[Survival analysis with competing risks: estimating failure probability].

Science.gov (United States)

Llorca, Javier; Delgado-Rodríguez, Miguel

2004-01-01

To show the impact of competing risks of death on survival analysis. We provide an example of survival time without chronic rejection after heart transplantation, where death before rejection acts as a competing risk. Using a computer simulation, we compare the Kaplan-Meier estimator and the multiple decrement model. The Kaplan-Meier method overestimated the probability of rejection. Next, we illustrate the use of the multiple decrement model to analyze secondary end points (in our example: death after rejection). Finally, we discuss Kaplan-Meier assumptions and why they fail in the presence of competing risks. Survival analysis should be adjusted for competing risks of death to avoid overestimation of the risk of rejection produced with the Kaplan-Meier method.

Pregnancy associated nasopharyngeal carcinoma: A retrospective case-control analysis of maternal survival outcomes

International Nuclear Information System (INIS)

Cheng, Yi-Kan; Zhang, Fan; Tang, Ling-Long; Chen, Lei; Zhou, Guan-Qun; Zeng, Mu-Sheng; Kang, Tie-Bang; Jia, Wei-Hua; Shao, Jian-Yong; Mai, Hai-Qiang; Guo, Ying; Ma, Jun

2015-01-01

Background: Pregnancy-associated nasopharyngeal carcinoma (PANPC) has been associated with poor survival. Recent advances in radiation technology and imaging techniques, and the introduction of chemotherapy have improved survival in nasopharyngeal carcinoma (NPC); however, it is not clear whether these changes have improved survival in PANPC. Therefore, the purpose of this study was to compare five-year maternal survival in patients with PANPC and non-pregnant patients with NPC. Methods: After adjusting for age, stage and chemotherapy mode, we conducted a retrospective case-control study among 36 non-metastatic PANPC patients and 36 non-pregnant NPC patients (control group) who were treated at our institution between 2000 and 2010. Results: The median age of both groups was 30 years (range, 23–35 years); median follow-up for all patients was 70 months. Locoregionally-advanced disease accounted for 83.3% of all patients with PANPC and 92.9% of patients who developed NPC during pregnancy. In both the PANPC and control groups, 31 patients (86.1%) received chemotherapy and all patients received definitive radiotherapy. The five-year rates for overall survival (70% vs. 78%, p = 0.72), distant metastasis-free survival (79% vs. 76%, p = 0.77), loco-regional relapse-free survival (97% vs. 91%, p = 0.69) and disease-free survival (69% vs. 74%, p = 0.98) were not significantly different between the PANPC and control groups. Multivariate analysis using a Cox proportional hazards model revealed that only N-classification was significantly associated with five-year OS. Conclusion: This study demonstrates that, in the modern treatment era, pregnancy itself may not negatively influence survival outcomes in patients with NPC; however, pregnancy may delay the diagnosis of NPC

Metagenomic Analysis of Hot Springs in Central India Reveals Hydrocarbon Degrading Thermophiles and Pathways Essential for Survival in Extreme Environments

Science.gov (United States)

Saxena, Rituja; Dhakan, Darshan B.; Mittal, Parul; Waiker, Prashant; Chowdhury, Anirban; Ghatak, Arundhuti; Sharma, Vineet K.

2017-01-01

Extreme ecosystems such as hot springs are of great interest as a source of novel extremophilic species, enzymes, metabolic functions for survival and biotechnological products. India harbors hundreds of hot springs, the majority of which are not yet explored and require comprehensive studies to unravel their unknown and untapped phylogenetic and functional diversity. The aim of this study was to perform a large-scale metagenomic analysis of three major hot springs located in central India namely, Badi Anhoni, Chhoti Anhoni, and Tattapani at two geographically distinct regions (Anhoni and Tattapani), to uncover the resident microbial community and their metabolic traits. Samples were collected from seven distinct sites of the three hot spring locations with temperature ranging from 43.5 to 98°C. The 16S rRNA gene amplicon sequencing of V3 hypervariable region and shotgun metagenome sequencing uncovered a unique taxonomic and metabolic diversity of the resident thermophilic microbial community in these hot springs. Genes associated with hydrocarbon degradation pathways, such as benzoate, xylene, toluene, and benzene were observed to be abundant in the Anhoni hot springs (43.5–55°C), dominated by Pseudomonas stutzeri and Acidovorax sp., suggesting the presence of chemoorganotrophic thermophilic community with the ability to utilize complex hydrocarbons as a source of energy. A high abundance of genes belonging to methane metabolism pathway was observed at Chhoti Anhoni hot spring, where methane is reported to constitute >80% of all the emitted gases, which was marked by the high abundance of Methylococcus capsulatus. The Tattapani hot spring, with a high-temperature range (61.5–98°C), displayed a lower microbial diversity and was primarily dominated by a nitrate-reducing archaeal species Pyrobaculum aerophilum. A higher abundance of cell metabolism pathways essential for the microbial survival in extreme conditions was observed at Tattapani. Taken together

Direct Survival Analysis: a new stock assessment method

Directory of Open Access Journals (Sweden)

Eduardo Ferrandis

2007-03-01

Full Text Available In this work, a new stock assessment method, Direct Survival Analysis, is proposed and described. The parameter estimation of the Weibull survival model proposed by Ferrandis (2007 is obtained using trawl survey data. This estimation is used to establish a baseline survival function, which is in turn used to estimate the specific survival functions in the different cohorts considered through an adaptation of the separable model of the fishing mortality rates introduced by Pope and Shepherd (1982. It is thus possible to test hypotheses on the evolution of survival during the period studied and to identify trends in recruitment. A link is established between the preceding analysis of trawl survey data and the commercial catch-at-age data that are generally obtained to evaluate the population using analytical models. The estimated baseline survival, with the proposed versions of the stock and catch equations and the adaptation of the Separable Model, may be applied to commercial catch-at-age data. This makes it possible to estimate the survival corresponding to the landing data, the initial size of the cohort and finally, an effective age of first capture, in order to complete the parameter model estimation and consequently the estimation of the whole survival and mortality, along with the reference parameters that are useful for management purposes. Alternatively, this estimation of an effective age of first capture may be obtained by adapting the demographic structure of trawl survey data to that of the commercial fleet through suitable selectivity models of the commercial gears. The complete model provides the evaluation of the stock at any age. The coherence (and hence the mutual “calibration” between the two kinds of information may be analysed and compared with results obtained by other methods, such as virtual population analysis (VPA, in order to improve the diagnosis of the state of exploitation of the population. The model may be

Neyman, Markov processes and survival analysis.

Science.gov (United States)

Yang, Grace

2013-07-01

J. Neyman used stochastic processes extensively in his applied work. One example is the Fix and Neyman (F-N) competing risks model (1951) that uses finite homogeneous Markov processes to analyse clinical trials with breast cancer patients. We revisit the F-N model, and compare it with the Kaplan-Meier (K-M) formulation for right censored data. The comparison offers a way to generalize the K-M formulation to include risks of recovery and relapses in the calculation of a patient's survival probability. The generalization is to extend the F-N model to a nonhomogeneous Markov process. Closed-form solutions of the survival probability are available in special cases of the nonhomogeneous processes, like the popular multiple decrement model (including the K-M model) and Chiang's staging model, but these models do not consider recovery and relapses while the F-N model does. An analysis of sero-epidemiology current status data with recurrent events is illustrated. Fix and Neyman used Neyman's RBAN (regular best asymptotic normal) estimates for the risks, and provided a numerical example showing the importance of considering both the survival probability and the length of time of a patient living a normal life in the evaluation of clinical trials. The said extension would result in a complicated model and it is unlikely to find analytical closed-form solutions for survival analysis. With ever increasing computing power, numerical methods offer a viable way of investigating the problem.

Advanced Online Survival Analysis Tool for Predictive Modelling in Clinical Data Science.

Science.gov (United States)

Montes-Torres, Julio; Subirats, José Luis; Ribelles, Nuria; Urda, Daniel; Franco, Leonardo; Alba, Emilio; Jerez, José Manuel

2016-01-01

One of the prevailing applications of machine learning is the use of predictive modelling in clinical survival analysis. In this work, we present our view of the current situation of computer tools for survival analysis, stressing the need of transferring the latest results in the field of machine learning to biomedical researchers. We propose a web based software for survival analysis called OSA (Online Survival Analysis), which has been developed as an open access and user friendly option to obtain discrete time, predictive survival models at individual level using machine learning techniques, and to perform standard survival analysis. OSA employs an Artificial Neural Network (ANN) based method to produce the predictive survival models. Additionally, the software can easily generate survival and hazard curves with multiple options to personalise the plots, obtain contingency tables from the uploaded data to perform different tests, and fit a Cox regression model from a number of predictor variables. In the Materials and Methods section, we depict the general architecture of the application and introduce the mathematical background of each of the implemented methods. The study concludes with examples of use showing the results obtained with public datasets.

SURVIVAL ANALYSIS AND LENGTH-BIASED SAMPLING

Directory of Open Access Journals (Sweden)

Masoud Asgharian

2010-12-01

Full Text Available When survival data are colleted as part of a prevalent cohort study, the recruited cases have already experienced their initiating event. These prevalent cases are then followed for a fixed period of time at the end of which the subjects will either have failed or have been censored. When interests lies in estimating the survival distribution, from onset, of subjects with the disease, one must take into account that the survival times of the cases in a prevalent cohort study are left truncated. When it is possible to assume that there has not been any epidemic of the disease over the past period of time that covers the onset times of the subjects, one may assume that the underlying incidence process that generates the initiating event times is a stationary Poisson process. Under such assumption, the survival times of the recruited subjects are called “lengthbiased”. I discuss the challenges one is faced with in analyzing these type of data. To address the theoretical aspects of the work, I present asymptotic results for the NPMLE of the length-biased as well as the unbiased survival distribution. I also discuss estimating the unbiased survival function using only the follow-up time. This addresses the case that the onset times are either unknown or known with uncertainty. Some of our most recent work and open questions will be presented. These include some aspects of analysis of covariates, strong approximation, functional LIL and density estimation under length-biased sampling with right censoring. The results will be illustrated with survival data from patients with dementia, collected as part of the Canadian Study of Health and Aging (CSHA.

Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves.

Science.gov (United States)

Guyot, Patricia; Ades, A E; Ouwens, Mario J N M; Welton, Nicky J

2012-02-01

The results of Randomized Controlled Trials (RCTs) on time-to-event outcomes that are usually reported are median time to events and Cox Hazard Ratio. These do not constitute the sufficient statistics required for meta-analysis or cost-effectiveness analysis, and their use in secondary analyses requires strong assumptions that may not have been adequately tested. In order to enhance the quality of secondary data analyses, we propose a method which derives from the published Kaplan Meier survival curves a close approximation to the original individual patient time-to-event data from which they were generated. We develop an algorithm that maps from digitised curves back to KM data by finding numerical solutions to the inverted KM equations, using where available information on number of events and numbers at risk. The reproducibility and accuracy of survival probabilities, median survival times and hazard ratios based on reconstructed KM data was assessed by comparing published statistics (survival probabilities, medians and hazard ratios) with statistics based on repeated reconstructions by multiple observers. The validation exercise established there was no material systematic error and that there was a high degree of reproducibility for all statistics. Accuracy was excellent for survival probabilities and medians, for hazard ratios reasonable accuracy can only be obtained if at least numbers at risk or total number of events are reported. The algorithm is a reliable tool for meta-analysis and cost-effectiveness analyses of RCTs reporting time-to-event data. It is recommended that all RCTs should report information on numbers at risk and total number of events alongside KM curves.

Using Survival Analysis to Evaluate Medical Equipment Battery Life.

Science.gov (United States)

Kuhajda, David

2016-01-01

As hospital medical device managers obtain more data, opportunities exist for using the data to improve medical device management, enhance patient safety, and evaluate costs of decisions. As a demonstration of the ability to use data analytics, this article applies survival analysis statistical techniques to assist in making decisions on medical equipment maintenance. The analysis was performed on a large amount of data related to failures of an infusion pump manufacturer's lithium battery and two aftermarket replacement lithium batteries from one hospital facility. The survival analysis resulted in statistical evidence showing that one of the third-party batteries had a lower survival curve than the infusion pump manufacturer's battery. This lower survival curve translates to a shorter expected life before replacement is needed. The data suggested that to limit unexpected failures, replacing batteries at a two-year interval, rather than the current industry recommendation of three years, may be warranted. For less than $5,400 in additional annual cost, the risk of unexpected battery failures can be reduced from an estimated 28% to an estimated 7%.

Modeling time-to-event (survival) data using classification tree analysis.

Science.gov (United States)

Linden, Ariel; Yarnold, Paul R

2017-12-01

Time to the occurrence of an event is often studied in health research. Survival analysis differs from other designs in that follow-up times for individuals who do not experience the event by the end of the study (called censored) are accounted for in the analysis. Cox regression is the standard method for analysing censored data, but the assumptions required of these models are easily violated. In this paper, we introduce classification tree analysis (CTA) as a flexible alternative for modelling censored data. Classification tree analysis is a "decision-tree"-like classification model that provides parsimonious, transparent (ie, easy to visually display and interpret) decision rules that maximize predictive accuracy, derives exact P values via permutation tests, and evaluates model cross-generalizability. Using empirical data, we identify all statistically valid, reproducible, longitudinally consistent, and cross-generalizable CTA survival models and then compare their predictive accuracy to estimates derived via Cox regression and an unadjusted naïve model. Model performance is assessed using integrated Brier scores and a comparison between estimated survival curves. The Cox regression model best predicts average incidence of the outcome over time, whereas CTA survival models best predict either relatively high, or low, incidence of the outcome over time. Classification tree analysis survival models offer many advantages over Cox regression, such as explicit maximization of predictive accuracy, parsimony, statistical robustness, and transparency. Therefore, researchers interested in accurate prognoses and clear decision rules should consider developing models using the CTA-survival framework. © 2017 John Wiley & Sons, Ltd.

Analysis of survival data with dependent censoring copula-based approaches

CERN Document Server

Emura, Takeshi

2018-01-01

This book introduces readers to copula-based statistical methods for analyzing survival data involving dependent censoring. Primarily focusing on likelihood-based methods performed under copula models, it is the first book solely devoted to the problem of dependent censoring. The book demonstrates the advantages of the copula-based methods in the context of medical research, especially with regard to cancer patients’ survival data. Needless to say, the statistical methods presented here can also be applied to many other branches of science, especially in reliability, where survival analysis plays an important role. The book can be used as a textbook for graduate coursework or a short course aimed at (bio-) statisticians. To deepen readers’ understanding of copula-based approaches, the book provides an accessible introduction to basic survival analysis and explains the mathematical foundations of copula-based survival models.

Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves

Directory of Open Access Journals (Sweden)

Guyot Patricia

2012-02-01

Full Text Available Abstract Background The results of Randomized Controlled Trials (RCTs on time-to-event outcomes that are usually reported are median time to events and Cox Hazard Ratio. These do not constitute the sufficient statistics required for meta-analysis or cost-effectiveness analysis, and their use in secondary analyses requires strong assumptions that may not have been adequately tested. In order to enhance the quality of secondary data analyses, we propose a method which derives from the published Kaplan Meier survival curves a close approximation to the original individual patient time-to-event data from which they were generated. Methods We develop an algorithm that maps from digitised curves back to KM data by finding numerical solutions to the inverted KM equations, using where available information on number of events and numbers at risk. The reproducibility and accuracy of survival probabilities, median survival times and hazard ratios based on reconstructed KM data was assessed by comparing published statistics (survival probabilities, medians and hazard ratios with statistics based on repeated reconstructions by multiple observers. Results The validation exercise established there was no material systematic error and that there was a high degree of reproducibility for all statistics. Accuracy was excellent for survival probabilities and medians, for hazard ratios reasonable accuracy can only be obtained if at least numbers at risk or total number of events are reported. Conclusion The algorithm is a reliable tool for meta-analysis and cost-effectiveness analyses of RCTs reporting time-to-event data. It is recommended that all RCTs should report information on numbers at risk and total number of events alongside KM curves.

ATM and p53 combined analysis predicts survival in glioblastoma multiforme patients: A clinicopathologic study.

Science.gov (United States)

Romano, Francesco Jacopo; Guadagno, Elia; Solari, Domenico; Borrelli, Giorgio; Pignatiello, Sara; Cappabianca, Paolo; Del Basso De Caro, Marialaura

2018-06-01

Glioblastoma is one of the most malignant cancers, with a distinguishing dismal prognosis: surgery followed by chemo- and radiotherapy represents the current standard of care, and chemo- and radioresistance underlie disease recurrence and short overall survival of patients suffering from this malignancy. ATM is a kinase activated by autophosphorylation upon DNA doublestrand breaks arising from errors during replication, byproducts of metabolism, chemotherapy or ionizing radiations; TP53 is one of the most popular tumor suppressor, with a preeminent role in DNA damage response and repair. To study the effects of the immunohistochemical expression of p-ATM and p53 in glioblastoma patients, 21 cases were retrospectively examined. In normal brain tissue, p-ATM was expressed only in neurons; conversely, in tumors cells, the protein showed a variable cytoplasmic expression (score: +,++,+++), with being completely undetectable in three cases. Statistical analysis revealed that high p-ATM score (++/+++) strongly correlated to shorter survival (P = 0.022). No difference in overall survival was registered between p53 normally expressed (NE) and overexpressed (OE) glioblastoma patients (P = 0.669). Survival analysis performed on the results from combined assessment of the two proteins showed that patients with NE p53 /low pATM score had longer overall survival than the NE p53/ high pATM score counterpart. Cox-regression analysis confirmed this finding (HR = 0.025; CI 95% = 0.002-0.284; P = 0.003). Our study outlined the immunohistochemical expression of p-ATM/p53 in glioblastomas and provided data on their possible prognostic/predictive of response role. A "non-oncogene addiction" to ATM for NEp53 glioblastoma could be postulated, strengthening the rationale for development of ATM inhibiting drugs. © 2018 Wiley Periodicals, Inc.

An exploratory discrete-time multilevel analysis of the effect of social support on the survival of elderly people in China

Science.gov (United States)

Feng, Zhixin; Jones, Kelvyn; Wang, Wenfei Winnie

2015-01-01

This study undertakes a survival analysis of elderly persons in China using Chinese Longitudinal Healthy Longevity Survey 2002–2008. Employing discrete-time multilevel models, we explored the effect of social support on the survival of elderly people in China. This study focuses on objective (living arrangements and received support) and subjective activities (perceived support) of social support, finding that the effect of different activities of social support on the survival of elderly people varies according to the availability of different support resources. Specifically, living with a spouse, financial independence, perceiving care support from any resource is associated with higher survival rates for elderly people. Separate analysis focusing on urban elderly and rural elderly revealed broadly similar results. There is a larger difference between those perceiving care support from family or social service and not perceiving care support in urban areas comparing to those in rural areas. Those who cannot pay medical expenses are the least likely to survive. The higher level of economic development in province has no significant effect on the survival of elderly people for the whole sample model and the elderly people in urban areas; however, there is a negative influence on the survival of the rural elderly people. PMID:25703671

Survival analysis for customer satisfaction: A case study

Science.gov (United States)

Hadiyat, M. A.; Wahyudi, R. D.; Sari, Y.

2017-11-01

Most customer satisfaction surveys are conducted periodically to track their dynamics. One of the goals of this survey was to evaluate the service design by recognizing the trend of satisfaction score. Many researchers recommended in redesigning the service when the satisfaction scores were decreasing, so that the service life cycle could be predicted qualitatively. However, these scores were usually set in Likert scale and had quantitative properties. Thus, they should also be analyzed in quantitative model so that the predicted service life cycle would be done by applying the survival analysis. This paper discussed a starting point for customer satisfaction survival analysis with a case study in healthcare service.

Metabolic profiling of hypoxic cells revealed a catabolic signature required for cell survival.

Directory of Open Access Journals (Sweden)

Christian Frezza

Full Text Available Hypoxia is one of the features of poorly vascularised areas of solid tumours but cancer cells can survive in these areas despite the low oxygen tension. The adaptation to hypoxia requires both biochemical and genetic responses that culminate in a metabolic rearrangement to counter-balance the decrease in energy supply from mitochondrial respiration. The understanding of metabolic adaptations under hypoxia could reveal novel pathways that, if targeted, would lead to specific death of hypoxic regions. In this study, we developed biochemical and metabolomic analyses to assess the effects of hypoxia on cellular metabolism of HCT116 cancer cell line. We utilized an oxygen fluorescent probe in anaerobic cuvettes to study oxygen consumption rates under hypoxic conditions without the need to re-oxygenate the cells and demonstrated that hypoxic cells can maintain active, though diminished, oxidative phosphorylation even at 1% oxygen. These results were further supported by in situ microscopy analysis of mitochondrial NADH oxidation under hypoxia. We then used metabolomic methodologies, utilizing liquid chromatography-mass spectrometry (LC-MS, to determine the metabolic profile of hypoxic cells. This approach revealed the importance of synchronized and regulated catabolism as a mechanism of adaptation to bioenergetic stress. We then confirmed the presence of autophagy under hypoxic conditions and demonstrated that the inhibition of this catabolic process dramatically reduced the ATP levels in hypoxic cells and stimulated hypoxia-induced cell death. These results suggest that under hypoxia, autophagy is required to support ATP production, in addition to glycolysis, and that the inhibition of autophagy might be used to selectively target hypoxic regions of tumours, the most notoriously resistant areas of solid tumours.

Statistical models and methods for reliability and survival analysis

CERN Document Server

Couallier, Vincent; Huber-Carol, Catherine; Mesbah, Mounir; Huber -Carol, Catherine; Limnios, Nikolaos; Gerville-Reache, Leo

2013-01-01

Statistical Models and Methods for Reliability and Survival Analysis brings together contributions by specialists in statistical theory as they discuss their applications providing up-to-date developments in methods used in survival analysis, statistical goodness of fit, stochastic processes for system reliability, amongst others. Many of these are related to the work of Professor M. Nikulin in statistics over the past 30 years. The authors gather together various contributions with a broad array of techniques and results, divided into three parts - Statistical Models and Methods, Statistical

Survival analysis in hematologic malignancies: recommendations for clinicians

Science.gov (United States)

Delgado, Julio; Pereira, Arturo; Villamor, Neus; López-Guillermo, Armando; Rozman, Ciril

2014-01-01

The widespread availability of statistical packages has undoubtedly helped hematologists worldwide in the analysis of their data, but has also led to the inappropriate use of statistical methods. In this article, we review some basic concepts of survival analysis and also make recommendations about how and when to perform each particular test using SPSS, Stata and R. In particular, we describe a simple way of defining cut-off points for continuous variables and the appropriate and inappropriate uses of the Kaplan-Meier method and Cox proportional hazard regression models. We also provide practical advice on how to check the proportional hazards assumption and briefly review the role of relative survival and multiple imputation. PMID:25176982

Genome analysis of Pseudoalteromonas flavipulchra JG1 reveals various survival advantages in marine environment.

Science.gov (United States)

Yu, Min; Tang, Kaihao; Liu, Jiwen; Shi, Xiaochong; Gulder, Tobias A M; Zhang, Xiao-Hua

2013-10-16

Competition between bacteria for habitat and resources is very common in the natural environment and is considered to be a selective force for survival. Many strains of the genus Pseudoalteromonas were confirmed to produce bioactive compounds that provide those advantages over their competitors. In our previous study, P. flavipulchra JG1 was found to synthesize a Pseudoalteromonas flavipulchra antibacterial Protein (PfaP) with L-amino acid oxidase activity and five small chemical compounds, which were the main competitive agents of the strain. In addition, the genome of this bacterium has been previously sequenced as Whole Genome Shotgun project (PMID: 22740664). In this study, more extensive genomic analysis was performed to identify specific genes or gene clusters which related to its competitive feature, and further experiments were carried out to confirm the physiological roles of these genes when competing with other microorganisms in marine environment. The antibacterial protein PfaP may also participate in the biosynthesis of 6-bromoindolyl-3-acetic acid, indicating a synergistic effect between the antibacterial macromolecule and small molecules. Chitinases and quorum quenching enzymes present in P. flavipulchra, which coincide with great chitinase and acyl homoserine lactones degrading activities of strain JG1, suggest other potential mechanisms contribute to antibacterial/antifungal activities. Moreover, movability and rapid response mechanisms to phosphorus starvation and other stresses, such as antibiotic, oxidative and heavy metal stress, enable JG1 to adapt to deleterious, fluctuating and oligotrophic marine environments. The genome of P. flavipulchra JG1 exhibits significant genetic advantages against other microorganisms, encoding antimicrobial agents as well as abilities to adapt to various adverse environments. Genes involved in synthesis of various antimicrobial substances enriches the antagonistic mechanisms of P. flavipulchra JG1 and affords

Causal inference in survival analysis using pseudo-observations.

Science.gov (United States)

Andersen, Per K; Syriopoulou, Elisavet; Parner, Erik T

2017-07-30

Causal inference for non-censored response variables, such as binary or quantitative outcomes, is often based on either (1) direct standardization ('G-formula') or (2) inverse probability of treatment assignment weights ('propensity score'). To do causal inference in survival analysis, one needs to address right-censoring, and often, special techniques are required for that purpose. We will show how censoring can be dealt with 'once and for all' by means of so-called pseudo-observations when doing causal inference in survival analysis. The pseudo-observations can be used as a replacement of the outcomes without censoring when applying 'standard' causal inference methods, such as (1) or (2) earlier. We study this idea for estimating the average causal effect of a binary treatment on the survival probability, the restricted mean lifetime, and the cumulative incidence in a competing risks situation. The methods will be illustrated in a small simulation study and via a study of patients with acute myeloid leukemia who received either myeloablative or non-myeloablative conditioning before allogeneic hematopoetic cell transplantation. We will estimate the average causal effect of the conditioning regime on outcomes such as the 3-year overall survival probability and the 3-year risk of chronic graft-versus-host disease. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Survival analysis of a treatment data for cancer of the larynx

International Nuclear Information System (INIS)

Khan, K.

2002-01-01

In this paper a survival analysis of the survival time is done. The Cox regression model is fitted to the survival time with the assumption of proportional hazard. A model is selected after inclusion and exclusion of factors and variables as explanatory variables. The assumption of proportional hazards is tested in the manner suggested by Harrell (1986). The assumption of proportional hazards is supported by these tests. However the plot of Schoenfeld residuals against dose gave a little evidence of non validity of the proportional hazard assumption. The assumption seems to be satisfied for variable time. The martingale residuals suggest no pattern for variable age. The functional form of dose is not linear. Hence the quadratic dose is used as an explanatory variable. A comparison of logistic regression analysis and survival analysis is also made in this paper. It can be concluded that Cox proportional hazards model is a better model than the logistic model as it is more parsimonious and utilizes more information. (author)

Ortholog-based screening and identification of genes related to intracellular survival.

Science.gov (United States)

Yang, Xiaowen; Wang, Jiawei; Bing, Guoxia; Bie, Pengfei; De, Yanyan; Lyu, Yanli; Wu, Qingmin

2018-04-20

Bioinformatics and comparative genomics analysis methods were used to predict unknown pathogen genes based on homology with identified or functionally clustered genes. In this study, the genes of common pathogens were analyzed to screen and identify genes associated with intracellular survival through sequence similarity, phylogenetic tree analysis and the λ-Red recombination system test method. The total 38,952 protein-coding genes of common pathogens were divided into 19,775 clusters. As demonstrated through a COG analysis, information storage and processing genes might play an important role intracellular survival. Only 19 clusters were present in facultative intracellular pathogens, and not all were present in extracellular pathogens. Construction of a phylogenetic tree selected 18 of these 19 clusters. Comparisons with the DEG database and previous research revealed that seven other clusters are considered essential gene clusters and that seven other clusters are associated with intracellular survival. Moreover, this study confirmed that clusters screened by orthologs with similar function could be replaced with an approved uvrY gene and its orthologs, and the results revealed that the usg gene is associated with intracellular survival. The study improves the current understanding of intracellular pathogens characteristics and allows further exploration of the intracellular survival-related gene modules in these pathogens. Copyright © 2018. Published by Elsevier B.V.

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

A Framework for RFID Survivability Requirement Analysis and Specification

Science.gov (United States)

Zuo, Yanjun; Pimple, Malvika; Lande, Suhas

Many industries are becoming dependent on Radio Frequency Identification (RFID) technology for inventory management and asset tracking. The data collected about tagged objects though RFID is used in various high level business operations. The RFID system should hence be highly available, reliable, and dependable and secure. In addition, this system should be able to resist attacks and perform recovery in case of security incidents. Together these requirements give rise to the notion of a survivable RFID system. The main goal of this paper is to analyze and specify the requirements for an RFID system to become survivable. These requirements, if utilized, can assist the system in resisting against devastating attacks and recovering quickly from damages. This paper proposes the techniques and approaches for RFID survivability requirements analysis and specification. From the perspective of system acquisition and engineering, survivability requirement is the important first step in survivability specification, compliance formulation, and proof verification.

A taylor series approach to survival analysis

International Nuclear Information System (INIS)

Brodsky, J.B.; Groer, P.G.

1984-09-01

A method of survival analysis using hazard functions is developed. The method uses the well known mathematical theory for Taylor Series. Hypothesis tests of the adequacy of many statistical models, including proportional hazards and linear and/or quadratic dose responses, are obtained. A partial analysis of leukemia mortality in the Life Span Study cohort is used as an example. Furthermore, a relatively robust estimation procedure for the proportional hazards model is proposed. (author)

51Cr - erythrocyte survival curves

International Nuclear Information System (INIS)

Paiva Costa, J. de.

1982-07-01

Sixteen patients were studied, being fifteen patients in hemolytic state, and a normal individual as a witness. The aim was to obtain better techniques for the analysis of the erythrocytes, survival curves, according to the recommendations of the International Committee of Hematology. It was used the radiochromatic method as a tracer. Previously a revisional study of the International Literature was made in its aspects inherent to the work in execution, rendering possible to establish comparisons and clarify phonomena observed in cur investigation. Several parameters were considered in this study, hindering both the exponential and the linear curves. The analysis of the survival curves of the erythrocytes in the studied group, revealed that the elution factor did not present a homogeneous answer quantitatively to all, though, the result of the analysis of these curves have been established, through listed programs in the electronic calculator. (Author) [pt

Comparative Analyses of Nonpathogenic, Opportunistic, and Totally Pathogenic Mycobacteria Reveal Genomic and Biochemical Variabilities and Highlight the Survival Attributes of Mycobacterium tuberculosis

Science.gov (United States)

Singh, Yadvir; Kohli, Sakshi; Ahmad, Javeed; Ehtesham, Nasreen Z.; Tyagi, Anil K.

2014-01-01

ABSTRACT Mycobacterial evolution involves various processes, such as genome reduction, gene cooption, and critical gene acquisition. Our comparative genome size analysis of 44 mycobacterial genomes revealed that the nonpathogenic (NP) genomes were bigger than those of opportunistic (OP) or totally pathogenic (TP) mycobacteria, with the TP genomes being smaller yet variable in size—their genomic plasticity reflected their ability to evolve and survive under various environmental conditions. From the 44 mycobacterial species, 13 species, representing TP, OP, and NP, were selected for genomic-relatedness analyses. Analysis of homologous protein-coding genes shared between Mycobacterium indicus pranii (NP), Mycobacterium intracellulare ATCC 13950 (OP), and Mycobacterium tuberculosis H37Rv (TP) revealed that 4,995 (i.e., ~95%) M. indicaus pranii proteins have homology with M. intracellulare, whereas the homologies among M. indicus pranii, M. intracellulare ATCC 13950, and M. tuberculosis H37Rv were significantly lower. A total of 4,153 (~79%) M. indicus pranii proteins and 4,093 (~79%) M. intracellulare ATCC 13950 proteins exhibited homology with the M. tuberculosis H37Rv proteome, while 3,301 (~82%) and 3,295 (~82%) M. tuberculosis H37Rv proteins showed homology with M. indicus pranii and M. intracellulare ATCC 13950 proteomes, respectively. Comparative metabolic pathway analyses of TP/OP/NP mycobacteria showed enzymatic plasticity between M. indicus pranii (NP) and M. intracellulare ATCC 13950 (OP), Mycobacterium avium 104 (OP), and M. tuberculosis H37Rv (TP). Mycobacterium tuberculosis seems to have acquired novel alternate pathways with possible roles in metabolism, host-pathogen interactions, virulence, and intracellular survival, and by implication some of these could be potential drug targets. PMID:25370496

Is Human Papillomavirus Associated with Prostate Cancer Survival?

Directory of Open Access Journals (Sweden)

Mariarosa Pascale

2013-01-01

Full Text Available The role of human papillomavirus (HPV in prostate carcinogenesis is highly controversial: some studies suggest a positive association between HPV infection and an increased risk of prostate cancer (PCa, whereas others do not reveal any correlation. In this study, we investigated the prognostic impact of HPV infection on survival in 150 primary PCa patients. One hundred twelve (74.67% patients had positive expression of HPV E7 protein, which was evaluated in tumour tissue by immunohistochemistry. DNA analysis on a subset of cases confirmed HPV infection and revealed the presence of genotype 16. In Kaplan-Meier analysis, HPV-positive cancer patients showed worse overall survival (OS (median 4.59 years compared to HPV-negative (median 8.24 years, P=0.0381. In multivariate analysis age (P<0.001, Gleason score (P<0.001, nuclear grading (P=0.002, and HPV status (P=0.034 were independent prognostic factors for OS. In our cohort, we observed high prevalence of HPV nuclear E7 oncoprotein and an association between HPV infection and PCa survival. In the debate about the oncogenic activity of HPV in PCa, our results further confirm the need for additional studies to clarify the possible role of HPV in prostate carcinogenesis.

Prognostic classification index in Iranian colorectal cancer patients: Survival tree analysis

Directory of Open Access Journals (Sweden)

Amal Saki Malehi

2016-01-01

Full Text Available Aims: The aim of this study was to determine the prognostic index for separating homogenous subgroups in colorectal cancer (CRC patients based on clinicopathological characteristics using survival tree analysis. Methods: The current study was conducted at the Research Center of Gastroenterology and Liver Disease, Shahid Beheshti Medical University in Tehran, between January 2004 and January 2009. A total of 739 patients who already have been diagnosed with CRC based on pathologic report were enrolled. The data included demographic and clinical-pathological characteristic of patients. Tree-structured survival analysis based on a recursive partitioning algorithm was implemented to evaluate prognostic factors. The probability curves were calculated according to the Kaplan-Meier method, and the hazard ratio was estimated as an interest effect size. Result: There were 526 males (71.2% of these patients. The mean survival time (from diagnosis time was 42.46± (3.4. Survival tree identified three variables as main prognostic factors and based on their four prognostic subgroups was constructed. The log-rank test showed good separation of survival curves. Patients with Stage I-IIIA and treated with surgery as the first treatment showed low risk (median = 34 months whereas patients with stage IIIB, IV, and more than 68 years have the worse survival outcome (median = 9.5 months. Conclusion: Constructing the prognostic classification index via survival tree can aid the researchers to assess interaction between clinical variables and determining the cumulative effect of these variables on survival outcome.

Association between obesity with disease-free survival and overall survival in triple-negative breast cancer: A meta-analysis.

Science.gov (United States)

Mei, Lin; He, Lin; Song, Yuhua; Lv, Yang; Zhang, Lijiu; Hao, Fengxi; Xu, Mengmeng

2018-05-01

To investigate the relationship between obesity and disease-free survival (DFS) and overall survival (OS) of triple-negative breast cancer. Citations were searched in PubMed, Cochrane Library, and Web of Science. Random effect model meta-analysis was conducted by using Revman software version 5.0, and publication bias was evaluated by creating Egger regression with STATA software version 12. Nine studies (4412 patients) were included for DFS meta-analysis, 8 studies (4392 patients) include for OS meta-analysis. There were no statistical significances between obesity with DFS (P = .60) and OS (P = .71) in triple-negative breast cancer (TNBC) patients. Obesity has no impact on DFS and OS in patients with TNBC.

PROGNOSTIC FACTORS OF SURVIVAL IN RENAL CANCER

Directory of Open Access Journals (Sweden)

A. V. Seriogin

2014-08-01

Full Text Available The purpose of the study was to reveal the independent anatomic, histological, and clinical factors of cancer-specific survival in patients with renal-cell carcinoma (RCC. For this, the authors retrospectively analyzed their experience with radical surgical treatments in 73 RCC patients operated on at the Department of Urology and Surgical Andrology, Russian Medical Academy of Postgraduate Education, from January 1, 1999 to December 31, 2004; their outcomes have become known by the present time. There was a statistically significant correlation of cancer-specific survival with its parameters, such as pathological stage of a tumor, its maximum pathological size, differentiation grade, involvement of regional lymph nodes, venous tumor thrombosis, level of thrombocytosis, and degree of the clinical symptoms of the disease. Multivariate analysis of survival in RCC in relation to the prognostic factors could reveal odd ratios for the limit values of significant prognostic factors. The statistically significant prognostic values established in the present study, as well as the molecular factors the implication of which is being now investigated can become in future an effective addition to the TNM staging system to define indications for certain treatments and to predict survival in RCC  

PROGNOSTIC FACTORS OF SURVIVAL IN RENAL CANCER

Directory of Open Access Journals (Sweden)

A. V. Seriogin

2009-01-01

Full Text Available The purpose of the study was to reveal the independent anatomic, histological, and clinical factors of cancer-specific survival in patients with renal-cell carcinoma (RCC. For this, the authors retrospectively analyzed their experience with radical surgical treatments in 73 RCC patients operated on at the Department of Urology and Surgical Andrology, Russian Medical Academy of Postgraduate Education, from January 1, 1999 to December 31, 2004; their outcomes have become known by the present time. There was a statistically significant correlation of cancer-specific survival with its parameters, such as pathological stage of a tumor, its maximum pathological size, differentiation grade, involvement of regional lymph nodes, venous tumor thrombosis, level of thrombocytosis, and degree of the clinical symptoms of the disease. Multivariate analysis of survival in RCC in relation to the prognostic factors could reveal odd ratios for the limit values of significant prognostic factors. The statistically significant prognostic values established in the present study, as well as the molecular factors the implication of which is being now investigated can become in future an effective addition to the TNM staging system to define indications for certain treatments and to predict survival in RCC  

Mediation analysis of the relationship between institutional research activity and patient survival

DEFF Research Database (Denmark)

Rochon, Justine; du Bois, Andreas; Lange, Theis

2014-01-01

BACKGROUND: Recent studies have suggested that patients treated in research-active institutions have better outcomes than patients treated in research-inactive institutions. However, little attention has been paid to explaining such effects, probably because techniques for mediation analysis...... existing so far have not been applicable to survival data. METHODS: We investigated the underlying mechanisms using a recently developed method for mediation analysis of survival data. Our analysis of the effect of research activity on patient survival was based on 352 patients who had been diagnosed...... mediated through either optimal surgery or chemotherapy. Taken together, about 26% of the beneficial effect of research activity was mediated through the proposed pathways. CONCLUSIONS: Mediation analysis allows proceeding from the question "Does it work?" to the question "How does it work?" In particular...

Solitary plasmacytoma: population-based analysis of survival trends and effect of various treatment modalities in the USA.

Science.gov (United States)

Thumallapally, Nishitha; Meshref, Ahmed; Mousa, Mohammed; Terjanian, Terenig

2017-01-05

Solitary plasmacytoma (SP) is a localized neoplastic plasma cell disorder with an annual incidence of less than 450 cases. Given the rarity of this disorder, it is difficult to conduct large-scale population studies. Consequently, very limited information on the disorder is available, making it difficult to estimate the incidence and survival rates. Furthermore, limited information is available on the efficacy of various treatment modalities in relation to primary tumor sites. The data for this retrospective study were drawn from the Surveillance, Epidemiology and End Results (SEER) database, which comprises 18 registries; patient demographics, treatment modalities and survival rates were obtained for those diagnosed with SP from 1998 to 2007. Various prognostic factors were analyzed via Kaplan-Meier analysis and log-rank test, with 5-year relative survival rate defined as the primary outcome of interest. Cox regression analysis was employed in the multivariate analysis. The SEER search from 1998 to 2007 yielded records for 1691 SP patients. The median age at diagnosis was 63 years. The patient cohort was 62.4% male, 37.6% female, 80% Caucasian, 14.6% African American and 5.4% other races. Additionally, 57.8% had osseous plasmacytoma, and 31.9% had extraosseous involvement. Unspecified plasmacytoma was noted in 10.2% of patients. The most common treatment modalities were radiotherapy (RT) (48.8%), followed by combination surgery with RT (21.2%) and surgery alone (11.6%). Univariate analysis of prognostic factors revealed that the survival outcomes were better for younger male patients who received RT with surgery (p multiple myeloma (MM) was noted in 551 patients. Age >60 years was associated with a lower 5-year survival in patients who progressed to MM compared to those who were diagnosed initially with MM (15.1 vs 16.6%). Finally, those who received RT and progressed to MM still had a higher chance of survival than those who were diagnosed with MM initially and

Causal inference in survival analysis using pseudo-observations

DEFF Research Database (Denmark)

Andersen, Per K; Syriopoulou, Elisavet; Parner, Erik T

2017-01-01

Causal inference for non-censored response variables, such as binary or quantitative outcomes, is often based on either (1) direct standardization ('G-formula') or (2) inverse probability of treatment assignment weights ('propensity score'). To do causal inference in survival analysis, one needs ...

Prognostic factors and survival in primary malignant astrocytomas of the spinal cord: a population-based analysis from 1973 to 2007.

Science.gov (United States)

Adams, Hadie; Avendaño, Javier; Raza, Shaan M; Gokaslan, Ziya L; Jallo, George I; Quiñones-Hinojosa, Alfredo

2012-05-20

Observational cross-sectional study. Using data from the population-based cancer registries of the Surveillance, Epidemiology and End Results (SEER) program, we analyzed demographic features, tumor and treatment characteristics, as well as survival rates in patients with primary malignant astrocytomas of the spinal cord (PMASC). PMASC is a rare neoplasm and is considered to carry the same dismal outcome as their cerebral counterparts. Our current knowledge is incomplete, and understanding the epidemiology, diagnosis, and optimal treatment still poses challenges. The SEER data from 1973 to 2007 were reviewed for pathologically confirmed primary anaplastic astrocytomas (AA) and glioblastomas of the spinal cord (C72.0). We compared the clinical features and outcomes of the cohort in uni- and multivariate fashion. Survival was calculated and compared using Kaplan-Meier curves and log-rank analysis. Our search criteria retrieved 135 patients diagnosed with PMASC. The median survival for PMASC was 13 months with 1-, 2-, and 5-year survival rates of 51.8%, 32.2%, and 18.7%. Patient diagnosed with AA had a median survival time of 17 months versus 10 months in patients diagnosed with glioblastomas. Adult patients observed markedly prolonged survival compared with the pediatric group, with a 16-month versus 9-month median survival, respectively. Multivariate analysis revealed age at diagnosis, pediatric and adult age groups, sex, tumor histology, and extent of resection as significant predictors of survival. Interestingly, outcomes did not significantly change throughout the last decades or by receiving radiotherapy. Outcome for patients diagnosed with PMASC remains poor and presents an ongoing challenge for professionals in the field of neurospinal medicine and surgery. In our analyses of AA, adult patients, males, and patients undergoing radical resections were associated with increased survival. However, incidence of these lesions is low; hence, building strong

Survival Analysis of Patients with End Stage Renal Disease

Science.gov (United States)

Urrutia, J. D.; Gayo, W. S.; Bautista, L. A.; Baccay, E. B.

2015-06-01

This paper provides a survival analysis of End Stage Renal Disease (ESRD) under Kaplan-Meier Estimates and Weibull Distribution. The data were obtained from the records of V. L. MakabaliMemorial Hospital with respect to time t (patient's age), covariates such as developed secondary disease (Pulmonary Congestion and Cardiovascular Disease), gender, and the event of interest: the death of ESRD patients. Survival and hazard rates were estimated using NCSS for Weibull Distribution and SPSS for Kaplan-Meier Estimates. These lead to the same conclusion that hazard rate increases and survival rate decreases of ESRD patient diagnosed with Pulmonary Congestion, Cardiovascular Disease and both diseases with respect to time. It also shows that female patients have a greater risk of death compared to males. The probability risk was given the equation R = 1 — e-H(t) where e-H(t) is the survival function, H(t) the cumulative hazard function which was created using Cox-Regression.

A spatial scan statistic for survival data based on Weibull distribution.

Science.gov (United States)

Bhatt, Vijaya; Tiwari, Neeraj

2014-05-20

The spatial scan statistic has been developed as a geographical cluster detection analysis tool for different types of data sets such as Bernoulli, Poisson, ordinal, normal and exponential. We propose a scan statistic for survival data based on Weibull distribution. It may also be used for other survival distributions, such as exponential, gamma, and log normal. The proposed method is applied on the survival data of tuberculosis patients for the years 2004-2005 in Nainital district of Uttarakhand, India. Simulation studies reveal that the proposed method performs well for different survival distribution functions. Copyright © 2013 John Wiley & Sons, Ltd.

Proteomic analysis reveals the mechanisms of Mycena dendrobii promoting transplantation survival and growth of tissue culture seedlings of Dendrobium officinale.

Science.gov (United States)

Xu, X B; Ma, X Y; Lei, H H; Song, H M; Ying, Q C; Xu, M J; Liu, S B; Wang, H Z

2015-06-01

Dendrobium officinale is an important traditional Chinese medicinal herb. Its seedlings generally show low survival and growth when transferred from in vitro tissue culture to a greenhouse or field environment. In this study, the effect of Mycena dendrobii on the survival and growth of D. officinale tissue culture seedlings and the mechanisms involved was explored. Mycena dendrobii were applied underneath the roots of D. officinale tissue culture seedlings. The seedling survival and growth were analysed. The root proteins induced by M. dendrobii were identified using two-dimensional (2-D) electrophoresis and matrix-assisted laser desorption/ionization time-of-flight MS (MALDI-TOF-MS). Mycena dendrobii treatment significantly enhanced survival and growth of D. officinale seedlings. Forty-one proteins induced by M. dendrobii were identified. Among them, 10 were involved in defence and stress response, two were involved in the formation of root or mycorrhizae, and three were related to the biosynthesis of bioactive constituents. These results suggest that enhancing stress tolerance and promoting new root formation induced by M. dendrobii may improve the survival and growth of D. officinale tissue culture seedlings. This study provides a foundation for future use of M. dendrobii in the large-scale cultivation of Dendrobiums. © 2015 The Society for Applied Microbiology.

Re-analysis of survival data of cancer patients utilizing additive homeopathy.

Science.gov (United States)

Gleiss, Andreas; Frass, Michael; Gaertner, Katharina

2016-08-01

In this short communication we present a re-analysis of homeopathic patient data in comparison to control patient data from the same Outpatient´s Unit "Homeopathy in malignant diseases" of the Medical University of Vienna. In this analysis we took account of a probable immortal time bias. For patients suffering from advanced stages of cancer and surviving the first 6 or 12 months after diagnosis, respectively, the results show that utilizing homeopathy gives a statistically significant (p<0.001) advantage over control patients regarding survival time. In conclusion, bearing in mind all limitations, the results of this retrospective study suggest that patients with advanced stages of cancer might benefit from additional homeopathic treatment until a survival time of up to 12 months after diagnosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Benign meningiomas: primary treatment selection affects survival

International Nuclear Information System (INIS)

Condra, Kellie S.; Buatti, John M.; Mendenhall, William M.; Friedman, William A.; Marcus, Robert B.; Rhoton, Albert L.

1997-01-01

Purpose: To examine the effect of primary treatment selection on outcomes for benign intracranial meningiomas at the University of Florida. Methods and Materials: For 262 patients, the impact of age, Karnofsky performance status, pathologic features, tumor size, tumor location, and treatment modality on local control and cause-specific survival was analyzed (minimum potential follow-up, 2 years; median follow-up, 8.2 years). Extent of surgery was classified by Simpson grade. Treatment groups: surgery alone (n = 229), surgery and postoperative radiotherapy (RT) (n = 21), RT alone (n = 7), radiosurgery alone (n = 5). Survival analysis: Kaplan-Meier method with univariate and multivariate analysis. Results: At 15 years, local control was 76% after total excision (TE) and 87% after subtotal excision plus RT (SE+RT), both significantly better (p = 0.0001) than after SE alone (30%). Cause-specific survival at 15 years was reduced after treatment with SE alone (51%), compared with TE (88%) or SE+RT (86%) (p = 0.0003). Recurrence after primary treatment portended decreased survival, independent of initial treatment group or salvage treatment selection (p = 0.001). Atypical pathologic features predicted reduced 15-year local control (54 vs. 71%) and cause-specific survival rates (57 vs. 86%). Multivariate analysis for cause-specific survival revealed treatment group (SE vs. others; p = 0.0001), pathologic features (atypical vs. typical; p = 0.0056), and Karnofsky performance status (≥80 vs. <80; p = 0.0153) as significant variables. Conclusion: Benign meningiomas are well managed by TE or SE+RT. SE alone is inadequate therapy and adversely affects cause-specific survival. Atypical pathologic features predict a poorer outcome, suggesting possible benefit from more aggressive treatment. Because local recurrence portends lower survival rates, primary treatment choice is important

PSMA targeted radioligandtherapy in metastatic castration resistant prostate cancer after chemotherapy, abiraterone and/or enzalutamide. A retrospective analysis of overall survival

Energy Technology Data Exchange (ETDEWEB)

Rahbar, K.; Schaefers, M. [University Hospital Muenster, Department of Nuclear Medicine, Muenster (Germany); Boegemann, M. [University Hospital Muenster, Department of Urology, Muenster (Germany); Yordanova, A.; Essler, M.; Ahmadzadehfar, H. [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Eveslage, M. [University Hospital Muenster, Institute of Biostatistics and Clinical Research, Muenster (Germany)

2018-01-15

Our aim was to evaluate overall survival and parameters prognosticating longer survival in a large and homogeneous group of patients treated with {sup 177}Lu-PSMA-617 radioligand therapy with heavily pretreated advanced metastatic castration resistant prostate cancer. A total of 104 patients were treated with 351 cycles of {sup 177}Lu-PSMA-617. Prostate specific antigen (PSA) changes after the first cycle of therapy were documented prior to a second cycle. Patients were followed-up for overall survival (OS). Any PSA decline, PSA decline ≥50%, initial PSA, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), visceral metastases and cumulative injected activity were analyzed and evaluated according to OS. Multivariable analysis with parameters with a p-value ≤0.05 in univariate analysis was performed, additionally adjusting for age and presence of visceral metastases. A total of 51 patients (49%) died during the observation period. The majority of patients (97%) presented with bone metastases, 77% with lymph node metastases and 32% with visceral metastases. All patients were treated with at least one line of chemotherapy. Either abiraterone or enzalutamide had been given in 100% of the patients. Any PSA decline occurred in 70 (67%) and a PSA decline ≥50% in 34 (33%) of patients after the first cycle. The median OS was 56.0 weeks (95%CI: 50.5-61.5). Initial PSA decline ≥50%, initial LDH, visceral metastases, second line chemotherapy or prior radium-223 did not have an effect on survival, whereas any initial PSA decline, initial ALP <220 U/L and cumulative injected activity ≥18.8 GBq were associated with a longer survival. A step-by-step analysis revealed a PSA decline ≥20.87% as the most noticeable cut-off prognosticating longer survival, which remained an independent prognosticator of improved OS in the multivariate analysis. {sup 177}Lu-PSMA-617 RLT is a new effective therapeutic and seems to prolong survival in patients with advanced m

A gene expression signature associated with survival in metastatic melanoma

Science.gov (United States)

Mandruzzato, Susanna; Callegaro, Andrea; Turcatel, Gianluca; Francescato, Samuela; Montesco, Maria C; Chiarion-Sileni, Vanna; Mocellin, Simone; Rossi, Carlo R; Bicciato, Silvio; Wang, Ena; Marincola, Francesco M; Zanovello, Paola

2006-01-01

Background Current clinical and histopathological criteria used to define the prognosis of melanoma patients are inadequate for accurate prediction of clinical outcome. We investigated whether genome screening by means of high-throughput gene microarray might provide clinically useful information on patient survival. Methods Forty-three tumor tissues from 38 patients with stage III and stage IV melanoma were profiled with a 17,500 element cDNA microarray. Expression data were analyzed using significance analysis of microarrays (SAM) to identify genes associated with patient survival, and supervised principal components (SPC) to determine survival prediction. Results SAM analysis revealed a set of 80 probes, corresponding to 70 genes, associated with survival, i.e. 45 probes characterizing longer and 35 shorter survival times, respectively. These transcripts were included in a survival prediction model designed using SPC and cross-validation which allowed identifying 30 predicting probes out of the 80 associated with survival. Conclusion The longer-survival group of genes included those expressed in immune cells, both innate and acquired, confirming the interplay between immunological mechanisms and the natural history of melanoma. Genes linked to immune cells were totally lacking in the poor-survival group, which was instead associated with a number of genes related to highly proliferative and invasive tumor cells. PMID:17129373

A gene expression signature associated with survival in metastatic melanoma

Directory of Open Access Journals (Sweden)

Rossi Carlo R

2006-11-01

Full Text Available Abstract Background Current clinical and histopathological criteria used to define the prognosis of melanoma patients are inadequate for accurate prediction of clinical outcome. We investigated whether genome screening by means of high-throughput gene microarray might provide clinically useful information on patient survival. Methods Forty-three tumor tissues from 38 patients with stage III and stage IV melanoma were profiled with a 17,500 element cDNA microarray. Expression data were analyzed using significance analysis of microarrays (SAM to identify genes associated with patient survival, and supervised principal components (SPC to determine survival prediction. Results SAM analysis revealed a set of 80 probes, corresponding to 70 genes, associated with survival, i.e. 45 probes characterizing longer and 35 shorter survival times, respectively. These transcripts were included in a survival prediction model designed using SPC and cross-validation which allowed identifying 30 predicting probes out of the 80 associated with survival. Conclusion The longer-survival group of genes included those expressed in immune cells, both innate and acquired, confirming the interplay between immunological mechanisms and the natural history of melanoma. Genes linked to immune cells were totally lacking in the poor-survival group, which was instead associated with a number of genes related to highly proliferative and invasive tumor cells.

Survival analysis of dialysis patients in selected hospitals of lahore city

International Nuclear Information System (INIS)

Ahmad, Z.; Shahzad, I.

2015-01-01

There are several reasons which are directly or indirectly relate to affect the survival time of End Stage Renal Disease (ESRD) patients. This study was done to analyse the survival rate of ESRD patients in Lahore city, and to evaluate the influence of various risk factors and prognostic factors on survival of these patients. Methods: A sample of 40 patients was taken from the Jinnah Hospital Lahore and Lahore General Hospital by using the convenience sampling technique. The Log Rank Test was used to determine the significant difference between the categories of qualitative variables of ESRD patients. Multivariate Cox Regression Analysis was used to analyse the effect of different clinical and socio-economic variables on the survival time of these patients. Results: Different qualitative variables like: age, marital status, BMI, comorbid factors, diabetes type, gender, income level, place, risk factor like diabetes, ischemic heart disease, hypertension and Hepatitis status were analysed on the basis of Log Rank Test. While age and comorbid factors were found to be statistically significant which showed that the distribution of age and comorbid factors were different. By using the Cox Regression analysis the coefficient of Mass, serum albumin and family history of diabetes were found to be significant. Conclusions: There were some of the factors which had been taken for the analysis came out less or more significant in patients of ESRD. So it was concluded that mostly clinical factors which were Mass of the Patient, Serum Albumin and Family History of Diabetes made significant contribution towards the survival status of patients. (author)

Survival analysis approach to account for non-exponential decay rate effects in lifetime experiments

International Nuclear Information System (INIS)

Coakley, K.J.; Dewey, M.S.; Huber, M.G.; Huffer, C.R.; Huffman, P.R.; Marley, D.E.; Mumm, H.P.; O'Shaughnessy, C.M.; Schelhammer, K.W.; Thompson, A.K.; Yue, A.T.

2016-01-01

In experiments that measure the lifetime of trapped particles, in addition to loss mechanisms with exponential survival probability functions, particles can be lost by mechanisms with non-exponential survival probability functions. Failure to account for such loss mechanisms produces systematic measurement error and associated systematic uncertainties in these measurements. In this work, we develop a general competing risks survival analysis method to account for the joint effect of loss mechanisms with either exponential or non-exponential survival probability functions, and a method to quantify the size of systematic effects and associated uncertainties for lifetime estimates. As a case study, we apply our survival analysis formalism and method to the Ultra Cold Neutron lifetime experiment at NIST. In this experiment, neutrons can escape a magnetic trap before they decay due to a wall loss mechanism with an associated non-exponential survival probability function.

Survival analysis approach to account for non-exponential decay rate effects in lifetime experiments

Energy Technology Data Exchange (ETDEWEB)

Coakley, K.J., E-mail: kevincoakley@nist.gov [National Institute of Standards and Technology, 325 Broadway, Boulder, CO 80305 (United States); Dewey, M.S.; Huber, M.G. [National Institute of Standards and Technology, 100 Bureau Drive, Stop 8461, Gaithersburg, MD 20899 (United States); Huffer, C.R.; Huffman, P.R. [North Carolina State University, 2401 Stinson Drive, Box 8202, Raleigh, NC 27695 (United States); Triangle Universities Nuclear Laboratory, 116 Science Drive, Box 90308, Durham, NC 27708 (United States); Marley, D.E. [National Institute of Standards and Technology, 100 Bureau Drive, Stop 8461, Gaithersburg, MD 20899 (United States); North Carolina State University, 2401 Stinson Drive, Box 8202, Raleigh, NC 27695 (United States); Mumm, H.P. [National Institute of Standards and Technology, 100 Bureau Drive, Stop 8461, Gaithersburg, MD 20899 (United States); O' Shaughnessy, C.M. [University of North Carolina at Chapel Hill, 120 E. Cameron Ave., CB #3255, Chapel Hill, NC 27599 (United States); Triangle Universities Nuclear Laboratory, 116 Science Drive, Box 90308, Durham, NC 27708 (United States); Schelhammer, K.W. [North Carolina State University, 2401 Stinson Drive, Box 8202, Raleigh, NC 27695 (United States); Triangle Universities Nuclear Laboratory, 116 Science Drive, Box 90308, Durham, NC 27708 (United States); Thompson, A.K.; Yue, A.T. [National Institute of Standards and Technology, 100 Bureau Drive, Stop 8461, Gaithersburg, MD 20899 (United States)

2016-03-21

In experiments that measure the lifetime of trapped particles, in addition to loss mechanisms with exponential survival probability functions, particles can be lost by mechanisms with non-exponential survival probability functions. Failure to account for such loss mechanisms produces systematic measurement error and associated systematic uncertainties in these measurements. In this work, we develop a general competing risks survival analysis method to account for the joint effect of loss mechanisms with either exponential or non-exponential survival probability functions, and a method to quantify the size of systematic effects and associated uncertainties for lifetime estimates. As a case study, we apply our survival analysis formalism and method to the Ultra Cold Neutron lifetime experiment at NIST. In this experiment, neutrons can escape a magnetic trap before they decay due to a wall loss mechanism with an associated non-exponential survival probability function.

A Retrospective Analysis of Precision Medicine Outcomes in Patients With Advanced Cancer Reveals Improved Progression-Free Survival Without Increased Health Care Costs.

Science.gov (United States)

Haslem, Derrick S; Van Norman, S Burke; Fulde, Gail; Knighton, Andrew J; Belnap, Tom; Butler, Allison M; Rhagunath, Sharanya; Newman, David; Gilbert, Heather; Tudor, Brian P; Lin, Karen; Stone, Gary R; Loughmiller, David L; Mishra, Pravin J; Srivastava, Rajendu; Ford, James M; Nadauld, Lincoln D

2017-02-01

The advent of genomic diagnostic technologies such as next-generation sequencing has recently enabled the use of genomic information to guide targeted treatment in patients with cancer, an approach known as precision medicine. However, clinical outcomes, including survival and the cost of health care associated with precision cancer medicine, have been challenging to measure and remain largely unreported. We conducted a matched cohort study of 72 patients with metastatic cancer of diverse subtypes in the setting of a large, integrated health care delivery system. We analyzed the outcomes of 36 patients who received genomic testing and targeted therapy (precision cancer medicine) between July 1, 2013, and January 31, 2015, compared with 36 historical control patients who received standard chemotherapy (n = 29) or best supportive care (n = 7). The average progression-free survival was 22.9 weeks for the precision medicine group and 12.0 weeks for the control group ( P = .002) with a hazard ratio of 0.47 (95% CI, 0.29 to 0.75) when matching on age, sex, histologic diagnosis, and previous lines of treatment. In a subset analysis of patients who received all care within the Intermountain Healthcare system (n = 44), per patient charges per week were $4,665 in the precision treatment group and $5,000 in the control group ( P = .126). These findings suggest that precision cancer medicine may improve survival for patients with refractory cancer without increasing health care costs. Although the results of this study warrant further validation, this precision medicine approach may be a viable option for patients with advanced cancer.

Survival after Second and Subsequent Recurrences in Osteosarcoma: A Retrospective Multicenter Analysis.

Science.gov (United States)

Tirtei, Elisa; Asaftei, Sebastian D; Manicone, Rosaria; Cesari, Marilena; Paioli, Anna; Rocca, Michele; Ferrari, Stefano; Fagioli, Franca

2017-05-01

Purpose Osteosarcoma (OS) is the most common primary bone tumor. Despite complete surgical removal and intensive chemotherapeutic treatment, 30%-35% of patients with OS have local or systemic recurrence. Some patients survive multiple recurrences, but overall survival after OS recurrence is poor. This analysis aims to describe and identify factors influencing post-relapse survival (PRS) after a second OS relapse. Methods This is a retrospective analysis of 60 patients with a second relapse of OS of the extremities in 2 Italian centers between 2003 and 2013. Results Treatment for first and subsequent relapses was planned according to institutional guidelines. After complete surgical remission (CSR) following the first recurrence, patients experienced a second OS relapse with a median disease-free interval (DFI) of 6 months. Lung disease was prevalent: 44 patients (76%) had pulmonary metastases. Survival after the second relapse was 22% at 5 years. Lung disease only correlated with better survival at 5 years (33.6%) compared with other sites of recurrence (5%; p = 0.008). Patients with a single pulmonary lesion had a better 5-year second PRS (42%; p = 0.02). Patients who achieved a second CSR had a 5-year second PRS of 33.4%. Chemotherapy (p<0.001) benefited patients without a third CSR. Conclusions This analysis confirms the importance of an aggressive, repeated surgical approach. Lung metastases only, the number of lesions, DFI and CSR influenced survival. It also confirms the importance of chemotherapy in patients in whom surgical treatment is not feasible.

Introduction to SURPH.1 analysis of release-recapture data for survival studies

International Nuclear Information System (INIS)

Smith, S.G.; Skalski, J.R.; Schlechte, J.W.; Hoffmann, A.; Cassen, V.

1994-12-01

Program SURPH is the culmination of several years of research to develop a comprehensive computer program to analyze survival studies of fish and wildlife populations. Development of this software was motivated by the advent of the PIT-tag (Passive Integrated Transponder) technology that permits the detection of salmonid smolt as they pass through hydroelectric facilities on the Snake and Columbia Rivers in the Pacific Northwest. Repeated detections of individually tagged smolt and analysis of their capture-histories permits estimates of downriver survival probabilities. Eventual installation of detection facilities at adult fish ladders will also permit estimation of ocean survival and upstream survival of returning salmon using the statistical methods incorporated in SURPH.1. However, the utility of SURPH.1 far exceeds solely the analysis of salmonid tagging studies. Release-recapture and radiotelemetry studies from a wide range of terrestrial and aquatic species have been analyzed using SURPH.1 to estimate discrete time survival probabilities and investigate survival relationships. The interactive computing environment of SURPH.1 was specifically developed to allow researchers to investigate the relationship between survival and capture processes and environmental, experimental and individual-based covariates. Program SURPH.1 represents a significant advancement in the ability of ecologists to investigate the interplay between morphologic, genetic, environmental and anthropogenic factors on the survival of wild species. It is hoped that this better understanding of risk factors affecting survival will lead to greater appreciation of the intricacies of nature and to improvements in the management of wild resources. This technical report is an introduction to SURPH.1 and provides a user guide for both the UNIX and MS-Windows reg-sign applications of the SURPH software

Multivariate Analysis of the Predictors of Survival for Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization: Focusing on Superselective Chemoembolization

International Nuclear Information System (INIS)

Ji, Suk Kyeong; Cho, Yun Ku; Ahn, Yong Sik; Kim, Mi Young; Park, Yoon Ok; Kim, Jae Kyun; Kim, Wan Tae

2008-01-01

While the prognostic factors of survival for patients with hepatocellular carcinoma (HCC) who underwent transarterial chemoembolization (TACE) are well known, the clinical significance of performing selective TACE for HCC patients has not been clearly documented. We tried to analyze the potential factors of disease-free survival for these patients, including the performance of selective TACE. A total of 151 patients with HCC who underwent TACE were retrospectively analyzed for their disease-free survival (a median follow- up of 23 months, range: 1-88 months). Univariate and multivariate analyses were performed for 20 potential factors by using the Cox proportional hazard model, including 19 baseline factors and one procedure-related factor (conventional versus selective TACE). The parameters that proved to be significant on the univariate analysis were subsequently tested with the multivariate model. Conventional or selective TACE was performed for 40 and 111 patients, respectively. Univariate and multivariate analyses revealed that tumor multiplicity, venous tumor thrombosis and selective TACE were the only three independent significant prognostic factors of disease-free survival (p = 0.002, 0.015 and 0.019, respectively). In our study, selective TACE was a favorable prognostic factor for the disease-free survival of patients with HCC who underwent TACE

Better midterm survival in women after transcatheter aortic valve implantation.

Science.gov (United States)

Takagi, Hisato; Umemoto, Takuya

2017-08-01

In previous meta-analyses demonstrating better midterm overall survival in women undergoing transcatheter aortic valve implantation (TAVI), unadjusted risk and odds ratios were combined. To determine whether female gender is independently associated with better survival after TAVI, we performed a meta-analysis pooling adjusted hazard ratios (HRs) based on multivariate Cox proportional hazard regression. MEDLINE and EMBASE were searched through September 2015 using PubMed and OVID. Studies considered for inclusion met the following criteria: the study population was patients undergoing TAVI; and main outcomes included midterm (mean or median ≥6 months) overall survival or all-cause mortality in women and men. An unadjusted and/or adjusted HR of all-cause mortality for women versus men was abstracted from each individual study. Of 1347 potentially relevant articles screened initially, 16 reports of eligible studies were identified and included. A primary meta-analysis of the 9 adjusted HRs demonstrated a significantly better midterm overall survival in women than men (N.=6891; HR=0.80; 95% confidence interval [CI]: 0.65 to 0.97; P=0.03). A secondary meta-analysis adding 5 statistically non-significant unadjusted HR also indicated better survival in women (N.=8645; HR=0.83; 95% CI: 0.72 to 0.96; P=0.01). Although statistical tests for the primary meta-analysis revealed funnel plot asymmetry in favor of women, the secondary meta-analysis produced a symmetrical funnel plot. Female gender may be independently associated with better midterm overall survival after TAVI.

