Sample records for kaplan-meier curves demonstrated

  1. About an adaptively weighted Kaplan-Meier estimate.

    PubMed

    Plante, Jean-François

    2009-09-01

    The minimum averaged mean squared error nonparametric adaptive weights use data from m possibly different populations to infer about one population of interest. The definition of these weights is based on the properties of the empirical distribution function. We use the Kaplan-Meier estimate to let the weights accommodate right-censored data and use them to define the weighted Kaplan-Meier estimate. The proposed estimate is smoother than the usual Kaplan-Meier estimate and converges uniformly in probability to the target distribution. Simulations show that the performances of the weighted Kaplan-Meier estimate on finite samples exceed that of the usual Kaplan-Meier estimate. A case study is also presented.

  2. The Kaplan-Meier Theatre

    ERIC Educational Resources Information Center

    Gerds, Thomas A.

    2016-01-01

    Survival is difficult to estimate when observation periods of individuals differ in length. Students imagine sailing the Titanic and then recording whether they "live" or "die." A clever algorithm is performed which results in the Kaplan-Meier estimate of survival.

  3. Competing risk bias was common in Kaplan-Meier risk estimates published in prominent medical journals.

    PubMed

    van Walraven, Carl; McAlister, Finlay A

    2016-01-01

    Risk estimates from Kaplan-Meier curves are well known to medical researchers, reviewers, and editors. In this study, we determined the proportion of Kaplan-Meier analyses published in prominent medical journals that are potentially biased because of competing events ("competing risk bias"). We randomly selected 100 studies that had at least one Kaplan-Meier analysis and were recently published in prominent medical journals. Susceptibility to competing risk bias was determined by examining the outcome and potential competing events. In susceptible studies, bias was quantified using a previously validated prediction model when the number of outcomes and competing events were given. Forty-six studies (46%) contained Kaplan-Meier analyses susceptible to competing risk bias. Sixteen studies (34.8%) susceptible to competing risk cited the number of outcomes and competing events; in six of these studies (6/16, 37.5%), the outcome risk from the Kaplan-Meier estimate (relative to the true risk) was biased upward by 10% or more. Almost half of Kaplan-Meier analyses published in medical journals are susceptible to competing risk bias and may overestimate event risk. This bias was found to be quantitatively important in a third of such studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Understanding survival analysis: Kaplan-Meier estimate.

    PubMed

    Goel, Manish Kumar; Khanna, Pardeep; Kishore, Jugal

    2010-10-01

    Kaplan-Meier estimate is one of the best options to be used to measure the fraction of subjects living for a certain amount of time after treatment. In clinical trials or community trials, the effect of an intervention is assessed by measuring the number of subjects survived or saved after that intervention over a period of time. The time starting from a defined point to the occurrence of a given event, for example death is called as survival time and the analysis of group data as survival analysis. This can be affected by subjects under study that are uncooperative and refused to be remained in the study or when some of the subjects may not experience the event or death before the end of the study, although they would have experienced or died if observation continued, or we lose touch with them midway in the study. We label these situations as censored observations. The Kaplan-Meier estimate is the simplest way of computing the survival over time in spite of all these difficulties associated with subjects or situations. The survival curve can be created assuming various situations. It involves computing of probabilities of occurrence of event at a certain point of time and multiplying these successive probabilities by any earlier computed probabilities to get the final estimate. This can be calculated for two groups of subjects and also their statistical difference in the survivals. This can be used in Ayurveda research when they are comparing two drugs and looking for survival of subjects.

  5. Extension of Kaplan-Meier methods in observational studies with time-varying treatment.

    PubMed

    Xu, Stanley; Shetterly, Susan; Powers, David; Raebel, Marsha A; Tsai, Thomas T; Ho, P Michael; Magid, David

    2012-01-01

    Inverse probability of treatment weighted Kaplan-Meier estimates have been developed to compare two treatments in the presence of confounders in observational studies. Recently, stabilized weights were developed to reduce the influence of extreme inverse probability of treatment-weighted weights in estimating treatment effects. The objective of this research was to use adjusted Kaplan-Meier estimates and modified log-rank and Wilcoxon tests to examine the effect of a treatment that varies over time in an observational study. We proposed stabilized weight adjusted Kaplan-Meier estimates and modified log-rank and Wilcoxon tests when the treatment was time-varying over the follow-up period. We applied these new methods in examining the effect of an anti-platelet agent, clopidogrel, on subsequent events, including bleeding, myocardial infarction, and death after a drug-eluting stent was implanted into a coronary artery. In this population, clopidogrel use may change over time based on a patient's behavior (e.g., nonadherence) and physicians' recommendations (e.g., end of duration of therapy). Consequently, clopidogrel use was treated as a time-varying variable. We demonstrate that 1) the sample sizes at three chosen time points are almost identical in the original and weighted datasets; and 2) the covariates between patients on and off clopidogrel were well balanced after stabilized weights were applied to the original samples. The stabilized weight-adjusted Kaplan-Meier estimates and modified log-rank and Wilcoxon tests are useful in presenting and comparing survival functions for time-varying treatments in observational studies while adjusting for known confounders. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  6. A versatile test for equality of two survival functions based on weighted differences of Kaplan-Meier curves.

    PubMed

    Uno, Hajime; Tian, Lu; Claggett, Brian; Wei, L J

    2015-12-10

    With censored event time observations, the logrank test is the most popular tool for testing the equality of two underlying survival distributions. Although this test is asymptotically distribution free, it may not be powerful when the proportional hazards assumption is violated. Various other novel testing procedures have been proposed, which generally are derived by assuming a class of specific alternative hypotheses with respect to the hazard functions. The test considered by Pepe and Fleming (1989) is based on a linear combination of weighted differences of the two Kaplan-Meier curves over time and is a natural tool to assess the difference of two survival functions directly. In this article, we take a similar approach but choose weights that are proportional to the observed standardized difference of the estimated survival curves at each time point. The new proposal automatically makes weighting adjustments empirically. The new test statistic is aimed at a one-sided general alternative hypothesis and is distributed with a short right tail under the null hypothesis but with a heavy tail under the alternative. The results from extensive numerical studies demonstrate that the new procedure performs well under various general alternatives with a caution of a minor inflation of the type I error rate when the sample size is small or the number of observed events is small. The survival data from a recent cancer comparative study are utilized for illustrating the implementation of the process. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Kaplan-Meier survival analysis overestimates cumulative incidence of health-related events in competing risk settings: a meta-analysis.

    PubMed

    Lacny, Sarah; Wilson, Todd; Clement, Fiona; Roberts, Derek J; Faris, Peter; Ghali, William A; Marshall, Deborah A

    2018-01-01

    Kaplan-Meier survival analysis overestimates cumulative incidence in competing risks (CRs) settings. The extent of overestimation (or its clinical significance) has been questioned, and CRs methods are infrequently used. This meta-analysis compares the Kaplan-Meier method to the cumulative incidence function (CIF), a CRs method. We searched MEDLINE, EMBASE, BIOSIS Previews, Web of Science (1992-2016), and article bibliographies for studies estimating cumulative incidence using the Kaplan-Meier method and CIF. For studies with sufficient data, we calculated pooled risk ratios (RRs) comparing Kaplan-Meier and CIF estimates using DerSimonian and Laird random effects models. We performed stratified meta-analyses by clinical area, rate of CRs (CRs/events of interest), and follow-up time. Of 2,192 identified abstracts, we included 77 studies in the systematic review and meta-analyzed 55. The pooled RR demonstrated the Kaplan-Meier estimate was 1.41 [95% confidence interval (CI): 1.36, 1.47] times higher than the CIF. Overestimation was highest among studies with high rates of CRs [RR = 2.36 (95% CI: 1.79, 3.12)], studies related to hepatology [RR = 2.60 (95% CI: 2.12, 3.19)], and obstetrics and gynecology [RR = 1.84 (95% CI: 1.52, 2.23)]. The Kaplan-Meier method overestimated the cumulative incidence across 10 clinical areas. Using CRs methods will ensure accurate results inform clinical and policy decisions. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed

    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.

  9. Kaplan-Meier Survival Analysis Overestimates the Risk of Revision Arthroplasty: A Meta-analysis.

    PubMed

    Lacny, Sarah; Wilson, Todd; Clement, Fiona; Roberts, Derek J; Faris, Peter D; Ghali, William A; Marshall, Deborah A

    2015-11-01

    Although Kaplan-Meier survival analysis is commonly used to estimate the cumulative incidence of revision after joint arthroplasty, it theoretically overestimates the risk of revision in the presence of competing risks (such as death). Because the magnitude of overestimation is not well documented, the potential associated impact on clinical and policy decision-making remains unknown. We performed a meta-analysis to answer the following questions: (1) To what extent does the Kaplan-Meier method overestimate the cumulative incidence of revision after joint replacement compared with alternative competing-risks methods? (2) Is the extent of overestimation influenced by followup time or rate of competing risks? We searched Ovid MEDLINE, EMBASE, BIOSIS Previews, and Web of Science (1946, 1980, 1980, and 1899, respectively, to October 26, 2013) and included article bibliographies for studies comparing estimated cumulative incidence of revision after hip or knee arthroplasty obtained using both Kaplan-Meier and competing-risks methods. We excluded conference abstracts, unpublished studies, or studies using simulated data sets. Two reviewers independently extracted data and evaluated the quality of reporting of the included studies. Among 1160 abstracts identified, six studies were included in our meta-analysis. The principal reason for the steep attrition (1160 to six) was that the initial search was for studies in any clinical area that compared the cumulative incidence estimated using the Kaplan-Meier versus competing-risks methods for any event (not just the cumulative incidence of hip or knee revision); we did this to minimize the likelihood of missing any relevant studies. We calculated risk ratios (RRs) comparing the cumulative incidence estimated using the Kaplan-Meier method with the competing-risks method for each study and used DerSimonian and Laird random effects models to pool these RRs. Heterogeneity was explored using stratified meta-analyses and

  10. A practical divergence measure for survival distributions that can be estimated from Kaplan-Meier curves.

    PubMed

    Cox, Trevor F; Czanner, Gabriela

    2016-06-30

    This paper introduces a new simple divergence measure between two survival distributions. For two groups of patients, the divergence measure between their associated survival distributions is based on the integral of the absolute difference in probabilities that a patient from one group dies at time t and a patient from the other group survives beyond time t and vice versa. In the case of non-crossing hazard functions, the divergence measure is closely linked to the Harrell concordance index, C, the Mann-Whitney test statistic and the area under a receiver operating characteristic curve. The measure can be used in a dynamic way where the divergence between two survival distributions from time zero up to time t is calculated enabling real-time monitoring of treatment differences. The divergence can be found for theoretical survival distributions or can be estimated non-parametrically from survival data using Kaplan-Meier estimates of the survivor functions. The estimator of the divergence is shown to be generally unbiased and approximately normally distributed. For the case of proportional hazards, the constituent parts of the divergence measure can be used to assess the proportional hazards assumption. The use of the divergence measure is illustrated on the survival of pancreatic cancer patients. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  11. HIS-based Kaplan-Meier plots--a single source approach for documenting and reusing routine survival information.

    PubMed

    Breil, Bernhard; Semjonow, Axel; Müller-Tidow, Carsten; Fritz, Fleur; Dugas, Martin

    2011-02-16

    Survival or outcome information is important for clinical routine as well as for clinical research and should be collected completely, timely and precisely. This information is relevant for multiple usages including quality control, clinical trials, observational studies and epidemiological registries. However, the local hospital information system (HIS) does not support this documentation and therefore this data has to generated by paper based or spreadsheet methods which can result in redundantly documented data. Therefore we investigated, whether integrating the follow-up documentation of different departments in the HIS and reusing it for survival analysis can enable the physician to obtain survival curves in a timely manner and to avoid redundant documentation. We analysed the current follow-up process of oncological patients in two departments (urology, haematology) with respect to different documentation forms. We developed a concept for comprehensive survival documentation based on a generic data model and implemented a follow-up form within the HIS of the University Hospital Muenster which is suitable for a secondary use of these data. We designed a query to extract the relevant data from the HIS and implemented Kaplan-Meier plots based on these data. To re-use this data sufficient data quality is needed. We measured completeness of forms with respect to all tumour cases in the clinic and completeness of documented items per form as incomplete information can bias results of the survival analysis. Based on the form analysis we discovered differences and concordances between both departments. We identified 52 attributes from which 13 were common (e.g. procedures and diagnosis dates) and were used for the generic data model. The electronic follow-up form was integrated in the clinical workflow. Survival data was also retrospectively entered in order to perform survival and quality analyses on a comprehensive data set. Physicians are now able to generate

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

    PubMed

    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.

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

    PubMed Central

    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

  14. Factors determining disease duration in Alzheimer's disease: a postmortem study of 103 cases using the Kaplan-Meier estimator and Cox regression.

    PubMed

    Armstrong, R A

    2014-01-01

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

  15. Analysis of censored data.

    PubMed

    Lucijanic, Marko; Petrovecki, Mladen

    2012-01-01

    Analyzing events over time is often complicated by incomplete, or censored, observations. Special non-parametric statistical methods were developed to overcome difficulties in summarizing and comparing censored data. Life-table (actuarial) method and Kaplan-Meier method are described with an explanation of survival curves. For the didactic purpose authors prepared a workbook based on most widely used Kaplan-Meier method. It should help the reader understand how Kaplan-Meier method is conceptualized and how it can be used to obtain statistics and survival curves needed to completely describe a sample of patients. Log-rank test and hazard ratio are also discussed.

  16. Understanding the gendered patterns of substance use initiation among adolescents living in rural, central Mexico

    PubMed Central

    Ayers, Stephanie; Marsiglia, Flavio; Hoffman, Steven; Urbaeva, Zhyldyz

    2012-01-01

    Background Little is known about the age of initiation and gender differences in substance use among adolescents in rural, central Mexico. Methods The cross-sectional data were collected from students enrolled in the Videobachillerato (VIBA) (video high school) program in Guanajuato, Mexico. Questionnaires asked students about the age at which they had used alcohol, cigarettes, or marijuana for the first time. Kaplan-Meier Survival Functions were used to estimate if males and females were significantly different in their cumulative probabilities of initiating substances over time. Results On average, alcohol is initiated at 14.7 years of age, cigarettes at 15.1 years of age, and marijuana at 16.5 years of age. Over time, males had a significantly higher probability of initiating alcohol (Kaplan-Meier Failure Curve: Χ2=26.35, p<0.001), cigarettes (Kaplan-Meier Failure Curve: Χ2=41.90, p<0.001), and marijuana (Kaplan-Meier Failure Curve: Χ2=38.01, p<0.001) compared to females. Conclusions These results highlight the gendered patterns of substance use initiation among adolescents in rural, central Mexico and underscore the need for gendered substance use prevention interventions with these adolescents. By putting forth efforts to understand substance use initiation patterns of adolescents living in rural, central Mexico, culturally specific and efficacious prevention efforts can be tailor-made to create lasting differences. PMID:22421555

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-01-01

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

  19. C-reactive protein-to-albumin ratio is a predictor of hepatitis B virus related decompensated cirrhosis: time-dependent receiver operating characteristics and decision curve analysis.

    PubMed

    Huang, Si-Si; Xie, Dong-Mei; Cai, Yi-Jing; Wu, Jian-Min; Chen, Rui-Chong; Wang, Xiao-Dong; Song, Mei; Zheng, Ming-Hua; Wang, Yu-Qun; Lin, Zhuo; Shi, Ke-Qing

    2017-04-01

    Hepatitis B virus (HBV) infection remains a major health problem and HBV-related-decompensated cirrhosis (HBV-DC) usually leads to a poor prognosis. Our aim was to determine the utility of inflammatory biomarkers in predicting mortality of HBV-DC. A total of 329 HBV-DC patients were enrolled. Survival estimates for the entire study population were generated using the Kaplan-Meier method. The prognostic values for model for end-stage liver disease (MELD) score, Child-Pugh score, and inflammatory biomarkers neutrophil/lymphocyte ratio, C-reactive protein-to-albumin ratio (CAR), and lymphocyte-to-monocyte ratio (LMR) for HBV-DC were compared using time-dependent receiver operating characteristic curves and time-dependent decision curves. The survival time was 23.1±15.8 months. Multivariate analysis identified age, CAR, LMR, and platelet count as prognostic independent risk factors. Kaplan-Meier analysis indicated that CAR of at least 1.0 (hazard ratio, 7.19; 95% confidence interval, 4.69-11.03), and LMR less than 1.9 (hazard ratio, 2.40; 95% confidence interval, 1.69-3.41) were independently associated with mortality of HBV-DC. The time-dependent receiver operating characteristic indicated that CAR showed the best performance in predicting mortality of HBV-DC compared with LMR, MELD score, and Child-Pugh score. The results were also confirmed by time-dependent decision curves. CAR and LMR were associated with the prognosis of HBV-DC. CAR was superior to LMR, MELD score, and Child-Pugh score in HBV-DC mortality prediction.

  20. A review and comparison of methods for recreating individual patient data from published Kaplan-Meier survival curves for economic evaluations: a simulation study.

    PubMed

    Wan, Xiaomin; Peng, Liubao; Li, Yuanjian

    2015-01-01

    In general, the individual patient-level data (IPD) collected in clinical trials are not available to independent researchers to conduct economic evaluations; researchers only have access to published survival curves and summary statistics. Thus, methods that use published survival curves and summary statistics to reproduce statistics for economic evaluations are essential. Four methods have been identified: two traditional methods 1) least squares method, 2) graphical method; and two recently proposed methods by 3) Hoyle and Henley, 4) Guyot et al. The four methods were first individually reviewed and subsequently assessed regarding their abilities to estimate mean survival through a simulation study. A number of different scenarios were developed that comprised combinations of various sample sizes, censoring rates and parametric survival distributions. One thousand simulated survival datasets were generated for each scenario, and all methods were applied to actual IPD. The uncertainty in the estimate of mean survival time was also captured. All methods provided accurate estimates of the mean survival time when the sample size was 500 and a Weibull distribution was used. When the sample size was 100 and the Weibull distribution was used, the Guyot et al. method was almost as accurate as the Hoyle and Henley method; however, more biases were identified in the traditional methods. When a lognormal distribution was used, the Guyot et al. method generated noticeably less bias and a more accurate uncertainty compared with the Hoyle and Henley method. The traditional methods should not be preferred because of their remarkable overestimation. When the Weibull distribution was used for a fitted model, the Guyot et al. method was almost as accurate as the Hoyle and Henley method. However, if the lognormal distribution was used, the Guyot et al. method was less biased compared with the Hoyle and Henley method.

  1. A Review and Comparison of Methods for Recreating Individual Patient Data from Published Kaplan-Meier Survival Curves for Economic Evaluations: A Simulation Study

    PubMed Central

    Wan, Xiaomin; Peng, Liubao; Li, Yuanjian

    2015-01-01

    Background In general, the individual patient-level data (IPD) collected in clinical trials are not available to independent researchers to conduct economic evaluations; researchers only have access to published survival curves and summary statistics. Thus, methods that use published survival curves and summary statistics to reproduce statistics for economic evaluations are essential. Four methods have been identified: two traditional methods 1) least squares method, 2) graphical method; and two recently proposed methods by 3) Hoyle and Henley, 4) Guyot et al. The four methods were first individually reviewed and subsequently assessed regarding their abilities to estimate mean survival through a simulation study. Methods A number of different scenarios were developed that comprised combinations of various sample sizes, censoring rates and parametric survival distributions. One thousand simulated survival datasets were generated for each scenario, and all methods were applied to actual IPD. The uncertainty in the estimate of mean survival time was also captured. Results All methods provided accurate estimates of the mean survival time when the sample size was 500 and a Weibull distribution was used. When the sample size was 100 and the Weibull distribution was used, the Guyot et al. method was almost as accurate as the Hoyle and Henley method; however, more biases were identified in the traditional methods. When a lognormal distribution was used, the Guyot et al. method generated noticeably less bias and a more accurate uncertainty compared with the Hoyle and Henley method. Conclusions The traditional methods should not be preferred because of their remarkable overestimation. When the Weibull distribution was used for a fitted model, the Guyot et al. method was almost as accurate as the Hoyle and Henley method. However, if the lognormal distribution was used, the Guyot et al. method was less biased compared with the Hoyle and Henley method. PMID:25803659

  2. Kaplan-Meier Meets Chemical Kinetics: Intrinsic Rate of SOD1 Amyloidogenesis Decreased by Subset of ALS Mutations and Cannot Fully Explain Age of Disease Onset.

    PubMed

    Abdolvahabi, Alireza; Shi, Yunhua; Rasouli, Sanaz; Croom, Corbin M; Aliyan, Amir; Martí, Angel A; Shaw, Bryan F

    2017-06-21

    Over 150 mutations in SOD1 (superoxide dismutase-1) cause amyotrophic lateral sclerosis (ALS), presumably by accelerating SOD1 amyloidogenesis. Like many nucleation processes, SOD1 fibrillization is stochastic (in vitro), which inhibits the determination of aggregation rates (and obscures whether rates correlate with patient phenotypes). Here, we diverged from classical chemical kinetics and used Kaplan-Meier estimators to quantify the probability of apo-SOD1 fibrillization (in vitro) from ∼10 3 replicate amyloid assays of wild-type (WT) SOD1 and nine ALS variants. The probability of apo-SOD1 fibrillization (expressed as a Hazard ratio) is increased by certain ALS-linked SOD1 mutations but is decreased or remains unchanged by other mutations. Despite this diversity, Hazard ratios of fibrillization correlated linearly with (and for three mutants, approximately equaled) Hazard ratios of patient survival (R 2 = 0.67; Pearson's r = 0.82). No correlation exists between Hazard ratios of fibrillization and age of initial onset of ALS (R 2 = 0.09). Thus, Hazard ratios of fibrillization might explain rates of disease progression but not onset. Classical kinetic metrics of fibrillization, i.e., mean lag time and propagation rate, did not correlate as strongly with phenotype (and ALS mutations did not uniformly accelerate mean rate of nucleation or propagation). A strong correlation was found, however, between mean ThT fluorescence at lag time and patient survival (R 2 = 0.93); oligomers of SOD1 with weaker fluorescence correlated with shorter survival. This study suggests that SOD1 mutations trigger ALS by altering a property of SOD1 or its oligomers other than the intrinsic rate of amyloid nucleation (e.g., oligomer stability; rates of intercellular propagation; affinity for membrane surfaces; and maturation rate).

  3. Applying Kaplan-Meier to Item Response Data

    ERIC Educational Resources Information Center

    McNeish, Daniel

    2018-01-01

    Some IRT models can be equivalently modeled in alternative frameworks such as logistic regression. Logistic regression can also model time-to-event data, which concerns the probability of an event occurring over time. Using the relation between time-to-event models and logistic regression and the relation between logistic regression and IRT, this…

  4. Genetics Home Reference: Meier-Gorlin syndrome

    MedlinePlus

    ... ORC1, encoding the largest subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin ... M, Skidmore DL, Samuels ME. Mutations in origin recognition complex gene ORC4 cause Meier-Gorlin syndrome. Nat ...

  5. Acetabular revision with impaction bone grafting and a cemented polyethylene acetabular component: comparison of the Kaplan-Meier analysis to the competing risk analysis in 62 revisions with 25 to 30 years follow-up.

    PubMed

    Te Stroet, M A J; Keurentjes, J C; Rijnen, W H C; Gardeniers, J W M; Verdonschot, N; Slooff, T J J H; Schreurs, B W

    2015-10-01

    We present the results of 62 consecutive acetabular revisions using impaction bone grafting and a cemented polyethylene acetabular component in 58 patients (13 men and 45 women) after a mean follow-up of 27 years (25 to 30). All patients were prospectively followed. The mean age at revision was 59.2 years (23 to 82). We performed Kaplan-Meier (KM) analysis and also a Competing Risk (CR) analysis because with long-term follow-up, the presence of a competing event (i.e. death) prevents the occurrence of the endpoint of re-revision. A total of 48 patients (52 hips) had died or had been re-revised at final review in March 2011. None of the deaths were related to the surgery. The mean Harris hip score of the ten surviving hips in ten patients was 76 points (45 to 99). The KM survivorship at 25 years for the endpoint 're-revision for any reason' was 58.0% (95% confidence interval (CI) 38 to 73) and for 're-revision for aseptic loosening' 72.1% (95% CI 51 to 85). With the CR analysis we calculated the KM analysis overestimates the failure rate with respectively 74% and 93% for these endpoints. The current study shows that acetabular impaction bone grafting revisions provide good clinical results at over 25 years. ©2015 The British Editorial Society of Bone & Joint Surgery.

  6. Analyzing survival curves at a fixed point in time for paired and clustered right-censored data

    PubMed Central

    Su, Pei-Fang; Chi, Yunchan; Lee, Chun-Yi; Shyr, Yu; Liao, Yi-De

    2018-01-01

    In clinical trials, information about certain time points may be of interest in making decisions about treatment effectiveness. Rather than comparing entire survival curves, researchers can focus on the comparison at fixed time points that may have a clinical utility for patients. For two independent samples of right-censored data, Klein et al. (2007) compared survival probabilities at a fixed time point by studying a number of tests based on some transformations of the Kaplan-Meier estimators of the survival function. However, to compare the survival probabilities at a fixed time point for paired right-censored data or clustered right-censored data, their approach would need to be modified. In this paper, we extend the statistics to accommodate the possible within-paired correlation and within-clustered correlation, respectively. We use simulation studies to present comparative results. Finally, we illustrate the implementation of these methods using two real data sets. PMID:29456280

  7. Edith Kaplan (1924-2009).

    PubMed

    Delis, Dean C

    2010-01-01

    This article honors the life accomplishments of Edith Kaplan. She is widely regarded as the mother of clinical neuropsychology; she passed away on September 3, 2009, at the age of 85. Her modifications to the original Wechsler Adult Intelligence Scale (WAIS) and Wechsler Memory Scale led to the development of a new school of clinical neuropsychology known as "the process approach," of which Kaplan is unequivocally regarded as the pioneer and chief architect. She is best known for her work in test development, and she is the lead or senior author on numerous assessment instruments designed for both children and adults that are used nationally and internationally. At the time of her death, Kaplan was working as a professor of psychology at Suffolk University, an adjunct professor of neurology and psychiatry at Boston University School of Medicine, and an affiliate professor of psychology at Clark University. And, of great importance to the field, she continued to be vigorously involved in her most beloved activity of all, teaching students about neuropsychology. 2009 APA, all rights reserved.

  8. On representing the prognostic value of continuous gene expression biomarkers with the restricted mean survival curve.

    PubMed

    Eng, Kevin H; Schiller, Emily; Morrell, Kayla

    2015-11-03

    Researchers developing biomarkers for cancer prognosis from quantitative gene expression data are often faced with an odd methodological discrepancy: while Cox's proportional hazards model, the appropriate and popular technique, produces a continuous and relative risk score, it is hard to cast the estimate in clear clinical terms like median months of survival and percent of patients affected. To produce a familiar Kaplan-Meier plot, researchers commonly make the decision to dichotomize a continuous (often unimodal and symmetric) score. It is well known in the statistical literature that this procedure induces significant bias. We illustrate the liabilities of common techniques for categorizing a risk score and discuss alternative approaches. We promote the use of the restricted mean survival (RMS) and the corresponding RMS curve that may be thought of as an analog to the best fit line from simple linear regression. Continuous biomarker workflows should be modified to include the more rigorous statistical techniques and descriptive plots described in this article. All statistics discussed can be computed via standard functions in the Survival package of the R statistical programming language. Example R language code for the RMS curve is presented in the appendix.

  9. A Response to Deborah Meier.

    ERIC Educational Resources Information Center

    Sarason, Seymour

    1998-01-01

    Meier is no bleeding-heart liberal who oversimplifies difficulties involved in creating classrooms and schools reflective of productive learning contexts. Larger system of school governance is inimical to creating such contexts. In his book "How Schools Might Be Governed and Why" (Teacher's College Press, 1997), author argues that the…

  10. The learning curve associated with the introduction of the subcutaneous implantable defibrillator.

    PubMed

    Knops, Reinoud E; Brouwer, Tom F; Barr, Craig S; Theuns, Dominic A; Boersma, Lucas; Weiss, Raul; Neuzil, Petr; Scholten, Marcoen; Lambiase, Pier D; Leon, Angel R; Hood, Margaret; Jones, Paul W; Wold, Nicholas; Grace, Andrew A; Olde Nordkamp, Louise R A; Burke, Martin C

    2016-07-01

    The subcutaneous implantable cardioverter defibrillator (S-ICD) was introduced to overcome complications related to transvenous leads. Adoption of the S-ICD requires implanters to learn a new implantation technique. The aim of this study was to assess the learning curve for S-ICD implanters with respect to implant-related complications, procedure time, and inappropriate shocks (IASs). In a pooled cohort from two clinical S-ICD databases, the IDE Trial and the EFFORTLESS Registry, complications, IASs at 180 days follow-up and implant procedure duration were assessed. Patients were grouped in quartiles based on experience of the implanter and Kaplan-Meier estimates of complication and IAS rates were calculated. A total of 882 patients implanted in 61 centres by 107 implanters with a median of 4 implants (IQR 1,8) were analysed. There were a total of 59 patients with complications and 48 patients with IAS. The complication rate decreased significantly from 9.8% in Quartile 1 (least experience) to 5.4% in Quartile 4 (most experience) (P = 0.02) and non-significantly for IAS from 7.9 to 4.8% (P = 0.10). Multivariable analysis demonstrated a hazard ratio of 0.78 (P = 0.045) for complications and 1.01 (P = 0.958) for IAS. Dual-zone programming increased with experience of the individual implanter (P < 0.001), which reduced IAS significantly in the multivariable model (HR 0.44, P = 0.01). Procedure time decreased from 75 to 65 min (P < 0.001). The complication rate and procedure time stabilized after Quartile 2 (>13 implants). There is a short and significant learning curve associated with physicians adopting the S-ICD. Performance stabilizes after 13 implants. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

  11. Survival analysis in telemetry studies: The staggered entry design

    USGS Publications Warehouse

    Pollock, K.H.; Winterstein, S.R.; Bunck, C.M.; Curtis, P.D.

    1989-01-01

    A simple description of the Kaplan-Meier procedure is presented with an example using northern bobwhite quail survival data. The Kaplan- Meier procedure was then generalized to allow gradual (or staggered) entry of animals into the study, allowing animals being lost (or censored) due to radio failure, radio loss, or emigration of the animal from the study area. Additionally, the applicability and generalization of the log rank test, a test to compare two survival distributions, was demonstrated. Computer program was developed and is available from authors.

  12. Robustness of survival estimates from radio-telemetry studies with uncertain relocation of individuals

    USGS Publications Warehouse

    Bunck, C.M.; Chen, C.-L.; Pollock, K.H.

    1995-01-01

    Traditional methods of estimating survival from radio-telemetry studies use either the Trent-Rongstad approach (Trent and Rongstad 1974, Heisey and Fuller 1985) or the Kaplan-Meier approach (Kaplan and Meier 1958; Pollock et al. 1989a,b). Both methods appear to require the assumption that relocation probability for animals with a functioning radio is 1. In practice this may not always be reasonable and, in fact, is unnecessary. The number of animals at risk (i.e., risk set) can be modified to account for uncertain relocation of individuals. This involves including only relocated animals in the risk set instead of also including animals not relocated but that were seen later. Simulation results show that estimators and tests for comparing survival curves should be based on this modification.

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

    PubMed

    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.

  14. An original approach was used to better evaluate the capacity of a prognostic marker using published survival curves.

