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Sample records for survival cox proportional

  1. Novel head and neck cancer survival analysis approach: random survival forests versus Cox proportional hazards regression.

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    Datema, Frank R; Moya, Ana; Krause, Peter; Bäck, Thomas; Willmes, Lars; Langeveld, Ton; Baatenburg de Jong, Robert J; Blom, Henk M

    2012-01-01

    Electronic patient files generate an enormous amount of medical data. These data can be used for research, such as prognostic modeling. Automatization of statistical prognostication processes allows automatic updating of models when new data is gathered. The increase of power behind an automated prognostic model makes its predictive capability more reliable. Cox proportional hazard regression is most frequently used in prognostication. Automatization of a Cox model is possible, but we expect the updating process to be time-consuming. A possible solution lies in an alternative modeling technique called random survival forests (RSFs). RSF is easily automated and is known to handle the proportionality assumption coherently and automatically. Performance of RSF has not yet been tested on a large head and neck oncological dataset. This study investigates performance of head and neck overall survival of RSF models. Performances are compared to a Cox model as the "gold standard." RSF might be an interesting alternative modeling approach for automatization when performances are similar. RSF models were created in R (Cox also in SPSS). Four RSF splitting rules were used: log-rank, conservation of events, log-rank score, and log-rank approximation. Models were based on historical data of 1371 patients with primary head-and-neck cancer, diagnosed between 1981 and 1998. Models contain 8 covariates: tumor site, T classification, N classification, M classification, age, sex, prior malignancies, and comorbidity. Model performances were determined by Harrell's concordance error rate, in which 33% of the original data served as a validation sample. RSF and Cox models delivered similar error rates. The Cox model performed slightly better (error rate, 0.2826). The log-rank splitting approach gave the best RSF performance (error rate, 0.2873). In accord with Cox and RSF models, high T classification, high N classification, and severe comorbidity are very important covariates in the

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

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    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/.

  3. High-dimensional, massive sample-size Cox proportional hazards regression for survival analysis.

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    Mittal, Sushil; Madigan, David; Burd, Randall S; Suchard, Marc A

    2014-04-01

    Survival analysis endures as an old, yet active research field with applications that spread across many domains. Continuing improvements in data acquisition techniques pose constant challenges in applying existing survival analysis methods to these emerging data sets. In this paper, we present tools for fitting regularized Cox survival analysis models on high-dimensional, massive sample-size (HDMSS) data using a variant of the cyclic coordinate descent optimization technique tailored for the sparsity that HDMSS data often present. Experiments on two real data examples demonstrate that efficient analyses of HDMSS data using these tools result in improved predictive performance and calibration.

  4. A flexible alternative to the Cox proportional hazards model for assessing the prognostic accuracy of hospice patient survival.

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    Branko Miladinovic

    Full Text Available Prognostic models are often used to estimate the length of patient survival. The Cox proportional hazards model has traditionally been applied to assess the accuracy of prognostic models. However, it may be suboptimal due to the inflexibility to model the baseline survival function and when the proportional hazards assumption is violated. The aim of this study was to use internal validation to compare the predictive power of a flexible Royston-Parmar family of survival functions with the Cox proportional hazards model. We applied the Palliative Performance Scale on a dataset of 590 hospice patients at the time of hospice admission. The retrospective data were obtained from the Lifepath Hospice and Palliative Care center in Hillsborough County, Florida, USA. The criteria used to evaluate and compare the models' predictive performance were the explained variation statistic R(2, scaled Brier score, and the discrimination slope. The explained variation statistic demonstrated that overall the Royston-Parmar family of survival functions provided a better fit (R(2 =0.298; 95% CI: 0.236-0.358 than the Cox model (R(2 =0.156; 95% CI: 0.111-0.203. The scaled Brier scores and discrimination slopes were consistently higher under the Royston-Parmar model. Researchers involved in prognosticating patient survival are encouraged to consider the Royston-Parmar model as an alternative to Cox.

  5. Extension of cox proportional hazard model for estimation of interrelated age-period-cohort effects on cancer survival.

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    Mdzinarishvili, Tengiz; Gleason, Michael X; Kinarsky, Leo; Sherman, Simon

    2011-02-23

    In the frame of the Cox proportional hazard (PH) model, a novel two-step procedure for estimating age-period-cohort (APC) effects on the hazard function of death from cancer was developed. In the first step, the procedure estimates the influence of joint APC effects on the hazard function, using Cox PH regression procedures from a standard software package. In the second step, the coefficients for age at diagnosis, time period and birth cohort effects are estimated. To solve the identifiability problem that arises in estimating these coefficients, an assumption that neighboring birth cohorts almost equally affect the hazard function was utilized. Using an anchoring technique, simple procedures for obtaining estimates of interrelated age at diagnosis, time period and birth cohort effect coefficients were developed.As a proof-of-concept these procedures were used to analyze survival data, collected in the SEER database, on white men and women diagnosed with LC in 1975-1999 and the age at diagnosis, time period and birth cohort effect coefficients were estimated. The PH assumption was evaluated by a graphical approach using log-log plots. Analysis of trends of these coefficients suggests that the hazard of death from LC for a given time from cancer diagnosis: (i) decreases between 1975 and 1999; (ii) increases with increasing the age at diagnosis; and (iii) depends upon birth cohort effects.The proposed computing procedure can be used for estimating joint APC effects, as well as interrelated age at diagnosis, time period and birth cohort effects in survival analysis of different types of cancer.

  6. Extension of Cox Proportional Hazard Model for Estimation of Interrelated Age-Period-Cohort Effects on Cancer Survival

    OpenAIRE

    Mdzinarishvili, Tengiz; Gleason, Michael X.; Kinarsky, Leo; Sherman, Simon

    2011-01-01

    In the frame of the Cox proportional hazard (PH) model, a novel two-step procedure for estimating age-period-cohort (APC) effects on the hazard function of death from cancer was developed. In the first step, the procedure estimates the influence of joint APC effects on the hazard function, using Cox PH regression procedures from a standard software package. In the second step, the coefficients for age at diagnosis, time period and birth cohort effects are estimated. To solve the identifiabili...

  7. Gradient lasso for Cox proportional hazards model.

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    Sohn, Insuk; Kim, Jinseog; Jung, Sin-Ho; Park, Changyi

    2009-07-15

    There has been an increasing interest in expressing a survival phenotype (e.g. time to cancer recurrence or death) or its distribution in terms of a subset of the expression data of a subset of genes. Due to high dimensionality of gene expression data, however, there is a serious problem of collinearity in fitting a prediction model, e.g. Cox's proportional hazards model. To avoid the collinearity problem, several methods based on penalized Cox proportional hazards models have been proposed. However, those methods suffer from severe computational problems, such as slow or even failed convergence, because of high-dimensional matrix inversions required for model fitting. We propose to implement the penalized Cox regression with a lasso penalty via the gradient lasso algorithm that yields faster convergence to the global optimum than do other algorithms. Moreover the gradient lasso algorithm is guaranteed to converge to the optimum under mild regularity conditions. Hence, our gradient lasso algorithm can be a useful tool in developing a prediction model based on high-dimensional covariates including gene expression data. Results from simulation studies showed that the prediction model by gradient lasso recovers the prognostic genes. Also results from diffuse large B-cell lymphoma datasets and Norway/Stanford breast cancer dataset indicate that our method is very competitive compared with popular existing methods by Park and Hastie and Goeman in its computational time, prediction and selectivity. R package glcoxph is available at http://datamining.dongguk.ac.kr/R/glcoxph.

  8. Modeling survival data extending the cox model

    CERN Document Server

    Therneau, Terry M

    2000-01-01

    Extending the Cox Model is aimed at researchers, practitioners, and graduate students who have some exposure to traditional methods of survival analysis The emphasis is on semiparametric methods based on the proportional hazards model The inclusion of examples with SAS and S-PLUS code will make the book accessible to most working statisticians

  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. Regularization Paths for Cox's Proportional Hazards Model via Coordinate Descent

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    Noah Simon

    2011-03-01

    Full Text Available We introduce a pathwise algorithm for the Cox proportional hazards model, regularized by convex combinations of l1 and l2 penalties (elastic net. Our algorithm fits via cyclical coordinate descent, and employs warm starts to find a solution along a regularization path. We demonstrate the efficacy of our algorithm on real and simulated data sets, and find considerable speedup between our algorithm and competing methods.

  11. An ensemble-based Cox proportional hazards regression framework for predicting survival in metastatic castration-resistant prostate cancer (mCRPC patients [version 1; referees: 1 approved, 2 approved with reservations

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    Richard Meier

    2016-11-01

    Full Text Available From March through August 2015, nearly 60 teams from around the world participated in the Prostate Cancer Dream Challenge (PCDC. Participating teams were faced with the task of developing prediction models for patient survival and treatment discontinuation using baseline clinical variables collected on metastatic castrate-resistant prostate cancer (mCRPC patients in the comparator arm of four phase III clinical trials. In total, over 2,000 mCRPC patients treated with first-line docetaxel comprised the training and testing data sets used in this challenge. In this paper we describe: (a the sub-challenges comprising the PCDC, (b the statistical metrics used to benchmark prediction performance, (c our analytical approach, and finally (d our team’s overall performance in this challenge. Specifically, we discuss our curated, ad-hoc, feature selection (CAFS strategy for identifying clinically important risk-predictors, the ensemble-based Cox proportional hazards regression framework used in our final submission, and the adaptation of our modeling framework based on the results from the intermittent leaderboard rounds. Strong predictors of patient survival were successfully identified utilizing our model building approach. Several of the identified predictors were new features created by our team via strategically merging collections of weak predictors. In each of the three intermittent leaderboard rounds, our prediction models scored among the top four models across all participating teams and our final submission ranked 9th place overall with an integrated area under the curve (iAUC of 0.7711 computed in an independent test set. While the prediction performance of teams placing between 2nd- 10th (iAUC: 0.7710-0.7789 was better than the current gold-standard prediction model for prostate cancer survival, the top-performing team, FIMM-UTU significantly outperformed all other contestants with an iAUC of 0.7915.  In summary, our ensemble-based Cox

  12. Survival analysis of cervical cancer using stratified Cox regression

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    Purnami, S. W.; Inayati, K. D.; Sari, N. W. Wulan; Chosuvivatwong, V.; Sriplung, H.

    2016-04-01

    Cervical cancer is one of the mostly widely cancer cause of the women death in the world including Indonesia. Most cervical cancer patients come to the hospital already in an advanced stadium. As a result, the treatment of cervical cancer becomes more difficult and even can increase the death's risk. One of parameter that can be used to assess successfully of treatment is the probability of survival. This study raises the issue of cervical cancer survival patients at Dr. Soetomo Hospital using stratified Cox regression based on six factors such as age, stadium, treatment initiation, companion disease, complication, and anemia. Stratified Cox model is used because there is one independent variable that does not satisfy the proportional hazards assumption that is stadium. The results of the stratified Cox model show that the complication variable is significant factor which influent survival probability of cervical cancer patient. The obtained hazard ratio is 7.35. It means that cervical cancer patient who has complication is at risk of dying 7.35 times greater than patient who did not has complication. While the adjusted survival curves showed that stadium IV had the lowest probability of survival.

  13. COX-2/EGFR expression and survival among women with adenocarcinoma of the lung.

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    Van Dyke, Alison L; Cote, Michele L; Prysak, Geoffrey M; Claeys, Gina B; Wenzlaff, Angie S; Murphy, Valerie C; Lonardo, Fulvio; Schwartz, Ann G

    2008-09-01

    Previous studies suggest that cyclooxygenase-2 (COX-2) expression may predict survival among patients with non-small cell lung cancer. COX-2 may interact with epidermal growth factor receptor (EGFR), suggesting that combined COX-2/EGFR expression may provide predictive value. The extent to which their independent or combined expression is associated with prognosis in women with adenocarcinoma of the lung is unknown. In the present study, we examined relationships between COX-2 expression (n = 238), EGFR expression (n = 158) and dual COX-2/EGFR expression (n = 157) and survival among women with adenocarcinoma of the lung. Overall survival was estimated by constructing Cox proportional hazards models adjusting for other significant variables and stratifying by stage at diagnosis and race. Clinical or demographic parameters were not associated with either COX-2 or EGFR expression. Patients with COX-2-positive tumors tended to have poorer prognosis than did patients with COX-2-negative tumors [hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.01-2.78]. African-Americans with COX-2-positive tumors had a statistically non-significant higher risk of death than African-Americans with COX-2-negative tumors (HR 5.58, 95% CI 0.64-48.37). No association between COX-2 expression and survival was observed among Caucasians (HR 1.29, 95% CI 0.72-2.30). EGFR expression was associated with a 44% reduction in the risk of death (HR 0.56, 95% CI 0.32-0.98). COX-2-/EGFR+ tumor expression, but not COX-2+/EGFR+ tumor expression, was associated with survival when compared with other combined expression results. In conclusion, COX-2 and EGFR expression, but not combined COX-2+/EGFR+ expression, independently predict survival of women with adenocarcinoma of the lung.

  14. Estimation in the cox proportional hazards model with left-truncated and interval-censored data.

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    Pan, Wei; Chappell, Rick

    2002-03-01

    We show that the nonparametric maximum likelihood estimate (NPMLE) of the regression coefficient from the joint likelihood (of the regression coefficient and the baseline survival) works well for the Cox proportional hazards model with left-truncated and interval-censored data, but the NPMLE may underestimate the baseline survival. Two alternatives are also considered: first, the marginal likelihood approach by extending Satten (1996, Biometrika 83, 355-370) to truncated data, where the baseline distribution is eliminated as a nuisance parameter; and second, the monotone maximum likelihood estimate that maximizes the joint likelihood by assuming that the baseline distribution has a nondecreasing hazard function, which was originally proposed to overcome the underestimation of the survival from the NPMLE for left-truncated data without covariates (Tsai, 1988, Biometrika 75, 319-324). The bootstrap is proposed to draw inference. Simulations were conducted to assess their performance. The methods are applied to the Massachusetts Health Care Panel Study data set to compare the probabilities of losing functional independence for male and female seniors.

  15. A semi-parametric generalization of the Cox proportional hazards regression model: Inference and Applications

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    Devarajan, Karthik; Ebrahimi, Nader

    2011-01-01

    The assumption of proportional hazards (PH) fundamental to the Cox PH model sometimes may not hold in practice. In this paper, we propose a generalization of the Cox PH model in terms of the cumulative hazard function taking a form similar to the Cox PH model, with the extension that the baseline cumulative hazard function is raised to a power function. Our model allows for interaction between covariates and the baseline hazard and it also includes, for the two sample problem, the case of two...

  16. Data generation for the Cox proportional hazards model with time-dependent covariates: a method for medical researchers.

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    Hendry, David J

    2014-02-10

    The proliferation of longitudinal studies has increased the importance of statistical methods for time-to-event data that can incorporate time-dependent covariates. The Cox proportional hazards model is one such method that is widely used. As more extensions of the Cox model with time-dependent covariates are developed, simulations studies will grow in importance as well. An essential starting point for simulation studies of time-to-event models is the ability to produce simulated survival times from a known data generating process. This paper develops a method for the generation of survival times that follow a Cox proportional hazards model with time-dependent covariates. The method presented relies on a simple transformation of random variables generated according to a truncated piecewise exponential distribution and allows practitioners great flexibility and control over both the number of time-dependent covariates and the number of time periods in the duration of follow-up measurement. Within this framework, an additional argument is suggested that allows researchers to generate time-to-event data in which covariates change at integer-valued steps of the time scale. The purpose of this approach is to produce data for simulation experiments that mimic the types of data structures applied that researchers encounter when using longitudinal biomedical data. Validity is assessed in a set of simulation experiments, and results indicate that the proposed procedure performs well in producing data that conform to the assumptions of the Cox proportional hazards model. Copyright © 2013 John Wiley & Sons, Ltd.

  17. A semi-parametric generalization of the Cox proportional hazards regression model: Inference and Applications.

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    Devarajan, Karthik; Ebrahimi, Nader

    2011-01-01

    The assumption of proportional hazards (PH) fundamental to the Cox PH model sometimes may not hold in practice. In this paper, we propose a generalization of the Cox PH model in terms of the cumulative hazard function taking a form similar to the Cox PH model, with the extension that the baseline cumulative hazard function is raised to a power function. Our model allows for interaction between covariates and the baseline hazard and it also includes, for the two sample problem, the case of two Weibull distributions and two extreme value distributions differing in both scale and shape parameters. The partial likelihood approach can not be applied here to estimate the model parameters. We use the full likelihood approach via a cubic B-spline approximation for the baseline hazard to estimate the model parameters. A semi-automatic procedure for knot selection based on Akaike's Information Criterion is developed. We illustrate the applicability of our approach using real-life data.

  18. Extensions and applications of the Cox-Aalen survival model.

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    Scheike, Thomas H; Zhang, Mei-Jie

    2003-12-01

    Cox's regression model is the standard regression tool for survival analysis in most applications. Often, however, the model only provides a rough summary of the effect of some covariates. Therefore, if the aim is to give a detailed description of covariate effects and to consequently calculate predicted probabilities, more flexible models are needed. In another article, Scheike and Zhang (2002, Scandinavian Journal of Statistics 29, 75-88), we suggested a flexible extension of Cox's regression model, which aimed at extending the Cox model only for those covariates where additional flexibility are needed. One important advantage of the suggested approach is that even though covariates are allowed a nonparametric effect, the hassle and difficulty of finding smoothing parameters are not needed. We show how the extended model also leads to simple formulae for predicted probabilities and their standard errors, for example, in the competing risk framework.

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

    DEFF Research Database (Denmark)

    Martinussen, Torben; Pipper, Christian Bressen

    2005-01-01

    Shared frailty models are of interest when one has clustered survival data and when focus is on comparing the lifetimes within clusters and further on estimating the correlation between lifetimes from the same cluster. It is well known that the positive stable model should be preferred to the gamma...... 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...

  20. Limitations of Cox Proportional Hazards Analysis in Mortality Prediction of Patients with Acute Coronary Syndrome

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    Babińska Magdalena

    2015-12-01

    Full Text Available The aim of this study was to evaluate the possibility of incorrect assessment of mortality risk factors in a group of patients affected by acute coronary syndrome, due to the lack of hazard proportionality in the Cox regression model. One hundred and fifty consecutive patients with acute coronary syndrome (ACS and no age limit were enrolled. Univariable and multivariable Cox proportional hazard analyses were performed. The proportional hazard assumptions were verified using Schoenfeld residuals, χ2 test and rank correlation coefficient t between residuals and time. In the total group of 150 patients, 33 (22.0% deaths from any cause were registered in the follow-up time period of 64 months. The non-survivors were significantly older and had increased prevalence of diabetes and erythrocyturia, longer history of coronary artery disease, higher concentrations of serum creatinine, cystatin C, uric acid, glucose, C-reactive protein (CRP, homocysteine and B-type natriuretic peptide (NT-proBNP, and lower concentrations of serum sodium. No significant differences in echocardiography parameters were observed between groups. The following factors were risk of death factors and fulfilled the proportional hazard assumption in the univariable model: smoking, occurrence of diabetes and anaemia, duration of coronary artery disease, and abnormal serum concentrations of uric acid, sodium, homocysteine, cystatin C and NT-proBNP, while in the multivariable model, the risk of death factors were: smoking and elevated concentrations of homocysteine and NT-proBNP. The study has demonstrated that violation of the proportional hazard assumption in the Cox regression model may lead to creating a false model that does not include only time-independent predictive factors.

  1. Application of cox proportional hazards model in case of tuberculosis patients in selected addis ababa health centres, ethiopia.

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    Tolosie, Kabtamu; Sharma, M K

    2014-01-01

    Introduction. Tuberculosis (TB) is a chronic infectious disease and mainly caused by mycobacterium tuberculosis (MTB). It has been one of the major causes of mortality in Ethiopia. The objective of the study was to identify factors that affect the survival of the patients with tuberculosis who started treatment for tuberculosis. Methods. This was a retrospective study in six randomly selected health centres in Addis Ababa, Ethiopia. The data were obtained from medical records of TB patients registered from September 2012 to August 2013 and treated under directly observed treatment surgery (DOTS) strategy. Kaplan Meier plots, logrank tests, and Wilcoxon tests were used to assess the survival pattern. Cox proportional hazards model for multivariable analysis was discussed. Results. Out of the total 826 registered TB patients, 105 (12.71%) died during the study period and 712 (87.29%) were censored. Based on Kaplan Meier survival curves, logrank test, and Wilcoxon test, it was found that the patients had statistically significant differences in survival experience with respect to age, body weight at initiation of treatment, TB patient category, and HIV status. Multivariable Cox hazards regression analysis revealed that the covariates age, TB patient category, HIV, and age by HIV interaction were significant risk factors associated with death status in TB patients. Conclusion. Deaths of individuals with diseases especially HIV coinfected and nonnew TB cases were high. Therefore, this needs to strengthen the follow-up of patients with TB treatment from the day of anti-TB treatment initiation to completion days.

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

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    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.

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

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    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.

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

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    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.

  5. Comparison of the Results of Cox Proportional Hazards Model and Parametric Models in the Study of Length of Stay in A Tertiary Teaching Hospital in Tehran, Iran

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    Ali Zare

    2011-10-01

    Full Text Available Survival analysis is a set of methods used for analysis of the data which exist until the occurrence of an event. This study aimed to compare the results of the use of the semi-parametric Cox model with parametric models to determine the factors influencing the length of stay of patients in the inpatient units of Women Hospital in Tehran, Iran. In this historical cohort study all 3421 charts of the patients admitted to Obstetrics, Surgery and Oncology units in 2008 were reviewed and the required patient data such as medical insurance coverage types, admission months, days and times, inpatient units, final diagnoses, the number of diagnostic tests, admission types were collected. The patient length of stay in hospitals leading to recoverys was considered as a survival variable. To compare the semi-parametric Cox model and parametric (including exponential, Weibull, Gompertz, log-normal, log-logistic and gamma models and find the best model fitted to studied data, Akaike's Information Criterion (AIC and Cox-Snell residual were used. P<0.05 was considered as statistically significant. AIC and Cox-Snell residual graph showed that the gamma model had the lowest AIC (4288.598 and the closest graph to the bisector. The results of the gamma model showed that factors affecting the patient length of stay were admission day, inpatient unit, related physician specialty, emergent admission, final diagnosis and the number of laboratory tests, radiographies and sonographies (P<0.05. The results showed that the gamma model provided a better fit to the studied data than the Cox proportional hazards model. Therefore, it is better for researchers of healthcare field to consider this model in their researches about the patient length of stay (LOS if the assumption of proportional hazards is not fulfilled.

  6. 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.

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    Puddu, Paolo Emilio; Menotti, Alessandro

    2012-07-23

    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. 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 (two protectors), were

  7. 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

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    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

  8. simPH: An R Package for Illustrating Estimates from Cox Proportional Hazard Models Including for Interactive and Nonlinear Effects

    Directory of Open Access Journals (Sweden)

    Christopher Gandrud

    2015-06-01

    Full Text Available The R package simPH provides tools for effectively communicating results from Cox proportional hazard (PH models, including models with interactive and nonlinear effects. The Cox (PH model is a popular tool for examining event data. However, previously available computational tools have not made it easy to explore and communicate quantities of interest and associated uncertainty estimated from them. This is especially true when the effects are interactions or nonlinear transformations of continuous variables. These transformations are especially useful with Cox PH models because they can be employed to correctly specifying models that would otherwise violate the nonproportional hazards assumption. Package simPH makes it easy to simulate and then plot quantities of interest for a variety of effects estimated from Cox PH models including interactive effects, nonlinear effects, as well as standard linear effects. Package simPH employs visual weighting in order to effectively communicate estimation uncertainty. There are options to show either the standard central interval of the simulation's distribution or the shortest probability interval - which can be useful for asymmetrically distributed estimates. This paper uses hypothetical and empirical examples to illustrate package simPH 's syntax and capabilities.

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

    African Journals Online (AJOL)

    Adejumo & Ahmadu

    ABSTRACT. Parametric models require that the distribution of survival time is known and the hazard function is completely specified except for the values of the unknown parameters. These include the Weibull model, the exponential model, and the log-normal model. In this research work, Weibull Model is used for ...

  10. 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

  11. Analysis of the camouflage effect in time of segregation in texturized regions using the Cox proportional hazard model

    Directory of Open Access Journals (Sweden)

    Eduardo Yoshio Nakano

    2012-11-01

    Full Text Available Humans have trichromatic vision. However variations in gene can cause deficiency in color vision resulting to dichromatism. The aim of this work was to verify the real efficiency of dichromats to break colour camouflage. Total of nine colour-blind individuals participated in this study and the variable considered was the time to segregation of camouflaged targets. The interest was to compare the response time in several conditions of camouflage and the analysis was performed using the Cox proportional hazard model.

  12. Gene-gene interaction analysis for the survival phenotype based on the Cox model.

    Science.gov (United States)

    Lee, Seungyeoun; Kwon, Min-Seok; Oh, Jung Mi; Park, Taesung

    2012-09-15

    For the past few decades, many statistical methods in genome-wide association studies (GWAS) have been developed to identify SNP-SNP interactions for case-control studies. However, there has been less work for prospective cohort studies, involving the survival time. Recently, Gui et al. (2011) proposed a novel method, called Surv-MDR, for detecting gene-gene interactions associated with survival time. Surv-MDR is an extension of the multifactor dimensionality reduction (MDR) method to the survival phenotype by using the log-rank test for defining a binary attribute. However, the Surv-MDR method has some drawbacks in the sense that it needs more intensive computations and does not allow for a covariate adjustment. In this article, we propose a new approach, called Cox-MDR, which is an extension of the generalized multifactor dimensionality reduction (GMDR) to the survival phenotype by using a martingale residual as a score to classify multi-level genotypes as high- and low-risk groups. The advantages of Cox-MDR over Surv-MDR are to allow for the effects of discrete and quantitative covariates in the frame of Cox regression model and to require less computation than Surv-MDR. Through simulation studies, we compared the power of Cox-MDR with those of Surv-MDR and Cox regression model for various heritability and minor allele frequency combinations without and with adjusting for covariate. We found that Cox-MDR and Cox regression model perform better than Surv-MDR for low minor allele frequency of 0.2, but Surv-MDR has high power for minor allele frequency of 0.4. However, when the effect of covariate is adjusted for, Cox-MDR and Cox regression model perform much better than Surv-MDR. We also compared the performance of Cox-MDR and Surv-MDR for a real data of leukemia patients to detect the gene-gene interactions with the survival time. leesy@sejong.ac.kr; tspark@snu.ac.kr.

  13. Survival analysis of gastric cancer patients using Cox model: a five year study

    Directory of Open Access Journals (Sweden)

    Biglarian A

    2009-08-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Gastric cancer is the second most common cancer and known as the second cause of death due to cancers worldwide. Adenocarcinoma is the most fatal cancer in Iran and a patient with this kind of cancer, has a lower lifetime than others. In this research, the survival of patients with gastric carcinoma who were registered at Taleghani Hospital, were studied."n"nMethods: 291 patients with Gastric carcinoma who had received care, chemotherapy or chemoradiotherapy, at Taleghani Hospital in Tehran from 2002 to 2007 were studied as a historical cohort. Their survival rates and its relationship with 12 risk factors were assessed."n"nResults: Of the 291 patients with Gastric carcinoma, 70.1 percent were men and others (29.9% were women. The mean age of men was 62.26 years and of women was 59.32 years at the time of diagnosis. Most of patients (93.91% were advanced stage and metastasis. The Cox proportional hazards model showed that age at diagnosis, tumor stage and histology type with survival time had significant relationships (p=0.039, p=0.042 and p=0.032 respectively."n"n Conclusion: The five-year survival rate and median lifetime of gastric cancer patients who underwent chemotherapy or chemoradiotherapy are very

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

    Science.gov (United States)

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

    2016-01-01

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

  15. A comparison between the use of Cox regression and the use of partial least squares-Cox regression to predict the survival of kidney-transplant patients

    Science.gov (United States)

    Solimun

    2017-05-01

    The aim of this research is to model survival data from kidney-transplant patients using the partial least squares (PLS)-Cox regression, which can both meet and not meet the no-multicollinearity assumption. The secondary data were obtained from research entitled "Factors affecting the survival of kidney-transplant patients". The research subjects comprised 250 patients. The predictor variables consisted of: age (X1), sex (X2); two categories, prior hemodialysis duration (X3), diabetes (X4); two categories, prior transplantation number (X5), number of blood transfusions (X6), discrepancy score (X7), use of antilymphocyte globulin(ALG) (X8); two categories, while the response variable was patient survival time (in months). Partial least squares regression is a model that connects the predictor variables X and the response variable y and it initially aims to determine the relationship between them. Results of the above analyses suggest that the survival of kidney transplant recipients ranged from 0 to 55 months, with 62% of the patients surviving until they received treatment that lasted for 55 months. The PLS-Cox regression analysis results revealed that patients' age and the use of ALG significantly affected the survival time of patients. The factor of patients' age (X1) in the PLS-Cox regression model merely affected the failure probability by 1.201. This indicates that the probability of dying for elderly patients with a kidney transplant is 1.152 times higher than that for younger patients.

  16. 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.

    Science.gov (United States)

    Austin, Peter C; Pencinca, Michael J; Steyerberg, Ewout W

    2017-06-01

    Predicting 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 Monte Carlo simulations for common measures of performance: concordance indices ( c, including various extensions to survival outcomes), Royston's D index, R2-type measures, and Chambless' adaptation of the integrated discrimination improvement to survival outcomes. We found that the increase in performance due to the inclusion of a risk factor tended to decrease as the performance of the reference model increased. Moreover, the increase in performance increased as the hazard ratio or the prevalence of a binary risk factor increased. Finally, for the concordance indices and R2-type measures, the absolute increase in predictive accuracy due to the inclusion of a risk factor was greater when the observed event rate was higher (low censoring). Amongst the different concordance indices, Chambless and Diao's c-statistic exhibited the greatest increase in predictive accuracy when a novel risk factor was added to an existing model. Amongst the different R2-type measures, O'Quigley et al.'s modification of Nagelkerke's R2 index and Kent and O'Quigley's [Formula: see text] displayed the greatest sensitivity to the addition of a novel risk factor or marker. These methods were then applied to a cohort of 8635 patients hospitalized with heart failure to examine the added benefit of a point-based scoring system for predicting mortality after initial adjustment with patient age alone.

  17. 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

  18. Application of random survival forests in understanding the determinants of under-five child mortality in Uganda in the presence of covariates that satisfy the proportional and non-proportional hazards assumption.

    Science.gov (United States)

    Nasejje, Justine B; Mwambi, Henry

    2017-09-07

    Uganda just like any other Sub-Saharan African country, has a high under-five child mortality rate. To inform policy on intervention strategies, sound statistical methods are required to critically identify factors strongly associated with under-five child mortality rates. The Cox proportional hazards model has been a common choice in analysing data to understand factors strongly associated with high child mortality rates taking age as the time-to-event variable. However, due to its restrictive proportional hazards (PH) assumption, some covariates of interest which do not satisfy the assumption are often excluded in the analysis to avoid mis-specifying the model. Otherwise using covariates that clearly violate the assumption would mean invalid results. Survival trees and random survival forests are increasingly becoming popular in analysing survival data particularly in the case of large survey data and could be attractive alternatives to models with the restrictive PH assumption. In this article, we adopt random survival forests which have never been used in understanding factors affecting under-five child mortality rates in Uganda using Demographic and Health Survey data. Thus the first part of the analysis is based on the use of the classical Cox PH model and the second part of the analysis is based on the use of random survival forests in the presence of covariates that do not necessarily satisfy the PH assumption. Random survival forests and the Cox proportional hazards model agree that the sex of the household head, sex of the child, number of births in the past 1 year are strongly associated to under-five child mortality in Uganda given all the three covariates satisfy the PH assumption. Random survival forests further demonstrated that covariates that were originally excluded from the earlier analysis due to violation of the PH assumption were important in explaining under-five child mortality rates. These covariates include the number of children under the

  19. Sample size and power for a logrank test and Cox proportional hazards model with multiple groups and strata, or a quantitative covariate with multiple strata.

    Science.gov (United States)

    Lachin, John M

    2013-11-10

    I describe general expressions for the evaluation of sample size and power for the K group Mantel-logrank test or the Cox proportional hazards (PH) model score test. Under an exponential model, the method of Lachin and Foulkes for the 2 group case is extended to the K ⩾2 group case using the non-centrality parameter of the K - 1 df chi-square test. I also show similar results to apply to the K group score test in a Cox PH model. Lachin and Foulkes employed a truncated exponential distribution to provide for a non-linear rate of enrollment. I present expressions for the mean time of enrollment and the expected follow-up time in the presence of exponential losses to follow-up. When used with the expression for the noncentrality parameter for the test, equations are derived for the evaluation of sample size and power under specific designs with r years of recruitment and T years total duration. I also describe sample size and power for a stratified-adjusted K group test and for the assessment of a group by stratum interaction. Similarly, I describe computations for a stratified-adjusted analysis of a quantitative covariate and a test of a stratum by covariate interaction in the Cox PH model. Copyright © 2013 John Wiley & Sons, Ltd.

  20. Predictors of time to relapse in amphetamine-type substance users in the matrix treatment program in Iran: a Cox proportional hazard model application.

    Science.gov (United States)

    Moeeni, Maryam; Razaghi, Emran M; Ponnet, Koen; Torabi, Fatemeh; Shafiee, Seyed Ali; Pashaei, Tahereh

    2016-07-26

    The aim of this study was to determine which predictors influence the risk of relapse among a cohort of amphetamine-type substance (ATS) users in Iran. A Cox proportional hazards model was conducted to determine factors associated with the relapse time in the Matrix treatment program provided by the Iranian National Center of Addiction Studies (INCAS) between March 2010 and October 2011. Participating in more treatment sessions was associated with a lower probability of relapse. On the other hand, patients with less family support, longer dependence on ATS, and those with an experience of casual sex and a history of criminal offenses were more likely to relapse. This study broadens our understanding of factors influencing the risk of relapse in ATS use among an Iranian sample. The findings can guide practitioners during the treatment program.

  1. Cox proportional hazards model of myopic regression for laser in situ keratomileusis flap creation with a femtosecond laser and with a mechanical microkeratome.

    Science.gov (United States)

    Lin, Meng-Yin; Chang, David C K; Hsu, Wen-Ming; Wang, I-Jong

    2012-06-01

    To compare predictive factors for postoperative myopic regression between laser in situ keratomileusis (LASIK) with a femtosecond laser and LASIK with a mechanical microkeratome. Nobel Eye Clinic, Taipei, Taiwan. Retrospective comparative study. Refractive outcomes were recorded 1 day, 1 week, and 1, 3, 6, 9, and 12 months after LASIK. A Cox proportional hazards model was used to evaluate the impact of the 2 flap-creating methods and other covariates on postoperative myopic regression. The femtosecond group comprised 409 eyes and the mechanical microkeratome group, 377 eyes. For both methods, significant predictors for myopic regression after LASIK included preoperative manifest spherical equivalent (P=.0001) and central corneal thickness (P=.027). Laser in situ keratomileusis with a mechanical microkeratome had a higher probability of postoperative myopic regression than LASIK with a femtosecond laser (P=.0002). After adjusting for other covariates in the Cox proportional hazards model, the cumulative risk for myopic regression with a mechanical microkeratome was higher than with a femtosecond laser 12 months postoperatively (P=.0002). With the definition of myopic regression as a myopic shift of 0.50 diopter (D) or more and residual myopia of -0.50 D or less, the risk estimate based on the mean covariates in all eyes in the femtosecond group and mechanical microkeratome group at 12 months was 43.6% and 66.9%, respectively. Laser in situ keratomileusis with a mechanical microkeratome had a higher risk for myopic regression than LASIK with a femtosecond laser through 12 months postoperatively. Copyright © 2012. Published by Elsevier Inc.

  2. Administration of the selective cyclooxygenase (COX)-2 inhibitor etodolac prolongs cardiac allograft survival in a mouse model.

    Science.gov (United States)

    Matsuyama, Masahide; Yoshimura, Rikio; Hase, Taro; Chargui, Jamel; Yoshimura, Norio; Touraine, Jean-Louis

    2010-01-01

    Etodolac, a selective cyclooxygenase-2 (COX-2) inhibitor, is a non-steroidal anti-inflammatory drug. COX-2 is a key factor in the progression of inflammation. Although inflammation is an essential pathologic feature of cardiac allograft rejection, the role of COX-2 in this process remains unclear. The aim of this study was to investigate the expression of COX and the effects of etodolac in a mouse cardiac allograft model. Balb/c mice (H-2d) were used as recipients and C57BL/6 (H-2b) mice as heart donors. Heart function was evaluated daily after transplantation by regular abdominal palpation of the heart and by laparotomy in cases where the beating became weak. Rejection was defined as total cessation of cardiac muscle contraction. COX-2 expression was analyzed by immunohistochemistry. Cardiac isograft was well tolerated (>150 days, n=5), while non-treated cardiac allograft was rapidly rejected (mean 10.9±2.4, n=7). In the etodolac-treated cardiac allograft (10 mg/kg/day by hypodermic injection), survival was extended to 18.53±2.1 days (n=7). The necrotic area and the grade of COX-2 immunostaining were more significantly reduced in the etodolac-treated cardiac allograft than in the non-treated cardiac allograft at day 14. These results indicate that etodolac contributes to protection against rejection after heart transplantation. Etodolac could therefore be used to suppress graft rejection by means of its anti-inflammatory properties.

  3. 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.

  4. 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.

  5. 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.

  6. Gene–gene interaction analysis for the survival phenotype based on the Cox model

    OpenAIRE

    Lee, Seungyeoun; Kwon, Min-Seok; Oh, Jung Mi; Park, Taesung

    2012-01-01

    Motivation: For the past few decades, many statistical methods in genome-wide association studies (GWAS) have been developed to identify SNP–SNP interactions for case-control studies. However, there has been less work for prospective cohort studies, involving the survival time. Recently, Gui et al. (2011) proposed a novel method, called Surv-MDR, for detecting gene–gene interactions associated with survival time. Surv-MDR is an extension of the multifactor dimensionality reduction (MDR) metho...

  7. Acoustic Telemetry Evaluation of Juvenile Salmonid Passage and Survival Proportions at John Day Dam, 2009

    Energy Technology Data Exchange (ETDEWEB)

    Weiland, Mark A.; Ploskey, Gene R.; Hughes, James S.; Deng, Zhiqun; Fu, Tao; Kim, Jin A.; Johnson, Gary E.; Fischer, Eric S.; Khan, Fenton; Zimmerman, Shon A.; Faber, Derrek M.; Carter, Kathleen M.; Boyd, James W.; Townsend, Richard L.; Skalski, J. R.; Monter, Tyrell J.; Cushing, Aaron W.; Wilberding, Matthew C.; Meyer, Matthew M.

    2011-09-28

    The overall purpose of the acoustic telemetry study at JDA during 2009 was to determine the best configuration and operation for JDA prior to conducting BiOp performance standard tests. The primary objective was to determine the best operation between 30% and 40% spill treatments. Route-specific and JDA to TDA forebay survival estimates, passage distribution, and timing/behavior metrics were used for comparison of 30% to a 40% spill treatments. A secondary objective was to evaluate the performance of TSWs installed in spill bays 15 and 16 and to estimate fish survival rates and passage efficiencies under 30% and 40% spill-discharge treatments each season.

  8. 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

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

    Science.gov (United States)

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

    2017-12-29

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

  10. Multilevel modelling of clustered grouped survival data using Cox regression model: an application to ART dental restorations.

    Science.gov (United States)

    Wong, May C M; Lam, K F; Lo, Edward C M

    2006-02-15

    In some controlled clinical trials in dental research, multiple failure time data from the same patient are frequently observed that result in clustered multiple failure time. Moreover, the treatments are often delivered by more than one operator and thus the multiple failure times are clustered according to a multilevel structure when the operator effects are assumed to be random. In practice, it is often too expensive or even impossible to monitor the study subjects continuously, but they are examined periodically at some regular pre-scheduled visits. Hence, discrete or grouped clustered failure time data are collected. The aim of this paper is to illustrate the use of the Monte Carlo Markov chain (MCMC) approach and non-informative prior in a Bayesian framework to mimic the maximum likelihood (ML) estimation in a frequentist approach in multilevel modelling of clustered grouped survival data. A three-level model with additive variance components model for the random effects is considered in this paper. Both the grouped proportional hazards model and the dynamic logistic regression model are used. The approximate intra-cluster correlation of the log failure times can be estimated when the grouped proportional hazards model is used. The statistical package WinBUGS is adopted to estimate the parameter of interest based on the MCMC method. The models and method are applied to a data set obtained from a prospective clinical study on a cohort of Chinese school children that atraumatic restorative treatment (ART) restorations were placed on permanent teeth with carious lesions. Altogether 284 ART restorations were placed by five dentists and clinical status of the ART restorations was evaluated annually for 6 years after placement, thus clustered grouped failure times of the restorations were recorded. Results based on the grouped proportional hazards model revealed that clustering effect among the log failure times of the different restorations from the same child was

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

    African Journals Online (AJOL)

    This work compared three estimation methods to handle tied survival time data under the semiparametric Cox proportional hazards model framework (the Exact, Breslow and Efron partial likelihood) and also two parametric proportional hazards models (the Exponential and Weibull) which utilized full likelihood estimation ...

  12. 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...... the restriction, but in testing its proportionality. The article illustrates its point by referring to two categories of decision: (A) proportionality-strong decisions, which illustrate a thorough and firm proportionality assessment, and (B) proportionality-weak decisions, which could have led to a different...

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

    Directory of Open Access Journals (Sweden)

    Nils Ternès

    2017-05-01

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

  14. Route-Specific Passage Proportions and Survival Rates for Fish Passing through John Day Dam, The Dalles Dam, and Bonneville Dam in 2010 and 2011

    Energy Technology Data Exchange (ETDEWEB)

    Ploskey, Gene R.; Weiland, Mark A.; Carlson, Thomas J.

    2012-06-04

    This report fulfills a request of the U.S. Army Engineer District, Portland, Oregon, to produce an interim report of estimates of route-specific fish passage proportions and survival rates for lower Columbia River dams in 2010 and 2011. The estimates are needed to update the Compass Model for the Columbia River Treaty and the new Biological Opinion before detail technical reports are published in late 2012. This report tabulates route-specific fish-passage proportions and survival rates for steelhead and Chinook salmon smolts passing through various sampled routes at John Day Dam, The Dalles Dam, and Bonneville Dam in 2010 and 2011. Results were compiled from analyses of data acquired in spring 2010 and 2011 studies that were specifically designed to estimate dam-passage and forebay-to-tailrace survival rates, travel time metrics, and spill passage efficiency, as stipulated by the 2008 Federal Columbia River Power System Biological Opinion and the Columbia Basin Fish Accords. The study designs allowed for estimation of route-specific fish passage proportions and survival rates as well as estimation of forebay-passage survival, all of which are summarized herein.

  15. Jointly modeling longitudinal proportional data and survival times with an application to the quality of life data in a breast cancer trial.

    Science.gov (United States)

    Song, Hui; Peng, Yingwei; Tu, Dongsheng

    2017-04-01

    Motivated by the joint analysis of longitudinal quality of life data and recurrence free survival times from a cancer clinical trial, we present in this paper two approaches to jointly model the longitudinal proportional measurements, which are confined in a finite interval, and survival data. Both approaches assume a proportional hazards model for the survival times. For the longitudinal component, the first approach applies the classical linear mixed model to logit transformed responses, while the second approach directly models the responses using a simplex distribution. A semiparametric method based on a penalized joint likelihood generated by the Laplace approximation is derived to fit the joint model defined by the second approach. The proposed procedures are evaluated in a simulation study and applied to the analysis of breast cancer data motivated this research.

  16. 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...

  17. 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...

  18. 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

  19. Cox regression model with doubly truncated data.

    Science.gov (United States)

    Rennert, Lior; Xie, Sharon X

    2017-10-26

    Truncation is a well-known phenomenon that may be present in observational studies of time-to-event data. While many methods exist to adjust for either left or right truncation, there are very few methods that adjust for simultaneous left and right truncation, also known as double truncation. We propose a Cox regression model to adjust for this double truncation using a weighted estimating equation approach, where the weights are estimated from the data both parametrically and nonparametrically, and are inversely proportional to the probability that a subject is observed. The resulting weighted estimators of the hazard ratio are consistent. The parametric weighted estimator is asymptotically normal and a consistent estimator of the asymptotic variance is provided. For the nonparametric weighted estimator, we apply the bootstrap technique to estimate the variance and confidence intervals. We demonstrate through extensive simulations that the proposed estimators greatly reduce the bias compared to the unweighted Cox regression estimator which ignores truncation. We illustrate our approach in an analysis of autopsy-confirmed Alzheimer's disease patients to assess the effect of education on survival. © 2017, The International Biometric Society.

  20. 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.

  1. Adverse Effects of COX-2 Inhibitors

    Directory of Open Access Journals (Sweden)

    Jagdish N. Sharma

    2005-01-01

    Full Text Available Cyclooxygenase-2 selective inhibitors (COXIBs were developed with the prime object of minimizing gastrointestinal adverse effects, which are seen with the use of traditional nonsteroidal anti-inflammatory drugs (NSAIDs. Their long-term use is limited by the development of hypertension, edema, and congestive heart failure in a significant proportion of patients. NSAIDs block the activity of both COX isozymes, COX-1 and COX-2, which mediate the enzymatic conversion of arachidonate to prostaglandin H2 (PGH2 and other prostaglandin (PG metabolites. It is well established that the cardiovascular profile of COX-2 inhibitors can be accounted for by inhibition of COX-dependent PG synthesis. Following the COX-mediated synthesis of PGH2 from arachidonate, PGH2 is metabolized to one of at least five bioactive PGs, including PGE2, PGI2, PGF2, PGD2, or thromboxane A2 (TXA2. These prostanoids have pleiotropic cardiovascular effects, altering platelet function and renal function, and they are acting either as vasodilators or vasoconstrictors. Although COX-1 and COX-2 exhibit similar biochemical activity in converting arachidonate to PGH2in vitro, the ultimate prostanoids they produce in vivo may be different due to differential regulation of COX-1 and COX-2, tissue distribution, and availability of the prostanoid synthases. PGs have been established as being critically involved in mitigating hypertension, helping to maintain medullary blood flow (MBF, promoting urinary salt excretion, and preserving the normal homeostasis of thrombosis, and the researchers found that the use of COX-2 inhibitors caused many serious complications in altering the normal body homeostasis. The purpose of the present research is to explain briefly the side effects of COX-2 inhibitors on the renal and cardiovascular system.

  2. Gene expression profiling for prognosis using Cox regression.

    Science.gov (United States)

    Pawitan, Y; Bjöhle, J; Wedren, S; Humphreys, K; Skoog, L; Huang, F; Amler, L; Shaw, P; Hall, P; Bergh, J

    2004-06-15

    Given the promise of rich biological information in microarray data we will expect an increasing demand for a robust, practical and well-tested methodology to provide patient prognosis based on gene expression data. In standard settings, with few clinical predictors, such a methodology has been provided by the Cox proportional hazard model, but no corresponding methodology is available to deal with the full set of genes in microarray data. Furthermore, we want the procedure to be able to deal with the general survival data that include censored information. Conceptually such a procedure can be constructed quite easily, but its implementation will never be straightforward due to computational problems. We have developed an approach that relies on an extension of the Cox proportional likelihood that allows random effects parameters. In this approach, we use the full set of genes in the analysis and deal with survival data in the most general way. We describe the development of the model and the steps in the implementation, including a fast computational formula based on a subsampling of the risk set and the singular value decomposition. Finally, we illustrate the methodology using a data set obtained from a cohort of breast cancer patients. Copyright 2004 John Wiley & Sons, Ltd.

  3. Evaluating survival model performance: a graphical approach.

    Science.gov (United States)

    Mandel, M; Galai, N; Simchen, E

    2005-06-30

    In the last decade, many statistics have been suggested to evaluate the performance of survival models. These statistics evaluate the overall performance of a model ignoring possible variability in performance over time. Using an extension of measures used in binary regression, we propose a graphical method to depict the performance of a survival model over time. The method provides estimates of performance at specific time points and can be used as an informal test for detecting time varying effects of covariates in the Cox model framework. The method is illustrated on real and simulated data using Cox proportional hazard model and rank statistics. Copyright 2005 John Wiley & Sons, Ltd.

  4. Reduced-rank hazard regression for modelling non-proportional hazards.

    Science.gov (United States)

    Perperoglou, Aris; le Cessie, Saskia; van Houwelingen, Hans C

    2006-08-30

    The Cox proportional hazards model is the most common method to analyse survival data. However, the proportional hazards assumption might not hold. The natural extension of the Cox model is to introduce time-varying effects of the covariates. For some covariates such as (surgical)treatment non-proportionality could be expected beforehand. For some other covariates the non-proportionality only becomes apparent if the follow-up is long enough. It is often observed that all covariates show similar decaying effects over time. Such behaviour could be explained by the popular (gamma-) frailty model. However, the (marginal) effects of covariates in frailty models are not easy to interpret. In this paper we propose the reduced-rank model for time-varying effects of covariates. Starting point is a Cox model with p covariates and time-varying effects modelled by q time functions (constant included), leading to a pxq structure matrix that contains the regression coefficients for all covariate by time function interactions. By reducing the rank of this structure matrix a whole range of models is introduced, from the very flexible full-rank model (identical to a Cox model with time-varying effects) to the very rigid rank one model that mimics the structure of a gamma-frailty model, but is easier to interpret. We illustrate these models with an application to ovarian cancer patients. Copyright (c) 2005 John Wiley & Sons, Ltd.

  5. Attenuation caused by infrequently updated covariates in survival analysis

    DEFF Research Database (Denmark)

    Andersen, Per Kragh; Liestøl, Knut

    2003-01-01

    Attenuation; Cox regression model; Measurement errors; Survival analysis; Time-dependent covariates......Attenuation; Cox regression model; Measurement errors; Survival analysis; Time-dependent covariates...

  6. Survival

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — These data provide information on the survival of California red-legged frogs in a unique ecosystem to better conserve this threatened species while restoring...

  7. Smoothed Cox regression

    OpenAIRE

    Dabrowska, Dorota M.

    1997-01-01

    Nonparametric regression was shown by Beran and McKeague and Utikal to provide a flexible method for analysis of censored failure times and more general counting processes models in the presence of covariates. We discuss application of kernel smoothing towards estimation in a generalized Cox regression model with baseline intensity dependent on a covariate. Under regularity conditions we show that estimates of the regression parameters are asymptotically normal at rate root-n, and we also dis...

  8. 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

  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. Survival Forests with R-Squared Splitting Rules.

    Science.gov (United States)

    Wang, Hong; Chen, Xiaolin; Li, Gang

    2017-12-21

    In modeling censored data, survival forest models are a competitive nonparametric alternative to traditional parametric or semiparametric models when the function forms are possibly misspecified or the underlying assumptions are violated. In this work, we propose a survival forest approach with trees constructed using a novel pseudo R2 splitting rules. By studying the well-known benchmark data sets, we find that the proposed model generally outperforms popular survival models such as random survival forest with different splitting rules, Cox proportional hazard model, and generalized boosted model in terms of C-index metric.

  11. COUNTRY-LEVEL SOCIOECONOMIC INDICATORS ASSOCIATED WITH SURVIVAL PROBABILITY OF BECOMING A CENTENARIAN AMONG OLDER EUROPEAN ADULTS: GENDER INEQUALITY, MALE LABOUR FORCE PARTICIPATION AND PROPORTIONS OF WOMEN IN PARLIAMENTS.

    Science.gov (United States)

    Kim, Jong In; Kim, Gukbin

    2017-03-01

    This study confirms an association between survival probability of becoming a centenarian (SPBC) for those aged 65 to 69 and country-level socioeconomic indicators in Europe: the gender inequality index (GII), male labour force participation (MLP) rates and proportions of seats held by women in national parliaments (PWP). The analysis was based on SPBC data from 34 countries obtained from the United Nations (UN). Country-level socioeconomic indicator data were obtained from the UN and World Bank databases. The associations between socioeconomic indicators and SPBC were assessed using correlation coefficients and multivariate regression models. The findings show significant correlations between the SPBC for women and men aged 65 to 69 and country-level socioeconomic indicators: GII (r=-0.674, p=0.001), MLP (r=0.514, p=0.002) and PWP (r=0.498, p=0.003). The SPBC predictors for women and men were lower GIIs and higher MLP and PWP (R 2=0.508, p=0.001). Country-level socioeconomic indicators appear to have an important effect on the probability of becoming a centenarian in European adults aged 65 to 69. Country-level gender equality policies in European counties may decrease the risk of unhealthy old age and increase longevity in elders through greater national gender equality; disparities in GII and other country-level socioeconomic indicators impact longevity probability. National longevity strategies should target country-level gender inequality.

  12. 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...... result is used to study functional summaries for log Gaussian Cox processes....

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

    Directory of Open Access Journals (Sweden)

    Francisco M. Ojeda

    2016-08-01

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

  14. A 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 ...

  15. Believing Badly | Cox | Philosophical Papers

    African Journals Online (AJOL)

    Believing Badly. Damian Cox, Michael Levine. Abstract. This paper explores the grounds upon which moral judgment of a person's beliefs is properly made. The beliefs in question are non-moral beliefs and the objects of moral judgment are individual instances of believing. We argue that instances of believing may be ...

  16. Survival analysis of orthodontic mini-implants.

    Science.gov (United States)

    Lee, Shin-Jae; Ahn, Sug-Joon; Lee, Jae Won; Kim, Seong-Hun; Kim, Tae-Woo

    2010-02-01

    Survival analysis is useful in clinical research because it focuses on comparing the survival distributions and the identification of risk factors. Our aim in this study was to investigate the survival characteristics and risk factors of orthodontic mini-implants with survival analyses. One hundred forty-one orthodontic patients (treated from October 1, 2000, to November 29, 2007) were included in this survival study. A total of 260 orthodontic mini-implants that had sandblasted (large grit) and acid-etched screw parts were placed between the maxillary second premolar and the first molar. Failures of the implants were recorded as event data, whereas implants that were removed because treatment ended and those that were not removed during the study period were recorded as censored data. A nonparametric life table method was used to visualize the hazard function, and Kaplan-Meier survival curves were generated to identify the variables associated with implant failure. Prognostic variables associated with implant failure were identified with the Cox proportional hazard model. Of the 260 implants, 22 failed. The hazard function for implant failure showed that the risk is highest immediately after placement. The survival function showed that the median survival time of orthodontic mini-implants is sufficient for relatively long orthodontic treatments. The Cox proportional hazard model identified that increasing age is a decisive factor for implant survival. The decreasing pattern of the hazard function suggested gradual osseointegration of orthodontic mini-implants. When implants are placed in a young patient, special caution is needed to lessen the increased probability of failure, especially immediately after placement.

  17. 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......) with Λ equal to the exponential of such a kernel smoothing. Special cases are shot noise Cox processes, log Gaussian Cox processes, and log shot noise Cox processes. We study the theoretical properties of Lévy-based Cox processes, including moment properties described by nth-order product densities......, mixing properties, specification of inhomogeneity, and spatio-temporal extensions...

  18. ABO blood group and breast cancer incidence and survival

    OpenAIRE

    Gates, Margaret A.; Xu, Mousheng; Chen, Wendy Y.; Kraft, Peter; Hankinson, Susan E.; Wolpin, Brian M.

    2012-01-01

    ABO blood type has been associated with risk and survival for several malignancies; however, data for an association with breast cancer are inconsistent. Our study population consisted of Nurses’ Health Study participants with self-reported serologic blood type and/or ABO genotype. Using Cox proportional hazards regression, we examined the association between serologic blood type and incident breast cancer among 67,697 women, including 3,107 cases. In addition, we examined the association wit...

  19. Flexible survival regression modelling

    DEFF Research Database (Denmark)

    Cortese, Giuliana; Scheike, Thomas H; Martinussen, Torben

    2009-01-01

    Regression analysis of survival data, and more generally event history data, is typically based on Cox's regression model. We here review some recent methodology, focusing on the limitations of Cox's regression model. The key limitation is that the model is not well suited to represent time-varyi...

  20. Individual social capital and survival

    DEFF Research Database (Denmark)

    Ejlskov, Linda; Mortensen, Rikke N; Overgaard, Charlotte

    2014-01-01

    BACKGROUND: The concept of social capital has received increasing attention as a determinant of population survival, but its significance is uncertain. We examined the importance of social capital on survival in a population study while focusing on gender differences. METHODS: We used data from...... a Danish regional health survey with a five-year follow-up period, 2007-2012 (n = 9288, 53.5% men, 46.5% women). We investigated the association between social capital and all-cause mortality, performing separate analyses on a composite measure as well as four specific dimensions of social capital while...... controlling for covariates. Analyses were performed with Cox proportional hazard models by which hazard ratios and 95% confidence intervals were calculated. RESULTS: For women, higher levels of social capital were associated with lower all-cause mortality regardless of age, socioeconomic status, health...

  1. Meta-analysis of survival prediction with Palliative Performance Scale.

    Science.gov (United States)

    Downing, Michael; Lau, Francis; Lesperance, Mary; Karlson, Nicholas; Shaw, Jack; Kuziemsky, Craig; Bernard, Steve; Hanson, Laura; Olajide, Lola; Head, Barbara; Ritchie, Christine; Harrold, Joan; Casarett, David

    2007-01-01

    This paper aims to reconcile the use of Palliative Performance Scale (PPSv2) for survival prediction in palliative care through an international collaborative study by five research groups. The study involves an individual patient data meta-analysis on 1,808 patients from four original datasets to reanalyze their survival patterns by age, gender, cancer status, and initial PPS score. Our findings reveal a strong association between PPS and survival across the four datasets. The Kaplan-Meier survival curves show each PPS level as distinct, with a strong ordering effect in which higher PPS levels are associated with increased length of survival. Using a stratified Cox proportional hazard model to adjust for study differences, we found females lived significantly longer than males, with a further decrease in hazard for females not diagnosed with cancer. Further work is needed to refine the reporting of survival times/probabilities and to improve prediction accuracy with the inclusion of other variables in the models.

  2. Multiwire proportional chamber development

    Science.gov (United States)

    Doolittle, R. F.; Pollvogt, U.; Eskovitz, A. J.

    1973-01-01

    The development of large area multiwire proportional chambers, to be used as high resolution spatial detectors in cosmic ray experiments is described. A readout system was developed which uses a directly coupled, lumped element delay-line whose characteristics are independent of the MWPC design. A complete analysis of the delay-line and the readout electronic system shows that a spatial resolution of about 0.1 mm can be reached with the MWPC operating in the strictly proportional region. This was confirmed by measurements with a small MWPC and Fe-55 X-rays. A simplified analysis was carried out to estimate the theoretical limit of spatial resolution due to delta-rays, spread of the discharge along the anode wire, and inclined trajectories. To calculate the gas gain of MWPC's of different geometrical configurations a method was developed which is based on the knowledge of the first Townsend coefficient of the chamber gas.

  3. The Principle of Proportionality

    DEFF Research Database (Denmark)

    Bennedsen, Morten; Meisner Nielsen, Kasper

    2005-01-01

    by analyzing the use of instruments to separate ownership from control across legal regimes in a sample of over 4,000 publicly traded firms from 14 Western European countries. First, we confirm the negative impact on firm value from disproportional ownership structures previously established in a sample......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...... of Asian firms by Claessens et al. (2002). Second, we show that dual class shares have a larger and more significant negative effect on firm value than pyramids and cross holdings. Third, we find that the impact of disproportionality and the underlying instruments is inversely related to the level...

  4. Two Artificial Neural Networks for Modeling Discrete Survival Time of Censored Data

    Directory of Open Access Journals (Sweden)

    Taysseer Sharaf

    2015-01-01

    Full Text Available Artificial neural network (ANN theory is emerging as an alternative to conventional statistical methods in modeling nonlinear functions. The popular Cox proportional hazard model falls short in modeling survival data with nonlinear behaviors. ANN is a good alternative to the Cox PH as the proportionality of the hazard assumption and model relaxations are not required. In addition, ANN possesses a powerful capability of handling complex nonlinear relations within the risk factors associated with survival time. In this study, we present a comprehensive comparison of two different approaches of utilizing ANN in modeling smooth conditional hazard probability function. We use real melanoma cancer data to illustrate the usefulness of the proposed ANN methods. We report some significant results in comparing the survival time of male and female melanoma patients.

  5. Inhibition of COX isoforms by nutraceuticals.

    Science.gov (United States)

    Seaver, Ben; Smith, Jerry Robert

    2004-01-01

    Humans have two isoforms of Prostaglandin H Synthase or cyclooxygenase: COX-1 and COX-2. COX-1 is cytoprotective. COX-2 inhibitors reduce inflammation without the risk of ulceration and kidney damage. The ideal nutraceutical would inhibit COX-2 synthesis while preserving COX-1 synthesis. The hypothesis for this research was that COX inhibitors would fall primarily into three categories: COX-2 specific inhibition, non-specific inhibition (COX-1 and COX-2), and minimal inhibition. The human Cayman COX inhibitor screening assay was used to determine the inhibitory concentration 50 (IC50) of COX-1/ COX-2 activity of each nutraceutical. The assay was run, in duplicate, with three concentrations of a suspected inhibitor, a standard curve of eight concentrations, a non-specific binding sample, and a maximum binding sample. The inhibition and concentration of each sample was then put on a multiple regression best-fit line and the IC50 determined. For comparison, ibuprofen, rofecoxib, naproxen, and indomethacin were used. Positive results were seen for ipriflavone, resveratrol, MSV-60, amentoflavone, ruscus extract and notoginseng. Glucosamine, nexrutine, and berberine did not inhibit either isoform.

  6. Semi-parametric regression model for survival data: graphical visualization with R.

    Science.gov (United States)

    Zhang, Zhongheng

    2016-12-01

    Cox proportional hazards model is a semi-parametric model that leaves its baseline hazard function unspecified. The rationale to use Cox proportional hazards model is that (I) the underlying form of hazard function is stringent and unrealistic, and (II) researchers are only interested in estimation of how the hazard changes with covariate (relative hazard). Cox regression model can be easily fit with coxph() function in survival package. Stratified Cox model may be used for covariate that violates the proportional hazards assumption. The relative importance of covariates in population can be examined with the rankhazard package in R. Hazard ratio curves for continuous covariates can be visualized using smoothHR package. This curve helps to better understand the effects that each continuous covariate has on the outcome. Population attributable fraction is a classic quantity in epidemiology to evaluate the impact of risk factor on the occurrence of event in the population. In survival analysis, the adjusted/unadjusted attributable fraction can be plotted against survival time to obtain attributable fraction function.

  7. Restrictions and Proportionality

    DEFF Research Database (Denmark)

    Werlauff, Erik

    2009-01-01

    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......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...

  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. 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."

  10. Decomposition of variance for spatial Cox processes

    DEFF Research Database (Denmark)

    Jalilian, Abdollah; Guan, Yongtao; Waagepetersen, Rasmus

    2013-01-01

    Spatial Cox point processes is a natural framework for quantifying the various sources of variation governing the spatial distribution of rain forest trees. We introduce a general criterion for variance decomposition for spatial Cox processes and apply it to specific Cox process models with addit...