A retrospective analysis of survival and prognostic factors after stereotactic radiosurgery for aggressive meningiomas

International Nuclear Information System (INIS)

Ferraro, Daniel J; Zoberi, Imran; Simpson, Joseph R; Jaboin, Jerry J; Funk, Ryan K; Blackett, John William; Ju, Michelle R; DeWees, Todd A; Chicoine, Michael R; Dowling, Joshua L; Rich, Keith M; Drzymala, Robert E

2014-01-01

While most meningiomas are benign, aggressive meningiomas are associated with high levels of recurrence and mortality. A single institution’s Gamma Knife radiosurgical experience with atypical and malignant meningiomas is presented, stratified by the most recent WHO classification. Thirty-one patients with atypical and 4 patients with malignant meningiomas treated with Gamma Knife radiosurgery between July 2000 and July 2011 were retrospectively reviewed. All patients underwent prior surgical resection. Overall survival was the primary endpoint and rate of disease recurrence in the brain was a secondary endpoint. Patients who had previous radiotherapy or prior surgical resection were included. Kaplan-Meier and Cox proportional hazards models were used to estimate survival and identify factors predictive of recurrence and survival. Post-Gamma Knife recurrence was identified in 11 patients (31.4%) with a median overall survival of 36 months and progression-free survival of 25.8 months. Nine patients (25.7%) had died. Three-year overall survival (OS) and progression-free survival (PFS) rates were 78.0% and 65.0%, respectively. WHO grade II 3-year OS and PFS were 83.4% and 70.1%, while WHO grade III 3-year OS and PFS were 33.3% and 0%. Recurrence rate was significantly higher in patients with a prior history of benign meningioma, nuclear atypia, high mitotic rate, spontaneous necrosis, and WHO grade III diagnosis on univariate analysis; only WHO grade III diagnosis was significant on multivariate analysis. Overall survival was adversely affected in patients with WHO grade III diagnosis, prior history of benign meningioma, prior fractionated radiotherapy, larger tumor volume, and higher isocenter number on univariate analysis; WHO grade III diagnosis and larger treated tumor volume were significant on multivariate analysis. Atypical and anaplastic meningiomas remain difficult tumors to treat. WHO grade III diagnosis and treated tumor volume were significantly

Effect of smoking on survival of patients with hepatocellular carcinoma.

Science.gov (United States)

Kolly, Philippe; Knöpfli, Marina; Dufour, Jean-François

2017-11-01

Lifestyle factors such as smoking, obesity and physical activity have gained interest in the field of hepatocellular carcinoma. These factors play a significant role in the development of hepatocellular carcinoma. Several studies revealed the impact of tobacco consumption on the development of hepatocellular carcinoma and its synergistic effects with viral etiologies (hepatitis B and C). The effects of smoking on survival in patients with a diagnosed hepatocellular carcinoma have not yet been investigated in a Western cohort where hepatitis C infection is a major risk factor. Using data from a prospective cohort of patients with hepatocellular carcinoma who were followed at the University Hospital of Bern, Switzerland, survival was compared by Kaplan-Meier analysis in smokers and nonsmokers, and multivariate Cox regression was applied to control for confounding variables. Of 238 eligible hepatocellular carcinoma patients, 64 were smokers at the time of inclusion and 174 were nonsmokers. Smokers had a significant worse overall survival than nonsmokers (hazard ratio 1.77, 95% confidence interval: 1.22-2.58, P=.003). Analysis of patients according to their underlying liver disease, revealed that smoking, and not nonsmoking, affected survival of hepatitis B virus and C virus-infected patients only. In this subgroup, smoking was an independent predictor for survival (hazard ratio 2.99, 95% confidence interval: 1.7-5.23, Phepatocellular carcinoma. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluating disease management program effectiveness: an introduction to survival analysis.

Science.gov (United States)

Linden, Ariel; Adams, John L; Roberts, Nancy

2004-01-01

Currently, the most widely used method in the disease management industry for evaluating program effectiveness is the "total population approach." This model is a pretest-posttest design, with the most basic limitation being that without a control group, there may be sources of bias and/or competing extraneous confounding factors that offer plausible rationale explaining the change from baseline. Survival analysis allows for the inclusion of data from censored cases, those subjects who either "survived" the program without experiencing the event (e.g., achievement of target clinical levels, hospitalization) or left the program prematurely, due to disenrollement from the health plan or program, or were lost to follow-up. Additionally, independent variables may be included in the model to help explain the variability in the outcome measure. In order to maximize the potential of this statistical method, validity of the model and research design must be assured. This paper reviews survival analysis as an alternative, and more appropriate, approach to evaluating DM program effectiveness than the current total population approach.

Survival Outcomes of Patients Treated with Hypofractionated Stereotactic Body Radiation Therapy for Parotid Gland Tumors: a Retrospective Analysis

International Nuclear Information System (INIS)

Karam, Sana D.; Snider, James W.; Wang, Hongkun; Wooster, Margaux; Lominska, Christopher; Deeken, John; Newkirk, Kenneth; Davidson, Bruce; Harter, K. William

2012-01-01

Background: to review a single-institution experience with the management of parotid malignancies treated by fractionated stereotactic body radiosurgery (SBRT). Findings: Between 2003 and 2011, 13 patients diagnosed with parotid malignancies were treated with adjuvant or definitive SBRT to a median dose of 33 Gy (range 25–40 Gy). There were 11 male and two female patients with a median age of 80. Ten patients declined conventional radiation treatment and three patients had received prior unrelated radiation therapy to neighboring structures with unavailable radiation records. Six patients were treated with definitive intent while seven patients were treated adjuvantly for adverse surgical or pathologic features. Five patients had clinical or pathologic evidence of lymph node disease. Conclusion: at a median follow-up of 14 months only one patient failed locally, and four failed distantly. The actuarial 2-year overall survival, progression-free survival, and local-regional control rates were 46, 84, and 47%, respectively. Statistical analysis revealed surgery as a positive predictor of overall survival while presence of gross disease was a negatively correlated factor (p < 0.05).

Surrogacy of progression-free survival (PFS) for overall survival (OS) in esophageal cancer trials with preoperative therapy: Literature-based meta-analysis.

Science.gov (United States)

Kataoka, K; Nakamura, K; Mizusawa, J; Kato, K; Eba, J; Katayama, H; Shibata, T; Fukuda, H

2017-10-01

There have been no reports evaluating progression-free survival (PFS) as a surrogate endpoint in resectable esophageal cancer. This study was conducted to evaluate the trial level correlations between PFS and overall survival (OS) in resectable esophageal cancer with preoperative therapy and to explore the potential benefit of PFS as a surrogate endpoint for OS. A systematic literature search of randomized trials with preoperative chemotherapy or preoperative chemoradiotherapy for esophageal cancer reported from January 1990 to September 2014 was conducted using PubMed and the Cochrane Library. Weighted linear regression using sample size of each trial as a weight was used to estimate coefficient of determination (R 2 ) within PFS and OS. The primary analysis included trials in which the HR for both PFS and OS was reported. The sensitivity analysis included trials in which either HR or median survival time of PFS and OS was reported. In the sensitivity analysis, HR was estimated from the median survival time of PFS and OS, assuming exponential distribution. Of 614 articles, 10 trials were selected for the primary analysis and 15 for the sensitivity analysis. The primary analysis did not show a correlation between treatment effects on PFS and OS (R 2 0.283, 95% CI [0.00-0.90]). The sensitivity analysis did not show an association between PFS and OS (R 2 0.084, 95% CI [0.00-0.70]). Although the number of randomized controlled trials evaluating preoperative therapy for esophageal cancer is limited at the moment, PFS is not suitable for primary endpoint as a surrogate endpoint for OS. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Survival Prediction in Pancreatic Ductal Adenocarcinoma by Quantitative Computed Tomography Image Analysis.

Science.gov (United States)

Attiyeh, Marc A; Chakraborty, Jayasree; Doussot, Alexandre; Langdon-Embry, Liana; Mainarich, Shiana; Gönen, Mithat; Balachandran, Vinod P; D'Angelica, Michael I; DeMatteo, Ronald P; Jarnagin, William R; Kingham, T Peter; Allen, Peter J; Simpson, Amber L; Do, Richard K

2018-04-01

Pancreatic cancer is a highly lethal cancer with no established a priori markers of survival. Existing nomograms rely mainly on post-resection data and are of limited utility in directing surgical management. This study investigated the use of quantitative computed tomography (CT) features to preoperatively assess survival for pancreatic ductal adenocarcinoma (PDAC) patients. A prospectively maintained database identified consecutive chemotherapy-naive patients with CT angiography and resected PDAC between 2009 and 2012. Variation in CT enhancement patterns was extracted from the tumor region using texture analysis, a quantitative image analysis tool previously described in the literature. Two continuous survival models were constructed, with 70% of the data (training set) using Cox regression, first based only on preoperative serum cancer antigen (CA) 19-9 levels and image features (model A), and then on CA19-9, image features, and the Brennan score (composite pathology score; model B). The remaining 30% of the data (test set) were reserved for independent validation. A total of 161 patients were included in the analysis. Training and test sets contained 113 and 48 patients, respectively. Quantitative image features combined with CA19-9 achieved a c-index of 0.69 [integrated Brier score (IBS) 0.224] on the test data, while combining CA19-9, imaging, and the Brennan score achieved a c-index of 0.74 (IBS 0.200) on the test data. We present two continuous survival prediction models for resected PDAC patients. Quantitative analysis of CT texture features is associated with overall survival. Further work includes applying the model to an external dataset to increase the sample size for training and to determine its applicability.

Survival after radiotherapy in gastric cancer: Systematic review and meta-analysis

International Nuclear Information System (INIS)

Valentini, Vincenzo; Cellini, Francesco; Minsky, Bruce D.; Mattiucci, Gian Carlo; Balducci, Mario; D'Agostino, Giuseppe; D'Angelo, Elisa; Dinapoli, Nicola; Nicolotti, Nicola; Valentini, Chiara; La Torre, Giuseppe

2009-01-01

Background and purpose: A systematic review and meta-analysis was performed to assess the impact of radiotherapy on both 3- and 5-year survival in patients with resectable gastric cancer. Methods: Randomized Clinical Trials (RCTs) in which radiotherapy, (preoperative, postoperative and/or intraoperative), was compared with surgery alone or surgery plus chemotherapy in resectable gastric cancer were identified by searching web-based databases and supplemented by manual examination of reference lists. Meta-analysis was performed using Risk Ratios (RRs). Random or fixed effects models were used to combine data. The methodological quality was evaluated by Chalmers' score. Results: Radiotherapy had a significant impact on 5-year survival. Using an intent to treat (ITT) and a Per Protocol (PP) analysis, the overall 5-year RR was 1.26 (95% CI: 1.08-1.48; NNT = 17) and 1.31 (95% CI: 1.04-1.66; NNT = 13), respectively. Although the quality of the studies was variable, the data were consistent and no clear publication bias was found. Conclusion: This meta-analysis showed a statistically significant 5-year survival benefit with the addition of radiotherapy in patients with resectable gastric cancer. Radiotherapy remains a standard component in the treatment of resectable gastric cancer and new RCTs need to address the impact of new conformal radiotherapy technologies.

A Genetic Screen Reveals that Synthesis of 1,4-Dihydroxy-2-Naphthoate (DHNA), but Not Full-Length Menaquinone, Is Required for Listeria monocytogenes Cytosolic Survival.

Science.gov (United States)

Chen, Grischa Y; McDougal, Courtney E; D'Antonio, Marc A; Portman, Jonathan L; Sauer, John-Demian

2017-03-21

Through unknown mechanisms, the host cytosol restricts bacterial colonization; therefore, only professional cytosolic pathogens are adapted to colonize this host environment. Listeria monocytogenes is a Gram-positive intracellular pathogen that is highly adapted to colonize the cytosol of both phagocytic and nonphagocytic cells. To identify L. monocytogenes determinants of cytosolic survival, we designed and executed a novel screen to isolate L. monocytogenes mutants with cytosolic survival defects. Multiple mutants identified in the screen were defective for synthesis of menaquinone (MK), an essential molecule in the electron transport chain. Analysis of an extensive set of MK biosynthesis and respiratory chain mutants revealed that cellular respiration was not required for cytosolic survival of L. monocytogenes but that, instead, synthesis of 1,4-dihydroxy-2-naphthoate (DHNA), an MK biosynthesis intermediate, was essential. Recent discoveries showed that modulation of the central metabolism of both host and pathogen can influence the outcome of host-pathogen interactions. Our results identify a potentially novel function of the MK biosynthetic intermediate DHNA and specifically highlight how L. monocytogenes metabolic adaptations promote cytosolic survival and evasion of host immunity. IMPORTANCE Cytosolic bacterial pathogens, such as Listeria monocytogenes and Francisella tularensis , are exquisitely evolved to colonize the host cytosol in a variety of cell types. Establishing an intracellular niche shields these pathogens from effectors of humoral immunity, grants access to host nutrients, and is essential for pathogenesis. Through yet-to-be-defined mechanisms, the host cytosol restricts replication of non-cytosol-adapted bacteria, likely through a combination of cell autonomous defenses (CADs) and nutritional immunity. Utilizing a novel genetic screen, we identified determinants of L. monocytogenes cytosolic survival and virulence and identified a role

Bernstein - Von Mises theorem and its application in survival analysis

Czech Academy of Sciences Publication Activity Database

Timková, Jana

2010-01-01

Roč. 22, č. 3 (2010), s. 115-122 ISSN 1210-8022. [16. letní škola JČMF Robust 2010. Králíky, 30.01.2010-05.02.2010] R&D Projects: GA AV ČR(CZ) IAA101120604 Institutional research plan: CEZ:AV0Z10750506 Keywords : Cox model * bayesian asymptotics * survival function Subject RIV: BB - Applied Statistics, Operational Research http://library.utia.cas.cz/separaty/2010/SI/timkova-bernstein - von mises theorem and its application in survival analysis.pdf

Survival Function Analysis of Planet Size Distribution

OpenAIRE

Zeng, Li; Jacobsen, Stein B.; Sasselov, Dimitar D.; Vanderburg, Andrew

2018-01-01

Applying the survival function analysis to the planet radius distribution of the Kepler exoplanet candidates, we have identified two natural divisions of planet radius at 4 Earth radii and 10 Earth radii. These divisions place constraints on planet formation and interior structure model. The division at 4 Earth radii separates small exoplanets from large exoplanets above. When combined with the recently-discovered radius gap at 2 Earth radii, it supports the treatment of planets 2-4 Earth rad...

Survival analysis of heart failure patients: A case study.

Science.gov (United States)

Ahmad, Tanvir; Munir, Assia; Bhatti, Sajjad Haider; Aftab, Muhammad; Raza, Muhammad Ali

2017-01-01

This study was focused on survival analysis of heart failure patients who were admitted to Institute of Cardiology and Allied hospital Faisalabad-Pakistan during April-December (2015). All the patients were aged 40 years or above, having left ventricular systolic dysfunction, belonging to NYHA class III and IV. Cox regression was used to model mortality considering age, ejection fraction, serum creatinine, serum sodium, anemia, platelets, creatinine phosphokinase, blood pressure, gender, diabetes and smoking status as potentially contributing for mortality. Kaplan Meier plot was used to study the general pattern of survival which showed high intensity of mortality in the initial days and then a gradual increase up to the end of study. Martingale residuals were used to assess functional form of variables. Results were validated computing calibration slope and discrimination ability of model via bootstrapping. For graphical prediction of survival probability, a nomogram was constructed. Age, renal dysfunction, blood pressure, ejection fraction and anemia were found as significant risk factors for mortality among heart failure patients.

Application of survival analysis methodology to the quantitative analysis of LC-MS proteomics data

KAUST Repository

Tekwe, C. D.; Carroll, R. J.; Dabney, A. R.

2012-01-01

positive, skewed and often left-censored, we propose using survival methodology to carry out differential expression analysis of proteins. Various standard statistical techniques including non-parametric tests such as the Kolmogorov-Smirnov and Wilcoxon

Effect of perioperative blood transfusion on the long-term survival of patients undergoing esophagectomy for esophageal cancer: a systematic review and meta-analysis.

Science.gov (United States)

Boshier, P R; Ziff, C; Adam, M E; Fehervari, M; Markar, S R; Hanna, G B

2017-12-18

Perioperative blood transfusion has been linked to poorer long-term survival in patients undergoing esophagectomy, presumably due to its potential immunomodulatory effects. This review aims to summarize existing evidence relating to the influence of blood transfusion on long-term survival following esophagectomy for esophageal cancer. A systematic literature search (up to February 2017) was conducted for studies reporting the effects of perioperative blood transfusion on survival following esophagectomy for esophageal cancer. Meta-analysis was used to summate survival outcomes. Twenty observational studies met the criteria for inclusion. Eighteen of these studies compared the outcomes of patients who received allogenic blood transfusion to patients who did not receive this intervention. Meta-analysis of outcomes revealed that allogenic blood transfusion significantly reduced long-term survival (HR = 1.49; 95% CI 1.26 to 1.76; P blood having lower long-term survival compared to patient who received between 0 and 2 units (HR = 1.59; 95% CI 1.31 to 1.93; P blood transfusion showed superior survival in the latter group. Factors associated with the requirement for perioperative blood transfusion included: intraoperative blood loss; preoperative hemoglobin; operative approach; operative time, and; presences of advanced disease. These findings indicate that perioperative blood transfusion is associated with significantly worse long-term survival in patients undergoing esophagectomy for esophageal cancer. Autologous donation of blood, meticulous intraoperative hemostasis, and avoidance of unnecessary transfusions may prevent additional deaths attributed to this intervention. © The Author(s) 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Survival Analysis and its Associated Factors of Beta Thalassemia Major in Hamadan Province

Directory of Open Access Journals (Sweden)

Reza Zamani

2015-05-01

Full Text Available Background: There currently is a lack of knowledge about the long-term survival of patients with beta thalassemia (BT, particularly in regions with low incidence of the disease. The aim of the present study was to determine the survival rate of the patients with BT major and the factors associated with the survival time. Methods: This retrospective cohort study was performed in Hamadan province, located in the west of Iran. The study included patients that referred to the provincial hospitals during 16 year period from 1997 to 2013. The follow up of each subject was calculated from the date of birth to the date of death. Demographic and clinical data were extracted from patients’ medical records using a checklist. Statistical analysis included the Kaplan-Meier method to analyze survivals, log-rank to compare curves between groups, and Cox regression for multivariate prognostic analysis. Results: A total of 133 patients with BT major were enrolled, 54.9% of whom were male and 66.2% were urban. The 10-, 20- and 30-year survival rate for all patients were 98.3%, 88.4% and 80.5%, respectively. Based on hazard ratio (HR, we found that accompanied diseases (P=0.01, blood type (P=0.03 and residency status (P=0.01 were significant predictors for the survival time of patients. Conclusion: The survival rate of BT patients has improved. Future researches such as prospective designs are required for the estimation of survival rate and to find other prognostic factors, which have reliable sources of data.

Trends in Testicular Cancer Survival: A Large Population-based Analysis.

Science.gov (United States)

Sui, Wilson; Morrow, David C; Bermejo, Carlos E; Hellenthal, Nicholas J

2015-06-01

To determine whether discrepancies in testicular cancer outcomes between Caucasians and non-Caucasians are changing over time. Although testicular cancer is more common in Caucasians, studies have shown that other races have worse outcomes. Using the Surveillance, Epidemiology, and End Results registry, we identified 29,803 patients diagnosed with histologically confirmed testicular cancer between 1983 and 2011. Of these, 12,650 patients (42%) had 10-year follow-up data. We stratified the patients by age group, stage, race, and year of diagnosis and assessed 10-year overall and cancer-specific survival in each cohort. Cox proportional hazard models were used to determine the relative contributions of each stratum to cancer-specific survival. Predicted overall 10-year survival of Caucasian patients with testicular cancer increased slightly from 88% to 89% over the period studied, whereas predicted cancer-specific 10-year survival dropped slightly from 94% to 93%. In contrast, non-Caucasian men demonstrated larger changes in 10-year overall (84%-86%) and cancer-specific (88%-91%) survival. On univariate analysis, race was significantly associated with testicular cancer death, with non-Caucasian men being 1.69 times more likely to die of testicular cancer than Caucasians (hazard ratio, 1.33-2.16; 95% confidence interval, testicular cancer. These data show a convergence in cancer-specific survival between racial groups over time, suggesting that diagnostic and treatment discrepancies may be improving for non-Caucasians. Copyright © 2015 Elsevier Inc. All rights reserved.

Outcome predictors in the management of intramedullary classic ependymoma: An integrative survival analysis.

Science.gov (United States)

Wang, Yinqing; Cai, Ranze; Wang, Rui; Wang, Chunhua; Chen, Chunmei

2018-06-01

This is a retrospective study.The aim of this study was to illustrate the survival outcomes of patients with classic ependymoma (CE) and identify potential prognostic factors.CE is the most common category of spinal ependymomas, but few published studies have discussed predictors of the survival outcome.A Boolean search of the PubMed, Embase, and OVID databases was conducted by 2 investigators independently. The objects were intramedullary grade II ependymoma according to 2007 WHO classification. Univariate Kaplan-Meier analysis and Log-Rank tests were performed to identify variables associated with progression-free survival (PFS) or overall survival (OS). Multivariate Cox regression was performed to assess hazard ratios (HRs) with 95% confidence intervals (95% CIs). Statistical analysis was performed by SPSS version 23.0 (IBM Corp.) with statistical significance defined as P analysis showed that patients who had undergone total resection (TR) had better PFS and OS than those with subtotal resection (STR) and biopsy (P = .002, P = .004, respectively). Within either univariate or multivariate analysis (P = .000, P = .07, respectively), histological type was an independent prognostic factor for PFS of CE [papillary type: HR 0.002, 95% CI (0.000-0.073), P = .001, tanycytic type: HR 0.010, 95% CI (0.000-0.218), P = .003].It was the first integrative analysis of CE to elucidate the correlation between kinds of factors and prognostic outcomes. Definite histological type and safely TR were foundation of CE's management. 4.

Orphan caribou, Rangifer tarandus, calves: A re-evaluation of overwinter survival data

Science.gov (United States)

Joly, Kyle

2000-01-01

Low sample size and high variation within populations reduce power of statistical tests. These aspects of statistical power appear to have affected an analysis comparing overwinter survival rates of non-orphan and orphan Caribou (Rangifer tarandus) calves by an earlier study for the Porcupine Caribou Herd. A re-evaluation of the data revealed that conclusions about a lack of significant difference in the overwinter survival rates between orphan and non-orphan calves were premature.

Gene expression profiling of canine osteosarcoma reveals genes associated with short and long survival times

Directory of Open Access Journals (Sweden)

Rao Nagesha AS

2009-09-01

Full Text Available Abstract Background Gene expression profiling of spontaneous tumors in the dog offers a unique translational opportunity to identify prognostic biomarkers and signaling pathways that are common to both canine and human. Osteosarcoma (OS accounts for approximately 80% of all malignant bone tumors in the dog. Canine OS are highly comparable with their human counterpart with respect to histology, high metastatic rate and poor long-term survival. This study investigates the prognostic gene profile among thirty-two primary canine OS using canine specific cDNA microarrays representing 20,313 genes to identify genes and cellular signaling pathways associated with survival. This, the first report of its kind in dogs with OS, also demonstrates the advantages of cross-species comparison with human OS. Results The 32 tumors were classified into two prognostic groups based on survival time (ST. They were defined as short survivors (dogs with poor prognosis: surviving fewer than 6 months and long survivors (dogs with better prognosis: surviving 6 months or longer. Fifty-one transcripts were found to be differentially expressed, with common upregulation of these genes in the short survivors. The overexpressed genes in short survivors are associated with possible roles in proliferation, drug resistance or metastasis. Several deregulated pathways identified in the present study, including Wnt signaling, Integrin signaling and Chemokine/cytokine signaling are comparable to the pathway analysis conducted on human OS gene profiles, emphasizing the value of the dog as an excellent model for humans. Conclusion A molecular-based method for discrimination of outcome for short and long survivors is useful for future prognostic stratification at initial diagnosis, where genes and pathways associated with cell cycle/proliferation, drug resistance and metastasis could be potential targets for diagnosis and therapy. The similarities between human and canine OS makes the

Survival analysis of heart failure patients: A case study.

Directory of Open Access Journals (Sweden)

Tanvir Ahmad

Full Text Available This study was focused on survival analysis of heart failure patients who were admitted to Institute of Cardiology and Allied hospital Faisalabad-Pakistan during April-December (2015. All the patients were aged 40 years or above, having left ventricular systolic dysfunction, belonging to NYHA class III and IV. Cox regression was used to model mortality considering age, ejection fraction, serum creatinine, serum sodium, anemia, platelets, creatinine phosphokinase, blood pressure, gender, diabetes and smoking status as potentially contributing for mortality. Kaplan Meier plot was used to study the general pattern of survival which showed high intensity of mortality in the initial days and then a gradual increase up to the end of study. Martingale residuals were used to assess functional form of variables. Results were validated computing calibration slope and discrimination ability of model via bootstrapping. For graphical prediction of survival probability, a nomogram was constructed. Age, renal dysfunction, blood pressure, ejection fraction and anemia were found as significant risk factors for mortality among heart failure patients.

Marital status independently predicts testis cancer survival--an analysis of the SEER database.

Science.gov (United States)

Abern, Michael R; Dude, Annie M; Coogan, Christopher L

2012-01-01

Previous reports have shown that married men with malignancies have improved 10-year survival over unmarried men. We sought to investigate the effect of marital status on 10-year survival in a U.S. population-based cohort of men with testis cancer. We examined 30,789 cases of testis cancer reported to the Surveillance, Epidemiology, and End Results (SEER 17) database between 1973 and 2005. All staging were converted to the 1997 AJCC TNM system. Patients less than 18 years of age at time of diagnosis were excluded. A subgroup analysis of patients with stages I or II non-seminomatous germ cell tumors (NSGCT) was performed. Univariate analysis using t-tests and χ(2) tests compared characteristics of patients separated by marital status. Multivariate analysis was performed using a Cox proportional hazard model to generate Kaplan-Meier survival curves, with all-cause and cancer-specific mortality as the primary endpoints. 20,245 cases met the inclusion criteria. Married men were more likely to be older (38.9 vs. 31.4 years), Caucasian (94.4% vs. 92.1%), stage I (73.1% vs. 61.4%), and have seminoma as the tumor histology (57.3% vs. 43.4%). On multivariate analysis, married status (HR 0.58, P married status (HR 0.60, P married and unmarried men (44.8% vs. 43.4%, P = 0.33). Marital status is an independent predictor of improved overall and cancer-specific survival in men with testis cancer. In men with stages I or II NSGCT, RPLND is an additional predictor of improved overall survival. Marital status does not appear to influence whether men undergo RPLND. Copyright © 2012 Elsevier Inc. All rights reserved.

Volumetric and MGMT parameters in glioblastoma patients: Survival analysis

International Nuclear Information System (INIS)

Iliadis, Georgios; Kotoula, Vassiliki; Chatzisotiriou, Athanasios; Televantou, Despina; Eleftheraki, Anastasia G; Lambaki, Sofia; Misailidou, Despina; Selviaridis, Panagiotis; Fountzilas, George

2012-01-01

In this study several tumor-related volumes were assessed by means of a computer-based application and a survival analysis was conducted to evaluate the prognostic significance of pre- and postoperative volumetric data in patients harboring glioblastomas. In addition, MGMT (O 6 -methylguanine methyltransferase) related parameters were compared with those of volumetry in order to observe possible relevance of this molecule in tumor development. We prospectively analyzed 65 patients suffering from glioblastoma (GBM) who underwent radiotherapy with concomitant adjuvant temozolomide. For the purpose of volumetry T1 and T2-weighted magnetic resonance (MR) sequences were used, acquired both pre- and postoperatively (pre-radiochemotherapy). The volumes measured on preoperative MR images were necrosis, enhancing tumor and edema (including the tumor) and on postoperative ones, net-enhancing tumor. Age, sex, performance status (PS) and type of operation were also included in the multivariate analysis. MGMT was assessed for promoter methylation with Multiplex Ligation-dependent Probe Amplification (MLPA), for RNA expression with real time PCR, and for protein expression with immunohistochemistry in a total of 44 cases with available histologic material. In the multivariate analysis a negative impact was shown for pre-radiochemotherapy net-enhancing tumor on the overall survival (OS) (p = 0.023) and for preoperative necrosis on progression-free survival (PFS) (p = 0.030). Furthermore, the multivariate analysis confirmed the importance of PS in PFS and OS of patients. MGMT promoter methylation was observed in 13/23 (43.5%) evaluable tumors; complete methylation was observed in 3/13 methylated tumors only. High rate of MGMT protein positivity (> 20% positive neoplastic nuclei) was inversely associated with pre-operative tumor necrosis (p = 0.021). Our findings implicate that volumetric parameters may have a significant role in the prognosis of GBM patients. Furthermore

OASIS 2: online application for survival analysis 2 with features for the analysis of maximal lifespan and healthspan in aging research.

Science.gov (United States)

Han, Seong Kyu; Lee, Dongyeop; Lee, Heetak; Kim, Donghyo; Son, Heehwa G; Yang, Jae-Seong; Lee, Seung-Jae V; Kim, Sanguk

2016-08-30

Online application for survival analysis (OASIS) has served as a popular and convenient platform for the statistical analysis of various survival data, particularly in the field of aging research. With the recent advances in the fields of aging research that deal with complex survival data, we noticed a need for updates to the current version of OASIS. Here, we report OASIS 2 (http://sbi.postech.ac.kr/oasis2), which provides extended statistical tools for survival data and an enhanced user interface. In particular, OASIS 2 enables the statistical comparison of maximal lifespans, which is potentially useful for determining key factors that limit the lifespan of a population. Furthermore, OASIS 2 provides statistical and graphical tools that compare values in different conditions and times. That feature is useful for comparing age-associated changes in physiological activities, which can be used as indicators of "healthspan." We believe that OASIS 2 will serve as a standard platform for survival analysis with advanced and user-friendly statistical tools for experimental biologists in the field of aging research.

Parametric and semiparametric models with applications to reliability, survival analysis, and quality of life

CERN Document Server

Nikulin, M; Mesbah, M; Limnios, N

2004-01-01

Parametric and semiparametric models are tools with a wide range of applications to reliability, survival analysis, and quality of life. This self-contained volume examines these tools in survey articles written by experts currently working on the development and evaluation of models and methods. While a number of chapters deal with general theory, several explore more specific connections and recent results in "real-world" reliability theory, survival analysis, and related fields.

Modelling lecturer performance index of private university in Tulungagung by using survival analysis with multivariate adaptive regression spline

Science.gov (United States)

Hasyim, M.; Prastyo, D. D.

2018-03-01

Survival analysis performs relationship between independent variables and survival time as dependent variable. In fact, not all survival data can be recorded completely by any reasons. In such situation, the data is called censored data. Moreover, several model for survival analysis requires assumptions. One of the approaches in survival analysis is nonparametric that gives more relax assumption. In this research, the nonparametric approach that is employed is Multivariate Regression Adaptive Spline (MARS). This study is aimed to measure the performance of private university’s lecturer. The survival time in this study is duration needed by lecturer to obtain their professional certificate. The results show that research activities is a significant factor along with developing courses material, good publication in international or national journal, and activities in research collaboration.

Mechanisms and mediation in survival analysis: towards an integrated analytical framework

Directory of Open Access Journals (Sweden)

Jonathan Pratschke

2016-02-01

Full Text Available Abstract Background A wide-ranging debate has taken place in recent years on mediation analysis and causal modelling, raising profound theoretical, philosophical and methodological questions. The authors build on the results of these discussions to work towards an integrated approach to the analysis of research questions that situate survival outcomes in relation to complex causal pathways with multiple mediators. The background to this contribution is the increasingly urgent need for policy-relevant research on the nature of inequalities in health and healthcare. Methods The authors begin by summarising debates on causal inference, mediated effects and statistical models, showing that these three strands of research have powerful synergies. They review a range of approaches which seek to extend existing survival models to obtain valid estimates of mediation effects. They then argue for an alternative strategy, which involves integrating survival outcomes within Structural Equation Models via the discrete-time survival model. This approach can provide an integrated framework for studying mediation effects in relation to survival outcomes, an issue of great relevance in applied health research. The authors provide an example of how these techniques can be used to explore whether the social class position of patients has a significant indirect effect on the hazard of death from colon cancer. Results The results suggest that the indirect effects of social class on survival are substantial and negative (-0.23 overall. In addition to the substantial direct effect of this variable (-0.60, its indirect effects account for more than one quarter of the total effect. The two main pathways for this indirect effect, via emergency admission (-0.12, on the one hand, and hospital caseload, on the other, (-0.10 are of similar size. Conclusions The discrete-time survival model provides an attractive way of integrating time-to-event data within the field of

Mechanisms and mediation in survival analysis: towards an integrated analytical framework.

Science.gov (United States)

Pratschke, Jonathan; Haase, Trutz; Comber, Harry; Sharp, Linda; de Camargo Cancela, Marianna; Johnson, Howard

2016-02-29

A wide-ranging debate has taken place in recent years on mediation analysis and causal modelling, raising profound theoretical, philosophical and methodological questions. The authors build on the results of these discussions to work towards an integrated approach to the analysis of research questions that situate survival outcomes in relation to complex causal pathways with multiple mediators. The background to this contribution is the increasingly urgent need for policy-relevant research on the nature of inequalities in health and healthcare. The authors begin by summarising debates on causal inference, mediated effects and statistical models, showing that these three strands of research have powerful synergies. They review a range of approaches which seek to extend existing survival models to obtain valid estimates of mediation effects. They then argue for an alternative strategy, which involves integrating survival outcomes within Structural Equation Models via the discrete-time survival model. This approach can provide an integrated framework for studying mediation effects in relation to survival outcomes, an issue of great relevance in applied health research. The authors provide an example of how these techniques can be used to explore whether the social class position of patients has a significant indirect effect on the hazard of death from colon cancer. The results suggest that the indirect effects of social class on survival are substantial and negative (-0.23 overall). In addition to the substantial direct effect of this variable (-0.60), its indirect effects account for more than one quarter of the total effect. The two main pathways for this indirect effect, via emergency admission (-0.12), on the one hand, and hospital caseload, on the other, (-0.10) are of similar size. The discrete-time survival model provides an attractive way of integrating time-to-event data within the field of Structural Equation Modelling. The authors demonstrate the efficacy

Global Activities and Plant Survival

DEFF Research Database (Denmark)

Bandick, Roger

2014-01-01

the highest exit rates. Moreover, the exit rates of globally engaged plants seem to be unaffected by increased foreign presence, whereas there appears to be a negative impact on the survival rates of non-exporting non-MNE plants. Finally, the result reveals that the survival ratio of plants of acquired...

Meta-Analysis of Microarray Data Identifies GAS6 Expression as an Independent Predictor of Poor Survival in Ovarian Cancer

Directory of Open Access Journals (Sweden)

Michelle Buehler

2013-01-01

Full Text Available Seeking new biomarkers for epithelial ovarian cancer, the fifth most common cause of death from all cancers in women and the leading cause of death from gynaecological malignancies, we performed a meta-analysis of three independent studies and compared the results in regard to clinicopathological parameters. This analysis revealed that GAS6 was highly expressed in ovarian cancer and therefore was selected as our candidate of choice. GAS6 encodes a secreted protein involved in physiological processes including cell proliferation, chemotaxis, and cell survival. We performed immunohistochemistry on various ovarian cancer tissues and found that GAS6 expression was elevated in tumour tissue samples compared to healthy control samples (. In addition, GAS6 expression was also higher in tumours from patients with residual disease compared to those without. Our data propose GAS6 as an independent predictor of poor survival, suggesting GAS6, both on the mRNA and on the protein level, as a potential biomarker for ovarian cancer. In clinical practice, the staining of a tumour biopsy for GAS6 may be useful to assess cancer prognosis and/or to monitor disease progression.

Using Survival Analysis to Understand Patterns of Sustainment within a System-Driven Implementation of Multiple Evidence-Based Practices for Children’s Mental Health Services

Directory of Open Access Journals (Sweden)

Lauren Brookman-Frazee

2018-03-01

Full Text Available Evidence-based practice (EBP implementation requires substantial resources in workforce training; yet, failure to achieve long-term sustainment can result in poor return on investment. There is limited research on EBP sustainment in mental health services long after implementation. This study examined therapists’ continued vs. discontinued practice delivery based on administrative claims for reimbursement for six EBPs [Cognitive Behavioral Interventions for Trauma in Schools (CBITS, Child–Parent Psychotherapy, Managing and Adapting Practices (MAP, Seeking Safety (SS, Trauma-Focused Cognitive Behavior Therapy (TF-CBT, and Positive Parenting Program] adopted in a system-driven implementation effort in public mental health services for children. Our goal was to identify agency and therapist factors associated with a sustained EBP delivery. Survival analysis (i.e., Kaplan–Meier survival functions, log-rank tests, and Cox regressions was used to analyze 19 fiscal quarters (i.e., approximately 57 months of claims data from the Prevention and Early Intervention Transformation within the Los Angeles County Department of Mental Health. These data comprised 2,322,389 claims made by 6,873 therapists across 88 agencies. Survival time was represented by the time elapsed from therapists’ first to final claims for each practice and for any of the six EBPs. Results indicate that therapists continued to deliver at least one EBP for a mean survival time of 21.73 months (median = 18.70. When compared to a survival curve of the five other EBPs, CBITS, SS, and TP demonstrated a higher risk of delivery discontinuation, whereas MAP and TF-CBT demonstrated a lower risk of delivery discontinuation. A multivariate Cox regression model revealed that agency (centralization and service setting and therapist (demographics, discipline, and case-mix characteristics characteristics were significantly associated with risk of delivery discontinuation for any of

Human papilloma virus and survival of oropharyngeal cancer patients treated with surgery and adjuvant radiotherapy.

Science.gov (United States)

Broglie, Martina A; Soltermann, Alex; Haile, Sarah R; Huber, Gerhard F; Stoeckli, Sandro J

2015-07-01

Impact of p16 protein, a surrogate marker for human papilloma virus induced cancer, p53 and EGFR as well as clinical factors on survival in a patient cohort with oropharyngeal squamous cell carcinoma (OPSCC) treated by surgical resection and adjuvant radiotherapy (RT) ± concomitant chemotherapy (CT). This is a retrospective analysis of patient's charts and tumor tissue. 57 patients were consecutively included and their tumor tissue assembled on a tissue microarray following immunohistochemical analysis. Survival times were estimated by means of Kaplan-Meier analysis. The importance of clinical and immunohistochemical factors for outcome was estimated by cox proportional hazard models. With 88% 5-year overall survival, 91% 5-year disease-specific survival and 91% 5-year disease-free survival, respectively, we found excellent survival rates in this surgically treated patient cohort of mainly advanced OPSCC (93% AJCC stage III or IV). The only factors positively influencing survival were p16 overexpression as well as p53 negativity and even more pronounced the combination of those biomarkers. Survival analysis of patients classified into three risk categories according to an algorithm based on p16, smoking, T- and N-category revealed a low, intermediate and high-risk group with significant survival differences between the low and the high-risk group. Patients with OPSCC can be successfully treated by surgery and adjuvant RT ± CT with a clear survival benefit of p16 positive, p53 negative patients. We recommend considering a combination of immunohistochemical (p16, p53) and clinical factors (smoking, T- and N-category) for risk stratification.

Survival and prognostic factors in non-small cell lung cancer patients with spinal bone metastases. A retrospective analysis of 303 patients

Energy Technology Data Exchange (ETDEWEB)

Rief, H.; Welzel, T.; Rieken, S.; Bischof, M.; Lindel, K.; Combs, S.E.; Debus, J. [University Hospital of Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); Muley, T. [University Hospital of Heidelberg, Thorax Clinic, Department of Thoracic Oncology, Heidelberg (Germany); Bruckner, T. [University Hospital of Heidelberg, Department of Medical Biometry, Heidelberg (Germany)

2014-01-15

For palliative care of spinal bone metastases, stability assessment is of crucial importance. Pathological fractures, instability-related patient immobility and the extent of bone metastasis have been reported to affect patient outcome and these parameters have therefore been used for treatment stratification. We report on stability-dependent fracture and survival rates in over 300 non-small cell lung cancer (NSCLC) patients. Data from 303 patients with 868 osteolytic metastases treated with radiotherapy (RT) between 2000 and 2012 were evaluated retrospectively. In NSCLC patients with bone metastases only, the retrospective 6- and 12-month overall survival (OS) rates were 76.7 and 47.2%, respectively. In patients with additional non-bone distant metastases, these values were 60.0 and 34.0%, respectively. Survival rates were significantly lower in patients with multiple bone metastases and in those suffering pathological fractures (p=0.017). No significant impact of histological type, location of spinal lesions or treatment regime was detected. Furthermore, stability assessment revealed no influence of vertebral column stability on patient outcome (p=0.739). Our analysis demonstrated a correlation between the pathological fractures of bone lesions, the number of bone metastases, additional distant metastases and survival. The results offer a rationale for future prospective investigations. (orig.)

Prognostic implications of serial risk score assessments in patients with pulmonary arterial hypertension: a Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) analysis.

Science.gov (United States)

Benza, Raymond L; Miller, Dave P; Foreman, Aimee J; Frost, Adaani E; Badesch, David B; Benton, Wade W; McGoon, Michael D

2015-03-01

Data from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) were used previously to develop a risk score calculator to predict 1-year survival. We evaluated prognostic implications of changes in the risk score and individual risk-score parameters over 12 months. Patients were grouped by decreased, unchanged, or increased risk score from enrollment to 12 months. Kaplan-Meier estimates of subsequent 1-year survival were made based on change in the risk score during the initial 12 months of follow-up. Cox regression was used for multivariable analysis. Of 2,529 patients in the analysis cohort, the risk score was decreased in 800, unchanged in 959, and increased in 770 at 12 months post-enrollment. Six parameters (functional class, systolic blood pressure, heart rate, 6-minute walk distance, brain natriuretic peptide levels, and pericardial effusion) each changed sufficiently over time to improve or worsen risk scores in ≥5% of patients. One-year survival estimates in the subsequent year were 93.7%, 90.3%, and 84.6% in patients with a decreased, unchanged, and increased risk score at 12 months, respectively. Change in risk score significantly predicted future survival, adjusting for risk at enrollment. Considering follow-up risk concurrently with risk at enrollment, follow-up risk was a much stronger predictor, although risk at enrollment maintained a significant effect on future survival. Changes in REVEAL risk scores occur in most patients with pulmonary arterial hypertension over a 12-month period and are predictive of survival. Thus, serial risk score assessments can identify changes in disease trajectory that may warrant treatment modifications. Copyright © 2015 International Society for Heart and Lung Transplantation. All rights reserved.

Dopamine neurons implanted into people with Parkinson's disease survive without pathology for 14 years

DEFF Research Database (Denmark)

Mendez, Ivar; Viñuela, Angel; Astradsson, Arnar

2008-01-01

Postmortem analysis of five subjects with Parkinson's disease 9-14 years after transplantation of fetal midbrain cell suspensions revealed surviving grafts that included dopamine and serotonin neurons without pathology. These findings are important for the understanding of the etiopathogenesis...

Contrasting patterns of survival and dispersal in multiple habitats reveal an ecological trap in a food-caching bird.

Science.gov (United States)

Norris, D Ryan; Flockhart, D T Tyler; Strickland, Dan

2013-11-01

A comprehensive understanding of how natural and anthropogenic variation in habitat influences populations requires long-term information on how such variation affects survival and dispersal throughout the annual cycle. Gray jays Perisoreus canadensis are widespread boreal resident passerines that use cached food to survive over the winter and to begin breeding during the late winter. Using multistate capture-recapture analysis, we examined apparent survival and dispersal in relation to habitat quality in a gray jay population over 34 years (1977-2010). Prior evidence suggests that natural variation in habitat quality is driven by the proportion of conifers on territories because of their superior ability to preserve cached food. Although neither adults (>1 year) nor juveniles (conifer territories, both age classes were less likely to leave high-conifer territories and, when they did move, were more likely to disperse to high-conifer territories. In contrast, survival rates were lower on territories that were adjacent to a major highway compared to territories that did not border the highway but there was no evidence for directional dispersal towards or away from highway territories. Our results support the notion that natural variation in habitat quality is driven by the proportion of coniferous trees on territories and provide the first evidence that high-mortality highway habitats can act as an equal-preference ecological trap for birds. Reproductive success, as shown in a previous study, but not survival, is sensitive to natural variation in habitat quality, suggesting that gray jays, despite living in harsh winter conditions, likely favor the allocation of limited resources towards self-maintenance over reproduction.

Nonparametric Bayesian inference for mean residual life functions in survival analysis.

Science.gov (United States)

Poynor, Valerie; Kottas, Athanasios

2018-01-19

Modeling and inference for survival analysis problems typically revolves around different functions related to the survival distribution. Here, we focus on the mean residual life (MRL) function, which provides the expected remaining lifetime given that a subject has survived (i.e. is event-free) up to a particular time. This function is of direct interest in reliability, medical, and actuarial fields. In addition to its practical interpretation, the MRL function characterizes the survival distribution. We develop general Bayesian nonparametric inference for MRL functions built from a Dirichlet process mixture model for the associated survival distribution. The resulting model for the MRL function admits a representation as a mixture of the kernel MRL functions with time-dependent mixture weights. This model structure allows for a wide range of shapes for the MRL function. Particular emphasis is placed on the selection of the mixture kernel, taken to be a gamma distribution, to obtain desirable properties for the MRL function arising from the mixture model. The inference method is illustrated with a data set of two experimental groups and a data set involving right censoring. The supplementary material available at Biostatistics online provides further results on empirical performance of the model, using simulated data examples. © The Author 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Survival analysis of patients with uveal melanoma after organ preserving and liquidation treatment

Directory of Open Access Journals (Sweden)

E. E. Grishina

2018-01-01

Full Text Available Rationale: Uveal melanoma is the most common primary malignancy of the eye.Aim: To evaluate survival in patients with uveal melanoma stratified according to the type of treatment and to identify factors significantly associated with their survival.Materials and methods: The study was performed on the data extracted from medical files and follow-up forms of patients with uveal melanoma seen in the Ophthalmological Clinical Hospital of the Department of Healthcare, Moscow, from 1977 to 2012. Analysis of survival was used to assess the life longevity of patients with uveal melanoma. The analysis was censored at January 2013, when vital status (dead or alive of all patients was assessed. The factors included into the study analysis, were those taken from the follow-up forms. The incidence of uveal melanoma in Moscow (2012 was 0.9 per 100,000 of the population, whereas its prevalence was 11.1 per 100,000.Results: 698 patients with uveal melanoma were included into the study, among them 260 (37% men (aged from 19 to 87 years, median age 60 years and 438 (63% women (aged from 18 to 93 years, median age 63 years; therefore, the proportion of women under the follow-up monitoring was by 26% higher than that of men. The liquidation treatment (mostly enucleation was performed in 358 (51% of the patients, whereas the organ preserving treatment in 340 (49%. At 5, 7, and 10 years of the follow-up, the disease-specific survival of patients with uveal melanoma after the organ preserving treatment (median survival has not been reached and after the liquidation treatment (median, 88 months were 89 ± 2, 83 ± 3, and 75 ± 4% versus 63 ± 3, 52 ± 4, and 47 ± 5%, respectively (р = 0.001. Overall survival and disease-specific survival of the patients after the liquidation treatment were significantly lower than in the patients after the organ-preserving treatment. According to multiple regression analysis, this was associated not with the type of

Analysis of single nucleotide variants of HFE gene and association to survival in The Cancer Genome Atlas GBM data.

Science.gov (United States)

Lee, Sang Y; Zhu, Junjia; Salzberg, Anna C; Zhang, Bo; Liu, Dajiang J; Muscat, Joshua E; Langan, Sara T; Connor, James R

2017-01-01

Human hemochromatosis protein (HFE) is involved in iron metabolism. Two major HFE polymorphisms, H63D and C282Y, have been associated with an increased risk of cancers. Previously, we reported decreased gender effects in overall survival based on H63D or C282Y HFE polymorphisms patients with glioblastoma multiforme (GBM). However, the effect of other single nucleotide variation (SNV) in the HFE gene on the cancer development and progression has not been systematically studied. To expand our finding in a larger sample, and to identify other HFE SNV, we analyzed the frequency of somatic SNV in HFE gene and its relationship to survival in GBM patients using The Cancer Genome Atlas (TCGA) GBM (Caucasian only) database. We found 9 SNVs with increased frequency in blood normal of TCGA GBM patients compared to the 1000Genome. Among 9 SNVs, 7 SNVs were located in the intron and 2 SNVs (i.e., H63D, C282Y) in the exon of HFE gene. The statistical analysis demonstrated that blood normal samples of TCGA GBM have more H63D (p = 0.0002, 95% Confidence interval (CI): 0.2119-0.3223) or C282Y (p = 0.0129, 95% CI: 0.0474-0.1159) HFE polymorphisms than 1000Genome. The Kaplan-Meier survival curve for the 264 GBM samples revealed no difference between wild type (WT) HFE and H63D, and WT HFE and C282Y GBM patients. In addition, there was no difference in the survival of male/female GBM patients based on HFE genotype. There was no correlation between HFE expression and survival. In conclusion, the current results suggest that somatic HFE polymorphisms do not impact GBM patients' survival in the TCGA data set of GBM.

Analysis of single nucleotide variants of HFE gene and association to survival in The Cancer Genome Atlas GBM data.

Directory of Open Access Journals (Sweden)

Sang Y Lee

Full Text Available Human hemochromatosis protein (HFE is involved in iron metabolism. Two major HFE polymorphisms, H63D and C282Y, have been associated with an increased risk of cancers. Previously, we reported decreased gender effects in overall survival based on H63D or C282Y HFE polymorphisms patients with glioblastoma multiforme (GBM. However, the effect of other single nucleotide variation (SNV in the HFE gene on the cancer development and progression has not been systematically studied. To expand our finding in a larger sample, and to identify other HFE SNV, we analyzed the frequency of somatic SNV in HFE gene and its relationship to survival in GBM patients using The Cancer Genome Atlas (TCGA GBM (Caucasian only database. We found 9 SNVs with increased frequency in blood normal of TCGA GBM patients compared to the 1000Genome. Among 9 SNVs, 7 SNVs were located in the intron and 2 SNVs (i.e., H63D, C282Y in the exon of HFE gene. The statistical analysis demonstrated that blood normal samples of TCGA GBM have more H63D (p = 0.0002, 95% Confidence interval (CI: 0.2119-0.3223 or C282Y (p = 0.0129, 95% CI: 0.0474-0.1159 HFE polymorphisms than 1000Genome. The Kaplan-Meier survival curve for the 264 GBM samples revealed no difference between wild type (WT HFE and H63D, and WT HFE and C282Y GBM patients. In addition, there was no difference in the survival of male/female GBM patients based on HFE genotype. There was no correlation between HFE expression and survival. In conclusion, the current results suggest that somatic HFE polymorphisms do not impact GBM patients' survival in the TCGA data set of GBM.

Fissure sealants in caries prevention:a practice-based study using survival analysis

OpenAIRE

Leskinen, K. (Kaja)

2010-01-01

Abstract The purpose of this study was to analyse the effectiveness and cost of fissure sealant treatment in preventing dental caries in children in a practice-based research network using survival analysis. The survival times of first permanent molars in children were analysed in three countries: in Finland (age cohorts 1970–1972 and 1980–1982), in Sweden (1980–1982) and in Greece (1980–1982), and additionally at two municipal health centres in Finland (age cohorts 1988–1990 in Kemi...

Emotional pain: surviving mental health problems related to childhood experiences.

Science.gov (United States)

Holm, A L; Bégat, I; Severinsson, E

2009-09-01

Emotional pain is described as intense by women who suffer from borderline personality disorder (BPD), and a high prevalence of reported childhood abuse was found in the literature and in research. The aim of this study was to explore the experiences of women suffering from BPD with focus on emotional pain related to childhood. An explorative design was used. Data were collected from in-depth interviews consisting of women suffering from BPD (n = 13) and an interpretive content analysis was used to analyse the text. The findings revealed two main themes: 'Power' and 'Assessment of vulnerability'. The main theme 'Power' resulted in two categories: 'Surviving the feeling of being forced' and 'Surviving the feeling of having to assume responsibility'. The other main theme 'Assessment of vulnerability' had two categories: 'Surviving the feeling of being victimized' and 'Surviving the feeling of not being loved'. The findings suggest that nursing care need to develop an understanding of how these women endure their emotional pain, and try to survive as fighting spirits and how struggling became their way of life.

Survival outcomes for oligometastasis in resected non-small cell lung cancer.

Science.gov (United States)

Shimada, Yoshihisa; Saji, Hisashi; Kakihana, Masatoshi; Kajiwara, Naohiro; Ohira, Tatsuo; Ikeda, Norihiko

2015-10-01

We investigated the factors associated with post-recurrence survival and the treatment for non-small-cell lung cancer patients with postoperative distant recurrence, especially oligometastasis. We reviewed the data of 272 patients with distant recurrence who underwent resection of non-small-cell lung cancer from January 2000 through December 2011. The type of distant recurrence was classified as oligometastasis (n = 76, 28%) or polymetastasis (n = 196, 72%). Forty-seven (62%) patients with oligometastasis received local therapy (surgery 5, radiotherapy 9, sequential local and systemic therapy 28, chemoradiotherapy 5). Multivariate analysis revealed older age, non-adenocarcinoma, shorter disease-free interval, no pulmonary metastasis, liver metastases, bone metastases, and polymetastasis had significant associations with unfavorable post-recurrence survival. Subgroup analysis of patients with oligometastasis showed histology and disease-free interval had a great impact on survival. Smoking history and histology were associated with survival in patients with lung oligometastasis, whereas systemic treatment and longer disease-free interval were related to increased post-recurrence survival in those with brain oligometastasis. This study showed that an oligometastatic state per se was a significant favorable factor. Optimization of personalized systemic treatment and adding local treatment are important in the management of patients with non-small-cell lung cancer and oligometastasis. © The Author(s) 2015.

Potential microRNA-mediated oncogenic intercellular communication revealed by pan-cancer analysis

Science.gov (United States)

Li, Yue; Zhang, Zhaolei

2014-11-01

Carcinogenesis consists of oncogenesis and metastasis, and intriguingly microRNAs (miRNAs) are involved in both processes. Although aberrant miRNA activities are prevalent in diverse tumor types, the exact mechanisms for how they regulate cancerous processes are not always clear. To this end, we performed a large-scale pan-cancer analysis via a novel probabilistic approach to infer recurrent miRNA-target interactions implicated in 12 cancer types using data from The Cancer Genome Atlas. We discovered ~20,000 recurrent miRNA regulations, which are enriched for cancer-related miRNAs/genes. Notably, miRNA 200 family (miR-200/141/429) is among the most prominent miRNA regulators, which is known to be involved in metastasis. Importantly, the recurrent miRNA regulatory network is not only enriched for cancer pathways but also for extracellular matrix (ECM) organization and ECM-receptor interactions. The results suggest an intriguing cancer mechanism involving miRNA-mediated cell-to-cell communication, which possibly involves delivery of tumorigenic miRNA messengers to adjacent cells via exosomes. Finally, survival analysis revealed 414 recurrent-prognostic associations, where both gene and miRNA involved in each interaction conferred significant prognostic power in one or more cancer types. Together, our comprehensive pan-cancer analysis provided not only biological insights into metastasis but also brought to bear the clinical relevance of the proposed recurrent miRNA-gene associations.

Impact of anastomotic leak on recurrence and survival after colorectal cancer surgery: a BioGrid Australia analysis.

Science.gov (United States)

Sammour, Tarik; Hayes, Ian P; Jones, Ian T; Steel, Malcolm C; Faragher, Ian; Gibbs, Peter

2018-01-01

There is conflicting evidence regarding the oncological impact of anastomotic leak following colorectal cancer surgery. This study aims to test the hypothesis that anastomotic leak is independently associated with local recurrence and overall and cancer-specific survival. Analysis of prospectively collected data from multiple centres in Victoria between 1988 and 2015 including all patients who underwent colon or rectal resection for cancer with anastomosis was presented. Overall and cancer-specific survival rates and rates of local recurrence were compared using Cox regression analysis. A total of 4892 patients were included, of which 2856 had completed 5-year follow-up. The overall anastomotic leak rate was 4.0%. Cox regression analysis accounting for differences in age, sex, body mass index, American Society of Anesthesiologists score and tumour stage demonstrated that anastomotic leak was associated with significantly worse 5-year overall survival (χ 2 = 6.459, P = 0.011) for colon cancer, but only if early deaths were included. There was no difference in 5-year colon cancer-specific survival (χ 2 = 0.582, P = 0.446) or local recurrence (χ 2 = 0.735, P = 0.391). For rectal cancer, there was no difference in 5-year overall survival (χ 2 = 0.266, P = 0.606), cancer-specific survival (χ 2 = 0.008, P = 0.928) or local recurrence (χ 2 = 2.192, P = 0.139). Anastomotic leak may reduce 5-year overall survival in colon cancer patients but does not appear to influence the 5-year overall survival in rectal cancer patients. There was no effect on local recurrence or cancer-specific survival. © 2016 Royal Australasian College of Surgeons.

Gene expression profiling, pathway analysis and subtype classification reveal molecular heterogeneity in hepatocellular carcinoma and suggest subtype specific therapeutic targets.

Science.gov (United States)

Agarwal, Rahul; Narayan, Jitendra; Bhattacharyya, Amitava; Saraswat, Mayank; Tomar, Anil Kumar

2017-10-01

A very low 5-year survival rate among hepatocellular carcinoma (HCC) patients is mainly due to lack of early stage diagnosis, distant metastasis and high risk of postoperative recurrence. Hence ascertaining novel biomarkers for early diagnosis and patient specific therapeutics is crucial and urgent. Here, we have performed a comprehensive analysis of the expression data of 423 HCC patients (373 tumors and 50 controls) downloaded from The Cancer Genome Atlas (TCGA) followed by pathway enrichment by gene ontology annotations, subtype classification and overall survival analysis. The differential gene expression analysis using non-parametric Wilcoxon test revealed a total of 479 up-regulated and 91 down-regulated genes in HCC compared to controls. The list of top differentially expressed genes mainly consists of tumor/cancer associated genes, such as AFP, THBS4, LCN2, GPC3, NUF2, etc. The genes over-expressed in HCC were mainly associated with cell cycle pathways. In total, 59 kinases associated genes were found over-expressed in HCC, including TTK, MELK, BUB1, NEK2, BUB1B, AURKB, PLK1, CDK1, PKMYT1, PBK, etc. Overall four distinct HCC subtypes were predicted using consensus clustering method. Each subtype was unique in terms of gene expression, pathway enrichment and median survival. Conclusively, this study has exposed a number of interesting genes which can be exploited in future as potential markers of HCC, diagnostic as well as prognostic and subtype classification may guide for improved and specific therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Integrative analysis of survival-associated gene sets in breast cancer.

Science.gov (United States)

Varn, Frederick S; Ung, Matthew H; Lou, Shao Ke; Cheng, Chao

2015-03-12

Patient gene expression information has recently become a clinical feature used to evaluate breast cancer prognosis. The emergence of prognostic gene sets that take advantage of these data has led to a rich library of information that can be used to characterize the molecular nature of a patient's cancer. Identifying robust gene sets that are consistently predictive of a patient's clinical outcome has become one of the main challenges in the field. We inputted our previously established BASE algorithm with patient gene expression data and gene sets from MSigDB to develop the gene set activity score (GSAS), a metric that quantitatively assesses a gene set's activity level in a given patient. We utilized this metric, along with patient time-to-event data, to perform survival analyses to identify the gene sets that were significantly correlated with patient survival. We then performed cross-dataset analyses to identify robust prognostic gene sets and to classify patients by metastasis status. Additionally, we created a gene set network based on component gene overlap to explore the relationship between gene sets derived from MSigDB. We developed a novel gene set based on this network's topology and applied the GSAS metric to characterize its role in patient survival. Using the GSAS metric, we identified 120 gene sets that were significantly associated with patient survival in all datasets tested. The gene overlap network analysis yielded a novel gene set enriched in genes shared by the robustly predictive gene sets. This gene set was highly correlated to patient survival when used alone. Most interestingly, removal of the genes in this gene set from the gene pool on MSigDB resulted in a large reduction in the number of predictive gene sets, suggesting a prominent role for these genes in breast cancer progression. The GSAS metric provided a useful medium by which we systematically investigated how gene sets from MSigDB relate to breast cancer patient survival. We used

Survival analysis and classification methods for forest fire size.

Science.gov (United States)

Tremblay, Pier-Olivier; Duchesne, Thierry; Cumming, Steven G

2018-01-01

Factors affecting wildland-fire size distribution include weather, fuels, and fire suppression activities. We present a novel application of survival analysis to quantify the effects of these factors on a sample of sizes of lightning-caused fires from Alberta, Canada. Two events were observed for each fire: the size at initial assessment (by the first fire fighters to arrive at the scene) and the size at "being held" (a state when no further increase in size is expected). We developed a statistical classifier to try to predict cases where there will be a growth in fire size (i.e., the size at "being held" exceeds the size at initial assessment). Logistic regression was preferred over two alternative classifiers, with covariates consistent with similar past analyses. We conducted survival analysis on the group of fires exhibiting a size increase. A screening process selected three covariates: an index of fire weather at the day the fire started, the fuel type burning at initial assessment, and a factor for the type and capabilities of the method of initial attack. The Cox proportional hazards model performed better than three accelerated failure time alternatives. Both fire weather and fuel type were highly significant, with effects consistent with known fire behaviour. The effects of initial attack method were not statistically significant, but did suggest a reverse causality that could arise if fire management agencies were to dispatch resources based on a-priori assessment of fire growth potentials. We discuss how a more sophisticated analysis of larger data sets could produce unbiased estimates of fire suppression effect under such circumstances.

Survival analysis of cancer risk reduction strategies for BRCA1/2 mutation carriers.

Science.gov (United States)

Kurian, Allison W; Sigal, Bronislava M; Plevritis, Sylvia K

2010-01-10

Women with BRCA1/2 mutations inherit high risks of breast and ovarian cancer; options to reduce cancer mortality include prophylactic surgery or breast screening, but their efficacy has never been empirically compared. We used decision analysis to simulate risk-reducing strategies in BRCA1/2 mutation carriers and to compare resulting survival probability and causes of death. We developed a Monte Carlo model of breast screening with annual mammography plus magnetic resonance imaging (MRI) from ages 25 to 69 years, prophylactic mastectomy (PM) at various ages, and/or prophylactic oophorectomy (PO) at ages 40 or 50 years in 25-year-old BRCA1/2 mutation carriers. With no intervention, survival probability by age 70 is 53% for BRCA1 and 71% for BRCA2 mutation carriers. The most effective single intervention for BRCA1 mutation carriers is PO at age 40, yielding a 15% absolute survival gain; for BRCA2 mutation carriers, the most effective single intervention is PM, yielding a 7% survival gain if performed at age 40 years. The combination of PM and PO at age 40 improves survival more than any single intervention, yielding 24% survival gain for BRCA1 and 11% for BRCA2 mutation carriers. PM at age 25 instead of age 40 offers minimal incremental benefit (1% to 2%); substituting screening for PM yields a similarly minimal decrement in survival (2% to 3%). Although PM at age 25 plus PO at age 40 years maximizes survival probability, substituting mammography plus MRI screening for PM seems to offer comparable survival. These results may guide women with BRCA1/2 mutations in their choices between prophylactic surgery and breast screening.

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.

TUG1, SPRY4-IT1, and HULC as valuable prognostic biomarkers of survival in cancer: A PRISMA-compliant meta-analysis.

Science.gov (United States)

Zhong, Yucheng; Chen, Zhicong; Guo, Shuyuan; Liao, Xinhui; Xie, Haibiao; Zheng, Yien; Cai, Bin; Huang, Peixian; Liu, Yuhan; Zhou, Qun; Liu, Yuchen; Huang, Weiren

2017-11-01

Long noncoding RNAs (LncRNAs) are involved in the development and progression of various cancers. Accumulating evidences indicated that expression of lncRNAs was related to the prognosis of tumors. Here, 3 well-known lncRNAs associated with cancer were gathered to prove the potential role of lncRNAs as novel predictors of survival in human cancer. This meta-analysis collected all eligible studies about TUG1, SPRY4-IT1, and HULC and explored the relationship between lncRNAs expression and lymph node metastasis (LNM) or overall survival (OS). A comprehensive, computerized literature search was undertaken by using PubMed, EMBASE, Cochrane Library, and Web of Science (up to October 10, 2017). Strength of association between 3 lncRNAs and cancer prognosis was assessed by computing the hazard ratios (HR) with its corresponding 95% confidence interval (CI). According to the inclusion and exclusion criteria, respectively, 10, 9, and 7 studies of 3 lncRNAs were included in this meta-analysis. In the current meta-analysis, it could be concluded that the expression of these 3 lncRNAs in tumor tissues is not a direct evidence of LNM. In general, there was a significant negative correlation between TUG1 levels and OS time (pooled HR 1.54, 95% CI 1.06-2.24), SPRY4-IT1 levels and OS time (pooled HR 2.12, 95% CI 1.58-2.86) and HULC levels and OS time (pooled HR 2.10, 95% CI 1.18-3.73). It could be revealed from the result that high level expression of these 3 lncRNAs might be correlated with a bad prognosis. In conclusion, the current meta-analysis demonstrated that TUG1, SPRY4-IT1, and HULC might serve as a moderate predictor of survival in human cancer.

Relation between delay and survival in 596 patients with breast cancer.

Science.gov (United States)

Machiavelli, M; Leone, B; Romero, A; Perez, J; Vallejo, C; Bianco, A; Rodriguez, R; Estevez, R; Chacon, R; Dansky, C

1989-01-01

To evaluate the influence of delay between first symptom and first treatment upon survival the medical records of 596 patients with breast cancer were reviewed. The following intervals were considered: less than 3 months; 3-6 months and greater than 6 months. Patients in the less than 3 months delay group had a better distribution by clinical stages and a 10-year survival rate higher than those in the longer delay groups (p = 0.034). However, within each stage no statistically significant difference in survival according to delay was observed. A Cox multivariate analysis revealed that performance status and stage of disease were independent predictors of survival, but not delay. Assuming the best prognosis for patients with clinical stages I and II and less than 3 months delay, the group with longer delay times had 15 deaths over what would have been predicted. This adverse effect was observed almost exclusively among patients over age 50 (14/15).

Prognostic nutritional index is associated with survival after total gastrectomy for patients with gastric cancer.