    PubMed

    Dantan, Etienne; Combescure, Christophe; Lorent, Marine; Ashton-Chess, Joanna; Daguin, Pascal; Classe, Jean-Marc; Giral, Magali; Foucher, Yohann

    2014-04-01

    Predicting chronic disease evolution from a prognostic marker is a key field of research in clinical epidemiology. However, the prognostic capacity of a marker is not systematically evaluated using the appropriate methodology. We proposed the use of simple equations to calculate time-dependent sensitivity and specificity based on published survival curves and other time-dependent indicators as predictive values, likelihood ratios, and posttest probability ratios to reappraise prognostic marker accuracy. The methodology is illustrated by back calculating time-dependent indicators from published articles presenting a marker as highly correlated with the time to event, concluding on the high prognostic capacity of the marker, and presenting the Kaplan-Meier survival curves. The tools necessary to run these direct and simple computations are available online at http://www.divat.fr/en/online-calculators/evalbiom. Our examples illustrate that published conclusions about prognostic marker accuracy may be overoptimistic, thus giving potential for major mistakes in therapeutic decisions. Our approach should help readers better evaluate clinical articles reporting on prognostic markers. Time-dependent sensitivity and specificity inform on the inherent prognostic capacity of a marker for a defined prognostic time. Time-dependent predictive values, likelihood ratios, and posttest probability ratios may additionally contribute to interpret the marker's prognostic capacity. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Kaplan SpellRead. What Works Clearinghouse Intervention Report

    ERIC Educational Resources Information Center

    What Works Clearinghouse, 2007

    2007-01-01

    "Kaplan SpellRead" (formerly known as "SpellRead Phonological Auditory Training"[R]) is a literacy program for struggling readers in grades 2 or above, including special education students, English language learners, and students more than two years below grade level in reading. "Kaplan SpellRead" integrates the…

  16. Metabolic acidosis status and mortality in patients on the end stage of renal disease.

    PubMed

    Raikou, Vaia D

    2016-12-01

    Uncorrected metabolic acidosis leads to higher death risk in dialysis patients. We observed the relationship between metabolic acidosis status and mortality rate in patients on renal replacement therapy during a median follow up time of 60 months. We studied 76 patients on an on-line hemodiafiltration. The dialysis adequacy was defined by Kt/V for urea. The Framingham risk score (FRS) points were used to determine the 10-year risk for coronary heart disease. We examined the impact of high or low serum bicarbonate concentrations on mortality rate and on 10-year risk for coronary heart disease via the Kaplan-Meier method. Cox's model was used to evaluate a combination of prognostic variables, such as dialysis adequacy defined by Kt/V for urea, age and serum bicarbonate concentrations. We divided the enrolled patients in three groups according to serum bicarbonate concentrations (< 20 mmol/L, 20-22 mmol/L and > 22 mmol/L). Kaplan-Meier survival curve for the impact of serum bicarbonate concentrations on overall mortality was found significant (log-rank = 7.8, P = 0.02). The prevalence of serum bicarbonate less or more than 20 mmol/L on high FRS (> 20%) by Kaplan-Meier curve was also found significant (log-rank = 4.9, P = 0.02). Cox's model revealed the significant predictive effect of serum bicarbonate on overall mortality ( P = 0.006, OR = 1.5, 95% CI = 1.12-1.98) in combination to Kt/V for urea and age. Uncorrected severe metabolic acidosis, defined by serum bicarbonate concentrations less than 20 mmol/L, is associated with a 10-year risk for coronary heart disease more than 20% and high overall mortality in patients on renal replacement therapy.

  17. A gap analysis approach to assess patient persistence with glaucoma medication.

    PubMed

    Lee, Paul P; Walt, John G; Chiang, Tina H; Guckian, Angela; Keener, John

    2007-10-01

    To develop an alternative method for analysis of patient persistence with prescribed medications using the prostaglandin class of intraocular pressure (IOP)-lowering drugs as a model. A retrospective study of prescription refill patterns. Patients with a pharmacy claim for a 2.5 ml bottle of latanoprost, travoprost, or bimatoprost between September 1, 2002 and December 31, 2002 were identified from a retail pharmacy database and were followed up for 12 months. Three separate analyses defined gaps in therapy as spans in excess of 45, 60, or 120 days without a refill for the same medication. Patients were categorized by the number of gaps in therapy and the cumulative length of gaps. A Kaplan-Meier analysis was conducted using a 120-day allowable refill period. For refill periods of 45, 60, and 120 days, 10.6%, 28.6%, and 77.5% of patients, respectively, had no gaps in therapy, and 32.6%, 53.4%, and 86.5%, respectively, had 30 days or fewer off therapy annually. According to the 45-day threshold analysis, 50.7% of patients had three or more gaps vs 18.5% in the 60-day analysis and none in the 120-day analysis. The Kaplan-Meier curve shows 88.6% and 76.1% of patients were persistent for 120 days and one year, respectively. Compared with Kaplan-Meier survival curves, the gap analysis approach may better parallel clinical experience with patient persistence, in which patients stop and restart medications for a variety of reasons over time. This method also may help to identify avenues for investigation of lack of persistency among many patients.

  18. The Delis-Kaplan Executive Function System: A Review

    ERIC Educational Resources Information Center

    Swanson, Jewel

    2005-01-01

    The Delis-Kaplan Executive Function System (D-KEFS; Delis, Kaplan, & Kramer, 2001a) is a set of standardized tests for comprehensively assessing higher-level cognitive functions, referred to as "executive functions," in both children and adults (aged 8 to 89). Executive functions draw on the individual's more fundamental or primary cognitive…

  19. Challenges in risk estimation using routinely collected clinical data: The example of estimating cervical cancer risks from electronic health-records.

    PubMed

    Landy, Rebecca; Cheung, Li C; Schiffman, Mark; Gage, Julia C; Hyun, Noorie; Wentzensen, Nicolas; Kinney, Walter K; Castle, Philip E; Fetterman, Barbara; Poitras, Nancy E; Lorey, Thomas; Sasieni, Peter D; Katki, Hormuzd A

    2018-06-01

    Electronic health-records (EHR) are increasingly used by epidemiologists studying disease following surveillance testing to provide evidence for screening intervals and referral guidelines. Although cost-effective, undiagnosed prevalent disease and interval censoring (in which asymptomatic disease is only observed at the time of testing) raise substantial analytic issues when estimating risk that cannot be addressed using Kaplan-Meier methods. Based on our experience analysing EHR from cervical cancer screening, we previously proposed the logistic-Weibull model to address these issues. Here we demonstrate how the choice of statistical method can impact risk estimates. We use observed data on 41,067 women in the cervical cancer screening program at Kaiser Permanente Northern California, 2003-2013, as well as simulations to evaluate the ability of different methods (Kaplan-Meier, Turnbull, Weibull and logistic-Weibull) to accurately estimate risk within a screening program. Cumulative risk estimates from the statistical methods varied considerably, with the largest differences occurring for prevalent disease risk when baseline disease ascertainment was random but incomplete. Kaplan-Meier underestimated risk at earlier times and overestimated risk at later times in the presence of interval censoring or undiagnosed prevalent disease. Turnbull performed well, though was inefficient and not smooth. The logistic-Weibull model performed well, except when event times didn't follow a Weibull distribution. We have demonstrated that methods for right-censored data, such as Kaplan-Meier, result in biased estimates of disease risks when applied to interval-censored data, such as screening programs using EHR data. The logistic-Weibull model is attractive, but the model fit must be checked against Turnbull non-parametric risk estimates. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Interview with Danny Kaplan

    ERIC Educational Resources Information Center

    Rossman, Allan; Kaplan, Danny

    2017-01-01

    Danny Kaplan is DeWitt Wallace Professor of Mathematics and Computer Science at Macalester College. He received Macalester's Excellence in teaching Award in 2006 and the CAUSE/USCOTS Lifetime Achievement Award in 2017. This interview took place via email on March 4-June 17, 2017. Topics covered in the interview include: (1) the current state of…

  1. Survival curve estimation with dependent left truncated data using Cox's model.

    PubMed

    Mackenzie, Todd

    2012-10-19

    The Kaplan-Meier and closely related Lynden-Bell estimators are used to provide nonparametric estimation of the distribution of a left-truncated random variable. These estimators assume that the left-truncation variable is independent of the time-to-event. This paper proposes a semiparametric method for estimating the marginal distribution of the time-to-event that does not require independence. It models the conditional distribution of the time-to-event given the truncation variable using Cox's model for left truncated data, and uses inverse probability weighting. We report the results of simulations and illustrate the method using a survival study.

  2. Design of a Kaplan turbine for a wide range of operating head -Curved draft tube design and model test verification-

    NASA Astrophysics Data System (ADS)

    KO, Pohan; MATSUMOTO, Kiyoshi; OHTAKE, Norio; DING, Hua

    2016-11-01

    As for turbomachine off-design performance improvement is challenging but critical for maximising the performing area. In this paper, a curved draft tube for a medium head Kaplan type hydro turbine is introduced and discussed for its significant effect on expanding operating head range. Without adding any extra structure and working fluid for swirl destruction and damping, a carefully designed outline shape of draft tube with the selected placement of center-piers successfully supresses the growth of turbulence eddy and the transport of the swirl to the outlet. Also, more kinetic energy is recovered and the head lost is improved. Finally, the model test results are also presented. The obvious performance improvement was found in the lower net head area, where the maximum efficiency improvement was measured up to 20% without compromising the best efficiency point. Additionally, this design results in a new draft tube more compact in size and so leads to better construction and manufacturing cost performance for prototype. The draft tube geometry parameter designing process was concerning the best efficiency point together with the off-design points covering various water net heads and discharges. The hydraulic performance and flow behavior was numerically previewed and visualized by solving Reynolds-Averaged Navier-Stokes equations with Shear Stress Transport turbulence model. The simulation was under the assumption of steady-state incompressible turbulence flow inside the flow passage, and the inlet boundary condition was the carefully simulated flow pattern from the runner outlet. For confirmation, the corresponding turbine efficiency performance of the entire operating area was verified by model test.

  3. Predicting long-term graft survival in adult kidney transplant recipients.

    PubMed

    Pinsky, Brett W; Lentine, Krista L; Ercole, Patrick R; Salvalaggio, Paolo R; Burroughs, Thomas E; Schnitzler, Mark A

    2012-07-01

    The ability to accurately predict a population's long-term survival has important implications for quantifying the benefits of transplantation. To identify a model that can accurately predict a kidney transplant population's long-term graft survival, we retrospectively studied the United Network of Organ Sharing data from 13,111 kidney-only transplants completed in 1988- 1989. Nineteen-year death-censored graft survival (DCGS) projections were calculated and compared with the population's actual graft survival. The projection curves were created using a two-part estimation model that (1) fits a Kaplan-Meier survival curve immediately after transplant (Part A) and (2) uses truncated observational data to model a survival function for long-term projection (Part B). Projection curves were examined using varying amounts of time to fit both parts of the model. The accuracy of the projection curve was determined by examining whether predicted survival fell within the 95% confidence interval for the 19-year Kaplan-Meier survival, and the sample size needed to detect the difference in projected versus observed survival in a clinical trial. The 19-year DCGS was 40.7% (39.8-41.6%). Excellent predictability (41.3%) can be achieved when Part A is fit for three years and Part B is projected using two additional years of data. Using less than five total years of data tended to overestimate the population's long-term survival, accurate prediction of long-term DCGS is possible, but requires attention to the quantity data used in the projection method.

  4. Public injury prevention system in the Italian manufacturing sector: What types of inspection are more effective?

    PubMed

    Farina, Elena; Bena, Antonella; Fedeli, Ugo; Mastrangelo, Giuseppe; Veronese, Michela; Agnesi, Roberto

    2016-04-01

    Literature suggests that more research is needed to clarify the effect of workplace inspections by governmental officers on injury rates. This paper aims to compare comprehensive and partial inspections in Italian manufacturing companies. Survival analysis was applied to the period free from injuries following inspection by means of the Kaplan-Meier method and of Cox models. Kaplan-Meier curves show that, compared to companies with a partial inspection, companies which had a comprehensive inspection had a higher survival through the entire period. Adjusting for confounders, the Cox model confirms a significant preventive effect of comprehensive inspection for companies with 10-30 employees, but not for those with >30 employees. The results suggest that the effect on injuries is greater if all aspects of safety are addressed during the inspection instead of focusing on a single aspect. These findings are interesting because they can help in planning effective prevention activities. © 2016 Wiley Periodicals, Inc.

  5. Hyperfibrinogenemia is a poor prognostic factor in diffuse large B cell lymphoma.

    PubMed

    Niu, Jun-Ying; Tian, Tian; Zhu, Hua-Yuan; Liang, Jin-Hua; Wu, Wei; Cao, Lei; Lu, Rui-Nan; Wang, Li; Li, Jian-Yong; Xu, Wei

    2018-06-02

    Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphomas worldwide. Previous studies indicated that hyperfibrinogenemia was a poor predictor in various tumors. The purpose of our study was to evaluate the prognostic effect of hyperfibrinogenemia in DLBCL. Data of 228 patients, who were diagnosed with DLBCL in our hospital between May 2009 and February 2016, were analyzed retrospectively. The Kaplan-Meier method and Cox regression were performed to find prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Receiver operator characteristic (ROC) curve and the areas under the curve were used to evaluate the predictive accuracy of predictors. Comparison of characters between groups indicated that patients with high National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score (4-8) and advanced stage (III-IV) were more likely to suffer from hyperfibrinogenemia. The Kaplan-Meier method revealed that patients with hyperfibrinogenemia showed inferior PFS (P < 0.001) and OS (P < 0.001) than those without hyperfibrinogenemia. Multivariate analysis showed that hyperfibrinogenemia was an independent prognostic factor associated with poor outcomes (HR = 1.90, 95% CI: 1.15-3.16 for PFS, P = 0.013; HR = 2.65, 95% CI: 1.46-4.79 for OS, P = 0.001). We combined hyperfibrinogenemia and NCCN-IPI to build a new prognostic index (NPI). The NPI was demonstrated to have a superior predictive effect on prognosis (P = 0.0194 for PFS, P = 0.0034 for OS). Hyperfibrinogenemia was demonstrated to be able to predict poor outcome in DLBCL, especially for patients with advanced stage and high NCCN-IPI score. Adding hyperfibrinogenemia to NCCN-IPI could significantly improve the predictive effect of NCCN-IPI.

  6. Prognostic value of MLH1 promoter methylation in male patients with esophageal squamous cell carcinoma.

    PubMed

    Wu, Dongping; Chen, Xiaoying; Xu, Yan; Wang, Haiyong; Yu, Guangmao; Jiang, Luping; Hong, Qingxiao; Duan, Shiwei

    2017-04-01

    The DNA mismatch repair (MMR) gene MutL homolog 1 ( MLH1 ) is critical for the maintenance of genomic integrity. Methylation of the MLH1 gene promoter was identified as a prognostic marker for numerous types of cancer including glioblastoma, colorectal, ovarian and gastric cancer. The present study aimed to determine whether MLH1 promoter methylation was associated with survival in male patients with esophageal squamous cell carcinoma (ESCC). Formalin-fixed, paraffin-embedded ESCC tissues were collected from 87 male patients. MLH1 promoter methylation was assessed using the methylation-specific polymerase chain reaction approach. Kaplan-Meier survival curves and log-rank tests were used to evaluate the association between MLH1 promoter methylation and overall survival (OS) in patients with ESCC. Cox regression analysis was used to obtain crude and multivariate hazard ratios (HR), and 95% confidence intervals (CI). The present study revealed that MLH1 promoter methylation was observed in 53/87 (60.9%) of male patients with ESCC. Kaplan-Meier survival analysis demonstrated that MLH1 promoter hypermethylation was significantly associated with poorer prognosis in patients with ESCC (P=0.048). Multivariate survival analysis revealed that MLH1 promoter hypermethylation was an independent predictor of poor OS in male patients with ESCC (HR=1.716; 95% CI=1.008-2.921). Therefore, MLH1 promoter hypermethylation may be a predictor of prognosis in male patients with ESCC.

  7. Curved sensors for compact high-resolution wide-field designs: prototype demonstration and optical characterization

    NASA Astrophysics Data System (ADS)

    Chambion, Bertrand; Gaschet, Christophe; Behaghel, Thibault; Vandeneynde, Aurélie; Caplet, Stéphane; Gétin, Stéphane; Henry, David; Hugot, Emmanuel; Jahn, Wilfried; Lombardo, Simona; Ferrari, Marc

    2018-02-01

    Over the recent years, a huge interest has grown for curved electronics, particularly for opto-electronics systems. Curved sensors help the correction of off-axis aberrations, such as Petzval Field Curvature, astigmatism, and bring significant optical and size benefits for imaging systems. In this paper, we first describe advantages of curved sensor and associated packaging process applied on a 1/1.8'' format 1.3Mpx global shutter CMOS sensor (Teledyne EV76C560) into its standard ceramic package with a spherical radius of curvature Rc=65mm and 55mm. The mechanical limits of the die are discussed (Finite Element Modelling and experimental), and electro-optical performances are investigated. Then, based on the monocentric optical architecture, we proposed a new design, compact and with a high resolution, developed specifically for a curved image sensor including optical optimization, tolerances, assembly and optical tests. Finally, a functional prototype is presented through a benchmark approach and compared to an existing standard optical system with same performances and a x2.5 reduction of length. The finality of this work was a functional prototype demonstration on the CEA-LETI during Photonics West 2018 conference. All these experiments and optical results demonstrate the feasibility and high performances of systems with curved sensors.

  8. Racial Differences in the Overall Survival of Hairy Cell Leukemia in the United States: A Population-Based Analysis of the Surveillance, Epidemiology, and End Results Database.

    PubMed

    Giri, Smith; Shrestha, Rajesh; Pathak, Ranjan; Bhatt, Vijaya Raj

    2015-08-01

    Several studies have reported excellent long-term overall survival (OS) of patients with hairy cell leukemia (HCL) without racial disparity. Studies in other cancers have demonstrated worse mortality among African American (AA) individuals. We used the Surveillance, Epidemiology, and End Results 18 database to identify HCL patients diagnosed between 1978 and 2011. Kaplan-Meier curves were plotted to estimate OS. Univariate analysis using the life table method and multivariate Cox regression model were used to determine the independent effect of race on OS. The study population included 78% men and had a median age of 56 years. Race included 93% white, 3.5% Asian/Pacific Islander, and 3.5% AA. The 10-year OS was significantly less for AA as compared with white and Asian/Pacific Islander individuals (54% vs. 72% vs. 75%; P < .001). A Kaplan-Meier survival curve showed a significantly worse OS for AA versus other races (P < .001). In a multivariate analysis, AA race remained an independent predictor for a worse OS (hazard ratio 1.77; 95% confidence interval, 1.30-2.40; P < .001) after adjusting for age, sex, year of diagnosis, and marital status. In this population-based study, only half of AA patients but more than two-thirds of HCL patients from other racial groups were alive at 10 years. Such drastic racial differences in OS of HCL patients at the population level mandates further evaluation of the contributory biological, socioeconomic, health system, and other factors. Understanding and overcoming such racial disparities might close the racial differences in OS of this potentially curable disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Serum Irisin Predicts Mortality Risk in Acute Heart Failure Patients.

    PubMed

    Shen, Shutong; Gao, Rongrong; Bei, Yihua; Li, Jin; Zhang, Haifeng; Zhou, Yanli; Yao, Wenming; Xu, Dongjie; Zhou, Fang; Jin, Mengchao; Wei, Siqi; Wang, Kai; Xu, Xuejuan; Li, Yongqin; Xiao, Junjie; Li, Xinli

    2017-01-01

    Irisin is a peptide hormone cleaved from a plasma membrane protein fibronectin type III domain containing protein 5 (FNDC5). Emerging studies have indicated association between serum irisin and many major chronic diseases including cardiovascular diseases. However, the role of serum irisin as a predictor for mortality risk in acute heart failure (AHF) patients is not clear. AHF patients were enrolled and serum was collected at the admission and all patients were followed up for 1 year. Enzyme-linked immunosorbent assay was used to measure serum irisin levels. To explore predictors for AHF mortality, the univariate and multivariate logistic regression analysis, and receiver-operator characteristic (ROC) curve analysis were used. To determine the role of serum irisin levels in predicting survival, Kaplan-Meier survival analysis was used. In this study, 161 AHF patients were enrolled and serum irisin level was found to be significantly higher in patients deceased in 1-year follow-up. The univariate logistic regression analysis identified 18 variables associated with all-cause mortality in AHF patients, while the multivariate logistic regression analysis identified 2 variables namely blood urea nitrogen and serum irisin. ROC curve analysis indicated that blood urea nitrogen and the most commonly used biomarker, NT-pro-BNP, displayed poor prognostic value for AHF (AUCs ≤ 0.700) compared to serum irisin (AUC = 0.753). Kaplan-Meier survival analysis demonstrated that AHF patients with higher serum irisin had significantly higher mortality (P<0.001). Collectively, our study identified serum irisin as a predictive biomarker for 1-year all-cause mortality in AHF patients though large multicenter studies are highly needed. © 2017 The Author(s). Published by S. Karger AG, Basel.

  10. Comparison of numerical and experimental results of the flow in the U9 Kaplan turbine model

    NASA Astrophysics Data System (ADS)

    Petit, O.; Mulu, B.; Nilsson, H.; Cervantes, M.

    2010-08-01

    The present work compares simulations made using the OpenFOAM CFD code with experimental measurements of the flow in the U9 Kaplan turbine model. Comparisons of the velocity profiles in the spiral casing and in the draft tube are presented. The U9 Kaplan turbine prototype located in Porjus and its model, located in Älvkarleby, Sweden, have curved inlet pipes that lead the flow to the spiral casing. Nowadays, this curved pipe and its effect on the flow in the turbine is not taken into account when numerical simulations are performed at design stage. To study the impact of the inlet pipe curvature on the flow in the turbine, and to get a better overview of the flow of the whole system, measurements were made on the 1:3.1 model of the U9 turbine. Previously published measurements were taken at the inlet of the spiral casing and just before the guide vanes, using the laser Doppler anemometry (LDA) technique. In the draft tube, a number of velocity profiles were measured using the LDA techniques. The present work extends the experimental investigation with a horizontal section at the inlet of the draft tube. The experimental results are used to specify the inlet boundary condition for the numerical simulations in the draft tube, and to validate the computational results in both the spiral casing and the draft tube. The numerical simulations were realized using the standard k-e model and a block-structured hexahedral wall function mesh.

  11. Estimating the Area Under ROC Curve When the Fitted Binormal Curves Demonstrate Improper Shape.

    PubMed

    Bandos, Andriy I; Guo, Ben; Gur, David

    2017-02-01

    The "binormal" model is the most frequently used tool for parametric receiver operating characteristic (ROC) analysis. The binormal ROC curves can have "improper" (non-concave) shapes that are unrealistic in many practical applications, and several tools (eg, PROPROC) have been developed to address this problem. However, due to the general robustness of binormal ROCs, the improperness of the fitted curves might carry little consequence for inferences about global summary indices, such as the area under the ROC curve (AUC). In this work, we investigate the effect of severe improperness of fitted binormal ROC curves on the reliability of AUC estimates when the data arise from an actually proper curve. We designed theoretically proper ROC scenarios that induce severely improper shape of fitted binormal curves in the presence of well-distributed empirical ROC points. The binormal curves were fitted using maximum likelihood approach. Using simulations, we estimated the frequency of severely improper fitted curves, bias of the estimated AUC, and coverage of 95% confidence intervals (CIs). In Appendix S1, we provide additional information on percentiles of the distribution of AUC estimates and bias when estimating partial AUCs. We also compared the results to a reference standard provided by empirical estimates obtained from continuous data. We observed up to 96% of severely improper curves depending on the scenario in question. The bias in the binormal AUC estimates was very small and the coverage of the CIs was close to nominal, whereas the estimates of partial AUC were biased upward in the high specificity range and downward in the low specificity range. Compared to a non-parametric approach, the binormal model led to slightly more variable AUC estimates, but at the same time to CIs with more appropriate coverage. The improper shape of the fitted binormal curve, by itself, ie, in the presence of a sufficient number of well-distributed points, does not imply

  12. Nonparametric estimation of the multivariate survivor function: the multivariate Kaplan-Meier estimator.

    PubMed

    Prentice, Ross L; Zhao, Shanshan

    2018-01-01

    The Dabrowska (Ann Stat 16:1475-1489, 1988) product integral representation of the multivariate survivor function is extended, leading to a nonparametric survivor function estimator for an arbitrary number of failure time variates that has a simple recursive formula for its calculation. Empirical process methods are used to sketch proofs for this estimator's strong consistency and weak convergence properties. Summary measures of pairwise and higher-order dependencies are also defined and nonparametrically estimated. Simulation evaluation is given for the special case of three failure time variates.

  13. Maternal smoking during pregnancy and the risk of pediatric cardiovascular diseases of the offspring: A population-based cohort study with up to 18-years of follow up.

    PubMed

    Leybovitz-Haleluya, Noa; Wainstock, Tamar; Landau, Daniella; Sheiner, Eyal

    2018-06-01

    Cigarette smoke is a well-known reproductive toxicant. We aimed to study the long-term effect of cigarette smoking during pregnancy on the risk for childhood cardiovascular morbidity of the offspring. A population-based cohort analysis was performed comparing total and subtypes of cardiovascular related pediatric hospitalizations among offspring of smoking mothers versus offspring of non-smoking mothers. The analysis included all singletons born between the years 1999-2014.A Kaplan-Meier survival curve was used to compare the cumulative cardiovascular morbidity, and a Cox proportional hazards model was constructed to adjust for confounders. The study population included 242,342 newborns which met inclusion criteria; among them 2861 were born to smoking mothers. Offspring of smoking mothers had higher rates of cardiovascular-related hospitalizations (1.3% vs. 0.6%, OR 2.1, 95% CI 1.5-2.9; p < 0.001; Kaplan-Meier log-rank test p < 0.001). Smoking exposure during pregnancy is associated with an increased risk for long-term pediatric cardiovascular morbidity of the offspring. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Understanding Art Testing: Past Influences, Norman C. Meier's Contributions, Present Concerns, and Future Possibilities.

    ERIC Educational Resources Information Center

    Clark, Gilbert; And Others

    This collection of 10 papers focuses on art testing and Norman C. Meier's role in this area of study. The titles written by Gilbert Clark are: (1) "Early Inquiry, Research, and Testing of Children's Art Abilities"; (2) "Norman C. Meier: A Critique of His Tests and Research"; and (3) "Recent Inquiry and Testing of…

  15. Prognostic value of inflammation-based markers in patients with pancreatic cancer administered gemcitabine and erlotinib.

    PubMed

    Lee, Jae Min; Lee, Hong Sik; Hyun, Jong Jin; Choi, Hyuk Soon; Kim, Eun Sun; Keum, Bora; Seo, Yeon Seok; Jeen, Yoon Tae; Chun, Hoon Jai; Um, Soon Ho; Kim, Chang Duck

    2016-07-15

    To evaluate the value of systemic inflammation-based markers as prognostic factors for advanced pancreatic cancer (PC). Data from 82 patients who underwent combination chemotherapy with gemcitabine and erlotinib for PC from 2011 to 2014 were collected retrospectively. Data that included the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio, and the C-reactive protein (CRP)-to-albumin (CRP/Alb) ratio were analyzed. Kaplan-Meier curves, and univariate and multivariate Cox proportional hazards regression analyses were used to identify the prognostic factors associated with progression-free survival (PFS) and overall survival (OS). The univariate analysis demonstrated the prognostic value of the NLR (P = 0.049) and the CRP/Alb ratio (P = 0.047) in relation to PFS, and a positive relationship between an increase in inflammation-based markers and a poor prognosis in relation to OS. The multivariate analysis determined that an increased NLR (hazard ratio = 2.76, 95%CI: 1.33-5.75, P = 0.007) is an independent prognostic factor for poor OS. There was no association between the PLR and the patients' prognoses in those who had received chemotherapy that comprised gemcitabine and erlotinib in combination. The Kaplan-Meier method and the log-rank test determined significantly worse outcomes in relation to PFS and OS in patients with an NLR > 5 or a CRP/Alb ratio > 5. Systemic inflammation-based markers, including increases in the NLR and the CRP/Alb ratio, may be useful for predicting PC prognoses.

  16. Exponential Decay Nonlinear Regression Analysis of Patient Survival Curves: Preliminary Assessment in Non-Small Cell Lung Cancer

    PubMed Central

    Stewart, David J.; Behrens, Carmen; Roth, Jack; Wistuba, Ignacio I.

    2010-01-01

    Background For processes that follow first order kinetics, exponential decay nonlinear regression analysis (EDNRA) may delineate curve characteristics and suggest processes affecting curve shape. We conducted a preliminary feasibility assessment of EDNRA of patient survival curves. Methods EDNRA was performed on Kaplan-Meier overall survival (OS) and time-to-relapse (TTR) curves for 323 patients with resected NSCLC and on OS and progression-free survival (PFS) curves from selected publications. Results and Conclusions In our resected patients, TTR curves were triphasic with a “cured” fraction of 60.7% (half-life [t1/2] >100,000 months), a rapidly-relapsing group (7.4%, t1/2=5.9 months) and a slowly-relapsing group (31.9%, t1/2=23.6 months). OS was uniphasic (t1/2=74.3 months), suggesting an impact of co-morbidities; hence, tumor molecular characteristics would more likely predict TTR than OS. Of 172 published curves analyzed, 72 (42%) were uniphasic, 92 (53%) were biphasic, 8 (5%) were triphasic. With first-line chemotherapy in advanced NSCLC, 87.5% of curves from 2-3 drug regimens were uniphasic vs only 20% of those with best supportive care or 1 drug (p<0.001). 54% of curves from 2-3 drug regimens had convex rapid-decay phases vs 0% with fewer agents (p<0.001). Curve convexities suggest that discontinuing chemotherapy after 3-6 cycles “synchronizes” patient progression and death. With postoperative adjuvant chemotherapy, the PFS rapid-decay phase accounted for a smaller proportion of the population than in controls (p=0.02) with no significant difference in rapid-decay t1/2, suggesting adjuvant chemotherapy may move a subpopulation of patients with sensitive tumors from the relapsing group to the cured group, with minimal impact on time to relapse for a larger group of patients with resistant tumors. In untreated patients, the proportion of patients in the rapid-decay phase increased (p=0.04) while rapid-decay t1/2 decreased (p=0.0004) with increasing

  17. Analysis of the Kaplan turbine draft tube effect

    NASA Astrophysics Data System (ADS)

    Motycak, L.; Skotak, A.; Obrovsky, J.

    2010-08-01

    The aim of this paper is to present information about possible problems and errors which can appear during numerical analyses of low head Kaplan turbines with a view to the runner - draft tube interaction. The setting of numerical model, grid size, used boundary conditions are the interface definition between runner and draft tube are discussed. There are available data from physical model tests which gives a great opportunity to compare CFD and experiment results and on the basis of this comparison to determine the approach to the CFD flow modeling. The main purpose for the Kaplan turbine model measurement was to gather the information about real flow field. The model tests were carried out in new hydraulic laboratory of CKD Blansko Engineering. The model tests were focused on the detailed velocity measurements downstream of the runner by differential pressure probe and on the velocity measurement downstream of the draft tube elbow by Particle Image Velocimetry method (PIV). The data from CFD simulation were compared to the velocity measurement results. In the paper also the design of the original draft tube modification due to flow improvement is discussed in the case of the Kaplan turbine uprating project. The results of the draft tube modification were confirmed by model tests in the hydraulic laboratory as well.

  18. Investigation of standardized administration of anti-platelet drugs and its effect on the prognosis of patients with coronary heart disease.

