within this complex milieu, but not vice versa. Collectively, each COX isoform plays a distinct role subject to subcellular environment and tissue/cell-specific conditions, leading to subtle compensatory differences during systemic inflammation. Copyright © 2018 by the American Society for Biochemistry and Molecular Biology, Inc.

  15. Long-Term Survival in Young Women: Hazards and Competing Risks after Thyroid Cancer

    International Nuclear Information System (INIS)

    Stroup, A. M.; Harrell, C. J.; Herget, K. A.

    2012-01-01

    Differentiated thyroid cancers (DTCs) are one of the most common and survivable cancers diagnosed in women. We examine factors associated with long-term survival and competing risks of death in women diagnosed with DTC under the age of 40 (<40) and aged 40 and older (40+). Methods. SEER data was used to identify DTCs diagnosed in women from 1975 to 2009. We examined overall (OS), disease-specific (DSS), other cancer (OCS), and non-cancer-related (NCS) survival using multivariate Cox proportional hazards modeling. Results. Observed survival was 97.2% for <40 (n=14,540) and 82.5% for 40+ (n=20,513). Distant stage (HR=1.96, 95% CI 1.23-3.07), non-Hispanic Black (HR=2.04, 95% CI 1.45-2.87), being unmarried (HR=1.26, 95% 1.03-1.54), and subsequent primary cancers (HR=4.63, 95% CI 3.76-5.71) were significant for OS in women <40. Age was an effect modifier for all survival outcomes. Racial disparities in NCS were most pronounced for young non-Hispanic black women (HR=3.36, 95% CI 2.17-5.22). Women in both age groups were more likely to die from other causes. Conclusions. Age at diagnosis remains one of the strongest prognostic factors for thyroid cancer survival. More directed efforts to ensure effective care for co morbid conditions are needed to reduce mortality from other causes.

  16. DOE Hazardous Waste Program

    International Nuclear Information System (INIS)

    Eyman, L.D.; Craig, R.B.

    1985-01-01

    The goal of the DOE Hazardous Waste Program is to support the implementation and improvement of hazardous-chemical and mixed-radioactive-waste management such that public health, safety, and the environment are protected and DOE missions are effectively accomplished. The strategy for accomplishing this goal is to define the character and magnitude of hazardous wastes emanating from DOE facilities, determine what DOE resources are available to address these problems, define the regulatory and operational constraints, and develop programs and plans to resolve hazardous waste issues. Over the longer term the program will support the adaptation and application of technologies to meet hazardous waste management needs and to implement an integrated, DOE-wide hazardous waste management strategy. 1 reference, 1 figure

  17. Software safety hazard analysis

    International Nuclear Information System (INIS)

    Lawrence, J.D.

    1996-02-01

    Techniques for analyzing the safety and reliability of analog-based electronic protection systems that serve to mitigate hazards in process control systems have been developed over many years, and are reasonably well understood. An example is the protection system in a nuclear power plant. The extension of these techniques to systems which include digital computers is not well developed, and there is little consensus among software engineering experts and safety experts on how to analyze such systems. One possible technique is to extend hazard analysis to include digital computer-based systems. Software is frequently overlooked during system hazard analyses, but this is unacceptable when the software is in control of a potentially hazardous operation. In such cases, hazard analysis should be extended to fully cover the software. A method for performing software hazard analysis is proposed in this paper

  18. Hazards in the theater.

    Science.gov (United States)

    Rossol, M; Hinkamp, D

    2001-01-01

    The authors offer a survey of the myriad and unique safety and health hazards faced past and present by performers and theatrical workers, from preproduction work, through the show, and during the strike (dismantling). Special emphasis is given to health hazards posed by the many new plastic resin systems and adhesives used in set, prop, and costume construction; the hazards of special-effect fogs, smokes, haze, dusts, and pyrotechnic emissions; and theatrical makeup.

  19. Disposal of hazardous wastes

    International Nuclear Information System (INIS)

    Barnhart, B.J.

    1978-01-01

    The Fifth Life Sciences Symposium entitled Hazardous Solid Wastes and Their Disposal on October 12 through 14, 1977 was summarized. The topic was the passage of the National Resources Conservation and Recovery Act of 1976 will force some type of action on all hazardous solid wastes. Some major points covered were: the formulation of a definition of a hazardous solid waste, assessment of long-term risk, list of specific materials or general criteria to specify the wastes of concern, Bioethics, sources of hazardous waste, industrial and agricultural wastes, coal wastes, radioactive wastes, and disposal of wastes

  20. Transport of hazardous goods

    International Nuclear Information System (INIS)

    1989-01-01

    The course 'Transport of hazardous goods' was held in Berlin in November 1988 in cooperation with the Bundesanstalt fuer Materialforschung und -pruefung. From all lecturs, two are recorded separately: 'Safety of tank trucks - requirements on the tank, development possibiities of active and passive safety' and 'Requirements on the transport of radioactive materials - possible derivations for other hazardous goods'. The other lectures deal with hazardous goods law, requirements on packinging, risk assessment, railroad transport, hazardous goods road network, insurance matters, EC regulations, and waste tourism. (HSCH) [de

  1. Spatial Proportional Reasoning Is Associated with Formal Knowledge about Fractions

    Science.gov (United States)

    Möhring, Wenke; Newcombe, Nora S.; Levine, Susan C.; Frick, Andrea

    2016-01-01

    Proportional reasoning involves thinking about parts and wholes (i.e., about fractional quantities). Yet, research on proportional reasoning and fraction learning has proceeded separately. This study assessed proportional reasoning and formal fraction knowledge in 8- to 10-year-olds. Participants (N = 52) saw combinations of cherry juice and water…

  2. Effect of uric acid on inflammatory COX-2 and ROS pathways in vascular smooth muscle cells.

    Science.gov (United States)

    Oğuz, Nurgül; Kırça, Mustafa; Çetin, Arzu; Yeşilkaya, Akın

    2017-10-01

    Hyperuricemia is thought to play a role in cardiovascular diseases (CVD), including hypertension, coronary artery disease and atherosclerosis. However, exactly how uric acid contributes to these pathologies is unknown. An underlying mechanism of inflammatory diseases, such as atherosclerosis, includes enhanced production of cyclooxygenase-2 (COX-2) and superoxide anion. Here, we aimed to examine the effect of uric acid on inflammatory COX-2 and superoxide anion production and to determine the role of losartan. Primarily cultured vascular smooth muscle cells (VSMCs) were time and dose-dependently induced by uric acid and COX-2 and superoxide anion levels were measured. COX-2 levels were determined by ELISA, and superoxide anion was measured by the superoxide dismutase (SOD)-inhibitable reduction of ferricytochrome c method. Uric acid elevated COX-2 levels in a time-dependent manner. Angiotensin-II receptor blocker, losartan, diminished uric-acid-induced COX-2 elevation. Uric acid also increased superoxide anion level in VSMCs. Uric acid plays an important role in CVD pathogenesis by inducing inflammatory COX-2 and ROS pathways. This is the first study demonstrating losartan's ability to reduce uric-acid-induced COX-2 elevation.

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

    Science.gov (United States)

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

    2018-03-15

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

  4. Over-expression of COX-2 mRNA in colorectal cancer

    NARCIS (Netherlands)

    Roelofs, H.M.J.; Morsche, R.H.M. te; Heumen, B.W.H van; Nagengast, F.M.; Peters, W.H.M.

    2014-01-01

    BACKGROUND: Cyclooxygenase-2 (COX-2, PTGS2) is an enzyme involved in the synthesis of prostaglandins and thromboxanes, which are regulators of biologic processes such as inflammation, cell proliferation and angiogenesis. COX-2 over-expression was reported in many (pre) malignant tissues, but data

  5. Prognostic significance of COX-2 and b-catenin in colorectal ...

    African Journals Online (AJOL)

    Both COX-2 and b-catenin expression correlated with a higher incidence of shorter disease free survival. Conclusion: Both b-catenin and COX-2 expression may play an important role in the evolution of colon carcinogenesis. Increased expression of both could be used as a marker of tumor progression and poor prognosis.

  6. Protective effect of NSAIDs on cancer and influence of COX-2 C-765G genotype

    NARCIS (Netherlands)

    C. Siemes (Claire); L.E. Visser (Loes); J.W.W. Coebergh (Jan Willem); A. Hofman (Albert); A.G. Uitterlinden (André); B.H.Ch. Stricker (Bruno)

    2008-01-01

    textabstractPurpose: Inhibition of COX-2 enzymes is a frequently suggested mechanism for the beneficial effects of NSAIDs on carcinogenesis. The aim of this study was to explore the role of cumulative NSAID use on four common non-skin related cancers and modification by COX-2 G-765C genotype.

  7. Expression of COX-2 and HER-2 in colorectal cancer and their correlation.

    Science.gov (United States)

    Wu, Qi-Bing; Sun, Guo-Ping

    2015-05-28

    To detect the expression of COX-2 and HER-2 in colorectal cancer and to analyze their correlation and clinical significance. A total of 1026 colorectal cancer surgical specimens were collected from patients treated from December 2002 to December 2007 at the First Affiliated Hospital of Anhui Medical University. All specimens were made into 4-μm slices. The expression of COX-2 and HER-2 were detected by immunohistochemistry using the streptavidin-biotin-peroxidase method. The correlations between COX-2 and HER-2 expression and colorectal cancer clinical features were analyzed. The positive rates of COX-2 and HER-2 expression in colorectal cancer were 77.97% (800/1026) and 46.20% (474/1026), respectively. There was a significant correlation between COX-2 and HER-2 expression in colorectal cancer (P colorectal cancer, the positive COX-2 and HER-2 expression rates were 82.80% (443/535) and 57.94% (310/535), respectively. In patients with poorly differentiated colorectal cancer, the positive expression rates were 74.49% (210/282) and 52.84% (149/282), respectively (P colorectal cancer. COX-2 and HER-2 expression had no significant correlation with sex, age, or tumor location. COX-2 and HER-2 are important markers for invasion and metastasis of colorectal cancer, and they act together to regulate the invasion and metastasis of colorectal cancer.

  8. Transactivation of EGFR by LPS induces COX-2 expression in enterocytes.

    Directory of Open Access Journals (Sweden)

    Steven J McElroy

    Full Text Available Necrotizing enterocolitis (NEC is the leading cause of gastrointestinal morbidity and mortality in preterm infants. NEC is characterized by an exaggerated inflammatory response to bacterial flora leading to bowel necrosis. Bacterial lipopolysaccharide (LPS mediates inflammation through TLR4 activation and is a key molecule in the pathogenesis of NEC. However, LPS also induces cyclooxygenase-2 (COX-2, which promotes intestinal barrier restitution through stimulation of intestinal cell survival, proliferation, and migration. Epidermal growth factor receptor (EGFR activation prevents experimental NEC and may play a critical role in LPS-stimulated COX-2 production. We hypothesized that EGFR is required for LPS induction of COX-2 expression. Our data show that inhibiting EGFR kinase activity blocks LPS-induced COX-2 expression in small intestinal epithelial cells. LPS induction of COX-2 requires Src-family kinase signaling while LPS transactivation of EGFR requires matrix metalloprotease (MMP activity. EGFR tyrosine kinase inhibitors block LPS stimulation of mitogen-activated protein kinase ERK, suggesting an important role of the MAPK/ERK pathway in EGFR-mediated COX-2 expression. LPS stimulates proliferation of IEC-6 cells, but this stimulation is inhibited with either the EGFR kinase inhibitor AG1478, or the selective COX-2 inhibitor Celecoxib. Taken together, these data show that EGFR plays an important role in LPS-induction of COX-2 expression in enterocytes, which may be one mechanism for EGF in inhibition of NEC.

  9. Comparison of COX2 expression between oral squamous cell carcinoma, leukoplakia and normal mucosa.

    Science.gov (United States)

    Amirchaghmaghi, Maryam; Mohtasham, Nooshin; Mozaffari, Pegah Mosannen

    2012-03-01

    To compare cyclooxygenase 2 expression (COX2-E) between normal, oral leukoplakia lesions and different grades of oral squamous cell carcinoma (SCC). Around 90 paraffin embedded blocks consisting of 45 SCC, 15 leukoplakia and 17 controls were selected for immunohistochemistry (IHC) for detection of COX2- E. COX2-E was divided in four grades, as A (0-10%), B (11- 40%), C (41-70%) and D (leukoplakia (p > 0.05). COX2-E in spinous layer of normal tissue was significantly lower than SCC (p = 0.000). COX2-E was significantly different in SCC grade 3 and leukoplakia (p = 0.001) and normal tissue (p = 0.000). COX2-E was significantly higher in SCC grade 3 compared to leukoplakia (basal layer) (p = 0.000). We showed a significant higher COX2-E in SCC lesions compared to leukoplakias and normal controls. In our study COX2-E was not significantly different in SCC grades 1, 2 and 3 (p < 0.05).

  10. A duplicated coxI gene is associated with cytoplasmic male sterility ...

    Indian Academy of Sciences (India)

    which have been implicated in male sterility (reviewed in. Keywords. Brassica juncea; coxI gene; cytoplasmic male sterility; somatic hybrid; transcript variation. ... drial recombination has led to duplication of coxI gene which appears to be associated with the CMS. Materials and methods. Plant material. B. juncea cv.

  11. Cyclooxygenase 1 (COX1) expression in Type 2 diabetes mellitus: A ...

    African Journals Online (AJOL)

    COX1 determines 6-Keto Prostaglandin F1a (6-k-PGF1a) level, plays a major role in vasodilation and restricts macrophage platelet aggregation. The aim of the present study was to compare the COX1 expression and level of reactive oxygen species (ROS) in T2DM patients and controls at different time periods in human ...

  12. Characterization and Sequencing of MT-Cox1 Gene in Khorasan ...

    African Journals Online (AJOL)

    The aim of this study was to investigate the nucleotide sequence of COX1 gene in mitochondrial genome of Khorasan native chicken and detect the possible mutations in the genome. For this purpose, after sampling and extracting DNA from the whole blood samples, the COX1 gene was amplified using specific primers and ...

  13. Nucleobindin co-localizes and associates with cyclooxygenase (COX-2 in human neutrophils.

    Directory of Open Access Journals (Sweden)

    Patrick Leclerc

    2008-05-01

    Full Text Available The inducible cyclooxygenase isoform (COX-2 is associated with inflammation, tumorigenesis, as well as with physiological events. Despite efforts deployed in order to understand the biology of this multi-faceted enzyme, much remains to be understood. Nucleobindin (Nuc, a ubiquitous Ca(2+-binding protein, possesses a putative COX-binding domain. In this study, we investigated its expression and subcellular localization in human neutrophils, its affinity for COX-2 as well as its possible impact on PGE(2 biosynthesis. Complementary subcellular localization approaches including nitrogen cavitation coupled to Percoll fractionation, immunofluorescence, confocal and electron microscopy collectively placed Nuc, COX-2, and all of the main enzymes involved in prostanoid synthesis, in the Golgi apparatus and endoplasmic reticulum of human neutrophils. Immunoprecipitation experiments indicated a high affinity between Nuc and COX-2. Addition of human recombinant (hr Nuc to purified hrCOX-2 dose-dependently caused an increase in PGE(2 biosynthesis in response to arachidonic acid. Co-incubation of Nuc with COX-2-expressing neutrophil lysates also increased their capacity to produce PGE(2. Moreover, neutrophil transfection with hrNuc specifically enhanced PGE(2 biosynthesis. Together, these results identify a COX-2-associated protein which may have an impact in prostanoid biosynthesis.

  14. Handbook of hazardous waste management

    International Nuclear Information System (INIS)

    Metry, A.A.

    1980-01-01

    The contents of this work are arranged so as to give the reader a detailed understanding of the elements of hazardous waste management. Generalized management concepts are covered in Chapters 1 through 5 which are entitled: Introduction, Regulations Affecting Hazardous Waste Management, Comprehensive Hazardous Waste Management, Control of Hazardous Waste Transportation, and Emergency Hazardous Waste Management. Chapters 6 through 11 deal with treatment concepts and are entitled: General Considerations for Hazardous Waste Management Facilities, Physical Treatment of Hazardous Wastes, Chemical Treatment of Hazardous Wastes, Biological Treatment of Hazardous Wastes, Incineration of Hazardous Wastes, and Hazardous Waste Management of Selected Industries. Chapters 12 through 15 are devoted to ultimate disposal concepts and are entitled: Land Disposal Facilities, Ocean Dumping of Hazardous Wastes, Disposal of Extremely Hazardous Wastes, and Generalized Criteria for Hazardous Waste Management Facilities

  15. Estimating sighting proportions of American alligator nests during helicopter survey

    Science.gov (United States)

    Rice, Kenneth G.; Percival, H. Franklin; Woodward, Allan R.

    2000-01-01

    Proportions of American alligator (Alligator mississippiensis) nests sighted during aerial survey in Florida were estimated based upon multiple surveys by different observers. We compared sighting proportions across habitats, nesting seasons, and observer experience levels. The mean sighting proportion across all habitats and years was 0.736 (SE=0.024). Survey counts corrected by the mean sighting proportion reliably predicted total nest counts (7?2=0.933). Sighting proportions did not differ by habitat type (P=0.668) or year P=0.328). Experienced observers detected a greater proportion of nests (P<0.0001) than did either less experienced or inexperienced observers. Reliable estimates of nest abundance can be derived from aerial counts of alligator nests when corrected by the appropriate sighting proportion.

  16. Relative Hazard Calculation Methodology

    International Nuclear Information System (INIS)

    DL Strenge; MK White; RD Stenner; WB Andrews

    1999-01-01

    The methodology presented in this document was developed to provide a means of calculating the RH ratios to use in developing useful graphic illustrations. The RH equation, as presented in this methodology, is primarily a collection of key factors relevant to understanding the hazards and risks associated with projected risk management activities. The RH equation has the potential for much broader application than generating risk profiles. For example, it can be used to compare one risk management activity with another, instead of just comparing it to a fixed baseline as was done for the risk profiles. If the appropriate source term data are available, it could be used in its non-ratio form to estimate absolute values of the associated hazards. These estimated values of hazard could then be examined to help understand which risk management activities are addressing the higher hazard conditions at a site. Graphics could be generated from these absolute hazard values to compare high-hazard conditions. If the RH equation is used in this manner, care must be taken to specifically define and qualify the estimated absolute hazard values (e.g., identify which factors were considered and which ones tended to drive the hazard estimation)

  17. Regulation, proportionality and discharges of radioactive wastes: UK perspective

    International Nuclear Information System (INIS)

    Morley, Bob; Butler, Gregg; Mc Glynn, Grace

    2008-01-01

    In recent years, the UK Government and the Regulators have made a commitment to further improve the operation of the regulatory regime and to its operating within the principles of proportionality, transparency, consistency and accountability which underpin the Government's approach to regulation in general. Particular emphasis was to be placed upon ensuring that there is greater consistency in the treatment of risk and hazard; proportionate and cost effective delivery of public, worker and environmental protection; and an open and transparently applied regulatory system. It is noteworthy that with regard to radiation protection, there are different limits for public doses and workforce doses, with the latter 15 times greater. Allowable doses for medical patients are higher still. This discrepancy raises a question in itself. This presentation focuses on the practical application of the regulatory regime with particular regard to environmental discharges and disposals. Under the Radioactive Substances Act 1993, Operators within the UK nuclear industry are required to employ Best Practicable Means (BPM) to control and minimise radioactive discharges to ensure that doses from discharges are As Low As Reasonably Achievable (ALARA). Scientific assessments to date indicate that there are no expectations of environmental harm from discharges at Sellafield (and hence likewise at other UK nuclear sites where the discharges are lower), even where those discharges have historically been up to two orders of magnitude higher than current levels. Current discharges result in doses which are a small fraction of those received by the UK population due to natural background radiation. In addition, there is no proven environmental harm from foreseeable future discharges from Sellafield or other UK nuclear sites. This is supported by independent work which illustrates that the public collective dose from Sellafield discharges is almost all delivered at risks of less that one in a

  18. Offsite transportation hazards assessment

    International Nuclear Information System (INIS)

    Burnside, M.E.

    1997-01-01

    This report documents the emergency preparedness Hazards Assessment for the offsite transportation of hazardous material from the Hanford Site. The assessment is required by the US Department of Energy (DOE) Order 151.1. Offsite transportation accidents are categorized using the DOE system to assist communication within the DOE and assure that appropriate assistance is provided to the people in charge at the scene. The assistance will initially include information about the load and the potential hazards. Local authorities will use the information to protect the public following a transportation accident. This Hazards Assessment will focus on the material being transported from the Hanford Site. Shipments coming to Hanford are the responsibility of the shipper and the carrier and, therefore, are not included in this Hazards Assessment, unless the DOE elects to be the shipper of record

  19. Prescribing COX-2s for patients new to cyclo-oxygenase inhibition therapy.

    Science.gov (United States)

    Cox, Emily R; Motheral, Brenda; Frisse, Mark; Behm, Andrew; Mager, Doug

    2003-11-01

    To profile the pattern of cyclo-oxygenase 2 inhibitor (COX-2) use, including length of therapy, medical conditions treated, and gastrointestinal (GI) risk profile of users. Descriptive retrospective analysis of medical and prescription claims data from a large preferred provider organization in the Midwest. During an index period of January through May 31, 2000, patients new to COX-2 therapy were evaluated 365 days before and after their first prescription. Among the inclusion criteria, patients had to have no previous use of COX-2 therapy, be at least 18 years of age, and be continuously eligible during the entire study period. Of the more than 300 000 members with at least 1 day of coverage in the index window, 1312 members met the inclusion criteria. The average age of COX-2 users was 49.5 years (SD = 11.4) and 60% were female. The number of days' supply of COX-2 agent obtained by members was highly skewed, with a mean of 116 days (SD = 119.5) and a median of 60 days. The medical conditions associated with COX-2 use included a variety of musculoskeletal conditions, the most common being low back pain (22%) and osteoarthritis (18%). Approximately 19% of members did not have a diagnosis associated with COX-2 use. Sixty-five percent of those new to COX-2 therapy did not have an indication of being at risk for GI events, and 68% had no indication for trying a lower-cost nonselective nonsteroidal anti-inflammatory drug (NSAID) prescription prior to beginning COX-2 therapy. Taken together, 45% did not have a GI risk factor or prior use of nonselective NSAID prescription therapy. These findings suggest that opportunities exist to encourage the cost-effective prescribing of COX-2 therapy. Possible methods include implementation of step therapy, academic detailing, and physician education programs, among others.

  20. Hazardous alcohol consumption is a major factor in male premature mortality in a typical Russian city: prospective cohort study 2003-2009.

    Directory of Open Access Journals (Sweden)

    Susannah Tomkins

    Full Text Available Russia has experienced massive fluctuations in mortality at working ages over the past three decades. Routine data analyses suggest that these are largely driven by fluctuations in heavy alcohol drinking. However, individual-level evidence supporting alcohol having a major role in Russian mortality comes from only two case-control studies, which could be subject to serious biases due to their design.A prospective study of mortality (2003-9 of 2000 men aged 25-54 years at recruitment was conducted in the city of Izhevsk, Russia. This cohort was free from key limitations inherent in the design of the two earlier case-control studies. Cox proportional hazards regression was used to estimate hazard ratios of all-cause mortality by alcohol drinking type as reported by a proxy informant. Hazardous drinkers were defined as those who either drank non-beverage alcohols or were reported to regularly have hangovers or other behaviours related to heavy drinking episodes. Over the follow-up period 113 men died. Compared to non-hazardous drinkers and abstainers, men who drank hazardously had appreciably higher mortality (HR = 3.4, 95% CI 2.2, 5.1 adjusted for age, smoking and education. The population attributable risk percent (PAR% for hazardous drinking was 26% (95% CI 14,37. However, larger effects were seen in the first two years of follow-up, with a HR of 4.6 (2.5, 8.2 and a corresponding PAR% of 37% (17, 51.This prospective cohort study strengthens the evidence that hazardous alcohol consumption has been a major determinant of mortality among working age men in a typical Russian city. As such the similar findings of the previous case-control studies cannot be explained as artefacts of limitations of their design. As Russia struggles to raise life expectancy, which even in 2009 was only 62 years among men, control of hazardous drinking must remain a top public health priority.

  1. Exploring selectivity requirements for COX-2 versus COX-1 binding of 2-(5-phenyl-pyrazol-1-yl)-5-methanesulfonylpyridines using topological and physico-chemical parameters.

    Science.gov (United States)

    Chakraborty, Santanu; Sengupta, Chandana; Roy, Kunal

    2005-04-01

    Considering the current need for development of selective cyclooxygenase-2 (COX-2) inhibitors, an attempt has been made to explore physico-chemical requirements of 2-(5-phenyl-pyrazol-1-yl)-5-methanesulfonylpyridines for binding with COX-1 and COX-2 enzyme subtypes and also to explore the selectivity requirements. In this study, E-states of different common atoms of the molecules (calculated according to Kier & Hall), first order valence connectivity and physicochemical parameters (hydrophobicity pi, Hammett sigma and molar refractivity MR of different ring substituents) were used as independent variables along with suitable dummy parameters in the stepwise regression method. The best equation describing COX-1 binding affinity [n = 25, Q2 = 0.606, R(a)2 = 0.702, R2 = 0.752, R = 0.867, s = 0.447, F = 15.2 (df 4, 20)] suggests that the COX-1 binding affinity increases in the presence of a halogen substituent at R1 position and a p-alkoxy or p-methylthio substituent at R2 position. Furthermore, a difluoromethyl group is preferred over a trifluoromethyl group at R position for the COX-1 binding. The best equation describing COX-2 binding affinity [n = 32, Q2 = 0.622, R(a)2= 0.692, R2 = 0.732, R = 0.856, s = 0.265, F = 18.4 (df 4, 27)] shows that the COX-2 binding affinity increases with the presence of a halogen substituent at R1 position and increase of size of R2 substituents. However, it decreases in case of simultaneous presence of 3-chloro and 4-methoxy groups on the phenyl nucleus and in the presence of highly lipophilic R2 substituents. The best selectivity relation [n = 25, Q2 = 0.455, R(a)2 = 0.605, R2 = 0.670, R = 0.819, s = 0.423, F = 10.2 (df 4, 20)] suggests that the COX-2 selectivity decreases in the presence of p-alkoxy group and electron-withdrawing para substituents at R2 position. Again, a trifluoro group is conductive for the selectivity instead of a difluoromethyl group at R position. Furthermore, branching may also play significant role in

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

    Science.gov (United States)

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

    2016-10-01

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

  3. Natural hazards science strategy

    Science.gov (United States)

    Holmes, Robert R.; Jones, Lucile M.; Eidenshink, Jeffery C.; Godt, Jonathan W.; Kirby, Stephen H.; Love, Jeffrey J.; Neal, Christina A.; Plant, Nathaniel G.; Plunkett, Michael L.; Weaver, Craig S.; Wein, Anne; Perry, Suzanne C.