Science.gov (United States)

Ishizuka, Mitsuru; Oyama, Yusuke; Abe, Akihito; Tago, Kazuma; Tanaka, Genki; Kubota, Keiichi

2014-08-01

To investigate the influence of clinical characteristics including nutritional markers on postoperative survival in patients undergoing total gastrectomy (TG) for gastric cancer (GC). One hundred fifty-four patients were enrolled. Uni- and multivariate analyses using the Cox proportional hazard model were performed to explore the most valuable clinical characteristic that was associated with postoperative survival. Multivariate analysis using twelve clinical characteristics selected from univariate analyses revealed that age (≤ 72/>72), carcinoembryonic antigen (≤ 20/>20) (ng/ml), white blood cell count (≤ 9.5/>9.5) (× 10(3)/mm(3)), prognostic nutritional index (PNI) (≤ 45/>45) and lymph node metastasis (negative/positive) were associated with postoperative survival. Kaplan-Meier analysis and log-rank test showed that patients with higher PNI (>45) had a higher postoperative survival rate than those with lower PNI (≤ 45) (p<0.001). PNI is associated with postoperative survival of patients undergoing TG for GC and is able to divide such patients into two independent groups before surgery. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Association between pretreatment Glasgow prognostic score and gastric cancer survival and clinicopathological features: a meta-analysis

Directory of Open Access Journals (Sweden)

Zhang CX

2016-06-01

Full Text Available Chun-Xiao Zhang,* Shu-Yi Wang,* Shuang-Qian Chen, Shuai-Long Yang, Lu Wan, Bin Xiong Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan, Hubei, People’s Republic of China *These authors contributed equally to this work Background: Glasgow prognostic score (GPS is widely known as a systemic inflammatory-based marker. The relationship between pretreatment GPS and gastric cancer (GC survival and clinicopathological features remains controversial. The aim of the study was to conduct a meta-analysis of published studies to evaluate the association between pretreatment GPS and survival and clinicopathological features in GC patients. Methods: We searched PubMed, Embase, MEDLINE, and BioMed databases for relevant studies. Combined analyses were used to assess the association between pretreatment GPS and overall survival, disease-free survival, and clinicopathological parameters by Stata Version 12.0. Results: A total of 14 studies were included in this meta-analysis, including 5,579 GC patients. The results indicated that pretreatment high GPS (HGPS predicted poor overall survival (hazard ratio =1.51, 95% CI: 1.37–1.66, P<0.01 and disease-free survival (hazard ratio =1.45, 95% CI: 1.26–1.68, P<0.01 in GC patients. Pretreatment HGPS was also significantly associated with advanced tumor–node–metastasis stage (odds ratio [OR] =3.09, 95% CI: 2.11–4.53, P<0.01, lymph node metastasis (OR =4.60, 95% CI: 3.23–6.56, P<0.01, lymphatic invasion (OR =3.04, 95% CI: 2.00–4.62, P<0.01, and venous invasion (OR =3.56, 95% CI: 1.81–6.99, P<0.01. Conclusion: Our meta-analysis indicated that pretreatment HGPS could be a predicative factor of poor survival outcome and clinicopathological features for GC patients. Keywords: Glasgow prognostic score, gastric cancer, survival, clinicopathological feature

Prediction of survival by texture-based automated quantitative assessment of regional disease patterns on CT in idiopathic pulmonary fibrosis

International Nuclear Information System (INIS)

Lee, Sang Min; Seo, Joon Beom; Oh, Sang Young; Lee, Sang Min; Kim, Namkug; Kim, Tae Hoon; Song, Jin Woo

2018-01-01

To retrospectively investigate whether the baseline extent and 1-year change in regional disease patterns on CT can predict survival of patients with idiopathic pulmonary fibrosis (IPF). A total of 144 IPF patients with CT scans at the time of diagnosis and 1 year later were included. The extents of five regional disease patterns were quantified using an in-house texture-based automated system. The fibrosis score was defined as the sum of the extent of honeycombing and reticular opacity. The Cox proportional hazard model was used to determine the independent predictors of survival. A total of 106 patients (73.6%) died during the follow-up period. Univariate analysis revealed that age, baseline forced vital capacity, total lung capacity, diffusing capacity of the lung for carbon monoxide, six-minute walk distance, desaturation , honeycombing, reticular opacity, fibrosis score, and interval changes in honeycombing and fibrosis score were significantly associated with survival. Multivariate analysis revealed that age, desaturation, fibrosis score and interval change in fibrosis score were significant independent predictors of survival (p = 0.003, <0.001, 0.001 and <0.001). The C-index for the developed model was 0.768. Texture-based, automated CT quantification of fibrosis can be used as an independent predictor of survival in IPF patients. (orig.)

Prediction of survival by texture-based automated quantitative assessment of regional disease patterns on CT in idiopathic pulmonary fibrosis

Energy Technology Data Exchange (ETDEWEB)

Lee, Sang Min; Seo, Joon Beom; Oh, Sang Young; Lee, Sang Min; Kim, Namkug [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Kim, Tae Hoon; Song, Jin Woo [University of Ulsan College of Medicine, Asan Medical Center, Department of Pulmonary and Critical Care Medicine, Seoul (Korea, Republic of)

2018-03-15

To retrospectively investigate whether the baseline extent and 1-year change in regional disease patterns on CT can predict survival of patients with idiopathic pulmonary fibrosis (IPF). A total of 144 IPF patients with CT scans at the time of diagnosis and 1 year later were included. The extents of five regional disease patterns were quantified using an in-house texture-based automated system. The fibrosis score was defined as the sum of the extent of honeycombing and reticular opacity. The Cox proportional hazard model was used to determine the independent predictors of survival. A total of 106 patients (73.6%) died during the follow-up period. Univariate analysis revealed that age, baseline forced vital capacity, total lung capacity, diffusing capacity of the lung for carbon monoxide, six-minute walk distance, desaturation{sub ,} honeycombing, reticular opacity, fibrosis score, and interval changes in honeycombing and fibrosis score were significantly associated with survival. Multivariate analysis revealed that age, desaturation, fibrosis score and interval change in fibrosis score were significant independent predictors of survival (p = 0.003, <0.001, 0.001 and <0.001). The C-index for the developed model was 0.768. Texture-based, automated CT quantification of fibrosis can be used as an independent predictor of survival in IPF patients. (orig.)

Mechanisms and mediation in survival analysis: towards an integrated analytical framework.

LENUS (Irish Health Repository)

Haase, Trutz

2016-02-29

A wide-ranging debate has taken place in recent years on mediation analysis and causal modelling, raising profound theoretical, philosophical and methodological questions. The authors build on the results of these discussions to work towards an integrated approach to the analysis of research questions that situate survival outcomes in relation to complex causal pathways with multiple mediators. The background to this contribution is the increasingly urgent need for policy-relevant research on the nature of inequalities in health and healthcare.

Integrated survival analysis using an event-time approach in a Bayesian framework.

Science.gov (United States)

Walsh, Daniel P; Dreitz, Victoria J; Heisey, Dennis M

2015-02-01

Event-time or continuous-time statistical approaches have been applied throughout the biostatistical literature and have led to numerous scientific advances. However, these techniques have traditionally relied on knowing failure times. This has limited application of these analyses, particularly, within the ecological field where fates of marked animals may be unknown. To address these limitations, we developed an integrated approach within a Bayesian framework to estimate hazard rates in the face of unknown fates. We combine failure/survival times from individuals whose fates are known and times of which are interval-censored with information from those whose fates are unknown, and model the process of detecting animals with unknown fates. This provides the foundation for our integrated model and permits necessary parameter estimation. We provide the Bayesian model, its derivation, and use simulation techniques to investigate the properties and performance of our approach under several scenarios. Lastly, we apply our estimation technique using a piece-wise constant hazard function to investigate the effects of year, age, chick size and sex, sex of the tending adult, and nesting habitat on mortality hazard rates of the endangered mountain plover (Charadrius montanus) chicks. Traditional models were inappropriate for this analysis because fates of some individual chicks were unknown due to failed radio transmitters. Simulations revealed biases of posterior mean estimates were minimal (≤ 4.95%), and posterior distributions behaved as expected with RMSE of the estimates decreasing as sample sizes, detection probability, and survival increased. We determined mortality hazard rates for plover chicks were highest at birth weights and/or whose nest was within agricultural habitats. Based on its performance, our approach greatly expands the range of problems for which event-time analyses can be used by eliminating the need for having completely known fate data.

Integrated survival analysis using an event-time approach in a Bayesian framework

Science.gov (United States)

Walsh, Daniel P.; Dreitz, VJ; Heisey, Dennis M.

2015-01-01

Event-time or continuous-time statistical approaches have been applied throughout the biostatistical literature and have led to numerous scientific advances. However, these techniques have traditionally relied on knowing failure times. This has limited application of these analyses, particularly, within the ecological field where fates of marked animals may be unknown. To address these limitations, we developed an integrated approach within a Bayesian framework to estimate hazard rates in the face of unknown fates. We combine failure/survival times from individuals whose fates are known and times of which are interval-censored with information from those whose fates are unknown, and model the process of detecting animals with unknown fates. This provides the foundation for our integrated model and permits necessary parameter estimation. We provide the Bayesian model, its derivation, and use simulation techniques to investigate the properties and performance of our approach under several scenarios. Lastly, we apply our estimation technique using a piece-wise constant hazard function to investigate the effects of year, age, chick size and sex, sex of the tending adult, and nesting habitat on mortality hazard rates of the endangered mountain plover (Charadrius montanus) chicks. Traditional models were inappropriate for this analysis because fates of some individual chicks were unknown due to failed radio transmitters. Simulations revealed biases of posterior mean estimates were minimal (≤ 4.95%), and posterior distributions behaved as expected with RMSE of the estimates decreasing as sample sizes, detection probability, and survival increased. We determined mortality hazard rates for plover chicks were highest at birth weights and/or whose nest was within agricultural habitats. Based on its performance, our approach greatly expands the range of problems for which event-time analyses can be used by eliminating the need for having completely known fate data.

Survival analysis and classification methods for forest fire size

Science.gov (United States)

2018-01-01

Factors affecting wildland-fire size distribution include weather, fuels, and fire suppression activities. We present a novel application of survival analysis to quantify the effects of these factors on a sample of sizes of lightning-caused fires from Alberta, Canada. Two events were observed for each fire: the size at initial assessment (by the first fire fighters to arrive at the scene) and the size at “being held” (a state when no further increase in size is expected). We developed a statistical classifier to try to predict cases where there will be a growth in fire size (i.e., the size at “being held” exceeds the size at initial assessment). Logistic regression was preferred over two alternative classifiers, with covariates consistent with similar past analyses. We conducted survival analysis on the group of fires exhibiting a size increase. A screening process selected three covariates: an index of fire weather at the day the fire started, the fuel type burning at initial assessment, and a factor for the type and capabilities of the method of initial attack. The Cox proportional hazards model performed better than three accelerated failure time alternatives. Both fire weather and fuel type were highly significant, with effects consistent with known fire behaviour. The effects of initial attack method were not statistically significant, but did suggest a reverse causality that could arise if fire management agencies were to dispatch resources based on a-priori assessment of fire growth potentials. We discuss how a more sophisticated analysis of larger data sets could produce unbiased estimates of fire suppression effect under such circumstances. PMID:29320497

Auto-SCT improves survival in systemic light chain amyloidosis: a retrospective analysis with 14-year follow-up.

Science.gov (United States)

Parmar, S; Kongtim, P; Champlin, R; Dinh, Y; Elgharably, Y; Wang, M; Bashir, Q; Shah, J J; Shah, N; Popat, U; Giralt, S A; Orlowski, R Z; Qazilbash, M H

2014-08-01

Optimal treatment approach continues to remain a challenge for systemic light chain amyloidosis (AL). So far, Auto-SCT is the only modality associated with long-term survival. However, failure to show survival benefit in randomized study raises questions regarding its efficacy. We present a comparative outcome analysis of Auto-SCT to conventional therapies (CTR) in AL patients treated over a 14-year period at our institution. Out of the 145 AL amyloidosis patients, Auto-SCT was performed in 80 patients with 1-year non-relapse mortality rate of 12.5%. Novel agents were used as part of induction therapy in 56% of transplant recipients vs 46% of CTR patients. Hematological and organ responses were seen in 74.6% and 39% in the Auto-SCT arm vs 53% and 12% in the CTR arm, respectively. The projected 5-year survival for Auto-SCT vs CTR was 63% vs 38%, respectively. Landmark analysis of patients alive at 1-year after diagnosis showed improved 5-year OS of 72% with Auto-SCT vs 65% in the CTR arm. In the multivariate analysis, age SCT were associated with improved survival. In conclusion, Auto-SCT is associated with long-term survival for patients with AL amyloidosis.

Survival of Probiotic Lactobacilli in Acidic Environments Is Enhanced in the Presence of Metabolizable Sugars

OpenAIRE

Corcoran, B. M.; Stanton, C.; Fitzgerald, G. F.; Ross, R. P.

2005-01-01

Lactobacillus rhamnosus GG is an industrially significant probiotic strain with proven health benefits. In this study, the effect of glucose on L. rhamnosus GG survival was analyzed in simulated gastric juice at pH 2.0. It was found that the presence of 19.4 mM glucose resulted in up to 6-log10-enhanced survival following 90 min of exposure. Further work with dilute HCl confirmed that glucose was the sole component responsible. Comparative analysis with other Lactobacillus strains revealed th...

Phylogenetic analysis reveals two genotypes of the emerging fungus Mucor indicus, an opportunistic human pathogen in immunocompromised patients.

Science.gov (United States)

Taj-Aldeen, Saad J; Almaslamani, Muna; Theelen, Bart; Boekhout, Teun

2017-07-12

Mucormycosis is a rare fungal infection caused by Mucor indicus. Phylogenetic analysis of many M. indicus isolates, mainly sampled from different clinical and environmental specimens collected worldwide, revealed two genotypes, I and II, based on ITS and D1/D2 LSU rDNA sequences. A retrospective review of the literature revealed 13 cases. Eight (76.9%) patients had disseminated infections, and the overall mortality rate was 30.7%. A pulmonary infection caused by M. indicus genotype I in a liver transplant recipient was disseminated to include the skin and was successfully treated with liposomal amphotericin B and aggressive surgery. M. indicus can infect a wide variety of patients with no real preference for the site of infection. We concluded that M. indicus has emerged as a significant cause of invasive mycosis in severely immunocompromised patients worldwide. Early diagnosis and initiation of appropriate therapy could enhance survival in these immunocompromised patient populations.

Cost-effectiveness Analysis in R Using a Multi-state Modeling Survival Analysis Framework: A Tutorial.

Science.gov (United States)

Williams, Claire; Lewsey, James D; Briggs, Andrew H; Mackay, Daniel F

2017-05-01

This tutorial provides a step-by-step guide to performing cost-effectiveness analysis using a multi-state modeling approach. Alongside the tutorial, we provide easy-to-use functions in the statistics package R. We argue that this multi-state modeling approach using a package such as R has advantages over approaches where models are built in a spreadsheet package. In particular, using a syntax-based approach means there is a written record of what was done and the calculations are transparent. Reproducing the analysis is straightforward as the syntax just needs to be run again. The approach can be thought of as an alternative way to build a Markov decision-analytic model, which also has the option to use a state-arrival extended approach. In the state-arrival extended multi-state model, a covariate that represents patients' history is included, allowing the Markov property to be tested. We illustrate the building of multi-state survival models, making predictions from the models and assessing fits. We then proceed to perform a cost-effectiveness analysis, including deterministic and probabilistic sensitivity analyses. Finally, we show how to create 2 common methods of visualizing the results-namely, cost-effectiveness planes and cost-effectiveness acceptability curves. The analysis is implemented entirely within R. It is based on adaptions to functions in the existing R package mstate to accommodate parametric multi-state modeling that facilitates extrapolation of survival curves.

Gene expression meta-analysis identifies chromosomal regions involved in ovarian cancer survival

DEFF Research Database (Denmark)

Thomassen, Mads; Jochumsen, Kirsten M; Mogensen, Ole

2009-01-01

the relation of gene expression and chromosomal position to identify chromosomal regions of importance for early recurrence of ovarian cancer. By use of *Gene Set Enrichment Analysis*, we have ranked chromosomal regions according to their association to survival. Over-representation analysis including 1...... using death (P = 0.015) and recurrence (P = 0.002) as outcome. The combined mutation score is strongly associated to upregulation of several growth factor pathways....

Imaging Flow Cytometry Analysis to Identify Differences of Survival Motor Neuron Protein Expression in Patients With Spinal Muscular Atrophy.

Science.gov (United States)

Arakawa, Reiko; Arakawa, Masayuki; Kaneko, Kaori; Otsuki, Noriko; Aoki, Ryoko; Saito, Kayoko

2016-08-01

Spinal muscular atrophy is a neurodegenerative disorder caused by the deficient expression of survival motor neuron protein in motor neurons. A major goal of disease-modifying therapy is to increase survival motor neuron expression. Changes in survival motor neuron protein expression can be monitored via peripheral blood cells in patients; therefore we tested the sensitivity and utility of imaging flow cytometry for this purpose. After the immortalization of peripheral blood lymphocytes from a human healthy control subject and two patients with spinal muscular atrophy type 1 with two and three copies of SMN2 gene, respectively, we used imaging flow cytometry analysis to identify significant differences in survival motor neuron expression. A bright detail intensity analysis was used to investigate differences in the cellular localization of survival motor neuron protein. Survival motor neuron expression was significantly decreased in cells derived from patients with spinal muscular atrophy relative to those derived from a healthy control subject. Moreover, survival motor neuron expression correlated with the clinical severity of spinal muscular atrophy according to SMN2 copy number. The cellular accumulation of survival motor neuron protein was also significantly decreased in cells derived from patients with spinal muscular atrophy relative to those derived from a healthy control subject. The benefits of imaging flow cytometry for peripheral blood analysis include its capacities for analyzing heterogeneous cell populations; visualizing cell morphology; and evaluating the accumulation, localization, and expression of a target protein. Imaging flow cytometry analysis should be implemented in future studies to optimize its application as a tool for spinal muscular atrophy clinical trials. Copyright © 2016 Elsevier Inc. All rights reserved.

EG-09EPIGENETIC PROFILING REVEALS A CpG HYPERMETHYLATION PHENOTYPE (CIMP) ASSOCIATED WITH WORSE PROGRESSION-FREE SURVIVAL IN MENINGIOMA

Science.gov (United States)

Olar, Adriana; Wani, Khalida; Mansouri, Alireza; Zadeh, Gelareh; Wilson, Charmaine; DeMonte, Franco; Fuller, Gregory; Jones, David; Pfister, Stefan; von Deimling, Andreas; Sulman, Erik; Aldape, Kenneth

2014-01-01

BACKGROUND: Methylation profiling of solid tumors has revealed biologic subtypes, often with clinical implications. Methylation profiles of meningioma and their clinical implications are not well understood. METHODS: Ninety-two meningioma samples (n = 44 test set and n = 48 validation set) were profiled using the Illumina HumanMethylation450 BeadChip. Unsupervised clustering and analyses for recurrence-free survival (RFS) were performed. RESULTS: Unsupervised clustering of the test set using approximately 900 highly variable markers identified two clearly defined methylation subgroups. One of the groups (n = 19) showed global hypermethylation of a set of markers, analogous to CpG island methylator phenotype (CIMP). These findings were reproducible in the validation set, with 18/48 samples showing the CIMP-positive phenotype. Importantly, of 347 highly variable markers common to both the test and validation set analyses, 107 defined CIMP in the test set and 94 defined CIMP in the validation set, with an overlap of 83 markers between the two datasets. This number is much greater than expected by chance indicating reproducibly of the hypermethylated markers that define CIMP in meningioma. With respect to clinical correlation, the 37 CIMP-positive cases displayed significantly shorter RFS compared to the 55 non-CIMP cases (hazard ratio 2.9, p = 0.013). In an effort to develop a preliminary outcome predictor, a 155-marker subset correlated with RFS was identified in the test dataset. When interrogated in the validation dataset, this 155-marker subset showed a statistical trend (p < 0.1) towards distinguishing survival groups. CONCLUSIONS: This study defines the existence of a CIMP phenotype in meningioma, which involves a substantial proportion (37/92, 40%) of samples with clinical implications. Ongoing work will expand this cohort and examine identification of additional biologic differences (mutational and DNA copy number analysis) to further characterize the aberrant

The Impact of Demographic and Socioeconomic Factors on Major Salivary Gland Cancer Survival.

Science.gov (United States)

Olarte, Lucia S; Megwalu, Uchechukwu C

2014-06-01

This study aimed to investigate the impact of demographic and socioeconomic factors on survival in patients with major salivary gland malignancies. Population-based study using the Surveillance, Epidemiology, and End Results (SEER) cancer database. The study cohort consisted of 10,735 men and women ages 20 and older who were diagnosed with major salivary gland carcinoma from 1973 to 2009. Kaplan-Meier analysis revealed that the overall and disease-specific survival was higher for women than for men (P impact on overall survival. Male sex (HR = 1.38; 95% CI, 1.27-1.49), increasing age, and single status (HR = 1.29; 95% CI, 1.19-1.39) had poor prognostic impact on disease-specific survival. For patients with salivary gland malignancies, there is a survival benefit for younger patients, female patients, and married patients. This highlights the significance of demographic factors on survival outcomes for patients with salivary gland malignancies and highlights areas for further research on health disparities. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Chemotherapy increases long-term survival in patients with adult medulloblastoma--a literature-based meta-analysis.

Science.gov (United States)

Kocakaya, Selin; Beier, Christoph Patrick; Beier, Dagmar

2016-03-01

Adult medulloblastoma is a potentially curable malignant entity with an incidence of 0.5-1 per million. Valid data on prognosis, treatment, and demographics are lacking, as most current knowledge stems from retrospective studies. Surgical resection followed by radiotherapy are accepted parts of treatment regimes; however, established prognostic factors and data clarifying the role of chemotherapy are missing. We investigated 227 publications from 1969-2013, with 907 identifiable, individual patients being available for meta-analysis. Demographic data, risk stratification, and treatment of these patients were similar to previous cohorts. The median overall survival (mOS) was 65 months (95% CI: 54.6-75.3) , the 5-year overall survival was 50.9% with 16% of the patients dying more than 5 years after diagnosis. Incomplete resection, clinical and radiological signs for brainstem infiltration, and abstinence from radiotherapy were predictive of worse outcome. Metastatic disease at tumor recurrence was identified as a new prognostic factor, while neither metastasis at initial diagnosis nor desmoplastic/classic histology was correlated with survival. Patients receiving chemotherapy first-line survived significantly longer (mOS: 108 mo, 95% CI: 68.6-148.4) than patients treated with radiation alone (mOS: 57 mo, 95% CI: 39.6-74.4) or patients who received chemotherapy at tumor recurrence. This effect was not biased by tumor stage or decade of treatment. Importantly, (neo)adjuvant chemotherapy also significantly increased the chance for long-term survival (>5 y) compared with radiotherapy alone or chemotherapy at tumor recurrence. This meta-analysis clarifies relevant prognostic factors and suggests that chemotherapy as part of first-line therapy improves overall survival and increases the proportion of patients with long-term survival. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions

Bayesian linear regression with skew-symmetric error distributions with applications to survival analysis

KAUST Repository

Rubio, Francisco J.; Genton, Marc G.

2016-01-01

are censored. The latter scenario is of interest in the context of accelerated failure time models, which are relevant in survival analysis. We present a simulation study that demonstrates good frequentist properties of the posterior credible intervals

Survival analysis II: Cox regression

NARCIS (Netherlands)

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

2011-01-01

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

Challenges in the estimation of Net SURvival: The CENSUR working survival group.

Science.gov (United States)

Giorgi, R

2016-10-01

Net survival, the survival probability that would be observed, in a hypothetical world, where the cancer of interest would be the only possible cause of death, is a key indicator in population-based cancer studies. Accounting for mortality due to other causes, it allows cross-country comparisons or trends analysis and provides a useful indicator for public health decision-making. The objective of this study was to show how the creation and formalization of a network comprising established research teams, which already had substantial and complementary experience in both cancer survival analysis and methodological development, make it possible to meet challenges and thus provide more adequate tools, to improve the quality and the comparability of cancer survival data, and to promote methodological transfers in areas of emerging interest. The Challenges in the Estimation of Net SURvival (CENSUR) working survival group is composed of international researchers highly skilled in biostatistics, methodology, and epidemiology, from different research organizations in France, the United Kingdom, Italy, Slovenia, and Canada, and involved in French (FRANCIM) and European (EUROCARE) cancer registry networks. The expected advantages are an interdisciplinary, international, synergistic network capable of addressing problems in public health, for decision-makers at different levels; tools for those in charge of net survival analyses; a common methodology that makes unbiased cross-national comparisons of cancer survival feasible; transfer of methods for net survival estimations to other specific applications (clinical research, occupational epidemiology); and dissemination of results during an international training course. The formalization of the international CENSUR working survival group was motivated by a need felt by scientists conducting population-based cancer research to discuss, develop, and monitor implementation of a common methodology to analyze net survival in order

Utilization pattern and survival outcomes of adjuvant therapies in high-grade nonretroperitoneal abdominal soft tissue sarcoma: A population-based study.

Science.gov (United States)

Green, William Ross; Chokshi, Ravi; Jabbour, Salma K; DeLaney, Thomas F; Mahmoud, Omar

2018-02-01

Nonretroperitoneal abdominal soft tissue sarcoma (NRA-STS) is a rare disease with limited data supporting its management. Our study aimed to reveal the utilization patterns of adjuvant therapy and its potential survival benefits using the National Cancer Data Base. The analysis included patients with resected high-grade NRA-STS. Chi-square analysis was used to evaluate distribution of patient and tumor-related factors within treatment groups. The Kaplan-Meier and Cox proportional hazards model were utilized to evaluate overall survival according to treatment approach. Multivariate analysis was used to determine the impact of these factors on patients' outcome. Matched propensity score analysis was implemented to control for imbalance of confounding variables. At median follow-up of 49 months, 5-year overall survival improved from 46% without adjuvant radiation therapy to 52% (P = 0.009) with radiotherapy delivery with a 30% reduction in hazard of death (95% confidence interval = 0.58-0.84). On multivariate analysis, age <50, tumor <8 cm, negative margins and radiotherapy delivery were significant predictors of improved survival. Chemotherapy was not associated with significant survival improvement (Hazard Ratios [HR]: 0.89, P = 0.28). Adjuvant radiotherapy was associated with improved survival in high-grade NRA-STS. Chemotherapy was not associated with a survival improvement; however, further studies are needed to refine treatment strategies. © 2017 John Wiley & Sons Australia, Ltd.

Reduced in-hospital survival rates of out-of-hospital cardiac arrest victims with obstructive pulmonary disease

DEFF Research Database (Denmark)

Blom, M T; Warnier, M J; Bardai, A

2013-01-01

) had comparable survival to ER (75% vs. 78%, OR 0.9 [95% CI: 0.6-1.3]) and to hospital admission (56% vs. 57%, OR 1.0 [0.7-1.4]). However, survival to hospital discharge was significantly lower among OPD patients (21% vs. 33%, OR 0.6 [0.4-0.9]). Multivariate regression analysis among patients who were...... with obstructive pulmonary disease (OPD) have a lower survival rate after OHCA than non-OPD patients. METHODS: We performed a community-based cohort study of 1172 patients with non-traumatic OHCA with ECG-documented VT/VF between 2005 and 2008. We compared survival to emergency room (ER), to hospital admission...... admitted to hospital (OPD: n=100, no OPD: n=561) revealed that OPD was an independent determinant of reduced 30-day survival rate (39% vs. 59%, adjusted OR 0.6 [0.4-1.0, p=0.035]). CONCLUSION: OPD-patients had lower survival rates after OHCA than non-OPD patients. Survival to ER and to hospital admission...

Effects of non-surgical factors on digital replantation survival rate: a meta-analysis.

Science.gov (United States)

Ma, Z; Guo, F; Qi, J; Xiang, W; Zhang, J

2016-02-01

This study aimed to evaluate the risk factors affecting survival rate of digital replantation by a meta-analysis. A computer retrieval of MEDLINE, OVID, EMBASE, and CNKI databases was conducted to identify citations for digital replantation with digit or finger or thumb or digital or fingertip and replantation as keywords. RevMan 5.2 software was used to calculate the pooled odds ratios. In total, there were 4678 amputated digits in 2641 patients. Gender and ischemia time had no significant influence on the survival rate of amputation replantation (P > 0.05). Age, injured hand, injury type, zone, and the method of preservation the amputated digit significantly influence the survival rate of digital replantation (P < 0.05). Children, right hand, crush, or avulsion and little finger are the risk factors that adversely affect the outcome. Level 5*. © The Author(s) 2015.

Application of survival analysis methodology to the quantitative analysis of LC-MS proteomics data.

Science.gov (United States)

Tekwe, Carmen D; Carroll, Raymond J; Dabney, Alan R

2012-08-01

Protein abundance in quantitative proteomics is often based on observed spectral features derived from liquid chromatography mass spectrometry (LC-MS) or LC-MS/MS experiments. Peak intensities are largely non-normal in distribution. Furthermore, LC-MS-based proteomics data frequently have large proportions of missing peak intensities due to censoring mechanisms on low-abundance spectral features. Recognizing that the observed peak intensities detected with the LC-MS method are all positive, skewed and often left-censored, we propose using survival methodology to carry out differential expression analysis of proteins. Various standard statistical techniques including non-parametric tests such as the Kolmogorov-Smirnov and Wilcoxon-Mann-Whitney rank sum tests, and the parametric survival model and accelerated failure time-model with log-normal, log-logistic and Weibull distributions were used to detect any differentially expressed proteins. The statistical operating characteristics of each method are explored using both real and simulated datasets. Survival methods generally have greater statistical power than standard differential expression methods when the proportion of missing protein level data is 5% or more. In particular, the AFT models we consider consistently achieve greater statistical power than standard testing procedures, with the discrepancy widening with increasing missingness in the proportions. The testing procedures discussed in this article can all be performed using readily available software such as R. The R codes are provided as supplemental materials. ctekwe@stat.tamu.edu.

Retrospective Analysis of the Survival Benefit of Induction Chemotherapy in Stage IVa-b Nasopharyngeal Carcinoma.

Science.gov (United States)

Lan, Xiao-Wen; Zou, Xue-Bin; Xiao, Yao; Tang, Jie; OuYang, Pu-Yun; Su, Zhen; Xie, Fang-Yun

2016-01-01

The value of adding induction chemotherapy to chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) remains controversial, yet high-risk patients with LA-NPC have poor outcomes after chemoradiotherapy. We aimed to assess the survival benefits of induction chemotherapy in stage IVa-b NPC. A total of 602 patients with stage IVa-b NPC treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy with or without induction chemotherapy were retrospectively analyzed. Overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, log-rank test and Cox regression analysis. In univariate analysis, 5-year OS was 83.2% for induction chemotherapy plus concurrent chemotherapy and 74.8% for concurrent chemotherapy alone, corresponding to an absolute risk reduction of 8.4% (P = 0.022). Compared to concurrent chemotherapy alone, addition of induction chemotherapy improved 5-year DMFS (83.2% vs. 74.4%, P = 0.018) but not 5-year LRFS (83.7% vs. 83.0%, P = 0.848) or PFS (71.9% vs. 66.0%, P = 0.12). Age, T category, N category, chemotherapy strategy and clinical stage were associated with 5-year OS (P = 0.017, P = 0.031, P = 0.007, P = 0.022, P = 0.001, respectively). In multivariate analysis, induction chemotherapy plus concurrent chemotherapy was an independent favorable prognostic factor for OS (HR, 0.62; 95% CI, 0.43-0.90, P = 0.012) and DMFS (HR, 0.57; 95% CI, 0.38-0.83, P = 0.004). In subgroup analysis, induction chemotherapy significantly improved 5-year DMFS in stage IVa (86.8% vs. 77.3%, P = 0.008), but provided no significant benefit in stage IVb. In patients with stage IVa-b NPC treated with IMRT, addition of induction chemotherapy to concurrent chemotherapy significantly improved 5-year OS and 5-year DMFS. This study provides a basis for selection of high risk patients in future clinical therapeutic

Multivariate Survival Mixed Models for Genetic Analysis of Longevity Traits

DEFF Research Database (Denmark)

Pimentel Maia, Rafael; Madsen, Per; Labouriau, Rodrigo

2014-01-01

A class of multivariate mixed survival models for continuous and discrete time with a complex covariance structure is introduced in a context of quantitative genetic applications. The methods introduced can be used in many applications in quantitative genetics although the discussion presented co...... applications. The methods presented are implemented in such a way that large and complex quantitative genetic data can be analyzed......A class of multivariate mixed survival models for continuous and discrete time with a complex covariance structure is introduced in a context of quantitative genetic applications. The methods introduced can be used in many applications in quantitative genetics although the discussion presented...... concentrates on longevity studies. The framework presented allows to combine models based on continuous time with models based on discrete time in a joint analysis. The continuous time models are approximations of the frailty model in which the hazard function will be assumed to be piece-wise constant...

Multivariate Survival Mixed Models for Genetic Analysis of Longevity Traits

DEFF Research Database (Denmark)

Pimentel Maia, Rafael; Madsen, Per; Labouriau, Rodrigo

2013-01-01

A class of multivariate mixed survival models for continuous and discrete time with a complex covariance structure is introduced in a context of quantitative genetic applications. The methods introduced can be used in many applications in quantitative genetics although the discussion presented co...... applications. The methods presented are implemented in such a way that large and complex quantitative genetic data can be analyzed......A class of multivariate mixed survival models for continuous and discrete time with a complex covariance structure is introduced in a context of quantitative genetic applications. The methods introduced can be used in many applications in quantitative genetics although the discussion presented...... concentrates on longevity studies. The framework presented allows to combine models based on continuous time with models based on discrete time in a joint analysis. The continuous time models are approximations of the frailty model in which the hazard function will be assumed to be piece-wise constant...

Modification of bacterial cell survival by postirradiation hypoxia

Energy Technology Data Exchange (ETDEWEB)

Vexler, F B; Eidus, L Kh

1986-01-27

It is shown that postirradiation hypoxia affects the survival of E.coli. Hypoxic conditions immediately after a single-dose irradiation diminish cell survival in nutrient medium. Increasing time intervals between irradiation and hypoxia decrease the efficiency of the latter, while 1 h after irradiation hypoxia does not modify the survival of irradiated cells. These findings reveal that the mechanisms of action of postirradiation hypoxia on eu- and prokaryotic cells are similar.

KMWin--a convenient tool for graphical presentation of results from Kaplan-Meier survival time analysis.

Science.gov (United States)

Gross, Arnd; Ziepert, Marita; Scholz, Markus

2012-01-01

Analysis of clinical studies often necessitates multiple graphical representations of the results. Many professional software packages are available for this purpose. Most packages are either only commercially available or hard to use especially if one aims to generate or customize a huge number of similar graphical outputs. We developed a new, freely available software tool called KMWin (Kaplan-Meier for Windows) facilitating Kaplan-Meier survival time analysis. KMWin is based on the statistical software environment R and provides an easy to use graphical interface. Survival time data can be supplied as SPSS (sav), SAS export (xpt) or text file (dat), which is also a common export format of other applications such as Excel. Figures can directly be exported in any graphical file format supported by R. On the basis of a working example, we demonstrate how to use KMWin and present its main functions. We show how to control the interface, customize the graphical output, and analyse survival time data. A number of comparisons are performed between KMWin and SPSS regarding graphical output, statistical output, data management and development. Although the general functionality of SPSS is larger, KMWin comprises a number of features useful for survival time analysis in clinical trials and other applications. These are for example number of cases and number of cases under risk within the figure or provision of a queue system for repetitive analyses of updated data sets. Moreover, major adjustments of graphical settings can be performed easily on a single window. We conclude that our tool is well suited and convenient for repetitive analyses of survival time data. It can be used by non-statisticians and provides often used functions as well as functions which are not supplied by standard software packages. The software is routinely applied in several clinical study groups.

KMWin--a convenient tool for graphical presentation of results from Kaplan-Meier survival time analysis.

Directory of Open Access Journals (Sweden)

Arnd Gross

Full Text Available BACKGROUND: Analysis of clinical studies often necessitates multiple graphical representations of the results. Many professional software packages are available for this purpose. Most packages are either only commercially available or hard to use especially if one aims to generate or customize a huge number of similar graphical outputs. We developed a new, freely available software tool called KMWin (Kaplan-Meier for Windows facilitating Kaplan-Meier survival time analysis. KMWin is based on the statistical software environment R and provides an easy to use graphical interface. Survival time data can be supplied as SPSS (sav, SAS export (xpt or text file (dat, which is also a common export format of other applications such as Excel. Figures can directly be exported in any graphical file format supported by R. RESULTS: On the basis of a working example, we demonstrate how to use KMWin and present its main functions. We show how to control the interface, customize the graphical output, and analyse survival time data. A number of comparisons are performed between KMWin and SPSS regarding graphical output, statistical output, data management and development. Although the general functionality of SPSS is larger, KMWin comprises a number of features useful for survival time analysis in clinical trials and other applications. These are for example number of cases and number of cases under risk within the figure or provision of a queue system for repetitive analyses of updated data sets. Moreover, major adjustments of graphical settings can be performed easily on a single window. CONCLUSIONS: We conclude that our tool is well suited and convenient for repetitive analyses of survival time data. It can be used by non-statisticians and provides often used functions as well as functions which are not supplied by standard software packages. The software is routinely applied in several clinical study groups.

Analysis on Lung Cancer Survival from 2001 to 2007 in Qidong, China

Directory of Open Access Journals (Sweden)

Jian ZHU

2011-01-01

Full Text Available Background and objective Lung cancer is one of the most important malignancies in China. Survival rates of lung cancer on the population-based cancer registry for the years 2001-2007 in Qidong were analysed in order to provide the basis for the prognosis assessment and the control of this cancer. Methods Total 4,451 registered lung cancer cases was followed up to December 31st, 2009. Death certificates only (DCO cases were excluded, leaving 4,382 cases for survival analysis. Cumulative observed survival rate (OS and relative survival rate (RS were calculated using Hakulinen’s method performed by the SURV 3.01 software developed at the Finnish Cancer Registry. Results The 1-, 3-, and 5-year OS rates were 23.73%, 11.89%, 10.01%, and the RS rates were 24.86%, 13.69%, 12.73%, respectively. The 1-, 3-, and 5-year RS of males vs females were 23.70% vs 27.89%, 12.58% vs 16.53%, and 11.73% vs 15.21%, respectively, with statisitically significant differences (χ2=13.77, P=0.032. RS of age groups of 15-34, 35-44, 45-54, 55-64, 65-74 and 75+ were 35.46%, 17.66%, 11.97%, 13.49%, 10.61%, 15.14%, respectively. Remarkable improvement could be seen for the 5-year RS in this setting if compared with that for the years 1972-2000. Conclusion The lung cancer survival outcomes in Qidong have been improved gradually for the past decades. Further measures on the prevention, diagnosis and treatment of lung cancer should be taken.

Predictors of survival in surgically treated patients of spinal metastasis

Directory of Open Access Journals (Sweden)

Pravin Padalkar

2011-01-01

Full Text Available Background: The spinal metastasis occurs in up to 40% of cancer patient. We compared the Tokuhashi and Tomita scoring systems, two commonly used scoring systems for prognosis in spinal metastases. We also assessed the different variables separately with respect to their value in predicting postsurgical life expectancy. Finally, we suggest criteria for selecting patients for surgery based on the postoperative survival pattern. Materials and Methods: We retrospectively analyzed 102 patients who had been operated for metastatic disease of the spine. Predictive scoring was done according to the scoring systems proposed by Tokuhashi and Tomita. Overall survival was assessed using Kaplan-Meier survival analysis. Using the log rank test and Cox regression model we assessed the value of the individual components of each scoring system for predicting survival in these patients. Result: The factors that were most significantly associated with survival were the general condition score (Karnofsky Performance Scale (P=.000, log rank test, metastasis to internal organs (P=.0002 log rank test, and number of extraspinal bone metastases (P=.0058. Type of primary tumor was not found to be significantly associated with survival according to the revised Tokuhashi scoring system (P=.9131, log rank test. Stepwise logistic regression revealed that the Tomita score correlated more closely with survival than the Tokuhashi score. Conclusion: The patient′s performance status, extent of visceral metastasis, and extent of bone metastases are significant predictors of survival in patients with metastatic disease. Both revised Tokuhashi and Tomita scores were significantly correlated with survival. A revised Tokuhashi score of 7 or more and a Tomita score of 6 or less indicated >50% chance of surviving 6 months postoperatively. We recommend that the Tomita score be used for prognostication in patients who are contemplating surgery, as it is simpler to score and has a higher

It's Deja Vu All over Again: Using Multiple-Spell Discrete-Time Survival Analysis.

Science.gov (United States)

Willett, John B.; Singer, Judith D.

1995-01-01

The multiple-spell discrete-time survival analysis method is introduced and illustrated using longitudinal data on exit from and reentry into the teaching profession. The method is applicable to many educational problems involving the sequential occurrence of disparate events or episodes. (SLD)

Meta-analysis of single-arm survival studies: a distribution-free approach for estimating summary survival curves with random effects.

Science.gov (United States)

Combescure, Christophe; Foucher, Yohann; Jackson, Daniel

2014-07-10

In epidemiologic studies and clinical trials with time-dependent outcome (for instance death or disease progression), survival curves are used to describe the risk of the event over time. In meta-analyses of studies reporting a survival curve, the most informative finding is a summary survival curve. In this paper, we propose a method to obtain a distribution-free summary survival curve by expanding the product-limit estimator of survival for aggregated survival data. The extension of DerSimonian and Laird's methodology for multiple outcomes is applied to account for the between-study heterogeneity. Statistics I(2)  and H(2) are used to quantify the impact of the heterogeneity in the published survival curves. A statistical test for between-strata comparison is proposed, with the aim to explore study-level factors potentially associated with survival. The performance of the proposed approach is evaluated in a simulation study. Our approach is also applied to synthesize the survival of untreated patients with hepatocellular carcinoma from aggregate data of 27 studies and synthesize the graft survival of kidney transplant recipients from individual data from six hospitals. Copyright © 2014 John Wiley & Sons, Ltd.

Estimating Probability of Default on Peer to Peer Market – Survival Analysis Approach

Directory of Open Access Journals (Sweden)

Đurović Andrija

2017-05-01

Full Text Available Arguably a cornerstone of credit risk modelling is the probability of default. This article aims is to search for the evidence of relationship between loan characteristics and probability of default on peer-to-peer (P2P market. In line with that, two loan characteristics are analysed: 1 loan term length and 2 loan purpose. The analysis is conducted using survival analysis approach within the vintage framework. Firstly, 12 months probability of default through the cycle is used to compare riskiness of analysed loan characteristics. Secondly, log-rank test is employed in order to compare complete survival period of cohorts. Findings of the paper suggest that there is clear evidence of relationship between analysed loan characteristics and probability of default. Longer term loans are more risky than the shorter term ones and the least risky loans are those used for credit card payoff.

Ensemble survival tree models to reveal pairwise interactions of variables with time-to-events outcomes in low-dimensional setting

Science.gov (United States)

Dazard, Jean-Eudes; Ishwaran, Hemant; Mehlotra, Rajeev; Weinberg, Aaron; Zimmerman, Peter

2018-01-01

Unraveling interactions among variables such as genetic, clinical, demographic and environmental factors is essential to understand the development of common and complex diseases. To increase the power to detect such variables interactions associated with clinical time-to-events outcomes, we borrowed established concepts from random survival forest (RSF) models. We introduce a novel RSF-based pairwise interaction estimator and derive a randomization method with bootstrap confidence intervals for inferring interaction significance. Using various linear and nonlinear time-to-events survival models in simulation studies, we first show the efficiency of our approach: true pairwise interaction-effects between variables are uncovered, while they may not be accompanied with their corresponding main-effects, and may not be detected by standard semi-parametric regression modeling and test statistics used in survival analysis. Moreover, using a RSF-based cross-validation scheme for generating prediction estimators, we show that informative predictors may be inferred. We applied our approach to an HIV cohort study recording key host gene polymorphisms and their association with HIV change of tropism or AIDS progression. Altogether, this shows how linear or nonlinear pairwise statistical interactions of variables may be efficiently detected with a predictive value in observational studies with time-to-event outcomes. PMID:29453930

Chemoembolization With Doxorubicin-Eluting Beads for Unresectable Hepatocellular Carcinoma: Five-Year Survival Analysis

Energy Technology Data Exchange (ETDEWEB)

Malagari, Katerina, E-mail: kmalag@otonet.gr [University of Athens, Second Department of Radiology (Greece); Pomoni, Mary [University of Athens, Imaging and Research Unit (Greece); Moschouris, Hippocrates, E-mail: hipmosch@gmail.com [Tzanion Hospital, Department of Radiology (Greece); Bouma, Evanthia [University of Athens, Imaging and Research Unit (Greece); Koskinas, John [Ippokration Hospital, University of Athens, Department of Internal Medicine and Hepatology (Greece); Stefaniotou, Aspasia [University of Athens, Imaging and Research Unit (Greece); Marinis, Athanasios [Tzanion Hospital, Department of Surgery (Greece); Kelekis, Alexios; Alexopoulou, Efthymia [University of Athens, Second Department of Radiology (Greece); Chatziioannou, Achilles [University of Athens, First Department of Radiology (Greece); Chatzimichael, Katerina [University of Athens, Second Department of Radiology (Greece); Dourakis, Spyridon [Ippokration Hospital, University of Athens, Department of Internal Medicine and Hepatology (Greece); Kelekis, Nikolaos [University of Athens, Second Department of Radiology (Greece); Rizos, Spyros [Tzanion Hospital, Department of Surgery (Greece); Kelekis, Dimitrios [University of Athens, Imaging and Research Unit (Greece)

2012-10-15

Purpose: The purpose of this study was to report on the 5-year survival of hepatocellular carcinoma (HCC) patients treated with DC Bead loaded with doxorubicin (DEB-DOX) in a scheduled scheme in up to three treatments and thereafter on demand. Materials and Methods: 173 HCC patients not suitable for curable treatments were prospectively enrolled (mean age 70.4 {+-} 7.4 years). Child-Pugh (Child) class was A/B (102/71 [59/41 %]), Okuda stage was 0/1/2 (91/61/19 [53.2/35.7/11.1 %]), and mean lesion diameter was 7.6 {+-} 2.1 cm. Lesion morphology was one dominant {<=}5 cm (22 %), one dominant >5 cm (41.6 %), multifocal {<=}5 (26 %), and multifocal >5 (10.4 %). Results: Overall survival at 1, 2, 3, 4, and 5 years was 93.6, 83.8, 62, 41.04, and 22.5 %, with higher rates achieved in Child class A compared with Child class B patients (95, 88.2, 61.7, 45, and 29.4 % vs. 91.5, 75, 50.7, 35.2, and 12.8 %). Mean overall survival was 43.8 months (range 1.2-64.8). Cumulative survival was better for Child class A compared with Child class B patients (p = 0.029). For patients with dominant lesions {<=}5 cm 1-, 2-, 3-, 4-, and 5-year survival rates were 100, 95.2, 71.4, 66.6, and 47.6 % for Child class A and 94.1, 88.2, 58.8, 41.2, 29.4, and 23.5 % for Child class B patients. Regarding DEB-DOX treatment, multivariate analysis identified number of lesions (p = 0.033), lesion vascularity (p < 0.0001), initially achieved complete response (p < 0.0001), and objective response (p = 0.046) as significant and independent determinants of 5-year survival. Conclusion: DEB-DOX results, with high rates of 5-year survival for patients, not amenable to curative treatments. Number of lesions, lesion vascularity, and local response were significant independent determinants of 5-year survival.

Chemoembolization With Doxorubicin-Eluting Beads for Unresectable Hepatocellular Carcinoma: Five-Year Survival Analysis

International Nuclear Information System (INIS)

Malagari, Katerina; Pomoni, Mary; Moschouris, Hippocrates; Bouma, Evanthia; Koskinas, John; Stefaniotou, Aspasia; Marinis, Athanasios; Kelekis, Alexios; Alexopoulou, Efthymia; Chatziioannou, Achilles; Chatzimichael, Katerina; Dourakis, Spyridon; Kelekis, Nikolaos; Rizos, Spyros; Kelekis, Dimitrios

2012-01-01

Purpose: The purpose of this study was to report on the 5-year survival of hepatocellular carcinoma (HCC) patients treated with DC Bead loaded with doxorubicin (DEB-DOX) in a scheduled scheme in up to three treatments and thereafter on demand. Materials and Methods: 173 HCC patients not suitable for curable treatments were prospectively enrolled (mean age 70.4 ± 7.4 years). Child-Pugh (Child) class was A/B (102/71 [59/41 %]), Okuda stage was 0/1/2 (91/61/19 [53.2/35.7/11.1 %]), and mean lesion diameter was 7.6 ± 2.1 cm. Lesion morphology was one dominant ≤5 cm (22 %), one dominant >5 cm (41.6 %), multifocal ≤5 (26 %), and multifocal >5 (10.4 %). Results: Overall survival at 1, 2, 3, 4, and 5 years was 93.6, 83.8, 62, 41.04, and 22.5 %, with higher rates achieved in Child class A compared with Child class B patients (95, 88.2, 61.7, 45, and 29.4 % vs. 91.5, 75, 50.7, 35.2, and 12.8 %). Mean overall survival was 43.8 months (range 1.2–64.8). Cumulative survival was better for Child class A compared with Child class B patients (p = 0.029). For patients with dominant lesions ≤5 cm 1-, 2-, 3-, 4-, and 5-year survival rates were 100, 95.2, 71.4, 66.6, and 47.6 % for Child class A and 94.1, 88.2, 58.8, 41.2, 29.4, and 23.5 % for Child class B patients. Regarding DEB-DOX treatment, multivariate analysis identified number of lesions (p = 0.033), lesion vascularity (p < 0.0001), initially achieved complete response (p < 0.0001), and objective response (p = 0.046) as significant and independent determinants of 5-year survival. Conclusion: DEB-DOX results, with high rates of 5-year survival for patients, not amenable to curative treatments. Number of lesions, lesion vascularity, and local response were significant independent determinants of 5-year survival.

Effect of donor ethnicity on kidney survival in different recipient pairs: an analysis of the OPTN/UNOS database.

Science.gov (United States)

Callender, C O; Cherikh, W S; Traverso, P; Hernandez, A; Oyetunji, T; Chang, D

2009-12-01

Previous multivariate analysis performed between April 1, 1994, and December 31, 2000 from the Organ Procurement Transplant Network/United Network for Organ Sharing (OPTN/UNOS) database has shown that kidneys from black donors were associated with lower graft survival. We compared graft and patient survival of different kidney donor-to-recipient ethnic combinations to see if this result still holds on a recent cohort of US kidney transplants. We included 72,495 recipients of deceased and living donor kidney alone transplants from 2001 to 2005. A multivariate Cox regression method was used to analyze the effect of donor-recipient ethnicity on graft and patient survival within 5 years of transplant, and to adjust for the effect of other donor, recipient, and transplant characteristics. Results are presented as hazard ratios (HR) with the 95% confidence limit (CL) and P values. Adjusted HRs of donor-recipient patient survival were: white to white (1); and white to black (1.22; P = .001). Graft survival HRs were black to black (1.40; P recipients. The graft and patient survival rates for Asian and Latino/Hispanic recipients, however, were not affected by donor ethnicity. This analysis underscores the need for research to better understand the reasons for these disparities and how to improve the posttransplant graft survival rates of black kidney recipients.

Application of survival analysis methodology to the quantitative analysis of LC-MS proteomics data

KAUST Repository

Tekwe, C. D.

2012-05-24

MOTIVATION: Protein abundance in quantitative proteomics is often based on observed spectral features derived from liquid chromatography mass spectrometry (LC-MS) or LC-MS/MS experiments. Peak intensities are largely non-normal in distribution. Furthermore, LC-MS-based proteomics data frequently have large proportions of missing peak intensities due to censoring mechanisms on low-abundance spectral features. Recognizing that the observed peak intensities detected with the LC-MS method are all positive, skewed and often left-censored, we propose using survival methodology to carry out differential expression analysis of proteins. Various standard statistical techniques including non-parametric tests such as the Kolmogorov-Smirnov and Wilcoxon-Mann-Whitney rank sum tests, and the parametric survival model and accelerated failure time-model with log-normal, log-logistic and Weibull distributions were used to detect any differentially expressed proteins. The statistical operating characteristics of each method are explored using both real and simulated datasets. RESULTS: Survival methods generally have greater statistical power than standard differential expression methods when the proportion of missing protein level data is 5% or more. In particular, the AFT models we consider consistently achieve greater statistical power than standard testing procedures, with the discrepancy widening with increasing missingness in the proportions. AVAILABILITY: The testing procedures discussed in this article can all be performed using readily available software such as R. The R codes are provided as supplemental materials. CONTACT: ctekwe@stat.tamu.edu.

Talent in Female Gymnastics: a Survival Analysis Based upon Performance Characteristics.

Science.gov (United States)

Pion, J; Lenoir, M; Vandorpe, B; Segers, V

2015-11-01

This study investigated the link between the anthropometric, physical and motor characteristics assessed during talent identification and dropout in young female gymnasts. 3 cohorts of female gymnasts (n=243; 6-9 years) completed a test battery for talent identification. Performance-levels were monitored over 5 years of competition. Kaplan-Meier and Cox Proportional Hazards analyses were conducted to determine the survival rate and the characteristics that influence dropout respectively. Kaplan-Meier analysis indicated that only 18% of the female gymnasts that passed the baseline talent identification test survived at the highest competition level 5 years later. The Cox Proportional Hazards Model indicated that gymnasts with a score in the best quartile for a specific characteristic significantly increased chances of survival by 45-129%. These characteristics being: basic motor skills (129%), shoulder strength (96%), leg strength (53%) and 3 gross motor coordination items (45-73%). These results suggest that tests batteries commonly used for talent identification in young female gymnasts may also provide valuable insights into future dropout. Therefore, multidimensional test batteries deserve a prominent place in the selection process. The individual test results should encourage trainers to invest in an early development of basic physical and motor characteristics to prevent attrition. © Georg Thieme Verlag KG Stuttgart · New York.

Tumor infiltrating lymphocytes: an intriguing player in the survival of colorectal cancer patients

Directory of Open Access Journals (Sweden)

Lardon Filip

2010-04-01

Full Text Available Abstract Background There is growing evidence that both local and systemic inflammatory responses play an important role in the progression of a variety of solid tumors. Colorectal cancer results from the cumulative effect of sequential genetic alterations, leading to the expression of tumor associated antigens possibly inducing a cellular anti-tumor immune response. It is well recognized that cytotoxic lymphocytes constitute one of the most important effector mechanisms of anti-tumor-immunity. However, their potential prognostic influence in colorectal cancer remains controversial. Aim of the study was to examine infiltration of CD3+ and CD8+ lymphocytes in colorectal cancer and their prognostic potential. Two-hundred-fifteen colorectal cancer cases, previously analyzed for microsatellite instability (MSI, were selected for immunohistochemical detection of CD3+, CD8+ infiltration and the expression of granzyme B. Prognostic relevance was assessed by survival analysis. Results Strong correlations were found between the infiltration of lymphocytes and several clinicopathological variables. Survival analysis revealed that intra-epithelial infiltration of CD3+ and CD8+ T lymphocytes and stromal infiltration of CD3+ lymphocytes had a major impact on the patients' overall survival in the univariate analysis, however independent of their association with MSI-status. In addition, it was also demonstrated that there was an important disease specific survival advantage for patients with microsatellite stable (MSS tumors containing intraepithelial CD8+ tumor infiltrating lymphocytes. When samples were analyzed for colon cancer and rectal cancer separately, the results of the overall population were confirmed in colon cancer only. When entered into a multiple Cox regression analysis adjusting for other possible important confounding factors, the strong impact of lymphocyte infiltration on overall survival was not maintained. Only early stage and young age

Tracheostomy mechanical ventilation in patients with amyotrophic lateral sclerosis: clinical features and survival analysis.

Science.gov (United States)

Spataro, Rossella; Bono, Valeria; Marchese, Santino; La Bella, Vincenzo

2012-12-15

Tracheostomy mechanical ventilation (TMV) is performed in amyotrophic lateral sclerosis (ALS) patients with a respiratory failure or when the non-invasive ventilation (NIV) is no longer effective. We evaluated the clinical characteristics and survival of a cohort of tracheostomized ALS patients, followed in a single ALS Clinical Center. Between 2001 and 2010, 87 out of 279 ALS patients were submitted to TMV. Onset was spinal in 62 and bulbar in 25. After tracheostomy, most patients were followed up through telephone interviews to caregivers. A complete survival analysis could be performed in fifty-two TMV patients. 31.3% ALS patients underwent tracheostomy, with a male prevalence (M/F=1.69) and a median age of 61 years (interquartile range=47-66). After tracheostomy, nearly all patients were under home care. TMV ALS patients were more likely than non-tracheostomized (NT) patients to be implanted with a PEG device, although the bulbar-/spinal-onset ratio did not differ between the two groups. Kaplan-Meyer analysis showed that tracheostomy increases median survival (TMV, 47 months vs NT, 31 months, p=0.008), with the greatest effect in patients younger than 60 at onset (TMV ≤ 60 years, 57.5 months vs NT ≤ 60 years, 38.5 months, p=0.002). TMV is increasingly performed in ALS patients. Nearly all TMV patients live at home and most of them are fed through a PEG device. Survival after tracheostomy is generally increased, with the stronger effect in patients younger than 60. This survival advantage is apparently lost when TMV is performed in patients older than 60. The results of this study might be useful for the decision-making process of patients and their families about this advanced palliative care. Copyright © 2012. Published by Elsevier B.V.

Global variations in cancer survival. Study Group on Cancer Survival in Developing Countries.

Science.gov (United States)

Sankaranarayanan, R; Swaminathan, R; Black, R J

1996-12-15

Population-based cancer registries from Algeria, China, Costa Rica, Cuba, India, the Philippines, and Thailand are collaborating with the International Agency for Research on Cancer in a study of cancer survival in developing countries. Comparisons with the SEER program results of the National Cancer Institute in the United States, and the EUROCARE study of survival in European countries revealed considerable differences in the survival of patients with certain tumors associated with intensive chemotherapeutic treatment regimes (Hodgkin's disease and testicular tumors), more modest differences in the survival of patients with tumors for which early diagnosis and treatment confer an improved prognosis (carcinomas of the large bowel, breast, and cervix), and only slight differences for tumors associated with poor prognosis (carcinomas of the stomach, pancreas, and lung). With limited resources to meet the challenge of the increasing incidence of cancer expected in the next few decades, health authorities in developing countries should be aware of the importance of investing in a range of cancer control activities, including primary prevention and early detection programs as well as treatment.

Tumour heterogeneity in non-small cell lung carcinoma assessed by CT texture analysis: a potential marker of survival

International Nuclear Information System (INIS)

Ganeshan, Balaji; Miles, Ken; Panayiotou, Elleny; Burnand, Kate; Dizdarevic, Sabina

2012-01-01

To establish the potential for tumour heterogeneity in non-small cell lung cancer (NSCLC) as assessed by CT texture analysis (CTTA) to provide an independent marker of survival for patients with NSCLC. Tumour heterogeneity was assessed by CTTA of unenhanced images of primary pulmonary lesions from 54 patients undergoing 18 F-fluorodeoxyglucose (FDG) PET-CT for staging of NSCLC. CTTA comprised image filtration to extract fine, medium and coarse features with quantification of the distribution of pixel values (uniformity) within the filtered images. Receiver operating characteristics identified thresholds for PET and CTTA parameters that were related to patient survival using Kaplan-Meier analysis. The median (range) survival was 29.5 (1-38) months. 24, 10, 14 and 6 patients had tumour stages I, II, III and IV respectively. PET stage and tumour heterogeneity assessed by CTTA were significant independent predictors of survival (PET stage: Odds ratio 3.85, 95% confidence limits 0.9-8.09, P = 0.002; CTTA: Odds ratio 56.4, 95% confidence limits 4.79-666, p = 0.001). SUV was not a significantly associated with survival. Assessment of tumour heterogeneity by CTTA of non-contrast enhanced images has the potential for to provide a novel, independent predictor of survival for patients with NSCLC. (orig.)

Survival Rate and Associated Factors of Childhood Leukemia in Iran: A Systematic Review and Meta Analysis

Directory of Open Access Journals (Sweden)

Yousef Veisani

2017-02-01

Full Text Available Context Resent reviews have shown that about 18% of all child cancers are leukemia. Track of the survival rate can help researchers improve quality of life of patients through improving screening or discovery of better treatments. Objectives This review aimed at estimating the 5-year survival rates and associated factors of childhood leukemia in Iran. Data Sources We carried out a systematic review through search of relevant studies published in English (PubMed, Scopus, Google scholar, and ISI and Persian databases (Magiran, Medlib, SID, and Iran Medex. Study Selection The study included all epidemiologic studies that estimated survival rate in children with leukemia in Iran during years 2002 to 2015, and a standardized manner was used for extraction of information. Data Extraction The entire text or summary of all searched articles was extracted and then, related articles were selected, and irrelevant ones were excluded. Fixed and random effects models were calculated by the STATA using standard meta-analysis methods. Heterogeneity was assessed by I² statistics. Results The overall 5-year survival rate in patients with childhood leukemia in Iran was 0.65 (95% CI, 0.62 to 0.67, 10 studies, in the acute lymphoblastic leukemia (ALL subtype was 71.0% (95% CI: 68.0 to 74.0, and in the acute myeloid leukemia (AML subtype was 46.0%. Results of the meta analysis showed significant poor survival with relapse (heart rate (HR 1.59, 95% confidence interval (CI 1.27 to 1.98 and white blood count (WBC counts ≥ 50,000 (HR 2.92, 95% CI 1.23 to 4.60. Conclusions The results showed that 5-year survival rates in patients with AML were lower than patients with ALL. The results of this meta analysis strongly support the need for future research, action, and guidance for clinicians to improve health-related quality of life and outcomes for children with leukemia.

Parameter resolution in two models for cell survival after radiation

International Nuclear Information System (INIS)

Di Cera, E.; Andreasi Bassi, F.; Arcovito, G.

1989-01-01

The resolvability of model parameters for the linear-quadratic and the repair-misrepair models for cell survival after radiation has been studied by Monte Carlo simulations as a function of the number of experimental data points collected in a given dose range and the experimental error. Statistical analysis of the results reveals the range of experimental conditions under which the model parameters can be resolved with sufficient accuracy, and points out some differences in the operational aspects of the two models. (orig.)

Comparing survival outcomes of gross total resection and subtotal resection with radiotherapy for craniopharyngioma: a meta-analysis.

Science.gov (United States)

Wang, Guoqing; Zhang, Xiaoyang; Feng, Mengzhao; Guo, Fuyou

2018-06-01

Recent studies suggest that subtotal resection (STR) followed by radiation therapy (RT) is an appealing alternative to gross total resection (GTR) for craniopharyngioma, but it remains controversial. We conducted a meta-analysis to determine whether GTR is superior to STR with RT for craniopharyngioma. A systematic search was performed for articles published until October 2017 in the PubMed, Embase, and Cochrane Central databases. The endpoints of interest are overall survival and progression-free survival. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated using a fixed or random-effects model. The data were analyzed using Review Manager 5.3 software. A total of 744 patients (seven cohort studies) were enrolled for analyses. There were no significant differences between the GTR and STR with RT groups when the authors compared the pooled HRs at the end of the follow-up period. Overall survival (pooled HR = 0.76, 95% CI: 0.46-1.25, P = 0.28) and progression-free survival (pooled HR = 1.52, 95% CI: 0.42-5.44, P = 0.52) were similar between the two groups. The current meta-analysis suggests that GTR and STR with RT have the similar survival outcomes for craniopharyngioma. Copyright © 2018 Elsevier Inc. All rights reserved.

ASURV: Astronomical SURVival Statistics

Science.gov (United States)

Feigelson, E. D.; Nelson, P. I.; Isobe, T.; LaValley, M.

2014-06-01

ASURV (Astronomical SURVival Statistics) provides astronomy survival analysis for right- and left-censored data including the maximum-likelihood Kaplan-Meier estimator and several univariate two-sample tests, bivariate correlation measures, and linear regressions. ASURV is written in FORTRAN 77, and is stand-alone and does not call any specialized libraries.

KMWin – A Convenient Tool for Graphical Presentation of Results from Kaplan-Meier Survival Time Analysis

Science.gov (United States)

Gross, Arnd; Ziepert, Marita; Scholz, Markus

2012-01-01

Background Analysis of clinical studies often necessitates multiple graphical representations of the results. Many professional software packages are available for this purpose. Most packages are either only commercially available or hard to use especially if one aims to generate or customize a huge number of similar graphical outputs. We developed a new, freely available software tool called KMWin (Kaplan-Meier for Windows) facilitating Kaplan-Meier survival time analysis. KMWin is based on the statistical software environment R and provides an easy to use graphical interface. Survival time data can be supplied as SPSS (sav), SAS export (xpt) or text file (dat), which is also a common export format of other applications such as Excel. Figures can directly be exported in any graphical file format supported by R. Results On the basis of a working example, we demonstrate how to use KMWin and present its main functions. We show how to control the interface, customize the graphical output, and analyse survival time data. A number of comparisons are performed between KMWin and SPSS regarding graphical output, statistical output, data management and development. Although the general functionality of SPSS is larger, KMWin comprises a number of features useful for survival time analysis in clinical trials and other applications. These are for example number of cases and number of cases under risk within the figure or provision of a queue system for repetitive analyses of updated data sets. Moreover, major adjustments of graphical settings can be performed easily on a single window. Conclusions We conclude that our tool is well suited and convenient for repetitive analyses of survival time data. It can be used by non-statisticians and provides often used functions as well as functions which are not supplied by standard software packages. The software is routinely applied in several clinical study groups. PMID:22723912

Characteristics of juvenile survivors reveal spatio-temporal differences in early life stage survival of Baltic cod

DEFF Research Database (Denmark)

Huwer, Bastian; Hinrichsen, H.H.; Böttcher, U.

2014-01-01

with previous modeling studies on the survival chances of early-stage larvae and with general spatio-temporal patterns of larval prey availability suggests that differences in survival are related to food availability during the early larval stage. Results are discussed in relation to the recruitment process...

Two-stage meta-analysis of survival data from individual participants using percentile ratios

Science.gov (United States)

Barrett, Jessica K; Farewell, Vern T; Siannis, Fotios; Tierney, Jayne; Higgins, Julian P T

2012-01-01

Methods for individual participant data meta-analysis of survival outcomes commonly focus on the hazard ratio as a measure of treatment effect. Recently, Siannis et al. (2010, Statistics in Medicine 29:3030–3045) proposed the use of percentile ratios as an alternative to hazard ratios. We describe a novel two-stage method for the meta-analysis of percentile ratios that avoids distributional assumptions at the study level. Copyright © 2012 John Wiley & Sons, Ltd. PMID:22825835

Survival Outcomes in Resected Extrahepatic Cholangiocarcinoma: Effect of Adjuvant Radiotherapy in a Surveillance, Epidemiology, and End Results Analysis

International Nuclear Information System (INIS)

Vern-Gross, Tamara Z.; Shivnani, Anand T.; Chen, Ke; Lee, Christopher M.; Tward, Jonathan D.; MacDonald, O. Kenneth; Crane, Christopher H.; Talamonti, Mark S.; Munoz, Louis L.; Small, William

2011-01-01

Purpose: The benefit of adjuvant radiotherapy (RT) after surgical resection for extrahepatic cholangiocarcinoma has not been clearly established. We analyzed survival outcomes of patients with resected extrahepatic cholangiocarcinoma and examined the effect of adjuvant RT. Methods and Materials: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 2003. The primary endpoint was the overall survival time. Cox regression analysis was used to perform univariate and multivariate analyses of the following clinical variables: age, year of diagnosis, histologic grade, localized (Stage T1-T2) vs. regional (Stage T3 or greater and/or node positive) stage, gender, race, and the use of adjuvant RT after surgical resection. Results: The records for 2,332 patients were obtained. Patients with previous malignancy, distant disease, incomplete or conflicting records, atypical histologic features, and those treated with preoperative/intraoperative RT were excluded. Of the remaining 1,491 patients eligible for analysis, 473 (32%) had undergone adjuvant RT. After a median follow-up of 27 months (among surviving patients), the median overall survival time for the entire cohort was 20 months. Patients with localized and regional disease had a median survival time of 33 and 18 months, respectively (p < .001). The addition of adjuvant RT was not associated with an improvement in overall or cause-specific survival for patients with local or regional disease. Conclusion: Patients with localized disease had significantly better overall survival than those with regional disease. Adjuvant RT was not associated with an improvement in long-term overall survival in patients with resected extrahepatic bile duct cancer. Key data, including margin status and the use of combined chemotherapy, was not available through the SEER database.