  11. Survival analysis of irish amyotrophic lateral sclerosis patients diagnosed from 1995-2010.

    Directory of Open Access Journals (Sweden)

    James Rooney

    Full Text Available INTRODUCTION: The Irish ALS register is a valuable resource for examining survival factors in Irish ALS patients. Cox regression has become the default tool for survival analysis, but recently new classes of flexible parametric survival analysis tools known as Royston-Parmar models have become available. METHODS: We employed Cox proportional hazards and Royston-Parmar flexible parametric modeling to examine factors affecting survival in Irish ALS patients. We further examined the effect of choice of timescale on Cox models and the proportional hazards assumption, and extended both Cox and Royston-Parmar models with time varying components. RESULTS: On comparison of models we chose a Royston-Parmar proportional hazards model without time varying covariates as the best fit. Using this model we confirmed the association of known survival markers in ALS including age at diagnosis (Hazard Ratio (HR 1.34 per 10 year increase; 95% CI 1.26-1.42, diagnostic delay (HR 0.96 per 12 weeks delay; 95% CI 0.94-0.97, Definite ALS (HR 1.47 95% CI 1.17-1.84, bulbar onset disease (HR 1.58 95% CI 1.33-1.87, riluzole use (HR 0.72 95% CI 0.61-0.85 and attendance at an ALS clinic (HR 0.74 95% CI 0.64-0.86. DISCUSSION: Our analysis explored the strengths and weaknesses of Cox proportional hazard and Royston-Parmar flexible parametric methods. By including time varying components we were able to gain deeper understanding of the dataset. Variation in survival between time periods appears to be due to missing data in the first time period. The use of age as timescale to account for confounding by age resolved breaches of the proportional hazards assumption, but in doing so may have obscured deficiencies in the data. Our study demonstrates the need to test for, and fully explore, breaches of the Cox proportional hazards assumption. Royston-Parmar flexible parametric modeling proved a powerful method for achieving this.

  12. Oracle inequalities for the lasso in the Cox model

    OpenAIRE

    Huang, Jian; Sun, Tingni; Ying, Zhiliang; Yu, Yi; Zhang, Cun-Hui

    2013-01-01

    We study the absolute penalized maximum partial likelihood estimator in sparse, high-dimensional Cox proportional hazards regression models where the number of time-dependent covariates can be larger than the sample size. We establish oracle inequalities based on natural extensions of the compatibility and cone invertibility factors of the Hessian matrix at the true regression coefficients. Similar results based on an extension of the restricted eigenvalue can be also proved by our method. Ho...

  13. Network-based survival analysis reveals subnetwork signatures for predicting outcomes of ovarian cancer treatment.

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    Full Text Available Cox regression is commonly used to predict the outcome by the time to an event of interest and in addition, identify relevant features for survival analysis in cancer genomics. Due to the high-dimensionality of high-throughput genomic data, existing Cox models trained on any particular dataset usually generalize poorly to other independent datasets. In this paper, we propose a network-based Cox regression model called Net-Cox and applied Net-Cox for a large-scale survival analysis across multiple ovarian cancer datasets. Net-Cox integrates gene network information into the Cox's proportional hazard model to explore the co-expression or functional relation among high-dimensional gene expression features in the gene network. Net-Cox was applied to analyze three independent gene expression datasets including the TCGA ovarian cancer dataset and two other public ovarian cancer datasets. Net-Cox with the network information from gene co-expression or functional relations identified highly consistent signature genes across the three datasets, and because of the better generalization across the datasets, Net-Cox also consistently improved the accuracy of survival prediction over the Cox models regularized by L(2 or L(1. This study focused on analyzing the death and recurrence outcomes in the treatment of ovarian carcinoma to identify signature genes that can more reliably predict the events. The signature genes comprise dense protein-protein interaction subnetworks, enriched by extracellular matrix receptors and modulators or by nuclear signaling components downstream of extracellular signal-regulated kinases. In the laboratory validation of the signature genes, a tumor array experiment by protein staining on an independent patient cohort from Mayo Clinic showed that the protein expression of the signature gene FBN1 is a biomarker significantly associated with the early recurrence after 12 months of the treatment in the ovarian cancer patients who are

  14. Obesity adversely affects survival in pancreatic cancer patients.

    Science.gov (United States)

    McWilliams, Robert R; Matsumoto, Martha E; Burch, Patrick A; Kim, George P; Halfdanarson, Thorvardur R; de Andrade, Mariza; Reid-Lombardo, Kaye; Bamlet, William R

    2010-11-01

    Higher body-mass index (BMI) has been implicated as a risk factor for developing pancreatic cancer, but its effect on survival has not been thoroughly investigated. The authors assessed the association of BMI with survival in a sample of pancreatic cancer patients and used epidemiologic and clinical information to understand the contribution of diabetes and hyperglycemia. A survival analysis using Cox proportional hazards by usual adult BMI was performed on 1861 unselected patients with pancreatic adenocarcinoma; analyses were adjusted for covariates that included clinical stage, age, and sex. Secondary analyses incorporated self-reported diabetes and fasting blood glucose in the survival model. BMI as a continuous variable was inversely associated with survival from pancreatic adenocarcinoma (hazard ratio [HR], 1.019 for each increased unit of BMI [kg/m2], Ppancreatic cancer. Although the mechanism of this association remains undetermined, diabetes and hyperglycemia do not appear to account for the observed association. Copyright © 2010 American Cancer Society.

  15. Racial differences in survival from gynecologic cancer.

    Science.gov (United States)

    Morgan, M A; Behbakht, K; Benjamin, I; Berlin, M; King, S A; Rubin, S C

    1996-12-01

    To determine whether survival from gynecologic cancer is different between African-American and white patients at an inner-city hospital with both a large clinic and a private service. We studied 538 patients (89 African American, 449 white) diagnosed with cervical, uterine, or ovarian cancer at a single institution from January 1, 1989 through December 31, 1993. Information was obtained on age, stage, site of disease, histology, and type of health insurance (public or commercial). Insurance coverage was used as a proxy for socioeconomic status. Overall survival was estimated by the method of Kaplan and Meier and compared by the log-rank test. Cox proportional hazard modeling was used to evaluate the effects of multiple factors on survival. African-American patients were significantly older and were more likely to have cervical cancer and public insurance than white patients. Overall survival was worse for African-American patients than for white patients (P whites, and African-American patients older than 65 years had a worse survival than whites of similar age. On multivariate analysis, only stage and insurance coverage were significant predictors of survival. African-American patients with gynecologic cancer at our institution have worse overall survival than white patients. The survival difference seems to be due predominantly to differences in socioeconomic status and stage at diagnosis.

  16. Association between the duration of palliative care service and survival in terminal cancer patients.

    Science.gov (United States)

    Lee, Yong Joo; Yang, Jung-Hwa; Lee, Jung-Wook; Yoon, Johi; Nah, Jung-Ran; Choi, Whan-Seok; Kim, Chul-Min

    2015-04-01

    Preliminary studies of early palliative care showed improved quality of life, less medical cost, and better survival time. But, most terminal cancer patients tend to be referred to palliative care late. For the proper care of terminal cancer patients, it is necessary to refer to hospice and palliative care timely. The aim of this study is to analyze the effect of the duration of palliative care services on the survival in terminal cancer patients. We reviewed 609 patients who had died from terminal cancer between January 2010 and December 2012. We analyzed correlations of age, first Palliative Performance Scale (PPS) level, duration of palliative care service, and survival time. The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. Duration of palliative care services was significantly correlated with survival time. In univariate Cox regression analysis, age, and each group of duration of palliative care service showed significant associations with survival. Final multivariate Cox regression model retained four parameters as independent prognostic factors for survival (age HR = 0.99 (p = 0.002), 1∼10 days HR = 2.64 (p care services showed poor prognostic factor. Timely referral system from the end of chemotherapy is warranted.

  17. 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...

  18. 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…

  19. Mental vulnerability and survival after cancer

    DEFF Research Database (Denmark)

    Nakaya, Naoki; Bidstrup, Pernille E; Eplov, Lene F

    2009-01-01

    BACKGROUND: It has been hypothesized that personality traits affect survival after cancer, but studies have produced inconsistent results. This study examined the association between mental vulnerability and survival after cancer in Denmark in a prospective cohort study. METHODS: Between 1976...... and 2001, 12733 residents of Copenhagen completed a questionnaire eliciting information on a 12-item mental vulnerability scale, as well as various personal data. Follow-up in the Danish Cancer Registry until 2003 identified 884 incident cases of primary cancer, and follow-up for death from the date...... of cancer diagnosis until 2003 identified 382 deaths. Mental vulnerability scores were divided into 4 approximately equal-sized groups. Cox proportional hazards regression models were used to estimate the hazard ratio (HR) of all-cause mortality. RESULTS: Multivariate HR for all-cause mortality for persons...

  20. COX-2 correlates with F-box protein, Skp2 expression and prognosis in human gastric carcinoma.

    Science.gov (United States)

    Honjo, Soichiro; Kase, Satoru; Osaki, Mitsuhiko; Ardyanto, Tonang Dwi; Kaibara, Nobuaki; Ito, Hisao

    2005-02-01

    The expression of cyclooxygenase (COX)-2 is induced by growth factors, tumor promoters and cytokines, and is correlated with carcinogenesis, tumor progression and inhibition of apoptosis. To clarify the pathological significance of COX-2, we examined the effect of a selective COX-2 inhibitor, NS398, on two human gastric carcinoma cell lines, MKN-45 and KATO-III, and the expression of Skp2, P27/Kip1 and COX-2 protein in human gastric carcinomas. NS398 inhibited cell growth in a time- and dose-dependent manner and exerted cell cycle arrest in the G0/G1 phase without induction of apoptosis in MKN-45, but had no effect in KATO-III. In MKN-45, NS398 induced up-regulation of P27/Kip1 and down-regulation of COX-2, cyclin D1 and Skp2. Immunohistochemistry using 63 surgically resected gastric carcinomas disclosed that COX-2 expression was correlated with Skp2 expression and that P27/Kip1 expression was inversely correlated with COX-2 and Skp2 expression. High levels of COX-2 or Skp2 were significantly correlated with poor survival (P=0.02 and P=0.004). Our results suggested that: a) NS398 induced inhibition of cell proliferation through cell cycle arrest and suppressed the expression of Skp2 in COX-2-expressing gastric carcinoma cells, and b) COX-2 contributes to the expression of Skp2 and poor survival in human gastric carcinomas.

  1. [A SAS marco program for batch processing of univariate Cox regression analysis for great database].

    Science.gov (United States)

    Yang, Rendong; Xiong, Jie; Peng, Yangqin; Peng, Xiaoning; Zeng, Xiaomin

    2015-02-01

    To realize batch processing of univariate Cox regression analysis for great database by SAS marco program. We wrote a SAS macro program, which can filter, integrate, and export P values to Excel by SAS9.2. The program was used for screening survival correlated RNA molecules of ovarian cancer. A SAS marco program could finish the batch processing of univariate Cox regression analysis, the selection and export of the results. The SAS macro program has potential applications in reducing the workload of statistical analysis and providing a basis for batch processing of univariate Cox regression analysis.

  2. Survival in Women with NSCLC

    Science.gov (United States)

    Katcoff, Hannah; Wenzlaff, Angela S.; Schwartz, Ann G.

    2014-01-01

    Introduction Although lung cancer is the leading cause of cancer death in women, few studies have investigated the hormonal influence on survival after a lung cancer diagnosis and results have been inconsistent. We evaluated the role of reproductive and hormonal factors in predicting overall survival in women with non–small-cell lung cancer (NSCLC). Methods Population-based lung cancer cases diagnosed between November 1, 2001 and October 31, 2005 were identified through the Metropolitan Detroit Surveillance, Epidemiology, and End Results Registry. Interview and follow-up data were collected for 485 women. Cox proportional hazard regression models were used to determine hazard ratios (HRs) for death after an NSCLC diagnosis associated with reproductive and hormonal variables. Results Use of hormone therapy (HT) was associated with improved survival (HR, 0.69; 95% confidence interval, 0.54–0.89), adjusting for stage, surgery, radiation, education level, pack-years of smoking, age at diagnosis, race, and a multiplicative interaction between stage and radiation. No other reproductive or hormonal factor was associated with survival after an NSCLC diagnosis. Increased duration of HT use before the lung cancer diagnosis (132 months or longer) was associated with improved survival (HR, 0.54; 95% confidence interval, 0.37–0.78), and this finding remained significant in women taking either estrogen alone or progesterone plus estrogen, never smokers, and smokers. Conclusion These findings suggest that HT use, in particular use of estrogen plus progesterone, and long-term HT use are associated with improved survival of NSCLC. PMID:24496005

  3. 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.

  4. Matérn thinned Cox processes

    DEFF Research Database (Denmark)

    Andersen, Ina Trolle; Hahn, Ute

    2016-01-01

    A class of spatial point process models that combine short range repulsion with medium range clustering is introduced. The model is motivated by patterns of centres of non-overlapping spherical cells in biological tissue which tend to have a clustering behaviour. Such a combination 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 for the intensity...

  5. Estimation and Inference for the Mediation Proportion.

    Science.gov (United States)

    Nevo, Daniel; Liao, Xiaomei; Spiegelman, Donna

    2017-09-20

    In epidemiology, public health and social science, mediation analysis is often undertaken to investigate the extent to which the effect of a risk factor on an outcome of interest is mediated by other covariates. A pivotal quantity of interest in such an analysis is the mediation proportion. A common method for estimating it, termed the "difference method", compares estimates from models with and without the hypothesized mediator. However, rigorous methodology for estimation and statistical inference for this quantity has not previously been available. We formulated the problem for the Cox model and generalized linear models, and utilize a data duplication algorithm together with a generalized estimation equations approach for estimating the mediation proportion and its variance. We further considered the assumption that the same link function hold for the marginal and conditional models, a property which we term "g-linkability". We show that our approach is valid whenever g-linkability holds, exactly or approximately, and present results from an extensive simulation study to explore finite sample properties. The methodology is illustrated by an analysis of pre-menopausal breast cancer incidence in the Nurses' Health Study. User-friendly publicly available software implementing those methods can be downloaded from the last author's website (SAS) or from CRAN (R).

  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. COX-2 in cancer: Gordian knot or Achilles heel?

    Science.gov (United States)

    Stasinopoulos, Ioannis; Shah, Tariq; Penet, Marie-France; Krishnamachary, Balaji; Bhujwalla, Zaver M

    2013-01-01

    The networks of blood and lymphatic vessels and of the extracellular matrix and their cellular and structural components, that are collectively termed the tumor microenvironment, are frequently co-opted and shaped by cancer cells to survive, invade, and form distant metastasis. With an enviable capacity to adapt to continually changing environments, cancer represents the epitome of functional chaos, a stark contrast to the hierarchical and organized differentiation processes that dictate the development and life of biological organisms. The consequences of changing landscapes such as hypoxia and acidic extracellular pH in and around tumors create a cascade of changes in multiple pathways and networks that become apparent only several years later as recurrence and metastasis. These molecular and phenotypic changes, several of which are mediated by COX-2, approach the complexities of a "Gordian Knot." We review evidence from our studies and from literature suggesting that cyclooxygenase-2 (COX-2) biology presents a nodal point in cancer biology and an "Achilles heel" of COX-2-dependent tumors.

  8. Box-Cox transformation for QTL mapping.

    Science.gov (United States)

    Yang, Runqing; Yi, Nengjun; Xu, Shizhong

    2006-01-01

    The maximum likelihood method of QTL mapping assumes that the phenotypic values of a quantitative trait follow a normal distribution. If the assumption is violated, some forms of transformation should be taken to make the assumption approximately true. The Box-Cox transformation is a general transformation method which can be applied to many different types of data. The flexibility of the Box-Cox transformation is due to a variable, called transformation factor, appearing in the Box-Cox formula. We developed a maximum likelihood method that treats the transformation factor as an unknown parameter, which is estimated from the data simultaneously along with the QTL parameters. The method makes an objective choice of data transformation and thus can be applied to QTL analysis for many different types of data. Simulation studies show that (1) Box-Cox transformation can substantially increase the power of QTL detection; (2) Box-Cox transformation can replace some specialized transformation methods that are commonly used in QTL mapping; and (3) applying the Box-Cox transformation to data already normally distributed does not harm the result.

  9. 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...

  10. Determinants of Under-Five Mortality in Rural Empowered Action Group States in India: An Application of Cox Frailty Model

    Directory of Open Access Journals (Sweden)

    Kalaivani Mani, MSc

    2012-11-01

    Full Text Available Objectives:In India there has been a decline in overall under-five mortality, with some states still showing very high mortality rates. It is argued that there is family clustering in mortality among children aged <5 years. We explored the effects of programmable (proximate determinants on under-five mortality by accounting for family-level clustering and adjusting for background variables using Cox frailty model in rural Empowered Action Group states (EAG in India and compared results with standard models.Methods:Analysis included 13,785 live births that occurred five years preceding the National Family Health Survey-3 (2005-06. The Cox frailty model and the traditional Cox proportional hazards models were used.Results:The Cox frailty model showed that mother’s age at birth, place of delivery, sex of the baby, composite variable of birth order and birth interval, baby size at birth, and breastfeeding were significant determinants of under-five mortality, after adjusting for the familial frailty effect. The hazard ratio was 1.41 (95% CI=1.14–1.75 for children born to mothers aged 12-19 years compared to mothers aged 20-30 years, 1.42 (95% CI=1.12–1.79 for small-sized than average-sized babies at birth, and 102 (95% CI=81–128 for non-breastfed than breastfed babies. Children had significantly lower mortality risks in the richest than poorest wealth quintile. The familial frailty effect was 2.86 in the rural EAG states. The hazard ratios for the determinants in all the three models were similar except the death of a previous child variable in the Cox frailty model, which had the highest R2 and lowest log-likelihood.Conclusions and Public Health Implications:While planning for the child survival program in rural EAG states, parental competence which explains the unobserved familial effect needs to be considered along with significant programmable determinants. The frailty models that provide statistically valid estimates of the covariate

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

    Directory of Open Access Journals (Sweden)

    Tomoyuki Bando

    2017-07-01

    Full Text Available 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.

  12. Viscum album-mediated COX-2 inhibition implicates destabilization of COX-2 mRNA.

    Science.gov (United States)

    Saha, Chaitrali; Hegde, Pushpa; Friboulet, Alain; Bayry, Jagadeesh; Kaveri, Srinivas V

    2015-01-01

    Extensive use of Viscum album (VA) preparations in the complementary therapy of cancer and in several other human pathologies has led to an increasing number of cellular and molecular approaches to explore the mechanisms of action of VA. We have recently demonstrated that, VA preparations exert a potent anti-inflammatory effect by selectively down-regulating the COX-2-mediated cytokine-induced secretion of prostaglandin E2 (PGE2), one of the important molecular signatures of inflammatory reactions. In this study, we observed a significant down-regulation of COX-2 protein expression in VA-treated A549 cells however COX-2 mRNA levels were unaltered. Therefore, we hypothesized that VA induces destabilisation of COX-2 mRNA, thereby depleting the available functional COX-2 mRNA for the protein synthesis and for the subsequent secretion of PGE2. To address this question, we analyzed the molecular degradation of COX-2 protein and its corresponding mRNA in A549 cell line. Using cyclohexamide pulse chase experiment, we demonstrate that, COX-2 protein degradation is not affected by the treatment with VA whereas experiments on transcriptional blockade with actinomycin D, revealed a marked reduction in the half life of COX-2 mRNA due to its rapid degradation in the cells treated with VA compared to that in IL-1β-stimulated cells. These results thus demonstrate that VA-mediated inhibition of PGE2 implicates destabilization of COX-2 mRNA.

  13. Viscum album-mediated COX-2 inhibition implicates destabilization of COX-2 mRNA.

    Directory of Open Access Journals (Sweden)

    Chaitrali Saha

    Full Text Available Extensive use of Viscum album (VA preparations in the complementary therapy of cancer and in several other human pathologies has led to an increasing number of cellular and molecular approaches to explore the mechanisms of action of VA. We have recently demonstrated that, VA preparations exert a potent anti-inflammatory effect by selectively down-regulating the COX-2-mediated cytokine-induced secretion of prostaglandin E2 (PGE2, one of the important molecular signatures of inflammatory reactions. In this study, we observed a significant down-regulation of COX-2 protein expression in VA-treated A549 cells however COX-2 mRNA levels were unaltered. Therefore, we hypothesized that VA induces destabilisation of COX-2 mRNA, thereby depleting the available functional COX-2 mRNA for the protein synthesis and for the subsequent secretion of PGE2. To address this question, we analyzed the molecular degradation of COX-2 protein and its corresponding mRNA in A549 cell line. Using cyclohexamide pulse chase experiment, we demonstrate that, COX-2 protein degradation is not affected by the treatment with VA whereas experiments on transcriptional blockade with actinomycin D, revealed a marked reduction in the half life of COX-2 mRNA due to its rapid degradation in the cells treated with VA compared to that in IL-1β-stimulated cells. These results thus demonstrate that VA-mediated inhibition of PGE2 implicates destabilization of COX-2 mRNA.

  14. Vulnerability survival analysis: a novel approach to vulnerability management

    Science.gov (United States)

    Farris, Katheryn A.; Sullivan, John; Cybenko, George

    2017-05-01

    Computer security vulnerabilities span across large, enterprise networks and have to be mitigated by security engineers on a routine basis. Presently, security engineers will assess their "risk posture" through quantifying the number of vulnerabilities with a high Common Vulnerability Severity Score (CVSS). Yet, little to no attention is given to the length of time by which vulnerabilities persist and survive on the network. In this paper, we review a novel approach to quantifying the length of time a vulnerability persists on the network, its time-to-death, and predictors of lower vulnerability survival rates. Our contribution is unique in that we apply the cox proportional hazards regression model to real data from an operational IT environment. This paper provides a mathematical overview of the theory behind survival analysis methods, a description of our vulnerability data, and an interpretation of the results.

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

    Science.gov (United States)

    Huang, Zhengnan; Zhang, Hongjiu; Boss, Jonathan; Goutman, Stephen A; Mukherjee, Bhramar; Dinov, Ivo D; Guan, Yuanfang

    2017-12-01

    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. 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.

  17. Preoperative Nutritional Risk Index to predict postoperative survival time in primary liver cancer patients.

    Science.gov (United States)

    Bo, Yacong; Yao, Mingjie; Zhang, Ling; Bekalo, Wolde; Lu, Weiquan; Lu, Quanjun

    2015-01-01

    We designed this study to determine the predictive value of Nutritional Risk Index (NRI) for postoperative survival time of patients who had undergone hepatectomy for primary liver cancer. The 620 patients who underwent hepatectomy for primary liver cancer (PLC) in the Department of Hepatobiliary Surgery, Cancer Hospital of Henan Province, Zhengzhou, China from December 1, 2008 to December 1, 2012 were followed up. A nutritional risk index (NRI) was used to screen the patients with malnutrition (NRI100) patients had longer postoperative survival time compared with malnourished patients. NRI values>100 was sig-nificantly associated with longer postoperative survival time. Cox proportional hazards model showed that NRI was an independent predictor of postoperative survival time and that NRI varied inversely with the risk of death. The patients with NRI values>100 survived longer than those with NRI values

  18. Matérn thinned Cox processes

    DEFF Research Database (Denmark)

    Andersen, Ina Trolle; Hahn, Ute

    A new class of spatial point process models that combines short range repulsion with medium range clustering is introduced. The model is motivated by patterns of centres of non-overlapping spherical cells in biological tissue which tend to have a clustering behaviour. Such a combination of cluste......A new class of spatial point process models that combines short range repulsion with medium range clustering is introduced. The model is motivated by patterns of centres of non-overlapping spherical cells in biological tissue which tend to have a clustering behaviour. Such a combination...... 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...

  19. 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.

  20. Chronic consequences of acute injuries: worse survival after discharge.

    Science.gov (United States)

    Shafi, Shahid; Renfro, Lindsay A; Barnes, Sunni; Rayan, Nadine; Gentilello, Larry M; Fleming, Neil; Ballard, David

    2012-09-01

    The Trauma Quality Improvement Program uses inhospital mortality to measure quality of care, which assumes patients who survive injury are not likely to suffer higher mortality after discharge. We hypothesized that survival rates in trauma patients who survive to discharge remain stable afterward. Patients treated at an urban Level I trauma center (2006-2008) were linked with the Social Security Administration Death Master File. Survival rates were measured at 30, 90, and 180 days and 1 and 2 years from injury among two groups of trauma patients who survived to discharge: major trauma (Abbreviated Injury Scale score ≥ 3 injuries, n = 2,238) and minor trauma (Abbreviated Injury Scale score ≤ 2 injuries, n = 1,171). Control groups matched to each trauma group by age and sex were simulated from the US general population using annual survival probabilities from census data. Kaplan-Meier and log-rank analyses conditional upon survival to each time point were used to determine changes in risk of mortality after discharge. Cox proportional hazards models with left truncation at the time of discharge were used to determine independent predictors of mortality after discharge. The survival rate in trauma patients with major injuries was 92% at 30 days posttrauma and declined to 84% by 3 years (p > 0.05 compared with general population). Minor trauma patients experienced a survival rate similar to the general population. Age and injury severity were the only independent predictors of long-term mortality given survival to discharge. Log-rank tests conditional on survival to each time point showed that mortality risk in patients with major injuries remained significantly higher than the general population for up to 6 months after injury. The survival rate of trauma patients with major injuries remains significantly lower than survival for minor trauma patients and the general population for several months postdischarge. Surveillance for early identification and treatment of

  1. 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.

  2. 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

  3. Cox regression with missing covariate data using a modified partial likelihood method

    DEFF Research Database (Denmark)

    Martinussen, Torben; Holst, Klaus K.; Scheike, Thomas H.

    2016-01-01

    Missing covariate values is a common problem in survival analysis. In this paper we propose a novel method for the Cox regression model that is close to maximum likelihood but avoids the use of the EM-algorithm. It exploits that the observed hazard function is multiplicative in the baseline hazard...

  4. Development of multiwire proportional chambers

    CERN Multimedia

    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.

  5. "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 ...

  6. Gray’s Time-Varying Coefficients Model for Posttransplant Survival of Pediatric Liver Transplant Recipients with a Diagnosis of Cancer

    Directory of Open Access Journals (Sweden)

    Yi Ren

    2013-01-01

    Full Text Available Transplantation is often the only viable treatment for pediatric patients with end-stage liver disease. Making well-informed decisions on when to proceed with transplantation requires accurate predictors of transplant survival. The standard Cox proportional hazards (PH model assumes that covariate effects are time-invariant on right-censored failure time; however, this assumption may not always hold. Gray’s piecewise constant time-varying coefficients (PC-TVC model offers greater flexibility to capture the temporal changes of covariate effects without losing the mathematical simplicity of Cox PH model. In the present work, we examined the Cox PH and Gray PC-TVC models on the posttransplant survival analysis of 288 pediatric liver transplant patients diagnosed with cancer. We obtained potential predictors through univariable (P<0.15 and multivariable models with forward selection (P<0.05 for the Cox PH and Gray PC-TVC models, which coincide. While the Cox PH model provided reasonable average results in estimating covariate effects on posttransplant survival, the Gray model using piecewise constant penalized splines showed more details of how those effects change over time.

  7. Constant Proportion Debt Obligations (CPDOs)

    DEFF Research Database (Denmark)

    Cont, Rama; Jessen, Cathrine

    2012-01-01

    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...

  8. 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.

  9. Survival after dementia diagnosis in five racial/ethnic groups.

    Science.gov (United States)

    Mayeda, Elizabeth R; Glymour, M Maria; Quesenberry, Charles P; Johnson, Julene K; Pérez-Stable, Eliseo J; Whitmer, Rachel A

    2017-07-01

    Information on anticipated survival time after dementia diagnosis among racially/ethnically diverse patients is needed to plan for care and evaluate disparities. Dementia-free health care members aged ≥64 years were followed (1/1/2000-12/31/2013) for dementia diagnosis and subsequent survival (n = 23,032 Asian American; n = 18,778 African American; n = 21,000 Latino; n = 4543 American Indian/Alaska Native; n = 206,490 white). Kaplan-Meier curves were estimated for survival after dementia diagnosis by race/ethnicity. We contrasted mortality patterns among people with versus without dementia using Cox proportional hazards models. After dementia diagnosis (n = 59,494), whites had shortest median survival (3.1 years), followed by American Indian/Alaska Natives (3.4 years), African Americans (3.7 years), Latinos (4.1 years), and Asian Americans (4.4 years). Longer postdiagnosis survival among racial/ethnic minorities compared with whites persisted after adjustment for comorbidities. Racial/ethnic mortality inequalities among dementia patients mostly paralleled mortality inequalities among people without dementia. Survival after dementia diagnosis differs by race/ethnicity, with shortest survival among whites and longest among Asian Americans. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  10. Social and ecological factors influencing offspring survival in wild macaques.

    Science.gov (United States)

    Kerhoas, Daphne; Perwitasari-Farajallah, Dyah; Agil, Muhammad; Widdig, Anja; Engelhardt, Antje

    2014-09-01

    Premature loss of offspring decreases direct fitness of parents. In gregarious mammals, both ecological and social variables impact offspring survival and may interact with each other in this regard. Although a number of studies have investigated factors influencing offspring loss in mammals, we still know very little on how different factors interact with one another. We therefore investigated fetal and infant mortality in 3 large groups of wild crested macaques (Macaca nigra) over a period of up to 5 years by including potential social causes such as maternal dominance rank, male immigration, between group encounters, and ecological conditions such as rainfall in a multivariate survival analysis using Cox proportional hazards model. Infant but not fetal survival was most impaired after a recent takeover of the alpha-male position by an immigrant male. Furthermore, infant survival probability increased when there was an increase in number of group adult females and rainfall. Fetal survival probability also increased with an increase of these 2 factors, but more in high-ranking than low-ranking females. Fetal survival, unlike that of infants, was also improved by an increase of intergroup encounter rates. Our study thus stresses the importance of survival analyses using a multivariate approach and encompassing more than a single offspring stage to investigate the determinants of female direct fitness. We further provide evidence for fitness costs and benefits of group living, possibly deriving from high pressures of both within- and between-group competition, in a wild primate population.

  11. Quantitative assessment of the association of COX-2 (Cyclooxygenase-2 immunoexpression with prognosis in human osteosarcoma: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Zhe Wang

    Full Text Available BACKGROUND: Numerous studies examining the relationship between Cyclooxygenase-2 (COX-2 immunoexpression and clinical outcome in osteosarcoma patients have yielded inconclusive results. METHODS: We accordingly conducted a meta-analysis of 9 studies (442 patients that evaluated the correlation between COX-2 immunoexpression and clinical prognosis (death. Pooled odds ratios (OR and risk ratios (RR with 95% confidence intervals (95% CI were calculated using the random-effects or fixed-effects model. RESULTS: Meta-analysis showed no significant association between COX-2 positivity and age, gender, tumor location, histology, stage, metastasis or 90% necrosis. Conversely, COX-2 immunoexpression was associated with overall survival rate (RR=2.12; 95% CI: 1.10-3.74; P=0.009 and disease-free survival rate (RR=1.63; 95% CI: 1.17-2.28; P=0.004 at 2 years. Sensitivity analysis performed by omitting low quality studies showed that the pooled results were stable. CONCLUSIONS: COX-2 positivity was associated with a lower 2-year overall survival rate and disease-free survival rate. COX-2 expression change is an independent prognostic factor in patients with osteosarcoma.

  12. ORACLE INEQUALITIES FOR THE LASSO IN THE COX MODEL.

    Science.gov (United States)

    Huang, Jian; Sun, Tingni; Ying, Zhiliang; Yu, Yi; Zhang, Cun-Hui

    2013-06-01

    We study the absolute penalized maximum partial likelihood estimator in sparse, high-dimensional Cox proportional hazards regression models where the number of time-dependent covariates can be larger than the sample size. We establish oracle inequalities based on natural extensions of the compatibility and cone invertibility factors of the Hessian matrix at the true regression coefficients. Similar results based on an extension of the restricted eigenvalue can be also proved by our method. However, the presented oracle inequalities are sharper since the compatibility and cone invertibility factors are always greater than the corresponding restricted eigenvalue. In the Cox regression model, the Hessian matrix is based on time-dependent covariates in censored risk sets, so that the compatibility and cone invertibility factors, and the restricted eigenvalue as well, are random variables even when they are evaluated for the Hessian at the true regression coefficients. Under mild conditions, we prove that these quantities are bounded from below by positive constants for time-dependent covariates, including cases where the number of covariates is of greater order than the sample size. Consequently, the compatibility and cone invertibility factors can be treated as positive constants in our oracle inequalities.

  13. Stromal compartment as a survival prognostic factor in advanced ovarian carcinoma.

    Science.gov (United States)

    Labiche, Alexandre; Heutte, Natacha; Herlin, Paulette; Chasle, Jacques; Gauduchon, Pascal; Elie, Nicolas

    2010-01-01

    We investigated the prognostic significance of stromal compartment on the overall survival of patients with advanced epithelial ovarian cancer. We evaluated retrospectively the stroma proportion of the tumor surgical specimens of 194 patients with stages III and IV disease, using histochemical staining and fully automatic virtual slide processing. The prognostic significance of stroma proportion and clinical parameters were evaluated using log-rank test and Cox regression. Stroma proportion was found to be an independent prognostic factor by both univariate (P = 0.016) and multivariate analyses (hazards ratio = 1.45, P = 0.011). The present data indicate that a high stroma proportion is related to a poor prognosis of stage III and IV ovarian carcinomas.

  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. 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.

  16. Disease proportions attributable to environment.

    Science.gov (United States)

    Saracci, Rodolfo; Vineis, Paolo

    2007-11-28

    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.

  17. 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.

  18. 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...

  19. 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.

  20. Risk Prediction of One-Year Mortality in Patients with Cardiac Arrhythmias Using Random Survival Forest.

    Science.gov (United States)

    Miao, Fen; Cai, Yun-Peng; Zhang, Yu-Xiao; Li, Ye; Zhang, Yuan-Ting

    2015-01-01

    Existing models for predicting mortality based on traditional Cox proportional hazard approach (CPH) often have low prediction accuracy. This paper aims to develop a clinical risk model with good accuracy for predicting 1-year mortality in cardiac arrhythmias patients using random survival forest (RSF), a robust approach for survival analysis. 10,488 cardiac arrhythmias patients available in the public MIMIC II clinical database were investigated, with 3,452 deaths occurring within 1-year followups. Forty risk factors including demographics and clinical and laboratory information and antiarrhythmic agents were analyzed as potential predictors of all-cause mortality. RSF was adopted to build a comprehensive survival model and a simplified risk model composed of 14 top risk factors. The built comprehensive model achieved a prediction accuracy of 0.81 measured by c-statistic with 10-fold cross validation. The simplified risk model also achieved a good accuracy of 0.799. Both results outperformed traditional CPH (which achieved a c-statistic of 0.733 for the comprehensive model and 0.718 for the simplified model). Moreover, various factors are observed to have nonlinear impact on cardiac arrhythmias prognosis. As a result, RSF based model which took nonlinearity into account significantly outperformed traditional Cox proportional hazard model and has great potential to be a more effective approach for survival analysis.

  1. Survival after dialysis discontinuation and hospice enrollment for ESRD.

    Science.gov (United States)

    O'Connor, Nina R; Dougherty, Meredith; Harris, Pamela S; Casarett, David J

    2013-12-01

    Textbooks report that patients with ESRD survive for 7-10 days after discontinuation of dialysis. Studies describing actual survival are limited, however, and research has not defined patient characteristics that may be associated with longer or shorter survival times. The goals of this study were to determine the mean life expectancy of patients admitted to hospice after discontinuation of dialysis, and to identify independent predictors of survival time. Data for demographics, clinical characteristics, and survival were obtained from 10 hospices for patients with ESRD who discontinued dialysis before hospice admission. Data were collected for patients admitted between January 1, 2008 and May 15, 2012. All hospices were members of the Coalition of Hospices Organized to Investigate Comparative Effectiveness network, which obtains de-identified data from an electronic medical record. Of 1947 patients who discontinued dialysis, the mean survival after hospice enrollment was 7.4 days (range, 0-40 days). Patients who discontinued dialysis had significantly shorter survival compared with other patients (n=124,673) with nonrenal hospice diagnoses (mean survival 54.4 days; hazard ratio, 2.96; 95% confidence interval, 2.82 to 3.09; P<0.001). A Cox proportional hazards model identified seven independent predictors of earlier mortality after dialysis discontinuation, including male sex, referral from a hospital, lower functional status (Palliative Performance Scale score), and the presence of peripheral edema. Patients who discontinue dialysis have significantly shorter survival than other hospice patients. Individual survival time varies greatly, but several variables can be used to predict survival and tailor a patient's care plan based on estimated prognosis.

  2. Alcohol consumption and non-Hodgkin lymphoma survival.

    Science.gov (United States)

    Han, Xuesong; Zheng, Tongzhang; Foss, Francine M; Ma, Shuangge; Holford, Theodore R; Boyle, Peter; Leaderer, Brian; Zhao, Ping; Dai, Min; Zhang, Yawei

    2010-06-01

    Epidemiological studies have shown that moderate alcohol drinkers have a lower death rate for all causes. Alcohol drinking has also been associated with reduced risk of non-Hodgkin lymphoma (NHL). Here, we examined the role of alcohol consumption on NHL survival by type of alcohol consumed and NHL subtype. A cohort of 575 female NHL incident cases diagnosed during 1996-2000 in Connecticut was followed-up for a median of 7.75 years. Demographic, clinical, and lifestyle information was collected at diagnosis. Survival analyses were conducted with Kaplan-Meier methods, and hazard ratios (HR) were estimated from Cox Proportional Hazards models. Compared to never drinkers, wine drinkers experienced better overall survival (75% vs. 69% five-year survival rates, p-value for log-rank test = 0.030) and better disease free survival (70% vs. 67% five-year disease-free survival rates, p-value for log-rank test = 0.049). Analysis by NHL subtype shows that the favorable effect of wine consumption was mainly seen for patients diagnosed with diffuse large B-cell lymphoma (DLBCL) (wine drinkers for more than 25 years vs. never drinkers: HR = 0.36, 95% CI 0.14-0.94 for overall survival; HR = 0.38, 95% CI 0.16-0.94 for disease-free survival), and the adverse effect of liquor consumption was also observed among DLBCL patients (liquor drinkers vs. never drinkers: HR=2.49, 95% CI 1.26-4.93 for disease-free survival). Our results suggest a moderate relationship between pre-diagnostic alcohol consumption and NHL survival, particularly for DLBCL. The results need to be replicated in larger studies. Pre-diagnostic behaviors might impact the prognosis and survival of NHL patients.

  3. CNS involvement and treatment with interferon-α are independent prognostic factors in Erdheim-Chester disease: a multicenter survival analysis of 53 patients.

    Science.gov (United States)

    Arnaud, Laurent; Hervier, Baptiste; Néel, Antoine; Hamidou, Mohamed A; Kahn, Jean-Emmanuel; Wechsler, Bertrand; Pérez-Pastor, Gemma; Blomberg, Bjørn; Fuzibet, Jean-Gabriel; Dubourguet, François; Marinho, António; Magnette, Catherine; Noel, Violaine; Pavic, Michel; Casper, Jochen; Beucher, Anne-Bérangère; Costedoat-Chalumeau, Nathalie; Aaron, Laurent; Salvatierra, Juan; Graux, Carlos; Cacoub, Patrice; Delcey, Véronique; Dechant, Claudia; Bindi, Pascal; Herbaut, Christiane; Graziani, Giorgio; Amoura, Zahir; Haroche, Julien

    2011-03-10

    Erdheim-Chester disease (ECD) is a rare form of non-Langerhans histiocytosis, with noncodified therapeutic management and high mortality. No treatment has yet been shown to improve survival in these patients. We conducted a multicenter prospective observational cohort study to assess whether extraskeletal manifestations and interferon-α treatment would influence survival in a large cohort of ECD patients. To achieve this goal, we thoroughly analyzed the clinical presentation of 53 patients with biopsy-proven ECD, and we performed a survival analysis using Cox proportional hazard model. Fifty-three patients (39 men and 14 women) with biopsy-proven ECD were followed up between November 1981 and November 2010. Forty-six patients (87%) received interferon-α and/or PEGylated interferon-α. Multivariate survival analysis using Cox proportional hazard model revealed that central nervous system involvement was an independent predictor of death (hazard ratio = 2.51; 95% confidence interval, 1.28-5.52; P = .006) in our cohort. Conversely, treatment with interferon-α was identified as an independent predictor of survival (hazard ratio = 0.32; 95% confidence interval, 0.14-0.70; P = .006). Although definitive confirmation would require a randomized controlled trial, these results suggest that interferon-α improves survival in ECD patients. This may be seen as a significant advance, as it is the first time a treatment is shown to improve survival in this multisystemic disease with high mortality.

  4. 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.

  5. History of thyroid disease and survival of ovarian cancer patients

    DEFF Research Database (Denmark)

    Minlikeeva, Albina N; Freudenheim, Jo L; Cannioto, Rikki A

    2017-01-01

    multivariate Cox proportional hazards models, we estimated associations between hyper- and hypothyroidism and medications prescribed for these conditions with 5-year all-cause survival among women diagnosed with invasive ovarian cancer. RESULTS: Overall, there was a nonsignificant association with history...... of hyperthyroidism (n=160 cases) and mortality (HR=1.22; 95% CI=0.97-1.53). Furthermore, diagnosis of hyperthyroidism within the 5 years before ovarian cancer diagnosis was associated with an increased risk of death (HR=1.94; 95% CI=1.19-3.18). A more modest association was observed with history of hypothyroidism (n......=624 cases) and mortality (HR=1.16; 95% CI=1.03-1.31). Neither duration of hypothyroidism nor use of thyroid medications was associated with survival. CONCLUSIONS: In this large study of women with ovarian cancer, we found that recent history of hyperthyroidism and overall history of hypothyroidism...

  6. COX-2 Induces Breast Cancer Stem Cells via EP4/PI3K/AKT/NOTCH/WNT Axis.

    Science.gov (United States)

    Majumder, Mousumi; Xin, Xiping; Liu, Ling; Tutunea-Fatan, Elena; Rodriguez-Torres, Mauricio; Vincent, Krista; Postovit, Lynne-Marie; Hess, David; Lala, Peeyush K

    2016-09-01

    Cancer stem-like cells (SLC) resist conventional therapies, necessitating searches for SLC-specific targets. We established that cyclo-oxygenase(COX)-2 expression promotes human breast cancer progression by activation of the prostaglandin(PG)E-2 receptor EP4. Present study revealed that COX-2 induces SLCs by EP4-mediated NOTCH/WNT signaling. Ectopic COX-2 over-expression in MCF-7 and SKBR-3 cell lines resulted in: increased migration/invasion/proliferation, epithelial-mesenchymal transition (EMT), elevated SLCs (spheroid formation), increased ALDH activity and colocalization of COX-2 and SLC markers (ALDH1A, CD44, β-Catenin, NANOG, OCT3/4, SOX-2) in spheroids. These changes were reversed with COX-2-inhibitor or EP4-antagonist (EP4A), indicating dependence on COX-2/EP4 activities. COX-2 over-expression or EP4-agonist treatments of COX-2-low cells caused up-regulation of NOTCH/WNT genes, blocked with PI3K/AKT inhibitors. NOTCH/WNT inhibitors also blocked COX-2/EP4 induced SLC induction. Microarray analysis showed up-regulation of numerous SLC-regulatory and EMT-associated genes. MCF-7-COX-2 cells showed increased mammary tumorigenicity and spontaneous multiorgan metastases in NOD/SCID/IL-2Rγ-null mice for successive generations with limiting cell inocula. These tumors showed up-regulation of VEGF-A/C/D, Vimentin and phospho-AKT, down-regulation of E-Cadherin and enrichment of SLC marker positive and spheroid forming cells. MCF-7-COX-2 cells also showed increased lung colonization in NOD/SCID/GUSB-null mice, an effect reversed with EP4-knockdown or EP4A treatment of the MCF-7-COX-2 cells. COX-2/EP4/ALDH1A mRNA expression in human breast cancer tissues were highly correlated with one other, more marked in progressive stage of disease. In situ immunostaining of human breast tumor tissues revealed co-localization of SLC markers with COX-2, supporting COX-2 inducing SLCs. High COX-2/EP4 mRNA expression was linked with reduced survival. Thus, EP4 represents a novel SLC

  7. Alcohol recidivism impairs long-term patient survival after orthotopic liver transplantation for alcoholic liver disease.

    Science.gov (United States)

    Cuadrado, Antonio; Fábrega, Emilio; Casafont, Fernando; Pons-Romero, Fernando

    2005-04-01

    The aim of this study was to evaluate the rate of alcohol recidivism after orthotopic liver transplantation (OLT) for alcoholic liver disease (ALD) and its influence on the allograft and patient survival, as well as the development of comorbidities and de novo cancers. The study was performed on 54 subjects previously analyzed and transplanted in our center for ALD, whose follow-up was prolonged to a mean of 99.2 (SD 31.7) months (range, 14-155). Medical records were reviewed, and data on alcohol consumption, therapeutic compliance, graft evolution, rejection, infections, comorbidities, rates of de novo malignancies and other clinical events, and survival were collected. Comparisons between groups were performed by the Fisher's exact test, and survival was assessed by the Kaplan-Meier method. Survival curves were compared using the Mantel-Cox statistic. The risk of death resulting from alcohol recidivism was analyzed with a Cox proportional hazards model. Fourteen patients who underwent transplantation for ALD (25.9%) returned to alcohol use between 5.0 and 86.9 months after OLT (median, 47.5). There was no significant association between the presence or absence of alcohol recidivism and the occurrence of graft rejection, infections, associated comorbidities after OLT, or compliance. The 5- and 10-year survival rates for patients with alcohol recidivism were 92.9% and 45.1%, respectively, compared with 92.4% and 85.5%, respectively, for patients without alcohol recidivism. These figures show significantly lower survival rates in recidivistic patients after 10 years (P < 0.01, Mantel-Cox). The fact that patients who resumed alcohol consumption have a worse 10-year survival rate might be attributed to a higher frequency of deaths, primarily from cancer and cardiovascular events.

  8. Reporting and methodological quality of survival analysis in articles published in Chinese oncology journals.

    Science.gov (United States)

    Zhu, Xiaoyan; Zhou, Xiaobin; Zhang, Yuan; Sun, Xiao; Liu, Haihua; Zhang, Yingying

    2017-12-01

    Survival analysis methods have gained widespread use in the filed of oncology. For achievement of reliable results, the methodological process and report quality is crucial. This review provides the first examination of methodological characteristics and reporting quality of survival analysis in articles published in leading Chinese oncology journals.To examine methodological and reporting quality of survival analysis, to identify some common deficiencies, to desirable precautions in the analysis, and relate advice for authors, readers, and editors.A total of 242 survival analysis articles were included to be evaluated from 1492 articles published in 4 leading Chinese oncology journals in 2013. Articles were evaluated according to 16 established items for proper use and reporting of survival analysis.The application rates of Kaplan-Meier, life table, log-rank test, Breslow test, and Cox proportional hazards model (Cox model) were 91.74%, 3.72%, 78.51%, 0.41%, and 46.28%, respectively, no article used the parametric method for survival analysis. Multivariate Cox model was conducted in 112 articles (46.28%). Follow-up rates were mentioned in 155 articles (64.05%), of which 4 articles were under 80% and the lowest was 75.25%, 55 articles were100%. The report rates of all types of survival endpoint were lower than 10%. Eleven of 100 articles which reported a loss to follow-up had stated how to treat it in the analysis. One hundred thirty articles (53.72%) did not perform multivariate analysis. One hundred thirty-nine articles (57.44%) did not define the survival time. Violations and omissions of methodological guidelines included no mention of pertinent checks for proportional hazard assumption; no report of testing for interactions and collinearity between independent variables; no report of calculation method of sample size. Thirty-six articles (32.74%) reported the methods of independent variable selection. The above defects could make potentially inaccurate

  9. Sex Disparity in Survival of Patients With Uveal Melanoma: Better Survival Rates in Women Than in Men in South Korea.

    Science.gov (United States)

    Park, San Jun; Oh, Chang-Mo; Yeon, Bora; Cho, Hyunsoon; Park, Kyu Hyung

    2017-03-01

    The purpose of this study was to determine the survival rate of patients with uveal melanoma and sex disparity in this rate in South Korea. We extracted incident uveal melanoma patients using the Korea Central Cancer Registry (KCCR) database, which covered the entire population from 1999 to 2012 in South Korea. We estimated all-cause survival probabilities and cancer-specific survival probabilities of patients with uveal melanoma and compared these probabilities between subgroups (sex, tumor site, age at diagnosis, etc.) using Kaplan-Meier methods and log-rank tests. We fitted the Cox-proportional hazards models for all-cause death and cancer death to determine sex disparities in survival. A total of 344 uveal melanoma patients (175 women, 51%) were ascertained. They comprised 283 patients with choroidal melanoma (82%) and 61 patients with ciliary body/iris melanoma (18%). The observed 5-year survival probability from all-cause death was 75% (95% confidence interval [CI]: 69%-79%); women with uveal melanoma showed higher survival probability (83% [95% CI: 76%-89%]) compared with men (66% [95% CI: 58%-73%], P Korea, which requires further investigation of mechanism of the sex disparity in uveal melanoma.

  10. COX-2 Elevates Oncogenic miR-526b in Breast Cancer by EP4 Activation.

    Science.gov (United States)

    Majumder, Mousumi; Landman, Erin; Liu, Ling; Hess, David; Lala, Peeyush K

    2015-06-01

    MicroRNAs (miRs) are small regulatory molecules emerging as potential biomarkers in cancer. Previously, it was shown that COX-2 expression promotes breast cancer progression via multiple mechanisms, including induction of stem-like cells (SLC), owing to activation of the prostaglandin E2 receptor EP4 (PTGER4). COX-2 overexpression also upregulated microRNA-526b (miR-526b), in association with aggressive phenotype. Here, the functional roles of miR-526b in breast cancer and the mechanistic role of EP4 signaling in miR-526b upregulation were examined. A positive correlation was noted between miR-526b and COX-2 mRNA expression in COX-2 disparate breast cancer cell lines. Stable overexpression of miR-526b in poorly metastatic MCF7 and SKBR3 cell lines resulted in increased cellular migration, invasion, EMT phenotype and enhanced tumorsphere formation in vitro, and lung colony formation in vivo in immunodeficient mice. Conversely, knockdown of miR-526b in aggressive MCF7-COX-2 and SKBR3-COX-2 cells reduced oncogenic functions and reversed the EMT phenotype, in vitro. Furthermore, it was determined that miR-526b expression is dependent on EP4 receptor activity and downstream PI3K-AKT and cyclic AMP (cAMP) signaling pathways. PI3K-AKT inhibitors blocked EP4 agonist-mediated miR-526b upregulation and tumorsphere formation in MCF7 and SKBR3 cells. NF-κB inhibitor abrogates EP agonist-stimulated miRNA expression in MCF7 and T47D cells, indicating that the NF-κB pathway is also involved in miR-526b regulation. In addition, inhibition of COX-2, EP4, PI3K, and PKA in COX-2-overexpressing cells downregulated miR-526b and its functions in vitro. Finally, miR-526b expression was significantly higher in cancerous than in noncancerous breast tissues and associated with reduced patient survival. In conclusion, miR-526b promotes breast cancer progression, SLC-phenotype through EP4-mediated signaling, and correlates with breast cancer patient survival. This study presents novel

  11. On intensities of modulated Cox measures

    Directory of Open Access Journals (Sweden)

    Jewgeni H. Dshalalow

    1998-01-01

    Full Text Available In this paper we introduce and study functionals of the intensities of random measures modulated by a stochastic process ξ, which occur in applications to stochastic models and telecommunications. Modulation of a random measure by ξ is specified for marked Cox measures. Particular cases of modulation by ξ as semi-Markov and semiregenerative processes enabled us to obtain explicit formulas for the named intensities. Examples in queueing (systems with state dependent parameters, Little's and Campbell's formulas demonstrate the use of the results.

  12. 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.

  13. Estimating multiple time-fixed treatment effects using a semi-Bayes semiparametric marginal structural Cox proportional hazards regression model.

    Science.gov (United States)

    Cole, Stephen R; Edwards, Jessie K; Westreich, Daniel; Lesko, Catherine R; Lau, Bryan; Mugavero, Michael J; Mathews, W Christopher; Eron, Joseph J; Greenland, Sander

    2017-10-27

    Marginal structural models for time-fixed treatments fit using inverse-probability weighted estimating equations are increasingly popular. Nonetheless, the resulting effect estimates are subject to finite-sample bias when data are sparse, as is typical for large-sample procedures. Here we propose a semi-Bayes estimation approach which penalizes or shrinks the estimated model parameters to improve finite-sample performance. This approach uses simple symmetric data-augmentation priors. Limited simulation experiments indicate that the proposed approach reduces finite-sample bias and improves confidence-interval coverage when the true values lie within the central "hill" of the prior distribution. We illustrate the approach with data from a nonexperimental study of HIV treatments. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Box-Cox symmetric distributions and applications to nutritional data

    OpenAIRE

    Ferrari, Silvia L. P.; Fumes, Giovana

    2016-01-01

    We introduce the Box-Cox symmetric class of distributions, which is useful for modeling positively skewed, possibly heavy-tailed, data. The new class of distributions includes the Box-Cox t, Box-Cox Cole-Gree, Box-Cox power exponential distributions, and the class of the log-symmetric distributions as special cases. It provides easy parameter interpretation, which makes it convenient for regression modeling purposes. Additionally, it provides enough flexibility to handle outliers. The usefuln...

  15. Survival Comparison of Patients With Cystic Fibrosis in Canada and the United States: A Population-Based Cohort Study.

    Science.gov (United States)

    Stephenson, Anne L; Sykes, Jenna; Stanojevic, Sanja; Quon, Bradley S; Marshall, Bruce C; Petren, Kristofer; Ostrenga, Josh; Fink, Aliza K; Elbert, Alexander; Goss, Christopher H

    2017-04-18

    In 2011, the median age of survival of patients with cystic fibrosis reported in the United States was 36.8 years, compared with 48.5 years in Canada. Direct comparison of survival estimates between national registries is challenging because of inherent differences in methodologies used, data processing techniques, and ascertainment bias. To use a standardized approach to calculate cystic fibrosis survival estimates and to explore differences between Canada and the United States. Population-based study. 42 Canadian cystic fibrosis clinics and 110 U.S. cystic fibrosis care centers. Patients followed in the Canadian Cystic Fibrosis Registry (CCFR) and U.S. Cystic Fibrosis Foundation Patient Registry (CFFPR) between 1990 and 2013. Cox proportional hazards models were used to compare survival between patients followed in the CCFR (n = 5941) and those in the CFFPR (n = 45 448). Multivariable models were used to adjust for factors known to be associated with survival. Median age of survival in patients with cystic fibrosis increased in both countries between 1990 and 2013; however, in 1995 and 2005, survival in Canada increased at a faster rate than in the United States (P cystic fibrosis survival between Canada and the United States persisted after adjustment for risk factors associated with survival, except for private-insurance status among U.S. patients. Differential access to transplantation, increased posttransplant survival, and differences in health care systems may, in part, explain the Canadian survival advantage. U.S. Cystic Fibrosis Foundation.

  16. Challenging the principle of proportionality.

    Science.gov (United States)

    Andersson, Anna-Karin Margareta

    2016-04-01

    The first objective of this article is to examine one aspect of the principle of proportionality (PP) as advanced by Alan Gewirth in his 1978 bookReason and Morality Gewirth claims that being capable of exercising agency to some minimal degree is a property that justifies having at least prima facie rights not to get killed. However, according to the PP, before the being possesses the capacity for exercising agency to that minimal degree, the extent of her rights depends on to what extent she approaches possession of agential capacities. One interpretation of PP holds that variations in degree of possession of the physical constitution necessary to exercise agency are morally relevant. The other interpretation holds that only variations in degree of actual mental capacity are morally relevant. The first of these interpretations is vastly more problematic than the other. The second objective is to argue that according to the most plausible interpretation of the PP, the fetus' level of development before at least the 20th week of pregnancy does not affect the fetus' moral rights status. I then suggest that my argument is not restricted to such fetuses, although extending my argument to more developed fetuses requires caution. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  17. Finding Risk Groups by Optimizing Artificial Neural Networks on the Area under the Survival Curve Using Genetic Algorithms.

    Directory of Open Access Journals (Sweden)

    Jonas Kalderstam

    Full Text Available We investigate a new method to place patients into risk groups in censored survival data. Properties such as median survival time, and end survival rate, are implicitly improved by optimizing the area under the survival curve. Artificial neural networks (ANN are trained to either maximize or minimize this area using a genetic algorithm, and combined into an ensemble to predict one of low, intermediate, or high risk groups. Estimated patient risk can influence treatment choices, and is important for study stratification. A common approach is to sort the patients according to a prognostic index and then group them along the quartile limits. The Cox proportional hazards model (Cox is one example of this approach. Another method of doing risk grouping is recursive partitioning (Rpart, which constructs a decision tree where each branch point maximizes the statistical separation between the groups. ANN, Cox, and Rpart are compared on five publicly available data sets with varying properties. Cross-validation, as well as separate test sets, are used to validate the models. Results on the test sets show comparable performance, except for the smallest data set where Rpart's predicted risk groups turn out to be inverted, an example of crossing survival curves. Cross-validation shows that all three models exhibit crossing of some survival curves on this small data set but that the ANN model manages the best separation of groups in terms of median survival time before such crossings. The conclusion is that optimizing the area under the survival curve is a viable approach to identify risk groups. Training ANNs to optimize this area combines two key strengths from both prognostic indices and Rpart. First, a desired minimum group size can be specified, as for a prognostic index. Second, the ability to utilize non-linear effects among the covariates, which Rpart is also able to do.

  18. Finding Risk Groups by Optimizing Artificial Neural Networks on the Area under the Survival Curve Using Genetic Algorithms.

    Science.gov (United States)

    Kalderstam, Jonas; Edén, Patrik; Ohlsson, Mattias

    2015-01-01

    We investigate a new method to place patients into risk groups in censored survival data. Properties such as median survival time, and end survival rate, are implicitly improved by optimizing the area under the survival curve. Artificial neural networks (ANN) are trained to either maximize or minimize this area using a genetic algorithm, and combined into an ensemble to predict one of low, intermediate, or high risk groups. Estimated patient risk can influence treatment choices, and is important for study stratification. A common approach is to sort the patients according to a prognostic index and then group them along the quartile limits. The Cox proportional hazards model (Cox) is one example of this approach. Another method of doing risk grouping is recursive partitioning (Rpart), which constructs a decision tree where each branch point maximizes the statistical separation between the groups. ANN, Cox, and Rpart are compared on five publicly available data sets with varying properties. Cross-validation, as well as separate test sets, are used to validate the models. Results on the test sets show comparable performance, except for the smallest data set where Rpart's predicted risk groups turn out to be inverted, an example of crossing survival curves. Cross-validation shows that all three models exhibit crossing of some survival curves on this small data set but that the ANN model manages the best separation of groups in terms of median survival time before such crossings. The conclusion is that optimizing the area under the survival curve is a viable approach to identify risk groups. Training ANNs to optimize this area combines two key strengths from both prognostic indices and Rpart. First, a desired minimum group size can be specified, as for a prognostic index. Second, the ability to utilize non-linear effects among the covariates, which Rpart is also able to do.

  19. 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.

  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. Assessing the effect of quantitative and qualitative predictors on gastric cancer individuals survival using hierarchical artificial neural network models.

    Science.gov (United States)

    Amiri, Zohreh; Mohammad, Kazem; Mahmoudi, Mahmood; Parsaeian, Mahbubeh; Zeraati, Hojjat

    2013-01-01

    There are numerous unanswered questions in the application of artificial neural network models for analysis of survival data. In most studies, independent variables have been studied as qualitative dichotomous variables, and results of using discrete and continuous quantitative, ordinal, or multinomial categorical predictive variables in these models are not well understood in comparison to conventional models. This study was designed and conducted to examine the application of these models in order to determine the survival of gastric cancer patients, in comparison to the Cox proportional hazards model. We studied the postoperative survival of 330 gastric cancer patients who suffered surgery at a surgical unit of the Iran Cancer Institute over a five-year period. Covariates of age, gender, history of substance abuse, cancer site, type of pathology, presence of metastasis, stage, and number of complementary treatments were entered in the models, and survival probabilities were calculated at 6, 12, 18, 24, 36, 48, and 60 months using the Cox proportional hazards and neural network models. We estimated coefficients of the Cox model and the weights in the neural network (with 3, 5, and 7 nodes in the hidden layer) in the training group, and used them to derive predictions in the study group. Predictions with these two methods were compared with those of the Kaplan-Meier product limit estimator as the gold standard. Comparisons were performed with the Friedman and Kruskal-Wallis tests. Survival probabilities at different times were determined using the Cox proportional hazards and a neural network with three nodes in the hidden layer; the ratios of standard errors with these two methods to the Kaplan-Meier method were 1.1593 and 1.0071, respectively, revealed a significant difference between Cox and Kaplan-Meier (P neural network, and the neural network and the standard (Kaplan-Meier), as well as better accuracy for the neural network (with 3 nodes in the hidden layer

  2. Proportional hazards modeling of saccadic response times during reading.

    Science.gov (United States)

    Nilsson, Mattias; Nivre, Joakim

    2013-07-01

    In this article we use proportional hazards models to examine how low-level processes affect the probability of making a saccade over time, through the period of fixation, during reading. We apply the Cox proportional hazards model to investigate how launch distance (relative to word beginning), fixation location (relative to word center), and word frequency affect the hazard of a saccadic response. This model requires that covariates have a constant impact on the hazard over time, the assumption of proportional hazards. We show that this assumption is not supported. The impact of the covariates changes with the time passed since fixation onset. To account for the non-proportional hazards we fit step functions of time, resulting in a model with time-varying effects on the hazard. We evaluate the ability to predict the timing of saccades on held-out fixation data. The model with time-varying effects performs better in predicting the timing of saccades for fixations as short as 100 ms and as long as 500 ms, when compared both to a baseline model without covariates and a model which assumes constant covariate effects. This result suggests that the time-varying effects model better recovers the time course of low-level processes that influence the decision to move the eyes. Copyright © 2013 Cognitive Science Society, Inc.

  3. Allergies, obesity, other risk factors and survival from pancreatic cancer.

    Science.gov (United States)

    Olson, Sara H; Chou, Joanne F; Ludwig, Emmy; O'Reilly, Eileen; Allen, Peter J; Jarnagin, William R; Bayuga, Sharon; Simon, Jennifer; Gonen, Mithat; Reisacher, William R; Kurtz, Robert C

    2010-11-15

    Survival from pancreatic adenocarcinoma remains extremely poor, approximately 5% at 5 years. Risk factors include smoking, high body mass index (BMI), family history of pancreatic cancer, and long-standing diabetes; in contrast, allergies are associated with reduced risk. Little is known about associations between these factors and survival. We analyzed overall survival in relation to risk factors for 475 incident cases who took part in a hospital based case-control study. Analyses were conducted separately for those who did (160) and did not (315) undergo tumor resection. Kaplan-Meier methods were used to describe survival according to smoking, BMI, family history, diabetes, and presence of allergies. Cox proportional hazards models were used to adjust for covariates. There was no association with survival based on smoking, family history, or history of diabetes in either group. Among patients with resection, those with allergies showed nonstatistically significant longer survival, a median of 33.1 months (95% CI: 19.0-52.5) vs. 21.8 months (95% CI: 18.0-33.1), p = 0.25. The adjusted hazard ratio (HR) was 0.72 (95% CI: 0.43-1.23), p = 0.23. Among patients without resection, those with self-reported allergies survived significantly longer than those without allergies: 13.3 months (95% CI: 10.6-16.9) compared to 10.4 months (95% CI: 8.8-11.0), p = 0.04, with an adjusted HR of 0.68 (95% CI: 0.49-0.95), p = 0.02. Obesity was nonsignificantly associated with poorer survival, particularly in the resected group (HR = 1.62, 95% CI: 0.76-3.44). The mechanisms underlying the association between history of allergies and improved survival are unknown. These novel results need to be confirmed in other studies.