    2012-01-01

    The mission of the U.S. Geological Survey (USGS) in natural hazards is to develop and apply hazard science to help protect the safety, security, and economic well-being of the Nation. The costs and consequences of natural hazards can be enormous, and each year more people and infrastructure are at risk. USGS scientific research—founded on detailed observations and improved understanding of the responsible physical processes—can help to understand and reduce natural hazard risks and to make and effectively communicate reliable statements about hazard characteristics, such as frequency, magnitude, extent, onset, consequences, and where possible, the time of future events.To accomplish its broad hazard mission, the USGS maintains an expert workforce of scientists and technicians in the earth sciences, hydrology, biology, geography, social and behavioral sciences, and other fields, and engages cooperatively with numerous agencies, research institutions, and organizations in the public and private sectors, across the Nation and around the world. The scientific expertise required to accomplish the USGS mission in natural hazards includes a wide range of disciplines that this report refers to, in aggregate, as hazard science.In October 2010, the Natural Hazards Science Strategy Planning Team (H–SSPT) was charged with developing a long-term (10-year) Science Strategy for the USGS mission in natural hazards. This report fulfills that charge, with a document hereinafter referred to as the Strategy, to provide scientific observations, analyses, and research that are critical for the Nation to become more resilient to natural hazards. Science provides the information that decisionmakers need to determine whether risk management activities are worthwhile. Moreover, as the agency with the perspective of geologic time, the USGS is uniquely positioned to extend the collective experience of society to prepare for events outside current memory. The USGS has critical statutory

  4. Minimizing the cancer-promotional activity of cox-2 as a central strategy in cancer prevention.

    Science.gov (United States)

    McCarty, Mark F

    2012-01-01

    A recent meta-analysis examining long-term mortality in subjects who participated in controlled studies evaluating the impact of daily aspirin on vascular risk, has concluded that aspirin confers substantial protection from cancer mortality. Remarkably, low-dose aspirin was as effective as higher-dose regimens; hence this protection may be achievable with minimal risk. There is reason to believe that this protection stems primarily from inhibition of cox-2 in pre-neoplastic lesions. Since safe aspirin regimens can only achieve a partial and transitory inhibition of cox-2, it may be feasible to complement the cancer-protective benefit of aspirin with other measures which decrease cox-2 expression or which limit the bioactivity of cox-2-derived PGE2. Oxidative stress boosts cox-2 expression by up-regulating activation of NF-kappaB and MAP kinases; NADPH oxidase activation may thus promote carcinogenesis by increasing cox-2 expression while also amplifying oxidant-mediated mutagenesis. A prospective cohort study has observed that relatively elevated serum bilirubin levels are associated with a marked reduction in subsequent cancer mortality; this may reflect bilirubin's physiological role as a potent inhibitor of NADPH oxidase. It may be feasible to mimic this protective effect by supplementing with spirulina, a rich source of a phycobilin which shares bilirubin's ability to inhibit NADPH oxidase. Ancillary antioxidant measures - phase 2 inducing phytochemicals, melatonin, N-acetylcysteine, and astaxanthin - may also aid cox-2 down-regulation. The cancer protection often associated with high-normal vitamin D status may be attributable, in part, to the ability of the activated vitamin D receptor to decrease cox-2 expression while promoting PGE2 catabolism and suppressing the expression of PGE2 receptors. Diets with a relatively low ratio of omega-6 to long-chain omega-3 fats may achieve cancer protection by antagonizing the production and bioactivity of PGE2. Growth

  5. Hazard screening application guide

    International Nuclear Information System (INIS)

    1992-06-01

    The basic purpose of hazard screening is to group precesses, facilities, and proposed modifications according to the magnitude of their hazards so as to determine the need for and extent of follow on safety analysis. A hazard is defined as a material, energy source, or operation that has the potential to cause injury or illness in human beings. The purpose of this document is to give guidance and provide standard methods for performing hazard screening. Hazard screening is applied to new and existing facilities and processes as well as to proposed modifications to existing facilities and processes. The hazard screening process evaluates an identified hazards in terms of the effects on people, both on-site and off-site. The process uses bounding analyses with no credit given for mitigation of an accident with the exception of certain containers meeting DOT specifications. The process is restricted to human safety issues only. Environmental effects are addressed by the environmental program. Interfaces with environmental organizations will be established in order to share information

  6. Inquiry pedagogy to promote emerging proportional reasoning in primary students

    Science.gov (United States)

    Fielding-Wells, Jill; Dole, Shelley; Makar, Katie

    2014-03-01

    Proportional reasoning as the capacity to compare situations in relative (multiplicative) rather than absolute (additive) terms is an important outcome of primary school mathematics. Research suggests that students tend to see comparative situations in additive rather than multiplicative terms and this thinking can influence their capacity for proportional reasoning in later years. In this paper, excerpts from a classroom case study of a fourth-grade classroom (students aged 9) are presented as they address an inquiry problem that required proportional reasoning. As the inquiry unfolded, students' additive strategies were progressively seen to shift to proportional thinking to enable them to answer the question that guided their inquiry. In wrestling with the challenges they encountered, their emerging proportional reasoning was supported by the inquiry model used to provide a structure, a classroom culture of inquiry and argumentation, and the proportionality embedded in the problem context.

  7. Comparison of PTCH1, COX-2, p53, and Ki-67 protein expression in basal cell carcinomas of nodular and superficial subtypes arising on the head and trunk.

    Science.gov (United States)

    Khalesi, Mohammad; Waterhouse, Mary; Whiteman, David C; Johns, Richard; Rosendahl, Cliff; Hackett, Timothy; Pollak, Thomas; Kimlin, Michael G; Hacker, Elke; Neale, Rachel E

    2016-10-01

    There is some evidence that basal cell carcinomas (BCCs) arising on different anatomic sites and developing to different histological subtypes differ in their pathophysiology. The expression of a number of proteins, including PTCH1, COX-2, p53, and Ki-67, is frequently altered in BCC development. This study sought to determine whether protein expression differs between BCCs at different anatomic sites and of different histological subtypes. Expression of PTCH1, COX-2, p53, and Ki-67 proteins was compared between: (i) BCCs arising on the head (n = 55) and trunk (n = 53), and (ii) nodular (n = 52) and superficial (n = 43) BCCs. The intensity of immunohistochemistry (IHC) staining (low, moderate, strong, very strong) for PTCH1 and COX-2 proteins was measured and the proportions of p53- and Ki-67-positive cells quantified. The proportion of cells expressing Ki-67 was higher in tumor tissue than in non-malignant epidermis, whereas the opposite was found for PTCH1. The IHC staining intensity for PTCH1 was substantially greater in truncal BCCs than in BCCs on the head (odds ratio [OR] 3.82, 95% confidence interval [CI] 1.63-8.96). The intensity of staining for PTCH1 was greater for superficial than for nodular BCCs (OR 3.70, 95% CI 1.53-8.97), and superficial BCCs showed a higher proportion of Ki-67-positive cells (OR 5.57, 95% CI 1.66-18.67). These differences suggest that the pathophysiology of BCC differs between lesions on the head and trunk and between nodular and superficial subtypes, perhaps indicating differences in their etiology. © 2016 The International Society of Dermatology.

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

    Science.gov (United States)

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

    2018-05-01

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

  9. Niacin and biosynthesis of PGD₂by platelet COX-1 in mice and humans.

    Science.gov (United States)

    Song, Wen-Liang; Stubbe, Jane; Ricciotti, Emanuela; Alamuddin, Naji; Ibrahim, Salam; Crichton, Irene; Prempeh, Maxwell; Lawson, John A; Wilensky, Robert L; Rasmussen, Lars Melholt; Puré, Ellen; FitzGerald, Garret A

    2012-04-01

    The clinical use of niacin to treat dyslipidemic conditions is limited by noxious side effects, most commonly facial flushing. In mice, niacin-induced flushing results from COX-1-dependent formation of PGD₂ and PGE₂ followed by COX-2-dependent production of PGE₂. Consistent with this, niacin-induced flushing in humans is attenuated when niacin is combined with an antagonist of the PGD₂ receptor DP1. NSAID-mediated suppression of COX-2-derived PGI₂ has negative cardiovascular consequences, yet little is known about the cardiovascular biology of PGD₂. Here, we show that PGD₂ biosynthesis is augmented during platelet activation in humans and, although vascular expression of DP1 is conserved between humans and mice, platelet DP1 is not present in mice. Despite this, DP1 deletion in mice augmented aneurysm formation and the hypertensive response to Ang II and accelerated atherogenesis and thrombogenesis. Furthermore, COX inhibitors in humans, as well as platelet depletion, COX-1 knockdown, and COX-2 deletion in mice, revealed that niacin evoked platelet COX-1-derived PGD₂ biosynthesis. Finally, ADP-induced spreading on fibrinogen was augmented by niacin in washed human platelets, coincident with increased thromboxane (Tx) formation. However, in platelet-rich plasma, where formation of both Tx and PGD₂ was increased, spreading was not as pronounced and was inhibited by DP1 activation. Thus, PGD₂, like PGI₂, may function as a homeostatic response to thrombogenic and hypertensive stimuli and may have particular relevance as a constraint on platelets during niacin therapy.

  10. Activating PTEN by COX-2 inhibitors antagonizes radiation-induced AKT activation contributing to radiosensitization

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Zhen [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Gan, Ye-Hua, E-mail: kqyehuagan@bjmu.edu.cn [Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China)

    2015-05-01

    Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AKT activation. - Highlights: • COX-2 inhibitor, celecoxib, could enhance radiosensitization. • Radiation induced PTEN inactivation (phosphorylation) and AKT activation. • COX-2 inhibitor induced PTEN expression and activation, and inactivated AKT. • COX-2 inhibitor enhanced radiosensitization through activating PTEN.

  11. Activating PTEN by COX-2 inhibitors antagonizes radiation-induced AKT activation contributing to radiosensitization

    International Nuclear Information System (INIS)

    Meng, Zhen; Gan, Ye-Hua

    2015-01-01

    Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AKT activation. - Highlights: • COX-2 inhibitor, celecoxib, could enhance radiosensitization. • Radiation induced PTEN inactivation (phosphorylation) and AKT activation. • COX-2 inhibitor induced PTEN expression and activation, and inactivated AKT. • COX-2 inhibitor enhanced radiosensitization through activating PTEN

  12. COX-2 verexpression in pretreatment biopsies predicts response of rectal cancers to neoadjuvant radiochemotherapy

    International Nuclear Information System (INIS)

    Smith, Fraser M.; Reynolds, John V.; Kay, Elaine W.; Crotty, Paul; Murphy, James O.; Hollywood, Donal; Gaffney, Eoin F.; Stephens, Richard B.; Kennedy, M. John

    2006-01-01

    Purpose: To determine the utility of COX-2 expression as a response predictor for patients with rectal cancer who are undergoing neoadjuvant radiochemotherapy (RCT). Methods and Materials: Pretreatment biopsies (PTB) from 49 patients who underwent RCT were included. COX-2 and proliferation in PTB were assessed by immunohistochemistry (IHC) and apoptosis was detected by TUNEL stain. Response to treatment was assessed by a 5-point tumor-regression grade (TRG) based on the ratio of residual tumor to fibrosis. Results: Good response (TRG 1 + 2), moderate response (TRG 3), and poor response (TRG 4 + 5) were seen in 21 patients (42%), 11 patients (22%), and 17 patients (34%), respectively. Patients with COX-2 overexpression in PTB were more likely to demonstrate moderate or poor response (TRG 3 + 4) to treatment than were those with normal COX-2 expression (p = 0.026, chi-square test). Similarly, poor response was more likely if patients had low levels of spontaneous apoptosis in PTBs (p = 0.0007, chi-square test). Conclusions: COX-2 overexpression and reduced apoptosis in PTB can predict poor response of rectal cancer to RCT. As COX-2 inhibitors are commercially available, their administration to patients who overexpress COX-2 warrants assessment in clinical trials in an attempt to increase overall response rates

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

    Science.gov (United States)

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

    2008-01-01

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

  14. Moral Hazard and Stability

    DEFF Research Database (Denmark)

    Tumennasan, Norovsambuu

    2014-01-01

    Economists perceive moral hazard as an undesirable problem because it undermines efficiency. Carefully designed contracts can mitigate the moral hazard problem, but this assumes that a team is already formed. This paper demonstrates that these contracts are sometimes the reason why teams do...... not form. Formally, we study the team formation problem in which the agents’ efforts are not verifiable and the size of teams does not exceed quota r . We show that if the team members cannot make transfers, then moral hazard affects stability positively in a large class of games. For example, a stable...

  15. Hepatic Ischemia and Reperfusion Injury in the Absence of Myeloid Cell-Derived COX-2 in Mice

    Science.gov (United States)

    Duarte, Sergio; Kato, Hiroyuki; Kuriyama, Naohisa; Suko, Kathryn; Ishikawa, Tomo-o; Busuttil, Ronald W.; Herschman, Harvey R.; Coito, Ana J.

    2014-01-01

    Cyclooxygenase-2 (COX-2) is a mediator of hepatic ischemia and reperfusion injury (IRI). While both global COX-2 deletion and pharmacologic COX-2 inhibition ameliorate liver IRI, the clinical use of COX-2 inhibitors has been linked to increased risks of heart attack and stroke. Therefore, a better understanding of the role of COX-2 in different cell types may lead to improved therapeutic strategies for hepatic IRI. Macrophages of myeloid origin are currently considered to be important sources of the COX-2 in damaged livers. Here, we used a Cox-2flox conditional knockout mouse (COX-2−M/−M) to examine the function of COX-2 expression in myeloid cells during liver IRI. COX-2−M/−M mice and their WT control littermates were subjected to partial liver ischemia followed by reperfusion. COX-2−M/−M macrophages did not express COX-2 upon lipopolysaccharide stimulation and COX-2−M/−M livers showed reduced levels of COX-2 protein post-IRI. Nevertheless, selective deletion of myeloid cell-derived COX-2 failed to ameliorate liver IRI; serum transaminases and histology were comparable in both COX-2−M/−M and WT mice. COX-2−M/−M livers, like WT livers, developed extensive necrosis, vascular congestion, leukocyte infiltration and matrix metalloproteinase-9 (MMP-9) expression post-reperfusion. In addition, myeloid COX-2 deletion led to a transient increase in IL-6 levels after hepatic reperfusion, when compared to controls. Administration of celecoxib, a selective COX-2 inhibitor, resulted in significantly improved liver function and histology in both COX-2−M/−M and WT mice post-reperfusion, providing evidence that COX-2-mediated liver IRI is caused by COX-2 derived from a source(s) other than myeloid cells. In conclusion, these results support the view that myeloid COX-2, including myeloid-macrophage COX-2, is not responsible for the hepatic IRI phenotype. PMID:24819536

  16. Southern Dietary Pattern is Associated with Hazard of Acute Coronary Heart Disease in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

    Science.gov (United States)

    Shikany, James M.; Safford, Monika M.; Newby, P. K.; Durant, Raegan W.; Brown, Todd M.; Judd, Suzanne E.

    2015-01-01

    Background The association of overall diet, as characterized by dietary patterns, with risk of incident acute coronary heart disease (CHD) has not been studied extensively in samples including sociodemographic and regional diversity. Methods and Results We used data from 17,418 participants in Reasons for Geographic and Racial Differences in Stroke (REGARDS), a national, population-based, longitudinal study of white and black adults aged ≥45 years, enrolled from 2003-2007. We derived dietary patterns with factor analysis, and used Cox proportional hazards regression to examine hazard of incident acute CHD events – nonfatal myocardial infarction and acute CHD death – associated with quartiles of consumption of each pattern, adjusted for various levels of covariates. Five primary dietary patterns emerged: Convenience, Plant-based, Sweets, Southern, and Alcohol and Salad. A total of 536 acute CHD events occurred over a median (IQR) 5.8 (2.1) years of follow-up. After adjustment for sociodemographics, lifestyle factors, and energy intake, highest consumers of the Southern pattern (characterized by added fats, fried food, eggs, organ and processed meats, and sugar-sweetened beverages) experienced a 56% higher hazard of acute CHD (comparing quartile 4 to quartile 1: HR = 1.56; 95% CI: 1.17, 2.08; P for trend across quartiles = 0.003). Adding anthropometric and medical history variables to the model attenuated the association somewhat (HR = 1.37; 95% CI: 1.01, 1.85; P = 0.036). Conclusions A dietary pattern characteristic of the southern US was associated with greater hazard of CHD in this sample of white and black adults in diverse regions of the US. PMID:26260732

  17. The proportionality as legal limit the right negotiating

    Directory of Open Access Journals (Sweden)

    Lucas Augusto da Silva Zolet

    2015-06-01

    Full Text Available This paper proposes a maximum of proportionality study and its maximum partial, especially of the Negotiating law perspective and in the sphere of legal limitation for proportionality in the practice of commercial freedoms. The constant use of the maximum of proportionality, as the basis of judicial decisions without proper methodological rigor, triggers a debate about the use of the Theory of Fundamental Rights as a mere rhetorical reference, including criticism of an incomplete legal basis of the principle of proportionality, which by means of judicial decisions can take on a different character or subverted that provided in the doctrine of Robert Alexy.     

  18. Multiwire proportional chamber for Moessbauer spectroscopy: development and results

    International Nuclear Information System (INIS)

    Costa, M.S. da.

    1985-12-01

    A new Multiwere proportional Chamber designed for Moessbauer Spectroscopy is presented. This detector allows transmission backscattering experiments using either photons or electrons. The Moessbauer data acquisition system, partially developed for this work is described. A simple method for determining the frontier between true proportional and semi-proportional regions of operation in gaseous detectors is proposed. The study of the tertiary gas mixture He-Ar-CH 4 leads to a straight forward way of energy calibration of the electron spectra. Moessbauer spectra using Fe-57 source are presented. In particular those obtained with backsattered electrons show the feasibility of depth selective analysis with gaseous proportional counters. (author) [pt

  19. COX-2 inhibition attenuates lung injury induced by skeletal muscle ischemia reperfusion in rats.

    Science.gov (United States)

    Wang, Liangrong; Shan, Yuanlu; Ye, Yuzhu; Jin, Lida; Zhuo, Qian; Xiong, Xiangqing; Zhao, Xiyue; Lin, Lina; Miao, JianXia

    2016-02-01

    Skeletal muscle ischemia reperfusion accounts for high morbidity and mortality, and cyclooxygenase (COX)-2 is implicated in causing muscle damage. Downregulation of aquaporin-1 (AQP-1) transmembrane protein is implicated in skeletal muscle ischemia reperfusion induced remote lung injury. The expression of COX-2 in lung tissue and the effect of COX-2 inhibition on AQP-1 expression and lung injury during skeletal muscle ischemia reperfusion are not known. We investigated the role of COX-2 in lung injury induced by skeletal muscle ischemia reperfusion in rats and evaluated the effects of NS-398, a specific COX-2 inhibitor. Twenty-four Sprague Dawley rats were randomized into 4 groups: sham group (SM group), sham+NS-398 group (SN group), ischemia reperfusion group (IR group) and ischemia reperfusion+NS-398 group (IN group). Rats in the IR and IN groups were subjected to 3h of bilateral ischemia followed by 6h of reperfusion in hindlimbs, and intravenous NS-398 8 mg/kg was administered in the IN group. In the SM and SN groups, rubber bands were in place without inflation. At the end of reperfusion, myeloperoxidase (MPO) activity, COX-2 and AQP-1 protein expression in lung tissue, PGE2 metabolite (PGEM), tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels in bronchoalveolar lavage (BAL) fluid were assessed. Histological changes in lung and muscle tissues and wet/dry (W/D) ratio were also evaluated. MPO activity, COX-2 expression, W/D ratio in lung tissue, and PGEM, TNF-α and IL-1β levels in BAL fluid were significantly increased, while AQP-1 protein expression downregulated in the IR group as compared to that in the SM group (Pinjury. COX-2 protein expression was upregulated in lung tissue in response to skeletal muscle ischemia reperfusion. COX-2 inhibition may modulate pulmonary AQP-1 expression and attenuate lung injury. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Illustrated techniques for performing the Cox-Maze IV procedure through a right mini-thoracotomy.

    Science.gov (United States)

    Robertson, Jason O; Saint, Lindsey L; Leidenfrost, Jeremy E; Damiano, Ralph J

    2014-01-01

    The Cox-Maze IV procedure has replaced the "cut-and-sew" technique of the original Cox-Maze operation with lines of ablation created using bipolar radiofrequency (RF) and cryothermal energy devices. In select patients, this procedure can be performed through a right mini-thoracotomy. This illustrated review is the first to detail the complete steps of the Cox-Maze IV procedure performed through a right mini-thoracotomy with careful attention paid to operative anatomy and advice. Pre- and post-operative management and outcomes are also discussed. This should be a practical guide for the practicing cardiac surgeon.

  1. The Distribution of the Interval between Events of a Cox Process with Shot Noise Intensity

    Directory of Open Access Journals (Sweden)

    Angelos Dassios

    2008-01-01

    Full Text Available Applying piecewise deterministic Markov processes theory, the probability generating function of a Cox process, incorporating with shot noise process as the claim intensity, is obtained. We also derive the Laplace transform of the distribution of the shot noise process at claim jump times, using stationary assumption of the shot noise process at any times. Based on this Laplace transform and from the probability generating function of a Cox process with shot noise intensity, we obtain the distribution of the interval of a Cox process with shot noise intensity for insurance claims and its moments, that is, mean and variance.

  2. Induced mutants of Cox's Orange Pippin apple with apparent increased self-compatibility. Pt. 2

    International Nuclear Information System (INIS)

    Church, R.M.; Lacey, C.N.D.; Richardson, P.

    1982-01-01

    Fruit set on clones of Cox's Orange Pippin apple which had been produced by gamma-irradiation, and found in a previous trial to crop when isolated from the pollen of other cultivars, was compared after open or hand-pollination. Some clones set more fruit than the unirradiated control trees when open pollinated or when hand-pollinated with pollen from the same tree or control Cox trees. Pollen from some mutant clones also improved set on standard Cox (EMLA). Estimates of the numbers of pollen tubes reaching the base of the style indicated that the increased set was due to enhanced tube growth. (orig.)

  3. Hazardous Waste Research Center

    Data.gov (United States)

    Federal Laboratory Consortium — The U.S. Army Engineer Waterways Experiment Station (WES) is playing a major role in development of technologies for cleanup of toxic and hazardous waste in military...

  4. Flood Hazard Boundaries

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The National Flood Hazard Layer (NFHL) data incorporates all Digital Flood Insurance Rate Map(DFIRM) databases published by FEMA, and any Letters Of Map Revision...

  5. Handling hazardous waste.

    Science.gov (United States)

    Fluke, C

    1988-01-01

    Hazardous waste management is a concern for every healthcare organization. A system for managing such waste must meet guidelines from various sources and be comprehensive enough to ensure the safety of the institution's employees and guests, and of the community. An integral part of a hazardous waste management system is employee training. "Employees must be trained to make use of the information that will be available to them. This includes knowing the hazards of the materials they use, how to use the appropriate protective clothing and equipment, what steps to take if there is an accidental release or over-exposure..." and much more. The institution's success in managing hazardous wastes and maintaining a safe environment will depend on the adequacy of its employee training.

  6. Introduction: Hazard mapping

    Science.gov (United States)

    Baum, Rex L.; Miyagi, Toyohiko; Lee, Saro; Trofymchuk, Oleksandr M

    2014-01-01

    Twenty papers were accepted into the session on landslide hazard mapping for oral presentation. The papers presented susceptibility and hazard analysis based on approaches ranging from field-based assessments to statistically based models to assessments that combined hydromechanical and probabilistic components. Many of the studies have taken advantage of increasing availability of remotely sensed data and nearly all relied on Geographic Information Systems to organize and analyze spatial data. The studies used a range of methods for assessing performance and validating hazard and susceptibility models. A few of the studies presented in this session also included some element of landslide risk assessment. This collection of papers clearly demonstrates that a wide range of approaches can lead to useful assessments of landslide susceptibility and hazard.

  7. Flood Hazard Area

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The National Flood Hazard Layer (NFHL) data incorporates all Digital Flood Insurance Rate Map(DFIRM) databases published by FEMA, and any Letters Of Map Revision...

  8. Natural Hazards Image Database

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Photographs and other visual media provide valuable pre- and post-event data for natural hazards. Research, mitigation, and forecasting rely on visual data for...

  9. GEEORD: A SAS macro for analyzing ordinal response variables with repeated measures through proportional odds, partial proportional odds, or non-proportional odds models.

    Science.gov (United States)

    Gao, Xiaoming; Schwartz, Todd A; Preisser, John S; Perin, Jamie

    2017-10-01

    A SAS macro, GEEORD, has been developed for the analysis of ordinal responses with repeated measures through a regression model that flexibly allows the proportional odds assumption to apply (or not) separately for each explanatory variable. Previously utilized in an analysis of a longitudinal orthognathic surgery clinical trial by Preisser et al. [1,2], the basis of GEEORD is the generalized estimating equations (GEE) method for cumulative logits models described by Lipsitz et al. [3]. The macro extends the capabilities for modeling correlated ordinal data of GEECAT, a SAS macro that allows the user to model correlated categorical response data [4]. The macro applies to independent ordinal responses as a special case. Examples are provided to demonstrate the convenient application of GEEORD to two different datasets. The macro's features are illustrated in fitting models to ordinal response variables in univariate and repeated measures settings; this includes the capacity to fit the non-proportional odds model, the partial proportional odds model, and the proportional odds model. The macro additionally provides relevant tests of the proportional odds assumption. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. K Basin Hazard Analysis

    International Nuclear Information System (INIS)

    PECH, S.H.

    2000-01-01

    This report describes the methodology used in conducting the K Basins Hazard Analysis, which provides the foundation for the K Basins Final Safety Analysis Report. This hazard analysis was performed in accordance with guidance provided by DOE-STD-3009-94, Preparation Guide for U. S. Department of Energy Nonreactor Nuclear Facility Safety Analysis Reports and implements the requirements of DOE Order 5480.23, Nuclear Safety Analysis Report

  11. K Basin Hazard Analysis

    Energy Technology Data Exchange (ETDEWEB)

    PECH, S.H.

    2000-08-23

    This report describes the methodology used in conducting the K Basins Hazard Analysis, which provides the foundation for the K Basins Final Safety Analysis Report. This hazard analysis was performed in accordance with guidance provided by DOE-STD-3009-94, Preparation Guide for U. S. Department of Energy Nonreactor Nuclear Facility Safety Analysis Reports and implements the requirements of DOE Order 5480.23, Nuclear Safety Analysis Report.

  12. K Basins Hazard Analysis

    International Nuclear Information System (INIS)

    WEBB, R.H.