    PubMed

    Ding, Chao; Zhang, Jianhua; Li, Rongcheng; Wang, Jiacai; Hu, Yongcang; Chen, Yanyan; Li, Xiannan; Xu, Yan

    2017-10-01

    The aim of the present study was to explore the effect of adherence to standardized administration of anti-platelet drugs on the prognosis of patients with coronary heart disease. A total of 144 patients newly diagnosed with coronary heart disease at Lu'an Shili Hospital of Anhui Province (Lu'an, China) between June 2010 and June 2012 were followed up. Kaplan-Meier curves and the Cox regression model were used to evaluate the effects of standardized administration of anti-platelet drugs on primary and secondary end-point events. Of the patients with coronary heart disease, 109 (76%) patients took standard anti-platelet drugs following discharge. Kaplan-Meier curve and Cox regression analysis showed that standardized administration of anti-platelet drugs reduced the risk of primary end-point events (including all-cause mortality, non-lethal myocardial infarction and stroke) of patients with coronary heart disease [hazard ratio (HR)=0.307; 95% confidence interval (CI): 0.099-0.953; P=0.041) and all-cause mortality (HR=0.162; 95% CI: 0.029-0.890; P=0.036); however, standardized administration had no predictive value with regard to secondary end-point events. Standardized administration of anti-platelet drugs obviously reduced the risk of primary end-point events in patients with coronary heart disease, and further analysis showed that only all-cause mortality exhibited a statistically significant reduction.

  19. Persistent fatigue in young athletes: measuring the clinical course and identifying variables affecting clinical recovery.

    PubMed

    Locke, S; Osborne, M; O'Rourke, P

    2011-02-01

    The objective of this paper is to measure the clinical course (months) in young athletes with persistent fatigue and to identify any covariates affecting the duration of recovery. This was a prospective longitudinal study of 68 athletes; 87% were elite (42 males, 26 females), aged 20.5±3.74 years (SD), who presented with the symptom of persistent fatigue. The collective duration to full clinical recovery was estimated using Kaplan-Meier product-limit curves, and covariates associated with prolonging recovery were identified from Cox proportional hazard models. The median recovery was 5 months (range 1-60 months). The range of presenting symptom duration was 0.5-36 months. The covariates identified were an increased duration of presenting symptoms [hazard ratio (HR), 1.06; 95% confidence interval (CI), 1.02-1.12; P=0.005] and the response of serum cortisol concentration to a standard exercise challenge (HR, 1.92; 95% CI, 1.09-3.38; P=0.03). Delay in recovery was not associated with categories of fatigue that included medical, training-related diagnoses, or other causes. In conclusion, the fatigued athlete represents a significant clinical problem with a median recovery of 5 months, whose collective clinical course to recovery can be estimated by Kaplan-Meier curves and appears to be a continuum. © 2009 John Wiley & Sons A/S.

  20. Long-term pediatric skin eruption-related hospitalizations in offspring conceived via fertility treatment.

    PubMed

    Krieger, Yuval; Wainstock, Tamar; Sheiner, Eyal; Harlev, Avi; Landau, Daniella; Horev, Amir; Bogdanov-Berezovsky, Alexander; Walfisch, Asnat

    2018-03-01

    Although concerns have been raised regarding the long-term health risks of offspring conceived following fertility treatments, limited information is available regarding their health status beyond the neonatal period. We aimed to evaluate the risk of long-term eruptive dermatological morbidity among children born following fertility treatments as compared to those conceived spontaneously. A population-based cohort study was conducted, including all singleton deliveries occurring between the years 1991 and 2014 at a single tertiary medical center. Fetuses with congenital malformations and multiple gestations were excluded. Children delivered following fertility treatment pregnancies and spontaneous pregnancies were compared. Hospitalizations of the offspring up to the age of 18 years involving cutaneous eruptions were evaluated. A Kaplan-Meier survival curve was used to compare cumulative morbidity incidence and a Cox regression model to control for confounders. During the study period, 242,187 singleton deliveries met the inclusion criteria, 1.8% of which were following fertility treatments (n = 4324). Eruptive dermatological morbidity of the offspring up to the age of 18 years was significantly more common in the fertility treatment group (1.5%) as compared to spontaneous pregnancies (1.1%; P = 0.023). The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of eruptive dermatological morbidity following fertility treatments (log-rank P = 0.007). Using the Cox regression model, while controlling for multiple confounders, fertility treatment was noted as an independent risk factor for long-term pediatric eruptive dermatological morbidity (adjusted HR = 1.43, CI 1.12-1.83, P = 0.004). Singletons conceived via fertility treatments appear to be at an increased risk for long-term eruptive dermatological morbidity. © 2018 The International Society of Dermatology.

  1. Survival curves to support quality improvement in hospitals with excess 30-day mortality after acute myocardial infarction, cerebral stroke and hip fracture: a before-after study.

    PubMed

    Kristoffersen, Doris Tove; Helgeland, Jon; Waage, Halfrid Persdatter; Thalamus, Jacob; Clemens, Dirk; Lindman, Anja Schou; Rygh, Liv Helen; Tjomsland, Ole

    2015-03-25

    To evaluate survival curves (Kaplan-Meier) as a means of identifying areas in the clinical pathway amenable to quality improvement. Observational before-after study. In Norway, annual public reporting of nationwide 30-day in-and-out-of-hospital mortality (30D) for three medical conditions started in 2011: first time acute myocardial infarction (AMI), stroke and hip fracture; reported for 2009. 12 of 61 hospitals had statistically significant lower/higher mortality compared with the hospital mean. Three hospitals with significantly higher mortality requested detailed analyses for quality improvement purposes: Telemark Hospital Trust Skien (AMI and stroke), Østfold Hospital Trust Fredrikstad (stroke), Innlandet Hospital Trust Gjøvik (hip fracture). Survival curves, crude and risk-adjusted 30D before (2008-2009) and after (2012-2013). Unadjusted survival curves for the outlier hospitals were compared to curves based on pooled data from the other hospitals for the 30-day period 2008-2009. For patients admitted with AMI (Skien), stroke (Fredrikstad) and hip fracture (Gjøvik), the curves suggested increased mortality from the initial part of the clinical pathway. For stroke (Skien), increased mortality appeared after about 8 days. The curve profiles were thought to reflect suboptimal care in various phases in the clinical pathway. This informed improvement efforts. For 2008-2009, hospital-specific curves differed from other hospitals: borderline significant for AMI (p=0.064), highly significant (p≤0.005) for the remainder. After intervention, no difference was found (p>0.188). Before-after comparison of the curves within each hospital revealed a significant change for Fredrikstad (p=0.006). For the three hospitals, crude 30D declined and they were non-outliers for risk-adjusted 30D for 2013. Survival curves as a supplement to 30D may be useful for identifying suboptimal care in the clinical pathway, and thus informing design of quality improvement projects

  2. Edith Kaplan and the Boston Process Approach.

    PubMed

    Libon, David J; Swenson, Rodney; Ashendorf, Lee; Bauer, Russell M; Bowers, Dawn

    2013-01-01

    The history including some of the intellectual origins of the Boston Process Approach and some misconceptions about the Boston Process Approach are reviewed. The influence of Gestalt psychology and Edith Kaplan's principal collaborators regarding the development of the Boston Process Approach is discussed.

  3. Prognostic evaluation of the elastic properties of the ascending aorta in dilated cardiomyopathy.

    PubMed

    Sciatti, Edoardo; Vizzardi, Enrico; Bonadei, Ivano; Fabbricatore, Davide; Prati, Francesco; Pagnoni, Mattia; Metra, Marco

    2018-05-13

    Nowadays there is an increased interest in the role of aortic stiffness in the pathophysiology of heart failure (HF), since it is a major determinant of left ventricular (LV) performance. We aimed at assessing the predictive value of the aortic stiffness parameters, measured by echocardiography, in patients affected by non-ischemic dilated cardiomyopathy (DCM) regarding three end-points: death, HF rehospitalization, combined death or HF rehospitalization in a long-term follow-up. 202 patients affected by non-ischemic DCM underwent an outpatient examination by echocardiography and blood pressure check at the brachial artery, in order to calculate aortic elastic properties (i.e., compliance, distensibility, stiffness index, Peterson's elastic modulus, M-mode strain). ROC curves, Kaplan-Meier curves and multivariable Cox regressions (correcting for age, LV ejection fraction (LVEF), atrial fibrillation, cardiac resynchronization therapy (CRT)) were run to assess the predictive ability of aortic elastic properties against the three endpoints. Mean follow-up was 9.83±2.80 years. 24.8% of patients died, while 34.7% were rehospitalized for HF cause and 44.6% experienced the combined endpoint. LVEF did not correlate with aortic elastic properties. ROC curves and Kaplan-Meier curves were elaborated. Aortic stiffness did not predict death in our cohort. Otherwise, all aortic elastic properties predicted HF rehospitalization and combined death or HF rehospitalization, after correcting for age, LVEF, atrial fibrillation, CRT. Elastic properties of the ascending aorta measured by echocardiography in patients with non-ischemic DCM predict long-term HF rehospitalization and combined death or HF rehospitalization, also after correcting for the confounding factors. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  4. Endolymphatic sac surgery versus tenotomy of the stapedius and tensor tympani muscles in the management of patients with unilateral definite Meniere's disease.

    PubMed

    Albu, Silviu; Babighian, Gregorio; Amadori, Maurizio; Trabalzini, Franco

    2015-12-01

    This study aims to compare the outcomes of patients with Meniere's disease submitted to either endolymphatic mastoid shunt (ES) or tenotomy of the stapedius and tensor tympani muscles (TSTM). This is a retrospective chart review of patients treated with ES or TSTM between 2000 and 2010 and followed up for at least 12 months. The main outcomes were represented by: (1) vertigo class, hearing stage and functional level according to the American Academy of Otolaryngology-Head and Neck Surgery criteria; (2) adjustment of dizziness handicap inventory (DHI) and (3) complete and substantial vertigo control using the Kaplan-Meier survival method. Sixty-three patients met the inclusion criteria: 34 underwent ES and 29 TSTM. The baseline demographic characteristics, the hearing stage, the functional level, the DHI and hearing levels were not different between the two groups. No significant difference in vertigo class was demonstrated: 66 % of TSTM patients attained class A compared to 44 % in the ES group (p = 0.14). Kaplan-Meier survival curves specific to class A showed significant differences, favoring TSTM (log-rank test, p = 0.022). TSTM patients demonstrated significantly improved functional level (p = 0.0004) and improved DHI scores (p = 0.001). Eight ES patients (25 %) demanded a second surgical attempt compared to none in the TSTM. Aural fullness was significantly improved in TSTM group (p = 0.01), while the difference in tinnitus improvement was non-significant. Hearing preservation was significantly better in TSTM group (p = 0.001). TSTM is a safe surgical procedure, with significant vertigo control rates, and important hearing preservation rates. More patients and longer follow-up are needed to support our preliminary findings.

  5. Long-Term Outcomes of Non-ST-Elevation Myocardial Infarction Without Creatine Kinase Elevation - The J-MINUET Study.

    PubMed

    Ishihara, Masaharu; Nakao, Koichi; Ozaki, Yukio; Kimura, Kazuo; Ako, Junya; Noguchi, Teruo; Fujino, Masashi; Yasuda, Satoshi; Suwa, Satoru; Fujimoto, Kazuteru; Nakama, Yasuharu; Morita, Takashi; Shimizu, Wataru; Saito, Yoshihiko; Hirohata, Atsushi; Morita, Yasuhiro; Inoue, Teruo; Okamura, Atsunori; Uematsu, Masaaki; Hirata, Kazuhito; Tanabe, Kengo; Shibata, Yoshisato; Owa, Mafumi; Tsujita, Kenichi; Funayama, Hiroshi; Kokubu, Nobuaki; Kozuma, Ken; Tobaru, Tetsuya; Oshima, Shigeru; Nakai, Michikazu; Nishimura, Kunihiro; Miyamoto, Yoshihiro; Ogawa, Hisao

    2017-06-23

    According to troponin-based criteria of myocardial infarction (MI), patients without elevation of creatine kinase (CK), formerly classified as unstable angina (UA), are now diagnosed as non-ST-elevation MI (NSTEMI), but little is known about their outcomes.Methods and Results:Between July 2012 and March 2014, 3,283 consecutive patients with MI were enrolled. Clinical follow-up data were obtained up to 3 years. The primary endpoint was a composite of all-cause death, non-fatal MI, non-fatal stroke, cardiac failure and urgent revascularization for UA. There were 2,262 patients with ST-elevation MI (STEMI), 563 NSTEMI with CK elevation (NSTEMI+CK) and 458 NSTEMI without CK elevation (NSTEMI-CK). From day 0, Kaplan-Meier curves for the primary endpoint began to diverge in favor of NSTEMI-CK for up to 30 days. The 30-day event rate was significantly lower in patients with NSTEMI-CK (3.3%) than in STEMI (8.6%, P<0.001) and NSTEMI+CK (9.9%, P<0.001). Later, the event curves diverged in favor of STEMI. The event rate from 31 days to 3 years was significantly lower in patients with STEMI (19.8%) than in NSTEMI+CK (33.6%, P<0.001) and NSTEMI-CK (34.2%, P<0.001). Kaplan-Meier curves from 31 days to 3 years were almost identical between NSTEMI+CK and NSTEMI-CK (P=0.91). Despite smaller infarct size and better short-term outcomes, long-term outcomes of NSTEMI-CK after convalescence were as poor as those for NSTEMI+CK and worse than for STEMI.

  6. Anterolateral Knee Extra-articular Stabilizers: A Robotic Sectioning Study of the Anterolateral Ligament and Distal Iliotibial Band Kaplan Fibers.

    PubMed

    Geeslin, Andrew G; Chahla, Jorge; Moatshe, Gilbert; Muckenhirn, Kyle J; Kruckeberg, Bradley M; Brady, Alex W; Coggins, Ashley; Dornan, Grant J; Getgood, Alan M; Godin, Jonathan A; LaPrade, Robert F

    2018-05-01

    when compared with ALL sectioning. On simulated pivot-shift testing, ALL sectioning led to significantly increased internal rotation and anterior translation at 15° and 30°; sectioning of the Kaplan fibers led to significantly increased tibial internal rotation at 15° and 30° and anterior translation at 15°. No significant difference was found when anterior tibial translation was compared between the ACL/ALL- and ACL/Kaplan fiber-deficient states on simulated pivot-shift testing or isolated anterior tibial load. The ALL and Kaplan fibers restrain internal rotation in the ACL-deficient knee. Sectioning the Kaplan fibers led to greater tibial internal rotation at higher flexion angles (60°-90°) as compared with ALL sectioning. Additionally, the ALL and Kaplan fibers contribute to restraint of the pivot shift and anterior tibial translation in the ACL-deficient knee. This study reports that the ALL and distal iliotibial band Kaplan fibers restrain anterior tibial translation, internal rotation, and pivot shift in the ACL-deficient knee. Furthermore, sectioning the Kaplan fibers led to significantly greater tibial internal rotation when compared with ALL sectioning at high flexion angles. These results demonstrate increased rotational knee laxity with combined ACL and anterolateral extra-articular knee injuries and may allow surgeons to optimize the care of patients with this injury pattern.

  7. Revision total knee arthroplasty for septic versus aseptic failure.

    PubMed

    Rajgopal, Ashok; Vasdev, Attique; Gupta, Himanshu; Dahiya, Vivek

    2013-12-01

    To compare the medium-term outcome of revision total knee arthroplasty (TKA) for septic versus aseptic failure. Records of 142 patients who underwent revision TKA by a single senior surgeon for septic (n=65) or aseptic (n=77) failure were reviewed. In the septic group, 67 knees in 42 women and 23 men were included. In the aseptic group, 88 knees in 51 women and 26 men were included. The Knee Society Score was measured. The Kaplan Meier survival curve at months 36, 60, and 95 was plotted, with revision as the end point. The survival rates at each specific time point between the 2 groups were compared using the Z test. The Knee Society Scores improved 18% from 51 to 69 in the septic group and 18% from 52 to 70 in the aseptic group (p=0.72). The range of motion improved 30% from 72 to 102 degrees in the septic group and 39% from 62 to 100 degrees in the aseptic group (p<0.001). Results of the 2 groups were similar in terms of the Knee Society Score, range of motion, and the Kaplan-Meier survivorship.

  8. Metastatic volume: an old oncologic concept and a new prognostic factor for stage IV melanoma patients.

    PubMed

    Panasiti, V; Curzio, M; Roberti, V; Lieto, P; Devirgiliis, V; Gobbi, S; Naspi, A; Coppola, R; Lopez, T; di Meo, N; Gatti, A; Trevisan, G; Londei, P; Calvieri, S

    2013-01-01

    The last melanoma staging system of the 2009 American Joint Committee on Cancer takes into account, for stage IV disease, the serum levels of lactate dehydrogenase (LDH) and the site of distant metastases. Our aim was to compare the significance of metastatic volume, as evaluated at the time of stage IV melanoma diagnosis, with other clinical predictors of prognosis. We conducted a retrospective multicentric study. To establish which variables were statistically correlated both with death and survival time, contingency tables were evaluated. The overall survival curves were compared using the Kaplan-Meier method. Metastatic volume and number of affected organs were statistically related to death. In detail, patients with a metastatic volume >15 cm(3) had a worse prognosis than those with a volume lower than this value (survival probability at 60 months: 6.8 vs. 40.9%, respectively). The Kaplan-Meier method confirmed that survival time was significantly related to the site(s) of metastases, to elevated LDH serum levels and to melanoma stage according to the latest system. Our results suggest that metastatic volume may be considered as a useful prognostic factor for survival among melanoma patients.

  9. ["That flesh, pink and perishable": analysis of disease-free survival analysis in breast cancer in Gipuzkoa (Spain) in the presence of competing risks].

    PubMed

    Martínez-Camblor, Pablo; Larrañaga, Nerea; Sarasqueta, Cristina; Mitxelena, María José; Basterretxea, Mikel

    2009-01-01

    To analyze time of disease-free survival and relative survival in women diagnosed with breast cancer in the province of Gipuzkoa within the context of competing risks by assessing differences between the direct use of the Kaplan-Meier estimator and the multiple decrement method on the one hand, and relative survival on the other. All registered breast cancer cases in Gipuzkoa in 1995 and 1996 with stages other than stage IV were included. An 8-year follow-up for recurrence and a 10-year follow-up for survival were performed. Time of disease-free survival was studied by the multiple decrement model. Observed survival and survival corrected by the expected mortality in the population (relative survival) were also studied. Estimation of the probability of recurrence at 8 years with the multiple decrement method was 8.8% lower than that obtained with the Kaplan-Meier method. The difference between the observed and relative survival rates at 10 years was 10.8%. Both results show how, in this case, the Kaplan-Meier estimator overestimates both the probability of recurrence and that of mortality from the disease. Two issues are often overlooked when performing survival analyses: firstly, because of the lack of independence between survival time and censoring time, the results obtained by the Kaplan-Meier estimator are uninterpretable; secondly, it is an incontrovertible fact that one way or another, everyone causes failures. In this approach, survival analyses must take into account the probability of failure in the general population of reference. The results obtained in this study show that superficial use of the Kaplan Meier estimator overestimates both the probability of recurrence and that of mortality caused by the disease.

  10. Eigentumors for prediction of treatment failure in patients with early-stage breast cancer using dynamic contrast-enhanced MRI: a feasibility study

    NASA Astrophysics Data System (ADS)

    Chan, H. M.; van der Velden, B. H. M.; E Loo, C.; Gilhuijs, K. G. A.

    2017-08-01

    We present a radiomics model to discriminate between patients at low risk and those at high risk of treatment failure at long-term follow-up based on eigentumors: principal components computed from volumes encompassing tumors in washin and washout images of pre-treatment dynamic contrast-enhanced (DCE-) MR images. Eigentumors were computed from the images of 563 patients from the MARGINS study. Subsequently, a least absolute shrinkage selection operator (LASSO) selected candidates from the components that contained 90% of the variance of the data. The model for prediction of survival after treatment (median follow-up time 86 months) was based on logistic regression. Receiver operating characteristic (ROC) analysis was applied and area-under-the-curve (AUC) values were computed as measures of training and cross-validated performances. The discriminating potential of the model was confirmed using Kaplan-Meier survival curves and log-rank tests. From the 322 principal components that explained 90% of the variance of the data, the LASSO selected 28 components. The ROC curves of the model yielded AUC values of 0.88, 0.77 and 0.73, for the training, leave-one-out cross-validated and bootstrapped performances, respectively. The bootstrapped Kaplan-Meier survival curves confirmed significant separation for all tumors (P  <  0.0001). Survival analysis on immunohistochemical subgroups shows significant separation for the estrogen-receptor subtype tumors (P  <  0.0001) and the triple-negative subtype tumors (P  =  0.0039), but not for tumors of the HER2 subtype (P  =  0.41). The results of this retrospective study show the potential of early-stage pre-treatment eigentumors for use in prediction of treatment failure of breast cancer.

  11. The Association of Individual and Regional Socioeconomic Status on Initial Peritonitis and Outcomes in Peritoneal Dialysis Patients: A Propensity Score-Matched Cohort Study.

    PubMed

    Wang, Qin; Hu, Ke-Jie; Ren, Ye-Ping; Dong, Jie; Han, Qing-Feng; Zhu, Tong-Ying; Chen, Jiang-Hua; Zhao, Hui-Ping; Chen, Meng-Hua; Xu, Rong; Wang, Yue; Hao, Chuan-Ming; Zhang, Xiao-Hui; Wang, Mei; Tian, Na; Wang, Hai-Yan

    2016-01-01

    ♦ Research indicates that the socioeconomic status (SES) of individuals and the area where they live are related to initial peritonitis and outcomes in peritoneal dialysis (PD). We conducted a retrospective, multi-center cohort study in China to examine these associations. ♦ Data on 2,171 PD patients were collected from 7 centers, including baseline demographic, socioeconomic, and laboratory data. We explored the potential risk factors for initial peritonitis and outcomes using univariate Cox regression and unadjusted binary logistic regression. Then, we used propensity score matching to balance statistically significant risk factors for initial peritonitis and outcomes, and Kaplan-Meier survival analysis to compare differences in peritonitis-free rates between different groups of participants after matching. ♦ A total of 563 (25.9%) initial episodes of peritonitis occurred during the study period. The Kaplan-Meier peritonitis-free rate curve showed high-income patients had a significantly lower risk than low-income patients (p = 0.007) after matching for age, hemoglobin, albumin, and regional SES and PD center. The risk of treatment failure was significantly lower in the high-income than the low-income group after matching for the organism causing peritonitis and PD center: odds ratio (OR) = 0.27 (0.09 - 0.80, p = 0.018). Regional SES and education were not associated with initial peritonitis and outcomes. ♦ Our study demonstrates low individual income is a risk factor for the initial onset of peritonitis and treatment failure after initial peritonitis. Copyright © 2016 International Society for Peritoneal Dialysis.

  12. Elucidation of the Strongest Predictors of Cardiovascular Events in Patients with Heart Failure.

    PubMed

    Fukuda, Hiroki; Shindo, Kazuhiro; Sakamoto, Mari; Ide, Tomomi; Kinugawa, Shintaro; Fukushima, Arata; Tsutsui, Hiroyuki; Ito, Shin; Ishii, Akira; Washio, Takashi; Kitakaze, Masafumi

    2018-06-20

    In previous retrospective studies, we identified the 50 most influential clinical predictors of cardiovascular outcomes in patients with heart failure (HF). The present study aimed to use the novel limitless-arity multiple-testing procedure to filter these 50 clinical factors and thus yield combinations of no more than four factors that could potentially predict the onset of cardiovascular events. A Kaplan-Meier analysis was used to investigate the importance of the combinations. In a multi-centre observational trial, we prospectively enrolled 213 patients with HF who were hospitalized because of exacerbation, discharged according to HF treatment guidelines and observed to monitor cardiovascular events. After the observation period, we stratified patients according to whether they experienced cardiovascular events (rehospitalisation or cardiovascular death). Among 77,562 combinations of fewer than five clinical parameters, we identified 151 combinations that could potentially explain the occurrence of cardiovascular events. Of these, 145 combinations included the use of inotropic agents, whereas the remaining 6 included the use of diuretics without bradycardia or tachycardia, suggesting that the high probability of cardiovascular events is exclusively determined by these two clinical factors. Importantly, Kaplan-Meier curves demonstrated that the use of inotropes or of diuretics without bradycardia or tachycardia were independent predictors of a markedly worse cardiovascular prognosis. Patients treated with either inotropic agents or diuretics without bradycardia or tachycardia were at a higher risk of cardiovascular events. The uses of these drugs, regardless of heart rate, are the strongest clinical predictors of cardiovascular events in patients with HF. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Assessment of the American Joint Commission on Cancer 8th Edition Staging System for Patients with Pancreatic Neuroendocrine Tumors: A Surveillance, Epidemiology, and End Results analysis.

    PubMed

    Li, Xiaogang; Gou, Shanmiao; Liu, Zhiqiang; Ye, Zeng; Wang, Chunyou

    2018-03-01

    Although several staging systems have been proposed for pancreatic neuroendocrine tumors (pNETs), the optimal staging system remains unclear. Here, we aimed to assess the application of the newly revised 8th edition American Joint Committee on Cancer (AJCC) staging system for exocrine pancreatic carcinoma (EPC) to pNETs, in comparison with that of other staging systems. We identified pNETs patients from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2014). Overall survival was analyzed using Kaplan-Meier curves with the log-rank test. The predictive accuracy of each staging system was assessed by the concordance index (c-index). Cox proportional hazards regression was conducted to calculate the impact of different stages. In total, 2424 patients with pNETs, including 2350 who underwent resection, were identified using SEER data. Patients with different stages were evenly stratified based on the 8th edition AJCC staging system for EPC. Kaplan-Meier curves were well separated in all patients and patients with resection using the 8th edition AJCC staging system for EPC. Moreover, the hazard ratio increased with worsening disease stage. The c-index of the 8th edition AJCC staging system for EPC was similar to that of the other systems. For pNETs patients, the 8th edition AJCC staging system for EPC exhibits good prognostic discrimination among different stages in both all patients and those with resection. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  14. Learning curve for the management of tyrosine kinase inhibitors as the first line of treatment for patients with metastatic renal cancer.

    PubMed

    Lendínez-Cano, G; Osman García, I; Congregado Ruiz, C B; Conde Sánchez, J M; Medina López, R A

    2018-03-07

    To analyse the learning curve for the management of tyrosine kinase inhibitors as the first line of treatment for patients with metastatic renal cancer. We evaluated 32 consecutive patients treated in our department for metastatic renal cancer with tyrosine kinase inhibitors (pazopanib or sunitinib) as first-line treatment between September 2012 and November 2015. We retrospectively analysed this sample. We measured the time to the withdrawal of the first-line treatment, the time to progression and overall survival using Kaplan-Meier curves. The learning curve was analysed with the cumulative sum (CUSUM) methodology. In our series, the median time to the withdrawal of the first-line treatment was 11 months (95% CI 4.9-17.1). The mean time to progression was 30.4 months (95% CI 22.7-38.1), and the mean overall survival was 34.9 months (95% CI 27.8-42). By applying the CUSUM methodology, we obtained a graph for the CUSUM value of the time to withdrawal of the first-line treatment (CUSUM TW), observing 3 well-differentiated phases: phase 1 or initial learning phase (1-15), phase 2 (16-26) in which the management of the drug progressively improved and phase 3 (27-32) of maximum experience or mastery of the management of these drugs. The number of treated patients needed to achieve the proper management of these patients was estimated at 15. Despite the limitations of the sample size and follow-up time, we estimated (in 15 patients) the number needed to reach the necessary experience in the management of these patients with tyrosine kinase inhibitors. We observed no relationship between the time to the withdrawal of the first-line treatment for any cause and progression. Copyright © 2018 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Some Supplementary Methods for the Analysis of the Delis-Kaplan Executive Function System

    ERIC Educational Resources Information Center

    Crawford, John R.; Garthwaite, Paul H.; Sutherland, David; Borland, Nicola

    2011-01-01

    Supplementary methods for the analysis of the Delis-Kaplan Executive Function System (Delis, Kaplan, & Kramer, 2001) are made available, including (a) quantifying the number of abnormally low achievement scores exhibited by an individual and accompanying this with an estimate of the percentage of the normative population expected to exhibit at…

  16. Multi-objective shape optimization of runner blade for Kaplan turbine

    NASA Astrophysics Data System (ADS)

    Semenova, A.; Chirkov, D.; Lyutov, A.; Chemy, S.; Skorospelov, V.; Pylev, I.

    2014-03-01

    Automatic runner shape optimization based on extensive CFD analysis proved to be a useful design tool in hydraulic turbomachinery. Previously the authors developed an efficient method for Francis runner optimization. It was successfully applied to the design of several runners with different specific speeds. In present work this method is extended to the task of a Kaplan runner optimization. Despite of relatively simpler blade shape, Kaplan turbines have several features, complicating the optimization problem. First, Kaplan turbines normally operate in a wide range of discharges, thus CFD analysis of each variant of the runner should be carried out for several operation points. Next, due to a high specific speed, draft tube losses have a great impact on the overall turbine efficiency, and thus should be accurately evaluated. Then, the flow in blade tip and hub clearances significantly affects the velocity profile behind the runner and draft tube behavior. All these features are accounted in the present optimization technique. Parameterization of runner blade surface using 24 geometrical parameters is described in details. For each variant of runner geometry steady state three-dimensional turbulent flow computations are carried out in the domain, including wicket gate, runner, draft tube, blade tip and hub clearances. The objectives are maximization of efficiency in best efficiency and high discharge operation points, with simultaneous minimization of cavitation area on the suction side of the blade. Multiobjective genetic algorithm is used for the solution of optimization problem, requiring the analysis of several thousands of runner variants. The method is applied to optimization of runner shape for several Kaplan turbines with different heads.

  17. Mathematical, numerical and experimental analysis of the swirling flow at a Kaplan runner outlet

    NASA Astrophysics Data System (ADS)

    Muntean, S.; Ciocan, T.; Susan-Resiga, R. F.; Cervantes, M.; Nilsson, H.

    2012-11-01

    The paper presents a novel mathematical model for a-priori computation of the swirling flow at Kaplan runners outlet. The model is an extension of the initial version developed by Susan-Resiga et al [1], to include the contributions of non-negligible radial velocity and of the variable rothalpy. Simple analytical expressions are derived for these additional data from three-dimensional numerical simulations of the Kaplan turbine. The final results, i.e. velocity components profiles, are validated against experimental data at two operating points, with the same Kaplan runner blades opening, but variable discharge.

  18. Kaplan turbine tip vortex cavitation - analysis and prevention

    NASA Astrophysics Data System (ADS)

    Motycak, L.; Skotak, A.; Kupcik, R.

    2012-11-01

    The work is focused on one type of Kaplan turbine runner cavitation - a tip vortex cavitation. For detailed description of the tip vortex, the CFD analysis is used. On the basis of this analysis it is possible to estimate the intensity of cavitating vortex core, danger of possible blade surface and runner chamber cavitation pitting. In the paper, the ways how to avoid the pitting effect of the tip vortex are described. In order to prevent the blade surface against pitting, the following possibilities as the change of geometry of the runner blade, dimension of tip clearance and finally the installation of the anti-cavitation lips are discussed. The knowledge of the shape and intensity of the tip vortex helps to design the anti-cavitation lips more sophistically. After all, the results of the model tests of the Kaplan runner with or without anti-cavitation lips and the results of the CFD analysis are compared.

  19. Clinical outcome of the metal-on-metal hybrid Corin Cormet 2000 hip resurfacing system: an up to 11-year follow-up study.

    PubMed

    Gross, Thomas P; Liu, Fei; Webb, Lee A

    2012-04-01

    This report extends the follow-up for the largest center of the first multicenter US Food and Drug Administration investigational device exemption study on metal-on-metal hip resurfacing arthroplasty up to 11 years. A single surgeon performed 373 hip resurfacing arthroplasties using the hybrid Corin Cormet 2000 system. The Kaplan-Meier survivorship at 11 years was 93% when revision for any reason was used as an end point and 91% if radiographic failures were included. The clinical results demonstrate an acceptable failure rate with use of this system. Loosening of the cemented femoral components was the most common source of failure and occurred at all follow-up intervals. A learning curve that persisted for at least 200 cases was confirmed. All femoral neck fractures occurred before 6 months postoperatively. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Meier-Gorlin syndrome.