  4. The Breslow estimator of the nonparametric baseline survivor function in Cox's regression model: some heuristics.

    Science.gov (United States)

    Hanley, James A

    2008-01-01

    Most survival analysis textbooks explain how the hazard ratio parameters in Cox's life table regression model are estimated. Fewer explain how the components of the nonparametric baseline survivor function are derived. Those that do often relegate the explanation to an "advanced" section and merely present the components as algebraic or iterative solutions to estimating equations. None comment on the structure of these estimators. This note brings out a heuristic representation that may help to de-mystify the structure.

  5. Treatment with finasteride and prostate cancer survival.

    Science.gov (United States)

    Kjellman, Anders; Friis, Søren; Granath, Fredrik; Gustafsson, Ove; Sørensen, Henrik Toft; Akre, Olof

    2013-08-01

    This study compared survival after diagnosis of prostate cancer (PC) in men previously treated with finasteride, in men previously treated with α-adrenoceptor antagonists, in men treated with both, and in men who had received neither type of medication. In total, 3791 men diagnosed with PC in northern Denmark were identified. The region's prescription database was used to identify all men prescribed finasteride and α-adrenoceptor antagonists and those who had received neither medication during the period 1989-2001. Among men with a diagnosis of PC, overall survival and disease-specific survival were assessed after diagnosis using Cox proportional hazards regression. The risk of being diagnosed with non-localized PC was estimated using conditional logistic regression. The adjusted hazard ratio (HR) for PC death and overall death after treatment with finasteride was 0.93 [95% confidence interval (CI) 0.76-1.14] and 0.92 (95% CI 0.77-1.10), respectively. Treatment with α-adrenoceptor antagonists was associated with a reduced risk of PC death and overall death (HR 0.78, 95% CI 0.67-0.90, and 0.82, 95% CI 0.73-0.93, respectively. The risk of being diagnosed with non-localized PC was increased for men taking finasteride (odds ratio 1.14, 95% CI 1.01-1.29) per 100 defined daily doses. Treatment with finasteride prior to a diagnosis of PC did not affect PC-specific survival, but increased the risk of being diagnosed with non-localized disease. Treatment with α-adrenoceptor antagonists was associated with better cause-specific survival and lower risk of non-localized disease.

  6. COX-2 expression in striated muscle under physiological conditions.

    Science.gov (United States)

    Sudbø, J; Reith, A; Flørenes, V A; Nesland, J M; Ristimäki, A; Bryne, M

    2003-11-01

    The role of cyclooxygenase-2 (COX-2) in disease has been extensively studied, (Annu Rev Med (2002) 53:35; N Engl J Med (2001) 345:433) but less information is available with respect to possible physiological functions of COX-2. Information on how and where COX-2 is expressed under physiological conditions may increase our understanding of its physiological role. Previous studies have revealed a COX-2 dependent production of prostanoids under physiological conditions, without entirely determining the source of this production. To assess COX-2 expression under normal conditions, we analyzed tissue specimens that were removed from 30 healthy study subjects in conjunction with surgical procedure related to insertion of dental implants and from three patients which had muscle tissue from Quadriceps femoris muscle removed as part of surgical treatment of soft tissue sarcomas not directly affecting the muscle tissue. Immunohistochemistry and immunoblotting (Western blotting) was used to assess the presence of COX-2 protein. In 25 of 30 patients (83%), COX-2 protein was expressed in striated muscle, as assessed by immunohistochemistry. All cases had COX-2 expression verified by Western blotting. In none of the 25 subjects with COX-2 expression did we notice concomitant inflammation of the adjacent submucosal tissue. It is a novel finding that COX-2 is expressed in striated muscle under physiological conditions. COX-2 activity in striated muscle is a possible explanation for the hitherto unknown localization of prostanoids synthesis under physiological conditions.

  7. Up-regulation of HB-EGF by the COX-2/PGE2 signaling associates with the cisplatin resistance and tumor recurrence of advanced HNSCC.

    Science.gov (United States)

    Yang, Cheng-Chieh; Tu, Hsi-Feng; Wu, Cheng-Hsien; Chang, Hsiu-Chuan; Chiang, Wei-Fan; Shih, Nai-Chia; Lee, Yong-Syu; Kao, Shou-Yen; Chang, Kuo-Wei

    2016-05-01

    When treating advanced HNSCC, a cisplatin-based systemic regimen benefit patient survival. However, chemoresistance will greatly reduce the effectiveness of this approach. The identification of molecules that contribute to cisplatin resistance may potentially improve the survival. Both HB-EGF and COX-2 have been reported to increase cisplatin-resistance. Here, we have focused on the regulation of HB-EGF/COX-2 and their roles in cisplatin resistance. IHC staining was used to measure the expression levels of HB-EGF and COX-2 on the tissue microarray from 43 tissue samples of patients with advanced HNSCC. siRNA, western blot and qRT-PCR were used to dissect the regulation between EGF, Akt, COX-2, PGE2, and cisplatin sensitivity. The correlation between HB-EGF, COX2 and HNSCC progression was analyzed by the receiver operating characteristic (ROC) curve and Kaplan-Meier disease free survival. Patients of advanced HNSCC patients with increased HB-EGF and COX-2 expression have higher tumor recurrent rates that was related to cisplatin resistance. The resistance was mediated via an increased expression of HB-EGF and COX-2. The activation of Akt by either EGF or areca nut extract were able to upregulate COX-2, which would increase the expression of HB-EGF in a PGE2 dependent manner. Inhibition and knockdown of COX-2 resulted in a decrease in HB-EGF. In the tissue samples from HNSCC patients, there was a significant positive correlation between the expression of COX-2 and HB-EGF. Our results suggested that COX-2 and HB-EGF are important in development of HNSCC cisplatin resistance. These findings may help the development of new strategies for overcoming cisplatin resistance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Thinking outside the box about COX-1 in Alzheimer's disease.

    Science.gov (United States)

    Frautschy, Sally A

    2010-06-01

    This article from Coma et al. shows that a salicylic acid derivative Triflusal, a platelet aggregation inhibitor and irreversible inhibitor of COX-1, can correct defects in axonal curvature and cognition in an AD transgenic mouse model (Tg2576) (Coma et al., 2010). Here we discuss the controversy over the role of COX-1 in AD, which has not been considered carefully in part due to the presumed adverse gastrointestinal effects of COX-1 antagonism. However, recent clinical data from this group as well as other groups challenges this assumption that COX-1 antagonism will be associated with side effects. Most importantly this article raises critical questions about the role of COX-1, versus COX-2 versus both in Abeta pathogenesis. The animal model data in this article as well as the recently published trial data suggest that COX-1 may play an important role in early pathogenesis and should not be ignored as a potential target for early intervention.

  9. Prognostic and survival analysis of presbyopia: The healthy twin study

    Science.gov (United States)

    Lira, Adiyani; Sung, Joohon

    2015-12-01

    Presbyopia, a vision condition in which the eye loses its flexibility to focus on near objects, is part of ageing process which mostly perceptible in the early or mid 40s. It is well known that age is its major risk factor, while sex, alcohol, poor nutrition, ocular and systemic diseases are known as common risk factors. However, many other variables might influence the prognosis. Therefore in this paper we developed a prognostic model to estimate survival from presbyopia. 1645 participants which part of the Healthy Twin Study, a prospective cohort study that has recruited Korean adult twins and their family members based on a nation-wide registry at public health agencies since 2005, were collected and analyzed by univariate analysis as well as Cox proportional hazard model to reveal the prognostic factors for presbyopia while survival curves were calculated by Kaplan-Meier method. Besides age, sex, diabetes, and myopia; the proposed model shows that education level (especially engineering program) also contribute to the occurrence of presbyopia as well. Generally, at 47 years old, the chance of getting presbyopia becomes higher with the survival probability is less than 50%. Furthermore, our study shows that by stratifying the survival curve, MZ has shorter survival with average onset time about 45.8 compare to DZ and siblings with 47.5 years old. By providing factors that have more effects and mainly associate with presbyopia, we expect that we could help to design an intervention to control or delay its onset time.

  10. Effect of socioeconomic position on survival after childhood cancer in Denmark

    DEFF Research Database (Denmark)

    Simony, Sofie B; Lund, Lasse W; Erdmann, Friederike

    2016-01-01

    was slightly but not statistically significantly better the higher the education of the mother or the father, and with maternal income. Significantly better survival was observed when parents were living together compared to living alone and worse survival when the child had siblings compared to none. Young......Background One fifth of all deaths among children in Europe are accounted for by cancer. If this is to be reduced there is a need for studies on not only biology and treatment approaches but also on how social factors influence cure rates. We investigated how various socioeconomic characteristics...... individual level parental socioeconomic variables and vital status through 2012 by linkage to population-based registries. Hazard ratios (HR) and 95% confidence intervals (CI) for dying were estimated using multivariate Cox proportional hazard models. Results For all children with cancer combined, survival...

  11. MethSurv: a web tool to perform multivariable survival analysis using DNA methylation data.

    Science.gov (United States)

    Modhukur, Vijayachitra; Iljasenko, Tatjana; Metsalu, Tauno; Lokk, Kaie; Laisk-Podar, Triin; Vilo, Jaak

    2017-12-21

    To develop a web tool for survival analysis based on CpG methylation patterns. We utilized methylome data from 'The Cancer Genome Atlas' and used the Cox proportional-hazards model to develop an interactive web interface for survival analysis. MethSurv enables survival analysis for a CpG located in or around the proximity of a query gene. For further mining, cluster analysis for a query gene to associate methylation patterns with clinical characteristics and browsing of top biomarkers for each cancer type are provided. MethSurv includes 7358 methylomes from 25 different human cancers. The MethSurv tool is a valuable platform for the researchers without programming skills to perform the initial assessment of methylation-based cancer biomarkers.

  12. Individual and Neighborhood Socioeconomic Status and Healthcare Resources in Relation to Black-White Breast Cancer Survival Disparities

    Directory of Open Access Journals (Sweden)

    Tomi F. Akinyemiju

    2013-01-01

    Full Text Available Background. Breast cancer survival has improved significantly in the US in the past 10–15 years. However, disparities exist in breast cancer survival between black and white women. Purpose. To investigate the effect of county healthcare resources and SES as well as individual SES status on breast cancer survival disparities between black and white women. Methods. Data from 1,796 breast cancer cases were obtained from the Surveillance Epidemiology and End Results and the National Longitudinal Mortality Study dataset. Cox Proportional Hazards models were constructed accounting for clustering within counties. Three sequential Cox models were fit for each outcome including demographic variables; demographic and clinical variables; and finally demographic, clinical, and county-level variables. Results. In unadjusted analysis, black women had a 53% higher likelihood of dying of breast cancer and 32% higher likelihood of dying of any cause (P<0.05 compared with white women. Adjusting for demographic variables explained away the effect of race on breast cancer survival (HR, 1.40; 95% CI, 0.99–1.97, but not on all-cause mortality. The racial difference in all-cause survival disappeared only after adjusting for county-level variables (HR, 1.27; CI, 0.95–1.71. Conclusions. Improving equitable access to healthcare for all women in the US may help eliminate survival disparities between racial and socioeconomic groups.

  13. Survival of acral lentiginous melanoma in the National Cancer Institute of Colombia.

    Science.gov (United States)

    Duarte, C A; Flórez, J P; López, H G; Meneses, M X; de Vries, E

    2017-03-01

    To determine survival of a cohort of patients with acral lentiginous melanoma (ALM), treated at the National Cancer Institute of Colombia, the largest referral hospital of the country. All patients diagnosed with an invasive ALM between 2003 and 2009 at the Colombian National Cancer Institute were included for analyses and followed for vital status and date of death. Using Kaplan-Meier methods, overall survival at 1, 3 and 5 years post diagnosis was determined, and Cox proportional hazards models were constructed for the variables showing a significant effect on survival in univariate analyses. Overall survival of this cohort of 90 patients was 77% at 1 year, 59% at 3 years and 54% at 5 years after diagnosis. Females had a better prognosis in univariate analyses but this advantage disappeared in multivariate models. Clinical stage was a strong predictor of survival, in univariate and multivariate models, particularly among elderly patients. Prognosis of ALM in Colombia is relatively poor, particularly for patients with higher clinical stage. The large proportions of ALM diagnosed in stage III and IV explain the relatively poor survival, and illustrate the importance of improving prognosis by lowering stage at diagnosis through better education and early detection programmes. © 2016 European Academy of Dermatology and Venereology.

  14. Comparison of methods for estimating the attributable risk in the context of survival analysis.

    Science.gov (United States)

    Gassama, Malamine; Bénichou, Jacques; Dartois, Laureen; Thiébaut, Anne C M

    2017-01-23

    The attributable risk (AR) measures the proportion of disease cases that can be attributed to an exposure in the population. Several definitions and estimation methods have been proposed for survival data. Using simulations, we compared four methods for estimating AR defined in terms of survival functions: two nonparametric methods based on Kaplan-Meier's estimator, one semiparametric based on Cox's model, and one parametric based on the piecewise constant hazards model, as well as one simpler method based on estimated exposure prevalence at baseline and Cox's model hazard ratio. We considered a fixed binary exposure with varying exposure probabilities and strengths of association, and generated event times from a proportional hazards model with constant or monotonic (decreasing or increasing) Weibull baseline hazard, as well as from a nonproportional hazards model. We simulated 1,000 independent samples of size 1,000 or 10,000. The methods were compared in terms of mean bias, mean estimated standard error, empirical standard deviation and 95% confidence interval coverage probability at four equally spaced time points. Under proportional hazards, all five methods yielded unbiased results regardless of sample size. Nonparametric methods displayed greater variability than other approaches. All methods showed satisfactory coverage except for nonparametric methods at the end of follow-up for a sample size of 1,000 especially. With nonproportional hazards, nonparametric methods yielded similar results to those under proportional hazards, whereas semiparametric and parametric approaches that both relied on the proportional hazards assumption performed poorly. These methods were applied to estimate the AR of breast cancer due to menopausal hormone therapy in 38,359 women of the E3N cohort. In practice, our study suggests to use the semiparametric or parametric approaches to estimate AR as a function of time in cohort studies if the proportional hazards assumption appears

  15. Adjuvant chemotherapy is associated with improved survival after esophagectomy without induction therapy for node-positive adenocarcinoma.

    Science.gov (United States)

    Speicher, Paul J; Englum, Brian R; Ganapathi, Asvin M; Mulvihill, Michael S; Hartwig, Matthew G; Onaitis, Mark W; D'Amico, Thomas A; Berry, Mark F

    2015-01-01

    This study investigated adjuvant chemotherapy (AC) use after esophagectomy without induction therapy for node-positive (pN+) adenocarcinoma using the National Cancer Database, including the impact of complications related to surgery (CRS) on outcomes. Predictors of AC use in 1694 patients in the National Cancer Data Base who underwent R0 esophagectomy from 2003-2011 without induction therapy for pN+ adenocarcinoma of the middle or lower esophagus and survived more than 30 days were identified with multivariable logistic regression. The impact of AC on survival was estimated using Kaplan-Meier and Cox-proportional hazards methods. AC was given to 874 of 1694 (51.6%) patients; 618 (70.7%) AC patients received radiation. Older age (adjusted odds ratio [AOR] 0.58/decade, p improved survival in multivariate analysis (hazard ratio 0.67, p = 0.008). Receiving radiation in addition to AC did not improve survival (p = 0.35). Although CRS was associated with worse survival, patients who had CRS but received AC had superior survival compared to patients who did not have CRS or get AC (p = 0.016). AC after esophagectomy is associated with improved survival but was only used in half of patients with pN+ esophageal adenocarcinoma. We also found that the addition of radiation to AC was not associated with a survival benefit. CRS predict worse long-term survival and lower the chance of getting AC, but even patients with CRS had improved survival when given AC.

  16. Family circumstances and survival from childhood acute lymphoblastic leukaemia in West Germany.

    Science.gov (United States)

    Erdmann, Friederike; Kaatsch, Peter; Schüz, Joachim

    2015-04-01

    Little is known about the relationship between family characteristics and survival from childhood acute lymphoblastic leukaemia (ALL), which we studied for the first time in German children. ALL cases were diagnosed between 1992 and 1994 and information on family characteristics was collected during a previously conducted nationwide case-control study. Children were followed for 10 years after diagnosis, as few disease-related events occur afterwards. Cox proportional hazards models estimating hazard ratios (HR) were calculated using overall as well as event-free survival methods. Second born children showed statistically significant better survival compared to first or later born children, with HRs ranging between 0.54 and 0.64 compared to firstborns. Somewhat poorer survival was observed for children having 3 or more siblings. A relationship was found for parental age at child's diagnosis, with poorer survival for children with younger parents (≤25 years of age at child's diagnosis), or with older fathers. The HR was statistically significant for fathers being ≥41years of age (HR of 2.1). No relationship between degree of urbanization of the place of residence at diagnosis and ALL survival was observed. Family circumstances may have an impact on survival from childhood ALL in Germany. Further research is warranted to elaborate the relationship of specific family characteristics and ALL survival and to investigate possible differential adherence to therapy and interactions with physicians. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Race and correlations between lymph node number and survival for patients with gastric cancer.

    Science.gov (United States)

    Nelson, Rebecca; Ko, Eun Bi; Arrington, Amanda; Lee, Wendy; Kim, Jae; Garcia-Aguilar, Julio; Kim, Joseph

    2013-03-01

    There is ongoing debate whether extended lymphadenectomy improves survival in gastric cancer patients who undergo surgical resection. We previously observed that Korean-American patients had the highest overall survival in Los Angeles County. Our objective was to assess lymph node (LN) number and its impact on survival for Korean-American gastric cancer patients. We utilized the National Cancer Institute's Surveillance, Epidemiology, and End Results registry to identify Korean-Americans with gastric adenocarcinoma treated with curative-intent gastrectomy between 1988 and 2008. We grouped patients according to examined LN number (1-15 and 16+) and compared characteristics. We performed similar analysis for white patients. Out of 982 Korean-American patients with gastric adenocarcinoma, most patients had 1-15 examined LNs (60 %). When we compared LN groups, we observed higher overall survival in the 1-15 group than the 16+ group (5-year survival, 59 % vs 52 %, respectively; p = 0.04). However, LN number was not prognostic of overall survival on stepwise Cox proportional hazards analysis. In contrast, LN number was prognostic for white patients. Although examined LN number may impact survival for white patients, outcomes of Korean-American gastric cancer patients were independent of LN number. Our data suggest that survival of Korean-American gastric cancer patients are comparable with outcomes from East Asian hospitals and may be independent of surgical technique.

  18. Combining gene signatures improves prediction of breast cancer survival.

    Directory of Open Access Journals (Sweden)

    Xi Zhao

    Full Text Available BACKGROUND: Several gene sets for prediction of breast cancer survival have been derived from whole-genome mRNA expression profiles. Here, we develop a statistical framework to explore whether combination of the information from such sets may improve prediction of recurrence and breast cancer specific death in early-stage breast cancers. Microarray data from two clinically similar cohorts of breast cancer patients are used as training (n = 123 and test set (n = 81, respectively. Gene sets from eleven previously published gene signatures are included in the study. PRINCIPAL FINDINGS: To investigate the relationship between breast cancer survival and gene expression on a particular gene set, a Cox proportional hazards model is applied using partial likelihood regression with an L2 penalty to avoid overfitting and using cross-validation to determine the penalty weight. The fitted models are applied to an independent test set to obtain a predicted risk for each individual and each gene set. Hierarchical clustering of the test individuals on the basis of the vector of predicted risks results in two clusters with distinct clinical characteristics in terms of the distribution of molecular subtypes, ER, PR status, TP53 mutation status and histological grade category, and associated with significantly different survival probabilities (recurrence: p = 0.005; breast cancer death: p = 0.014. Finally, principal components analysis of the gene signatures is used to derive combined predictors used to fit a new Cox model. This model classifies test individuals into two risk groups with distinct survival characteristics (recurrence: p = 0.003; breast cancer death: p = 0.001. The latter classifier outperforms all the individual gene signatures, as well as Cox models based on traditional clinical parameters and the Adjuvant! Online for survival prediction. CONCLUSION: Combining the predictive strength of multiple gene signatures improves

  19. Brachytherapy Improves Survival in Stage III Endometrial Cancer With Cervical Involvement

    Energy Technology Data Exchange (ETDEWEB)

    Bingham, Brian [Department of Radiation Oncology, Vanderbilt University, Nashville, Tennessee (United States); Orton, Andrew; Boothe, Dustin [Department of Radiation Oncology, University of Utah, Salt Lake City, Utah (United States); Stoddard, Greg [Division of Epidemiology, University of Utah, Salt Lake City, Utah (United States); Huang, Y. Jessica; Gaffney, David K. [Department of Radiation Oncology, University of Utah, Salt Lake City, Utah (United States); Poppe, Matthew M., E-mail: Matthew.poppe@hci.utah.edu [Department of Radiation Oncology, University of Utah, Salt Lake City, Utah (United States)

    2017-04-01

    Purpose: To evaluate the survival benefit of adding vaginal brachytherapy (BT) to pelvic external beam radiation therapy (EBRT) in women with stage III endometrial cancer. Methods and Materials: The National Cancer Data Base was used to identify patients with stage III endometrial cancer from 2004 to 2013. Only women who received adjuvant EBRT were analyzed. Women were grouped according to receipt of BT. Logistic regression modeling was used to identify predictors of receiving BT. Log–rank statistics were used to compare survival outcomes. Cox proportional hazards modeling was used to evaluate the effect of BT on survival. A propensity score–matched analysis was also conducted among women with cervical involvement. Results: We evaluated 12,988 patients with stage III endometrial carcinoma, 39% of whom received EBRT plus BT. Women who received BT were more likely to have endocervical or cervical stromal involvement (odds ratios 2.03 and 1.77; P<.01, respectively). For patients receiving EBRT alone, the 5-year survival was 66% versus 69% with the addition of BT at 5 years (P<.01). Brachytherapy remained significantly predictive of decreased risk of death (hazard ratio 0.86; P<.01) on multivariate Cox regression. The addition of BT to EBRT did not affect survival among women without cervical involvement (P=.84). For women with endocervical or cervical stromal invasion, the addition of BT significantly improved survival (log–rank P<.01). Receipt of EBRT plus BT was associated with improved survival in women with positive and negative surgical margins, and receiving chemotherapy did not alter the benefit of BT. Propensity score–matched analysis results confirmed the benefit of BT among women with cervical involvement (hazard ratio 0.80; P=.01). Conclusions: In this population of women with stage III endometrial cancer the addition of BT to EBRT was associated with an improvement in survival for women with endocervical or cervical stromal invasion.

  20. The effect of health insurance on childhood cancer survival in the United States.

    Science.gov (United States)

    Lee, Jong Min; Wang, Xiaoyan; Ojha, Rohit P; Johnson, Kimberly J

    2017-12-15

    The effect of health insurance on childhood cancer survival has not been well studied. Using Surveillance, Epidemiology, and End Results (SEER) data, this study was designed to assess the association between health insurance status and childhood cancer survival. Data on cancers diagnosed among children less than 15 years old from 2007 to 2009 were obtained from the SEER 18 registries. The effect of health insurance at diagnosis on 5-year childhood cancer mortality was estimated with marginal survival probabilities, restricted mean survival times, and Cox proportional hazards (PH) regression analyses, which were adjusted for age, sex, race/ethnicity, and county-level poverty. Among 8219 childhood cancer cases, the mean survival time was 1.32 months shorter (95% confidence interval [CI], -4.31 to 1.66) after 5 years for uninsured children (n = 131) versus those with private insurance (n = 4297), whereas the mean survival time was 0.62 months shorter (95% CI, -1.46 to 0.22) for children with Medicaid at diagnosis (n = 2838). In Cox PH models, children who were uninsured had a 1.26-fold higher risk of cancer death (95% CI, 0.84-1.90) than those who were privately insured at diagnosis. The risk for those with Medicaid was similar to the risk for those with private insurance at diagnosis (hazard ratio, 1.06; 95% CI, 0.93-1.21). Overall, the results suggest that cancer survival is largely similar for children with Medicaid and those with private insurance at diagnosis. Slightly inferior survival was observed for those who were uninsured in comparison with those with private insurance at diagnosis. The latter result is based on a small number of uninsured children and should be interpreted cautiously. Further study is needed to confirm and clarify the reasons for these patterns. Cancer 2017;123:4878-85. © 2017 American Cancer Society. © 2017 American Cancer Society.

  1. Epithelial ovarian cancer mortality among Hispanic women: Sub-ethnic disparities and survival trend across time: An analysis of SEER 1992-2013.

    Science.gov (United States)

    Chen, Chen; Markossian, Talar W; Silva, Abigail; Tarasenko, Yelena N

    2018-02-01

    Over the past half century the proportion of Hispanics in the US population has been steadily increasing, and groups of Hispanic origin have diversified. Despite notable racial and ethnic disparities in ovarian cancer (OC) mortality, population-based studies on OC among Hispanic females are lacking. To examine sub-ethnic disparities in OC mortality and survival trends using the Surveillance, Epidemiology, and End Results Program (SEER) 18 data on Hispanic women diagnosed with epithelial OC during 1992-2013. The disparities in OC 5 year survival and mortality were examined using log-rank tests and Cox proportional hazards models, adjusted for sociodemographic and pathological characteristics, time of diagnosis, receipt of resection surgery and county socioeconomic status. Trends in 5-year survival rates were examined using joinpoint regression models. The 5-year survival was lowest in Puerto Ricans (median survival: 33 months; survival rate: 31.07%) and was highest in the "Other" Hispanic subgroup (median survival: 59 months; survival rate: 49.14%) (log-rank test: P survival rates: from 43.37% to 48.94% (APC = 0.41, P = 0.40) and from 48.72% to 53.46% (APC = 0.29, P = 0.50), respectively. OC mortality in Hispanic patients varied by sub-ethnicity. This heterogeneity should be considered in future cancer data collection, reports and research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. 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.

  3. Binding Energy Calculation of Patchouli Alcohol Isomer Cyclooxygenase Complexes Suggested as COX-1/COX-2 Selective Inhibitor

    Directory of Open Access Journals (Sweden)

    Sentot Joko Raharjo

    2014-01-01

    Full Text Available To understand the structural features that dictate the selectivity of the two isoforms of the prostaglandin H2 synthase (PGHS/COX, the three-dimensional (3D structure of COX-1/COX-2 was assessed by means of binding energy calculation of virtual molecular dynamic with using ligand alpha-Patchouli alcohol isomers. Molecular interaction studies with COX-1 and COX-2 were done using the molecular docking tools by Hex 8.0. Interactions were further visualized by using Discovery Studio Client 3.5 software tool. The binding energy of molecular interaction was calculated by AMBER12 and Virtual Molecular Dynamic 1.9.1 software. The analysis of the alpha-Patchouli alcohol isomer compounds showed that all alpha-Patchouli alcohol isomers were suggested as inhibitor of COX-1 and COX-2. Collectively, the scoring binding energy calculation (with PBSA Model Solvent of alpha-Patchouli alcohol isomer compounds (CID442384, CID6432585, CID3080622, CID10955174, and CID56928117 was suggested as candidate for a selective COX-1 inhibitor and CID521903 as nonselective COX-1/COX-2.

  4. Functional status and survival after kidney transplantation1–12

    Science.gov (United States)

    Reese, Peter P.; Bloom, Roy D.; Shults, Justine; Thomasson, Arwin; Mussell, Adam; Rosas, Sylvia E.; Johansen, Kirsten L.; Abt, Peter; Levine, Matthew; Caplan, Arthur; Feldman, Harold I.; Karlawish, Jason

    2013-01-01

    Background Older patients constitute a growing proportion of U.S. kidney transplant recipients and often have a high burden of comorbidities. A summary measure of health such as functional status might enable transplant professionals to better evaluate and counsel these patients about their prognosis after transplant. Methods We linked UNOS registry data about post-transplant survival with pre-transplant functional status data (physical function [PF] scale of the Medical Outcomes Study Short Form-36) among individuals undergoing kidney transplant from 6/1/2000 – 5/31/2006. We examined the relationship between survival and functional status with multivariable Cox regression, adjusted for age. Using logistic regression models for three-year survival, we also estimated the reduction in deaths in the hypothetical scenario that recipients with poor functional status in this cohort experienced modest improvements in function. Results The cohort comprised 10,875 kidney transplant recipients (KTRs) with a mean age of 50 years; 14% were ≥65. Differences in three-year mortality between highest and lowest PF groups ranged from 3% among recipients <35 years to 14% among recipients ≥65 years. In multivariable Cox regression, worse PF was associated with higher mortality (HR 1.66 for lowest versus highest PF quartiles; p<0.001). Interactions between PF and age were non-significant. We estimated that 11% fewer deaths would occur if KTRs with the lowest functional status experienced modest improvements in function. Conclusions Across a wide age range, functional status was an independent predictor of post-transplant survival. Functional status assessment may be a useful tool with which to counsel patients about post-transplant outcomes. PMID:24113514

  5. Penalized estimation for proportional hazards models with current status data.

    Science.gov (United States)

    Lu, Minggen; Li, Chin-Shang

    2017-12-30

    We provide a simple and practical, yet flexible, penalized estimation method for a Cox proportional hazards model with current status data. We approximate the baseline cumulative hazard function by monotone B-splines and use a hybrid approach based on the Fisher-scoring algorithm and the isotonic regression to compute the penalized estimates. We show that the penalized estimator of the nonparametric component achieves the optimal rate of convergence under some smooth conditions and that the estimators of the regression parameters are asymptotically normal and efficient. Moreover, a simple variance estimation method is considered for inference on the regression parameters. We perform 2 extensive Monte Carlo studies to evaluate the finite-sample performance of the penalized approach and compare it with the 3 competing R packages: C1.coxph, intcox, and ICsurv. A goodness-of-fit test and model diagnostics are also discussed. The methodology is illustrated with 2 real applications. Copyright © 2017 John Wiley & Sons, Ltd.

  6. 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.

  7. Transcription factor interactions mediate EGF-dependent COX-2 expression.

    Science.gov (United States)

    Xu, Kaiming; Shu, Hui-Kuo G

    2013-08-01

    Cyclooxygenase-2 (COX-2) is linked to poor prognosis in patients with malignant gliomas. Amplification/overexpression of epidermal growth factor receptor (EGFR) is commonly seen in these tumors. EGFR signaling, through activation of the p38-MAPK/PKC-δ/Sp1 cascade, plays an essential role in the regulation of COX-2 expression in glioma cells. Here, we report that Src kinase contributes upstream to this signaling cascade. In addition, more detailed analysis revealed the involvement of FOXM1, a member of the forkhead box family of transcriptional activators, in EGF-dependent COX-2 induction. FOXM1 protein increased after stimulation with EGF, although its role in modulating COX-2 expression does not depend on this increase. While a conventional FOXM1 responsive element resides in a distal region (-2872/-2539 relative to the transcriptional start site) of the COX-2 promoter, this is not required for EGF-dependent induction of COX-2. Instead, FOXM1 forms a cooperative interaction with Sp1 at the Sp1-binding site (-245/-240 relative to the start site) of the COX-2 promoter to mediate EGF-induced COX-2 expression. Definition of this novel interaction provides a clearer understanding of the mechanistic basis for EGF induction of COX-2. These data provide a guide for the evaluation of potential newer therapeutic targets that have relevance in this disease. ©2013 AACR.

  8. Biochemical Control With Radiotherapy Improves Overall Survival in Intermediate and High-Risk Prostate Cancer Patients Who Have an Estimated 10-Year Overall Survival of >90%

    Energy Technology Data Exchange (ETDEWEB)

    Herbert, Christopher, E-mail: cherbert@bccancer.bc.ca [Department of Radiation Oncology, British Columbia Cancer Agency, Vancouver Centre, Vancouver, BC (Canada); Liu, Mitchell; Tyldesley, Scott; Morris, W. James [Department of Radiation Oncology, British Columbia Cancer Agency, Vancouver Centre, Vancouver, BC (Canada); Joffres, Michel [Department of Health Sciences, Simon Fraser University, Surrey, BC (Canada); Khaira, Mandip; Kwan, Winkle [Department of Radiation Oncology, British Columbia Cancer Agency, Fraser Valley Centre, Surrey, BC (Canada); Moiseenko, Vitali [Department of Medical Physics, British Columbia Cancer Agency, Vancouver Centre, Vancouver, BC (Canada); Pickles, Thomas [Department of Radiation Oncology, British Columbia Cancer Agency, Vancouver Centre, Vancouver, BC (Canada)

    2012-05-01

    Purpose: To identify subgroups of patients with carcinoma of the prostate treated with radical radiotherapy that have improved overall survival when disease is biochemically controlled. Methods and Materials: A cohort of 1,060 prostate cancer patients treated with radical radiotherapy was divided into nine subgroups based on National Comprehensive Cancer Network risk category and estimated 10-year overall survival (eOS 10y) derived from the age adjusted Charlson Comorbidity Index. Patients with and without biochemical control were compared with respect to overall survival. Actuarial estimates of overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used for analysis of overall survival. Results: Median follow-up was 125 months (range, 51-176 months). Only the subgroups with high or intermediate risk disease and an eOS 10y of >90% had a statistically significantly improved overall survival when prostate cancer was biochemically controlled. In all other groups, biochemical control made no significant difference to overall survival. In the subgroup with high-risk disease and eOS 10y >90%, actuarial overall survival was 86.3% (95% confidence interval [CI] 78.5%-94.1%) and 62.1% (95% CI 52.9%-71.3%) for patients with biochemical control and biochemical relapse respectively (p = 0.002). In the intermediate risk group with eOS >90%, actuarial overall survival was 95.3% (95% CI 89.0%-100%) and 79.8% (95% CI 68.0%-91.6%) for biochemically controlled and biochemically relapsed patients (p = 0.033). On multivariate analysis, National Comprehensive Cancer Network risk group (p = 0.005), biochemical control (p = 0.033) and eOS 10y (p < 0.001) were statistically significant. Conclusion: Biochemical control translates into improved overall survival in patients with high or intermediate risk disease and an estimated 10-year overall survival of >90%.

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. A model checking method for the proportional hazards model with recurrent gap time data.

    Science.gov (United States)

    Huang, Chiung-Yu; Luo, Xianghua; Follmann, Dean A

    2011-07-01

    Recurrent events are the natural outcome in many medical and epidemiology studies. To assess covariate effects on the gaps between consecutive recurrent events, the Cox proportional hazards model is frequently employed in data analysis. The validity of statistical inference, however, depends on the appropriateness of the Cox model. In this paper, we propose a class of graphical techniques and formal tests for checking the Cox model with recurrent gap time data. The building block of our model checking method is an averaged martingale-like process, based on which a class of multiparameter stochastic processes is proposed. This maneuver is very general and can be used to assess different aspects of model fit. Numerical simulations are conducted to examine finite-sample performance, and the proposed model checking techniques are illustrated with data from the Danish Psychiatric Central Register.

  18. What happens after discharge? An analysis of long-term survival in cardiac surgical patients requiring prolonged intensive care.

    Science.gov (United States)

    Elfstrom, K Miriam; Hatefi, Dustin; Kilgo, Patrick D; Puskas, John D; Thourani, Vinod H; Guyton, Robert A; Halkos, Michael E

    2012-01-01

    Cardiac surgical patients with postoperative complications frequently require prolonged intensive care yet survive to hospital discharge. From January 1, 2002 to December 31, 2007, 11,541 consecutive patients underwent cardiac operations at a single academic institution. Of these, 11,084 (95.9%) survived to hospital discharge and comprised the study sample. Patients were retrospectively categorized into four groups according to intensive care unit (ICU) length of stay (LOS): 14 days. Survival at 12 months was determined using the Social Security Death Index. Kaplan-Meier (KM) survival curves and Cox proportional hazards regression modeling (hazard ratio, HR) were used to analyze group differences in survival. One-year survival among the four groups according to ICU LOS was: 14 days, 68.3% (265/388) (p 14 days (HR = 1.90) compared to patients with ICU LOS 14 days (HR = 1.63). Although cardiac surgery patients with major postoperative complications frequently survive to hospital discharge, survival after discharge is significantly reduced in patients requiring prolonged ICU care. Reduced survival in patients with a high risk of complications and anticipated long ICU stays should be considered when discussing surgical versus nonsurgical options. © 2011 Wiley Periodicals, Inc.

  19. Impact of scalp location on survival in head and neck melanoma: A retrospective cohort study.

    Science.gov (United States)

    Xie, Charles; Pan, Yan; McLean, Catriona; Mar, Victoria; Wolfe, Rory; Kelly, John

    2017-03-01

    Scalp melanomas have more aggressive clinicopathological features than other melanomas and mortality rates more than twice that of melanoma located elsewhere. We sought to describe the survival of patients with scalp melanoma versus other cutaneous head and neck melanoma (CHNM), and explore a possible independent negative impact of scalp location on CHNM survival. A retrospective cohort study was performed of all invasive primary CHNM cases seen at a tertiary referral center over a 20-year period. Melanoma-specific survival (MSS) was compared between scalp melanoma and other invasive CHNM. Multivariable Cox proportional hazards regression was performed to determine associations with survival. On univariate analysis, patients with scalp melanoma had worse MSS than other CHNM (hazard ratio 2.22, 95% confidence interval 1.59-3.11). Scalp location was not associated with MSS in CHNM on multivariable analysis (hazard ratio 1.11, 95% confidence interval 0.77-1.61) for all tumors together, but remained independently associated with MSS for the 0.76- to 1.50-mm thickness stratum (hazard ratio 5.51, 95% confidence interval 1.55-19.59). Disease recurrence was not assessed because of unavailable data. The poorer survival of scalp melanoma is largely explained by greater Breslow thickness and a higher proportion of male patients. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  20. Comparison of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 (COX-2) inhibitors use in Australia and Nova Scotia (Canada).

    Science.gov (United States)

    Barozzi, Nadia; Sketris, Ingrid; Cooke, Charmaine; Tett, Susan

    2009-07-01

    Cyclooxygenase-2 (COX-2) inhibitors were marketed aggressively and their rapid uptake caused safety concerns and budgetary challenges in Canada and Australia. The objectives of this study were to compare and contrast COX-2 inhibitors and nonselective nonsteroidal anti-inflammatory drug (ns-NSAID) use in Nova Scotia (Canada) and Australia and to identify lessons learned from the two jurisdictions. Ns-NSAID and COX-2 inhibitor Australian prescription data (concession beneficiaries) were downloaded from the Medicare Australia website (2001-2006). Similar Pharmacare data were obtained for Nova Scotia (seniors and those receiving Community services). Defined daily doses per 1000 beneficiaries day(-1) were calculated. COX-2 inhibitors/all NSAIDs ratios were calculated for Australia and Nova Scotia. Ns-NSAIDs were divided into low, moderate and high risk for gastrointestinal side-effects and the proportions of use in each group were determined. Which drugs accounted for 90% of use was also calculated. Overall NSAID use was different in Australia and Nova Scotia. However, ns-NSAID use was similar. COX-2 inhibitor dispensing was higher in Australia. The percentage of COX-2 inhibitor prescriptions over the total NSAID use was different in the two countries. High-risk NSAID use was much higher in Australia. Low-risk NSAID prescribing increased in Nova Scotia over time. The low-risk/high-risk ratio was constant throughout over the period in Australia and increased in Nova Scotia. There are significant differences in Australia and Nova Scotia in use of NSAIDs, mainly due to COX-2 prescribing. Nova Scotia has a higher proportion of low-risk NSAID use. Interventions to provide physicians with information on relative benefits and risks of prescribing specific NSAIDs are needed, including determining their impact.

  1. Elevated expression of cyclooxygenase-2 is a negative prognostic factor for disease free survival and overall survival in patients with breast carcinoma.

    Science.gov (United States)

    Denkert, Carsten; Winzer, Klaus-Jürgen; Müller, Berit-Maria; Weichert, Wilko; Pest, Sören; Köbel, Martin; Kristiansen, Glen; Reles, Angela; Siegert, Antje; Guski, Hans; Hauptmann, Steffen

    2003-06-15

    Cyclooxygenases regulate the production of prostaglandins and play a role in tumor development and progression. The authors investigated the prognostic impact of expression of the cyclooxygenase (COX) isoforms, COX-1 and COX-2, on disease-free survival and progression-free survival in patients with primary breast carcinoma as well as the association between COX expression and other clinicopathologic parameters. In this study COX isoform expression was determined by immunohistochemistry in a cohort of 221 patients with primary breast carcinoma. Expression of COX-2 was detected in 36% of breast carcinoma samples and was associated significantly with several clinicopathologic parameters, including positive lymph node status (P disease-free survival (P = 0.0007) and overall survival (P = 0.02). In a multivariate analysis, expression of COX-2 was of borderline significance for disease-free survival (relative risk, 1.90; 95% confidence interval, 1.00-3.59), adjusting for tumor size, histologic grade, number of positive lymph nodes, and patient age. Elevated expression of COX-1 in tumor tissue had no statistically significant influence on patient prognosis. The current data suggest that increased expression of COX-2 may play a role in the progression of primary breast carcinoma. It remains to be investigated whether treatment with selective inhibitors of COX-2 may be an additional therapeutic option for patients with breast carcinoma. Copyright 2003 American Cancer Society.

  2. Immune phenotypes predict survival in patients with glioblastoma multiforme

    Directory of Open Access Journals (Sweden)

    Haouraa Mostafa

    2016-09-01

    Full Text Available Abstract Background Glioblastoma multiforme (GBM, a common primary malignant brain tumor, rarely disseminates beyond the central nervous system and has a very bad prognosis. The current study aimed at the analysis of immunological control in individual patients with GBM. Methods Immune phenotypes and plasma biomarkers of GBM patients were determined at the time of diagnosis using flow cytometry and ELISA, respectively. Results Using descriptive statistics, we found that immune anomalies were distinct in individual patients. Defined marker profiles proved highly relevant for survival. A remarkable relation between activated NK cells and improved survival in GBM patients was in contrast to increased CD39 and IL-10 in patients with a detrimental course and very short survival. Recursive partitioning analysis (RPA and Cox proportional hazards models substantiated the relevance of absolute numbers of CD8 cells and low numbers of CD39 cells for better survival. Conclusions Defined alterations of the immune system may guide the course of disease in patients with GBM and may be prognostically valuable for longitudinal studies or can be applied for immune intervention.

  3. Graphing survival curve estimates for time-dependent covariates.

    Science.gov (United States)

    Schultz, Lonni R; Peterson, Edward L; Breslau, Naomi

    2002-01-01

    Graphical representation of statistical results is often used to assist readers in the interpretation of the findings. This is especially true for survival analysis where there is an interest in explaining the patterns of survival over time for specific covariates. For fixed categorical covariates, such as a group membership indicator, Kaplan-Meier estimates (1958) can be used to display the curves. For time-dependent covariates this method may not be adequate. Simon and Makuch (1984) proposed a technique that evaluates the covariate status of the individuals remaining at risk at each event time. The method takes into account the change in an individual's covariate status over time. The survival computations are the same as the Kaplan-Meier method, in that the conditional survival estimates are the function of the ratio of the number of events to the number at risk at each event time. The difference between the two methods is that the individuals at risk within each level defined by the covariate is not fixed at time 0 in the Simon and Makuch method as it is with the Kaplan-Meier method. Examples of how the two methods can differ for time dependent covariates in Cox proportional hazards regression analysis are presented.

  4. Social determinants of health and 5-year survival of colorectal cancer.

    Science.gov (United States)

    Heidarnia, Mohammad Ali; Monfared, Esmat Davoudi; Akbari, Mohammad Esmail; Yavari, Parvin; Amanpour, Farzaneh; Mohseni, Maryam

    2013-01-01

    Early in the 21st century, cancers are the second cause of death worldwide. Colon cancer is third most common cancer and one of the few amenable to early diagnosis and treatment. Evaluation of factors affecting this cancer is important to increase survival time. Some of these factors affecting all diseases including cancer are social determinants of health. According to the importance of this disease and relation with these factors, this study was conducted to assess the relationship between social determinants of health and colon cancer survival. This was a cross-sectional, descriptive study for patients with colon cancer registered in the Cancer Research Center of Shahid Beheshti University of Medical Science, from April 2005 to November 2006, performed using questionnaires filled by telephone interview with patients (if patients had died, with family members). Data was analyzed with SPSS software (version 19) for descriptive analysis and STATA software for survival analysis including log rank test and three step Cox Proportional Hazard regression. Five hundred fifty nine patients with ages ranging from 23 to 88 years with mean ± standard deviation of 63 ± 11.8 years were included in the study. The five year survival was 68.3%( 387 patients were alive and 172 patients were dead by the end of the study). The Cox proportional hazard regression showed 5-year survival was related to age (HR=0.53, p=0.042 for>50 years versusmanual versus non manual jobs), region of residency (HR=3.49, p=0.018 for west versus south regions), parents in childhood (HR=2.87, p=0.012 for having both parents versus not having), anatomical cancer location (HR=2.16, psurvival of colon cancer and it may be better to consider these factors in addition to developing cancer treatment and to focus on these determinants of health in long-time planning.

  5. Adjuvant Sunitinib for High-risk Renal Cell Carcinoma After Nephrectomy: Subgroup Analyses and Updated Overall Survival Results

    DEFF Research Database (Denmark)

    Motzer, Robert J; Ravaud, Alain; Patard, Jean-Jacques

    2018-01-01

    the relationship between baseline factors and DFS, pattern of recurrence, and updated overall survival (OS). DESIGN, SETTING, AND PARTICIPANTS: Data for 615 patients randomized to sunitinib (n=309) or placebo (n=306) in the S-TRAC trial. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Subgroup DFS analyses...... by baseline risk factors were conducted using a Cox proportional hazards model. Baseline risk factors included: modified University of California Los Angeles integrated staging system criteria, age, gender, Eastern Cooperative Oncology Group performance status (ECOG PS), weight, neutrophil-to-lymphocyte ratio...

  6. Socioeconomic status and event free survival in pediatric acute lymphoblastic leukemia: a population-based cohort study.

    Science.gov (United States)

    Gupta, Sumit; Sutradhar, Rinku; Guttmann, Astrid; Sung, Lillian; Pole, Jason D

    2014-12-01

    The impact of socioeconomic status (SES) upon childhood cancer outcomes has not been extensively examined. Our objective was to determine the association between SES and event-free survival (EFS) among children with acute lymphoblastic leukemia (ALL) diagnosed in Ontario, Canada from 1995-2011 (N=1541) using Cox proportional hazards. Neither neighborhood-level median income quintile, distance from tertiary center, or rural residence significantly predicted EFS in the context of a universal healthcare system. Immigrant children experienced significantly superior EFS; confounding by ethnicity could not be ruled out. Confirmatory studies using additional individual-level SES variables are warranted. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Modeling survival: application of the Andersen-Gill model to Yellowstone grizzly bears

    Science.gov (United States)

    Johnson, Christopher J.; Boyce, Mark S.; Schwartz, Charles C.; Haroldson, Mark A.

    2004-01-01

     Wildlife ecologists often use the Kaplan-Meier procedure or Cox proportional hazards model to estimate survival rates, distributions, and magnitude of risk factors. The Andersen-Gill formulation (A-G) of the Cox proportional hazards model has seen limited application to mark-resight data but has a number of advantages, including the ability to accommodate left-censored data, time-varying covariates, multiple events, and discontinuous intervals of risks. We introduce the A-G model including structure of data, interpretation of results, and assessment of assumptions. We then apply the model to 22 years of radiotelemetry data for grizzly bears (Ursus arctos) of the Greater Yellowstone Grizzly Bear Recovery Zone in Montana, Idaho, and Wyoming, USA. We used Akaike's Information Criterion (AICc) and multi-model inference to assess a number of potentially useful predictive models relative to explanatory covariates for demography, human disturbance, and habitat. Using the most parsimonious models, we generated risk ratios, hypothetical survival curves, and a map of the spatial distribution of high-risk areas across the recovery zone. Our results were in agreement with past studies of mortality factors for Yellowstone grizzly bears. Holding other covariates constant, mortality was highest for bears that were subjected to repeated management actions and inhabited areas with high road densities outside Yellowstone National Park. Hazard models developed with covariates descriptive of foraging habitats were not the most parsimonious, but they suggested that high-elevation areas offered lower risks of mortality when compared to agricultural areas.

  8. Increased Expression of the GLUT-1 Gene is Associated With Worse Overall Survival in Resected Pancreatic Adenocarcinoma

    Science.gov (United States)

    Davis-Yadley, Ashley H.; Abbott, Andrea M.; Pimiento, Jose M.; Chen, Dung-Tsa; Malafa, Mokenge P.

    2015-01-01

    Objectives There is currently no reliable method to predict the risk of relapse after curative resection of early-stage pancreatic adenocarcinoma. Increased glucose metabolism observed on 18F-fluorodeoxyglucose positron emission tomography (PET) by malignant cells, the Warburg effect, is a well-known characteristic of the malignant phenotype. We investigated the role of glucose transporter type 1 (GLUT-1) gene expression, a glucose cell plasma membrane transporter, in early-stage pancreatic cancer. Methods Associations between GLUT-1 gene expression with PET maximum standardized uptake values (SUVmax) and histologic grade were investigated in early-stage pancreatic adenocarcinoma patients. Multivariate analysis was conducted to determine predictors of prognosis. Cox proportional hazards model was used for survival analysis. Results Sixty-three patients had GLUT-1 gene analysis performed, and 50 patients had both GLUT-1 analysis and PET scan. Patients with high GLUT-1 gene expression had a decreased overall survival by univariate analysis using Cox proportional hazards model (HR=2.82, p=0.001) and remained significant on multivariate analysis (HR=2.54, p=0.03). There was no correlation of GLUT-1 gene expression with histologic grade or PET SUVmax. Conclusion Increased GLUT-1 gene expression was associated with a decreased overall survival in pancreatic adenocarcinoma. This supports increased GLUT-1 gene expression as a potential prognostic marker in resected pancreatic adenocarcinoma. PMID:26692443

  9. 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...

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

    DEFF Research Database (Denmark)

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

    2001-01-01

    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...

  11. 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

  12. Increased COX-2 expression in patients with ovarian cancer | Lin ...

    African Journals Online (AJOL)

    This result was further confirmed by semi-quantitative RTPCR and Western blot. It was found that COX-2 was significantly up-regulated in ovarian cancer group in comparison with normal group on mRNA level. On protein level, COX-2 was also highly increased in ovarian cancer group. This study provides novel candidate ...

  13. Metastatic breast cancer - age has a significant effect on survival

    African Journals Online (AJOL)

    1991-03-02

    Mar 2, 1991 ... months for patients aged 55 - 64 years (P= 0,08; Cox model). The median survival improves again to 24,6 months ... in the very old (aged 75 - 84 years) (P = 0,52; Cox model). The more favourable prognosis in the elderly ... po Box 667, Pretoria, 0001 RSA. Accepted 18 Ocr 1990. tic breast cancer seen in ...

  14. ABO blood group and breast cancer incidence and survival

    National Research Council Canada - National Science Library

    Gates, Margaret A; Xu, Mousheng; Chen, Wendy Y; Kraft, Peter; Hankinson, Susan E; Wolpin, Brian M

    2012-01-01

    ...‐reported serologic blood type and/or ABO genotype. Using Cox proportional hazards regression, we examined the association between serologic blood type and incident breast cancer among 67,697 women, including 3,107 cases...

  15. 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......; 41 for p53). Occupational histories and smoking habits were available for majority of the cases. Most of the adenocarcinoma cases with exposure history data had been exposed to wood dust at work in the past (88%, 14/16). For smokers, 63% (12/19) presented with SSC, whereas 64% (7/11) of nonsmokers...... the exposures and p53 accumulation were found; however, the p53 accumulation pattern (p = 0.062 for wood dust exposure) resembled that of COX-2 expression. In summary, our findings show increased COX-2 expression in SNC adenocarcinoma with wood dust exposure, suggesting a role for inflammatory components...

  16. 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  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.

  17. High RBM3 expression is associated with an improved survival and oxaliplatin response in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Siesing, Christina; Sorbye, Halfdan; Dragomir, Anca

    2017-01-01

    Background: High expression of the RNA-binding motif protein 3 (RBM3) has been shown to correlate, with prolonged survival in several malignant diseases and with the benefit of platinum-based chemotherapy in ovarian cancer. The aim of this study was to evaluate RBM3 in metastatic colorectal cancer...... (mCRC) as a prognostic factor for overall survival and in relation to benefit of first-line chemotherapy. Methods: Immunohistochemical staining was conducted and evaluated in tumours from 455 mCRC patients. Kaplan-Meier analysis and Cox regression proportional hazards models were used to access...... RBM3 expression is an independent predictor of prolonged survival in mCRC patients, in particular in patients treated with first-line oxaliplatin based chemotherapy....

  18. Long-term Survival Outcomes by Smoking Status in Surgical and Nonsurgical Patients With Non-small Cell Lung Cancer

    Science.gov (United States)

    Meguid, Robert A.; Hooker, Craig M.; Harris, James; Xu, Li; Westra, William H.; Sherwood, J. Timothy; Sussman, Marc; Cattaneo, Stephen M.; Shin, James; Cox, Solange; Christensen, Joani; Prints, Yelena; Yuan, Nance; Zhang, Jennifer; Yang, Stephen C.

    2010-01-01

    Background: Survival outcomes of never smokers with non-small cell lung cancer (NSCLC) who undergo surgery are poorly characterized. This investigation compared surgical outcomes of never and current smokers with NSCLC. Methods: This investigation was a single-institution retrospective study of never and current smokers with NSCLC from 1975 to 2004. From an analytic cohort of 4,546 patients with NSCLC, we identified 724 never smokers and 3,822 current smokers. Overall, 1,142 patients underwent surgery with curative intent. For survival analysis by smoking status, hazard ratios (HRs) were estimated using Cox proportional hazard modeling and then further adjusted by other covariates. Results: Never smokers were significantly more likely than current smokers to be women (P cancer diagnosis has little impact on the long-term survival of patients with NSCLC, especially after curative surgery. Despite different etiologies between lung cancer in never and current smokers the prognosis is equally dismal. PMID:20507946

  19. Global Partial Likelihood for Nonparametric Proportional Hazards Models.

    Science.gov (United States)

    Chen, Kani; Guo, Shaojun; Sun, Liuquan; Wang, Jane-Ling

    2010-01-01

    As an alternative to the local partial likelihood method of Tibshirani and Hastie and Fan, Gijbels, and King, a global partial likelihood method is proposed to estimate the covariate effect in a nonparametric proportional hazards model, λ(t|x) = exp{ψ(x)}λ(0)(t). The estimator, ψ̂(x), reduces to the Cox partial likelihood estimator if the covariate is discrete. The estimator is shown to be consistent and semiparametrically efficient for linear functionals of ψ(x). Moreover, Breslow-type estimation of the cumulative baseline hazard function, using the proposed estimator ψ̂(x), is proved to be efficient. The asymptotic bias and variance are derived under regularity conditions. Computation of the estimator involves an iterative but simple algorithm. Extensive simulation studies provide evidence supporting the theory. The method is illustrated with the Stanford heart transplant data set. The proposed global approach is also extended to a partially linear proportional hazards model and found to provide efficient estimation of the slope parameter. This article has the supplementary materials online.

  20. Survival rates and predictors of survival among colorectal cancer patients in a Malaysian tertiary hospital.

    Science.gov (United States)

    Magaji, Bello Arkilla; Moy, Foong Ming; Roslani, April Camilla; Law, Chee Wei

    2017-05-18

    Colorectal cancer is the third most commonly diagnosed malignancy and the fourth leading cause of cancer-related death globally. It is the second most common cancer among both males and females in Malaysia. The economic burden of colorectal cancer is likely to increase over time owing to its current trend and aging population. Cancer survival analysis is an essential indicator for early detection and improvement in cancer treatment. However, there was a scarcity of studies concerning survival of colorectal cancer patients as well as its predictors. Therefore, we aimed to determine the 1-, 3- and 5-year survival rates, compare survival rates among ethnic groups and determine the predictors of survival among colorectal cancer patients. This was an ambidirectional cohort study conducted at the University Malaya Medical Centre (UMMC) in Kuala Lumpur, Malaysia. All Malaysian citizens or permanent residents with histologically confirmed diagnosis of colorectal cancer seen at UMMC from 1 January 2001 to 31 December 2010 were included in the study. Demographic and clinical characteristics were extracted from the medical records. Patients were followed-up until death or censored at the end of the study (31st December 2010). Censored patients' vital status (whether alive or dead) were cross checked with the National Registration Department. Survival analyses at 1-, 3- and 5-year intervals were performed using the Kaplan-Meier method. Log-rank test was used to compare the survival rates, while Cox proportional hazard regression analysis was carried out to determine the predictors of 5-year colorectal cancer survival. Among 1212 patients, the median survival for colorectal, colon and rectal cancers were 42.0, 42.0 and 41.0 months respectively; while the 1-, 3-, and 5-year relative survival rates ranged from 73.8 to 76.0%, 52.1 to 53.7% and 40.4 to 45.4% respectively. The Chinese patients had the lowest 5-year survival compared to Malay and Indian patients. Based on the 814

  1. Development of a model to predict breast cancer survival using data from the National Cancer Data Base.

    Science.gov (United States)

    Asare, Elliot A; Liu, Lei; Hess, Kenneth R; Gordon, Elisa J; Paruch, Jennifer L; Palis, Bryan; Dahlke, Allison R; McCabe, Ryan; Cohen, Mark E; Winchester, David P; Bilimoria, Karl Y

    2016-02-01

    With the large amounts of data on patient, tumor, and treatment factors available to clinicians, it has become critically important to harness this information to guide clinicians in discussing a patient's prognosis. However, no widely accepted survival calculator is available that uses national data and includes multiple prognostic factors. Our objective was to develop a model for predicting survival among patients diagnosed with breast cancer using the National Cancer Data Base (NCDB) to serve as a prototype for the Commission on Cancer's "Cancer Survival Prognostic Calculator." A retrospective cohort of patients diagnosed with breast cancer (2003-2006) in the NCDB was included. A multivariable Cox proportional hazards regression model to predict overall survival was developed. Model discrimination by 10-fold internal cross-validation and calibration was assessed. There were 296,284 patients for model development and internal validation. The c-index for the 10-fold cross-validation ranged from 0.779 to 0.788 after inclusion of all available pertinent prognostic factors. A plot of the observed versus predicted 5 year overall survival showed minimal deviation from the reference line. This breast cancer survival prognostic model to be used as a prototype for building the Commission on Cancer's "Cancer Survival Prognostic Calculator" will offer patients and clinicians an objective opportunity to estimate personalized long-term survival based on patient demographic characteristics, tumor factors, and treatment delivered. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Similar survival of patients with multiple vs. single primary melanomas based on Utah SEER data (1973-2011).

    Science.gov (United States)

    Grossman, Douglas; Farnham, James M; Hyngstrom, John; Klapperich, Marki E; Secrest, Aaron M; Empey, Sarah; Bowen, Glen M; Wada, David; Andtbacka, Robert H I; Grossmann, Kenneth; Bowles, Tawnya L; Cannon-Albright, Lisa A

    2018-02-27

    Survival data are mixed comparing patients with multiple primary melanomas (MPM) to those with single primary melanomas (SPM). To compare MPM vs. SPM patient survival, using a matching method that avoids potential biases associated with other analytic approaches. Records of 14,138 individuals obtained from the Surveillance, Epidemiology, and End-Results registry of all melanomas diagnosed or treated in Utah from 1973-2011 were reviewed. A single matched control patient was selected randomly from the SPM cohort for each MPM patient, with the restriction that they survived at least as long as the interval between the first and second diagnoses for the matched MPM patient. Survival curves (n=887 MPM, 887 SPM) without covariates showed a significant survival disadvantage for MPM patients (chi-squared = 39.29, p < 0.001). However, a multivariate Cox proportional hazards model showed no significant survival difference (hazard ratio = 1.07, p = 0.55). Restricting the multivariate analysis to invasive melanomas also showed no significant survival difference (hazard ratio = 0.99, p = 0.96). Breslow depth, ulceration status, and specific cause of death was not available for all patients. Patients with MPM had similar survival time as patients with SPM. Copyright © 2018. Published by Elsevier Inc.

  3. THE INFLUENCE OF POLYMORPHISM IN THE INFLAMMATORY GENES IL-1, ß IL-6, IL-10, PPAR?2 AND COX-2 IN PATIENTS WITH MULTIPLE MYELOMA UNDERGOING AUTOLOGOUS BONE MARROW TRANSPLANTATION

    DEFF Research Database (Denmark)

    Vangsted, Annette; Klausen, Tobias W.; Gimsing, Peter

    2007-01-01

    longer survival as compared to the homozygous wild type allele TT carriers (relative risk=2.1; p=0.008). There was no statistically significant difference between men and woman. The polymorphism in IL-6 G-174C, IL-10 C592A, PPAR?2 Pro12 Ala, COX-2 A-1195G, and COX-2 T8473C did not influence overall...

  4. Increasing incidence and survival in oral cancer: a nationwide Danish study from 1980 to 2014

    DEFF Research Database (Denmark)

    Karnov, Kirstine Kim Schmidt; Grønhøj, Christian; Jensen, David Hebbelstrup

    2017-01-01

    regression analysis in relation to location, gender, age, and calendar year at diagnosis. Results: Altogether, 8299 patients with oral cancer were identified, 5062 (61%) of whom were males and 3237 (39%) were females. The median age at diagnosis was 63 years. The AAIR of patients with OC increased from 1......Background: Oral carcinomas (OCs) make up a significant proportion of head and neck carcinomas (HNCs) and are an important cause of morbidity and mortality globally. The purpose of this population-based study was to determine trends in incidence and survival in OC in the Danish population from 1980...... to 2014. Material and methods: This study covered all patients registered in the nationwide Danish cancer registry (DCR) in the period 1980–2014. Age-adjusted incidence rate (AAIR) per 100,000 and annual percentage change (APC) were evaluated. Also, 5-year overall survival (OS) was calculated with Cox...

  5. Survival Analysis of Breast Cancer Subtypes in Patients With Spinal Metastases

    DEFF Research Database (Denmark)

    Wang, Miao; Jensen, Anders Bonde; Morgen, Soeren Smith

    2014-01-01

    hazards regression model unadjusted and adjusted by age were used. RESULTS: Patients with ER-negative (-) breast cancer had 11 months shorter median survival duration (10.6 vs. 21.5 mo) and 48% higher mortality risk (P=0.03) than those with ER-positive (+) breast cancer. Patients with PgR (-) status had...... in determining breast cancer subtypes and predicting patients' response to adjuvant treatments. METHODS: Until August 2013, we retrieved 151 surgically treated patients with breast cancer spinal metastases and followed up all the patients for at least 2 years. Survival duration analysis and Cox proportional...... from score "5" to "3" in Tokuhashi scoring system and from "slow growth" to "moderate growth" in Tomita scoring system. Spine surgeons should be critical before performing high-risk extensive surgery in patients with ER/HR (-) status, and especially, in those with triple-negative status. LEVEL...