    1999-01-01

    This report describes the methodology used in conducting the K Basins Hazard Analysis, which provides the foundation for the K Basins Safety Analysis Report (HNF-SD-WM-SAR-062/Rev.4). This hazard analysis was performed in accordance with guidance provided by DOE-STD-3009-94, Preparation Guide for U. S. Department of Energy Nonreactor Nuclear Facility Safety Analysis Reports and implements the requirements of DOE Order 5480.23, Nuclear Safety Analysis Report

  13. Carbon Structure Hazard Control

    Science.gov (United States)

    Yoder, Tommy; Greene, Ben; Porter, Alan

    2015-01-01

    Carbon composite structures are widely used in virtually all advanced technology industries for a multitude of applications. The high strength-to-weight ratio and resistance to aggressive service environments make them highly desirable. Automotive, aerospace, and petroleum industries extensively use, and will continue to use, this enabling technology. As a result of this broad range of use, field and test personnel are increasingly exposed to hazards associated with these structures. No single published document exists to address the hazards and make recommendations for the hazard controls required for the different exposure possibilities from damaged structures including airborne fibers, fly, and dust. The potential for personnel exposure varies depending on the application or manipulation of the structure. The effect of exposure to carbon hazards is not limited to personnel, protection of electronics and mechanical equipment must be considered as well. The various exposure opportunities defined in this document include pre-manufacturing fly and dust, the cured structure, manufacturing/machining, post-event cleanup, and post-event test and/or evaluation. Hazard control is defined as it is applicable or applied for the specific exposure opportunity. The carbon exposure hazard includes fly, dust, fiber (cured/uncured), and matrix vapor/thermal decomposition products. By using the recommendations in this document, a high level of confidence can be assured for the protection of personnel and equipment.

  14. The characteristics and stability of a range of Cox's Orange Pippin apple mutants showing different growth habits

    International Nuclear Information System (INIS)

    Lacey, C.N.D.; Campbell, A.I.

    1979-01-01

    Seven hundred and fifty gamma-irradiated scions of Cox's Orange Pippin apple were grown to produce a V 1 generation and were then multiplied to produce a V 2 of 13158 individual trees. 272 obvious vegetative mutants, mainly dwarf or compact types, were found in this population and classified according to growth habit. These were propagated to produce clones of the mutant types (V 3 ) and a study of these clonal mutants as compared with their original (V 2 ) characteristics showed that while the vast majority of the selected mutants produced dwarf or compact clones, no clear indication of final cropping performance could be drawn from the original phenotype of the selected V 2 mutants. The majority of mutants produced were not of commercial value, and the main reasons for the rejection of V 3 clones depended, in many cases, on the phenotype of the V 2 selection. Thus while all types of V 2 mutant produced approximately the same proportion of acceptable trees, the reason for the rejection of the V 3 clones varies with the V 2 phenotype. Therefore selection can be carried out at an early stage in a mutation breeding programme to reduce the proportion of certain unwanted types such as mericlinal chimaeras as that otherwise are carried forward to yield trials. From the orchard trials of 82 mutant clones. 24 were short-listed for possible commercial introduction. All were derived from the less extreme mutant types. (Auth.)

  15. EXPERIENCE AND PERSPECTIVES OF PROPORTIONAL ELECTORAL SYSTEM IN UKRAINE

    OpenAIRE

    Скоропад Тетяна Іванівна

    2015-01-01

    The existing approaches to the typology of electoral systems is analized, the features of the majority, proportional and mixed electoral systems are clarified. The evolution of the Ukrainian electoral system during the period of independence is characterized. Proportional electoral system is seen as a factor in ensuring the stability and effectiveness of elected bodies.

  16. The Improved Estimation of Ratio of Two Population Proportions

    Science.gov (United States)

    Solanki, Ramkrishna S.; Singh, Housila P.

    2016-01-01

    In this article, first we obtained the correct mean square error expression of Gupta and Shabbir's linear weighted estimator of the ratio of two population proportions. Later we suggested the general class of ratio estimators of two population proportions. The usual ratio estimator, Wynn-type estimator, Singh, Singh, and Kaur difference-type…

  17. 34 CFR Appendix to Part 81 - Illustrations of Proportionality

    Science.gov (United States)

    2010-07-01

    ... expended in the second preceding fiscal year and provides for a reduction in grant amount proportional to... did not provide for a proportional reduction in the grant award, the LEA would be required to return..., determines that the proposed programs are sound and the application is in compliance with Federal law, and...

  18. Golden proportions as predictors of attractiveness and malocclusion

    Directory of Open Access Journals (Sweden)

    Ahluwalia Rajiv

    2014-01-01

    Conclusion: Facial proportions of the attractive females were significantly different from those with malocclusion, but did not show a constant trend of being closer to the golden number. Furthermore, the golden proportions were not analogous with the facial esthetics of the attractive females.

  19. Fairness of seat allocation methods in proportional representation ...

    African Journals Online (AJOL)

    Fairness of seat allocation methods in proportional representation. L van Eck, S E Visagie, H C de Kock. Abstract. In this paper the fairness of some methods of allocating seats in a proportional representation (PR) voting system is investigated. Different PR systems are in use throughout the democratic world, but the primary ...

  20. Attention Modulation by Proportion Congruency: The Asymmetrical List Shifting Effect

    Science.gov (United States)

    Abrahamse, Elger L.; Duthoo, Wout; Notebaert, Wim; Risko, Evan F.

    2013-01-01

    Proportion congruency effects represent hallmark phenomena in current theorizing about cognitive control. This is based on the notion that proportion congruency determines the relative levels of attention to relevant and irrelevant information in conflict tasks. However, little empirical evidence exists that uniquely supports such an attention…

  1. Sexual dimorphism based on body proportions and ontogenetic ...

    African Journals Online (AJOL)

    Sexual dimorphism in the Brazilian electric ray Narcine brasiliensis from the south-western Atlantic coast was evaluated based on body proportions and ontogenetic changes. All regions of the body were found to have differences in body proportions between the sexes, except the spiracles. The nature of allometric and ...

  2. The principle of proportionality and European contract law

    NARCIS (Netherlands)

    Cauffman, C.; Rutgers, J.; Sirena, P.

    2015-01-01

    The paper investigates the role of the principle of proportionality within contract law, in balancing the rights and obligations of the contracting parties. It illustrates that the principle of proportionality is one of the general principles which govern contractual relations, and as such it is an

  3. Two encyclopedia contributions

    DEFF Research Database (Denmark)

    Andersen, Per Kragh

    2003-01-01

    censoring; Cox regression model; counting process; event history analysis; intensity process; multi-state model; non-parametric inference; parametric models; survival analysis; Cox's proportional hazards model; hazard function, regression model; time-dependent covariate; time scale...

  4. Recollections on the early days of the Marcé Society for Perinatal Mental Health from Professor John Cox.

    Science.gov (United States)

    Cox, John L; Wisner, Katherine L

    2016-02-01

    Dr. Katherine Wisner interviewed Dr. John Cox, a founding member of the Marcé Society. Dr. Cox discussed the beginnings of the Marcé Society, his views about the current Society, and his vision for the future.

  5. Isolation of linoleic and alpha-linolenic acids as COX-1 and -2 inhibitors in rose hip.

    Science.gov (United States)

    Jäger, A K; Petersen, K N; Thomasen, G; Christensen, S Brøgger

    2008-07-01

    Rose hip has previously shown clinical efficacy in the treatment of osteoarthritis, and organic solvent extracts of rose hip have showed inhibition of cyclooxygenase-1 and -2. A petroleum ether extract of rose hip was fractioned by VLC on silica; on a C-18 column and by HPLC. Each step was COX-1/2 activity-guided. The bioassay-guided fractionation led to the isolation of linoleic acid (the IC50 for COX-1 was 85 microm and 0.6 microM for COX-2) and alpha-linolenic acid (the IC50 for COX-1 was 52 microM and 12 microM for COX-2). The COX-2/COX-1 ratio was 0.007 for linoleic acid and 0.2 for alpha-linolenic acid. Linoleic acid and alpha-linolenic acid contribute to the COX-1 and -2 inhibitory activity of rose hip.

  6. COX-2 expression induced by diesel particles involves chromatin modification and degradation of HDAC1

    Science.gov (United States)

    Cyclooxygenase-2 (COX-2) plays an important role in the inflammatory response induced by physiologic and stress stimuli. Exposure to diesel exhaust particulate matter (DEP) has been shown to induce pulmonary inflammation and exacerbate asthma and chronic obstructive pulmonary dis...

  7. Do the COX-2 inhibitors still have a role to play?

    African Journals Online (AJOL)

    Adele

    rofecoxib caused an approximate doubling of risk). The drug was immediately withdrawn from the market. The study was published in 2005. Several questioned ... (by coxibs or NSNSAIDs) reduces urine output and renal func- tion further. COX-2 ...

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

    LENUS (Irish Health Repository)

    Barry, M

    2009-06-01

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

  9. Overcoming paclitaxel resistance in uterine endometrial cancer using a COX-2 inhibitor.

    Science.gov (United States)

    Hasegawa, Kiyoshi; Ishikawa, Kunimi; Kawai, Satoshi; Torii, Yutaka; Kawamura, Kyoko; Kato, Rina; Tsukada, Kazuhiko; Udagawa, Yasuhiro

    2013-12-01

    Cyclooxygenase (COX)-2 inhibitors have been reported to potentially modulate the resistance of cancer cells to chemotherapeutic drugs by affecting multidrug resistance 1 (MDR1) expression. In the present study, we investigated the association between COX-2 and MDR1 expression in endometrial cancers and evaluated the effects of the COX-2 inhibitor, etodolac, in combination with paclitaxel on paclitaxel-resistant endometrial cancer cells. The relationship between COX-2 and MDR1 mRNA expression was examined by quantitative PCR in 36 endometrial cancer specimens. The paclitaxel-resistant cell line OMC-2P was established from OMC-2 cells. Paclitaxel (1 µg/ml) with or without etodolac (10 µg/ml) was added to OMC-2 and OMC-2P cells, and COX-2 and MDR1 mRNA expression levels were examined. The concentration of prostaglandin E2 (PGE2) in the supernatant of each cell line was examined by enzyme-linked immunosorbent assay. The function of MDR1 was determined by intracellular accumulation of rhodamine 123 using flow cytometry, and the concentration of intracellular paclitaxel was determined by high-performance liquid chromatography. We found a positive relationship between COX-2 and MDR1 mRNA expression in endometrial cancer. Both COX-2 mRNA expression and PGE2 production were elevated in resistant OMC-2P cells when compared to non-resistant OMC-2 cells. Additionally, MDR1 mRNA expression was markedly upregulated in OMC-2P cells. In OMC-2 cells, COX-2 and MDR1 mRNA levels were significantly upregulated by paclitaxel treatment and downregulated by co-administration with etodolac. In OMC-2P cells, COX-2 mRNA expression was also significantly upregulated by paclitaxel treatment and tended to be downregulated by co-administration with etodolac. Moreover, co-administration of paclitaxel and etodolac suppressed the induction of MDR1 mRNA. Rhodamine 123 efflux was increased in OMC-2P cells when compared to the efflux in the OMC-2 cells and was increased in response to paclitaxel

  10. Inhibition of 5-LOX, COX-1, and COX-2 increases tendon healing and reduces muscle fibrosis and lipid accumulation after rotator cuff repair.

    Science.gov (United States)

    Oak, Nikhil R; Gumucio, Jonathan P; Flood, Michael D; Saripalli, Anjali L; Davis, Max E; Harning, Julie A; Lynch, Evan B; Roche, Stuart M; Bedi, Asheesh; Mendias, Christopher L

    2014-12-01

    The repair and restoration of function after chronic rotator cuff tears are often complicated by muscle atrophy, fibrosis, and fatty degeneration of the diseased muscle. The inflammatory response has been implicated in the development of fatty degeneration after cuff injuries. Licofelone is a novel anti-inflammatory drug that inhibits 5-lipoxygenase (5-LOX), as well as cyclooxygenase (COX)-1 and COX-2 enzymes, which play important roles in inducing inflammation after injuries. While previous studies have demonstrated that nonsteroidal anti-inflammatory drugs and selective inhibitors of COX-2 (coxibs) may prevent the proper healing of muscles and tendons, studies about bone and cartilage have demonstrated that drugs that inhibit 5-LOX concurrently with COX-1 and COX-2 may enhance tissue regeneration. After the repair of a chronic rotator cuff tear in rats, licofelone would increase the load to failure of repaired tendons and increase the force production of muscle fibers. Controlled laboratory study. Rats underwent supraspinatus release followed by repair 28 days later. After repair, rats began a treatment regimen of either licofelone or a vehicle for 14 days, at which time animals were euthanized. Supraspinatus muscles and tendons were then subjected to contractile, mechanical, histological, and biochemical analyses. Compared with controls, licofelone-treated rats had a grossly apparent decrease in inflammation and increased fibrocartilage formation at the enthesis, along with a 62% increase in the maximum load to failure and a 51% increase in peak stress to failure. Licofelone resulted in a marked reduction in fibrosis and lipid content in supraspinatus muscles as well as reduced expression of several genes involved in fatty infiltration. Despite the decline in fibrosis and fat accumulation, muscle fiber specific force production was reduced by 23%. The postoperative treatment of cuff repair with licofelone may reduce fatty degeneration and enhance the development

  11. Efficacy and safety of COX-2 inhibitors for advanced non-small-cell lung cancer with chemotherapy: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Dai P

    2018-02-01

    Full Text Available Ping Dai, Jing Li, Xiao-Ping Ma, Jian Huang, Juan-Juan Meng, Ping Gong Department of Oncology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, People’s Republic of China Background: The study of cyclooxygenase-2 (COX-2 inhibitors is now mired in controversy. We performed a meta-analysis to assess the efficacy and safety profile of COX-2 inhibitors in patients with advanced non-small-cell lung cancer (NSCLC.Patients and methods: A literature search of PubMed, EMBASE, the Cochrane Central databases, and ClinicalTrials.gov, up until March 26, 2017, identified relevant randomized controlled trials. Data analysis was performed using Stata 12.0.Results: Six eligible trials (1,794 patients were selected from the 407 studies that were identified initially. A significant difference, favoring COX-2 inhibitors plus chemotherapy over chemotherapy alone, was observed in the overall response rate (relative risk [RR] =1.25, 95% confidence interval [CI]: 1.06–1.48. Further, we conducted two subgroup analyses according to the type of COX-2 inhibitors (celecoxib, rofecoxib, or apricoxib and treatment line (first or second chemotherapy. The first-line treatment includes: NP (changchun red bean + cisplatin or carboplatin, GP (double fluorine cytidine + cisplatin or carboplatin, or TP (paclitaxel + cisplatin or carboplatin, docetaxel + cisplatin or carboplatin. The second-line treatment includes two internationally recognized compounds, one is docetaxel and the other is the pemetrexed, both of which are individually selected. In subgroup analysis, significantly increased overall response rate (ORR results were found for rofecoxib plus chemotherapy (RR =1.56, 95% CI: 1.08–2.25 and COX-2 inhibitor given with first-line chemotherapy (RR =1.27, 95% CI: 1.07–1.50. However, there was no difference between COX-2 inhibitors plus chemotherapy and chemotherapy alone in overall survival (hazard ratio [HR] =1.04, 95% CI: 0.91–1

  12. Acid-degradable Dextran as an Image Guided siRNA Carrier for COX-2 Downregulation.

    Science.gov (United States)

    Chen, Zhihang; Krishnamachary, Balaji; Penet, Marie-France; Bhujwalla, Zaver M

    2018-01-01

    Purpose: Effective in vivo delivery of siRNA to silence genes is a highly sought-after goal in the treatment of multiple diseases. Cyclooxygenase-2 (COX-2) is a major mediator of inflammation and its effective and specific downregulation has been of major interest to treat conditions ranging from auto-immune diseases to gastric inflammation and cancer. Here we developed a novel and efficient method to produce a multiple imaging reporter labeled cationic dextran nanopolymer with cleavable positive charge groups for COX-2 siRNA delivery. Methods: Small molecules containing amine groups were conjugated to the dextran scaffold through acetal bonds that were cleaved in weak acid conditions. With multiple imaging reporters located on different regions of the nanopolymer, cleavage of acetal bonds was visualized and quantified by imaging, for the first time, in cancer cells and tumors. Results: The biocompatibility of dextran and the rapid cleavage and release of amine groups minimized proinflammatory side effects and COX-2 induction observed with other siRNA carriers, to successfully achieve COX-2 downregulation in cancer cells and tumors. Imaging results confirmed that this nanoplex, consisting of the dextran nanopolymer with COX-2 siRNA, accumulated in tumors, and the amine functional groups were rapidly cleaved in cancer cells and tumors. Along with effective downregulation of COX-2, we also demonstrated, for the first time, effective downregulation of its major product prostaglandin E 2 (PGE 2 ). Conclusions: We successfully developed an efficient method to produce an acid-degradable dextran nanopolymer containing cleavable amine groups as the siRNA carrier. Because of its biocompatibility, this degradable dextran delivered COX-2 siRNA within tumors and efficiently downregulated COX-2 expression.

  13. COX-2 in Radiotherapy; a potential target for radioprotection and radiosensitization.

    Science.gov (United States)

    Cheki, Mohsen; Yahyapour, Rasoul; Farhood, Bagher; Rezaeyan, Abolhassan; Shabeeb, Dheyauldeen; Amini, Peyman; Rezapoor, Saeed; Najafi, Masoud

    2018-02-18

    Each year, millions of people die from cancer. Radiotherapy is one of the main treatment strategies for cancer patients. Despite the beneficial roles of treatment with radiation, several side effects may threaten normal tissues of patients in the years after treatment. Moreover, high incidences of second primary cancers may reduce therapeutic ratio of radiotherapy. The search for appropriate targets of radiosensitization of tumor cells as well as radioprotection of normal tissues is one of the most interesting aims in radiobiology. Cyclooxygenase-2 (COX-2), as an inflammatory mediator has attracted interests for both aims. COX-2 activity is associated with ROS production and inflammatory signs in normal tissues. These effects further amplify radiation toxicity in irradiated cells as well as adjacent cells through a phenomenon known as Bystander effect. Increased COX-2 expression in distant non-irradiated tissues causes oxidative DNA damage and elevated cancer risk. Moreover, in tumors, the activation of this enzyme can increase resistance of malignant cells to radiotherapy. Hence, the inhibition of COX-2 has been proposed for better therapeutic response and amelioration of normal tissues. Celecoxib is one of the most studied COX-2 inhibitor for radiosensitization and radioprotection, while some other inhibitors have shown interesting results. In this review, we describe the role of COX-2 in radiation normal tissue injury as well as irradiated bystander and non-targeted cells. In addition, mechanisms of COX-2 induced tumor resistance to radiotherapy and the potential role of COX-2 inhibition are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Leptin upregulates COX-2 and its downstream products in aortic endothelial cells.

    Science.gov (United States)

    Chen, Yuelin; Shen, Yuechun; Nie, Ya; Chen, Zhongxin; Wang, Huang; Liao, Huang; Li, Jun

    2017-11-01

    The adipocyte-derived hormone leptin is associated with hypertension. The involvement of cyclooxygenase-2 (COX-2) and its downstream vasomotor products prostaglandin (PG) and thromboxane (TX)A 2 in the mechanisms of action of leptin have remained elusive. The aim of the present study was to investigate the effects of leptin on the expression of COX-2 by rat aortic endothelial cells (RAECs) and the concentration of its products, represented by 6-keto PGF 1α and TXB 2 , in the culture media. RAECs were isolated, cultured and identified by immunofluorescence staining. The RAECs were incubated with different concentrations of leptin (10 -10 , 10 -9 and 10 -8 M) for various durations (36 or 48 h). COX-2 mRNA and protein expression in the cells was detected by reverse-transcription quantitative PCR and western blot analysis, respectively. The vasodilator 6-keto PGF 1α and the vasoconstrictor TXB 2 were detected in the supernatant by ELISA. The cultured cells displayed specific factor VIII expression in the cytoplasm. Compared with the PBS-treated control group, leptin significantly increased the expression of COX-2 mRNA and protein in a time- and dose-dependent manner (P0.05). In conclusion, leptin significantly increased the expression of inflammatory marker COX-2 and its downstream product 6-keto PGF 1α , while also decreasing the TXB 2 /6-keto PGF 1α ratio in vitro . These observations suggested that COX-2 may have an important role in the effects of leptin on inflammation, such as the low-inflammatory disease hypertension. However, selective COX-2 inhibitors may increase the risk of hypertension due to inhibiting 6-keto PGF 1α , the vasodilator product of COX-2.

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

    Science.gov (United States)

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

    2013-12-01

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

  16. Prostacyclin mediates endothelial COX-2-dependent neuroprotective effects during excitotoxic brain injury

    Directory of Open Access Journals (Sweden)

    An Y

    2014-05-01

    Full Text Available Ying An,1,2 Natalya Belevych,1,2 Yufen Wang,1,2 Hao Zhang,1 Jason S Nasse,3 Harvey Herschman,4 Qun Chen,1,2 Andrew Tarr,1,2 Xiaoyu Liu,1,2 Ning Quan1,21Institute for Behavior Medicine Research, 2Department of Oral Biology, College of Dentistry, 3Neuroscience Graduate Studies Program, The Ohio State University, Columbus, OH, USA; 4Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA, USAAbstract: In a previous study, we found that intracerebral administration of excitotoxin (RS-(tetrazole-5yl glycine caused increased neural damage in the brain in an endothelial COX-2 deleted mouse line (Tie2Cre COX-2flox/flox. In this study, we investigated whether prostacyclin might mediate this endothelial COX-2-dependent neuroprotection. Administration of excitotoxin into the striatum induced the production of prostacyclin (PGI2 in wild type, but not in endothelial COX-2 deleted mice. Inhibition of PGI2 synthase exacerbated brain lesions induced by the excitotoxin in wild type, but not in endothelial COX-2 deleted mice. Administration of a PGI2 agonist reduced neural damage in both wild type and endothelial COX-2 deleted mice. Increased PGI2 synthase expression was found in infiltrating neutrophils. In an ex vivo assay, PGI2 reduced the excitotoxin-induced calcium influx into neurons, suggesting a cellular mechanism for PGI2 mediated neuroprotection. These results reveal that PGI2 mediates endothelial COX-2 dependent neuroprotection.Keywords: neural injury, prostaglandins, neutrophil, conditional COX-2 deletion, PGI2

  17. Chemical process hazards analysis

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-02-01

    The Office of Worker Health and Safety (EH-5) under the Assistant Secretary for the Environment, Safety and Health of the US Department (DOE) has published two handbooks for use by DOE contractors managing facilities and processes covered by the Occupational Safety and Health Administration (OSHA) Rule for Process Safety Management of Highly Hazardous Chemicals (29 CFR 1910.119), herein referred to as the PSM Rule. The PSM Rule contains an integrated set of chemical process safety management elements designed to prevent chemical releases that can lead to catastrophic fires, explosions, or toxic exposures. The purpose of the two handbooks, ``Process Safety Management for Highly Hazardous Chemicals`` and ``Chemical Process Hazards Analysis,`` is to facilitate implementation of the provisions of the PSM Rule within the DOE. The purpose of this handbook ``Chemical Process Hazards Analysis,`` is to facilitate, within the DOE, the performance of chemical process hazards analyses (PrHAs) as required under the PSM Rule. It provides basic information for the performance of PrHAs, and should not be considered a complete resource on PrHA methods. Likewise, to determine if a facility is covered by the PSM rule, the reader should refer to the handbook, ``Process Safety Management for Highly Hazardous Chemicals`` (DOE- HDBK-1101-96). Promulgation of the PSM Rule has heightened the awareness of chemical safety management issues within the DOE. This handbook is intended for use by DOE facilities and processes covered by the PSM rule to facilitate contractor implementation of the PrHA element of the PSM Rule. However, contractors whose facilities and processes not covered by the PSM Rule may also use this handbook as a basis for conducting process hazards analyses as part of their good management practices. This handbook explains the minimum requirements for PrHAs outlined in the PSM Rule. Nowhere have requirements been added beyond what is specifically required by the rule.

  18. Transportation of hazardous materials emergency preparedness hazards assessment

    International Nuclear Information System (INIS)

    Blanchard, A.

    2000-01-01

    This report documents the Emergency Preparedness Hazards Assessment (EPHA) for the Transportation of Hazardous Materials (THM) at the Department of Energy (DOE) Savannah River Site (SRS). This hazards assessment is intended to identify and analyze those transportation hazards significant enough to warrant consideration in the SRS Emergency Management Program

  19. Transportation of Hazardous Materials Emergency Preparedness Hazards Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Blanchard, A.

    2000-02-28

    This report documents the Emergency Preparedness Hazards Assessment (EPHA) for the Transportation of Hazardous Materials (THM) at the Department of Energy (DOE) Savannah River Site (SRS). This hazards assessment is intended to identify and analyze those transportation hazards significant enough to warrant consideration in the SRS Emergency Management Program.

  20. Transportation of Hazardous Materials Emergency Preparedness Hazards Assessment

    International Nuclear Information System (INIS)

    Blanchard, A.

    2000-01-01

    This report documents the Emergency Preparedness Hazards Assessment (EPHA) for the Transportation of Hazardous Materials (THM) at the Department of Energy (DOE) Savannah River Site (SRS). This hazards assessment is intended to identify and analyze those transportation hazards significant enough to warrant consideration in the SRS Emergency Management Program

  1. Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling

    Science.gov (United States)

    Yang, Hongwei; Tang, Ya-ping; Sun, Hao; Song, Yunping; Chen, Chu

    2013-01-01

    SUMMARY Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here we show that synaptic and cognitive impairments following repeated exposure to Δ9-tetrahydrocannabinol (Δ9-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids, in the brain. COX-2 induction by Δ9-THC is mediated via CB1 receptor-coupled G-protein βγ subunits. Pharmacological or genetic inhibition of COX-2 blocks down-regulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ9-THC exposures. Ablation of COX-2 also eliminates Δ9-THC-impaired hippocampal long-term synaptic plasticity, spatial, and fear memories. Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ9-THC in Alzheimer’s disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2. PMID:24267894

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

    Science.gov (United States)

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

    2009-11-04

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

  3. DPPC regulates COX-2 expression in monocytes via phosphorylation of CREB

    International Nuclear Information System (INIS)

    Morris, R.H.K.; Tonks, A.J.; Jones, K.P.; Ahluwalia, M.K.; Thomas, A.W.; Tonks, A.; Jackson, S.K.

    2008-01-01

    The major phospholipid in pulmonary surfactant dipalmitoyl phosphatidylcholine (DPPC) has been shown to modulate inflammatory responses. Using human monocytes, this study demonstrates that DPPC significantly increased PGE 2 (P < 0.05) production by 2.5-fold when compared to untreated monocyte controls. Mechanistically, this effect was concomitant with an increase in COX-2 expression which was abrogated in the presence of a COX-2 inhibitor. The regulation of COX-2 expression was independent of NF-κB activity. Further, DPPC increased the phosphorylation of the cyclic AMP response element binding protein (CREB; an important nuclear transcription factor important in regulating COX-2 expression). In addition, we also show that changing the fatty acid groups of PC (e.g. using L-α-phosphatidylcholine β-arachidonoyl-γ-palmitoyl (PAPC)) has a profound effect on the regulation of COX-2 expression and CREB activation. This study provides new evidence for the anti-inflammatory activity of DPPC and that this activity is at least in part mediated via CREB activation of COX-2

  4. [Cox-maze III procedure for atrial fibrillation. A preliminary study].