Estimation of Unemployment Duration in Botoşani County Using Survival Analysis

Directory of Open Access Journals (Sweden)

Darabă Gabriel

2017-01-01

Full Text Available In this paper we aim at estimating the unemployment duration in Botosani County in order tostudy the impact of individual characteristics (gender, age, place of residence, unemploymentbenefit, etc. on the length of unemployment spells. We use Cox regression model to measure theeffects of gender, age, residential environment, etc. on the hazard rate of leaving unemploymentandKaplan-Meier estimator to compare survival probabilities among different categories ofunemployed persons. The study is carried out on a sample of 200 unemployment spellsregisteredwith the Employment Agency of Botoşani County from January 2012 to December 2015. Theresults reveal that place of residence, unemployment benefit and unemployed category have asignificant impact on unemployment spells.

Survival Analysis of Factors Influencing Cyclic Fatigue of Nickel-Titanium Endodontic Instruments

Directory of Open Access Journals (Sweden)

Eva Fišerová

2015-01-01

Full Text Available Objective. The aim of this study was to validate a survival analysis assessing the effect of type of rotary system, canal curvature, and instrument size on cyclic resistance. Materials and Methods. Cyclic fatigue testing was carried out in stainless steel artificial canals with radii of curvature of 3 or 5 mm and the angle of curvature of 60 degrees. All the instruments were new and 25 mm in working length, and ISO colour coding indicated the instrument size (yellow for size 20; red for size 25. Wizard Navigator instruments, Mtwo instruments, ProTaper instruments, and Revo-S instruments were passively rotated at 250 rotations per minute, and the time fracture was being recorded. Subsequently, fractographic analysis of broken tips was performed by scanning electron microscope. The data were then analysed by the Kaplan-Meier estimator of the survival function, the Cox proportional hazards model, the Wald test for regression covariates, and the Wald test for significance of regression model. Conclusion. The lifespan registered for the tested instruments was Mtwo > Wizard Navigator > Revo-S > ProTaper; 5 mm radius > 3 mm radius; and yellow > red in ISO colour coding system.

Survival analysis of colorectal cancer patients with tumor recurrence using global score test methodology

Energy Technology Data Exchange (ETDEWEB)

Zain, Zakiyah, E-mail: zac@uum.edu.my; Ahmad, Yuhaniz, E-mail: yuhaniz@uum.edu.my [School of Quantitative Sciences, Universiti Utara Malaysia, UUM Sintok 06010, Kedah (Malaysia); Azwan, Zairul, E-mail: zairulazwan@gmail.com, E-mail: farhanaraduan@gmail.com, E-mail: drisagap@yahoo.com; Raduan, Farhana, E-mail: zairulazwan@gmail.com, E-mail: farhanaraduan@gmail.com, E-mail: drisagap@yahoo.com; Sagap, Ismail, E-mail: zairulazwan@gmail.com, E-mail: farhanaraduan@gmail.com, E-mail: drisagap@yahoo.com [Surgery Department, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Bandar Tun Razak, Kuala Lumpur (Malaysia); Aziz, Nazrina, E-mail: nazrina@uum.edu.my

2014-12-04

Colorectal cancer is the third and the second most common cancer worldwide in men and women respectively, and the second in Malaysia for both genders. Surgery, chemotherapy and radiotherapy are among the options available for treatment of patients with colorectal cancer. In clinical trials, the main purpose is often to compare efficacy between experimental and control treatments. Treatment comparisons often involve several responses or endpoints, and this situation complicates the analysis. In the case of colorectal cancer, sets of responses concerned with survival times include: times from tumor removal until the first, the second and the third tumor recurrences, and time to death. For a patient, the time to recurrence is correlated to the overall survival. In this study, global score test methodology is used in combining the univariate score statistics for comparing treatments with respect to each survival endpoint into a single statistic. The data of tumor recurrence and overall survival of colorectal cancer patients are taken from a Malaysian hospital. The results are found to be similar to those computed using the established Wei, Lin and Weissfeld method. Key factors such as ethnic, gender, age and stage at diagnose are also reported.

Relative Quantitative Proteomic Analysis of Brucella abortus Reveals Metabolic Adaptation to Multiple Environmental Stresses.

Science.gov (United States)

Zai, Xiaodong; Yang, Qiaoling; Yin, Ying; Li, Ruihua; Qian, Mengying; Zhao, Taoran; Li, Yaohui; Zhang, Jun; Fu, Ling; Xu, Junjie; Chen, Wei

2017-01-01

Brucella spp. are facultative intracellular pathogens that cause chronic brucellosis in humans and animals. The virulence of Brucella primarily depends on its successful survival and replication in host cells. During invasion of the host tissue, Brucella is simultaneously subjected to a variety of harsh conditions, including nutrient limitation, low pH, antimicrobial defenses, and extreme levels of reactive oxygen species (ROS) via the host immune response. This suggests that Brucella may be able to regulate its metabolic adaptation in response to the distinct stresses encountered during its intracellular infection of the host. An investigation into the differential proteome expression patterns of Brucella grown under the relevant stress conditions may contribute toward a better understanding of its pathogenesis and adaptive response. Here, we utilized a mass spectrometry-based label-free relative quantitative proteomics approach to investigate and compare global proteomic changes in B. abortus in response to eight different stress treatments. The 3 h short-term in vitro single-stress and multi-stress conditions mimicked the in vivo conditions of B. abortus under intracellular infection, with survival rates ranging from 3.17 to 73.17%. The proteomic analysis identified and quantified a total of 2,272 proteins and 74% of the theoretical proteome, thereby providing wide coverage of the B. abortus proteome. By including eight distinct growth conditions and comparing these with a control condition, we identified a total of 1,221 differentially expressed proteins (DEPs) that were significantly changed under the stress treatments. Pathway analysis revealed that most of the proteins were involved in oxidative phosphorylation, ABC transporters, two-component systems, biosynthesis of secondary metabolites, the citrate cycle, thiamine metabolism, and nitrogen metabolism; constituting major response mechanisms toward the reconstruction of cellular homeostasis and metabolic

Characteristics of the tomato chromoplast revealed by proteomic analysis

OpenAIRE

Barsan, Cristina; Sanchez-Bel, Paloma; Rombaldi, César Valmor; Egea, Isabel; Rossignol, Michel; Kuntz, Marcel; Zouine, Mohamed; Latché, Alain; Bouzayen, Mondher; Pech, Jean-Claude

2010-01-01

Chromoplasts are non-photosynthetic specialized plastids that are important in ripening tomato fruit (Solanum lycopersicum) since, among other functions, they are the site of accumulation of coloured compounds. Analysis of the proteome of red fruit chromoplasts revealed the presence of 988 proteins corresponding to 802 Arabidopsis unigenes, among which 209 had not been listed so far in plastidial databanks. These data revealed several features of the chromoplast. Proteins of lipid metabolism ...

The survival analysis of beta thalassemia major patients in South East of Iran

International Nuclear Information System (INIS)

Roudbari, M.; Soltani-Rad, M.; Roudbari, S.

2008-01-01

The objective was to determine the survival of beta-thalassemia major patients with transfusion, and its related factors in Southeast of Iran. This cross-sectional study was performed in Zahedan, Iran in 2007. The sample included patients who were referred from all over the Zahedan Thalassemia Center from 1998 to 2006. The data were collected using the patient's records, which were recorded by the staff during transfusion. The data included demographic and medical information blood group, blood RH, the kind of transfused blood [KTB], annual number of transfusions [ANOT], accompanied disease [AD], Hemoglobin [Hb] and ferritin level. For data analysis, the Kaplan-Meyer method, and Long Rank test together with Cox Regression were used. Forty-six of 578 patients died and 99% survived for the first year. The ages survival proportions were 5 (97.9%), 10 (97%), 15 (92.1%), and 20 (81.2%) years. The survival time showed significant relationships with the ANOT p=0.0053, KTB p=0.003, Hb=0.002 and ferritin level p=0.0087, and AD p=0.00. Using regular transfusion, paying attention to screening of transfused blood, increasing the families knowledge on the disease to prevent the bearing of thalassemia fetus, are recommended; finally, the detection and treating of the AD, are of great importance to extend the lifetime of the patients. (author)

Repair models of cell survival and corresponding computer program for survival curve fitting

International Nuclear Information System (INIS)

Shen Xun; Hu Yiwei

1992-01-01

Some basic concepts and formulations of two repair models of survival, the incomplete repair (IR) model and the lethal-potentially lethal (LPL) model, are introduced. An IBM-PC computer program for survival curve fitting with these models was developed and applied to fit the survivals of human melanoma cells HX118 irradiated at different dose rates. Comparison was made between the repair models and two non-repair models, the multitar get-single hit model and the linear-quadratic model, in the fitting and analysis of the survival-dose curves. It was shown that either IR model or LPL model can fit a set of survival curves of different dose rates with same parameters and provide information on the repair capacity of cells. These two mathematical models could be very useful in quantitative study on the radiosensitivity and repair capacity of cells

Covariate analysis of bivariate survival data

Energy Technology Data Exchange (ETDEWEB)

Bennett, L.E.

1992-01-01

The methods developed are used to analyze the effects of covariates on bivariate survival data when censoring and ties are present. The proposed method provides models for bivariate survival data that include differential covariate effects and censored observations. The proposed models are based on an extension of the univariate Buckley-James estimators which replace censored data points by their expected values, conditional on the censoring time and the covariates. For the bivariate situation, it is necessary to determine the expectation of the failure times for one component conditional on the failure or censoring time of the other component. Two different methods have been developed to estimate these expectations. In the semiparametric approach these expectations are determined from a modification of Burke's estimate of the bivariate empirical survival function. In the parametric approach censored data points are also replaced by their conditional expected values where the expected values are determined from a specified parametric distribution. The model estimation will be based on the revised data set, comprised of uncensored components and expected values for the censored components. The variance-covariance matrix for the estimated covariate parameters has also been derived for both the semiparametric and parametric methods. Data from the Demographic and Health Survey was analyzed by these methods. The two outcome variables are post-partum amenorrhea and breastfeeding; education and parity were used as the covariates. Both the covariate parameter estimates and the variance-covariance estimates for the semiparametric and parametric models will be compared. In addition, a multivariate test statistic was used in the semiparametric model to examine contrasts. The significance of the statistic was determined from a bootstrap distribution of the test statistic.

Transcriptional Network Analysis Reveals Drought Resistance Mechanisms of AP2/ERF Transgenic Rice

Directory of Open Access Journals (Sweden)

Hongryul Ahn

2017-06-01

Full Text Available This study was designed to investigate at the molecular level how a transgenic version of rice “Nipponbare” obtained a drought-resistant phenotype. Using multi-omics sequencing data, we compared wild-type rice (WT and a transgenic version (erf71 that had obtained a drought-resistant phenotype by overexpressing OsERF71, a member of the AP2/ERF transcription factor (TF family. A comprehensive bioinformatics analysis pipeline, including TF networks and a cascade tree, was developed for the analysis of multi-omics data. The results of the analysis showed that the presence of OsERF71 at the source of the network controlled global gene expression levels in a specific manner to make erf71 survive longer than WT. Our analysis of the time-series transcriptome data suggests that erf71 diverted more energy to survival-critical mechanisms related to translation, oxidative response, and DNA replication, while further suppressing energy-consuming mechanisms, such as photosynthesis. To support this hypothesis further, we measured the net photosynthesis level under physiological conditions, which confirmed the further suppression of photosynthesis in erf71. In summary, our work presents a comprehensive snapshot of transcriptional modification in transgenic rice and shows how this induced the plants to acquire a drought-resistant phenotype.

Mechanical dyssynchrony evaluated by tissue Doppler cross-correlation analysis is associated with long-term survival in patients after cardiac resynchronization therapy

DEFF Research Database (Denmark)

Risum, Niels; Williams, Eric S; Khouri, Michel G

2013-01-01

Aims Pre-implant assessment of longitudinal mechanical dyssynchrony using cross-correlation analysis (XCA) was tested for association with long-term survival and compared with other tissue Doppler imaging (TDI)-derived indices. Methods and results In 131 patients referred for cardiac resynchroniz......Aims Pre-implant assessment of longitudinal mechanical dyssynchrony using cross-correlation analysis (XCA) was tested for association with long-term survival and compared with other tissue Doppler imaging (TDI)-derived indices. Methods and results In 131 patients referred for cardiac......-max was independently associated with improved survival when adjusted for QRS > 150 ms and aetiology {hazard ratio (HR) 0.35 [95% confidence interval (CI) 0.16-0.77], P = 0.01}. Maximal activation delay performed significantly better than Yu index, OWD, and the presence of left bundle branch block (P ..., for difference between parameters). In subgroup analysis, patients without dyssynchrony and QRS between 120 and 150 ms showed a particularly poor survival [HR 4.3 (95% CI 1.46-12.59), P

Acute lymphoblastic leukemia in children and adolescents: prognostic factors and analysis of survival

Science.gov (United States)

Lustosa de Sousa, Daniel Willian; de Almeida Ferreira, Francisco Valdeci; Cavalcante Félix, Francisco Helder; de Oliveira Lopes, Marcos Vinicios

2015-01-01

Objective To describe the clinical and laboratory features of children and adolescents with acute lymphoblastic leukemia treated at three referral centers in Ceará and evaluate prognostic factors for survival, including age, gender, presenting white blood cell count, immunophenotype, DNA index and early response to treatment. Methods Seventy-six under 19-year-old patients with newly diagnosed acute lymphoblastic leukemia treated with the Grupo Brasileiro de Tratamento de Leucemia da Infância – acute lymphoblastic leukemia-93 and -99 protocols between September 2007 and December 2009 were analyzed. The diagnosis was based on cytological, immunophenotypic and cytogenetic criteria. Associations between variables, prognostic factors and response to treatment were analyzed using the chi-square test and Fisher's exact test. Overall and event-free survival were estimated by Kaplan–Meier analysis and compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors. Results The average age at diagnosis was 6.3 ± 0.5 years and males were predominant (65%). The most frequently observed clinical features were hepatomegaly, splenomegaly and lymphadenopathy. Central nervous system involvement and mediastinal enlargement occurred in 6.6% and 11.8%, respectively. B-acute lymphoblastic leukemia was more common (89.5%) than T-acute lymphoblastic leukemia. A DNA index >1.16 was found in 19% of patients and was associated with favorable prognosis. On Day 8 of induction therapy, 95% of the patients had lymphoblast counts <1000/μL and white blood cell counts <5.0 × 109/L. The remission induction rate was 95%, the induction mortality rate was 2.6% and overall survival was 72%. Conclusion The prognostic factors identified are compatible with the literature. The 5-year overall and event-free survival rates were lower than those reported for developed countries. As shown by the multivariate analysis, age and baseline white

Acute lymphoblastic leukemia in children and adolescents: prognostic factors and analysis of survival

Directory of Open Access Journals (Sweden)

Daniel Willian Lustosa de Sousa

2015-08-01

Full Text Available OBJECTIVE: To describe the clinical and laboratory features of children and adolescents with acute lymphoblastic leukemia treated at three referral centers in Ceará and evaluate prognostic factors for survival, including age, gender, presenting white blood cell count, immunophenotype, DNA index and early response to treatment.METHODS: Seventy-six under 19-year-old patients with newly diagnosed acute lymphoblastic leukemia treated with the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia-93 and -99 protocols between September 2007 and December 2009 were analyzed. The diagnosis was based on cytological, immunophenotypic and cytogenetic criteria. Associations between variables, prognostic factors and response to treatment were analyzed using the chi-square test and Fisher's exact test. Overall and event-free survival were estimated by Kaplan-Meier analysis and compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors.RESULTS: The average age at diagnosis was 6.3 ± 0.5 years and males were predominant (65%. The most frequently observed clinical features were hepatomegaly, splenomegaly and lymphadenopathy. Central nervous system involvement and mediastinal enlargement occurred in 6.6% and 11.8%, respectively. B-acute lymphoblastic leukemia was more common (89.5% than T-acute lymphoblastic leukemia. A DNA index >1.16 was found in 19% of patients and was associated with favorable prognosis. On Day 8 of induction therapy, 95% of the patients had lymphoblast counts <1000/µL and white blood cell counts <5.0 Ã- 109/L. The remission induction rate was 95%, the induction mortality rate was 2.6% and overall survival was 72%.CONCLUSION: The prognostic factors identified are compatible with the literature. The 5-year overall and event-free survival rates were lower than those reported for developed countries. As shown by the multivariate analysis, age

Transcriptional regulation of rod photoreceptor homeostasis revealed by in vivo NRL targetome analysis.

Directory of Open Access Journals (Sweden)

Hong Hao

Full Text Available A stringent control of homeostasis is critical for functional maintenance and survival of neurons. In the mammalian retina, the basic motif leucine zipper transcription factor NRL determines rod versus cone photoreceptor cell fate and activates the expression of many rod-specific genes. Here, we report an integrated analysis of NRL-centered gene regulatory network by coupling chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq data from Illumina and ABI platforms with global expression profiling and in vivo knockdown studies. We identified approximately 300 direct NRL target genes. Of these, 22 NRL targets are associated with human retinal dystrophies, whereas 95 mapped to regions of as yet uncloned retinal disease loci. In silico analysis of NRL ChIP-Seq peak sequences revealed an enrichment of distinct sets of transcription factor binding sites. Specifically, we discovered that genes involved in photoreceptor function include binding sites for both NRL and homeodomain protein CRX. Evaluation of 26 ChIP-Seq regions validated their enhancer functions in reporter assays. In vivo knockdown of 16 NRL target genes resulted in death or abnormal morphology of rod photoreceptors, suggesting their importance in maintaining retinal function. We also identified histone demethylase Kdm5b as a novel secondary node in NRL transcriptional hierarchy. Exon array analysis of flow-sorted photoreceptors in which Kdm5b was knocked down by shRNA indicated its role in regulating rod-expressed genes. Our studies identify candidate genes for retinal dystrophies, define cis-regulatory module(s for photoreceptor-expressed genes and provide a framework for decoding transcriptional regulatory networks that dictate rod homeostasis.

Breast cancer detection and survival among women with cosmetic breast implants: systematic review and meta-analysis of observational studies.

Science.gov (United States)

Lavigne, Eric; Holowaty, Eric J; Pan, Sai Yi; Villeneuve, Paul J; Johnson, Kenneth C; Fergusson, Dean A; Morrison, Howard; Brisson, Jacques

2013-04-29

To evaluate whether the stage distribution among women diagnosed as having breast cancer differs between those who have received breast implants for cosmetic purposes and those with no implants and to evaluate whether cosmetic breast augmentation before the detection of breast cancer is a predictor of post-diagnosis survival. Systematic review of observational studies with two meta-analyses. Systematic search of the literature published before September 2012 conducted in Medline, Embase, Global health, CINAHL, IPAB, and PsycINFO. Eligible publications were those that included women diagnosed as having breast cancer and who had had augmentation mammaplasty for cosmetic purposes. The overall odds ratio of the first meta-analysis based on 12 studies was 1.26 (95% confidence interval 0.99 to 1.60; P=0.058; I(2)=35.6%) for a non-localized stage of breast cancer at diagnosis comparing women with implants who had breast cancer and women without implants who had breast cancer. The second meta-analysis, based on five studies, evaluated the relation between cosmetic breast implantation and survival. This meta-analysis showed reduced survival after breast cancer among women who had implants compared with those who did not (overall hazard ratio for breast cancer specific mortality 1.38, 95% confidence interval 1.08 to 1.75). The research published to date suggests that cosmetic breast augmentation adversely affects the survival of women who are subsequently diagnosed as having breast cancer. These findings should be interpreted with caution, as some studies included in the meta-analysis on survival did not adjust for potential confounders. Further investigations are warranted regarding diagnosis and prognosis of breast cancer among women with breast implants.

Conditional survival is greater than overall survival at diagnosis in patients with osteosarcoma and Ewing's sarcoma.

Science.gov (United States)

Miller, Benjamin J; Lynch, Charles F; Buckwalter, Joseph A

2013-11-01

Conditional survival is a measure of the risk of mortality given that a patient has survived a defined period of time. These estimates are clinically helpful, but have not been reported previously for osteosarcoma or Ewing's sarcoma. We determined the conditional survival of patients with osteosarcoma and Ewing's sarcoma given survival of 1 or more years. We used the Surveillance, Epidemiology, and End Results (SEER) Program database to investigate cases of osteosarcoma and Ewing's sarcoma in patients younger than 40 years from 1973 to 2009. The SEER Program is managed by the National Cancer Institute and provides survival data gathered from population-based cancer registries. We used an actuarial life table analysis to determine any cancer cause-specific 5-year survival estimates conditional on 1 to 5 years of survival after diagnosis. We performed a similar analysis to determine 20-year survival from the time of diagnosis. The estimated 5-year survival improved each year after diagnosis. For local/regional osteosarcoma, the 5-year survival improved from 74.8% at baseline to 91.4% at 5 years-meaning that if a patient with localized osteosarcoma lives for 5 years, the chance of living for another 5 years is 91.4%. Similarly, the 5-year survivals for local/regional Ewing's sarcoma improved from 72.9% at baseline to 92.5% at 5 years, for metastatic osteosarcoma 35.5% at baseline to 85.4% at 5 years, and for metastatic Ewing's sarcoma 31.7% at baseline to 83.6% at 5 years. The likelihood of 20-year cause-specific survival from the time of diagnosis in osteosarcoma and Ewing's sarcoma was almost 90% or greater after 10 years of survival, suggesting that while most patients will remain disease-free indefinitely, some experience cancer-related complications years after presumed eradication. The 5-year survival estimates of osteosarcoma and Ewing's sarcoma improve with each additional year of patient survival. Knowledge of a changing risk profile is useful in counseling

Impact of T and N substage on survival and disease relapse in adjuvant rectal cancer: a pooled analysis

International Nuclear Information System (INIS)

Gunderson, Leonard L.; Sargent, Daniel J.; Tepper, Joel E.; O'Connell, Michael J.; Allmer, Cristine; Smalley, Steven R.; Martenson, James A.; Haller, Daniel G.; Mayer, Robert J.; Rich, Tyvin A.; Ajani, Jaffer A.; Macdonald, John S.; Goldberg, Richard M.

2002-01-01

Purpose: To determine the rates of survival and disease control by TNM and MAC stage in three randomized North American rectal adjuvant studies. Materials and Methods: Data were merged from 2551 eligible patients on NCCTG 79-47-51 (n=200), NCCTG 86-47-51 (n=656), and INT 114 (n=1695). All patients received postoperative radiation, and 96% were randomized to receive concomitant and maintenance chemotherapy. Five-year follow-up was available in 94% of patients and 7-yr follow-up in 84%. Kaplan-Meier curves were used to estimate the distribution of overall survival (OS) and disease-free survival (DFS), and p values were derived using the log-rank test. Time to local and distant relapse was estimated using cumulative incidence methodology. Analyses were adjusted for treatment effect using Cox proportional hazards models. Results: OS and DFS were dependent on both TN stage and NT stage (N substage within T stage and T substage within N stage). Even among N2 patients (4 or more LN+), T stage influenced 5-yr OS (T1-2, 69%; T3, 48%; T4, 38%). Three risk groups of patients were defined: (1) intermediate: T3N0, T1-2N1; (2) moderately high: T4N0, T1-2N2, T3N1; and (3) high: T3N2, T4N1, T4N2. For Group 1, 5-yr OS was 74% and 81%, and 5-yr DFS was 66% and 74%. For Group 2, 5-yr OS ranged from 61% to 69%, and for Group 3, OS ranged from 33% to 48%. Cumulative incidence rates of local relapse and distant metastases revealed similar differences by TN and NT stage, as seen in the survival analyses. Conclusion: Patients with a single high-risk factor of either extension beyond the rectal wall (T3N0) or nodal involvement (T1-2N1) have improved OS, DFS, and disease control when compared to those with both high risk factors. Different treatment strategies may be indicated for intermediate- (T3N0, T1-2N1) vs. moderately high or high-risk patients in view of differential survival and rates of relapse. For future trial design, it may be preferable to perform separate studies, or a planned

Mathematical analysis of 51Cr-labelled red cell survival curves in congenital haemolytic anaemias

International Nuclear Information System (INIS)

Kasfiki, A.G.; Antipas, S.E.; Dimitriou, P.A.; Gritzali, F.A.; Melissinos, K.G.

1982-01-01

The parameters of 51 Cr labelled red cell survival curves were calculated in 26 patients with homozygous β-thalassaemia, 8 with sickle-cell anaemia and 3 with s-β-thalassaemia, using a non-linear weighted least squares analysis computer program. In thalassaemic children the calculated parameters denote that the shorting of the mean cell life is due to early senescence alone, while there is some evidence that in thalassaemic adults additional extracellular destruction mechanisms participate as well. Red cell survival curves from patients with sickle-cell anaemia and s-β-thalassaemia resemble each other, while their parameters indicate an initial rapid loss of radioactivity, early senescence and the presence of extracellular red cell destruction factors. (orig.)

SURVIVAL ANALYSIS AND GROWTH OF Cordia trichotoma, BORAGINACEAE, LAMIALES, IN MATO GROSSO DO SUL STATE, BRAZIL

Directory of Open Access Journals (Sweden)

Sergio Luiz Salvadori

2013-12-01

Full Text Available http://dx.doi.org/10.5902/1980509812357The evaluation of a plant survival percentage and growth may reflect its competitive ability in plantcommunity. Cordia trichotoma is a common native tree in Mato Grosso do Sul State and one of the mostpromising for planting. This study monitored the survival percentage and growth of Cordia trichotomaunder different conditions such as weeding and receiving or not fertilization. The experiment started inSeptember 2008 and it was concluded in March 2010. The seeds collection and sowing were held in urbanarea of Mundo Novo Municipality and the area for permanent planting to measure seedlings survival andgrowth was set at Japorã Municipality, Fazenda Santa Clara. Seedlings were planted in two categories: theuse or not of fertilizer and crowing resulting in four distinct groups: block fertilizer bare earth (ATN, bareland block without fertilizer (BTN, fertilizer and crown block (AC and without fertilizer and crownedblock (BC. The results indicated high survival of Cordia trichotoma in the seedling transplant system from bed to bags. The BC block showed the highest percentage of survival, but the smaller increments in height.The AC, ATN and BTN blocks presented the same survival pattern and similar average growth. However,there may be differences in nutritional and chemical composition of the soil suggesting sector analysis forfuture studies.

Receipt of maintenance therapy is most predictive of survival in older acute lymphoblastic leukemia patients treated with intensive induction chemotherapy regimens.

Science.gov (United States)

Landsburg, Daniel J; Stadtmauer, Edward; Loren, Alison; Goldstein, Steven; Frey, Noelle; Nasta, Sunita D; Porter, David L; Tsai, Donald E; Perl, Alexander E; Hexner, Elizabeth O; Luger, Selina

2013-08-01

While the prognosis for older adults diagnosed with acute lymphoblastic leukemia (ALL) is frequently poor, long-term survival can be achieved in patients treated with curative intent. We reviewed the outcomes of 37 patients age ≥60 treated at our institution with either DVP- or hyperCVAD-based chemotherapy regimens from 2003-2011. In this patient population, a complete response rate of 92%, relapse rate of 56% and median overall survival of 18.1 months was experienced. Univariate analysis revealed that receipt of maintenance therapy vs. no maintenance therapy was associated with a statistically-significant impact on overall survival (p = 0.001, HR 0.15 for death), while disease-related characteristics including high-risk white blood cell count at diagnosis and Philadelphia chromosome status as well as treatment-related factors including chemotherapy regimen or completion of intensive therapy were not. Many patients were unable to initiate or remain on maintenance therapy due to toxicities including infections and cytopenias. Our analysis reveals the benefit of prolonged therapy in the treatment of older adults with ALL as well as the high incidence of treatment-related toxicity experienced by these patients. Copyright © 2013 Wiley Periodicals, Inc.

Survival Impact of Adjuvant Radiation Therapy in Masaoka Stage II to IV Thymomas: A Systematic Review and Meta-analysis

International Nuclear Information System (INIS)

Lim, Yu Jin; Kim, Eunji; Kim, Hak Jae; Wu, Hong-Gyun; Yan, Jinchun; Liu, Qin; Patel, Shilpen

2016-01-01

Purpose: To evaluate the survival impact of postoperative radiation therapy (PORT) in stage II to IV thymomas, using systematic review and meta-analysis. Methods and Materials: A database search was conducted with EMBASE, PubMed, Web of Science, Cochrane Library, and Ovid from inception to August 2015. Thymic carcinomas were excluded, and studies comparing overall survival (OS) with and without PORT in thymomas were included. The hazard ratios (HRs) of OS were extracted, and a random-effects model was used in the pooled analysis. Results: Seven retrospective series with a total of 1724 patients were included and analyzed. Almost all of the patients underwent macroscopically complete resection, and thymoma histology was confirmed by the World Health Organization criteria. In the overall analysis of stage II to IV thymomas, OS was not altered with the receipt of PORT (HR 0.79, 95% confidence interval [CI] 0.58-1.08). Although PORT was not associated with survival difference in Masaoka stage II disease (HR 1.45, 95% CI 0.83-2.55), improved OS was observed with the addition of PORT in the discrete pooled analysis of stage III to IV (HR 0.63, 95% CI 0.40-0.99). Significant heterogeneity and publication bias were not found in the analyses. Conclusions: From the present meta-analysis of sole primary thymomas, we suggest the potential OS benefit of PORT in locally advanced tumors with macroscopically complete resection, but not in stage II disease. Further investigations with sufficient survival data are needed to establish detailed treatment indications.

Survival Impact of Adjuvant Radiation Therapy in Masaoka Stage II to IV Thymomas: A Systematic Review and Meta-analysis

Energy Technology Data Exchange (ETDEWEB)

Lim, Yu Jin; Kim, Eunji [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Hak Jae, E-mail: khjae@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Wu, Hong-Gyun [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of); Yan, Jinchun [Department of Radiation Oncology, Dalian Medical University, Liaoning (China); Department of Radiation Oncology, Fudan University Cancer Hospital, Shanghai (China); Liu, Qin [The Wistar Institute, Philadelphia, Pennsylvania (United States); Patel, Shilpen [Department of Radiation Oncology, University of Washington Medical Center, Seattle, Washington (United States)

2016-04-01

Purpose: To evaluate the survival impact of postoperative radiation therapy (PORT) in stage II to IV thymomas, using systematic review and meta-analysis. Methods and Materials: A database search was conducted with EMBASE, PubMed, Web of Science, Cochrane Library, and Ovid from inception to August 2015. Thymic carcinomas were excluded, and studies comparing overall survival (OS) with and without PORT in thymomas were included. The hazard ratios (HRs) of OS were extracted, and a random-effects model was used in the pooled analysis. Results: Seven retrospective series with a total of 1724 patients were included and analyzed. Almost all of the patients underwent macroscopically complete resection, and thymoma histology was confirmed by the World Health Organization criteria. In the overall analysis of stage II to IV thymomas, OS was not altered with the receipt of PORT (HR 0.79, 95% confidence interval [CI] 0.58-1.08). Although PORT was not associated with survival difference in Masaoka stage II disease (HR 1.45, 95% CI 0.83-2.55), improved OS was observed with the addition of PORT in the discrete pooled analysis of stage III to IV (HR 0.63, 95% CI 0.40-0.99). Significant heterogeneity and publication bias were not found in the analyses. Conclusions: From the present meta-analysis of sole primary thymomas, we suggest the potential OS benefit of PORT in locally advanced tumors with macroscopically complete resection, but not in stage II disease. Further investigations with sufficient survival data are needed to establish detailed treatment indications.

Novel Inflammation-Based Prognostic Score for Predicting Survival in Patients with Metastatic Urothelial Carcinoma.

Directory of Open Access Journals (Sweden)

Yu-Li Su

Full Text Available We developed a novel inflammation-based model (NPS, which consisted of a neutrophil to lymphocyte ratio (NLR and platelet count (PC, for assessing the prognostic role in patients with metastatic urothelial carcinoma (UC.We performed a retrospective analysis of patients with metastatic UC who underwent systemic chemotherapy between January 1997 and December 2014 in Kaohsiung Chang Gung Memorial Hospital. The defined cutoff values for the NLR and PC were 3.0 and 400 × 103/μL, respectively. Patients were scored 1 for either an elevated NLR or PC, and 0 otherwise. The NPS was calculated by summing the scores, ranging from 0 to 2. The primary endpoint was overall survival (OS by using Kaplan-Meier analysis. Multivariate Cox regression analysis was used to identify the independent prognostic factors for OS.In total, 256 metastatic UC patients were enrolled. Univariate analysis revealed that patients with either a high NLR or PC had a significantly shorter survival rate compared with those with a low NLR (P = .001 or PC (P < .0001. The median OS in patients with NPS 0, 1, and 2 was 19.0, 12.8, and 9.3 months, respectively (P < .0001. Multivariate analysis revealed that NPS, along with the histologic variant, liver metastasis, age, and white cell count, was an independent factor facilitating OS prediction (hazard ratio 1.64, 95% confidence interval 1.20-2.24, P = .002.The NLR and PC are independent prognostic factors for OS in patients with metastatic UC. The NPS model has excellent discriminant ability for OS.

Comparative genome analysis of Megasphaera sp. reveals niche specialization and its potential role in the human gut.

Directory of Open Access Journals (Sweden)

Sudarshan Anand Shetty

Full Text Available With increasing number of novel bacteria being isolated from the human gut ecosystem, there is a greater need to study their role in the gut ecosystem and their effect on the host health. In the present study, we carried out in silico genome-wide analysis of two novel Megasphaera sp. isolates NM10 (DSM25563 and BL7 (DSM25562, isolated from feces of two healthy individuals and validated the key features by in vitro studies. The analysis revealed the general metabolic potential, adaptive features and the potential effects of these isolates on the host. The comparative genome analysis of the two human gut isolates NM10 and BL7 with ruminal isolate Megasphaera elsdenii (DSM20460 highlighted the differential adaptive features for their survival in human gut. The key findings include features like bile resistance, presence of various sensory and regulatory systems, stress response systems, membrane transporters and resistance to antibiotics. Comparison of the "glycobiome" based on the genomes of the ruminal isolate with the human gut isolates NM10 and BL revealed the presence of diverse and unique sets of Carbohydrate-Active enzymes (CAZymes amongst these isolates, with a higher collection of CAZymes in the human gut isolates. This could be attributed to the difference in host diet and thereby the environment, consequently suggesting host specific adaptation in these isolates. In silico analysis of metabolic potential predicted the ability of these isolates to produce important metabolites like short chain fatty acids (butyrate, acetate, formate, and caproate, vitamins and essential amino acids, which was further validated by in vitro experiments. The ability of these isolates to produce important metabolites advocates for a potential healthy influence on the host. Further in vivo studies including transcriptomic and proteomic analysis will be required for better understanding the role and impact of these Megasphaera sp. isolates NM10 and BL7 on the

Estimation of failure criteria in multivariate sensory shelf life testing using survival analysis.

Science.gov (United States)

Giménez, Ana; Gagliardi, Andrés; Ares, Gastón

2017-09-01

For most food products, shelf life is determined by changes in their sensory characteristics. A predetermined increase or decrease in the intensity of a sensory characteristic has frequently been used to signal that a product has reached the end of its shelf life. Considering all attributes change simultaneously, the concept of multivariate shelf life allows a single measurement of deterioration that takes into account all these sensory changes at a certain storage time. The aim of the present work was to apply survival analysis to estimate failure criteria in multivariate sensory shelf life testing using two case studies, hamburger buns and orange juice, by modelling the relationship between consumers' rejection of the product and the deterioration index estimated using PCA. In both studies, a panel of 13 trained assessors evaluated the samples using descriptive analysis whereas a panel of 100 consumers answered a "yes" or "no" question regarding intention to buy or consume the product. PC1 explained the great majority of the variance, indicating all sensory characteristics evolved similarly with storage time. Thus, PC1 could be regarded as index of sensory deterioration and a single failure criterion could be estimated through survival analysis for 25 and 50% consumers' rejection. The proposed approach based on multivariate shelf life testing may increase the accuracy of shelf life estimations. Copyright © 2017 Elsevier Ltd. All rights reserved.

The costs of treating acute heart failure: an economic analysis of the SURVIVE trial.

Science.gov (United States)

de Lissovoy, Gregory; Fraeman, Kathy; Salon, Jeff; Chay Woodward, Tatia; Sterz, Raimund

2008-01-01

To estimate the incremental cost per life year gained with levosimendan relative to dobutamine in treatment of acute heart failure based on the Survival of Patients with Acute Heart Failure in Need of Intravenous Inotropic Support (SURVIVE) trial. SURVIVE enrolled 1,327 patients (levosimendan 664, dobutamine 663) from nine nations with 180-day survival from date of randomisation as the primary endpoint. Hospital resource utilisation was determined via clinical case reports. Unit costs were derived from hospital payment schedules for France, Germany and the UK, and represent a third-party payer perspective. Cost-effectiveness analysis was performed for a subset of the SURVIVE patient population selected in accordance with current levosimendan labeling. Mortality in the levosimendan group was 26 versus 28% for dobutamine (hazard ratio 0.91, 95% confidence interval 0.74-1.13, p=0.40). Initial hospitalisation length of stay was identical (levosimendan 14.4, dobutamine 14.5, p=0.98). Slightly lower rates of readmission were observed for levosimendan relative to dobutamine at 31 (p=0.13) and 180 days (p=0.23). Mean costs excluding study drug were equivalent for the index admission (levosimendan euro5,060, dobutamine euro4,952; p=0.91) and complete episode (levosimendan euro5,396, dobutamine euro5,275; p=0.93). At an acquisition cost of euro600 per vial, there is at least 50% likelihood that levosimendan is cost effective relative to dobutamine if willingness to pay is equal to or greater than euro15,000 per life year gained.

Adjuvant brachytherapy removes survival disadvantage of local disease extension in stage IIIC endometrial cancer: a SEER registry analysis.

Science.gov (United States)

Rossi, Peter J; Jani, Ashesh B; Horowitz, Ira R; Johnstone, Peter A S

2008-01-01

To assess the role of radiotherapy (RT) in women with Stage IIIC endometrial cancer. The 17-registry Survival, Epidemiology, and End Results (SEER) database was searched for patients with lymph node-positive non-Stage IV epithelial endometrial cancer diagnosed and treated between 1988 and 1998. Two subgroups were identified: those with organ-confined Stage IIIC endometrial cancer and those with Stage IIIC endometrial cancer with direct extension of the primary tumor. RT was coded as external beam RT (EBRT) or brachytherapy (BT). Observed survival (OS) was reported with a minimum of 5 years of follow-up; the survival curves were compared using the log-rank test. The therapy data revealed 611 women with Stage IIIC endometrial cancer during this period. Of these women, 51% were treated with adjuvant EBRT, 21% with EBRT and BT, and 28% with no additional RT (NAT). Of the 611 patients, 293 had organ-confined Stage IIIC endometrial cancer and 318 patients had Stage IIIC endometrial cancer with direct extension of the primary tumor. The 5-year OS rate for all patients was 40% with NAT, 56% after EBRT, and 64% after EBRT/BT. Adjuvant RT improved survival compared with NAT (p primary tumor was present, the addition of BT to EBRT was even more beneficial.

Prognostic factors for survival in patients with Ewing's sarcoma using the surveillance, epidemiology, and end results (SEER) program database.

Science.gov (United States)

Duchman, Kyle R; Gao, Yubo; Miller, Benjamin J

2015-04-01

The current study aims to determine cause-specific survival in patients with Ewing's sarcoma while reporting clinical risk factors for survival. The Surveillance, Epidemiology, and End Results (SEER) Program database was used to identify patients with osseous Ewing's sarcoma from 1991 to 2010. Patient, tumor, and socioeconomic variables were analyzed to determine prognostic factors for survival. There were 1163 patients with Ewing's sarcoma identified in the SEER Program database. The 10-year cause-specific survival for patients with non-metastatic disease at diagnosis was 66.8% and 28.1% for patients with metastatic disease. Black patients demonstrated reduced survival at 10 years with an increased frequency of metastatic disease at diagnosis as compared to patients of other race, while Hispanic patients more frequently presented with tumor size>10cm. Univariate analysis revealed that metastatic disease at presentation, tumor size>10cm, axial tumor location, patient age≥20 years, black race, and male sex were associated with decreased cause-specific survival at 10 years. Metastatic disease at presentation, axial tumor location, tumor size>10cm, and age≥20 years remained significant in the multivariate analysis. Patients with Ewing's sarcoma have decreased cause-specific survival at 10 years when metastatic at presentation, axial tumor location, tumor size>10cm, and patient age≥20 years. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinicopathological analysis of recurrence patterns and prognostic factors for survival after hepatectomy for colorectal liver metastasis

Directory of Open Access Journals (Sweden)

Okuda Junji

2010-09-01

Full Text Available Abstract Background Hepatectomy is recommended as the most effective therapy for liver metastasis from colorectal cancer (CRCLM. It is crucial to elucidate the prognostic clinicopathological factors. Methods Eighty-three patients undergoing initial hepatectomy for CRCLM were retrospectively analyzed with respect to characteristics of primary colorectal and metastatic hepatic tumors, operation details and prognosis. Results The overall 5-year survival rate after initial hepatectomy for CRCLM was 57.5%, and the median survival time was 25 months. Univariate analysis clarified that the significant prognostic factors for poor survival were depth of primary colorectal cancer (≥ serosal invasion, hepatic resection margin ( Conclusions Optimal surgical strategies in conjunction with effective chemotherapeutic regimens need to be established in patients with risk factors for recurrence and poor outcomes as listed above.

Sociocultural Factors of Survival of Males and Females in Economically Active Age: a Regional Analysis

Directory of Open Access Journals (Sweden)

Evgeniya Khasanovna Tukhtarova

2018-03-01

Full Text Available The period, when a person starts and completes his or her professional carrier and labour participation, in general, coincides with the age when the self-preservation behaviour develops. It is a time when a person aims for a healthy and safe lifestyle. During this period, an individual assumes the main standards, values of the self-preservation behaviour inherent in an ethnic, social and cultural macro-environment. To research the sociocultural factors of survival, we applied econometric modelling to demographic processes using the discrete and probabilistic indicators of the mortality tables of male and female in economically active age. The econometric model included the elements of spatiotemporal characteristics of territories. These characteristics are interrelated with the indicators of survival probability and the indicator of average life expectancy in the regions of Russia. We choose the major sociocultural factors by the correlation ratio of indicators and their sensitivity. The econometric analysis has revealed a high degree of sensitivity of a territorial variation of demographic and sociocultural factors in the regions of Russia, including a gender aspect. The most significant socio-economic factors, which determine the self-preservation behaviour of males, are the following: 1 the size of Gross Regional Product per capita; 2 quality of health infrastructure; 3 fixed investments; 4 population with monetary income under the subsistence minimum (share coefficient of income differentials. The female have the same hierarchy of socio-economic factors, except for the sensitivity of variables to the regional differentiation of signs. The household poverty factor has little significance for the women and it is the main difference between male and female. The built model has shown the predictive importance in the assessment of the above-mentioned factors in short and medium-term prospects.

Propensity Score Matched Comparison of Intensity Modulated Radiation Therapy vs Stereotactic Body Radiation Therapy for Localized Prostate Cancer: A Survival Analysis from the National Cancer Database

Directory of Open Access Journals (Sweden)

Anthony Ricco

2017-08-01

Full Text Available PurposeNo direct comparisons between extreme hypofractionation and conventional fractionation have been reported in randomized trials for the treatment of localized prostate cancer. The goal of this study is to use a propensity score matched (PSM analysis with the National Cancer Database (NCDB for the comparison of stereotactic body radiation therapy (SBRT and intensity modulated radiation therapy (IMRT for organ confined prostate cancer.MethodsMen with localized prostate cancer treated with radiation dose ≥72 Gy for IMRT and ≥35 Gy for SBRT to the prostate only were abstracted from the NCDB. Men treated with previous surgery, brachytherapy, or proton therapy were excluded. Matching was performed to eliminate confounding variables via PSM. Simple 1–1 nearest neighbor matching resulted in a matched sample of 5,430 (2,715 in each group. Subset analyses of men with prostate-specific antigen (PSA > 10, GS = 7, and GS > 7 yielded matched samples of 1,020, 2,194, and 247, respectively.ResultsNo difference in survival was noted between IMRT and SBRT at 8 years (p = 0.65. Subset analyses of higher risk men with PSA > 10 or GS = 7 histology or GS > 7 histology revealed no difference in survival between IMRT and SBRT (p = 0.58, p = 0.68, and p = 0.62, respectively. Variables significant for survival for the matched group included: age (p < 0.0001, primary payor (p = 0.0001, Charlson/Deyo Score (p = 0.0002, PSA (p = 0.0013, Gleason score (p < 0.0001, and use of hormone therapy (p = 0.02.ConclusionUtilizing the NCDB, there is no difference in survival at 8 years comparing IMRT to SBRT in the treatment of localized prostate cancer. Subset analysis confirmed no difference in survival even for intermediate- and high-risk patients based on Gleason Score and PSA.

Meta-regression analysis of commensal and pathogenic Escherichia coli survival in soil and water.

Science.gov (United States)

Franz, Eelco; Schijven, Jack; de Roda Husman, Ana Maria; Blaak, Hetty

2014-06-17

The extent to which pathogenic and commensal E. coli (respectively PEC and CEC) can survive, and which factors predominantly determine the rate of decline, are crucial issues from a public health point of view. The goal of this study was to provide a quantitative summary of the variability in E. coli survival in soil and water over a broad range of individual studies and to identify the most important sources of variability. To that end, a meta-regression analysis on available literature data was conducted. The considerable variation in reported decline rates indicated that the persistence of E. coli is not easily predictable. The meta-analysis demonstrated that for soil and water, the type of experiment (laboratory or field), the matrix subtype (type of water and soil), and temperature were the main factors included in the regression analysis. A higher average decline rate in soil of PEC compared with CEC was observed. The regression models explained at best 57% of the variation in decline rate in soil and 41% of the variation in decline rate in water. This indicates that additional factors, not included in the current meta-regression analysis, are of importance but rarely reported. More complete reporting of experimental conditions may allow future inference on the global effects of these variables on the decline rate of E. coli.

Revealed social preference for potable groundwater: An Eastern Iowa case study

Science.gov (United States)

Raunikar, R. P.; Bernknopf, R. L.; Forney, W.; Mishra, S.

2011-12-01

The spatially explicit land use and land cover information provided by Landsat moderate-resolution land imagery (MRLI) is needed to more efficiently balance the production of goods and services over landscapes. For example, economic trade-offs are needed to provide both clean groundwater resources and other non-environmental goods and services produced by activities that affect the vadose zone and thus contribute to contamination of groundwater. These trade-off choices are made by numerous economic agents and are constrained by many social institutions including governmental regulations at many levels, contractual obligations and traditions. In effect, on a social level, society acts as if it values groundwater by foregoing other goods to protect these resources. The result of the protection afforded to groundwater resources is observable by measuring contamination in well samples. This observed level of groundwater contamination risk is the revealed preference of society as a whole for clean groundwater. We observed the risk of groundwater contamination in a sampling of well data from our study area (35 counties of Eastern Iowa.) We used a proportional hazard model to quantify the nitrate contamination survival implied by the panel of 19,873 well data, where remaining below a 10 mg/ml maximum contamination level (MCL) is defined as survival. We tested the data for evidence that the levels of protection provided to these resources is correlated with aquifer and vadose zone characteristics and geographic location and whether it changed over time and with economic and other conditions. We demonstrate the use of a nitrate conditioned hazard function for projecting the survival of wells based on nitrate exposure information over the 1940 to 2010 time period. We discuss results of simulations of the survival process that demonstrate the economic significance of this approach. We find that aquifer survival has been significantly improving over time. The principle of

Correlation of hedgehog signal activation with chemoradiotherapy sensitivity and survival in esophageal squamous cell carcinomas

International Nuclear Information System (INIS)

Zhu Weiguo; You Zhenbin; Li Tao; Yu Changhua; Tao Guangzhou; Hu Mingli; Chen Xiaofei

2011-01-01

The objective of this study was to investigate the significance of hedgehog signaling pathway in chemoradiotherapy sensitivity and its effect on the prognosis of esophageal squamous cell carcinoma. In the present study, we used the method of immunohistochemistry to examine the expression status of two hedgehog components, PTCH1 and glioma-associated oncogene GLI-1, in 100 pre-treated biopsy specimens of esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy. We find that high levels of PTCH1 and GLI-1 were detected in 76.0 and 72.0% of esophageal squamous cell carcinoma, respectively. Significant associations of high PTCH1 and GLI-1 expression with large tumor size (both P=0.01), locoregional progression (P=0.001 and 0.003, respectively) and the lack of complete response to chemoradiotherapy (P=0.008 and 0.01, respectively) were observed. Univariate analysis revealed that high PTCH1 and GLI-1 expression was associated with poor locoregional progression-free survival, distant progression-free survival and overall survival. Furthermore, esophageal squamous cell carcinoma patients with high PTCH1 and GLI-1 expression have the shorter survival time than the subgroups with negative and low PTCH1 and GLI-1 expression. In multivariate analysis, PTCH1 and GLI-1 expression status were both evaluated as independent prognostic factors for locoregional progression-free survival, distant progression-free survival and overall survival. These findings suggest an important role for the activation of hedgehog signaling in esophageal squamous cell carcinoma progression and that PTCH1 and GLI-1 expression may be significantly associated with esophageal squamous cell carcinoma resistance to chemoradiotherapy. (author)

Survival analysis using primary care electronic health record data: A systematic review of the literature.

Science.gov (United States)

Hodgkins, Adam Jose; Bonney, Andrew; Mullan, Judy; Mayne, Darren John; Barnett, Stephen

2018-01-01

An emerging body of research involves observational studies in which survival analysis is applied to data obtained from primary care electronic health records (EHRs). This systematic review of these studies examined the utility of using this approach. An electronic literature search of the Scopus, PubMed, Web of Science, CINAHL, and Cochrane databases was conducted. Search terms and exclusion criteria were chosen to select studies where survival analysis was applied to the data extracted wholly from EHRs used in primary care medical practice. A total of 46 studies that met the inclusion criteria for the systematic review were examined. All were published within the past decade (2005-2014) with a majority ( n = 26, 57%) being published between 2012 and 2014. Even though citation rates varied from nil to 628, over half ( n = 27, 59%) of the studies were cited 10 times or more. The median number of subjects was 18,042 with five studies including over 1,000,000 patients. Of the included studies, 35 (76%) were published in specialty journals and 11 (24%) in general medical journals. The many conditions studied largely corresponded well with conditions important to general practice. Survival analysis applied to primary care electronic medical data is a research approach that has been frequently used in recent times. The utility of this approach was demonstrated by the ability to produce research with large numbers of subjects, across a wide range of conditions and with the potential of a high impact. Importantly, primary care data were thus available to inform primary care practice.

Determinants of malignant pleural mesothelioma survival and burden of disease in France: a national cohort analysis.

Science.gov (United States)

Chouaid, Christos; Assié, Jean Baptiste; Andujar, Pascal; Blein, Cecile; Tournier, Charlène; Vainchtock, Alexandre; Scherpereel, Arnaud; Monnet, Isabelle; Pairon, Jean Claude

2018-04-01

This study was undertaken to determine the healthcare burden of malignant pleural mesothelioma (MPM) in France and to analyze its associations with socioeconomic deprivation, population density, and management outcomes. A national hospital database was used to extract incident MPM patients in years 2011 and 2012. Cox models were used to analyze 1- and 2-year survival according to sex, age, co-morbidities, management, population-density index, and social deprivation index. The analysis included 1,890 patients (76% men; age: 73.6 ± 10.0 years; 84% with significant co-morbidities; 57% living in urban zones; 53% in highly underprivileged areas). Only 1% underwent curative surgical procedure; 65% received at least one chemotherapy cycle, 72% of them with at least one pemetrexed and/or bevacizumab administration. One- and 2-year survival rates were 64% and 48%, respectively. Median survival was 14.9 (95% CI: 13.7-15.7) months. The mean cost per patient was 27,624 ± 17,263 euros (31% representing pemetrexed and bevacizumab costs). Multivariate analyses retained men, age >70 years, chronic renal failure, chronic respiratory failure, and never receiving pemetrexed as factors of poor prognosis. After adjusting the analysis to age, sex, and co-morbidities, living in rural/semi-rural area was associated with better 2-year survival (HR: 0.83 [95% CI: 0.73-0.94]; P < 0.01); social deprivation index was not significantly associated with survival. With approximately 1,000 new cases per year in France, MPMs represents a significant national health care burden. Co-morbidities, sex, age, and living place appear to be significant factors of prognosis. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Lamb survival analysis from birth to weaning in Iranian Kermani sheep.

Science.gov (United States)

Barazandeh, Arsalan; Moghbeli, Sadrollah Molaei; Vatankhah, Mahmood; Hossein-Zadeh, Navid Ghavi

2012-04-01

Survival records from 1,763 Kermani lambs born between 1996 and 2004 from 294 ewes and 81 rams were used to determine genetic and non-genetic factors affecting lamb survival. Traits included were lamb survival across five periods from birth to 7, 14, 56, 70, and 90 days of age. Traits were analyzed under Weibull proportional hazard sire models. Several binary analyses were also conducted using animal models. Statistical models included the fixed class effects of sex of lamb, month and year of birth, a covariate effect of birth weight, and random genetic effects of both sire (in survival analyses) and animal (in binary analyses). The average survival to 90 days of age was 94.8%. Hazard rates ranged from 1.00 (birth to 90 days of age) to 1.73 (birth to 7 days of age) between the two sexes indicating that male lambs were at higher risk of mortality than females (P lamb survival and lamb birth weight, suggesting that viability and birth weight could be considered simultaneously in the selection programs to obtain optimal birth weight in Kermani lambs. Estimates of heritabilities from survival analyses were medium and ranged from 0.23 to 0.29. In addition, heritability estimates obtained from binary analyses were low and varied from 0.04 to 0.09. The results of this study suggest that progress in survival traits could be possible through managerial strategies and genetic selection.

Split Course Hyperfractionated Accelerated Radio-Chemotherapy (SCHARC) for patients with advanced head and neck cancer: Influence of protocol deviations and hemoglobin on overall survival, a retrospective analysis

International Nuclear Information System (INIS)

Stadler, Peter; Putnik, Kurt; Kreimeyer, Thore; Sprague, Lisa D; Koelbl, Oliver; Schäfer, Christof

2006-01-01

The advantage of hyperfractionated accelerated radiation therapy for advanced head and neck cancer has been reported. Furthermore, randomized trials and meta-analyses have confirmed the survival benefit of additional chemotherapy to radiotherapy. We retrospectively analyzed the efficiency and toxicity of the Regensburg standard therapy protocol 'SCHARC' and the overall survival of our patients. From 1997 to 2004, 64 patients suffering from advanced head and neck cancer (88 % stage IV, 12 % stage III) were assigned to receive the SCHARC protocol. Around half of the patients were diagnosed with oro-hypopharynx carcinoma (52 %), one third with tongue and floor of mouth tumors (29 %) and one fifth (19 %) suffered from H & N cancer at other sites. The schedule consisted of one therapy block with 30 Gy in 20 fractions over a two week period with concomitant chemotherapy (d 1–5: 20 mg/m 2 /d DDP + 750–1000 mg/m 2 /d 5FU (cont. infusion). This therapy block was repeated after a fortnight break up to a cumulative dose of 60 Gy and followed by a boost up to 70 Gy (69–70.5 Gy). All patients assigned to this scheme were included in the survival evaluation. Forty patients (63 %) received both radiation and chemotherapy according to the protocol. The mean follow up was 2.3 years (829 d) and the median follow up was 1.9 years (678 d), respectively. The analysis of survival revealed an estimated 3 year overall survival rate of 57 %. No patient died of complications, 52 patients (80 %) had acute grade 2–3 mucositis, and 33 patients (58 %) suffered from acute grade 3 skin toxicity. Leucopenia was no major problem (mean nadir 3.4 g/nl, no patient < 1.0 g/nl) and the mean hemoglobin value decreased from 13.2 to 10.5 g/dl. Univariate analysis of survival showed a better outcome for patients with a hemoglobin nadir >10.5 g/dl and for patients who completed the protocol. The SCHARC protocol was effective in patients diagnosed with advanced head and neck cancer. It led

Split course hyperfractionated accelerated radio-chemotherapy (SCHARC) for patients with advanced head and neck cancer: influence of protocol deviations and hemoglobin on overall survival, a retrospective analysis.

Science.gov (United States)

Stadler, Peter; Putnik, Kurt; Kreimeyer, Thore; Sprague, Lisa D; Koelbl, Oliver; Schäfer, Christof

2006-12-07

The advantage of hyperfractionated accelerated radiation therapy for advanced head and neck cancer has been reported. Furthermore, randomized trials and meta-analyses have confirmed the survival benefit of additional chemotherapy to radiotherapy. We retrospectively analyzed the efficiency and toxicity of the Regensburg standard therapy protocol "SCHARC" and the overall survival of our patients. From 1997 to 2004, 64 patients suffering from advanced head and neck cancer (88 % stage IV, 12 % stage III) were assigned to receive the SCHARC protocol. Around half of the patients were diagnosed with oro-hypopharynx carcinoma (52 %), one third with tongue and floor of mouth tumors (29 %) and one fifth (19 %) suffered from H & N cancer at other sites. The schedule consisted of one therapy block with 30 Gy in 20 fractions over a two week period with concomitant chemotherapy (d 1-5: 20 mg/m2/d DDP + 750-1000 mg/m2/d 5FU (cont. infusion). This therapy block was repeated after a fortnight break up to a cumulative dose of 60 Gy and followed by a boost up to 70 Gy (69-70.5 Gy). All patients assigned to this scheme were included in the survival evaluation. Forty patients (63 %) received both radiation and chemotherapy according to the protocol. The mean follow up was 2.3 years (829 d) and the median follow up was 1.9 years (678 d), respectively. The analysis of survival revealed an estimated 3 year overall survival rate of 57 %. No patient died of complications, 52 patients (80 %) had acute grade 2-3 mucositis, and 33 patients (58 %) suffered from acute grade 3 skin toxicity. Leucopenia was no major problem (mean nadir 3.4 g/nl, no patient hemoglobin value decreased from 13.2 to 10.5 g/dl. Univariate analysis of survival showed a better outcome for patients with a hemoglobin nadir >10.5 g/dl and for patients who completed the protocol. The SCHARC protocol was effective in patients diagnosed with advanced head and neck cancer. It led to long-term disease control and survival in

The survival of Coxiella burnetii in soils

Science.gov (United States)

Evstigneeva, A. S.; Ul'Yanova, T. Yu.; Tarasevich, I. V.

2007-05-01

Coxiella burnetii is a pathogen of Q-fever—a widespread zoonosis. The effective adaptation of C. burnetii to intracellular existence is in contrast with its ability to survive in the environment outside the host cells and its resistance to chemical and physical agents. Its mechanism of survival remains unknown. However, its survival appears to be related to the developmental cycle of the microorganism itself, i.e., to the formation of its dormant forms. The survival of Coxiella burnetii was studied for the first time. The pathogenic microorganism was inoculated into different types of soil and cultivated under different temperatures. The survival of the pathogen was verified using a model with laboratory animals (mice). Viable C. burnetii were found in the soil even 20 days after their inoculation. The relationship between the organic carbon content in the soils and the survival of C. burnetii was revealed. Thus, the results obtained were the first to demonstrate that the soil may serve as a reservoir for the preservation and further spreading of the Q-fever pathogen in the environment, on the one hand, and reduce the risk of epidemics, on the other.

Causal Mediation Analysis of Survival Outcome with Multiple Mediators.

Science.gov (United States)

Huang, Yen-Tsung; Yang, Hwai-I

2017-05-01

Mediation analyses have been a popular approach to investigate the effect of an exposure on an outcome through a mediator. Mediation models with multiple mediators have been proposed for continuous and dichotomous outcomes. However, development of multimediator models for survival outcomes is still limited. We present methods for multimediator analyses using three survival models: Aalen additive hazard models, Cox proportional hazard models, and semiparametric probit models. Effects through mediators can be characterized by path-specific effects, for which definitions and identifiability assumptions are provided. We derive closed-form expressions for path-specific effects for the three models, which are intuitively interpreted using a causal diagram. Mediation analyses using Cox models under the rare-outcome assumption and Aalen additive hazard models consider effects on log hazard ratio and hazard difference, respectively; analyses using semiparametric probit models consider effects on difference in transformed survival time and survival probability. The three models were applied to a hepatitis study where we investigated effects of hepatitis C on liver cancer incidence mediated through baseline and/or follow-up hepatitis B viral load. The three methods show consistent results on respective effect scales, which suggest an adverse estimated effect of hepatitis C on liver cancer not mediated through hepatitis B, and a protective estimated effect mediated through the baseline (and possibly follow-up) of hepatitis B viral load. Causal mediation analyses of survival outcome with multiple mediators are developed for additive hazard and proportional hazard and probit models with utility demonstrated in a hepatitis study.

Survival analysis of postoperative nausea and vomiting in patients receiving patient-controlled epidural analgesia

Directory of Open Access Journals (Sweden)

Shang-Yi Lee

2014-11-01

Conclusion: Survival analysis using Cox regression showed that the average consumption of opioids played an important role in postoperative nausea and vomiting, a result not found by logistic regression. Therefore, the incidence of postoperative nausea and vomiting in patients cannot be reliably determined on the basis of a single visit at one point in time.

Nitrosourea efficacy in high-grade glioma: a survival gain analysis summarizing 504 cohorts with 24193 patients.

Science.gov (United States)

Wolff, Johannes E A; Berrak, Su; Koontz Webb, Susannah E; Zhang, Ming

2008-05-01

Even though past studies have suggested efficacy of nitrosourea drugs in patients with high-grade glioma and temozolomide has recently been shown significantly to be beneficial, no conclusive comparisons between these agents have been published. We performed a survival gain analysis of 364 studies describing 24,193 patients with high-grade glioma treated in 504 cohorts, and compared the effects of drugs. The most frequent diagnoses were glioblastoma multiforme (GBM) (72%) and anaplastic astrocytoma (22%). The mean overall survival (mOS) was 14.1 months. The outcome was influenced by several of the known prognostic factors including the histological grade, if the tumors were newly diagnosed or recurrent, the completeness of resection, patients' age, and gender. This information allowed the calculation of a predicted mOS for each cohort based on their prognostic factors independent of treatment. Survival gain to characterize the influence of treatment was subsequently defined and validated as the difference between the observed and the predicted mOS. In 62 CCNU-treated cohorts and 15 ACNU-treated cohorts the survival gain was 5.3 months and 8.9 months (P < 0.0005), respectively. No detectable survival gain for patients treated with various BCNU-containing regimens was found. Conclusion CCNU- and ACNU-containing regimens were superior to BCNU containing regiments.

Association of body mass index and survival in pediatric leukemia: a meta-analysis.

Science.gov (United States)

Orgel, Etan; Genkinger, Jeanine M; Aggarwal, Divya; Sung, Lillian; Nieder, Michael; Ladas, Elena J

2016-03-01

Obesity is a worldwide epidemic in children and adolescents. Adult cohort studies have reported an association between higher body mass index (BMI) and increased leukemia-related mortality; whether a similar effect exists in childhood leukemia remains controversial. We conducted a meta-analysis to determine whether a higher BMI at diagnosis of pediatric acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) is associated with worse event-free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR). We searched 4 electronic databases from inception through March 2015 without language restriction and included studies in pediatric ALL or AML (0-21 y of age) reporting BMI as a predictor of survival or relapse. Higher BMI, defined as obese (≥95%) or overweight/obese (≥85%), was compared with lower BMI [nonoverweight/obese (children with a higher BMI (RR: 1.35; 95% CI: 1.20, 1.51) than in those at a lower BMI. A higher BMI was associated with significantly increased mortality (RR: 1.31; 95% CI: 1.09, 1.58) and a statistically nonsignificant trend toward greater risk of relapse (RR: 1.17; 95% CI: 0.99, 1.38) compared with a lower BMI. In AML, a higher BMI was significantly associated with poorer EFS and OS (RR: 1.36; 95% CI: 1.16, 1.60 and RR: 1.56; 95% CI: 1.32, 1.86, respectively) than was a lower BMI. Higher BMI at diagnosis is associated with poorer survival in children with pediatric ALL or AML. © 2016 American Society for Nutrition.

Prognostic value of pre-treatment DCE-MRI parameters in predicting disease free and overall survival for breast cancer patients undergoing neoadjuvant chemotherapy

International Nuclear Information System (INIS)

Pickles, Martin D.; Manton, David J.; Lowry, Martin; Turnbull, Lindsay W.

2009-01-01

The purpose of this study was to investigate whether dynamic contrast enhanced MRI (DCE-MRI) data, both pharmacokinetic and empirical, can predict, prior to neoadjuvant chemotherapy, which patients are likely to have a shorter disease free survival (DFS) and overall survival (OS) interval following surgery. Traditional prognostic parameters were also included in the survival analysis. Consequently, a comparison of the prognostic value could be made between all the parameters studied. MR examinations were conducted on a 1.5 T system in 68 patients prior to the initiation of neoadjuvant chemotherapy. DCE-MRI consisted of a fast spoiled gradient echo sequence acquired over 35 phases with a mean temporal resolution of 11.3 s. Both pharmacokinetic and empirical parameters were derived from the DCE-MRI data. Kaplan-Meier survival plots were generated for each parameter and group comparisons were made utilising logrank tests. The results from the 54 patients entered into the univariate survival analysis demonstrated that traditional prognostic parameters (tumour grade, hormonal status and size), empirical parameters (maximum enhancement index, enhancement index at 30 s, area under the curve and initial slope) and adjuvant therapies demonstrated significant differences in survival intervals. Further multivariate Cox regression survival analysis revealed that empirical enhancement parameters contributed the greatest prediction of both DFS and OS in the resulting models. In conclusion, this study has demonstrated that in patients who exhibit high levels of perfusion and vessel permeability pre-treatment, evidenced by elevated empirical DCE-MRI parameters, a significantly lower disease free survival and overall survival can be expected.