  6. Modelling time-varying effects in Cox model under order restrictions

    OpenAIRE

    Salanti, Georgia; Ulm, Kurt

    2003-01-01

    The violation of the proportional hazards assumption in Cox model occurs quite often in studies concerning solid tumours or leukaemia. Then the time varying coefficients model is its most popular extension used. The function f(t) that measures the time variation of a covariate, can be assessed through several smoothing techniques, such as cubic splines. However, for practical propose, it is more convenient to assess f(t) by a step function. The main drawback of this approach is the lack of s...

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

    DEFF Research Database (Denmark)

    Scheike, Thomas Harder; Juul, Anders

    2004-01-01

    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......-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...

  8. Survival on Home Dialysis in New Zealand

    Science.gov (United States)

    Marshall, Mark R.; Walker, Rachael C.; Polkinghorne, Kevan R.; Lynn, Kelvin L.

    2014-01-01

    Background New Zealand (NZ) has a high prevalence of both peritoneal dialysis (PD) and home haemodialysis (HD) relative to other countries, and probably less selection bias. We aimed to determine if home dialysis associates with better survival than facility HD by simultaneous comparisons of the three modalities. Methods We analysed survival by time-varying dialysis modality in New Zealanders over a 15-year period to 31-Dec-2011, adjusting for patient co-morbidity by Cox proportional hazards multivariate regression. Results We modelled 6,419 patients with 3,254 deaths over 20,042 patient-years of follow-up. Patients treated with PD and facility HD are similar; those on home HD are younger and healthier. Compared to facility HD, home dialysis (as a unified category) associates with an overall 13% lower mortality risk. Home HD associates with a 52% lower mortality risk. PD associates with a 20% lower mortality risk in the early period (3 years), with no overall net effect. There was effect modification and less observable benefit associated with PD in those with diabetes mellitus, co-morbidity, and in NZ Maori and Pacific People. There was no effect modification by age or by era. Conclusion Our study supports the culture of home dialysis in NZ, and suggests that the extent and duration of survival benefit associated with early PD may be greater than appreciated. We are planning further analyses to exclude residual confounding from unmeasured co-morbidity and other sociodemographic factors using database linkage to NZ government datasets. Finally, our results suggest further research into the practice of PD in NZ Maori and Pacific People, as well as definitive study to determine the best timing for switching from PD in the late phase. PMID:24806458

  9. Survival on home dialysis in New Zealand.

    Directory of Open Access Journals (Sweden)

    Mark R Marshall

    Full Text Available BACKGROUND: New Zealand (NZ has a high prevalence of both peritoneal dialysis (PD and home haemodialysis (HD relative to other countries, and probably less selection bias. We aimed to determine if home dialysis associates with better survival than facility HD by simultaneous comparisons of the three modalities. METHODS: We analysed survival by time-varying dialysis modality in New Zealanders over a 15-year period to 31-Dec-2011, adjusting for patient co-morbidity by Cox proportional hazards multivariate regression. RESULTS: We modelled 6,419 patients with 3,254 deaths over 20,042 patient-years of follow-up. Patients treated with PD and facility HD are similar; those on home HD are younger and healthier. Compared to facility HD, home dialysis (as a unified category associates with an overall 13% lower mortality risk. Home HD associates with a 52% lower mortality risk. PD associates with a 20% lower mortality risk in the early period (3 years, with no overall net effect. There was effect modification and less observable benefit associated with PD in those with diabetes mellitus, co-morbidity, and in NZ Maori and Pacific People. There was no effect modification by age or by era. CONCLUSION: Our study supports the culture of home dialysis in NZ, and suggests that the extent and duration of survival benefit associated with early PD may be greater than appreciated. We are planning further analyses to exclude residual confounding from unmeasured co-morbidity and other sociodemographic factors using database linkage to NZ government datasets. Finally, our results suggest further research into the practice of PD in NZ Maori and Pacific People, as well as definitive study to determine the best timing for switching from PD in the late phase.

  10. Young patients with colorectal cancer have poor survival in the first twenty months after operation and predictable survival in the medium and long-term: Analysis of survival and prognostic markers

    Directory of Open Access Journals (Sweden)

    Wickramarachchi RE

    2010-09-01

    Full Text Available Abstract Objectives This study compares clinico-pathological features in young (50 years with colorectal cancer, survival in the young and the influence of pre-operative clinical and histological factors on survival. Materials and methods A twelve year prospective database of colorectal cancer was analysed. Fifty-three young patients were compared with forty seven consecutive older patients over fifty years old. An analysis of survival was undertaken in young patients using Kaplan Meier graphs, non parametric methods, Cox's Proportional Hazard Ratios and Weibull Hazard models. Results Young patients comprised 13.4 percent of 397 with colorectal cancer. Duration of symptoms and presentation in the young was similar to older patients (median, range; young patients; 6 months, 2 weeks to 2 years, older patients; 4 months, 4 weeks to 3 years, p > 0.05. In both groups, the majority presented without bowel obstruction (young - 81%, older - 94%. Cancer proximal to the splenic flexure was present more in young than in older patients. Synchronous cancers were found exclusively in the young. Mucinous tumours were seen in 16% of young and 4% of older patients (p Conclusion If patients, who are less than 40 years old with colorectal cancer, survive twenty months after operation, the prognosis improves and their survival becomes predictable.

  11. Proportion of injured drivers presenting to a tertiary care emergency department who engage in future impaired driving activities.

    Science.gov (United States)

    Purssell, Roy; Brown, Douglas; Brubacher, Jeffery R; Wilson, Jean; Fang, Ming; Schulzer, Michael; Mak, Edwin; Abu-Laban, Riyad B; Simons, Richard; Walker, Tristan

    2010-02-01

    We determined the rate of, and predictive factors for, subsequent impaired driving activity (IDA) by injured drivers treated in a Canadian tertiary care emergency department (ED) following a motor vehicle crash (MVC). We retrospectively identified all drivers injured in a MVC who presented to our tertiary care, urban ED (1999-2003) and had their blood alcohol content (BAC) measured. Injured drivers were categorized by BAC: group 1, BAC = 0; group 2, 0 17.3 mM. IDA was defined as any of the following: a conviction for impaired driving; a 24-h or 90-day license suspension for impaired driving; involvement in alcohol-related MVC. Time to IDA following the index event between groups was compared with Kaplan-Meier survival analyses. Effects of covariates on time to IDA were analyzed using Cox proportional hazards models. During the study period, 1489 injured drivers met study criteria: 1171 in group 1, 51 in group 2, and 267 in group 3. During an average follow-up of 52.4 months, 82 (30.7%) group 3 drivers engaged in subsequent IDA, compared with 80 (6.8%) group 1 drivers (p impaired drivers who present to hospital engage in repeat IDA following discharge. Besides impairment at time of hospital visit, the best predictor of future IDA is a history of IDA prior to the index event.

  12. A simple prognostic model for overall survival in metastatic renal cell carcinoma

    Science.gov (United States)

    Assi, Hazem I.; Patenaude, Francois; Toumishey, Ethan; Ross, Laura; Abdelsalam, Mahmoud; Reiman, Tony

    2016-01-01

    Introduction: The primary purpose of this study was to develop a simpler prognostic model to predict overall survival for patients treated for metastatic renal cell carcinoma (mRCC) by examining variables shown in the literature to be associated with survival. Methods: We conducted a retrospective analysis of patients treated for mRCC at two Canadian centres. All patients who started first-line treatment were included in the analysis. A multivariate Cox proportional hazards regression model was constructed using a stepwise procedure. Patients were assigned to risk groups depending on how many of the three risk factors from the final multivariate model they had. Results: There were three risk factors in the final multivariate model: hemoglobin, prior nephrectomy, and time from diagnosis to treatment. Patients in the high-risk group (two or three risk factors) had a median survival of 5.9 months, while those in the intermediate-risk group (one risk factor) had a median survival of 16.2 months, and those in the low-risk group (no risk factors) had a median survival of 50.6 months. Conclusions: In multivariate analysis, shorter survival times were associated with hemoglobin below the lower limit of normal, absence of prior nephrectomy, and initiation of treatment within one year of diagnosis. PMID:27217858

  13. Survival in women with NSCLC: the role of reproductive history and hormone use.

    Science.gov (United States)

    Katcoff, Hannah; Wenzlaff, Angela S; Schwartz, Ann G

    2014-03-01

    Although lung cancer is the leading cause of cancer death in women, few studies have investigated the hormonal influence on survival after a lung cancer diagnosis and results have been inconsistent. We evaluated the role of reproductive and hormonal factors in predicting overall survival in women with non-small-cell lung cancer (NSCLC). Population-based lung cancer cases diagnosed between November 1, 2001 and October 31, 2005 were identified through the Metropolitan Detroit Surveillance, Epidemiology, and End Results Registry. Interview and follow-up data were collected for 485 women. Cox proportional hazard regression models were used to determine hazard ratios (HRs) for death after an NSCLC diagnosis associated with reproductive and hormonal variables. Use of hormone therapy (HT) was associated with improved survival (HR, 0.69; 95% confidence interval, 0.54-0.89), adjusting for stage, surgery, radiation, education level, pack-years of smoking, age at diagnosis, race, and a multiplicative interaction between stage and radiation. No other reproductive or hormonal factor was associated with survival after an NSCLC diagnosis. Increased duration of HT use before the lung cancer diagnosis (132 months or longer) was associated with improved survival (HR, 0.54; 95% confidence interval, 0.37-0.78), and this finding remained significant in women taking either estrogen alone or progesterone plus estrogen, never smokers, and smokers. These findings suggest that HT use, in particular use of estrogen plus progesterone, and long-term HT use are associated with improved survival of NSCLC.

  14. Important prognostic factors for the long-term survival of lung cancer subjects in Taiwan

    Directory of Open Access Journals (Sweden)

    Ko Albert

    2008-11-01

    Full Text Available Abstract Background This study used a large-scale cancer database in determination of prognostic factors for the survival of lung cancer subjects in Taiwan. Methods Total of 24,910 subjects diagnosed with lung cancer was analysed. Survival estimates by Kaplan-Meier methods. Cox proportional-hazards model estimated the death risk (hazard ratio (HR for various prognostic factors. Results The prognostic indicators associated with a higher risk of lung cancer deaths are male gender (males versus females; HR = 1.07, 95% confidence intervals (CI: 1.03–1.11, males diagnosed in later periods (shown in 1991–1994 versus 1987–1990; HR = 1.13, older age at diagnosis, large cell carcinoma (LCC/small cell carcinoma (SCC, and supportive care therapy over chemotherapy. The overall 5-year survival rate for lung cancer death was significantly poorer for males (21.3% than females (23.6%. Subjects with squamous cell carcinoma (SQCC and treatment by surgical resection alone had better prognosis. We find surgical resections to markedly increase 5-year survival rate from LCC, decreased risk of death from LCC, and no improved survival from SCC. Conclusion Gender and clinical characteristics (i.e. diagnostic period, diagnostic age, histological type and treatment modality play important roles in determining lung cancer survival.

  15. 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...

  16. Building a Nomogram for Survey-Weighted Cox Models Using R

    Directory of Open Access Journals (Sweden)

    Marinela Capanu

    2015-03-01

    Full Text Available Nomograms have become very useful tools among clinicians as they provide individualized predictions based on the characteristics of the patient. For complex design survey data with survival outcome, Binder (1992 proposed methods for fitting survey-weighted Cox models, but to the best of our knowledge there is no available software to build a nomogram based on such models. This paper introduces an R package, SvyNom, to accomplish this goal and illustrates its use on a gastric cancer dataset. Validation and calibration routines are also included.

  17. Participation of COX-1 and COX-2 in the contractile effect of phenylephrine in prepubescent and old rats

    Science.gov (United States)

    Guevara-Balcazar, Gustavo; Ramirez-Sanchez, Israel; Mera-Jimenez, Elvia; Rubio-Gayosso, Ivan; Aguilar-Najera, Maria Eugenia

    2017-01-01

    Vascular reactivity can be influenced by the vascular region, animal age, and pathologies present. Prostaglandins (produced by COX-1 and COX-2) play an important role in the contractile response to phenylephrine in the abdominal aorta of young rats. Although these COXs are found in many tissues, their distribution and role in vascular reactivity are not clear. At a vascular level, they take part in the homeostasis functions involved in many physiological and pathologic processes (e.g., arterial pressure and inflammatory processes). The aim of this study was to analyze changes in the contractile response to phenylephrine of thoracic/abdominal aorta and the coronary artery during aging in rats. Three groups of rats were formed and sacrificed at three distinct ages: prepubescent, young and old adult. The results suggest that there is a higher participation of prostanoids in the contractile effect of phenylephrine in pre-pubescent rats, and a lower participation of the same in old rats. Contrarily, there seems to be a higher participation of prostanoids in the contractile response of the coronary artery of older than pre-pubescent rats. Considering that the changes in the expression of COX-2 were similar for the three age groups and the two tissues tested, and that expression of COX-1 is apparently greater in older rats, COX-1 and COX-2 may lose functionality in relation to their corresponding receptors during aging in rats. PMID:28706454

  18. Marital Status and Survival in Patients with Carcinoid Tumors

    Directory of Open Access Journals (Sweden)

    Erin K. Greenleaf

    2016-01-01

    Full Text Available Background Marital status is a known prognostic factor in overall and disease-specific survival in several types of cancer. The impact of marital status on survival in patients with carcinoid tumors remains unknown. We hypothesized that married patients have higher rates of survival than similar unmarried patients with carcinoid tumors. Methods Using the Surveillance, Epidemiology, and End Results database, we identified 23,126 people diagnosed with a carcinoid tumor between 2000 and 2011 and stratified them according to marital status. Univariate and multivariable analyses were performed to compare the characteristics and outcomes between patient cohorts. Overall and cancer-related survival were analyzed using the Kaplan–Meier method. Multivariable survival analyses were performed using Cox proportional hazards models (hazards ratio [HR], controlling for demographics and tumor-related and treatment-related variables. Propensity score analysis was performed to determine surgical intervention distributions among married and unmarried (ie, single, separated, divorced, widowed patients. Results Marital status was significantly related to both overall and cancer-related survival in patients with carcinoid tumors. Divorced and widowed patients had worse overall survival (HR, 1.33 [95% confidence interval {CI}, 1.08–1.33] and 1.34 [95% CI, 1.22–1.46], respectively and cancer-related survival (HR, 1.15 [95% CI, 1.00–1.31] and 1.15 [95% CI, 1.03–1.29], respectively than married patients over five years. Single and separated patients had worse overall survival (HR, 1.20 [95% CI, 1.08–1.33] and 1.62 [95% CI, 1.25–2.11], respectively than married patients over five years, but not worse cancer-related survival. Unmarried patients were more likely than matched married patients to undergo definitive surgical intervention (62.67% vs 53.11%, respectively, P < 0.0001. Conclusions Even after controlling for other prognostic factors, married patients

  19. Parthenolide inhibits cancer stem-like side population of nasopharyngeal carcinoma cells via suppression of the NF-κB/COX-2 pathway.

    Science.gov (United States)

    Liao, Kun; Xia, Bin; Zhuang, Qun-Ying; Hou, Meng-Jun; Zhang, Yu-Jing; Luo, Bing; Qiu, Yang; Gao, Yan-Fang; Li, Xiao-Jie; Chen, Hui-Feng; Ling, Wen-Hua; He, Cheng-Yong; Huang, Yi-Jun; Lin, Yu-Chun; Lin, Zhong-Ning

    2015-01-01

    Cancer stem cells play a central role in the pathogenesis of nasopharyngeal carcinoma and contribute to both disease initiation and relapse. In this study, cyclooxygenase-2 (COX-2) was found to regulate cancer stem-like side population cells of nasopharyngeal carcinoma cells and enhance cancer stem-like cells' characteristics such as higher colony formation efficiency and overexpression of stemness-associated genes. The regulatory effect of COX-2 on cancer stem-like characteristics may be mediated by ABCG2. COX-2 overexpression by a gain-of-function experiment increased the proportion of side population cells and their cancer stemness properties. The present study also demonstrated that in contrast to the classical chemotherapy drug 5-fluorouracil, which increased the proportion of side population cells and upregulated the expression of COX-2, parthenolide, a naturally occurring small molecule, preferentially targeted the side population cells of nasopharyngeal carcinoma cells and downregulated COX-2. Moreover, we found that the cancer stem-like cells' phenotype was suppressed by using COX-2 inhibitors NS-398 and CAY10404 or knocking down COX-2 with siRNA and shRNA. These findings suggest that COX-2 inhibition is the mechanism by which parthenolide induces cell death in the cancer stem-like cells of nasopharyngeal carcinoma. In addition, parthenolide exhibited an inhibitory effect on nuclear factor-kappa B (NF-κB) nucler translocation by suppressing both the phosphorylation of IκB kinase complex and IκBα degradation. Taken together, these results suggest that parthenolide may exert its cancer stem cell-targeted chemotherapy through the NF-κB/COX-2 pathway.

  20. Perioperative beta-blocker use and survival in lung cancer patients.

    Science.gov (United States)

    Cata, Juan P; Villarreal, John; Keerty, Dinesh; Thakar, Dilip R; Liu, Diane D; Sood, Anil K; Gottumukkala, Vijaya

    2014-03-01

    To assess the effect of perioperative beta blockers on recurrence and overall survival after non-small cell lung cancer surgery. Retrospective study. Academic medical center. The medical records of patients with stage 1, 2, and 3a non-small cell lung cancer were divided into three different groups: those patients who never received beta blockers perioperatively, those receiving nonselective beta blockers within 60 days of surgery, and those taking selective beta blockers within 60 days of surgery. Recurrence-free survival and overall survival were the main clinical endpoints. Univariate log-rank tests and multivariate Cox proportional hazards models were used to assess the effects of selective beta blockers, nonselective beta blockers, or no beta blockers on recurrence-free survival and overall survival. The analysis included records of 435 patients. Univariate analyses showed that the use of both selective and nonselective beta blockers was associated with decreased recurrence-free survival (P = 0.014) and overall survival (P = 0.009). However, these findings were not sustained after adjusting for possible confounding variables in the multivariate analysis. The hazard ratios for recurrence-free survival (selective beta blockers vs no beta blocker use were: 1.304; 95% confidence intervals [CI] 0.973 - 1.747; P = 0.075; for nonselective beta blockers vs no beta blockers: 0.989; 95% CI 0.639 - 1.532; P = 0.962. The hazard ratios for overall survival were: selective beta blocker use vs no beta blockers: 1.335; 95% CI 0.966 - 1.846; P = 0.080; nonselective beta blocker use vs no beta blocker use: 1.108; 95% CI 0.678 - 1.812; P = 0.682. Administration of beta blockers during the perioperative period did not improve recurrence-free or overall survival in patients undergoing resection of non-small cell lung cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Impact of donor-to-recipient weight ratio on survival after bilateral lung transplantation.

    Science.gov (United States)

    Delom, F; Danner-Boucher, I; Dromer, C; Thumerel, M; Marthan, R; Nourry-Lecaplain, L; Magnan, A; Jougon, J; Fessart, D

    2014-06-01

    The aim of this study was to investigate the relationship between donor-to-recipient weight ratio and post-transplantation survival. From February 1988 to November 2006, 255 adult bilateral lung transplantation patients from 2 different centers were retrospectively analyzed. The cohort was divided into 4 groups depending on the quartile ranges of the donor-to-recipient weight ratio. A time-to-event analysis was performed for risk of death after transplantation conditional on 5-year survival using Kaplan-Meier and Cox proportional hazards models. The mean weight ratio for the study cohort was 1.23 ± 0.39. For all lung transplant recipients during the study period, survival rate at 5 years was 58%. Median survival was 6.3 years in the cohort subgroup with weight ratio ratio >1.23. Weight ratio >1.23 recipients had a significant survival advantage out to 5 years compared with weight ratio ratio. Weight ratio strata affected overall survival, with quartile 1 (lower weight ratio recipients) experiencing the lowest 5-year survival (39.1%), followed by quartile 2 (57.8%), quartile 4 (68.2%), and quartile 3 (70.3%) recipients. The effect of weight ratio strata on survival was statistically significant for the quartile 1 recipients (lower quartile) as compared with the 3 other quartiles. Our findings show a statistically significant effect of donor-to-recipient weight ratios on bilateral lung transplantation survival. A higher donor-to-recipient weight ratio was associated with improved survival after bilateral lung transplantation and likely reflects a mismatch between a relatively overweight donor vs recipient. In contrast, a lower donor-to-recipient ratio was associated with increased mortality after bilateral lung transplantation. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Improved Survival Among Children with Spina Bifida in the United States

    Science.gov (United States)

    Shin, Mikyong; Kucik, James E.; Siffel, Csaba; Lu, Chengxing; Shaw, Gary M.; Canfield, Mark A.; Correa, Adolfo

    2015-01-01

    Objective To evaluate trends in survival among children with spina bifida by race/ethnicity and possible prognostic factors in 10 regions of the United States. Study design A retrospective cohort study was conducted of 5165 infants with spina bifida born during 1979-2003, identified by 10 birth defects registries in the United States. Survival probabilities and adjusted hazard ratios were estimated for race/ethnicity and other characteristics using the Cox proportional hazard model. Results During the study period, the 1-year survival probability among infants with spina bifida showed improvements for whites (from 88% to 96%), blacks (from 79% to 88%), and Hispanics (from 88% to 93%). The impact of race/ethnicity on survival varied by birth weight, which was the strongest predictor of survival through age 8. There was little racial/ethnic variation in survival among children born of very low birth weight. Among children born of low birth weight, the increased risk of mortality to Hispanics was approximately 4-6 times that of whites. The black-white disparity was greatest among children born of normal birth weight. Congenital heart defects did not affect the risk of mortality among very low birth weight children but increased the risk of mortality 4-fold among children born of normal birth weight. Conclusions The survival of infants born with spina bifida has improved; however, improvements in survival varied by race/ethnicity, and blacks and Hispanics continued to have poorer survival than whites in the most recent birth cohort from 1998-2002. Further studies are warranted to elucidate possible reasons for the observed differences in survival. PMID:22727874

  3. (COX6b1) from the Ailuropoda melanoleuca

    African Journals Online (AJOL)

    Administrator

    2011-05-16

    gorf/gorf.html). Protein structure of the. COX6b1 sequence cloned was deduced using predict protein software (http:// cubic. Bioc. columbia.edu/predictprotein/). Multiple sequence alignment was performed by DNAMAN 6.0. The.

  4. 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...

  5. Breast Cancer Heterogeneity: MR Imaging Texture Analysis and Survival Outcomes.

    Science.gov (United States)

    Kim, Jae-Hun; Ko, Eun Sook; Lim, Yaeji; Lee, Kyung Soo; Han, Boo-Kyung; Ko, Eun Young; Hahn, Soo Yeon; Nam, Seok Jin

    2017-03-01

    Purpose To determine the relationship between tumor heterogeneity assessed by means of magnetic resonance (MR) imaging texture analysis and survival outcomes in patients with primary breast cancer. Materials and Methods Between January and August 2010, texture analysis of the entire primary breast tumor in 203 patients was performed with T2-weighted and contrast material-enhanced T1-weighted subtraction MR imaging for preoperative staging. Histogram-based uniformity and entropy were calculated. To dichotomize texture parameters for survival analysis, the 10-fold cross-validation method was used to determine cutoff points in the receiver operating characteristic curve analysis. The Cox proportional hazards model and Kaplan-Meier analysis were used to determine the association of texture parameters and morphologic or volumetric information obtained at MR imaging or clinical-pathologic variables with recurrence-free survival (RFS). Results There were 26 events, including 22 recurrences (10 local-regional and 12 distant) and four deaths, with a mean follow-up time of 56.2 months. In multivariate analysis, a higher N stage (RFS hazard ratio, 11.15 [N3 stage]; P = .002, Bonferroni-adjusted α = .0167), triple-negative subtype (RFS hazard ratio, 16.91; P breast cancers that appeared more heterogeneous on T2-weighted images (higher entropy) and those that appeared less heterogeneous on contrast-enhanced T1-weighted subtraction images (lower entropy) exhibited poorer RFS. © RSNA, 2016 Online supplemental material is available for this article.

  6. Comparing Smoothing Techniques for Fitting the Nonlinear Effect of Covariate in Cox Models.

    Science.gov (United States)

    Roshani, Daem; Ghaderi, Ebrahim

    2016-02-01

    Cox model is a popular model in survival analysis, which assumes linearity of the covariate on the log hazard function, While continuous covariates can affect the hazard through more complicated nonlinear functional forms and therefore, Cox models with continuous covariates are prone to misspecification due to not fitting the correct functional form for continuous covariates. In this study, a smooth nonlinear covariate effect would be approximated by different spline functions. We applied three flexible nonparametric smoothing techniques for nonlinear covariate effect in the Cox models: penalized splines, restricted cubic splines and natural splines. Akaike information criterion (AIC) and degrees of freedom were used to smoothing parameter selection in penalized splines model. The ability of nonparametric methods was evaluated to recover the true functional form of linear, quadratic and nonlinear functions, using different simulated sample sizes. Data analysis was carried out using R 2.11.0 software and significant levels were considered 0.05. Based on AIC, the penalized spline method had consistently lower mean square error compared to others to selection of smoothed parameter. The same result was obtained with real data. Penalized spline smoothing method, with AIC to smoothing parameter selection, was more accurate in evaluate of relation between covariate and log hazard function than other methods.

  7. Efficient estimation of the partly linear additive Cox model

    OpenAIRE

    Huang, Jian

    1999-01-01

    The partly linear additive Cox model is an extension of the (linear) Cox model and allows flexible modeling of covariate effects semiparametrically. We study asymptotic properties of the maximum partial likelihood estimator of this model with right-censored data using polynomial splines. We show that, with a range of choices of the smoothing parameter (the number of spline basis functions) required for estimation of the nonparametric components, the estimator of the finite-d...

  8. Survival and prognostic factors for survival, cancer specific survival and disease free interval in 239 patients with Hurthle cell carcinoma: a single center experience.

    Science.gov (United States)

    Oluic, Branisav; Paunovic, Ivan; Loncar, Zlatibor; Djukic, Vladimir; Diklic, Aleksandar; Jovanovic, Milan; Garabinovic, Zeljko; Slijepcevic, Nikola; Rovcanin, Branislav; Micic, Dusan; Filipovic, Aleksandar; Zivaljevic, Vladan

    2017-05-25

    Hurthle cell carcinoma makes up 3 to 5% of all thyroid cancers and is considered to be a true rarity. The aim of our study was to analyze clinical characteristics and survival rates of patients with Hurthle cell carcinoma. Clinical data regarding basic demographic characteristics, tumor grade, type of surgical treatment and vital status were collected. Methods of descriptive statistics and Kaplan-Meier survival curves were used for statistical analysis. Cox proportional hazards regression was used to identify independent predictors. During the period from 1995 to 2014, 239 patients with Hurthle cell carcinoma were treated at our Institution. The average age of the patients was 54.3, with female to male ratio of 3.6:1 and average tumor size was 41.8 mm. The overall recurrence rate was 12.1%, with average time for relapse of 90.74 months and average time without any signs of the disease of 222.4 months. Overall 5-year, 10-year and 20-year survival rates were 89.4%, 77.2%, 61.9% respectively. The 5-year, 10-year and 20-year cancer specific survival rates were 94.6%, 92.5%, 87.4%, respectively. When disease free interval was observed, 5-year, 10-year and 20-year rates were 91.1%, 86.2%, 68.5%, respectively. The affection of both thyroid lobes and the need for reoperation due to local relapse were unfavorable independent prognostic factors, while total thyroidectomy as primary procedure was favorable predictive factor for cancer specific survival. Hurthle cell carcinoma is a rare tumor with an encouraging prognosis and after adequate surgical treatment recurrences are rare.

  9. COX-2/PGE2: molecular ambassadors of Kaposi's sarcoma-associated herpes virus oncoprotein-v-FLIP

    Science.gov (United States)

    Sharma-Walia, N; Patel, K; Chandran, K; Marginean, A; Bottero, V; Kerur, N; Paul, A G

    2012-01-01

    Kaposi's sarcoma herpesvirus (KSHV) latent oncoprotein viral FLICE (FADD-like interferon converting enzyme)-like inhibitory protein (v-FLIP) or K13, a potent activator of NF-κB, has well-established roles in KSHV latency and oncogenesis. KSHV-induced COX-2 represents a novel strategy employed by KSHV to promote latency and inflammation/angiogenesis/invasion. Here, we demonstrate that v-FLIP/K13 promotes tumorigenic effects via the induction of host protein COX-2 and its inflammatory metabolite PGE2 in an NF-κB-dependent manner. In addition to our previous studies demonstrating COX-2/PGE2's role in transcriptional regulation of KSHV latency promoter and latent gene expression, the current study adds to the complexity that though LANA-1 (latency associated nuclear antigen) is utilizing COX-2/PGE2 as critical factors for its transcriptional regulation, it is the v-FLIP/K13 gene in the KSHV latency cluster that maintains continuous COX-2/PGE2 levels in the infected cells. We demonstrate that COX-2 inhibition, via its chemical inhibitors (NS-398 or celecoxib), reduced v-FLIP/K13-mediated NF-κB induction, and extracellular matrix (ECM) interaction-mediated signaling, mitochondrial antioxidant enzyme manganese superoxide dismutase (MnSOD) levels, and subsequently downregulated detachment-induced apoptosis (anoikis) resistance. vFLIP expression mediated the secretion of cytokines, and spindle cell differentiation activated the phosphorylation of p38, RSK, FAK, Src, Akt and Rac1-GTPase. The COX-2 inhibition in v-FLIP/K13-HMVECs reduced inflammation and invasion/metastasis-related genes, along with reduced anchorage-independent colony formation via modulating ‘extrinsic' as well as ‘intrinsic' cell death pathways. COX-2 blockade in v-FLIP/K13-HMVEC cells drastically augmented cell death induced by removal of essential growth/survival factors secreted in the microenvironment. Transformed cells obtained from anchorage-independent colonies of COX-2 inhibitor-treated v

  10. 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...

  11. Modeling age-of-onset: Cox model with latent major gene effects

    Energy Technology Data Exchange (ETDEWEB)

    Li, H.; Thompson, E.A. [Univ. of Washington, Seattle, WA (United States)

    1994-09-01

    Analysis of age-of-onset is a key factor in the segregation and linkage analysis of complex genetic traits, but is complicated by the censoring of unaffected individuals. Most previous work has used parametric distributional assumptions, but it is hard to characterize the distribution of age-of-onset by a single distribution. Other approaches discretize age-of-onset and use logistic regression to model incidence; this approach does not use the information fully. Frailty models have been used for age-of-oset in the biostatistics literature, but these models do not lend themselves to modeling the correlations due to genetic effects which segregate within a family. Here, we propose use of the Cox model with latent major gene effects; conditional on the major genotypes, Cox`s proportional hazards model is used for age-of-onset for each individual. This is a semiparametric model; we do not specify the baseline hazard function. Likelihood analysis of such models is restricted by the difficulty in evaluating of maximizing the likelihood, especially when data are available for some of the members of an extended pedigree. Markov chain Monte Carlo permits genotypic configurations to be realized from the posterior distributions given a current model and the observed data. Hence methods for likelihood analysis can be developed: Monte Carlo EM is used for estimation of the parameters and their variance-covariance matrix. Markers and observed covariates are easily incorporated into this analysis. We present the model, methods for likelihood analysis and the results of a simulation study. The results are comparable with those based on a Cox model with known genotypic dependence in a pedigree. An early-onset Alzheimer`s pedigree and some breast cancer pedigrees have been used as real data examples. Some possible extensions are also discussed.

  12. Exact Tests for Hardy-Weinberg Proportions

    National Research Council Canada - National Science Library

    Engels, William R

    2009-01-01

    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...

  13. Adaptive bayesian analysis for binomial proportions

    CSIR Research Space (South Africa)

    Das, Sonali

    2008-10-01

    Full Text Available decision procedure to conduct statistical inference. The authors use the -divergence measure to quantify the perturbation of the posterior distribution of the proportion in different time points. They present a simulation study to compare the statistical...

  14. Heart transplantation with ABO-identical versus ABO-compatible cardiac grafts: influence on long-term survival.

    Science.gov (United States)

    Sjögren, Johan; Ljungdahl-Waller, Fredrik; Senneby, Erik; Ekmehag, Björn; Koul, Bansi; Nilsson, Johan

    2010-12-01

    To compare identical versus compatible, ABO blood group matching effects on rejection and long-term survival after heart transplantation (HT). Data were collected from 196 patients who underwent HT at Lund University Hospital between 1988 and 2008. Cox proportion hazard regression analysis was used to identify factors associated with reduced long-term survival. One hundred and sixty six patients (85%) had an identical ABO blood group match and 30 patients (15%) had a compatible, ABO blood group match. Four non-pharmacological variables reducing overall survival were identified: recipient blood group AB, age >55 years, ischemic time, and year of transplantation. Two pharmacological variables improved overall survival: glucocorticoids and cyclosporine. There was no significant difference in long-term survival between patients with identical blood groups compared to compatible ABO blood group matching. However, there was a trend towards graft failure as cause of death being more common in the compatible ABO group match compared identical blood group match (13% versus 5%, p=0.118). Six factors associated with overall survival were identified. One of these was related to blood group AB. No significant difference in survival following identical, versus compatible, ABO matching was demonstrated.

  15. Effect of Induction Therapy on Graft Survival in Primary Pediatric Heart Transplantation: A Propensity Score Analysis of the UNOS Database.

    Science.gov (United States)

    Butts, Ryan; Davis, Melanie; Savage, Andrew; Burnette, Ali; Kavarana, Minoo; Bradley, Scott; Atz, Andrew; Nietert, Paul J

    2017-06-01

    The use of induction therapy in pediatric heart transplantation has increased. The aim of this study was to investigate the effects of induction therapy on graft survival. The United Network for Organ Sharing database was queried for isolated pediatric heart transplants from January 1, 1994, to December 31, 2013. Propensity scores for induction treatment were calculated by estimating probability of induction using a logistic regression model. Transplants were then matched between induction treatment groups based on the propensity score, reducing potential biases. Using only propensity score matched transplants, the effect of induction therapy on graft survival was investigated using Cox-proportional hazards. Subgroup analyses were performed based on age, race, recipient cardiac diagnosis, HLA, and recipient panel-reactive antibody (PRA). Of 4565 pediatric primary heart transplants from 1994 to 2013, 3741 had complete data for the propensity score calculation. There were 2792 transplants successfully matched (induction, n = 1396; no induction, n = 1396). There were no significant differences in transplant and pretransplant covariates between induction and no induction groups. In the Cox-proportional hazards model, the use of induction of was not associated with graft loss (hazard ratio [HR], 0.88; 95% confidence interval [95% CI], 0.75-1.01; P = 0.07). In subgroup analyses, induction therapy may be associated with improved survival in patients with PRA greater than 50% (HR, 0.57; 95% CI, 0.34-0.97) and congenital heart disease (HR, 0.78; 95% CI, 0.64-0.96). Induction therapy is not associated with improved graft survival in primary pediatric heart transplantation. However, in pediatric heart transplant recipients with PRA greater than 50% or congenital heart disease, induction therapy is associated with improved survival.

  16. Assessment of survival of patients with metastatic clear cell renal cell carcinoma after radical cytoreductive nephrectomy versus no surgery: a SEER analysis

    Directory of Open Access Journals (Sweden)

    Wen-Jun Xiao

    2015-04-01

    Full Text Available Purposes To examine the factors related to the choice of cytoreductive nephrectomy (CN for patients with metastatic clear cell renal cell carcinoma (mCCRCC, and compare the population-based survival rates of patients treated with or without surgery in the modern targeted therapy era. Materials and Methods From 2006 to 2009, patients with mCCRCC were identified from SEER database. The factors that affected patients to be submitted to CN were examined and propensity scores for each patient were calculated. Then patients were matched based upon propensity scores. Univariable and multivariable cox regression models were used to compare survival rates of patients treated with or without surgery. Finally, sensitivity analysis for the cox model on a hazard ratio scale was performed. Results Age, race, tumor size, T stage and N stage were associated with nephrectomy univariablely. After the match based upon propensity scores, the 1-, 2-, and 3-year cancer-specific survival rate estimates were 45.1%, 27.9%, and 21.7% for the no-surgery group vs 70.6%, 52.2%, and 41.7% for the surgery group, respectively (hazard ratio 0.42, 95%CI: 0.35-0.52, log-rank P<0.001. In multivariable Cox proportional hazard regression model, race, T stage, N stage and median household income were significantly associated with survival. Sensitivity analysis on a hazard ratio scale indicated that the hazard ratio might be above 1.00 only when the unknown factor had an opposite effect on survival which was 3-fold than CN. Conclusion The results of our study showed that CN significantly improves the survival of patients with metastatic CCRCC even in the targeted therapy era.

  17. Partially Linear Single Index Cox Regression Model in Nested Case-Control Studies.

    Science.gov (United States)

    Shang, Shulian; Liu, Mengling; Zeleniuch-Jacquotte, Anne; Clendenen, Tess V; Krogh, Vittorio; Hallmans, Goran; Lu, Wenbin

    2013-11-01

    The nested case-control (NCC) design is widely used in epidemiologic studies as a cost-effective subcohort sampling method to study the association between a disease and its potential risk factors. NCC data are commonly analyzed using Thomas' partial likelihood approach under the Cox proportional hazards model assumption. However, the linear modeling form in the Cox model may be insufficient for practical applications, especially when there are a large number of risk factors under investigation. In this paper, we consider a partially linear single index proportional hazard model, which includes a linear component for covariates of interest to yield easily interpretable results and a nonparametric single index component to adjust for multiple confounders effectively. We propose to approximate the nonparametric single index function by polynomial splines and estimate the parameters of interest using an iterative algorithm based on the partial likelihood. Asymptotic properties of the resulting estimators are established. The proposed methods are evaluated using simulations and applied to an NCC study of ovarian cancer.

  18. Prognostic factors in gastric cancer evaluated by using Cox regression model.

    Science.gov (United States)

    Ghiandoni, G; Rocchi, M B; Signoretti, P; Belbusti, F

    1998-06-01

    To identify the most relevant short-term predictor variables in gastric cancer removal. A retrospective survival analysis executed by using the Cox regression model; the follow-up period is included between 18 and 90 months. A district general hospital surgery unit: "Divisione di Chirurgia Generale, Ospedale Civile di Urbino" (Marche, Italy). One hundred and twenty nine consecutive patients operated for gastric cancer. Surgery (total or subtotal gastrectomy). Survival times. Lymph node involvement (N) (p extension (T) (p < 0.001) and the age of the patients (p < 0.05) have been recognized as significant prognostic factors. Results show that the short-term prognosis largely depends on both the earliness of the diagnosis and the age of the patients.

  19. Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia patients with BCR-ABL T315I mutation

    DEFF Research Database (Denmark)

    Nicolini, Franck E; Mauro, Michael J; Martinelli, Giovanni

    2009-01-01

    The BCR-ABL T315I mutation represents a major mechanism of resistance to tyrosine kinase inhibitors (TKIs). The objectives of this retrospective observational study were to estimate overall and progression-free survival for chronic myeloid leukemia in chronic-phase (CP), accelerated-phase (AP......), or blastic-phase (BP) and Philadelphia chromosome-positive (Ph)(+) acute lymphoblastic leukemia (ALL) patients with T315I mutation. Medical records of 222 patients from 9 countries were reviewed; data were analyzed using log-rank tests and Cox proportional hazard models. Median age at T315I mutation...

  20. SAS macros for point and interval estimation of area under the receiver operating characteristic curve for non-proportional and proportional hazards Weibull models.

    Science.gov (United States)

    Mannan, Haider; Stevenson, Chris

    2010-08-01

    For prediction of risk of cardiovascular end points using survival models the proportional hazards assumption is often not met. Thus, non-proportional hazards models are more appropriate for developing risk prediction equations in such situations. However, computer program for evaluating the prediction performance of such models has been rarely addressed. We therefore developed SAS macro programs for evaluating the discriminative ability of a non-proportional hazards Weibull model developed by Anderson (1991) and that of a proportional hazards Weibull model using the area under receiver operating characteristic (ROC) curve. Two SAS macro programs for non-proportional hazards Weibull model using Proc NLIN and Proc NLP respectively and model validation using area under ROC curve (with its confidence limits) were written with SAS IML language. A similar SAS macro for proportional hazards Weibull model was also written. The computer program was applied to data on coronary heart disease incidence for a Framingham population cohort. The five risk factors considered were current smoking, age, blood pressure, cholesterol and obesity. The predictive ability of the non-proportional hazard Weibull model was slightly higher than that of its proportional hazard counterpart. An advantage of SAS Proc NLP in terms of the example provided here is that it provides significance level for the parameter estimates whereas Proc NLIN does not. The program is very useful for evaluating the predictive performance of non-proportional and proportional hazards Weibull models.

  1. 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.

  2. Trends and territorial inequalities of incidence and survival of childhood leukaemia and their relations to socioeconomic status in Hungary, 1971-2015.

    Science.gov (United States)

    Jakab, Zsuzsanna; Juhasz, Attila; Nagy, Csilla; Schuler, Dezso; Garami, Miklos

    2017-09-01

    The Hungarian Childhood Cancer Registry, a population-based national registry of the Hungarian Paediatric Haemato-Oncology Network founded in 1971, monitors the incidence and mortality of childhood cancer. Our aims were to carry out a longitudinal study to investigate the trends and spatial inequalities of incidence and survival of leukaemia, and the association between survival and deprivation in Hungary. All cases of childhood leukaemia and myelodysplasia were analysed (3157 cases, 1971-2015, age: 0-14 years). Time trends and the annual percentage change in direct standardized incidence and mortality were assessed. Survival and association with deprivation were assessed using the Kaplan-Meier method and Cox regression. Incidence rates of leukaemia (23.5-56.0/million) increased with an average annual percent change (AAPC) of 1%, determined by an increase in the incidence of acute lymphoblastic leukaemia (14.6-39.2/million, AAPC: 1.25%). Kaplan-Meier analysis showed a significant improvement in overall survival over the study period. Starting from 25% of cases surviving 5 years in the 70s; the overall 5-year survival reached 80% by 2010. Survival differences were observed with sex, leukaemia type and age at diagnosis. A reverse association was found in the survival probability of leukaemia by degree of deprivation. The Cox proportional hazards model verified a significant reverse association with deprivation [hazard ratio=1.08 (1.04-1.12)]. This is the first nationwide study to confirm the prognostic role of deprivation on the basis of a large cohort of patients with childhood leukaemia during a 45-year period. To maintain further improvement in treatment results, it is important to detect inequalities. Our results showed that deprivation may also be important in the survival of leukaemia.

  3. A nonparametric method for predicting survival probabilities

    NARCIS (Netherlands)

    van der Klaauw, B.; Vriend, S.

    2015-01-01

    Public programs often use statistical profiling to assess the risk that applicants will become long-term dependent on the program. The literature uses linear probability models and (Cox) proportional hazard models to predict duration outcomes. These either focus on one threshold duration or impose

  4. A study of phosphorylated ERK1/2 and COX-2 in early stage (T1-T2) oral squamous cell carcinomas.

    Science.gov (United States)

    Søland, Tine M; Husvik, Camilla; Koppang, Hanna Strømme; Boysen, Morten; Sandvik, Leiv; Clausen, Ole Petter Fraas; Christoffersen, Thoralf; Bryne, Magne

    2008-10-01

    Histomorphological grading at the invasive front of oral squamous cell carcinomas (OSCCs) may provide useful prognostic information. In the present study, we investigated the presence and prognostic value of activated phosphorylated extracellular signal-regulated kinases 1 and 2 (p-ERK1/2) and cyclo-oxygenase-2 (COX-2) both at the invasive front and in central/superficial parts of OSCCs. Using immunohistochemistry, we assessed the presence of p-ERK1/2 and COX-2 in 53 early stage OSCCs. Clinical data were recorded prospectively. The end point was disease-free survival. p-ERK1/2 staining was present in almost all tumours. The staining was mostly nuclear in the cells of the invasive front and either nuclear or nuclear/cytoplasmic in central/superficial tumour parts. COX-2 was observed in almost all tumours (98%) and the staining was often restricted to focal areas. Most tumours were COX-2 negative at the invasive front. The lowest P-value in survival analyses was P = 0.06 for p-ERK1/2 at the invasive front. COX-2, the histomorphological grading systems and TNM stage were of no prognostic value. p-ERK1/2 was present in almost all tumours and p-ERK1/2 may be a prognostic marker at the invasive front of OSCCs. In early stage OSCCs, most tumours did not express COX-2 at the invasive front.

  5. Cyclo-oxygenase (COX) inhibitors for treating preterm labour.

    Science.gov (United States)

    Reinebrant, Hanna E; Pileggi-Castro, Cynthia; Romero, Carla L T; Dos Santos, Rafaela A N; Kumar, Sailesh; Souza, João Paulo; Flenady, Vicki

    2015-06-05

    Preterm birth is a major cause of perinatal mortality and morbidity. Cyclo-oxygenase (COX) inhibitors inhibit uterine contractions, are easily administered and appear to have few maternal side effects. However, adverse effects have been reported in the fetus and newborn as a result of exposure to COX inhibitors. To assess the effects on maternal and neonatal outcomes of COX inhibitors administered as a tocolytic agent to women in preterm labour when compared with (i) placebo or no intervention and (ii) other tocolytics. In addition, to compare the effects of non-selective COX inhibitors with COX-2 selective inhibitors. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (24 August 2014). We also contacted recognised experts and searched reference lists of retrieved studies. All published and unpublished randomised trials in which COX inhibitors were used for tocolysis for women in labour between 20 and 36 completed weeks' gestation. Two review authors independently evaluated methodological quality and extracted data. We sought additional information from study authors. Results are presented using risk ratio (RR; dichotomous data) and mean difference (MD; continuous data) with 95% confidence interval (CI). The number needed to treat for benefit (NNTB) and the number needed to treat for harm (NNTH) were calculated for statistically different categorical outcomes. With the addition of seven studies with a total of 684 women, this review now includes outcome data from 20 studies including 1509 women. The non-selective COX inhibitor indomethacin was used in 15 studies. The overall quality of the included studies was considered moderate to low.Three small studies (102 women), two of which were conducted in the 1980's, compared COX inhibition (indomethacin only) with placebo. No difference was shown in birth less than 48 hours after trial entry (average RR 0.20, 95% CI 0.03 to 1.28; two studies with 70 women). Indomethacin resulted in a reduction in

  6. Testing Departure from Hardy-Weinberg Proportions.

    Science.gov (United States)

    Wang, Jian; Shete, Sanjay

    2017-01-01

    The Hardy-Weinberg principle, one of the most important principles in population genetics, was originally developed for the study of allele frequency changes in a population over generations. It is now, however, widely used in studies of human diseases to detect inbreeding, population stratification, and genotyping errors. For assessment of deviation from Hardy-Weinberg proportions in data, the most popular approaches include the asymptotic Pearson's chi-squared goodness-of-fit test and the exact test. Pearson's chi-squared goodness-of-fit test is simple and straightforward, but is very sensitive to a small sample size or rare allele frequency. The exact test of Hardy-Weinberg proportions is preferable in these situations. The exact test can be performed through complete enumeration of heterozygote genotypes or on the basis of the Markov chain Monte Carlo procedure. In this chapter, we describe the Hardy-Weinberg principle and the commonly used Hardy-Weinberg proportion tests and their applications, and we demonstrate how the chi-squared test and exact test of Hardy-Weinberg proportions can be performed step-by-step using the popular software programs SAS, R, and PLINK, which have been widely used in genetic association studies, along with numerical examples. We also discuss approaches for testing Hardy-Weinberg proportions in case-control study designs that are better than traditional approaches for testing Hardy-Weinberg proportions in controls only. Finally, we note that deviation from the Hardy-Weinberg proportions in affected individuals can provide evidence for an association between genetic variants and diseases.

  7. 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.

  8. Skp2 expression unfavorably impacts survival in resectable esophageal squamous cell carcinoma

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    Liang Yi

    2012-05-01

    Full Text Available Abstract Background The correlation of S-phase kinase–associated protein 2 (Skp2 with metastasis and prognosis in esophageal squamous cell carcinoma (ESCC is controversial. The purpose of this study was to explore whether there was a correlation between the expression of Skp2 evaluated by immunohistochemistry and the clinical outcome of patients with operable ESCC, and to further determine the possible mechanism of the impact of Skp2 on survival. Methods Tissue microarrays that included 157 surgically resected ESCC specimens was successfully generated for immunohistochemical evaluation. The clinical/prognostic significance of Skp2 expression was analyzed. Kaplan-Meier analysis was used to compare the postoperative survival between groups. The prognostic impact of clinicopathologic variables and Skp2 expression was evaluated using a Cox proportional hazards model. A cell proliferation assay and a colony formation assay were performed in ESCC cell lines to determine the function of Skp2 on the progression of ESCC in vitro. Results Skp2 expression correlated closely with the T category (p = 0.035 and the pathological tumor-node-metastasis (TNM stage (p = 0.027. High expression of Skp2 was associated with poor overall survival in resectable ESCC (p = 0.01. The multivariate Cox regression analysis demonstrated that pathological T category, pathological N category, cell differentiation, and negative Skp2 expression were independent factors for better overall survival. In vitro assays of ESCC cell lines demonstrated that Skp2 promoted the proliferative and colony-forming capacity of ESCCs. Conclusions Negative Skp2 expression in primary resected ESCC is an independent factor for better survival. Skp2 may play a pro-proliferative role in ESCC cells.

  9. Unbiased split variable selection for random survival forests using maximally selected rank statistics.

    Science.gov (United States)

    Wright, Marvin N; Dankowski, Theresa; Ziegler, Andreas

    2017-04-15

    The most popular approach for analyzing survival data is the Cox regression model. The Cox model may, however, be misspecified, and its proportionality assumption may not always be fulfilled. An alternative approach for survival prediction is random forests for survival outcomes. The standard split criterion for random survival forests is the log-rank test statistic, which favors splitting variables with many possible split points. Conditional inference forests avoid this split variable selection bias. However, linear rank statistics are utilized by default in conditional inference forests to select the optimal splitting variable, which cannot detect non-linear effects in the independent variables. An alternative is to use maximally selected rank statistics for the split point selection. As in conditional inference forests, splitting variables are compared on the p-value scale. However, instead of the conditional Monte-Carlo approach used in conditional inference forests, p-value approximations are employed. We describe several p-value approximations and the implementation of the proposed random forest approach. A simulation study demonstrates that unbiased split variable selection is possible. However, there is a trade-off between unbiased split variable selection and runtime. In benchmark studies of prediction performance on simulated and real datasets, the new method performs better than random survival forests if informative dichotomous variables are combined with uninformative variables with more categories and better than conditional inference forests if non-linear covariate effects are included. In a runtime comparison, the method proves to be computationally faster than both alternatives, if a simple p-value approximation is used. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  10. Racial and Ethnic Disparities in Cancer Survival: The Contribution of Tumor, Sociodemographic, Institutional, and Neighborhood Characteristics.

    Science.gov (United States)

    Ellis, Libby; Canchola, Alison J; Spiegel, David; Ladabaum, Uri; Haile, Robert; Gomez, Scarlett Lin

    2018-01-01

    Purpose Racial/ethnic disparities in cancer survival in the United States are well documented, but the underlying causes are not well understood. We quantified the contribution of tumor, treatment, hospital, sociodemographic, and neighborhood factors to racial/ethnic survival disparities in California. Materials and Methods California Cancer Registry data were used to estimate population-based cancer-specific survival for patients diagnosed with breast, prostate, colorectal, or lung cancer between 2000 and 2013 for each racial/ethnic group (non-Hispanic black, Hispanic, Asian American and Pacific Islander, and separately each for Chinese, Japanese, and Filipino) compared with non-Hispanic whites. The percentage contribution of factors to overall racial/ethnic survival disparities was estimated from a sequence of multivariable Cox proportional hazards models. Results In baseline models, black patients had the lowest survival for all cancer sites, and Asian American and Pacific Islander patients had the highest, compared with whites. Mediation analyses suggested that stage at diagnosis had the greatest influence on overall racial/ethnic survival disparities accounting for 24% of disparities in breast cancer, 24% in prostate cancer, and 16% to 30% in colorectal cancer. Neighborhood socioeconomic status was an important factor in all cancers, but only for black and Hispanic patients. The influence of marital status on racial/ethnic disparities was stronger in men than in women. Adjustment for all covariables explained approximately half of the overall survival disparities in breast, prostate, and colorectal cancer, but it explained only 15% to 40% of disparities in lung cancer. Conclusion Overall reductions in racial/ethnic survival disparities were driven largely by reductions for black compared with white patients. Stage at diagnosis had the largest effect on racial/ethnic survival disparities, but earlier detection would not entirely eliminate them. The influences

  11. Inherited variation at MC1R and ASIP and association with melanoma-specific survival.

    Science.gov (United States)

    Taylor, Nicholas J; Reiner, Anne S; Begg, Colin B; Cust, Anne E; Busam, Klaus J; Anton-Culver, Hoda; Dwyer, Terence; From, Lynn; Gallagher, Richard P; Gruber, Stephen B; Rosso, Stefano; White, Kirsten A; Zanetti, Roberto; Orlow, Irene; Thomas, Nancy E; Rebbeck, Timothy R; Berwick, Marianne; Kanetsky, Peter A

    2015-06-01

    Melanocortin-1 receptor (MC1R) is a marker of melanoma risk in populations of European ancestry. However, MC1R effects on survival are much less studied. We investigated associations between variation at MC1R and survival in an international, population-based series of single primary melanoma patients enrolled into the Genes, Environment, and Melanoma study. MC1R genotype data was available for 2,200 participants with a first incident primary melanoma diagnosis. We estimated the association of MC1R genotypes with melanoma-specific survival (i.e., death caused by melanoma) and overall survival using COX proportional hazards modeling, adjusting for established prognostic factors for melanoma. We also conducted stratified analyses by Breslow thickness, tumor site, phenotypic index, and age. In addition, we evaluated haplotypes involving polymorphisms near the Agouti signaling protein gene (ASIP) locus for their impacts on survival. Melanoma-specific survival was inversely associated with carriage of MC1R variants in the absence of consensus alleles compared to carriage of at least one consensus allele (hazard ratio (HR) = 0.60; 95% confidence interval (CI): 0.40, 0.90). MC1R results for overall survival were consistent with no association. We did not observe any statistical evidence of heterogeneity of effect estimates in stratified analyses. We observed increased hazard of melanoma-specific death among carriers of the risk haplotype TG near the ASIP locus (HR = 1.37; 95% CI: 0.91, 2.04) when compared to carriers of the most common GG haplotype. Similar results were noted for overall survival. Upon examining the ASIP TG/TG diplotype, we observed considerably increased hazard of melanoma-specific death (HR = 5.11; 95% CI: 1.88, 13.88) compared to carriers of the most common GG/GG diplotype. Our data suggest improved melanoma-specific survival among carriers of two inherited MC1R variants. © 2014 UICC.

  12. Circulating 25-hydroxyvitamin D and survival in women with ovarian cancer.

    Science.gov (United States)

    Webb, Penelope M; de Fazio, Anna; Protani, Melinda M; Ibiebele, Torukiri I; Nagle, Christina M; Brand, Alison H; Blomfield, Penelope I; Grant, Peter; Perrin, Lewis C; Neale, Rachel E

    2015-07-01

    Vitamin D status might be associated with cancer survival. Survival after ovarian cancer is poor, but the association with vitamin D has rarely been examined. We evaluated the association between serum 25-hydroxyvitamin D [25(OH)D], a marker of vitamin D status, and ovarian cancer survival. Participants were women with invasive ovarian cancer diagnosed between 2002 and 2005 who participated in the Australian Ovarian Cancer Study. Serum samples, collected at diagnosis (n = 670) or after completion of primary treatment and before recurrence (n = 336), were assayed for 25(OH)D. Sociodemographic, dietary, and lifestyle data came from questionnaires self-completed at recruitment, and clinical and survival data were from medical records, supplemented by linkage to the Australian National Death Index (October 2011). Cox proportional hazards regression was used to estimate HRs and 95% CIs for the association between circulating 25(OH)D and survival. Overall, 59% of the women died during follow-up, with 95% of deaths resulting from ovarian cancer. Circulating 25(OH)D concentrations (mean: 44 nmol/L) were significantly associated with age, state of residence, season of blood collection, and body mass index but not with tumor histology, stage or grade, or comorbidities. Higher 25(OH)D concentrations at diagnosis were significantly associated with longer survival (adjusted HR: 0.93; 95% CI: 0.88, 0.99 per 10 nmol/L), but there was no significant association with progression-free survival or for 25(OH)D measured after primary treatment. In our cohort, higher serum 25(OH)D concentrations at diagnosis were associated with longer survival among women with ovarian cancer. If confirmed in other studies, this suggests that vitamin D status at diagnosis may be an independent predictor of prognosis. Furthermore, if the association is found to be causal, improving vitamin D status may improve ovarian cancer survival rates. © 2015 American Society for Nutrition.

  13. Survival of patients with ovarian cancer in central and northern Denmark, 1998-2009.

    Science.gov (United States)

    Grann, Anne Fia; Nørgaard, Mette; Blaakær, Jan; Søgaard-Andersen, Erik; Jacobsen, Jacob Bonde

    2011-01-01

    To examine time trends of survival and mortality of ovarian cancer in the central and northern Denmark regions during the period 1998-2009. We conducted a cohort study including women recorded with a first-time diagnosis of ovarian cancer in the Danish National Registry of Patients (DNRP) between 1998 and 2009. Patients were followed for survival through the Danish Civil Registration System. We determined survival stratified by age, and used Cox proportional hazard regression analyses to obtain mortality rate ratios (MRRs) to assess changes over time. We found no improvement in overall ovarian cancer survival between 1998 and 2009. One-year survival was 71% in 1998-2000 and 68% in 2007-2009. Three-year survival declined from 48% in 1998-2000 to 46% in 2007-2009 (predicted), and 5-year survival declined from 40% in 1998-2000 to 37% in 2007-2009 (predicted). Compared with the period 1998-2000, the age-adjusted 1-year MRR was 1.05 (95% confidence interval CI: 0.86-1.28) for the period 2007-2009, and the predicted age-adjusted 3- and 5-year MRRs were 0.96 (95% CI: 0.83-1.12) and 0.99 (95% CI: 0.86-1.14), respectively. Results are not adjusted for tumor stage as this information was not available. We also observed a decline in the annual number of incident ovarian cancer patients during the study period, most pronounced in the youngest age group. The survival of ovarian cancer patients did not improve during the study period. This lack of improvement contrasts with the national cancer strategies implemented during this last decade, focusing on improving the survival of ovarian cancer patients.

  14. Health-Related Quality of Life and Survival of Cholangiocarcinoma Patients in Northeastern Region of Thailand.

    Directory of Open Access Journals (Sweden)

    Somkiattiyos Woradet

    Full Text Available In northeast Thailand, cholangiocarcinoma (CCA is a major cause of mortality. Patients with CCA have a poor prognosis and short-term survival. The purpose of this study was to investigate the association between health-related quality of life (HRQOL and survival time, and to explore whether change in HRQOL score is related to survival among CCA patients. The study was performed between February 2011 and January 2012, and included 171 patients with newly diagnosed CCA from 5 tertiary hospitals in four provinces of northeast Thailand. The HRQOL was measured at baseline, 1 month, and 2 months after diagnosis by the FACT-Hep questionnaire (Thai version 4. The outcome was survival time from diagnosis. Cox's proportional hazard model was used to evaluate the association between HRQOL and survival time. A higher overall score on HRQOL was associated with a significantly better survival (HR per 5 units increase in HRQOL was 0.92, 95% CI: 0.88-0.96. Two of the separate domains contributing to the overall HRQOL-functional well-being and hepatobiliary cancer subscale-were found to have independent effects on survival, even after adjustment for potential confounding variables, and the other domains of HRQOL. CCA patient whose HRQOL scores had improved (≥9 units at the 1st month of follow up had a reduced probability of dying from the disease (HR: 0.56, 0.32-0.95 after adjustment for the same confounding factors. A positive association between HRQOL at diagnosis and survival time was found. An improvement in HRQOL score in the first months after diagnosis further increases survival.

  15. Tobacco Cessation May Improve Lung Cancer Patient Survival.

    Science.gov (United States)

    Dobson Amato, Katharine A; Hyland, Andrew; Reed, Robert; Mahoney, Martin C; Marshall, James; Giovino, Gary; Bansal-Travers, Maansi; Ochs-Balcom, Heather M; Zevon, Michael A; Cummings, K Michael; Nwogu, Chukwumere; Singh, Anurag K; Chen, Hongbin; Warren, Graham W; Reid, Mary

    2015-07-01

    This study characterizes tobacco cessation patterns and the association of cessation with survival among lung cancer patients at Roswell Park Cancer Institute: an NCI Designated Comprehensive Cancer Center. Lung cancer patients presenting at this institution were screened with a standardized tobacco assessment, and those who had used tobacco within the past 30 days were automatically referred to a telephone-based cessation service. Demographic, clinical information, and self-reported tobacco use at last contact were obtained via electronic medical records and the Roswell Park Cancer Institute tumor registry for all lung cancer patients referred to the service between October 2010 and October 2012. Descriptive statistics and Cox proportional hazards models were used to assess whether tobacco cessation and other factors were associated with lung cancer survival through May 2014. Calls were attempted to 313 of 388 lung cancer patients referred to the cessation service. Eighty percent of patients (250 of 313) were successfully contacted and participated in at least one telephone-based cessation call; 40.8% (102 of 250) of persons contacted reported having quit at the last contact. After controlling for age, pack year history, sex, Eastern Cooperative Oncology Group performance status, time between diagnosis and last contact, tumor histology, and clinical stage, a statistically significant increase in survival was associated with quitting compared with continued tobacco use at last contact (HR = 1.79; 95% confidence interval: 1.14-2.82) with a median 9 month improvement in overall survival. Tobacco cessation among lung cancer patients after diagnosis may increase overall survival.

  16. Germline Genetic Variants and Lung Cancer Survival in African Americans.

    Science.gov (United States)

    Jones, Carissa C; Bush, William S; Crawford, Dana C; Wenzlaff, Angela S; Schwartz, Ann G; Wiencke, John K; Wrensch, Margaret R; Blot, William J; Chanock, Stephen J; Grogan, Eric L; Aldrich, Melinda C

    2017-08-01

    Background: African Americans have the highest lung cancer mortality in the United States. Genome-wide association studies (GWASs) of germline variants influencing lung cancer survival have not yet been conducted with African Americans. We examined five previously reported GWAS catalog variants and explored additional genome-wide associations among African American lung cancer cases. Methods: Incident non-small cell lung cancer cases ( N = 286) in the Southern Community Cohort Study were genotyped on the Illumina HumanExome BeadChip. We used Cox proportional hazards models to estimate HRs and 95% confidence intervals (CIs) for overall mortality. Two independent African American studies ( N = 316 and 298) were used for replication. Results: One previously reported variant, rs1878022 on 12q23.3, was significantly associated with mortality (HR = 0.70; 95% CI: 0.54-0.92). Replication findings were in the same direction, although attenuated (HR = 0.87 and 0.94). Meta-analysis had a HR of 0.83 (95% CI, 0.71-0.97). Analysis of common variants identified an association between chromosome 6q21.33 and mortality (HR = 0.46; 95% CI, 0.33-0.66). Conclusions: We identified an association between rs1878022 in CMKLR1 and lung cancer survival. However, our results in African Americans have a different direction of effect compared with a prior study in European Americans, suggesting a different genetic architecture or presence of gene-environment interactions. We also identified variants on chromosome 6 within the gene-rich HLA region, which has been previously implicated in lung cancer risk and survival. Impact: We found evidence that inherited genetic risk factors influence lung cancer survival in African Americans. Replication in additional populations is necessary to confirm potential genetic differences in lung cancer survival across populations. Cancer Epidemiol Biomarkers Prev; 26(8); 1288-95. ©2017 AACR . ©2017 American Association for Cancer Research.