    Science.gov (United States)

    García-Villarreal, Ovidio A

    2016-01-01

    To compare the efectiveness of the cut-and-sew Cox-maze III procedure against the Cox-maze IV peocedure by means of intraoperative bipolar radiofrequency delivery clamp. From January 2011 to October 2014, 50 patients were operated on with surgery for atrial fibrillation. All cases underwent mitral valve surgery as the first procedure, and secondarily a surgical procedure for atrial fibrillation was also performed. There were 2 groups. Group I (Cox-maze III «cut-and-sew»), and Group II (Cox-maze IV, intraoperative bipolar radiofrequency ablation). Group I was formed by 36 patients, and Group II by 14. All cases had atrial fibrillation longer than 1 year. The end-point was freedom of atrial fibrillation. There was no statistically significant difference between both groups regarding the basal and operative characteristics. Operative mortality was of 2 cases in the Group I, and no cases for Group II (P=0.9). A high tendency to eliminate atrial fibrillation in favour of Group I was observed (92% vs 53%, P<.001) in a 6 months follow-up. Classic standard Cox-maze III procedure showed superiority to eliminate atrial fibrillation over the Cox-maze IV procedure made with bipolar radiofrequency ablation clamp in patients with concomitant mitral valve disease. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  5. Which Mixed-Member Proportional Electoral Formula Fits You Best? Assessing the Proportionality Principle of Positive Vote Transfer Systems

    DEFF Research Database (Denmark)

    Bochsler, Daniel

    2014-01-01

    Mixed-member proportional systems (MMP) are a family of electoral systems which combine district-based elections with a proportional seat allocation. Positive vote transfer systems belong to this family. This article explains why they might be better than their siblings, and examines under which ...

  6. Association of COX-2 Promoter Polymorphisms -765G/C and -1195A/G with Migraine.

    Science.gov (United States)

    Mozaffari, Elahe; Doosti, Abbas; Arshi, Asghar; Faghani, Mostafa

    2016-12-01

    Migraine is a common debilitating primary headache disorder with current head pain attacks, which contributes to physical activity dysfunctions in chronic pain phase. PGE2 and PGI2 are two important prostaglandins synthesised by COX-2 enzymes, involved in migraine pain signals. COX-2 modulation is essential in treatment and pathogenesis of migraine. This study aimed to investigating the association between COX-2 gene polymorphisms with the risk of migraine susceptibility in migraine patients with related and unrelated parents. This case- control study was based on 100 migraine patients and 100 non-migraine subjects in Bushehr province, Iran in 2013. Genomic DNA of blood samples was extracted and genotyping of COX-2-765G>C (rs20417) and COX-2-1195A>G (rs689466) gene variants was investigated by PCR-RFLP method. Statistical analyses were accomplished using the SPSS software package. There was a significant differences in the frequencies of the COX-2-765G>C and COX-2-1195A>G genotypes between migraine patients and controls ( P ≤0.05). COX-2-765CC , COX-2-765CG , COX-2-1195GG and COX-2-1195AG genotypes can increase the risk of migraine significantly. As the first study in Iran, we are hopeful to achieve greater results about the relevancy of COX-2 gene, migraine and pain signals pathway by repeating these experiments on more samples.

  7. IDENTIFICATION OF AIRCRAFT HAZARDS

    Energy Technology Data Exchange (ETDEWEB)

    K.L. Ashley

    2005-03-23

    Aircraft hazards were determined to be potentially applicable to a repository at Yucca Mountain in the ''Monitored Geological Repository External Events Hazards Screening Analysis'' (BSC 2004, Section 6.4.1). That determination was conservatively based on limited knowledge of flight data in the area of concern and on crash data for aircraft of the type flying near Yucca Mountain. The purpose of this report is to identify specific aircraft hazards that may be applicable to a Monitored Geologic Repository (MGR) at Yucca Mountain using NUREG-0800, ''Standard Review Plan for the Review of Safety Analysis Reports for Nuclear Power Plants'' (NRC 1987, Section 3.5.1.6), as guidance for the inclusion or exclusion of identified aircraft hazards. NUREG-0800 is being used here as a reference because some of the same considerations apply. The intended use of this report is to provide inputs for further screening and analysis of the identified aircraft hazards based on the criteria that apply to Category 1 and 2 event sequence analyses as defined in 10 CFR 63.2 (see Section 4). The scope of this technical report includes the evaluation of military, private, and commercial use of airspace in the 100-mile regional setting of the MGR at Yucca Mountain with the potential for reducing the regional setting to a more manageable size after consideration of applicable screening criteria (see Section 7).

  8. Natural Hazards, Second Edition

    Science.gov (United States)

    Rouhban, Badaoui

    Natural disaster loss is on the rise, and the vulnerability of the human and physical environment to the violent forces of nature is increasing. In many parts of the world, disasters caused by natural hazards such as earthquakes, floods, landslides, drought, wildfires, intense windstorms, tsunami, and volcanic eruptions have caused the loss of human lives, injury, homelessness, and the destruction of economic and social infrastructure. Over the last few years, there has been an increase in the occurrence, severity, and intensity of disasters, culminating with the devastating tsunami of 26 December 2004 in South East Asia.Natural hazards are often unexpected or uncontrollable natural events of varying magnitude. Understanding their mechanisms and assessing their distribution in time and space are necessary for refining risk mitigation measures. This second edition of Natural Hazards, (following a first edition published in 1991 by Cambridge University Press), written by Edward Bryant, associate dean of science at Wollongong University, Australia, grapples with this crucial issue, aspects of hazard prediction, and other issues. The book presents a comprehensive analysis of different categories of hazards of climatic and geological origin.

  9. Identification of Aircraft Hazards

    International Nuclear Information System (INIS)

    K. Ashley

    2006-01-01

    Aircraft hazards were determined to be potentially applicable to a repository at Yucca Mountain in ''Monitored Geological Repository External Events Hazards Screening Analysis'' (BSC 2005 [DIRS 174235], Section 6.4.1). That determination was conservatively based upon limited knowledge of flight data in the area of concern and upon crash data for aircraft of the type flying near Yucca Mountain. The purpose of this report is to identify specific aircraft hazards that may be applicable to a monitored geologic repository (MGR) at Yucca Mountain, using NUREG-0800, ''Standard Review Plan for the Review of Safety Analysis Reports for Nuclear Power Plants'' (NRC 1987 [DIRS 103124], Section 3.5.1.6), as guidance for the inclusion or exclusion of identified aircraft hazards. The intended use of this report is to provide inputs for further screening and analysis of identified aircraft hazards based upon the criteria that apply to Category 1 and Category 2 event sequence analyses as defined in 10 CFR 63.2 [DIRS 176544] (Section 4). The scope of this report includes the evaluation of military, private, and commercial use of airspace in the 100-mile regional setting of the repository at Yucca Mountain with the potential for reducing the regional setting to a more manageable size after consideration of applicable screening criteria (Section 7)

  10. IDENTIFICATION OF AIRCRAFT HAZARDS

    International Nuclear Information System (INIS)

    K.L. Ashley

    2005-01-01

    Aircraft hazards were determined to be potentially applicable to a repository at Yucca Mountain in the ''Monitored Geological Repository External Events Hazards Screening Analysis'' (BSC 2004, Section 6.4.1). That determination was conservatively based on limited knowledge of flight data in the area of concern and on crash data for aircraft of the type flying near Yucca Mountain. The purpose of this report is to identify specific aircraft hazards that may be applicable to a Monitored Geologic Repository (MGR) at Yucca Mountain using NUREG-0800, ''Standard Review Plan for the Review of Safety Analysis Reports for Nuclear Power Plants'' (NRC 1987, Section 3.5.1.6), as guidance for the inclusion or exclusion of identified aircraft hazards. NUREG-0800 is being used here as a reference because some of the same considerations apply. The intended use of this report is to provide inputs for further screening and analysis of the identified aircraft hazards based on the criteria that apply to Category 1 and 2 event sequence analyses as defined in 10 CFR 63.2 (see Section 4). The scope of this technical report includes the evaluation of military, private, and commercial use of airspace in the 100-mile regional setting of the MGR at Yucca Mountain with the potential for reducing the regional setting to a more manageable size after consideration of applicable screening criteria (see Section 7)

  11. Identification of Aircraft Hazards

    Energy Technology Data Exchange (ETDEWEB)

    K. Ashley

    2006-12-08

    Aircraft hazards were determined to be potentially applicable to a repository at Yucca Mountain in ''Monitored Geological Repository External Events Hazards Screening Analysis'' (BSC 2005 [DIRS 174235], Section 6.4.1). That determination was conservatively based upon limited knowledge of flight data in the area of concern and upon crash data for aircraft of the type flying near Yucca Mountain. The purpose of this report is to identify specific aircraft hazards that may be applicable to a monitored geologic repository (MGR) at Yucca Mountain, using NUREG-0800, ''Standard Review Plan for the Review of Safety Analysis Reports for Nuclear Power Plants'' (NRC 1987 [DIRS 103124], Section 3.5.1.6), as guidance for the inclusion or exclusion of identified aircraft hazards. The intended use of this report is to provide inputs for further screening and analysis of identified aircraft hazards based upon the criteria that apply to Category 1 and Category 2 event sequence analyses as defined in 10 CFR 63.2 [DIRS 176544] (Section 4). The scope of this report includes the evaluation of military, private, and commercial use of airspace in the 100-mile regional setting of the repository at Yucca Mountain with the potential for reducing the regional setting to a more manageable size after consideration of applicable screening criteria (Section 7).

  12. Visualizing Proportions and Dissimilarities by Space-filling Maps

    DEFF Research Database (Denmark)

    Carrizosa, Emilio; Guerrero, Vanesa; Morales, Dolores Romero

    2017-01-01

    In this paper we address the problem of visualizing a set of individuals, which have attached a statistical value given as a proportion, and a dissimilarity measure. Each individual is represented as a region within the unit square, in such a way that the area of the regions represent the proport......In this paper we address the problem of visualizing a set of individuals, which have attached a statistical value given as a proportion, and a dissimilarity measure. Each individual is represented as a region within the unit square, in such a way that the area of the regions represent...

  13. Knox meets Cox: adapting epidemiological space-time statistics to demographic studies.

    Science.gov (United States)

    Schmertmann, Carl P; Assuçãon, Renato M; Potter, Joseph E

    2010-08-01

    Many important questions and theories in demography focus on changes over time, and on how those changes differ over geographic and social space. Space-time analysis has always been important in studying fertility transitions, for example. However demographers have seldom used formal statistical methods to describe and analyze time series of maps. One formal method, used widely in epidemiology, criminology, and public health, is Knox 's space-time interaction test. In this article, we discuss the potential of the Knox test in demographic research and note some possible pitfalls. We demonstrate how to use familiar proportional hazards models to adapt the Knox test for demographic applications. These adaptations allow for nonrepeatable events and for the incorporation of structural variables that change in space and time. We apply the modified test to data on the onset offertility decline in Brazil over 1960-2000 and show how the modified method can produce maps indicating where and when diffusion effects seem strongest, net of covariate effects.

  14. Seismic hazard map of the western hemisphere

    Science.gov (United States)

    Shedlock, K.M.; Tanner, J.G.

    1999-01-01

    Vulnerability to natural disasters increases with urbanization and development of associated support systems (reservoirs, power plants, etc.). Catastrophic earthquakes account for 60% of worldwide casualties associated with natural disasters. Economic damage from earthquakes is increasing, even in technologically advanced countries with some level of seismic zonation, as shown by the 1989 Loma Prieta, CA ($6 billion), 1994 Northridge, CA ($ 25 billion), and 1995 Kobe, Japan (> $ 100 billion) earthquakes. The growth of megacities in seismically active regions around the world often includes the construction of seismically unsafe buildings and infrastructures, due to an insufficient knowledge of existing seismic hazard. Minimization of the loss of life, property damage, and social and economic disruption due to earthquakes depends on reliable estimates of seismic hazard. National, state, and local governments, decision makers, engineers, planners, emergency response organizations, builders, universities, and the general public require seismic hazard estimates for land use planning, improved building design and construction (including adoption of building construction codes), emergency response preparedness plans, economic forecasts, housing and employment decisions, and many more types of risk mitigation. The seismic hazard map of the Americas is the concatenation of various national and regional maps, involving a suite of approaches. The combined maps and documentation provide a useful global seismic hazard framework and serve as a resource for any national or regional agency for further detailed studies applicable to their needs. This seismic hazard map depicts Peak Ground Acceleration (PGA) with a 10% chance of exceedance in 50 years for the western hemisphere. PGA, a short-period ground motion parameter that is proportional to force, is the most commonly mapped ground motion parameter because current building codes that include seismic provisions specify the

  15. Seismic hazard map of the western hemisphere

    Directory of Open Access Journals (Sweden)

    J. G. Tanner

    1999-06-01

    Full Text Available Vulnerability to natural disasters increases with urbanization and development of associated support systems (reservoirs, power plants, etc.. Catastrophic earthquakes account for 60% of worldwide casualties associated with natural disasters. Economic damage from earthquakes is increasing, even in technologically advanced countries with some level of seismic zonation, as shown by the 1989 Loma Prieta, CA ($ 6 billion, 1994 Northridge, CA ($ 25 billion, and 1995 Kobe, Japan (> $ 100 billion earthquakes. The growth of megacities in seismically active regions around the world often includes the construction of seismically unsafe buildings and infrastructures, due to an insufficient knowledge of existing seismic hazard. Minimization of the loss of life, property damage, and social and economic disruption due to earthquakes depends on reliable estimates of seismic hazard. National, state, and local governments, decision makers, engineers, planners, emergency response organizations, builders, universities, and the general public require seismic hazard estimates for land use planning, improved building design and construction (including adoption of building construction codes, emergency response preparedness plans, economic forecasts, housing and employment decisions, and many more types of risk mitigation. The seismic hazard map of the Americas is the concatenation of various national and regional maps, involving a suite of approaches. The combined maps and documentation provide a useful global seismic hazard framework and serve as a resource for any national or regional agency for further detailed studies applicable to their needs. This seismic hazard map depicts Peak Ground Acceleration (PGA with a 10% chance of exceedance in 50 years for the western hemisphere. PGA, a short-period ground motion parameter that is proportional to force, is the most commonly mapped ground motion parameter because current building codes that include seismic provisions

  16. Hazardous fluid leak detector

    Science.gov (United States)

    Gray, Harold E.; McLaurin, Felder M.; Ortiz, Monico; Huth, William A.

    1996-01-01

    A device or system for monitoring for the presence of leaks from a hazardous fluid is disclosed which uses two electrodes immersed in deionized water. A gas is passed through an enclosed space in which a hazardous fluid is contained. Any fumes, vapors, etc. escaping from the containment of the hazardous fluid in the enclosed space are entrained in the gas passing through the enclosed space and transported to a closed vessel containing deionized water and two electrodes partially immersed in the deionized water. The electrodes are connected in series with a power source and a signal, whereby when a sufficient number of ions enter the water from the gas being bubbled through it (indicative of a leak), the water will begin to conduct, thereby allowing current to flow through the water from one electrode to the other electrode to complete the circuit and activate the signal.

  17. The perception of hazards

    International Nuclear Information System (INIS)

    Fritzsche, A.F.

    1986-01-01

    The fourth chapter deals with the profusion of factors determining the differing assessment of hazards by our society. Subjective factors influencing risk perception comprise, among others, general knowledge and recognition of a hazard; the degree of voluntariness when taking the risk and its influencibility; the problem of large scale accidents; immediate and delayed results. Next to the objective and the subjective risks, the individual and the social or collective risks are assessed differently. The author dicusses in detail recent investigations into and study methods for the determination of risk perception, while eliminating systematic trends from subjective perception since common assessments are shared by whole groups of individuals time and again which allow a better understanding of today's handling of hazards. (HSCH) [de

  18. The hazards of bad sleep-Sleep duration and quality as predictors of adolescent alcohol and cannabis use.

    Science.gov (United States)

    Mike, Thomas B; Shaw, Daniel S; Forbes, Erika E; Sitnick, Stephanie L; Hasler, Brant P

    2016-11-01

    Although an association between adolescent sleep and substance use is supported by the literature, few studies have characterized the longitudinal relationship between early adolescent sleep and subsequent substance use. The current study examined the prospective association between the duration and quality of sleep at age 11 and alcohol and cannabis use throughout adolescence. The present study, drawn from a cohort of 310 boys taking part in a longitudinal study in Western Pennsylvania, includes 186 boys whose mothers completed the Child Sleep Questionnaire; sleep duration and quality at age 11 were calculated based on these reports. At ages 20 and 22, participants were interviewed regarding lifetime alcohol and cannabis use. Cox proportional hazard analysis was used to determine the association between sleep and substance use. After accounting for race, socioeconomic status, neighborhood danger, active distraction, internalizing problems, and externalizing problems, both the duration and quality of sleep at age 11 were associated with multiple earlier substance use outcomes. Specifically, less sleep was associated with earlier use, intoxication, and repeated use of both alcohol and cannabis. Lower sleep quality was associated with earlier alcohol use, intoxication, and repeated use. Additionally, lower sleep quality was associated with earlier cannabis intoxication and repeated use, but not first use. Both sleep duration and sleep quality in early adolescence may have implications for the development of alcohol and cannabis use throughout adolescence. Further studies to understand the mechanisms linking sleep and substance use are warranted. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. The Hazards of Bad Sleep – Sleep Duration and Quality as Predictors of Adolescent Alcohol and Cannabis Use*

    Science.gov (United States)

    Mike, Thomas B.; Shaw, Daniel S.; Forbes, Erika E.; Sitnick, Stephanie L.; Hasler, Brant P.

    2016-01-01

    Background Although an association between adolescent sleep and substance use is supported by the literature, few studies have characterized the longitudinal relationship between early adolescent sleep and subsequent substance use. The current study examined the prospective association between the duration and quality of sleep at age 11 and alcohol and cannabis use throughout adolescence. Methods The present study, drawn from a cohort of 310 boys taking part in a longitudinal study in Western Pennsylvania, includes 186 boys whose mothers completed the Child Sleep Questionnaire; sleep duration and quality at age 11 were calculated based on these reports. At ages 20 and 22, participants were interviewed regarding lifetime alcohol and cannabis use. Cox proportional hazard analysis was used to determine the association between sleep and substance use. Results After accounting for race, socioeconomic status, neighborhood danger, active distraction, internalizing problems, and externalizing problems, both the duration and quality of sleep at age 11 were associated with multiple earlier substance use outcomes. Specifically, less sleep was associated with earlier use, intoxication, and repeated use of both alcohol and cannabis. Lower sleep quality was associated with earlier alcohol use, intoxication, and repeated use. Additionally, lower sleep quality was associated with earlier cannabis intoxication and repeated use, but not first use. Conclusions Both sleep duration and sleep quality in early adolescence may have implications for the development of alcohol and cannabis use throughout adolescence. Further studies to understand the mechanisms linking sleep and substance use are warranted. PMID:27659736

  20. Proteomic Analysis Shows Constitutive Secretion of MIF and p53-associated Activity of COX-2-/- Lung Fibroblasts.

    Science.gov (United States)

    Dave, Mandar; Islam, Abul B M M K; Jensen, Roderick V; Rostagno, Agueda; Ghiso, Jorge; Amin, Ashok R

    2017-12-01

    The differential expression of two closelyassociated cyclooxygenase isozymes, COX-1 and COX-2, exhibited functions beyond eicosanoid metabolism. We hypothesized that COX-1 or COX-2 knockout lung fibroblasts may display altered protein profiles which may allow us to further differentiate the functional roles of these isozymes at the molecular level. Proteomic analysis shows constitutive production of macrophage migration inhibitory factor (MIF) in lung fibroblasts derived from COX-2 -/- but not wild-type (WT) or COX-1 -/- mice. MIF was spontaneously released in high levels into the extracellular milieu of COX2 -/- fibroblasts seemingly from the preformed intracellular stores, with no change in the basal gene expression of MIF. The secretion and regulation of MIF in COX-2 -/- was "prostaglandin-independent." GO analysis showed that concurrent with upregulation of MIF, there is a significant surge in expression of genes related to fibroblast growth, FK506 binding proteins, and isomerase activity in COX-2 -/- cells. Furthermore, COX-2 -/- fibroblasts also exhibit a significant increase in transcriptional activity of various regulators, antagonists, and co-modulators of p53, as well as in the expression of oncogenes and related transcripts. Integrative Oncogenomics Cancer Browser (IntroGen) analysis shows downregulation of COX-2 and amplification of MIF and/or p53 activity during development of glioblastomas, ependymoma, and colon adenomas. These data indicate the functional role of the MIF-COX-p53 axis in inflammation and cancer at the genomic and proteomic levels in COX-2-ablated cells. This systematic analysis not only shows the proinflammatory state but also unveils a molecular signature of a pro-oncogenic state of COX-1 in COX-2 ablated cells. Copyright © 2017 Beijing Institute of Genomics, Chinese Academy of Sciences and Genetics Society of China. Production and hosting by Elsevier B.V. All rights reserved.

  1. Proteomic Analysis Shows Constitutive Secretion of MIF and p53-associated Activity of COX-2−/− Lung Fibroblasts

    Directory of Open Access Journals (Sweden)

    Mandar Dave

    2017-12-01

    Full Text Available The differential expression of two closelyassociated cyclooxygenase isozymes, COX-1 and COX-2, exhibited functions beyond eicosanoid metabolism. We hypothesized that COX-1 or COX-2 knockout lung fibroblasts may display altered protein profiles which may allow us to further differentiate the functional roles of these isozymes at the molecular level. Proteomic analysis shows constitutive production of macrophage migration inhibitory factor (MIF in lung fibroblasts derived from COX-2−/− but not wild-type (WT or COX-1−/− mice. MIF was spontaneously released in high levels into the extracellular milieu of COX2−/− fibroblasts seemingly from the preformed intracellular stores, with no change in the basal gene expression of MIF. The secretion and regulation of MIF in COX-2−/− was “prostaglandin-independent.” GO analysis showed that concurrent with upregulation of MIF, there is a significant surge in expression of genes related to fibroblast growth, FK506 binding proteins, and isomerase activity in COX-2−/− cells. Furthermore, COX-2−/− fibroblasts also exhibit a significant increase in transcriptional activity of various regulators, antagonists, and co-modulators of p53, as well as in the expression of oncogenes and related transcripts. Integrative Oncogenomics Cancer Browser (IntroGen analysis shows downregulation of COX-2 and amplification of MIF and/or p53 activity during development of glioblastomas, ependymoma, and colon adenomas. These data indicate the functional role of the MIF-COX-p53 axis in inflammation and cancer at the genomic and proteomic levels in COX-2-ablated cells. This systematic analysis not only shows the proinflammatory state but also unveils a molecular signature of a pro-oncogenic state of COX-1 in COX-2 ablated cells.

  2. The expression of COX-2 in VEGF-treated endothelial cells is mediated through protein tyrosine kinase

    Directory of Open Access Journals (Sweden)

    Pravit Akarasereenont

    2002-01-01

    Full Text Available Cyclooxygenase (COX, existing as the COX-1 and COX-2 isoforms, converts arachidonic acid to prostaglandin H2, which is then further metabolized to various prostaglandins. Vascular endothelial growth factor (VEGF has been shown to play important roles in inflammation and is upregulated by the prostaglandin E series through COX-2 in several cell types. Here, we have investigated the effects of VEGF on the COX isoform expressed in human umbilical vein endothelial cells (HUVEC. The signalling mechanism of the COX isoform expressed in endothelial cells activated with VEGF will be also investigated using the tyrosine kinase inhibitor, genistein, and protein kinase C inhibitor, staurosporine. The activity of COX2 was assessed by measuring the production of 6-keto-prostaglandin F1α in the presence of exogenous arachidonic acids (10 μM, 10 min by enzyme immunoassay. The expression of COX isoform protein was detected by immunoblot using specific antibodies. Untreated HUVEC contained no COX-2 protein. In HUVEC treated with VEGF (0.01-50 ng/ml, COX-2 protein, but not COX-1, and COX activity were increased in a dose-dependent manner. Interestingly, the increased COX-2 protein and activity in response to VEGF (10 ng/ml was inhibited by the tyrosine kinase inhibitor, genistein (0.05-5 μg/ml, but not by the protein kinase C inhibitor, staurosporine (0.1-10 ng/ml. Thus, the induction of COX-2 by VEGF in endothelial cells was mediated through protein tyrosine kinase, and the uses of specific COX-2 inhibitors in these conditions, in which VEGF was involved, might have a role.

  3. DC motor proportional control system for orthotic devices

    Science.gov (United States)

    Blaise, H. T.; Allen, J. R.

    1972-01-01

    Multi-channel proportional control system for operation of dc motors for use with externally-powered orthotic arm braces is described. Components of circuitry and principles of operation are described. Schematic diagram of control circuit is provided.

  4. Proportion of patients in the Uganda rheumatic heart disease ...

    African Journals Online (AJOL)

    . The optimum management strategy was determined according to ... Conclusion: There is a high proportion of patients with severe disease that require surgical treatment yet they cannot access this therapy due to absence of local expertise.

  5. Onsite transportation hazards assessment

    International Nuclear Information System (INIS)

    Burnside, M.E.

    1998-01-01

    This report documents the emergency preparedness Hazards Assessment for the onsite transportation of hazardous material at the Hanford Site. The assessment is required by US Department of Energy (DOE) Order 5500.3A and provides the technical basis for the emergency classification and response procedures. A distinction is made between onsite for the purpose of emergency preparedness and onsite for the purpose of applying US Department of Transportation (DOT) regulations. Onsite for the purpose of emergency preparedness is considered to be within the physical boundary of the entire Hanford Site. Onsite for the purpose of applying DOT regulations is north of the Wye Barricade

  6. Hazard Communication Standard

    International Nuclear Information System (INIS)

    Sichak, S.