Prognostic value of pre-treatment DCE-MRI parameters in predicting disease free and overall survival for breast cancer patients undergoing neoadjuvant chemotherapy

Energy Technology Data Exchange (ETDEWEB)

Pickles, Martin D. [Centre for Magnetic Resonance Investigations, Division of Cancer, Postgraduate Medical School, University of Hull, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ (United Kingdom)], E-mail: m.pickles@hull.ac.uk; Manton, David J. [Centre for Magnetic Resonance Investigations, Division of Cancer, Postgraduate Medical School, University of Hull, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ (United Kingdom)], E-mail: d.j.manton@hull.ac.uk; Lowry, Martin [Centre for Magnetic Resonance Investigations, Division of Cancer, Postgraduate Medical School, University of Hull, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ (United Kingdom)], E-mail: m.lowry@hull.ac.uk; Turnbull, Lindsay W. [Centre for Magnetic Resonance Investigations, Division of Cancer, Postgraduate Medical School, University of Hull, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ (United Kingdom)], E-mail: l.w.turnbull@hull.ac.uk

2009-09-15

The purpose of this study was to investigate whether dynamic contrast enhanced MRI (DCE-MRI) data, both pharmacokinetic and empirical, can predict, prior to neoadjuvant chemotherapy, which patients are likely to have a shorter disease free survival (DFS) and overall survival (OS) interval following surgery. Traditional prognostic parameters were also included in the survival analysis. Consequently, a comparison of the prognostic value could be made between all the parameters studied. MR examinations were conducted on a 1.5 T system in 68 patients prior to the initiation of neoadjuvant chemotherapy. DCE-MRI consisted of a fast spoiled gradient echo sequence acquired over 35 phases with a mean temporal resolution of 11.3 s. Both pharmacokinetic and empirical parameters were derived from the DCE-MRI data. Kaplan-Meier survival plots were generated for each parameter and group comparisons were made utilising logrank tests. The results from the 54 patients entered into the univariate survival analysis demonstrated that traditional prognostic parameters (tumour grade, hormonal status and size), empirical parameters (maximum enhancement index, enhancement index at 30 s, area under the curve and initial slope) and adjuvant therapies demonstrated significant differences in survival intervals. Further multivariate Cox regression survival analysis revealed that empirical enhancement parameters contributed the greatest prediction of both DFS and OS in the resulting models. In conclusion, this study has demonstrated that in patients who exhibit high levels of perfusion and vessel permeability pre-treatment, evidenced by elevated empirical DCE-MRI parameters, a significantly lower disease free survival and overall survival can be expected.

The survival-reproduction association becomes stronger when conditions are good.

Science.gov (United States)

Robert, Alexandre; Bolton, Mark; Jiguet, Frédéric; Bried, Joël

2015-11-07

Positive covariations between survival and reproductive performance (S-R covariation) are generally interpreted in the context of fixed or dynamic demographic heterogeneity (i.e. persistent differences between individuals, or dynamic variation in resource acquisition), but the processes underlying covariations are still unknown. We used multi-event modelling to investigate how environmental and individual features influence S-R covariation patterns in a long-lived seabird, the Monteiro's storm petrel (Oceanodroma monteiroi). Our analysis reveals that a strong positive association between individual breeding success and subsequent survival occurs only when conditions are favourable to reproduction (in favourable years, in high-quality nests and in nest-faithful breeders). This finding reflects differences in the main causes of breeding failure and mortality under favourable and unfavourable conditions, which in turn lead to distinct patterns of S-R covariation. We suggest, in particular, that resource-related sources of demographic heterogeneity do not generate a strong S-R covariation, in contrast with hidden and unpredictable sources of variation. © 2015 The Author(s).

Roles of TRPM8 Ion Channels in Cancer: Proliferation, Survival, and Invasion

Directory of Open Access Journals (Sweden)

Nelson S. Yee

2015-10-01

Full Text Available The goal of this article is to provide a critical review of the transient receptor potential melastatin-subfamily member 8 (TRPM8 in cancers, with an emphasis on its roles in cellular proliferation, survival, and invasion. The TRPM8 ion channels regulate Ca²⁺ homeostasis and function as a cellular sensor and transducer of cold temperature. Accumulating evidence has demonstrated that TRPM8 is aberrantly expressed in a variety of malignant solid tumors. Clinicopathological analysis has shown that over-expression of TRPM8 correlates with tumor progression. Experimental data have revealed important roles of TRPM8 channels in cancer cells proliferation, survival, and invasion, which appear to be dependent on the cancer type. Recent reports have begun to reveal the signaling mechanisms that mediate the biological roles of TRPM8 in tumor growth and metastasis. Determining the mechanistic roles of TRPM8 in cancer is expected to elucidate the impact of thermal and chemical stimuli on the formation and progression of neoplasms. Translational research and clinical investigation of TRPM8 in malignant diseases will help exploit these ion channels as molecular biomarkers and therapeutic targets for developing precision cancer medicine.

Predictive model for survival in patients with gastric cancer.

Science.gov (United States)

Goshayeshi, Ladan; Hoseini, Benyamin; Yousefli, Zahra; Khooie, Alireza; Etminani, Kobra; Esmaeilzadeh, Abbas; Golabpour, Amin

2017-12-01

Gastric cancer is one of the most prevalent cancers in the world. Characterized by poor prognosis, it is a frequent cause of cancer in Iran. The aim of the study was to design a predictive model of survival time for patients suffering from gastric cancer. This was a historical cohort conducted between 2011 and 2016. Study population were 277 patients suffering from gastric cancer. Data were gathered from the Iranian Cancer Registry and the laboratory of Emam Reza Hospital in Mashhad, Iran. Patients or their relatives underwent interviews where it was needed. Missing values were imputed by data mining techniques. Fifteen factors were analyzed. Survival was addressed as a dependent variable. Then, the predictive model was designed by combining both genetic algorithm and logistic regression. Matlab 2014 software was used to combine them. Of the 277 patients, only survival of 80 patients was available whose data were used for designing the predictive model. Mean ?SD of missing values for each patient was 4.43?.41 combined predictive model achieved 72.57% accuracy. Sex, birth year, age at diagnosis time, age at diagnosis time of patients' family, family history of gastric cancer, and family history of other gastrointestinal cancers were six parameters associated with patient survival. The study revealed that imputing missing values by data mining techniques have a good accuracy. And it also revealed six parameters extracted by genetic algorithm effect on the survival of patients with gastric cancer. Our combined predictive model, with a good accuracy, is appropriate to forecast the survival of patients suffering from Gastric cancer. So, we suggest policy makers and specialists to apply it for prediction of patients' survival.

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.

Support vector methods for survival analysis: a comparison between ranking and regression approaches.

Science.gov (United States)

Van Belle, Vanya; Pelckmans, Kristiaan; Van Huffel, Sabine; Suykens, Johan A K

2011-10-01

To compare and evaluate ranking, regression and combined machine learning approaches for the analysis of survival data. The literature describes two approaches based on support vector machines to deal with censored observations. In the first approach the key idea is to rephrase the task as a ranking problem via the concordance index, a problem which can be solved efficiently in a context of structural risk minimization and convex optimization techniques. In a second approach, one uses a regression approach, dealing with censoring by means of inequality constraints. The goal of this paper is then twofold: (i) introducing a new model combining the ranking and regression strategy, which retains the link with existing survival models such as the proportional hazards model via transformation models; and (ii) comparison of the three techniques on 6 clinical and 3 high-dimensional datasets and discussing the relevance of these techniques over classical approaches fur survival data. We compare svm-based survival models based on ranking constraints, based on regression constraints and models based on both ranking and regression constraints. The performance of the models is compared by means of three different measures: (i) the concordance index, measuring the model's discriminating ability; (ii) the logrank test statistic, indicating whether patients with a prognostic index lower than the median prognostic index have a significant different survival than patients with a prognostic index higher than the median; and (iii) the hazard ratio after normalization to restrict the prognostic index between 0 and 1. Our results indicate a significantly better performance for models including regression constraints above models only based on ranking constraints. This work gives empirical evidence that svm-based models using regression constraints perform significantly better than svm-based models based on ranking constraints. Our experiments show a comparable performance for methods

Relative Quantitative Proteomic Analysis of Brucella abortus Reveals Metabolic Adaptation to Multiple Environmental Stresses

Directory of Open Access Journals (Sweden)

Xiaodong Zai

2017-11-01

Full Text Available Brucella spp. are facultative intracellular pathogens that cause chronic brucellosis in humans and animals. The virulence of Brucella primarily depends on its successful survival and replication in host cells. During invasion of the host tissue, Brucella is simultaneously subjected to a variety of harsh conditions, including nutrient limitation, low pH, antimicrobial defenses, and extreme levels of reactive oxygen species (ROS via the host immune response. This suggests that Brucella may be able to regulate its metabolic adaptation in response to the distinct stresses encountered during its intracellular infection of the host. An investigation into the differential proteome expression patterns of Brucella grown under the relevant stress conditions may contribute toward a better understanding of its pathogenesis and adaptive response. Here, we utilized a mass spectrometry-based label-free relative quantitative proteomics approach to investigate and compare global proteomic changes in B. abortus in response to eight different stress treatments. The 3 h short-term in vitro single-stress and multi-stress conditions mimicked the in vivo conditions of B. abortus under intracellular infection, with survival rates ranging from 3.17 to 73.17%. The proteomic analysis identified and quantified a total of 2,272 proteins and 74% of the theoretical proteome, thereby providing wide coverage of the B. abortus proteome. By including eight distinct growth conditions and comparing these with a control condition, we identified a total of 1,221 differentially expressed proteins (DEPs that were significantly changed under the stress treatments. Pathway analysis revealed that most of the proteins were involved in oxidative phosphorylation, ABC transporters, two-component systems, biosynthesis of secondary metabolites, the citrate cycle, thiamine metabolism, and nitrogen metabolism; constituting major response mechanisms toward the reconstruction of cellular

Effect of Warfarin Treatment on Survival of Patients With Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL).

Science.gov (United States)

Preston, Ioana R; Roberts, Kari E; Miller, Dave P; Sen, Ginny P; Selej, Mona; Benton, Wade W; Hill, Nicholas S; Farber, Harrison W

2015-12-22

Long-term anticoagulation is recommended in idiopathic pulmonary arterial hypertension (IPAH). In contrast, limited data support anticoagulation in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc-PAH). We assessed the effect of warfarin anticoagulation on survival in IPAH and SSc-PAH patients enrolled in Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), a longitudinal registry of group I PAH. Patients who initiated warfarin on study (n=187) were matched 1:1 with patients never on warfarin, by enrollment site, etiology, and diagnosis status. Descriptive analyses were conducted to compare warfarin users and nonusers by etiology. Survival analyses with and without risk adjustment were performed from the time of warfarin initiation or a corresponding quarterly update in matched pairs to avoid immortal time bias. Time-varying covariate models were used as sensitivity analyses. Mean warfarin treatment was 1 year; mean international normalized ratios were 1.9 (IPAH) and 2.0 (SSc-PAH). Two-thirds of patients initiating warfarin discontinued treatment before the last study assessment. There was no survival difference with warfarin in IPAH patients (adjusted hazard ratio, 1.37; P=0.21) or in SSc-PAH patients (adjusted hazard ratio, 1.60; P=0.15) in comparison with matched controls. However, SSc-PAH patients receiving warfarin within the previous year (hazard ratio, 1.57; P=0.031) or any time postbaseline (hazard ratio, 1.49; P=0.046) had increased mortality in comparison with warfarin-naïve patients. No significant survival advantage was observed in IPAH patients who started warfarin. In SSc-PAH patients, long-term warfarin was associated with poorer survival than in patients not receiving warfarin, even after adjusting for confounders. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214. © 2015 The Authors.

Setting the stage for medieval plague: Pre-black death trends in survival and mortality.

Science.gov (United States)

DeWitte, Sharon N

2015-11-01

The 14(th) -century Black Death was one of the most devastating epidemics in human history, killing tens of millions of people in a short period of time. It is not clear why mortality rates during the epidemic were so high. One possibility is that the affected human populations were particularly stressed in the 14(th) century, perhaps as a result of repeated famines in areas such as England. This project examines survival and mortality in two pre-Black Death time periods, 11-12(th) centuries vs 13(th) century CE, to determine if demographic conditions were deteriorating before the epidemic occurred. This study is done using a sample of individuals from several London cemeteries that have been dated, in whole or in part, either to the 11-12(th) centuries (n = 339) or 13(th) century (n = 258). Temporal trends in survivorship and mortality are assessed via Kaplan-Meier survival analysis and by modeling time period as a covariate affecting the Gompertz hazard of adult mortality. The age-at-death distributions from the two pre-Black Death time periods are significantly different, with fewer older adults in 13(th) century. The results of Kaplan-Meier survival analysis indicate reductions in survival before the Black Death, with significantly lower survival in the 13(th) century (Mantel Cox p < 0.001). Last, hazard analysis reveals increases in mortality rates before the Black Death. Together, these results suggest that health in general was declining in the 13(th) century, and this might have led to high mortality during the Black Death. This highlights the importance of considering human context to understand disease in past and living human populations. © 2015 Wiley Periodicals, Inc.

Survival and prognostic factors in patients treated with stereotactic radiotherapy for brain metastases

DEFF Research Database (Denmark)

Leth, Thomas; Oettingen, Gorm von; Lassen-Ramshad, Yasmin A.

2015-01-01

Abstract Background. Stereotactic radiation therapy (SRT) of brain metastases is used with good effect around the world, but no consensus exists regarding which prognostic factors that are related to favourable or unfavourable prognosis after the treatment. A better definition of these factors...... will ensure a more precise application of the treatment. Material and methods. A consecutive cohort of the 198 patients treated for brain metastases with SRT without concurrent whole-brain radiation therapy at our department from 2001 to 2012 was retrospectively analysed. Results. Median survival was seven...... months and median time to clinical cerebral progression was eight months. The multivariate analysis revealed age ≥ 65 years, Performance Status ≥ 2, extracranial metastases and size of metastasis > 20 mm as independent prognostic factors related to shorter survival. No factors were independently related...

An Approach to Addressing Selection Bias in Survival Analysis

Science.gov (United States)

Carlin, Caroline S.; Solid, Craig A.

2014-01-01

This work proposes a frailty model that accounts for non-random treatment assignment in survival analysis. Using Monte Carlo simulation, we found that estimated treatment parameters from our proposed endogenous selection survival model (esSurv) closely parallel the consistent two-stage residual inclusion (2SRI) results, while offering computational and interpretive advantages. The esSurv method greatly enhances computational speed relative to 2SRI by eliminating the need for bootstrapped standard errors, and generally results in smaller standard errors than those estimated by 2SRI. In addition, esSurv explicitly estimates the correlation of unobservable factors contributing to both treatment assignment and the outcome of interest, providing an interpretive advantage over the residual parameter estimate in the 2SRI method. Comparisons with commonly used propensity score methods and with a model that does not account for non-random treatment assignment show clear bias in these methods that is not mitigated by increased sample size. We illustrate using actual dialysis patient data comparing mortality of patients with mature arteriovenous grafts for venous access to mortality of patients with grafts placed but not yet ready for use at the initiation of dialysis. We find strong evidence of endogeneity (with estimate of correlation in unobserved factors ρ̂ = 0.55), and estimate a mature-graft hazard ratio of 0.197 in our proposed method, with a similar 0.173 hazard ratio using 2SRI. The 0.630 hazard ratio from a frailty model without a correction for the non-random nature of treatment assignment illustrates the importance of accounting for endogeneity. PMID:24845211

Rethinking plant functional types in Earth System Models: pan-tropical analysis of tree survival across environmental gradients

Science.gov (United States)

Johnson, D. J.; Needham, J.; Xu, C.; Davies, S. J.; Bunyavejchewin, S.; Giardina, C. P.; Condit, R.; Cordell, S.; Litton, C. M.; Hubbell, S.; Kassim, A. R. B.; Shawn, L. K. Y.; Nasardin, M. B.; Ong, P.; Ostertag, R.; Sack, L.; Tan, S. K. S.; Yap, S.; McDowell, N. G.; McMahon, S.

2016-12-01

Terrestrial carbon cycling is a function of the growth and survival of trees. Current model representations of tree growth and survival at a global scale rely on coarse plant functional traits that are parameterized very generally. In view of the large biodiversity in the tropical forests, it is important that we account for the functional diversity in order to better predict tropical forest responses to future climate changes. Several next generation Earth System Models are moving towards a size-structured, trait-based approach to modelling vegetation globally, but the challenge of which and how many traits are necessary to capture forest complexity remains. Additionally, the challenge of collecting sufficient trait data to describe the vast species richness of tropical forests is enormous. We propose a more fundamental approach to these problems by characterizing forests by their patterns of survival. We expect our approach to distill real-world tree survival into a reasonable number of functional types. Using 10 large-area tropical forest plots that span geographic, edaphic and climatic gradients, we model tree survival as a function of tree size for hundreds of species. We found surprisingly few categories of size-survival functions emerge. This indicates some fundamental strategies at play across diverse forests to constrain the range of possible size-survival functions. Initial cluster analysis indicates that four to eight functional forms are necessary to describe variation in size-survival relations. Temporal variation in size-survival functions can be related to local environmental variation, allowing us to parameterize how demographically similar groups of species respond to perturbations in the ecosystem. We believe this methodology will yield a synthetic approach to classifying forest systems that will greatly reduce uncertainty and complexity in global vegetation models.

When will I succeed in my first-year diploma? Survival analysis in Dutch higher education

NARCIS (Netherlands)

Bruinsma, Marjon; Jansen, Ellen P. W. A.

2009-01-01

The goal of this study was to illustrate survival analysis with higher education data and gain insight into a limited set of factors that predict when students passed their first-year examination at a Dutch university. Study participants consisted of 565 first-year students in four departments. Data

Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age

DEFF Research Database (Denmark)

Deelen, Joris; Beekman, Marian; Uh, Hae-Won

2014-01-01

descent (≥ 85 years) and 16 121 younger controls (controls. In addition, we performed a subset analysis in cases aged ≥ 90 years. We observed genome-wide significant association with longevity, as reflected...... by survival to ages beyond 90 years, at a novel locus, rs2149954, on chromosome 5q33.3 (OR = 1.10, P = 1.74 × 10(-8)). We also confirmed association of rs4420638 on chromosome 19q13.32 (OR = 0.72, P = 3.40 × 10(-36)), representing the TOMM40/APOE/APOC1 locus. In a prospective meta-analysis (n = 34 103......, independent of blood pressure. We report on the first GWAS-identified longevity locus on chromosome 5q33.3 influencing survival in the general European population. The minor allele of this locus associates with low blood pressure in middle age, although the contribution of this allele to survival may be less...

The costs of parental care: a meta-analysis of the trade-off between parental effort and survival in birds.

Science.gov (United States)

Santos, E S A; Nakagawa, S

2012-09-01

A fundamental premise of life-history theory is that organisms that increase current reproductive investment suffer increased mortality. Possibly the most studied life-history phenotypic relationship is the trade-off between parental effort and survival. However, evidence supporting this trade-off is equivocal. Here, we conducted a meta-analysis to test the generality of this tenet. Using experimental studies that manipulated parental effort in birds, we show that (i) the effect of parental effort on survival was similar across species regardless of phylogeny; (ii) individuals that experienced reduced parental effort had similar survival probabilities than control individuals, regardless of sex; and (iii) males that experienced increased parental effort were less likely to survive than control males, whereas females that experienced increased effort were just as likely to survive as control females. Our results suggest that the trade-off between parental effort and survival is more complex than previously assumed. Finally, our study provides recommendations of unexplored avenues of future research into life-history trade-offs. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

Survival analysis in patients with metastatic spinal disease: the influence of surgery, histology, clinical and neurologic status

Directory of Open Access Journals (Sweden)

Matheus Fernandes de Oliveira

2015-04-01

Full Text Available Spine is the most common site for skeletal metastasis in patients with malignancy. Vertebral involvement quantification, neurological status, general health status and primary tumor histology are factors to set surgical planning and therapeutic targets. We evaluated the impact of general clinical and neurological status, histologic type and surgery in survival. Method : The study sample consisted of consecutive patients admitted from July 2010 to January 2013 for treatment. Results : Sixty eight patients were evaluated. 23 were female and 45 were male. Main primary neoplasic sites were: breast, prostate, lung/pleura and linfoproliferative. Thirty three out of 68 received surgical treatment, 2 received percutaneous biopsy and 33 had nonsurgical treatment. Survival : Log Rank curves revealed no statistical significant difference according to histological type, surgical approach and Frankel Score. Karnofsky Score was statistically different. Conclusion : Histological type and clinical status were statistically associated with life expectancy in vertebral metastatic disease.

Somatic mutation load of estrogen receptor-positive breast tumors predicts overall survival: an analysis of genome sequence data.

Science.gov (United States)

Haricharan, Svasti; Bainbridge, Matthew N; Scheet, Paul; Brown, Powel H

2014-07-01

Breast cancer is one of the most commonly diagnosed cancers in women. While there are several effective therapies for breast cancer and important single gene prognostic/predictive markers, more than 40,000 women die from this disease every year. The increasing availability of large-scale genomic datasets provides opportunities for identifying factors that influence breast cancer survival in smaller, well-defined subsets. The purpose of this study was to investigate the genomic landscape of various breast cancer subtypes and its potential associations with clinical outcomes. We used statistical analysis of sequence data generated by the Cancer Genome Atlas initiative including somatic mutation load (SML) analysis, Kaplan-Meier survival curves, gene mutational frequency, and mutational enrichment evaluation to study the genomic landscape of breast cancer. We show that ER(+), but not ER(-), tumors with high SML associate with poor overall survival (HR = 2.02). Further, these high mutation load tumors are enriched for coincident mutations in both DNA damage repair and ER signature genes. While it is known that somatic mutations in specific genes affect breast cancer survival, this study is the first to identify that SML may constitute an important global signature for a subset of ER(+) tumors prone to high mortality. Moreover, although somatic mutations in individual DNA damage genes affect clinical outcome, our results indicate that coincident mutations in DNA damage response and signature ER genes may prove more informative for ER(+) breast cancer survival. Next generation sequencing may prove an essential tool for identifying pathways underlying poor outcomes and for tailoring therapeutic strategies.

Association of phase angle on bioelectrical impedance analysis and dialysis frequency with survival of chronic hemodialysis patients

Science.gov (United States)

Muzasti, R. A.; Lubis, H. R.

2018-03-01

Phase angle, a parameter by Bioelectrical Impedance Analysis, can detect body composition changes, so it can be used as a prognostic indicator in some chronic conditions. This study was for determining the relationship between PhA and hemodiálisis frequency with the survival of chronic hemodiálisis patients. This longitudinal retrospective study involved 173 chronic hemodiálisis patients at Rasyida Renal Hospital. The Kaplan-Meier method is used to determine the survival. Cox proportional hazard analysis is used to determine which variables significantly increase mortality. During the study period, 89 patients underwent hemodiálysis 3x a week (4 hours/session), and 84 patients underwent HD 2x a week (5 hours/session). Demographic and clinical characteristics in both groups were similar. There was no difference in PhA value in groups of 3x a week and group 2x a week (4.02 ± 1.13 vs 4.25 ± 1.12). Patients with twice a week hemodiálisis had a shorter survival than the 3x week group (35.14 ± 2.76 vs 38.62 ± 3.03) although it was not statistically significant (p = 0.126).

Body mass index and breast cancer survival

DEFF Research Database (Denmark)

Guo, Qi; Burgess, Stephen; Turman, Constance

2017-01-01

Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival...... from breast cancer. Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between...... the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis. Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER...

A Case of Swyer Syndrome Associated with Advanced Gonadal Dysgerminoma Involving Long Survival

Directory of Open Access Journals (Sweden)

Salete Da Silva Rios

2015-03-01

Full Text Available Swyer syndrome is caused by abnormal sex differentiation during the embryonic period, resulting in incomplete intrauterine masculinization and undifferentiated gonads. The current case report describes a patient with Swyer syndrome associated with stage 3 gonadal dysgerminoma who has survived for 23 years. At age 18, this patient sought assistance for primary amenorrhea from the Gynecological Services Department of the University of Brasília Hospital. A physical examination revealed that the patient was at Tanner stage 4 with respect to axillary hair, breasts, and pubic hair; she presented with a eutrophic vagina and a small cervix. She was treated with a combination of estrogens and progestogens to induce cycling. Approximately 4 years later, a complex tumor was found and resected; a histopathological analysis revealed that this tumor was a right adnexal dysgerminoma with peritoneal affection. The patient was also subjected to chemotherapy. Her follow-up has continued to the present time, with no signs of tumor recurrence. In conclusion, this report describes an extremely rare case in which Swyer syndrome was associated with ovarian dysgerminoma; relative to similar patients, the described patient has survived for an unusually prolonged time.

Pediatric differentiated thyroid carcinoma in stage I: risk factor analysis for disease free survival

International Nuclear Information System (INIS)

Wada, Nobuyuki; Rino, Yasushi; Masuda, Munetaka; Ito, Koichi; Sugino, Kiminori; Mimura, Takashi; Nagahama, Mitsuji; Kitagawa, Wataru; Shibuya, Hiroshi; Ohkuwa, Keiko; Nakayama, Hirotaka; Hirakawa, Shohei

2009-01-01

To examine the outcomes and risk factors in pediatric differentiated thyroid carcinoma (DTC) patients who were defined as TNM stage I because some patients develop disease recurrence but treatment strategy for such stage I pediatric patients is still controversial. We reviewed 57 consecutive TNM stage I patients (15 years or less) with DTC (46 papillary and 11 follicular) who underwent initial treatment at Ito Hospital between 1962 and 2004 (7 males and 50 females; mean age: 13.1 years; mean follow-up: 17.4 years). Clinicopathological results were evaluated in all patients. Multivariate analysis was performed to reveal the risk factors for disease-free survival (DFS) in these 57 patients. Extrathyroid extension and clinical lymphadenopathy at diagnosis were found in 7 and 12 patients, respectively. Subtotal/total thyroidectomy was performed in 23 patients, modified neck dissection in 38, and radioactive iodine therapy in 10. Pathological node metastasis was confirmed in 37 patients (64.9%). Fifteen patients (26.3%) exhibited local recurrence and 3 of them also developed metachronous lung metastasis. Ten of these 15 achieved disease-free after further treatments and no patients died of disease. In multivariate analysis, male gender (p = 0.017), advanced tumor (T3, 4a) stage (p = 0.029), and clinical lymphadenopathy (p = 0.006) were risk factors for DFS in stage I pediatric patients. Male gender, tumor stage, and lymphadenopathy are risk factors for DFS in stage I pediatric DTC patients. Aggressive treatment (total thyroidectomy, node dissection, and RI therapy) is considered appropriate for patients with risk factors, whereas conservative or stepwise approach may be acceptable for other patients

Finite-size scaling of survival probability in branching processes

OpenAIRE

Garcia-Millan, Rosalba; Font-Clos, Francesc; Corral, Alvaro

2014-01-01

Branching processes pervade many models in statistical physics. We investigate the survival probability of a Galton-Watson branching process after a finite number of generations. We reveal the finite-size scaling law of the survival probability for a given branching process ruled by a probability distribution of the number of offspring per element whose standard deviation is finite, obtaining the exact scaling function as well as the critical exponents. Our findings prove the universal behavi...

[Comparison liver resection with transarterial chemoembolization for Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma patients on long-term survival after SPSS propensity score matching].

Science.gov (United States)

Ke, Yang; Zhong, Jianhong; Guo, Zhe; Liang, Yongrong; Li, Lequn; Xiang, Bangde

2014-03-18

To compare the long-term survival of patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) undergoing either liver resection or transarterial chemoembolization (TACE) after propensity score matching (PSM). One hundred sixty-seven and 70 BCLC-B HCC patients undergoing liver resection and TACE were retrospectively collected. PSM function of SPSS software was conducted to reduce confounding bias between the groups. And then survival analysis was performed for the matched data. Fifty-three pairs of patients were successfully matched. And then survival analysis showed that the median survival periods and their 95% confidence intervals were 35.0 (26.3-43.7)months in the liver resection group versus 20.0(15.0-25.0) months in the TACE group. The 1, 3, 5 and 7-year survival rates were 91.0%, 49.0%, 30.0% and 17.0% in the liver resection group versus 73.0%, 25.0%, 8.0% and 5.0% respectively in the TACE group (P = 0.001). Cox regression analysis revealed that TACE, total bilirubin ≥ 34.2 µmol/L, alpha fetoprotein ≥ 400 ng/ml and tumor number ≥ 3 were independent risk factors of survival (hazard ratio >1, P < 0.05). The balance of covariates may be achieved through PSM. And for patients with BCLC-B HCC, liver resection provides better long-term overall survival than TACE.

Stadium IB - IIA cervical cancer patient’s survival rate after receiving definitive radiation and radical operation therapy followed by adjuvant radiation therapy along with analysis of factors affecting the patient’s survival rate

Science.gov (United States)

Ruslim, S. K.; Purwoto, G.; Widyahening, I. S.; Ramli, I.

2017-08-01

To evaluate the characteristics and overall survival rates of early stage cervical cancer (FIGO IB-IIA) patients who receive definitive radiation therapy and those who are prescribed adjuvant postoperative radiation and to conduct a factors analysis of the variables that affect the overall survival rates in both groups of therapy. The medical records of 85 patients with cervical cancer FIGO stages IB-IIA who were treated at the Department of Radiotherapy of Cipto Mangunkusumo Hospital were reviewed and analyzed to determine their overall survival and the factors that affected it between a definitive radiation group and an adjuvant postoperative radiation group. There were 25 patients in the definitive radiation and 60 patients in the adjuvant radiation group. The overall survival rates in the adjuvant radiation group at years one, two, and three were 96.7%, 95%, and 93.3%, respectively. Negative lymph node metastasis had an average association with overall survival (p 12 g/dl was a factor with an average association with the overall survival (p cervical cancer FIGO stage IB-IIA patients who received definitive radiation or adjuvant postoperative radiation. Negative lymph node metastasis had an effect on the overall survival rate in the adjuvant postoperative radiation group, while a preradiation Hb level >12 g/dl tended to affect the overall survival in the definitive radiation group patients.

Comparative Pan-Genome Analysis of Piscirickettsia salmonis Reveals Genomic Divergences within Genogroups

Directory of Open Access Journals (Sweden)

Guillermo Nourdin-Galindo

2017-10-01

Full Text Available Piscirickettsia salmonis is the etiological agent of salmonid rickettsial septicemia, a disease that seriously affects the salmonid industry. Despite efforts to genomically characterize P. salmonis, functional information on the life cycle, pathogenesis mechanisms, diagnosis, treatment, and control of this fish pathogen remain lacking. To address this knowledge gap, the present study conducted an in silico pan-genome analysis of 19 P. salmonis strains from distinct geographic locations and genogroups. Results revealed an expected open pan-genome of 3,463 genes and a core-genome of 1,732 genes. Two marked genogroups were identified, as confirmed by phylogenetic and phylogenomic relationships to the LF-89 and EM-90 reference strains, as well as by assessments of genomic structures. Different structural configurations were found for the six identified copies of the ribosomal operon in the P. salmonis genome, indicating translocation throughout the genetic material. Chromosomal divergences in genomic localization and quantity of genetic cassettes were also found for the Dot/Icm type IVB secretion system. To determine divergences between core-genomes, additional pan-genome descriptions were compiled for the so-termed LF and EM genogroups. Open pan-genomes composed of 2,924 and 2,778 genes and core-genomes composed of 2,170 and 2,228 genes were respectively found for the LF and EM genogroups. The core-genomes were functionally annotated using the Gene Ontology, KEGG, and Virulence Factor databases, revealing the presence of several shared groups of genes related to basic function of intracellular survival and bacterial pathogenesis. Additionally, the specific pan-genomes for the LF and EM genogroups were defined, resulting in the identification of 148 and 273 exclusive proteins, respectively. Notably, specific virulence factors linked to adherence, colonization, invasion factors, and endotoxins were established. The obtained data suggest that these

Radiation therapy: A major factor in the five-year survival analysis of women with breast cancer in Lagos, Nigeria

International Nuclear Information System (INIS)

Makanjuola, Samira B.L.; Popoola, Abiodun O.; Oludara, Mobolaji A.

2014-01-01

Purpose: This retrospective study was carried out to examine five-year survival from breast cancer cases diagnosed between 2005 and May 2008 in Nigerian women. Material and methods: Two hundred and twenty-four patients were entered into the study. Five-year survival was evaluated using proportional hazard model proposed by Cox to assess variables such as age of diagnosis, menopausal status, and stage of the disease in the two treatment groups: surgery/chemotherapy or surgery/chemotherapy/radiotherapy. Results: Findings revealed that the different staging of disease and treatment are independent predictors of disease outcome whereas age of diagnosis and menopausal status although associated with low hazards, are not significant. TNM Stage I (Hazard Ratio = 0.153, 95% CI 0.45–0.51, P = 0.003), II (Hazard Ratio = 0.245, 95% CI 0.12–0.46, P = 0.0001), and III (Hazard Ratio = 0.449, 95% CI 0.31–0.46, P = 0.0001) showed significantly greater survival rates compared to TNM Stage IV for patients receiving surgery/chemotherapy. Similarly, for patients receiving surgery/chemotherapy/radiotherapy TNM Stage II (Hazard Ratio = 0.110, 95% CI 0.02–0.46, P = 0.003) and III (Hazard Ratio = 0.238, 95% CI 0.07–0.73, P = 0.012) also showed significantly greater survival rates compared to TNM Stage IV. Treatment had a significant impact on survival independent of stage, age, and menopausal status. Patients receiving surgery/chemotherapy/radiotherapy had a significant increase in survival outcome for TNM Stage (II, P = 0.045; III, P = 0.0001); age groups (40–49, P = 0.021; 50–59, P = 0.016; 60–69, P = 0.017; >70, P = 0.025); and menopausal status (premenopausal, P = 0.049; postmenopausal, P = 0.0001) compared to those receiving surgery/chemotherapy. Conclusion: The five-year breast cancer survival rate in Lagos, Nigeria 24.1% (54/224) is relatively poor compared to most countries in the world and needs to be improved. Poor survival rates are mainly attributed to late

Assessing survivability to support power grid investment decisions

International Nuclear Information System (INIS)

Koziolek, Anne; Avritzer, Alberto; Suresh, Sindhu; Menasché, Daniel S.; Diniz, Morganna; Souza e Silva, Edmundo de; Leão, Rosa M.; Trivedi, Kishor; Happe, Lucia

2016-01-01

The reliability of power grids has been subject of study for the past few decades. Traditionally, detailed models are used to assess how the system behaves after failures. Such models, based on power flow analysis and detailed simulations, yield accurate characterizations of the system under study. However, they fall short on scalability. In this paper, we propose an efficient and scalable approach to assess the survivability of power systems. Our approach takes into account the phased-recovery of the system after a failure occurs. The proposed phased-recovery model yields metrics such as the expected accumulated energy not supplied between failure and full recovery. Leveraging the predictive power of the model, we use it as part of an optimization framework to assist in investment decisions. Given a budget and an initial circuit to be upgraded, we propose heuristics to sample the solution space in a principled way accounting for survivability-related metrics. We have evaluated the feasibility of this approach by applying it to the design of a benchmark distribution automation circuit. Our empirical results indicate that the combination of survivability and power flow analysis can provide meaningful investment decision support for power systems engineers. - Highlights: • We propose metrics and models for scalable survivability analysis of power systems. • The survivability model captures the system phased-recovery, from failure to repair. • The survivability model is used as a building block of an optimization framework. • Heuristics assist in investment options accounting for survivability-related metrics.

[Analysis of clinicopathologic and survival characteristics in patients with right-or left-sided colon cancer].

Science.gov (United States)

Hu, Junjie; Zhou, Zhixiang; Liang, Jianwei; Zhou, Haitao; Wang, Zheng; Zhang, Xingmao; Zeng, Weigen

2015-07-28

This study aimed to clarify the clinical and histological parameters, and survival difference between right- and left-sided colon cancer. We retrospectively analyzed the medical records (2006.1-2009.12) of 1 088 consecutive colon cancer patients who received surgery at our hospital. Right- and left-sided colon cancers were compared regarding the clinical and histological parameters. The survival analysis was performed by the Kaplan-Meier method, and the log-rank test was used to determine the statistical significance of differences. Right-sided colon cancer was associated with older age, a more advanced state, and poorly differentiated and undifferentiated adenocarcinoma (25.2% vs 13.2%), mucinous adenocarcinoma (33.5% vs 17.3%) and vascular invasion (9.9% vs 3.9%) were more commonly seen in right-sided colon cancer compared with right-sided colon cancer, and all these differences were statistically significant. Median overall survival was right, 67 months; and left, 68 months. The five-years overall survival of right- and left-sided colon cancer was I/II stage, 91.4% vs 88.6% (P = 0.819); III stage, 66.1% vs 75.4% (P = 0.010); and IV stage, 27.8% vs 38.5% (P = 0.020) respectively. Right- and left-sided colon cancers are significantly different regarding clinical and histological parameters. Right-sided colon cancers in stage III and IV have a worse prognosis.

Preoperative Comorbidity Correlates Inversely with Survival after Intestinal and Multivisceral Transplantation in Adults

Directory of Open Access Journals (Sweden)

Rajesh Sivaprakasam

2013-01-01

Full Text Available We investigated the relationship between preoperative comorbidity and postoperative survival after intestinal transplantation. Each patient received a score for preoperative comorbidity. Each comorbidity was given a score based on the degree it impaired function (score range 0–3. A total score was derived from the summation of individual comorbidity scores. Patients (72 adults (M : F, 33 : 39 received an isolated intestinal graft (27 or a cluster graft (45. Mean (standard deviation survival was 1501 (1444 days. The Kaplan-Meier analysis revealed a significant inverse association between survival and comorbidity score (logrank test for trend, . Patients grouped into comorbidity scores of 0 and 1, 2 and 3, 4 and 5, 6, and above had hazard ratios (95% confidence intervals for death (compared to group 0 + 1, which increased with comorbidity scores: 1.945 (0.7622–5.816, 5.075 (3.314–36.17, and 13.77 (463.3–120100, respectively, (. Receiver-operator curves at 1, 3, 5, and 10 years postoperative had “C” statistics of 0.88, 0.85, 0.88, and 0.92, respectively. When evaluating patients for transplantation, the degree of comorbidity should be considered as a major factor influencing postoperative survival.

Improved survival after rectal cancer in Denmark

DEFF Research Database (Denmark)

Bülow, S; Harling, H; Iversen, L H

2010-01-01

Objective In 1995, an analysis showed an inferior prognosis after rectal cancer in Denmark compared with the other Scandinavian countries. The Danish Colorectal Cancer Group (DCCG) was established with the aim of improving the prognosis, and in this study we present a survival analysis of patients...... treated from 1994 to 2006. Method The study was based on the National Rectal Cancer Registry and the National Colorectal Cancer Database, supplemented with data from the Central Population Registry. The analysis included actuarial overall and relative survival. Results A total of 10 632 patients were...

Persistent elevation of postoperative neutrophil-to-lymphocyte ratio: A better predictor of survival in gastric cancer than elevated preoperative neutrophil-to-lymphocyte ratio.

Science.gov (United States)

Min, Kyueng-Whan; Kwon, Mi Jung; Kim, Dong-Hoon; Son, Byoung Kwan; Kim, Eun-Kyung; Oh, Young Ha; Wi, Young Chan

2017-10-25

Postoperative neutrophil-to-lymphocyte ratio change (NLRc) reflects the dynamic change of balance between host inflammatory response and immune response after treatment. In gastric cancer, an elevated initial NLR (iNLR) is reported to be a prognostic predictor, but the clinical application of the NLRc remains unclear. The NLRc was assessed in 734 patients undergoing total/subtotal gastrectomy and endoscopic submucosal dissection for gastric adenocarcinoma. The iNLR and NLRc were recorded within 10 days of the first diagnosis and 3-6 months after surgery, respectively. Using receiver operating characteristic (ROC) curves, we investigated the relationship between NLRc or iNLR and patient survival. The analysis revealed a higher predictive power for correlating patient survival with the NLRc compared with iNLR. NLRc was defined as negative (lower than iNLR) and positive (higher than iNLR). A positive NLRc was frequently observed in patients with advanced AJCC stage, local recurrence, distant metastasis, perineural invasion, and adjuvant chemotherapy (all p < 0.05). Univariate and multivariate analyses revealed a significant relationship between patient survival and NLRc (all p < 0.05) but no association between survival and iNLR. The NLRc could be a better indicator than iNLR for predicting survival in patients with gastric cancer.

Survival benefit of radiotherapy to patients with small cell esophagus carcinoma: an analysis of Surveillance Epidemiology and End Results (SEER) data.

Science.gov (United States)

Song, Yaqi; Wang, Wanwei; Tao, Guangzhou; Zhu, Weiguo; Zhou, Xilei; Pan, Peng

2016-03-29

Small cell esophageal carcinoma (SCEC) is a rare malignant tumor. So far, few studies are found to research the effect of radiotherapy (RT) to it. This study is designed to explore the prognostic factors, and analyze survival benefit of RT to patients with SCEC. Patients with SCEC were more likely to be in female, older, higher disease stage than those with non-small cell esophageal carcinoma. RT was used in more than 50% SCEC patients. RT tended be reduced as the disease stage raise in SCEC. Univariate and multivariate analysis showed that age, year, disease stage, and RT were the prognostic factors of survival (P 0.05) and nearly 30% risks of death in distant stage (P > 0.05). SCEC patients between 1973 and 2012 were searched from the Surveillance Epidemiology and End Results (SEER) data. Clinical factors including age, year, sex, race, stage, surgery, and RT were summarized. Univariate and multivariate analysis were performed to explore the independent prognostic factors of SCEC. Cox regression survival analysis was performed to evaluate the effect of RT to SCEC based on different stages. Stage, age, year, and RT are independent prognostic factors of SCEC. Survival benefit of RT exists in any disease stage, but is only statistically significant in localized stage of SCEC.

ROCK I Has More Accurate Prognostic Value than MET in Predicting Patient Survival in Colorectal Cancer.

Science.gov (United States)

Li, Jian; Bharadwaj, Shruthi S; Guzman, Grace; Vishnubhotla, Ramana; Glover, Sarah C

2015-06-01

Colorectal cancer remains the second leading cause of death in the United States despite improvements in incidence rates and advancements in screening. The present study evaluated the prognostic value of two tumor markers, MET and ROCK I, which have been noted in other cancers to provide more accurate prognoses of patient outcomes than tumor staging alone. We constructed a tissue microarray from surgical specimens of adenocarcinomas from 108 colorectal cancer patients. Using immunohistochemistry, we examined the expression levels of tumor markers MET and ROCK I, with a pathologist blinded to patient identities and clinical outcomes providing the scoring of MET and ROCK I expression. We then used retrospective analysis of patients' survival data to provide correlations with expression levels of MET and ROCK I. Both MET and ROCK I were significantly over-expressed in colorectal cancer tissues, relative to the unaffected adjacent mucosa. Kaplan-Meier survival analysis revealed that patients' 5-year survival was inversely correlated with levels of expression of ROCK I. In contrast, MET was less strongly correlated with five-year survival. ROCK I provides better efficacy in predicting patient outcomes, compared to either tumor staging or MET expression. As a result, ROCK I may provide a less invasive method of assessing patient prognoses and directing therapeutic interventions. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Coding variants in NOD-like receptors: An association study on risk and survival of colorectal cancer.

Science.gov (United States)

Huhn, Stefanie; da Silva Filho, Miguel I; Sanmuganantham, Tharmila; Pichulik, Tica; Catalano, Calogerina; Pardini, Barbara; Naccarati, Alessio; Polakova-Vymetálkova, Veronika; Jiraskova, Katerina; Vodickova, Ludmila; Vodicka, Pavel; Löffler, Markus W; Courth, Lioba; Wehkamp, Jan; Din, Farhat V N; Timofeeva, Maria; Farrington, Susan M; Jansen, Lina; Hemminki, Kari; Chang-Claude, Jenny; Brenner, Hermann; Hoffmeister, Michael; Dunlop, Malcolm G; Weber, Alexander N R; Försti, Asta

2018-01-01

Nod-like receptors (NLRs) are important innate pattern recognition receptors and regulators of inflammation or play a role during development. We systematically analysed 41 non-synonymous single nucleotide polymorphisms (SNPs) in 21 NLR genes in a Czech discovery cohort of sporadic colorectal cancer (CRC) (1237 cases, 787 controls) for their association with CRC risk and survival. Five SNPs were found to be associated with CRC risk and eight with survival at 5% significance level. In a replication analysis using data of two large genome-wide association studies (GWASs) from Germany (DACHS: 1798 cases and 1810 controls) and Scotland (2210 cases and 9350 controls) the associations found in the Czech discovery set were not confirmed. However, expression analysis in human gut-related tissues and immune cells revealed that the NLRs associated with CRC risk or survival in the discovery set were expressed in primary human colon or rectum cells, CRC tissue and/or cell lines, providing preliminary evidence for a potential involvement of NLRs in general in CRC development and/or progression. Most interesting was the finding that the enigmatic development-related NLRP5 (also known as MATER) was not expressed in normal colon tissue but in colon cancer tissue and cell lines. Future studies may show whether regulatory variants instead of coding variants might affect the expression of NLRs and contribute to CRC risk and survival.

Landscape‐level patterns in fawn survival across North America

Science.gov (United States)

Gingery, Tess M.; Diefenbach, Duane R.; Wallingford, Bret D.; Rosenberry, Christopher S.

2018-01-01

A landscape‐level meta‐analysis approach to examining early survival of ungulates may elucidate patterns in survival not evident from individual studies. Despite numerous efforts, the relationship between fawn survival and habitat characteristics remains unclear and there has been no attempt to examine trends in survival across landscape types with adequate replication. In 2015–2016, we radiomarked 98 white‐tailed deer (Odocoileus virginianus) fawns in 2 study areas in Pennsylvania. By using a meta‐analysis approach, we compared fawn survival estimates from across North America using published data from 29 populations in 16 states to identify patterns in survival and cause‐specific mortality related to landscape characteristics, predator communities, and deer population density. We modeled fawn survival relative to percentage of agricultural land cover and deer density. Estimated average survival to 3–6 months of age was 0.414 ± 0.062 (SE) in contiguous forest landscapes (no agriculture) and for every 10% increase in land area in agriculture, fawn survival increased 0.049 ± 0.014. We classified cause‐specific mortality as human‐caused, natural (excluding predation), and predation according to agriculturally dominated, forested, and mixed (i.e., both agricultural and forest cover) landscapes. Predation was the greatest source of mortality in all landscapes. Landscapes with mixed forest and agricultural cover had greater proportions and rates of human‐caused mortalities, and lower proportions and rates of mortality due to predators, when compared to forested landscapes. Proportion and rate of natural deaths did not differ among landscapes. We failed to detect any relationship between fawn survival and deer density. The results highlight the need to consider multiple spatial scales when accounting for factors that influence fawn survival. Furthermore, variation in mortality sources and rates among landscapes indicate the potential for

Interaction of the effects of hyperthermia and ionizing radiation on cell survival

International Nuclear Information System (INIS)

Loshek, D.D.

1976-09-01

The literature concerning the effects of hyperthermia and radiation on cellular reproductive integrity is reviewed. The cell line and the physical and biological aspects of the experiments are described. Preliminary experiments revealed that the experimental stability was adequate for inter-experiment comparisons, provided that sufficient control data were obtained. Further experiments provided a cursory examination of several aspects of the interaction between radiation and hyperthermia. A simple sensitization model that would account for the observed results for any single value of the perturbing radiation or hyperthermia dose was developed. Using the concept of the survival surface, this simple model was expanded to describe simultaneously survivals for any combination of the radiation and hyperthermia dose. The interaction component of this model is first order in both hyperthermia exposure and radiation dose. The mechanism by which radiation contributes to the interaction was investigated by altering the radiation quality. The results suggest that high LET events contribute to the interaction. The mechanism by which hyperthermia contributes to the interaction was investigated by altering the hyperthermia temperature. A thermodynamic analysis of the data reveals parallels with the effects of hyperthermia and radiation on protein, suggesting a possible involvement of protein denaturation in cell inactivation. (author)

The survival analysis on localized prostate cancer treated with neoadjuvant endocrine therapy followed by intensity modulated radiation therapy

International Nuclear Information System (INIS)

Gao Hong; Li Gaofeng; Wu Qinhong; Li Xuenan; Zhong Qiuzi; Xu Yonggang

2010-01-01

Objective: To retrospectively investigate clinical outcomes and prognostic factors in localized prostate cancer treated with neoadjuvant endocrine therapy followed by intensity modulated radiotherapy (IMRT). Methods: Between March 2003 and October 2008, 54 localized prostate cancer treated by IMRT were recruited. All patients had received endocrine therapy before IMRT. The endocrine therapy included surgical castration or medical castration in combination with antiandrogens. The target of IMRT was the prostate and seminal vesicles with or without pelvis. The biochemical failure was defined according to the phoenix definition. By using the risk grouping standard proposed by D'Amico, patients were divided into three groups: low-risk group (n = 5), intermediate-risk group (n = 12), and high-risk group (n = 37). Kaplan-Meier method was used to calculate the overall survival rate. Prognostic factors were analyzed by univariate and multiple Cox regression analysis. Results: The follow-up rate was 98%. The number of patients under follow-up was 39 at 3 years and 25 at 5 years. Potential prognostic factors, including risk groups, mode of endocrine therapy, time of endocrine therapy, phoenix grouping before IMRT, the prostate specific antigen doubling time (PSADT) before radiotherapy, PSA value before IMRT, interval of endocrine therapy and IMRT, irradiation region, and irradiation dose were analyzed by survival analysis. In univariate analysis, time of endocrine therapy (75 % vs 95 %, χ 2 = 6. 45, P = 0. 011), phoenix grouping before IMRT (87% vs 96%, χ 2 = 4. 36, P = 0. 037), interval of endocrine therapy and IMRT (80% vs 95%, χ 2 = 11.60, P= 0. 001), irradiation dose (75% vs 91%, χ 2 =5.92, P= 0. 015) were statistically significant prognostic factors for 3 - year overall survival , and risk groups (85 vs 53 vs 29, χ 2 = 6. 40, P =0. 041) and PSADT before IMRT (62 vs 120, U =24. 50, P =0. 003) were significant factors for the median survival time. In the multiple Cox

The Survival Processing Effect with Intentional Learning of Ad Hoc Categories

Directory of Open Access Journals (Sweden)

Anastasiya Savchenko

2014-04-01

Full Text Available Previous studies have shown that memory is adapted to remember information when it is processed in a survival context. This study investigates how procedural changes in Marinho (2012 study might have led to her failure to replicate the survival mnemonic advantage. In two between-subjects design experiments, participants were instructed to learn words from ad hoc categories and to rate their relevance to a survival or a control scenario. No survival advantage was obtained in either experiment. The Adjusted Ratio of Clustering (ARC scores revealed that including the category labels made the participants rely more on the category structure of the list. Various procedural aspects of the conducted experiments are discussed as possible reasons underlying the absence of the survival effect.

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

Gender, Race, and Survival: A Study in Non-Small-Cell Lung Cancer Brain Metastases Patients Utilizing the Radiation Therapy Oncology Group Recursive Partitioning Analysis Classification

International Nuclear Information System (INIS)

Videtic, Gregory M.M.; Reddy, Chandana A.; Chao, Samuel T.; Rice, Thomas W.; Adelstein, David J.; Barnett, Gene H.; Mekhail, Tarek M.; Vogelbaum, Michael A.; Suh, John H.

2009-01-01

Purpose: To explore whether gender and race influence survival in non-small-cell lung cancer (NSCLC) in patients with brain metastases, using our large single-institution brain tumor database and the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) brain metastases classification. Methods and materials: A retrospective review of a single-institution brain metastasis database for the interval January 1982 to September 2004 yielded 835 NSCLC patients with brain metastases for analysis. Patient subsets based on combinations of gender, race, and RPA class were then analyzed for survival differences. Results: Median follow-up was 5.4 months (range, 0-122.9 months). There were 485 male patients (M) (58.4%) and 346 female patients (F) (41.6%). Of the 828 evaluable patients (99%), 143 (17%) were black/African American (B) and 685 (83%) were white/Caucasian (W). Median survival time (MST) from time of brain metastasis diagnosis for all patients was 5.8 months. Median survival time by gender (F vs. M) and race (W vs. B) was 6.3 months vs. 5.5 months (p = 0.013) and 6.0 months vs. 5.2 months (p = 0.08), respectively. For patients stratified by RPA class, gender, and race, MST significantly favored BFs over BMs in Class II: 11.2 months vs. 4.6 months (p = 0.021). On multivariable analysis, significant variables were gender (p = 0.041, relative risk [RR] 0.83) and RPA class (p < 0.0001, RR 0.28 for I vs. III; p < 0.0001, RR 0.51 for II vs. III) but not race. Conclusions: Gender significantly influences NSCLC brain metastasis survival. Race trended to significance in overall survival but was not significant on multivariable analysis. Multivariable analysis identified gender and RPA classification as significant variables with respect to survival.

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

Science.gov (United States)

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

2016-03-01

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

Common germline polymorphisms associated with breast cancer-specific survival

DEFF Research Database (Denmark)

Pirie, Ailith; Guo, Qi; Kraft, Peter

2015-01-01

in the meta-analysis. Fifty-four of these were evaluated in the full set of 37,954 breast cancer cases with 2,900 events and the two additional variants were evaluated in a reduced sample size of 30,000 samples in order to ensure independence from the previously published studies. Five variants reached...... evaluated in the pooled analysis of over 37,000 breast cancer cases for association with breast cancer-specific survival. Previous associations were evaluated using a one-sided test based on the reported direction of effect. RESULTS: Fifty-six variants from 45 previous publications were evaluated......-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium. METHODS: A literature review was conducted of all previously published associations between common germline variants and three survival outcomes...

Predicting and Modelling of Survival Data when Cox's Regression Model does not hold

DEFF Research Database (Denmark)

Scheike, Thomas H.; Zhang, Mei-Jie

2002-01-01

Aalen model; additive risk model; counting processes; competing risk; Cox regression; flexible modeling; goodness of fit; prediction of survival; survival analysis; time-varying effects......Aalen model; additive risk model; counting processes; competing risk; Cox regression; flexible modeling; goodness of fit; prediction of survival; survival analysis; time-varying effects...

Survival and psychomotor development with early betaine treatment in patients with severe methylenetetrahydrofolate reductase deficiency.

Science.gov (United States)

Diekman, Eugene F; de Koning, Tom J; Verhoeven-Duif, Nanda M; Rovers, Maroeska M; van Hasselt, Peter M

2014-02-01

The impact of betaine treatment on outcome in patients with severe methylenetetrahydrofolate reductase (MTHFR) deficiency is presently unclear. To investigate the effect of betaine treatment on development and survival in patients with severe MTHFR deficiency. MEDLINE, EMBASE, and Cochrane databases between January 1960 and December 2012. Studies that described patients with severe MTHFR deficiency who received betaine treatment. We identified 15 case reports and case series, totaling 36 patients. Data included the following: (1) families with 2 or more patients with severe MTHFR deficiency, of whom at least 1 received betaine, or (2) single patients with severe MTHFR deficiency treated with betaine. To define severe MTHFR deficiency, methionine, homocysteine, MTHFR enzyme activity in fibroblasts, or mutations (in the MTHFR gene) had to be described as well as the effect of treatment (survival and/or psychomotor development). We compared the outcome in treated vs untreated patients and early- vs late-treated patients. Sensitivity analysis was performed to address definition of early treatment. To further assess the impact of treatment on mortality, we performed a subanalysis in families with at least 1 untreated deceased patient. Survival and psychomotor development. Eleven of 36 patients (31%) died. All deaths occurred in patients who did not receive treatment or in patients in whom treatment was delayed. In contrast, all 5 early-treated patients survived. Subgroup analysis of patients with deceased siblings-their genotypically identical controls-revealed that betaine treatment prevented mortality (P = .002). In addition, psychomotor development in surviving patients treated with betaine was normal in all 5 early-treated patients but in none of the 19 surviving patients with delayed treatment (P psychomotor development in patients with severe MTHFR deficiency, highlighting the importance of timely recognition through newborn screening.

Treatment of primary liver tumors with Yttrium-90 microspheres (TheraSphere) in high risk patients: analysis of survival and toxicities.

Science.gov (United States)

Reardon, Kelli A; McIntosh, Alyson F; Shilling, A Tanner; Hagspiel, Klaus D; Al-Osaimi, Abdullah; Berg, Carl; Caldwell, Stephen H; Northup, Patrick G; Angle, Fritz; Mulder, Robert; Rich, Tyvin A

2009-02-01

This retrospective study was undertaken to obtain information regarding the survival and toxicities after Yttrium-90 microspheres treatment in patients with primary liver malignancies. Baseline, treatment, and follow-up data were collected and analyzed for 21 patients treated with Yttrium-90 microspheres. Survival analysis was then performed. The results of this study showed that median survival for all the patients was 120 days. Twenty of 21 patients were categorized as high-risk with a median survival of 114 days. It was also found that one high-risk patient has survived 858 days with no recurrence of disease. Acute grade 3-5 toxicities were recorded for nine patients and consisted of elevations in AST and bilirubin, thrombocytopenia, abdominal pain, ascites, nausea, fatigue, and death. This study concluded that Yttrium-90 is a low-toxicity, outpatient alternative for individuals with liver cancer and without many options. The maximal value, however, may lie in the treatment of low-risk patients.

Transcriptome analysis reveals key differentially expressed genes involved in wheat grain development

Directory of Open Access Journals (Sweden)

Yonglong Yu

2016-04-01

Full Text Available Wheat seed development is an important physiological process of seed maturation and directly affects wheat yield and quality. In this study, we performed dynamic transcriptome microarray analysis of an elite Chinese bread wheat cultivar (Jimai 20 during grain development using the GeneChip Wheat Genome Array. Grain morphology and scanning electron microscope observations showed that the period of 11–15 days post-anthesis (DPA was a key stage for the synthesis and accumulation of seed starch. Genome-wide transcriptional profiling and significance analysis of microarrays revealed that the period from 11 to 15 DPA was more important than the 15–20 DPA stage for the synthesis and accumulation of nutritive reserves. Series test of cluster analysis of differential genes revealed five statistically significant gene expression profiles. Gene ontology annotation and enrichment analysis gave further information about differentially expressed genes, and MapMan analysis revealed expression changes within functional groups during seed development. Metabolic pathway network analysis showed that major and minor metabolic pathways regulate one another to ensure regular seed development and nutritive reserve accumulation. We performed gene co-expression network analysis to identify genes that play vital roles in seed development and identified several key genes involved in important metabolic pathways. The transcriptional expression of eight key genes involved in starch and protein synthesis and stress defense was further validated by qRT-PCR. Our results provide new insight into the molecular mechanisms of wheat seed development and the determinants of yield and quality.

Atrial fibrillation and survival in colorectal cancer

Directory of Open Access Journals (Sweden)

Justin Timothy A

2004-11-01

Full Text Available Abstract Background Survival in colorectal cancer may correlate with the degree of systemic inflammatory response to the tumour. Atrial fibrillation may be regarded as an inflammatory complication. We aimed to determine if atrial fibrillation is a prognostic factor in colorectal cancer. Patients and methods A prospective colorectal cancer patient database was cross-referenced with the hospital clinical-coding database to identify patients who had underwent colorectal cancer surgery and were in atrial fibrillation pre- or postoperatively. Results A total of 175 patients underwent surgery for colorectal cancer over a two-year period. Of these, 13 patients had atrial fibrillation pre- or postoperatively. Atrial fibrillation correlated with worse two-year survival (p = 0.04; log-rank test. However, in a Cox regression analysis, atrial fibrillation was not significantly associated with survival. Conclusion The presence or development of atrial fibrillation in patients undergoing surgery for colorectal cancer is associated with worse overall survival, however it was not found to be an independent factor in multivariate analysis.

Ancient DNA reveals that bowhead whale lineages survived Late Pleistocene climate change and habitat shifts

DEFF Research Database (Denmark)

Foote, Andrew David; Kaschner, Kristin; Schultze, Sebastian E.

2013-01-01

that a true Arctic species, the bowhead whale (Balaena mysticetus), shifted its range and tracked its core suitable habitat northwards during the rapid climate change of the Pleistocene-Holocene transition. Late Pleistocene lineages survived into the Holocene and effective female population size increased...

Repair or Replacement for Isolated Tricuspid Valve Pathology? Insights from a Surgical Analysis on Long-Term Survival

Science.gov (United States)

Farag, Mina; Arif, Rawa; Sabashnikov, Anton; Zeriouh, Mohamed; Popov, Aron-Frederik; Ruhparwar, Arjang; Schmack, Bastian; Dohmen, Pascal M.; Szabó, Gábor; Karck, Matthias; Weymann, Alexander

2017-01-01

Background Long-term follow-up data concerning isolated tricuspid valve pathology after replacement or reconstruction is limited. Current American Heart Association guidelines equally recommend repair and replacement when surgical intervention is indicated. Our aim was to investigate and compare operative mortality and long-term survival in patients undergoing isolated tricuspid valve repair surgery versus replacement. Material/Methods Between 1995 and 2011, 109 consecutive patients underwent surgical correction of tricuspid valve pathology at our institution for varying structural pathologies. A total of 41 (37.6%) patients underwent tricuspid annuloplasty/repair (TAP) with or without ring implantation, while 68 (62.3%) patients received tricuspid valve replacement (TVR) of whom 36 (53%) were mechanical and 32 (47%) were biological prostheses. Results Early survival at 30 days after surgery was 97.6% in the TAP group and 91.1% in the TVR group. After 6 months, 89.1% in the TAP group and 87.8% in the TVR group were alive. In terms of long-term survival, there was no further mortality observed after one year post surgery in both groups (Log Rank p=0.919, Breslow p=0.834, Tarone-Ware p=0.880) in the Kaplan-Meier Survival analysis. The 1-, 5-, and 8-year survival rates were 85.8% for TAP and 87.8% for TVR group. Conclusions Surgical repair of the tricuspid valve does not show survival benefit when compared to replacement. Hence valve replacement should be considered generously in patients with reasonable suspicion that regurgitation after repair will reoccur. PMID:28236633

Improved Survival With Radiation Therapy in High-Grade Soft Tissue Sarcomas of the Extremities: A SEER Analysis

International Nuclear Information System (INIS)

Koshy, Matthew; Rich, Shayna E.; Mohiuddin, Majid M.

2010-01-01

Purpose: The benefit of radiation therapy in extremity soft tissue sarcomas remains controversial. The purpose of this study was to determine the effect of radiation therapy on overall survival among patients with primary soft tissue sarcomas of the extremity who underwent limb-sparing surgery. Methods and Materials: A retrospective study from the Surveillance, Epidemiology, and End Results (SEER) database that included data from January 1, 1988, to December 31, 2005. A total of 6,960 patients constituted the study population. Overall survival curves were constructed using the Kaplan-Meir method and for patients with low- and high-grade tumors. Hazard ratios were calculated based on multivariable Cox proportional hazards models. Results: Of the cohort, 47% received radiation therapy. There was no significant difference in overall survival among patients with low-grade tumors by radiation therapy. In high-grade tumors, the 3-year overall survival was 73% in patients who received radiation therapy vs. 63% for those who did not receive radiation therapy (p < 0.001). On multivariate analysis, patients with high-grade tumors who received radiation therapy had an improved overall survival (hazard ratio 0.67, 95% confidence interval 0.57-0.79). In patients receiving radiation therapy, 13.5% received it in a neoadjuvant setting. The incidence of patients receiving neoadjuvant radiation did not change significantly between 1988 and 2005. Conclusions: To our knowledge, this is the largest population-based study reported in patients undergoing limb-sparing surgery for soft tissue sarcomas of the extremities. It reports that radiation was associated with improved survival in patients with high-grade tumors.

Iterative Bayesian Model Averaging: a method for the application of survival analysis to high-dimensional microarray data

Directory of Open Access Journals (Sweden)

Raftery Adrian E

2009-02-01

Full Text Available Abstract Background Microarray technology is increasingly used to identify potential biomarkers for cancer prognostics and diagnostics. Previously, we have developed the iterative Bayesian Model Averaging (BMA algorithm for use in classification. Here, we extend the iterative BMA algorithm for application to survival analysis on high-dimensional microarray data. The main goal in applying survival analysis to microarray data is to determine a highly predictive model of patients' time to event (such as death, relapse, or metastasis using a small number of selected genes. Our multivariate procedure combines the effectiveness of multiple contending models by calculating the weighted average of their posterior probability distributions. Our results demonstrate that our iterative BMA algorithm for survival analysis achieves high prediction accuracy while consistently selecting a small and cost-effective number of predictor genes. Results We applied the iterative BMA algorithm to two cancer datasets: breast cancer and diffuse large B-cell lymphoma (DLBCL data. On the breast cancer data, the algorithm selected a total of 15 predictor genes across 84 contending models from the training data. The maximum likelihood estimates of the selected genes and the posterior probabilities of the selected models from the training data were used to divide patients in the test (or validation dataset into high- and low-risk categories. Using the genes and models determined from the training data, we assigned patients from the test data into highly distinct risk groups (as indicated by a p-value of 7.26e-05 from the log-rank test. Moreover, we achieved comparable results using only the 5 top selected genes with 100% posterior probabilities. On the DLBCL data, our iterative BMA procedure selected a total of 25 genes across 3 contending models from the training data. Once again, we assigned the patients in the validation set to significantly distinct risk groups (p

Tracheostomy and invasive mechanical ventilation in amyotrophic lateral sclerosis: decision-making factors and survival analysis.

Science.gov (United States)

Kimura, Fumiharu

2016-04-28

Invasive and/or non-invasive mechanical ventilation are most important options of respiratory management in amyotrophic lateral sclerosis. We evaluated the frequency, clinical characteristics, decision-making factors about ventilation and survival analysis of 190 people with amyotrophic lateral sclerosis patients from 1990 until 2013. Thirty-one percentage of patients underwent tracheostomy invasive ventilation with the rate increasing more than the past 20 years. The ratio of tracheostomy invasive ventilation in patients >65 years old was significantly increased after 2000 (25%) as compared to before (10%). After 2010, the standard use of non-invasive ventilation showed a tendency to reduce the frequency of tracheostomy invasive ventilation. Mechanical ventilation prolonged median survival (75 months in tracheostomy invasive ventilation, 43 months in non-invasive ventilation vs natural course, 32 months). The life-extending effects by tracheostomy invasive ventilation were longer in younger patients ≤65 years old at the time of ventilation support than in older patients. Presence of partners and care at home were associated with better survival. Following factors related to the decision to perform tracheostomy invasive ventilation: patients ≤65 years old: greater use of non-invasive ventilation: presence of a spouse: faster tracheostomy: higher progression rate; and preserved motor functions. No patients who underwent tracheostomy invasive ventilation died from a decision to withdraw mechanical ventilation. The present study provides factors related to decision-making process and survival after tracheostomy and help clinicians and family members to expand the knowledge about ventilation.

Seasonal and Annual Survival of East-Atlantic Pale-Bellied Brent Geese Branta hrota Assessed by Capture-Recapture Analysis

DEFF Research Database (Denmark)

Clausen, P.; Frederiksen, M.; Percival, S. M.

2001-01-01

areas by intensive field studies. In this paper we use standard capture-recapture analysis to investigate seasonal and annual survival rates of the population. We divided the year into three periods with different spatial distribution of the geese, autumn (September-December), winter (Jan...... spring to autumn (0.982 MSR), -resulting in an overall annual survival rate of 0.870. We discuss the variation in seasonal and annual mortality rates in relation to constraints faced by the birds such as seasonal changes in availability of food resources, severe winters, long-distance migration...

Single molecule analysis of c-myb alternative splicing reveals novel classifiers for precursor B-ALL.