    PubMed

    de Munnik, Sonja A; Hoefsloot, Elisabeth H; Roukema, Jolt; Schoots, Jeroen; Knoers, Nine V A M; Brunner, Han G; Jackson, Andrew P; Bongers, Ernie M H F

    2015-09-17

    Meier-Gorlin syndrome (MGS) is a rare autosomal recessive primordial dwarfism disorder, characterized by microtia, patellar applasia/hypoplasia, and a proportionate short stature. Associated clinical features encompass feeding problems, congenital pulmonary emphysema, mammary hypoplasia in females and urogenital anomalies, such as cryptorchidism and hypoplastic labia minora and majora. Typical facial characteristics during childhood comprise a small mouth with full lips and micro-retrognathia. During ageing, a narrow, convex nose becomes more prominent. The diagnosis MGS should be considered in patients with at least two of the three features of the clinical triad of microtia, patellar anomalies, and pre- and postnatal growth retardation. In patients with short stature and/or microtia, the patellae should be assessed with care by ultrasonography before age 6 or radiography thereafter. Mutations in one of five genes (ORC1, ORC4, ORC6, CDT1, and CDC6) of the pre-replication complex, involved in DNA-replication, are detected in approximately 67-78% of patients with MGS. Patients with ORC1 and ORC4 mutations appear to have the most severe short stature and microcephaly. Management should be directed towards in-depth investigation, treatment and prevention of associated problems, such as growth retardation, feeding problems, hearing loss, luxating patellae, knee pain, gonarthrosis, and possible pulmonary complications due to congenital pulmonary emphysema with or without broncho- or laryngomalacia. Growth hormone treatment is ineffective in most patients with MGS, but may be effective in patients in whom growth continues to decrease after the first year of life (usually growth velocity normalizes after the first year) and with low levels of IGF1. At present, few data is available about reproduction of females with MGS, but the risk of premature labor might be increased. Here, we propose experience-based guidelines for the regular care and treatment of MGS patients.

  1. Influences of age, sex, and LDL-C change on cardiovascular risk reduction with pravastatin treatment in elderly Japanese patients: A post hoc analysis of data from the Pravastatin Anti-atherosclerosis Trial in the Elderly (PATE)

    PubMed Central

    Ouchi, Yasuyoshi; Ohashi, Yasuo; Ito, Hideki; Saito, Yasushi; Ishikawa, Toshitsugu; Akishita, Masahiro; Shibata, Taro; Nakamura, Haruo; Orimo, Hajime

    2006-01-01

    Background: The Pravastatin Anti-atherosclerosis Trial in the Elderly (PATE) found that the prevalence of cardiovascular events (CVEs) was significantly lower with standard-dose (10–20 mg/d) pravastatin treatment compared with low-dose (5 mg/d) pravastatin treatment in elderly (aged ⩾ 60 years) Japanese patients with hypercholesterolemia. Small differences in on-treatment total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels between the 2 dose groups in the PATE study were associated with significant differences in CVE prevalence. However, the reasons for these differences have not been determined. How sex and age differences influence the effectiveness of pravastatin also remains unclear. Objectives: The aims of this study were to determine the relationship between reduction in LDL-C level and CVE risk reduction in the PATE study and to assess the effects of sex and age on the effectiveness of pravastatin treatment (assessed using CVE risk reduction). Methods: In this post hoc analysis, Cox regression analysis was performed to study the relationship between on-treatment (pravastatin 5–20 mg/d) LDL-C level and CVE risk reduction using age, sex, smoking status, presence of diabetes mellitus and/or hypertension, history of cardiovascular disease (CVD), and high-density lipoprotein cholesterol level as adjustment factors. To explore risk reduction due to unspecified mechanisms other than LDLrC reduction, an estimated Kaplan-Meier curve from the Cox regression analysis was calculated and compared with the empirical (observed) Kaplan-Meier curve. Results: A total of 665 patients (527 women, 138 men; mean [SD] age, 72.8 [5.7] years) were enrolled in PATE and were followed up for a mean of 3.9 years (range, 3–5 years). Of those patients, 50 men and 173 women were ⩾75 years of age. Data from 619 patients were included in the present analysis. In the calculation of model-based Kaplan-Meier curves, data from an additional 32 patients were

  2. Influences of age, sex, and LDL-C change on cardiovascular risk reduction with pravastatin treatment in elderly Japanese patients: A post hoc analysis of data from the Pravastatin Anti-atherosclerosis Trial in the Elderly (PATE).

    PubMed

    Ouchi, Yasuyoshi; Ohashi, Yasuo; Ito, Hideki; Saito, Yasushi; Ishikawa, Toshitsugu; Akishita, Masahiro; Shibata, Taro; Nakamura, Haruo; Orimo, Hajime

    2006-07-01

    The Pravastatin Anti-atherosclerosis Trial in the Elderly (PATE) found that the prevalence of cardiovascular events (CVEs) was significantly lower with standard-dose (10-20 mg/d) pravastatin treatment compared with low-dose (5 mg/d) pravastatin treatment in elderly (aged ⩾ 60 years) Japanese patients with hypercholesterolemia. Small differences in on-treatment total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels between the 2 dose groups in the PATE study were associated with significant differences in CVE prevalence. However, the reasons for these differences have not been determined. How sex and age differences influence the effectiveness of pravastatin also remains unclear. The aims of this study were to determine the relationship between reduction in LDL-C level and CVE risk reduction in the PATE study and to assess the effects of sex and age on the effectiveness of pravastatin treatment (assessed using CVE risk reduction). In this post hoc analysis, Cox regression analysis was performed to study the relationship between on-treatment (pravastatin 5-20 mg/d) LDL-C level and CVE risk reduction using age, sex, smoking status, presence of diabetes mellitus and/or hypertension, history of cardiovascular disease (CVD), and high-density lipoprotein cholesterol level as adjustment factors. To explore risk reduction due to unspecified mechanisms other than LDLrC reduction, an estimated Kaplan-Meier curve from the Cox regression analysis was calculated and compared with the empirical (observed) Kaplan-Meier curve. A total of 665 patients (527 women, 138 men; mean [SD] age, 72.8 [5.7] years) were enrolled in PATE and were followed up for a mean of 3.9 years (range, 3-5 years). Of those patients, 50 men and 173 women were ⩾75 years of age. Data from 619 patients were included in the present analysis. In the calculation of model-based Kaplan-Meier curves, data from an additional 32 patients were excluded from the LDL-C analysis because there were no

  3. Censoring: a new approach for detection limits in total-reflection X-ray fluorescence

    NASA Astrophysics Data System (ADS)

    Pajek, M.; Kubala-Kukuś, A.; Braziewicz, J.

    2004-08-01

    It is shown that the detection limits in the total-reflection X-ray fluorescence (TXRF), which restrict quantification of very low concentrations of trace elements in the samples, can be accounted for using the statistical concept of censoring. We demonstrate that the incomplete TXRF measurements containing the so-called "nondetects", i.e. the non-measured concentrations falling below the detection limits and represented by the estimated detection limit values, can be viewed as the left random-censored data, which can be further analyzed using the Kaplan-Meier (KM) method correcting for nondetects. Within this approach, which uses the Kaplan-Meier product-limit estimator to obtain the cumulative distribution function corrected for the nondetects, the mean value and median of the detection limit censored concentrations can be estimated in a non-parametric way. The Monte Carlo simulations performed show that the Kaplan-Meier approach yields highly accurate estimates for the mean and median concentrations, being within a few percent with respect to the simulated, uncensored data. This means that the uncertainties of KM estimated mean value and median are limited in fact only by the number of studied samples and not by the applied correction procedure for nondetects itself. On the other hand, it is observed that, in case when the concentration of a given element is not measured in all the samples, simple approaches to estimate a mean concentration value from the data yield erroneous, systematically biased results. The discussed random-left censoring approach was applied to analyze the TXRF detection-limit-censored concentration measurements of trace elements in biomedical samples. We emphasize that the Kaplan-Meier approach allows one to estimate the mean concentrations being substantially below the mean level of detection limits. Consequently, this approach gives a new access to lower the effective detection limits for TXRF method, which is of prime interest for

  4. Abnormal early cleavage events predict early embryo demise: sperm oxidative stress and early abnormal cleavage.

    PubMed

    Burruel, Victoria; Klooster, Katie; Barker, Christopher M; Pera, Renee Reijo; Meyers, Stuart

    2014-10-13

    Human embryos resulting from abnormal early cleavage can result in aneuploidy and failure to develop normally to the blastocyst stage. The nature of paternal influence on early embryo development has not been directly demonstrated although many studies have suggested effects from spermatozoal chromatin packaging, DNA damage, centriolar and mitotic spindle integrity, and plasma membrane integrity. The goal of this study was to determine whether early developmental events were affected by oxidative damage to the fertilizing sperm. Survival analysis was used to compare patterns of blastocyst formation based on P2 duration. Kaplan-Meier survival curves demonstrate that relatively few embryos with short (<1 hr) P2 times reached blastocysts, and the two curves diverged beginning on day 4, with nearly all of the embryos with longer P2 times reaching blastocysts by day 6 (p < .01). We determined that duration of the 2nd to 3rd mitoses were sensitive periods in the presence of spermatozoal oxidative stress. Embryos that displayed either too long or too short cytokineses demonstrated an increased failure to reach blastocyst stage and therefore survive for further development. Although paternal-derived gene expression occurs later in development, this study suggests a specific role in early mitosis that is highly influenced by paternal factors.

  5. Comparison of Exposure in the Kaplan Versus the Kocher Approach in the Treatment of Radial Head Fractures.

    PubMed

    Barnes, Leslie Fink; Lombardi, Joseph; Gardner, Thomas R; Strauch, Robert J; Rosenwasser, Melvin P

    2018-01-01

    The aim of this study was to compare the complete visible surface area of the radial head, neck, and coronoid in the Kaplan and Kocher approaches to the lateral elbow. The hypothesis was that the Kaplan approach would afford greater visibility due to the differential anatomy of the intermuscular planes. Ten cadavers were dissected with the Kaplan and Kocher approaches, and the visible surface area was measured in situ using a 3-dimensional digitizer. Six measurements were taken for each approach by 2 surgeons, and the mean of these measurements were analyzed. The mean surface area visible with the lateral collateral ligament (LCL) preserved in the Kaplan approach was 616.6 mm 2 in comparison with the surface area of 136.2 mm 2 visible in the Kocher approach when the LCL was preserved. Using a 2-way analysis of variance, the difference between these 2 approaches was statistically significant. When the LCL complex was incised in the Kocher approach, the average visible surface area of the Kocher approach was 456.1 mm 2 and was statistically less than the Kaplan approach. The average surface area of the coronoid visible using a proximally extended Kaplan approach was 197.8 mm 2 . The Kaplan approach affords significantly greater visible surface area of the proximal radius than the Kocher approach.

  6. Prior history of non-melanoma skin cancer is associated with increased mortality in patients with chronic lymphocytic leukemia

    PubMed Central

    Toro, Jorge R.; Blake, Patrick W.; Björkholm, Magnus; Kristinsson, Sigurdur Y.; Wang, Zhuoqiao; Landgren, Ola

    2009-01-01

    We investigated whether a previous diagnosis of non-melanoma skin cancer among chronic lymphocytic leukemia patients is a predictor of poor outcome. Using the Swedish Cancer Registry, we conducted a population-based study to evaluate the survival patterns among chronic lymphocytic leukemia patients with and without non-melanoma skin cancer. Cox proportional hazards regression models were used and Kaplan-Meier curves were constructed. Of a total of 12,041 chronic lymphocytic leukemia cases identified, 236 cases, including 111 squamous cell cancer, had a prior history of non-melanoma skin cancer. Chronic lymphocytic leukemia patients with a prior history of non-melanoma skin cancer had a 1.29-fold (95% CI 1.10–1.52; p=0.0024) increased risk of dying; and those with a history of squamous cell cancer had a further elevated 1.86-fold (95% CI 1.46–2.36; p<0.0001) risk of dying. Kaplan-Meier plots showed that patients with a history of non-melanoma skin cancer, particularly those with squamous cell cancer, had significantly poorer survival than chronic lymphocytic leukemia patients without non-melanoma skin cancer (p<0.0001; log-rank test). Non-melanoma skin cancer may be a novel clinical predictor of worse chronic lymphocytic leukemia outcome. PMID:19794092

  7. Predictive Factors for Visual Field Conversion: Comparison of Scanning Laser Polarimetry and Optical Coherence Tomography.

    PubMed

    Diekmann, Theresa; Schrems-Hoesl, Laura M; Mardin, Christian Y; Laemmer, Robert; Horn, Folkert K; Kruse, Friedrich E; Schrems, Wolfgang A

    2018-02-01

    The purpose of this study was to compare the ability of scanning laser polarimetry (SLP) and spectral-domain optical coherence tomography (SD-OCT) to predict future visual field conversion of subjects with ocular hypertension and early glaucoma. All patients were recruited from the Erlangen glaucoma registry and examined using standard automated perimetry, 24-hour intraocular pressure profile, and optic disc photography. Peripapillary retinal nerve fiber layer thickness (RNFL) measurements were obtained by SLP (GDx-VCC) and SD-OCT (Spectralis OCT). Positive and negative predictive values (PPV, NPV) were calculated for morphologic parameters of SLP and SD-OCT. Kaplan-Meier survival curves were plotted and log-rank tests were performed to compare the survival distributions. Contingency tables and Venn-diagrams were calculated to compare the predictive ability. The study included 207 patients-75 with ocular hypertension, 85 with early glaucoma, and 47 controls. Median follow-up was 4.5 years. A total of 29 patients (14.0%) developed visual field conversion during follow-up. SLP temporal-inferior RNFL [0.667; 95% confidence interval (CI), 0.281-0.935] and SD-OCT temporal-inferior RNFL (0.571; 95% CI, 0.317-0.802) achieved the highest PPV; nerve fiber indicator (0.923; 95% CI, 0.876-0.957) and SD-OCT mean (0.898; 95% CI, 0.847-0.937) achieved the highest NPV of all investigated parameters. The Kaplan-Meier curves confirmed significantly higher survival for subjects within normal limits of measurements of both devices (P<0.001). Venn diagrams tested with McNemar test statistics showed no significant difference for PPV (P=0.219) or NPV (P=0.678). Both GDx-VCC and SD-OCT demonstrate comparable results in predicting future visual field conversion if taking typical scans for GDx-VCC. In addition, the likelihood ratios suggest that GDx-VCC's nerve fiber indicator<30 may be the most useful parameter to confirm future nonconversion. (http://www.ClinicalTrials.gov number, NTC

  8. Individualism, Nationalism, and Universalism: The Educational Ideals of Mordecai M. Kaplan's Philosophy of Jewish Education

    ERIC Educational Resources Information Center

    Ackerman, Ari

    2008-01-01

    This article will examine educational ideals by exploring the relation between the individual, the collective, and humanity in Kaplan's Jewish and educational philosophy. Generally the goals of individualism, nationalism, and universalism are seen as mutually exclusive. By contrast, Kaplan argues for the symbiotic relationship between…

  9. Numerical investigation of hub clearance flow in a Kaplan turbine

    NASA Astrophysics Data System (ADS)

    Wu, H.; Feng, J. J.; Wu, G. K.; Luo, X. Q.

    2012-11-01

    In this paper, the flow field considering the hub clearance flow in a Kaplan turbine has been investigated through using the commercial CFD code ANSYS CFX based on high-quality structured grids generated by ANSYS ICEM CFD. The turbulence is simulated by k-ω based shear stress transport (SST) turbulence model together with automatic near wall treatments. Four kinds of simulations have been conducted for the runner geometry without hub clearance, with only the hub front clearance, with only the rear hub clearance, and with both front and rear clearance. The analysis of the obtained results is focused on the flow structure of the hub clearance flow, the effect on the turbine performance including hydraulic efficiency and cavitation performance, which can improve the understanding on the flow field in a Kaplan turbine.

  10. Hypermethylation of testis derived transcript gene promoter significantly correlates with worse outcomes in glioblastoma patients.

    PubMed

    Wang, Li-jia; Bai, Yu; Bao, Zhao-shi; Chen, Yan; Yan, Zhuo-hong; Zhang, Wei; Zhang, Quan-geng

    2013-01-01

    Glioblastoma is the most common and lethal cancer of the central nervous system. Global genomic hypomethylation and some CpG island hypermethylation are common hallmarks of these malignancies, but the effects of these methylation abnormalities on glioblastomas are still largely unclear. Methylation of the O6-methylguanine-DNA methyltransferase promoter is currently an only confirmed molecular predictor of better outcome in temozolomide treatment. To better understand the relationship between CpG island methylation status and patient outcome, this study launched DNA methylation profiles for thirty-three primary glioblastomas (pGBMs) and nine secondary glioblastomas (sGBMs) with the expectation to identify valuable prognostic and therapeutic targets. We evaluated the methylation status of testis derived transcript (TES) gene promoter by microarray analysis of glioblastomas and the prognostic value for TES methylation in the clinical outcome of pGBM patients. Significance analysis of microarrays was used for genes significantly differently methylated between 33 pGBM and nine sGBM. Survival curves were calculated according to the Kaplan-Meier method, and differences between curves were assessed using the log-rank test. Then, we treated glioblastoma cell lines (U87 and U251) with 5-aza-2-deoxycytidines (5-aza-dC) and detected cell biological behaviors. Microarray data analysis identified TES promoter was hypermethylated in pGBMs compared with sGBMs (P < 0.05). Survival curves from the Kaplan-Meier method analysis revealed that the patients with TES hypermethylation had a short overall survival (P < 0.05). This abnormality is also confirmed in glioblastoma cell lines (U87 and U251). Treating these cells with 5-aza-dC released TES protein expression resulted in significant inhibition of cell growth (P = 0.013). Hypermethylation of TES gene promoter highly correlated with worse outcome in pGBM patients. TES might represent a valuable prognostic marker for glioblastoma.

  11. Unsteady load on an oscillating Kaplan turbine runner

    NASA Astrophysics Data System (ADS)

    Puolakka, O.; Keto-Tokoi, J.; Matusiak, J.

    2013-02-01

    A Kaplan turbine runner oscillating in turbine waterways is subjected to a varying hydrodynamic load. Numerical simulation of the related unsteady flow is time-consuming and research is very limited. In this study, a simplified method based on unsteady airfoil theory is presented for evaluation of the unsteady load for vibration analyses of the turbine shaft line. The runner is assumed to oscillate as a rigid body in spin and axial heave, and the reaction force is resolved into added masses and dampings. The method is applied on three Kaplan runners at nominal operating conditions. Estimates for added masses and dampings are considered to be of a magnitude significant for shaft line vibration. Moderate variation in the added masses and minor variation in the added dampings is found in the frequency range of interest. Reference results for added masses are derived by solving the boundary value problem for small motions of inviscid fluid using the finite element method. Good correspondence is found in the added mass estimates of the two methods. The unsteady airfoil method is considered accurate enough for design purposes. Experimental results are needed for validation of unsteady load analyses.

  12. Postoperative evaluation of palatoplasty using the modified Kaplan method.

    PubMed

    Isago, Tsukasa; Nozaki, Motohiro; Honda, Takashi; Kikuchi, Yuji

    2005-01-01

    Bilateral buccal mucosal flaps were used for a pushback operation of the nasal mucosa as well as the oral mucosa. Two flaps from the buccal mucosal areas were inserted into the nasal mucosal raw surface at the hard and soft palatal border to achieve nasal mucosal pushback. Forty-four children with cleft palates were retrospectively studied to investigate the velopharyngeal function, articulation, and craniofacial morphology following primary palatoplasty using the modified Kaplan method. 72.7% showed good velopharyngeal function. Articulation disorders were found in 26 of the 44 subjects (59.1%). A craniofacial morphological analysis revealed no major changes in the SNA (sella-nasion point A angle) and SNB (sella-nasion point B angle) and no cases of a marked loss of maxillary mandibular balance. In addition, no significant differences were observed in the maxillary length and width. The results of these palatoplasties by the modified Kaplan method indicated that the use of bilateral buccal mucosal flaps for the pushback of the nasal mucosa was effective in preventing the contraction of the maxillary and mandibular corpal lengths.

  13. Research on the cavitation characteristic of Kaplan turbine under sediment flow condition

    NASA Astrophysics Data System (ADS)

    Weili, L.; Jinling, L.; Xingqi, L.; Yuan, L.

    2010-08-01

    The sediment concentration in many rivers in our world is very high, and the Kaplan turbine running in these rivers are usually seriously abraded. Since the existence of sand, the probability of cavitation is greatly enhanced. Under the joint action and mutual promotion of cavitation and sand erosion, serious abrasion could be made, the hydraulic performance of the Kaplan turbine may be descended, and the safety and stability of turbine are greatly threatened. Therefore, it is very important and significant to investigate the cavitation characteristic of Kaplan turbine under sediment flow condition. In this paper, numerical simulation of cavitation characteristic in pure water and solid-liquid two-phase flow in Kaplan turbine was performed. The solid-liquid two-fluid model were adopted in the numerical simulation, and the pressure, velocity and particle concentration distributive regularity on turbine blade surface under different diameter and concentration was revealed. Particle trajectory model was used to investigate the region and degree of runner blade abrasion in different conditions. The results showed that serious sand abrasion could be found near the blade head and outlet in large flow rate working condition. Relatively slight abrasion may be found near blade flange in small flow rate working condition. The more the sediment concentration and the large the sand diameter, the serious the runner is abraded, and the greater the efficiency is decreased. further analysis of the combined effects of wear and abrasion was performed. The result shows that the cavitation in silt flow is more serious than in pure water. The runner cavitation performance become worse under high sand concentration and large particle diameter, and the efficiency decrease greatly with the increase of sediment concentration.

  14. What is the learning curve for the anterior approach for total hip arthroplasty?

    PubMed

    de Steiger, Richard Noel; Lorimer, Michelle; Solomon, Michael

    2015-12-01

    There are many factors that may affect the learning curve for total hip arthroplasty (THA) and surgical approach is one of these. There has been renewed interest in the direct anterior approach for THA with variable outcomes reported, but few studies have documented a surgeon's individual learning curve when using this approach. (1) What was the revision rate for all surgeons adopting the anterior approach for placement of a particular implant? (2) What was the revision rate for surgeons who performed > 100 cases in this fashion? (3) Is there a minimum number of cases required to complete a learning curve for this procedure? The Australian Orthopaedic Association National Joint Replacement Registry prospectively collects data on all primary and revision joint arthroplasty surgery. We analyzed all conventional THAs performed up to December 31, 2013, with a primary diagnosis of osteoarthritis using a specific implant combination and secondarily those associated with surgeons performing more than 100 procedures. Ninety-five percent of these procedures were performed through the direct anterior approach. Procedures using this combination were ordered from earliest (first procedure date) to latest (last procedure date) for each individual surgeon. Using the order number for each surgeon, five operation groups were defined: one to 15 operations, 16 to 30 operations, 31 to 50 operations, 51 to 100 operations, and > 100 operations. The primary outcome measure was time to first revision using Kaplan-Meier estimates of survivorship. Sixty-eight surgeons performed 5499 THAs using the specified implant combination. The cumulative percent revision at 4 years for all 68 surgeons was 3% (95% confidence interval [CI], 2.5-3.8). For surgeons who had performed over 100 operations, the cumulative revision rate was 3% (95% CI, 2.0-3.5). It was not until surgeons had performed over 50 operations that there was no difference in the cumulative percent revision compared with over 100

  15. A Simple Experiment Demonstrating the Relationship between Response Curves and Absorption Spectra.

    ERIC Educational Resources Information Center

    Li, Chia-yu

    1984-01-01

    Describes an experiment for recording two individual spectrophotometer response curves. The two curves are directly related to the power of transmitted beams that pass through a solvent and solution. An absorption spectrum of the solution can be constructed from the calculated rations of the curves as a function of wavelength. (JN)

  16. Registry of Hospital Das Clínicas of the University of São Paulo Medical School: First Official Solid Organ and Tissue Transplantation Report – 2008

    PubMed Central

    Azeka, Estela; Auler Júnior, José Otavio Costa; Fernandes, Paulo Manuel Pego; Nahas, Willian Carlos; Fiorelli, Alfredo Inácio; Tannuri, Uenis; Cristofani, Lílian Maria; Caiero, Marcelo Tadeu; Dulley, Frederico Luiz; de Oliveira Paggiaro, André; Bacchella, Telesforo

    2009-01-01

    OBJECTIVE: The aim of this study was to report a single center experience of organ and tissue transplantation INTRODUCTION: This is the first report of organ and tissue transplantation at the Hospital das Clínicas of the University of Sao Paulo Medical School. METHODS: We collected data from each type of organ transplantation from 2002 to 2007. The data collected were patient characteristics and actuarial survival Kaplan-Meier curves at 30 days, one year, and five years RESULTS: There were a total of 3,321 transplants at our institution and the 5-year survival curve ranged from 53% to 88%. CONCLUSION: This report shows that solid organ and tissue transplants are feasible within the institution and allow us to expect that the quality of transplantation will improve in the future. PMID:19219318

  17. Numerical simulation of turbulence flow in a Kaplan turbine -Evaluation on turbine performance prediction accuracy-

    NASA Astrophysics Data System (ADS)

    Ko, P.; Kurosawa, S.

    2014-03-01

    The understanding and accurate prediction of the flow behaviour related to cavitation and pressure fluctuation in a Kaplan turbine are important to the design work enhancing the turbine performance including the elongation of the operation life span and the improvement of turbine efficiency. In this paper, high accuracy turbine and cavitation performance prediction method based on entire flow passage for a Kaplan turbine is presented and evaluated. Two-phase flow field is predicted by solving Reynolds-Averaged Navier-Stokes equations expressed by volume of fluid method tracking the free surface and combined with Reynolds Stress model. The growth and collapse of cavitation bubbles are modelled by the modified Rayleigh-Plesset equation. The prediction accuracy is evaluated by comparing with the model test results of Ns 400 Kaplan model turbine. As a result that the experimentally measured data including turbine efficiency, cavitation performance, and pressure fluctuation are accurately predicted. Furthermore, the cavitation occurrence on the runner blade surface and the influence to the hydraulic loss of the flow passage are discussed. Evaluated prediction method for the turbine flow and performance is introduced to facilitate the future design and research works on Kaplan type turbine.

  18. Association between ERCC1 and TS mRNA levels and disease free survival in colorectal cancer patients receiving oxaliplatin and fluorouracil (5-FU) adjuvant chemotherapy.

    PubMed

    Li, Sheng; Zhu, Liangjun; Yao, Li; Xia, Lei; Pan, Liangxi

    2014-08-29

    Aim was to explore the association of ERCC1 and TS mRNA levels with the disease free survival (DFS) in Chinese colorectal cancer (CRC) patients receiving oxaliplatin and 5-FU based adjuvant chemotherapy. Total 112 Chinese stage II-III CRC patients were respectively treated by four different chemotherapy regimens after curative operation. The TS and ERCC1 mRNA levels in primary tumor were measured by real-time RT-PCR. Kaplan-Meier curves and log-rank tests were used for DFS analysis. The Cox proportional hazards model was used for prognostic analysis. In univariate analysis, the hazard ratio (HR) for the mRNA expression levels of TS and ERCC1 (logTS: HR = 0.820, 95% CI = 0.600 - 1.117, P = 0.210; logERCC1: HR = 1.054, 95% CI = 0.852 - 1.304, P = 0.638) indicated no significant association of DFS with the TS and ERCC1 mRNA levels. In multivariate analyses, tumor stage (IIIc: reference, P = 0.083; IIb: HR = 0.240, 95% CI = 0.080 - 0.724, P = 0.011; IIc: HR < 0.0001, P = 0.977; IIIa: HR = 0.179, 95% CI = 0.012 - 2.593, P = 0.207) was confirmed to be the independent prognostic factor for DFS. Moreover, the Kaplan-Meier DFS curves showed that TS and ERCC1 mRNA levels were not significantly associated with the DFS (TS: P = 0.264; ERCC1: P = 0.484). The mRNA expression of ERCC1 and TS were not applicable to predict the DFS of Chinese stage II-III CRC patients receiving 5-FU and oxaliplatin based adjuvant chemotherapy.

  19. Pure fetal histology subtype was associated with better prognosis of children with hepatoblastoma: A Chinese population-based study.

    PubMed

    Qiao, Guo-liang; Chen, Zhen; Wang, Chen; Ge, Juntao; Zhang, Zhen; Li, Long; Ren, Jun

    2016-03-01

    The aim of this study is to identify the association between histologic types and the prognosis of hepatoblastoma (HB) in a large Asian cohort of a single institution and to explore the interaction of histologic types with other independently risk factors in the process of affecting prognosis of HB. We retrospectively reviewed 176 children with HB (82 female, 94 male) managed in our institution between May 1, 2001 and July 30, 2014. Prognostic factors were evaluated using Kaplan-Meier curves and Cox proportional hazards models. For the entire cohort of 176 patients, the overall median survival was 80.4 months(95% CI: 71.6-89.2 months), and the 5-year event-free survival and overall survival rates were 54.6 and 66.7%. Descriptive survival statistics and Kaplan-Meier curves suggested that alpha fetoprotein levels, tumor metastases, multifocality, histologic types, and Pre-Treatment Extent of Disease staging System stage had prognostic significance in this relatively selected cohort. Moreover, after eliminating the impact of the interaction of different classification methods of histologic types, pure fetal histologic (PFH) was an independent prognostic factor of HB (hazard ratio [HR]: 2.752, P = 0.021). Further stratification analysis showed that the impaction of other identified risk factors on the influence of PFH on the prognosis of HB patients was different. We have confirmed that the HB prognostic factors of HB and PFH was associated with better prognosis of children with HB based on an Asian population. PFH showed different significance in the process of affecting prognosis of HB with the interaction of other independent risk factors. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  20. Muscle strength and physical performance as predictors of mortality, hospitalization, and disability in the oldest old.

    PubMed

    Legrand, Delphine; Vaes, Bert; Matheï, Catharina; Adriaensen, Wim; Van Pottelbergh, Gijs; Degryse, Jean-Marie

    2014-06-01

    To evaluate the predictive value of muscle strength and physical performance in the oldest old for all-cause mortality; hospitalization; and the onset of disability, defined as a decline in activities of daily living (ADLs), independent of muscle mass, inflammatory markers, and comorbidities. A prospective, observational, population-based follow-up study. Three well-circumscribed areas of Belgium. Five hundred sixty participants aged 80 and older were followed for 33.5 months (interquartile range 31.1-35.6 months). Grip strength, Short Physical Performance Battery (SPPB) score, and muscle mass were measured at baseline; ADLs at baseline and after 20 months; and all-cause mortality and time to first hospitalization from inclusion onward. Kaplan-Meier curves and Cox proportional hazards models were calculated for all-cause mortality and hospitalization. Logistic regression analysis was used to determine predictors of decline in ADLs. Kaplan-Meier curves showed significantly higher all-cause mortality and hospitalization in subjects in the lowest tertile of grip strength and SPPB score. The adjusted Cox proportional hazards model showed that participants with high grip strength or a high SPPB score had a lower risk of mortality and hospitalization, independent of muscle mass, inflammatory markers, and comorbidity. A relationship was found between SPPB score and decline in ADLs, independent of muscle mass, inflammation, and comorbidity. In people aged 80 and older, physical performance is a strong predictor of mortality, hospitalization, and disability, and muscle strength is a strong predictor of mortality and hospitalization. All of these relationships were independent of muscle mass, inflammatory markers, and comorbidity. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

  1. A Simple Method for Evaluating Within Sample Prognostic Balance Achieved by Published Comorbidity Summary Measures.

    PubMed

    Egleston, Brian L; Uzzo, Robert G; Beck, J Robert; Wong, Yu-Ning

    2015-08-01

    To demonstrate how a researcher can investigate the appropriateness of a published comorbidity summary measure for use with a given sample. Surveillance, Epidemiology, and End Results linked to Medicare claims data. We examined Kaplan-Meier estimated survival curves for four diseases within strata of a comorbidity summary measure, the Charlson Comorbidity Index. We identified individuals with early-stage kidney cancer diagnosed from 1995 to 2009. We recorded comorbidities present in the year before diagnosis. The use of many comorbidity summary measures is valid under appropriate conditions. One condition is that the relationships of the comorbidities with the outcome of interest in a researcher's own population are comparable to the relationships in a published algorithm's population. The original comorbidity weights from the Charlson Comorbidity Index seemed adequate for three of the diseases in our sample. We found evidence that the Charlson Comorbidity Index might underestimate the impact of one disease in our sample. Examination of survival curves within strata defined by a comorbidity summary measure can be a useful tool for determining whether a published method appropriately accounts for comorbidities. A comorbidity score is only as good as those variables included. © Health Research and Educational Trust.