    1991-01-01

    The current rate of technological advances has brought with it an overwhelming increase in the usage of chemicals in the workplace and in the home. Coupled to this increase has been a heightened awareness in the potential for acute and chronic injuries attributable to chemical insults. The Hazard Communication Standard has been introduced with the desired goal of reducing workplace exposures to hazardous substances and thereby achieving a corresponding reduction in adverse health effects. It was created and proclaimed by the US Department of Labor and regulated by the Occupational Safety and Health Administration. 1 tab

  7. Transportation of hazardous goods

    CERN Multimedia

    TS Department

    2008-01-01

    A general reminder: any transportation of hazardous goods by road is subject to the European ADR rules. The goods concerned are essentially the following: Explosive substances and objects; Gases (including aerosols and non-flammable gases such as helium and nitrogen); Flammable substances and liquids (inks, paints, resins, petroleum products, alcohols, acetone, thinners); Toxic substances (acids, thinners); Radioactive substances; Corrosive substances (paints, acids, caustic products, disinfectants, electrical batteries). Any requests for the transport of hazardous goods must be executed in compliance with the instructions given at this URL: http://ts-dep.web.cern.ch/ts-dep/groups/he/HH/adr.pdf Heavy Handling Section TS-HE-HH 73793 - 160364

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

    Science.gov (United States)

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

    2017-07-01

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

  9. MicroRNA-128 inhibits proliferation and invasion of glioma cells by targeting COX-2.

    Science.gov (United States)

    Lin, Yihai; Wu, Zhangyi

    2018-03-07

    MicroRNAs (miRNA), a class of small noncoding RNAs, regulates message RNA (mRNA) by targeting the 3'-untranslated region (3'-UTR) resulting in suppression of gene expression. In this study, we identified the expression and function of miR-128, which was found to be downregulated in glioma tissues and glioma cells by real time PCR. Overexpression of miR-128 mimics into LN229 and U251 cells could inhibit proliferation and invasion of glioma cells. However, the inhibitory effects of miR-128 mimics on the invasion and proliferation of glioma cells were reversed by overexpression of cyclooxygenase-2 (COX-2). Our data showed that COX-2 was a candidate target of miR-128. Luciferase activity of 3'-UTR of COX-2 was reduced in the presence of miR-128. Additionally, miR-128 obviously decreased COX-2 mRNA stability determined by real time PCR. Contrarily, we found that miR-128 inhibitor significantly increased the COX-2 mRNA expression, and elevated the protein expression of MMP9 and ki67, and promoted the proliferation of glioma cells. Furthermore, luciferase activity of the 3'-UTR was upregulated by miR-128 inhibitor. All of these results supported that miR-128 was a direct regulator of COX-2. Further studies proved that COX-2 was elevated in glioma tissues and its expression was negatively correlated with the levels of miR-128. These findings may establish miR-128 as a new potential target for the treatment of patients with gliomas. Copyright © 2017. Published by Elsevier B.V.

  10. COX-2 mediates PM2.5-induced apoptosis and inflammation in vascular endothelial cells.

    Science.gov (United States)

    Yin, Jie; Xia, Weiwei; Li, Yuanyuan; Guo, Chuchu; Zhang, Yue; Huang, Songming; Jia, Zhanjun; Zhang, Aihua

    2017-01-01

    Emerging evidence demonstrated that particulate matter 2.5 (PM2.5) exposure served as an important risk factor of cardiovascular diseases. Some studies also reported that COX-2/mPGES-1/PGE2 cascade played a pathogenic role in vascular injury. However, the relationship between the PM2.5 exposure and the activation of COX-2/mPGES-1/PGE2 cascade in endothelial cells is still unknown. In the present study, mouse aorta endothelial cells were exposed to PM2.5. Strikingly, following the PM2.5 treatment, we observed dose- and time-dependent upregulation of COX-2 at both protein and mRNA levels as determined by Western blotting and qRT-PCR, respectively. However, COX-1 mRNA expression was not affected by PM2.5 treatment. Next, we examined mPGES-1 expression. As expected, mPGES-1 protein was markedly increased by PM2.5 exposure in line with a significant increment of PGE2 release in medium. At the same time, we observed a dose-dependent upregulation of another two PGE2 synthases of mPGES-2 and cPGES determined by qRT-PCR. Inhibition of COX-2 by using a specific COX-2 inhibitor NS-398 markedly blocked cell apoptosis, inflammation, and PGE2 secretion. Taken together, these results suggested that PM2.5 could activate inflammatory axis of COX-2/PGES/PGE2 in vascular endothelial cells to promote cell apoptosis and inflammatory response.

  11. CONVERGENT SYNTHESIS AND EVALUATION OF 18F-LABELED AZULENIC COX2 PROBES FOR CANCER IMAGING

    Directory of Open Access Journals (Sweden)

    Donald D. Nolting

    2013-01-01

    Full Text Available The overall objectives of this research are to (i develop azulene-based PET probes and (ii image COX2 as a potential biomarker of breast cancer. Several lines of research have demonstrated that COX2 is overexpressed in breast cancer and that its presence correlates with poor prognoses. While other studies have reported that COX2 inhibition can be modulated and used beneficially as a chemopreventive strategy in cancer, no viable mechanism for achieving that approach has yet been developed. This shortfall could be circumvented through in vivo imaging of COX2 activity, particularly using sensitive imaging techniques such as PET. Toward that goal, our laboratory focuses on the development of novel 18F-labled COX2 probes. We began the synthesis of the probes by transforming tropolone into a lactone, which was subjected to an [8+2] cycloaddition reaction to yield 2-methylazulene as the core ring of the probe. After exploring numerous synthetic routes, the final target molecule and precursor PET compounds were prepared successfully using convergent synthesis. Conventional 18F labeling methods caused precursor decomposition, which prompted us to hypothesize that the acidic protons of the methylene moiety between the azulene and thiazole rings were readily abstracted by a strong base such as potassium carbonate. Ultimately, this caused the precursors to disintegrate. This observation was supported after successfully using an 18F labeling strategy that employed a much milder phosphate buffer. The 18F-labeled COX2 probe was tested in a breast cancer xenograft mouse model. The data obtained via successive whole-body PET/CT scans indicated probe accumulation and retention in the tumor. Overall, the probe was stable in vivo and no defluorination was observed. A biodistribution study and Western blot analysis corroborate with the imaging data. In conclusion, this novel COX2 PET probe was shown to be a promising agent for cancer imaging and deserves further

  12. Niacin and biosynthesis of PGD2 by platelet COX-1 in mice and humans

    Science.gov (United States)

    Song, Wen-Liang; Stubbe, Jane; Ricciotti, Emanuela; Alamuddin, Naji; Ibrahim, Salam; Crichton, Irene; Prempeh, Maxwell; Lawson, John A.; Wilensky, Robert L.; Rasmussen, Lars Melholt; Puré, Ellen; FitzGerald, Garret A.

    2012-01-01

    The clinical use of niacin to treat dyslipidemic conditions is limited by noxious side effects, most commonly facial flushing. In mice, niacin-induced flushing results from COX-1–dependent formation of PGD2 and PGE2 followed by COX-2–dependent production of PGE2. Consistent with this, niacin-induced flushing in humans is attenuated when niacin is combined with an antagonist of the PGD2 receptor DP1. NSAID-mediated suppression of COX-2–derived PGI2 has negative cardiovascular consequences, yet little is known about the cardiovascular biology of PGD2. Here, we show that PGD2 biosynthesis is augmented during platelet activation in humans and, although vascular expression of DP1 is conserved between humans and mice, platelet DP1 is not present in mice. Despite this, DP1 deletion in mice augmented aneurysm formation and the hypertensive response to Ang II and accelerated atherogenesis and thrombogenesis. Furthermore, COX inhibitors in humans, as well as platelet depletion, COX-1 knockdown, and COX-2 deletion in mice, revealed that niacin evoked platelet COX-1–derived PGD2 biosynthesis. Finally, ADP-induced spreading on fibrinogen was augmented by niacin in washed human platelets, coincident with increased thromboxane (Tx) formation. However, in platelet-rich plasma, where formation of both Tx and PGD2 was increased, spreading was not as pronounced and was inhibited by DP1 activation. Thus, PGD2, like PGI2, may function as a homeostatic response to thrombogenic and hypertensive stimuli and may have particular relevance as a constraint on platelets during niacin therapy. PMID:22406532

  13. Computer use and health hazard: perceptions from Nigeria's ...

    African Journals Online (AJOL)

    Findings revealed that some of the respondents have not experienced any health hazards associated with prolonged use of the computer, while some proportion indicated that they had experienced the combination of headache, vision and ergonomic related problems. At the 5% level of significance, analysis revealed that ...

  14. The synthesis of isotopic fluorine and iodine-labeled COX-II inhibitor and in vitro validation

    Energy Technology Data Exchange (ETDEWEB)

    An, Gwang Gil; Lee, Tae Sub; Lee, Kyo Chul; Moon, Byung Seok; Choi, Chang Woon; Chun, Kwon Soo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2005-07-01

    In these day, NASIDs (non-steroidal antiinflammatory drugs) such as aspirin, diclofenac and ibuprofen are the most common medications used to reduce pain and inflammation. However, they act by inhibiting both COX-I and COX-II which can cause serious gastrointestinal side effects such as ulcers, stomach perforations and bleeds. COX-I produces prostaglandins believed to be responsible for the protection of the stomach lining. However, COX-II produces prostaglandins believed to be responsible for pain and inflammation. Recently, the most widely studied selective COX-II inhibitor such as celecoxib and rofecoxib' one work by inhibiting the effect of COX-II on pain and inflammation without inhibiting COX-I which protects gastrointestinal lining.

  15. The synthesis of isotopic fluorine and iodine-labeled COX-II inhibitor and in vitro validation

    International Nuclear Information System (INIS)

    An, Gwang Gil; Lee, Tae Sub; Lee, Kyo Chul; Moon, Byung Seok; Choi, Chang Woon; Chun, Kwon Soo

    2005-01-01

    In these day, NASIDs (non-steroidal antiinflammatory drugs) such as aspirin, diclofenac and ibuprofen are the most common medications used to reduce pain and inflammation. However, they act by inhibiting both COX-I and COX-II which can cause serious gastrointestinal side effects such as ulcers, stomach perforations and bleeds. COX-I produces prostaglandins believed to be responsible for the protection of the stomach lining. However, COX-II produces prostaglandins believed to be responsible for pain and inflammation. Recently, the most widely studied selective COX-II inhibitor such as celecoxib and rofecoxib' one work by inhibiting the effect of COX-II on pain and inflammation without inhibiting COX-I which protects gastrointestinal lining

  16. High COX-2 expression is associated with increased angiogenesis, proliferation and tumoural inflammatory infiltrate in canine malignant mammary tumours: a multivariate survival study.

    Science.gov (United States)

    Carvalho, M I; Pires, I; Prada, J; Raposo, T P; Gregório, H; Lobo, L; Queiroga, F L

    2017-06-01

    COX-2 expression affects mammary tumourigenesis by promoting angiogenesis and cell proliferation, encouraging metastatic spread and tumour-associated inflammation. Samples of canine mammary tumours (n = 109) were submitted to immunohistochemistry to detect COX-2, CD31, VEGF, Ki-67, CD3 and MAC387 expression. Concurrent high expression of COX-2/CD31, COX-2/VEGF, COX-2/Ki-67, COX-2/CD3 and COX-2/MAC was associated with elevated grade of malignancy, presence of intravascular emboli and presence of lymph node metastasis. Tumours with high COX-2 (P COX-2 and high CD31 (P = 0.008); high VEGF (P COX-2/CD31 and high COX-2/VEGF retained their significance after multivariate analysis arising as independent predictors of OS. Present data highlight the importance of COX-2 in canine mammary tumourigenesis. © 2016 John Wiley & Sons Ltd.

  17. ["Golden proportion" and its application to calculate dentition].

    Science.gov (United States)

    Vadachkoriia, N R; Gumberidze, N Sh; Mandzhavidze, N A

    2007-01-01

    Within an evolutionary process, the nature has created the standard of aesthetics - a "gold proportion" on the basis of which, the parts of human body, to be more exact, teeth and denture correspond to each other and to own parts by the size, which is the ideal precondition for ideal appearance. The charming smile serves as the proof, that teeth in denture are located by a principle of "gold proportion". A "gold proportion" is the corner stone of beauty and it can be applied with success in stomatology. Proportion is the certain ratio between parts, and proportional means a proper correlation of parts among themselves. It is reputed, that knowledge about "gold proportion" Pythagor has got from products of the Egyptian and Babylon scientists. And this is true, proportions of cult constructions, bas-relieves, pyramids in Giza, home appliances and ornaments from Tutanhamon tomb testify, that under their creation the Egyptian masters were guided by a principle of "gold proportion". The facade of ancient Greek temple Parthenon is built by a principle of "gold proportion". During archeological digs of this temple the compasses which sculptors and architects of an ancient world used has been found. The "gold proportion" is mentioned in the work which has reached us "Beginning" the author is the scientist of antique epoch Euclid. In 1509, in Venice the book of Luka Pacholi the "Divine proportion" has been published, its illustration is attributed to Leonardo de Vinci. This work has been recognized as a "Hymn of a gold proportion". In 1885 the German researcher professor Zeising published his work - "Aesthetic researches". When Zeising has received numerical values of piece length, he saw that they coincided with figures of some numerical sequence, which was offered by the great Italian mathematician of Middle Ages Fibonacci (or Leonardo Pisano). In his composition the "Abacus Book" Leonardo Fibonacci showed aforesaid sequence of numbers, by means of which he has explained

  18. Hazardous solvent substitution

    International Nuclear Information System (INIS)

    Twitchell, K.E.

    1995-01-01

    Eliminating hazardous solvents is good for the environment, worker safety, and the bottom line. However, even though we are motivated to find replacements, the big question is 'What can we use as replacements for hazardous solvents?'You, too, can find replacements for your hazardous solvents. All you have to do is search for them. Search through the vendor literature of hundreds of companies with thousands of products. Ponder the associated material safety data sheets, assuming of course that you can obtain them and, having obtained them, that you can read them. You will want to search the trade magazines and other sources for product reviews. You will want to talk to users about how well the product actually works. You may also want to check US Environmental Protection Agency (EPA) and other government reports for toxicity and other safety information. And, of course, you will want to compare the product's constituent chemicals with the many hazardous constituency lists to ensure the safe and legal use of the product in your workplace

  19. Hazardous industrial waste management

    International Nuclear Information System (INIS)

    Quesada, Hilda; Salas, Juan Carlos; Romero, Luis Guillermo

    2007-01-01

    The appropriate managing of hazardous wastes is a problem little dealed in the wastes management in the country. A search of available information was made about the generation and handling to internal and external level of the hazardous wastes by national industries. It was worked with eleven companies of different types of industrial activities for, by means of a questionnaire, interviews and visits, to determine the degree of integral and suitable handling of the wastes that they generate. It was concluded that exist only some isolated reports on the generation of hazardous industrial wastes and handling. The total quantity of wastes generated in the country was impossible to establish. The companies consulted were deficient in all stages of the handling of their wastes: generation, accumulation and storage, transport, treatment and final disposition. The lack of knowledge of the legislation and of the appropriate managing of the wastes is showed as the principal cause of the poor management of the residues. The lack of state or private entities entrusted to give services of storage, transport, treatment and final disposition of hazardous wastes in the country was evident. (author) [es

  20. Health Care Wide Hazards

    Science.gov (United States)

    ... Other Hazards (Lack of) PPE Slips/Trips/Falls Stress Tuberculosis Universal Precautions Workplace Violence Use of Medical Lasers Health Effects Use ... Needlesticks Noise Mercury Inappropriate PPE Slips/Trips/Falls ... of Universal Precautions Workplace Violence For more information, see Other Healthcare Wide ...

  1. Overconfidence and Moral Hazard

    DEFF Research Database (Denmark)

    de la Rosa, Leonidas Enrique

    2011-01-01

    In this paper, I study the effects of overconfidence on incentive contracts in a moral-hazard framework. Agent overconfidence can have conflicting effects on the equilibrium contract. On the one hand, an optimistic or overconfident agent disproportionately values success-contingent payments...

  2. PERMITTING HAZARDOUS WASTE INCINERATORS

    Science.gov (United States)

    This publication is a compilation of information presented at a seminar series designed to address the issues that affect the issuance of hazardous waste incineration permits and to improve the overall understanding of trial burn testing. pecifically, the document provides guidan...

  3. On nonparametric hazard estimation.

    Science.gov (United States)

    Hobbs, Brian P

    The Nelson-Aalen estimator provides the basis for the ubiquitous Kaplan-Meier estimator, and therefore is an essential tool for nonparametric survival analysis. This article reviews martingale theory and its role in demonstrating that the Nelson-Aalen estimator is uniformly consistent for estimating the cumulative hazard function for right-censored continuous time-to-failure data.

  4. Assessing storm erosion hazards

    NARCIS (Netherlands)

    Ranasinghe, Ranasinghe W M R J B; Callaghan, D.; Ciavola, Paolo; Coco, Giovanni

    2017-01-01

    The storm erosion hazard on coasts is usually expressed as an erosion volume and/or associated episodic coastline retreat. The accurate assessment of present-day and future storm erosion volumes is a key task for coastal zone managers, planners and engineers. There are four main approaches that can

  5. Stop radiation hazards

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    Brief general advice is presented for the employer unused to handling radioactive materials or using x-ray techniques. Topics mentioned are the definition of radiation and its hazards, measuring and monitoring the working environment, how to decide on and obtain equipment, standards and regulations, codes of practice, records, training, and useful sources of information. (U.K.)

  6. Koeberg radiation hazards

    International Nuclear Information System (INIS)

    Hall, A.V.

    1980-01-01

    The author discusses the article by J.K. Basson, B.C. Winkler and J. Walmsley on the assessment of environmental radiation hazards from the Koeberg nuclear power station. He gives his own evaluation of the safety of the Koeberg nuclear power station and suggests an alternative reactor site

  7. Health hazards related to ergonomic work conditions.

    Science.gov (United States)

    Kilbom, A; Broberg, E

    1988-01-01

    Health hazards related to unsuitable ergonomic work conditions among female employees in Sweden are reviewed. The statistics on reported occupational strain injuries form an important source of information on prevention. The report rate is higher among men than among women, but in some high risk occupations the figures are similar. Reported cases concerning neck, arm and shoulder disorders constitute a larger proportion among women. This finding probably reflects differences in work load characteristics, women more often performing repetitive monotonous work tasks in the manufacturing industry. Serious ergonomic problems exist for women in the service sector although the statistical evidence for increased morbidity is not yet available.

  8. The Impact Hazard

    Science.gov (United States)

    Morrison, David

    1994-01-01

    The Earth has been subject to hypervelocity impacts from comets and asteroids since its formation, and such impacts have played an important role in the evolution of life on our planet. We now recognize not only the historical role of impacts, but the contemporary hazard posed by such events. In the absence of a complete census of potentially threatening Earth-crossing asteroids or comets (called collectively Near Earth Objects, or NEOs), or even of a comprehensive cur-rent search program to identify NEOs, we can consider the hazard only from a probabilistic perspective. We know the steep power-law relationship between NEO numbers and size, with many more small bodies than large ones. We also know that few objects less than about 50 m in diameter (with kinetic energy near 10 megatons) penetrate the atmosphere and are capable of doing surface damage. But there is a spectrum of possible impact hazards associated with objects from this 10-megaton threshold all the way up to NEOs 5 km or larger in diameter, which are capable of inflicting severe damage on the environment, leading to mass extinction's of species. Detailed analysis has shown that, in general, the larger the object the greater the hazard, even when allowance is made for the infrequency of large impacts. Most of the danger to human life is associated with impacts by objects roughly 2 km or larger (energy greater than 1 million megatons), which can inject sufficient submicrometer dust into the atmosphere to produce a severe short-term global cooling with subsequent loss of crops, leading to starvation. Hazard estimates suggest that the chance of such an event occurring during a human lifetime is about 1:5000, and the global probability of death from such impacts is of the order of 1:20000, values that can be compared with risks associated with other natural hazards such as earthquakes, volcanic eruptions, and severe storms. However, the impact hazard differs from the others in that it can be largely

  9. Diversity of sponge mitochondrial introns revealed by cox 1 sequences of Tetillidae

    Directory of Open Access Journals (Sweden)

    Rot Chagai

    2010-09-01

    Full Text Available Abstract Background Animal mitochondrial introns are rare. In sponges and cnidarians they have been found in the cox 1 gene of some spirophorid and homosclerophorid sponges, as well as in the cox 1 and nad 5 genes of some Hexacorallia. Their sporadic distribution has raised a debate as to whether these mobile elements have been vertically or horizontally transmitted among their hosts. The first sponge found to possess a mitochondrial intron was a spirophorid sponge from the Tetillidae family. To better understand the mode of transmission of mitochondrial introns in sponges, we studied cox 1 intron distribution among representatives of this family. Results Seventeen tetillid cox 1 sequences were examined. Among these sequences only six were found to possess group I introns. Remarkably, three different forms of introns were found, named introns 714, 723 and 870 based on their different positions in the cox 1 alignment. These introns had distinct secondary structures and encoded LAGLIDADG ORFs belonging to three different lineages. Interestingly, sponges harboring the same intron form did not always form monophyletic groups, suggesting that their introns might have been transferred horizontally. To evaluate whether the introns were vertically or horizontally transmitted in sponges and cnidarians we used a host parasite approach. We tested for co-speciation between introns 723 (the introns with the highest number of sponge representatives and their nesting cox 1 sequences. Reciprocal AU tests indicated that the intron and cox 1 tree are significantly different, while a likelihood ratio test was not significant. A global test of co-phylogeny had significant results; however, when cnidarian sequences were analyzed separately the results were not significant. Conclusions The co-speciation analyses thus suggest that a vertical transmission of introns in the ancestor of sponges and cnidarians, followed by numerous independent losses, cannot solely

  10. Hazardous material reduction initiative

    International Nuclear Information System (INIS)

    Nichols, D.H.

    1995-02-01

    The Hazardous Material Reduction Initiative (HMRI) explores using the review of purchase requisitions to reduce both the use of hazardous materials and the generation of regulated and nonregulated wastes. Based on an 11-month program implemented at the Hanford Site, hazardous material use and waste generation was effectively reduced by using a centralized procurement control program known as HMRI. As expected, several changes to the original proposal were needed during the development/testing phase of the program to accommodate changing and actual conditions found at the Hanford Site. The current method requires a central receiving point within the Procurement Organization to review all purchase requisitions for potentially Occupational Safety and Health Administration (OSHA) hazardous products. Those requisitions (approximately 4% to 6% of the total) are then forwarded to Pollution Prevention personnel for evaluation under HMRI. The first step is to determine if the requested item can be filled by existing or surplus material. The requisitions that cannot filled by existing or surplus material are then sorted into two groups based on applicability to the HMRI project. For example, laboratory requests for analytical reagents or standards are excluded and the purchase requisitions are returned to Procurement for normal processing because, although regulated, there is little opportunity for source reduction due to the strict protocols followed. Each item is then checked to determine if it is regulated or not. Regulated items are prioritized based on hazardous contents, quantity requested, and end use. Copies of these requisitions are made and the originals are returned to Procurement within 1-hr. Since changes to the requisition can be made at later stages during procurement, the HMRI fulfills one of its original premises in that it does not slow the procurement process

  11. Tank farms hazards assessment

    International Nuclear Information System (INIS)

    Broz, R.E.

    1994-01-01

    Hanford contractors are writing new facility specific emergency procedures in response to new and revised US Department of Energy (DOE) Orders on emergency preparedness. Emergency procedures are required for each Hanford facility that has the potential to exceed the criteria for the lowest level emergency, an Alert. The set includes: (1) a facility specific procedure on Recognition and Classification of Emergencies, (2) area procedures on Initial Emergency Response and, (3) an area procedure on Protective Action Guidance. The first steps in developing these procedures are to identify the hazards at each facility, identify the conditions that could release the hazardous material, and calculate the consequences of the releases. These steps are called a Hazards Assessment. The final product is a document that is similar in some respects to a Safety Analysis Report (SAR). The document could br produced in a month for a simple facility but could take much longer for a complex facility. Hanford has both types of facilities. A strategy has been adopted to permit completion of the first version of the new emergency procedures before all the facility hazards Assessments are complete. The procedures will initially be based on input from a task group for each facility. This strategy will but improved emergency procedures in place sooner and therefore enhance Hanford emergency preparedness. The purpose of this document is to summarize the applicable information contained within the Waste Tank Facility ''Interim Safety Basis Document, WHC-SD-WM-ISB-001'' as a resource, since the SARs covering Waste Tank Operations are not current in all cases. This hazards assessment serves to collect, organize, document and present the information utilized during the determination process

  12. Effects of progesterone on iNOS, COX-2, and collagen expression in the cervix.

    Science.gov (United States)

    Marx, Stephen G; Wentz, Melissa J; Mackay, Lynette B; Schlembach, Dietmar; Maul, Holger; Fittkow, Cordula; Given, Randal; Vedernikov, Yurij; Saade, George R; Garfield, Robert E

    2006-06-01

    This study examines the relationship between inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the control of cervical ripening and parturition under normal (normal term pregnancy) and abnormal (preterm labor and prolongation of pregnancy) conditions by (a) measuring changes in the collagen both visually and quantitatively, (b) localizing and characterizing iNOS and COX-2 under normal conditions, and (c) characterizing the changes in iNOS and COX-2 under abnormal conditions. Cervices are obtained from estrus and timed pregnant Sprague-Dawley rats (n=4-10 per group). Preterm labor is induced with Onapristone (3 mg/rat; progesterone antagonist) and the prolongation of pregnancy with progesterone (2.5 mg, twice daily). Collagen changes are measured and visualized with the picrosirius polarization method. RT-PCR is used to characterize the mRNA expression (plabor, increasing the iNOS and COX-2 mRNA (p<0.05). The increase demonstrated a positive correlation (Spearman r = 0.456; p=0.03). Progesterone prolonged pregnancy, decreasing the iNOS and COX-2 mRNA (p=0.036). In conclusion, there may be an interaction between the nitric oxide and prostaglandin pathways in cervical ripening and parturition.

  13. Analysis of Gene Expression in Human Dermal Fibroblasts Treated with Senescence-Modulating COX Inhibitors

    Directory of Open Access Journals (Sweden)

    Jeong A. Han

    2017-06-01

    Full Text Available We have previously reported that NS-398, a cyclooxygenase-2 (COX-2–selective inhibitor, inhibited replicative cellular senescence in human dermal fibroblasts and skin aging in hairless mice. In contrast, celecoxib, another COX-2–selective inhibitor, and aspirin, a non-selective COX inhibitor, accelerated the senescence and aging. To figure out causal factors for the senescence-modulating effect of the inhibitors, we here performed cDNA microarray experiment and subsequent Gene Set Enrichment Analysis. The data showed that several senescence-related gene sets were regulated by the inhibitor treatment. NS-398 up-regulated gene sets involved in the tumor necrosis factor β receptor pathway and the fructose and mannose metabolism, whereas it down-regulated a gene set involved in protein secretion. Celecoxib up-regulated gene sets involved in G2M checkpoint and E2F targets. Aspirin up-regulated the gene set involved in protein secretion, and down-regulated gene sets involved in RNA transcription. These results suggest that COX inhibitors modulate cellular senescence by different mechanisms and will provide useful information to understand senescence-modulating mechanisms of COX inhibitors.

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

    Directory of Open Access Journals (Sweden)

    Albert Cohen

    2017-04-01

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

  15. PROPERTIES OF WOOD AND RICE HUSK PARTICLEBOARD IN DIFFERENT PROPORTIONS

    Directory of Open Access Journals (Sweden)

    Rafael Rodolfo de Melo

    2010-03-01

    Full Text Available This work aimed at evaluating the quality of particleboard manufactured with different wood proportions (Eucalyptus grandis and rice husk. The composites were produced in the proportions 0, 20, 40, 60, 80, and 100% of rice husk with the use of urea-formaldehyde and tannin-formaldehyde adhesives. In order to characterize the quality of the particleboards, physical properties (density; moisture content; water absorption and thickness swelling after 2 and 24 hours of immersion in water and mechanical properties (static bending; internal bonding and screw withdrawal were considered. Results showed that increasing rice husk proportion caused larger instability and a decrease in the resistance of particleboards. Particleboards manufactured with tannin-formaldehyde resins presented higher quality when compared to urea-formaldehyde. 