Directory of Open Access Journals (Sweden)

Ye E Zhou

Full Text Available The c-Myb transcription factor, a key regulator of proliferation and differentiation in hematopoietic and other cell types, has an N-terminal DNA binding domain and a large C-terminal domain responsible for transcriptional activation, negative regulation and determining target gene specificity. Overexpression and rearrangement of the c-myb gene (MYB has been reported in some patients with leukemias and other types of cancers, implicating activated alleles of c-myb in the development of human tumors. Alternative RNA splicing can produce variants of c-myb with qualitatively distinct transcriptional activities that may be involved in transformation and leukemogenesis. Here, by performing a detailed, single molecule assay we found that c-myb alternative RNA splicing was elevated and much more complex in leukemia samples than in cell lines or CD34+ hematopoietic progenitor cells from normal donors. The results revealed that leukemia samples express more than 60 different c-myb splice variants, most of which have multiple alternative splicing events and were not detectable by conventional microarray or PCR approaches. For example, the single molecule assay detected 21 and 22 splice variants containing the 9B and 9S exons, respectively, most of which encoded unexpected variant forms of c-Myb protein. Furthermore, the detailed analysis identified some splice variants whose expression correlated with poor survival in a small cohort of precursor B-ALL samples. Our findings indicate that single molecule assays can reveal complexities in c-myb alternative splicing that have potential as novel biomarkers and could help explain the role of c-Myb variants in the development of human leukemia.

Survival predictors of preterm neonates: Hospital based study in Iran (2010-2011).

Science.gov (United States)

Haghighi, Ladan; Nojomi, Marzieh; Mohabbatian, Behnaz; Najmi, Zahra

2013-12-01

Preterm birth (PTB) is responsible for 70% of neonatal mortalities. Various factors influence the risk of neonatal mortality in different populations. Our objective was to evaluate neonatal survival rate of preterm infants, and to define its predictors in Iranian population. This retrospective cohort study included all preterm (26-37 weeks) infants (n=1612) born alive in Shahid Akbar-abadi university hospital, during one year period (April 2010-2011). These infants were evaluated for fetal-neonatal, maternal, and pregnancy data. Survival analysis was performed and viability threshold and risk factors of neonatal mortality were evaluated. Total overall mortality rate was 9.1%. Survival rate were 11.11% for extremely low birth weights (LBW) and 45.12% for very early PTBs. The smallest surviving infant was a 750 gr female with gestational age (GA) of 30 weeks and the youngest infants was a 970 gram female with GA of 25weeks plus 2 days. History of previous dead neonate, need to cardio-pulmonary resuscitation (CPR), need to neonatal intensive care unit (NICU) admission, postnatal administration of surfactant, presence of anomalies, Apgar score <7, multiple pregnancy, non-cephalic presentation, early PTB, very early PTB, LBW, very low birth weight (VLBW) and extremely low birth weight (ELBW), were risk factors for mortality in preterm neonates. Our study revealed that neonatal survival rate is dramatically influenced by birth weight especially under 1000grams, GA especially below 30 weeks, neonatal anomalies, history of previous dead fetus, multiple pregnancy, non- cephalic presentation, and need for NICU admission, resuscitation and respiratory support with surfactant.

Cra negatively regulates acid survival in Yersinia pseudotuberculosis.

Science.gov (United States)

Hu, Yangbo; Lu, Pei; Zhang, Yong; Li, Yunlong; Li, Lamei; Huang, Li; Chen, Shiyun

2011-04-01

Survival in acidic environments is important for successful infection of gastrointestinal pathogens. Many bacteria have evolved elaborate mechanisms by inducing or repressing gene expression, which subsequently provide pH homeostasis and enable acid survival. In this study, we employed comparative proteomic analysis to identify the acid-responsive proteins of a food-borne enteric bacterium, Yersinia pseudotuberculosis. The expression level of eight proteins involved in carbohydrate metabolism was up- or downregulated over twofold at pH 4.5 compared with pH 7.0. The role of a global transcriptional regulator catabolite repressor/activator Cra was further studied in this acid survival process. lacZ-fusion analysis showed that expression of cra was repressed under acidic pH. Deletion of the cra gene increased acid survival by 10-fold, whereas complementation restored the wild-type phenotype. These results lead us to propose that, in response to acidic pH, the expression of cra gene is downregulated to increase acid survival. This is the first study to demonstrate the regulatory role of Cra in acid survival in an enteric bacterium. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Using team cognitive work analysis to reveal healthcare team interactions in a birthing unit.

Science.gov (United States)

Ashoori, Maryam; Burns, Catherine M; d'Entremont, Barbara; Momtahan, Kathryn

2014-01-01

Cognitive work analysis (CWA) as an analytical approach for examining complex sociotechnical systems has shown success in modelling the work of single operators. The CWA approach incorporates social and team interactions, but a more explicit analysis of team aspects can reveal more information for systems design. In this paper, Team CWA is explored to understand teamwork within a birthing unit at a hospital. Team CWA models are derived from theories and models of teamwork and leverage the existing CWA approaches to analyse team interactions. Team CWA is explained and contrasted with prior approaches to CWA. Team CWA does not replace CWA, but supplements traditional CWA to more easily reveal team information. As a result, Team CWA may be a useful approach to enhance CWA in complex environments where effective teamwork is required. This paper looks at ways of analysing cognitive work in healthcare teams. Team Cognitive Work Analysis, when used to supplement traditional Cognitive Work Analysis, revealed more team information than traditional Cognitive Work Analysis. Team Cognitive Work Analysis should be considered when studying teams.

Using team cognitive work analysis to reveal healthcare team interactions in a birthing unit

Science.gov (United States)

Ashoori, Maryam; Burns, Catherine M.; d'Entremont, Barbara; Momtahan, Kathryn

2014-01-01

Cognitive work analysis (CWA) as an analytical approach for examining complex sociotechnical systems has shown success in modelling the work of single operators. The CWA approach incorporates social and team interactions, but a more explicit analysis of team aspects can reveal more information for systems design. In this paper, Team CWA is explored to understand teamwork within a birthing unit at a hospital. Team CWA models are derived from theories and models of teamworkand leverage the existing CWA approaches to analyse team interactions. Team CWA is explained and contrasted with prior approaches to CWA. Team CWA does not replace CWA, but supplements traditional CWA to more easily reveal team information. As a result, Team CWA may be a useful approach to enhance CWA in complex environments where effective teamwork is required. Practitioner Summary: This paper looks at ways of analysing cognitive work in healthcare teams. Team Cognitive Work Analysis, when used to supplement traditional Cognitive Work Analysis, revealed more team information than traditional Cognitive Work Analysis. Team Cognitive Work Analysis should be considered when studying teams PMID:24837514

Additive interaction in survival analysis

DEFF Research Database (Denmark)

Rod, Naja Hulvej; Lange, Theis; Andersen, Ingelise

2012-01-01

It is a widely held belief in public health and clinical decision-making that interventions or preventive strategies should be aimed at patients or population subgroups where most cases could potentially be prevented. To identify such subgroups, deviation from additivity of absolute effects...... an empirical example of interaction between education and smoking on risk of lung cancer. We argue that deviations from additivity of effects are important for public health interventions and clinical decision-making, and such estimations should be encouraged in prospective studies on health. A detailed...... is the relevant measure of interest. Multiplicative survival models, such as the Cox proportional hazards model, are often used to estimate the association between exposure and risk of disease in prospective studies. In Cox models, deviations from additivity have usually been assessed by surrogate measures...

Meta-analysis of racial disparities in survival in association with socioeconomic status among men and women with colon cancer.

Science.gov (United States)

Du, Xianglin L; Meyer, Tamra E; Franzini, Luisa

2007-06-01

Few studies have addressed racial disparities in survival for colon cancer by adequately incorporating both treatment and socioeconomic factors, and the findings from those studies have been inconsistent. The objectives of the current study were to systematically review the existing literature and provide a more stable estimate of the measures of association between socioeconomic status and racial disparities in survival for colon cancer by undertaking a meta-analysis. For this meta-analysis, the authors searched the MEDLINE database to identify articles published in English from 1966 to August 2006 that met the following inclusion criteria: original research articles that addressed the association between race/ethnicity and survival in patients with colon or colorectal cancer after adjusting for socioeconomic status. In total, 66 full articles were reviewed, and 56 of those articles were excluded, which left 10 studies for the final analysis. The pooled hazard ratio (HR) for African Americans compared with Caucasians was 1.14 (95% confidence interval [95% CI], 1.00-1.29) for all-cause mortality and 1.13 (95% CI, 1.01-1.28) for colon cancer-specific mortality. The test for homogeneity of the HR was statistically significant across the studies for all-cause mortality (Q=31.69; Pcolon cancer-specific mortality (Q=7.45; P=.114). Racial disparities in survival for colon cancer between African Americans and Caucasians were only marginally significant after adjusting for socioeconomic factors and treatment. Attempts to modify treatment and socioeconomic factors with the objective of reducing racial disparities in health outcomes may have important clinical and public health implications. (c) 2007 American Cancer Society.

An overview of equipment survivability studies at Sandia National Laboratories (SNL)

International Nuclear Information System (INIS)

Bonzon, L.L.; Craft, Ch.M.; McCulloch, W.H.; Sebrell, W.A.

1983-01-01

The USNRC sponsors a number of programs at Sandia National Laboratories (SNL) specifically addressing safety-related equipment survivability. The major thrust of these programs has been the physical testing of equipment. Test results illustrate the importance of a dedicated equipment design effort giving particular attention to the safety implications of the equipment operation. Several equipment survivability tests here have revealed equipment design and test-related deficiencies

Association between response rates and survival outcomes in patients with newly diagnosed multiple myeloma. A systematic review and meta-regression analysis.

Science.gov (United States)

Mainou, Maria; Madenidou, Anastasia-Vasiliki; Liakos, Aris; Paschos, Paschalis; Karagiannis, Thomas; Bekiari, Eleni; Vlachaki, Efthymia; Wang, Zhen; Murad, Mohammad Hassan; Kumar, Shaji; Tsapas, Apostolos

2017-06-01

We performed a systematic review and meta-regression analysis of randomized control trials to investigate the association between response to initial treatment and survival outcomes in patients with newly diagnosed multiple myeloma (MM). Response outcomes included complete response (CR) and the combined outcome of CR or very good partial response (VGPR), while survival outcomes were overall survival (OS) and progression-free survival (PFS). We used random-effect meta-regression models and conducted sensitivity analyses based on definition of CR and study quality. Seventy-two trials were included in the systematic review, 63 of which contributed data in meta-regression analyses. There was no association between OS and CR in patients without autologous stem cell transplant (ASCT) (regression coefficient: .02, 95% confidence interval [CI] -0.06, 0.10), in patients undergoing ASCT (-.11, 95% CI -0.44, 0.22) and in trials comparing ASCT with non-ASCT patients (.04, 95% CI -0.29, 0.38). Similarly, OS did not correlate with the combined metric of CR or VGPR, and no association was evident between response outcomes and PFS. Sensitivity analyses yielded similar results. This meta-regression analysis suggests that there is no association between conventional response outcomes and survival in patients with newly diagnosed MM. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Neutrophil-to-lymphocyte ratio as an independent predictor for survival in patients with localized clear cell renal cell carcinoma after radiofrequency ablation: a propensity score matching analysis.

Science.gov (United States)

Chang, Xiaofeng; Zhang, Fan; Liu, Tieshi; Wang, Wei; Guo, Hongqian

2017-06-01

To investigate the role of neutrophil-to-lymphocyte ratio as a prognostic indicator in patients with localized clear cell renal cell carcinoma treated with radiofrequency ablation. We retrospectively analyzed data from patients with renal cell carcinoma who underwent radiofrequency ablation from 2006 to 2013. The Kaplan-Meier method was used to generate the survival curves according to different categories of neutrophil-to-lymphocyte ratio. Relationships between preoperative neutrophil-to-lymphocyte ratio or the change of neutrophil-to-lymphocyte ratio and survival were evaluated with multivariable Cox proportional hazards regression analysis. A propensity score matching analysis was carried out to avoid confounding bias. A total of 185 patients were included in present study. When stratified by preoperative neutrophil-to-lymphocyte ratio cutoff value of 2.79, 5-year recurrence-free survival, 5-year disease-free survival, and 5-year overall survival rates of neutrophil-to-lymphocyte ratio analysis, 5-year recurrence-free survival, 5-year disease-free survival, and 5-year overall survival rates of neutrophil-to-lymphocyte ratio ratio with the change of neutrophil-to-lymphocyte ratio, patients with both preoperative neutrophil-to-lymphocyte ratio ≥2.79 and the change of neutrophil-to-lymphocyte ratio ≥0.40 had the worst disease-free survival. Results of multivariable analysis showed that preoperative neutrophil-to-lymphocyte ratio and the change of neutrophil-to-lymphocyte ratio correlated with cancer relapse remarkably. High preoperative neutrophil-to-lymphocyte ratio and elevated postoperative neutrophil-to-lymphocyte ratio are associated with significant increase in risk of local recurrence as well as distant metastasis. The combination of neutrophil-to-lymphocyte ratio with the other prognostic indicators can be applied in the evaluation of relapse risk in patients with clear cell renal cell carcinoma after radiofrequency ablation.

Hypofractionated radiation therapy for invasive thyroid carcinoma in dogs: a retrospective analysis of survival

International Nuclear Information System (INIS)

Brearley, M.J.; Hayes, A.M.; Murphy, S.

1999-01-01

Thirteen dogs with invasive thyroid carcinoma (WHO classification T2b or T3b) seen between January 1991 and October 1997 were treated by external beam Irradiation. Four once-weekly fractions of 9 gray of 4 MeV X-rays were administered. Four of the dogs died of progression of the primary disease and four from metastatic spread. Of the remaining dogs, three died of unrelated problems, although two were still alive at the time of the censor. Kaplan-Meier analysis of the survival time from first dose to death from either primary or metastatic disease gave a median survival time of 96 weeks (mean 85 weeks, range six to 247 weeks). Radiographic evidence of pulmonary metastatic disease at presentation had no prognostic value whereas crude growth rate was a highly significant factor. The present series Indicates that radiation therapy should be considered an important modality for the control of invasive thyroid carcinoma in the dog

Rural factors and survival from cancer: analysis of Scottish cancer registrations.

Science.gov (United States)

Campbell, N C; Elliott, A M; Sharp, L; Ritchie, L D; Cassidy, J; Little, J

2000-06-01

In this survival study 63,976 patients diagnosed with one of six common cancers in Scotland were followed up. Increasing distance from a cancer centre was associated with less chance of diagnosis before death for stomach, breast and colorectal cancers and poorer survival after diagnosis for prostate and lung cancers.

Investigation of Prognostic Factors and Survival without Recurrence in Patients with Breast Cancer

Directory of Open Access Journals (Sweden)

Ahmad Abdollahi

2017-01-01

Full Text Available Background: One of the major consequences of breast cancer is the recurrence of the disease. The objective of present study was to estimate the 7-year survival without recurrence as well as the effective prognostic factors in recurrence. Materials and Methods: This historical cohort survival analysis was conducted on 1329 patients diagnosed with breast cancer in Motahari Breast Clinic, Shiraz, Iran between 2004 and 2011. We estimated the rate of survival without recurrence through the Kaplan–Meier method and the difference between the survival curves was investigated using the log-rank test. Furthermore, Cox regression model was used to model the effective factors in local recurrence as well as metastasis. Results: The mean age of the patients was 54.8 ± 11.4 years. Estrogen receptor positive, progesterone receptor positive, and human epidermal growth factor receptor-2 positive were observed in 70.6%, 66.6%, and 34.4% of the cases, respectively. The mean of the follow-up period was 3.7 ± 1.8 years in all patients. The results of the Kaplan–Meier method revealed 1-, 3-, 5-, and 7-year rate of survival without recurrence as 96.4%, 78.4%, 66.3%, and 54.8%, respectively. There was a significant relationship between survival without recurrence and histology grade (hazard ratio [HR] = 1.66, P = 0.009, neural invasion (HR = 1.74, P = 0.006, and progesterone receptors (HR = 0.69, P = 0.031. Conclusion: In this study, the rate of survival without recurrence in breast cancer was 54.8%. Among factors, histology grade and neural involvement at the time of diagnosis increased the chance of recurrence and progesterone receptors caused a longer interval between diagnosis and recurrence.

First recovery in anorexia nervosa patients in the long-term course: a discrete-time survival analysis.

Science.gov (United States)

Herzog, W; Schellberg, D; Deter, H C

1997-02-01

The results of a 12-year follow-up study of occurrence and timing of first recovery in 69 hospitalized patients with severe anorexia nervosa (AN) are presented. For the first time discrete-time survival analysis methods were used to determine the likelihood of recovery in AN patients. Furthermore, predictors gleaned from pretreatment-posttreatment studies of long-term outcome in AN could be evaluated as to their effect on a change in the time course structure of the likelihood of first recovery. Results show that AN condition did not improve until after 6 years after the first inpatient treatment in 50% of patients. However, a restricter-type AN and low serum creatinine levels were predictors for earlier recovery. One specific effect was that AN patients who show purging behavior in combination with additional social disturbances have a lower chance of recovering. The use of discrete-time survival analysis methodology in further prospective studies will contribute to the development of more tailored treatment of AN, which also takes the individual phase of illness and specific aspects of the symptomatology into account.

Relationships between mastitis and functional longevity in Danish Black and White dairy cattle estimated using survival analysis

NARCIS (Netherlands)

Neerhof, H.J.; Madsen, P.; Ducrucq, V.; Vollema, A.R.; Jensen, I.; Korsgaard, I.R.

2000-01-01

The relationship between mastitis and functional longevity was assessed with survival analysis on data of Danish Black and White dairy cows. Different methods of including the effect of mastitis treatment on the culling decision by a farmer in the model were compared. The model in which mastitis

Polymorphisms of LIG4, BTBD2, HMGA2, and RTEL1 genes involved in the double-strand break repair pathway predict glioblastoma survival.

Science.gov (United States)

Liu, Yanhong; Shete, Sanjay; Etzel, Carol J; Scheurer, Michael; Alexiou, George; Armstrong, Georgina; Tsavachidis, Spyros; Liang, Fu-Wen; Gilbert, Mark; Aldape, Ken; Armstrong, Terri; Houlston, Richard; Hosking, Fay; Robertson, Lindsay; Xiao, Yuanyuan; Wiencke, John; Wrensch, Margaret; Andersson, Ulrika; Melin, Beatrice S; Bondy, Melissa

2010-05-10

Glioblastoma (GBM) is the most common and aggressive type of glioma and has the poorest survival. However, a small percentage of patients with GBM survive well beyond the established median. Therefore, identifying the genetic variants that influence this small number of unusually long-term survivors may provide important insight into tumor biology and treatment. Among 590 patients with primary GBM, we evaluated associations of survival with the 100 top-ranking glioma susceptibility single nucleotide polymorphisms from our previous genome-wide association study using Cox regression models. We also compared differences in genetic variation between short-term survivors (STS; or= 36 months), and explored classification and regression tree analysis for survival data. We tested results using two independent series totaling 543 GBMs. We identified LIG4 rs7325927 and BTBD2 rs11670188 as predictors of STS in GBM and CCDC26 rs10464870 and rs891835, HMGA2 rs1563834, and RTEL1 rs2297440 as predictors of LTS. Further survival tree analysis revealed that patients >or= 50 years old with LIG4 rs7325927 (V) had the worst survival (median survival time, 1.2 years) and exhibited the highest risk of death (hazard ratio, 17.53; 95% CI, 4.27 to 71.97) compared with younger patients with combined RTEL1 rs2297440 (V) and HMGA2 rs1563834 (V) genotypes (median survival time, 7.8 years). Polymorphisms in the LIG4, BTBD2, HMGA2, and RTEL1 genes, which are involved in the double-strand break repair pathway, are associated with GBM survival.

Rituximab is associated with improved survival in Burkitt lymphoma: a retrospective analysis from two US academic medical centers.

Science.gov (United States)

Wildes, Tanya M; Farrington, Laura; Yeung, Cecilia; Harrington, Alexandra M; Foyil, Kelley V; Liu, Jingxia; Kreisel, Friederike; Bartlett, Nancy L; Fenske, Timothy S

2014-02-01

Burkitt lymphoma (BL) is a rare, highly aggressive B-cell malignancy treated most successfully with brief-duration, high-intensity chemotherapeutic regimens. The benefit of the addition of rituximab to these regimens remains uncertain. We sought to examine the effectiveness of chemotherapy with and without rituximab in patients with BL. This study is a retrospective cohort study of all adult patients with BL diagnosed and treated with modern, dose-intense chemotherapeutic regimens from 1998-2008 at two tertiary care institutions. All cases were confirmed by application of WHO 2008 criteria by hematopathologists. Medical records were reviewed for patient-, disease-, and treatment- related factors as well as treatment response and survival. Factors associated with survival were analyzed using Cox proportional hazards modeling. A total of 35 patients were analyzed: 18 patients received rituximab with chemotherapy (R-chemo) and 17 received chemotherapy (chemo) alone. The median age was 42 (range 20-74 years); 57% were male; 71% had Ann Arbor Stage IV disease; 33% had central nervous system involvement; 78% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. R-chemo was associated with significantly longer overall survival (OS) than chemo alone (5-year OS 70% and 29%, respectively, p = 0.040). On multivariate regression analysis, poor performance status and central nervous system involvement were associated with poorer survival. The addition of rituximab to chemotherapy was associated with improved OS in patients with Burkitt lymphoma. Poor performance status and central nervous system involvement were prognostically significant on multivariate analysis.

Attributing death to cancer: cause-specific survival estimation.

Directory of Open Access Journals (Sweden)

Mathew A

2002-10-01

Full Text Available Cancer survival estimation is an important part of assessing the overall strength of cancer care in a region. Generally, the death of a patient is taken as the end point in estimation of overall survival. When calculating the overall survival, the cause of death is not taken into account. With increasing demand for better survival of cancer patients it is important for clinicians and researchers to know about survival statistics due to disease of interest, i.e. net survival. It is also important to choose the best method for estimating net survival. Increase in the use of computer programmes has made it possible to carry out statistical analysis without guidance from a bio-statistician. This is of prime importance in third- world countries as there are a few trained bio-statisticians to guide clinicians and researchers. The present communication describes current methods used to estimate net survival such as cause-specific survival and relative survival. The limitation of estimation of cause-specific survival particularly in India and the usefulness of relative survival are discussed. The various sources for estimating cancer survival are also discussed. As survival-estimates are to be projected on to the population at large, it becomes important to measure the variation of the estimates, and thus confidence intervals are used. Rothman′s confidence interval gives the most satisfactory result for survival estimate.

Survival and its predictors from age 75 to 85 in men and women belonging to cohorts with marked survival differences to age 75

DEFF Research Database (Denmark)

Heikkinen, E; Kauppinen, M; Schroll, M

2016-01-01

focusing on different domains of health, functional capacity, and physical and social activities. RESULTS: The proportion of survivors to age 75 was markedly smaller among the Finnish men and women than Danish or Swedish subjects. In the local population no marked differences in survival from age 75 to 85...... among three local Nordic populations using survival data on national cohorts as background information. METHODS: The data were derived from national registers and from samples of 75-year old living in Denmark, Sweden, and Finland. The subjects were invited to take part in interviews and examinations...... were observed between the groups of men, while women survived longer than men and longer in Göteborg than in Glostrup or Jyväskylä. Univariate models revealed 12 predictors of survival. In the multivariate models, the significant predictors among men related to physical fitness, whereas among women...

Prehospital critical care for out-of-hospital cardiac arrest: An observational study examining survival and a stakeholder-focused cost analysis.

Science.gov (United States)

von Vopelius-Feldt, Johannes; Powell, Jane; Morris, Richard; Benger, Jonathan

2016-12-07

Survival rates from out-of-hospital cardiac arrest (OHCA) remain low, despite remarkable efforts to improve care. A number of ambulance services in the United Kingdom (UK) have developed prehospital critical care teams (CCTs) which attend critically ill patients, including OHCA. However, current scientific evidence describing CCTs attending OHCA is sparse and research to date has not demonstrated clear benefits from this model of care. This prospective, observational study will describe the effect of CCTs on survival from OHCA, when compared to advanced-life-support (ALS), the current standard of prehospital care in the UK. In addition, we will describe the association between individual critical care interventions and survival, and also the costs of CCTs for OHCA. To examine the effect of CCTs on survival from OHCA, we will use routine Utstein variables data already collected in a number of UK ambulance trusts. We will use propensity score matching to adjust for imbalances between the CCT and ALS groups. The primary outcome will be survival to hospital discharge, with the secondary outcome of survival to hospital admission. We will record the critical care interventions delivered during CCT attendance at OHCA. We will describe frequencies and aim to use multiple logistic regression to examine possible associations with survival. Finally, we will undertake a stakeholder-focused cost analysis of CCTs for OHCA. This will utilise a previously published Emergency Medical Services (EMS) cost analysis toolkit and will take into account the costs incurred from use of a helicopter and the proportion of these costs currently covered by charities in the UK. Prehospital critical care for OHCA is not universally available in many EMS. In the UK, it is variable and largely funded through public donations to charities. If this study demonstrates benefit from CCTs at an acceptable cost to the public or EMS commissioners, it will provide a rationale to increase funding and service

Lung Shunt Fraction prior to Yttrium-90 Radioembolization Predicts Survival in Patients with Neuroendocrine Liver Metastases: Single-Center Prospective Analysis

Energy Technology Data Exchange (ETDEWEB)

Ludwig, Johannes M. [Yale University, Division of Interventional Radiology, Department of Radiology and Biomedical Imaging (United States); Ambinder, Emily McIntosh [John Hopkins University School of Medicine, Department of Diagnostic Radiology (United States); Ghodadra, Anish [University of Pittsburgh School of Medicine, Interventional Radiology, Department of Radiology (United States); Xing, Minzhi [Yale University, Division of Interventional Radiology, Department of Radiology and Biomedical Imaging (United States); Prajapati, Hasmukh J. [The University of Tennessee Health Science Center, Division of Interventional Radiology, Department of Radiology (United States); Kim, Hyun S., E-mail: kevin.kim@yale.edu [Yale University, Division of Interventional Radiology, Department of Radiology and Biomedical Imaging (United States)

2016-07-15

ObjectiveTo investigate survival outcomes following radioembolization with Yttrium-90 (Y90) for neuroendocrine tumor liver metastases (NETLMs). This study was designed to assess the efficacy of Y90 radioembolization and to evaluate lung shunt fraction (LSF) as a predictor for survival.MethodsA single-center, prospective study of 44 consecutive patients (median age: 58.5 years, 29.5 % male) diagnosed with pancreatic (52.3 %) or carcinoid (47.7 %) NETLMs from 2006 to 2012 who underwent Y90 radioembolization was performed. Patients’ baseline characteristics, including LSF and median overall survival (OS) from first Y90 radioembolization, were recorded and compared between patients with high (≥10 %) and low (<10 %) LSF. Baseline comparisons were performed using Fisher’s exact tests for categorical and Mann–Whitney U test for continuous variables. Survival was calculated using the Kaplan–Meier method. Univariate (Wilcoxon rank-sum test) and multivariate analyses (Cox Proportional Hazard Model) for risk factor analysis were performed.ResultsThere was no statistically significant difference in age, gender, race, tumor properties, or previous treatments between patients with high (n = 15) and low (n = 29) LSF. The median OS was 27.4 months (95 %CI 12.73–55.23), with 4.77 months (95 %CI 2.87–26.73) for high and 42.77 months (95 %CI 18.47–59.73) for low LSF (p = 0.003). Multivariate analysis identified high LSF (p = 0.001), total serum bilirubin >1.2 mg (p = 0.016), and lack of pretreatment with octreotide (p = 0.01) as independent prognostic factors for poorer survival. Tumor type and total radiation dose did not predict survival.ConclusionsLSF ≥10 %, elevated bilirubin levels, and lack of pretreatment with octreotide were found to be independent prognostic factors for poorer survival in patients with NETLMs.

Survival, causes of death, and prognostic factors in systemic sclerosis: analysis of 947 Brazilian patients.

Science.gov (United States)

Sampaio-Barros, Percival D; Bortoluzzo, Adriana B; Marangoni, Roberta G; Rocha, Luiza F; Del Rio, Ana Paula T; Samara, Adil M; Yoshinari, Natalino H; Marques-Neto, João Francisco

2012-10-01

To analyze survival, prognostic factors, and causes of death in a large cohort of patients with systemic sclerosis (SSc). From 1991 to 2010, 947 patients with SSc were treated at 2 referral university centers in Brazil. Causes of death were considered SSc-related and non-SSc-related. Multiple logistic regression analysis was used to identify prognostic factors. Survival at 5 and 10 years was estimated using the Kaplan-Meier method. One hundred sixty-eight patients died during the followup. Among the 110 deaths considered related to SSc, there was predominance of lung (48.1%) and heart (24.5%) involvement. Most of the 58 deaths not related to SSc were caused by infection, cardiovascular or cerebrovascular disease, and cancer. Male sex, modified Rodnan skin score (mRSS) > 20, osteoarticular involvement, lung involvement, and renal crisis were the main prognostic factors associated to death. Overall survival rate was 90% for 5 years and 84% for 10 years. Patients presented worse prognosis if they had diffuse SSc (85% vs 92% at 5 yrs, respectively, and 77% vs 87% at 10 yrs, compared to limited SSc), male sex (77% vs 90% at 5 yrs and 64% vs 86% at 10 yrs, compared to female sex), and mRSS > 20 (83% vs 90% at 5 yrs and 66% vs 86% at 10 yrs, compared to mRSS < 20). Survival was worse in male patients with diffuse SSc, and lung and heart involvement represented the main causes of death in this South American series of patients with SSc.

Parent-child communication and marijuana initiation: evidence using discrete-time survival analysis.

Science.gov (United States)

Nonnemaker, James M; Silber-Ashley, Olivia; Farrelly, Matthew C; Dench, Daniel

2012-12-01

This study supplements existing literature on the relationship between parent-child communication and adolescent drug use by exploring whether parental and/or adolescent recall of specific drug-related conversations differentially impact youth's likelihood of initiating marijuana use. Using discrete-time survival analysis, we estimated the hazard of marijuana initiation using a logit model to obtain an estimate of the relative risk of initiation. Our results suggest that parent-child communication about drug use is either not protective (no effect) or - in the case of youth reports of communication - potentially harmful (leading to increased likelihood of marijuana initiation). Copyright © 2012 Elsevier Ltd. All rights reserved.

Analysis of Survival of Patients with Chronic Myeloid Leukemia Treated with Imatinib in the Last 15 Years in Lebanon.

Science.gov (United States)

Massoud, Marcel; Sakr, Riwa; Kerbage, Fouad; Makdissi, Joseph; Hawi, Jenny; Rached, Layale; Nasr, Fady; Chahine, Georges

2017-07-01

In the 2000s, the introduction of the tyrosine kinase inhibitor (TKI), imatinib, improved the survival outcomes of patients with chronic myeloid leukemia (CML). In Lebanon, we rapidly adopted this treatment strategy. To the best of our knowledge, this is the first study reporting the survival rates of Lebanese CML patients. We examined the rates of major molecular response (MMR) and complete cytogenetic response (CCyR) and analyzed the overall survival, progression-free survival, and event-free survival of CML patients treated with front-line imatinib in 3 university hospitals in Lebanon. We retrospectively reviewed the medical records of 46 patients diagnosed with CML and treated with front-line imatinib 400 mg/day from 2000 and followed up to 2015. In all patients, initially, 2 diagnostic tests were performed: cytogenetic analysis and qualitative molecular testing of the BCR-ABL transcript. The male-to-female sex ratio was 3:1. The median age at diagnosis was 49 years, and the mean age was 44.52 years. At diagnosis, 46 patients were in the chronic phase. All patients started imatinib 400 mg/day. Of the 46 patients, 35 had a typical karyotype, 8 an atypical karyotype, and 3 hypoploidism. The MMR rate at 18 months was 58.69%. The cumulative CCyR rate at 18 months of therapy with imatinib at the standard dose was 67.39%. The event-free survival rate was 75.86% and 74.14% at 5 and 8 years, respectively. The progression-free survival rate was 77.59% and 75.86% at 5 and 8 years, respectively. The overall survival rate was 98.27% and 98.27% at 5 and 8 years, respectively. Of the 46 patients, 12 developed disease progression and were salvaged by second-generation TKIs. These 12 patients were still alive with a MMR. In our study population, the achievement of a MMR and CCyR and overall survival, progression-free survival, and event-free survival were similar to previous published data. Reaching high survival rates with a first-generation TKI in a country with limited

Examining the Influence of Campus Climate on Students' Time to Degree: A Multilevel Discrete-Time Survival Analysis

Science.gov (United States)

Zhou, Ji; Castellanos, Michelle

2013-01-01

Utilizing longitudinal data of 3477 students from 28 institutions, we examine the effects of structural diversity and quality of interracial relation on students' persistence towards graduation within six years. We utilize multilevel discrete-time survival analysis to account for the longitudinal persistence patterns as well as the nested…

Repurposing Lesogaberan to Promote Human Islet Cell Survival and β-Cell Replication

Directory of Open Access Journals (Sweden)

Jide Tian

2017-01-01

Full Text Available The activation of β-cell’s A- and B-type gamma-aminobutyric acid receptors (GABAA-Rs and GABAB-Rs can promote their survival and replication, and the activation of α-cell GABAA-Rs promotes their conversion into β-cells. However, GABA and the most clinically applicable GABA-R ligands may be suboptimal for the long-term treatment of diabetes due to their pharmacological properties or potential side-effects on the central nervous system (CNS. Lesogaberan (AZD3355 is a peripherally restricted high-affinity GABAB-R-specific agonist, originally developed for the treatment of gastroesophageal reflux disease (GERD that appears to be safe for human use. This study tested the hypothesis that lesogaberan could be repurposed to promote human islet cell survival and β-cell replication. Treatment with lesogaberan significantly enhanced replication of human islet cells in vitro, which was abrogated by a GABAB-R antagonist. Immunohistochemical analysis of human islets that were grafted into immune-deficient mice revealed that oral treatment with lesogaberan promoted human β-cell replication and islet cell survival in vivo as effectively as GABA (which activates both GABAA-Rs and GABAB-Rs, perhaps because of its more favorable pharmacokinetics. Lesogaberan may be a promising drug candidate for clinical studies of diabetes intervention and islet transplantation.

Biofilm formation enhances Helicobacter pylori survivability in vegetables.

Science.gov (United States)

Ng, Chow Goon; Loke, Mun Fai; Goh, Khean Lee; Vadivelu, Jamuna; Ho, Bow

2017-04-01

To date, the exact route and mode of transmission of Helicobacter pylori remains elusive. The detection of H. pylori in food using molecular approaches has led us to postulate that the gastric pathogen may survive in the extragastric environment for an extended period. In this study, we show that H. pylori prolongs its survival by forming biofilm and micro-colonies on vegetables. The biofilm forming capability of H. pylori is both strain and vegetable dependent. H. pylori strains were classified into high and low biofilm formers based on their highest relative biofilm units (BU). High biofilm formers survived longer on vegetables compared to low biofilm formers. The bacteria survived better on cabbage compared to other vegetables tested. In addition, images captured on scanning electron and confocal laser scanning microscopes revealed that the bacteria were able to form biofilm and reside as micro-colonies on vegetable surfaces, strengthening the notion of possible survival of H. pylori on vegetables for an extended period of time. Taken together, the ability of H. pylori to form biofilm on vegetables (a common food source for human) potentially plays an important role in its survival, serving as a mode of transmission of H. pylori in the extragastric environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Analysis of survival for patients with chronic kidney disease primarily related to renal cancer surgery.

Science.gov (United States)

Wu, Jitao; Suk-Ouichai, Chalairat; Dong, Wen; Antonio, Elvis Caraballo; Derweesh, Ithaar H; Lane, Brian R; Demirjian, Sevag; Li, Jianbo; Campbell, Steven C

2018-01-01

To evaluate predictors of long-term survival for patients with chronic kidney disease primarily due to surgery (CKD-S). Patients with CKD-S have generally good survival that approximates patients who do not have CKD even after renal cancer surgery (RCS), yet there may be heterogeneity within this cohort. From 1997 to 2008, 4 246 patients underwent RCS at our centre. The median (interquartile range [IQR]) follow-up was 9.4 (7.3-11.0) years. New baseline glomerular filtration rate (GFR) was defined as highest GFR between nadir and 6 weeks after RCS. We retrospectively evaluated three cohorts: no-CKD (new baseline GFR of ≥60 mL/min/1.73 m 2 ); CKD-S (new baseline GFR of cancer-related survival (NRCRS) for the CKD-S cohort. Kaplan-Meier analysis assessed the longitudinal impact of new baseline GFR (45-60 mL/min/1.73 m 2 vs <45 mL/min/1.73 m 2 ) and Cox regression evaluated relative impact of preoperative GFR, new baseline GFR, and relevant demographics/comorbidities. Of the 4 246 patients who underwent RCS, 931 had CKD-S and 1 113 had CKD-M/S, whilst 2 202 had no-CKD even after RCS. Partial/radical nephrectomy (PN/RN) was performed in 54%/46% of the patients, respectively. For CKD-S, 641 patients had a new baseline GFR of 45-60 mL/min/1.73 m 2 and 290 had a new baseline GFR of <45 mL/min/1.73 m 2 . Kaplan-Meier analysis showed significantly reduced NRCRS for patients with CKD-S with a GFR of <45 mL/min/1.73 m 2 compared to those with no-CKD or CKD-S with a GFR of 45-60 mL/min/1.73 m 2 (both P ≤ 0.004), and competing risk analysis confirmed this (P < 0.001). Age, gender, heart disease, and new baseline GFR were all associated independently with NRCRS for patients with CKD-S (all P ≤ 0.02). Our data suggest that CKD-S is heterogeneous, and patients with a reduced new baseline GFR have compromised survival, particularly if <45 mL/min/1.73 m 2 . Our findings may have implications regarding choice of PN/RN in patients at risk of developing

Long-term survival of two dogs after mitral valve plasty

Directory of Open Access Journals (Sweden)

Isamu Kanemoto

2017-04-01

Full Text Available Two small 9-year-old dogs received mitral valve plasty (MVP for severe mitral regurgitation that could not be controlled via drug administration. MVP consisted of chordal reconstruction using expanded polytetrafluoroethylene (ePTFE sutures and semicircular suture annuloplasty using polypropylene sutures. In both cases, the clinical signs dramatically improved after MVP, although postoperative echocardiography revealed slight residual mitral regurgitant flow. Both dogs survived for several years after MVP without any signs of cardiac distress; one dog survived for 9 years and 1 month, and the other dog survived for 7 years and 10 months. These findings highlight the durability of ePTFE sutures as artificial chordae and the excellence of semicircular suture annuloplasty in small dogs.

Use of a Survival Analysis Technique in Understanding Game Performance in Instructional Games. CRESST Report 812

Science.gov (United States)

Kim, Jinok; Chung, Gregory K. W. K.

2012-01-01

In this study we compared the effects of two math game designs on math and game performance, using discrete-time survival analysis (DTSA) to model players' risk of not advancing to the next level in the game. 137 students were randomly assigned to two game conditions. The game covered the concept of a unit and the addition of like-sized fractional…

Outcome of cardiopulmonary resuscitation - predictors of survival

International Nuclear Information System (INIS)

Ishtiaq, O.; Iqbal, M.; Zubair, M.; Qayyum, R.; Adil, M.

2008-01-01

To assess the outcomes of patients undergoing cardiopulmonary resuscitation (CPR). Data were collected retrospectively of all adult patients who underwent CPR. Clinical outcomes of interest were survival at the end of CPR and survival at discharge from hospital. Factors associated with survival were evaluated using logistic regression analysis. Of the 159 patients included, 55 (35%) were alive at the end of CPR and 17 (11%) were discharged alive from the hospital. At the end of CPR, univariate logistic regression analysis found the following factors associated with survival: cardiac arrest within hospital as compared to outside the hospital (odds ratio = 2.8, 95% CI = 1.27-6.20, p-value = 0.01), both cardiac and pulmonary arrest as compared to either cardiac or pulmonary arrest (odds ratio = 0.37, 95% CI = 0.19- 0.73, p-value = 0.004), asystole as cardiac rhythm at presentation (odds ratio = 0.47, 95% CI = 0.24-0.93, p-value = 0.03), and total atropine dose given during CPR (odds ratio = 0.78, 95% CI = 0.62-0.97, p-value = 0.02). In multivariate logistic regression, cardiac arrest within hospital (odds ratio = 2.52, 95% CI = 1.06-5.99, p-value = 0.04) and both cardiac and pulmonary arrest as compared to cardiac or pulmonary arrest (odds ratio = 0.44, 95% CI = 0.21-0.91, p-value = 0.03) were associated with survival at the end of CPR. At the time of discharge from hospital, univariate logistic regression analysis found following factors that were associated with survival: cardiac arrest within hospital (odds ratio = 8.4, 95% CI = 1.09-65.64, p-value = 0.04), duration of CPR (odds ratio = 0.91, 95% CI = 0.85-0.96, p-value = 0.001), and total atropine dose given during CPR (odds ratio = 0.68, 95% CI = 0.47-0.99, p-value = 0.05). In multivariate logistic regression analysis cardiac arrest within hospital (odds ratio 8.69, 95% CI = 1.01-74.6, p-value = 0.05) and duration of CPR (odds ratio 0.92, 95% CI = 0.87-0.98, p-value = 0.01) were associated with survival at

Survival benefit of postoperative radiation in papillary meningioma: Analysis of the National Cancer Data Base.

Science.gov (United States)

Sumner, Whitney A; Amini, Arya; Hankinson, Todd C; Foreman, Nicholas K; Gaspar, Laurie E; Kavanagh, Brian D; Karam, Sana D; Rusthoven, Chad G; Liu, Arthur K

2017-01-01

Papillary meningioma represents a rare subset of World Health Organization (WHO) Grade III meningioma that portends an overall poor prognosis. There is relatively limited data regarding the benefit of postoperative radiation therapy (PORT). We used the National Cancer Data Base (NCDB) to compare overall survival (OS) outcomes of surgically resected papillary meningioma cases undergoing PORT compared to post-operative observation. The NCDB was queried for patients with papillary meningioma, diagnosed between 2004 and 2013, who underwent upfront surgery with or without PORT. Overall survival (OS) was determined using the Kaplan-Meier method. Univariate (UVA) and multivariate (MVA) analyses were performed. In total, 190 patients were identified; 89 patients underwent PORT, 101 patients were observed. Eleven patients received chemotherapy (6 with PORT, 5 without). 2-Year OS was significantly improved with PORT vs. no PORT (93.0% vs. 74.4%), as was 5-year OS (78.5% vs. 62.5%) (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.27-0.85; p  = 0.01). On MVA, patients receiving PORT had improved OS compared to observation (HR, 0.41; 95% CI, 0.22-0.76; p  = 0.005). On subset analysis by age group, the benefit of PORT vs. no PORT was significant in patients ≤18 years ( n  = 13), with 2-year OS of 85.7% vs. 50.0% (HR, 0.08; 95% CI, 0.01-0.80; p  = 0.032) and for patients >18 years ( n  = 184), with 2-year OS of 94.7% vs. 76.1% (HR, 0.55; 95% CI, 0.31-1.00; p  = 0.049), respectively. In this large contemporary analysis, PORT was associated with improved survival for both adult and pediatric patients with papillary meningioma. PORT should be considered in those who present with this rare, aggressive tumor.

Association between Pre-Transplant Serum Malondialdehyde Levels and Survival One Year after Liver Transplantation for Hepatocellular Carcinoma

Directory of Open Access Journals (Sweden)

Leonardo Lorente

2016-04-01

Full Text Available Previous studies have found higher levels of serum malondialdehyde (MDA in hepatocellular carcinoma (HCC patients compared to healthy controls and higher MDA concentrations in tumoral tissue of HCC patients than in non-tumoral tissue. However, the association between pre-transplant serum levels of MDA and survival in HCC patients after liver transplantation (LT has not been described, and the aim of the present study was to determine whether such an association exists. In this observational study we measured serum MDA levels in 127 patients before LT. We found higher pre-LT serum MDA levels in 15 non-surviving than in 112 surviving patients one year after LT (p = 0.02. Exact binary logistic regression analysis revealed that pre-LT serum levels of MDA over 3.37 nmol/mL were associated with mortality after one year of LT (Odds ratio = 5.38; 95% confidence interval (CI = from 1.580 to infinite; p = 0.007 adjusting for age of the deceased donor. The main finding of our study was that there is an association between serum MDA levels before LT for HCC and 1-year survival after LT.

Association between Pre-Transplant Serum Malondialdehyde Levels and Survival One Year after Liver Transplantation for Hepatocellular Carcinoma

Science.gov (United States)

Lorente, Leonardo; Rodriguez, Sergio T.; Sanz, Pablo; Abreu-González, Pedro; Díaz, Dácil; Moreno, Antonia M.; Borja, Elisa; Martín, María M.; Jiménez, Alejandro; Barrera, Manuel A.

2016-01-01

Previous studies have found higher levels of serum malondialdehyde (MDA) in hepatocellular carcinoma (HCC) patients compared to healthy controls and higher MDA concentrations in tumoral tissue of HCC patients than in non-tumoral tissue. However, the association between pre-transplant serum levels of MDA and survival in HCC patients after liver transplantation (LT) has not been described, and the aim of the present study was to determine whether such an association exists. In this observational study we measured serum MDA levels in 127 patients before LT. We found higher pre-LT serum MDA levels in 15 non-surviving than in 112 surviving patients one year after LT (p = 0.02). Exact binary logistic regression analysis revealed that pre-LT serum levels of MDA over 3.37 nmol/mL were associated with mortality after one year of LT (Odds ratio = 5.38; 95% confidence interval (CI) = from 1.580 to infinite; p = 0.007) adjusting for age of the deceased donor. The main finding of our study was that there is an association between serum MDA levels before LT for HCC and 1-year survival after LT. PMID:27058525

A survival analysis on critical components of nuclear power plants

International Nuclear Information System (INIS)

Durbec, V.; Pitner, P.; Riffard, T.

1995-06-01

Some tubes of heat exchangers of nuclear power plants may be affected by Primary Water Stress Corrosion Cracking (PWSCC) in highly stressed areas. These defects can shorten the lifetime of the component and lead to its replacement. In order to reduce the risk of cracking, a preventive remedial operation called shot peening was applied on the French reactors between 1985 and 1988. To assess and investigate the effects of shot peening, a statistical analysis was carried on the tube degradation results obtained from in service inspection that are regularly conducted using non destructive tests. The statistical method used is based on the Cox proportional hazards model, a powerful tool in the analysis of survival data, implemented in PROC PHRED recently available in SAS/STAT. This technique has a number of major advantages including the ability to deal with censored failure times data and with the complication of time-dependant co-variables. The paper focus on the modelling and a presentation of the results given by SAS. They provide estimate of how the relative risk of degradation changes after peening and indicate for which values of the prognostic factors analyzed the treatment is likely to be most beneficial. (authors). 2 refs., 3 figs., 6 tabs

Postmastectomy Radiation Therapy Is Associated With Improved Survival in Node-Positive Male Breast Cancer: A Population Analysis

Energy Technology Data Exchange (ETDEWEB)

Abrams, Matthew J., E-mail: mabrams@tuftsmedicalcenter.org [Department of Radiation Oncology, Tufts University School of Medicine, Tufts Medical Center, Boston, Massachusetts (United States); Koffer, Paul P. [Department of Radiation Oncology, Tufts University School of Medicine, Tufts Medical Center, Boston, Massachusetts (United States); Wazer, David E. [Department of Radiation Oncology, Tufts University School of Medicine, Tufts Medical Center, Boston, Massachusetts (United States); Department of Radiation Oncology, The Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island (United States); Hepel, Jaroslaw T. [Department of Radiation Oncology, The Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island (United States)

2017-06-01

Purpose: Because of its rarity, there are no randomized trials investigating postmastectomy radiation therapy (PMRT) in male breast cancer. This study retrospectively examines the impact of PMRT in male breast cancer patients in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Methods and Materials: The SEER database 8.3.2 was queried for men ages 20+ with a diagnosis of localized or regional nonmetastatic invasive ductal/lobular carcinoma from 1998 to 2013. Included patients were treated by modified radical mastectomy (MRM), with or without adjuvant external beam radiation. Univariate and multivariate analyses evaluated predictors for PMRT use after MRM. Kaplan-Meier overall survival (OS) curves of the entire cohort and a case-matched cohort were calculated and compared by the log-rank test. Cox regression was used for multivariate survival analyses. Results: A total of 1933 patients were included in the unmatched cohort. There was no difference in 5-year OS between those who received PMRT and those who did not (78% vs 77%, respectively, P=.371); however, in the case-matched analysis, PMRT was associated with improved OS at 5 years (83% vs 54%, P<.001). On subset analysis of the unmatched cohort, PMRT was associated with improved OS in men with 1 to 3 positive nodes (5-year OS 79% vs 72% P=.05) and those with 4+ positive nodes (5-year OS 73% vs 53% P<.001). On multivariate analysis of the unmatched cohort, independent predictors for improved OS were use of PMRT: HR=0.551 (0.412-0.737) and estrogen receptor–positive disease: HR=0.577 (0.339-0.983). Predictors for a survival detriment were higher grade 3/4: HR=1.825 (1.105-3.015), larger tumor T2: HR=1.783 (1.357-2.342), T3/T4: HR=2.683 (1.809-3.978), higher N-stage: N1 HR=1.574 (1.184-2.091), N2/N3: HR=2.328 (1.684-3.218), black race: HR=1.689 (1.222-2.336), and older age 81+: HR=4.164 (1.497-11.582). Conclusions: There may be a survival benefit with the

A multi-year analysis of passage and survival at McNary Dam, 2004-09

Science.gov (United States)

Adams, Noah S.; Walker, C.E.; Perry, R.W.

2011-01-01

We analyzed 6 years (2004–09) of passage and survival data collected at McNary Dam to determine how dam operations and environmental conditions affect passage and survival of juvenile salmonids. A multinomial logistic regression was used to examine how environmental variables and dam operations relate to passage behavior of juvenile salmonids at McNary Dam. We used the Cormack-Jolly-Seber release-recapture model to determine how the survival of juvenile salmonids passing through McNary Dam relates to environmental variables and dam operations. Total project discharge and the proportion of flow passing the spillway typically had a positive effect on survival for all species and routes. As the proportion of water through the spillway increased, the number of fish passing the spillway increased, as did overall survival. Additionally, survival generally was higher at night. There was no meaningful difference in survival for fish that passed through the north or south portions of the spillway or powerhouse. Similarly, there was no difference in survival for fish released in the north, middle, or south portions of the tailrace. For subyearling Chinook salmon migrating during the summer season, increased temperatures had a drastic effect on passage and survival. As temperature increased, survival of subyearling Chinook salmon decreased through all passage routes and the number of fish that passed through the turbines increased. During years when the temporary spillway weirs (TSWs) were installed, passage through the spillway increased for spring migrants. However, due to the changes made in the location of the TSW between years and the potential effect of other confounding environmental conditions, it is not certain if the increase in spillway passage was due solely to the presence of the TSWs. The TSWs appeared to improve forebay survival during years when they were operated.

Stereotactic Radiosurgery in the Management of Brain Metastases: An Institutional Retrospective Analysis of Survival

International Nuclear Information System (INIS)

Frazier, James L.; Batra, Sachin; Kapor, Sumit; Vellimana, Ananth; Gandhi, Rahul; Carson, Kathryn A.; Shokek, Ori; Lim, Michael; Kleinberg, Lawrence; Rigamonti, Daniele

2010-01-01

Purpose: The objective of this study was to report our experience with stereotactic radiosurgery performed with the Gamma Knife (GK) in the treatment of patients with brain metastases and to compare survival for those treated with radiosurgery alone with survival for those treated with radiosurgery and whole-brain radiotherapy. Methods and Materials: Prospectively collected demographic and clinical characteristics and treatment and survival data on 237 patients with intracranial metastases who underwent radiosurgery with the GK between 2003 and 2007 were reviewed. Kaplan-Meier and Cox proportional hazards regression analyses were used to compare survival by demographic and clinical characteristics and treatment. Results: The mean age of the patient population was 56 years. The most common tumor histologies were non-small-cell lung carcinoma (34.2%) and breast cancer (13.9%). The median overall survival time was 8.5 months from the time of treatment. The median survival times for patients with one, two/three, and four or more brain metastases were 8.5, 9.4, and 6.7 months, respectively. Patients aged 65 years or greater and those aged less than 65 years had median survival times of 7.8 and 9 months, respectively (p = 0.008). The Karnofsky Performance Score (KPS) at the time of treatment was a significant predictor of survival: those patients with a KPS of 70 or less had a median survival of 2.9 months compared with 10.3 months (p = 0.034) for those with a KPS of 80 or greater. There was no statistically significant difference in survival between patients treated with radiosurgery alone and those treated with radiosurgery plus whole-brain radiotherapy. Conclusions: Radiosurgery with the GK is an efficacious treatment modality for brain metastases. A KPS greater than 70, histology of breast cancer, smaller tumor volume, and age less than 65 years were associated with a longer median survival in our study.

Correlation Between Ki-67 Index, World Health Organization Grade and Patient Survival in Glial Tumors With Astrocytic Differentiation

Science.gov (United States)

Dzhenkov, Deyan L; Kitanova, Martina; Donev, Ivan S; Ghenev, Peter

2017-01-01

Background Glioblastoma multiforme (GBM) is a class IV astrocytic tumor, the most malignant of the four groups of World Health Organization (WHO) tumors with astrocytic differentiation. Aim The aim of this study was to estab­lish whether a correlation exists between the Ki-67 index of tumors with astrocytic differentiation, WHO grade, and patient survival. Materials and methods A retrospective non-clinical approach to patient selection was chosen for the aim of the study. A total of 47 patients diagnosed and treated for CNS tumors with astrocytic differentiation in the St. Marina University Hospital, Varna, Bulgaria, from September 2012 to July 2016 were retrospectively included into the study cohort. The cases were tested for their immunohistochemistry (IHC) reaction with Ki-67 after their original Hematoxylin and Eosin and IHC slides were reviewed by a single author and blind coded. The Ki-67 positivity index of the nuclei was estimated after digitalization of the slides and calculated by the ImmunoRatio automated count­ing tool. The individual Ki-67 index and patient survival of each case were statistically compared. Results The histopathological groups, after the blind Ki-67 index automated calculation was carried out, revealed no WHO grade I, two WHO grade II samples, four WHO grade III samples and 41 WHO grade IV cases, and these were included in the analysis. The two samples of WHO grade II astrocytic tumors had a mean Ki-67 index of 25%; however, they comprised tumors with an individual index of 43% and 7%, both individual values with a highly unlikely index for this group. The four samples of WHO grade III had a mean Ki-67 index of 4%, standard deviation ±2.16 (p>0.05), with the lowest index being 1% and the highest one being 6%. Both WHO grade II and III did not include enough samples to allow for a proper statistical analysis of patient survival. The 41 GBM cases had a mean Ki-67 index of 17.34%, standard deviation ±10.79 (p>0

Pretreatment combination of platelet counts and neutrophil–lymphocyte ratio predicts survival of nasopharyngeal cancer patients receiving intensity-modulated radiotherapy

Directory of Open Access Journals (Sweden)

Lin YH

2017-05-01

Full Text Available Yu-Hsuan Lin,1 Kuo-Ping Chang,2 Yaoh-Shiang Lin,2,3 Ting-Shou Chang2–4 1Department of Otolaryngology, Head and Neck Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 2Department of Otolaryngology, Head and Neck Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, 3Department of Otolaryngology, Head and Neck Surgery, National Defense Medical Center, Taipei, 4Institute of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China Background: Increased cancer-related inflammation has been associated with unfavorable clinical outcomes. The combination of platelet count and neutrophil–lymphocyte ratio (COP-NLR has related outcomes in several cancers, except for nasopharyngeal carcinoma (NPC. This study evaluated the prognostic value of COP-NLR in predicting outcome in NPC patients treated with intensity-modulated radiotherapy (IMRT.Materials and methods: We analyzed the data collected from 232 NPC patients. Pretreatment total platelet counts, neutrophil–lymphocyte ratio (NLR, and COP-NLR score were evaluated as potential predictors. Optimal cutoff values for NLR and platelets were determined using receiver operating curve. Patients with both elevated NLR (>3 and platelet counts (>300×109/L were assigned a COP-NLR score of 2; those with one elevated or no elevated value were assigned a COP-NLR a score of 1 or 0. Cox proportional hazards model was used to test the association of these factors and relevant 3-year survivals.Results: Patients (COP-NLR scores 1 and 2=85; score 0=147 were followed up for 55.19 months. Univariate analysis showed no association between pretreatment NLR >2.23 and platelet counts >290.5×109/L and worse outcomes. Multivariate analysis revealed that those with COP-NLR scores of 0 had better 3-year disease-specific survival (P=0.02, overall survival (P=0.024, locoregional relapse-free survival (P=0.004, and distant

How can survival processing improve memory encoding?

Science.gov (United States)

Luo, Meng; Geng, Haiyan

2013-11-01

We investigated the psychological mechanism of survival processing advantage from the perspective of false memory in two experiments. Using a DRM paradigm in combination with analysis based on signal detection theory, we were able to separately examine participants' utilization of verbatim representation and gist representation. Specifically, in Experiment 1, participants rated semantically related words in a survival scenario for a survival condition but rated pleasantness of words in the same DRM lists for a non-survival control condition. The results showed that participants demonstrated more gist processing in the survival condition than in the pleasantness condition; however, the degree of item-specific processing in the two encoding conditions did not significantly differ. In Experiment 2, the control task was changed to a category rating task, in which participants were asked to make category ratings of words in the category lists. We found that the survival condition involved more item-specific processing than did the category condition, but we found no significant difference between the two encoding conditions at the level of gist processing. Overall, our study demonstrates that survival processing can simultaneously promote gist and item-specific representations. When the control tasks only promoted either item-specific representation or gist representation, memory advantages of survival processing occurred.

Using simulation to interpret a discrete time survival model in a complex biological system: fertility and lameness in dairy cows.

Directory of Open Access Journals (Sweden)

Christopher D Hudson

Full Text Available The ever-growing volume of data routinely collected and stored in everyday life presents researchers with a number of opportunities to gain insight and make predictions. This study aimed to demonstrate the usefulness in a specific clinical context of a simulation-based technique called probabilistic sensitivity analysis (PSA in interpreting the results of a discrete time survival model based on a large dataset of routinely collected dairy herd management data. Data from 12,515 dairy cows (from 39 herds were used to construct a multilevel discrete time survival model in which the outcome was the probability of a cow becoming pregnant during a given two day period of risk, and presence or absence of a recorded lameness event during various time frames relative to the risk period amongst the potential explanatory variables. A separate simulation model was then constructed to evaluate the wider clinical implications of the model results (i.e. the potential for a herd's incidence rate of lameness to influence its overall reproductive performance using PSA. Although the discrete time survival analysis revealed some relatively large associations between lameness events and risk of pregnancy (for example, occurrence of a lameness case within 14 days of a risk period was associated with a 25% reduction in the risk of the cow becoming pregnant during that risk period, PSA revealed that, when viewed in the context of a realistic clinical situation, a herd's lameness incidence rate is highly unlikely to influence its overall reproductive performance to a meaningful extent in the vast majority of situations. Construction of a simulation model within a PSA framework proved to be a very useful additional step to aid contextualisation of the results from a discrete time survival model, especially where the research is designed to guide on-farm management decisions at population (i.e. herd rather than individual level.

Association of collagen architecture with glioblastoma patient survival.

Science.gov (United States)

Pointer, Kelli B; Clark, Paul A; Schroeder, Alexandra B; Salamat, M Shahriar; Eliceiri, Kevin W; Kuo, John S

2017-06-01

OBJECTIVE Glioblastoma (GBM) is the most malignant primary brain tumor. Collagen is present in low amounts in normal brain, but in GBMs, collagen gene expression is reportedly upregulated. However, to the authors' knowledge, direct visualization of collagen architecture has not been reported. The authors sought to perform the first direct visualization of GBM collagen architecture, identify clinically relevant collagen signatures, and link them to differential patient survival. METHODS Second-harmonic generation microscopy was used to detect collagen in a GBM patient tissue microarray. Focal and invasive GBM mouse xenografts were stained with Picrosirius red. Quantitation of collagen fibers was performed using custom software. Multivariate survival analysis was done to determine if collagen is a survival marker for patients. RESULTS In focal xenografts, collagen was observed at tumor brain boundaries. For invasive xenografts, collagen was intercalated with tumor cells. Quantitative analysis showed significant differences in collagen fibers for focal and invasive xenografts. The authors also found that GBM patients with more organized collagen had a longer median survival than those with less organized collagen. CONCLUSIONS Collagen architecture can be directly visualized and is different in focal versus invasive GBMs. The authors also demonstrate that collagen signature is associated with patient survival. These findings suggest that there are collagen differences in focal versus invasive GBMs and that collagen is a survival marker for GBM.

Analyzing proteasomal subunit expression reveals Rpt4 as a prognostic marker in stage II colorectal cancer.

LENUS (Irish Health Repository)

2012-02-01

Colorectal cancer is a leading cause of cancer-related deaths worldwide. Early diagnosis and treatment of colorectal cancer is the key to improving survival rates and as such a need exists to identify patients who may benefit from adjuvant chemotherapy. The dysregulation of the ubiquitin-proteasome system (UPS) has been implicated in oncogenesis and cancer cell survival, and proteasome inhibitors are in clinical use for a number of malignancies including multiple myeloma. In our study, we examined the protein expression of several key components of the UPS in colorectal cancer using immunohistochemistry to determine expression levels of ubiquitinylated proteins and the proteasomal subunits, 20S core and Rpt4 in a cohort of 228 patients with colon cancer. Multivariate Cox analysis revealed that neither the intensity of either ubiquitinylated proteins or the 20S core was predictive in either Stage II or III colon cancer for disease free survival or overall survival. In contrast, in Stage II patients increased Rpt4 staining was significantly associated with disease free survival (Cox proportional hazard ratio 0.605; p = 0.0217). Our data suggest that Rpt4 is an independent prognostic variable for Stage II colorectal cancer and may aid in the decision of which patients undergo adjuvant chemotherapy.

Single-Cell Analysis of SMN Reveals Its Broader Role in Neuromuscular Disease

Directory of Open Access Journals (Sweden)

Natalia Rodriguez-Muela

2017-02-01

Full Text Available The mechanism underlying selective motor neuron (MN death remains an essential question in the MN disease field. The MN disease spinal muscular atrophy (SMA is attributable to reduced levels of the ubiquitous protein SMN. Here, we report that SMN levels are widely variable in MNs within a single genetic background and that this heterogeneity is seen not only in SMA MNs but also in MNs derived from controls and amyotrophic lateral sclerosis (ALS patients. Furthermore, cells with low SMN are more susceptible to cell death. These findings raise the important clinical implication that some SMN-elevating therapeutics might be effective in MN diseases besides SMA. Supporting this, we found that increasing SMN across all MN populations using an Nedd8-activating enzyme inhibitor promotes survival in both SMA and ALS-derived MNs. Altogether, our work demonstrates that examination of human neurons at the single-cell level can reveal alternative strategies to be explored in the treatment of degenerative diseases.

Main Clinical Outcomes of Feldspathic Porcelain and Glass-Ceramic Laminate Veneers: A Systematic Review and Meta-Analysis of Survival and Complication Rates.

Science.gov (United States)

Morimoto, Susana; Albanesi, Rafael Borges; Sesma, Newton; Agra, Carlos Martins; Braga, Mariana Minatel

2016-01-01

The aim of this study was to perform a systematic review and meta-analysis based on clinical trials that evaluated the main outcomes of glass-ceramic and feldspathic porcelain laminate veneers. A systematic search was carried out in Cochrane and PubMed databases. From the selected studies, the survival rates for porcelain and glass-ceramic veneers were extracted, as were complication rates of clinical outcomes: debonding, fracture/chipping, secondary caries, endodontic problems, severe marginal discoloration, and influence of incisal coverage and enamel/dentin preparation. The Cochran Q test and the I(2) statistic were used to evaluate heterogeneity. Out of the 899 articles initially identified, 13 were included for analysis. Metaregression analysis showed that the types of ceramics and follow-up periods had no influence on failure rate. The estimated overall cumulative survival rate was 89% (95% CI: 84% to 94%) in a median follow-up period of 9 years. The estimated survival for glass-ceramic was 94% (95% CI: 87% to 100%), and for feldspathic porcelain veneers, 87% (95% CI: 82% to 93%). The meta-analysis showed rates for the following events: debonding: 2% (95% CI: 1% to 4%); fracture/chipping: 4% (95% CI: 3% to 6%); secondary caries: 1% (95% CI: 0% to 3%); severe marginal discoloration: 2% (95% CI: 1% to 10%); endodontic problems: 2% (95% CI: 1% to 3%); and incisal coverage odds ratio: 1.25 (95% CI: 0.33 to 4.73). It was not possible to perform meta-analysis of the influence of enamel/dentin preparation on failure rates. Glass-ceramic and porcelain laminate veneers have high survival rates. Fracture/ chipping was the most frequent complication, providing evidence that ceramic veneers are a safe treatment option that preserve tooth structure.

A survival analysis of GBM patients in the West of Scotland pre- and post-introduction of the Stupp regime.

Science.gov (United States)

Teo, Mario; Martin, Sean; Owusu-Agyemang, Kevin; Nowicki, Stefan; Clark, Brian; Mackinnon, Mairi; Stewart, Willie; Paul, James; St George, Jerome

2014-06-01

It is now accepted that the concomitant administration of temozolomide with radiotherapy (Stupp regime), in the treatment of patients with newly diagnosed glioblastoma multiforme (GBM), significantly improves survival and this practice has been adopted locally since 2004. However, survival outcomes in cancer can vary in different population groups, and outcomes can be affected by a number of local factors including socioeconomic status. In the West of Scotland, we have one of the worse socioeconomic status and overall health record for a western European country. With the ongoing reorganisation and rationalisation in the National Health Service, the addition of prolonged courses of chemotherapy to patients' management significantly adds to the financial burden of a cash stripped NHS. A survival analysis in patients with GBM was therefore performed, comparing outcomes of pre- and post-introduction of the Stupp regime, to justify the current practice. Prospectively collected clinical data were analysed in 105 consecutive patients receiving concurrent chemoradiotherapy (Stupp regime) following surgical treatment of GBM between December 2004 and February 2009. This was compared to those of 106 consecutive GBM patients who had radical radiotherapy (pre-Stupp regime) post-surgery between January 2001 and February 2006. The median overall survival for the post-Stupp cohort was 15.3 months (range, 2.83-50.5 months), with 1-year and 2-year overall survival rates of 65.7% and 19%, respectively. This was in comparison with the median overall pre-Stupp survival of 10.7 months, with 1-year and 2-year survival rates of 42.6% and 12%, respectively (log-rank test, p GBM patients in the West of Scotland.

Survival of probiotic lactobacilli in acidic environments is enhanced in the presence of metabolizable sugars.