  2. Nonparametric Discrete Survival Function Estimation with Uncertain Endpoints Using an Internal Validation Subsample

    PubMed Central

    Zee, Jarcy; Xie, Sharon X.

    2015-01-01

    Summary When a true survival endpoint cannot be assessed for some subjects, an alternative endpoint that measures the true endpoint with error may be collected, which often occurs when obtaining the true endpoint is too invasive or costly. We develop an estimated likelihood function for the situation where we have both uncertain endpoints for all participants and true endpoints for only a subset of participants. We propose a nonparametric maximum estimated likelihood estimator of the discrete survival function of time to the true endpoint. We show that the proposed estimator is consistent and asymptotically normal. We demonstrate through extensive simulations that the proposed estimator has little bias compared to the naïve Kaplan-Meier survival function estimator, which uses only uncertain endpoints, and more efficient with moderate missingness compared to the complete-case Kaplan-Meier survival function estimator, which uses only available true endpoints. Finally, we apply the proposed method to a dataset for estimating the risk of developing Alzheimer's disease from the Alzheimer's Disease Neuroimaging Initiative. PMID:25916510

  3. Intrathecal oligoclonal bands synthesis in multiple sclerosis: is it always a prognostic factor?

    PubMed

    Frau, Jessica; Villar, Luisa Maria; Sardu, Claudia; Secci, Maria Antonietta; Schirru, Lucia; Ferraro, Diana; Coghe, Giancarlo; Lorefice, Lorena; Fenu, Giuseppe; Bedin, Roberta; Sola, Patrizia; Marrosu, Maria Giovanna; Cocco, Eleonora

    2018-02-01

    Oligoclonal IgM (OCMB) and IgG (OCGB) bands were found to be associated with poor multiple sclerosis (MS) prognosis. We aimed to evaluate the prognostic value of OCMB/OCGB in a cohort of Sardinian MS patients. We recruited patients from the University of Cagliari. They underwent lumbar puncture for diagnostic purposes. Demographic and the following clinical data were recorded: clinical course; time to reach EDSS 3 and 6; EDSS at last follow-up; and MS treatments. The influence of gender, clinical course, age at onset, treatments, and OCGB/OCMB on reaching EDSS 3 was analysed using Cox regression. Kaplan-Meier curves were used to study the time to reach EDSS 3 considering OCMB/OCGB and therapies. The enrolled number of subjects was 503. The variables influencing the achievement of EDSS 3.0 were: male gender (p = 0.005); progressive course (p = 0.001); age at onset (p < 0.001); and disease-modifying drugs (p < 0.001). The OCGB/OCMB status was not significant. Kaplan-Meier analysis showed no difference in time to reach EDSS 3 for patients with and without OCGB or OCMB in both treated and non-treated groups. Our study did not confirm the poor prognostic value of OCMB/OCGB. These results may be influenced by the peculiar genetic background associated with the risk of MS in Sardinians.

  4. Increased expression of Nlp, a potential oncogene in ovarian cancer, and its implication in carcinogenesis.

    PubMed

    Qu, Danni; Qu, Hongyan; Fu, Ming; Zhao, Xuelian; Liu, Rong; Sui, Lihua; Zhan, Qimin

    2008-08-01

    Nlp (Ninein-like protein), a novel centrosome protein involved in microtubule nucleation, has been studied extensively in our laboratory, and its overexpression has been found in some human tumors. To understand the role of Nlp in human ovarian cancer development, we studied the correlation of Nlp expression with clinicopathological parameters and survival in epithelial ovarian cancer, and the impact of Nlp overexpression on ovarian cancer cells. Nlp expression in normal, borderline, benign and malignant epithelial ovarian tissues was examined by immunohistochemistry. The correlation between Nlp expression and tumor grade, FIGO stage and histological type was also evaluated. Survival was calculated using Kaplan-Meier estimates. Cell proliferation and apoptosis were assayed after stable transfection of pEGFP-C3-Nlp or empty vector in human ovarian cancer cell line SKOV3. Nlp was positive in 1 of 10 (10%) normal ovarian tissues, 5 of 34 (14.7%) benign tumors, 9 of 26 (34.6%) borderline tumors and 73 of 131 (56.0%) ovarian tumors. Nlp immunoreactivity intensity significantly correlated with tumor grade, but not with FIGO stage or histological type. Kaplan-Meier curves showed that Nlp overexpression was marginally associated with decreased overall survival. Overexpression of Nlp enhanced proliferation and inhibited apoptosis induced by paclitaxel in the SKOV3 cell line. Overexpression of Nlp in ovarian tumors raises the possibility that Nlp may play a role in ovarian carcinogenesis.

  5. Chemokine-like factor-like MARVEL transmembrane domain-containing 3 expression is associated with a favorable prognosis in esophageal squamous cell carcinoma.

    PubMed

    Han, Tianci; Shu, Tianci; Dong, Siyuan; Li, Peiwen; Li, Weinan; Liu, Dali; Qi, Ruiqun; Zhang, Shuguang; Zhang, Lin

    2017-05-01

    Decreased expression of human chemokine-like factor-like MARVEL transmembrane domain-containing 3 (CMTM3) has been identified in a number of human tumors and tumor cell lines, including gastric and testicular cancer, and PC3, CAL27 and Tca-83 cell lines. However, the association between CMTM3 expression and the clinicopathological features and prognosis of esophageal squamous cell carcinoma (ESCC) patients remains unclear. The aim of the present study was to investigate the correlation between CMTM3 expression and clinicopathological parameters and prognosis in ESCC. CMTM3 mRNA and protein expression was analyzed in ESCC and paired non-tumor tissues by quantitative real-time polymerase chain reaction, western blotting and immunohistochemical analysis. The Kaplan-Meier method was used to plot survival curves and the Cox proportional hazards regression model was also used for univariate and multivariate survival analysis. The results revealed that CMTM3 mRNA and protein expression levels were lower in 82.5% (30/40) and 75% (30/40) of ESCC tissues, respectively, when compared with matched non-tumor tissues. Statistical analysis demonstrated that CMTM3 expression was significantly correlated with lymph node metastasis (P=0.002) and clinical stage (P<0.001) in ESCC tissues. Furthermore, the survival time of ESCC patients exhibiting low CMTM3 expression was significantly shorter than that of ESCC patients exhibiting high CMTM3 expression (P=0.01). In addition, Kaplan-Meier survival analysis revealed that the overall survival time of patients exhibiting low CMTM3 expression was significantly decreased compared with patients exhibiting high CMTM3 expression (P=0.010). Cox multivariate analysis indicated that CMTM3 protein expression was an independent prognostic predictor for ESCC after resection. This study indicated that CMTM3 expression is significantly decreased in ESCC tissues and CMTM3 protein expression in resected tumors may present an effective prognostic

  6. Further insight into the phenotype associated with a mutation in the ORC6 gene, causing Meier-Gorlin syndrome 3.

    PubMed

    Shalev, Stavit Allon; Khayat, Morad; Etty, Daniel-Spiegl; Elpeleg, Orly

    2015-03-01

    Mutations in genes encoding the origin recognition complex subunits cause Meier-Gorlin syndrome. The disease manifests a triad of short stature, small ears, and small and/or absent patellae with variable expressivity. We report on the identification of a homozygous deleterious mutation in the ORC6 gene in previously described fetuses at the severe end of the Meier-Gorlin spectrum. The phenotype included severe intrauterine growth retardation, dislocation of knees, gracile bones, clubfeet, and small mandible and chest. To date, the clinical presentation of ORC6-associated Meier-Gorlin syndrome has been mild compared to other the phenotype associated with other loci. The present report expands the clinical phenotype associated with ORC6 mutations to include severely abnormal embryological development suggesting a possible genotype-phenotype correlation. © 2015 Wiley Periodicals, Inc.

  7. Coexpression of aPKCλ/ι and IL-6 in prostate cancer tissue correlates with biochemical recurrence.

    PubMed

    Ishiguro, Hitoshi; Akimoto, Kazunori; Nagashima, Yoji; Kagawa, Eriko; Sasaki, Takeshi; Sano, Jin-yu; Takagawa, Ryo; Fujinami, Kiyoshi; Sasaki, Kazunori; Aoki, Ichiro; Ohno, Shigeo; Kubota, Yoshinobu; Uemura, Hiroji

    2011-08-01

    Atypical protein kinase C λ/ι (aPKCλ/ι) and interleukin-6 (IL-6) have been implicated in prostate cancer progression, the mechanisms of which have been demonstrated both in vitro and in vivo. However, the clinical significance of the correlation between the expressions of these factors remains to be clarified. In the present study, we report a significant correlation between aPKCλ/ι and IL-6 proteins in prostate cancer tissue by immunohistochemical staining. We evaluated the association of both proteins by analyzing clinicopathological parameters using chi-square test, Kaplan-Meier with log-rank test, and a Cox proportional hazard regression model in univariate and multivariate analyses. The results again showed that the expression of aPKCλ/ι and IL-6 correlates in prostate cancer tissue (P < 0.001). Atypical protein kinase C λ/ι was also found to correlate with the Gleason score (P < 0.001) and with biochemical recurrence after prostatectomy (P = 0.02). Furthermore, aPKCλ/ι correlated with biochemical recurrence in a Kaplan-Meier and log-rank test (P = 0.01) and Cox analysis (P = 0.02 in the univariate analysis, P = 0.02 in the multivariate analysis). The coexpression of aPKCλ/ι and IL-6 also correlated with biochemical recurrence by Kaplan-Meier and log-rank test (P = 0.005) and Cox analysis (P = 0.01 in the univariate analysis, P = 0.03 in the multivariate analysis). These results indicate a strong correlation between aPKCλ/ι and IL-6 in prostate tumors, and that the aPKCλ/ι-IL-6 axis is a reliable prognostic factor for the biochemical recurrence of this cancer. © 2011 Japanese Cancer Association.

  8. Meier-Gorlin syndrome mutations disrupt an Orc1 CDK inhibitory domain and cause centrosome reduplication.

    PubMed

    Hossain, Manzar; Stillman, Bruce

    2012-08-15

    Like DNA replication, centrosomes are licensed to duplicate once per cell division cycle to ensure genetic stability. In addition to regulating DNA replication, the Orc1 subunit of the human origin recognition complex controls centriole and centrosome copy number. Here we report that Orc1 harbors a PACT centrosome-targeting domain and a separate domain that differentially inhibits the protein kinase activities of Cyclin E-CDK2 and Cyclin A-CDK2. A cyclin-binding motif (Cy motif) is required for Orc1 to bind Cyclin A and inhibit Cyclin A-CDK2 kinase activity but has no effect on Cyclin E-CDK2 kinase activity. In contrast, Orc1 inhibition of Cyclin E-CDK2 kinase activity occurs by a different mechanism that is affected by Orc1 mutations identified in Meier-Gorlin syndrome patients. The cyclin/CDK2 kinase inhibitory domain of Orc1, when tethered to the PACT domain, localizes to centrosomes and blocks centrosome reduplication. Meier-Gorlin syndrome mutations that disrupt Cyclin E-CDK2 kinase inhibition also allow centrosome reduplication. Thus, Orc1 contains distinct domains that control centrosome copy number and DNA replication. We suggest that the Orc1 mutations present in some Meier-Gorlin syndrome patients contribute to the pronounced microcephaly and dwarfism observed in these individuals by altering centrosome duplication in addition to DNA replication defects.

  9. Number of positive nodes is superior to the lymph node ratio and American Joint Committee on Cancer N staging for the prognosis of surgically treated head and neck squamous cell carcinomas.

    PubMed

    Roberts, Thomas J; Colevas, A Dimitrios; Hara, Wendy; Holsinger, F Christopher; Oakley-Girvan, Ingrid; Divi, Vasu

    2016-05-01

    Recent changes in head and neck cancer epidemiology have created a need for improved lymph node prognostics. This article compares the prognostic value of the number of positive nodes (pN) with the value of the lymph node ratio (LNR) and American Joint Committee on Cancer (AJCC) N staging in surgical patients. The Surveillance, Epidemiology, and End Results database was used to identify cases of head and neck squamous cell carcinomas from 2004 to 2012. The sample was grouped by the AJCC N stage, LNR, and pN and was analyzed with Kaplan-Meier and multivariate Cox proportional hazards models. The sample was also analyzed by the site of the primary tumor. This study identified 12,437 patients. Kaplan-Meier survival curves showed superior prognostic ability for LNR and pN staging in comparison with AJCC staging. Patients with a pN value > 5 had the worst overall survival (5-year survival rate, 16%). Patients with oropharyngeal tumors had better outcomes for all groupings, and a pN value > 5 for oropharyngeal cancers was associated with decreased survival. Multivariate regressions demonstrated larger hazard ratios (HRs) and a lower Akaike information criterion for the pN model versus the AJCC stage and LNR models. The HRs were 1.78 (95% confidence interval, 1.62-1.95) for a pN value of 1, 2.53 (95% confidence interval, 2.32-2.75) for a pN value of 2 to 5, and 4.64 (95% confidence interval, 4.18-5.14) for a pN value > 5. The pN models demonstrated superior prognostic value in comparison with the LNR and AJCC N staging. Future modifications of the nodal staging system should be based on the pN with a separate system for oropharyngeal cancers. Future trials should consider examining adjuvant treatment escalation in patients with >5 lymph nodes. Cancer 2016;122:1388-1397. © 2016 American Cancer Society. © 2015 American Cancer Society.

  10. Downregulation of SASH1 correlates with poor prognosis in cervical cancer.

    PubMed

    Xie, J; Zhang, W; Zhang, J; Lv, Q-Y; Luan, Y-F

    2017-10-01

    The aim of this study was to analyze the association of SASH1 expression with clinicopathological features and prognosis in patients suffering cervical cancer. The expressions of SASH1 mRNA and protein in cervical cancer tissues and matched normal cervical tissues were detected by Real-time PCR and Immunohistochemistry. Based on the above findings, the association among SASH1 expression and clinicopathological features was analyzed. Overall survival was evaluated using the Kaplan-Meier method. The variables were used in univariate and multivariate analysis by the Cox proportional hazards model. The results demonstrated that both SASH1 mRNA and proteins were downregulated in cervical cancer tissues compared with those in matched normal tissues (both p < 0.05). Also, decreased SASH1 expression in cervical cancer was found to be significantly associated with high FIGO Stage (p = 0.001), lymph nodes metastasis (p = 0.003) and differentiation (p = 0.018). Furthermore, Kaplan-Meier analysis demonstrated that low SASH1 expression level was associated with poorer overall survival (p < 0.01). Univariate and multivariate analyses indicated that status of SASH1 was an independent prognostic factor for patients with cervical cancer. These findings suggested that SASH1 can be useful as a new prognostic marker and therapeutic target in cervical cancer patients.

  11. Adding gauge fields to Kaplan's fermions

    NASA Astrophysics Data System (ADS)

    Blum, T.; Kärkkäinen, Leo

    1994-04-01

    We experiment with adding dynamical gauge field to Kaplan (defect) fermions. In the case of U (1) gauge theory we use an inhomogenous Higgs mechanism to restrict the 3d gauge dynamics to a planar 2d defect. In our simulations the 3d theory produce the correct 2d gauge dynamics. We measure fermion propagators with dynamical gauge fields. They posses the correct chiral structure. The fermions at the boundary of the support of the gauge field (waveguide) are non-chiral, and have a mass two times heavier than the chiral modes. Moreover, these modes cannot be excited by a source at the defect; implying that they are dynamically decoupled. We have also checked that the anomaly relation is fullfilled for the case of a smooth external gauge field.

  12. Numerical and in-situ investigations of water hammer effects in Drava river Kaplan turbine hydropower plants

    NASA Astrophysics Data System (ADS)

    Bergant, A.; Gregorc, B.; Gale, J.

    2012-11-01

    This paper deals with critical flow regimes that may induce unacceptable water hammer in Kaplan turbine hydropower plants. Water hammer analysis should be performed for normal, emergency and catastrophic operating conditions. Hydropower plants with Kaplan turbines are usually comprised of relatively short inlet and outlet conduits. The rigid water hammer theory can be used for this case. For hydropower plants with long penstocks the elastic water hammer should be used. Some Kaplan turbine units are installed in systems with long open channels. In this case, water level oscillations in the channels should be carefully investigated. Computational results are compared with results of measurements in recently rehabilitated seven Drava river hydroelectric power plants in Slovenia. Water hammer in the six power plants is controlled by appropriate adjustment of the wicket gates and runner blades closing/opening manoeuvres. Due to very long inflow and outflow open channels in Zlatoličje HPP a special vaned pressure regulating device attenuates extreme pressures in Kaplan turbine flow-passage system and controls unsteady flow in both open channels. Comparisons of results include normal operating regimes. The agreement between computed and measured results is reasonable.

  13. Time trends in recurrence of juvenile nasopharyngeal angiofibroma: Experience of the past 4 decades.

    PubMed

    Mishra, Anupam; Mishra, Subhash Chandra

    2016-01-01

    An analysis of time distribution of juvenile nasopharyngeal angiofibroma (JNA) from the last 4 decades is presented. Sixty recurrences were analyzed as per actuarial survival. SPSS software was used to generate Kaplan-Meier (KM) curves and time distributions were compared by Log-rank, Breslow and Tarone-Ware test. The overall recurrence rate was 17.59%. Majority underwent open transpalatal approach(es) without embolization. The probability of detecting a recurrence was 95% in first 24months and comparison of KM curves of 4 different time periods was not significant. This is the first and largest series to address the time-distribution. The required follow up period is 2years. Our recurrence is just half of the largest series (reported so far) suggesting the superiority of transpalatal techniques. The similarity of curves suggests less likelihood for recent technical advances to influence the recurrence that as per our hypothesis is more likely to reflect tumor biology per se. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. XRF and XANES Data for Kaplan U Paper

    EPA Pesticide Factsheets

    The dataset contains two XRF images of iron and uranium distribution on plant roots and a database of XANES data used to produce XANES spectra figure for Figure 7 in the published paper.This dataset is associated with the following publication:Kaplan, D., R. Kukkadapu, J. Seaman, B. Arey, A. Dohnalkova, S. Buettner, D. Li, T. Varga, K. Scheckel, and P. Jaffe. Iron Mineralogy and Uranium-Binding Environment in the Rhizosphere of a Wetland Soil. D. Barcelo SCIENCE OF THE TOTAL ENVIRONMENT. Elsevier BV, AMSTERDAM, NETHERLANDS, 569: 53-64, (2016).

  15. A capture-recapture survival analysis model for radio-tagged animals

    USGS Publications Warehouse

    Pollock, K.H.; Bunck, C.M.; Winterstein, S.R.; Chen, C.-L.; North, P.M.; Nichols, J.D.

    1995-01-01

    In recent years, survival analysis of radio-tagged animals has developed using methods based on the Kaplan-Meier method used in medical and engineering applications (Pollock et al., 1989a,b). An important assumption of this approach is that all tagged animals with a functioning radio can be relocated at each sampling time with probability 1. This assumption may not always be reasonable in practice. In this paper, we show how a general capture-recapture model can be derived which allows for some probability (less than one) for animals to be relocated. This model is not simply a Jolly-Seber model because it is possible to relocate both dead and live animals, unlike when traditional tagging is used. The model can also be viewed as a generalization of the Kaplan-Meier procedure, thus linking the Jolly-Seber and Kaplan-Meier approaches to survival estimation. We present maximum likelihood estimators and discuss testing between submodels. We also discuss model assumptions and their validity in practice. An example is presented based on canvasback data collected by G. M. Haramis of Patuxent Wildlife Research Center, Laurel, Maryland, USA.

  16. [Burden of diverticular disease: an observational analysis based on Italian real-world data.

    PubMed

    Mennini, Francesco Saverio; Sciattella, Paolo; Marcellusi, Andrea; Toraldo, Bernardo; Koch, Maurizio

    2018-01-01

    Diverticular disease (DD) represent a wide variety of conditions associated with the presence of diverticula in the colon. The most serious form is an acute episode of diverticulitis which can lead to hospitalization and surgery with various types of consequences. The main aim of this study was to evaluate, from both cross-sectional and longitudinal perspective, the economic burden of diverticulitis in the real practice. A deterministic linkage was performed at individual user level between the different administrative sources of the Marche Region through anonymised ID number for a period of analysis between 1 January 2008 and 31 December 2014. We enrolled all patients with at least one hospitalization for "diverticulitis of the colon without mention of haemorrhage" (ICD-9-CM code 562.11) or "diverticulitis of the colon with haemorrhage" (ICD-9-CM code 562.13) as primary or secondary diagnosis. Cost and outcome were analysed considering transversally (for contemporaneous) and longitudinal (for cohort) perspective. Hospital mortality at one year after discharge was evaluated by mortality rates and Kaplan-Meier curve considering the surgery performed (or not performed) during the index hospitalization. Considering the cross-sectional perspective, 427 patients per year were estimated (about 35 patients per 100,000 adult residents) with an average number of hospitalization equal to 1.14. The direct healthcare costs incurred by the Marche region for episodes of diverticulitis in 2008-2014 amounted to approximately € 11.4 million (€ 1.6 million a year), of which € 10.9 million (95.5%) for the hospitalizations, € 246,000 (2.1%) for pharmaceutical treatment and € 270,000 (2.4%) for specialist outpatient services. The cohort analysis estimates an intra-hospital mortality rate equal to 5.9 per 100 patients' year (5.5 for non-surgery patients and 8.9 for surgery patients - P<0.05). Kaplan-Meier curve demonstrate that there were no differences between intra

  17. [Value of the albumin to globulin ratio in predicting severity and prognosis in myasthenia gravis patients].

    PubMed

    Yang, D H; Su, Z Q; Chen, Y; Chen, Z B; Ding, Z N; Weng, Y Y; Li, J; Li, X; Tong, Q L; Han, Y X; Zhang, X

    2016-03-08

    To assess the predictive value of the albumin to globulin ratio (AGR) in evaluation of disease severity and prognosis in myasthenia gravis patients. A total of 135 myasthenia gravis (MG) patients were enrolled between February 2009 and March 2015. The AGR was detected on the first day of hospitalization and ranked from lowest to highest, and the patients were divided into three equal tertiles according to the AGR values, which were T1 (AGR <1.34), T2 (1.34≤AGR≤1.53) and T3 (AGR>1.53). The Kaplan-Meier curve was used to evaluate the prognostic value of AGR. Cox model analysis was used to evaluate the relevant factors. Multivariate Logistic regression analysis was used to find the predictors of myasthenia crisis during hospitalization. The median length of hospital stay for each tertile was: for the T1 21 days (15-35.5), T2 18 days (14-27.5), and T3 16 days (12-22.5) (P<0.01), and Kaplan-Meier curves showed significant difference among the three groups. In the univariate model, serum albumin, creatinine, AGR and MGFA clinical classification were related to prognosis of myasthenia gravis. At the multivariate Cox regression analysis, the AGR (P<0.001) and MGFA clinical classification (P<0.001) were independent predictive factors of disease severity and prognosis in myasthenia gravis patients. Respectively, the hazard ratio (HR) were 4.655 (95% CI: 2.355-9.202) and 0.596 (95% CI: 0.492-0.723). Multivariate Logistic regression analysis showed the AGR (P<0.001) and MGFA clinical classification were related to myasthenia crisis. The AGR may represent a simple, potentially useful predictive biomarker for evaluating the disease severity and prognosis of patients with myasthenia gravis.

  18. A modified TNM staging system for non-metastatic colorectal cancer based on nomogram analysis of SEER database.

    PubMed

    Kong, Xiangxing; Li, Jun; Cai, Yibo; Tian, Yu; Chi, Shengqiang; Tong, Danyang; Hu, Yeting; Yang, Qi; Li, Jingsong; Poston, Graeme; Yuan, Ying; Ding, Kefeng

    2018-01-08

    To revise the American Joint Committee on Cancer TNM staging system for colorectal cancer (CRC) based on a nomogram analysis of Surveillance, Epidemiology, and End Results (SEER) database, and to prove the rationality of enhancing T stage's weighting in our previously proposed T-plus staging system. Total 115,377 non-metastatic CRC patients from SEER were randomly grouped as training and testing set by ratio 1:1. The Nomo-staging system was established via three nomograms based on 1-year, 2-year and 3-year disease specific survival (DSS) Logistic regression analysis of the training set. The predictive value of Nomo-staging system for the testing set was evaluated by concordance index (c-index), likelihood ratio (L.R.) and Akaike information criteria (AIC) for 1-year, 2-year, 3-year overall survival (OS) and DSS. Kaplan-Meier survival curve was used to valuate discrimination and gradient monotonicity. And an external validation was performed on database from the Second Affiliated Hospital of Zhejiang University (SAHZU). Patients with T1-2 N1 and T1N2a were classified into stage II while T4 N0 patients were classified into stage III in Nomo-staging system. Kaplan-Meier survival curves of OS and DSS in testing set showed Nomo-staging system performed better in discrimination and gradient monotonicity, and the external validation in SAHZU database also showed distinctly better discrimination. The Nomo-staging system showed higher value in L.R. and c-index, and lower value in AIC when predicting OS and DSS in testing set. The Nomo-staging system showed better performance in prognosis prediction and the weight of lymph nodes status in prognosis prediction should be cautiously reconsidered.

  19. Dynamic contrast–enhanced magnetic resonance imaging in patients with pulmonary arterial hypertension

    PubMed Central

    Condliffe, Robin; Marshall, Helen; Elliot, Charlie; Kiely, David G.; Wild, Jim M.

    2014-01-01

    Abstract Dynamic contrast–enhanced (DCE) time-resolved magnetic resonance (MR) imaging is a technique whereby the passage of an intravenous contrast bolus can be tracked through the pulmonary vascular system. The aim of this study was to investigate the prognostic significance of DCE-MR pulmonary blood transit times in patients with pulmonary arterial hypertension (PAH). Seventy-nine patients diagnosed with PAH underwent pulmonary DCE imaging at 1.5 T using a time-resolved three-dimensional spoiled gradient echo sequence. The prognostic significance of two DCE parameters, full width at half maximum (FWHM) of the first-pass clearance curve and pulmonary transit time (PTT), along with demographic and invasive catheter measurements, was evaluated by univariate and bivariate Cox proportional hazards regression and Kaplan-Meier analysis. DCE-MR transit times were most closely correlated with cardiac index (CI) and pulmonary vascular resistance index (PVRI) and were both found to be accurate for detecting reduced CI (FWHM area under the curve [AUC] at receiver operating characteristic analysis = 0.91 and PTT AUC = 0.92, respectively) and for detecting elevated PVRI (FWHM AUC = 0.88 and PTT AUC = 0.84, respectively). During the follow-up period, 25 patients died. Patients with longer measurements of FWHM (P = 0.0014) and PTT (P = 0.004) were associated with poor outcome at Kaplan-Meier analysis, and both parameters were strong predictors of adverse outcome from Cox proportional hazards analysis (P = 0.013 and 0.010, respectively). At bivariate analysis, DCE measurements predicted mortality independent of age, gender, and World Health Organization functional class; however, invasive hemodynamic indexes CI, PVRI, and DCE measurements were not independent of one another. In conclusion, DCE-MR transit times predict mortality in patients with PAH and are closely associated with clinical gold standards CI and PVRI. PMID:25006422

  20. Dynamic contrast-enhanced magnetic resonance imaging in patients with pulmonary arterial hypertension.

    PubMed

    Swift, Andrew J; Telfer, Adam; Rajaram, Smitha; Condliffe, Robin; Marshall, Helen; Capener, Dave; Hurdman, Judith; Elliot, Charlie; Kiely, David G; Wild, Jim M

    2014-03-01

    Dynamic contrast-enhanced (DCE) time-resolved magnetic resonance (MR) imaging is a technique whereby the passage of an intravenous contrast bolus can be tracked through the pulmonary vascular system. The aim of this study was to investigate the prognostic significance of DCE-MR pulmonary blood transit times in patients with pulmonary arterial hypertension (PAH). Seventy-nine patients diagnosed with PAH underwent pulmonary DCE imaging at 1.5 T using a time-resolved three-dimensional spoiled gradient echo sequence. The prognostic significance of two DCE parameters, full width at half maximum (FWHM) of the first-pass clearance curve and pulmonary transit time (PTT), along with demographic and invasive catheter measurements, was evaluated by univariate and bivariate Cox proportional hazards regression and Kaplan-Meier analysis. DCE-MR transit times were most closely correlated with cardiac index (CI) and pulmonary vascular resistance index (PVRI) and were both found to be accurate for detecting reduced CI (FWHM area under the curve [AUC] at receiver operating characteristic analysis = 0.91 and PTT AUC = 0.92, respectively) and for detecting elevated PVRI (FWHM AUC = 0.88 and PTT AUC = 0.84, respectively). During the follow-up period, 25 patients died. Patients with longer measurements of FWHM (P = 0.0014) and PTT (P = 0.004) were associated with poor outcome at Kaplan-Meier analysis, and both parameters were strong predictors of adverse outcome from Cox proportional hazards analysis (P = 0.013 and 0.010, respectively). At bivariate analysis, DCE measurements predicted mortality independent of age, gender, and World Health Organization functional class; however, invasive hemodynamic indexes CI, PVRI, and DCE measurements were not independent of one another. In conclusion, DCE-MR transit times predict mortality in patients with PAH and are closely associated with clinical gold standards CI and PVRI.

  1. Red cell distribution width and its association with mortality in neonatal sepsis.

    PubMed

    Martin, Snehal L; Desai, Saumil; Nanavati, Ruchi; Colah, Roshan B; Ghosh, Kanjaksha; Mukherjee, Malay B

    2018-01-08

    Neonatal sepsis is a major cause of mortality in the developing countries. However, with current severity scores and laboratory parameters, predicting outcomes of neonatal sepsis is a serious challenge. Red cell distribution width (RDW) is a readily available pragmatic means to predict outcomes of various comorbidities in adults and children, without causing any additional blood loss. However, its utility in neonates remains unexplored. Hence, the objective of the present study was to evaluate the association of RDW with neonatal sepsis and its role as a predictive marker for mortality. This Prospective observational study was carried out in a Level IIIB NICU for a period of 3 years. It involved comparison of RDW values of septic neonates with those of controls (matched for gestational age and birth weight) with an equal allocation ratio. A total of 251 septic neonates along with 251 controls >28 weeks of gestational age were enrolled. The RDW was derived from complete blood count done within first 6 hours of life. After arranging the RDW (median; interquartile range (IQR)), the values were categorized as those above the 50th percentile i.e. ≥20% and those below the 50th percentile i.e. <20%. The cumulative survival rates of the above two groups were assessed using the Kaplan-Meier curve and the log rank test. RDW levels were significantly higher among the neonatal sepsis cases (19.90%) as compared to the controls (18.90%) with a p value of < .001. RDW was significantly higher amongst the nonsurvivors than survivors (p < .003). Kaplan-Meier curve showed that septic neonates having RDW values ≥20% had significantly increased mortality (p < .02) with a hazard ratio of 0.5. High RDW is associated with neonatal sepsis and is an independent outcome predictor for mortality associated with neonatal sepsis.