  17. Diurnal cortisol and survival in epithelial ovarian cancer.

    Science.gov (United States)

    Schrepf, Andrew; Thaker, Premal H; Goodheart, Michael J; Bender, David; Slavich, George M; Dahmoush, Laila; Penedo, Frank; DeGeest, Koen; Mendez, Luis; Lubaroff, David M; Cole, Steven W; Sood, Anil K; Lutgendorf, Susan K

    2015-03-01

    Hypothalamic-pituitary-adrenal (HPA) deregulation is commonly observed in cancer patients, but its clinical significance is not well understood. We prospectively examined the association between HPA activity, tumor-associated inflammation, and survival in ovarian cancer patients prior to treatment. Participants were 113 women with ovarian cancer who provided salivary cortisol for three days prior to treatment for calculation of cortisol slope, variability, and night cortisol. Cox proportional hazard regression analyses were used to examine associations between cortisol and survival in models adjusting for disease stage, tumor grade, cytoreduction and age. On a subsample of 41 patients with advanced disease ascites fluid was assayed for levels of interleukin-6 (IL-6) and correlated with cortisol variables. Each cortisol measure was associated with decreased survival time, adjusting for covariates (all pcortisol was associated with a 46% greater likelihood of death. Patients in the high night cortisol group survived an estimated average of 3.3 years compared to 7.3 years for those in the low night cortisol group. Elevated ascites IL-6 was associated with each cortisol measure (all r>36, all pcortisol rhythms assessed prior to treatment are associated with decreased survival in ovarian cancer and increased inflammation in the vicinity of the tumor. HPA abnormalities may reflect poor endogenous control of inflammation, dysregulation caused by tumor-associated inflammation, broad circadian disruption, or some combination of these factors. Nocturnal cortisol may have utility as a non-invasive measure of HPA function and/or disease severity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. 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.

  19. Opioids, survival, and advanced cancer in the hospice setting.

    Science.gov (United States)

    Azoulay, Daniel; Jacobs, Jeremy M; Cialic, Ron; Mor, Eliana Ein; Stessman, Jochanan

    2011-02-01

    Although pain is common among advanced cancer patients, it can be controlled in a large proportion of patients. Several barriers hinder this, including the concern that opioids hasten death. We examined whether opioids influence survival among advanced cancer patients. Retrospective observational study from September 2006 to October 2007. In-patient hospice unit. Participants were 114 consecutive hospice patients (mean age 71.7 ± 13.9 years). Analysis of survival (days) following admission, according to opioid usage. Standardized Oral Morphine Equivalents (OME mg/d) were calculated. On admission 74.6% received opioids, rising to 92.1% at death. Mean opioid dosage was OME of 146 ± 245 mg/d, and mean survival was 12.3 ± 12.15 days. Mean survival, according to opioid dosage of 0, 1 to 119, and greater than or equal to 120 OME mg/d respectively at admission, was 16.7 ± 13.4, 11.2 ± 12.1, 10.0 ± 10.2 (P = .009), and according to dose at death was 17.0 ± 15.1, 12.3 ± 12.1, 11.1 ± 11.3 (P = ns). Increasing overall opioid dosage was associated with improved survival compared with no change or decreasing overall dosage (mean survival 14.0 ± 12.7 days versus 9.3 ± 9.8 versus 9.1 ± 11.4, days respectively, P = .01). Adjusting for clinical variables in Cox proportional hazards models, no significant association was found between mortality and of the following aspects of opioid usage: (1) dose on admission (Hazard Ratio [HR] 1.009, 95% confidence interval [CI] 0.999-1.019); (2) dose at death (HR 1.004, 95% CI 0.996-1.013); (3) mean dose (HR 1.006, 95% CI 0.997-1.016); (4) overall dose increase (HR 0.733, 95% CI 0.417-1.288) and decrease (HR 0.967, 95% CI 0.472-1.984); (5) day-by-day dosage changes (HR 1.005, 95% CI 0.996-1.013). Opioid usage, even at high dosages, had no effect on survival among advanced cancer patients in a hospice setting. Copyright © 2011 American Medical Directors Association. Published by Elsevier Inc. All rights reserved.

  20. Light induces translocation of NF-κB p65 to the mitochondria and suppresses expression of cytochrome c oxidase subunit III (COX III) in the rat retina

    Energy Technology Data Exchange (ETDEWEB)

    Tomita, Hiroshi, E-mail: htomita@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Soft-Path Engineering Research Center (SPERC), Faculty of Science and Engineering, Iwate University, Morioka 020-8551 (Japan); Clinical Research, Innovation and Education Center, Tohoku University Hospital, 1-1 Seiryo, Aoba, Sendai, Miyagi 980-8574 (Japan); Tabata, Kitako, E-mail: ktabata@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Takahashi, Maki, E-mail: mqdelta@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Nishiyama, Fumiaki, E-mail: t2114018@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Sugano, Eriko, E-mail: sseriko@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Soft-Path Engineering Research Center (SPERC), Faculty of Science and Engineering, Iwate University, Morioka 020-8551 (Japan)

    2016-05-13

    The transcription factor nuclear factor kappaB (NF-κB) plays various roles in cell survival, apoptosis, and inflammation. In the rat retina, NF-κB activity increases after exposure to damaging light, resulting in degeneration of photoreceptors. Here, we report that in dark-adapted rats exposed for 6 h to bright white light, the p65 subunit of retinal NF-κB translocates to the mitochondria, an event associated with a decrease in expression of cytochrome c oxidase subunit III (COX III). However, sustained exposure for 12 h depleted p65 from the mitochondria, and enhanced COX III expression. Treatment with the protective antioxidant PBN prior to light exposure prevents p65 depletion in the mitochondria and COX III upregulation during prolonged exposure, and apoptosis in photoreceptor cells. These results indicate that COX III expression is sensitive to the abundance of NF-κB p65 in the mitochondria, which, in turn, is affected by exposure to damaging light. - Highlights: • Damaging light exposure of the retina induces NF-κB p65 mitochondrial translocation. • NF-κB p65 mitochondrial translocation is associated with the decrease of COX III expression. • Prolonged light exposure depletes mitochondrial p65 resulting in the increase in COX III expression. • NF-κB p65 and COX III expression play an important role in the light-induced photoreceptor degeneration.

  1. Trends of Incidence and Survival of Gastrointestinal Neuroendocrine Tumors in the United States: A Seer Analysis

    Directory of Open Access Journals (Sweden)

    Vassiliki L. Tsikitis, Betsy C. Wertheim, Marlon A. Guerrero

    2012-01-01

    Full Text Available OBJECTIVES: To examine trends in detection and survival of hollow viscus gastrointestinal neuroendocrine tumors (NETs across time and geographic regions of the U.S.METHODS: We used the Surveillance, Epidemiology and End Results (SEER database to investigate 19,669 individuals with newly diagnosed gastrointestinal NETs. Trends in incidence were tested using Poisson regression. Cox proportional hazards regression was used to examine survival.RESULTS: Incidence increased over time for NETs of all gastrointestinal sites (all P < 0.001, except appendix. Rates have risen faster for NETs of the small intestine and rectum than stomach and colon. Rectal NETs were detected at a faster pace among blacks than whites (P < 0.001 and slower in the East than other regions (P < 0.001. We observed that appendiceal and rectal NETs carry the best prognosis and survival of small intestinal and colon NETs has improved for both men and women. Colon NETs showed different temporal trends in survival according to geographic region (Pinteraction = 0.028. Improved prognosis was more consistent across the country for small intestinal NETs.CONCLUSIONS: Incidence of gastrointestinal NETs has increased, accompanied by inconsistently improved survival for different anatomic sites among certain groups defined by race and geographic region.

  2. The effect of clinical performance on the survival estimates of direct restorations

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    Kyou-Li Kim

    2013-02-01

    Full Text Available Objectives In most retrospective studies, the clinical performance of restorations had not been considered in survival analysis. This study investigated the effect of including the clinically unacceptable cases according to modified United States Public Health Service (USPHS criteria into the failed data on the survival analysis of direct restorations as to the longevity and prognostic variables. Materials and Methods Nine hundred and sixty-seven direct restorations were evaluated. The data of 204 retreated restorations were collected from the records, and clinical performance of 763 restorations in function was evaluated according to modified USPHS criteria by two observers. The longevity and prognostic variables of the restorations were compared with a factor of involving clinically unacceptable cases into the failures using Kaplan-Meier survival analysis and Cox proportional hazard model. Results The median survival times of amalgam, composite resin and glass ionomer were 11.8, 11.0 and 6.8 years, respectively. Glass ionomer showed significantly lower longevity than composite resin and amalgam. When clinically unacceptable restorations were included into the failure, the median survival times of them decreased to 8.9, 9.7 and 6.4 years, respectively. Conclusions After considering the clinical performance, composite resin was the only material that showed a difference in the longevity (p < 0.05 and the significantly higher relative risk of student group than professor group disappeared in operator groups. Even in the design of retrospective study, clinical evaluation needs to be included.

  3. Does Lung Donation by Heart Donors Have an Impact on Survival in Heart Transplant Recipients?

    Science.gov (United States)

    Xia, Y; Friedmann, P; Bello, R; Goldstein, D; D'Alessandro, D

    2017-02-01

    Lung procurement is increasing during multiorgan recovery and substantially alters the explant process. This study evaluated whether lung donation by a heart donor affects survival in heart transplant recipients. Retrospective analysis of United Network for Organ Sharing (UNOS) adult heart transplantation data from 1998 to 2012 was performed. Lung donors (LDs) were defined as those having at least one lung procured and transplanted. Non-LDs had neither lung transplanted. Heart transplant recipients who had previous transplants, who had heterotopic transplants, who were waitlisted for other organs or who were temporarily delisted were excluded from the analysis. Kaplan-Meier survival analysis and Cox proportional hazards regression were performed. Of 23 590 heart transplant recipients meeting criteria during the study period, 8638 (36.6%) transplants were from LDs. Donors in the LD group had less history of cigarette use (15.5% vs. 29.5%, p < 0.001). On univariate analysis, LDs were associated with improved patient survival (p < 0.001). On multivariate analysis, LDs were not significantly associated with patient survival (adjusted hazard ratio 0.98, 95% confidence interval 0.94-1.03). Analysis of the UNOS registry suggested that donor pulmonary status and lung procurement had no detrimental effect on survival in heart transplant recipients, supporting the present practice of using donor lungs whenever possible. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  4. Sociodemographic disparities in survival for adolescents and young adults with cancer differ by health insurance status.

    Science.gov (United States)

    DeRouen, Mindy C; Parsons, Helen M; Kent, Erin E; Pollock, Brad H; Keegan, Theresa H M

    2017-08-01

    To investigate associations of sociodemographic factors-race/ethnicity, neighborhood socioeconomic status (SES), and health insurance-with survival for adolescents and young adults (AYAs) with invasive cancer. Data on 80,855 AYAs with invasive cancer diagnosed in California 2001-2011 were obtained from the California Cancer Registry. We used multivariable Cox proportional hazards regression to estimate overall survival. Associations of public or no insurance with greater risk of death were observed for 11 of 12 AYA cancers examined. Compared to Whites, Blacks experienced greater risk of death, regardless of age or insurance, while greater risk of death among Hispanics and Asians was more apparent for younger AYAs and for those with private/military insurance. More pronounced neighborhood SES disparities in survival were observed among AYAs with private/military insurance, especially among younger AYAs. Lacking or having public insurance was consistently associated with shorter survival, while disparities according to race/ethnicity and neighborhood SES were greater among AYAs with private/military insurance. While health insurance coverage associates with survival, remaining racial/ethnic and socioeconomic disparities among AYAs with cancer suggest additional social factors also need consideration in intervention and policy development.

  5. Long-term survival outcomes by smoking status in surgical and nonsurgical patients with non-small cell lung cancer: comparing never smokers and current smokers.

    Science.gov (United States)

    Meguid, Robert A; Hooker, Craig M; Harris, James; Xu, Li; Westra, William H; Sherwood, J Timothy; Sussman, Marc; Cattaneo, Stephen M; Shin, James; Cox, Solange; Christensen, Joani; Prints, Yelena; Yuan, Nance; Zhang, Jennifer; Yang, Stephen C; Brock, Malcolm V

    2010-09-01

    Survival outcomes of never smokers with non-small cell lung cancer (NSCLC) who undergo surgery are poorly characterized. This investigation compared surgical outcomes of never and current smokers with NSCLC. This investigation was a single-institution retrospective study of never and current smokers with NSCLC from 1975 to 2004. From an analytic cohort of 4,546 patients with NSCLC, we identified 724 never smokers and 3,822 current smokers. Overall, 1,142 patients underwent surgery with curative intent. For survival analysis by smoking status, hazard ratios (HRs) were estimated using Cox proportional hazard modeling and then further adjusted by other covariates. Never smokers were significantly more likely than current smokers to be women (P cancer diagnosis has little impact on the long-term survival of patients with NSCLC, especially after curative surgery. Despite different etiologies between lung cancer in never and current smokers the prognosis is equally dismal.

  6. Influence of socioeconomic factors on survival after breast cancer-A nationwide cohort study of women diagnosed with breast cancer in Denmark 1983-1999

    DEFF Research Database (Denmark)

    Dalton, Susanne Oksbjerg; Ross, Lone; During, M.

    2007-01-01

    The reasons for social inequality in breast cancer survival are far from established. Our study aims to study the importance of a range of socioeconomic factors and comorbid disorders on survival after breast cancer surgery in Denmark where the health care system is tax-funded and uniform. All 25......,897 Danish women who underwent protocol-based treatment for breast cancer in 1983-1999 were identified in a clinical database and information on socioeconomic variables and both somatic and psychiatric comorbid disorders was obtained from population-based registries. We used Cox proportional hazards models...... to estimate the association between socioeconomic position and overall survival and further to analyse breast cancer specific deaths in a competing risk set-up regarding all other causes of death as competing risks. The adjusted hazard ratio (HR) for death was reduced in women with higher education (HR, 0...

  7. Proportional loss functions for debris flow events

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    C. M. Rheinberger

    2013-08-01

    Full Text Available Quantitative risk assessments of debris flows and other hydrogeological hazards require the analyst to predict damage potentials. A common way to do so is by use of proportional loss functions. In this paper, we analyze a uniquely rich dataset of 132 buildings that were damaged in one of five large debris flow events in Switzerland. Using the double generalized linear model, we estimate proportional loss functions that may be used for various prediction purposes including hazard mapping, landscape planning, and insurance pricing. Unlike earlier analyses, we control for confounding effects of building characteristics, site specifics, and process intensities as well as for overdispersion in the data. Our results suggest that process intensity parameters are the most meaningful predictors of proportional loss sizes. Cross-validation tests suggest that the mean absolute prediction errors of our models are in the range of 11%, underpinning the accurateness of the approach.

  8. The effect of comorbidity on the use of adjuvant chemotherapy and survival from colon cancer: a retrospective cohort study

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    Purdie Gordon

    2009-04-01

    Full Text Available Abstract Background Comorbidity has a well documented detrimental effect on cancer survival. However it is difficult to disentangle the direct effects of comorbidity on survival from indirect effects via the influence of comorbidity on treatment choice. This study aimed to assess the impact of comorbidity on colon cancer patient survival, the effect of comorbidity on treatment choices for these patients, and the impact of this on survival among those with comorbidity. Methods This retrospective cohort study reviewed 589 New Zealanders diagnosed with colon cancer in 1996–2003, followed until the end of 2005. Clinical and outcome data were obtained from clinical records and the national mortality database. Cox proportional hazards and logistic regression models were used to assess the impact of comorbidity on cancer specific and all-cause survival, the effect of comorbidity on chemotherapy recommendations for stage III patients, and the impact of this on survival among those with comorbidity. Results After adjusting for age, sex, ethnicity, area deprivation, smoking, stage, grade and site of disease, higher Charlson comorbidity score was associated with poorer all-cause survival (HR = 2.63 95%CI:1.82–3.81 for Charlson score ≥ 3 compared with 0. Comorbidity count and several individual conditions were significantly related to poorer all-cause survival. A similar, but less marked effect was seen for cancer specific survival. Among patients with stage III colon cancer, those with a Charlson score ≥ 3 compared with 0 were less likely to be offered chemotherapy (19% compared with 84% despite such therapy being associated with around a 60% reduction in excess mortality for both all-cause and cancer specific survival in these patients. Conclusion Comorbidity impacts on colon cancer survival thorough both physiological burden of disease and its impact on treatment choices. Some patients with comorbidity may forego chemotherapy unnecessarily

  9. Dose escalation of radiotherapy for metastatic spinal cord compression (MSCC) in patients with relatively favorable survival prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Rades, Dirk [Luebeck Univ. (Germany). Dept. of Radiation Oncology; Hamburg Univ. (Germany). Dept. of Radiation Oncology; Panzner, Annika [Luebeck Univ. (Germany). Dept. of Radiation Oncology; Rudat, Volker [Saad Specialist Hospital, Al-Khobar (Saudi Arabia). Dept. of Radiation Oncology; Hamburg Univ. (Germany). Dept. of Radiation Oncology; Karstens, Johann H. [Medical School Hannover (Germany). Dept. of Radiation Oncology; Schild, Steven E. [Mayo Clinic, Scottsdale, AZ (United States). Dept. of Radiation Oncology

    2011-11-15

    Local control of metastatic spinal cord compression (MSCC) is particularly important for long-term survivors. Radiotherapy alone is the most common treatment for MSCC. The most frequently used schedule world wide is 30 Gy/10 fractions. This study investigated whether patients with favorable survival prognoses benefit from a dose escalation beyond 30 Gy. Data from 191 patients treated with 30 Gy/10 fractions were matched to 191 patients (1:1) receiving higher doses (37.5 Gy/15 fractions or 40 Gy/20 fractions). All patients had favorable survival prognoses based on a validated scoring system and were matched for age, gender, tumor type, performance status, number of involved vertebrae, visceral or other bone metastases, interval from tumor diagnosis to radiotherapy, ambulatory status, and time developing motor deficits. Both groups were compared for local control, progression-free survival, overall survival, and functional outcome. Local control rates at 2 years were 71 % after 30 Gy and 92 % after higher doses (p = 0.012). Two-year progression-free survival rates were 68 % and 90 %, respectively (p = 0.013). Two-year overall survival rates were 53 % and 68 %, respectively (p = 0.032). Results maintained significance in the multivariate analyses (Cox proportional hazards model; stratified model) with respect to local control (p = 0.011; p = 0.012), progression-free survival (p = 0.010; p = 0.018), and overall survival (p = 0.014; p = 0.015). Functional outcome was similar in both groups. Motor function improved in 40 % of patients after 30 Gy and 41 % after higher doses (p = 0.98). Escalation of the radiation dose beyond 30 Gy resulted in significantly better local control, progression-free survival, and overall survival in patients with favorable survival prognoses. (orig.)

  10. Induction regimen and survival in simultaneous heart-kidney transplant recipients.

    Science.gov (United States)

    Ariyamuthu, Venkatesh K; Amin, Alpesh A; Drazner, Mark H; Araj, Faris; Mammen, Pradeep P A; Ayvaci, Mehmet; Mete, Mutlu; Ozay, Fatih; Ghanta, Mythili; Mohan, Sumit; Mohan, Prince; Tanriover, Bekir

    2017-11-15

    Induction therapy in simultaneous heart-kidney transplantation (SHKT) is not well studied in the setting of contemporary maintenance immunosuppression consisting of tacrolimus (TAC), mycophenolic acid (MPA), and prednisone (PRED). We analyzed the Organ Procurement and Transplant Network registry from January 1, 2000, to March 3, 2015, for recipients of SHKT (N = 623) maintained on TAC/MPA/PRED at hospital discharge. The study cohort was further stratified into 3 groups by induction choice: induction (n = 232), rabbit anti-thymoglobulin (r-ATG; n = 204), and interleukin-2 receptor-α (n = 187) antagonists. Survival rates were estimated using the Kaplan-Meier estimator. Multivariable inverse probability weighted Cox proportional hazard regression models were used to assess hazard ratios associated with post-transplant mortality as the primary outcome. The study cohort was censored on March 4, 2016, to allow at least 1-year of follow-up. During the study period, the number of SHKTs increased nearly 5-fold. The Kaplan-Meier survival curve showed superior outcomes with r-ATG compared with no induction or interleukin-2 receptor-α induction. Compared with the no-induction group, an inverse probability weighted Cox proportional hazard model showed no independent association of induction therapy with the primary outcome. In sub-group analysis, r-ATG appeared to lower mortality in sensitized patients with panel reactive antibody of 10% or higher (hazard ratio, 0.19; 95% confidence interval, 0.05-0.71). r-ATG may provide a survival benefit in SHKT, especially in sensitized patients maintained on TAC/MPA/PRED at hospital discharge. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  11. Evaluation of the immunoexpression of COX-1, COX-2 and p53 in Crohn's disease Avaliação da imunoexpressão de COX-1, COX-2 e p53 na doença de Crohn

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    Mônica Romero

    2008-12-01

    Full Text Available BACKGROUND: Crohn's disease accompanied by nonspecific or idiopathic ulcerative proctocolitis corresponds to a condition called intestinal inflammatory disease. The immunoexpression of cyclooxygenase 2 (COX-2 in Crohn's disease becomes more marked with progression of the disease and the presence of wild-type p53 suppresses the transcription of COX-2. AIMS: To investigate the immunoexpression of cyclooxygenase 1 (COX-1, COX-2 and p53 in Crohn's ileocolitis and to correlated this expression with clinical and histopathological parameters. METHODS: Forty-five cases of Crohn's disease, 16 cases of actinic colitis (diseased-control group and 11 cases without a history of intestinal disease (normal control group were studied. Hematoxylin-eosin-stained sections were submitted to histopathological analysis and the immunohistochemical expression of COX-1, COX-2 and p53 was evaluated by the streptavidin-biotin-peroxidase method. RESULTS: Sixty percent of the Crohn's disease patients were women and 40% were men, with 75.5% whites and 25.5% non-whites. The disease involved the terminal ileum in 44.5% of cases, ileum in 33.3%, colon in 20% and duodenum-ileum in 2.2%. A significant association was observed between COX-2 immunoreactivity and age RACIONAL: A doença de Crohn, junto com a colite ulcerativa idiopática ou inespecífica constituem a doença inflamatória intestinal. A imunoexpressão de ciclooxigenase 2 (COX-2 na doença de Crohn acentua-se com a progressão da doença, enquanto que a presença do tipo selvagem de p53 suprime a transcrição de COX-2. OBJETIVOS: Investigar a imunoexpressão de ciclooxigenase 1 (COX-1, COX-2 e p53 na doença de Crohn e correlacionar os achados com parâmetros clínico-histopatológicos. MÉTODOS: Foram estudados 45 casos de doença de Crohn (grupo teste, 16 casos de colite actínica (grupo controle-doente e 11 casos sem história de doença intestinal (grupo controle normal. A avaliação histopatológica foi feita

  12. Individual patient data meta-analysis of survival data using Poisson regression models

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    Crowther Michael J

    2012-03-01

    Full Text Available Abstract Background An Individual Patient Data (IPD meta-analysis is often considered the gold-standard for synthesising survival data from clinical trials. An IPD meta-analysis can be achieved by either a two-stage or a one-stage approach, depending on whether the trials are analysed separately or simultaneously. A range of one-stage hierarchical Cox models have been previously proposed, but these are known to be computationally intensive and are not currently available in all standard statistical software. We describe an alternative approach using Poisson based Generalised Linear Models (GLMs. Methods We illustrate, through application and simulation, the Poisson approach both classically and in a Bayesian framework, in two-stage and one-stage approaches. We outline the benefits of our one-stage approach through extension to modelling treatment-covariate interactions and non-proportional hazards. Ten trials of hypertension treatment, with all-cause death the outcome of interest, are used to apply and assess the approach. Results We show that the Poisson approach obtains almost identical estimates to the Cox model, is additionally computationally efficient and directly estimates the baseline hazard. Some downward bias is observed in classical estimates of the heterogeneity in the treatment effect, with improved performance from the Bayesian approach. Conclusion Our approach provides a highly flexible and computationally efficient framework, available in all standard statistical software, to the investigation of not only heterogeneity, but the presence of non-proportional hazards and treatment effect modifiers.

  13. Individual patient data meta-analysis of survival data using Poisson regression models.

    Science.gov (United States)

    Crowther, Michael J; Riley, Richard D; Staessen, Jan A; Wang, Jiguang; Gueyffier, Francois; Lambert, Paul C

    2012-03-23

    An Individual Patient Data (IPD) meta-analysis is often considered the gold-standard for synthesising survival data from clinical trials. An IPD meta-analysis can be achieved by either a two-stage or a one-stage approach, depending on whether the trials are analysed separately or simultaneously. A range of one-stage hierarchical Cox models have been previously proposed, but these are known to be computationally intensive and are not currently available in all standard statistical software. We describe an alternative approach using Poisson based Generalised Linear Models (GLMs). We illustrate, through application and simulation, the Poisson approach both classically and in a Bayesian framework, in two-stage and one-stage approaches. We outline the benefits of our one-stage approach through extension to modelling treatment-covariate interactions and non-proportional hazards. Ten trials of hypertension treatment, with all-cause death the outcome of interest, are used to apply and assess the approach. We show that the Poisson approach obtains almost identical estimates to the Cox model, is additionally computationally efficient and directly estimates the baseline hazard. Some downward bias is observed in classical estimates of the heterogeneity in the treatment effect, with improved performance from the Bayesian approach. Our approach provides a highly flexible and computationally efficient framework, available in all standard statistical software, to the investigation of not only heterogeneity, but the presence of non-proportional hazards and treatment effect modifiers.

  14. 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

  15. Seizure following the Use of the COX-2 Inhibitor Etoricoxib

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    Valentina Arnao

    2017-01-01

    Full Text Available We describe a case of epileptic seizures occurring after the use of a COX-2 inhibitor. A 61-year-old man was admitted to our department because of a generalized tonic-clonic seizure. EEG showed generalized slowdown of the activity. Neuroimaging and blood samples studies did not evidence alterations, but a careful pharmacological history revealed that the patient had taken the COX-2 inhibitor etoricoxib to treat lumbago few days before the onset of clinical symptoms. No seizures were reported after etoricoxib discontinuation and an EEG resulted to be normal two months after this. Conclusion. Knowing the pharmacological history of a patient is important for understanding the clinical presentation and selecting appropriate treatment. This is, to the best of our knowledge, the first reported case of generalized seizures associated with the use of COX-2 inhibitors.

  16. BOX-COX REGRESSION METHOD IN TIME SCALING

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    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. Geometric anisotropic spatial point pattern analysis and Cox processes

    DEFF Research Database (Denmark)

    Møller, Jesper; Toftaker, Håkon

    We consider spatial point processes with a pair correlation function g(u) which depends only on the lag vector u between a pair of points. Our interest is in statistical models with a special kind of ‘structured’ anisotropy: g is geometric anisotropy if it is elliptical but not spherical. In part......We consider spatial point processes with a pair correlation function g(u) which depends only on the lag vector u between a pair of points. Our interest is in statistical models with a special kind of ‘structured’ anisotropy: g is geometric anisotropy if it is elliptical but not spherical....... 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...

  18. Survival outcomes in elderly men undergoing radical prostatectomy in Australia.

    Science.gov (United States)

    Ranasinghe, Weranja; Wang, Luke L; Persad, Raj; Bolton, Damien; Lawrentschuk, Nathan; Sengupta, Shomik

    2017-09-18

    To investigate the outcomes of patients older than 75 years of age in Victoria undergoing radical prostatectomy for prostate cancer. Data on all men undergoing radical prostatectomy in Victoria between 1 January 2004 and 31 December 2014 were obtained from the Victorian Cancer Registry. Tumour characteristics including Gleason grade, stage of disease and cause of death were obtained. Statistical analysis was performed using chi-squared test, Cox proportional hazards method and Kaplan-Meier analysis. A total of 14 686 men underwent radical prostatectomy during the defined period, with a median follow-up of 58 months. Of these, 332 were men over the age of 75. All parameters are comparisons between patients >75 years of age and men 75 years had a higher proportion of Gleason grade ≥8 disease (16.6% versus 11.4%, P 75 years had lower rates of 5- and 10-year overall survival (67.3% versus 96.3% and 27.7% versus 89.1%) and lower rates of 5- and 10-year prostate cancer-specific survival (96.2% versus 99.3% and 94.3% versus 97.4%), respectively. Age was an independent risk factor for prostate cancer specific and overall mortality on multivariate analysis (hazard ratio 1.49, 95% confidence interval 1.32-1.68; P < 0.001 and hazard ratio 4.26, 95% confidence interval 2.15-8.42; P < 0.001), when adjusted for stage and grade. Older men undergoing radical prostatectomy in Victoria had higher-grade disease but similar stage. Age was an independent risk factor for worse prostate cancer-specific and overall survival. © 2017 Royal Australasian College of Surgeons.

  19. Thyroid function and survival following breast cancer.

    Science.gov (United States)

    Brandt, J; Borgquist, S; Almquist, M; Manjer, J

    2016-11-01

    Thyroid function has been associated with breast cancer risk, and breast cancer cell growth and proliferation. It is not clear whether thyroid function affects prognosis following breast cancer but, if so, this could have an important clinical impact. The present study analysed prospectively collected measurements of free tri-iodothyronine (T3), free thyroxine (T4), thyroid-stimulating hormone (TSH) and thyroid peroxidase antibodies (TPO-Ab) in relation to breast cancer survival. The Malmö Diet and Cancer Study is a prospective cohort study of 17 035 women in Sweden. Study enrolment was conducted between 1991 and 1996. Patients with incident breast cancer were identified through record linkage with cancer registries until 31 December 2006. Information on vital status was collected from the Swedish Cause of Death Registry, with the endpoint breast cancer mortality (31 December 2013). Hazard ratios (HRs) with 95 per cent confidence intervals (c.i.) were obtained by Cox proportional hazards analysis. Some 766 patients with incident breast cancer were identified, of whom 551 were eligible for analysis. Compared with patients in the first free T4 tertile, breast cancer mortality was lower among those in the second tertile (HR 0·49, 95 per cent c.i. 0·28 to 0·84). There was an indication, although non-significant, of lower breast cancer mortality among patients in the second TSH tertile (HR 0·63, 0·37 to 1·09) and in those with positive TPO-Ab status (HR 0·61, 0·30 to 1·23). Free T3 showed no clear association with mortality. In the present study, there was a positive association between free T4 levels and improved breast cancer survival. © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

  20. Association of MTHFR gene polymorphisms with breast cancer survival

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    Mechanic Leah E

    2006-10-01

    Full Text Available Abstract Background Two functional single nucleotide polymorphisms (SNPs in the 5,10-methylenetetrahydrofolate reductase (MTHFR gene, C677T and A1298C, lead to decreased enzyme activity and affect chemosensitivity of tumor cells. We investigated whether these MTHFR SNPs were associated with breast cancer survival in African-American and Caucasian women. Methods African-American (n = 143 and Caucasian (n = 105 women, who had incident breast cancer with surgery, were recruited between 1993 and 2003 from the greater Baltimore area, Maryland, USA. Kaplan-Meier survival and multivariate Cox proportional hazards regression analyses were used to examine the relationship between MTHFR SNPs and disease-specific survival. Results We observed opposite effects of the MTHFR polymorphisms A1298C and C677T on breast cancer survival. Carriers of the variant allele at codon 1298 (A/C or C/C had reduced survival when compared to homozygous carriers of the common A allele [Hazard ratio (HR = 2.05; 95% confidence interval (CI, 1.05–4.00]. In contrast, breast cancer patients with the variant allele at codon 677 (C/T or T/T had improved survival, albeit not statistically significant, when compared to individuals with the common C/C genotype (HR = 0.65; 95% CI, 0.31–1.35. The effects were stronger in patients with estrogen receptor-negative tumors (HR = 2.70; 95% CI, 1.17–6.23 for A/C or C/C versus A/A at codon 1298; HR = 0.36; 95% CI, 0.12–1.04 for C/T or T/T versus C/C at codon 677. Interactions between the two MTHFR genotypes and race/ethnicity on breast cancer survival were also observed (A1298C, pinteraction = 0.088; C677T, pinteraction = 0.026. Conclusion We found that the MTHFR SNPs, C677T and A1298C, were associated with breast cancer survival. The variant alleles had opposite effects on disease outcome in the study population. Race/ethnicity modified the association between the two SNPs and breast cancer survival.

  1. No prognostic value added by vitamin D pathway SNPs to current prognostic system for melanoma survival.

    Science.gov (United States)

    Luo, Li; Orlow, Irene; Kanetsky, Peter A; Thomas, Nancy E; Fang, Shenying; Lee, Jeffrey E; Berwick, Marianne; Lee, Ji-Hyun

    2017-01-01

    The prognostic improvement attributed to genetic markers over current prognostic system has not been well studied for melanoma. The goal of this study is to evaluate the added prognostic value of Vitamin D Pathway (VitD) SNPs to currently known clinical and demographic factors such as age, sex, Breslow thickness, mitosis and ulceration (CDF). We utilized two large independent well-characterized melanoma studies: the Genes, Environment, and Melanoma (GEM) and MD Anderson studies, and performed variable selection of VitD pathway SNPs and CDF using Random Survival Forest (RSF) method in addition to Cox proportional hazards models. The Harrell's C-index was used to compare the performance of model predictability. The population-based GEM study enrolled 3,578 incident cases of cutaneous melanoma (CM), and the hospital-based MD Anderson study consisted of 1,804 CM patients. Including both VitD SNPs and CDF yielded C-index of 0.85, which provided slight but not significant improvement by CDF alone (C-index = 0.83) in the GEM study. Similar results were observed in the independent MD Anderson study (C-index = 0.84 and 0.83, respectively). The Cox model identified no significant associations after adjusting for multiplicity. Our results do not support clinically significant prognostic improvements attributable to VitD pathway SNPs over current prognostic system for melanoma survival.

  2. No prognostic value added by vitamin D pathway SNPs to current prognostic system for melanoma survival.

    Directory of Open Access Journals (Sweden)

    Li Luo

    Full Text Available The prognostic improvement attributed to genetic markers over current prognostic system has not been well studied for melanoma. The goal of this study is to evaluate the added prognostic value of Vitamin D Pathway (VitD SNPs to currently known clinical and demographic factors such as age, sex, Breslow thickness, mitosis and ulceration (CDF. We utilized two large independent well-characterized melanoma studies: the Genes, Environment, and Melanoma (GEM and MD Anderson studies, and performed variable selection of VitD pathway SNPs and CDF using Random Survival Forest (RSF method in addition to Cox proportional hazards models. The Harrell's C-index was used to compare the performance of model predictability. The population-based GEM study enrolled 3,578 incident cases of cutaneous melanoma (CM, and the hospital-based MD Anderson study consisted of 1,804 CM patients. Including both VitD SNPs and CDF yielded C-index of 0.85, which provided slight but not significant improvement by CDF alone (C-index = 0.83 in the GEM study. Similar results were observed in the independent MD Anderson study (C-index = 0.84 and 0.83, respectively. The Cox model identified no significant associations after adjusting for multiplicity. Our results do not support clinically significant prognostic improvements attributable to VitD pathway SNPs over current prognostic system for melanoma survival.

  3. Increased tumour ADC value during chemotherapy predicts improved survival in unresectable pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nishiofuku, Hideyuki; Tanaka, Toshihiro; Kichikawa, Kimihiko [Nara Medical University, Department of Radiology and IVR Center, Kashihara-city, Nara (Japan); Marugami, Nagaaki [Nara Medical University, Department of Endoscopy and Ultrasound, Kashihara-city, Nara (Japan); Sho, Masayuki; Akahori, Takahiro; Nakajima, Yoshiyuki [Nara Medical University, Department of Surgery, Kashihara-city, Nara (Japan)

    2016-06-15

    To investigate whether changes to the apparent diffusion coefficient (ADC) of primary tumour in the early period after starting chemotherapy can predict progression-free survival (PFS) or overall survival (OS) in patients with unresectable pancreatic adenocarcinoma. Subjects comprised 43 patients with histologically confirmed unresectable pancreatic cancer treated with first-line chemotherapy. Minimum ADC values in primary tumour were measured using the selected area ADC (sADC), which excluded cystic and necrotic areas and vessels, and the whole tumour ADC (wADC), which included whole tumour components. Relative changes in ADC were calculated from baseline to 4 weeks after initiation of chemotherapy. Relationships between ADC and both PFS and OS were modelled by Cox proportional hazards regression. Median PFS and OS were 6.1 and 11.0 months, respectively. In multivariate analysis, sADC change was the strongest predictor of PFS (hazard ratio (HR), 4.5; 95 % confidence interval (CI), 1.7-11.9; p = 0.002). Multivariate Cox regression analysis for OS revealed sADC change and CRP as independent predictive markers, with sADC change as the strongest predictive biomarker (HR, 6.7; 95 % CI, 2.7-16.6; p = 0.001). Relative changes in sADC could provide a useful imaging biomarker to predict PFS and OS with chemotherapy for unresectable pancreatic adenocarcinoma. (orig.)

  4. The role of COX-2 inhibitors in pain modulation.

    Science.gov (United States)

    Camu, Frederic; Shi, Lin; Vanlersberghe, Caroline

    2003-01-01

    NSAIDs are the analgesics that are most commonly used world-wide. In the past few years, there have been significant advances in explaining the mechanism of action and clinical efficacy of the drugs belonging to this pharmacological family. Recent data relating to the role of cyclo-oxygenase (COX)-2 in the development of neuronal hyperexcitability and pain hypersensitivity have opened new perspectives in our understanding of the therapeutic effects of these drugs in several painful conditions. The main objective of this brief review is to deal with some physiopathological and pharmacological aspects concerning the role of NSAIDs, with special reference to COX-2 inhibitors, in the treatment of pain.

  5. Lily Pad Doubling: Proportional Reasoning Development

    Science.gov (United States)

    Robichaux-Davis, Rebecca R.

    2017-01-01

    Progressing from additive to multiplicative thinking is critical for the development of middle school students' proportional reasoning abilities. Yet, many middle school mathematics teachers lack a thorough understanding of additive versus multiplicative situations. This article describes a sequence of instructional activities used to develop the…

  6. Using Artwork to Explore Proportional Reasoning

    Science.gov (United States)

    Bush, Sarah B.; Karp, Karen S.; Nadler, Jennifer; Gibbons, Katie

    2016-01-01

    Having an answer to "When are we ever going to use this in real life?" is important to middle school mathematics teachers. The activity described in this article awakened sixth graders' understanding of how artists use mathematics. By exploring ratio and proportionality in different paintings, students realized the use of proportional…

  7. Author: IM Rautenbach PROPORTIONALITY AND THE LIMITATION ...

    African Journals Online (AJOL)

    10332324

    , and they refer to other ... basis of all different constitutional languages and cultures".3 Cohen-Eliya and Porat describe proportionality as ... with reference to its German origin6 and its application in Western Europe, on the one hand, and the ...

  8. Large-Scale Analysis of Art Proportions

    DEFF Research Database (Denmark)

    Jensen, Karl Kristoffer

    2014-01-01

    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...

  9. Factors predicting resource utilization and survival after major amputation.

    Science.gov (United States)

    Henry, Antonia J; Hevelone, Nathanael D; Hawkins, Alexander T; Watkins, Michael T; Belkin, Michael; Nguyen, Louis L

    2013-03-01

    Major amputation is associated with increased short-term healthcare resource utilization (RU), early mortality, and socioeconomic status (SES) disparities. Our objective is to study patient-specific and SES-related predictors of long-term RU and survival after amputation. This retrospective analysis identified 364 adult patients who underwent index major amputation for critical limb ischemia from January 1995 through December 2000 at two tertiary centers with outcomes through December 2010. Age, gender, SES (race, income, insurance, and marital status), comorbidities (congestive heart failure [CHF], diabetes, diabetes with complications, and renal failure [RF]), subsequent procedures, cumulative length of stay (cLOS), and mortality were analyzed. Bivariate and multivariate Poisson regression for subsequent procedures and cLOS and Cox proportional hazard modeling for all-cause mortality were undertaken. During a mean follow-up of 3.25 years, amputation patients had mean cLOS of 71.2 days per person-year (median, 17.6), 19.5 readmissions per person-year (median, 2.1), 0.57 amputation-related procedures (median, 0), and 0.31 cardiovascular procedures (median, 0). Below-knee amputation as the index procedure was performed in 70% of patients, and 25% had additional amputation procedures. Of readmissions at ≤ 30 days, 52% were amputation-related. Overall mortality during follow-up was 86.9%; 37 patients (10.2%) died within 30 days. Among patients surviving >30 days, multivariate Poisson regression demonstrated that younger age (incidence rate ratio [IRR], 0.98), public insurance (IRR, 1.63), CHF (IRR, 1.60), and RF (IRR, 2.12) were associated with increased cLOS. Diabetes with complications (IRR, 1.90) and RF (IRR, 2.47) affected subsequent amputation procedures. CHF (IRR, 1.83) and RF (IRR, 3.67) were associated with a greater number of cardiovascular procedures. Cox proportional hazard modeling indicated older age (hazard ratio [HR], 1.04), CHF (HR, 2.26), and RF (HR

  10. COX-1 and COX-2 inhibition in horse blood by phenylbutazone, flunixin, carprofen and meloxicam: an in vitro analysis.

    Science.gov (United States)

    Beretta, C; Garavaglia, G; Cavalli, M

    2005-10-01

    We report on the inhibitory activity of the NSAIDs meloxicam, carprofen, phenylbutazone and flunixin, on blood cyclooxygenases in the horse using in vitro enzyme-linked assays. As expected, comparison of IC50 indicated that meloxicam and carprofen are more selective inhibitors of COX-2 than phenylbutazone and flunixin; meloxicam was the most advantageous for horses of four NSAIDs examined. However at IC80, phenylbutazone (+134.4%) and flunixin (+29.7%) had greater COX-2 selectivity than at IC50, and meloxicam (-41.2%) and carprofen (-12.9%) had lower COX-2 selectivity than at IC50. We therefore propose that the selectivity of NSAIDs should be assessed at the 80% as well as 50% inhibition level.

  11. The McGill Brisbane Symptom Score in relation to survival in pancreatic adenocarcinoma: a validation study.

    Science.gov (United States)

    Doi, Suhail A R; Furuya-Kanamori, Luis; Engel, Jessica M; Jamal, Mohammad H; Stankowski, Rachel V; Barkun, Jeffrey; Onitilo, Adedayo A

    2016-07-01

    The McGill Brisbane Symptom Score (MBSS) is a clinical score for pancreatic cancer patients upon initial presentation that takes into account four variables (weight loss, abdominal pain, jaundice, and history of smoking) to stratify them into two MBSS intensity categories. Several studies have suggested that these categories are strongly associated with eventual survival in patients with resectable (rPCa) and unresectable (uPCa) pancreatic cancer. This study aimed to validate the MBSS in a cohort of patients with pancreatic cancer from a single institution. Survival time by resection status and MBSS intensity category were analyzed among 633 patients from our institution between 2001 and 2010. Hazard ratios for death using Cox proportional hazards models, with age as the timescale, adjustment for sex and year of diagnosis, and stratified by adjuvant chemotherapy status were estimated. Median survival time was the longest in patients with low-intensity MBSS and rPCa (817 days), whereas the shortest survival time was found among patients with uPCa regardless of MBSS status (144-147 days). After consideration of age and chemotherapy status, high-intensity MBSS was associated with poorer survival for both rPCa (HR 1.64; 95 % CI 1.07-2.52) and uPCa (HR 1.35; 95 % CI 1.06-1.72). Preoperative MBSS intensity is a useful prognostic indicator of survival in resectable as well as unresectable pancreatic cancer.

  12. Prognostic value of DCE-MRI in breast cancer patients undergoing neoadjuvant chemotherapy: a comparison with traditional survival indicators

    Energy Technology Data Exchange (ETDEWEB)

    Pickles, Martin D.; Lowry, Martin; Turnbull, Lindsay W. [Hull York Medical School at University of Hull, Hull Royal Infirmary, Centre for Magnetic Resonance Investigations, Hull (United Kingdom); Manton, David J. [Hull and East Yorkshire Hospitals NHS Trust, Radiation Physics Department, Hull (United Kingdom)

    2015-04-01

    To determine associations between dynamic contrast-enhanced MR imaging (DCE-MRI) parameters and survival intervals in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy (NAC), surgery, and adjuvant therapies. Further, to compare the prognostic value of DCE-MRI parameters against traditional survival indicators. DCE-MRI and MR tumour volume measures were obtained prior to treatment and post 2nd NAC cycle. To demonstrate which parameters were associated with survival, Cox's proportional hazards models (CPHM) were employed. To avoid over-parameterisation, only those MR parameters with at least a borderline significant result were entered into the final CPHM. When considering disease-free survival positive axillary nodal status (hazard ratio [HR] 6.79), younger age (HR 3.37), negative oestrogen receptor status (HR 3.24), pre-treatment Maximum Enhancement Index (MaxEI) (HR 6.51), and percentage change in MaxEI (HR 1.02) represented the retained CPHM covariates. Similarly, positive axillary nodal status (HR 11.47), negative progesterone receptor status (HR 4.37) and percentage change in AUC{sub 90} (HR 1.01) represented the retained predictive variables for overall survival. Multivariate survival analysis has demonstrated that DCE-MRI parameters obtained prior to NAC and/or post 2nd cycle can provide independent prognostic information that can complement traditional prognostic indicators available prior to treatment. (orig.)

  13. Survival rate in nasopharyngeal carcinoma improved by high caseload volume: a nationwide population-based study in Taiwan

    Directory of Open Access Journals (Sweden)

    Chou Pesus

    2011-08-01

    Full Text Available Abstract Background Positive correlation between caseload and outcome has previously been validated for several procedures and cancer treatments. However, there is no information linking caseload and outcome of nasopharyngeal carcinoma (NPC treatment. We used nationwide population-based data to examine the association between physician case volume and survival rates of patients with NPC. Methods Between 1998 and 2000, a total of 1225 patients were identified from the Taiwan National Health Insurance Research Database. Survival analysis, the Cox proportional hazards model, and propensity score were used to assess the relationship between 10-year survival rates and physician caseloads. Results As the caseload of individual physicians increased, unadjusted 10-year survival rates increased (p p = 0.001 after adjusting for comorbidities, hospital, and treatment modality. When analyzed by propensity score, the adjusted 10-year survival rate differed significantly between patients treated by high-volume physicians and patients treated by low/medium-volume physicians (75% vs. 61%; p Conclusions Our data confirm a positive volume-outcome relationship for NPC. After adjusting for differences in the case mix, our analysis found treatment of NPC by high-volume physicians improved 10-year survival rate.

  14. Survival predictors of Burkitt's lymphoma in children, adults and elderly in the United States during 2000-2013.

    Science.gov (United States)

    Mukhtar, Fahad; Boffetta, Paolo; Risch, Harvey A; Park, Jong Y; Bubu, Omonigho M; Womack, Lindsay; Tran, Thuan V; Zgibor, Janice C; Luu, Hung N

    2017-04-01

    Burkitt's Lymphoma (BL) has three peaks of occurrence, in children, adults and elderly, at 10, 40 and 70 years respectively. To the best of our knowledge, no study has been conducted to assess predictors of survival in the three age groups. We hypothesized that survival predictors may differ by age group. We, therefore, sought to determine survival predictors for BL in these three groups: children (elderly (>70 years of age). Using the Surveillance, Epidemiology, and End Results (SEER) database covering the years 2000-2013, we identified 797 children, 1,994 adults and 757 elderly patients newly diagnosed with BL. We used adjusted Cox proportional hazards regression models to determine prognostic factors for survival for each age group. Five-year relative survival in BL for children, adults and elderly were 90.4, 47.8 and 28.9%, respectively. Having at least Stage II disease and multiple primaries were associated with higher mortality in the elderly group. In adults, multiple primaries, Stage III or IV disease, African American race and bone marrow primary were associated with increased mortality whereas Stage IV disease and multiple primaries were associated with worse outcome in children. These findings demonstrate commonalities and differences in predictors of survival that may have implications for management of BL patients. © 2016 UICC.

  15. An Incident Cohort Study Comparing Survival on Home Hemodialysis and Peritoneal Dialysis (Australia and New Zealand Dialysis and Transplantation Registry)

    Science.gov (United States)

    Nadeau-Fredette, Annie-Claire; Hawley, Carmel M.; Pascoe, Elaine M.; Chan, Christopher T.; Clayton, Philip A.; Polkinghorne, Kevan R.; Boudville, Neil; Leblanc, Martine

    2015-01-01

    Background and objectives Home dialysis is often recognized as a first-choice therapy for patients initiating dialysis. However, studies comparing clinical outcomes between peritoneal dialysis and home hemodialysis have been very limited. Design, setting, participants, & measurements This Australia and New Zealand Dialysis and Transplantation Registry study assessed all Australian and New Zealand adult patients receiving home dialysis on day 90 after initiation of RRT between 2000 and 2012. The primary outcome was overall survival. The secondary outcomes were on-treatment survival, patient and technique survival, and death-censored technique survival. All results were adjusted with three prespecified models: multivariable Cox proportional hazards model (main model), propensity score quintile–stratified model, and propensity score–matched model. Results The study included 10,710 patients on incident peritoneal dialysis and 706 patients on incident home hemodialysis. Treatment with home hemodialysis was associated with better patient survival than treatment with peritoneal dialysis (5-year survival: 85% versus 44%, respectively; log-rank Pdialysis. PMID:26068181

  16. Survival and hepatitis status among Asian Americans with hepatocellular carcinoma treated without liver transplantation

    Directory of Open Access Journals (Sweden)

    Hassan Manal M

    2009-02-01

    Full Text Available Abstract Background Chronic hepatitis B virus (HBV and hepatitis C virus (HCV are established causes of HCC. HCC patients are often diagnosed late and receive palliative therapies, however, the survival of Asian American patients with HCC treated without transplantation has not been well studied. We reviewed our institution's experience to determine predictors and rates of survival in Asian American HCC patients treated without transplantation. Methods We identified Asian American patients with HCC referred to M. D. Anderson Cancer Center. Patients were tested for HBV and HCV. Survival curves were generated by Kaplan-Meier method. Multivariate Cox proportional hazards regression was used to test the relationship between prognostic factors and survival. Results Of 82 Asian American HCC patients, most had advanced disease (65% and received treatment (68%; however, only 11% had surgical resection. 94% had positive anti-HBc and 61% had positive HBsAg. 20% had positive anti-HCV. There were no significant changes in the rates of HBV and HCV over time. Male gender, high alpha-fetoprotein levels, and stage IV disease were associated with shorter survival Overall median survival was 9.2 months (95% CI 6.5–11.9, and the survival of HCV and HBV patients was not statistically different. Conclusion The survival rate of Asian American patients with advanced HCC, for whom transplantation was not available, was low. Timely hepatitis screening and interventions by primary care physicians may be the most logical solution to reduce the burden of hepatitis-associated HCC among Asian Americans.

  17. The Heart Failure Overweight/Obesity Survival Paradox: The Missing Sex Link.

    Science.gov (United States)

    Vest, Amanda R; Wu, Yuping; Hachamovitch, Rory; Young, James B; Cho, Leslie

    2015-11-01

    This study sought to determine whether body mass index (BMI) has a differential impact on survival for females versus males with advanced systolic heart failure (HF). Females have a survival advantage in HF, the mechanisms of which are unclear. There is also a proposed "obesity survival paradox" in which excess adiposity promotes HF survival. We reviewed 3,811 patients with left ventricular ejection fraction ≤40% who had undergone cardiopulmonary exercise testing between 1995 and 2011. The endpoint was all-cause mortality. Multivariable analysis was performed using a Cox proportional hazards model. Because of the nonlinearity of BMI, a restricted cubic spline was used. An interaction term was added to investigate the impact of BMI on mortality by sex. The unadjusted data demonstrated an overall obesity survival paradox in HF. This survival paradox disappeared for males after adjustment for potential confounders, with overweight and obese males showing higher adjusted mortality hazard ratios compared with normal weight males. Conversely, females in the overweight BMI range (25.0 to 29.9 kg/m(2)) had the lowest adjusted mortality (hazard ratio: 0.84; 95% confidence interval: 0.77 to 0.93; p = 0.0005 compared with normal weight females) with a nadir in mortality hazard just below BMI 30 kg/m(2). The multivariable model supported a differential impact of BMI on mortality in males versus females (p for interaction obesity survival paradox disappeared after adjustment for confounders. Overweight and obese males had higher adjusted mortality than normal weight males, whereas a BMI in the overweight range was associated with a significant survival benefit in females. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  18. Survival Following Veno-Venous Extracorporeal Membrane Oxygenation and Mortality in a Diverse Patient Population.

    Science.gov (United States)

    Mosca, Matthew S; Narotsky, David L; Liao, Ming; Mochari-Greenberger, Heidi; Beck, James; Mongero, Linda; Bacchetta, Matthew

    2015-12-01

    Racial and ethnic disparities in cardiovascular disease are well established; however, there is limited information about survival differences following veno-venous extracorporeal membrane oxygenation (VV-ECMO) in contemporary adult populations. The purpose of this study was to assess survival at discharge, 30 days, and at 1 year following institution of VV-ECMO in an ethnically diverse population, and to examine potential risk factors for mortality. This was a single-center study of 41 patients (49% female, 27% minorities, 7% > 65 years) who received VV-ECMO between the years 2004 and 2013 at an academic medical center. Kaplan-Meier estimates were calculated to assess survival up to 1 year, and cox proportional hazard models were used to evaluate the association between risk factors, mortality, and confounders. Overall, 76% (n = 31) of VV-ECMO patients survived to discharge and 30 days and 71% (n = 29) survived to 1 year. Whites (n = 30) had a higher survival at 1 year compared to minorities (n = 11) (83% vs. 36%, respectively, p = .01). Minorities had a significantly increased risk of mortality at 30 days (hazard ratio [HR] = 5.07, 95% confidence interval [CI] = 1.42-18.09) and at 1 year (HR = 5.19, 95% CI = 1.63-16.55). Race/ethnicity remained a significant independent predictor of survival at 30 days except when history of shock or lung transplantation was included in adjusted regression models. VV-ECMO was associated with an excellent overall survival up to 1 year. Racial/ethnic minorities had a 5-fold increased risk for 30-day mortality, which was largely explained by a lower likelihood of lung transplantation and increased risk of shock.

  19. Prognostic factors for locoregional recurrence and survival in stage IIIC breast carcinoma: impact of adjuvant radiotherapy.

    Science.gov (United States)

    Kuru, B

    2011-04-01

    The aims of the present study were to define the prognostic factors for locoregional recurrence (LRR) and survival in stage IIIC breast carcinoma as well as to examine the impact of adjuvant radiotherapy on the outcome of the disease. The records of 586 consecutive patients with stage IIIC breast carcinoma who underwent modified radical mastectomy were evaluated, and the prognostic factors for LRR and survival were analysed. Survival curves were generated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard model. Five-year LRR and survival of stage IIIC breast carcinoma were 15 percent and 41.3 percent, respectively. Five-year LRR was significantly lower and five-year survival was significantly higher for all patients as well as for T1-2 patients with one to three apical node involvements who were treated with adjuvant radiotherapy. In multivariate analysis, apical node involvement, age below 35 years, T4 tumour, grade 3, extracapsular extension and lymphovascular invasion decreased survival, whereas adjuvant tamoxifen and adjuvant radiotherapy (risk ratio [RR] 0.51, 95 percent confidence interval [CI] 0.39-0.67) increased survival. Adjuvant radiotherapy was the sole independent factor that was found to be significantly associated with decreased LRR (RR 0.25, 95 percent CI 0.16-0.38). Radiotherapy decreased LRR and increased survival significantly in all stage IIIC patients and in the subgroup of T1-2 patients with one to three apical node involvements. Thus, it should be considered in the treatment of stage IIIC breast carcinoma.

  20. Perspective for safer alternatives. COX-2-selective NSAID's

    NARCIS (Netherlands)

    Van Roon, E.N.; Brouwers, J.R.B.J.; Posthuma, R.M.

    2000-01-01

    On the Dutch market soon the first COX-2-selective NSAID's will become available. Because these agents selective inhibit the isoenzyme that is involved in inflammation, these drugs will show a better effectiveness/safety ratio, compared to classic NSAID's. In this article we present the current

  1. Targeting Estrogen-Induced COX-2 Activity in Lymphangioleiomyomatosis (LAM)

    Science.gov (United States)

    2013-10-01

    expression in TSC2- reexpressing LAM patient-derived cells (Fig. 1g). To address how estradiol exerts its action on COX-2 expression and prostaglandin...lymphangioleiomyomatosis. Journal of medical genetics 37:55-57. Auricchio, N., I. Malinowska, R. Shaw, B.D. Manning, and D.J. Kwiatkowski. Therapeutic trial of metformin

  2. 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.

  3. COX-2 inhibition in osteoarthritis:effects on cartilage

    NARCIS (Netherlands)

    Mastbergen, Simon Carl

    2005-01-01

    The topic of this thesis was to provide more insight in the direct effects of one of the selective COX-2 inhibitors, celecoxib on articular cartilage. Issues of major relevance to clinical practice since it is essential that compounds used to treat osteoarthritis do not impair the ability of

  4. A Box-Cox normal model for response times

    NARCIS (Netherlands)

    Klein Entink, R.H.; Fox, J.P.; Linden, W.J. van der

    2009-01-01

    The log-transform has been a convenient choice in response time modelling on test items. However, motivated by a dataset of the Medical College Admission Test where the lognormal model violated the normality assumption, the possibilities of the broader class of Box–Cox transformations for response

  5. 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

  6. A Conversation with Sally Coxe: A Primate Partnership Culture

    Directory of Open Access Journals (Sweden)

    Riane Eisler

    2017-10-01

    Full Text Available IJPS Editor-in-Chief Riane Eisler talks with Sally Coxe, founding director of the Bonobo Conservation Initiative (BCI, dedicated to protecting these uniquely peaceful primates who share more than 98 percent of our human species’ genes and are on the brink of extinction, as well as protecting their rainforest home.

  7. Increased COX-2 expression in patients with ovarian cancer

    African Journals Online (AJOL)

    ajl yemi

    2011-10-26

    Oct 26, 2011 ... role for COX-2 as mediators of ovarian cancer and as markers of disease activity. Key words: Ovarian cancer, ... history of ovarian and/or breast cancer, and nulliparity, whereas the oral contraceptive pill .... BSA overnight at 4°C, membranes were incubated for 2 h at room temperature in agitation with the ...

  8. ST6Gal1, Cox-2 and HB-EGF mRNA Expression in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Aliakbar Taherian

    2015-01-01

    Full Text Available Background: ST6Gal1, Cox-2 and HB-EGF genes are involved in different tumors and their enhanced expressions often correlate with poor prognosis. In this study we assay the expressions of these genes by reverse transcriptase-PCR in 54 breast cancer samples. Methods: Tissue samples were either formalin-fixed for histopathological examination or frozen for reverse transcriptase-PCR. Image program was used for the densitometry of the image of the gels and the expression of different genes was normalized with beta actin expression. The student's t-test and correlation matrix were used for data analyses. Results: We observed significantly higher expressions of ST6Gal1 (P= 0.040, Cox- 2 (P= 0.001 and HB-EGF (P= 0.009 in the tumor region compared to the margin samples. A significant correlation was found between HB-EGF and Cox-2 expression (P= 0.001. There was a positive correlation between total score, tumor size, histology grade and nuclear grade but there was a reverse correlation between age and tumor size, histology grade and total score. Conclusion: Expressions of ST6Gal1, Cox-2 and HB-EGF in breast tumor samples in this and a number of other studies emphasize their role as important markers in breast cancer. The use of medications to inhibit either their individual expressions or the possible inhibition of all three genes may improve patient survival and prevent metastasis.

  9. Enhanced Cluster Computing Performance Through Proportional Fairness

    OpenAIRE

    Bonald, Thomas; Roberts, James

    2014-01-01

    International audience; The performance of cluster computing depends on how concurrent jobs share multiple data center resource types like CPU, RAM and disk storage. Recent research has discussed efficiency and fairness requirements and identified a number of desirable scheduling objectives including so-called dominant resource fairness (DRF). We argue here that proportional fairness (PF), long recognized as a desirable objective in sharing network bandwidth between ongoing flows, is preferab...

  10. In vitro COX-1 and COX-2 enzyme inhibitory activities of iridoids from Penstemon barbatus, Castilleja tenuiflora, Cresentia alata and Vitex mollis.

    Science.gov (United States)

    Ramírez-Cisneros, M Ángeles; Rios, María Yolanda; Aguilar-Guadarrama, A Berenice; Rao, Praveen P N; Aburto-Amar, Rola; Rodríguez-López, Verónica

    2015-10-15

    A group of sixteen iridoids isolated from plants used as anti-inflammatory remedies in Mexican folk medicine were evaluated for their potential to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. From these assays, loganic acid (10) was identified as the most promising compound with both COX-1 (36.0 ± 0.6%) and COX-2 (80.8 ± 4.0%) inhibition at 10 μM. Compound 10 shows a better inhibition against the COX-2 enzyme. Other iridoids tested in the present study showed weak or no inhibition against these enzymes. Furthermore, herein are presented key interactions of iridoid 10 with COX-1 and COX-2 enzymes through molecular docking studies. These studies suggest that 10 exhibits anti-inflammatory activity due to COX inhibition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Student Obstacles in Ratio and Proportion Learning

    Science.gov (United States)

    Andini, W.; Jupri, Al

    2017-02-01

    Ratio and proportion are mathematics topics that are learned in elementary school. In the learning process, teachers often found students who have difficulties in learning these topics. Analysing the difficulties on the topics is important for teachers, as an attempt to doa reflection of the learning process and as a reference in devising a learning plan, including for anticipation of the possibility of these barriers that might appear in the next learning process. This research used as the qualitative method, and involved 49 students of grade 5 and one teacher. From the analysis of the data, i.e., student test results and observation of the learning, we found some obstacles that faced by students, such as students confused in understanding about ratio and proportion topic, students found it difficult in completing the problem which have different contexts, the learning material of ratio and proportion topic that presented in textbooks are still partial (not depth), and the lack of ability of the teacher in creating problems.

  12. A Note Comparing Component-Slope, Scheffé, and Cox Parameterizations of the Linear Mixture Experiment Model

    Energy Technology Data Exchange (ETDEWEB)

    Piepel, Gregory F.

    2006-05-01

    A mixture experiment involves combining two or more components in various proportions and collecting data on one or more responses. A linear mixture model may adequately represent the relationship between a response and mixture component proportions and be useful in screening the mixture components. The Scheffé and Cox parameterizations of the linear mixture model are commonly used for analyzing mixture experiment data. With the Scheffé parameterization, the fitted coefficient for a component is the predicted response at that pure component (i.e., single-component mixture). With the Cox parameterization, the fitted coefficient for a mixture component is the predicted difference in response at that pure component and at a pre-specified reference composition. This paper presents a new component-slope parameterization, in which the fitted coefficient for a mixture component is the predicted slope of the linear response surface along the direction determined by that pure component and at a pre-specified reference composition. The component-slope, Scheffé, and Cox parameterizations of the linear mixture model are compared and their advantages and disadvantages are discussed.