Science.gov (United States)

Corcoran, B M; Stanton, C; Fitzgerald, G F; Ross, R P

2005-06-01

Lactobacillus rhamnosus GG is an industrially significant probiotic strain with proven health benefits. In this study, the effect of glucose on L. rhamnosus GG survival was analyzed in simulated gastric juice at pH 2.0. It was found that the presence of 19.4 mM glucose resulted in up to 6-log10-enhanced survival following 90 min of exposure. Further work with dilute HCl confirmed that glucose was the sole component responsible. Comparative analysis with other Lactobacillus strains revealed that enhanced survival was apparent in all strains, but at different pH values. The presence of glucose at concentrations from 1 to 19.4 mM enhanced L. rhamnosus GG survival from 6.4 to 8 log10 CFU ml(-1) in simulated gastric juice. The mechanisms behind the protective effect of glucose were investigated. Addition of N',N'-dicyclohexylcarbodiimide to simulated gastric juice caused survival to collapse, which was indicative of a prominent role in inhibition of F0F1-ATPase. Further work with neomycin-resistant mutants that exhibited 38% to 48% of the F0F1-ATPase activity of the parent confirmed this, as the survival in the presence of glucose of these mutants decreased 3 x 10(6)-fold compared with the survival of the wild type (which had a viability of 8.02 log10 CFU ml(-1)). L. rhamnosus GG survival in acidic conditions occurred only in the presence of sugars that it could metabolize efficiently. To confirm the involvement of glycolysis in the glucose effect, iodoacetic acid was used to inhibit glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity. The reduction in GAPDH activity caused survival to decrease by 8.30 log10 CFU ml(-1) in the presence of glucose. The data indicate that glucose provides ATP to F0F1-ATPase via glycolysis, enabling proton exclusion and thereby enhancing survival during gastric transit.

The goya mouse mutant reveals distinct newly identified roles for MAP3K1 in the development and survival of cochlear sensory hair cells.

Science.gov (United States)

Parker, Andrew; Cross, Sally H; Jackson, Ian J; Hardisty-Hughes, Rachel; Morse, Susan; Nicholson, George; Coghill, Emma; Bowl, Michael R; Brown, Steve D M

2015-12-01

Mitogen-activated protein kinase, MAP3K1, plays an important role in a number of cellular processes, including epithelial migration during eye organogenesis. In addition, studies in keratinocytes indicate that MAP3K1 signalling through JNK is important for actin stress fibre formation and cell migration. However, MAP3K1 can also act independently of JNK in the regulation of cell proliferation and apoptosis. We have identified a mouse mutant, goya, which exhibits the eyes-open-at-birth and microphthalmia phenotypes. In addition, these mice also have hearing loss. The goya mice carry a splice site mutation in the Map3k1 gene. We show that goya and kinase-deficient Map3k1 homozygotes initially develop supernumerary cochlear outer hair cells (OHCs) that subsequently degenerate, and a progressive profound hearing loss is observed by 9 weeks of age. Heterozygote mice also develop supernumerary OHCs, but no cellular degeneration or hearing loss is observed. MAP3K1 is expressed in a number of inner-ear cell types, including outer and inner hair cells, stria vascularis and spiral ganglion. Investigation of targets downstream of MAP3K1 identified an increase in p38 phosphorylation (Thr180/Tyr182) in multiple cochlear tissues. We also show that the extra OHCs do not arise from aberrant control of proliferation via p27KIP1. The identification of the goya mutant reveals a signalling molecule involved with hair-cell development and survival. Mammalian hair cells do not have the ability to regenerate after damage, which can lead to irreversible sensorineural hearing loss. Given the observed goya phenotype, and the many diverse cellular processes that MAP3K1 is known to act upon, further investigation of this model might help to elaborate upon the mechanisms underlying sensory hair cell specification, and pathways important for their survival. In addition, MAP3K1 is revealed as a new candidate gene for human sensorineural hearing loss. © 2015. Published by The Company of

The goya mouse mutant reveals distinct newly identified roles for MAP3K1 in the development and survival of cochlear sensory hair cells

Directory of Open Access Journals (Sweden)

Andrew Parker

2015-12-01

Full Text Available Mitogen-activated protein kinase, MAP3K1, plays an important role in a number of cellular processes, including epithelial migration during eye organogenesis. In addition, studies in keratinocytes indicate that MAP3K1 signalling through JNK is important for actin stress fibre formation and cell migration. However, MAP3K1 can also act independently of JNK in the regulation of cell proliferation and apoptosis. We have identified a mouse mutant, goya, which exhibits the eyes-open-at-birth and microphthalmia phenotypes. In addition, these mice also have hearing loss. The goya mice carry a splice site mutation in the Map3k1 gene. We show that goya and kinase-deficient Map3k1 homozygotes initially develop supernumerary cochlear outer hair cells (OHCs that subsequently degenerate, and a progressive profound hearing loss is observed by 9 weeks of age. Heterozygote mice also develop supernumerary OHCs, but no cellular degeneration or hearing loss is observed. MAP3K1 is expressed in a number of inner-ear cell types, including outer and inner hair cells, stria vascularis and spiral ganglion. Investigation of targets downstream of MAP3K1 identified an increase in p38 phosphorylation (Thr180/Tyr182 in multiple cochlear tissues. We also show that the extra OHCs do not arise from aberrant control of proliferation via p27KIP1. The identification of the goya mutant reveals a signalling molecule involved with hair-cell development and survival. Mammalian hair cells do not have the ability to regenerate after damage, which can lead to irreversible sensorineural hearing loss. Given the observed goya phenotype, and the many diverse cellular processes that MAP3K1 is known to act upon, further investigation of this model might help to elaborate upon the mechanisms underlying sensory hair cell specification, and pathways important for their survival. In addition, MAP3K1 is revealed as a new candidate gene for human sensorineural hearing loss.

Association of drug transporter expression with mortality and progression-free survival in stage IV head and neck squamous cell carcinoma.

Directory of Open Access Journals (Sweden)

Rolf Warta

Full Text Available Drug transporters such as P-glycoprotein (ABCB1 have been associated with chemotherapy resistance and are considered unfavorable prognostic factors for survival of cancer patients. Analyzing mRNA expression levels of a subset of drug transporters by quantitative reverse transcription polymerase chain reaction (qRT-PCR or protein expression by tissue microarray (TMA in tumor samples of therapy naïve stage IV head and neck squamous cell carcinoma (HNSCC (qRT-PCR, n = 40; TMA, n = 61, this in situ study re-examined the significance of transporter expression for progression-free survival (PFS and overall survival (OS. Data from The Cancer Genome Atlas database was used to externally validate the respective findings (n = 317. In general, HNSCC tended to lower expression of drug transporters compared to normal epithelium. High ABCB1 mRNA tumor expression was associated with both favorable progression-free survival (PFS, p = 0.0357 and overall survival (OS, p = 0.0535. Similar results were obtained for the mRNA of ABCC1 (MRP1, multidrug resistance-associated protein 1; PFS, p = 0.0183; OS, p = 0.038. In contrast, protein expression of ATP7b (copper transporter ATP7b, mRNA expression of ABCG2 (BCRP, breast cancer resistance protein, ABCC2 (MRP2, and SLC31A1 (hCTR1, human copper transporter 1 did not correlate with survival. Cluster analysis however revealed that simultaneous high expression of SLC31A1, ABCC2, and ABCG2 indicates poor survival of HNSCC patients. In conclusion, this study militates against the intuitive dogma where high expression of drug efflux transporters indicates poor survival, but demonstrates that expression of single drug transporters might indicate even improved survival. Prospectively, combined analysis of the 'transportome' should rather be performed as it likely unravels meaningful data on the impact of drug transporters on survival of patients with HNSCC.

Metabolomics analysis reveals the metabolic and functional roles of flavonoids in light-sensitive tea leaves.

Science.gov (United States)

Zhang, Qunfeng; Liu, Meiya; Ruan, Jianyun

2017-03-20

As the predominant secondary metabolic pathway in tea plants, flavonoid biosynthesis increases with increasing temperature and illumination. However, the concentration of most flavonoids decreases greatly in light-sensitive tea leaves when they are exposed to light, which further improves tea quality. To reveal the metabolism and potential functions of flavonoids in tea leaves, a natural light-sensitive tea mutant (Huangjinya) cultivated under different light conditions was subjected to metabolomics analysis. The results showed that chlorotic tea leaves accumulated large amounts of flavonoids with ortho-dihydroxylated B-rings (e.g., catechin gallate, quercetin and its glycosides etc.), whereas total flavonoids (e.g., myricetrin glycoside, epigallocatechin gallate etc.) were considerably reduced, suggesting that the flavonoid components generated from different metabolic branches played different roles in tea leaves. Furthermore, the intracellular localization of flavonoids and the expression pattern of genes involved in secondary metabolic pathways indicate a potential photoprotective function of dihydroxylated flavonoids in light-sensitive tea leaves. Our results suggest that reactive oxygen species (ROS) scavenging and the antioxidation effects of flavonoids help chlorotic tea plants survive under high light stress, providing new evidence to clarify the functional roles of flavonoids, which accumulate to high levels in tea plants. Moreover, flavonoids with ortho-dihydroxylated B-rings played a greater role in photo-protection to improve the acclimatization of tea plants.

Fontan fenestration closure and event-free survival.

Science.gov (United States)

Imielski, Bartlomiej R; Woods, Ronald K; Mussatto, Kathleen A; Cao, Yumei; Simpson, Pippa M; Tweddell, James S

2013-01-01

The purpose of the present study was to evaluate the association of open and closed Fontan fenestration status with event-free survival. All patients who underwent a fenestrated Fontan procedure at our institution from January 1994 through June 2007 were reviewed. Patient information was obtained from the medical records. The patients were assigned to 1 of 2 study groups, open or closed, according to their most recent fenestration status. Clinically relevant morbid events were tabulated, and Kaplan-Meier event analysis was used to create event-free probability curves with log-rank comparisons. A total of 161 patients were classified as open and 51 as closed. The median interval to an event was 1.1 years (interquartile range, 0.1-3.3 years) after the Fontan procedure. The median interval to closure was 1.2 years (interquartile range, 0.7-3.3 years). The median interval to an event was 1.5 years (interquartile range, 0.1-4.6 years) in the closed group and 1.1 years (interquartile range, 0.1-3.3 years) in the open group. Event-free probability analysis revealed no significant difference between the 2 groups (P = .15). The median follow-up arterial oxygen saturation was greater in the closed group (96.0%; interquartile range, 94.0%-97.0%) than in the open group (91.0%; interquartile range, 86.0%-95.0%; P < .0001). Fenestration closure was associated with greater arterial oxygen saturation but not greater event-free survival. The interval to an event was slightly less than the interval to fenestration closure, suggesting potential merit in the evaluation of earlier fenestration closure. Adoption of specific fenestration management guidelines might help improve the overall outcomes and enhance the quality of future studies. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Long survival in a patient with metastatic colorrectal carcinoma: reality or utopia?

Science.gov (United States)

Illán, Andrea; Aires, Jonathan; Quintana, Laura

2017-09-01

We report the case of a 42-year-old male patient with mucinous-type metastatic colorectal carcinoma of eight years of evolution. He has received multiple lines of cytostatic treatment with acceptable tolerance and without significant impairment in his quality of life. At present, it is estimated that the overall survival of metastatic colon cancer in cytostatic treatment is around 24 months. However, a small subset of patients may present prolonged survivals of 5 to 10 years after diagnosis, revealing heterogeneity of tumor behavior and response to treatment. Our clinical case represents a long survivor patient despite the advanced stage of his oncological mucinous-colorrectal disease, endorsed in the scientific literature as having worse rates of objective response and less survival. There are different therapeutic approaches that can achieve a significant overall survival. It is essential in clinical practice to use all drugs available to achieve increase of progression-free survival and overall survival, with maintenance of an adequate quality of life.

Edge Contrast of the FLAIR Hyperintense Region Predicts Survival in Patients with High-Grade Gliomas following Treatment with Bevacizumab.

Science.gov (United States)

Bahrami, N; Piccioni, D; Karunamuni, R; Chang, Y-H; White, N; Delfanti, R; Seibert, T M; Hattangadi-Gluth, J A; Dale, A; Farid, N; McDonald, C R

2018-04-05

Treatment with bevacizumab is standard of care for recurrent high-grade gliomas; however, monitoring response to treatment following bevacizumab remains a challenge. The purpose of this study was to determine whether quantifying the sharpness of the fluid-attenuated inversion recovery hyperintense border using a measure derived from texture analysis-edge contrast-improves the evaluation of response to bevacizumab in patients with high-grade gliomas. MRIs were evaluated in 33 patients with high-grade gliomas before and after the initiation of bevacizumab. Volumes of interest within the FLAIR hyperintense region were segmented. Edge contrast magnitude for each VOI was extracted using gradients of the 3D FLAIR images. Cox proportional hazards models were generated to determine the relationship between edge contrast and progression-free survival/overall survival using age and the extent of surgical resection as covariates. After bevacizumab, lower edge contrast of the FLAIR hyperintense region was associated with poorer progression-free survival ( P = .009) and overall survival ( P = .022) among patients with high-grade gliomas. Kaplan-Meier curves revealed that edge contrast cutoff significantly stratified patients for both progression-free survival (log-rank χ 2 = 8.3, P = .003) and overall survival (log-rank χ 2 = 5.5, P = .019). Texture analysis using edge contrast of the FLAIR hyperintense region may be an important predictive indicator in patients with high-grade gliomas following treatment with bevacizumab. Specifically, low FLAIR edge contrast may partially reflect areas of early tumor infiltration. This study adds to a growing body of literature proposing that quantifying features may be important for determining outcomes in patients with high-grade gliomas. © 2018 by American Journal of Neuroradiology.

Clinical Outcomes of Volume-Modulated Arc Therapy in 205 Patients with Nasopharyngeal Carcinoma: An Analysis of Survival and Treatment Toxicities.

Directory of Open Access Journals (Sweden)

Rui Guo

Full Text Available To investigate the clinical efficacy and treatment toxicity of volume-modulated arc therapy (VMAT for nasopharyngeal carcinoma (NPC.205 VMAT-treated NPC patients from our cancer center were prospectively entrolled. All patients received 68-70 Gy irradiation based on the planning target volume of the primary gross tumor volume. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group Late Radiation Morbidity Scoring Criteria.The median follow-up period was 37.3 months (range, 6.3-45.1 months. The 3-year estimated local failure-free survival, regional failure-free survival, locoregional failure-free survival, distant metastasis-free survival, disease-free survival and overall survival were 95.5%, 97.0%, 94.0%, 92.1%, 86.8% and 97.0%, respectively. Cox regression analysis showed primary gross tumor volume, N stage and EBV-DNA to be independent predictors of VMAT outcomes (P < 0.05. The most common acute and late side effects were grade 2-3 mucositis (78% and xerostomia (83%, 61%, 34%, and 9% at 3, 6, 12 and 24 months after VMAT, respectively.VMAT for the primary treatment of NPC achieved very high locoregional control with a favorable toxicity profile. The time-saving benefit of VMAT will enable more patients to receive precision radiotherapy.

Smad2 and Smad6 as predictors of overall survival in oral squamous cell carcinoma patients

Directory of Open Access Journals (Sweden)

Snitcovsky Igor

2010-05-01

Full Text Available Abstract Background To test if the expression of Smad1-8 mRNAs were predictive of survival in patients with oral squamous cell carcinoma (SCC. Patients and Methods We analyzed, prospectively, the expression of Smad1-8, by means of Ribonuclease Protection Assay in 48 primary, operable, oral SCC. In addition, 21 larynx, 10 oropharynx and 4 hypopharynx SCC and 65 matched adjacent mucosa, available for study, were also included. For survival analysis, patients were categorized as positive or negative for each Smad, according to median mRNA expression. We also performed real-time quantitative PCR (QRTPCR to asses the pattern of TGFβ1, TGFβ2, TGFβ3 in oral SCC. Results Our results showed that Smad2 and Smad6 mRNA expression were both associated with survival in Oral SCC patients. Cox Multivariate analysis revealed that Smad6 positivity and Smad2 negativity were both predictive of good prognosis for oral SCC patients, independent of lymph nodal status (P = 0.003 and P = 0.029, respectively. In addition, simultaneously Smad2- and Smad6+ oral SCC group of patients did not reach median overall survival (mOS whereas the mOS of Smad2+/Smad6- subgroup was 11.6 months (P = 0.004, univariate analysis. Regarding to TGFβ isoforms, we found that Smad2 mRNA and TGFβ1 mRNA were inversely correlated (p = 0.05, R = -0.33, and that seven of the eight TGFβ1+ patients were Smad2-. In larynx SCC, Smad7- patients did not reach mOS whereas mOS of Smad7+ patients were only 7.0 months (P = 0.04. No other correlations were found among Smad expression, clinico-pathological characteristics and survival in oral, larynx, hypopharynx, oropharynx or the entire head and neck SCC population. Conclusion Smad6 together with Smad2 may be prognostic factors, independent of nodal status in oral SCC after curative resection. The underlying mechanism which involves aberrant TGFβ signaling should be better clarified in the future.

Prognostic factors for long-term outcome after percutaneous thermal ablation for hepatocellular carcinoma: a survival analysis of 137 consecutive patients

Energy Technology Data Exchange (ETDEWEB)

Xu, H.-X. [Department of Medical Ultrasonics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Lu, M.-D. [Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Xie, X.-Y. [Department of Medical Ultrasonics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Yin, X.-Y. [Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Kuang, M. [Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Chen, J.-W. [Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Xu, Z.-F. [Department of Medical Ultrasonics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Liu, G.-J. [Department of Medical Ultrasonics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China)

2005-09-01

AIM: To identify prognostic factors for long-term outcome for patients with hepatocellular carcinoma (HCC) after percutaneous microwave or radiofrequency ablation. MATERIALS AND METHODS: In total, 137 consecutive patients with HCC underwent microwave or radiofrequency ablation with curative intent; 16 possible prognostic factors were evaluated for their association with overall survival (OS) and disease-free survival (DFS) using univariate and multivariate analysis. RESULTS: The median OS and DFS were 27.0 months and 8.2 months, respectively. OS rates for all patients at 1, 2, 3, 4 and 5 years were 73.9%, 52.1%, 42.8%, 26.2% and 20.1%, respectively. DFS rates at 1, 2, 3 and 4 years were 38.1%, 21.9%, 18.8%, and 14.1%, respectively. Pretreatment serum alpha-fetoprotein (AFP) >200 ng/ml, pretreatment serum albumin {<=}35 g/dl, liver function Child's class C and incomplete ablation were found to be significant predictors for OS by univariate analysis. Using multivariate analysis, incomplete ablation was identified to be the most significant independent predictor for OS. Other independent predictors for OS were serum albumin level, serum AFP level and Child-Pugh classification. Recurrence after hepatectomy and prothrombin time >14 s were identified to be significant predictors for DFS by univariate analysis, and the former was the only independent predictor for DFS by multivariate analysis. CONCLUSION: Prognosis for patients with HCC after thermal ablation with curative intent was determined by treatment response to ablation, pretreatment serum AFP, and liver function reserve. Tumour response to treatment was the most predictive factor for long-term survival and was related to tumour size, thus careful selection of patients for ablation therapy is recommended.

Prognostic factors for long-term outcome after percutaneous thermal ablation for hepatocellular carcinoma: a survival analysis of 137 consecutive patients

International Nuclear Information System (INIS)

Xu, H.-X.; Lu, M.-D.; Xie, X.-Y.; Yin, X.-Y.; Kuang, M.; Chen, J.-W.; Xu, Z.-F.; Liu, G.-J.

2005-01-01

AIM: To identify prognostic factors for long-term outcome for patients with hepatocellular carcinoma (HCC) after percutaneous microwave or radiofrequency ablation. MATERIALS AND METHODS: In total, 137 consecutive patients with HCC underwent microwave or radiofrequency ablation with curative intent; 16 possible prognostic factors were evaluated for their association with overall survival (OS) and disease-free survival (DFS) using univariate and multivariate analysis. RESULTS: The median OS and DFS were 27.0 months and 8.2 months, respectively. OS rates for all patients at 1, 2, 3, 4 and 5 years were 73.9%, 52.1%, 42.8%, 26.2% and 20.1%, respectively. DFS rates at 1, 2, 3 and 4 years were 38.1%, 21.9%, 18.8%, and 14.1%, respectively. Pretreatment serum alpha-fetoprotein (AFP) >200 ng/ml, pretreatment serum albumin ≤35 g/dl, liver function Child's class C and incomplete ablation were found to be significant predictors for OS by univariate analysis. Using multivariate analysis, incomplete ablation was identified to be the most significant independent predictor for OS. Other independent predictors for OS were serum albumin level, serum AFP level and Child-Pugh classification. Recurrence after hepatectomy and prothrombin time >14 s were identified to be significant predictors for DFS by univariate analysis, and the former was the only independent predictor for DFS by multivariate analysis. CONCLUSION: Prognosis for patients with HCC after thermal ablation with curative intent was determined by treatment response to ablation, pretreatment serum AFP, and liver function reserve. Tumour response to treatment was the most predictive factor for long-term survival and was related to tumour size, thus careful selection of patients for ablation therapy is recommended

An analysis of the survivability of sensor darts in impacts with trees.

Energy Technology Data Exchange (ETDEWEB)

Prentice, John K. (Sci-Tac, Inc., Boulder, CO.); Gardner, David Randall

2005-07-01

A methodology was developed for computing the probability that the sensor dart for the 'Near Real-Time Site Characterization for Assured HDBT Defeat' Grand-Challenge LDRD project will survive deployment over a forested region. The probability can be decomposed into three approximately independent probabilities that account for forest coverage, branch density and the physics of an impact between the dart and a tree branch. The probability that a dart survives an impact with a tree branch was determined from the deflection induced by the impact. If a dart that was deflected so that it impacted the ground at an angle of attack exceeding a user-specified, threshold value, the dart was assumed to not survive the impact with the branch; otherwise it was assumed to have survived. A computer code was developed for calculating dart angle of attack at impact with the ground and a Monte Carlo scheme was used to calculate the probability distribution of a sensor dart surviving an impact with a branch as a function of branch radius, length, and height from the ground. Both an early prototype design and the current dart design were used in these studies. As a general rule of thumb, it we observed that for reasonably generic trees and for a threshold angle of attack of 5{sup o} (which is conservative for dart survival), the probability of reaching the ground with an angle of attack less than the threshold is on the order of 30% for the prototype dart design and 60% for the current dart design, though these numbers should be treated with some caution.

SubID, a non-median dichotomization tool for heterogeneous populations, reveals the pan-cancer significance of INPP4B and its regulation by EVI1 in AML.

Directory of Open Access Journals (Sweden)

Irakli Dzneladze

Full Text Available Our previous studies demonstrated that INPP4B, a member of the PI3K/Akt signaling pathway, is overexpressed in a subset of AML patients and is associated with lower response to chemotherapy and shorter survival. INPP4B expression analysis in AML revealed a right skewed frequency distribution with 25% of patients expressing significantly higher levels than the majority. The 75% low/25% high cut-off revealed the prognostic power of INPP4B expression status in AML, which would not have been apparent with a standard median cut-off approach. Our identification of a clinically relevant non-median cut-off for INPP4B indicated a need for a generalizable non-median dichotomization approach to optimally study clinically relevant genes. To address this need, we developed Subgroup Identifier (SubID, a tool which examines the relationship between a continuous variable (e.g. gene expression, and a test parameter (e.g. CoxPH or Fisher's exact P values. In our study, Fisher's exact SubID was used to reveal EVI1 as a transcriptional regulator of INPP4B in AML; a finding which was validated in vitro. Next, we used CoxPH SubID to conduct a pan-cancer analysis of INPP4B's prognostic significance. Our analysis revealed that INPP4Blow is associated with shorter survival in kidney clear cell, liver hepatocellular, and bladder urothelial carcinomas. Conversely, INPP4Blow was shown to be associated with increased survival in pancreatic adenocarcinoma in three independent datasets. Overall, our study describes the development and application of a novel subgroup identification tool used to identify prognostically significant rare subgroups based upon gene expression, and for investigating the association between a gene with skewed frequency distribution and potentially important upstream and downstream genes that relate to the index gene.

SubID, a non-median dichotomization tool for heterogeneous populations, reveals the pan-cancer significance of INPP4B and its regulation by EVI1 in AML.

Science.gov (United States)

Dzneladze, Irakli; Woolley, John F; Rossell, Carla; Han, Youqi; Rashid, Ayesha; Jain, Michael; Reimand, Jüri; Minden, Mark D; Salmena, Leonardo

2018-01-01

Our previous studies demonstrated that INPP4B, a member of the PI3K/Akt signaling pathway, is overexpressed in a subset of AML patients and is associated with lower response to chemotherapy and shorter survival. INPP4B expression analysis in AML revealed a right skewed frequency distribution with 25% of patients expressing significantly higher levels than the majority. The 75% low/25% high cut-off revealed the prognostic power of INPP4B expression status in AML, which would not have been apparent with a standard median cut-off approach. Our identification of a clinically relevant non-median cut-off for INPP4B indicated a need for a generalizable non-median dichotomization approach to optimally study clinically relevant genes. To address this need, we developed Subgroup Identifier (SubID), a tool which examines the relationship between a continuous variable (e.g. gene expression), and a test parameter (e.g. CoxPH or Fisher's exact P values). In our study, Fisher's exact SubID was used to reveal EVI1 as a transcriptional regulator of INPP4B in AML; a finding which was validated in vitro. Next, we used CoxPH SubID to conduct a pan-cancer analysis of INPP4B's prognostic significance. Our analysis revealed that INPP4Blow is associated with shorter survival in kidney clear cell, liver hepatocellular, and bladder urothelial carcinomas. Conversely, INPP4Blow was shown to be associated with increased survival in pancreatic adenocarcinoma in three independent datasets. Overall, our study describes the development and application of a novel subgroup identification tool used to identify prognostically significant rare subgroups based upon gene expression, and for investigating the association between a gene with skewed frequency distribution and potentially important upstream and downstream genes that relate to the index gene.

Foxp3 overexpression in tumor cells predicts poor survival in oral squamous cell carcinoma

International Nuclear Information System (INIS)

Song, Jing-Jing; Zhao, Si-Jia; Fang, Juan; Ma, Da; Liu, Xiang-Qi; Chen, Xiao-Bing; Wang, Yun; Cheng, Bin; Wang, Zhi

2016-01-01

Forkhead Box P3 (Foxp3) is a regulatory T cells marker, and its expression correlates with prognosis in a number of malignancies. The aim of this study is to determine the relationship of Foxp3 expression with clinicopathological parameters and prognosis in oral squamous cell carcinoma (OSCC). Foxp3 expression was examined using immunohistochemistry (IHC) in paraffin-embedded tissue samples from 273 OSCC patients. Statistical analysis was performed to evaluate the associations between Foxp3 expression, the clinicopathologic characteristics and prognostic factors in OSCC. Foxp3 protein expression was significantly associated with lymph node metastasis (P <0.01). Both univariate and multivariate analyses revealed that Foxp3 was an independent factor for both 5 years overall survival (OS) and relapse-free survival (RFS) (both P <0.01). Patients with Foxp3 overexpression had shorter OS and RFS. Our results determined that elevated Foxp3 protein expression was a predictive factor of outcome in OSCC and could act as a promising therapeutic target

Comparison of a radiomic biomarker with volumetric analysis for decoding tumour phenotypes of lung adenocarcinoma with different disease-specific survival

International Nuclear Information System (INIS)

Yuan, Mei; Zhang, Yu-Dong; Pu, Xue-Hui; Zhong, Yan; Yu, Tong-Fu; Li, Hai; Wu, Jiang-Fen

2017-01-01

To compare a multi-feature-based radiomic biomarker with volumetric analysis in discriminating lung adenocarcinomas with different disease-specific survival on computed tomography (CT) scans. This retrospective study obtained institutional review board approval and was Health Insurance Portability and Accountability Act (HIPAA) compliant. Pathologically confirmed lung adenocarcinoma (n = 431) manifested as subsolid nodules on CT were identified. Volume and percentage solid volume were measured by using a computer-assisted segmentation method. Radiomic features quantifying intensity, texture and wavelet were extracted from the segmented volume of interest (VOI). Twenty best features were chosen by using the Relief method and subsequently fed to a support vector machine (SVM) for discriminating adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA) from invasive adenocarcinoma (IAC). Performance of the radiomic signatures was compared with volumetric analysis via receiver-operating curve (ROC) analysis and logistic regression analysis. The accuracy of proposed radiomic signatures for predicting AIS/MIA from IAC achieved 80.5% with ROC analysis (Az value, 0.829; sensitivity, 72.1%; specificity, 80.9%), which showed significantly higher accuracy than volumetric analysis (69.5%, P = 0.049). Regression analysis showed that radiomic signatures had superior prognostic performance to volumetric analysis, with AIC values of 81.2% versus 70.8%, respectively. The radiomic tumour-phenotypes biomarker exhibited better diagnostic accuracy than traditional volumetric analysis in discriminating lung adenocarcinoma with different disease-specific survival. (orig.)

Comparison of a radiomic biomarker with volumetric analysis for decoding tumour phenotypes of lung adenocarcinoma with different disease-specific survival

Energy Technology Data Exchange (ETDEWEB)

Yuan, Mei; Zhang, Yu-Dong; Pu, Xue-Hui; Zhong, Yan; Yu, Tong-Fu [First Affiliated Hospital of Nanjing Medical University, Department of Radiology, Nanjing, Jiangsu Province (China); Li, Hai [First Affiliated Hospital of Nanjing Medical University, Department of Pathology, Nanjing (China); Wu, Jiang-Fen [GE Healthcare, Shanghai (China)

2017-11-15

To compare a multi-feature-based radiomic biomarker with volumetric analysis in discriminating lung adenocarcinomas with different disease-specific survival on computed tomography (CT) scans. This retrospective study obtained institutional review board approval and was Health Insurance Portability and Accountability Act (HIPAA) compliant. Pathologically confirmed lung adenocarcinoma (n = 431) manifested as subsolid nodules on CT were identified. Volume and percentage solid volume were measured by using a computer-assisted segmentation method. Radiomic features quantifying intensity, texture and wavelet were extracted from the segmented volume of interest (VOI). Twenty best features were chosen by using the Relief method and subsequently fed to a support vector machine (SVM) for discriminating adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA) from invasive adenocarcinoma (IAC). Performance of the radiomic signatures was compared with volumetric analysis via receiver-operating curve (ROC) analysis and logistic regression analysis. The accuracy of proposed radiomic signatures for predicting AIS/MIA from IAC achieved 80.5% with ROC analysis (Az value, 0.829; sensitivity, 72.1%; specificity, 80.9%), which showed significantly higher accuracy than volumetric analysis (69.5%, P = 0.049). Regression analysis showed that radiomic signatures had superior prognostic performance to volumetric analysis, with AIC values of 81.2% versus 70.8%, respectively. The radiomic tumour-phenotypes biomarker exhibited better diagnostic accuracy than traditional volumetric analysis in discriminating lung adenocarcinoma with different disease-specific survival. (orig.)

Combined high-field intraoperative magnetic resonance imaging and endoscopy increase extent of resection and progression-free survival for pituitary adenomas

Science.gov (United States)

Sylvester, Peter T.; Evans, John A.; Zipfel, Gregory J.; Chole, Richard A.; Uppaluri, Ravindra; Haughey, Bruce H.; Getz, Anne E.; Silverstein, Julie; Rich, Keith M.; Kim, Albert H.; Dacey, Ralph G.

2014-01-01

Purpose The clinical benefit of combined intraoperative magnetic resonance imaging (iMRI) and endoscopy for transsphenoidal pituitary adenoma resection has not been completely characterized. This study assessed the impact of microscopy, endoscopy, and/or iMRI on progression-free survival, extent of resection status (gross-, near-, and subtotal resection), and operative complications. Methods Retrospective analyses were performed on 446 transsphenoidal pituitary adenoma surgeries at a single institution between 1998 and 2012. Multivariate analyses were used to control for baseline characteristics, differences during extent of resection status, and progression-free survival analysis. Results Additional surgery was performed after iMRI in 56/156 cases (35.9 %), which led to increased extent of resection status in 15/156 cases (9.6 %). Multivariate ordinal logistic regression revealed no increase in extent of resection status following iMRI or endoscopy alone; however, combining these modalities increased extent of resection status (odds ratio 2.05, 95 % CI 1.21–3.46) compared to conventional transsphenoidal microsurgery. Multivariate Cox regression revealed that reduced extent of resection status shortened progression-free survival for near- versus gross-total resection [hazard ratio (HR) 2.87, 95 % CI 1.24–6.65] and sub- versus near-total resection (HR 2.10; 95 % CI 1.00–4.40). Complication comparisons between microscopy, endoscopy, and iMRI revealed increased perioperative deaths for endoscopy versus microscopy (4/209 and 0/237, respectively), but this difference was non-significant considering multiple post hoc comparisons (Fisher exact, p = 0.24). Conclusions Combined use of endoscopy and iMRI increased pituitary adenoma extent of resection status compared to conventional transsphenoidal microsurgery, and increased extent of resection status was associated with longer progression-free survival. Treatment modality combination did not significantly impact

Meta-analysis of CDKN2A methylation to find its role in prostate cancer development and progression, and also to find the effect of CDKN2A expression on disease-free survival (PRISMA).

Science.gov (United States)

Cao, Zipei; Wei, Lijuan; Zhu, Weizhi; Yao, Xuping

2018-03-01

Reduction of cyclin-dependent kinase inhibitor 2A (CDKN2A) (p16 and p14) expression through DNA methylation has been reported in prostate cancer (PCa). This meta-analysis was conducted to assess the difference of p16 and p14 methylation between PCa and different histological types of nonmalignant controls and the correlation of p16 or p14 methylation with clinicopathological features of PCa. According to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement criteria, articles were searched in PubMed, Embase, EBSCO, Wanfang, and CNKI databases. The strength of correlation was calculated by the pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). Trial sequential analysis (TSA) was used to estimate the required population information for significant results. A total of 20 studies published from 1997 to 2017 were identified in this meta-analysis, including 1140 PCa patients and 530 cases without cancer. Only p16 methylation in PCa was significantly higher than in benign prostatic lesions (OR = 4.72, P = .011), but had a similar level in PCa and adjacent tissues or high-grade prostatic intraepithelial neoplasias (HGPIN). TSA revealed that this analysis on p16 methylation is a false positive result in cancer versus benign prostatic lesions (the estimated required information size of 5116 participants). p16 methylation was not correlated with PCa in the urine and blood. Besides, p16 methylation was not linked to clinical stage, prostate-specific antigen (PSA) level, and Gleason score (GS) of patients with PCa. p14 methylation was not correlated with PCa in tissue and urine samples. No correlation was observed between p14 methylation and clinical stage or GS. CDKN2A mutation and copy number alteration were not associated with prognosis of PCa in overall survival and disease-free survival. CDKN2A expression was not correlated with the prognosis of PCa in overall survival (492 cases) (P > .1

Alcohol Consumption and Survival after a Breast Cancer Diagnosis: A Literature-Based Meta-analysis and Collaborative Analysis of Data for 29,239 Cases

Science.gov (United States)

Ali, Alaa M.G.; Schmidt, Marjanka K.; Bolla, Manjeet K.; Wang, Qin; Gago-Dominguez, M.; Castelao, J. Esteban; Carracedo, Angel; Garzón, Victor Muñoz; Bojesen, Stig E.; Nordestgaard, Børge G.; Flyger, Henrik; Chang-Claude, Jenny; Vrieling, Alina; Rudolph, Anja; Seibold, Petra; Nevanlinna, Heli; Muranen, Taru A.; Aaltonen, Kirsimari; Blomqvist, Carl; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Horio, Akiyo; John, Esther M.; Sherman, Mark; Lissowska, Jolanta; Figueroa, Jonine; Garcia-Closas, Montserrat; Anton-Culver, Hoda; Shah, Mitul; Hopper, John L.; Trichopoulou, Antonia; Bueno-de-Mesquita, Bas; Krogh, Vittorio; Weiderpass, Elisabete; Andersson, Anne; Clavel-Chapelon, Françoise; Dossus, Laure; Fagherazzi, Guy; Peeters, Petra H.; Olsen, Anja; Wishart, Gordon C.; Easton, Douglas F.; Borgquist, Signe; Overvad, Kim; Barricarte, Aurelio; González, Carlos A.; Sánchez, María-José; Amiano, Pilar; Riboli, Elio; Key, Tim; Pharoah, Paul D.

2015-01-01

Background Evidence for an association of alcohol consumption with prognosis after a diagnosis of breast cancer has been inconsistent. We have reviewed and summarized the published evidence and evaluated the association using individual patient data from multiple case cohorts. Methods A MEDLINE search to identify studies published up to January 2013 was performed. We combined published estimates of survival time for “moderate drinkers” versus nondrinkers. An analysis of individual participant data using Cox regression was carried out using data from 11 case cohorts. Results We identified 11 published studies suitable for inclusion in the meta-analysis. Moderate post-diagnosis alcohol consumption was not associated with overall survival [HR, 0.95; 95% confidence interval (CI), 0.85–1.05], but there was some evidence of better survival associated with prediagnosis consumption (HR, 0.80; 95% CI, 0.73–0.88). Individual data on alcohol consumption for 29,239 cases with 4,839 deaths were available from the 11 case cohorts, all of which had data on estrogen receptor (ER) status. For women with ER-positive disease, there was little evidence that pre- or postdiagnosis alcohol consumption is associated with breast cancer–specific mortality, with some evidence of a negative association with all-cause mortality. On the basis of a single study, moderate postdiagnosis alcohol intake was associated with a small reduction in breast cancer–specific mortality for women with ER-negative disease. There was no association with prediagnosis intake for women with ER-negative disease. Conclusion There was little evidence that pre- or post-diagnosis alcohol consumption is associated with breast cancer–specific mortality for women with ER-positive disease. There was weak evidence that moderate post-diagnosis alcohol intake is associated with a small reduction in breast cancer–specific mortality in ER-negative disease. Impact Considering the totality of the evidence, moderate

Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma.

Science.gov (United States)

Facon, Thierry; Dimopoulos, Meletios A; Dispenzieri, Angela; Catalano, John V; Belch, Andrew; Cavo, Michele; Pinto, Antonello; Weisel, Katja; Ludwig, Heinz; Bahlis, Nizar J; Banos, Anne; Tiab, Mourad; Delforge, Michel; Cavenagh, Jamie D; Geraldes, Catarina; Lee, Je-Jung; Chen, Christine; Oriol, Albert; De La Rubia, Javier; White, Darrell; Binder, Daniel; Lu, Jin; Anderson, Kenneth C; Moreau, Philippe; Attal, Michel; Perrot, Aurore; Arnulf, Bertrand; Qiu, Lugui; Roussel, Murielle; Boyle, Eileen; Manier, Salomon; Mohty, Mohamad; Avet-Loiseau, Herve; Leleu, Xavier; Ervin-Haynes, Annette; Chen, Guang; Houck, Vanessa; Benboubker, Lotfi; Hulin, Cyrille

2018-01-18

This FIRST trial final analysis examined survival outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) treated with lenalidomide and low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks). The primary endpoint was progression-free survival (PFS; primary comparison: Rd continuous vs MPT). Overall survival (OS) was a key secondary endpoint (final analysis prespecified ≥60 months' follow-up). Patients were randomized to Rd continuous (n = 535), Rd18 (n = 541), or MPT (n = 547). At a median follow-up of 67 months, PFS was significantly longer with Rd continuous vs MPT (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.59-0.79; P < .00001) and was similarly extended vs Rd18. Median OS was 10 months longer with Rd continuous vs MPT (59.1 vs 49.1 months; HR, 0.78; 95% CI, 0.67-0.92; P = .0023), and similar with Rd18 (62.3 months). In patients achieving complete or very good partial responses, Rd continuous had an ≈30-month longer median time to next treatment vs Rd18 (69.5 vs 39.9 months). Over half of all patients who received second-line treatment were given a bortezomib-based therapy. Second-line outcomes were improved in patients receiving bortezomib after Rd continuous and Rd18 vs after MPT. No new safety concerns, including risk for secondary malignancies, were observed. Treatment with Rd continuous significantly improved survival outcomes vs MPT, supporting Rd continuous as a standard of care for patients with transplant-ineligible NDMM. This trial was registered at www.clinicaltrials.gov as #NCT00689936 and EudraCT as 2007-004823-39. © 2018 by The American Society of Hematology.

Cancer survival for Aboriginal and Torres Strait Islander Australians: a national study of survival rates and excess mortality.

Science.gov (United States)

Condon, John R; Zhang, Xiaohua; Baade, Peter; Griffiths, Kalinda; Cunningham, Joan; Roder, David M; Coory, Michael; Jelfs, Paul L; Threlfall, Tim

2014-01-31

National cancer survival statistics are available for the total Australian population but not Indigenous Australians, although their cancer mortality rates are known to be higher than those of other Australians. We aimed to validate analysis methods and report cancer survival rates for Indigenous Australians as the basis for regular national reporting. We used national cancer registrations data to calculate all-cancer and site-specific relative survival for Indigenous Australians (compared with non-Indigenous Australians) diagnosed in 2001-2005. Because of limited availability of Indigenous life tables, we validated and used cause-specific survival (rather than relative survival) for proportional hazards regression to analyze time trends and regional variation in all-cancer survival between 1991 and 2005. Survival was lower for Indigenous than non-Indigenous Australians for all cancers combined and for many cancer sites. The excess mortality of Indigenous people with cancer was restricted to the first three years after diagnosis, and greatest in the first year. Survival was lower for rural and remote than urban residents; this disparity was much greater for Indigenous people. Survival improved between 1991 and 2005 for non-Indigenous people (mortality decreased by 28%), but to a much lesser extent for Indigenous people (11%) and only for those in remote areas; cancer survival did not improve for urban Indigenous residents. Cancer survival is lower for Indigenous than other Australians, for all cancers combined and many individual cancer sites, although more accurate recording of Indigenous status by cancer registers is required before the extent of this disadvantage can be known with certainty. Cancer care for Indigenous Australians needs to be considerably improved; cancer diagnosis, treatment, and support services need to be redesigned specifically to be accessible and acceptable to Indigenous people.

Progression-free survival, post-progression survival, and tumor response as surrogate markers for overall survival in patients with extensive small cell lung cancer

Directory of Open Access Journals (Sweden)

Hisao Imai

2015-01-01

Full Text Available Objectives: The effects of first-line chemotherapy on overall survival (OS might be confounded by subsequent therapies in patients with small cell lung cancer (SCLC. We examined whether progression-free survival (PFS, post-progression survival (PPS, and tumor response could be valid surrogate endpoints for OS after first-line chemotherapies for patients with extensive SCLC using individual-level data. Methods: Between September 2002 and November 2012, we analyzed 49 cases of patients with extensive SCLC who were treated with cisplatin and irinotecan as first-line chemotherapy. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level. Results: Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.97, p < 0.05, R 2 = 0.94, PFS was moderately correlated with OS (r = 0.58, p < 0.05, R 2 = 0.24, and tumor shrinkage was weakly correlated with OS (r = 0.37, p < 0.05, R 2 = 0.13. The best response to second-line treatment, and the number of regimens employed after progression beyond first-line chemotherapy were both significantly associated with PPS ( p ≤ 0.05. Conclusion: PPS is a potential surrogate for OS in patients with extensive SCLC. Our findings also suggest that subsequent treatment after disease progression following first-line chemotherapy may greatly influence OS.

Serum albumin predicts survival in patients with hilar cholangiocarcinoma.

Science.gov (United States)

Waghray, Abhijeet; Sobotka, Anastasia; Marrero, Carlos Romero; Estfan, Bassam; Aucejo, Federico; Narayanan Menon, K V

2017-02-01

Hilar cholangiocarcinoma is a devastating malignancy with incidence varying by geography and other risk factors. Rapid progression of disease and delays in diagnosis restrict the number of patients eligible for curative therapy. The objective of this study was to determine prognostic factors of overall survival in all patients presenting with hilar cholangiocarcinoma. All adult patients with histologically confirmed hilar cholangiocarcinoma from 2003 to 2013 were evaluated for predictors of survival using demographic factors, laboratory data, symptoms and radiological characteristics at presentation. A total of 116 patients were identified to have pathological diagnosis of hilar cholangiocarcinoma and were included in the analysis. Patients with a serum albumin level >3.0 g/dL (P 3.0 g/dL was identified as an independent predictor of overall survival (hazard ratio 0.31; 95% confidence interval 0.14-0.70) with a survival benefit of 44 weeks. This study was the largest analysis to date of prognostic factors in patients with hilar cholangiocarcinoma. A serum albumin level >3.0 g/dL conferred an independent survival advantage with a significantly greater length of survival. © The Author(s) 2016. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-Sen University.

Molecular Infectious Disease Epidemiology: Survival Analysis and Algorithms Linking Phylogenies to Transmission Trees

Science.gov (United States)

Kenah, Eben; Britton, Tom; Halloran, M. Elizabeth; Longini, Ira M.

2016-01-01

Recent work has attempted to use whole-genome sequence data from pathogens to reconstruct the transmission trees linking infectors and infectees in outbreaks. However, transmission trees from one outbreak do not generalize to future outbreaks. Reconstruction of transmission trees is most useful to public health if it leads to generalizable scientific insights about disease transmission. In a survival analysis framework, estimation of transmission parameters is based on sums or averages over the possible transmission trees. A phylogeny can increase the precision of these estimates by providing partial information about who infected whom. The leaves of the phylogeny represent sampled pathogens, which have known hosts. The interior nodes represent common ancestors of sampled pathogens, which have unknown hosts. Starting from assumptions about disease biology and epidemiologic study design, we prove that there is a one-to-one correspondence between the possible assignments of interior node hosts and the transmission trees simultaneously consistent with the phylogeny and the epidemiologic data on person, place, and time. We develop algorithms to enumerate these transmission trees and show these can be used to calculate likelihoods that incorporate both epidemiologic data and a phylogeny. A simulation study confirms that this leads to more efficient estimates of hazard ratios for infectiousness and baseline hazards of infectious contact, and we use these methods to analyze data from a foot-and-mouth disease virus outbreak in the United Kingdom in 2001. These results demonstrate the importance of data on individuals who escape infection, which is often overlooked. The combination of survival analysis and algorithms linking phylogenies to transmission trees is a rigorous but flexible statistical foundation for molecular infectious disease epidemiology. PMID:27070316

Improvement in survival of patients with oral cavity squamous cell carcinoma: An international collaborative study.

Science.gov (United States)

Amit, Moran; Yen, Tzu-Chen; Liao, Chun-Ta; Chaturvedi, Pankaj; Agarwal, Jai Prakash; Kowalski, Luiz P; Ebrahimi, Ardalan; Clark, Jonathan R; Kreppel, Matthias; Zöller, Joachim; Fridman, Eran; Bolzoni, Villaret A; Shah, Jatin P; Binenbaum, Yoav; Patel, Snehal G; Gil, Ziv

2013-12-15

An association between the survival of patients with oral cavity squamous cell carcinoma (OCSCC) and advancements in diagnosis and therapy has not been established. This was a retrospective, longitudinal, international, population-based study of 2738 patients who underwent resection of OCSCC during 2 different decades. Characteristics of patients from 7 international cancer centers who received treatment between 1990 and 2000 (group A; n = 735) were compared with patients who received treatment between 2001 and 2011 (group B; n = 2003). Patients in group B had more advanced tumors and tended to develop distant metastases more frequently than patients in group A (P = .005). More group B patients underwent selective neck dissection and received adjuvant radiotherapy (P < .001). Outcome analysis revealed a significant improvement in 5-year overall survival, from 59% for group A to 70% for group B (P < .001). There was also a significant improvement in disease-specific survival associated with operations performed before and after 2000 (from 69% to 81%, respectively; P < .001). Surgery after 2000, negative margins, adjuvant treatment, and early stage disease were independent predictors of a better outcome in multivariate analysis. The decade of treatment was an independent prognostic factor for cancer-specific mortality (hazard ratio, 0.42; 95% confidence interval, 0.3-0.6). The survival rate of patients with OCSCC improved significantly during the past 2 decades despite older age, more advanced disease stage, and a higher rate of distant metastases. The current results suggest that the prognosis for patients with OCSCC has improved over time, presumably because of advances in imaging and therapy. © 2013 American Cancer Society.

Sequence analysis of serum albumins reveals the molecular evolution of ligand recognition properties.

Science.gov (United States)

Fanali, Gabriella; Ascenzi, Paolo; Bernardi, Giorgio; Fasano, Mauro

2012-01-01

Serum albumin (SA) is a circulating protein providing a depot and carrier for many endogenous and exogenous compounds. At least seven major binding sites have been identified by structural and functional investigations mainly in human SA. SA is conserved in vertebrates, with at least 49 entries in protein sequence databases. The multiple sequence analysis of this set of entries leads to the definition of a cladistic tree for the molecular evolution of SA orthologs in vertebrates, thus showing the clustering of the considered species, with lamprey SAs (Lethenteron japonicum and Petromyzon marinus) in a separate outgroup. Sequence analysis aimed at searching conserved domains revealed that most SA sequences are made up by three repeated domains (about 600 residues), as extensively characterized for human SA. On the contrary, lamprey SAs are giant proteins (about 1400 residues) comprising seven repeated domains. The phylogenetic analysis of the SA family reveals a stringent correlation with the taxonomic classification of the species available in sequence databases. A focused inspection of the sequences of ligand binding sites in SA revealed that in all sites most residues involved in ligand binding are conserved, although the versatility towards different ligands could be peculiar of higher organisms. Moreover, the analysis of molecular links between the different sites suggests that allosteric modulation mechanisms could be restricted to higher vertebrates.

Metabolic profiling reveals potential metabolic markers associated with Hypoxia Inducible Factor-mediated signalling in hypoxic cancer cells.

Science.gov (United States)

Armitage, Emily G; Kotze, Helen L; Allwood, J William; Dunn, Warwick B; Goodacre, Royston; Williams, Kaye J

2015-10-28

Hypoxia inducible factors (HIFs) plays an important role in oxygen compromised environments and therefore in tumour survival. In this research, metabolomics has been applied to study HIFs metabolic function in two cell models: mouse hepatocellular carcinoma and human colon carcinoma, whereby the metabolism has been profiled for a range of oxygen potentials. Wild type cells have been compared to cells deficient in HIF signalling to reveal its effect on cellular metabolism under normal oxygen conditions as well as low oxygen, hypoxic and anoxic environments. Characteristic responses to hypoxia that were conserved across both cell models involved the anti-correlation between 2-hydroxyglutarate, 2-oxoglutarate, fructose, hexadecanoic acid, hypotaurine, pyruvate and octadecenoic acid with 4-hydroxyproline, aspartate, cysteine, glutamine, lysine, malate and pyroglutamate. Further to this, network-based correlation analysis revealed HIF specific pathway responses to each oxygen condition that were also conserved between cell models. From this, 4-hydroxyproline was revealed as a regulating hub in low oxygen survival of WT cells while fructose appeared to be in HIF deficient cells. Pathways surrounding these hubs were built from the direct connections of correlated metabolites that look beyond traditional pathways in order to understand the mechanism of HIF response to low oxygen environments.

The analysis of survival data in nephrology: basic concepts and methods of Cox regression

NARCIS (Netherlands)

van Dijk, Paul C.; Jager, Kitty J.; Zwinderman, Aeilko H.; Zoccali, Carmine; Dekker, Friedo W.

2008-01-01

How much does the survival of one group differ from the survival of another group? How do differences in age in these two groups affect such a comparison? To obtain a quantity to compare the survival of different patient groups and to account for confounding effects, a multiple regression technique

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2).

Science.gov (United States)

Allemani, Claudia; Weir, Hannah K; Carreira, Helena; Harewood, Rhea; Spika, Devon; Wang, Xiao-Si; Bannon, Finian; Ahn, Jane V; Johnson, Christopher J; Bonaventure, Audrey; Marcos-Gragera, Rafael; Stiller, Charles; Azevedo e Silva, Gulnar; Chen, Wan-Qing; Ogunbiyi, Olufemi J; Rachet, Bernard; Soeberg, Matthew J; You, Hui; Matsuda, Tomohiro; Bielska-Lasota, Magdalena; Storm, Hans; Tucker, Thomas C; Coleman, Michel P

2015-03-14

Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less

Survival study of enterotoxigenic Escherichia colistrain in seawater and wastewater microcosms.

Science.gov (United States)

Boukef Ben Omrane, I; El Bour, M; Mejri, S; Mraouna, R; Got, P; Troussellier, M; Boudabous, A

2011-01-01

In order to survey osmotic and oligotrophic stress consequence on pathogenic enterobacteria discharged in marine areas, we examined enterotoxigenic Escherichia coli (ETEC) and a reference (Ecoli O126:B16) strains during their survival (47 days) in wastewater microcosms, submerged in natural seawater and maintained in laboratory conditions. The results revealed that the survival time for the two strains was prolonged when bacterial cells were previously incubated in wastewater, with less cellular membrane damage. In addition, the wild clinical E. coli strain showed a better survival capacity than the reference E. coli strain one. For both, we noted some modifications in biochemical profiles relatively to the initial state, notably when they were previously incubated in wastewater microcosm.

An overview of equipment survivability studies at Sandia National Labs. (SNL): Chapter 3

International Nuclear Information System (INIS)

Bonzon, L.L.; Craft, C.M.; McCulloch, W.H.; Sebrell, W.A.

1983-01-01

The USNRC sponsors a number of programs at Sandia National Laboratories (SNL) specifically addressing safety-related equipment survivability. The major thrust of these programs has been the physical testing of equipment. Test results illustrate the importance of a dedicated equipment design effort giving particular attention to the safety implications of the equipment operation. Several equipment survivability tests here have revealed equipment design and test-related deficiencies

Split Course Hyperfractionated Accelerated Radio-Chemotherapy (SCHARC for patients with advanced head and neck cancer: Influence of protocol deviations and hemoglobin on overall survival, a retrospective analysis

Directory of Open Access Journals (Sweden)

Sprague Lisa D

2006-12-01

Full Text Available Abstract Background The advantage of hyperfractionated accelerated radiation therapy for advanced head and neck cancer has been reported. Furthermore, randomized trials and meta-analyses have confirmed the survival benefit of additional chemotherapy to radiotherapy. We retrospectively analyzed the efficiency and toxicity of the Regensburg standard therapy protocol "SCHARC" and the overall survival of our patients. Methods From 1997 to 2004, 64 patients suffering from advanced head and neck cancer (88 % stage IV, 12 % stage III were assigned to receive the SCHARC protocol. Around half of the patients were diagnosed with oro-hypopharynx carcinoma (52 %, one third with tongue and floor of mouth tumors (29 % and one fifth (19 % suffered from H & N cancer at other sites. The schedule consisted of one therapy block with 30 Gy in 20 fractions over a two week period with concomitant chemotherapy (d 1–5: 20 mg/m2/d DDP + 750–1000 mg/m2/d 5FU (cont. infusion. This therapy block was repeated after a fortnight break up to a cumulative dose of 60 Gy and followed by a boost up to 70 Gy (69–70.5 Gy. All patients assigned to this scheme were included in the survival evaluation. Results Forty patients (63 % received both radiation and chemotherapy according to the protocol. The mean follow up was 2.3 years (829 d and the median follow up was 1.9 years (678 d, respectively. The analysis of survival revealed an estimated 3 year overall survival rate of 57 %. No patient died of complications, 52 patients (80 % had acute grade 2–3 mucositis, and 33 patients (58 % suffered from acute grade 3 skin toxicity. Leucopenia was no major problem (mean nadir 3.4 g/nl, no patient 10.5 g/dl and for patients who completed the protocol. Conclusion The SCHARC protocol was effective in patients diagnosed with advanced head and neck cancer. It led to long-term disease control and survival in about 50 % of the patients with significant but acceptable toxicity. Most patients

Survival of patients with non-small cell lung cancer without treatment: a systematic review and meta-analysis

Directory of Open Access Journals (Sweden)

Wao Hesborn

2013-02-01

Full Text Available Abstract Background Lung cancer is considered a terminal illness with a five-year survival rate of about 16%. Informed decision-making related to the management of a disease requires accurate prognosis of the disease with or without treatment. Despite the significance of disease prognosis in clinical decision-making, systematic assessment of prognosis in patients with lung cancer without treatment has not been performed. We conducted a systematic review and meta-analysis of the natural history of patients with confirmed diagnosis of lung cancer without active treatment, to provide evidence-based recommendations for practitioners on management decisions related to the disease. Specifically, we estimated overall survival when no anticancer therapy is provided. Methods Relevant studies were identified by search of electronic databases and abstract proceedings, review of bibliographies of included articles, and contacting experts in the field. All prospective or retrospective studies assessing prognosis of lung cancer patients without treatment were eligible for inclusion. Data on mortality was extracted from all included studies. Pooled proportion of mortality was calculated as a back-transform of the weighted mean of the transformed proportions using the random-effects model. To perform meta-analysis of median survival, published methods were used to pool the estimates as mean and standard error under the random-effects model. Methodological quality of the studies was examined. Results Seven cohort studies (4,418 patients and 15 randomized controlled trials (1,031 patients were included in the meta-analysis. All studies assessed mortality without treatment in patients with non-small cell lung cancer (NSCLC. The pooled proportion of mortality without treatment in cohort studies was 0.97 (95% CI: 0.96 to 0.99 and 0.96 in randomized controlled trials (95% CI: 0.94 to 0.98 over median study periods of eight and three years, respectively. When data

Transcriptome analysis of Neisseria meningitidis in human whole blood and mutagenesis studies identify virulence factors involved in blood survival.

Directory of Open Access Journals (Sweden)

Hebert Echenique-Rivera

2011-05-01

Full Text Available During infection Neisseria meningitidis (Nm encounters multiple environments within the host, which makes rapid adaptation a crucial factor for meningococcal survival. Despite the importance of invasion into the bloodstream in the meningococcal disease process, little is known about how Nm adapts to permit survival and growth in blood. To address this, we performed a time-course transcriptome analysis using an ex vivo model of human whole blood infection. We observed that Nm alters the expression of ≈30% of ORFs of the genome and major dynamic changes were observed in the expression of transcriptional regulators, transport and binding proteins, energy metabolism, and surface-exposed virulence factors. In particular, we found that the gene encoding the regulator Fur, as well as all genes encoding iron uptake systems, were significantly up-regulated. Analysis of regulated genes encoding for surface-exposed proteins involved in Nm pathogenesis allowed us to better understand mechanisms used to circumvent host defenses. During blood infection, Nm activates genes encoding for the factor H binding proteins, fHbp and NspA, genes encoding for detoxifying enzymes such as SodC, Kat and AniA, as well as several less characterized surface-exposed proteins that might have a role in blood survival. Through mutagenesis studies of a subset of up-regulated genes we were able to identify new proteins important for survival in human blood and also to identify additional roles of previously known virulence factors in aiding survival in blood. Nm mutant strains lacking the genes encoding the hypothetical protein NMB1483 and the surface-exposed proteins NalP, Mip and NspA, the Fur regulator, the transferrin binding protein TbpB, and the L-lactate permease LctP were sensitive to killing by human blood. This increased knowledge of how Nm responds to adaptation in blood could also be helpful to develop diagnostic and therapeutic strategies to control the devastating

Pro-survival role for Parkinson's associated gene DJ-1 revealed in trophically impaired dopaminergic neurons.

Directory of Open Access Journals (Sweden)

Liviu Aron

2010-04-01

Full Text Available The mechanisms underlying the selective death of substantia nigra (SN neurons in Parkinson disease (PD remain elusive. While inactivation of DJ-1, an oxidative stress suppressor, causes PD, animal models lacking DJ-1 show no overt dopaminergic (DA neuron degeneration in the SN. Here, we show that aging mice lacking DJ-1 and the GDNF-receptor Ret in the DA system display an accelerated loss of SN cell bodies, but not axons, compared to mice that only lack Ret signaling. The survival requirement for DJ-1 is specific for the GIRK2-positive subpopulation in the SN which projects exclusively to the striatum and is more vulnerable in PD. Using Drosophila genetics, we show that constitutively active Ret and associated Ras/ERK, but not PI3K/Akt, signaling components interact genetically with DJ-1. Double loss-of-function experiments indicate that DJ-1 interacts with ERK signaling to control eye and wing development. Our study uncovers a conserved interaction between DJ-1 and Ret-mediated signaling and a novel cell survival role for DJ-1 in the mouse. A better understanding of the molecular connections between trophic signaling, cellular stress and aging could uncover new targets for drug development in PD.

Serum microRNA-122 predicts survival in patients with liver cirrhosis.

Directory of Open Access Journals (Sweden)

Oliver Waidmann

Full Text Available BACKGROUND: Liver cirrhosis is associated with high morbidity and mortality. MicroRNAs (miRs circulating in the blood are an emerging new class of biomarkers. In particular, the serum level of the liver-specific miR-122 might be a clinically useful new parameter in patients with acute or chronic liver disease. AIM: Here we investigated if the serum level of miR-122 might be a prognostic parameter in patients with liver cirrhosis. METHODS: 107 patients with liver cirrhosis in the test cohort and 143 patients in the validation cohort were prospectively enrolled into the present study. RNA was extracted from the sera obtained at the time of study enrollment and the level of miR-122 was assessed. Serum miR-122 levels were assessed by quantitative reverse-transcription PCR (RT-PCR and were compared to overall survival time and to different complications of liver cirrhosis. RESULTS: Serum miR-122 levels were reduced in patients with hepatic decompensation in comparison to patients with compensated liver disease. Patients with ascites, spontaneous bacterial peritonitis and hepatorenal syndrome had significantly lower miR-122 levels than patients without these complications. Multivariate Cox regression analysis revealed that the miR-122 serum levels were associated with survival independently from the MELD score, sex and age. CONCLUSIONS: Serum miR-122 is a new independent marker for prediction of survival of patients with liver cirrhosis.

High E6 Gene Expression Predicts for Distant Metastasis and Poor Survival in Patients With HPV-Positive Oropharyngeal Squamous Cell Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Khwaja, Shariq S.; Baker, Callie; Haynes, Wesley; Spencer, Christopher R.; Gay, Hiram; Thorstad, Wade [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Adkins, Douglas R. [Division of Medical Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri (United States); Nussenbaum, Brian [Department of Otolaryngology – Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri (United States); Chernock, Rebecca D. [Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri (United States); Lewis, James S. [Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee (United States); Wang, Xiaowei, E-mail: xwang@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

2016-07-15

Purpose: Patients with human papillomavirus (HPV)–positive oropharyngeal squamous cell carcinoma (OPSCC) have a favorable prognosis. As a result, de-escalation clinical trials are under way. However, approximately 10% of patients will experience distant recurrence even with standard-of-care treatment. Here, we sought to identify novel biomarkers to better risk-stratify HPV-positive patients with OPSCC. Methods and Materials: Gene expression profiling by RNA sequencing (RNA-seq) and quantitative polymerase chain reaction was performed on HPV-positive OPSCC primary tumor specimens from patients with and without distant metastasis (DM). Results: RNA-seq analysis of 39 HPV-positive OPSCC specimens revealed that patients with DM had 2-fold higher E6 gene expression levels than did patients without DM (P=.029). This observation was confirmed in a validation cohort comprising 93 patients with HPV-positive OPSCC. The mean normalized E6 expression level in the 17 recurring primary specimens was 13 ± 2 compared with 8 ± 1 in the remaining 76 nonrecurring primaries (P=.001). Receiver operating characteristic analysis established an E6 expression level of 7.3 as a cutoff for worse recurrence-free survival (RFS). Patients from this cohort with high E6 gene expression (E6-high) (n=51, 55%) had more cancer-related deaths (23% vs 2%, P<.001) and DM (26% vs 5%, P<.001) than did patients with low E6 gene expression (E6-low) (n=42, 45%). Kaplan-Meier survival analysis revealed that E6-high had worse RFS (95% vs 69%, P=.004) and cancer-specific survival (97% vs 79%, P=.007). E6-high maintained statistical significance in multivariate regression models balancing surgery, chemotherapy, nodal stage, and smoking status. Gene set enrichment analysis demonstrated that tumors with high E6 expression were associated with P53, epidermal growth factor receptor, activating transcription factor-2, and transforming growth factor-β signaling pathways. Conclusion: High E6 gene expression

EXPLORATORY DATA ANALYSIS AND MULTIVARIATE STRATEGIES FOR REVEALING MULTIVARIATE STRUCTURES IN CLIMATE DATA

Directory of Open Access Journals (Sweden)

2016-12-01

Full Text Available This paper is on data analysis strategy in a complex, multidimensional, and dynamic domain. The focus is on the use of data mining techniques to explore the importance of multivariate structures; using climate variables which influences climate change. Techniques involved in data mining exercise vary according to the data structures. The multivariate analysis strategy considered here involved choosing an appropriate tool to analyze a process. Factor analysis is introduced into data mining technique in order to reveal the influencing impacts of factors involved as well as solving for multicolinearity effect among the variables. The temporal nature and multidimensionality of the target variables is revealed in the model using multidimensional regression estimates. The strategy of integrating the method of several statistical techniques, using climate variables in Nigeria was employed. R2 of 0.518 was obtained from the ordinary least square regression analysis carried out and the test was not significant at 5% level of significance. However, factor analysis regression strategy gave a good fit with R2 of 0.811 and the test was significant at 5% level of significance. Based on this study, model building should go beyond the usual confirmatory data analysis (CDA, rather it should be complemented with exploratory data analysis (EDA in order to achieve a desired result.

Cancer Cell-derived Exosomes Induce Mitogen-activated Protein Kinase-dependent Monocyte Survival by Transport of Functional Receptor Tyrosine Kinases*

Science.gov (United States)

Song, Xiao; Ding, Yanping; Liu, Gang; Yang, Xiao; Zhao, Ruifang; Zhang, Yinlong; Zhao, Xiao; Anderson, Gregory J.; Nie, Guangjun

2016-01-01

Tumor-associated macrophages (TAM) play pivotal roles in cancer initiation and progression. Monocytes, the precursors of TAMs, normally undergo spontaneous apoptosis within 2 days, but can subsist in the inflammatory tumor microenvironment for continuous survival and generation of sufficient TAMs. The mechanisms underlying tumor-driving monocyte survival remain obscure. Here we report that cancer cell-derived exosomes were crucial mediators for monocyte survival in the inflammatory niche. Analysis of the survival-promoting molecules in monocytes revealed that cancer cell-derived exosomes activated Ras and extracellular signal-regulated kinases in the mitogen-activated protein kinase (MAPK) pathway, resulting in the prevention of caspase cleavage. Phosphorylated receptor tyrosine kinases (RTKs), such as phosphorylated epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER-2), were abundantly expressed in cancer cell-derived exosomes. Knock-out of EGFR or/and HER-2, or alternatively, inhibitors against their phosphorylation significantly disturbed the exosome-mediated activation of the MAPK pathway, inhibition of caspase cleavage, and increase in survival rate in monocytes. Moreover, the deprived survival-stimulating activity of exosomes due to null expression of EGFR and HER-2 could be restored by activation of another RTK, insulin receptor. Overall, our study uncovered a mechanism of tumor-associated monocyte survival and demonstrated that cancer cell-derived exosomes can stimulate the MAPK pathway in monocytes through transport of functional RTKs, leading to inactivation of apoptosis-related caspases. This work provides insights into the long sought question on monocyte survival prior to formation of plentiful TAMs in the tumor microenvironment. PMID:26895960

Chronic exposure to chlorpyrifos reveals two modes of action in the springtail Folsomia candida.