  2. Pre-Treatment Anemia Is a Poor Prognostic Factor in Soft Tissue Sarcoma Patients

    PubMed Central

    Szkandera, Joanna; Gerger, Armin; Liegl-Atzwanger, Bernadette; Stotz, Michael; Samonigg, Hellmut; Ploner, Ferdinand; Stojakovic, Tatjana; Leithner, Andreas; Pichler, Martin

    2014-01-01

    Background Anemia refers to low hemoglobin (Hb) levels, represents a common symptom and complication in cancer patients and was reported to negatively influence survival in patients with various malignancies. In the present study, we aimed to explore the prognostic impact of pre-operative Hb levels on clinical outcome in a large cohort of soft tissue sarcoma (STS) patients after curative surgery. Methods Retrospective data from 367 STS patients, which were operated between 1998 and 2013, were included in the study. Cut-off levels for anemia were defined as Hb<13 g/dl in males and Hb<12 g/dl in females according to the current WHO guidelines. The impact of pre-operative Hb levels on cancer-specific survival (CSS) and overall survival (OS) was assessed using Kaplan-Meier curves. Additionally, Hb levels were compared for the prognostic influence on CSS and OS applying univariate and multivariate Cox proportional models. Results Hb level was associated with established prognostic factors, including age, tumor grade, size and depth (p<0.05). Kaplan-Meier curves showed that low Hb levels were significantly associated with decreased CSS and OS in STS patients (p<0.001 for both endpoints, log-rank test). In multivariate analysis, we found an independent association between low Hb levels and poor CSS and OS (HR = 0.46, Cl 95% = 0.25–0.85, p = 0.012; HR = 0.34, Cl 95% = 0.23–0.51, p<0.001). Conclusion The present data underline a negative prognostic impact of low pre-operative Hb levels on clinical outcome in STS patients. Thus, Hb levels may provide an additional and cost-effective tool to discriminate between STS patients that are at high risk of mortality. PMID:25207808

  3. The role of the AMOP domain in MUC4/Y-promoted tumour angiogenesis and metastasis in pancreatic cancer.

    PubMed

    Tang, Jie; Zhu, Yi; Xie, Kunling; Zhang, Xiaoyu; Zhi, Xiaofei; Wang, Weizhi; Li, Zheng; Zhang, Qun; Wang, Linjun; Wang, Jiwei; Xu, Zekuan

    2016-06-10

    MUC4 is a high molecular weight membrane protein that is overexpressed in pancreatic cancer (PC) and is associated with the development and progression of this disease. However, the exact mechanisms through which MUC4 domains promote these biological processes have rarely been studied, partly because of its high molecular weight, difficulty to overexpress it. Here, we use MUC4/Y, one of the MUC4 transcript variants, as a model molecule to investigate the AMOP-domain of MUC4(MUC/Y). We used cell proliferation, migration, invasion and tube formation assays in vitro to explore the abilities of AMOP domain in PC. In vivo, the matrigel plug assay, orthotopic implantation and Kaplan-Meier survival curves were used to check the results we observed in vitro. Finally, we discovered the underlying mechanism through western blot and immunofluorescence. We found that MUC4/Y overexpression could enhance the angiogenic and metastatic properties of PC cells, both in vitro and in vivo. However, the deletion of AMOP domain could cutback these phenomena. Additionally, Kaplan-Meier survival curves showed that mice injected with MUC4/Y overexpressed cells had shorter survival time, compared with empty-vector-transfected cells (MUC4/Y-EV), or cells expressing MUC4/Y without the AMOP domain (MUC4/Y-AMOP(△)). Our data also showed that overexpression of MUC4/Y could activate NOTCH3 signaling, increasing the expression of downstream genes: VEGF-A, MMP-9 and ANG-2. The AMOP domain had an important role in MUC4/Y (MUC4)-mediated tumour angiogenesis and metastasis of PC cells; and the NOTCH3 signaling was involved. These findings provided new insights into PC therapies. Our study also supplies a new method to study other high molecular membrane proteins.

  4. Coronary artery bypass surgery: are outcomes influenced by demographics or ability to pay?

    PubMed

    Mancini, M C; Cush, E M; Sweatman, K; Dansby, J

    2001-05-01

    To examine the relation of financial status and demographics to the outcomes of coronary artery bypass surgery (CABG) in the public hospital setting. Coronary artery bypass surgery is one of the most expensive and frequently performed surgical procedures in the United States. Considerable controversy surrounds the accessibility to quality cardiac care of indigent and minority populations. This study examines the hypothesis that demographics rather than access to care and economics influences outcomes in CABG. A retrospective review of 1,556 charts of patients who underwent CABG at Louisiana State University Health Sciences Center-Shreveport, a public hospital, during a 10-year period was performed. The parameters analyzed included sex, age, race, education, ejection fraction, comorbidities, surgical parameters, economics, complications, and cost of care. Comparisons were made between the insured and uninsured groups. Univariate statistical analysis was used to assess differences between groups. Kaplan-Meier survival curves were also generated. Two thirds of the patients were uninsured. The mean age of the uninsured patients was significantly lower than that of the insured patients. Ejection fractions were comparable. Comorbidities were similar, with a greater percentage of tobacco use in the uninsured population. Kaplan-Meier survival curves showed that the uninsured group had better overall survival and that the insured group manifested an increased rate of late death. The financially challenged population appears to present for treatment earlier in life with coronary artery disease. Risk factors between the two groups were similar, except that tobacco use appears to be a significant problem in the disadvantaged population. The disease severity in both populations appeared to be similar; however, the uninsured patients had equivalent early survival with better late survival. Access to care in both groups was equal. In the public hospital setting for the disease

  5. Mixture models for undiagnosed prevalent disease and interval-censored incident disease: applications to a cohort assembled from electronic health records.

    PubMed

    Cheung, Li C; Pan, Qing; Hyun, Noorie; Schiffman, Mark; Fetterman, Barbara; Castle, Philip E; Lorey, Thomas; Katki, Hormuzd A

    2017-09-30

    For cost-effectiveness and efficiency, many large-scale general-purpose cohort studies are being assembled within large health-care providers who use electronic health records. Two key features of such data are that incident disease is interval-censored between irregular visits and there can be pre-existing (prevalent) disease. Because prevalent disease is not always immediately diagnosed, some disease diagnosed at later visits are actually undiagnosed prevalent disease. We consider prevalent disease as a point mass at time zero for clinical applications where there is no interest in time of prevalent disease onset. We demonstrate that the naive Kaplan-Meier cumulative risk estimator underestimates risks at early time points and overestimates later risks. We propose a general family of mixture models for undiagnosed prevalent disease and interval-censored incident disease that we call prevalence-incidence models. Parameters for parametric prevalence-incidence models, such as the logistic regression and Weibull survival (logistic-Weibull) model, are estimated by direct likelihood maximization or by EM algorithm. Non-parametric methods are proposed to calculate cumulative risks for cases without covariates. We compare naive Kaplan-Meier, logistic-Weibull, and non-parametric estimates of cumulative risk in the cervical cancer screening program at Kaiser Permanente Northern California. Kaplan-Meier provided poor estimates while the logistic-Weibull model was a close fit to the non-parametric. Our findings support our use of logistic-Weibull models to develop the risk estimates that underlie current US risk-based cervical cancer screening guidelines. Published 2017. This article has been contributed to by US Government employees and their work is in the public domain in the USA. Published 2017. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

  6. Rediscovery of Trust: Erikson, Kaplan, and the Myth of Foster Care.

    ERIC Educational Resources Information Center

    Ocasio, Jeannette; Knight, Janette

    Trust, in much the same way as hope, represents one of the essential components of a healthy upbringing. This article investigates the concept of trust as set forth in Eric Erikson's and Louise Kaplan's theories of basic trust, with particular emphasis on definition and development. The article analyzes some of the criteria that have been…

  7. A cyclostationary multi-domain analysis of fluid instability in Kaplan turbines

    NASA Astrophysics Data System (ADS)

    Pennacchi, P.; Borghesani, P.; Chatterton, S.

    2015-08-01

    Hydraulic instabilities represent a critical problem for Francis and Kaplan turbines, reducing their useful life due to increase of fatigue on the components and cavitation phenomena. Whereas an exhaustive list of publications on computational fluid-dynamic models of hydraulic instability is available, the possibility of applying diagnostic techniques based on vibration measurements has not been investigated sufficiently, also because the appropriate sensors seldom equip hydro turbine units. The aim of this study is to fill this knowledge gap and to exploit fully, for this purpose, the potentiality of combining cyclostationary analysis tools, able to describe complex dynamics such as those of fluid-structure interactions, with order tracking procedures, allowing domain transformations and consequently the separation of synchronous and non-synchronous components. This paper will focus on experimental data obtained on a full-scale Kaplan turbine unit, operating in a real power plant, tackling the issues of adapting such diagnostic tools for the analysis of hydraulic instabilities and proposing techniques and methodologies for a highly automated condition monitoring system.

  8. Increased Prognostic Value of Query Amyloid Late Enhancement Score in Light-Chain Cardiac Amyloidosis.

    PubMed

    Wan, Ke; Sun, Jiayu; Han, Yuchi; Liu, Hong; Yang, Dan; Li, Weihao; Wang, Jie; Cheng, Wei; Zhang, Qing; Zeng, Zhi; Chen, Yucheng

    2018-02-23

    Late gadolinium enhancement (LGE) pattern is a powerful imaging biomarker for prognosis of cardiac amyloidosis. It is unknown if the query amyloid late enhancement (QALE) score in light-chain (AL) amyloidosis could provide increased prognostic value compared with LGE pattern.Methods and Results:Seventy-eight consecutive patients with AL amyloidosis underwent contrast-enhanced cardiovascular magnetic resonance imaging. Patients with cardiac involvement were grouped by LGE pattern and analyzed using QALE score. Receiver operating characteristic curve was used to identify the optimal cut-off for QALE score in predicting all-cause mortality. Survival of these patients was analyzed with the Kaplan-Meier method and multivariate Cox regression. During a median follow-up of 34 months, 53 of 78 patients died. The optimal cut-off for QALE score to predict mortality at 12-month follow-up was 9.0. On multivariate Cox analysis, QALE score ≥9 (HR, 5.997; 95% CI: 2.665-13.497; P<0.001) and log N-terminal pro-brain natriuretic peptide (HR, 1.525; 95% CI: 1.112-2.092; P=0.009) were the only 2 independent predictors of all-cause mortality. On Kaplan-Meier analysis, patients with subendocardial LGE can be further risk stratified using QALE score ≥9. The QALE scoring system provides powerful independent prognostic value in AL cardiac amyloidosis. QALE score ≥9 has added value to differentiate prognosis in AL amyloidosis patients with a subendocardial LGE pattern.

  9. High lncRNA H19 expression as prognostic indicator: data mining in female cancers and polling analysis in non-female cancers.

    PubMed

    Peng, Li; Yuan, Xiao-Qing; Liu, Zhao-Yang; Li, Wen-Ling; Zhang, Chao-Yang; Zhang, Ya-Qin; Pan, Xi; Chen, Jun; Li, Yue-Hui; Li, Guan-Cheng

    2017-01-03

    Upregulation of lncRNA H19 expression is associated with an unfavorable prognosis in some cancers. However, the prognostic value of H19 in female-specific cancers has remained uncharacterized. In this study, the prognostic power of high H19 expression in female cancer patients from the TCGA datasets was analyzed using Kaplan-Meier survival curves and Cox's proportional hazard modeling. In addition, in a meta-analysis of non-female cancer patients from TCGA datasets and 12 independent studies, hazard ratios (HRs) with 95% confidence interval (CI) for overall survival (OS) and disease-free survival (DFS)/relapse-free survival (RFS)/metastasis-free survival (MFS)/progression-free survival (PFS) were pooled to assess the prognostic value of high H19 expression. Kaplan-Meier analysis revealed that patients with uterine corpus cancer and higher H19 expression had a shorter OS (HR=2.710, p<0.05), while females with cervical cancer and increased H19 expression had a shorter RFS (HR=2.261, p<0.05). Multivariate Cox regression analysis showed that high H19 expression could independently predict a poorer prognosis in cervical cancer patients (HR=4.099, p<0.05). In the meta-analysis, patients with high H19 expression showed a poorer outcome in non-female cancer (p<0.05). These results suggest that high lncRNA H19 expression is predictive of an unfavorable prognosis in two female cancers (uterine corpus endometrioid cancer and cervical cancer) as well as in non-female cancer patients.

  10. On the importance of accounting for competing risks in pediatric cancer trials designed to delay or avoid radiotherapy: I. Basic concepts and first analyses.

    PubMed

    Tai, Bee-Choo; Grundy, Richard G; Machin, David

    2010-04-01

    In trials designed to delay or avoid irradiation among children with malignant brain tumor, although irradiation after disease progression is an important event, patients who have disease progression may decline radiotherapy (RT), or those without disease progression may opt for elective RT. To accurately describe the cumulative need for RT in such instances, it is crucial to account for these distinct events and to evaluate how each contributes to the delay or advancement of irradiation via a competing risks analysis. We describe the summary of competing events in such trials using competing risks methods based on cumulative incidence functions and Gray's test. The results obtained are contrasted with standard survival methods based on Kaplan-Meier curves, cause-specific hazard functions and log-rank test. The Kaplan-Meier method overestimates all event-specific rates. The cause-specific hazard analysis showed reduction in hazards for all events (A: RT after progression; B: no RT after progression; C: elective RT) among children with ependymoma. For event A, a higher cumulative incidence was reported for ependymoma. Although Gray's test failed to detect any difference (p = 0.331) between histologic subtypes, the log-rank test suggested marginal evidence (p = 0.057). Similarly, for event C, the log-rank test found stronger evidence of reduction in hazard among those with ependymoma (p = 0.005) as compared with Gray's test (p = 0.086). To evaluate treatment differences, failing to account for competing risks using appropriate methodology may lead to incorrect interpretations.

  11. The preoperative plasma fibrinogen level is an independent prognostic factor for overall survival of breast cancer patients who underwent surgical treatment.

    PubMed

    Wen, Jiahuai; Yang, Yanning; Ye, Feng; Huang, Xiaojia; Li, Shuaijie; Wang, Qiong; Xie, Xiaoming

    2015-12-01

    Previous studies have suggested that plasma fibrinogen contributes to tumor cell proliferation, progression and metastasis. The current study was performed to evaluate the prognostic relevance of preoperative plasma fibrinogen in breast cancer patients. Data of 2073 consecutive breast cancer patients, who underwent surgery between January 2002 and December 2008 at the Sun Yat-sen University Cancer Center, were retrospectively evaluated. Plasma fibrinogen levels were routinely measured before surgeries. Participants were grouped by the cutoff value estimated by the receiver operating characteristic (ROC) curve analysis. Overall survival (OS) was assessed using Kaplan-Meier analysis, and multivariate Cox proportional hazards regression model was performed to evaluate the independent prognostic value of plasma fibrinogen level. The optimal cutoff value of preoperative plasma fibrinogen was determined to be 2.83 g/L. The Kaplan-Meier analysis showed that patients with high fibrinogen levels had shorter OS than patients with low fibrinogen levels (p < 0.001). Multivariate analysis suggested preoperative plasma fibrinogen as an independent prognostic factor for OS in breast cancer patients (HR = 1.475, 95% confidence interval (CI): 1.177-1.848, p = 0.001). Subgroup analyses revealed that plasma fibrinogen level was an unfavorable prognostic parameter in stage II-III, Luminal subtypes and triple-negative breast cancer patients. Elevated preoperative plasma fibrinogen was independently associated with poor prognosis in breast cancer patients and may serve as a valuable parameter for risk assessment in breast cancer patients. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Further delineation of the ear, patella, short stature syndrome (Meier-Gorlin syndrome).

    PubMed

    Boles, R G; Teebi, A S; Schwartz, D; Harper, J F

    1994-07-01

    Two daughters of phenotypically normal parents are described with severe proportional dwarfism with microcephaly, peculiar craniofacial anomalies, microtia, absent patellae, joint hyperextensibility, and other anomalies. Intrafamilial variability is minimal. This combination of anomalies has many similarities to the six cases previously described with the Ear, Patellae, Short stature syndrome (Meier-Gorlin syndrome), which is distinguished by the triad of microtia, absent patellae and growth retardation. Autosomal recessive inheritance is strongly suggested by the presence of two pairs of affected siblings and the equal sex ratio.

  13. Air injection test on a Kaplan turbine: prototype - model comparison

    NASA Astrophysics Data System (ADS)

    Angulo, M.; Rivetti, A.; Díaz, L.; Liscia, S.

    2016-11-01

    Air injection is a very well-known resource to reduce pressure pulsation magnitude in turbines, especially on Francis type. In the case of large Kaplan designs, even when not so usual, it could be a solution to mitigate vibrations arising when tip vortex cavitation phenomenon becomes erosive and induces structural vibrations. In order to study this alternative, aeration tests were performed on a Kaplan turbine at model and prototype scales. The research was focused on efficiency of different air flow rates injected in reducing vibrations, especially at the draft tube and the discharge ring and also in the efficiency drop magnitude. It was found that results on both scales presents the same trend in particular for vibration levels at the discharge ring. The efficiency drop was overestimated on model tests while on prototype were less than 0.2 % for all power output. On prototype, air has a beneficial effect in reducing pressure fluctuations up to 0.2 ‰ of air flow rate. On model high speed image computing helped to quantify the volume of tip vortex cavitation that is strongly correlated with the vibration level. The hydrophone measurements did not capture the cavitation intensity when air is injected, however on prototype, it was detected by a sonometer installed at the draft tube access gallery.

  14. A Bayesian CUSUM plot: Diagnosing quality of treatment.

    PubMed

    Rosthøj, Steen; Jacobsen, Rikke-Line

    2017-12-01

    To present a CUSUM plot based on Bayesian diagnostic reasoning displaying evidence in favour of "healthy" rather than "sick" quality of treatment (QOT), and to demonstrate a technique using Kaplan-Meier survival curves permitting application to case series with ongoing follow-up. For a case series with known final outcomes: Consider each case a diagnostic test of good versus poor QOT (expected vs. increased failure rates), determine the likelihood ratio (LR) of the observed outcome, convert LR to weight taking log to base 2, and add up weights sequentially in a plot showing how many times odds in favour of good QOT have been doubled. For a series with observed survival times and an expected survival curve: Divide the curve into time intervals, determine "healthy" and specify "sick" risks of failure in each interval, construct a "sick" survival curve, determine the LR of survival or failure at the given observation times, convert to weights, and add up. The Bayesian plot was applied retrospectively to 39 children with acute lymphoblastic leukaemia with completed follow-up, using Nordic collaborative results as reference, showing equal odds between good and poor QOT. In the ongoing treatment trial, with 22 of 37 children still at risk for event, QOT has been monitored with average survival curves as reference, odds so far favoring good QOT 2:1. QOT in small patient series can be assessed with a Bayesian CUSUM plot, retrospectively when all treatment outcomes are known, but also in ongoing series with unfinished follow-up. © 2017 John Wiley & Sons, Ltd.

  15. [Usage of Calendula officinalis in the prevention and treatment of radiodermatitis: a randomized double-blind controlled clinical trial].

    PubMed

    Schneider, Franciane; Danski, Mitzy Tannia Reichembach; Vayego, Stela Adami

    2015-04-01

    To evaluate the efficacy of Calendula officinalis in relation to Essential Fatty Acids for the prevention and treatment of radiodermatitis. This is a randomized double-blind controlled clinical trial with 51 patients with head and neck cancer in radiotherapy treatment divided into two groups: control (27) and experimental (24). There is statistically significant evidence (p-value = 0.0120) that the proportion of radiodermatitis grade 2 in Essential Fatty Acids group is higher than Calendula group. Through the Kaplan-Meier survival curve we observed that Essential Fatty Acids group has always remained below the Calendula group survival curve, due to the lower risk of developing radiodermatitis grade 1, which makes the usage of Calendula more effective, with statistical significance (p-value = 0.00402). Calendula showed better therapeutic response than the Essential Fatty Acids in the prevention and treatment of radiodermatitis. Brazilian Registry of Clinical Trials: RBR-237v4b.

  16. Using the weighted area under the net benefit curve for decision curve analysis.

    PubMed

    Talluri, Rajesh; Shete, Sanjay

    2016-07-18

    Risk prediction models have been proposed for various diseases and are being improved as new predictors are identified. A major challenge is to determine whether the newly discovered predictors improve risk prediction. Decision curve analysis has been proposed as an alternative to the area under the curve and net reclassification index to evaluate the performance of prediction models in clinical scenarios. The decision curve computed using the net benefit can evaluate the predictive performance of risk models at a given or range of threshold probabilities. However, when the decision curves for 2 competing models cross in the range of interest, it is difficult to identify the best model as there is no readily available summary measure for evaluating the predictive performance. The key deterrent for using simple measures such as the area under the net benefit curve is the assumption that the threshold probabilities are uniformly distributed among patients. We propose a novel measure for performing decision curve analysis. The approach estimates the distribution of threshold probabilities without the need of additional data. Using the estimated distribution of threshold probabilities, the weighted area under the net benefit curve serves as the summary measure to compare risk prediction models in a range of interest. We compared 3 different approaches, the standard method, the area under the net benefit curve, and the weighted area under the net benefit curve. Type 1 error and power comparisons demonstrate that the weighted area under the net benefit curve has higher power compared to the other methods. Several simulation studies are presented to demonstrate the improvement in model comparison using the weighted area under the net benefit curve compared to the standard method. The proposed measure improves decision curve analysis by using the weighted area under the curve and thereby improves the power of the decision curve analysis to compare risk prediction models in

  17. Wisconsin's BadgerCare Plus reform: impact on low-income families' enrollment and retention in public coverage.

    PubMed

    Leininger, Lindsey Jeanne; Friedsam, Donna; Dague, Laura; Mok, Shannon; Hynes, Emma; Bergum, Alison; Aksamitauskas, Milda; Oliver, Thomas; DeLeire, Thomas

    2011-02-01

    To examine the impact of a Wisconsin health care reform enacted in early 2008 on public insurance enrollment and retention. Administrative data covering the period January 2007 to November 2009. We calculate unadjusted enrollment trends and exit rates stratified by age, income group, and enrollment mode. Kaplan-Meier curves and Cox proportional hazards models are estimated to assess the impact of the reform on program exits. Overall enrollment increased by approximately one-third and exit rates decreased by approximately one-fifth. The majority of new enrollment came from the previously income eligible. Wisconsin's enactment of eligibility expansions coupled with administrative simplification and targeted marketing and outreach efforts were successful in enrolling and retaining low-income children and families in public coverage. © Health Research and Educational Trust.

  18. Item response theory analyses of the Delis-Kaplan Executive Function System card sorting subtest.

    PubMed

    Spencer, Mercedes; Cho, Sun-Joo; Cutting, Laurie E

    2018-02-02

    In the current study, we examined the dimensionality of the 16-item Card Sorting subtest of the Delis-Kaplan Executive Functioning System assessment in a sample of 264 native English-speaking children between the ages of 9 and 15 years. We also tested for measurement invariance for these items across age and gender groups using item response theory (IRT). Results of the exploratory factor analysis indicated that a two-factor model that distinguished between verbal and perceptual items provided the best fit to the data. Although the items demonstrated measurement invariance across age groups, measurement invariance was violated for gender groups, with two items demonstrating differential item functioning for males and females. Multigroup analysis using all 16 items indicated that the items were more effective for individuals whose IRT scale scores were relatively high. A single-group explanatory IRT model using 14 non-differential item functioning items showed that for perceptual ability, females scored higher than males and that scores increased with age for both males and females; for verbal ability, the observed increase in scores across age differed for males and females. The implications of these findings are discussed.

  19. Going Large or Going Small in Plant Design: Comparison between a P.P. with three small Kaplan turbines and a P.P. with just one Large Kaplan turbine

    NASA Astrophysics Data System (ADS)

    Castro-Otero, C.

    2017-04-01

    Very often small turbine manufacturers are requested to produce sizeable turbines, too large in terms of physical dimensions, power or designing capacity. In these cases clever alternative solutions should be found to meet customers’ needs. For instance: in the old times twin runner Francis turbines were an option instead of one large machine, or if a too large Pelton turbine cannot be manufactured or designed, a good option is to install a medium size Francis and a small Pelton. Likewise, a similar approach needs to be taken should the manufacturer be asked for a too large Kaplan. Facing this situation a good option is to install three or more small Kaplan turbines. This particular case was studied in depth and after all the considerations had been made, the following question arouse: Is this a way out for the manufacturer or is it really the best option for the customer? The choice made as a way out for the manufacturer became the best option for the customer and a success for both parties. This paper aims to encourage developers and engineering firms to search for more options than the traditional one to find the best option in plant design.

  20. External validation of a Cox prognostic model: principles and methods

    PubMed Central

    2013-01-01

    Background A prognostic model should not enter clinical practice unless it has been demonstrated that it performs a useful role. External validation denotes evaluation of model performance in a sample independent of that used to develop the model. Unlike for logistic regression models, external validation of Cox models is sparsely treated in the literature. Successful validation of a model means achieving satisfactory discrimination and calibration (prediction accuracy) in the validation sample. Validating Cox models is not straightforward because event probabilities are estimated relative to an unspecified baseline function. Methods We describe statistical approaches to external validation of a published Cox model according to the level of published information, specifically (1) the prognostic index only, (2) the prognostic index together with Kaplan-Meier curves for risk groups, and (3) the first two plus the baseline survival curve (the estimated survival function at the mean prognostic index across the sample). The most challenging task, requiring level 3 information, is assessing calibration, for which we suggest a method of approximating the baseline survival function. Results We apply the methods to two comparable datasets in primary breast cancer, treating one as derivation and the other as validation sample. Results are presented for discrimination and calibration. We demonstrate plots of survival probabilities that can assist model evaluation. Conclusions Our validation methods are applicable to a wide range of prognostic studies and provide researchers with a toolkit for external validation of a published Cox model. PMID:23496923

  1. Gamma Knife radiosurgery for intracranial hemangioblastoma.

    PubMed

    Silva, Danilo; Grabowski, Mathew M; Juthani, Rupa; Sharma, Mayur; Angelov, Lilyana; Vogelbaum, Michael A; Chao, Samuel; Suh, John; Mohammadi, Alireza; Barnett, Gene H

    2016-09-01

    Gamma knife radiosurgery (GKRS) has become a treatment option for intracranial hemangioblastomas, especially in patients with poor clinical status and also high-risk surgical candidates. The objective of this study was to analyze clinical outcome and tumor control rates. Retrospective chart review revealed 12 patients with a total of 20 intracranial hemangioblastomas treated with GKRS from May 1998 until December 2014. Kaplan-Meier plots were used to calculate the actuarial local tumor control rates and rate of recurrence following GKRS. Univariate analysis, including log rank test and Wilcoxon test were used on the Kaplan-Meier plots to evaluate the predictors of tumor progression. Two-tailed p value of <0.05 was considered as significant. Median follow-up was 64months (2-184). Median tumor volume pre-GKRS was 946mm(3) (79-15970), while median tumor volume post-GKRS was 356mm(3) (30-5404). Complications were seen in two patients. Tumor control rates were 100% at 1year, 90% at 3years, and 85% at 5years, using the Kaplan-Meier method. There were no statistically significant univariate predictors of progression identified, although there was a trend towards successful tumor control in solid tumors (p=0.07). GKRS is an effective and safe option for treating intracranial hemangioblastoma with favorable tumor control rates. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. High lncRNA H19 expression as prognostic indicator: data mining in female cancers and polling analysis in non-female cancers

    PubMed Central

    Peng, Li; Liu, Zhao-Yang; Li, Wen-Ling; Zhang, Chao-Yang; Zhang, Ya-Qin; Pan, Xi; Chen, Jun; Li, Yue-Hui

    2017-01-01

    Upregulation of lncRNA H19 expression is associated with an unfavorable prognosis in some cancers. However, the prognostic value of H19 in female-specific cancers has remained uncharacterized. In this study, the prognostic power of high H19 expression in female cancer patients from the TCGA datasets was analyzed using Kaplan-Meier survival curves and Cox's proportional hazard modeling. In addition, in a meta-analysis of non-female cancer patients from TCGA datasets and 12 independent studies, hazard ratios (HRs) with 95% confidence interval (CI) for overall survival (OS) and disease-free survival (DFS)/relapse-free survival (RFS)/metastasis-free survival (MFS)/progression-free survival (PFS) were pooled to assess the prognostic value of high H19 expression. Kaplan-Meier analysis revealed that patients with uterine corpus cancer and higher H19 expression had a shorter OS (HR=2.710, p<0.05), while females with cervical cancer and increased H19 expression had a shorter RFS (HR=2.261, p<0.05). Multivariate Cox regression analysis showed that high H19 expression could independently predict a poorer prognosis in cervical cancer patients (HR=4.099, p<0.05). In the meta-analysis, patients with high H19 expression showed a poorer outcome in non-female cancer (p<0.05). These results suggest that high lncRNA H19 expression is predictive of an unfavorable prognosis in two female cancers (uterine corpus endometrioid cancer and cervical cancer) as well as in non-female cancer patients. PMID:27926484

  3. Graft survival of diabetic versus nondiabetic donor tissue after initial keratoplasty.

    PubMed

    Vislisel, Jesse M; Liaboe, Chase A; Wagoner, Michael D; Goins, Kenneth M; Sutphin, John E; Schmidt, Gregory A; Zimmerman, M Bridget; Greiner, Mark A

    2015-04-01

    To compare corneal graft survival using tissue from diabetic and nondiabetic donors in patients undergoing initial Descemet stripping automated endothelial keratoplasty (DSAEK) or penetrating keratoplasty (PKP). A retrospective chart review of pseudophakic eyes that underwent DSAEK or PKP was performed. The primary outcome measure was graft failure. Cox proportional hazard regression and Kaplan-Meier survival analyses were used to compare diabetic versus nondiabetic donor tissue for all keratoplasty cases. A total of 183 eyes (136 DSAEK, 47 PKP) were included in the statistical analysis. Among 24 procedures performed using diabetic donor tissue, there were 4 cases (16.7%) of graft failure (3 DSAEK, 1 PKP), and among 159 procedures performed using nondiabetic donor tissue, there were 18 cases (11.3%) of graft failure (12 DSAEK, 6 PKP). Cox proportional hazard ratio of graft failure for all cases comparing diabetic with nondiabetic donor tissue was 1.69, but this difference was not statistically significant (95% confidence interval, 0.56-5.06; P = 0.348). There were no significant differences in Kaplan-Meier curves comparing diabetic with nondiabetic donor tissue for all cases (P = 0.380). Statistical analysis of graft failure by donor diabetes status within each procedure type was not possible because of the small number of graft failure events involving diabetic tissue. We found similar rates of graft failure in all keratoplasty cases when comparing tissue from diabetic and nondiabetic donors, but further investigation is needed to determine whether diabetic donor tissue results in different graft failure rates after DSAEK compared with PKP.

  4. The prognostic value of preoperative inflammation-based prognostic scores and nutritional status for overall survival in resected patients with nonmetastatic Siewert type II/III adenocarcinoma of esophagogastric junction.

    PubMed

    Zhang, Lixiang; Su, Yezhou; Chen, Zhangming; Wei, Zhijian; Han, Wenxiu; Xu, Aman

    2017-07-01

    Immune and nutritional status of patients have been reported to predict postoperative complications, recurrence, and prognosis of patients with cancer. Therefore, this retrospective study aimed to explore the prognostic value of preoperative inflammation-based prognostic scores [neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR)] and nutritional status [prognostic nutritional index (PNI), body mass index (BMI), hemoglobin, albumin, and prealbumin] for overall survival (OS) in adenocarcinoma of esophagogastric junction (AEG) patients. A total of 355 patients diagnosed with Siewert type II/III AEG and underwent surgery between October 2010 and December 2011 were followed up until October 2016. Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff values of NLR, PLR, and PNI. Kaplan-Meier curves and Cox regression analyses were used to calculate the OS characteristics. The ideal cutoff values for predicting OS were 3.5 for NLR, 171 for PLR, and 51.3 for PNI according to the ROC curve. The patients with hemoglobin <120 g/L (P = .001), prealbumin <180 mg/L (P = .000), PNI <51.3 (P = .010), NLR >3.5 (P = .000), PLR >171 (P = .006), and low BMI group (P = .000) had shorter OS. And multivariate survival analysis using the Cox proportional hazards model showed that the tumor-node-metastasis stage, BMI, NLR, and prealbumin levels were independent risk factors for the OS. Our study demonstrated that preoperative prealbumin, BMI, and NLR were independent prognostic factors of AEG patients.