  13. PGE2 production in oral cancer cell lines is COX-2-dependent.

    Science.gov (United States)

    Husvik, C; Khuu, C; Bryne, M; Halstensen, T S

    2009-02-01

    It has been suggested that epithelial cyclooxygenase-2 (COX-2) promotes oral carcinogenesis and carcinoma malignancy through increased prostaglandin E(2) (PGE(2)) production. Although oral squamous cell carcinomas (OSCC) often express COX-2, they may also produce PGE(2) in a COX-1-dependent manner. We used 6 isolated cell lines to investigate which COX isoforms OSCC may use for PGE(2) production. COX-1 and -2 expression patterns divided the 6 OSCC cell lines into 3 distinct groups: both COX isoforms low, only COX-1 high, or both COX isoforms high. Multicolor immunohistofluorescence staining confirmed the COX-expression profiles in organotypic 3D cultures and the COX-2 dominance in OSCC tumors. Epidermal growth factor (EGF) stimulation induced COX-2 (but not COX-1) expression and increased PGE(2) production, which was attenuated by COX-2 (but not COX-1) specific inhibition or siRNA-mediated COX-2 gene knockdown. Thus, PGE(2) production in OSCC cell lines was COX-2-dependent.

  14. The Dynamics of Naval Power System with Integrator Proportional and Derivative Integrator Proportional Regulators

    Directory of Open Access Journals (Sweden)

    Florentiu Deliu

    2011-09-01

    Full Text Available The essay analyses the dynamics activity of the naval power system regulators using the integrator proportional and derivative integrator proportional regulators, system that provides the necessary energy for ship consumers so that the voltage and the frequency is always within nominal values.

  15. Treatment and survival of patients harboring histological variants of glioblastoma.

    Science.gov (United States)

    Ortega, Alicia; Nuño, Miriam; Walia, Sartaaj; Mukherjee, Debraj; Black, Keith L; Patil, Chirag G

    2014-10-01

    It is unclear whether the survival difference observed between glioblastoma (GBM), giant cell glioblastoma (gcGBM), and gliosarcoma (GSM) patients is due to differences in tumor histology, patient demographics, and/or treatment regimens. The USA National Cancer Database was utilized to evaluate patients diagnosed with GBM, gcGBM, and GSM between 1998 and 2011. Kaplan-Meier survival estimates and Cox proportional hazards models were utilized to estimate overall survival. A cohort of 69,935 patients was analyzed; 67,509 (96.5%) of these patients had GBM, 592 (0.9%) gcGBM, and 1834 (2.6%) GSM. The median age for GBM and GSM patients was 61 versus 56 years for gcGBM (p<0.0001). Higher extent of resection (p<0.0001) and radiation (p=0.001) were observed in gcGBM patients compared to other histologies. Multivariate analysis showed that gcGBM patients had a 20% reduction in the hazards of mortality (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.69-0.93) compared to GBM, while GSM patients trended towards higher hazards of mortality (HR 1.04, 95% CI 0.96-1.12) than the GBM cohort. Previous studies have suggested a disparity in the survival of patients with GBM tumors and their histological variants. Using a large cohort of patients treated at hospitals nationwide, this study found a 20% reduction in the hazards of mortality in gcGBM patients compared to GBM. Similarly, gcGBM patients had a 24% reduction in the hazards of mortality compared to the GSM cohort. GSM patients had a 3% increase in the hazards of mortality compared to GBM. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Adjuvant chemotherapy and overall survival in adult medulloblastoma.

    Science.gov (United States)

    Kann, Benjamin H; Lester-Coll, Nataniel H; Park, Henry S; Yeboa, Debra N; Kelly, Jacqueline R; Baehring, Joachim M; Becker, Kevin P; Yu, James B; Bindra, Ranjit S; Roberts, Kenneth B

    2017-02-01

    Although chemotherapy is used routinely in pediatric medulloblastoma (MB) patients, its benefit for adult MB is unclear. We evaluated the survival impact of adjuvant chemotherapy in adult MB. Using the National Cancer Data Base, we identified patients aged 18 years and older who were diagnosed with MB in 2004-2012 and underwent surgical resection and adjuvant craniospinal irradiation (CSI). Patients were divided into those who received adjuvant CSI and chemotherapy (CRT) or CSI alone (RT). Predictors of CRT compared with RT were evaluated with univariable and multivariable logistic regression. Survival analysis was limited to patients receiving CSI doses between 23 and 36 Gy. Overall survival (OS) was evaluated using the Kaplan-Meier estimator, log-rank test, multivariable Cox proportional hazards modeling, and propensity score matching. Of the 751 patients included, 520 (69.2%) received CRT, and 231 (30.8%) received RT. With median follow-up of 5.0 years, estimated 5-year OS was superior in patients receiving CRT versus RT (86.1% vs 71.6%, P < .0001). On multivariable analysis, after controlling for risk factors, CRT was associated with superior OS compared with RT (HR: 0.53; 95%CI: 0.32-0.88, P = .01). On planned subgroup analyses, the 5 year OS of patients receiving CRT versus RT was improved for M0 patients (P < .0001), for patients receiving 36 Gy CSI (P = .0007), and for M0 patients receiving 36 Gy CSI (P = .0008). This national database analysis demonstrates that combined postoperative chemotherapy and radiotherapy are associated with superior survival for adult MB compared with radiotherapy alone, even for M0 patients who receive high-dose CSI.

  17. Empirical likelihood method in survival analysis

    CERN Document Server

    Zhou, Mai

    2015-01-01

    Add the Empirical Likelihood to Your Nonparametric ToolboxEmpirical Likelihood Method in Survival Analysis explains how to use the empirical likelihood method for right censored survival data. The author uses R for calculating empirical likelihood and includes many worked out examples with the associated R code. The datasets and code are available for download on his website and CRAN.The book focuses on all the standard survival analysis topics treated with empirical likelihood, including hazard functions, cumulative distribution functions, analysis of the Cox model, and computation of empiric

  18. Survival data and prognostic factors seen in Pakistani patients with esophageal cancer.

    Science.gov (United States)

    Alidina, A; Gaffar, A; Hussain, F; Islam, M; Vaziri, I; Burney, I; Valimohd, A; Jafri, W

    2004-01-01

    Esophageal cancer is common in Pakistan. An attempt has been made for the first time to look at the survival data and prognostic factors associated with esophageal cancer in this region. We did a retrospective review of 263 cases seen at the Aga Khan University Hospital in Karachi. Data analysis was done using the Kaplan-Meier method and the Cox proportional hazard model. Squamous cell carcinoma was noted in 81% of the cases, whereas adenocarcinoma was the second most common. At the time of diagnosis, early-stage disease was found in 25%, locally advanced in 41% and metastatic in 34% of all cases. Mean age at diagnosis was 56 years, with 59% males and 41% females. Survival data were available in 89 cases. Median survival was 7 months. On univariate analysis, the following factors were of prognostic significance: obstruction, histology, albumin level at diagnosis, age and platelet count. On multivariate analysis, three factors were found prognostic: presence or absence of obstruction, squamous cell carcinoma versus adenocarcinoma and platelet count. We found that patients with squamous cell carcinoma and absence of thrombocytopenia and obstruction had a better overall survival. However, this is a limited retrospective analysis; we therefore recommend that these prognostic factors be evaluated in larger studies.

  19. Will-to-live and survival in a 10-year follow-up among older people.

    Science.gov (United States)

    Karppinen, Helena; Laakkonen, Marja-Liisa; Strandberg, Timo E; Tilvis, Reijo S; Pitkälä, Kaisu H

    2012-11-01

    there is little research how older people's will-to-live predicts their survival. to investigate how many years home-dwelling older people wish to live and how this will-to-live predicts their survival. as a part of the Drugs and Evidence-Based Medicine in the Elderly (DEBATE) study, 400 home-dwelling individuals aged 75-90 were recruited into a cardiovascular prevention trial in Helsinki. In 2000, a questionnaire about the wishes of their remaining life was completed by 283 participants. Participants were inquired how many years they would still wish to live, and divided into three groups according to their response: group 1: wishes to live 10 years. Mortality was confirmed from central registers during a 10-year follow-up. The adjusted Cox proportional hazard model was used to determine how will-to-live predicted survival. in group 1 wishing to live less than 5 years, the mean age and the Charlson comorbidity index were the highest, and subjective health the poorest. There were no differences between the groups in cognitive functioning or feeling depressed. Mortality was the highest (68.0%) among those wishing to live will-to-live was a strong predictor for survival among older people irrespective of age, gender and comorbidities.

  20. Use and duration of chemotherapy and its impact on survival in early-stage ovarian cancer.

    Science.gov (United States)

    Dinkelspiel, Helen E; Tergas, Ana I; Zimmerman, Lilli A; Burke, William M; Hou, June Y; Chen, Ling; Hillyer, Grace; Neugut, Alfred I; Hershman, Dawn L; Wright, Jason D

    2015-05-01

    Although 5-year survival for early-stage ovarian cancer is favorable, prognosis at recurrence is poor, necessitating appropriate initial management. We examined the patterns of care and the impact of the duration of chemotherapy on survival for women with early-stage ovarian cancer. We used the SEER-Medicare database to identify women ≥ 65 years of age with stage I ovarian cancer diagnosed from 1992 to 2009. Patients were categorized as low-risk (non-clear cell histology, stage IA or IB, grade 1 or 2) or high-risk (clear cell histology, grade 3, or stage IC). We used multivariable logistic regression models to determine predictors of chemotherapy use and duration and Cox proportional hazards models to evaluate the effect of chemotherapy use and duration on survival. We identified 1394 patients. Among low-risk patients, 32.9% received adjuvant chemotherapy and the use of chemotherapy increased with time. Among high-risk patients, 71.9% received adjuvant chemotherapy; 44.2% had ≤ 3 months of treatment, and 55.8% had > 3 months of treatment. Older patients were less likely to receive chemotherapy, while those with higher stage and grade were more likely to receive chemotherapy (Pearly-stage ovarian cancer patients, practice patterns are widely divergent. Extended duration chemotherapy does not appear to impact survival for women with high-risk disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Multimodality treatment of brain metastases: an institutional survival analysis of 275 patients

    Directory of Open Access Journals (Sweden)

    Demakas John J

    2011-07-01

    Full Text Available Abstract Background Whole brain radiation therapy (WBRT, surgical resection, stereotactic radiosurgery (SRS, and combinations of the three modalities are used in the management of patients with metastatic brain tumors. We present the previously unreported survival outcomes of 275 patients treated for newly diagnosed brain metastases at Cancer Care Northwest and Gamma Knife of Spokane between 1998 and 2008. Methods The effects treatment regimen, age, Eastern Cooperative Oncology Group-Performance Status (ECOG-PS, primary tumor histology, number of brain metastases, and total volume of brain metastases have on patient overall survival were analyzed. Statistical analysis was performed using Kaplan-Meier survival curves, Andersen 95% confidence intervals, approximate confidence intervals for log hazard-ratios, and multivariate Cox proportional hazard models. Results The median clinical follow up time was 7.2 months. On multivariate analysis, survival statistically favored patients treated with SRS alone when compared to patients treated with WBRT alone (p Conclusions In our analysis, patients benefited from a combined modality treatment approach and physicians must consider patient age, performance status, and primary tumor histology when recommending specific treatments regimens.

  2. A Simpler Creatinine Index Can Predict Long-Term Survival in Chinese Hemodialysis Patients

    Science.gov (United States)

    Lee, Szu-Ying; Yang, Chung-Wei; Hung, Szu-Chun; Chiang, Chih-Kang; Huang, Jenq-Wen; Hung, Kuan-Yu

    2016-01-01

    Background Low lean body mass (LBM) is an indicator of malnutrition inflammation syndrome, which is common in hemodialysis (HD) patients. The creatinine index (CI) has been validated as a reliable method to estimate LBM and evaluate the protein-energy status of HD patients. However, the traditional creatinine index formula was complex. We sought to investigate the impact of CI derived from a new simple formula on Chinese HD patient outcomes. Methods In this retrospective cohort study, we enrolled 1269 patients who initiated HD between February 1981 and February 2012 and followed them until the end of February 2013. CI was calculated using the simple creatinine kinetic model (CKM) formula. Multiple linear regression analysis and Cox regression proportional hazard analysis were used to define independent variables and compare survival between groups. Results The 1269 HD patients were categorized into 3 groups according to the tertiles of calculated CI between men and women. Each group consisted of 423 patients (50.6% men, 49.4% women). Patients in the highest sex-specific tertile of CI had longer overall survival (HR, 0.46; P 0.002). BMI did not significantly associate with survival after adjustment (HR,0.99; P 0.613). Conclusions CI derived from the simple CKM formula serves as a good parameter than BMI to predict the survival of HD patients. The formula could extend its convenient use in clinical practice for HD patients. PMID:27780214

  3. Small sample bias in the gamma frailty model for univariate survival.

    Science.gov (United States)

    Barker, Peter; Henderson, Robin

    2005-06-01

    The gamma frailty model is a natural extension of the Cox proportional hazards model in survival analysis. Because the frailties are unobserved, an E-M approach is often used for estimation. Such an approach is shown to lead to finite sample underestimation of the frailty variance, with the corresponding regression parameters also being underestimated as a result. For the univariate case, we investigate the source of the bias with simulation studies and a complete enumeration. The rank-based E-M approach, we note, only identifies frailty through the order in which failures occur; additional frailty which is evident in the survival times is ignored, and as a result the frailty variance is underestimated. An adaption of the standard E-M approach is suggested, whereby the non-parametric Breslow estimate is replaced by a local likelihood formulation for the baseline hazard which allows the survival times themselves to enter the model. Simulations demonstrate that this approach substantially reduces the bias, even at small sample sizes. The method developed is applied to survival data from the North West Regional Leukaemia Register.

  4. A prospective study of phobic anxiety, risk of ovarian cancer, and survival among patients.

    Science.gov (United States)

    Poole, Elizabeth M; Kubzansky, Laura D; Sood, Anil K; Okereke, Olivia I; Tworoger, Shelley S

    2016-05-01

    In ovarian cancer patients and mouse models, psychosocial stress is associated with higher circulating markers of angiogenesis and cell migration, impaired immune response, and increasing tumor burden and aggressiveness. In the Nurses' Health Studies (NHS/NHSII), we assessed whether phobic anxiety, a marker of chronic distress, was associated with risk of incident ovarian cancer as well as survival among ovarian cancer patients. We used Cox proportional hazards regression to model the relative risks (RRs) and 95 % confidence intervals (CI) of ovarian cancer incidence and survival by categories of the Crown-Crisp phobic anxiety index (CCI). We identified 779 cases of ovarian cancer during 2,497,892 person-years of follow-up. For baseline CCI (NHS: 1988; NHSII: 1993), we observed a statistically nonsignificant increased risk of epithelial ovarian cancer (RR for CCI ≥ 4 vs. 0 or 1: 1.14; 95 % CI 0.96-1.36). However, when we updated CCI (NHS: 2004; NHSII: 2005), the associations were attenuated. Pre-diagnosis CCI was not associated with ovarian cancer survival (RR for ≥4 vs. 0 or 1: 1.00; 95 % CI 0.77-1.31); results were similar for post-diagnosis CCI. Distress, as measured by phobic anxiety symptoms, was not associated with ovarian cancer risk, although we cannot rule out a modest association. Future research should explore the role of phobic anxiety and other forms of psychological distress and ovarian cancer risk and survival.

  5. Melanoma of the Foot Is Associated With Advanced Disease and Poorer Survival.

    Science.gov (United States)

    Adams, Barbara E; Peng, Peter D; Williams, Mitzi L

    2017-10-13

    The purpose of the present study was to review the outcomes and assess the prognostic factors associated with foot melanoma. We hypothesized that primary melanoma of the foot would be more likely to present at an advanced stage and be associated with poorer outcomes. Both univariate and multivariate analyses were conducted to examine the relationships between patients' demographic, clinical, and pathologic characteristics and deaths within 5 years. Categorical data were summarized as frequencies and percentages and continuous variables as mean ± standard deviation. The primary outcome measure was overall survival. On univariate analysis, the significant prognostic variables found included Breslow thickness, ulceration, sentinel node positivity, and localized presentation on the toe. Age, sex, and race were not prognostically significant in this model. Multivariate Cox proportional hazards analysis resulted in a model of foot melanoma with ulceration and location on the toe as independent prognostic variables. The 5-year survival rate for melanoma of the toe was 50%. The results of the present study have shown that physicians should have a low threshold to biopsy suspicious lesions of the foot and ankle. Advanced disease and poorer survival were noted with toe melanoma. An ulcerative lesion of the foot was also associated with poorer survival. Copyright © 2017 The American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  6. Multiparametric analysis of magnetic resonance images for glioma grading and patient survival time prediction

    Energy Technology Data Exchange (ETDEWEB)

    Garzon, Benjamin (Dept. of Circulation and Medical Imaging, NTNU, Trondheim (Norway)), email: benjamin.garzon@ntnu.no; Emblem, Kyrre E. (The Interventional Center, Rikshospitalet, Oslo Univ. Hospital, Oslo (Norway); Dept. of Radiology, MGH-HST AA Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston (United States)); Mouridsen, Kim (Center of Functionally Integrative Neuroscience, Aarhus Univ., Aarhus (Denmark)); Nedregaard, Baard; Due-Toennessen, Paulina; Nome, Terje; Hald, John K. (Dept. of Radiology and Nuclear Medicine, Rikshospitalet, Oslo Univ. Hospital, Oslo (Norway)); Bjoernerud, Atle (The Interventional Center, Rikshospitalet, Oslo Univ. Hospital, Oslo (Norway)); Haaberg, Asta K. (Dept. of Circulation and Medical Imaging, NTNU, Trondheim (Norway); Dept. of Medical Imaging, St Olav' s Hospital, Trondheim (Norway)); Kvinnsland, Yngve (NordicImagingLab, Bergen (Norway))

    2011-11-15

    Background. A systematic comparison of magnetic resonance imaging (MRI) options for glioma diagnosis is lacking. Purpose. To investigate multiple MR-derived image features with respect to diagnostic accuracy in tumor grading and survival prediction in glioma patients. Material and Methods. T1 pre- and post-contrast, T2 and dynamic susceptibility contrast scans of 74 glioma patients with histologically confirmed grade were acquired. For each patient, a set of statistical features was obtained from the parametric maps derived from the original images, in a region-of-interest encompassing the tumor volume. A forward stepwise selection procedure was used to find the best combinations of features for grade prediction with a cross-validated logistic model and survival time prediction with a cox proportional-hazards regression. Results. Presence/absence of enhancement paired with kurtosis of the FM (first moment of the first-pass curve) was the feature combination that best predicted tumor grade (grade II vs. grade III-IV; median AUC 0.96), with the main contribution being due to the first of the features. A lower predictive value (median AUC = 0.82) was obtained when grade IV tumors were excluded. Presence/absence of enhancement alone was the best predictor for survival time, and the regression was significant (P < 0.0001). Conclusion. Presence/absence of enhancement, reflecting transendothelial leakage, was the feature with highest predictive value for grade and survival time in glioma patients

  7. Post-exposure therapeutic efficacy of COX-2 inhibition against Burkholderia pseudomallei.

    Directory of Open Access Journals (Sweden)

    Saja Asakrah

    Full Text Available Burkholderia pseudomallei is a Gram-negative, facultative intracellular bacillus and the etiologic agent of melioidosis, a severe disease in Southeast Asia and Northern Australia. Like other multidrug-resistant pathogens, the inherent antibiotic resistance of B. pseudomallei impedes treatment and highlights the need for alternative therapeutic strategies that can circumvent antimicrobial resistance mechanisms. In this work, we demonstrate that host prostaglandin E2 (PGE2 production plays a regulatory role in the pathogenesis of B. pseudomallei. PGE2 promotes B. pseudomallei intracellular survival within macrophages and bacterial virulence in a mouse model of pneumonic melioidosis. PGE2-mediated immunosuppression of macrophage bactericidal effector functions is associated with increased arginase 2 (Arg2 expression and decreased nitric oxide (NO production. Treatment with a commercially-available COX-2 inhibitor suppresses the growth of B. pseudomallei in macrophages and affords significant protection against rapidly lethal pneumonic melioidosis when administered post-exposure to B. pseudomallei-infected mice. COX-2 inhibition may represent a novel immunotherapeutic strategy to control infection with B. pseudomallei and other intracellular pathogens.

  8. A class of Box-Cox transformation models for recurrent event data.

    Science.gov (United States)

    Sun, Liuquan; Tong, Xingwei; Zhou, Xian

    2011-04-01

    In this article, we propose a class of Box-Cox transformation models for recurrent event data, which includes the proportional means models as special cases. The new model offers great flexibility in formulating the effects of covariates on the mean functions of counting processes while leaving the stochastic structure completely unspecified. For the inference on the proposed models, we apply a profile pseudo-partial likelihood method to estimate the model parameters via estimating equation approaches and establish large sample properties of the estimators and examine its performance in moderate-sized samples through simulation studies. In addition, some graphical and numerical procedures are presented for model checking. An example of application on a set of multiple-infection data taken from a clinic study on chronic granulomatous disease (CGD) is also illustrated.

  9. Prognostic value of CT findings to predict survival outcomes in patients with pancreatic neuroendocrine neoplasms: a single institutional study of 161 patients

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Wook; Kim, Hyoung Jung; Kim, Kyung Won; Byun, Jae Ho; Kim, So Yeon [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul (Korea, Republic of); Song, Ki Byung [University of Ulsan College of Medicine, Department of Surgery, Asan Medical Center, Seoul (Korea, Republic of); Ramaiya, Nikhil H.; Tirumani, Sree Harsha [Harvard Medical School, Department of Imaging, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, MA (United States); Hong, Seung-Mo [University of Ulsan College of Medicine, Department of Pathology, Asan Medical Center, Seoul (Korea, Republic of)

    2016-05-15

    To evaluate the prognostic value of CT to predict recurrence-free and overall survival in patients with pancreatic neuroendocrine neoplasms (PanNENs). Between January 2004 and December 2012, 161 consecutive patients who underwent preoperative triphasic CT and surgical resection with curative intent for PanNENs were identified. The tumour consistency, margin, presence of calcification, pancreatic duct dilatation, bile duct dilatation, vascular invasion, and hepatic metastases were evaluated. The tumour size, arterial enhancement ratio, and portal enhancement ratio were measured. The Cox proportional hazard model was used to determine the association between CT features and recurrence-free survival and overall survival. By multivariate analysis, tumour size (>3 cm) (hazard ratio, 3.314; p = 0.006), portal enhancement ratio (≤1.1) (hazard ratio, 2.718; p = 0.006), and hepatic metastases (hazard ratio, 4.374; p = 0.003) were independent significant variables for worse recurrence-free survival. Portal enhancement ratio (≤1.1) (hazard ratio, 5.951; p = 0.001) and hepatic metastases (hazard ratio, 4.122; p = 0.021) were independent significant variables for worse overall survival. Portal enhancement ratio (≤1.1) and hepatic metastases assessed on CT were common independent prognostic factors for worse recurrence-free survival and overall survival in patients with PanNENs. (orig.)

  10. Treatment Patterns and Differences in Survival of Non-Small Cell Lung Cancer Patients Between Academic and Non-Academic Hospitals in the Netherlands.

    Science.gov (United States)

    van der Linden, Naomi; Bongers, Mathilda L; Coupé, Veerle M H; Smit, Egbert F; Groen, Harry J M; Welling, Alle; Schramel, Franz M N H; Uyl-de Groot, Carin A

    2017-09-01

    The aims of this study are to analyze differences in survival between academic and non-academic hospitals and to provide insight into treatment patterns for non-small cell lung cancer (NSCLC). Results show the state of NSCLC survival and care in the Netherlands. The Netherlands Cancer Registry provided data on NSCLC survival for all Dutch hospitals. We used the Kaplan-Meier estimate to calculate median survival time by hospital type and a Cox proportional hazards model to estimate the relative risk of mortality (expressed as hazard ratios) for patients diagnosed in academic versus non-academic hospitals, with adjustment for age, gender, and tumor histology, and stratifying for disease stage. Data on treatment patterns in Dutch hospitals was obtained from 4 hospitals (2 academic, 2 non-academic). A random sample of patients diagnosed with NSCLC from January 2009 until January 2011 was identified through hospital databases. Data was obtained on patient characteristics, tumor characteristics, and treatments. The Cox proportional hazards model shows a significantly decreased hazard ratio of mortality for patients diagnosed in academic hospitals, as opposed to patients diagnosed in non-academic hospitals. This is specifically true for primary radiotherapy patients and patients who receive systemic treatment for non-metastasized NSCLC. Patients diagnosed in academic hospitals have better median overall survival than patients diagnosed in non-academic hospitals, especially for patients treated with radiotherapy, systemic treatment, or combinations. This difference may be caused by residual confounding since the estimates were not adjusted for performance status. A wide variety of surgical, radiotherapeutic, and systemic treatments is prescribed. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. 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.

  12. Measurement of proportional counter gas gain

    CERN Document Server

    Borisov, A; Goryachev, V N; Kojine, A

    2000-01-01

    A method of evaluation of proportional counter gas gain from arbitrary current measurements has been developed. It provides absolute value of the gain in range from 1 to 10**8 with moderate current sensitivity and without knowledge of used radioactive source properties. As an example we present dependence of the gain versus voltage for drift lubes of ATLAS Muon Spectrometer filled with mixtures Ar-CO//2(93-7) and Ar-N//2-CH//4(91-4-5) at 3 bar absolute pressure. Results are compared with the gain obtained from ADC measurements. 7 Refs.

  13. Residential road traffic noise exposure and colorectal cancer survival - A Danish cohort study

    DEFF Research Database (Denmark)

    Roswall, Nina; Bidstrup, Pernille Envold; Raaschou-Nielsen, Ole

    2017-01-01

    traffic noise at different time-windows, and overall and CRC-specific mortality. Furthermore, we investigated interaction with sex, age, prognostic factors, and comorbidity. Mortality Rate Ratios (MRR) were calculated in unadjusted models, and adjusted for railway noise, lifestyle factors......BACKGROUND: Residential traffic noise exposure may entail sleep disruption and compromised circadian functioning; two factors which have been associated with a poor colorectal cancer (CRC) prognosis. Hence, the aim of the present study was to investigate the association between residential road...... traffic noise and CRC survival. METHODS AND MATERIALS: Road traffic noise was calculated for all residential addresses from 1987 to February 2012 for incident CRC cases (n = 1,234) in a cohort of 57,053 Danes. We used Cox Proportional Hazard Models to investigate the association between residential road...

  14. History of Comorbidities and Survival of Ovarian Cancer Patients, Results from the Ovarian Cancer Association Consortium

    DEFF Research Database (Denmark)

    Minlikeeva, Albina N; Freudenheim, Jo L; Eng, Kevin H

    2017-01-01

    carcinoma who participated in 23 studies included in the Ovarian Cancer Association Consortium, we explored associations between histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, and neurological diseases and overall and progression-free survival...... with ovarian cancer outcome in the overall sample nor in strata defined by histologic subtype, weight status, age at diagnosis, or stage of disease (local/regional vs. advanced).Conclusions: Histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, or neurologic....... Using Cox proportional hazards regression models adjusted for age at diagnosis, stage of disease, histology, and study site, we estimated pooled HRs and 95% confidence intervals to assess associations between each comorbidity and ovarian cancer outcomes.Results: None of the comorbidities were associated...

  15. Prognostic factors for survival in adult patients with recurrent glioblastoma: a decision-tree-based model.

    Science.gov (United States)

    Audureau, Etienne; Chivet, Anaïs; Ursu, Renata; Corns, Robert; Metellus, Philippe; Noel, Georges; Zouaoui, Sonia; Guyotat, Jacques; Le Reste, Pierre-Jean; Faillot, Thierry; Litre, Fabien; Desse, Nicolas; Petit, Antoine; Emery, Evelyne; Lechapt-Zalcman, Emmanuelle; Peltier, Johann; Duntze, Julien; Dezamis, Edouard; Voirin, Jimmy; Menei, Philippe; Caire, François; Dam Hieu, Phong; Barat, Jean-Luc; Langlois, Olivier; Vignes, Jean-Rodolphe; Fabbro-Peray, Pascale; Riondel, Adeline; Sorbets, Elodie; Zanello, Marc; Roux, Alexandre; Carpentier, Antoine; Bauchet, Luc; Pallud, Johan

    2017-11-20

    We assessed prognostic factors in relation to OS from progression in recurrent glioblastomas. Retrospective multicentric study enrolling 407 (training set) and 370 (external validation set) adult patients with a recurrent supratentorial glioblastoma treated by surgical resection and standard combined chemoradiotherapy as first-line treatment. Four complementary multivariate prognostic models were evaluated: Cox proportional hazards regression modeling, single-tree recursive partitioning, random survival forest, conditional random forest. Median overall survival from progression was 7.6 months (mean, 10.1; range, 0-86) and 8.0 months (mean, 8.5; range, 0-56) in the training and validation sets, respectively (p = 0.900). Using the Cox model in the training set, independent predictors of poorer overall survival from progression included increasing age at histopathological diagnosis (aHR, 1.47; 95% CI [1.03-2.08]; p = 0.032), RTOG-RPA V-VI classes (aHR, 1.38; 95% CI [1.11-1.73]; p = 0.004), decreasing KPS at progression (aHR, 3.46; 95% CI [2.10-5.72]; p < 0.001), while independent predictors of longer overall survival from progression included surgical resection (aHR, 0.57; 95% CI [0.44-0.73]; p < 0.001) and chemotherapy (aHR, 0.41; 95% CI [0.31-0.55]; p < 0.001). Single-tree recursive partitioning identified KPS at progression, surgical resection at progression, chemotherapy at progression, and RTOG-RPA class at histopathological diagnosis, as main survival predictors in the training set, yielding four risk categories highly predictive of overall survival from progression both in training (p < 0.0001) and validation (p < 0.0001) sets. Both random forest approaches identified KPS at progression as the most important survival predictor. Age, KPS at progression, RTOG-RPA classes, surgical resection at progression and chemotherapy at progression are prognostic for survival in recurrent glioblastomas and should inform the treatment decisions.

  16. 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.

  17. Viking-Age Sails: Form and Proportion

    Science.gov (United States)

    Bischoff, Vibeke

    2017-04-01

    Archaeological ship-finds have shed much light on the design and construction of vessels from the Viking Age. However, the exact proportions of their sails remain unknown due to the lack of fully preserved sails, or other definite indicators of their proportions. Key Viking-Age ship-finds from Scandinavia—the Oseberg Ship, the Gokstad Ship and Skuldelev 3—have all revealed traces of rigging. In all three finds, the keelson—with the mast position—is preserved, together with fastenings for the sheets and the tack, indicating the breadth of the sail. The sail area can then be estimated based on practical experience of how large a sail the specific ship can carry, in conjunction with hull form and displacement. This article presents reconstructions of the form and dimensions of rigging and sail based on the archaeological finds, evidence from iconographic and written sources, and ethnographic parallels with traditional Nordic boats. When these sources are analysed, not only do the similarities become apparent, but so too does the relative disparity between the archaeological record and the other sources. Preferential selection in terms of which source is given the greatest merit is therefore required, as it is not possible to afford them all equal value.

  18. 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.

  19. Rural AIDS Diagnoses in Florida: Changing Demographics and Factors Associated With Survival

    Science.gov (United States)

    Trepka, Mary Jo; Niyonsenga, Theophile; Maddox, Lorene M.; Lieb, Spencer

    2012-01-01

    Purpose To compare demographic characteristics and predictors of survival of rural residents diagnosed with acquired immunodeficiency syndrome (AIDS) with those of urban residents. Methods Florida surveillance data for people diagnosed with AIDS during 1993–2007 were merged with 2000 Census data using ZIP code tabulation areas (ZCTA). Rural status was classified based on the ZCTA’s rural-urban commuting area classification. Survival rates were compared between rural and urban areas using survival curves and Cox proportional hazards models controlling for demographic, clinical, and area-level socioeconomic and health care access factors. Findings Of the 73,590 people diagnosed with AIDS, 1,991 (2.7%) resided in rural areas. People in the most recent rural cohorts were more likely than those in earlier cohorts to be female, non-Hispanic black, older, and have a reported transmission mode of heterosexual sex. There were no statistically significant differences in the 3-, 5-, or 10-year survival rates between rural and urban residents. Older age at the time of diagnosis, diagnosis during the 1993–1995 period, other/unknown transmission mode, and lower CD4 count/percent categories were associated with lower survival in both rural and urban areas. In urban areas only, being non-Hispanic black or Hispanic, being US born, more poverty, less community social support, and lower physician density were also associated with lower survival. Conclusions In rural Florida, the demographic characteristics of people diagnosed with AIDS have been changing, which may necessitate modifications in the delivery of AIDS-related services. Rural residents diagnosed with AIDS did not have a significant survival disadvantage relative to urban residents. PMID:23802929

  20. Pre-diagnosis diet and survival after a diagnosis of ovarian cancer.

    Science.gov (United States)

    Playdon, Mary C; Nagle, Christina M; Ibiebele, Torukiri I; Ferrucci, Leah M; Protani, Melinda M; Carter, Jonathan; Hyde, Simon E; Neesham, Deborah; Nicklin, James L; Mayne, Susan T; Webb, Penelope M

    2017-06-06

    The relationship between diet and survival after ovarian cancer diagnosis is unclear as a result of a limited number of studies and inconsistent findings. We examined the association between pre-diagnostic diet and overall survival in a population-based cohort (n=811) of Australian women diagnosed with invasive epithelial ovarian cancer between 2002 and 2005. Diet was measured by validated food frequency questionnaire. Deaths were ascertained up to 31 August 2014 via medical record review and Australian National Death Index linkage. We conducted Cox proportional hazards regression analysis, controlling for diagnosis age, tumour stage, grade and subtype, residual disease, smoking status, body mass index, physical activity, marital status, and energy intake. We observed improved survival with highest compared with lowest quartile of fibre intake (hazard ratio (HR)=0.69, 95% CI: 0.53-0.90, P-trend=0.002). There was a suggestion of better survival for women with highest compared with lowest intake category of green leafy vegetables (HR=0.79, 95% CI: 0.62-0.99), fish (HR=0.74, 95% CI: 0.57-0.95), poly- to mono-unsaturated fat ratio (HR=0.76, 95% CI: 0.59-0.98), and worse survival with higher glycaemic index (HR=1.28, 95% CI: 1.01-1.65, P-trend=0.03). The associations we observed between healthy components of diet pre-diagnosis and ovarian cancer survival raise the possibility that dietary choices after diagnosis may improve survival.

  1. DNA Repair Gene Polymorphisms in Relation to Non-Small Cell Lung Cancer Survival

    Directory of Open Access Journals (Sweden)

    Yuliang Su

    2015-07-01

    Full Text Available Background: Single nucleotide polymorphisms (SNPs in the DNA repair genes are suspected to be related to the survival of lung cancer patients due to their possible influence on DNA repair capacity (DRC. However, the study results are inconsistent. Methods: A follow-up study of 610 non-small cell lung cancer (NSCLC patients was conducted to investigate genetic polymorphisms associated with the DNA repair genes in relation to NSCLC survival; 6 SNPs were genotyped, including XRCC1 (rs25487 G>A, hOGG1 (rs1052133 C>G, MUTYH (rs3219489 G>C, XPA (rs1800975 G>A, ERCC2 (rs1799793 G>A and XRCC3 (rs861539 C>T. Kaplan-Meier survival curve and Cox proportional hazards regression analyses were performed. SNP-SNP interaction was also examined using the survival tree analysis. Results: Advanced disease stage and older age at diagnosis were associated with poor prognosis of NSCLC. Patients with the variant ‘G' allele of hOGG1 rs1052133 had poor overall survival compared with those with the homozygous wild ‘CC' genotype, especially in female patients, adenocarcinoma histology, early stage, light smokers and without family history of cancer. For never smoking female lung cancer patients, individuals carrying homozygous variant ‘AA' genotype of XPA had shorter survival time compared to those with wild ‘G' alleles. Furthermore, females carrying homozygous variant XPA and hOGG1 genotypes simultaneously had 2.78-fold increased risk for death. Among all 6 polymorphisms, the homozygous variant ‘AA' of XPA carriers had poor prognosis compared to the carriers of wild ‘G' alleles of XPA together with other base excision repair (BER polymorphisms. Conclusions: Besides disease stage and age, the study found DNA repair gene polymorphisms were associated with lung cancer survival.

  2. Associations of ATM Polymorphisms With Survival in Advanced Esophageal Squamous Cell Carcinoma Patients Receiving Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Du, Zhongli [State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Department of Etiology and Carcinogenesis (Beijing Key Laboratory for Carcinogenesis and Cancer Prevention), Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Zhang, Wencheng [Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Zhou, Yuling; Yu, Dianke; Chen, Xiabin; Chang, Jiang; Qiao, Yan; Zhang, Meng; Huang, Ying; Wu, Chen [State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Department of Etiology and Carcinogenesis (Beijing Key Laboratory for Carcinogenesis and Cancer Prevention), Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Xiao, Zefen, E-mail: xiaozefen@sina.com [Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Tan, Wen, E-mail: tanwen@cicams.ac.cn [State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Department of Etiology and Carcinogenesis (Beijing Key Laboratory for Carcinogenesis and Cancer Prevention), Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); and others

    2015-09-01

    Purpose: To investigate whether single nucleotide polymorphisms (SNPs) in the ataxia telangiectasia mutated (ATM) gene are associated with survival in patients with esophageal squamous cell carcinoma (ESCC) receiving radiation therapy or chemoradiation therapy or surgery only. Methods and Materials: Four tagSNPs of ATM were genotyped in 412 individuals with clinical stage III or IV ESCC receiving radiation therapy or chemoradiation therapy, and in 388 individuals with stage I, II, or III ESCC treated with surgery only. Overall survival time of ESCC among different genotypes was estimated by Kaplan-Meier plot, and the significance was examined by log-rank test. The hazard ratios (HRs) and 95% confidence intervals (CIs) for death from ESCC among different genotypes were computed by a Cox proportional regression model. Results: We found 2 SNPs, rs664143 and rs664677, associated with survival time of ESCC patients receiving radiation therapy. Individuals with the rs664143A allele had poorer median survival time compared with the rs664143G allele (14.0 vs 20.0 months), with the HR for death being 1.45 (95% CI 1.12-1.89). Individuals with the rs664677C allele also had worse median survival time than those with the rs664677T allele (14.0 vs 23.5 months), with the HR of 1.57 (95% CI 1.18-2.08). Stratified analysis showed that these associations were present in both stage III and IV cancer and different radiation therapy techniques. Significant associations were also found between the SNPs and locosregional progression or progression-free survival. No association between these SNPs and survival time was detected in ESCC patients treated with surgery only. Conclusion: These results suggest that the ATM polymorphisms might serve as independent biomarkers for predicting prognosis in ESCC patients receiving radiation therapy.

  3. Survival Trends in Elderly Patients with Glioblastoma in the United States: a Population-based Study.

    Science.gov (United States)

    Shah, Binay Kumar; Bista, Amir; Sharma, Sandhya

    2016-09-01

    Concomitant and adjuvant temozolomide along with radiotherapy following surgery (the Stupp regimen) is the preferred therapy for young patients with glioblastoma as well as for elderly (>70 years) ones with favorable risk factors. This study investigated the survival trend since the introduction of the use of the Stupp regimen in elderly patients in a population-based setting. Surveillance, Epidemiology, and End Results 18 database was used to identify patients aged ≥70 years with glioblastoma as the first primary cancer diagnosed from 1999 to 2010. Chi-square test, Kaplan-Meier analysis with log-rank test and Cox proportional hazard method were used for analysis. A total of 5,575 patients were included in the survival analysis. Survival in Stupp era (year of diagnosis ≥2005) was significantly better compared to the pre-Stupp era with p<0.001 by log-rank test, with 1-, 2- and 3-year overall survival of 18.8% vs. 12.9%, 6.5% vs. 2.1% and 3.1% vs. 0.9% respectively, and hazard ratio for death in 3 years in the Stupp era was 0.87 (95% confidence interval=0.82-0.92; p<0.001) when compared with the pre-Stupp era. Factors such as younger age (<85 years), female sex, married status, Caucasian race and total resection favored better survival compared to their counterparts. This study shows that the survival of elderly patients with glioblastoma has improved since the introduction of the Stupp regimen. However, there are significant differences in survival rates among various cohorts. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  4. Immigration factors and prostate cancer survival among Hispanic men in California: does neighborhood matter?

    Science.gov (United States)

    Schupp, Clayton W; Press, David J; Gomez, Scarlett Lin

    2014-05-01

    Hispanics are more likely than other racial/ethnic groups in the United States to be diagnosed with later stage of prostate cancer, yet they have lower prostate cancer mortality rates. The authors evaluated the impact of nativity and neighborhood-level Hispanic ethnic enclave on prostate cancer survival among Hispanics. A total of 35,427 Hispanic men diagnosed with invasive prostate cancer from 1995 through 2008 in the California Cancer Registry were studied; vital status data were available through 2010. Block group-level neighborhood measures were developed from US Census data. Stage-stratified Cox proportional hazards models were used to assess the effect of nativity and ethnic enclave on prostate cancer survival. In models adjusted for neighborhood socioeconomic status and other individual factors, foreign-born Hispanics were found to have a significantly lower risk of prostate cancer survival (hazards ratio [HR], 0.81; 95% confidence interval [95% CI], 0.75-0.87). Living in an ethnic enclave appeared to modify this effect, with the survival advantage slightly more pronounced in the high ethnic enclave neighborhoods (HR, 0.78; 95% CI, 0.71-0.86) compared with low ethnic enclave neighborhoods (HR, 0.86; 95% CI, 0.76-0.98). Despite lower socioeconomic status, Hispanic immigrants have better survival after prostate cancer than US-born Hispanics and this pattern was more striking among those living in ethnic enclaves. Identifying the modifiable individual and neighborhood-level factors that facilitate this survival advantage in Hispanic immigrants may help to inform specific interventions to improve survival among all patients. © 2014 American Cancer Society.

  5. Survival rates and risk factors for mortality in systemic lupus erythematosus patients in a Chinese center.

    Science.gov (United States)

    Wu, Ge; Jia, Xiaoyuan; Gao, Dan; Zhao, Zhanzheng

    2014-07-01

    This paper aims to study the survival and risk factors affecting the long-term prognosis of Chinese patients with systemic lupus erythematosus (SLE). We collected clinical data of 1,072 SLE patients at the time of diagnosis. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazard regression model for the risk factors affecting prognosis. Of the original 1,072 recruited SLE patients, 665 (570 females and 95 males) were successfully followed up. Mean follow-up was 5.47 ± 4.62 years. Mean age of onset was 29.4 ± 13.4 years. Eighty-one patients did not survive during follow-up; infection, followed by cardiovascular disease, renal failure and SLE disease activity were the leading causes of death. The 5- and 10-year survival rates were 91.2 and 79.6 %, respectively. Moreover, the 5-year survival rates of female and male patients were 92.6 and 81.6 % respectively, and the 10-year survival rates were 80.8 and 62.3 %, respectively. Univariate analyses indicated that male gender, older age of onset, hypertension, increased blood creatinine levels, and high-density lipoprotein cholesterol at the time of diagnosis of SLE were risk factors for all-cause mortality. After adjusting for potential confounders by multivariate analysis, male gender, older age of onset, and high SLEDAI scores at the time of diagnosis were independent risk factors for all-cause mortality in SLE patients. The long-term survival of Chinese SLE patients is comparable to that of other countries. Older age of onset, high disease activity, and decline in renal function are independent risk factors for mortality in patients with SLE.

  6. Effect of socioeconomic status as measured by education level on survival in breast cancer clinical trials.

    Science.gov (United States)

    Herndon, James E; Kornblith, Alice B; Holland, Jimmie C; Paskett, Electra D

    2013-02-01

    This paper aims to investigate the effect of socioeconomic status, as measured by education, on the survival of breast cancer patients treated on 10 studies conducted by the Cancer and Leukemia Group B. Sociodemographic data, including education, were reported by the patient at trial enrollment. Cox proportional hazards model stratified by treatment arm/study was used to examine the effect of education on survival among patients with early stage and metastatic breast cancer, after adjustment for known prognostic factors. The patient population included 1020 patients with metastatic disease and 5146 patients with early stage disease. Among metastatic patients, factors associated with poorer survival in the final multivariable model included African American race, never married, negative estrogen receptor status, prior hormonal therapy, visceral involvement, and bone involvement. Among early stage patients, significant factors associated with poorer survival included African American race, separated/widowed, post/perimenopausal, negative/unknown estrogen receptor status, negative progesterone receptor status, >4 positive nodes, tumor diameter >2 cm, and education. Having not completed high school was associated with poorer survival among early stage patients. Among metastatic patients, non-African American women who lacked a high school degree had poorer survival than other non-African American women, and African American women who lacked a high school education had better survival than educated African American women. Having less than a high school education is a risk factor for death among patients with early stage breast cancer who participated in a clinical trial, with its impact among metastatic patients being less clear. Post-trial survivorship plans need to focus on women with low social status, as measured by education. Copyright © 2011 John Wiley & Sons, Ltd.

  7. A Box-Cox normal model for response times.

    Science.gov (United States)

    Klein Entink, R H; van der Linden, W J; Fox, J-P

    2009-11-01

    The log-transform has been a convenient choice in response time modelling on test items. However, motivated by a dataset of the Medical College Admission Test where the lognormal model violated the normality assumption, the possibilities of the broader class of Box-Cox transformations for response time modelling are investigated. After an introduction and an outline of a broader framework for analysing responses and response times simultaneously, the performance of a Box-Cox normal model for describing response times is investigated using simulation studies and a real data example. A transformation-invariant implementation of the deviance information criterium (DIC) is developed that allows for comparing model fit between models with different transformation parameters. Showing an enhanced description of the shape of the response time distributions, its application in an educational measurement context is discussed at length.

  8. Artificial neural networks--a method for prediction of survival following liver resection for colorectal cancer metastases.

    Science.gov (United States)

    Spelt, L; Nilsson, J; Andersson, R; Andersson, B

    2013-06-01

    To construct an artificial neural network (ANN) model to predict survival after liver resection for colorectal cancer (CRC) metastases. CRC liver metastases are fatal if untreated and resection can possibly be curative. Predictive models stratify patients into risk categories to predict prognosis and select those who can benefit from aggressive multidisciplinary treatment and intensive follow-up. Standard linear models assume proportional hazards, whereas more flexible non-linear survival models based on ANNs may better predict individual long-term survival. Clinicopathological and perioperative data on patients who underwent liver resection for CRC metastases between 1994 and 2009 were studied retrospectively. A five-fold cross-validated ANN model was constructed. Risk variables were ranked and minimised through calibrated ANNs. Time dependent hazard ratio (HR) was calculated using the ANN. Performance of the ANN model and Cox regression were analysed using Harrell's C-index. 241 patients with a median age of 66 years were included. There were no perioperative deaths and median survival was 56 months. Of 28 potential risk variables, the ANN selected six: age, preoperative chemotherapy, size of largest metastasis, haemorrhagic complications, preoperative CEA-level and number of metastases. The C-index was 0.72 for the ANN model and 0.66 for Cox regression. For the first time ANNs were used to successfully predict individual long-term survival for patients following liver resection for CRC metastases. In the future, more complex prognostic factors can be incorporated into the ANN model to increase its predictive ability. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. The Association between Phase Angle of Bioelectrical Impedance Analysis and Survival Time in Advanced Cancer Patients: Preliminary Study.

    Science.gov (United States)

    Lee, So Yeon; Lee, Yong Joo; Yang, Jung-Hwa; Kim, Chul-Min; Choi, Whan-Seok

    2014-09-01

    A frequent manifestation of advanced cancer patients is malnutrition, which is correlated with poor prognosis and high mortality. Bioelectrical impedance analysis (BIA) is an easy-to-use and non-invasive technique to evaluate changes in body composition and nutritional status. We investigated BIA-derived phase angle as a prognostic indicator for survival in advanced cancer patients. Twenty-eight patients treated at the hospice center of Seoul St. Mary's Hospital underwent BIA measurements from January, 2013 to May, 2013. We also evaluated palliative prognostic index (PPI) and palliative performance scale to compare with the prognostic value of phase angle. Cox's proportional hazard models were constructed to evaluate the prognostic effect of phase angle. The Kaplan Meier method was used to calculate survival. Using univariate Cox analysis, phase angle (hazard ratio [HR], 0.61/per degree increase; 95% confidence interval [CI], 0.42 to 0.89; P = 0.010), PPI (HR, 1.21; 95% CI, 1.00 to 1.47; P = 0.048) were found to be significantly associated with survival. Adjusting age, PPI, body mass index, phase angle significantly showed association with survival in multivariate analysis (HR, 0.64/per degree increase; 95% CI, 0.42 to 0.95; P = 0.028). Survival time of patients with phase angle ≥ 4.4° was longer than patients with phase angle < 4.4° (log rank, 6.208; P-value = 0.013). Our data suggest BIA-derived phase angle may serve as an independent prognostic indicator in advanced cancer patients.

  10. Dual, but not selective, COX-1 and COX-2 inhibitors, attenuate acetic acid-evoked bladder irritation in the anaesthetised female cat.

    Science.gov (United States)

    Wibberley, Alexandra; McCafferty, Gerald P; Evans, Christopher; Edwards, Richard M; Hieble, J Paul

    2006-05-01

    Non-selective cyclooxygenase (COX) inhibitors exert effects on lower urinary tract function in several species. The exact contributions of COX-1 and COX-2 isozymes have not been studied much. The present studies investigated the effects of non- and selective COX inhibitors on bladder irritation in the cat.Chloralose-anaesthetised female cats were catheterised through the bladder dome for cystometric evaluation of bladder responses to intravesical infusion of saline or acetic acid. Bladder capacity, voiding efficiency, threshold pressure, and reflex-evoked bladder contraction amplitude and duration were measured. The cat COX selectivity of the doses of inhibitors examined was determined using an in vitro whole-blood assay and analysis of plasma levels. Pretreatment with indomethacin or ketoprofen (non-selective COX inhibitors; 0.3 mg kg(-1) i.v.) inhibited acetic acid-evoked irritation (characterised by a decrease in bladder capacity in vehicle pretreated animals). FR-122047 (selective COX-1 inhibitor), NS-398 and nimesulide (selective COX-2 inhibitors; 1 and 3 mg kg(-1) i.v.) had no effects on bladder irritation. Analysis of plasma levels of the doses examined and determination of COX-1 and COX-2 inhibition in cat whole blood confirmed the reported selectivity of these compounds in this species. The present studies suggest that dual COX inhibition is required to attenuate acetic acid-evoked bladder irritation in the cat.

  11. A Note on Implementing Box-Cox Quantile Regression

    OpenAIRE

    Wilke, Ralf A.; Fitzenberger, Bernd; Zhang, Xuan

    2005-01-01

    The Box-Cox quantile regression model using the two stage method introduced by Chamberlain (1994) and Buchinsky (1995) provides an attractive extension of linear quantile regression techniques. However, a major numerical problem exists when implementing this method which has not been addressed so far in the literature. We suggest a simple solution modifying the estimator slightly. This modification is easy to implement. The modified estimator is still [square root] n-consistent and its asympt...

  12. Some functional limit theorems for compound Cox processes

    Energy Technology Data Exchange (ETDEWEB)

    Korolev, Victor Yu. [Faculty of Computational Mathematics and Cybernetics, Moscow State University, Moscow (Russian Federation); Institute of Informatics Problems FRC CSC RAS (Russian Federation); Chertok, A. V. [Faculty of Computational Mathematics and Cybernetics, Moscow State University, Moscow (Russian Federation); Euphoria Group LLC (Russian Federation); Korchagin, A. Yu. [Faculty of Computational Mathematics and Cybernetics, Moscow State University, Moscow (Russian Federation); Kossova, E. V. [Higher School of Economics National Research University, Moscow (Russian Federation); Zeifman, Alexander I. [Vologda State University, S.Orlova, 6, Vologda (Russian Federation); Institute of Informatics Problems FRC CSC RAS, ISEDT RAS (Russian Federation)

    2016-06-08

    An improved version of the functional limit theorem is proved establishing weak convergence of random walks generated by compound doubly stochastic Poisson processes (compound Cox processes) to Lévy processes in the Skorokhod space under more realistic moment conditions. As corollaries, theorems are proved on convergence of random walks with jumps having finite variances to Lévy processes with variance-mean mixed normal distributions, in particular, to stable Lévy processes.

  13. Obesity and survival in population-based patients with pancreatic cancer in the San Francisco Bay Area.

    Science.gov (United States)

    Gong, Zhihong; Holly, Elizabeth A; Bracci, Paige M

    2012-12-01

    Obesity has been consistently associated with increased risk of pancreatic cancer incidence and mortality. However, studies of obesity and overall survival in patients with pancreatic cancer are notably lacking, especially in population-based studies. Active and passive follow-up were used to determine vital status and survival for 510 pancreatic cancer patients diagnosed from 1995 to 1999 in a large population-based case-control study in the San Francisco Bay Area. Survival rates were computed using Kaplan-Meier methods. Hazard ratios (HR) and 95 % confidence intervals (CI) were estimated in multivariable Cox proportional hazards models as measures of the association between pre-diagnostic obesity and pancreatic cancer survival. An elevated hazard ratio of 1.3 (95 % CI, 0.91-1.81) was observed for obese [body mass index (BMI) ≥ 30] compared with normal range BMI (patients. Associations between BMI and overall survival did not statistically significantly vary by known prognostic and risk factors (all p-interaction ≥0.18), yet elevated HRs consistently were observed for obese compared with normal BMI patients [localized disease at diagnosis (HR, 3.1), surgical resection (HR, 1.6), ever smokers (HR, 1.6), diabetics (HR, 3.3)]. Poor survival was observed among men, older patients, more recent and current smokers, whereas improved survival was observed for Asian/Pacific Islanders. Our results in general provide limited support for an association between pre-diagnostic obesity and decreased survival in patients with pancreatic cancer. Patterns of reduced survival associated with obesity in some patient subgroups could be due to chance and require assessment in larger pooled studies.

  14. Long-Term Survival Outcomes of Cancer-Directed Surgery for Malignant Pleural Mesothelioma: Propensity Score Matching Analysis.

    Science.gov (United States)

    Nelson, David B; Rice, David C; Niu, Jiangong; Atay, Scott; Vaporciyan, Ara A; Antonoff, Mara; Hofstetter, Wayne L; Walsh, Garrett L; Swisher, Stephen G; Roth, Jack A; Tsao, Anne; Gomez, Daniel; Giordano, Sharon H; Mehran, Reza; Sepesi, Boris

    2017-10-10

    Purpose Small observational studies have shown a survival advantage to undergoing cancer-directed surgery for malignant pleural mesothelioma (MPM); however, it is unclear if these results are generalizable. Our purpose was to evaluate survival after treatment of MPM with cancer-directed surgery and to explore the effect surgery interaction with chemotherapy or radiation therapy on survival by using the National Cancer Database. Patients and Methods Patients with microscopically proven MPM were identified within the National Cancer Database (2004 to 2014). Propensity score matching was performed 1:2 and among this cohort, a Cox proportional hazards regression model was used to identify predictors of survival. Median survival was calculated by using the Kaplan-Meier method. Results Of 20,561 patients with MPM, 6,645 were identified in the matched cohort, among whom 2,166 underwent no therapy, 2,015 underwent chemotherapy alone, 850 underwent cancer-directed surgery alone, 988 underwent surgery with chemotherapy, and 274 underwent trimodality therapy. The remaining 352 patients underwent another combination of surgery, radiation, or chemotherapy. Thirty-day and 90-day mortality rates were 6.3% and 15.5%. Cancer-directed surgery, chemotherapy, and radiation therapy were independently associated with improved survival (hazard ratio, 0.77, 0.74, and 0.88, respectively). Stratified analysis revealed that surgery-based multimodality therapy demonstrated an improved survival compared with surgery alone, with no significant difference between surgery-based multimodality therapies; however, the largest estimated effect was when cancer-directed surgery, chemotherapy, and radiation therapy were combined (hazard ratio, 0.52). For patients with the epithelial subtype who underwent trimodality therapy, median survival was extended from 14.5 months to 23.4 months. Conclusion MPM is an aggressive and rapidly fatal disease. Surgery-based multimodality therapy was associated with

  15. Effect of a mentor-based, supportive-expressive program, Be Resilient to Breast Cancer, on survival in metastatic breast cancer: a randomised, controlled intervention trial.

    Science.gov (United States)

    Ye, Zeng Jie; Qiu, Hong Zhong; Liang, Mu Zi; Liu, Mei Ling; Li, Peng Fei; Chen, Peng; Sun, Zhe; Yu, Yuan Liang; Wang, Shu Ni; Zhang, Zhang; Liao, Kun Lun; Peng, Cai Fen; Huang, Hui; Hu, Guang Yun; Zhu, Yun Fei; Zeng, Zhen; Hu, Qu; Zhao, Jing Jing

    2017-11-07

    Because of medical advances, metastatic breast cancer (MBC) is now viewed as a chronic disease, rather than an imminent death sentence. Helping women live with this disease requires more than a medical approach to symptoms. Thus, a mentor-based and supportive-expressive program 'Be Resilient to Breast Cancer' (BRBC) was designed to help Chinese women with MBC enhance their resilience levels, biopsychosocial functions, and potentially extend their life span. A total of 226 women with MBC were randomly assigned, in a 1 : 1 ratio, to an intervention group (IG) that participated in BRBC or to a control group (CG) that received no intervention. Be Resilient to Breast Cancer was conducted for 120 min once a week. Primary outcomes were cancer-specific survival and secondary outcomes were resilience, Allostatic Load Index (ALI), anxiety, depression, and quality of life (QoL). The Cox proportional-hazards model was used for survival analysis and growth mixture models were performed for secondary outcomes. Be Resilient to Breast Cancer did not significantly prolong 3- or 5-year survival (median survival, 36.7 months in IG and 31.5 months in CG). The hazard ratio for death was 0.736 (95% CI, 0.525-1.133, P=0.076; univariate Cox model) and 0.837 (95% CI, 0.578-1.211, P=0.345; multivariate Cox analysis). The IG improved in anxiety (ES=0.85, Presilience (ES=0.67, Presilience, QoL, ALI, and emotional distress.

  16. Bariatric Surgery Significantly Improves Body Proportion

    Science.gov (United States)

    Kang, Thomas; Wooldridge, James; Periou, Laura; Richardson, William S.

    2012-01-01

    Background It is well known that bariatric surgery provides excellent weight loss and resolution of comorbid conditions. We propose an additional benefit: Because body proportion is an independent predictor of diabetes and cardiovascular risk, we hypothesize that bariatric surgery results in improved body proportion and may thus improve health risk independent of overall weight loss and resolution of comorbid conditions. Methods A total of 168 patients underwent laparoscopic bariatric surgery at our institution from December 2006 to September 2009. Prospective data gathered preoperatively and at 3, 6, and 12 months postoperatively included body mass index (BMI); excess weight loss (EWL); waist-hip ratio (WHR); and discontinuation of hypertensive, hyperlipidemic, and diabetic medications. Results Of the 168 patients, 122 underwent Roux-en-Y gastric bypass, 40 gastric band, and 6 gastric sleeve procedures. Mean preoperative BMI was 48.6 kg/m2 (SD  =  7.8 kg/m2). Mean EWL was 33.7 lbs (SD  =  11.9 lbs) at 3 months, 46.35 lbs (SD  =  15.58 lbs) at 6 months, and 52.48 lbs (SD  =  24.19 lbs) at 1 year. Mean WHR was 0.91 (SD  =  0.1) preoperatively, 0.87 (SD  =  0.1) at 3 months (P < .0001), 0.87 (SD  =  0.09) at 6 months (P < .0001), and 0.86 (SD  =  0.1) at 1 year (P  =  .0006). At 1-year follow-up, 52% of patients had discontinued hypertensive medications, 64% had discontinued diabetic medications, and 56% had discontinued hyperlipidemic medications. Conclusions Along with well-known improvements in overall weight and comorbid conditions, bariatric surgery significantly improves body proportion, which may decrease health risk. Continued follow-up will determine if this change is long term or if patients will revert to preoperative WHRs. Future studies with sufficient power to study individual bariatric procedures will determine which procedures, if any, provide patients with the greatest

  17. 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.

  18. High RBM3 expression is associated with an improved survival and oxaliplatin response in patients with metastatic colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Christina Siesing

    Full Text Available High expression of the RNA-binding motif protein 3 (RBM3 has been shown to correlate, with prolonged survival in several malignant diseases and with the benefit of platinum-based chemotherapy in ovarian cancer. The aim of this study was to evaluate RBM3 in metastatic colorectal cancer (mCRC as a prognostic factor for overall survival and in relation to benefit of first-line chemotherapy.Immunohistochemical staining was conducted and evaluated in tumours from 455 mCRC patients. Kaplan-Meier analysis and Cox regression proportional hazards models were used to access the impact of RBM3 expression on overall survival (OS and progression-free survival (PFS.High RBM3 expression, both nuclear and cytoplasmic, was an independent prognostic factor for prolonged OS (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.50-0.90 and HR 0.66, 95% CI 0.48-0.91, respectively. PFS was significantly longer in patients with high RBM3 expression who had received first-line oxaliplatin based treatment, compared to those who had received irinotecan based treatment, both regarding nuclear and cytoplasmic expression (p-value 0.020 and 0.022 respectively.High RBM3 expression is an independent predictor of prolonged survival in mCRC patients, in particular in patients treated with first-line oxaliplatin based chemotherapy.

  19. 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.

  20. Survival of women with breast cancer in central and northern Denmark, 1998-2009.

    Science.gov (United States)

    Lietzen, Lone Winther; Sørensen, Gitte Vrelits; Ording, Anne Gulbech; Garne, Jens Peter; Christiansen, Peer; Nørgaard, Mette; Jacobsen, Jacob

    2011-01-01

    Breast cancer is the most common cancer among women worldwide. The Nordic countries have relatively high survival, but Denmark has a lower survival than neighboring countries. A breast cancer screening program was introduced in 2007 and 2008 in the northern and central regions of Denmark respectively. We aimed to examine possible changes in survival of Danish breast cancer patients in central and northern Denmark in the period 1998-2009. From the northern and central Denmark regions, we included all women (n = 13,756) with an incident diagnosis of breast cancer, as recorded in the Danish National Registry of Patients during the period January 1, 1998 through December 31, 2009. We calculated age-stratified survival and used Cox proportional hazard regression to estimate mortality rate ratios (MRRs) for all breast cancer patients. Median age was 62 years (21-102 years). The overall 1-year survival improved steadily over the period from 90.9% in 1998-2000 to 94.4% in 2007-2009, corresponding to a 1-year age adjusted MRR of 0.68 in 2007-2009 compared with the reference period 1998-2000. We estimated the 5-year survival to improve from 70.0% in 1998-2000 to 74.7% in 2007-2009, corresponding to a 5-year age adjusted MRR of 0.82 in 2007-2009 compared with the reference period 1998-2000. For middle-aged women (50-74 years) 1-year survival increased from 92.8% in 1998-2000 to 96.6% in 2008-2009, and 5-year survival was expected to increase from 73.9% in 1998-2000 to 80.2% in 2007-2009. Among younger women (15-49 years) and elderly women (>75 years), 1-year survival and 5-year predicted survival did not change over the two time periods. Survival of breast cancer patients has improved in Denmark over the period 1998-2009, and this change was most distinct in women aged 50-74 years. Survival improved even before the implementation of a formal breast cancer screening program.