  16. A reduced feedback proportional fair multiuser scheduling scheme

    KAUST Repository

    Shaqfeh, Mohammad

    2011-12-01

    Multiuser switched-diversity scheduling schemes were recently proposed in order to overcome the heavy feedback requirements of conventional opportunistic scheduling schemes by applying a threshold-based, distributed and ordered scheduling mechanism. A slight reduction in the prospected multiuser diversity gains is an acceptable trade-off for great savings in terms of required channel-state-information feedback messages. In this work, we propose a novel proportional fair multiuser switched-diversity scheduling scheme and we demonstrate that it can be optimized using a practical and distributed method to obtain the per-user feedback thresholds. We demonstrate by numerical examples that our reduced feedback proportional fair scheduler operates within 0.3 bits/sec/Hz from the achievable rates by the conventional full feedback proportional fair scheduler in Rayleigh fading conditions. © 2011 IEEE.

  17. Multiaxial low cycle fatigue life under non-proportional loading

    International Nuclear Information System (INIS)

    Itoh, Takamoto; Sakane, Masao; Ohsuga, Kazuki

    2013-01-01

    A simple and clear method of evaluating stress and strain ranges under non-proportional multiaxial loading where principal directions of stress and strain are changed during a cycle is needed for assessing multiaxial fatigue. This paper proposes a simple method of determining the principal stress and strain ranges and the severity of non-proportional loading with defining the rotation angles of the maximum principal stress and strain in a three dimensional stress and strain space. This study also discusses properties of multiaxial low cycle fatigue lives for various materials fatigued under non-proportional loadings and shows an applicability of a parameter proposed by author for multiaxial low cycle fatigue life evaluation

  18. High gain proportional rf control stability at TESLA cavities

    Directory of Open Access Journals (Sweden)

    Elmar Vogel

    2007-05-01

    Full Text Available Fast proportional rf control is used as the basis for rf field regulation in actual linear accelerator projects like the international linear collider (ILC and the European x-ray free electron laser (XFEL based on TESLA technology. Additional control loops improve the field regulation by treating repetitive effects and compensating the beam loading. Nevertheless, the ability for high gain operation of the fast loops is desirable for the strong suppression of nonpredictive and nonrepetitive disturbances. TESLA cavities host nine fundamental modes (FMs where only one is used for beam acceleration. The unwanted FMs have a significant influence on the proportional rf control loop stability at high gains. Within this paper, the stability of proportional rf control loops taking the FMs and digitalization effects into account will be discussed in detail together with measures enabling a significant increase of the gain values.

  19. Prospective Teachers Proportional Reasoning and Presumption of Student Work

    Directory of Open Access Journals (Sweden)

    Mujiyem Sapti

    2015-08-01

    Full Text Available This study aimed to describe the proportional reasoning of prospective teachers and their predictions about students' answers. Subjects were 4 prospective teacher  7th semester Department of Mathematics Education, Muhammadiyah University of Purworejo. Proportional reasoning task used to obtain research data. Subjects were asked to explain their reasoning and write predictions of student completion. Data was taken on October 15th, 2014. Interviews were conducted after the subjects completed the task and recorded with audio media. The research data were subject written work and interview transcripts. Data were analyzed using qualitative analysis techniques. In solving the proportional reasoning task, subjects using the cross product. However, they understand the meaning of the cross product. Subject also could predict students' reasoning on the matter.

  20. An effective modification to simplify the right atrial lesion set of the Cox-cryomaze.

    Science.gov (United States)

    Cheema, Faisal H; Younus, Muhammad J; Pasha, Arham; Cox, James L; Roberts, Harold G

    2013-07-01

    Reluctance to perform biatrial Cox-cryomaze is primarily to avoid the vexation of creating a right-atrial-lesion (RAL) set of Cox-Maze-III. An alternative pattern of RAL set includes (i) a horizontal atriotomy, continued medially as a linear cryolesion across the posterior tricuspid annulus, (ii) a cavocaval lesion, and (iii) a lateral cryolesion from the midportion of the atriotomy to the tip of the right atrial appendage (RAA). This latter lesion is a substitute for a cryolesion that, in past, was directed medially by a stab wound in the tip of the RAA to the anterior tricuspid annulus. Use of the simplified RAL set, therefore, allows for more deftly achieving a complete biatrial Cox-cryomaze. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  1. Is Australia's national medicines policy failing? The case of COX-2 inhibitors.

    Science.gov (United States)

    Vitry, Agnes; Lexchin, Joel; Mansfield, Peter R

    2007-01-01

    Australia has a National Medicines Policy with aims that include quality use of medicines, but policy stakeholders failed to protect Australia from the COX-2 (cyclo-oxygenase-2) inhibitor disaster. Drug regulators did not warn prescribers appropriately about potential cardiovascular risks. The Pharmaceutical Benefits Scheme did not limit unjustified drug expenditures on COX-2 inhibitors. Drug companies ran intense and misleading promotional campaigns on COX-2 inhibitors without adequate controls. Independent drug information was insufficient to counter the effects of the millions of dollars spent on advertising. Core elements of the National Medicines Policy--in particular the drug approval process, the post-marketing surveillance system, the control of drug promotion, and the quality of independent drug information--require major reappraisal if we want to avoid similar disasters in the future.

  2. Proportional Motor Recovery After Stroke: Implications for Trial Design.

    Science.gov (United States)

    Stinear, Cathy M; Byblow, Winston D; Ackerley, Suzanne J; Smith, Marie-Claire; Borges, Victor M; Barber, P Alan

    2017-03-01

    Recovery of upper-limb motor impairment after first-ever ischemic stroke is proportional to the degree of initial impairment in patients with a functional corticospinal tract (CST). This study aimed to investigate whether proportional recovery occurs in a more clinically relevant sample including patients with intracerebral hemorrhage and previous stroke. Patients with upper-limb weakness were assessed 3 days and 3 months poststroke with the Fugl-Meyer scale. Transcranial magnetic stimulation was used to test CST function, and patients were dichotomized according to the presence of motor evoked potentials in the paretic wrist extensors. Linear regression modeling of Δ Fugl-Meyer score between 3 days and 3 months was performed, with predictors including initial impairment (66 - baseline Fugl-Meyer score), age, sex, stroke type, previous stroke, comorbidities, and upper-limb therapy dose. One hundred ninety-two patients were recruited, and 157 completed 3-month follow-up. Patients with a functional CST made a proportional recovery of 63% (95% confidence interval, 55%-70%) of initial motor impairment. The recovery of patients without a functional CST was not proportional to initial impairment and was reduced by greater CST damage. Recovery of motor impairment in patients with intact CST is proportional to initial impairment and unaffected by previous stroke, type of stroke, or upper-limb therapy dose. Novel interventions that interact with the neurobiological mechanisms of recovery are needed. The generalizability of proportional recovery is such that patients with intracerebral hemorrhage and previous stroke may usefully be included in interventional rehabilitation trials. URL: http://www.anzctr.org.au. Unique identifier: ANZCTR12611000755932. © 2017 American Heart Association, Inc.

  3. Design, Synthesis, and Biological Evaluation of New Peptide Analogues as Selective COX-2 Inhibitors.

    Science.gov (United States)

    Ahmaditaba, Mohammad A; Shahosseini, Soraya; Daraei, Bahram; Zarghi, Afshin; Houshdar Tehrani, Mohammad H

    2017-10-01

    A new class of peptide derivatives possessing SO 2 Me and N 3 pharmacophores at the para position of a phenyl ring bound to different aromatic amino acids were synthesized based on solid-phase synthesis methodology, and evaluated as selective cyclooxygenase-2 (COX-2) inhibitors. One of the analogues, i.e., compound 2a as the representative of this series, was recognized as the highest selective COX-2 inhibitor with a COX-2 selectivity index of >500. The structure-activity relationships (SARs) acquired indicated that compound 2a containing a 4-(methylsulfonyl)benzoyl group as a pharmacophore and tyrosine as a ring bearing amino acid in the second position and glutamic acid as the C-terminal amino acid can give the essential geometry to provide selective COX-2 inhibitory activity. Antiproliferative activity of the synthesized peptides (1a-7b) was also determined against four different human cancer cell lines, including MCF-7, HepG2, A549, and HeLa. According to our results, A549, HepG2, and MCF7 seemed to be more sensitive cell lines than HeLa cells encountering these compounds, which gave inhibitory action with IC 50 values from 4.8 to 64.4 µM. In this regard, compounds 3a and 2b displayed the best inhibitory activity against the cell lines. Moreover, a good correlation was observed between the antiproliferative potency and the COX-2 inhibitory activity of compounds 1a, 2a, 2b, and 5b. Such findings suggest that one of the mechanism of anticancer activity of these peptides may be through the COX-2 inhibitory action. © 2017 Deutsche Pharmazeutische Gesellschaft.

  4. Expression of VEGF and Cox-2 in Patients with Esophageal Squamous Cell Carcinoma

    Science.gov (United States)

    Luz, Caio Cesar Floriano; Noguti, Juliana; Araújo, Leandro; Simão Gomes, Thiago; Mara, Gianni; Silva, Marcelo De Souza; Artigiani Neto, Ricardo

    2018-01-27

    Esophageal cancer is a highly aggressive neoplasm. In Brazil, it is the sixth most frequent among men and fifteenth among women. The most common type is squamous cell carcinoma (SCC), responsible for 96% of cases. Twenty-eight specimens of Esophael squamous cell carcinoma (ESCC) were obtained by surgery procedures.The tissues were fixed in formalin and embedded in paraffin. In each case, all available hematoxylin and eosin stained sections were examined and a representative block was selected. The ages of these patients ranged from 40 to 93 years, with a mean age of 60 years. Results: The histological grade of tumors was 4 well-differentiated, 19 moderately differentiated and 5 poorly differentiated. Expression of Cox-2 and VEGF in ESCC was demonstrated in 23 (82,14%) and 13 (44,43%) cases, respectively. Adjacent normal mucosa was positive in 11 (39,29%) samples and 9 (32,15%) samples for Cox-2 and VEGF, respectively. No relationship between the expression of Cox-2 and VEGF with the clinicopathological parameters, including gender, age, surgical margin, lymph node status and tumor differentiation. The median follow-up period was 60 months. Survival analysis of patients with ESCC showed no relationship with the expression of Cox-2 and VEGF. Conclusion: VEGF and Cox-2 are expressed in ESCC. Cox-2, VEGF, play a significant role in the origin and development of ESCC and the inhibitors of these proteins could prove to be an important therapeutic tool in the control of this disease. Creative Commons Attribution License

  5. The first characterization of free radicals formed from cellular COX-catalyzed peroxidation.

    Science.gov (United States)

    Gu, Yan; Xu, Yi; Law, Benedict; Qian, Steven Y

    2013-04-01

    Through free radical-mediated peroxidation, cyclooxygenase (COX) can metabolize dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA) to form well-known bioactive metabolites, namely, the 1-series of prostaglandins (PGs1) and the 2-series of prostaglandins (PGs2), respectively. Unlike PGs2, which are generally viewed as proinflammatory and procarcinogenic PGs, PGs1 may possess anti-inflammatory and anti-cancer activity. Previous studies using ovine COX along with spin trapping and the LC/ESR/MS technique have shown that certain exclusive free radicals are generated from different free radical reactions in DGLA and AA peroxidation. However, it has been unclear whether the differences were associated with the contrasting bioactivity of DGLA vs AA. The aim of this study was to refine the LC/MS and spin trapping technique to make it possible for the association between free radicals and cancer cell growth to be directly tested. Using a colon cancer cell line, HCA-7 colony 29, and LC/MS along with a solid-phase extraction, we were able to characterize the reduced forms of radical adducts (hydroxylamines) as the free radicals generated from cellular COX-catalyzed peroxidation. For the first time, free radicals formed in the COX-catalyzed peroxidation of AA vs DGLA and their association with cancer cell growth were assessed (cell proliferation via MTS and cell cycle distribution via propidium iodide staining) in the same experimental setting. The exclusive free radicals formed from the COX-catalyzed peroxidation of AA and DGLA were shown to be correlated with the cell growth response. Our results indicate that free radicals generated from the distinct radical reactions in COX-catalyzed peroxidation may represent the novel metabolites of AA and DGLA that correspond to their contrasting bioactivity. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Molecular docking and analgesic studies of Erythrina variegata׳s derived phytochemicals with COX enzymes.

    Science.gov (United States)

    Uddin, Mir Muhammad Nasir; Emran, Talha Bin; Mahib, Muhammad Mamunur Rashid; Dash, Raju

    2014-01-01

    Secondary metabolites from plants are a good source for the NSAID drug development. We studied the analgesic activity of ethanolic extract of Erythrina variegata L. (Fabaceae) followed by molecular docking analysis. The analgesic activity of Erythrina variegata L. is evaluated by various methods viz., acetic acid-induced writhing test, hot plate and tail immersion test. Subsequently, molecular docking analysis has been performed to identify compounds having activity against COX-1 and COX-2 enzymes by using GOLD docking fitness. The result of preliminary phytochemical screening revealed that the extract contains alkaloids and flavonoids. In analgesic activity tests, the extract at the doses of 50, 100 and 200 mg/kg body weight (b.w.) produced a increase in pain threshold in a dose dependent manner. In acetic acid induced writhing test, the inhibitory effect was similar to the reference drug diclofenac sodium. The extract showed 18.89% writhing inhibitory effect at the dose 200 mg/kg b.w., whereas diclofenac sodium showed 79.42% inhibition of writhing at a dose of 10 mg/kg b.w. The results of tail immersion and hot plate test also showed potential analgesic activity of the extract which is also comparable to the standard drug morphine (5 mg/kg b.w.). Docking studies shows that phaseollin of Erythrina variegata L. has the best fitness score against the COX-1 which is 56.64 and 59.63 for COX- 2 enzyme. Phaseollin of Erythrina variegata L. detected with significant fitness score and hydrogen bonding against COX-1 and COX-2 is reported for further validation.

  7. TCDD Induced Pericardial Edema and Relative COX-2 Expression in Medaka (Oryzias Latipes) Embryos

    Science.gov (United States)

    Dong, Wu; Matsumura, Fumio; Kullman, Seth W.

    2010-01-01

    Exposure to dioxin and other aryl hydrocarbon receptor (AhR) ligands results in multiple, specific developmental cardiovascular phenotypes including pericardial edema and circulatory failure in small aquarium fish models. Although phenotypes are well described, mechanistic underpinnings for such toxicities remain elusive. Here we suggest that AhR activation results in stimulation of inflammation and “eicosanoid” pathways, which contribute to the observed developmental, cardiovascular phenotypes. We demonstrate that medaka embryos exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.05–1 ppb) during early development result in a dose-related increase in the prevalence of pericardial edema and that this phenotype correlates with an increase in cyclooxygenase-2 (COX-2) gene expression. Those individuals exhibiting the edema phenotype had significantly greater COX-2 mRNA than their nonedematous cohort. Selective pharmacological inhibition of COX-2, with NS-398, and genetic knock down of COX-2 with a translation initiation morpholino significantly attenuated prevalence and severity of edema phenotype. Subsequently, exposures of medaka embryos to arachidonic acid (AA) resulted in recapitulation of the pericardial edema phenotype and significantly increased COX-2 expression only in those individuals exhibiting the edema phenotype compared with their nonedematous cohort. AA exposure does not result in significant induction of cytochrome P450 1A expression, suggesting that pericardial edema can be induced independent of AhR/aryl hydrocarbon receptor nuclear translocator/dioxin response element interactions. Results from this study demonstrate that developmental exposure to TCDD results in an induction of inflammatory mediators including COX-2, which contribute to the onset, and progression of heart dysmorphogenesis in the medaka model. PMID:20801906

  8. Avalanche localization and its effects in proportional counters

    International Nuclear Information System (INIS)

    Fischer, J.; Okuno, H.; Walenta, A.H.

    1977-11-01

    Avalanche development around the anode wire in a gas proportional counter is investigated. In the region of proportional gas amplification, the avalanche is found to be well localized on one side of the anode wire, where the electrons arrive along the field lines from the point of primary ionization. Induced signals on electrodes surrounding the anode wire are used to measure the azimuthal position of the avalanche on the anode wire. Practical applications of the phenomena such as left-right assignment in drift chambers and measurement of the angular direction of the primary ionization electrons drifting towards the anode wire are discussed

  9. A multiball read-out for the spherical proportional counter

    Science.gov (United States)

    Giganon, A.; Giomataris, I.; Gros, M.; Katsioulas, I.; Navick, X. F.; Tsiledakis, G.; Savvidis, I.; Dastgheibi-Fard, A.; Brossard, A.

    2017-12-01

    We present a novel concept of proportional gas amplification for the read-out of the spherical proportional counter. The standard single-ball read-out presents limitations for large diameter spherical detectors and high-pressure operations. We have developed a multi-ball read-out system which consists of several balls placed at a fixed distance from the center of the spherical vessel. Such a module can tune the volume electric field at the desired value and can also provide detector segmentation with individual ball read-out. In the latter case, the large volume of the vessel becomes a spherical time projection chamber with 3D capabilities.

  10. Identification of secondary particles by proportional and drift chambers

    International Nuclear Information System (INIS)

    Allison, W.W.M.

    1975-01-01

    The present status of the theory and experiment of the ionization loss of relativistic particles in thin proportional counters is described. The results of an experiment to compare complete calibrated energy spectra with the Monte Carlo predictions, to investigate different statistical treatments of the data, and to distinguish pions and protons on line are presented. Two devices are described designed to separate kaons, pions and protons under realistic conditions, one of them being an array of 32x128 cylindrical proportional chambers, the other - a drift chamber. Their advantages and limitations are discussed

  11. Gain stabilisation of gas-flow proportional counters

    International Nuclear Information System (INIS)

    Denecke, B.; Grosse, G.; Szabo, T.

    1998-01-01

    A stabilisation of the gas gain for proportional counters with a continuous gas flow is described. New gas-flow systems for two end-window counters and one pressurised proportional counter were developed. The gas density of the counting-gas flow is stabilised by a two-stage back-pressure regulation system. The pressure in the gas flow is compared with the pressure in a reference vessel. During one month of operation the gain was stable within ±0.3%

  12. Targeted Deletion and Lipidomic Analysis Identify Epithelial Cell COX-2 as a Major Driver of Chemically-induced Skin Cancer

    Science.gov (United States)

    Jiao, Jing; Ishikawa, Tomo-o; Dumlao, Darren S.; Norris, Paul C.; Magyar, Clara E.; Mikulec, Carol; Catapang, Art; Dennis, Edward A.; Fischer, Susan M.; Herschman, Harvey R.

    2014-01-01

    Pharmacologic and global gene deletion studies demonstrate that cyclooxygenase-2 (PTGS2/COX2) plays a critical role in DMBA/TPA-induced skin tumor induction. While many cell types in the tumor microenvironment express COX-2, the cell types in which COX-2 expression is required for tumor promotion are not clearly established. Here, cell-type specific Cox-2 gene deletion reveals a vital role for skin epithelial cell COX-2 expression in DMBA/TPA tumor induction. In contrast, myeloid Cox-2 gene deletion has no effect on DMBA/TPA tumorigenesis. The infrequent, small tumors that develop on mice with an epithelial cell-specific Cox-2 gene deletion have decreased proliferation and increased cell differentiation properties. Blood vessel density is reduced in tumors with an epithelial cell-specific Cox-2 gene deletion, compared to littermate control tumors, suggesting a reciprocal relationship in tumor progression between COX-2 expressing tumor epithelial cells and microenvironment endothelial cells. Lipidomics analysis of skin and tumors from DMBA/TPA-treated mice suggests that the prostaglandins PGE2 and PGF2α are likely candidates for the epithelial cell COX-2-dependent eicosanoids that mediate tumor progression. This study both illustrates the value of cell-type specific gene deletions in understanding the cellular roles of signal-generating pathways in complex microenvironments and emphasizes the benefit of a systems-based lipidomic analysis approach to identify candidate lipid mediators of biological responses. PMID:25063587

  13. A computational prospect to aspirin side effects: aspirin and COX-1 interaction analysis based on non-synonymous SNPs.

    Science.gov (United States)

    Marjan, Mojtabavi Naeini; Hamzeh, Mesrian Tanha; Rahman, Emamzadeh; Sadeq, Vallian

    2014-08-01

    Aspirin (ASA) is a commonly used nonsteroidal anti-inflammatory drug (NSAID), which exerts its therapeutic effects through inhibition of cyclooxygenase (COX) isoform 2 (COX-2), while the inhibition of COX-1 by ASA leads to apparent side effects. In the present study, the relationship between COX-1 non-synonymous single nucleotide polymorphisms (nsSNPs) and aspirin related side effects was investigated. The functional impacts of 37 nsSNPs on aspirin inhibition potency of COX-1 with COX-1/aspirin molecular docking were computationally analyzed, and each SNP was scored based on DOCK Amber score. The data predicted that 22 nsSNPs could reduce COX-1 inhibition, while 15 nsSNPs showed increasing inhibition level in comparison to the regular COX-1 protein. In order to perform a comparing state, the Amber scores for two Arg119 mutants (R119A and R119Q) were also calculated. Moreover, among nsSNP variants, rs117122585 represented the closest Amber score to R119A mutant. A separate docking computation validated the score and represented a new binding position for ASA that acetyl group was located within the distance of 3.86Å from Ser529 OH group. This could predict an associated loss of activity of ASA through this nsSNP variant. Our data represent a computational sub-population pattern for aspirin COX-1 related side effects, and provide basis for further research on COX-1/ASA interaction. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. FosB transcription factor regulates COX-2 expression in colorectal cancer cells without affecting PGE2 expression.

    Science.gov (United States)

    Cervantes-Madrid, Diana Lizeth; Nagi, Sabah; Asting Gustafsson, Annika

    2017-03-01

    The expression levels of cyclooxygenase (COX)-2 and the prostaglandin E2 (PGE2) content have been associated with poor prognosis in patients with colorectal cancer (CRC). There is a strong correlation between COX-2 expression and PGE2 production in tissues from CRC patients, suggesting an important role for COX-2 on the regulation of PGE2 production. Previous studies by the present authors, where CRC patients were divided into high- or low-COX-2 expressing tumors, displayed important differences in the expression levels of several transcription factors involved in carcinogenesis. Among them, FBJ murine osteosarcoma viral oncogene homolog B (FosB), which is a member of the activator protein-1 complex, was the highest upregulated transcription factor in patients with high expression levels of COX-2. The present study aimed to investigate the role of FosB on the COX-2/PGE2 axis in CRC cells with high COX-2 expression levels. Interference RNA technology was used to knockdown FosB expression in HCA-7 cells, and 72 h later the messenger (m)RNA expression levels of COX-1 and COX-2, as well as the PGE2 content, were measured. The results indicated that FosB knockdown decreased the expression levels of COX-2 but did not affect the PGE2 content or the mRNA expression levels of COX-1. The present findings suggest an important role for FosB on the regulation of COX-2 expression, but no effect on the regulation of the PGE2 levels. In addition, the present results imply independent regulatory mechanisms for COX-2 expression and PGE2 content.

  15. Cyclopamine and jervine induce COX-2 overexpression in human erythroleukemia cells but only cyclopamine has a pro-apoptotic effect

    Energy Technology Data Exchange (ETDEWEB)

    Ghezali, Lamia; Leger, David Yannick; Limami, Youness [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Cook-Moreau, Jeanne [Université de Limoges, FR 3503 GEIST, UMR CNRS 7276 “Contrôle de la réponse immune B et lymphoproliférations”, Faculté de Médecine, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Beneytout, Jean-Louis [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Liagre, Bertrand, E-mail: bertrand.liagre@unilim.fr [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France)

    2013-04-15

    Erythroleukemia is generally associated with a very poor response and survival to current available therapeutic agents. Cyclooxygenase-2 (COX-2) has been described to play a crucial role in the proliferation and differentiation of leukemia cells, this enzyme seems to play an important role in chemoresistance in different cancer types. Previously, we demonstrated that diosgenin, a plant steroid, induced apoptosis in HEL cells with concomitant COX-2 overexpression. In this study, we investigated the antiproliferative and apoptotic effects of cyclopamine and jervine, two steroidal alkaloids with similar structures, on HEL and TF1a human erythroleukemia cell lines and, for the first time, their effect on COX-2 expression. Cyclopamine, but not jervine, inhibited cell proliferation and induced apoptosis in these cells. Both compounds induced COX-2 overexpression which was responsible for apoptosis resistance. In jervine-treated cells, COX-2 overexpression was NF-κB dependent. Inhibition of NF-κB reduced COX-2 overexpression and induced apoptosis. In addition, cyclopamine induced apoptosis and COX-2 overexpression via PKC activation. Inhibition of the PKC pathway reduced both apoptosis and COX-2 overexpression in both cell lines. Furthermore, we demonstrated that the p38/COX-2 pathway was involved in resistance to cyclopamine-induced apoptosis since p38 inhibition reduced COX-2 overexpression and increased apoptosis in both cell lines. - Highlights: ► Cyclopamine alone but not jervine induces apoptosis in human erythroleukemia cells. ► Cyclopamine and jervine induce COX-2 overexpression. ► COX-2 overexpression is implicated in resistance to cyclopamine-induced apoptosis. ► Apoptotic potential of jervine is restrained by NF-κB pathway activation. ► PKC is involved in cyclopamine-induced apoptosis and COX-2 overexpression.

  16. Cyclopamine and jervine induce COX-2 overexpression in human erythroleukemia cells but only cyclopamine has a pro-apoptotic effect

    International Nuclear Information System (INIS)

    Ghezali, Lamia; Leger, David Yannick; Limami, Youness; Cook-Moreau, Jeanne; Beneytout, Jean-Louis; Liagre, Bertrand

    2013-01-01

    Erythroleukemia is generally associated with a very poor response and survival to current available therapeutic agents. Cyclooxygenase-2 (COX-2) has been described to play a crucial role in the proliferation and differentiation of leukemia cells, this enzyme seems to play an important role in chemoresistance in different cancer types. Previously, we demonstrated that diosgenin, a plant steroid, induced apoptosis in HEL cells with concomitant COX-2 overexpression. In this study, we investigated the antiproliferative and apoptotic effects of cyclopamine and jervine, two steroidal alkaloids with similar structures, on HEL and TF1a human erythroleukemia cell lines and, for the first time, their effect on COX-2 expression. Cyclopamine, but not jervine, inhibited cell proliferation and induced apoptosis in these cells. Both compounds induced COX-2 overexpression which was responsible for apoptosis resistance. In jervine-treated cells, COX-2 overexpression was NF-κB dependent. Inhibition of NF-κB reduced COX-2 overexpression and induced apoptosis. In addition, cyclopamine induced apoptosis and COX-2 overexpression via PKC activation. Inhibition of the PKC pathway reduced both apoptosis and COX-2 overexpression in both cell lines. Furthermore, we demonstrated that the p38/COX-2 pathway was involved in resistance to cyclopamine-induced apoptosis since p38 inhibition reduced COX-2 overexpression and increased apoptosis in both cell lines. - Highlights: ► Cyclopamine alone but not jervine induces apoptosis in human erythroleukemia cells. ► Cyclopamine and jervine induce COX-2 overexpression. ► COX-2 overexpression is implicated in resistance to cyclopamine-induced apoptosis. ► Apoptotic potential of jervine is restrained by NF-κB pathway activation. ► PKC is involved in cyclopamine-induced apoptosis and COX-2 overexpression

  17. Correcting hazard ratio estimates for outcome misclassification using multiple imputation with internal validation data.