  5. Censoring approach to the detection limits in X-ray fluorescence analysis

    NASA Astrophysics Data System (ADS)

    Pajek, M.; Kubala-Kukuś, A.

    2004-10-01

    We demonstrate that the effect of detection limits in the X-ray fluorescence analysis (XRF), which limits the determination of very low concentrations of trace elements and results in appearance of the so-called "nondetects", can be accounted for using the statistical concept of censoring. More precisely, the results of such measurements can be viewed as the left random censored data, which can further be analyzed using the Kaplan-Meier method correcting the data for the presence of nondetects. Using this approach, the results of measured, detection limit censored concentrations can be interpreted in a nonparametric manner including the correction for the nondetects, i.e. the measurements in which the concentrations were found to be below the actual detection limits. Moreover, using the Monte Carlo simulation technique we show that by using the Kaplan-Meier approach the corrected mean concentrations for a population of the samples can be estimated within a few percent uncertainties with respect of the simulated, uncensored data. This practically means that the final uncertainties of estimated mean values are limited in fact by the number of studied samples and not by the correction procedure itself. The discussed random-left censoring approach was applied to analyze the XRF detection-limit-censored concentration measurements of trace elements in biomedical samples.

  6. Flight demonstrations of curved, descending approaches and automatic landings using time referenced scanning beam guidance

    NASA Technical Reports Server (NTRS)

    White, W. F. (Compiler)

    1978-01-01

    The Terminal Configured Vehicle (TCV) program operates a Boeing 737 modified to include a second cockpit and a large amount of experimental navigation, guidance and control equipment for research on advanced avionics systems. Demonstration flights to include curved approaches and automatic landings were tracked by a phototheodolite system. For 50 approaches during the demonstration flights, the following results were obtained: the navigation system, using TRSB guidance, delivered the aircraft onto the 3 nautical mile final approach leg with an average overshoot of 25 feet past centerline, subjet to a 2-sigma dispersion of 90 feet. Lateral tracking data showed a mean error of 4.6 feet left of centerline at the category 1 decision height (200 feet) and 2.7 feet left of centerline at the category 2 decision height (100 feet). These values were subject to a sigma dispersion of about 10 feet. Finally, the glidepath tracking errors were 2.5 feet and 3.0 feet high at the category 1 and 2 decision heights, respectively, with a 2 sigma value of 6 feet.

  7. Clinical outcomes in patients with node-negative breast cancer treated based on the recurrence score results: evidence from a large prospectively designed registry.

    PubMed

    Stemmer, Salomon M; Steiner, Mariana; Rizel, Shulamith; Soussan-Gutman, Lior; Ben-Baruch, Noa; Bareket-Samish, Avital; Geffen, David B; Nisenbaum, Bella; Isaacs, Kevin; Fried, Georgeta; Rosengarten, Ora; Uziely, Beatrice; Svedman, Christer; McCullough, Debbie; Maddala, Tara; Klang, Shmuel H; Zidan, Jamal; Ryvo, Larisa; Kaufman, Bella; Evron, Ella; Karminsky, Natalya; Goldberg, Hadassah; Shak, Steven; Liebermann, Nicky

    2017-01-01

    The 21-gene Recurrence Score® (RS) assay is a validated prognostic/predictive tool in ER + early-stage breast cancer. However, clinical outcome data from prospective studies in RS ≥ 11 patients are lacking, as are relevant real-life clinical practice data. In this retrospective analysis of a prospectively designed registry, we evaluated treatments/clinical outcomes in patients undergoing RS-testing through Clalit Health Services. The analysis included N0 ER + HER2-negative breast cancer patients who were RS-tested from 1/2006 through 12/2010. Medical records were reviewed to verify treatments/recurrences/survival. The cohort included 1801 patients (median follow-up, 6.2 years). Median age was 60 years, 50.4% were grade 2 and 81.1% had invasive ductal carcinoma; 48.9% had RS < 18, 40.7% RS 18-30, and 10.4% RS ≥ 31, with chemotherapy use of 1.4, 23.7, and 87.2%, respectively. The 5-year Kaplan-Meier estimates for distant recurrence were 0.8, 3.0, and 8.6%, for patients with RS < 18, RS 18-30 and RS ≥ 31, respectively; the corresponding 5-year Kaplan-Meier estimates for breast cancer death were 0.0, 0.9, and 6.2%. Chemotherapy-untreated patients with RS < 11 ( n  = 304) and 11-25 ( n  = 1037) (TAILORx categorizatio n ) had 5-year Kaplan-Meier estimates for distant recurrence risk/breast cancer death of 1.0%/0.0% and 1.3%/0.4%, respectively. Our results extend those of the prospective TAILORx trial: the 5-year Kaplan-Meier estimates for distant recurrence and breast cancer death rate for the RS < 18 patients were very low supporting the use of endocrine therapy alone. Furthermore, in chemotherapy-untreated patients with RS 11-25 (where TAILORx patients were randomized to chemoendocrine or endocrine therapy alone), 5-year distant recurrence rates were also very low, suggesting that chemotherapy would not have conferred clinically meaningful benefit.

  8. Analyzing hydro abrasive erosion in Kaplan turbine: A case study from India

    NASA Astrophysics Data System (ADS)

    Rai, Anant Kr.; Kumar, Arun

    2016-10-01

    Sediment flow through hydro turbine causes erosion of hydraulic components resulting in drop of turbine efficiency, particularly in hydropower plants of the Himalayan region. The measurement of erosion and monitoring of sediment flow in turbine are major concerns in erosion study. Attempts have been made to study erosion mainly in Pelton and Francis turbines. In this study, a simple and effective method has been presented to measure erosion in a Kaplan turbine of a run-of-river scheme Chilla hydropower plant in foothills of Himalaya. Recent techniques were used to measure sediment parameters like concentration, size, shape and mineral content. A standard erosion model is applied to estimate the erosion in Kaplan turbine blade, runner chamber and draft tube cone. A calibration factor has been proposed to apply the erosion model for site specific conditions. It has been found that the outer trailing edges of the turbine blade and upper runner chamber are most erosion prone zones. Sediment analysis revealed that effective operation can reduce erosion in turbine components. The estimated erosion values from model are found to be consistent with measured values. Finally, suggestions for design improvements and effective operation of erosion affected hydropower plants are given.

  9. 18F-Fluorodeoxyglucose PET/CT and dynamic contrast-enhanced MRI as imaging biomarkers in malignant pleural mesothelioma.

    PubMed

    Hall, David O; Hooper, Clare E; Searle, Julie; Darby, Michael; White, Paul; Harvey, John E; Braybrooke, Jeremy P; Maskell, Nick A; Masani, Vidan; Lyburn, Iain D

    2018-02-01

    The purpose of this study was to compare the use of fluorine-18-fluorodeoxyglucose (F-FDG) PET with computed tomography (CT) and dynamic contrast-enhanced (DCE) MRI to predict prognosis and monitor treatment in malignant pleural mesothelioma. F-FDG PET/CT and DCE-MRI studies carried out as part of the South West Area Mesothelioma Pemetrexed trial were used. F-FDG PET/CT and DCE-MRI studies were carried out before treatment, and after two cycles of chemotherapy, on patients treated with pemetrexed and cisplatin. A total of 73 patients were recruited, of whom 65 had PET/CT and DCE-MRI scans. Baseline measurements from F-FDG PET/CT (maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis) and DCE-MRI (integrated area under the first 90s of the curve and washout slope) were compared with overall survival (OS) using Kaplan-Meier and Cox regression analyses, and changes in imaging measurements were compared with disease progression. PET/CT and DCE-MRI measurements were not correlated with each other. Maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis were significantly related to OS with Cox regression analysis and Kaplan-Meir analysis, and DCE-MRI washout curve shape was significantly related to OS. DCE-MRI curve shape can be combined with F-FDG PET/CT to give additional prognostic information. Changes in measurements were not related to progression-free survival. F-FDG PET/CT and DCE-MRI give prognostic information in malignant pleural mesothelioma. Neither PET/CT nor DCE-MRI is useful for monitoring disease progression.

  10. Numerical investigation of tip clearance cavitation in Kaplan runners

    NASA Astrophysics Data System (ADS)

    Nikiforova, K.; Semenov, G.; Kuznetsov, I.; Spiridonov, E.

    2016-11-01

    There is a gap between the Kaplan runner blade and the shroud that makes for a special kind of cavitation: cavitation in the tip leakage flow. Two types of cavitation caused by the presence of clearance gap are known: tip vortex cavitation that appears at the core of the rolled up vortex on the blade suction side and tip clearance cavitation that appears precisely in the gap between the blade tip edge and the shroud. In the context of this work numerical investigation of the model Kaplan runner has been performed taking into account variable tip clearance for several cavitation regimes. The focus is put on investigation of structure and origination of mechanism of cavitation in the tip leakage flow. Calculations have been performed with the help of 3-D unsteady numerical model for two-phase medium. Modeling of turbulent flow in this work has been carried out using full equations of Navier-Stokes averaged by Reynolds with correction for streamline curvature and system rotation. For description of this medium (liquid-vapor) simplification of Euler approach is used; it is based on the model of interpenetrating continuums, within the bounds of this two- phase medium considered as a quasi-homogeneous mixture with the common velocity field and continuous distribution of density for both phases. As a result, engineering techniques for calculation of cavitation conditioned by existence of tip clearance in model turbine runner have been developed. The detailed visualization of the flow was carried out and vortex structure on the suction side of the blade was reproduced. The range of frequency with maximum value of pulsation was assigned and maximum energy frequency was defined; it is based on spectral analysis of the obtained data. Comparison between numerical computation results and experimental data has been also performed. The location of cavitation zone has a good agreement with experiment for all analyzed regimes.

  11. Adenosine triphosphate stress myocardial perfusion imaging for risk stratification of patients aged 70 years and older with suspected coronary artery disease.

    PubMed

    Yao, Zhiming; Zhu, Hui; Li, Wenchan; Chen, Congxia; Wang, Hua; Shi, Lei; Zhang, Wenjie

    2017-04-01

    We investigated the cardiac risk stratification value of adenosine triphosphate stress myocardial perfusion imaging (ATP-MPI) in patients aged 70 years and older with suspected coronary artery disease (CAD). We identified a series of 415 consecutive patients aged 70 years and older with suspected CAD, who had undergone ATP-MPI with 99m Tc-MIBI. The presence of a fixed and/or reversible perfusion defect was considered as an abnormal MPI. Follow-up was available in 399 patients (96.1%) over 3.45 ± 1.71 years after excluding 16 patients who underwent early coronary revascularization <60 days after MPI. The major adverse cardiac events (MACE), including cardiac death, nonfatal infarction, and late coronary revascularization, were recorded. One hundred twenty-five (31.3%) patients had abnormal MPI and the remaining had normal MPI. A multivariable analysis using Cox regression demonstrated that abnormal MPI was independently associated with MACE (hazard ratio 19.50 and 95% confidence interval 5.91-64.31, P value .000). The patients with SSS > 8 had significantly higher cumulative MACE rate than patients with SSS ≤ 8 had (37.8% vs 5.2%, respectively, P < .001). The Kaplan-Meier cumulative MACE-free survival in patients with abnormal MPI (57.0%) was significantly lower than that in patients with normal MPI (89.6%), P < .0001. Among patients with SSS > 8, the Kaplan-Meier cumulative MACE-free survival were 36.9% in patients ≥80 years old and 49.5% in patients 70-79 years old, respectively, P < .05. However, among patients with SSS ≤ 8, there was no difference between the Kaplan-Meier cumulative MACE-free survivals of these two age groups. ATP-MPI data are useful for the prediction of major adverse cardiac events in patients aged 70 years and older with suspected CAD.

  12. How do knee implants perform past the second decade? Nineteen- to 25-year followup of the Press-fit Condylar design TKA.

    PubMed

    Patil, Shantanu; McCauley, Julie C; Pulido, Pamela; Colwell, Clifford W

    2015-01-01

    At 14- to 17-year followup, we reported successful outcomes of the Press-fit Condylar total knee arthroplasty (TKA) system in 160 TKAs performed between 1986 and 1989. However, there are few published reports on TKA survivorship and patient function that include patients evaluated into the third decade after surgery. The study purpose was to determine (1) the survivorship of the implant; and (2) knee function in patients with this TKA system at a mean 20-year followup. We ascertained revision status of all living patients (42 of 160 knees) and all patients (22 knees) who died since the previous study. Among patients alive at the latest followup, Knee Society function scores were obtained and radiographs were evaluated. Kaplan-Meier survivorship analysis with 95% confidence intervals was performed with revision for any reason and aseptic loosening as endpoints. A competing risks analysis with 95% confidence intervals was also performed for revision for any reason as the endpoint. At the mean 20-year (range, 19-25 years) followup, all living patients retained their original implants from the index TKA, exclusive of three polyethylene exchanges. This study demonstrates an 87% Kaplan-Meier survivorship for revision for any reason (95% confidence interval [CI], 80%-92%) and a 98% Kaplan-Meier survivorship for revision for aseptic loosening (95% CI, 93%-99%). Competing risks survivorship was 79% (95% CI, 70%-85%) at 25 years for revision for any reason. Mean Knee Society function score was 46.9. Since the previous study, three revisions have been performed, all for polyethylene wear. The Press-fit Condylar implant system continues to be successful, maintaining longevity up to 25-year followup. This is one of the longest followup studies, reporting continued successes over 20 years, and should serve as a benchmark for current-generation implants. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

  13. Applications of statistics to medical science, IV survival analysis.

    PubMed

    Watanabe, Hiroshi

    2012-01-01

    The fundamental principles of survival analysis are reviewed. In particular, the Kaplan-Meier method and a proportional hazard model are discussed. This work is the last part of a series in which medical statistics are surveyed.

  14. Nested Cohort - R software package

    Cancer.gov

    NestedCohort is an R software package for fitting Kaplan-Meier and Cox Models to estimate standardized survival and attributable risks for studies where covariates of interest are observed on only a sample of the cohort.

  15. Complementary Chinese herbal medicine therapy improves survival of patients with gastric cancer in Taiwan: A nationwide retrospective matched-cohort study.

    PubMed

    Hung, Kuo-Feng; Hsu, Ching-Ping; Chiang, Jen-Huai; Lin, Hung-Jen; Kuo, Yi-Ting; Sun, Mao-Feng; Yen, Hung-Rong

    2017-03-06

    Many patients with gastric cancer seek traditional medicine consultations in Asian countries. This study aimed to investigate the prescription of Chinese herbal medicine (CHM) and its benefits for the patients with gastric cancer in Taiwan. From the Registry for Catastrophic Illness Patients Database, we included all patients with gastric cancer whose age at diagnosis was ≥18 from 1997 to 2010 in Taiwan. We used 1:1 frequency matching by age, sex, Charlson comorbidity score, treatment and index year to compare the CHM users and non-CHM users. We used the Cox regression model to compare the hazard ratios (HR) for the risk of mortality and the Kaplan-Meier curve for the survival time. There was a total of 1333 patients in the CHM-cohort and 44786 patients in the non-CHM cohort. After matching, we compared 962 newly diagnosed CHM users and 962 non-CHM users. Adjusted HRs (aHR) were higher among patients of above 60-year-old group, with a Charlson Comorbidity Index score ≥2 before the index date, and those who need surgery combined with chemotherapy or radiotherapy. CHM users had a lower HR of mortality risk (adjusted HR: 0.55, 95% CI: 0.48-0.62). Compared to the non-CHM users, the aHR among CHM-users is 0.37 (95% CI:0.2-0.67) for those who used CHM more than 180 days annually. The Kaplan-Meier curve revealed that the survival probability was higher for complementary CHM-users. Bai-Hua-She-She-Cao (Herba Hedyotidis Diffusae) was the most commonly used single herb and Xiang-Sha-Liu-Jun-Zi-Tang was the most commonly used herbal formula among CHM prescriptions. Complementary CHM improves the overall survival among patients with gastric cancer in Taiwan. Further ethnopharmacological investigations and clinical trials are required to validate the efficacy and safety. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  16. Estimating Loss to Follow-Up in HIV-Infected Patients on Antiretroviral Therapy: The Effect of the Competing Risk of Death in Zambia and Switzerland

    PubMed Central

    Mwango, Albert; Stringer, Jeffrey; Ledergerber, Bruno; Mulenga, Lloyd; Bucher, Heiner C.; Westfall, Andrew O.; Calmy, Alexandra; Boulle, Andrew; Chintu, Namwinga; Egger, Matthias; Chi, Benjamin H.

    2011-01-01

    Background Loss to follow-up (LTFU) is common in antiretroviral therapy (ART) programmes. Mortality is a competing risk (CR) for LTFU; however, it is often overlooked in cohort analyses. We examined how the CR of death affected LTFU estimates in Zambia and Switzerland. Methods and Findings HIV-infected patients aged ≥18 years who started ART 2004–2008 in observational cohorts in Zambia and Switzerland were included. We compared standard Kaplan-Meier curves with CR cumulative incidence. We calculated hazard ratios for LTFU across CD4 cell count strata using cause-specific Cox models, or Fine and Gray subdistribution models, adjusting for age, gender, body mass index and clinical stage. 89,339 patients from Zambia and 1,860 patients from Switzerland were included. 12,237 patients (13.7%) in Zambia and 129 patients (6.9%) in Switzerland were LTFU and 8,498 (9.5%) and 29 patients (1.6%), respectively, died. In Zambia, the probability of LTFU was overestimated in Kaplan-Meier curves: estimates at 3.5 years were 29.3% for patients starting ART with CD4 cells <100 cells/µl and 15.4% among patients starting with ≥350 cells/µL. The estimates from CR cumulative incidence were 22.9% and 13.6%, respectively. Little difference was found between naïve and CR analyses in Switzerland since only few patients died. The results from Cox and Fine and Gray models were similar: in Zambia the risk of loss to follow-up and death increased with decreasing CD4 counts at the start of ART, whereas in Switzerland there was a trend in the opposite direction, with patients with higher CD4 cell counts more likely to be lost to follow-up. Conclusions In ART programmes in low-income settings the competing risk of death can substantially bias standard analyses of LTFU. The CD4 cell count and other prognostic factors may be differentially associated with LTFU in low-income and high-income settings. PMID:22205933

  17. MO-DE-207B-03: Improved Cancer Classification Using Patient-Specific Biological Pathway Information Via Gene Expression Data

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Young, M; Craft, D

    Purpose: To develop an efficient, pathway-based classification system using network biology statistics to assist in patient-specific response predictions to radiation and drug therapies across multiple cancer types. Methods: We developed PICS (Pathway Informed Classification System), a novel two-step cancer classification algorithm. In PICS, a matrix m of mRNA expression values for a patient cohort is collapsed into a matrix p of biological pathways. The entries of p, which we term pathway scores, are obtained from either principal component analysis (PCA), normal tissue centroid (NTC), or gene expression deviation (GED). The pathway score matrix is clustered using both k-means and hierarchicalmore » clustering, and a clustering is judged by how well it groups patients into distinct survival classes. The most effective pathway scoring/clustering combination, per clustering p-value, thus generates various ‘signatures’ for conventional and functional cancer classification. Results: PICS successfully regularized large dimension gene data, separated normal and cancerous tissues, and clustered a large patient cohort spanning six cancer types. Furthermore, PICS clustered patient cohorts into distinct, statistically-significant survival groups. For a suboptimally-debulked ovarian cancer set, the pathway-classified Kaplan-Meier survival curve (p = .00127) showed significant improvement over that of a prior gene expression-classified study (p = .0179). For a pancreatic cancer set, the pathway-classified Kaplan-Meier survival curve (p = .00141) showed significant improvement over that of a prior gene expression-classified study (p = .04). Pathway-based classification confirmed biomarkers for the pyrimidine, WNT-signaling, glycerophosphoglycerol, beta-alanine, and panthothenic acid pathways for ovarian cancer. Despite its robust nature, PICS requires significantly less run time than current pathway scoring methods. Conclusion: This work validates the PICS method to

  18. Elevated levels of serum nidogen-2 in esophageal squamous cell carcinoma.

    PubMed

    Chai, Annie Wai Yeeng; Cheung, Arthur Kwok Leung; Dai, Wei; Ko, Josephine Mun Yee; Lee, Nikki Pui Yue; Chan, Kin Tak; Law, Simon Ying-Kit; Lung, Maria Li

    2018-02-14

    Nidogen-2 (NID2), a secretory basement membrane protein, has been implicated as a potential biomarker in ovarian cancer and hepatocellular carcinoma. In this study, we aimed to investigate the utility of detecting serum NID2 levels for identification of esophageal squamous cell carcinoma (ESCC) patients and prediction of poor survival outcome. Using an in-house NID2 enzyme-linked immunosorbent assay (ELISA), serum samples from 101 ESCC patients and 50 healthy controls were screened for their NID2 levels. The serum NID2 levels in ESCC patients (median 24.4 μg/L) are significantly higher (p= 4.3e-09) than that of the healthy controls (median 15.85 μg/L). The receiver operating characteristic (ROC) curve demonstrated an area under the curve of 0.756. At the threshold of 17.95 μg/L, the sensitivity and specificity achieved are 0.76 and 0.63, respectively. Kaplan-Meier survival analysis revealed that patients with high serum NID2 levels (⩾ 32.6 μg/L) have significantly higher risk of death (HR = 1.984, 95% CI: 1.175-3.349; log-rank p-value = 0.012) compared to those with low serum NID2 levels (< 20.0 μg/L). In conclusion, we show that detecting the elevation of serum NID2 levels has potential diagnostic and prognostic value for ESCC patients.

  19. Low Survival Rates of Oral and Oropharyngeal Squamous Cell Carcinoma

    PubMed Central

    da Silva Júnior, Francisco Feliciano; dos Santos, Karine de Cássia Batista; Ferreira, Stefania Jeronimo

    2017-01-01

    Aim To assess the epidemiological and clinical factors that influence the prognosis of oral and oropharyngeal squamous cell carcinoma (SCC). Methods One hundred and twenty-one cases of oral and oropharyngeal SCC were selected. The survival curves for each variable were estimated using the Kaplan-Meier method. The Cox regression model was applied to assess the effect of the variables on survival. Results Cancers at an advanced stage were observed in 103 patients (85.1%). Cancers on the tongue were more frequent (23.1%). The survival analysis was 59.9% in one year, 40.7% in two years, and 27.8% in 5 years. There was a significant low survival rate linked to alcohol intake (p = 0.038), advanced cancer staging (p = 0.003), and procedures without surgery (p < 0.001). When these variables were included in the Cox regression model only surgery procedures (p = 0.005) demonstrated a significant effect on survival. Conclusion The findings suggest that patients who underwent surgery had a greater survival rate compared with those that did not. The low survival rates and the high percentage of patients diagnosed at advanced stages demonstrate that oral and oropharyngeal cancer patients should receive more attention. PMID:28638410

  20. The Educational Philosophies of Mordecai Kaplan and Michael Rosenak: Surprising Similarities and Illuminating Differences

    ERIC Educational Resources Information Center

    Schein, Jeffrey; Caplan, Eric

    2014-01-01

    The thoughts of Mordecai Kaplan and Michael Rosenak present surprising commonalities as well as illuminating differences. Similarities include the perception that Judaism and Jewish education are in crisis, the belief that Jewish peoplehood must include commitment to meaningful content, the need for teachers to teach from a position of…

  1. Curve Boxplot: Generalization of Boxplot for Ensembles of Curves.

    PubMed

    Mirzargar, Mahsa; Whitaker, Ross T; Kirby, Robert M

    2014-12-01

    In simulation science, computational scientists often study the behavior of their simulations by repeated solutions with variations in parameters and/or boundary values or initial conditions. Through such simulation ensembles, one can try to understand or quantify the variability or uncertainty in a solution as a function of the various inputs or model assumptions. In response to a growing interest in simulation ensembles, the visualization community has developed a suite of methods for allowing users to observe and understand the properties of these ensembles in an efficient and effective manner. An important aspect of visualizing simulations is the analysis of derived features, often represented as points, surfaces, or curves. In this paper, we present a novel, nonparametric method for summarizing ensembles of 2D and 3D curves. We propose an extension of a method from descriptive statistics, data depth, to curves. We also demonstrate a set of rendering and visualization strategies for showing rank statistics of an ensemble of curves, which is a generalization of traditional whisker plots or boxplots to multidimensional curves. Results are presented for applications in neuroimaging, hurricane forecasting and fluid dynamics.

  2. Real-world effectiveness of everolimus-based therapy versus fulvestrant monotherapy in HR(+)/HER2(-) metastatic breast cancer.

    PubMed

    Hao, Yanni; Lin, Peggy L; Xie, Jipan; Li, Nanxin; Koo, Valerie; Ohashi, Erika; Wu, Eric Q; Rogerio, Jaqueline

    2015-08-01

    Assessing real-world effectiveness of everolimus-based therapy (EVE) versus fulvestrant monotherapy (FUL) among postmenopausal women with hormone receptor-positive (HR(+))/HER2(-) metastatic breast cancer (mBC) after progression on nonsteroidal aromatase inhibitor (NSAI). Medical charts of community-based patients who received EVE or FUL for mBC after NSAI were examined. Progression-free survival (PFS), time on treatment and time to chemotherapy were compared using Kaplan-Meier curves and Cox proportional hazards models adjusting for line of therapy and patient characteristics. 192 patients received EVE and 156 FUL. After adjusting for patient characteristics, EVE was associated with significantly longer PFS than FUL (hazard ratio: 0.71; p = 0.045). EVE was associated with better PFS than FUL among NSAI-refractory postmenopausal HR(+)/HER2(-) mBC patients.

  3. Clozapine, Diabetes Mellitus, Cardiovascular Risk and Mortality: Results of a 21-year Naturalistic Study in Patients with Schizophrenia and Schizoaffective Disorder.

    PubMed

    Nemani, Katlyn L; Greene, M Claire; Ulloa, Melissa; Vincenzi, Brenda; Copeland, Paul M; Al-Khadari, Sulaiman; Henderson, David C

    2017-11-22

    The goal of this 21-year naturalistic study of clozapine treated patients was to examine the cardiovascular risk factors following clozapine initiation and resultant mortality estimates from cardiovascular disease. Data was collected from medical records of clozapine treated patients with schizophrenia or schizoaffective disorder from January 1992 to February 2012. Demographics, clozapine dosage and laboratory results were extracted at 12-month intervals. At clozapine initiation, the mean age of 96 patients was 36.4 years ±7.6 years; N=27(28%) were women. The mean duration of clozapine use was 13 years. The Kaplan-Meier estimate for 21-year cardiovascular events was 29%, while the Kaplan-Meier estimate for 21-year mortality from cardiovascular disease was 10%. The mean cardiovascular risk increased during the first ten years (p<.01), while a slight decrease occurred beyond ten years (p<.01). Patients involved in cardiometabolic research showed a greater decrease in cardiovascular risk factors over 21 years (p = .05). The Kaplan-Meier estimate for 21-year all-cause mortality was 22%. Forty-one patients were diagnosed with diabetes (42.7%), compared to a nationwide prevalence of 13.7% in a similar age group. These results support the hypothesis that clozapine-treated patients are at risk for cardiovascular events and death secondary to an increased risk of medical disorders. Interventions that target weight loss, smoking cessation, and lipid profile improvement may alleviate the increased risk of cardiovascular mortality.

  4. Competing approaches to analysis of failure times with competing risks.

    PubMed

    Farley, T M; Ali, M M; Slaymaker, E

    2001-12-15

    For the analysis of time to event data in contraceptive studies when individuals are subject to competing causes for discontinuation, some authors have recently advocated the use of the cumulative incidence rate as a more appropriate measure to summarize data than the complement of the Kaplan-Meier estimate of discontinuation. The former method estimates the rate of discontinuation in the presence of competing causes, while the latter is a hypothetical rate that would be observed if discontinuations for the other reasons could not occur. The difference between the two methods of analysis is the continuous time equivalent of a debate that took place in the contraceptive literature in the 1960s, when several authors advocated the use of net (adjusted or single decrement life table rates) rates in preference to crude rates (multiple decrement life table rates). A small simulation study illustrates the interpretation of the two types of estimate - the complement of the Kaplan-Meier estimate corresponds to a hypothetical rate where discontinuations for other reasons did not occur, while the cumulative incidence gives systematically lower estimates. The Kaplan-Meier estimates are more appropriate when estimating the effectiveness of a contraceptive method, but the cumulative incidence estimates are more appropriate when making programmatic decisions regarding contraceptive methods. Other areas of application, such as cancer studies, may prefer to use the cumulative incidence estimates, but their use should be determined according to the application. Copyright 2001 John Wiley & Sons, Ltd.

  5. Communicating projected survival with treatments for chronic kidney disease: patient comprehension and perspectives on visual aids.

    PubMed

    Dowen, Frances; Sidhu, Karishma; Broadbent, Elizabeth; Pilmore, Helen

    2017-09-21

    Mortality in end stage renal disease (ESRD) is higher than many malignancies. There is no data about the optimal way to present information about projected survival to patients with ESRD. In other areas, graphs have been shown to be more easily understood than narrative. We examined patient comprehension and perspectives on graphs in communicating projected survival in chronic kidney disease (CKD). One hundred seventy-seven patients with CKD were shown 4 different graphs presenting post transplantation survival data. Patients were asked to interpret a Kaplan Meier curve, pie chart, histogram and pictograph and answer a multi-choice question to determine understanding. We measured interpretation, usefulness and preference for the graphs. Most patients correctly interpreted the graphs. There was asignificant difference in the percentage of correct answers when comparing different graph types (p = 0.0439). The pictograph was correctly interpreted by 81% of participants, the histogram by 79%, pie chart by 77% and Kaplan Meier by 69%. Correct interpretation of the histogram was associated with educational level (p = 0.008) and inversely associated with age > 65 (p = 0.008). Of those who interpreted all four graphs correctly, there was an association with employment (p = 0.001) and New Zealand European ethnicity (p = 0.002). 87% of patients found the graphs useful. The pie chart was the most preferred graph (p 0.002). The readability of the graphs may have been improved with an alternative colour choice, especially in the setting of visual impairment. Visual aids, can be beneficial adjuncts to discussing survival in CKD.

  6. Glioblastoma: does the pre-treatment geometry matter? A postcontrast T1 MRI-based study.

    PubMed

    Pérez-Beteta, Julián; Martínez-González, Alicia; Molina, David; Amo-Salas, Mariano; Luque, Belén; Arregui, Elena; Calvo, Manuel; Borrás, José M; López, Carlos; Claramonte, Marta; Barcia, Juan A; Iglesias, Lidia; Avecillas, Josué; Albillo, David; Navarro, Miguel; Villanueva, José M; Paniagua, Juan C; Martino, Juan; Velásquez, Carlos; Asenjo, Beatriz; Benavides, Manuel; Herruzo, Ismael; Delgado, María Del Carmen; Del Valle, Ana; Falkov, Anthony; Schucht, Philippe; Arana, Estanislao; Pérez-Romasanta, Luis; Pérez-García, Víctor M

    2017-03-01

    The potential of a tumour's volumetric measures obtained from pretreatment MRI sequences of glioblastoma (GBM) patients as predictors of clinical outcome has been controversial. Mathematical models of GBM growth have suggested a relation between a tumour's geometry and its aggressiveness. A multicenter retrospective clinical study was designed to study volumetric and geometrical measures on pretreatment postcontrast T1 MRIs of 117 GBM patients. Clinical variables were collected, tumours segmented, and measures computed including: contrast enhancing (CE), necrotic, and total volumes; maximal tumour diameter; equivalent spherical CE width and several geometric measures of the CE "rim". The significance of the measures was studied using proportional hazards analysis and Kaplan-Meier curves. Kaplan-Meier and univariate Cox survival analysis showed that total volume [p = 0.034, Hazard ratio (HR) = 1.574], CE volume (p = 0.017, HR = 1.659), spherical rim width (p = 0.007, HR = 1.749), and geometric heterogeneity (p = 0.015, HR = 1.646) were significant parameters in terms of overall survival (OS). Multivariable Cox analysis for OS provided the later two parameters as age-adjusted predictors of OS (p = 0.043, HR = 1.536 and p = 0.032, HR = 1.570, respectively). Patients with tumours having small geometric heterogeneity and/or spherical rim widths had significantly better prognosis. These novel imaging biomarkers have a strong individual and combined prognostic value for GBM patients. • Three-dimensional segmentation on magnetic resonance images allows the study of geometric measures. • Patients with small width of contrast enhancing areas have better prognosis. • The irregularity of contrast enhancing areas predicts survival in glioblastoma patients.