  1. A randomized phase II study investigating the addition of the specific COX-2 inhibitor celecoxib to docetaxel plus carboplatin as first-line chemotherapy for stage IC to IV epithelial ovarian cancer, Fallopian tube or primary peritoneal carcinomas : the DoCaCel study

    NARCIS (Netherlands)

    Reyners, A. K. L.; de Munck, L.; Erdkamp, F. L. G.; Smit, W. M.; Hoekman, K.; Lalisang, R. I.; de Graaf, H.; Wymenga, A. N. M.; Polee, M.; Hollema, H.; van Vugt, M. A. T. M.; Schaapveld, M.; Willemse, P. H. B.

    2012-01-01

    In ovarian cancer, cyclooxygenase-2 (COX-2) overexpression is prognostic for poor survival. We investigated the efficacy of celecoxib (C), a selective COX-2 inhibitor, added to docetaxel (Taxotere)/carboplatin (DC) in advanced ovarian cancer. In a phase II, randomized study, 400 mg celecoxib b.i.d.

  2. Association of Disease Location and Treatment With Survival in Diffuse Large B-Cell Lymphoma of the Eye and Ocular Adnexal Region.

    Science.gov (United States)

    Ahmed, Aseef H; Foster, C Stephen; Shields, Carol L

    2017-10-01

    Primary diffuse large B-cell lymphoma (DLBCL) of the ocular region is rare, and the utility of surgery and radiation therapy remains unresolved. To explore the clinical characteristics and determine factors associated with overall survival in primary vitreoretinal lymphoma (PVRL) and ocular adnexal (OA)-uveal DLBCL. This retrospective analysis included 396 patients with ophthalmic DLBCL from January 1, 1973, through December 31, 2014, using the Surveillance, Epidemiology, and End Results database. The median follow-up was 39.0 months (interquartile range, 5.1-72.9 months). All patients diagnosed with primary DLBCL of the eye or retina (PVRL) or the eyelid, conjunctiva, choroid, ciliary body, lacrimal gland, or orbit (OA-uveal lymphoma) were included. Patients diagnosed at autopsy or with additional neoplastic disease were excluded. Patient demographic characteristics, disease location, treatment modalities, and overall survival. Forty-seven patients with PVRL (24 women [51.1%] and 23 men [48.9%]) and 349 with OA-uveal DLBCL (192 women [55.0%] and 157 men [45.0%]) had a similar mean (SD) age at diagnosis (69.6 [12.3] vs 66.1 [17.7] years). No difference in the use of surgery or radiation therapy by location was found. For all PVRL and OA-uveal DLBCL, a Cox proportional hazards regression model affirmed that age older than 60 years was associated with increased risk for death (hazard ratio [HR], 2.7; 95% CI, 1.9-4.0; P DLBCL, 59.1% (SE, 2.8%; Mantel-Cox test, P = .007). Median overall survival was lower in PVRL (38.0 months; 95% CI, 14.2-61.8 months) than in OA-uveal DLBCL (96.0 months; 95% CI, 67.3-124.7 months; Mantel-Cox test, P = .007). In addition, median overall survival in ophthalmic-only disease was higher (84.0 months; 95% CI, 63.2-104.8 months) than that in primary DLBCL that occurred outside the central nervous system and ophthalmic regions (46.0 months; 95% CI, 44.4-47.6 months; Mantel-Cox test, P DLBCL differed by 17.7%, and overall survival

  3. Nomogram Prediction of Survival and Recurrence in Patients With Extrahepatic Bile Duct Cancer Undergoing Curative Resection Followed by Adjuvant Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Song, Changhoon [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Kyubo, E-mail: kyubokim@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Chie, Eui Kyu [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of); Kim, Jin Ho [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Jang, Jin-Young; Kim, Sun Whe [Department of Surgery, Seoul National University College of Medicine, Seoul (Korea, Republic of); Han, Sae-Won; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Bang, Yung-Jue [Department of Internal Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Ha, Sung W. [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of)

    2013-11-01

    Purpose: To develop nomograms for predicting the overall survival (OS) and relapse-free survival (RFS) in patients with extrahepatic bile duct cancer undergoing adjuvant chemoradiation therapy after curative resection. Methods and Materials: From January 1995 through August 2006, a total of 166 consecutive patients underwent curative resection followed by adjuvant chemoradiation therapy. Multivariate analysis using Cox proportional hazards regression was performed, and this Cox model was used as the basis for the nomograms of OS and RFS. We calculated concordance indices of the constructed nomograms and American Joint Committee on Cancer (AJCC) staging system. Results: The OS rate at 2 years and 5 years was 60.8% and 42.5%, respectively, and the RFS rate at 2 years and 5 years was 52.5% and 38.2%, respectively. The model containing age, sex, tumor location, histologic differentiation, perineural invasion, and lymph node involvement was selected for nomograms. The bootstrap-corrected concordance index of the nomogram for OS and RFS was 0.63 and 0.62, respectively, and that of AJCC staging for OS and RFS was 0.50 and 0.52, respectively. Conclusions: We developed nomograms that predicted survival and recurrence better than AJCC staging. With caution, clinicians may use these nomograms as an adjunct to or substitute for AJCC staging for predicting an individual's prognosis and offering tailored adjuvant therapy.

  4. Lung cancer associated hypercalcemia: An analysis of factors influencing survival and prognosis in 34 cases

    Directory of Open Access Journals (Sweden)

    Su-jie ZHANG

    2012-06-01

    Full Text Available Objectives  To explore the factors influencing survival time in lung cancer associated hypercalcemia patients. Methods  Thirty-four patients with pathologically confirmed lung cancer complicated with hypercalcemia, who were treated at the Department of Oncology in General Hospital of PLA from Jan. 2001 to Dec. 2010, were enrolled in this study. The clinical data analyzed included sex, age, pathological type of the malignancies, organ metastasis (bone, lung, liver, kidney, brain, number of distal metastatic site, mental status, interval between final diagnosis of lung cancer and of hypercalcemia, peak value of blood calcium during the disease course, treatment methods and so on. Survival analysis was performed with the Kaplan-Meier method and Cox analysis with statistic software SPSS 18.0 to identify the potential prognostic factors. Results  The highest blood calcium level ranged from 2.77 to 4.87mmol/L, and the median value was 2.94mmol/L. The patients' survival time after diagnosis of hypercalcemia varied from 1 day to 1067 days, and the median survival time was 92 days. With the log-rank test, age above 50 years old, hypercalcemia occurring over 90 days after diagnosis of cancer, central nervous system symptoms and renal metastasis were predictors for poor survival (P=0.048, P=0.001, P=0.000, P=0.003. In the COX proportional hazard model analysis, age above 50 years old, hypercalcemia occurring over 90 days after cancer diagnosis, central nervous system symptoms and renal metastasis were significant prognostic factors for poor survival (HR=11.483, P=0.006; HR=4.371, P=0.002; HR=6.064, P=0.026; HR=8.502, P=0.011. Conclusions  Patients with lung cancer associated hypercalcemia have a shorter survival time and poor prognosis. Age above 50 years old, hypercalcemia occurring over 90 days after cancer diagnosis, central nervous system symptoms and renal metastasis are significant factors of poor prognosis.

  5. Inter-country and ethnic variation in colorectal cancer survival: Comparisons between a Philippine population, Filipino-Americans and Caucasians

    Directory of Open Access Journals (Sweden)

    Gondos Adam

    2010-03-01

    Full Text Available Abstract Background Previous population-based studies showed differences in international and within country colorectal cancer survival estimates, but few investigated the role of prognostic factors. Using a "high resolution approach", we aimed to determine the effect of ethnicity and health care by comparing Filipino-Americans with Philippine residents, who have the same ethnicity, and with Caucasians living in the US, who have the same health care system. Methods Using databases from the Manila and Rizal Cancer Registries and the United States Surveillance, Epidemiology and End Results, age-adjusted five-year absolute and relative survival estimates were computed and compared between Filipino-American colorectal cancer patients, cancer patients from the Philippines and Caucasian patients. Cox proportional hazards modelling was used to determine factors affecting survival differences. Results Much lower 5-year relative survival estimates were obtained for Philippine residents (37% as compared to those in Filipino-Americans (60.3% and Caucasians (62.4%. Differences in age, stage and receipt of surgery explained a large proportion of the survival differences between Philippine residents and Filipino-Americans. However, strong excess risk of death for Philippine residents remained after controlling for these and other variables (relative risk, RR, 2.03, 95% confidence interval, 95% CI, 1.83-2.25. Conclusions Strong survival disadvantages of Philippine residents compared to Filipino-American patients were disclosed, which most likely reflect differences in access to and utilization of health care. Health education and advocacy, for both patients and health practitioners, should likewise be given priority.

  6. Thrombophilia and arteriovenous fistula survival in ESRD.

    Science.gov (United States)

    Salmela, Birgitta; Hartman, Jari; Peltonen, Seija; Albäck, Anders; Lassila, Riitta

    2013-06-01

    The role of thrombophilia in failing arteriovenous fistula (AVF) among patients with ESRD undergoing hemodialysis is not established. This study aimed to assess whether AVF primary patency is associated with thrombophilia and coagulation abnormalities. This observational study screened 219 patients between 2002 and 2004 for thrombophilia before AVF surgery. Thrombophilia included factor V Leiden and prothrombin G20210A mutations, protein C and antithrombin activities, and protein S. Coagulation abnormalities included high factor VIII:C, homocysteine, fibrinogen, and d-dimer levels; presence of antiphospholipid antibodies; and short thrombin time. We reviewed patient charts for comorbid conditions, AVF maturation and interventions, kidney transplantation, and patient survival (mean follow-up duration, 3.6 [range, 2.3-5.8] years). Primary patency from the AVF placement and functional primary patency from the first AVF cannulation were analyzed with Kaplan-Meier and Cox proportional hazards models. Thrombophilia was present in 9% of the patients, and coagulation abnormalities occurred in 77%. One-year primary patency was 68%; 46% of the AVF failures occurred before the initiation of hemodialysis. Female sex (hazard ratio [HR], 2.6; 95% confidence interval [CI], 1.7-4.1) and thrombophilia (HR, 2.2; 95% CI, 1.2-4.2) were independent risk factors for loss of primary patency. Thrombophilia mutations or low antithrombin level (HR, 3.8), female sex (HR, 2.5), and diabetes (HR, 1.9) were associated with shortened functional primary patency of AVF. Against the background of frequent coagulation abnormalities, thrombophilia and female sex predispose patients with ESRD to access failure, mostly due to thrombosis or stenosis.

  7. 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.

  8. Environmental drivers of sapwood and heartwood proportions

    Science.gov (United States)

    Thurner, Martin; Beer, Christian

    2017-04-01

    Recent advances combining information on stem volume from remote sensing with allometric relationships derived from forest inventory databases have led to spatially continuous estimates of stem, branch, root and foliage biomass in northern boreal and temperate forests. However, a separation of stem biomass into sapwood and heartwood mass has remained unsolved, despite their important differences in biogeochemical function, for instance concerning their contribution to tree respiratory costs. Although relationships between sapwood cross-sectional area and supported leaf area are well established, less is known about relations between sapwood or heartwood mass and other traits (e.g. stem mass), since these biomass compartments are more difficult to measure in practice. Here we investigate the variability in sapwood and heartwood proportions and determining environmental factors. For this task we explore an available biomass and allometry database (BAAD) and study relative sapwood and heartwood area, volume, mass and density in dependence of tree species, age and climate. First, a theoretical framework on how to estimate sap- and heartwood mass from stem mass is developed. Subsequently, the underlying assumptions and relationships are explored with the help of the BAAD. The established relationships can be used to derive spatially continuous sapwood and heartwood mass estimates by applying them to remote sensing based stem volume products. This would be a fundamental step forward to a data-driven estimate of autotrophic respiration.

  9. Association between pre-transplant dialysis modality and patient and graft survival after kidney transplantation

    DEFF Research Database (Denmark)

    Kramer, Anneke; Jager, Kitty J; Fogarty, Damian G

    2012-01-01

    Previous studies have found inconsistent associations between pre-transplant dialysis modality and subsequent post-transplant survival. We aimed to examine this relationship using the instrumental variable method and to compare the results with standard Cox regression.......Previous studies have found inconsistent associations between pre-transplant dialysis modality and subsequent post-transplant survival. We aimed to examine this relationship using the instrumental variable method and to compare the results with standard Cox regression....

  10. ABO blood group and breast cancer incidence and survival.

    Science.gov (United States)

    Gates, Margaret A; Xu, Mousheng; Chen, Wendy Y; Kraft, Peter; Hankinson, Susan E; Wolpin, Brian M

    2012-05-01

    ABO blood type has been associated with risk and survival for several malignancies; however, data for an association with breast cancer are inconsistent. Our study population consisted of Nurses' Health Study participants with self-reported serologic blood type and/or ABO genotype. Using Cox proportional hazards regression, we examined the association between serologic blood type and incident breast cancer among 67,697 women, including 3,107 cases. In addition, we examined the association with ABO genotype in a nested case-control study of 1,138 invasive breast cancer cases and 1,090 matched controls. Finally, we evaluated the association between serologic blood type and survival among 2,036 participants with breast cancer. No clear association was seen between serologic blood type or ABO genotype and risk of total breast cancer, invasive breast cancer or breast cancer subtypes. Compared to women with blood type O, the age-adjusted incidence rate ratios for serologic blood type and total breast cancer were 1.06 (95% CI, 0.98-1.15) for type A, 1.06 (95% CI, 0.93-1.22) for AB and 1.08 (95% CI, 0.96-1.20) for B. In genetic analyses, odds ratios for invasive breast cancer were 1.05 (95% CI, 0.87-1.27) for A/O, 1.21 (95% CI, 0.86-1.69) for A/A, 0.84 (95% CI, 0.56-1.26) for A/B, 0.84 (95% CI, 0.63-1.13) for B/O and 1.17 (95% CI, 0.35-3.86) for B/B, compared to O/O. No significant association was noted between blood type and overall or breast cancer-specific mortality. Our results suggest no association between ABO blood group and breast cancer risk or survival. Copyright © 2011 UICC.

  11. Family history and survival after colorectal cancer diagnosis.

    Science.gov (United States)

    Bass, Adam J; Meyerhardt, Jeffrey A; Chan, Jennifer A; Giovannucci, Edward L; Fuchs, Charles S

    2008-03-15

    A history of colorectal cancer in a first-degree relative is a recognized risk factor for developing this malignancy. The influence of a family history of colorectal cancer on survival after a diagnosis of colorectal cancer was examined in a large cohort of women. We analyzed data from 1001 women diagnosed with colorectal cancer while participating in a prospective cohort study. Data on family history were obtained before cancer diagnosis. We computed Cox proportional hazards for cancer-specific and overall mortality according to a family history of colorectal cancer, adjusting for other predictors for survival. Before diagnosis, 16% of colorectal patients reported a history of colorectal cancer in a first-degree relative. Patients with a history of colorectal cancer in 1 or more first-degree relatives experienced an adjusted hazard ratio (HR) for overall mortality of 1.32 (95% confidence interval [CI], 1.01-1.72) and colorectal cancer-specific mortality of 1.38 (95% CI, 1.02-1.86) when compared with those without a family history. Moreover, patients with 2 or more affected relatives had an HR for overall mortality of 2.07 (95% CI, 1.14-3.76) and cancer-specific mortality of 2.19 (95% CI, 1.10-4.38). The significant deleterious effect of family history was limited to patients with advanced disease at presentation and cancers originating in the colon. Among women with colorectal cancer, a history of colorectal cancer in a first-degree relative was associated with a significant decrease in survival. Additional study is needed to validate these findings and determine whether specific germline polymorphisms correlate with clinical outcomes. Copyright (c) 2008 American Cancer Society.

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

    Science.gov (United States)

    Li, Zhiguo; Owzar, Kouros

    2016-06-01

    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.

  13. Breast Cancer Survival Defined by the ER/PR/HER2 Subtypes and a Surrogate Classification according to Tumor Grade and Immunohistochemical Biomarkers

    Directory of Open Access Journals (Sweden)

    Carol A. Parise

    2014-01-01

    Full Text Available Introduction. ER, PR, and HER2 are routinely available in breast cancer specimens. The purpose of this study is to contrast breast cancer-specific survival for the eight ER/PR/HER2 subtypes with survival of an immunohistochemical surrogate for the molecular subtype based on the ER/PR/HER2 subtypes and tumor grade. Methods. We identified 123,780 cases of stages 1–3 primary female invasive breast cancer from California Cancer Registry. The surrogate classification was derived using ER/PR/HER2 and tumor grade. Kaplan-Meier survival analysis and Cox proportional hazards modeling were used to assess differences in survival and risk of mortality for the ER/PR/HER2 subtypes and surrogate classification within each stage. Results. The luminal B/HER2− surrogate classification had a higher risk of mortality than the luminal B/HER2+ for all stages of disease. There was no difference in risk of mortality between the ER+/PR+/HER2− and ER+/PR+/HER2+ in stage 3. With one exception in stage 3, the ER-negative subtypes all had an increased risk of mortality when compared with the ER-positive subtypes. Conclusions. Assessment of survival using ER/PR/HER2 illustrates the heterogeneity of HER2+ subtypes. The surrogate classification provides clear separation in survival and adjusted mortality but underestimates the wide variability within the subtypes that make up the classification.

  14. Physical activity level significantly affects the survival of patients with end-stage lung disease on a waiting list for lung transplantation.

    Science.gov (United States)

    Komatsu, Teruya; Oshima, Ayako; Chen-Yoshikawa, Toyofumi F; Harashima, Shin-Ichi; Aoyama, Akihiro; Inagaki, Nobuya; Date, Hiroshi

    2017-12-01

    Our objective was to investigate the factors predicting the survival of patients on the waiting list for lung transplantation (LT) during the waiting period, with a special emphasis on the physical activity level. The study included 70 patients with end-stage pulmonary disease who were on the waiting list for LT at Kyoto University Hospital. We examined the association between the baseline characteristics, including the body mass index and body composition, serum albumin, serum C-reactive protein (CRP), steroid administration, physical activity level (calculated by the food frequency questionnaire) and survival during the waiting period using Kaplan-Meier curves and Cox proportional hazard regression models. A physical activity level of ≤1.2 was correlated with significantly decreased survival (1-year survival: 68 vs. 90.9%, p = 0.0089), with a hazard ratio (HR) of 2.24 (95% confidence interval (CI) 1.22-4.19, p = 0.0001). Hypo-albumin (HR 2.024, 95% CI 1.339-6.009, p = 0.004), a high level of CRP (HR 2.551, CI 1.229-4.892, p = 0.02), and the administration of steroids (HR 2.258, CI 1.907-5.032, p = 0.024) were also significant predictors of survival. Low levels of physical activity during the waiting period for LT led to decreased survival times among LT candidates.

  15. Effects of feed species and HUFA composition on survival and growth of the longsnout seahorse (Hippocampus reidi

    Directory of Open Access Journals (Sweden)

    Patrick eSchubert

    2016-04-01

    Full Text Available Globally, wild seahorse populations are threatened due to, habitat destruction and unsustainable human exploitation among others. Furthermore, aquaculture-based mass-scale rearing is still uncommon due to the low survival rates of seahorse juveniles and exceptionally high feed costs. Previous studies have demonstrated the importance of both highly unsaturated fatty acid (HUFA supplies and a copepod-based rearing for seahorse survival and growth. As the latter is expensive, the question arises as to how high survival rates of seahorse juveniles can be assured under low- to moderate-cost feed regimes. In particular, it remains unknown whether the diet species or their dietary HUFA profiles determine the successful development of seahorse fry.Therefore, the aims of this study were to assess the dependence of growth and survival rates of Hippocampus reidi brood on the animal feed and to infer the impact of feed species vs. dietary HUFA profiles on juvenile growth. A nutrition experiment was conducted where juveniles were treated either with enriched Artemia nauplii (low-cost diet Art or with a mixed diet of Artemia and copepods (moderate-cost diet Art/Cop. Larval survival and growth were analyzed using Cox proportional-hazard and mixed linear model analyses. We found that i both diets enabled good survival, ii diet Art/Cop resulted in superior weight and height growth, and iii the differential effects of diets Art/Cop and Art cannot be explained by their different HUFA compositions alone.From an economical point of view, our findings of high survival rates and relatively high growth rates with the medium-cost treatment Art/Cop may open new possibilities for the large-scale rearing of seahorses. Even the application of a low-cost Art diet might be appropriate for seahorse aquacultures as both survival and growth rates are only marginally lower compared to the former diet.

  16. Assessing household health expenditure with Box-Cox censoring models.

    Science.gov (United States)

    Chaze, Jean-Paul

    2005-09-01

    In order to assess the combined presence of zero expenditures and a heavily skewed distribution of positive expenditures, the Box-Cox transformation with location parameter is used to define a set of models generalising the standard Tobit, Heckman selection and double-hurdle models. Extended flexibility with respect to previous specifications is introduced, notably regarding negative transformation parameters, which may prove necessary for medical expenditures, and corner-solution outcomes. An illustration is provided by the analysis of household health expenditure in Switzerland. Copyright (c) 2005 John Wiley & Sons, Ltd.

  17. Multiple HPV genotype infection impact on invasive cervical cancer presentation and survival.

    Science.gov (United States)

    Nogueira Dias Genta, Maria Luiza; Martins, Toni Ricardo; Mendoza Lopez, Rossana V; Sadalla, José Carlos; de Carvalho, João Paulo Mancusi; Baracat, Edmund Chada; Levi, José Eduardo; Carvalho, Jesus Paula

    2017-01-01

    Invasive cervical cancer (ICC) is the third most common malignant neoplasm affecting Brazilian women. Little is known about the impact of specific HPV genotypes in the prognosis of ICC. We hypothesized that HPV genotype would impact ICC clinical presentation and survival. Women diagnosed with ICC at the Instituto do Câncer do Estado de São Paulo (ICESP) between May 2008 and June 2012 were included in the study and were followed until December 2015. HPV genotype was detected from formalin-fixed paraffin-embedded (FFPE) tumor tissue samples using Onclarity™ system (BD Viper™ LT automated system). 292 patients aged 50±14 years were analyzed. HPVDNA was detected in 84% of patients. The HPV genotypes studied were: HPV16 (64%), HPV18 (10%), HPV33-58 (7%), HPV45 (5%), HPV31 (4%) and other high-risk HPV genotypes (11%). HPV genotypes showed different distributions regarding histological type and clinical stage. Patients were followed for 35±21 months. The overall survival at 5 years after diagnosis of cervical cancer was 54%. Age, clinical staging, histological type and multiple HPV genotypes infection detected in the same tumor specimen were associated with poorer overall survival on multivariate Cox proportional hazard analysis (pgenotype affected survival. Multiple HPV genotype infection was associated with poorer ICC survival in our study, compared with single genotype infection. HPV genotyping from FFPE tumor tissue using an automated assay such as the Onclarity BD™ assay provides a simpler alternative for routine clinical use. This is the largest study employing an automated HPV genotyping assay using FFPE of ICC. Multiple HPV genotype infection adversely influenced survival.

  18. Extremes in body mass index affect overall survival in women with cervical cancer.

    Science.gov (United States)

    Clark, Leslie H; Jackson, Amanda L; Soo, Adrianne E; Orrey, Danielle C; Gehrig, Paola A; Kim, Kenneth H

    2016-06-01

    To examine the effect of BMI on pathologic findings, cancer recurrence and survival in cervical cancer patients. A retrospective cohort study of cervical cancer patients treated from July 2000 to March 2013 was performed. BMI was calculated, and patients were classified by BMI. The primary outcome was overall survival (OS). Secondary outcomes included stage, histopathology, disease-specific survival (DSS) and recurrence free survival (RFS). Kaplan-Meier survival curves were generated and compared using Cox proportional hazard ratios. Of 632 eligible patients, 24 (4%) were underweight, 191 (30%) were normal weight, 417 (66%) were overweight/obese. There was no difference in age (p=0.91), stage at presentation (p=0.91), grade (p=0.46), or histology (p=0.76) between weight categories. There were fewer White patients in the underweight (54%) and overweight/obese (58%) groups compared to the normal weight (71%) group (p=0.04). After controlling for prognostic factors, underweight and overweight/obese patients had worse median RFS than normal weight patients (7.6 v 25.0months, p=0.01 and 20.3 v 25.0months, p=0.03). Underweight patients also had worse OS (10.4 v 28.4months, p=0.031) and DSS (13.8 v 28.4months, p=0.04) compared to normal weight patients. Overweight/obese patients had worse OS than normal weight patients (22.2 v 28.4months, p=0.03) and a trend toward worse DSS (21.9 v 28.4months, p=0.09). Both extremes of weight (underweight and overweight/obesity) were associated with worse survival in patients with cervical cancer. Optimizing weight in cervical cancer patients may improve outcomes in these patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Parathyroid carcinoma survival: improvements in the era of intact parathyroid hormone monitoring?

    Directory of Open Access Journals (Sweden)

    Steve R. Martinez

    2013-02-01

    Full Text Available The intact parathyroid hormone (iPTH assay is a critical test in the diagnosis and management of PTH-mediated hypercalcemia, including parathyroid carcinoma (PCa. We hypothesized that the survival of patients diagnosed with PCa has improved since adoption of the iPTH assay into clinical practice. We identified all confirmed cases of PCa within the Surveillance, Epidemiology and End Results database from 1973 to 2006. Patients were categorized into two eras based upon introduction of the iPTH assay: 1973 to 1997 (era I and 1997 to 2006 (era II, when the iPTH assay was in standard use. We estimated overall survival (OS and disease-specific survival (DSS using the Kaplan-Meier method, with differences among survival curves assessed via log rank. Multivariate Cox proportional hazards models compared the survival rates between treatment eras while controlling for patient age, sex, race/ethnicity, tumor size, nodal status, extent of disease, and type of surgery. Multivariate models included patients undergoing potentially curative surgery and excluded those with dis- tant metastases. Risks of overall and disease-specific mortality were reported as hazard ratios with 95% confidence intervals. Study criteria were met by 370 patients. Median survival was 15.6 years. Five-year rates of OS and DSS were 78% and 88% for era I and 82% and 96% for era II. On multivariate analysis, age, black race, and unknown extent of disease predicted an increased risk of death from any cause. Treatment era did not predict OS. No factor predicted PCa-specific mortality. In multivariate analysis, neither OS nor DSS have improved in the current era that utilizes iPTH for the detection and management of PCa.

  20. Impact of individual and neighborhood factors on disparities in prostate cancer survival.

    Science.gov (United States)

    DeRouen, Mindy C; Schupp, Clayton W; Koo, Jocelyn; Yang, Juan; Hertz, Andrew; Shariff-Marco, Salma; Cockburn, Myles; Nelson, David O; Ingles, Sue A; John, Esther M; Gomez, Scarlett L

    2018-01-09

    We addressed the hypothesis that individual-level factors act jointly with social and built environment factors to influence overall survival for men with prostate cancer and contribute to racial/ethnic and socioeconomic (SES) survival disparities. We analyzed multi-level data, combining (1) individual-level data from the California Collaborative Prostate Cancer Study, a population-based study of non-Hispanic White (NHW), Hispanic, and African American prostate cancer cases (N = 1800) diagnosed from 1997 to 2003, with (2) data on neighborhood SES (nSES) and social and built environment factors from the California Neighborhoods Data System, and (3) data on tumor characteristics, treatment and follow-up through 2009 from the California Cancer Registry. Multivariable, stage-stratified Cox proportional hazards regression models with cluster adjustments were used to assess education and nSES main and joint effects on overall survival, before and after adjustment for social and built environment factors. African American men had worse survival than NHW men, which was attenuated by nSES. Increased risk of death was associated with residence in lower SES neighborhoods (quintile 1 (lowest nSES) vs. 5: HR = 1.56, 95% CI: 1.11-2.19) and lower education (survival. Both individual- and contextual-level SES influence overall survival of men with prostate cancer. Additional research is needed to identify the mechanisms underlying these robust associations. Copyright © 2018. Published by Elsevier Ltd.

  1. Survival analysis of female dogs with mammary tumors after mastectomy: epidemiological, clinical and morphological aspects

    Directory of Open Access Journals (Sweden)

    Maria Luíza de M. Dias

    2016-03-01

    Full Text Available Abstract: Mammary gland tumors are the most common type of tumors in bitches but research on survival time after diagnosis is scarce. The purpose of this study was to investigate the relationship between survival time after mastectomy and a number of clinical and morphological variables. Data was collected retrospectively on bitches with mammary tumors seen at the Small Animal Surgery Clinic Service at the University of Brasília. All subjects had undergone mastectomy. Survival analysis was conducted using Cox's proportional hazard method. Of the 139 subjects analyzed, 68 died and 71 survived until the end of the study (64 months. Mean age was 11.76 years (SD=2.71, 53.84% were small dogs. 76.92% of the tumors were malignant, and 65.73% had both thoracic and inguinal glands affected. Survival time in months was associated with age (hazard rate ratios [HRR] =1.23, p-value =1.4x10-4, animal size (HRR between giant and small animals =2.61, p-value =0.02, nodule size (HRR =1.09, p-value =0.03, histological type (HRR between solid carcinoma and carcinoma in a mixed tumor =2.40, p-value =0.02, time between diagnosis and surgery (TDS, with HRR =1.21, p-value =2.7x10-15, and the interaction TDS*follow-up time (HRR =0.98, p-value =1.6x10-11. The present study is one of the few on the subject matter. Several important covariates were evaluated and age, animal size, nodule size, histological type, TDS and TDS*follow up time were identified as significantly associated to survival time.

  2. Military service, deployments, and exposures in relation to amyotrophic lateral sclerosis survival.

    Directory of Open Access Journals (Sweden)

    John D Beard

    Full Text Available Military veterans may have higher rates of amyotrophic lateral sclerosis (ALS mortality than non-veterans. Few studies, with sparse exposure information and mixed results, have studied relationships between military-related factors and ALS survival. We evaluated associations between military-related factors and ALS survival among U.S. military veteran cases.We followed 616 medical record-confirmed cases from enrollment (2005-2010 in the Genes and Environmental Exposures in Veterans with Amyotrophic Lateral Sclerosis study until death or July 25, 2013, whichever came first. We ascertained vital status information from several sources within the Department of Veterans Affairs. We obtained information regarding military service, deployments, and 39 related exposures via standardized telephone interviews. We used Cox proportional hazards regression models to estimate hazard ratios (HRs and 95% confidence intervals. We adjusted for potential confounding and missing covariate data biases via inverse probability weights. We also used inverse probability weights to adjust for potential selection bias among a case group that included a disproportionate number of long-term survivors at enrollment.We observed 446 deaths during 24,267 person-months of follow-up (median follow-up: 28 months. Survival was shorter for cases who served before 1950, were deployed to World War II, or mixed and applied burning agents, with HRs between 1.58 and 2.57. Longer survival was associated with exposure to: paint, solvents, or petrochemical substances; local food not provided by the Armed Forces; or burning agents or Agent Orange in the field with HRs between 0.56 and 0.73.Although most military-related factors were not associated with survival, associations we observed with shorter survival are potentially important because of the large number of military veterans.

  3. Survival analysis of patients with interval cancer undergoing gastric cancer screening by endoscopy.

    Science.gov (United States)

    Hamashima, Chisato; Shabana, Michiko; Okamoto, Mikizo; Osaki, Yoneatsu; Kishimoto, Takuji

    2015-01-01

    Interval cancer is a key factor that influences the effectiveness of a cancer screening program. To evaluate the impact of interval cancer on the effectiveness of endoscopic screening, the survival rates of patients with interval cancer were analyzed. We performed gastric cancer-specific and all-causes survival analyses of patients with screen-detected cancer and patients with interval cancer in the endoscopic screening group and radiographic screening group using the Kaplan-Meier method. Since the screening interval was 1 year, interval cancer was defined as gastric cancer detected within 1 year after a negative result. A Cox proportional hazards model was used to investigate the risk factors associated with gastric cancer-specific and all-causes death. A total of 1,493 gastric cancer patients (endoscopic screening group: n = 347; radiographic screening group: n = 166; outpatient group: n = 980) were identified from the Tottori Cancer Registry from 2001 to 2008. The gastric cancer-specific survival rates were higher in the endoscopic screening group than in the radiographic screening group and the outpatients group. In the endoscopic screening group, the gastric cancer-specific survival rate of the patients with screen-detected cancer and the patients with interval cancer were nearly equal (P = 0.869). In the radiographic screening group, the gastric cancer-specific survival rate of the patients with screen-detected cancer was higher than that of the patients with interval cancer (P = 0.009). For gastric cancer-specific death, the hazard ratio of interval cancer in the endoscopic screening group was 0.216 for gastric cancer death (95%CI: 0.054-0.868) compared with the outpatient group. The survival rate and the risk of gastric cancer death among the patients with screen-detected cancer and patients with interval cancer were not significantly different in the annual endoscopic screening. These results suggest the potential of endoscopic screening in reducing

  4. The Changing Face of Survival in Rett Syndrome and MECP2-Related Disorders.

    Science.gov (United States)

    Tarquinio, Daniel C; Hou, Wei; Neul, Jeffrey L; Kaufmann, Walter E; Glaze, Daniel G; Motil, Kathleen J; Skinner, Steven A; Lee, Hye-Seung; Percy, Alan K

    2015-11-01

    Survival in Rett syndrome remains unclear. Although early estimates were grim, more recent data suggest that survival into adulthood is typical. We aimed to define survival in Rett syndrome more clearly and identify risk factors for early death. Participants with clinical Rett Syndrome or methyl-CpG-binding protein 2 mutations without clinical RTT were recruited through the Rett Syndrome Natural History study from 2006 to 2015. Clinical details were collected, and survival was determined using the Kaplan-Meier estimator. Risk factors were assessed using Cox proportional hazards models. Among 1189 valid participants, 51 died (range 3.9-66.6 years) during the 9-year follow-up period. Those who died included 36 (3.9%) classic Rett syndrome females, 5 (5.9%) atypical severe Rett syndrome females, 1 (2.4%) non-Rett syndrome female, the single atypical severe male, 6 (30%) non-Rett syndrome males, and 2 (7.1%) methyl-CpG-binding protein 2 duplication syndrome males. All atypical mild Rett syndrome females, methyl-CpG-binding protein 2 duplication syndrome females, and the single classic Rett syndrome male remain alive. Most deaths were due to cardiorespiratory issues. Only one died from severe malnutrition, scoliosis, and extreme frailty. Survival for classic and atypical Rett syndrome was greater than 70% at 45 years. Overall severity and several modifiable risk factors, including ambulation, weight, and seizures, were associated with mortality in classic Rett syndrome. Survival into the fifth decade is typical in Rett syndrome, and death due to extreme frailty has become rare. Although the leading cause of death remains cardiorespiratory compromise, many risk factors for early death are modifiable. Intense therapeutic interventions could further improve the prognosis for individuals with Rett syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Embolotherapy for Neuroendocrine Tumor Liver Metastases: Prognostic Factors for Hepatic Progression-Free Survival and Overall Survival

    Energy Technology Data Exchange (ETDEWEB)

    Chen, James X. [Hospital of the University of Pennsylvania, Division of Interventional Radiology, Department of Radiology (United States); Rose, Steven [University of San Diego Medical Center, Division of Interventional Radiology, Department of Radiology (United States); White, Sarah B. [Medical College of Wisconsin, Division of Interventional Radiology, Department of Radiology (United States); El-Haddad, Ghassan [Moffitt Cancer Center, Division of Interventional Radiology, Department of Radiology (United States); Fidelman, Nicholas [University of San Francisco Medical Center, Division of Interventional Radiology, Department of Radiology (United States); Yarmohammadi, Hooman [Memorial Sloan Kettering Cancer Center, Division of Interventional Radiology, Department of Radiology (United States); Hwang, Winifred; Sze, Daniel Y.; Kothary, Nishita [Stanford University Medical Center, Division of Interventional Radiology, Department of Radiology (United States); Stashek, Kristen [Hospital of the University of Pennsylvania, Department of Pathology (United States); Wileyto, E. Paul [University of Pennsylvania, Department of Biostatistics and Epidemiology (United States); Salem, Riad [Northwestern Memorial Hospital, Division of Interventional Radiology, Department of Radiology (United States); Metz, David C. [Hospital of the University of Pennsylvania, Division of Gastroenterology, Department of Medicine (United States); Soulen, Michael C., E-mail: michael.soulen@uphs.upenn.edu [Hospital of the University of Pennsylvania, Division of Interventional Radiology, Department of Radiology (United States)

    2017-01-15

    PurposeThe purpose of the study was to evaluate prognostic factors for survival outcomes following embolotherapy for neuroendocrine tumor (NET) liver metastases.Materials and MethodsThis was a multicenter retrospective study of 155 patients (60 years mean age, 57 % male) with NET liver metastases from pancreas (n = 71), gut (n = 68), lung (n = 8), or other/unknown (n = 8) primary sites treated with conventional transarterial chemoembolization (TACE, n = 50), transarterial radioembolization (TARE, n = 64), or transarterial embolization (TAE, n = 41) between 2004 and 2015. Patient-, tumor-, and treatment-related factors were evaluated for prognostic effect on hepatic progression-free survival (HPFS) and overall survival (OS) using unadjusted and propensity score-weighted univariate and multivariate Cox proportional hazards models.ResultsMedian HPFS and OS were 18.5 and 125.1 months for G1 (n = 75), 12.2 and 33.9 months for G2 (n = 60), and 4.9 and 9.3 months for G3 tumors (n = 20), respectively (p < 0.05). Tumor burden >50 % hepatic volume demonstrated 5.5- and 26.8-month shorter median HPFS and OS, respectively, versus burden ≤50 % (p < 0.05). There were no significant differences in HPFS or OS between gut or pancreas primaries. In multivariate HPFS analysis, there were no significant differences among embolotherapy modalities. In multivariate OS analysis, TARE had a higher hazard ratio than TACE (unadjusted Cox model: HR 2.1, p = 0.02; propensity score adjusted model: HR 1.8, p = 0.11), while TAE did not differ significantly from TACE.ConclusionHigher tumor grade and tumor burden prognosticated shorter HPFS and OS. TARE had a higher hazard ratio for OS than TACE. There were no significant differences in HPFS among embolotherapy modalities.

  6. [Survival of patients with heart failure in primary care].

    Science.gov (United States)

    Sarría-Santamera, Antonio; Prado-Galbarro, Francisco Javier; Martín-Martínez, María Auxiliadora; Carmona, Rocío; Gamiño Arroyo, Ana Estela; Sánchez-Piedra, Carlos; Garrido Elustondo, Sofía; del Cura González, Isabel

    2015-01-01

    To describe survival of patients with chronic heart failure (HF) followed up in primary care (PC) and analyse the effect of sex, age, clinical and health services factors, and income levels on survival. Longitudinal observational study of a retrospective cohort of patients with information extracted from electronic medical records. PC Area 7 of the Community of Madrid. Patients 24 year and older with at least one visit to PC in 2006. Incident cases of HF followed up from 2006 to 2010 or until death. Survival analysis with Kaplan-Meier and Cox proportional hazard multivariate regression. A total of 3,061 cases were identified in a cohort of 227,984 patients. The survival rate was 65% at 5 years, with 519 patients dying with a median survival of 49 months. Factors associated with increased risk of mortality were, age (HR=1.04, 1.03-1.05), and having a diagnosis of ischemic heart disease (HR=1.45, 1.15- 1.78), or diabetes (HR=1.52, 1.17-1.95). Factors with a significant protective effect were: female sex (HR=0.72, 0.59-0.86), non-pensioner (HR=0.43, 0.23-0.84), having received the influenza vaccine annually (HR=0.01, 0.00-0.06), prescribed lipid-lowering drugs (HR=0.78, 0.61-0.99) or ACE inhibitors (HR=0.73, 0.60-0.88), and blood tests having been requested (HR=0.97, 0.95-1.00), X-rays (HR=0.81, 0.74-0.88), or electrocardiograms (HR=0.90, 0.81-0.99) in PC. Data from patients with HF followed up in PC indicate that their survival is better than that obtained in other countries, supporting the argument of a better evolution of HF in Mediterranean countries. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  7. Effects of chemical immobilization on survival of African buffalo in the Kruger National Park

    Science.gov (United States)

    Oosthuizen, W.C.; Cross, P.C.; Bowers, J.A.; Hay, C.; Ebinger, M.R.; Buss, P.; Hofmeyr, M.; Cameron, E.Z.

    2009-01-01

    Capturing, immobilizing, and fitting radiocollars are common practices in studies of large mammals, but success is based on the assumptions that captured animals are representative of the rest of the population and that the capture procedure has negligible effects. We estimated effects of chemical immobilization on mortality rates of African buffalo (Syncerus caffer) in the Kruger National Park, South Africa. We used a Cox proportional hazards approach to test for differences in mortality among age, sex, and capture classes of repeatedly captured radiocollared buffalo. Capture variables did not improve model fit and the Cox regression did not indicate increased risk of death for captured individuals up to 90 days postcapture [exp (??) = 1.07]. Estimated confidence intervals, however, span from a halving to a doubling of the mortality rate (95% CI = 0.56-2.02). Therefore, capture did not influence survival of captured individuals using data on 875 captures over a 5-year period. Consequently, long-term research projects on African buffalo involving immobilization, such as associated with research on bovine tuberculosis, should result in minimal capture mortality, but monitoring of possible effects should continue.

  8. Second Primary Malignant Neoplasms and Survival in Adolescent and Young Adult Cancer Survivors.

    Science.gov (United States)

    Keegan, Theresa H M; Bleyer, Archie; Rosenberg, Aaron S; Li, Qian; Goldfarb, Melanie

    2017-11-01

    Although the increased incidence of second primary malignant neoplasms (SPMs) is a well-known late effect after cancer, few studies have compared survival after an SPM to survival of the same cancer occurring as first primary malignant neoplasm (PM) by age. To assess the survival impact of SPMs in adolescents and young adults (AYAs) (15-39 years) compared with that of pediatric (cancer in 13 Surveillance, Epidemiology and End Results regions in the United States diagnosed from 1992 to 2008 and followed through 2013. Data analysis was performed between June 2016 and January 2017. Five-year relative survival was calculated overall and for each cancer occurring as a PM or SPM by age at diagnosis. The impact of SPM status on cancer-specific death was examined using multivariable Cox proportional hazards regression. A total of 15 954 pediatric, 125 750 AYAs, and 878 370 older adult patients diagnosed as having 14 cancers occurring as a PM or SPM were included. Overall, 5-year survival after an SPM was 33.1% lower for children, 20.2% lower for AYAs, and 8.3% lower for older adults compared with a PM at the same age. For the most common SPMs in AYAs, the absolute difference in 5-year survival was 42% lower for secondary non-Hodgkin lymphoma, 19% for secondary breast carcinoma, 15% for secondary thyroid carcinoma, and 13% for secondary soft-tissue sarcoma. Survival by SPM status was significantly worse in younger vs older patients for thyroid, Hodgkin lymphoma, non-Hodgkin lymphoma, acute myeloid leukemia, soft-tissue sarcoma, and central nervous system cancer. Adolescents and young adults with secondary Hodgkin lymphoma (hazard ratio [95% CI], 3.5 [1.7-7.1]); soft-tissue sarcoma (2.8 [2.1-3.9]); breast carcinoma (2.1 [1.8-2.4]); acute myeloid leukemia (1.9 [1.5-2.4]); and central nervous system cancer (1.8 [1.2-2.8]) experienced worse survival compared with AYAs with the same PMs. The adverse impact of SPMs on survival is substantial for AYAs and may partially

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

    DEFF Research Database (Denmark)

    Norregaard, Rikke; Madsen, Kirsten Morill; Hansen, Pernille Bl

    2011-01-01

    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......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...... osmolality in COX-2(-/-) mice irrespective of gender. Hypothalamic AVP mRNA level increased and was unchanged between COX-2(-/-) and WT after WD. AVP peptide content was higher in COX-2(-/-) compared with WT. At baseline, plasma AVP concentration was elevated in conscious chronically catheterized COX-2...

  10. 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.

  11. SURPH 2.1; SURvival Under Proportional Hazards, Techncial Manual 2003.

    Energy Technology Data Exchange (ETDEWEB)

    Lady, James; Westhagen, Peter; Skalski, John

    2003-07-01

    This document is primarily a description of the user interface for SURPH2.1. It is not a description of the statistical theory and calculations behind SURPH. The best source for that information is the SURPH.1 manual. This document describes the user interface to SURPH 2.1. The format of the input data file has been changed since SURPH 1.0 and SURPH 2.0 to make it simpler and more intuitive. A conversion program to convert a data file from previous versions of SURPH to the input data file format for SURPH 2.1 is provided (Section 1.3.1). This project is funded by the Bonneville Power Administration, US Department of Energy, under Contract No. 004126, Project No. 89-107-00, as part of the BPA's program to protect, mitigate, and enhance fish and wildlife affected by the development and operation of hydroelectric facilities on the Columbia River and its tributaries.

  12. Resíduos generalizados de Cox-Snell na avaliação do ajuste de modelos Cox-Snell generalized residuals in the evaluation of model fitting

    Directory of Open Access Journals (Sweden)

    Ana Lúcia Souza da Silva

    2004-10-01

    Full Text Available Vários tipos de resíduos têm sido propostos para modelos de sobrevivência, sendo os mais adequados resultado dos resíduos generalizados de Cox e Snell (1968. O objetivo com este trabalho é avaliar a adequacidade de modelos por meio de gráficos de diagnósticos gerados a partir dos resíduos generalizados de Cox-Snell. Para ilustrar a teoria, foram feitas três aplicações. A primeira aplicação visou a ilustrar a lógica existente entre a plotagem dos resíduos ordenados de três distribuições, normal (0,1, logística (0,1 e valor extremo (0,1 versus as estatísticas de ordem esperadas desses resíduos de acordo com as distribuições assumidas. Para a segunda aplicação, foram utilizados dados de tempo de vida de isolantes, obtidos em Nelson (1990. A partir da verificação por meio dos gráficos de diagnósticos utilizando-se os resíduos generalizados de Cox-Snell, encontrou-se que o modelo apropriado para o tempo de vida dos isolantes era o log-normal. Para a terceira aplicação, foram analisados dados censurados referentes ao tempo de vida de pacientes, obtidos em Collett (1994. Avaliou-se a adequacidade de vários modelos por meio dos resíduos de Cox-Snell adaptados para dados de sobrevivência. Pelos resultados constatou-se que o modelo Weibull foi o mais adequado.Several kinds of residuals have been proposed for survival models, the most suitable for this purpose are Cox and Snell (1968 generalized residuals. The objective of this work was to evaluate the adequacy of models by graphical diagnostics using Cox-Snell generalized residuals. To illustrate the theory three applications were considered. The first application sought to illustrate the heuristics by plotting ordered residuals from three distributions: normal (0,1, logistics (0,1 and extreme value (0,1, versus the expected order statistics of these residuals in consonance with the assumed distributions. The second application consisted of lifetime data of electric

  13. Association of Compliance With Process-Related Quality Metrics and Improved Survival in Oral Cavity Squamous Cell Carcinoma.

    Science.gov (United States)

    Graboyes, Evan M; Gross, Jennifer; Kallogjeri, Dorina; Piccirillo, Jay F; Al-Gilani, Maha; Stadler, Michael E; Nussenbaum, Brian

    2016-05-01

    Quality metrics for patients with head and neck cancer are available, but it is unknown whether compliance with these metrics is associated with improved patient survival. To identify whether compliance with various process-related quality metrics is associated with improved survival in patients with oral cavity squamous cell carcinoma who receive definitive surgery with or without adjuvant therapy. A retrospective cohort study was conducted at a tertiary academic medical center among 192 patients with previously untreated oral cavity squamous cell carcinoma who underwent definitive surgery with or without adjuvant therapy between January 1, 2003, and December 31, 2010. Data analysis was performed from January 26 to August 7, 2015. Surgery with or without adjuvant therapy. Compliance with a collection of process-related quality metrics possessing face validity that covered pretreatment evaluation, treatment, and posttreatment surveillance was evaluated. Association between compliance with these quality metrics and overall survival, disease-specific survival, and disease-free survival was calculated using univariable and multivariable Cox proportional hazards analysis. Among 192 patients, compliance with the individual quality metrics ranged from 19.7% to 93.6% (median, 82.8%). No pretreatment or surveillance metrics were associated with improved survival. Compliance with the following treatment-related quality metrics was associated with improved survival: elective neck dissection with lymph node yield of 18 or more, no unplanned surgery within 14 days of the index surgery, no unplanned 30-day readmissions, and referral for adjuvant radiotherapy for pathologic stage III or IV disease. Increased compliance with a "clinical care signature" composed of these 4 metrics was associated with improved overall survival, disease-specific survival, and disease-free survival on univariable analysis (log-rank test; P metrics was associated with improved overall survival (100

  14. Estimating haplotype effects for survival data

    DEFF Research Database (Denmark)

    Scheike, Thomas; Martinussen, Torben; Silver, J

    2010-01-01

    Genetic association studies often investigate the effect of haplotypes on an outcome of interest. Haplotypes are not observed directly, and this complicates the inclusion of such effects in survival models. We describe a new estimating equations approach for Cox's regression model to assess haplo...... in this article to investigate possible haplotype effects of the PAF-receptor on cardiovascular events in patients with coronary artery disease, and compare our results to those based on the EM algorithm....

  15. 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 ...

  16. COX-2 gene expression is correlated with cognitive function in recurrent depressive disorder.

    Science.gov (United States)

    Gałecki, Piotr; Talarowska, Monika; Bobińska, Kinga; Szemraj, Janusz

    2014-02-28

    Cyclooxygenase-2(COX-2) may be a key inflammatory enzyme involved in recurrent depressive disorder(rDD). In rDD group, COX-2 expression were higher and significant correlations occurred between COX-2 expression and cognitive functions. In controls there was no significant association between analysed variables. Thus, the COX-2 enzyme may be important for cognitive functioning in rDD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Lagerstedt Kristina

    2011-06-01

    Full Text Available Abstract Background 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. Method 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. Results 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. Conclusions 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.

  18. [Comparison of the Cost-Effectiveness of the SOX and COX Regimens in Patients with Unresectable Advanced and Recurrent Colorectal Cancer Using a Clinical Decision Analysis Approach].

    Science.gov (United States)

    Nagase, Satoshi; Iyoda, Tomokazu; Kanno, Hiroshi; Akase, Tomohide; Arakawa, Ichiro; Inoue, Tadao; Uetsuka, Yoshio

    2016-10-01

    Phase III clinical trials have comfirmed that the S-1 plus oxaliplatin(SOX)is inferior to the capecitabine plus oxaliplatin (COX)regimen in the treatment of metastatic colorectal cancer.On the basis of these findings, we compared, using a clinical decision analysis-based approach, the cost-effectiveness of the SOX and COX regimens.Herein, we simulated the expected effects and costs of the SOX and COX regimens using the markov model.Clinical data were obtained from Hong's 2012 report.The cost data comprised the costs for pharmacist labor, material, inspection, and treatment for adverse event, as well as the total cost of care at the advanced stage.The result showed that the expected cost of the SOX and COX regimen was 1,538,330 yen, and 1,429,596 yen, respectively, with an expected survival rate of 29.18 months, and 28.63 months, respectively.The incremental cost-effectiveness ratio of the SOX regimen was 197,698 yen/month; thus, the SOX regimen was found to be more cost-effective that the COX regimen.

  19. Staging and survival of rectal cancer in Vila Nova de Gaia, Portugal.

    Science.gov (United States)

    Abreu, Miguel Henriques; Matos, Eduarda; Castro Poças, Fernando; Rocha, Rosa; Pinto, Jorge; Lopes, Carlos

    2010-02-01

    In the county of Vila Nova de Gaia (northern Portugal) in the period of 2004-2006, there were an average of 35 new cases of colorectal cancer per 100,000 population, which constitutes one of the highest rates in the world. The latest research has shown that there are many differences between colon and rectal cancers, thereby justifying an independent approach. The study pertained to the period 1995-2004, by using the census of 1991 and 2001 for calculating specific rates. The 399 diagnosed cases of rectal cancer were drawn from a specialized and active cancer registry, oncological registry of Gaia. Overall survival was calculated using the Kaplan-Meier method and the curves were compared using a Log Rank test. The effect of topography and histological type on survival was obtained by controlling the stage disease, using a Cox proportional hazards regression model. There was a slight predominance of males, with a ratio between sexes of 1 : 3. The 50% overall survival rate after 5 years increased over time. The localization of the tumour and the histological type, after adjusting by stage, were not significant factors in the prognosis. Our study shows an increase in the number of cases over time, particularly in elderly women. The cumulative risk of having rectal cancer remains unchanged from 1981 to 2004. Unlike other studies, an increase in early lesions was not observed.

  20. Survival rate and pressure ulcer prevalence in patients with and without dementia: a retrospective study.

    Science.gov (United States)

    Jaul, E; Rosenzweig, J P; Meiron, O

    2017-07-02

    This retrospective study aimed to investigate the prevalence of pressure ulcers (PUs) in older patients with advanced dementia versus older patients without dementia but with other comorbidities, such as diabetes, ischaemic heart disease and chronic renal failure. PUs were thought to be more prevalent and to present a higher risk of mortality in patients with dementia. PUs were assessed on admission using the European Pressure Ulcer Advisory Panel (EPUAP) staging system. Patients were classified as either with or without dementia according to Reisberg's functional assessment staging test (FAST). The prevalence of PUs and the survival rates were analysed and compared in both groups. The combined effect of PUs and dementia on survival was assessed using the Cox proportional hazard model. The median survival rate of patients with PUs and dementia was 63 days, significantly lower than in patients with PUs without dementia 117 days. Both groups had similar other comorbidities. These findings underscore the requirement for geriatricians and health professionals to be more vigilant in examining PUs as dementia progresses.

  1. History of Comorbidities and Survival of Ovarian Cancer Patients, Results from the Ovarian Cancer Association Consortium.

    Science.gov (United States)

    Minlikeeva, Albina N; Freudenheim, Jo L; Eng, Kevin H; Cannioto, Rikki A; Friel, Grace; Szender, J Brian; Segal, Brahm; Odunsi, Kunle; Mayor, Paul; Diergaarde, Brenda; Zsiros, Emese; Kelemen, Linda E; Köbel, Martin; Steed, Helen; deFazio, Anna; Jordan, Susan J; Fasching, Peter A; Beckmann, Matthias W; Risch, Harvey A; Rossing, Mary Anne; Doherty, Jennifer A; Chang-Claude, Jenny; Goodman, Marc T; Dörk, Thilo; Edwards, Robert; Modugno, Francesmary; Ness, Roberta B; Matsuo, Keitaro; Mizuno, Mika; Karlan, Beth Y; Goode, Ellen L; Kjær, Susanne K; Høgdall, Estrid; Schildkraut, Joellen M; Terry, Kathryn L; Cramer, Daniel W; Bandera, Elisa V; Paddock, Lisa E; Kiemeney, Lambertus A; Massuger, Leon F A G; Sutphen, Rebecca; Anton-Culver, Hoda; Ziogas, Argyrios; Menon, Usha; Gayther, Simon A; Ramus, Susan J; Gentry-Maharaj, Aleksandra; Pearce, Celeste L; Wu, Anna H; Kupryjanczyk, Jolanta; Jensen, Allan; Webb, Penelope M; Moysich, Kirsten B

    2017-09-01

    Background: Comorbidities can affect survival of ovarian cancer patients by influencing treatment efficacy. However, little evidence exists on the association between individual concurrent comorbidities and prognosis in ovarian cancer patients.Methods: Among patients diagnosed with invasive ovarian carcinoma who participated in 23 studies included in the Ovarian Cancer Association Consortium, we explored associations between histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, and neurological diseases and overall and progression-free survival. Using Cox proportional hazards regression models adjusted for age at diagnosis, stage of disease, histology, and study site, we estimated pooled HRs and 95% confidence intervals to assess associations between each comorbidity and ovarian cancer outcomes.Results: None of the comorbidities were associated with ovarian cancer outcome in the overall sample nor in strata defined by histologic subtype, weight status, age at diagnosis, or stage of disease (local/regional vs. advanced).Conclusions: Histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, or neurologic diseases were not associated with ovarian cancer overall or progression-free survival.Impact: These previously diagnosed chronic diseases do not appear to affect ovarian cancer prognosis. Cancer Epidemiol Biomarkers Prev; 26(9); 1470-3. ©2017 AACR. ©2017 American Association for Cancer Research.

  2. Driver Mutations Determine Survival in Smokers and Never Smokers with Stage IIIB/IV Lung Adenocarcinomas

    Science.gov (United States)

    Paik, Paul K.; Johnson, Melissa L.; D’Angelo, Sandra P.; Sima, Camelia S.; Ang, Daphne; Dogan, Snjezana; Miller, Vincent A.; Ladanyi, Marc; Kris, Mark G.; Riely, Gregory J.

    2012-01-01

    Background We previously demonstrated that stage IIIB/IV non-small cell lung cancer (NSCLC) never smokers lived 50% longer than former/current smokers. This observation persisted after adjusting for age, performance status, and gender. We hypothesized that smoking-dependent differences in the distribution of driver mutations might explain differences in prognosis between these subgroups. Methods We reviewed 293 never smokers and 382 former/current smokers with lung adenocarcinoma who underwent testing for EGFR and KRAS mutations and rearrangements in ALK between 2009 and 2010. Clinical outcomes and patient characteristics were collected. Survival probabilities were estimated using the Kaplan-Meier method. Group comparison was performed with log-rank tests and Cox proportional hazards methods. Results While the overall incidence of these mutations was nearly identical (55% never smokers vs. 57% current/former smokers, p=0.48), there were significant differences in the distribution of mutations between these groups: EGFR mutations- 37% never smokers vs. 14% former/current smokers (pnever smokers vs. 43% former/current smokers (pnever smokers vs. 2% former/current smokers (pnever smokers and former/current smokers, prognosis differed significantly by genotype. Patients harboring KRAS mutations demonstrated the poorest survival. Smoking status, however, had no influence on survival within each genotype. Conclusion Never smokers and former/current smokers with lung adenocarcinomas are not homogeneous subgroups. Each is made up of individuals whose tumors have a unique distribution of driver mutations which are associated with different prognoses, irrespective of smoking history. PMID:22605530

  3. Morphologic complexity of epithelial architecture for predicting invasive breast cancer survival

    Directory of Open Access Journals (Sweden)

    Tambasco Mauro

    2010-12-01

    Full Text Available Abstract Background Precise criteria for optimal patient selection for adjuvant chemotherapy remain controversial and include subjective components such as tumour morphometry (pathological grade. There is a need to replace subjective criteria with objective measurements to improve risk assessment and therapeutic decisions. We assessed the prognostic value of fractal dimension (an objective measure of morphologic complexity for invasive ductal carcinoma of the breast. Methods We applied fractal analysis to pan-cytokeratin stained tissue microarray (TMA cores derived from 379 patients. Patients were categorized according to low (1.75, N = 90 fractal dimension. Cox proportional-hazards regression was used to assess the relationship between disease-specific and overall survival and fractal dimension, tumour size, grade, nodal status, estrogen receptor status, and HER-2/neu status. Results Patients with higher fractal score had significantly lower disease-specific 10-year survival (25.0%, 56.4%, and 69.4% for high, intermediate, and low fractal dimension, respectively, p Conclusion Except for nodal status, morphologic complexity of breast epithelium as measured quantitatively by fractal dimension was more strongly and significantly associated with disease-specific and overall survival than standard prognosticators.

  4. Effect of Dialysis Modality on Survival of Hepatitis C-Infected ESRF Patients

    Science.gov (United States)

    Bose, Bhadran; McDonald, Stephen P.; Hawley, Carmel M.; Brown, Fiona G.; Badve, Sunil V.; Wiggins, Kathryn J.; Bannister, Kym M.; Boudville, Neil; Clayton, Philip

    2011-01-01

    Summary Background and objectives Hepatitis C virus (HCV) infection is associated with increased mortality and morbidity in end-stage renal failure (ESRF) patients. Despite a lower incidence and risk of transmission of HCV infection with peritoneal dialysis (PD), the optimal dialysis modality for HCV-infected ESRF patients is not known. The aim of this study was to evaluate the impact of dialysis modality on the survival of HCV-infected ESRF patients. Design, setting, participants, & measurements The study included all adult incident ESRF patients in Australia and New Zealand who commenced dialysis between January 1, 1994, and December 31, 2008, and were HCV antibody-positive at the time of dialysis commencement. Time to all-cause mortality was compared between hemodialysis (HD) and PD according to modality assignment at day 90, using Cox proportional hazards model analysis. Results A total of 424 HCV-infected ESRF patients commenced dialysis during the study period and survived for at least 90 days (PD n = 134; HD n = 290). Mortality rates were comparable between PD and HD in the first year (10.7 versus 13.8 deaths per 100 patient-years, respectively; adjusted hazard ratio [HR] 0.65, 95% CI 0.34 to 1.26) and thereafter (20 versus 15.9 deaths per 100 patient-years, respectively; HR 1.27, 95% CI 0.86 to 1.88). Conclusions The survival of HCV-infected ESRF patients is comparable between PD and HD. PMID:21903989

  5. Increasing incidence and survival in oral cancer: a nationwide Danish study from 1980 to 2014.

    Science.gov (United States)

    Karnov, Kirstine Kim Schmidt; Grønhøj, Christian; Jensen, David Hebbelstrup; Wessel, Irene; Charabi, Birgitte Wittenborg; Specht, Lena; Kjaer, Andreas; von Buchwald, Christian

    2017-09-01

    Oral carcinomas (OCs) make up a significant proportion of head and neck carcinomas (HNCs) and are an important cause of morbidity and mortality globally. The purpose of this population-based study was to determine trends in incidence and survival in OC in the Danish population from 1980 to 2014. This study covered all patients registered in the nationwide Danish cancer registry (DCR) in the period 1980-2014. Age-adjusted incidence rate (AAIR) per 100,000 and annual percentage change (APC) were evaluated. Also, 5-year overall survival (OS) was calculated with Cox regression analysis in relation to location, gender, age, and calendar year at diagnosis. Altogether, 8299 patients with oral cancer were identified, 5062 (61%) of whom were males and 3237 (39%) were females. The median age at diagnosis was 63 years. The AAIR of patients with OC increased from 1.9 per 100,000 in 1980 to 3.5 per 100,000 in 2014, and we observed a significant increase in 5-year OS of 12% points (a relative increase of 38%) from the period 1980-1984 to 2005-2009. Women were found to have a better prognosis than men. We found an unexpected increase in the age-standardized incidence of OC during the last 30 years in Denmark, and also an improvement in survival. The 5-year OS was significantly better in recent years even when we adjusted the analysis for relevant covariates.

  6. [A new perspective of survival data on clinical epidemiology: introduction of competitive risk model].

    Science.gov (United States)

    Nie, Z Q; Ou, Y Q; Qu, Y J; Yuan, H Y; Liu, X Q

    2017-08-10

    Competing risks occur frequently in the analysis of survival data that should be dealt with competing risk models. Competing risk is an event whose occurrence precludes the occurrence of the primary event of interest. Previous commonly used Kaplan-Meier method tends to overestimate the cumulative survival functions, while the traditional Cox proportional hazards model falsely evaluates the effects of covariates on the hazard related to the occurrence of the event. There are few domestic reports mentioning the concept, application and methodology of competing risk model as well as the implementation procedures or resolution of model conditions and parameters. The current work aims to explain the core concept and methodology of the competing risk model and to illustrate the process of analysis on cumulative incidence rate, using both the cause-specific hazard function model and the sub-distribution hazard function model. Software macro code in SAS 9.4 is also provided to assist clinical researchers to further understand the application of the model so to properly analyze the survival data.