Science.gov (United States)

Jager, Tjalling; Crommentuijn, Trudie; van Gestel, Cornelis A M; Kooijman, Sebastiaan A L M

2007-01-01

Organophosphates are popular insecticides, but relatively little is known about their chronic effects on ecologically relevant endpoints. In this paper, we examine a life-cycle experiment with the springtail Folsomia candida, exposed via food to chlorpyrifos (CPF). The results for all endpoints (survival, growth and reproduction) were analyzed using the DEBtox model. Growth was unaffected by CPF, even at concentrations causing severe effects on survival and reproduction. Model analysis suggests that CPF directly affects the process of egg production. For the short-term response (45 days), this single mode of action accurately agreed with the data. However, the full data set (120 days) revealed a dose-related decrease in reproduction at low concentrations after prolonged exposure, not covered by the same mechanism. It appears that CPF interacts with senescence by increasing oxidative damage. This assumption fits the data well, but has little consequences for the predicted response at the population level.

Factors affecting survival outcomes of patients with non-metastatic Ewing's sarcoma family tumors in the spine: a retrospective analysis of 63 patients in a single center.

Science.gov (United States)

Wan, Wei; Lou, Yan; Hu, Zhiqi; Wang, Ting; Li, Jinsong; Tang, Yu; Wu, Zhipeng; Xu, Leqin; Yang, Xinghai; Song, Dianwen; Xiao, Jianru

2017-01-01

Little information has been published in the literature regarding survival outcomes of patients with Ewing's sarcoma family tumors (ESFTs) of the spine. The purpose of this study is to explore factors that may affect the prognosis of patients with non-metastatic spinal ESFTs. A retrospective analysis of survival outcomes was performed in patients with non-metastatic spinal ESFTs. Univariate and multivariate analyses were employed to identify prognostic factors for recurrence and survival. Recurrence-free survival (RFS) and overall survival (OS) were defined as the date of surgery to the date of local relapse and death. Kaplan-Meier methods were applied to estimate RFS and OS. Log-rank test was used to analyze single factors for RFS and OS. Factors with p values ≤0.1 were subjected to multivariate analysis. A total of 63 patients with non-metastatic spinal ESFTs were included in this study. The mean follow-up period was 35.1 months (range 1-155). Postoperative recurrence was detected in 25 patients, and distant metastasis and death occurred in 22 and 36 patients respectively. The result of multivariate analysis suggested that age older than 25 years and neoadjuvant chemotherapy were favorable independent prognostic factors for RFS and OS. In addition, total en-bloc resection, postoperative chemotherapy, radiotherapy and non-distant metastasis were favorable independent prognostic factors for OS. Age older than 25 years and neoadjuvant chemotherapy are favorable prognostic factors for both RFS and OS. In addition, total en-bloc resection, postoperative chemotherapy, radiotherapy and non-distant metastasis are closely associated with favorable survival.

In silico and in vivo analysis of Toxoplasma gondii epitopes by correlating survival data with peptide-MHC-I binding affinities.

Science.gov (United States)

Huang, Si-Yang; Jensen, Maria Risager; Rosenberg, Carina Agerbo; Zhu, Xing-Quan; Petersen, Eskild; Vorup-Jensen, Thomas

2016-07-01

Protein antigens comprising peptide motifs with high binding affinity to major histocompatibility complex class I (MHC-I) molecules are expected to induce a stronger cytotoxic T-lymphocyte response and thus provide better protection against infection with microorganisms where cytotoxic T-cells are the main effector arm of the immune system. Data on cyst formation and survival were extracted from past studies on the DNA immunization of mice with plasmids coding for Toxoplasma gondii antigens. From in silico analyses of the vaccine antigens, the correlation was tested between the predicted affinity for MHC-I molecules of the vaccine peptides and the survival of immunized mice after challenge with T. gondii. ELISPOT analysis was used for the experimental testing of peptide immunogenicity. Predictions for the Db MHC-I molecule produced a strong, negative correlation between survival and the dissociation constant of vaccine-derived peptides. The in silico analyses of nine T. gondii antigens identified peptides with a predicted dissociation constant in the interval from 10nM to 40μM. ELISPOT assays with splenocytes from T. gondii-infected mice further supported the importance of the peptide affinity for MHC-I. In silico analysis clearly helped the search for protective vaccine antigens. The ELISPOT analysis confirmed that the predicted T-cell epitopes were immunogenic by their ability to release interferon gamma in spleen cells. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Analysis of prognostic factors for survival in patients with primary spinal chordoma using the SEER Registry from 1973 to 2014.

Science.gov (United States)

Pan, Yue; Lu, Lingyun; Chen, Junquan; Zhong, Yong; Dai, Zhehao

2018-04-06

Spinal chordomas are rare primary osseous tumors that arise from the remnants of the notochord. They are commonly considered slow-growing, locally invasive neoplasms with little tendency to metastasize, but the high recurrent rate of spinal chordomas may seriously affect the survival rate and quality of life of patients. The aim of the study is to describe the epidemiological data and determine the prognostic factors for decreased survival in patients with primary spinal chordoma. The Surveillance, Epidemiology, and End Results (SEER) Registry database, a US population-based cancer registry database, was used to identify all patients diagnosed with primary spinal chordoma from 1973 to 2014. We utilized Kaplan-Meier method and Cox proportional hazards regression analysis to evaluate the association between patients overall survival and relevant characteristics, including age, gender, race, disease stage, treatment methods, primary tumor site, marital status, and urban county background. In the data set between 1973 and 2014, a total of 808 patients were identified with primary spinal chordoma. The overall rate of distant metastatic cases in our cohort was only 7.7%. Spinal chordoma was more common occurred in men (62.6%) than women (37.3%). Majority of neoplasms were found in the White (87.9%), while the incidence of the Black is relatively infrequent (3.3%). Three hundred fifty-seven spinal chordomas (44.2%) were located in the vertebral column, while 451 patients' tumor (55.8%) was located in the sacrum or pelvis. Age ≥ 60 years (HR = 2.72; 95%CI, 1.71 to 2.89), distant metastasis (HR = 2.16; 95%CI, 1.54 to 3.02), and non-surgical therapy (HR = 2.14; 95%CI, 1.72 to 2.69) were independent risk factors for survival reduction in analysis. Survival did not significantly differ as a factor of tumor site (vertebrae vs sacrum/pelvis) for primary spinal chordoma (HR = 0.93, P = 0.16). Race (P = 0.52), gender (P = 0.11), marital status (P = 0.94), and

Blowfly puparia in a hermetic container: survival under decreasing oxygen conditions.

Science.gov (United States)

Mądra-Bielewicz, Anna; Frątczak-Łagiewska, Katarzyna; Matuszewski, Szymon

2017-09-01

Despite widely accepted standards for sampling and preservation of insect evidence, unrepresentative samples or improperly preserved evidence are encountered frequently in forensic investigations. Here, we report the results of laboratory studies on the survival of Lucilia sericata and Calliphora vomitoria (Diptera: Calliphoridae) intra-puparial forms in hermetic containers, which were stimulated by a recent case. It is demonstrated that the survival of blowfly intra-puparial forms inside airtight containers is dependent on container volume, number of puparia inside, and their age. The survival in both species was found to increase with an increase in the volume of air per 1 mg of puparium per day of development in a hermetic container. Below 0.05 ml of air, no insect survived, and above 0.2 ml of air per 1 mg of puparium per day, survival reached its maximum. These results suggest that blowflies reveal a single, general pattern of survival under decreasing oxygen conditions and that this pattern is a product of number of developing insects, their age and the initial amount of available air. Implications for forensic entomology are discussed.

Farm-by-farm analysis of microsatellite, mtDNA and SNP genotype data reveals inbreeding and crossbreeding as threats to the survival of a native Spanish pig breed.

Science.gov (United States)

Herrero-Medrano, J M; Megens, H J; Crooijmans, R P; Abellaneda, J M; Ramis, G

2013-06-01

The Chato Murciano (CM), a pig breed from the Murcia region in the southeastern region of Spain, is a good model for endangered livestock populations. The remaining populations are bred on approximately 15 small farms, and no herdbook exists. To assess the genetic threats to the integrity and survival of the CM breed, and to aid in designing a conservation program, three genetic marker systems - microsatellites, SNPs and mtDNA - were applied across the majority of the total breeding stock. In addition, mtDNA and SNPs were genotyped in breeds that likely contributed genetically to the current CM gene pool. The analyses revealed the levels of genetic diversity within the range of other European local breeds (H(e) = 0.53). However, when the eight farms that rear at least 10 CM pigs were independently analyzed, high levels of inbreeding were found in some. Despite the evidence for recent crossbreeding with commercial breeds on a few farms, the entire breeding stock remains readily identifiable as CM, facilitating the design of traceability assays. The genetic management of the breed is consistent with farm size, farm owner and presence of other pig breeds on the farm, demonstrating the highly ad hoc nature of current CM breeding. The results of genetic diversity and substructure of the entire breed, as well as admixture and crossbreeding obtained in the present study, provide a benchmark to develop future conservation strategies. Furthermore, this study demonstrates that identifying farm-based practices and farm-based breeding stocks can aid in the design of a sustainable breeding program for minority breeds. © 2012 The Authors, Animal Genetics © 2012 Stichting International Foundation for Animal Genetics.

Comparative analysis of the survival and gene expression of pathogenic strains Vibrio harveyi after starvation.

Science.gov (United States)

Sun, Jingjing; Gao, Xiaojian; Qun, Jiang; Du, Xuedi; Bi, Keran; Zhang, Xiaojun; Lin, Li

2016-11-01

This study aimed to evaluate the survival and gene expression of Vibrio harveyi under starvation conditions. The microcosms V. harveyi were incubated in sterilized seawater for 4 weeks at room temperature. Overall, the cell numeration declined rapidly about 10 3 CFU/ml during starvation, with a tiny rebound at day 21. Scanning electron microscopy revealed that rod-shaped cells became sphere with a rippled cell surface. By polymerase chain reaction (PCR) assay, nine genes, named luxR, toxR, vhhB, flaA, topA, fur, rpoS, mreB and ftsZ, were detected in the non-starved cells. In the starved cells, the expression levels of the detected genes declined substantially ranging from 0.005-fold to 0.028-fold compared to the non-starved cells performed by reverse transcription quantitative real-time PCR with 16S rRNA as the internal control. In the recovering cells, the expression levels of the detected genes, except luxR and mreB, were upregulated dramatically compared to the wild, especially topA (23.720-fold), fur (39.400-fold) and toxR (9.837-fold), validating that the expressions of both the metabolism and virulence genes were important for growth and survival of V. harveyi. The results may shed a new light on understanding of stress adaptation in bacteria. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Analysis of global gene expression in Brachypodium distachyon reveals extensive network plasticity in response to abiotic stress.

Directory of Open Access Journals (Sweden)

Henry D Priest

Full Text Available Brachypodium distachyon is a close relative of many important cereal crops. Abiotic stress tolerance has a significant impact on productivity of agriculturally important food and feedstock crops. Analysis of the transcriptome of Brachypodium after chilling, high-salinity, drought, and heat stresses revealed diverse differential expression of many transcripts. Weighted Gene Co-Expression Network Analysis revealed 22 distinct gene modules with specific profiles of expression under each stress. Promoter analysis implicated short DNA sequences directly upstream of module members in the regulation of 21 of 22 modules. Functional analysis of module members revealed enrichment in functional terms for 10 of 22 network modules. Analysis of condition-specific correlations between differentially expressed gene pairs revealed extensive plasticity in the expression relationships of gene pairs. Photosynthesis, cell cycle, and cell wall expression modules were down-regulated by all abiotic stresses. Modules which were up-regulated by each abiotic stress fell into diverse and unique gene ontology GO categories. This study provides genomics resources and improves our understanding of abiotic stress responses of Brachypodium.

Association of the AA genotype of the BCL2 (-938C>A) promoter polymorphism with better survival in ovarian cancer.

Science.gov (United States)

Heubner, Martin; Wimberger, Pauline; Otterbach, Friedrich; Kasimir-Bauer, Sabine; Siffert, Winfried; Kimmig, Rainer; Nückel, Holger

2009-01-01

Bcl-2 plays a key role in the regulation of apoptosis. Recently, a novel regulatory single nucleotide polymorphism (-938C>A) in the inhibitory P2 BCL2 promoter was described. In this study we investigated its potential association with survival in epithelial ovarian cancer. Patients (n=110) with primary epithelial ovarian cancer were retrospectively genotyped by pyrosequencing. Genotype distribution was not significantly different between 110 ovarian cancer patients and 120 healthy controls, suggesting that genotypes of this polymorphism do not increase the susceptibility to ovarian cancer. Kaplan-Meier curves showed a significant association of the AA genotype with increased survival (p=0.002). Multivariate analysis revealed that the BCL2-938AC/CC genotype (hazard ratio 4.5; p=0.003) was an independent prognostic factor compared to other prognostic factors such as age, histological grade or tumor stage. The results suggest a role for the BCL2-938C>A polymorphism as a marker for survival in patients with epithelial ovarian cancer.

Re-Analysis of Metagenomic Sequences from Acute Flaccidmyelitis Patients Reveals Alternatives to Enterovirus D68 Infection

Science.gov (United States)

2015-07-13

caused in some cases by infection with enterovirus D68. We found that among the patients whose symptoms were previously attributed to enterovirus D68...distribution is unlimited. Re-analysis of metagenomic sequences from acute flaccidmyelitis patients reveals alternatives to enterovirus D68...Street Baltimore, MD 21218 -2685 ABSTRACT Re-analysis of metagenomic sequences from acute flaccidmyelitis patients reveals alternatives to enterovirus

Peritumoral interstitial fluid flow velocity predicts survival in cervical carcinoma

International Nuclear Information System (INIS)

Hompland, Tord; Lund, Kjersti V.; Ellingsen, Christine; Kristensen, Gunnar B.; Rofstad, Einar K.

2014-01-01

Background and purpose: High tumor interstitial fluid pressure (IFP) is associated with poor outcome in locally advanced carcinoma of the uterine cervix. We have recently developed a noninvasive assay of the IFP of tumors, and in this assay, the outward interstitial fluid flow velocity at the tumor surface (v 0 ) is measured by Gd-DTPA-based DCE-MRI and used as a parameter for IFP. Here, we investigated the independent prognostic significance of v 0 in cervical cancer patients given cisplatin-based concurrent chemoradiotherapy with curative intent. Patients: The study involved 62 evaluable patients from a cohort of 74 consecutive patients (Stage IB through IIIB) with a median follow-up of 5.5 years. Results: The actuarial disease-free survival (DFS) and overall survival (OS) at 5 years were 67% and 76%, respectively. Significant associations were found between v 0 dichotomized about the median value and DFS and OS, both in the total patient cohort and a subcohort of 40 Stage IIB patients. Multivariate analysis involving stage, tumor volume, lymph node status, and v 0 revealed that only v 0 provided independent prognostic information about DFS and OS. Conclusion: This investigation demonstrates a strong, independent prognostic impact of the pretreatment peritumoral fluid flow velocity in cervical cancer

Spheroid Culture of Head and Neck Cancer Cells Reveals an Important Role of EGFR Signalling in Anchorage Independent Survival.

Science.gov (United States)

Braunholz, Diana; Saki, Mohammad; Niehr, Franziska; Öztürk, Merve; Borràs Puértolas, Berta; Konschak, Robert; Budach, Volker; Tinhofer, Ingeborg

2016-01-01

In solid tumours millions of cells are shed into the blood circulation each day. Only a subset of these circulating tumour cells (CTCs) survive, many of them presumable because of their potential to form multi-cellular clusters also named spheroids. Tumour cells within these spheroids are protected from anoikis, which allows them to metastasize to distant organs or re-seed at the primary site. We used spheroid cultures of head and neck squamous cell carcinoma (HNSCC) cell lines as a model for such CTC clusters for determining the role of the epidermal growth factor receptor (EGFR) in cluster formation ability and cell survival after detachment from the extra-cellular matrix. The HNSCC cell lines FaDu, SCC-9 and UT-SCC-9 (UT-SCC-9P) as well as its cetuximab (CTX)-resistant sub-clone (UT-SCC-9R) were forced to grow in an anchorage-independent manner by coating culture dishes with the anti-adhesive polymer poly-2-hydroxyethylmethacrylate (poly-HEMA). The extent of apoptosis, clonogenic survival and EGFR signalling under such culture conditions was evaluated. The potential of spheroid formation in suspension culture was found to be positively correlated with the proliferation rate of HNSCC cell lines as well as their basal EGFR expression levels. CTX and gefitinib blocked, whereas the addition of EGFR ligands promoted anchorage-independent cell survival and spheroid formation. Increased spheroid formation and growth were associated with persistent activation of EGFR and its downstream signalling component (MAPK/ERK). Importantly, HNSCC cells derived from spheroid cultures retained their clonogenic potential in the absence of cell-matrix contact. Addition of CTX under these conditions strongly inhibited colony formation in CTX-sensitive cell lines but not their resistant subclones. Altogether, EGFR activation was identified as crucial factor for anchorage-independent survival of HNSCC cells. Targeting EGFR in CTC cluster formation might represent an attractive anti

A synbiotic improves the immunity of white shrimp, Litopenaeus vannamei: Metabolomic analysis reveal compelling evidence.

Science.gov (United States)

Huynh, Truong-Giang; Cheng, Ann-Chang; Chi, Chia-Chun; Chiu, Kuo-Hsun; Liu, Chun-Hung

2018-05-18

In this study, we examined the synergistic effects of a diet-administered synbiotic comprising galactooligosaccharide (GOS) and the probiotic Lactobacillus plantarum 7-40 on immune responses, immune-related gene expressions, and disease resistance to Vibrio alginolyticus in white shrimp Litopenaeus vannamei. To unravel the regulatory role of the synbiotic in activating the immune system of shrimp, 1 H nuclear magnetic resonance (NMR)-based metabolomic analysis were used to investigate hepatopancreas metabolites, then significantly altered metabolites were confirmed in both the hepatopancreas and plasma by reverse-phase high-performance liquid chromatography (RP-HPLC) and spectrophotometric analysis. Shrimp were fed four experimental diets for 60 days, including a basal diet with no GOS or probiotic (control), 0.4% GOS (PRE), probiotic (PRO), and 0.4% GOS in combination with the probiotic (SYN). Results showed that the SYN diet significantly increased survival of L. vannamei 24 h after a V. alginolyticus injection. Immune parameters such as phenoloxidase activity, respiratory bursts, phagocytic activity and gene expressions, including prophenoloxidase I, serine proteinase, and peroxinectin, of shrimp fed the SYN diet significantly increased, compared to the other treatments and control. In addition, results from the 1 H NMR analysis revealed that 22 hepatopancreas metabolites were matched and identified between the SYN and control groups, among which three metabolites, i.e., inosine monophosphate (IMP), valine, and betaine, significantly increased in the SYN group. Confirmation using RP-HPLC and spectrophotometric methods showed that IMP presented high amounts in the hepatopancreas, but not in the plasma of shrimp; in contrast, valine and betaine metabolites were in high concentrations in both the hepatopancreas and plasma. Our results suggested that GOS and the probiotic had a synergistic effect on enhancing immunity and disease resistance of L. vannamei against

Survival benefit of TIPS versus serial paracentesis in patients with refractory ascites: a single institution case-control propensity score analysis

International Nuclear Information System (INIS)

Gaba, R.C.; Parvinian, A.; Casadaban, L.C.; Couture, P.M.; Zivin, S.P.; Lakhoo, J.; Minocha, J.; Ray, C.E.; Knuttinen, M.G.; Bui, J.T.

2015-01-01

Aim: To compare the impact of covered stent-graft transjugular intrahepatic portosystemic shunt (TIPS) versus serial paracentesis on survival of patients with medically refractory ascites. Materials and methods: In this retrospective study, cirrhotic patients who underwent covered stent-graft TIPS for refractory ascites from 2003–2013 were compared with similar patients who underwent serial paracentesis during 2009–2013. Demographic and liver disease data, Model for End-Stage Liver Disease (MELD) scores, and survival outcomes were obtained from hospital electronic medical records and the social security death index. After propensity score weighting to match study group characteristics, survival outcomes were compared using Kaplan–Meier statistics with log-rank analysis. Results: Seventy TIPS (70% men, mean age 55.7 years, mean MELD 15.1) and 80 paracentesis (58% men, mean age 53.5 years, mean MELD 22.5) patients were compared. The TIPS haemodynamic success rate was 100% (mean portosystemic pressure gradient reduction 13 mmHg). Paracentesis patients underwent a mean of 7.9 procedures. After propensity score weighting to balance group features, TIPS patients showed a trend toward enhanced survival compared with paracentesis patients (median survival 1037 versus 262 days, p = 0.074). TIPS conferred a significant increase or trend toward improved survival compared with paracentesis at 1 (66% versus 44%, p = 0.018), 2 (56% versus 38%, p = 0.057), and 3 year (49% versus 32%, p = 0.077) time points. Thirty and 90 day mortality rates were not statistically increased by TIPS. Conclusion: Covered stent-graft TIPS improves intermediate- to long-term survival without significantly increasing short-term mortality of ascites patients, and suggests a greater potential role for TIPS in properly selected ascitic patients when medical management fails. - Highlights: • The survival benefit of TIPS for patients with refractory ascites remains unproven. • A case

Network survivability performance

Science.gov (United States)

1993-11-01

This technical report has been developed to address the survivability of telecommunications networks including services. It responds to the need for a common understanding of, and assessment techniques for network survivability, availability, integrity, and reliability. It provides a basis for designing and operating telecommunications networks to user expectations for network survivability and a foundation for continuing industry activities in the subject area. This report focuses on the survivability of both public and private networks and covers a wide range of users. Two frameworks are established for quantifying and categorizing service outages, and for classifying network survivability techniques and measures. The performance of the network survivability techniques is considered; however, recommended objectives are not established for network survivability performance.

Myositis-associated usual interstitial pneumonia has a better survival than idiopathic pulmonary fibrosis.

Science.gov (United States)

Aggarwal, Rohit; McBurney, Christine; Schneider, Frank; Yousem, Samuel A; Gibson, Kevin F; Lindell, Kathleen; Fuhrman, Carl R; Oddis, Chester V

2017-03-01

To compare the survival outcomes between myositis-associated usual interstitial pneumonia (MA-UIP) and idiopathic pulmonary fibrosis (IPF-UIP). Adult MA-UIP and IPF-UIP patients were identified using CTD and IPF registries. The MA-UIP cohort included myositis or anti-synthetase syndrome patients with interstitial lung disease while manifesting UIP on high-resolution CT chest and/or a lung biopsy revealing UIP histology. IPF subjects met American Thoracic Society criteria and similarly had UIP histopathology. Kaplan-Meier survival curves compared cumulative and pulmonary event-free survival (event = transplant or death) between (i) all MA-UIP and IPF-UIP subjects, (ii) MA-UIP with biopsy proven UIP (n = 25) vs IPF-UIP subjects matched for age, gender and baseline forced vital capacity (±10%). Cox proportional hazards ratios compared the survival controlling for co-variates. Eighty-one IPF-UIP and 43 MA-UIP subjects were identified. The median cumulative and event-free survival time in IPF vs MA-UIP was 5.25/1.8 years vs 16.2/10.8 years, respectively. Cumulative and event-free survival was significantly worse in IPF-UIP vs MA-UIP [hazards ratio of IPF-UIP was 2.9 (95% CI: 1.5, 5.6) and 5.0 (95% CI: 2.8, 8.7) (P < 0.001), respectively]. IPF-UIP event-free survival (but not cumulative) remained significantly worse than MA-UIP with a hazards ratio of 6.4 (95% CI: 3.0, 13.8) after controlling for age at interstitial lung disease diagnosis, gender, ethnicity and baseline forced vital capacity%. Respiratory failure was the most common cause of death in both groups. A sub-analysis of 25 biopsy-proven MA-UIP subjects showed similar results. MA-UIP patients demonstrated a significant survival advantage over a matched IPF cohort, suggesting that despite similar histological and radiographic findings at presentation, the prognosis of MA-UIP is superior to that of IPF-UIP. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology

Analysis of 5 year survival of esophageal cancer treated by radiotherapy

International Nuclear Information System (INIS)

Takegawa, Yoshihiro; Ohgushi, Ikuyo; Hiraki, Yoshio; Honke, Yoshifumi; Matsuki, Tsutomu; Yokoyama, Takashi; Yoshida, Mineo.

1987-01-01

Since 1984, a total of 1,419 patients with carcinoma of the esophagus were treated at the Department of Radiology of 17 hospitals in Chugoku-Shikoku province. The five year survival rate was 7.3 % (42/578 cases). Thirty-nine out of the forty-two cases were analyzed according to the tumor extent, localization and types of the X-ray findings. In addition, 95 patients (67 had been reported in other journals and 28 in this report) who have survived more than 5 years after radical radiotherapy were analyzed. (author)

Protein content and functional characteristics of serum-purified exosomes from patients with colorectal cancer revealed by quantitative proteomics.

Science.gov (United States)

Chen, Yanyu; Xie, Yong; Xu, Lai; Zhan, Shaohua; Xiao, Yi; Gao, Yanpan; Wu, Bin; Ge, Wei

2017-02-15

Tumor cells of colorectal cancer (CRC) release exosomes into the circulation. These exosomes can mediate communication between cells and affect various tumor-related processes in their target cells. We present a quantitative proteomics analysis of the exosomes purified from serum of patients with CRC and normal volunteers; data are available via ProteomeXchange with identifier PXD003875. We identified 918 proteins with an overlap of 725 Gene IDs in the Exocarta proteins list. Compared with the serum-purified exosomes (SPEs) of normal volunteers, we found 36 proteins upregulated and 22 proteins downregulated in the SPEs of CRC patients. Bioinformatics analysis revealed that upregulated proteins are involved in processes that modulate the pretumorigenic microenvironment for metastasis. In contrast, differentially expressed proteins (DEPs) that play critical roles in tumor growth and cell survival were principally downregulated. Our study demonstrates that SPEs of CRC patients play a pivotal role in promoting the tumor invasiveness, but have minimal influence on putative alterations in tumor survival or proliferation. According to bioinformatics analysis, we speculate that the protein contents of exosomes might be associated with whether they are involved in premetastatic niche establishment or growth and survival of metastatic tumor cells. This information will be helpful in elucidating the pathophysiological functions of tumor-derived exosomes, and aid in the development of CRC diagnostics and therapeutics. © 2016 UICC.

Comparative genome analysis of pathogenic and non-pathogenic Clavibacter strains reveals adaptations to their lifestyle.

Science.gov (United States)

Załuga, Joanna; Stragier, Pieter; Baeyen, Steve; Haegeman, Annelies; Van Vaerenbergh, Johan; Maes, Martine; De Vos, Paul

2014-05-22

The genus Clavibacter harbors economically important plant pathogens infecting agricultural crops such as potato and tomato. Although the vast majority of Clavibacter strains are pathogenic, there is an increasing number of non-pathogenic isolates reported. Non-pathogenic Clavibacter strains isolated from tomato seeds are particularly problematic because they affect the current detection and identification tests for Clavibacter michiganensis subsp. michiganensis (Cmm), which is regulated with a zero tolerance in tomato seed. Their misidentification as pathogenic Cmm hampers a clear judgment on the seed quality and health. To get more insight in the genetic features linked to the lifestyle of these bacteria, a whole-genome sequence of the tomato seed-borne non-pathogenic Clavibacter LMG 26808 was determined. To gain a better understanding of the molecular determinants of pathogenicity, the genome sequence of LMG 26808 was compared with that of the pathogenic Cmm strain (NCPPB 382). The comparative analysis revealed that LMG 26808 does not contain plasmids pCM1 and pCM2 and also lacks the majority of important virulence factors described so far for pathogenic Cmm. This explains its apparent non-pathogenic nature in tomato plants. Moreover, the genome analysis of LMG 26808 detected sequences from a plasmid originating from a member of Enterobacteriaceae/Klebsiella relative. Genes received that way and coding for antibiotic resistance may provide a competitive advantage for survival of LMG 26808 in its ecological niche. Genetically, LMG 26808 was the most similar to the pathogenic Cmm NCPPB 382 but contained more mobile genetic elements. The genome of this non-pathogenic Clavibacter strain contained also a high number of transporters and regulatory genes. The genome sequence of the non-pathogenic Clavibacter strain LMG 26808 and the comparative analyses with other pathogenic Clavibacter strains provided a better understanding of the genetic bases of virulence and

Hyperfractionated Accelerated Radiotherapy (HART) for Anaplastic Thyroid Carcinoma: Toxicity and Survival Analysis

Energy Technology Data Exchange (ETDEWEB)

Dandekar, Prasad [Head and Neck/Thyroid Unit, Royal Marsden NHS Foundation Trust, Sutton, Surrey (United Kingdom); Harmer, Clive; Barbachano, Yolanda [Department of Clinical Research and Development, Royal Marsden NHS Foundation Trust, Sutton, Surrey (United Kingdom); Rhys-Evans, Peter; Harrington, Kevin; Nutting, Christopher [Head and Neck-Thyroid Unit, Royal Marsden NHS Foundation Trust, Chelsea, London (United Kingdom); Newbold, Kate [Head and Neck/Thyroid Unit, Royal Marsden NHS Foundation Trust, Sutton, Surrey (United Kingdom); Consultant Clinical Oncologist, Royal Marsden NHS Foundation Trust, Chelsea, London (United Kingdom)

2009-06-01

Purpose: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers, and the current protocol of hyperfractionated accelerated radiotherapy was initiated to improve survival while limiting toxicities. Methods and Materials: All patients with ATC from 1991 to 2002 were accrued and received megavoltage radiotherapy from the mastoid processes to the carina up to 60 Gy in twice-daily fractions of 1.8 and 2 Gy, 6 hours apart. Results: Thirty-one patients were accrued with a median age of 69 years, and 55% were women. Debulking was performed in 26%, and total thyroidectomy, in 6%, whereas 68% received radical radiotherapy alone. Local control data were available for 27 patients: 22% had a complete response, 26% had a partial response, 15% showed progressive disease, and 37% showed static disease. Median overall survival for all 31 patients was 70 days (95% confidence interval, 40-99). There was no significant difference in median survival between patients younger (70 days) and older than 70 years (42 days), between men (70 days) and women (49days), and between patients receiving postoperative radiotherapy (77 days) and radical radiotherapy alone (35 days). Grade III or higher skin erythema was seen in 56% patients; desquamation in 21%; dysphagia in 74%; and esophagitis in 79%. Conclusion: The current protocol failed to offer a significant survival benefit, was associated with severe toxicities, and thus was discontinued. There is a suggestion that younger patients with operable disease have longer survival, but this would require a larger study to confirm it.

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], PFasting blood glucose and diabetes did not affect the results. Higher BMI is associated with decreased survival in pancreatic 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.

Sparing Sphincters and Laparoscopic Resection Improve Survival by Optimizing the Circumferential Resection Margin in Rectal Cancer Patients.

Science.gov (United States)

Keskin, Metin; Bayraktar, Adem; Sivirikoz, Emre; Yegen, Gülcin; Karip, Bora; Saglam, Esra; Bulut, Mehmet Türker; Balik, Emre

2016-02-01

The goal of rectal cancer treatment is to minimize the local recurrence rate and extend the disease-free survival period and survival. For this aim, obtainment of negative circumferential radial margin (CRM) plays an important role. This study evaluated predictive factors for positive CRM status and its effect on patient survival in mid- and distal rectal tumors.Patients who underwent curative resection for rectal cancer were included. The main factors were demographic data, tumor location, surgical technique, neoadjuvant therapy, tumor diameter, tumor depth, lymph node metastasis, mesorectal integrity, CRM, the rate of local recurrence, distant metastasis, and overall and disease-free survival. Statistical analyses were performed by using the Chi-squared test, Fisher exact test, Student t test, Mann-Whitney U test and the Mantel-Cox log-rank sum test.A total of 420 patients were included, 232 (55%) of whom were male. We observed no significant differences in patient characteristics or surgical treatment between the patients who had positive CRM and who had negative CRM, but a higher positive CRM rate was observed in patients undergone abdominoperineal resection (APR) (P CRM status. Logistic regression analysis revealed that APR (P CRM status. Moreover, positive CRM was associated with decreased 5-year overall and disease-free survival (P = 0.002 and P = 0.004, respectively).This large single-institution series demonstrated that APR and open resection were independent predictive factors for positive CRM status in rectal cancer. Positive CRM independently decreased the 5-year overall and disease-free survival rates.

IMP3 expression in human ovarian cancer is associated with improved survival

DEFF Research Database (Denmark)

Noske, Aurelia; Faggad, Areeg; Wirtz, Ralph

2009-01-01

The insulin-like growth factor-II mRNA-binding protein IMP3 plays an important role in embryogenesis and recent reports suggest an involvement in tumorigenesis. Although IMP3 expression has been well studied in mouse and human fetal and adult gonads, its role in ovarian cancer is unknown. We...... investigated the expression of IMP3 at protein and mRNA levels in a cohort of primary ovarian carcinomas and in 11 ovarian cancer cell lines. Western blot analysis revealed an expression of IMP3 in all ovarian cancer cell lines and immunohistochemistry demonstrated a positive cytoplasmic staining in 32 of 68...... carcinomas (47%). In contrast, epithelium of borderline tumors, as well as, benign ovarian lesions and normal ovaries exhibited only weak or no IMP3 expression. In univariate Kaplan-Meier analysis, IMP3 protein expression was significantly associated with better overall survival (P=0.048). To confirm...

Global surveillance of cancer survival 1995–2009: analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2)

Science.gov (United States)

Allemani, Claudia; Weir, Hannah K; Carreira, Helena; Harewood, Rhea; Spika, Devon; Wang, Xiao-Si; Bannon, Finian; Ahn, Jane V; Johnson, Christopher J; Bonaventure, Audrey; Marcos-Gragera, Rafael; Stiller, Charles; Silva, Gulnar Azevedo e; Chen, Wan-Qing; Ogunbiyi, Olufemi J; Rachet, Bernard; Soeberg, Matthew J; You, Hui; Matsuda, Tomohiro; Bielska-Lasota, Magdalena; Storm, Hans; Tucker, Thomas C; Coleman, Michel P

2015-01-01

Summary Background Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. Methods Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15–99 years) and 75 000 children (age 0–14 years) diagnosed with cancer during 1995–2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. Findings 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005–09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15–19% in North America, and as low as 7–9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10–20% between 1995–99 and 2005–09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer

No survival benefit from adding cetuximab or panitumumab to oxaliplatin-based chemotherapy in the first-line treatment of metastatic colorectal cancer in KRAS wild type patients: a meta-analysis.

Directory of Open Access Journals (Sweden)

Si-wei Zhou

Full Text Available The efficacy of combined therapies of oxaliplatin-based chemotherapy and anti-epidermal growth factor receptor (anti-EGFR monoclonal antibodies (MAbs remains controversial in colorectal cancer (CRC. The aim of this study is to estimate the efficacy and safety of adding cetuximab or panitumumab to oxaliplatin-based chemotherapy in the first line treatment in KRAS wild type patients with metastatic colorectal cancer (mCRC through meta-analysis.Medline, EMBASE, and Cochrane library, American Society of Clinical Oncology (ASCO and European Society for Medical Oncology (ESMO were searched. Eligible studies were randomized controlled trials (RCTs which evaluated oxaliplatin-based chemotherapy with or without anti-EGFR drugs (cetuximab or panitumumab in untreated KRAS wild type patients with mCRC. The outcomes included overall survival (OS, progression-free survival (PFS, overall response rate (ORR and toxicities. Hazard ratios (HR and risk ratio (RR were used for the meta-analysis and were expressed with 95% confidence intervals.This meta-analysis included four RCTs with 1270 patients, and all of the patients were administered oxaliplatin-based chemotherapy regimens with or without anti-EGFR MAbs. The result of heterogeneity of OS was not significant. Compared with chemotherapy alone, the addition of cetuximab or panitumumab didn't result in significant improvement in OS (HR = 1.00, 95%CI [0.88, 1.13], P = 0.95 or PFS (HR = 0.86, 95%CI [0.71, 1.04], P = 0.13. The subgroup analysis of cetuximab also revealed no significant benefit in OS (HR = 1.02, 95%CI [0.89, 1.18], P = 0.75 or in PFS (HR = 0.87, 95%CI [0.65, 1.17], P = 0.36. Patients who received combined therapy didn't have a higher ORR (Risk Ratio = 1.08, 95%CI [0.86, 1.36]. Toxicities slightly increased in anti-EGFR drugs group.The addition of cetuximab or panitumumab to oxaliplatin-based chemotherapy in first-line treatment of mCRC in wild type KRAS population did not improve efficacy in

Working Conditions and Factory Survival: Evidence from Better Factories Cambodia

OpenAIRE

Robertson, Raymond; Brown, Drusilla; Dehejia, Rajeev

2016-01-01

A large and growing literature has identified several conditions, including exporting, that contribute to plant survival. A prevailing sentiment suggests that anti-sweatshop activity against plants in developing countries adds the risk of making survival more difficult by imposing external constraints that may interfere with optimizing behavior. Using a relatively new plant-level panel dataset from Cambodia, this paper applies survival analysis to estimate the relationship between changes in ...

The thrombopoietin/MPL/Bcl-xL pathway is essential for survival and self-renewal in human preleukemia induced by AML1-ETO

Science.gov (United States)

Chou, Fu-Sheng; Griesinger, Andrea; Wunderlich, Mark; Lin, Shan; Link, Kevin A.; Shrestha, Mahesh; Goyama, Susumu; Mizukawa, Benjamin; Shen, Shuhong; Marcucci, Guido

2012-01-01

AML1-ETO (AE) is a fusion product of translocation (8;21) that accounts for 40% of M2 type acute myeloid leukemia (AML). In addition to its role in promoting preleukemic hematopoietic cell self-renewal, AE represses DNA repair genes, which leads to DNA damage and increased mutation frequency. Although this latter function may promote leukemogenesis, concurrent p53 activation also leads to an increased baseline apoptotic rate. It is unclear how AE expression is able to counterbalance this intrinsic apoptotic conditioning by p53 to promote survival and self-renewal. In this report, we show that Bcl-xL is up-regulated in AE cells and plays an essential role in their survival and self-renewal. Further investigation revealed that Bcl-xL expression is regulated by thrombopoietin (THPO)/MPL-signaling induced by AE expression. THPO/MPL-signaling also controls cell cycle reentry and mediates AE-induced self-renewal. Analysis of primary AML patient samples revealed a correlation between MPL and Bcl-xL expression specifically in t(8;21) blasts. Taken together, we propose that survival signaling through Bcl-xL is a critical and intrinsic component of a broader self-renewal signaling pathway downstream of AML1-ETO–induced MPL. PMID:22337712

The Impact of Chemoembolization Endpoints on Survival in Hepatocellular Carcinoma Patients

Science.gov (United States)

Jin, Brian; Wang, Dingxin; Lewandowski, Robert J.; Riaz, Ahsun; Ryu, Robert K.; Sato, Kent T.; Larson, Andrew C.; Salem, Riad; Omary, Reed A.

2010-01-01

OBJECTIVE To investigate the relationship between angiographic embolic endpoints of transarterial chemoembolization (TACE) and survival in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS This study retrospectively assessed 105 patients with surgically unresectable HCC who underwent TACE. Patients were classified according to a previously established subjective angiographic chemoembolization endpoint (SACE) scale. Only one patient was classified as SACE level 1 and thus excluded from all subsequent analysis. Survival was evaluated with Kaplan-Meier analysis. Multivariate analysis with Cox’s proportional hazard regression model was used to determine independent prognostic risk factors of survival. RESULTS Overall median survival was 21.1 months (95% confidence interval [CI], 15.9–26.4). Patients embolized to SACE levels 2 and 3 were aggregated and had a significantly higher median survival (25.6 months; 95% CI, 16.2–35.0) than patients embolized to SACE level 4 (17.1 months; 95% CI, 13.3–20.9) (p = 0.035). Multivariate analysis indicated that SACE level 4 (Hazard ratio [HR], 2.49; 95% CI, 1.41–4.42; p = 0.002), European Cooperative Oncology Group performance status > 0 (HR, 1.97; 95% CI, 1.15–3.37; p = 0.013), American Joint Committee on Cancer stage 3 or 4 (HR, 2.42; 95% CI, 1.27–4.60; p = 0.007), and Child-Pugh class B (HR, 1.94; 95% CI, 1.09–3.46; p = 0.025) were all independent negative prognostic indicators of survival. CONCLUSION Embolization to an intermediate, sub-stasis endpoint (SACE levels 2 and 3) during TACE improves survival compared to embolization to a higher, stasis endpoint (SACE level 4). Interventional oncologists should consider targeting these intermediate, sub-stasis angiographic endpoints during TACE. PMID:21427346

Differential proteomic analysis reveals novel links between primary metabolism and antibiotic production in Amycolatopsis balhimycina

DEFF Research Database (Denmark)

Gallo, G.; Renzone, G.; Alduina, R.

2010-01-01

A differential proteomic analysis, based on 2-DE and MS procedures, was performed on Amycolatopsis balhimycina DSM5908, the actinomycete producing the vancomycin-like antibiotic balhimycin. A comparison of proteomic profiles before and during balhimycin production characterized differentially...... available over the World Wide Web as interactive web pages (http://www.unipa.it/ampuglia/Abal-proteome-maps). Functional clustering analysis revealed that differentially expressed proteins belong to functional groups involved in central carbon metabolism, amino acid metabolism and protein biosynthesis...... intermediates, were upregulated during antibiotic production. qRT-PCR analysis revealed that 8 out of 14 upregulated genes showed a positive correlation between changes at translational and transcriptional expression level. Furthermore, proteomic analysis of two nonproducing mutants, restricted to a sub...

Survival-related profile, pathways, and transcription factors in ovarian cancer.

Directory of Open Access Journals (Sweden)

Anne P G Crijns

2009-02-01

Full Text Available BACKGROUND: Ovarian cancer has a poor prognosis due to advanced stage at presentation and either intrinsic or acquired resistance to classic cytotoxic drugs such as platinum and taxoids. Recent large clinical trials with different combinations and sequences of classic cytotoxic drugs indicate that further significant improvement in prognosis by this type of drugs is not to be expected. Currently a large number of drugs, targeting dysregulated molecular pathways in cancer cells have been developed and are introduced in the clinic. A major challenge is to identify those patients who will benefit from drugs targeting these specific dysregulated pathways.The aims of our study were (1 to develop a gene expression profile associated with overall survival in advanced stage serous ovarian cancer, (2 to assess the association of pathways and transcription factors with overall survival, and (3 to validate our identified profile and pathways/transcription factors in an independent set of ovarian cancers. METHODS AND FINDINGS: According to a randomized design, profiling of 157 advanced stage serous ovarian cancers was performed in duplicate using approximately 35,000 70-mer oligonucleotide microarrays. A continuous predictor of overall survival was built taking into account well-known issues in microarray analysis, such as multiple testing and overfitting. A functional class scoring analysis was utilized to assess pathways/transcription factors for their association with overall survival. The prognostic value of genes that constitute our overall survival profile was validated on a fully independent, publicly available dataset of 118 well-defined primary serous ovarian cancers. Furthermore, functional class scoring analysis was also performed on this independent dataset to assess the similarities with results from our own dataset. An 86-gene overall survival profile discriminated between patients with unfavorable and favorable prognosis (median survival, 19

Treatment and survival outcomes of small cell carcinoma of the esophagus: an analysis of the National Cancer Data Base.

Science.gov (United States)

Wong, Andrew T; Shao, Meng; Rineer, Justin; Osborn, Virginia; Schwartz, David; Schreiber, David

2017-02-01

Given the paucity of esophageal small cell carcinoma (SCC) cases, there are few large studies evaluating this disease. In this study, the National Cancer Data Base (NCDB) was utilized to analyze the clinical features, treatment, and survival of patients with esophageal SCC in a large, population-based dataset. We selected patients diagnosed with esophageal SCC from 1998 to 2011. Patients were identified as having no treatment, chemotherapy alone, radiation ± sequential chemotherapy, concurrent chemoradiation, and esophagectomy ± chemotherapy and/or radiation. Overall survival (OS) was analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis was conducted to identify factors associated with OS. A total of 583 patients were identified. Most patients had stage IV disease (41.7%). Regarding treatment selection, chemoradiation was the most commonly utilized for patients with nonmetasatic disease, whereas chemotherapy alone was most common for metastatic patients. Esophagectomy (median survival 44.9 months with 3 year OS 50.5%) was associated with the best OS for patients with localized (node-negative) disease compared with chemotherapy alone (p < 0.001) or chemoradiation (p = 0.01). For locoregional (node-positive) disease, treatment with chemoradiation resulted in a median survival of 17.8 months and a 3 year OS 31.6%. On multivariate analysis, treatment with chemotherapy alone (p = 0.003) was associated with worse OS while esophagectomy (p = 0.04) was associated with improved OS compared to chemoradiation. Esophageal SCC is an aggressive malignancy with most patients presenting with metastatic disease. Either esophagectomy or chemoradiation as part of multimodality treatment appear to improve OS for selected patients with nonmetastatic disease. © 2016 International Society for Diseases of the Esophagus.

Clinical performance of ART restorations in primary teeth: a survival analysis.

Science.gov (United States)

Faccin, Elise Sasso; Ferreira, Simone Helena; Kramer, Paulo Floriani; Ardenghi, Thiago Machado; Feldens, Carlos Alberto

2009-01-01

To assess the survival of Atraumatic Restorative Treatment (ART) restorations in primary teeth performed in a dental clinical setting. One hundred and five single-surface ART restorations placed in 56 preschool children (mean age 31 months) were included. Final-year dental students performed the restorations using standard ART procedures with hand instruments. A resin-modified glass ionomer cement (Vitremer 3M/ESPE) was used as a restorative material. Performances of the restorations were assessed directly by the ART evaluation criteria. Follow-up period ranged from 6 to 48 months. Survival estimates for restoration longevity were evaluated using the Kaplan-Meier method. Log-rank test (P ART restorations were 89%, 85% and 72% in 6 to 11, 12 to 24 and 25 to 48 months of evaluation respectively. Differences in success rates among demographic and clinical characteristics were not statistically significant. High survivals rates of the ART restorations found in this study seem to indicate the reliability of this approach as an appropriate treatment option for primary teeth in a clinical setting.

WE-H-BRA-08: A Monte Carlo Cell Nucleus Model for Assessing Cell Survival Probability Based On Particle Track Structure Analysis

Energy Technology Data Exchange (ETDEWEB)

Lee, B [Northwestern Memorial Hospital, Chicago, IL (United States); Georgia Institute of Technology, Atlanta, GA (Georgia); Wang, C [Georgia Institute of Technology, Atlanta, GA (Georgia)

2016-06-15

Purpose: To correlate the damage produced by particles of different types and qualities to cell survival on the basis of nanodosimetric analysis and advanced DNA structures in the cell nucleus. Methods: A Monte Carlo code was developed to simulate subnuclear DNA chromatin fibers (CFs) of 30nm utilizing a mean-free-path approach common to radiation transport. The cell nucleus was modeled as a spherical region containing 6000 chromatin-dense domains (CDs) of 400nm diameter, with additional CFs modeled in a sparser interchromatin region. The Geant4-DNA code was utilized to produce a particle track database representing various particles at different energies and dose quantities. These tracks were used to stochastically position the DNA structures based on their mean free path to interaction with CFs. Excitation and ionization events intersecting CFs were analyzed using the DBSCAN clustering algorithm for assessment of the likelihood of producing DSBs. Simulated DSBs were then assessed based on their proximity to one another for a probability of inducing cell death. Results: Variations in energy deposition to chromatin fibers match expectations based on differences in particle track structure. The quality of damage to CFs based on different particle types indicate more severe damage by high-LET radiation than low-LET radiation of identical particles. In addition, the model indicates more severe damage by protons than of alpha particles of same LET, which is consistent with differences in their track structure. Cell survival curves have been produced showing the L-Q behavior of sparsely ionizing radiation. Conclusion: Initial results indicate the feasibility of producing cell survival curves based on the Monte Carlo cell nucleus method. Accurate correlation between simulated DNA damage to cell survival on the basis of nanodosimetric analysis can provide insight into the biological responses to various radiation types. Current efforts are directed at producing cell

Analyzing age-specific genetic effects on human extreme age survival in cohort-based longitudinal studies

DEFF Research Database (Denmark)

Tan, Qihua; Jacobsen, Rune; Sørensen, Mette

2013-01-01

The analysis of age-specific genetic effects on human survival over extreme ages is confronted with a deceleration pattern in mortality that deviates from traditional survival models and sparse genetic data available. As human late life is a distinct phase of life history, exploring the genetic...... effects on extreme age survival can be of special interest to evolutionary biology and health science. We introduce a non-parametric survival analysis approach that combines population survival information with individual genotype data in assessing the genetic effects in cohort-based longitudinal studies...

Predictors of survival among HIV-positive children on ART in ...

African Journals Online (AJOL)

... 16(4): 335–343. Open Access article distributed in terms of the Creative Commons Attribution License ... and adjusted hazard ratios respectively. The results reveal ... Children who were initiated early on ART had higher survival probability over time (HR: 0.35 [95% ..... workers they will have desirable clinical outcomes.

Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice.

Science.gov (United States)

Kiilerich, Pia; Myrmel, Lene Secher; Fjære, Even; Hao, Qin; Hugenholtz, Floor; Sonne, Si Brask; Derrien, Muriel; Pedersen, Lone Møller; Petersen, Rasmus Koefoed; Mortensen, Alicja; Licht, Tine Rask; Rømer, Maria Unni; Vogel, Ulla Birgitte; Waagbø, Linn Jeanette; Giallourou, Natasa; Feng, Qiang; Xiao, Liang; Liu, Chuan; Liaset, Bjørn; Kleerebezem, Michiel; Wang, Jun; Madsen, Lise; Kristiansen, Karsten

2016-06-01

Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein/sucrose ratio precipitated obesity and reduced survival relative to mice fed a low-fat diet. By contrast, intake of a high-fat diet with a high protein/sucrose ratio attenuated lifelong weight gain and adipose tissue expansion, and survival was not significantly altered relative to low-fat-fed mice. Our findings support the notion that reduced survival in response to high-fat/high-sucrose feeding is linked to obesity development. Digital gene expression analyses, further validated by qPCR, demonstrated that the protein/sucrose ratio modulated global gene expression over time in liver and adipose tissue, affecting pathways related to metabolism and inflammation. Analysis of fecal bacterial DNA using the Mouse Intestinal Tract Chip revealed significant changes in the composition of the gut microbiota in relation to host age and dietary fat content, but not the protein/sucrose ratio. Accordingly, dietary fat rather than the protein/sucrose ratio or adiposity is a major driver shaping the gut microbiota, whereas the effect of a high-fat diet on survival is dependent on the protein/sucrose ratio. Copyright © 2016 the American Physiological Society.

Stomatin-like protein 2 is overexpressed in epithelial ovarian cancer and predicts poor patient survival

International Nuclear Information System (INIS)

Sun, Fei; Ding, Wen; He, Jie-Hua; Wang, Xiao-Jing; Ma, Ze-Biao; Li, Yan-Fang

2015-01-01

Stomatin-like protein 2 (SLP-2, also known as STOML2) is a stomatin homologue of uncertain function. SLP-2 overexpression has been suggested to be associated with cancer progression, resulting in adverse clinical outcomes in patients. Our study aim to investigate SLP-2 expression in epithelial ovarian cancer cells and its correlation with patient survival. SLP-2 mRNA and protein expression levels were analysed in five epithelial ovarian cancer cell lines and normal ovarian epithelial cells using real-time PCR and western blotting analysis. SLP-2 expression was investigated in eight matched-pair samples of epithelial ovarian cancer and adjacent noncancerous tissues from the same patients. Using immunohistochemistry, we examined the protein expression of paraffin-embedded specimens from 140 patients with epithelial ovarian cancer, 20 cases with borderline ovarian tumours, 20 cases with benign ovarian tumours, and 20 cases with normal ovarian tissues. Statistical analyses were applied to evaluate the clinicopathological significance of SLP-2 expression. SLP-2 mRNA and protein expression levels were significantly up-regulated in epithelial ovarian cancer cell lines and cancer tissues compared with normal ovarian epithelial cells and adjacent noncancerous ovarian tissues. Immunohistochemistry analysis revealed that the relative overexpression of SLP-2 was detected in 73.6 % (103/140) of the epithelial ovarian cancer specimens, 45.0 % (9/20) of the borderline ovarian specimens, 30.0 % (6/20) of the benign ovarian specimens and none of the normal ovarian specimens. SLP-2 protein expression in epithelial ovarian cancer was significantly correlated with the tumour stage (P < 0.001). Epithelial ovarian cancer patients with higher SLP-2 protein expression levels had shorter progress free survival and overall survival times compared to patients with lower SLP-2 protein expression levels. Multivariate analyses showed that SLP-2 expression levels were an independent prognostic

Prediction of kidney survival in children with primary focal segmental glomerulosclerosis (a two-center study.

Directory of Open Access Journals (Sweden)

Alaleh Gheissari

2007-07-01

Full Text Available BACKGROUND: Focal segmental glomerulosclerosis (FSGS is one of the most common glomerulopathies in children leading to end stage renal disease (ESRD. Different values of median renal survival have been reported among different ethnicities and races. Many factors are assumed to be responsible for ESRD in these patients. In this study, we tried to determine median renal survival (MRS and also some clinical and histopathological features predisposing FSGS
patients to ESRD in two referral hospitals in Tehran.
METHODS: The study involved 103 FSGS patients (61 males and 42 females with a mean age of 7.08 ± 0.68 years. The diagnosis was made based on kidney biopsies. All kidney biopsies were studied by light and immunofluorescent microscopes. Ocular grids (counting squares were used as the standard method to calculate the percentage of cortical interstitial fibrosis (CIF. The percentage of glomerular sclerosis was presented as renal injury score. Glomerular filtration rate (GFR950 ml/min was considered as renal death or the end point. Patients were followed for 1 to 15 years, until occurrence of renal death.
RESULTS: The MRS was 9.04 ± 1.8 yrs. The renal survival reached 72%, 47% and 17% after 5, 10 and 15 years, respectively. Univariate analysis showed significant reverse correlation (P<0.05 between renal survival and the following variables: hypertension, anemia, GFR at the time of first admission and also renal injury score >50%, peritubular fibrosis, periglomerular fibrosis, tubular atrophy and CIFC20%. However, multivariate analysis revealed only a reverse correlation between renal survival with CIFC20% and also hypertension (P<0.0001 and P<0.05, respectively.
CONCLUSIONS: In our patients, FSGS showed a rapid course towards ESRD compared with patients of western countries. Perhaps some ethnic and genetic factors such as angiotensin converting enzyme genotypes

Number of Lymph Nodes Removed and Survival after Gastric Cancer Resection: An Analysis from the US Gastric Cancer Collaborative.

Science.gov (United States)

Gholami, Sepideh; Janson, Lucas; Worhunsky, David J; Tran, Thuy B; Squires, Malcolm Hart; Jin, Linda X; Spolverato, Gaya; Votanopoulos, Konstantinos I; Schmidt, Carl; Weber, Sharon M; Bloomston, Mark; Cho, Clifford S; Levine, Edward A; Fields, Ryan C; Pawlik, Timothy M; Maithel, Shishir K; Efron, Bradley; Norton, Jeffrey A; Poultsides, George A

2015-08-01

Examination of at least 16 lymph nodes (LNs) has been traditionally recommended during gastric adenocarcinoma resection to optimize staging, but the impact of this strategy on survival is uncertain. Because recent randomized trials have demonstrated a therapeutic benefit from extended lymphadenectomy, we sought to investigate the impact of the number of LNs removed on prognosis after gastric adenocarcinoma resection. We analyzed patients who underwent gastrectomy for gastric adenocarcinoma from 2000 to 2012, at 7 US academic institutions. Patients with M1 disease or R2 resections were excluded. Disease-specific survival (DSS) was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses. Of 742 patients, 257 (35%) had 7 to 15 LNs removed and 485 (65%) had ≥16 LNs removed. Disease-specific survival was not significantly longer after removal of ≥16 vs 7 to 15 LNs (10-year survival, 55% vs 47%, respectively; p = 0.53) for the entire cohort, but was significantly improved in the subset of patients with stage IA to IIIA (10-year survival, 74% vs 57%, respectively; p = 0.018) or N0-2 disease (72% vs 55%, respectively; p = 0.023). Similarly, for patients who were classified to more likely be "true N0-2," based on frequentist analysis incorporating both the number of positive and of total LNs removed, the hazard ratio for disease-related death (adjusted for T stage, R status, grade, receipt of neoadjuvant and adjuvant therapy, and institution) significantly decreased as the number of LNs removed increased. The number of LNs removed during gastrectomy for adenocarcinoma appears itself to have prognostic implications for long-term survival. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Identification of novel genetic markers of breast cancer survival

DEFF Research Database (Denmark)

Guo, Qi; Schmidt, Marjanka K; Kraft, Peter

2015-01-01

BACKGROUND: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival. METHODS: We conducted a large meta-analysis ......BACKGROUND: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival. METHODS: We conducted a large meta......-analysis of studies in populations of European ancestry, including 37954 patients with 2900 deaths from breast cancer. Each study had been genotyped for between 200000 and 900000 single nucleotide polymorphisms (SNPs) across the genome; genotypes for nine million common variants were imputed using a common reference...... panel from the 1000 Genomes Project. We also carried out subtype-specific analyses based on 6881 estrogen receptor (ER)-negative patients (920 events) and 23059 ER-positive patients (1333 events). All statistical tests were two-sided. RESULTS: We identified one new locus (rs2059614 at 11q24...

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.

Italian regional health system structure and expected cancer survival.

Science.gov (United States)

Vercelli, Marina; Lillini, Roberto; Quaglia, Alberto; Capocaccia, Riccardo

2014-01-01

Few studies deal with the association of socioeconomic and health system resource variables with cancer survival at the Italian regional level, where the greatest number of decisions about social and health policies and resource allocations are taken. The present study aimed to describe the causal relationships between socioeconomic and health system resource factors and regional cancer survival and to compute the expected cancer survival at provincial, regional and area levels. Age-standardized relative survival at 5 years from diagnosis of cases incident in 1995-1998 and followed up to 2004 were derived by gender for 11 sites from the Italian Association of Cancer Registries data bank. The socioeconomic and health system resource variables, describing at a regional level the macro-economy, demography, labor market, and health resources for 1995-2005, came from the Health for All database. A principal components factor analysis was applied to the socioeconomic and health system resource variables. For every site, linear regression models were computed considering the relative survival at 5 years as a dependent variable and the principal components factor analysis factors as independent variables. The factors described the socioeconomic and health-related features of the regional systems and were causally related to the characteristics of the patient taken in charge. The models built by the factors allowed computation of the expected relative survival at 5 years with very good concordance with those observed at regional, macro-regional and national levels. In the regions without any cancer registry, survival was coherent with that of neighboring regions with similar socioeconomic and health system resources characteristics. The models highlighted the causal correlations between socioeconomic and health system resources and cancer survival, suggesting that they could be good evaluation tools for the efficiency of the resources allocation and use.

Assessment of the relationship between ACE I/D gene polymorphism and renal allograft survival.

Science.gov (United States)

Yang, Chun-Hua; Lu, Yi; Chen, Xue-Xia; Xian, Wen-Feng; Tu, Wei-Feng; Li, Hong-Yan

2015-12-01

The relationship between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and renal allograft survival after renal transplantation from the published reports are still debatable. This study was performed to evaluate the relationship between the ACE I/D gene polymorphism and renal allograft survival after renal transplantation using meta-analysis. Eligible studies were identified from PubMed and Cochrane Library on 1 November 2014, and eligible studies were recruited and synthesized using a meta-analysis methodology. Twelve investigations were included in this meta-analysis for the assessment of the relationship between the ACE I/D gene polymorphism and renal allograft survival. In this meta-analysis, the ACE I/D gene polymorphism was not associated with renal allograft survival after renal transplantation for overall populations, Caucasians, Brazilians and Africans. Interestingly, the ACE D allele and DD genotype were associated with renal allograft survival after renal transplantation in the Asian population. ACE D allele and DD genotype were associated with renal allograft survival after renal transplantation in the Asian population. However, more studies should be performed to confirm this association. © The Author(s) 2015.

Comparative analysis reveals that polyploidy does not decelerate diversification in fish.

Science.gov (United States)

Zhan, S H; Glick, L; Tsigenopoulos, C S; Otto, S P; Mayrose, I

2014-02-01

While the proliferation of the species-rich teleost fish has been ascribed to an ancient genome duplication event at the base of this group, the broader impact of polyploidy on fish evolution and diversification remains poorly understood. Here, we investigate the association between polyploidy and diversification in several fish lineages: the sturgeons (Acipenseridae: Acipenseriformes), the botiid loaches (Botiidae: Cypriniformes), Cyprininae fishes (Cyprinidae: Cypriniformes) and the salmonids (Salmonidae: Salmoniformes). Using likelihood-based evolutionary methodologies, we co-estimate speciation and extinction rates associated with polyploid vs. diploid fish lineages. Family-level analysis of Acipenseridae and Botiidae revealed no significant difference in diversification rates between polyploid and diploid relatives, while analysis of the subfamily Cyprininae revealed higher polyploid diversification. Additionally, order-level analysis of the polyploid Salmoniformes and its diploid sister clade, the Esociformes, did not support a significantly different net diversification rate between the two groups. Taken together, our results suggest that polyploidy is generally not associated with decreased diversification in fish - a pattern that stands in contrast to that previously observed in plants. While there are notable differences in the time frame examined in the two studies, our results suggest that polyploidy is associated with different diversification patterns in these two major branches of the eukaryote tree of life. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Analysis of the Indicence and Survival of Female Breast Cancer Patients in Beijing Over a 20-Year Period

Institute of Scientific and Technical Information of China (English)

Qijun Wang; Weixing Zhu; Xiumei Xing; Chenxu Qu

2006-01-01

OBJECTIVE To provide evidence for breast cancer prevention and control through epidemiological analysis of the incidence, mortality and survival rate of female breast cancer patients in Beijing.METHODS The female registration data in the Beijing urban area from 1982 to 2001 were retrospectively reviewed. The incidence, mortality and survival rate of female breast cancer patients were analyzed using routine and life-table statistical methods.RESULTS During the period of 1982 to 2001, there was a trend of an average annual increase of female breast cancer incidence of 4.6% in urban Beijing, and of 4.9% in the world-population standardized incidence.The epidemiological features of urban Beijing female breast cancer showed:(1)The incidence distribution of different age groups from 25 to 80 years elevated with two peaks at ages of 45～ and 70～ years; (2)There was an elevation in each age group over the last 20 years; (3)The incidence rate at ages of 35 to 64 reached 95.3/105, causing breast cancer to become the number one cancer in females. The changes in the survival rate showed the following: the 5-year observed survival rate (OSR)increased from 62.0% in 1982～1983 to 68.7% in 1987～1988, and the relative-survival rate (RSR) increased from 66.3% to 74.2%. The 10-year OSR and RSR in 1987～1988 were 60.3% and 65.1%, and at 15 years 57.5% and 61.3%, respectively. The mortality rate of breast cancer patients fluctuated from 8 to 10 per 105 population over the 20 years of study.CONCLUSION There is a trend of an annual increase in female breast cancer in Beijing. The 5-year survival is being improved gradually while the mortality remains stable. The results demonstrate that the principles of "early prevention, diagnosis and treatment" for breast cancer are effective in Beijing.

Demographic analysis reveals gradual senescence in the flatworm Macrostomum lignano

Directory of Open Access Journals (Sweden)

Braeckman Bart P

2009-07-01

Full Text Available Abstract Free-living flatworms ("Turbellaria" are appropriate model organisms to gain better insight into the role of stem cells in ageing and rejuvenation. Ageing research in flatworms is, however, still scarce. This is partly due to culture difficulties and the lack of a complete set of demographic data, including parameters such as median lifespan and age-specific mortality rate. In this paper, we report on the first flatworm survival analysis. We used the species Macrostomum lignano, which is an emerging model for studying the reciprocal influence between stem cells, ageing and rejuvenation. This species has a median lifespan of 205 ± 13 days (average ± standard deviation [SD] and a 90th percentile lifespan of 373 ± 32 days. The maximum lifespan, however, is more than 745 days, and the average survival curve is characterised by a long tail because a small number of individuals lives twice as long as 90% of the population. Similar to earlier observations in a wide range of animals, in M. lignano the age-specific mortality rate increases exponentially, but levels off at the oldest ages. To compare the senescence of M. lignano with that of other ageing models, we determined the mortality rate doubling time, which is 0.20 ± 0.02 years. As a result, we can conclude that M. lignano shows gradual senescence at a rate similar to the vertebrate ageing models Rattus norvegicus and Mus musculus. We argue that M. lignano is a suitable model for ageing and rejuvenation research, and especially for the role of stem cells in these processes, due to its accessible stem cell system and regeneration capacity, and the possibility of combining stem cell studies with demographic analyses.

Survival of Patients with Oral Cavity Cancer in Germany

Science.gov (United States)

Listl, Stefan; Jansen, Lina; Stenzinger, Albrecht; Freier, Kolja; Emrich, Katharina; Holleczek, Bernd; Katalinic, Alexander; Gondos, Adam; Brenner, Hermann

2013-01-01

The purpose of the present study was to describe the survival of patients diagnosed with oral cavity cancer in Germany. The analyses relied on data from eleven population-based cancer registries in Germany covering a population of 33 million inhabitants. Patients with a diagnosis of oral cavity cancer (ICD-10: C00-06) between 1997 and 2006 are included. Period analysis for 2002–2006 was applied to estimate five-year age-standardized relative survival, taking into account patients' sex as well as grade and tumor stage. Overall five-year relative survival for oral cavity cancer patients was 54.6%. According to tumor localization, five-year survival was 86.5% for lip cancer, 48.1% for tongue cancer and 51.7% for other regions of the oral cavity. Differences in survival were identified with respect to age, sex, tumor grade and stage. The present study is the first to provide a comprehensive overview on survival of oral cavity cancer patients in Germany. PMID:23349710

Analysis of survival in breast cancer patients by using different parametric models

Science.gov (United States)

Enera Amran, Syahila; Asrul Afendi Abdullah, M.; Kek, Sie Long; Afiqah Muhamad Jamil, Siti

2017-09-01

In biomedical applications or clinical trials, right censoring was often arising when studying the time to event data. In this case, some individuals are still alive at the end of the study or lost to follow up at a certain time. It is an important issue to handle the censoring data in order to prevent any bias information in the analysis. Therefore, this study was carried out to analyze the right censoring data with three different parametric models; exponential model, Weibull model and log-logistic models. Data of breast cancer patients from Hospital Sultan Ismail, Johor Bahru from 30 December 2008 until 15 February 2017 was used in this study to illustrate the right censoring data. Besides, the covariates included in this study are the time of breast cancer infection patients survive t, age of each patients X1 and treatment given to the patients X2 . In order to determine the best parametric models in analysing survival of breast cancer patients, the performance of each model was compare based on Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC) and log-likelihood value using statistical software R. When analysing the breast cancer data, all three distributions were shown consistency of data with the line graph of cumulative hazard function resembles a straight line going through the origin. As the result, log-logistic model was the best fitted parametric model compared with exponential and Weibull model since it has the smallest value in AIC and BIC, also the biggest value in log-likelihood.

Survival of Sami cancer patients

Directory of Open Access Journals (Sweden)