    Science.gov (United States)

    Ni, Jiayi; Leong, Aaron; Dasgupta, Kaberi; Rahme, Elham

    2017-08-01

    Outcome misclassification may occur in observational studies using administrative databases. We evaluated a two-step multiple imputation approach based on complementary internal validation data obtained from two subsamples of study participants to reduce bias in hazard ratio (HR) estimates in Cox regressions. We illustrated this approach using data from a surveyed sample of 6247 individuals in a study of statin-diabetes association in Quebec. We corrected diabetes status and onset assessed from health administrative data against self-reported diabetes and/or elevated fasting blood glucose (FBG) assessed in subsamples. The association between statin use and new onset diabetes was evaluated using administrative data and the corrected data. By simulation, we assessed the performance of this method varying the true HR, sensitivity, specificity, and the size of validation subsamples. The adjusted HR of new onset diabetes among statin users versus non-users was 1.61 (95% confidence interval: 1.09-2.38) using administrative data only, 1.49 (0.95-2.34) when diabetes status and onset were corrected based on self-report and undiagnosed diabetes (FBG ≥ 7 mmol/L), and 1.36 (0.92-2.01) when corrected for self-report and undiagnosed diabetes/impaired FBG (≥ 6 mmol/L). In simulations, the multiple imputation approach yielded less biased HR estimates and appropriate coverage for both non-differential and differential misclassification. Large variations in the corrected HR estimates were observed using validation subsamples with low participation proportion. The bias correction was sometimes outweighed by the uncertainty introduced by the unknown time of event occurrence. Multiple imputation is useful to correct for outcome misclassification in time-to-event analyses if complementary validation data are available from subsamples. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  18. Hazard perception in traffic. [previously knows as: Hazard perception.

    NARCIS (Netherlands)

    2008-01-01

    Hazard perception is an essential part of the driving task. There are clear indications that insufficient skills in perceiving hazards play an important role in the occurrence of crashes, especially those involving novice drivers. Proper hazard perception not only consists of scanning and perceiving

  19. Associations between COX-2 polymorphisms, blood cholesterol and risk of acute coronary syndrome

    DEFF Research Database (Denmark)

    Vogel, Ulla Birgitte; Segel, Stine; Dethlefsen, Claus

    2010-01-01

    the enzyme levels of COX-2, were associated with risk of ACS and if alcohol intake, smoking, and use of NSAID would modify the associations. We also wanted to investigate associations with blood lipid levels. Methods: A case–cohort study including 1031 ACS cases and a sub-cohort of 1703 persons was nested...... significant interactions between genotypes and alcohol intake, smoking and NSAID use in relation to risk of ACS. Among males, there was interaction between COX-2 T8473C and alcohol in relation to total cholesterol, non-HDL cholesterol and LDL levels (p for interaction: 0.003, 0.007 and 0.01, respectively...

  20. The polyacetylene falcarindiol with COX-1 activity isolated from Aegopodium podagraria L.

    Science.gov (United States)

    Prior, Rikke M; Lundgaard, Nanna H; Light, Marnie E; Stafford, Gary I; van Staden, Johannes; Jäger, Anna K

    2007-08-15

    Extracts of Aegopodium podagraria L. were screened in vitro for cyclooxygenase-1 (COX-1) inhibitory activity. The isolation of the active compound falcarindiol was achieved by bioassay-guided fractionation. The identification of the active compound was confirmed by (1)H NMR and (13)C NMR. The IC(50)-value of falcarindiol was 0.3 microM in the COX-1 assay. A quantitative determination of the seasonal variation in the content of falcarindiol in different plant parts was carried out by HPLC analysis. The flowers from Aegopodium podagraria collected in June 2006 had the highest concentration of falcarindiol (88 mg/g plant material).

  1. Non-Asymptotic Oracle Inequalities for the High-Dimensional Cox Regression via Lasso.

    Science.gov (United States)

    Kong, Shengchun; Nan, Bin

    2014-01-01

    We consider finite sample properties of the regularized high-dimensional Cox regression via lasso. Existing literature focuses on linear models or generalized linear models with Lipschitz loss functions, where the empirical risk functions are the summations of independent and identically distributed (iid) losses. The summands in the negative log partial likelihood function for censored survival data, however, are neither iid nor Lipschitz.We first approximate the negative log partial likelihood function by a sum of iid non-Lipschitz terms, then derive the non-asymptotic oracle inequalities for the lasso penalized Cox regression using pointwise arguments to tackle the difficulties caused by lacking iid Lipschitz losses.

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

    Science.gov (United States)

    Gandy, Axel; Jensen, Uwe

    2009-12-01

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

  3. Moral hazard in ecology

    Czech Academy of Sciences Publication Activity Database

    Fayle, Tom Maurice

    2015-01-01

    Roč. 3, Article no. 3 (2015), s. 1-2 R&D Projects: GA ČR GA14-32302S Grant - others:Australian Research Council Discovery Grant(AU) DP140101541 Institutional support: RVO:60077344 Keywords : economic crisis * moral hazard * power asymmetry Subject RIV: EH - Ecology, Behaviour http://journal.frontiersin.org/article/10.3389/fevo.2015.00003/full

  4. Immobilisation of hazardous waste

    International Nuclear Information System (INIS)

    Cope, C.B.

    1983-01-01

    Hazardous waste, e.g. radioactive waste, particularly that containing caesium-137, is immobilised by mixing with cement and solidifiable organic polymeric material. When first mixed, the organic material is preferably liquid and at this time can be polymerisable or already polymerised. The hardening can result from cooling or further polymerisation e.g. cross-linking. The organic material may be wax, or a polyester which may be unsaturated and cross-linkable by reaction with styrene. (author)

  5. Radiation hazard control report

    International Nuclear Information System (INIS)

    Morishima, Hiroshige; Koga, Taeko; Hisanaga, Saemi; Miki, Ryota; Kawai, Hiroshi; Aoki, Yutaka; Sone, Koji; Okada, Hirokazu

    1990-01-01

    The report describes the radiation hazard control activities performed at the Atomic Energy Research Institute of Kinki University, Japan, during the one-year period from April 1989 to March 1990. Personal radiation hazard control is outlined first focusing on results of physical examination and data of personal exposure dose equivalent. Radiation control in laboratory is then described. Dose equivalent at various places is discussed on the basis of monthly total dose equivalent measured on film badges, measurements made by TLD, and observations made through a continuous radiations monitoring system. The concentration of radiations in air and water is discussed focusing on their measured concentrations in air at the air outlets of tracer/accelerator facilities, and radioactivity in waste water sampled in the reactor facilities and tracer/accelerator facilities. Another discussion is made on the surface contamination density over the floors, draft systems, sink surface, etc. Concerning outdoor radiation hazard control, furthermore, TLD measurements of environmental gamma-rays, data on total gamma-ray radioactivity in environmental samples, and analysis of gamma-ray emitting nuclides in environmental samples are described and discussed. (N.K.)

  6. PUREX facility hazards assessment

    International Nuclear Information System (INIS)

    Sutton, L.N.

    1994-01-01

    This report documents the hazards assessment for the Plutonium Uranium Extraction Plant (PUREX) located on the US Department of Energy (DOE) Hanford Site. Operation of PUREX is the responsibility of Westinghouse Hanford Company (WHC). This hazards assessment was conducted to provide the emergency planning technical basis for PUREX. DOE Order 5500.3A requires an emergency planning hazards assessment for each facility that has the potential to reach or exceed the lowest level emergency classification. In October of 1990, WHC was directed to place PUREX in standby. In December of 1992 the DOE Assistant Secretary for Environmental Restoration and Waste Management authorized the termination of PUREX and directed DOE-RL to proceed with shutdown planning and terminal clean out activities. Prior to this action, its mission was to reprocess irradiated fuels for the recovery of uranium and plutonium. The present mission is to establish a passively safe and environmentally secure configuration at the PUREX facility and to preserve that condition for 10 years. The ten year time frame represents the typical duration expended to define, authorize and initiate follow-on decommissioning and decontamination activities

  7. FEMA DFIRM Flood Hazard Areas

    Data.gov (United States)

    Minnesota Department of Natural Resources — FEMA flood hazard delineations are used by the Federal Emergency Management Agency (FEMA) to designate the Special Flood Hazard Area (SFHA) and for insurance rating...

  8. Seismic hazard maps for Haiti

    Science.gov (United States)

    Frankel, Arthur; Harmsen, Stephen; Mueller, Charles; Calais, Eric; Haase, Jennifer

    2011-01-01

    We have produced probabilistic seismic hazard maps of Haiti for peak ground acceleration and response spectral accelerations that include the hazard from the major crustal faults, subduction zones, and background earthquakes. The hazard from the Enriquillo-Plantain Garden, Septentrional, and Matheux-Neiba fault zones was estimated using fault slip rates determined from GPS measurements. The hazard from the subduction zones along the northern and southeastern coasts of Hispaniola was calculated from slip rates derived from GPS data and the overall plate motion. Hazard maps were made for a firm-rock site condition and for a grid of shallow shear-wave velocities estimated from topographic slope. The maps show substantial hazard throughout Haiti, with the highest hazard in Haiti along the Enriquillo-Plantain Garden and Septentrional fault zones. The Matheux-Neiba Fault exhibits high hazard in the maps for 2% probability of exceedance in 50 years, although its slip rate is poorly constrained.

  9. Methods of calculus for neutron spectrometry in proportional counters

    International Nuclear Information System (INIS)

    Butragueno Casado, J.L.; Blazquez Martinez, J.B.; Barrado Menendez, J.M.

    1976-01-01

    Response functions for cylindrical proportional counters with hydrogenated gases have been determined, taking in account only wall effect, by means of two independent calculus methods. One of them is a Monte Carlo application and the other one analytica at all. Results of both methods have been compared. (Author)

  10. Methods of calculus for neutron spectrometry in proportional counters

    International Nuclear Information System (INIS)

    Butragueno, J.L.; Blazquez, J.B.; Barrado, J.M.

    1976-01-01

    Response functions for cylindrical proportional counters with hidrogenated gases have been determined, taking in account only wall effect, by means of two independent calculus methods. One of them is a Montecarlo application and the other one analytical at all. Results of both methods have been compared. (author) [es

  11. The Case of Lesotho's Mixed Member Proportional System | Kapa ...

    African Journals Online (AJOL)

    preparation of the 2002 poll, prominent among which has been the introduction of the Mixed Member Proportional (MMP) electoral system. Through this model, Lesotho enjoyed a large degree of political stability as almost all parties that contested the poll got representation in the national parliament. However, following the ...

  12. The proportional odds cumulative incidence model for competing risks

    DEFF Research Database (Denmark)

    Eriksson, Frank; Li, Jianing; Scheike, Thomas

    2015-01-01

    We suggest an estimator for the proportional odds cumulative incidence model for competing risks data. The key advantage of this model is that the regression parameters have the simple and useful odds ratio interpretation. The model has been considered by many authors, but it is rarely used in pr...

  13. Nature and proportion of total injuries at the Stellenbosch Rugby ...

    African Journals Online (AJOL)

    Objective. The purpose of this study was to compare the nature and proportion of total injuries occurring at Stellenbosch Rugby Football Club in Stellenbosch, South Africa, between the years 1973 - 1975 and 2003 - 2005. Design. Retrospective, descriptive study. Main outcome measures. Injured rugby players from the ...

  14. The proportion of asthma and patterns of asthma medications ...

    African Journals Online (AJOL)

    The proportion of asthma and patterns of asthma medications prescriptions among adult patients in the chest, accident and emergency units of a tertiary health care ... Methods: A retrospective chart review at Mulago Hospital chest clinic and A&E department from January 1st 2009 to December 31st 2009 was performed.

  15. determining the optimum proportion of shea waste in anaerobic co

    African Journals Online (AJOL)

    DEPT OF AGRICULTURAL ENGINEERING

    fermentation treatments with varying proportions of shea waste and cattle manure were investi- gated. It was found out that only the treatment ... energy consumed and five billion, the other. 40% (ICC, 2001). There is a close relationship .... Organic dry matter concentration of 7% for all treatment substrates and the hydraulic.

  16. Differences in body composition, body proportions and timing of ...

    African Journals Online (AJOL)

    The purpose of this study was to assess differences in body composition, proportions and timing of puberty between stunted and non-stunted South African adolescents in the North West Province, South Africa. A total of 259 black adolescents (118 boys, 141 girls), aged 13-18 years were measured. The following data were ...

  17. Attentional Control and the Relatedness Proportion Effect in Semantic Priming

    Science.gov (United States)

    Hutchison, Keith A.

    2007-01-01

    In 2 experiments, participants completed both an attentional control battery (OSPAN, antisaccade, and Stroop tasks) and a modified semantic priming task. The priming task measured relatedness proportion (RP) effects within subjects, with the color of the prime indicating the probability that the to-be-named target would be related. In Experiment…

  18. Position sensitive proportional counters as focal plane detectors

    International Nuclear Information System (INIS)

    Ford, J.L.C. Jr.

    1979-01-01

    The rise time and charge division techniques for position decoding with RC-line proportional counters are reviewed. The advantages that these detectors offer as focal plane counters for nuclear spectroscopy performed with magnetic spectrographs are discussed. The theory of operation of proportional counters as position sensing devices is summarized, as well as practical aspects affecting their application. Factors limiting the position and energy resolutions obtainable with a focal plane proportional counter are evaluated and measured position and energy loss values are presented for comparison. Detector systems capable of the multiparameter measurements required for particle identification, background suppression and ray-tracing are described in order to illustrate the wide applicability of proportional counters within complex focal plane systems. Examples of the use of these counters other than with magnetic spectrographs are given in order to demonstrate their usefulness in not only nuclear physics but also in fields such as solid state physics, biology, and medicine. The influence of the new focal plane detector systems on future magnetic spectrograph designs is discussed. (Auth.)

  19. Design considerations for a micromachined proportional control valve

    NARCIS (Netherlands)

    Groen, Maarten; Brouwer, Dannis Michel; Wiegerink, Remco J.; Lötters, Joost Conrad

    2012-01-01

    Precise mass flow control is an essential requirement for novel, small-scale fluidic systems. However, a small-volume, low-leakage proportional control valve for minute fluid flows has not yet been designed or manufactured. A survey is therefore made of the primary design considerations of a

  20. 16 CFR 240.9 - Proportionally equal terms.

    Science.gov (United States)

    2010-01-01

    ... ADVERTISING ALLOWANCES AND OTHER MERCHANDISING PAYMENTS AND SERVICES § 240.9 Proportionally equal terms. (a... type of service, or payments for more than one type of service, all the services or payments should be... 12 cents a case purchased for expenditures on either newspaper advertising or handbills. Example 1: A...

  1. Geometric proportions in Islamic architecture: case of the Sidi El ...

    African Journals Online (AJOL)

    In the next step the measurements of heights, widths, lengths and angles of different architectural elements were compared in order to find arithmetic and harmonic proportions. The last ones were found especially in the golden number Φ, equal to 1.618. In addition, the cubit of time was computed and found equal to 0.4375 ...

  2. Development of proportional counters using photosensitive gases and liquids

    International Nuclear Information System (INIS)

    Anderson, D.F.

    1984-10-01

    An introduction to the history and to the principle of operation of wire chambers using photosensitive gases and liquids is presented. Their use as light sensors coupled to Gas Scintillation Proportional Counters and BaF 2 , as well as their use in Cherenkov Ring imaging, is discussed in some detail. 42 references, 21 figures

  3. Transposition of Knowledge: Encountering Proportionality in an Algebra Task

    Science.gov (United States)

    Lundberg, Anna. L. V.; Kilhamn, Cecilia

    2018-01-01

    This article reports on an analysis of the process in which "knowledge to be taught" was transposed into "knowledge actually taught," concerning a task including proportional relationships in an algebra setting in a grade 6 classroom. We identified affordances and constraints of the task by describing the mathematical…

  4. Non-Proportionality of Organic Scintillators and BGO

    Science.gov (United States)

    Nassalski, A.; Moszy¿ski, M.; Syntfeld-Ka¿uch, A.; ¿widerski, ¿.; Szcze¿¿niak, T.

    2008-06-01

    According to the present knowledge the non-proportionality of the light yield of scintillators appears to be the fundamental limitation of energy resolution. Thus, the understanding of its origin is of the great importance for a development of new scintillators with enhanced energy resolution. In this respect, the non-proportional response of the typical organic scintillators was studied in comparison to that of a BGO crystal. The studies covered tests of BC408 plastic, BC501A liquid scintillator and anthracene organic crystal. The measurements showed a much larger range of energies presenting non-proportional response compared to that known for inorganic scintillators. In the case of anthracene the non-proportionality covers energy range up to about 500 keV, while for the BC408 plastic and BC501A liquid scintillators, it is above 4 MeV energy lost by gamma quanta. The observed effect can be related to a strong quenching of the light for charged particles in organic scintillators, which is much larger than that observed in inorganic scintillators.

  5. Performance Evaluation of Proportional Fair Scheduling Algorithm with Measured Channels

    DEFF Research Database (Denmark)

    Sørensen, Troels Bundgaard; Pons, Manuel Rubio

    2005-01-01

    Motivated by the promising performance results of the proportional fair (PF) packet scheduling algorithm, often quoted in connection with WCDMA High Speed Downlink Packet Access (HSDPA), we have performed an evaluation of the PF gain in comparison to the simpler round robin (RR) scheduler when...

  6. The influence of proportion of Hereford breeding in a multibreed ...

    African Journals Online (AJOL)

    Unknown

    performance traits into a "new breed" that is in harmony with the production environment and market requirements. (Lin, 1996; Schoeman, 1999). The aim of this study was to assess the contribution of the Hereford breed in a multibreed beef cattle herd in an intensive production system and to obtain the desired proportion of ...

  7. What proportion of abortion seekers in Calabar are really pregnant ...

    African Journals Online (AJOL)

    Context: The incidence of induced abortion and the associated health risks are high in Calabar, Nigeria. There is need to confirm whether all the women subjected to these procedures are really pregnant. Objective: To determine what proportion of women seeking abortion services in Calabar were really pregnant.

  8. Neutron sensitivity improvement in boron-lined proportional counters

    International Nuclear Information System (INIS)

    Dighe, P.M.; Prasad, K.R.; Kataria, S.K.

    2002-01-01

    Various techniques have been employed to improve the neutron sensitivity of boron-coated proportional counters developed indigenously. A boron-lined proportional counter (67 mm ID x 750 mm length) of 17 cps/nv thermal neutron sensitivity is developed by coating 92% enriched 10 B on the inner wall of the counter. This counter can be used for low thermal neutron flux (∼0.2 nv) at various applications such as neutron area monitoring, reactor start-up instrumentation, assay of fissile materials and detection of fuel failure. An improvement in sensitivity was also achieved by summing the output signals from four 10 B lined counters and two BF 3 proportional counters. The summation did not change the susceptibility of the device to gamma interference. In view of the scarcity of enriched 10 B isotope, indigenously available natural boron coated two prototype proportional counters are developed of 0.8 cps/nv and 1.1 cps/nv thermal neutron sensitivity. Efforts have been made to improve the sensitivity with boron coated 3-dimensional structures introduced into the sensitive volume. Tests in thermal neutron flux showed 50% improvement in the sensitivity due to the introduction of additional boron coated wires. Another counter with 51 boron-coated annular discs (23 mm OD X 10 mm ID X 1 mm thick) mounted perpendicular to the axis of the cathode showed 1.7 cps/nv neutron sensitivity, an improvement by a factor of 2.5. (author)

  9. One-step quantitative cortisol dipstick with proportional reading

    NARCIS (Netherlands)

    Leung, Wingman; Chan, Puiyee; Bosgoed, F.; Lehmann, Karin; Renneberg, Ilka; Lehmann, Matthias; Renneberg, Reinhard

    2003-01-01

    Rapid quantitative immuno-detection of haptens by the lateral flow assay without “typical” competitive inhibition results is studied. In the present study, we describe an immuno-threshold-based assay for the quantification of cortisol. It gives a signal which is directly proportional to the cortisol

  10. Development of a honeycomb gas proportional counter array for ...

    Indian Academy of Sciences (India)

    Home; Journals; Pramana – Journal of Physics; Volume 60; Issue 5. Development of a honeycomb gas proportional counter array for photon multiplicity measurements in high multiplicity environment. M S Ganti M M Aggarwal S K Badyal V S Bhatia S Chattopadhyay A K Dubey M R Majumdar M S Ganti A Kumar T K Nayak ...

  11. An Axiomatization of the Proportional Rule in Financial Networks

    NARCIS (Netherlands)

    Csoka, Péter; Herings, P. Jean-Jacques

    2017-01-01

    The most important rule to determine payments in real-life bankruptcy problems is the proportional rule. Many bankruptcy problems are characterized by network aspects and default may occur as a result of contagion. Indeed, in financial networks with defaulting agents, the values of the agents'

  12. COX-2 expression positively correlates with PD-L1 expression in human melanoma cells.

    Science.gov (United States)

    Botti, Gerardo; Fratangelo, Federica; Cerrone, Margherita; Liguori, Giuseppina; Cantile, Monica; Anniciello, Anna Maria; Scala, Stefania; D'Alterio, Crescenzo; Trimarco, Chiara; Ianaro, Angela; Cirino, Giuseppe; Caracò, Corrado; Colombino, Maria; Palmieri, Giuseppe; Pepe, Stefano; Ascierto, Paolo Antonio; Sabbatino, Francesco; Scognamiglio, Giosuè

    2017-02-23

    The resistance to PD-1/PD-L1 inhibitors for the treatment of melanoma have prompted investigators to implement novel clinical trials which combine immunotherapy with different treatment modalities. Moreover is also important to investigate the mechanisms which regulate the dynamic expression of PD-L1 on tumor cells and PD-1 on T cells in order to identify predictive biomarkers of response. COX-2 is currently investigated as a major player of tumor progression in several type of malignancies including melanoma. In the present study we investigated the potential relationship between COX-2 and PD-L1 expression in melanoma. Tumor samples obtained from primary melanoma lesions and not matched lymph node metastases were analyzed for both PD-L1 and COX-2 expression by IHC analysis. Status of BRAF and NRAS mutations was analyzed by sequencing and PCR. Co-localization of PD-L1 and COX-2 expression was analyzed by double fluorescence staining. Lastly the BRAF V600E A375 and NRAS Q61R SK-MEL-2 melanoma cell lines were used to evaluate the effect of COX-2 inhibition by celecoxib on expression of PD-L1 in vitro. BRAF V600E/V600K and NRAS Q61R/Q61L were detected in 57.8 and 8.9% of the metastatic lesions, and in 65.9 and 6.8% of the primary tumors, respectively. PD-L1 and COX-2 expression were heterogeneously expressed in both primary melanoma lesions and not matched lymph node metastases. A significantly lower number of PD-L1 negative lesions was found in primary tumors as compared to not matched metastatic lesions (P = 0.002). COX-2 expression significantly correlated with PD-L1 expression in both primary (P = 0.001) and not matched metastatic (P = 0.048) lesions. Furthermore, in melanoma tumors, cancer cells expressing a higher levels of COX-2 also co-expressed a higher level of PD-L1. Lastly, inhibition of COX-2 activity by celecoxib down-regulated the expression of PD-L1 in both BRAF V600E A375 and NRAS Q61R SK-MEL-2 melanoma cell lines. COX-2 expression correlates

  13. Industrial hazard and safety handbook

    CERN Document Server

    King, Ralph W

    1979-01-01

    Industrial Hazard and Safety Handbook (Revised Impression) describes and exposes the main hazards found in industry, with emphasis on how these hazards arise, are ignored, are identified, are eliminated, or are controlled. These hazard conditions can be due to human stresses (for example, insomnia), unsatisfactory working environments, as well as secret industrial processes. The book reviews the cost of accidents, human factors, inspections, insurance, legal aspects, planning for major emergencies, organization, and safety measures. The text discusses regulations, codes of practice, site layou

  14. Volcanic hazards to airports

    Science.gov (United States)

    Guffanti, M.; Mayberry, G.C.; Casadevall, T.J.; Wunderman, R.

    2009-01-01

    Volcanic activity has caused significant hazards to numerous airports worldwide, with local to far-ranging effects on travelers and commerce. Analysis of a new compilation of incidents of airports impacted by volcanic activity from 1944 through 2006 reveals that, at a minimum, 101 airports in 28 countries were affected on 171 occasions by eruptions at 46 volcanoes. Since 1980, five airports per year on average have been affected by volcanic activity, which indicates that volcanic hazards to airports are not rare on a worldwide basis. The main hazard to airports is ashfall, with accumulations of only a few millimeters sufficient to force temporary closures of some airports. A substantial portion of incidents has been caused by ash in airspace in the vicinity of airports, without accumulation of ash on the ground. On a few occasions, airports have been impacted by hazards other than ash (pyroclastic flow, lava flow, gas emission, and phreatic explosion). Several airports have been affected repeatedly by volcanic hazards. Four airports have been affected the most often and likely will continue to be among the most vulnerable owing to continued nearby volcanic activity: Fontanarossa International Airport in Catania, Italy; Ted Stevens Anchorage International Airport in Alaska, USA; Mariscal Sucre International Airport in Quito, Ecuador; and Tokua Airport in Kokopo, Papua New Guinea. The USA has the most airports affected by volcanic activity (17) on the most occasions (33) and hosts the second highest number of volcanoes that have caused the disruptions (5, after Indonesia with 7). One-fifth of the affected airports are within 30 km of the source volcanoes, approximately half are located within 150 km of the source volcanoes, and about three-quarters are within 300 km; nearly one-fifth are located more than 500 km away from the source volcanoes. The volcanoes that have caused the most impacts are Soufriere Hills on the island of Montserrat in the British West Indies

  15. Efek ekstrak daun singkong (Manihot utilissima terhadap ekspresi COX-2 pada monosit yang dipapar LPS E.coli (The effect of Manihot utilissima extracts on COX-2 expression of monocytes induced by LPS E. coli

    Directory of Open Access Journals (Sweden)

    Zahara Meilawaty

    2013-12-01

    Full Text Available Background: Periodontal disease is a common and widespread disease in the community. Gram negative bacteria have a role inperiodontitis. These bacteria secrete a variety of products such as endotoxin lipopolysaccharide (LPS, which causes the occurrenceof inflammation or infection. The body defense responses are neutrophils and mononuclear cells (monocytes and macrophages. Inresponse to defense mechanism, the body will be expressed enzyme cyclooxygenase (COX which functions convert arachidonic acidto prostaglandins. Cassava leaf cells known to play a role in reducing inflammation, but the mechanism for inhibiting COX-2, is notknown. Purpose: The study was aimed to determine the effect of cassava leaf extract (Manihot utilissima on expression of enzyme COX-2 in monocytes which were exposed by LPS E. coli. Methods: This study was in vitro experimental studies with the design of posttestonly control group design. The sample was the cassava leaves extract (Manihot utilissima at concentration of 12.5 % and 25 %. Theexpression of COX-2 was determined by immunocytochemistry method. Isolated monocytes were incubated in cassava leaf extract, andthen exposed to LPS, after washing imunostaning procedure was performed using a monoclonal antibody (MAb anti-human COX-2.The research data was the number of monocytes that express COX-2. Results: Expression of COX-2 in the group cassava leaf extractwas higher than the group that induced by LPS E. coli only. Conclusion: Cassava leaf extract did not inhibit the expression of COX-2in monocytes which were exposed by LPS E. coli.Latar belakang: Penyakit periodontal merupakan penyakit umum dan tersebar luas di masyarakat. Bakteri yang banyak berperanpada periodontitis adalah Gram negatif. Bakteri ini mengeluarkan berbagai produk antara lain endotoksin lipopolisakarida (LPS yangmenyebabkan inflamasi atau infeksi. Respon pertahanan tubuh pertama adalah netrofil dan sel mononuklear (monosit dan makrofag.Pada respon

  16. Hazards in the chemical laboratory

    International Nuclear Information System (INIS)

    Bretherick, L.