  7. Survival outcomes for first-line antiretroviral therapy in India's ART program.

    Science.gov (United States)

    Dandona, Rakhi; Rewari, Bharat B; Kumar, G Anil; Tanwar, Sukarma; Kumar, S G Prem; Vishnumolakala, Venkata S; Duber, Herbert C; Gakidou, Emmanuela; Dandona, Lalit

    2016-10-11

    Little is known about survival outcomes of HIV patients on first-line antiretroviral therapy (ART) on a large-scale in India, or facility level factors that influence patient survival to guide further improvements in the ART program in India. We examined factors at the facility level in addition to patient factors that influence survival of adult HIV patients on ART in the publicly-funded ART program in a high- and a low-HIV prevalence state. Retrospective chart review in public sector ART facilities in the combined states of Andhra Pradesh and Telangana (APT) before these were split in 2014 and in Rajasthan (RAJ), the high- and a low-HIV prevalence states, respectively. Records of adults initiating ART between 2007-12 and 2008-13 in APT and RAJ, respectively, were reviewed and facility-level information collected at all ART centres and a sample of link ART centres. Survival probability was estimated using Kaplan-Meier method, and determinants of mortality explored with facility and patient-level factors using Cox proportional hazard model. Based on data from 6581 patients, the survival probability of ART at 60 months was 76.3 % (95 % CI 73.0-79.2) in APT and 78.3 % (74.4-81.7) in RAJ. The facilities with cumulative ART patient load above the state average had lower mortality in APT (Hazard ratio [HR] 0.74, 0.57-0.95) but higher in RAJ (HR 1.37, 1.01-1.87). Facilities with higher proportion of lost to follow-up patients in APT had higher mortality (HR 1.47, 1.06-2.05), as did those with higher ART to pre-ART patient ratio in RAJ (HR 1.62, 1.14-2.29). In both states, there was higher hazard for mortality in patients with CD4 count 100 cells/mm 3 or less at ART initiation, males, and in patients with TB co-infection. These data from the majority of facilities in a high- and a low-HIV burden state of India over 5 years reveal reasonable and similar survival outcomes in the two states. The facilities with higher ART load in the longer established ART program in

  8. A high-fat diet activates oncogenic Kras and COX2 to induce development of pancreatic ductal adenocarcinoma in mice.

    Science.gov (United States)

    Philip, Bincy; Roland, Christina L; Daniluk, Jaroslaw; Liu, Yan; Chatterjee, Deyali; Gomez, Sobeyda B; Ji, Baoan; Huang, Haojie; Wang, Huamin; Fleming, Jason B; Logsdon, Craig D; Cruz-Monserrate, Zobeida

    2013-12-01

    Obesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC), but it is not clear how obesity contributes to pancreatic carcinogenesis. The oncogenic form of KRAS is expressed during early stages of PDAC development and is detected in almost all of these tumors. However, there is evidence that mutant KRAS requires an additional stimulus to activate its full oncogenic activity and that this stimulus involves the inflammatory response. We investigated whether the inflammation induced by a high-fat diet, and the accompanying up-regulation of cyclooxygenase-2 (COX2), increases Kras activity during pancreatic carcinogenesis in mice. We studied mice with acinar cell-specific expression of KrasG12D (LSL-Kras/Ela-CreERT mice) alone or crossed with COX2 conditional knockout mice (COXKO/LSL-Kras/Ela-CreERT). We also studied LSL-Kras/PDX1-Cre mice. All mice were fed isocaloric diets with different amounts of fat, and a COX2 inhibitor was administered to some LSL-Kras/Ela-CreERT mice. Pancreata were collected from mice and analyzed for Kras activity, levels of phosphorylated extracellular-regulated kinase, inflammation, fibrosis, pancreatic intraepithelial neoplasia (PanIN), and PDACs. Pancreatic tissues from LSL-Kras/Ela-CreERT mice fed high-fat diets (HFDs) had increased Kras activity, fibrotic stroma, and numbers of PanINs and PDACs than LSL-Kras/Ela-CreERT mice fed control diets; the mice fed the HFDs also had shorter survival times than mice fed control diets. Administration of a COX2 inhibitor to LSL-Kras/Ela-CreERT mice prevented these effects of HFDs. We also observed a significant reduction in survival times of mice fed HFDs. COXKO/LSL-Kras/Ela-CreERT mice fed HFDs had no evidence for increased numbers of PanIN lesions, inflammation, or fibrosis, as opposed to the increases observed in LSL-Kras/Ela-CreERT mice fed HFDs. In mice, an HFD can activate oncogenic Kras via COX2, leading to pancreatic inflammation and fibrosis and development of PanINs and PDAC. This

  9. Cardioprotective actions of curcumin on the pathogenic NFAT/COX-2/prostaglandin E2pathway induced during Trypanosoma cruzi infection.

    Science.gov (United States)

    Hernández, Matías; Wicz, Susana; Corral, Ricardo S

    2016-11-15

    Diverse cardiovascular signaling routes have been considered critical for Chagas cardiomyopathy caused by the protozoan parasite Trypanosoma cruzi. Along this line, T. cruzi infection and endothelin-1 (ET-1) have been shown to cooperatively activate the Ca 2+ /NFAT cascade in cardiomyocytes, leading to cyclooxygenase type 2 (COX-2) induction and increased release of prostanoids and prohypertrophic peptides. To determine whether the well-known cardioprotective and anti-inflammatory effects of curcumin (Cur) could be helpful to interfere with this key machinery for pathogenesis of Chagas myocarditis. Cur treatment was evaluated through in vivo studies using a murine model of acute T. cruzi infection and in vitro experiments using ET-1-stimulated and parasite-infected mouse cardiomyocytes. Cur-treated and untreated infected mice were followed-up to estimate survival postinfection and heart tissues from both groups were analyzed for inflammatory infiltration by histopathology, whereas parasite load, induction of arachidonic acid pathway and natriuretic peptide expression were determined by real-time PCR. Molecular analysis of Cur myocardial targets included intracellular calcium measurement, NFAT and COX-2 induction in transfected cells, and assessment of NFAT, COX-2 and microsomal prostaglandin E synthase-1 (mPGES-1) levels by immunoblotting, prostaglandin E 2 (PGE 2 ) by ELISA, b-type natriuretic peptide (BNP) by real-time PCR, and PGE 2 /EP4 receptor/BNP interaction by transwell experiments. Cur treatment of acute Chagas mice enhanced survival and proved to hinder relevant inflammatory processes in the heart, including leukocyte recruitment, activation of the eicosanoid pathway and BNP overexpression, without modifying parasite burden in the organ. Cur was capable of blocking Ca 2+ -dependent NFATc1 transcriptional activity, COX-2 and mPGES-1 induction, and subsequent PGE 2 production in ET-1-stimulated and parasite-infected cardiomyocytes. Furthermore, the decline

  10. Radiosensitizing potential of the selective cyclooygenase-2 (COX-2) inhibitor meloxicam on human glioma cells

    NARCIS (Netherlands)

    Bijnsdorp, Irene; Kuipers, Gitta; Lafleur, M.; Slotman, Ben; Sminia, Peter; Berg, van de Jaap; Rijn, van Johannes; Wedekind, Laurine

    2007-01-01

    The COX-2 protein is frequently overexpressed in human malignant gliomas. This expression has been associated with their aggressive growth characteristics and poor prognosis for patients. Targeting the COX-2 pathway might improve glioma therapy. In this study, the effects of the selective COX-2

  11. Crosstalk between osteoprotegerin (OPG), fatty acid synthase (FASN) and, cycloxygenase-2 (COX-2) in breast cancer: implications in carcinogenesis.

    Science.gov (United States)

    Goswami, Sudeshna; Sharma-Walia, Neelam

    2016-09-13

    , GSK3β, and induced apoptosis by caspase-3/7 and caspase-9 activation. But a more efficient and effective decrease in lipid bodies/cell and survival kinase signaling was observed upon combining the drug treatments for the aggressive cancer cells. Collectively, the novel biological crosstalk between OPG, FASN, and COX-2 advocates for combinatorial drug treatment to block these players of carcinogenesis as a promising therapeutic target to treat highly invasive breast cancer.

  12. Crosstalk between osteoprotegerin (OPG), fatty acid synthase (FASN) and, cycloxygenase-2 (COX-2) in breast cancer: implications in carcinogenesis

    Science.gov (United States)

    Goswami, Sudeshna; Sharma-Walia, Neelam

    2016-01-01

    , GSK3β, and induced apoptosis by caspase-3/7 and caspase-9 activation. But a more efficient and effective decrease in lipid bodies/cell and survival kinase signaling was observed upon combining the drug treatments for the aggressive cancer cells. Collectively, the novel biological crosstalk between OPG, FASN, and COX-2 advocates for combinatorial drug treatment to block these players of carcinogenesis as a promising therapeutic target to treat highly invasive breast cancer. PMID:27270654

  13. Survival Analysis

    CERN Document Server

    Miller, Rupert G

    2011-01-01

    A concise summary of the statistical methods used in the analysis of survival data with censoring. Emphasizes recently developed nonparametric techniques. Outlines methods in detail and illustrates them with actual data. Discusses the theory behind each method. Includes numerous worked problems and numerical exercises.

  14. Modelling survival

    DEFF Research Database (Denmark)

    Ashauer, Roman; Albert, Carlo; Augustine, Starrlight

    2016-01-01

    well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates...

  15. Successful performance of Cox-Maze procedure on beating heart using bipolar radiofrequency ablation: a feasibility study in animals.

    Science.gov (United States)

    Gaynor, Sydney L; Ishii, Yosuke; Diodato, Michael D; Prasad, Sunil M; Barnett, Kara M; Damiano, Nicholas R; Byrd, Gregory D; Wickline, Samuel A; Schuessler, Richard B; Damiano, Ralph J

    2004-11-01

    The Cox-Maze procedure is the gold standard for the surgical treatment of atrial fibrillation with proven long-term efficacy. However, its application has been limited by its complexity and significant morbidity. The purpose of this study was to test the feasibility and safety of performing the Cox-Maze procedure using bipolar radiofrequency ablation on the beating heart without cardiopulmonary bypass. After median sternotomy, 6 Hanford mini-pigs underwent a modified Cox-Maze procedure using bipolar radiofrequency energy. The animals survived for 30 days. Atrial function, coronary artery, pulmonary vein anatomy, and valve function were assessed by magnetic resonance imaging. At reoperation, pacing documented electrical isolation of the pulmonary veins. Induction of atrial fibrillation was attempted by burst pacing with cholinergic stimulation. Histologic assessment was performed after sacrifice. There were no perioperative mortalities or neurologic events. At 30 days, atrial fibrillation was unable to be induced, and pulmonary vein isolation was confirmed by pacing. Magnetic resonance imaging assessment revealed no coronary artery or pulmonary vein stenoses. Although atrial ejection fraction decreased slightly from 0.344 +/- 0.0114 to 0.300 +/- 0.055 (p = 0.18), atrial contractility was preserved in every animal. Histologic assessment showed all lesions to be transmural, and there were no significant stenoses of the coronary vessels or injuries to the valves. Virtually all of the lesions of the Cox-Maze procedure can be performed without cardiopulmonary bypass using bipolar radiofrequency energy. There were no late stenoses of the pulmonary veins. Clinical trials of this new technology on the beating heart are warranted.

  16. Thrombosis is reduced by inhibition of COX-1, but unaffected by inhibition of COX-2, in an acute model of platelet activation in the mouse.

    Directory of Open Access Journals (Sweden)

    Paul C Armstrong

    Full Text Available Clinical use of selective inhibitors of cyclooxygenase (COX-2 appears associated with increased risk of thrombotic events. This is often hypothesised to reflect reduction in anti-thrombotic prostanoids, notably PGI(2, formed by COX-2 present within endothelial cells. However, whether COX-2 is actually expressed to any significant extent within endothelial cells is controversial. Here we have tested the effects of acute inhibition of COX on platelet reactivity using a functional in vivo approach in mice.A non-lethal model of platelet-driven thromboembolism in the mouse was used to assess the effects of aspirin (7 days orally as control diclofenac (1 mg.kg(-1, i.v. and parecoxib (0.5 mg.kg(-1, i.v. on thrombus formation induced by collagen or the thromboxane (TX A(2-mimetic, U46619. The COX inhibitory profiles of the drugs were confirmed in mouse tissues ex vivo. Collagen and U46619 caused in vivo thrombus formation with the former, but not latter, sensitive to oral dosing with aspirin. Diclofenac inhibited COX-1 and COX-2 ex vivo and reduced thrombus formation in response to collagen, but not U46619. Parecoxib inhibited only COX-2 and had no effect upon thrombus formation caused by either agonist.Inhibition of COX-1 by diclofenac or aspirin reduced thrombus formation induced by collagen, which is partly dependent upon platelet-derived TXA(2, but not that induced by U46619, which is independent of platelet TXA(2. These results are consistent with the model demonstrating the effects of COX-1 inhibition in platelets, but provide no support for the hypothesis that acute inhibition of COX-2 in the circulation increases thrombosis.

  17. Cyclooxygenase 2-dependent and independent activation of Akt through casein kinase 2α contributes to human bladder cancer cell survival

    Directory of Open Access Journals (Sweden)

    Fujimoto Kiyohide

    2011-05-01

    Full Text Available Abstract Background Survival rate for patients presenting muscle invasive bladder cancer is very low, and useful therapeutic target has not been identified yet. In the present study, new COX2 downstream signals involved in urothelial carcinoma cell survival were investigated in vitro and in vivo. Methods COX2 gene was silenced by siRNA transfection. Orthotopic implantation animal model and transurethral instillation of siRNA with atelocollagen was constructed to examine the effects of COX2 knockdown in vivo. Cell cycle was examined by flowcytoketry. Surgical specimens derived from patients with urinary bladder cancer (all were initially diagnosed cases were used for immunohistochemical analysis of the indicated protein expression in urothelial carcinoma cells. Results Treatment with the COX2 inhibitor or knockdown of COX2 reduced expression of casein kinase (CK 2 α, a phophorylated Akt and urokinase type plasminogen activator (uPA, resulting in p27 induction, cell cycle arrest at G1 phase and cell growth suppression in human urothelial carcinoma cell lines expressing COX2. Silencing of CK2α exhibited the similar effects. Even in UMUC3 cells lacking the COX2 gene, COX2 inhibition also inhibited cell growth through down-regulation of the CK2α-Akt/uPA axis. The mouse orthotropic bladder cancer model demonstrated that the COX2 inhibitor, meloxicam significantly reduced CK2α, phosphorylated Akt and uPA expression, whereas induced p27 by which growth and invasiveness of bladder cancer cells were strongly inhibited. Immunohistochemically, high expression of COX2, CK2α and phosphorylated form of Akt was found in high-grade, invasive carcinomas as well as carcinoma in situ, but not in low-grade and noninvasive phenotypes. Conclusions COX2-dependent and independent activation of CK2α-Akt/uPA signal is mainly involved in urothelial carcinoma cell survival, moreover, not only COX2 but also CK2α could be direct targets of COX2 inhibitors.

  18. The Role of Prostaglandins and COX-Enzymes in Chondrogenic Differentiation of ATDC5 Progenitor Cells.

    Directory of Open Access Journals (Sweden)

    Marjolein M J Caron

    Full Text Available NSAIDs are used to relieve pain and decrease inflammation by inhibition of cyclooxygenase (COX-catalyzed prostaglandin (PG synthesis. PGs are fatty acid mediators involved in cartilage homeostasis, however the action of their synthesizing COX-enzymes in cartilage differentiation is not well understood. In this study we hypothesized that COX-1 and COX-2 have differential roles in chondrogenic differentiation.ATDC5 cells were differentiated in the presence of COX-1 (SC-560, Mofezolac or COX-2 (NS398, Celecoxib specific inhibitors. Specificity of the NSAIDs and inhibition of specific prostaglandin levels were determined by EIA. Prostaglandins were added during the differentiation process. Chondrogenic outcome was determined by gene- and protein expression analyses.Inhibition of COX-1 prevented Col2a1 and Col10a1 expression. Inhibition of COX-2 resulted in decreased Col10a1 expression, while Col2a1 remained unaffected. To explain this difference expression patterns of both COX-enzymes as well as specific prostaglandin concentrations were determined. Both COX-enzymes are upregulated during late chondrogenic differentiation, whereas only COX-2 is briefly expressed also early in differentiation. PGD2 and PGE2 followed the COX-2 expression pattern, whereas PGF2α and TXA2 levels remained low. Furthermore, COX inhibition resulted in decreased levels of all tested PGs, except for PGD2 and PGF2α in the COX-1 inhibited condition. Addition of PGE2 and PGF2α resulted in increased expression of chondrogenic markers, whereas TXA2 increased expression of hypertrophic markers.Our findings point towards a differential role for COX-enzymes and PG-production in chondrogenic differentiation of ATDC5 cells. Ongoing research is focusing on further elucidating the functional partition of cyclooxygenases and specific prostaglandin production.

  19. Effect of beta blocker combined with COX-2 inhibitor on colonic anastomosis in rats.

    Science.gov (United States)

    Benjamin, Barak; Hazut, Ofir; Shaashua, Lee; Benish, Marganit; Zmora, Niv; Barshack, Iris; Hoffman, Aviad; Ben-Eliyahu, Shamgar; Zmora, Oded

    2010-12-01

    Pharmacologic modulation of the perioperative physiologic stress response, using the beta-blocker propranolol, combined with the COX-2 inhibitor etodolac, has been shown to reduce metastatic spread and increase survival rates following surgery for primary tumor excision in rodents. Prior to implantation of this pharmacological approach in clinical trials in patients with colon cancer, the safety of this technique has to be evaluated. This study assessed the effects of these drugs on the healing of colonic anastomosis in rats. Forty-eight F344 rats were divided into two groups, which were given seven daily subcutaneous injections of either vehicle, or propranolol (up to 1.2 mg/kg/day) combined with etodolac (12.5 mg/kg/day), starting the day before surgery. Each animal underwent laparotomy, colotomy of the descending colon, and anastomosis. Anastomotic leak rate and bursting pressure were compared at 1 week after the operation. The harvested anastomosis was histologically assessed for wound healing parameters. Forty-three rats survived the operation and were eligible for analysis at 1 week. No significant difference in survival, anastomotic leakage, or bursting pressure was found between animals that received propranolol and etodolac versus those receiving vehicle (drugs 179 mmHg ± 45.4; vehicle 187 mmHg, SD ± 35.0, p = 0.54). Histologic assessment of fibrosis, necrosis, cell infiltration, and tissue reaction zone did not differ between the two groups. Perioperative administration of propranolol and etodolac seems safe in colon operations in rats and does not affect anastomotic failure or colon healing.

  20. The effects of body mass index on complications and survival outcomes in patients with cervical carcinoma undergoing curative chemoradiation therapy.

    Science.gov (United States)

    Kizer, Nora T; Thaker, Premal H; Gao, Feng; Zighelboim, Israel; Powell, Matthew A; Rader, Janet S; Mutch, David G; Grigsby, Perry W

    2011-03-01

    The effect of body mass index (BMI) on treatment outcomes for patients with locally advanced cervical carcinoma who receive definitive chemoradiation is unclear. The cohort in this study included all patients with cervical carcinoma (n = 404) who had stage IB(1) disease and positive lymph nodes or stage ≥IB(2) disease and received treatment at the authors' facility between January 1998 and January 2008. The mean follow-up was 47.2 months. BMI was calculated using the National Institute of Health online calculator. BMI categories were created according to the World Health Organization classification system. Primary outcomes were overall survival, disease-free survival, and complication rate. Univariate and multivariate analyses were performed. Kaplan-Meier survival curves were generated and compared using Cox proportional hazard models. On multivariate analysis, compared with normal weight (BMI 18.5-24.9 kg/m(2) ), a BMI 24.9 kg/m(2) , respectively. A BMI 24.9 kg/m(2) (radiation enteritis: 16.7% vs 13.6%, respectively; P = .03; fistula: 11.1% vs 8.8%, respectively; P = .05; bowel obstruction: 33.3% vs 4.4%, respectively; P cervical cancer had diminished overall survival and more complications than normal weight and obese patients. Copyright © 2010 American Cancer Society.

  1. Influence of Educational Level, Stage, and Histological Type on Survival of Oral Cancer in a Brazilian Population

    Science.gov (United States)

    Dantas, Thinali Sousa; de Barros Silva, Paulo Goberlânio; Sousa, Eric Fernandes; da Cunha, Maria do PSS; de Aguiar, Andréa Silvia Walter; Costa, Fábio Wildson Gurgel; Mota, Mário Rogério Lima; Alves, Ana Paula Negreiros Nunes; Sousa, Fabrício Bitu

    2016-01-01

    Abstract The mortality rate associated with oral cancer is estimated at approximately 12,300 deaths per year, and the survival rate is only 40% to 50% for diagnosed patients and is closely related to the duration of time between disease perception and its diagnosis and treatment. Socioeconomic risk factors are determinants of the incidence and mortality related to oral cancer. We conducted a retrospective, cross-sectional study of 573 records of patients with oral cancer at Haroldo Juaçaba Hospital – Cancer Institute of Ceará from 2000 to 2009 to evaluate the influence of socioeconomic factors on survival and epidemiological behavior of this neoplasia in a Brazilian population. In this study, patients with oral cancer were males greater than 60 years of age, presented squamous cell carcinoma in the floor of mouth and were characterized by low education levels. A total of 573 lesions were found in oral cavities. Cox proportional hazards regression model showed that the histological type, tumor stage, and low degree of education significantly influenced survival. A lower patient survival rate was correlated with a more advanced stage of disease and a worse prognosis. Squamous cell carcinoma is associated with a higher mortality when compared with other histological types of malign neoplasia. PMID:26817864

  2. Polymorphisms in genes of the de novo lipogenesis pathway and overall survival of hepatocellular carcinoma patients undergoing transarterial chemoembolization.

    Science.gov (United States)

    Wu, You-Sheng; Bao, Deng-Ke; Dai, Jing-Yao; Chen, Cheng; Zhang, Hong-Xin; Yang, YeFa; Xing, Jin-Liang; Huang, Xiao-Jun; Wan, Shao-Gui

    2015-01-01

    Aberrant expression of genes in de novo lipogenesis (DNL) pathway were associated with various cancers, including hepatocellular carcinoma (HCC). Single nucleotide polymorphisms (SNPs) of DNL genes have been reported to be associated with prognosis of some malignancies. However, the effects of SNPs in DNL genes on overall survival of HCC patients receiving transarterial chemoembolization (TACE) treatment are still unknown. In present study, nine SNPs in three genes (ACLY, ACACA and FASN) in DNL pathway were genotyped using the Sequenom iPLEX genotyping system in a hospital-based cohort with 419 HCC patients treated with TACE, and their associations with HCC overall survival were evaluated by Cox proportional hazard regression analysis under three genetic models (additive, dominant and recessive). Although we did not find any significant results in total analysis (all p>0.05), our stratified data showed that SNP rs9912300 in ACLY gene was significantly associated with overall survival of HCC patients with lower AFP level and SNP rs11871275 in ACACA gene was significantly associated with overall survival of HCC patients with higher AFP level. We further identified the significant interactions between AFP level and SNP rs9912300 or rs11871275 in the joint analysis. Conclusively, our data suggest that genetic variations in genes of DNL pathway may be a potential biomarker for predicting clinical outcome of HCC patients treated with TACE.

  3. Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Candido-dos-Reis, Francisco J; Song, Honglin; Goode, Ellen L

    2015-01-01

    PURPOSE: To analyze the effect of germline mutations in BRCA1 and BRCA2 on mortality in patients with ovarian cancer up to 10 years after diagnosis. EXPERIMENTAL DESIGN: We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival time data for 4......,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analyzed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analyzed using...... Fine and Gray model. RESULTS: The combined 10-year overall survival rate was 30% [95% confidence interval (CI), 28%-31%] for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The HR for BRCA1 was 0.53 at time zero and increased over time becoming...

  4. Reoperative retroperitoneal lymph node dissection for metastatic germ cell tumors: analysis of local recurrence and predictors of survival.

    Science.gov (United States)

    Pedrosa, Jose A; Masterson, Timothy A; Rice, Kevin R; Bihrle, Richard; Beck, Stephen D W; Foster, Richard S

    2014-06-01

    While reoperative retroperitoneal lymph node dissection results in durable long-term survival, outcomes are comparatively worse than in patients who undergo initial adequate resection. We identified predictors of cancer specific survival and correlated technical aspects of initial resection to local recurrence in patients treated with repeat retroperitoneal lymph node dissection. We reviewed subsequent data on 203 patients treated with reoperation for recurrent retroperitoneal germ cell tumor after initial retroperitoneal lymph node dissection with local relapse. We used multivariate Cox proportion hazard models for cancer specific survival and multivariate logistic regression for local recurrence. The only 2 factors associated with local recurrence at lymph node dissection were incomplete lumbar vessel division at initial resection (ptumor markers (p=0.02), M1b stage (pTumor biology and inadequate surgical technique (incomplete lumbar ligation) are associated with local recurrence after initial retroperitoneal lymph node dissection. Decreased cancer specific survival is expected in this population, mostly driven by active cancer in the final pathology specimen. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  5. Proportional Hazards Model with Covariate Measurement Error and Instrumental Variables.

    Science.gov (United States)

    Song, Xiao; Wang, Ching-Yun

    2014-12-01

    In biomedical studies, covariates with measurement error may occur in survival data. Existing approaches mostly require certain replications on the error-contaminated covariates, which may not be available in the data. In this paper, we develop a simple nonparametric correction approach for estimation of the regression parameters in the proportional hazards model using a subset of the sample where instrumental variables are observed. The instrumental variables are related to the covariates through a general nonparametric model, and no distributional assumptions are placed on the error and the underlying true covariates. We further propose a novel generalized methods of moments nonparametric correction estimator to improve the efficiency over the simple correction approach. The efficiency gain can be substantial when the calibration subsample is small compared to the whole sample. The estimators are shown to be consistent and asymptotically normal. Performance of the estimators is evaluated via simulation studies and by an application to data from an HIV clinical trial. Estimation of the baseline hazard function is not addressed.

  6. A comparison of the conditional inference survival forest model to random survival forests based on a simulation study as well as on two applications with time-to-event data.

    Science.gov (United States)

    Nasejje, Justine B; Mwambi, Henry; Dheda, Keertan; Lesosky, Maia

    2017-07-28

    Random survival forest (RSF) models have been identified as alternative methods to the Cox proportional hazards model in analysing time-to-event data. These methods, however, have been criticised for the bias that results from favouring covariates with many split-points and hence conditional inference forests for time-to-event data have been suggested. Conditional inference forests (CIF) are known to correct the bias in RSF models by separating the procedure for the best covariate to split on from that of the best split point search for the selected covariate. In this study, we compare the random survival forest model to the conditional inference model (CIF) using twenty-two simulated time-to-event datasets. We also analysed two real time-to-event datasets. The first dataset is based on the survival of children under-five years of age in Uganda and it consists of categorical covariates with most of them having more than two levels (many split-points). The second dataset is based on the survival of patients with extremely drug resistant tuberculosis (XDR TB) which consists of mainly categorical covariates with two levels (few split-points). The study findings indicate that the conditional inference forest model is superior to random survival forest models in analysing time-to-event data that consists of covariates with many split-points based on the values of the bootstrap cross-validated estimates for integrated Brier scores. However, conditional inference forests perform comparably similar to random survival forests models in analysing time-to-event data consisting of covariates with fewer split-points. Although survival forests are promising methods in analysing time-to-event data, it is important to identify the best forest model for analysis based on the nature of covariates of the dataset in question.

  7. A study of dentists' preferred maxillary anterior tooth width proportions: comparing the recurring esthetic dental proportion to other mathematical and naturally occurring proportions.

    Science.gov (United States)

    Ward, Daniel H

    2007-01-01

    Presently, there are no generally accepted standards for designing smiles using tooth proportion relationships. The purpose of this study was to determine whether North American dentists prefer smile designs created using the recurring esthetic dental (RED) proportion, other mathematically defined tooth proportion relationships, or naturally occurring tooth-to-tooth width proportions previously reported to occur in the North American population. Three hundred and one North American dentists were surveyed to determine their preferences of imaged smiles exhibiting different anterior tooth width proportions and the primary proportion influencing their decision. One-sample t-tests were used to compare preferences of constructed smiles. Pearson's Chi-square test was used to assess the independence of the relationship between the subjects' demographic attributes and the factors reported as being instrumental in their decision processes. Fifty-seven percent of dentists surveyed preferred the smiles with the 70% RED proportion over the smiles with the naturally occurring maxillary anterior tooth width proportions in normal-length teeth. Dentists preferred the smiles of the naturally occurring maxillary tooth proportions (70%) and the 70% RED proportion (75%) over the golden proportion. In smiles with tall teeth, the golden proportion was preferred by 58% of the surveyed dentists over the naturally occurring tooth-to-tooth width proportions as previously defined by Preston. Sixty-two percent of dentists cited the overall balance as the primary factor affecting their selection. Twenty-three percent made their selection based on the size of the maxillary central incisors, whereas 15% used other teeth or factors. Smiles created using the principles of the RED proportion were preferred by a majority of dentists surveyed. The majority of dentists reported that overall balance was the primary factor affecting their selection. The RED proportion may be useful in creating smiles

  8. Automated Box-Cox Transformations for Improved Visual Encoding.

    Science.gov (United States)

    Maciejewski, Ross; Pattath, Avin; Ko, Sungahn; Hafen, Ryan; Cleveland, William S; Ebert, David S

    2013-01-01

    The concept of preconditioning data (utilizing a power transformation as an initial step) for analysis and visualization is well established within the statistical community and is employed as part of statistical modeling and analysis. Such transformations condition the data to various inherent assumptions of statistical inference procedures, as well as making the data more symmetric and easier to visualize and interpret. In this paper, we explore the use of the Box-Cox family of power transformations to semiautomatically adjust visual parameters. We focus on time-series scaling, axis transformations, and color binning for choropleth maps. We illustrate the usage of this transformation through various examples, and discuss the value and some issues in semiautomatically using these transformations for more effective data visualization.

  9. Effects of Maternal Nutrition, Resource Use and Multi-Predator Risk on Neonatal White-Tailed Deer Survival

    Science.gov (United States)

    Duquette, Jared F.; Belant, Jerrold L.; Svoboda, Nathan J.; Beyer, Dean E.; Lederle, Patrick E.

    2014-01-01

    Growth of ungulate populations is typically most sensitive to survival of neonates, which in turn is influenced by maternal nutritional condition and trade-offs in resource selection and avoidance of predators. We assessed whether resource use, multi-predator risk, maternal nutritional effects, hiding cover, or interactions among these variables best explained variation in daily survival of free-ranging neonatal white-tailed deer (Odocoileus virginianus) during their post-partum period (14 May–31 Aug) in Michigan, USA. We used Cox proportional hazards mixed-effects models to assess survival related to covariates of resource use, composite predation risk of 4 mammalian predators, fawn body mass at birth, winter weather, and vegetation growth phenology. Predation, particularly from coyotes (Canis latrans), was the leading cause of mortality; however, an additive model of non-ideal resource use and maternal nutritional effects explained 71% of the variation in survival. This relationship suggested that dams selected areas where fawns had poor resources, while greater predation in these areas led to additive mortalities beyond those related to resource use alone. Also, maternal nutritional effects suggested that severe winters resulted in dams producing smaller fawns, which decreased their likelihood of survival. Fawn resource use appeared to reflect dam avoidance of lowland forests with poor forage and greater use by wolves (C. lupus), their primary predator. While this strategy led to greater fawn mortality, particularly by coyotes, it likely promoted the life-long reproductive success of dams because many reached late-age (>10 years old) and could have produced multiple generations of fawns. Studies often link resource selection and survival of ungulates, but our results suggested that multiple factors can mediate that relationship, including multi-predator risk. We emphasize the importance of identifying interactions among biological and environmental factors

  10. Prognostic Factors for Survival at 6-Month Follow-up of Hospitalized Patients with Decompensated Congestive Heart Failure.

    Science.gov (United States)

    Cheraghi, Mostafa; Sadeghi, Masoumeh; Sarrafzadegan, Nizal; Pourmoghadas, Ali; Ramezani, Mohammad Arash

    2010-01-01

    The prevalence of Congestive Heart Failure (CHF) is increasing in recent years. Factors associated with mortality in CHF patients are important to be determined in order to select therapeutic modality by physicians. The purpose of the current study was to declare predictors of 6-months survival in patients hospitalized for decompensated CHF in Isfahan. A cohort of 301 hospitalized patients with decompensated CHF were recruited in this study. The diagnosis of CHF was based on previous hospitalizations and Framingham criteria for heart failure (HF). Information regarding past history, accompanying diseases such as cerebrovascular accidents (CVA), chronic obstructive pulmonary diseases (COPD), clinical data, medications and echocardiography were obtained by a cardiologist. Patients were followed for their survival for 6 months by telephone calls. Kaplan-Meier method was used for uni variate survival analysis and Cox proportional hazard model was used for multivariate analysis. Mean age of patients was 71.9 ± 12.2 years and 59.8% was male. During 6-months follow-up 138 (45.8%) patients died. Mean survival was 119.2 ± 4.4 days (Mean ± SEM). Significant prognostic factors for 6 months survival were high education level (HR = 0.74, CI 95% 0.59-0.93), COPD (HR = 1.91, CI 95% 1.2-3.04), CVA (HR = 1.69, CI 95% 1.03-2.78), Angiotensin Converting enzyme (ACE) inhibitors use (HR = 0.44, CI 95% 0.3-0.66) and Diuretics (HR = 0.63, CI 95% 0.41-0.96). Six-month survival of hospitalized decompensated CHF patients in Iran is not favorable. Many factors particularly accompanying diseases and medications affected the patient's 6-months survival.

  11. Severe nutritional risk predicts decreased long-term survival in geriatric patients undergoing pancreaticoduodenectomy for benign disease.

    Science.gov (United States)

    Sanford, Dominic E; Sanford, Angela M; Fields, Ryan C; Hawkins, William G; Strasberg, Steven M; Linehan, David C

    2014-12-01

    Weight loss and malnutrition are poorly tolerated by geriatric patients, and pancreaticoduodenectomy (PD) can result in chronic malabsorption and weight loss. We sought to determine how preoperative severe nutritional risk (SNR), as defined by the American College of Surgeons National Surgical Quality Improvement Program/American Geriatric Society Best Practice Guidelines, affects long-term survival after PD for benign disease among geriatric and nongeriatric patients. All patients undergoing PD for nonmalignant conditions at a single center between 1995 and 2013 were followed for survival, excluding patients who died within 90 days of surgery. Survival of geriatric (age ≥65 years) and nongeriatric (age patients with and without SNR was compared using Kaplan Meier methods. Cox regression was performed. There were 320 patients who underwent PD for benign disease. Over the course of the study, the proportion of geriatric patients undergoing PD for benign conditions increased from 25% to 46%. In addition to being older, geriatric patients undergoing PD for benign disease were significantly more likely to have coronary artery disease (CAD) and hypertension. Geriatric patients with preoperative SNR had significantly decreased long-term survival after PD for benign disease (p patients dead at 5 years compared with 1 in 14 patients without SNR. Survival was not significantly different among nongeriatric patients with and without SNR. In geriatric patients, age, CAD, and SNR were significantly associated with decreased survival on both univariate and multivariate analysis. Severe nutritional risk can be a useful predictor of long-term survival in geriatric patients undergoing PD, and could improve patient risk stratification preoperatively. Nonoperative management should be strongly considered in geriatric patients with SNR, when malignancy is not suspected. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  12. Effects of maternal nutrition, resource use and multi-predator risk on neonatal white-tailed deer survival.

    Directory of Open Access Journals (Sweden)

    Jared F Duquette

    Full Text Available Growth of ungulate populations is typically most sensitive to survival of neonates, which in turn is influenced by maternal nutritional condition and trade-offs in resource selection and avoidance of predators. We assessed whether resource use, multi-predator risk, maternal nutritional effects, hiding cover, or interactions among these variables best explained variation in daily survival of free-ranging neonatal white-tailed deer (Odocoileus virginianus during their post-partum period (14 May-31 Aug in Michigan, USA. We used Cox proportional hazards mixed-effects models to assess survival related to covariates of resource use, composite predation risk of 4 mammalian predators, fawn body mass at birth, winter weather, and vegetation growth phenology. Predation, particularly from coyotes (Canis latrans, was the leading cause of mortality; however, an additive model of non-ideal resource use and maternal nutritional effects explained 71% of the variation in survival. This relationship suggested that dams selected areas where fawns had poor resources, while greater predation in these areas led to additive mortalities beyond those related to resource use alone. Also, maternal nutritional effects suggested that severe winters resulted in dams producing smaller fawns, which decreased their likelihood of survival. Fawn resource use appeared to reflect dam avoidance of lowland forests with poor forage and greater use by wolves (C. lupus, their primary predator. While this strategy led to greater fawn mortality, particularly by coyotes, it likely promoted the life-long reproductive success of dams because many reached late-age (>10 years old and could have produced multiple generations of fawns. Studies often link resource selection and survival of ungulates, but our results suggested that multiple factors can mediate that relationship, including multi-predator risk. We emphasize the importance of identifying interactions among biological and

  13. The impact of pregnancy on breast cancer survival in women who carry a BRCA1 or BRCA2 mutation.

    Science.gov (United States)

    Valentini, Adriana; Lubinski, Jan; Byrski, Tomasz; Ghadirian, Parviz; Moller, Pal; Lynch, Henry T; Ainsworth, Peter; Neuhausen, Susan L; Weitzel, Jeffrey; Singer, Christian F; Olopade, Olufunmilayo I; Saal, Howard; Lyonnet, Dominique Stoppa; Foulkes, William D; Kim-Sing, Charmaine; Manoukian, Siranoush; Zakalik, Dana; Armel, Susan; Senter, Leigha; Eng, Charis; Grunfeld, Eva; Chiarelli, Anna M; Poll, Aletta; Sun, Ping; Narod, Steven A

    2013-11-01

    Physicians are often approached by young women with a BRCA mutation and a recent history of breast cancer who wish to have a baby. They wish to know if pregnancy impacts upon their future risks of cancer recurrence and survival. To date, there is little information on the survival experience of women who carry a mutation in one of the BRCA genes and who become pregnant. From an international multi-center cohort study of 12,084 women with a BRCA1 or BRCA2 mutation, we identified 128 case subjects who were diagnosed with breast cancer while pregnant or who became pregnant after a diagnosis of breast cancer. These women were age-matched to 269 mutation carriers with breast cancer who did not become pregnant (controls). Subjects were followed from the date of breast cancer diagnosis until the date of last follow-up or death from breast cancer. The Kaplan-Meier method was used to estimate 15-year survival rates. The hazard ratio for survival associated with pregnancy was calculated using a left-truncated Cox proportional hazard model, adjusting for other prognostic factors. Among women who were diagnosed with breast cancer when pregnant or who became pregnant thereafter, the 15-year survival rate was 91.5 %, compared to a survival of 88.6 % for women who did not become pregnant (adjusted hazard ratio = 0.76; 95 % CI 0.31-1.91; p = 0.56). Pregnancy concurrent with or after a diagnosis of breast cancer does not appear to adversely affect survival among BRCA1/2 mutation carriers.

  14. Survival after traumatic spinal cord injury in Denmark: a hospital-based study among patients injured in 1990-2012.

    Science.gov (United States)

    Noe, B B; Stapelfeldt, C M; Parner, E T; Mikkelsen, E M

    2017-04-01

    Hospital-based cohort study at Spinal Cord Injury Centre of Western Denmark (VCR). To examine the overall survival and mortality over time adjusted for age at the time of injury and gender. Review of medical records of traumatic spinal cord injury (TSCI) patients admitted at VCR between 1990 and 2012. The patients were followed up until death, emigration or end of study (December 2014). Survival and mortality rate ratios (MRRs) with 95% confidence intervals (CI) were estimated for sub-groups defined by year of injury (1990-1994, 1995-1999, 2000-2004, 2005-2009 and 2010-2012). Mortality was analysed using Cox proportional hazard regression. Adjustment for gender and age at injury was performed (restricted cubic splines). In total, 665 patients (males 82%) were followed; 136 (20%) patients died during the observation period. Two-year survival varied from 93% in 2005-2009 to 98% in 2000-2004. Using 1990-1994 as a reference, the adjusted MRRs varied between 1.22 (CI: 0.43; 3.42) and 0.48 (CI: 0.13; 2.71). The 5- and 10-year survival varied between 85% (2005-2009) and 95% (1990-1994), and between 77% (2005-2009) and 91% (1990-1994), respectively. No trend over time was observed either for 2-, 5- or 10-year survival. Men's mortality did not differ consistently from that of women. Except for the most recent time period, the overall survival after TSCI was higher among those aged injury. Survival after TSCI in Denmark did not change considerably from 1990 to 2014, and there seemed to be no gender difference. Mortality was highest among patients above 60 years of age at injury.

  15. Does comorbidity explain the ethnic inequalities in cervical cancer survival in New Zealand? A retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Fleming Steven T

    2011-04-01

    Full Text Available Abstract Background There are large ethnic differences in cervical cancer survival in New Zealand that are only partly explained by stage at diagnosis. We investigated the association of comorbidity with cervical cancer survival, and whether comorbidity accounted for the previously observed ethnic differences in survival. Methods The study involved 1,594 cervical cancer cases registered during 1994-2005. Comorbidity was measured using hospital events data and was classified using the Elixhauser instrument; effects on survival of individual comorbid conditions from the Elixhauser instrument were also assessed. Cox regression was used to estimate adjusted cervical cancer mortality hazard ratios (HRs. Results Comorbidity during the year before diagnosis was associated with cervical cancer-specific survival: those with an Elixhauser count of ≥3 (compared with a count of zero had a HR of 2.17 (1.32-3.56. The HR per unit of Elixhauser count was 1.25 (1.11-1.40. However, adjustment for the Elixhauser instrument made no difference to the mortality HRs for Māori and Asian women (compared to 'Other' women, and made only a trivial difference to that for Pacific women. In contrast, concurrent adjustment for 12 individual comorbid conditions from the Elixhauser instrument reduced the Māori HR from 1.56 (1.19-2.05 to 1.44 (1.09-1.89, i.e. a reduction in the excess risk of 21%; and reduced the Pacific HR from 1.95 (1.21-3.13 to 1.62 (0.98-2.68, i.e. a reduction in the excess risk of 35%. Conclusions Comorbidity is associated with cervical cancer-specific survival in New Zealand, but accounts for only a moderate proportion of the ethnic differences in survival.

  16. 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.

  17. Does ifosfamide therapy improve survival of patients with dedifferentiated chondrosarcoma?

    Science.gov (United States)

    Kawaguchi, Satoshi; Sun, Tao; Lin, Patrick P; Deavers, Michael; Harun, Nusrat; Lewis, Valerae O

    2014-03-01

    Dedifferentiated chondrosarcoma remains a significant therapeutic challenge. Studies performed to date have not identified efficacious chemotherapy regimens for this disease. We sought to (1) evaluate the disease-specific survival at 2 and 5 years of patients with dedifferentiated chondrosarcoma; (2) assess the prognostic variables (both patient- and treatment-related), including the use of chemotherapy with ifosfamide, that relate to survivorship; and (3) assess specific toxicities associated with ifosfamide use. Data from 41 patients with dedifferentiated chondrosarcoma diagnosed and treated at the University of Texas MD Anderson Cancer Center from 1986 to 2010 were analyzed for demographics, treatments, oncologic outcomes, and prognostic variables. There were 14 women and 27 men. The mean age at diagnosis was 58 years (range, 26-86 years). Seven patients presented with metastasis. Surgical resection alone was performed in 11 patients; resection and chemotherapy in 26 patients; resection and radiotherapy in two patients; and resection, chemotherapy, and radiotherapy in two patients. Ifosfamide-based regimens were used for 16 patients. In general, ifosfamide was used when the tumor was located in the trunk or if cisplatin was discontinued as a result of toxicity. Minimum followup was 8 months (median, 68 months; range, 8-281 months). Survival was estimated using Kaplan-Meier plots and analyzed by using the Cox proportional hazards model. Disease-specific survival rates at 2 and 5 years were 33% and 15%, respectively. Multivariate analysis revealed that treatment without ifosfamide-based chemotherapy was the only independent negative prognostic factor for disease-specific survival (hazard ratio, 0.4; 95% confidence interval, 0.17-0.92; p = 0.03). Ifosfamide was discontinued in a patient as a result of renal dysfunction and was decreased in dose in another patient who developed encephalopathy. In this small retrospective study, it appeared that ifosfamide

  18. Ovarian cancer survival population differences: a "high resolution study" comparing Philippine residents, and Filipino-Americans and Caucasians living in the US

    Directory of Open Access Journals (Sweden)

    Uy Gemma

    2009-09-01

    Full Text Available Abstract Background In contrast to most other forms of cancer, data from some developing and developed countries show surprisingly similar survival rates for ovarian cancer. We aimed to compare ovarian cancer survival in Philippine residents, Filipino-Americans and Caucasians living in the US, using a high resolution approach, taking potential differences in prognostic factors into account. Methods Using databases from the SEER 13 and from the Manila and Rizal Cancer Registries, age-adjusted five-year absolute and relative survival estimates were computed using the period analysis method and compared between Filipino-American ovarian cancer patients with cancer patients from the Philippines and Caucasians in the US. Cox proportional hazards modelling was used to determine factors affecting survival differences. Results Despite more favorable distribution of age and cancer morphology and similar stage distribution, 5-year absolute and relative survival were lower in Philippine residents (Absolute survival, AS, 44%, Standard Error, SE, 2.9 and Relative survival, RS, 49.7%, SE, 3.7 than in Filipino-Americans (AS, 51.3%, SE, 3.1 and RS, 54.1%, SE, 3.4. After adjustment for these and additional covariates, strong excess risk of death for Philippine residents was found (Relative Risk, RR, 2.45, 95% confidence interval, 95% CI, 1.99-3.01. In contrast, no significant differences were found between Filipino-Americans and Caucasians living in the US. Conclusion Multivariate analyses disclosed strong survival disadvantages of Philippine residents compared to Filipino-American patients, for which differences in access to health care might have played an important role. Survival is no worse among Filipino-Americans than among Caucasians living in the US.

  19. Targeting COX-2 expression by natural compounds: a promising alternative strategy to synthetic COX-2 inhibitors for cancer chemoprevention and therapy.

    Science.gov (United States)

    Cerella, Claudia; Sobolewski, Cyril; Dicato, Mario; Diederich, Marc

    2010-12-15

    Cyclooxygenase (COX)-2 is a pro-inflammatory immediate early response protein, chronically up-regulated in many pathological conditions. In autoimmune diseases, it is responsible for degenerative effects whereas in cancer, it correlates with poor prognosis. A constitutive expression of COX-2 is triggered since the earliest steps of carcinogenesis. Consequently, strategies aimed at inhibiting COX-2 enzymatic activity have been clinically applied for the treatment of autoimmune disorders; in addition, the same approaches are currently investigated for anti-cancer purposes. However, COX-2 protein inhibitors (i.e., NSAIDs and COXIBs) are not amenable to prolonged administration since they may cause severe side effects, and efforts are underway to identify alternative approaches for chemoprevention/therapy. COX-2 expression is a multi-step process, highly regulated at transcriptional and post-transcriptional levels. Defects in the modulation of one or both of these steps may be found in pathological conditions. Targeting COX-2 expression may therefore represent a promising strategy, by which the same preventive and therapeutic benefits may be gained while avoiding the severe side effects of COX-2 enzymatic inhibition. Naturally occurring compounds derived from plants/organisms represent a huge source of biologically active molecules, that remains largely unexplored. Derived from plants/organisms used in traditional forms of medicine or as dietary supplements, these compounds have been experimentally investigated for their anti-inflammatory and anti-cancer potential. In this review, we will analyze how natural compounds may modulate the multistep regulation of COX-2 gene expression and discuss their potential as a new generation of COX-2 targeting agents alternative to the synthetic COX-2 inhibitors. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. Real-world impact of non-breast cancer-specific death on overall survival in resectable breast cancer.

    Science.gov (United States)

    Fu, Jianfei; Wu, Lunpo; Jiang, Mengjie; Li, Dan; Jiang, Ting; Fu, Wei; Wang, Liangjing; Du, Jinlin

    2017-07-01

    The real-world occurrence rate of non-breast cancer-specific death (non-BCSD) and its impact on patients with breast cancer are poorly recognized. Women with resectable breast cancer from 1990 to 2007 in the Surveillance, Epidemiology, and End Results database (n = 199,963) were analyzed. The outcome events of breast cancer were classified as breast cancer-specific death (BCSD), non-BCSD, or survival. Binary logistics was used to estimate the occurrence rates of non-BCSD and BCSD with different clinicopathological factors. The Gray method was used to measure the cumulative incidence of non-BCSD and BCSD. The ratio of non-BCSDs to all causes of death and stacked cumulative incidence function plots were used to present the impact of non-BCSD on overall survival (OS). Models of Cox proportional hazards regression and competing risk regression were compared to highlight the suitable model. There were 12,879 non-BCSDs (6.44%) and 28,784 BCSDs (14.39%). The oldest age group (>62 years), black race, and a single or divorced marital status were associated with more non-BCSDs. With adjustments for age, a hormone receptor-positive (HoR+) status was no longer related to increased non-BCSDs. In patients with grade 1, stage I disease and an HoR+ status as well as the oldest subgroup, a great dilution of non-BCSD on all causes of death could be observed, and this led to incorrect interpretations. The inaccuracy, caused by the commonly used Cox proportional hazards model, could be corrected by a competing risk model. OS was largely impaired by non-BCSD during early breast cancer. For some future clinical trial planning, especially for the oldest patients and those with HoR+ breast cancer, non-BCSD should be considered a competing risk event. Cancer 2017;123:2432-43. © 2017 American Cancer Society. © 2017 American Cancer Society.

  1. Creation of a model to predict survival in patients with refractory coeliac disease using a multinational registry.

    Science.gov (United States)

    Rubio-Tapia, A; Malamut, G; Verbeek, W H M; van Wanrooij, R L J; Leffler, D A; Niveloni, S I; Arguelles-Grande, C; Lahr, B D; Zinsmeister, A R; Murray, J A; Kelly, C P; Bai, J C; Green, P H; Daum, S; Mulder, C J J; Cellier, C

    2016-10-01

    Refractory coeliac disease is a severe complication of coeliac disease with heterogeneous outcome. To create a prognostic model to estimate survival of patients with refractory coeliac disease. We evaluated predictors of 5-year mortality using Cox proportional hazards regression on subjects from a multinational registry. Bootstrap resampling was used to internally validate the individual factors and overall model performance. The mean of the estimated regression coefficients from 400 bootstrap models was used to derive a risk score for 5-year mortality. The multinational cohort was composed of 232 patients diagnosed with refractory coeliac disease across seven centres (range of 11-63 cases per centre). The median age was 53 years and 150 (64%) were women. A total of 51 subjects died during a 5-year follow-up (cumulative 5-year all-cause mortality = 30%). From a multiple variable Cox proportional hazards model, the following variables were significantly associated with 5-year mortality: age at refractory coeliac disease diagnosis (per 20 year increase, hazard ratio = 2.21; 95% confidence interval, CI: 1.38-3.55), abnormal intraepithelial lymphocytes (hazard ratio = 2.85; 95% CI: 1.22-6.62), and albumin (per 0.5 unit increase, hazard ratio = 0.72; 95% CI: 0.61-0.85). A simple weighted three-factor risk score was created to estimate 5-year survival. Using data from a multinational registry and previously reported risk factors, we create a prognostic model to predict 5-year mortality among patients with refractory coeliac disease. This new model may help clinicians to guide treatment and follow-up. © 2016 John Wiley & Sons Ltd.

  2. Application of Survival Analysis and Multistate Modeling to Understand Animal Behavior: Examples from Guide Dogs

    Science.gov (United States)

    Asher, Lucy; Harvey, Naomi D.; Green, Martin; England, Gary C. W.

    2017-01-01

    Epidemiology is the study of patterns of health-related states or events in populations. Statistical models developed for epidemiology could be usefully applied to behavioral states or events. The aim of this study is to present the application of epidemiological statistics to understand animal behavior where discrete outcomes are of interest, using data from guide dogs to illustrate. Specifically, survival analysis and multistate modeling are applied to data on guide dogs comparing dogs that completed training and qualified as a guide dog, to those that were withdrawn from the training program. Survival analysis allows the time to (or between) a binary event(s) and the probability of the event occurring at or beyond a specified time point. Survival analysis, using a Cox proportional hazards model, was used to examine the time taken to withdraw a dog from training. Sex, breed, and other factors affected time to withdrawal. Bitches were withdrawn faster than dogs, Labradors were withdrawn faster, and Labrador × Golden Retrievers slower, than Golden Retriever × Labradors; and dogs not bred by Guide Dogs were withdrawn faster than those bred by Guide Dogs. Multistate modeling (MSM) can be used as an extension of survival analysis to incorporate more than two discrete events or states. Multistate models were used to investigate transitions between states of training to qualification as a guide dog or behavioral withdrawal, and from qualification as a guide dog to behavioral withdrawal. Sex, breed (with purebred Labradors and Golden retrievers differing from F1 crosses), and bred by Guide Dogs or not, effected movements between states. We postulate that survival analysis and MSM could be applied to a wide range of behavioral data and key examples are provided. PMID:28804710

  3. Expression profiles of loneliness-associated genes for survival prediction in cancer patients.

    Science.gov (United States)

    You, Liang-Fu; Yeh, Jia-Rong; Su, Mu-Chun

    2014-01-01

    Influence of loneliness on human survival has been established epidemiologically, but genomic research remains undeveloped. We identified 34 loneliness-associated genes which were statistically significant for high- lonely and low-lonely individuals. With the univariate Cox proportional hazards regression model, we obtained corresponding regression coefficients for loneliness-associated genes fo individual cancer patients. Furthermore, risk scores could be generated with the combination of gene expression level multiplied by corresponding regression coefficients of loneliness-associated genes. We verified that high-risk score cancer patients had shorter mean survival time than their low-risk score counterparts. Then we validated the loneliness-associated gene signature in three independent brain cancer cohorts with Kaplan-Meier survival curves (n=77, 85 and 191), significantly separable by log-rank test with hazard ratios (HR) >1 and p-values loneliness-associated gene signature in bone cancer (HR=5.10, p-value=4.69e-3), lung cancer (HR=2.86, p-value=4.71e-5), ovarian cancer (HR=1.97, p-value=3.11e-5), and leukemia (HR=2.06, p-value=1.79e-4) cohorts. The last lymphoma cohort proved to have an HR=3.50, p-value=1.15e-7. Loneliness- associated genes had good survival prediction for cancer patients, especially bone cancer patients. Our study provided the first indication that expression of loneliness-associated genes are related to survival time of cancer patients.

  4. Incident Atrial Fibrillation and Disability-Free Survival in the Cardiovascular Health Study.

    Science.gov (United States)

    Wallace, Erin R; Siscovick, David S; Sitlani, Colleen M; Dublin, Sascha; Mitchell, Pamela H; Odden, Michelle C; Hirsch, Calvin H; Thielke, Stephen; Heckbert, Susan R

    2016-04-01

    To assess the associations between incident atrial fibrillation (AF) and disability-free survival and risk of disability. Prospective cohort study. Cardiovascular Health Study. Individuals aged 65 and older and enrolled in fee-for-service Medicare followed between 1991 and 2009 (MN = 4,046). Individuals with prevalent AF, activity of daily living (ADL) disability, or a history of stroke or heart failure at baseline were excluded. Incident AF was identified according to annual study electrocardiogram, hospital discharge diagnosis, or Medicare claims. Disability-free survival was defined as survival free of ADL disability (any difficulty or inability in bathing, dressing, eating, using the toilet, walking around the home, or getting out of a bed or chair). ADLs were assessed at annual study visits or in a telephone interview. Association between incident AF and disability-free survival or risk of disability was estimated using Cox proportional hazards models. Over an average of 7.0 years of follow-up, 660 individuals (16.3%) developed incident AF, and 3,112 (77%) became disabled or died. Incident AF was associated with shorter disability-free survival (hazard ratio (HR) for death or ADL disability = 1.71, 95% confidence interval (CI) = 1.55-1.90) and a higher risk of ADL disability (HR = 1.36, 95% CI = 1.18-1.58) than in individuals with no history of AF. This association persisted after adjustment for interim stroke and heart failure. These results suggest that AF is a risk factor for shorter functional longevity in older adults, independent of other risk factors and comorbid conditions. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  5. Tumor subtype-specific associations of hormone-related reproductive factors on breast cancer survival.

    Directory of Open Access Journals (Sweden)

    Nan Song

    Full Text Available It is inconclusive whether reproductive factors, which are known as risk factors of breast cancer, also influence survival. We investigated overall and subtype-specific associations between reproductive factors and breast cancer survival.Among 3,430 incident breast cancer patients who enrolled in the Seoul Breast Cancer Study, 269 patients (7.8% died and 528 patients (15.4% recurred. The overall and subtype-specific associations of reproductive factors including age at menarche and menopause, duration of estrogen exposure, menstrual cycle, parity, age at first full-term pregnancy, number of children, age at last birth, time since the last birth, and duration of breastfeeding, on overall and disease-free survival (OS and DFS were estimated by hazard ratios (HRs and 95% confidence intervals (95% CIs using a multivariate Cox proportional hazard model.An older age at menarche (HR for OS=1.10, 95% CI=1.03-1.19, a greater number of children (≥ 4 vs. 2, HR for DFS=1.58, 95% CI=1.11-2.26, and a shorter time since last birth (<5 vs. ≥ 20 years, HR for DFS=1.67, 95% CI=1.07-2.62 were associated with worse survival while longer duration of estrogen exposure with better survival (HR for DFS=0.97, 95% CI=0.96-0.99. In the stratified analyses by subtypes, those associations were more pronounced among women with hormone receptor and human epidermal growth factor 2 positive (HR+ HER2+ tumors.It is suggested that reproductive factors, specifically age at menarche, number of children, time since last birth, and duration of estrogen exposure, could influence breast tumor progression, especially in the HR+ HER2+ subtype.

  6. Lean body mass predicts long-term survival in Chinese patients on peritoneal dialysis.

    Directory of Open Access Journals (Sweden)

    Jenq-Wen Huang

    Full Text Available BACKGROUND: Reduced lean body mass (LBM is one of the main indicators in malnutrition inflammation syndrome among patients on dialysis. However, the influence of LBM on peritoneal dialysis (PD patients' outcomes and the factors related to increasing LBM are seldom reported. METHODS: We enrolled 103 incident PD patients between 2002 and 2003, and followed them until December 2011. Clinical characteristics, PD-associated parameters, residual renal function, and serum chemistry profiles of each patient were collected at 1 month and 1 year after initiating PD. LBM was estimated using creatinine index corrected with body weight. Multiple linear regression analysis, Kaplan-Meier survival analysis, and Cox regression proportional hazard analysis were used to define independent variables and compare survival between groups. RESULTS: Using the median LBM value (70% for men and 64% for women, patients were divided into group 1 (n = 52; low LBM and group 2 (n = 51; high LBM. Group 1 patients had higher rates of peritonitis (1.6 vs. 1.1/100 patient months; p<0.05 and hospitalization (14.6 vs. 9.7/100 patient months; p<0.05. Group 1 patients also had shorter overall survival and technique survival (p<0.01. Each percentage point increase in LBM reduced the hazard ratio for mortality by 8% after adjustment for diabetes, age, sex, and body mass index (BMI. Changes in residual renal function and protein catabolic rate were independently associated with changes in LBM in the first year of PD. CONCLUSIONS: LBM serves as a good parameter in addition to BMI to predict the survival of patients on PD. Preserving residual renal function and increasing protein intake can increase LBM.

  7.  Alkaline phosphatase normalization is a biomarker of improved survival in primary sclerosing cholangitis.

    Science.gov (United States)

    Hilscher, Moira; Enders, Felicity B; Carey, Elizabeth J; Lindor, Keith D; Tabibian, James H

    2016-01-01

     Introduction. Recent studies suggest that serum alkaline phosphatase may represent a prognostic biomarker in patients with primary sclerosing cholangitis. However, this association remains poorly understood. Therefore, the aim of this study was to investigate the prognostic significance and clinical correlates of alkaline phosphatase normalization in primary sclerosing cholangitis. This was a retrospective cohort study of patients with a new diagnosis of primary sclerosing cholangitis made at an academic medical center. The primary endpoint was time to hepatobiliaryneoplasia, liver transplantation, or liver-related death. Secondary endpoints included occurrence of and time to alkaline phosphatase normalization. Patients who did and did not achieve normalization were compared with respect to clinical characteristics and endpoint-free survival, and the association between normalization and the primary endpoint was assessed with univariate and multivariate Cox proportional-hazards analyses. Eighty six patients were included in the study, with a total of 755 patient-years of follow-up. Thirty-eight patients (44%) experienced alkaline phosphatase normalization within 12 months of diagnosis. Alkaline phosphatase normalization was associated with longer primary endpoint-free survival (p = 0.0032) and decreased risk of requiring liver transplantation (p = 0.033). Persistent normalization was associated with even fewer adverse endpoints as well as longer survival. In multivariate analyses, alkaline phosphatase normalization (adjusted hazard ratio 0.21, p = 0.012) and baseline bilirubin (adjusted hazard ratio 4.87, p = 0.029) were the only significant predictors of primary endpoint-free survival. Alkaline phosphatase normalization, particularly if persistent, represents a robust biomarker of improved long-term survival and decreased risk of requiring liver transplantation in patients with primary sclerosing cholangitis.

  8. Integrative analysis of micro-RNA, gene expression, and survival of glioblastoma multiforme.

    Science.gov (United States)

    Huang, Yen-Tsung; Hsu, Thomas; Kelsey, Karl T; Lin, Chien-Ling

    2015-02-01

    Glioblastoma multiforme (GBM), the most common type of malignant brain tumor, is highly fatal. Limited understanding of its rapid progression necessitates additional approaches that integrate what is known about the genomics of this cancer. Using a discovery set (n = 348) and a validation set (n = 174) of GBM patients, we performed genome-wide analyses that integrated mRNA and micro-RNA expression data from GBM as well as associated survival information, assessing coordinated variability in each as this reflects their known mechanistic functions. Cox proportional hazards models were used for the survival analyses, and nonparametric permutation tests were performed for the micro-RNAs to investigate the association between the number of associated genes and its prognostication. We also utilized mediation analyses for micro-RNA-gene pairs to identify their mediation effects. Genome-wide analyses revealed a novel pattern: micro-RNAs related to more gene expressions are more likely to be associated with GBM survival (P = 4.8 × 10(-5)). Genome-wide mediation analyses for the 32,660 micro-RNA-gene pairs with strong association (false discovery rate [FDR] micro-RNAs and mediated their prognostic effects as well. We further constructed a gene signature using the 16 genes, which was highly associated with GBM survival in both the discovery and validation sets (P = 9.8 × 10(-6)). This comprehensive study discovered mediation effects of micro-RNA to gene expression and GBM survival and provided