    1987-01-01

    The contents of this book are: Preface; Introduction; Health and Safety at Work Act 1974; Safety Planning and Management; Fire Protection; Reactive Chemical Hazards; Chemical Hazards and Toxicology; Health Care and First Aid; Hazardous Chemicals; Precautions against Radiations; and An American View

  17. 77 FR 17573 - Hazard Communication

    Science.gov (United States)

    2012-03-26

    ... liquids, process safety management, and most substance-specific health standards, to ensure consistency... expensive chemical hazard management and communication. In this way, the modifications are in line with the... are hazardous. The standard provides definitions of health and physical hazards to use as the criteria...

  18. Mutation in mitochondrial complex IV subunit COX5A causes pulmonary arterial hypertension, lactic acidemia, and failure to thrive.

    Science.gov (United States)

    Baertling, Fabian; Al-Murshedi, Fathiya; Sánchez-Caballero, Laura; Al-Senaidi, Khalfan; Joshi, Niranjan P; Venselaar, Hanka; van den Brand, Mariël Am; Nijtmans, Leo Gj; Rodenburg, Richard Jt

    2017-06-01

    COX5A is a nuclear-encoded subunit of mitochondrial respiratory chain complex IV (cytochrome c oxidase). We present patients with a homozygous pathogenic variant in the COX5A gene. Clinical details of two affected siblings suffering from early-onset pulmonary arterial hypertension, lactic acidemia, failure to thrive, and isolated complex IV deficiency are presented. We show that the variant lies within the evolutionarily conserved COX5A/COX4 interface domain, suggesting that it alters the interaction between these two subunits during complex IV biogenesis. In patient skin fibroblasts, the enzymatic activity and protein levels of complex IV and several of its subunits are reduced. Lentiviral complementation rescues complex IV deficiency. The monomeric COX1 assembly intermediate accumulates demonstrating a function of COX5A in complex IV biogenesis. A potential therapeutic lead is demonstrated by showing that copper supplementation leads to partial rescue of complex IV deficiency in patient fibroblasts. © 2017 Wiley Periodicals, Inc.

  19. COX-1 (PTGS1) and COX-2 (PTGS2) polymorphisms, NSAID interactions, and risk of colon and rectal cancer in two independent populations

    Science.gov (United States)

    Makar, Karen W; Poole, Elizabeth M; Resler, Alexa J; Seufert, Brenna; Curtin, Karen; Kleinstein, Sarah E; Duggan, David; Kulmacz, Richard J; Hsu, Li; Whitton, John; Carlson, Christopher S; Rimorin, Christine F; Caan, Bette J; Baron, John A; Potter, John D; Slattery, Martha L; Ulrich, Cornelia M

    2014-01-01

    Purpose Nonsteroidal anti-inflammatory drugs (NSAIDs) target the prostaglandin H synthase enzymes, cyclooxygenase (COX)-1 and -2, and reduce colorectal cancer risk. Genetic variation in the genes encoding these enzymes may be associated with changes in colon and rectal cancer risk and in NSAID efficacy. Methods We genotyped candidate polymorphisms and tagSNPs in PTGS1 (COX-1) and PTGS2 (COX-2) in a population-based case-control study (Diet, Activity and Lifestyle Study, DALS) of colon cancer (n=1470 cases/1837 controls) and rectal cancer (n=583/775), and independently among cases and controls from the Colon Cancer Family Registry (CCFR; colon n= 959/1535, rectal n= 505/839). Results In PTGS2, a functional polymorphism (−765G>C; rs20417) was associated with a 2-fold increased rectal cancer risk (p=0.05) in the DALS study. This association replicated with a significant nearly 5-fold increased risk of rectal cancer in the CCFR study (ORCC vs GG=4.88; 95%CI=1.54–15.45; ORGC vs GG=1.36; 95%CI: 0.95–1.94). Genotype-NSAID interactions were observed in the DALS study for PTGS1 and rectal cancer risk, and for PTGS2 and colon cancer risk, but were no longer significant after correcting for multiple comparisons and did not replicate in the CCFR. No significant associations between PTGS1 polymorphisms and colon or rectal cancer risk were observed. Conclusions These findings suggest that polymorphisms in PTGS2 may be associated with rectal cancer risk and impact the protective effects of NSAIDs. PMID:24022467

  20. Analysis of multi-species point patterns using multivariate log Gaussian Cox processes

    DEFF Research Database (Denmark)

    Waagepetersen, Rasmus; Guan, Yongtao; Jalilian, Abdollah

    Multivariate log Gaussian Cox processes are flexible models for multivariate point patterns. However, they have so far only been applied in bivariate cases. In this paper we move beyond the bivariate case in order to model multi-species point patterns of tree locations. In particular we address...

  1. Two-step estimation procedures for inhomogeneous shot-noise Cox processes

    DEFF Research Database (Denmark)

    Prokesová, Michaela; Dvorák, Jirí; Jensen, Eva B. Vedel

    In the present paper we develop several two-step estimation procedures for inhomogeneous shot-noise Cox processes. The intensity function is parametrized by the inhomogeneity parameters while the pair-correlation function is parametrized by the interaction parameters. The suggested procedures...

  2. A duplicated coxI gene is associated with cytoplasmic male sterility ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 86; Issue 2. A duplicated coxI gene is associated with cytoplasmic male sterility in an alloplasmic Brassica juncea line derived from somatic hybridization with Diplotaxis catholica. Aruna Pathania Rajesh Kumar V. Dinesh Kumar Ashutosh K. K. Dwivedi P. B. Kirti P. Prakash V. L. ...

  3. Cytotoxic of Ganoderma lucidum in Colon Cancer through Cyclooxygenase 2 (COX-2 as Its Molecular Target

    Directory of Open Access Journals (Sweden)

    Agustina Setiawati

    2017-05-01

    Full Text Available Many studies were designed explore chemopreventive activity of natural products on colon cancer especially addressing COX-2 as molecular target. Another promising source of natural product that potentially exhibit anticancer activity on colon cancer is Ganoderma lucidum. This study assessed selectivity of cytotoxic effect of G. lucidum extract on WiDr to Vero cells and investigated molecular mechanism on COX-2. G. lucidum ex-tract was prepared by reflux extraction method; in vitro anticancer was assayed by MTT method on WiDr and Vero cell line. This study applied apoptosis induction assay to observe cell death mechanism using double staining method; further COX-2 expression was stained by immunocytochemistry method. G. lucidum extract has cytotoxic effect on WiDr cells with IC50 135 µg/mL. However, the cytotoxic effect had low selectivity to-wards Vero cells with Selectivity Index (SI 3.66. The extract induced apoptosis and suppressed COX-2 ex-pression in WiDr cells. G. lucidum extract was potential to be developed as anticancer agent towards colon cancer.

  4. Dual Regulating Effect of Shaoyao-Gangcao-Tang on COX- 2 ...

    African Journals Online (AJOL)

    through the differential regulation of cell adhesion molecules and chemokines expression [9]. These data indicate that 15d-PGJ2 can tightly regulate the resolution of acute inflammation. As the key enzyme of regulating PGE2 generation, COX-2 has been thought to be a pro- inflammatory mediator. However, Gilroy et al [10].

  5. Cyclooxygenase 1 (COX1 expression in Type 2 diabetes mellitus: A preliminary study from north India

    Directory of Open Access Journals (Sweden)

    Sushma Verma

    2016-01-01

    Conclusion: Although COX1 is known to be a “housekeeping” gene, our study showed that its expression can be correlated with the disease condition and be used as a marker. However, further studies are required in more number of samples from other ethnic populations to confirm the findings.

  6. Effect of Ginkgo biloba extract on the expressions of Cox-2 and GST ...

    African Journals Online (AJOL)

    2014-03-01

    Mar 1, 2014 ... Its underlying biological mechanism remains unclear and no well-documented drug and ... Objectives: To explore the effect of EGb on expressions of cyclooxygenase-2 (Cox-2) and glutathione S-transferase Pi. (GST-Pi) in the ..... in an animal model of Parkinson's disease: Therapeutic perspectives. Nutri-.

  7. Effect of Ginkgo biloba extract on the expressions of Cox-2 and GST ...

    African Journals Online (AJOL)

    Objectives: This study was performed to explore the effect of EGb on expressions of cyclooxygenase-2 (Cox-2) and glutathione S-transferase Pi (GST-Pi) in the pathogenesis of HCC risk. Methods: 120 Wistar rats were divided into three groups at random: normal control group (control group), HCC risk group without ...

  8. ZN2+ INDUCES COX-2 EXPRESSION THROUGH DOWNREGULATION OF LIPID PHOSPHATASE PTEN

    Science.gov (United States)

    Zn2+ Induces COX-2 Expression through Downregulation of Lipid Phosphatase PTEN Weidong Wu*, James M. Samet, Philip A. Bromberg*?, Young E. Whang?, and Lee M. Graves* ?*CEMALB, ?Department of Medicine, and ?Department of Pharmacology, UNC-Chapel Hill, NC27599; Human Studie...

  9. Elevated COX2 expression and PGE2 production by downregulation of RXRα in senescent macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Huimin, E-mail: huiminchen.jq@gmail.com [Department of Geratology, Liaoning Jinqiu Hospital, Shenyang 110015 (China); Ma, Feng [Institute of Immunology, Zhejiang University of Medicine, Hangzhou 310058 (China); Hu, Xiaona; Jin, Ting; Xiong, Chuhui [Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001 (China); Teng, Xiaochun, E-mail: tengxiaochun@126.com [Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001 (China)

    2013-10-11

    Highlights: •Downregulation of RXRα in senescent macrophage. •RXRα suppresses NF-κB activity and COX2 expression. •Increased PGE2 production due to downregulation of RXRα. -- Abstract: Increased systemic level of inflammatory cytokines leads to numerous age-related diseases. In senescent macrophages, elevated prostaglandin E2 (PGE2) production contributes to the suppression of T cell function with aging, which increases the susceptibility to infections. However, the regulation of these inflammatory cytokines and PGE2 with aging still remains unclear. We have verified that cyclooxygenase (COX)-2 expression and PGE2 production are higher in LPS-stimulated macrophages from old mice than that from young mice. Downregulation of RXRα, a nuclear receptor that can suppress NF-κB activity, mediates the elevation of COX2 expression and PGE2 production in senescent macrophages. We also have found less induction of ABCA1 and ABCG1 by RXRα agonist in senescent macrophages, which partially accounts for high risk of atherosclerosis in aged population. Systemic treatment with RXRα antagonist HX531 in young mice increases COX2, TNF-α, and IL-6 expression in splenocytes. Our study not only has outlined a mechanism of elevated NF-κB activity and PGE2 production in senescent macrophages, but also provides RXRα as a potential therapeutic target for treating the age-related diseases.

  10. Effect of Ginkgo biloba extract on the expressions of Cox-2 and GST ...

    African Journals Online (AJOL)

    Cox-2) and glutathione S-transferase Pi. (GST-Pi) in the pathogenesis of HCC. Methods: 120 Wistar rats were divided into three groups at random: normal control group (control group), HCC risk group without treatment (HCC risk group), HCC risk ...

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

    Science.gov (United States)

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

    2015-01-01

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

  12. Do the COX-2 inhibitors still have a role to play? : guest editorial ...

    African Journals Online (AJOL)

    Do the COX-2 inhibitors still have a role to play? : guest editorial. A Beeton. Abstract. No Abstract Available Southern African Journal of Anaesthesia & Analgesia Vol.11(2) 2005: 55-60. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Article Metrics. Metrics ...

  13. Effects of long-term use of the preferential COX-2 inhibitor meloxicam on growing pigs

    NARCIS (Netherlands)

    Gorissen, Ben M C|info:eu-repo/dai/nl/372825788; Uilenreef, Joost J|info:eu-repo/dai/nl/30483095X; Bergmann, Willie|info:eu-repo/dai/nl/36275585X; Meijer, Ellen|info:eu-repo/dai/nl/375288015; van Rietbergen, Bert; van der Staay, Franz Josef|info:eu-repo/dai/nl/074262653; Weeren, P René van; Wolschrijn, Claudia F|info:eu-repo/dai/nl/271539496

    2017-01-01

    Meloxicam, a preferential COX-2 inhibitor, is a commonly used NSAID in pigs. Besides having potential side effects on the gastrointestinal tract, this type of drug might potentially affect osteogenesis and chondrogenesis, processes relevant to growing pigs. Therefore, the effects of long-term

  14. TGF-β Suppresses COX-2 Expression by Tristetraprolin-Mediated RNA Destabilization in A549 Human Lung Cancer Cells

    Science.gov (United States)

    Kang, Soyeong; Min, Ahrum; Im, Seock-Ah; Song, Sang-Hyun; Kim, Sang Gyun; Kim, Hyun-Ah; Kim, Hee-Jun; Oh, Do-Youn; Jong, Hyun-Soon; Kim, Tae-You; Bang, Yung-Jue

    2015-01-01

    Purpose Overexpression of cyclooxygenase 2 (COX-2) is thought to promote survival of transformed cells. Transforming growth factor β (TGF-β) exerts anti-proliferative effects on a broad range of epithelial cells. In the current study, we investigated whether TGF-β can regulate COX-2 expression in A549 human lung adenocarcinoma cells, which are TGF-β-responsive and overexpress COX-2. Materials and Methods Western blotting, Northern blotting, and mRNA stability assays were performed to demonstrate that COX-2 protein and mRNA expression were suppressed by TGF-β. We also evaluated the effects of tristetraprolin (TTP) on COX-2 mRNA using RNA interference. Results We demonstrated that COX-2 mRNA and protein expression were both significantly suppressed by TGF-β. An actinomycin D chase experiment demonstrated that COX-2 mRNA was more rapidly degraded in the presence of TGF-β, suggesting that TGF-β–induced inhibition of COX-2 expression is achieved via decreased mRNA stability. We also found that TGF-β rapidly and transiently induced the expression of TTP, a well-known mRNA destabilizing factor, before suppression of COX-2 mRNA expression was observed. Using RNA interference, we confirmed that increased TTP levels play a pivotal role in the destabilization of COX-2 mRNA by TGF-β. Furthermore, we showed that Smad3 is essential to TTP-dependent down-regulation of COX-2 expression in response to TGF-β. Conclusion The results of this study show that TGF-β down-regulated COX-2 expression via mRNA destabilization mediated by Smad3/TTP in A549 cells. PMID:25544576

  15. Combination therapy of PKCζ and COX-2 inhibitors synergistically suppress melanoma metastasis.

    Science.gov (United States)

    Zhou, Ping; Qin, Jiaqi; Li, Yuan; Li, Guoxia; Wang, Yinsong; Zhang, Ning; Chen, Peng; Li, Chunyu

    2017-09-02

    Metastatic malignant melanoma is one of the most aggressive malignancies and its treatment remains challenging. Recent studies demonstrate that the melanoma metastasis has correlations with the heightened activations of protein kinase C ζ (PKCζ) and cyclooxygenase-2 (COX-2) signaling pathways. Targeted inhibitions for PKCζ and COX-2 have been considered as the promising strategies for the treatment of melanoma metastasis. Thus, the PKCζ inhibitor J-4 and COX-2 inhibitor Celecoxib were combined to treat melanoma metastasis in this study. The Transwell assay, Wound-healing assay and Adhesion assay were used to evaluate the inhibition of combined therapy of J-4 and Celecoxib on melanoma cells invasion, migration and adhesion in vitro, respectively. The impaired actin polymerization was observed by confocal microscope and inactivated signal pathways about PKCζ and COX-2 were confirmed by the Western blotting assay. The B16-F10/C57BL mouse melanoma model was used to test the inhibition of combined therapy of J-4 and Celecoxib on melanoma metastasis in vivo. The in vitro results showed that the combination of J-4 and Celecoxib exerted synergistic inhibitory effects on the migration, invasion and adhesion of melanoma B16-F10 and A375 cells with combination index less than 1. The actin polymerization and phosphorylation of Cofilin required in cell migration were severely impaired, which is due to the inactivation of PKCζ related signal pathways and the decrease of COX-2. The combined inhibition of PKCζ and COX-2 induced Mesenchymal-Epithelial Transition (MET) in melanoma cells with the expression of E-Cadherin increasing and Vimentin decreasing. The secretion of MMP-2/MMP-9 also significantly decreased after the combination treatment. In C57BL/6 mice intravenously injected with B16-F10 cells (5 × 10 4 cells/mouse), co-treatment of J-4 and Celecoxib also severely suppressed melanoma lung metastasis. The body weight monitoring and HE staining results indicated the

  16. Activated human B cells stimulate COX-2 expression in follicular dendritic cell-like cells via TNF-α.

    Science.gov (United States)

    Kim, Jini; Lee, Seungkoo; Jeoung, Dooil; Kim, Young-Myeong; Choe, Jongseon

    2018-02-01

    In spite of the potential importance of cyclooxygenase (COX)-2 expression in the germinal center, its underlying cellular and molecular mechanisms are largely unknown. COX-2 is the key enzyme generating pleiotropic prostaglandins. Based on our previous findings, we hypothesized that lymphocytes would stimulate COX-2 expression in follicular dendritic cell (FDC) by liberating cytokines. In this study, we examined the effect of tonsillar lymphocytes on COX-2 expression in FDC-like cells by immunoblotting. B but not T cells induced COX-2 protein in a time- and dose-dependent manner. Sub-fractionation analysis of B cell subsets revealed that activated but not resting B cells were responsible for the COX-2 induction. Confocal microscopy of frozen tonsils demonstrated that FDCs indeed express COX-2 in situ, in line with the in vitro results. To identify the stimulating molecule, we added neutralizing antibodies to the coculture of FDC-like cells and B cells. COX-2 induction in FDC-like cells was markedly inhibited by TNF-α neutralizing antibody. Finally, the actual production of TNF-α by activated B cells was confirmed by an enzyme immunoassay. The current study implies an unrecognized cellular interaction between FDC and B cells leading to COX-2 expression during immune inflammatory responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. NORMAL QUALITY OF LIFE AFTER THE COX MAZE PROCEDURE FOR ATRIAL FIBRILLATION.

    Science.gov (United States)

    Melby, Spencer J; Zierer, Andreas; Lubahn, Jordon G; Bailey, Marci S; Cox, James L; Schuessler, Richard B; Damiano, Ralph J

    2008-05-01

    BACKGROUND/OBJECTIVE: Atrial fibrillation(AF) has been shown in numerous studies to significantly decrease patient quality of life. The Cox-Maze procedure has excellent long-term efficacy in curing AF. However, it is unknown whether this procedure improves long-term quality of life in these patients. The purpose of this study was to examine late quality of life in patients that underwent a lone Cox-Maze procedure. METHODS: Between 1987 and 2003, 163 patients underwent a Cox-Maze procedure for lone AF at our institution. Of these, 68 patients agreed and completed the Medical Outcomes Study Short Form 36 Health Survey. Scores from the age-matched general US population were normalized to a mean of 50 and standard deviation of 10 to facilitate comparison. Collected data were compared to the norm-based score for each domain using a one-sample t-test. Four patients were removed from analysis because of AF recurrence. RESULTS: There were 52 males(81%). Mean age was 52.6±9.5 years. Preoperatively, 37 patients(58%) had paroxysmal and 25 patients(39%) had persistent or permanent AF. The mean duration of AF before surgery was 9.8±8.2 years. There was no statistical difference in norm-based scores between the Cox-Maze procedure group and the age-matched general US population in any of the eight health domains at a mean follow-up of 8.7±3.7 years. CONCLUSION: Our results suggest that the Cox-Maze procedure cures atrial fibrillation in the majority of patients, and that those patients that are cured obtain a normal quality of life as compared to the general population at late follow-up.

  18. CD36 deficiency leads to choroidal involution via COX2 down-regulation in rodents.

    Directory of Open Access Journals (Sweden)

    Marianne Houssier

    2008-02-01

    Full Text Available BACKGROUND: In the Western world, a major cause of blindness is age-related macular degeneration (AMD. Recent research in angiogenesis has furthered the understanding of choroidal neovascularization, which occurs in the "wet" form of AMD. In contrast, very little is known about the mechanisms of the predominant, "dry" form of AMD, which is characterized by retinal atrophy and choroidal involution. The aim of this study is to elucidate the possible implication of the scavenger receptor CD36 in retinal degeneration and choroidal involution, the cardinal features of the dry form of AMD. METHODS AND FINDINGS: We here show that deficiency of CD36, which participates in outer segment (OS phagocytosis by the retinal pigment epithelium (RPE in vitro, leads to significant progressive age-related photoreceptor degeneration evaluated histologically at different ages in two rodent models of CD36 invalidation in vivo (Spontaneous hypertensive rats (SHR and CD36-/- mice. Furthermore, these animals developed significant age related choroidal involution reflected in a 100%-300% increase in the avascular area of the choriocapillaries measured on vascular corrosion casts of aged animals. We also show that proangiogenic COX2 expression in RPE is stimulated by CD36 activating antibody and that CD36-deficient RPE cells from SHR rats fail to induce COX2 and subsequent vascular endothelial growth factor (VEGF expression upon OS or antibody stimulation in vitro. CD36-/- mice express reduced levels of COX2 and VEGF in vivo, and COX2-/- mice develop progressive choroidal degeneration similar to what is seen in CD36 deficiency. CONCLUSIONS: CD36 deficiency leads to choroidal involution via COX2 down-regulation in the RPE. These results show a novel molecular mechanism of choroidal degeneration, a key feature of dry AMD. These findings unveil a pathogenic process, to our knowledge previously undescribed, with important implications for the development of new therapies.

  19. Extracellular histones disarrange vasoactive mediators release through a COX-NOS interaction in human endothelial cells.

    Science.gov (United States)

    Pérez-Cremades, Daniel; Bueno-Betí, Carlos; García-Giménez, José Luis; Ibañez-Cabellos, José Santiago; Hermenegildo, Carlos; Pallardó, Federico V; Novella, Susana

    2017-08-01

    Extracellular histones are mediators of inflammation, tissue injury and organ dysfunction. Interactions between circulating histones and vascular endothelial cells are key events in histone-mediated pathologies. Our aim was to investigate the implication of extracellular histones in the production of the major vasoactive compounds released by human endothelial cells (HUVECs), prostanoids and nitric oxide (NO). HUVEC exposed to increasing concentrations of histones (0.001 to 100 μg/ml) for 4 hrs induced prostacyclin (PGI2) production in a dose-dependent manner and decreased thromboxane A2 (TXA2) release at 100 μg/ml. Extracellular histones raised cyclooxygenase-2 (COX-2) and prostacyclin synthase (PGIS) mRNA and protein expression, decreased COX-1 mRNA levels and did not change thromboxane A2 synthase (TXAS) expression. Moreover, extracellular histones decreased both, eNOS expression and NO production in HUVEC. The impaired NO production was related to COX-2 activity and superoxide production since was reversed after celecoxib (10 μmol/l) and tempol (100 μmol/l) treatments, respectively. In conclusion, our findings suggest that extracellular histones stimulate the release of endothelial-dependent mediators through an up-regulation in COX-2-PGIS-PGI2 pathway which involves a COX-2-dependent superoxide production that decreases the activity of eNOS and the NO production. These effects may contribute to the endothelial cell dysfunction observed in histone-mediated pathologies. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  20. Artesunate inhibits the growth and induces apoptosis of human gastric cancer cells by downregulating COX-2.

    Science.gov (United States)

    Zhang, Ping; Luo, He-Sheng; Li, Ming; Tan, Shi-Yun

    2015-01-01

    Artesunate, a derivative of artemisinin isolated from Artemisia annua L., has been traditionally used to treat malaria, and artesunate has demonstrated cytotoxic effects against a variety of cancer cells. However, there is little available information about the antitumor effects of artesunate on human gastric cancer cells. In the present study, we investigated the antitumor effect of artesunate on human gastric cancer cells and whether its antitumor effect is associated with reduction in COX-2 expression. The effects of artesunate on the growth and apoptosis of gastric cancer cells were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis of annexin V-fluorescein isothiocyanate/propidium iodide staining, rhodamine 123 staining, and Western blot analysis. Results indicate that artesunate exhibits antiproliferative effects and apoptosis-inducing activities. Artesunate markedly inhibited gastric cancer cell proliferation in a time- and dose-dependent manner and induced apoptosis in gastric cancer cells a dose-dependent manner, which was associated with a reduction in COX-2 expression. Treatment with the selective COX-2 inhibitor celecoxib, or transient transfection of gastric cancer cells with COX-2 siRNA, also inhibited cell proliferation and induced apoptosis. Furthermore, the treatment with artesunate promoted the expression of proapoptotic factor Bax and suppressed the expression of antiapoptotic factor Bcl-2. In addition, caspase-3 and caspase-9 were activated, and artesunate induced loss of mitochondrial membrane potential, suggesting that the apoptosis is mediated by mitochondrial pathways. These results demonstrate that artesunate has an effect on anti-gastric cancer cells. One of the antitumor mechanisms of artesunate may be that its inhibition of COX-2 led to reduced proliferation and induction of apoptosis, connected with mitochondrial dysfunction. Artesunate might be a potential therapeutic