  7. A Review of Arteriovenous Fistulae Creation in Octogenarians.

    PubMed

    Diandra, Jennifer Clarissa; Lo, Zhiwen Joseph; Ang, Wei-Wen; Feng, Jue Fei; Narayanan, Sriram; Tan, Glenn Wei Leong; Chandrasekar, Sadhana

    2018-01-01

    To analyze the outcomes of arteriovenous fistulae (AVFs) creation in octogenarians. A retrospective study of 47 AVFs created in patients aged 80 years and above from 2008 to 2014. Patient and AVF characteristics and outcomes were evaluated. Predictors of patency were analyzed with multivariate analysis and Kaplan-Meier patency, and survival analysis was performed. Forty-seven of 1,259 AVFs created were for octogenarians (4%). Mean age was 83 years old (range: 80-91 years), with 27 male (57%) and 35 with tunneled dialysis catheters in situ (75%). There were a total of 15 (32%) radiocephalic AVFs, 30 (64%) brachial-cephalic AVFs, and 2 (4%) brachial-basilic transposition AVFs. At 12 months, assisted primary patency rate was 28% (13 patients) while primary failure rate was 72% (34 patients). Subset analysis showed brachial-cephalic AVFs to have the highest assisted primary patency rate at 33%. Within 24 months, tunneled dialysis catheter-related sepsis rate was 31% (11 patients). Multivariate analysis did not reveal any factor to be statistically significant in predicting AVF patency. Kaplan-Meier survival curve showed a 50% survival rate at 63 months after AVF creation. In view of high AVF primary failure rate and relatively low tunneled dialysis catheter bacteremia rate, long-term tunneled dialysis catheters as the main form of hemodialysis renal access may be a viable option. However, with 50% of end-stage renal failure patients surviving up to 63 months after AVF creation, the risks and benefits of long-term tunneled dialysis catheters must be balanced against those of AVF creation. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Increased pulse wave velocity in patients with acute lacunar infarction doubled the risk of future ischemic stroke.

    PubMed

    Saji, Naoki; Murotani, Kenta; Shimizu, Hirotaka; Uehara, Toshiyuki; Kita, Yasushi; Toba, Kenji; Sakurai, Takashi

    2017-04-01

    The aim of this study was to determine whether pulse wave velocity (PWV), a marker of vascular endothelial impairment and arteriosclerosis, predicts future ischemic stroke in patients who developed acute lacunar infarction. Patients with a first-ever ischemic stroke due to acute lacunar infarction were enrolled in this study. An oscillometric device (Form PWV/ABI; Omron Colin, Tokyo, Japan) was used to measure brachial-ankle PWV 1 week after stroke onset. Patients were followed for at least 5 years. The main end point of the study was recurrent ischemic stroke. Event-free survival was analyzed using Kaplan-Meier plots and log-rank tests. The risk of recurrent ischemic stroke was estimated using the Cox proportional-hazards model. Of the 156 patients (61% male, mean age: 69.2±11.3 years) assessed in this study, 29 developed recurrent ischemic stroke. The median brachial-ankle PWV value was 20.4 m s -1 . Patients with high PWV values had a greater risk of recurrent ischemic stroke than patients with low PWV values (28% vs. 15%, P=0.08). Kaplan-Meier curve analysis showed that patients with high PWV values had a less favorable (that is, free of recurrent ischemic stroke) survival time (P=0.015). A multivariate Cox proportional-hazards model identified high PWV as an independent predictor of recurrent ischemic stroke after adjusting for age, sex and blood pressure (hazard ratio 2.35, 95% confidence interval, 1.02-5.70, P=0.044). In patients with acute lacunar infarction, a high PWV predicts a twofold greater risk of future ischemic stroke, independent of patient age, sex and blood pressure levels.

  9. Report of 111 Consecutive Patients Enrolled in the International Serial Transverse Enteroplasty (STEP) Data Registry: A Retrospective Observational Study

    PubMed Central

    Jones, Brian A; Hull, Melissa A; Potanos, Kristina M; Zurakowski, David; Fitzgibbons, Shimae C; Ching, Y Avery; Duggan, Christopher; Jaksic, Tom; Kim, Heung Bae

    2016-01-01

    Background The International Serial Transverse Enteroplasty (STEP) Data Registry is a voluntary online database created in 2004 to collect information on patients undergoing the STEP procedure. The aim of this study was to identify preoperative factors significantly associated with 1) transplantation or death, or 2) attainment of enteral autonomy following STEP. Study Design Data were collected from September 2004 to January 2010. Univariate and multivariate logistic regression analyses were applied to determine predictors of transplantation/death or enteral autonomy post-STEP. Time to reach full enteral nutrition was estimated using a Kaplan-Meier curve. Results Fourteen of the 111 patients in the Registry were excluded due to inadequate follow-up. Of the remaining 97 patients, 11 patients died, and 5 progressed to intestinal transplantation. On multivariate analysis, higher direct bilirubin and shorter pre-STEP bowel length were independently predictive of progression to transplantation or death (p = .05 and p < .001, respectively). Of the 78 patients who were ≥7 days of age and required parenteral nutrition (PN) at the time of STEP, 37 (47%) achieved enteral autonomy after the first STEP. Longer pre-STEP bowel length was also independently associated with enteral autonomy (p = .002). The median time to reach enteral autonomy based on Kaplan-Meier analysis was 21 months (95% CI: 12-30). Conclusions Overall mortality post-STEP was 11%. Pre-STEP risk factors for progressing to transplantation or death were higher direct bilirubin and shorter bowel length. Among patients who underwent STEP for short bowel syndrome, 47% attained full enteral nutrition post-STEP. Patients with longer pre-STEP bowel length were significantly more likely to achieve enteral autonomy. PMID:23357726

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

    PubMed

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

    2018-05-01

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

  11. Survival and mortality among users and non-users of hydroxyurea with sickle cell disease.

    PubMed

    de Araujo, Olinda Maria Rodrigues; Ivo, Maria Lúcia; Ferreira Júnior, Marcos Antonio; Pontes, Elenir Rose Jardim Cury; Bispo, Ieda Maria Gonçalves Pacce; de Oliveira, Eveny Cristine Luna

    2015-01-01

    to estimate survival, mortality and cause of death among users or not of hydroxyurea with sickle cell disease. cohort study with retrospective data collection, from 1980 to 2010 of patients receiving inpatient treatment in two Brazilian public hospitals. The survival probability was determined using the Kaplan-Meier estimator, survival calculations (SPSS version 10.0), comparison between survival curves, using the log rank method. The level of significance was p=0.05. of 63 patients, 87% had sickle cell anemia, with 39 using hydroxyurea, with a mean time of use of the drug of 20.0±10.0 years and a mean dose of 17.37±5.4 to 20.94±7.2 mg/kg/day, raising the fetal hemoglobin. In the comparison between those using hydroxyurea and those not, the survival curve was greater among the users (p=0.014). A total of 10 deaths occurred, with a mean age of 28.1 years old, and with Acute Respiratory Failure as the main cause. the survival curve is greater among the users of hydroxyurea. The results indicate the importance of the nurse incorporating therapeutic advances of hydroxyurea in her care actions.

  12. The effect of semirigid dressings on below-knee amputations.

    PubMed

    MacLean, N; Fick, G H

    1994-07-01

    The effect of using semirigid dressings (SRDs) on the residual limb of individuals who have had below-knee amputations as a consequence of peripheral vascular disease was investigated, with the primary question being: Does the time to readiness for prosthetic fitting for patients treated with the SRDs differ from that of patients treated with soft dressings? Forty patients entered the study and were alternately assigned to one of two groups. Nineteen patients were assigned to the SRD group, and 21 patients were assigned to the soft dressing group. The time from surgery to readiness for prosthetic fitting was recorded for each patient. Kaplan-Meier survival curves were generated for each group, and the results were analyzed with the log-rank test. There was a difference between the two curves, and an examination of the curves suggests that the expected time to readiness for prosthetic fitting for patients treated with the SRDs would be less than half that of patients treated with soft dressings. The results suggest that a patient may be ready for prosthetic fitting sooner if treated with SRDs instead of soft dressings.

  13. Single Versus Double Lung Retransplantation Does Not Affect Survival Based on Previous Transplant Type.

    PubMed

    Schumer, Erin M; Rice, Jonathan D; Kistler, Amanda M; Trivedi, Jaimin R; Black, Matthew C; Bousamra, Michael; van Berkel, Victor

    2017-01-01

    Survival following retransplantation with a single lung is worse than after double lung transplant. We sought to characterize survival of patients who underwent lung retransplantation based on the type of their initial transplant, single or double. The United Network for Organ Sharing database was queried for adult patients who underwent lung retransplantation from 2005 onward. Patients were excluded if they underwent more than one retransplantation. The patient population was divided into 4 groups based on first followed by second transplant type, respectively: single then single, double then single, double then double, and single then double. Descriptive analysis and Kaplan-Meier survival analysis were performed. A p value less than 0.05 was considered significant. A total of 410 patients underwent retransplantation in the study time period. Overall mean survival for all patients who underwent retransplantation was 1,213 days. Kaplan-Meier survival analysis demonstrated no difference in graft survival between the 4 study groups (p = 0.146). There was no significant difference in graft survival between recipients of retransplant with single or double lungs when stratified by previous transplant type. These results suggest that when retransplantation is performed, single lung retransplantation should be considered, regardless of previous transplant type, in an effort to maximize organ resources. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  14. Reduced miR-300 expression predicts poor prognosis in patients with laryngeal squamous cell carcinoma.

    PubMed

    He, F-Y; Liu, H-J; Guo, Q; Sheng, J-L

    2017-02-01

    miR-300 has been demonstrated to play an important role in the progression of several tumors, but its role in tumorigenesis of laryngeal squamous cell carcinoma (LSCC) is still unclear. The purpose of this study was to explore miR-300 expression in LSCC patients and analyze its association with clinicopathological factors and prognosis. In the present study, we measured the expression level of miR-300 in LSCC tissues by RT-PCR. Associations between miRNA-300 expressions and various clinicopathological characteristics were analyzed. Patient survival and their differences were determined by Kaplan-Meier method and log-rank test. The univariate and multivariate analysis were performed using the Cox proportional hazard analysis. miR-300 expression was significantly increased in LSCC tissues compared with that in adjacent non-cancerous tissues (p < 0.01). In addition, lymph node metastasis (p = 0.004) and TNM stage (p = 0.001) were obvious influence factors for the expression of miR-300. More importantly, Kaplan-Meier analysis showed that LSCC patients with low miR-300 expression tended to have shorter overall survival (p < 0.001). Finally, multivariate analysis revealed that miR-300 expression was an independent prognostic factor for LSCC patients. Our results pointed to miR-300 as a powerful prognostic marker in LSCC and as a novel target for tumor-suppressive therapy.

  15. Overexpression of epithelial cell adhesion molecule protein is associated with favorable prognosis in an unselected cohort of ovarian cancer patients.

    PubMed

    Battista, Marco Johannes; Cotarelo, Cristina; Jakobi, Sina; Steetskamp, Joscha; Makris, Georgios; Sicking, Isabel; Weyer, Veronika; Schmidt, Marcus

    2014-07-01

    The aim of this study was to evaluate the prognostic influence of epithelial cell adhesion molecule (EpCAM) in an unselected cohort of ovarian cancer (OC) patients. Expression of EpCAM was determined by immunohistochemistry in an unselected cohort of 117 patients with OC. Univariable and multivariable Cox regression analyses adjusted for age, tumor stage, histological grading, histological subtype, postoperative tumor burden and completeness of chemotherapy were performed in order to determine the prognostic influence of EpCAM. The Kaplan-Meier method is used to estimate survival rates. Univariable Cox regression analysis showed that overexpression of EpCAM is associated with favorable prognosis in terms of progression-free survival (PFS) (p = 0.011) and disease-specific survival (DSS) (p = 0.003). In multivariable Cox regression analysis, overexpression of EpCAM retains its significance independent of established prognostic factors for longer PFS [hazard ratios (HR) 0.408, 95 % confidence interval (CI) 0.197-0.846, p = 0.003] but not for PFS (HR 0.666, 95 % CI 0.366-1.212, p = 0.183). Kaplan-Meier plots demonstrate an influence on 5-year PFS rates (0 vs. 27.6 %, p = 0.048) and DSS rates (11.8 vs. 54.0 %, p = 0.018). These findings support the hypothesis that the expression of EpCAM is associated with favorable prognosis in OC.

  16. Collagen Triple Helix Repeat Containing-1 (CTHRC1) Expression in Oral Squamous Cell Carcinoma (OSCC): Prognostic Value and Clinico-Pathological Implications

    PubMed Central

    Lee, Chia Ee; Vincent-Chong, Vui King; Ramanathan, Anand; Kallarakkal, Thomas George; Karen-Ng, Lee Peng; Ghani, Wan Maria Nabillah; Rahman, Zainal Ariff Abdul; Ismail, Siti Mazlipah; Abraham, Mannil Thomas; Tay, Keng Kiong; Mustafa, Wan Mahadzir Wan; Cheong, Sok Ching; Zain, Rosnah Binti

    2015-01-01

    BACKGROUND: Collagen Triple Helix Repeat Containing 1 (CTHRC1) is a protein often found to be over-expressed in various types of human cancers. However, correlation between CTHRC1 expression level with clinico-pathological characteristics and prognosis in oral cancer remains unclear. Therefore, this study aimed to determine mRNA and protein expression of CTHRC1 in oral squamous cell carcinoma (OSCC) and to evaluate the clinical and prognostic impact of CTHRC1 in OSCC. METHODS: In this study, mRNA and protein expression of CTHRC1 in OSCCs were determined by quantitative PCR and immunohistochemistry, respectively. The association between CTHRC1 and clinico-pathological parameters were evaluated by univariate and multivariate binary logistic regression analyses. Correlation between CTHRC1 protein expressions with survival were analysed using Kaplan-Meier and Cox regression models. RESULTS: Current study demonstrated CTHRC1 was significantly overexpressed at the mRNA level in OSCC. Univariate analyses indicated a high-expression of CTHRC1 that was significantly associated with advanced stage pTNM staging, tumour size ≥ 4 cm and positive lymph node metastasis (LNM). However, only positive LNM remained significant after adjusting with other confounder factors in multivariate logistic regression analyses. Kaplan-Meier survival analyses and Cox model demonstrated that patients with high-expression of CTHRC1 protein were associated with poor prognosis and is an independent prognostic factor in OSCC. CONCLUSION: This study indicated that over-expression of CTHRC1 potentially as an independent predictor for positive LNM and poor prognosis in OSCC. PMID:26664254

  17. A Meier-Gorlin syndrome mutation impairs the ORC1-nucleosome association.

    PubMed

    Zhang, Wei; Sankaran, Saumya; Gozani, Or; Song, Jikui

    2015-05-15

    Recent studies have identified several genetic mutations within the BAH domain of human Origin Recognition Complex subunit 1 (hORC1BAH), including the R105Q mutation, implicated in Meier-Gorlin Syndrome (MGS). However, the pathological role of the hORC1 R105Q mutation remains unclear. In this study, we have investigated the interactions of the hORC1BAH domain with histone H4K20me2, DNA, and the nucleosome core particle labeled with H4Kc20me2, a chemical analog of H4K20me2. Our study revealed a nucleosomal DNA binding site for hORC1BAH. The R105Q mutation reduces the hORC1BAH-DNA binding affinity, leading to impaired hORC1BAH-nucleosome interaction, which likely influences DNA replication initiation and MGS pathogenesis. This study provides an etiologic link between the hORC1 R105Q mutation and MGS.

  18. Comparative pathogenicity of Vibrio spp., Photobacterium damselae ssp. damselae and five isolates of Aeromonas salmonicida ssp. achromogenes in juvenile Atlantic halibut (Hippoglossus hippoglossus).

    PubMed

    Bowden, T J; Bricknell, I R; Preziosi, B M

    2018-01-01

    Juvenile Atlantic halibut (~100 mg, Hippoglossus hippoglossus) were exposed to Vibrio proteolyticus, a Vibrio spp. isolate, Photobacterium damselae ssp. damselae and five different isolates of Aeromonas salmonicida ssp. achromogenes via an hour-long bath immersion to ascertain their variation in pathogenicity to this fish species. Results were analysed using Kaplan-Meier survival analysis. Analysis of the data from challenges using A. salmonicida ssp. achromogenes revealed three survival values of zero and a spread of values from 0 to 28.43. Challenges using a Vibrio spp isolate, V. proteolyticus and P. damselae resulted in Kaplan-Meier survival estimates of 31.21, 50.41 and 57.21, respectively. As all bacterial species tested could induce juvenile halibut mortalities, they must all be considered as potential pathogens. However, the degree of pathogenicity of A. salmonicida is isolate dependent. © 2017 John Wiley & Sons Ltd.

  19. Parental consanguineous marriages and clinical response to chemotherapy in locally advanced breast cancer patients.

    PubMed

    Saadat, Mostafa; Khalili, Maryam; Omidvari, Shahpour; Ansari-Lari, Maryam

    2011-03-28

    The main aim of the present study was investigating the association between parental consanguinity and clinical response to chemotherapy in females affected with locally advanced breast cancer. A consecutive series of 92 patients were prospectively included in this study. Clinical assessment of treatment was accomplished by comparing initial tumor size with preoperative tumor size using revised RECIST guideline (version 1.1). Clinical response defined as complete response, partial response and no response. The Kaplan-Meier survival analysis were used to evaluate the association of parental marriages (first cousin vs unrelated marriages) and clinical response to chemotherapy (complete and partial response vs no response). Number of courses of chemotherapy was considered as time, in the analysis. Kaplan-Meier analysis revealed that offspring of unrelated marriages had poorer response to chemotherapy (log rank statistic=5.10, df=1, P=0.023). Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  20. An evaluation of treatment strategies for head and neck cancer in an African American population.

    PubMed

    Ignacio, D N; Griffin, J J; Daniel, M G; Serlemitsos-Day, M T; Lombardo, F A; Alleyne, T A

    2013-07-01

    This study evaluated treatment strategies for head and neck cancers in a predominantly African American population. Data were collected utilizing medical records and the tumour registry at the Howard University Hospital. Kaplan-Meier method was used for survival analysis and Cox proportional hazards regression analysis predicted the hazard of death. Analysis revealed that the main treatment strategy was radiation combined with platinum for all stages except stage I. Cetuximab was employed in only 1% of cases. Kaplan-Meier analysis revealed stage II patients had poorer outcome than stage IV while Cox proportional hazard regression analysis (p = 0.4662) showed that stage I had a significantly lower hazard of death than stage IV (HR = 0.314; p = 0.0272). Contributory factors included tobacco and alcohol but body mass index (BMI) was inversely related to hazard of death. There was no difference in survival using any treatment modality for African Americans.

  1. Use of Serum Transthyretin as a Prognostic Indicator and Predictor of Outcome in Cardiac Amyloid Disease Associated With Wild-Type Transthyretin.

    PubMed

    Hanson, Jacquelyn L S; Arvanitis, Marios; Koch, Clarissa M; Berk, John L; Ruberg, Frederick L; Prokaeva, Tatiana; Connors, Lawreen H

    2018-02-01

    Wild-type transthyretin amyloidosis (ATTRwt), an underappreciated cause of heart failure in older adults, is challenging to diagnose and monitor in the absence of validated, disease-specific biomarkers. We examined the prognostic use and survival association of serum TTR (transthyretin) concentration in ATTRwt. Patients with biopsy-proven ATTRwt were retrospectively identified. Serum TTR, cardiac biomarkers, and echocardiographic parameters were assessed at baseline and follow-up evaluations. Statistical analyses included Kaplan-Meier method, Cox proportional hazard survival models, and receiver-operating characteristic curve analysis. Median serum TTR concentration at presentation was 23 mg/dL (n=116). Multivariate predictors of shorter overall survival were decreased TTR, left ventricular ejection fraction and elevated cTn-I (cardiac troponin I); an inclusive model demonstrated superior accuracy in 4-year survival prediction by receiver-operating characteristic curve analysis (area under the curve, 0.77). TTR values lower than the normal limit, <18 mg/dL, were associated with shorter survival (2.8 versus 4.1 years; P =0.03). Further, TTR values at 1- and 2-year follow-ups were significantly lower ( P <0.001) in untreated patients (n=23) compared with those treated with TTR stabilizer, diflunisal (n=12), after baseline evaluation. During 2-year follow-up, unchanged TTR corresponded to increased cTn-I ( P =0.006) in untreated patients; conversely, the diflunisal-treated group showed increased TTR ( P =0.001) and stabilized cTn-I and left ventricular ejection fraction at 1 year. In this series of biopsy-proven ATTRwt, lower baseline serum TTR concentration was associated with shorter survival as an independent predictor of outcome. Longitudinal analysis demonstrated that decreasing TTR corresponded to worsening cardiac function. These data suggest that TTR may be a useful prognostic marker and predictor of outcome in ATTRwt. © 2018 American Heart Association, Inc.

  2. The diagnostic effect of serum miR-196b as biomarker in colorectal cancer

    PubMed Central

    Xu, Chunjie; Gu, Lei

    2017-01-01

    The microRNA, miR-196b, serves a role in normal cell differentiation, proliferation and tumorigenesis of different types of cancer. The aim of the present study was to explore the serum expression of miR-196b in colorectal cancer (CRC) and its correlation with clinicopathological features. Sera samples were obtained from 103 patients with CRC, 51 patients with colorectal adenoma (Ad) and 100 healthy individuals for the present study. The serum expression of miR-196b in sera samples of the three cohorts was detected using reverse transcription-quantitative polymerase chain reaction. The diagnostic value of miR-196b in the serum of the patients with CRC was evaluated by receiver operating characteristic (ROC) curve and survival analysis, using the Kaplan-Meier method, which was performed with the data from a 5-year follow-up. The expression of miR-196b in the serum of patients with CRC was significantly higher compared with that in Ad patients or healthy individuals (all P<0.001), and the overexpression of serum miR-196b was clearly associated with lymph node invasion, differentiation, and the tumor-lymph nodes-metastasis stage (all P<0.05). ROC curve analysis demonstrated that, comparing patients with CRC with healthy individuals, the area under the curve of serum miR-196b was 0.8135, and its specificity and sensitivity were 63 and 87.38%, respectively, at a diagnostic threshold of −4.785. Patients with CRC of miR-196b-high status had shorter overall survival and disease-free survival rates compared with those of miR-196b-low status. In conclusion, the results of the present study demonstrated that serum miR-196b is upregulated in CRC, and may have an application as a diagnostic and prognostic biomarker for patients with CRC. PMID:28123705

  3. The TP53 gene polymorphisms and survival of sporadic breast cancer patients.

    PubMed

    Bišof, V; Salihović, M Peričić; Narančić, N Smolej; Skarić-Jurić, T; Jakić-Razumović, J; Janićijević, B; Rudan, P

    2012-06-01

    The TP53 gene polymorphisms, Arg72Pro and PIN3 (+16 bp), can have prognostic and predictive value in different cancers including breast cancer. The aim of the present study is to investigate a potential association between different genotypes of these polymorphisms and clinicopathological variables with survival of breast cancer patients in Croatian population. Ninety-four women with sporadic breast cancer were retrospectively analyzed. Median follow-up period was 67.9 months. The effects of basic clinical and histopathological characteristics of tumor on survival were tested by Cox's proportional hazards regression analysis. The TNM stage was associated with overall survival by Kaplan-Meier analysis, univariate, and multivariate Cox's proportional hazards regression analysis, while grade was associated with survival by Kaplan-Meier analysis and univariate Cox's proportional hazards regression analysis. Different genotypes of the Arg72Pro and PIN3 (+16 bp) polymorphisms had no significant impact on survival in breast cancer patients. However, in subgroup of patients treated with chemotherapy without anthracycline, the A2A2 genotype of the PIN3 (+16 bp) polymorphism was associated with poorer overall survival than other genotypes by Kaplan-Meier analysis (P = 0.048). The TP53 polymorphisms, Arg72Pro and PIN3 (+16 bp), had no impact on survival in unselected sporadic breast cancer patients in Croatian population. However, the results support the role of the A2A2 genotype of the PIN3 (+16 bp) polymorphism as a marker for identification of patients that may benefit from anthracycline-containing chemotherapy.

  4. Abdominal Circumference Versus Body Mass Index as Predictors of Lower Extremity Overuse Injury Risk.

    PubMed

    Nye, Nathaniel S; Kafer, Drew S; Olsen, Cara; Carnahan, David H; Crawford, Paul F

    2018-02-01

    Abdominal circumference (AC) is superior to body mass index (BMI) as a measure of risk for various health outcomes. Our objective was to compare AC and BMI as predictors of lower extremity overuse injury (LEOI) risk. Retrospective review of electronic medical records of 79,868 US Air Force personnel over a 7-year period (2005-2011) for incidence of new LEOI. Subjects were stratified by BMI and AC. Injury risk for BMI/AC subgroups was calculated using Kaplan-Meier curves and Cox proportional-hazards regression. Receiver operating characteristic curves with area under the curve were used to compare each model's predictive value. Cox proportional-hazards regression showed significant risk association between elevated BMI, AC, and all injury types, with hazard ratios ranging 1.230-3.415 for obese versus normal BMI and 1.665-3.893 for high-risk versus low-risk AC (P < .05 for all measures). Receiver operating characteristic curves with area under the curve showed equivalent performance between BMI and AC for predicting all injury types. However, the combined model (AC and BMI) showed improved predictive ability over either model alone for joint injury, overall LEOI, and most strongly for osteoarthritis. Although AC and BMI alone performed similarly well, a combined approach using BMI and AC together improved risk estimation for LEOI.

  5. Comparative Study of Barotrauma Risk during Fish Passage through Kaplan Turbines

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Richmond, Marshall C.; Romero-Gomez, Pedro; Serkowski, John A.

    Rapid pressure changes in hydroelectric turbine flows can cause barotrauma that can be hazardous to the passage of fish, in particular migratory juvenile salmonids. Although numerous laboratory tests have evaluated the effect of rapid decompression in fish species of relevance, numerical modeling studies offer the advantage of predicting, for new turbine designs, the potential risks of mortality and injury from rapid pressure change during turbine passage. However, rapid pressure change is only one of several hydraulic risks encountered by fish during turbine passage in addition to blade strike, shear, and turbulence. To better understand the role of rapid pressure changes,more » the present work focuses on the application of a computational fluid dynamics based method for evaluating the risk of pressure-related mortality to fish passing through an early 1960s era original hydroelectric Kaplan turbine at Wanapum Dam (Columbia River, Washington), and a modern advanced Kaplan turbine installed in 2005. The results show that the modeling approach acceptably reproduced the nadir pressure distributions compared to field data previously collected at the site using an autonomous sensor. Our findings show that the new advanced-design unit performs better, in terms of reduced barotrauma risk to fish from exposure to low pressures, than the original turbine unit. The outcomes allow for comparative analyses of turbine designs and operations prior to installation, an advantage that can potentially be integrated in the process of designing new turbine units to achieve superior environmental performance. Overall, the results show that modern turbine designs can achieve the multiple objectives of increasing power generation, lowering cavitation potential, and reducing barotrauma risks to passing fish.« less

  6. Gut microbiota composition and relapse risk in pediatric MS: A pilot study.

    PubMed

    Tremlett, Helen; Fadrosh, Douglas W; Faruqi, Ali A; Hart, Janace; Roalstad, Shelly; Graves, Jennifer; Lynch, Susan; Waubant, Emmanuelle

    2016-04-15

    We explored the association between baseline gut microbiota (16S rRNA biomarker sequencing of stool samples) in 17 relapsing-remitting pediatric MS cases and risk of relapse over a mean 19.8 months follow-up. From the Kaplan-Meier curve, 25% relapsed within an estimated 166 days from baseline. A shorter time to relapse was associated with Fusobacteria depletion (p=0.001 log-rank test), expansion of the Firmicutes (p=0.003), and presence of the Archaea Euryarchaeota (p=0.037). After covariate adjustments for age and immunomodulatory drug exposure, only absence (vs. presence) of Fusobacteria was associated with relapse risk (hazard ratio=3.2 (95% CI: 1.2-9.0), p=0.024). Further investigation is warranted. Findings could offer new targets to alter the MS disease course. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. A Follow-Up Study on Return to Work in the Year After Reporting an Occupational Injury Stratified by Outcome of the Workers' Compensation System.

    PubMed

    Rudbeck, Marianne; Johansen, Jens Peter; Omland, Øyvind

    2018-06-01

    The aim of this study was to compare return rates to work between different groups according to the decision from the workers' compensation. Register data on disability benefits were used to describe return rates to work in Kaplan-Meier curves and association with decision on compensation claims. Disability benefits were granted by the municipalities independently of any compensation claim if sick-listed. Claimants with ongoing claims were the group with the largest proportion remaining on disability benefits. Claimants with rejected claims returned to work at the same rate (occupational disease) or slower (industrial accident) than claimants with recognized claim without compensation the subsequent year and at a faster rate after decision. Compensation claims and proceedings of the workers' compensation system probably increase time to return to work; other factors such as health and social difficulties, however, may explain some of these differences.

  8. Do clinical data and human papilloma virus genotype influence spontaneous regression in grade I cervical intraepithelial neoplasia?

    PubMed

    Cortés-Alaguero, Caterina; González-Mirasol, Esteban; Morales-Roselló, José; Poblet-Martinez, Enrique

    2017-03-15

    To determine whether medical history, clinical examination and human papilloma virus (HPV) genotype influence spontaneous regression in cervical intraepithelial neoplasia grade I (CIN-I). We retrospectively evaluated 232 women who were histologically diagnosed as have CIN-I by means of Kaplan-Meier curves, the pattern of spontaneous regression according to the medical history, clinical examination, and HPV genotype. Spontaneous regression occurred in most patients and was influenced by the presence of multiple HPV genotypes but not by the HPV genotype itself. In addition, regression frequency was diminished when more than 50% of the cervix surface was affected or when an abnormal cytology was present at the beginning of follow-up. The frequency of regression in CIN-I is high, making long-term follow-up and conservative management advisable. Data from clinical examination and HPV genotyping might help to anticipate which lesions will regress.

  9. Women with hypertrophic cardiomyopathy have worse survival.

    PubMed

    Geske, Jeffrey B; Ong, Kevin C; Siontis, Konstantinos C; Hebl, Virginia B; Ackerman, Michael J; Hodge, David O; Miller, Virginia M; Nishimura, Rick A; Oh, Jae K; Schaff, Hartzell V; Gersh, Bernard J; Ommen, Steve R

    2017-12-07

    Sex differences in hypertrophic cardiomyopathy (HCM) remain unclear. We sought to characterize sex differences in a large HCM referral centre population. Three thousand six hundred and seventy-three adult patients with HCM underwent evaluation between January 1975 and September 2012 with 1661 (45.2%) female. Kaplan-Meier survival curves were assessed via log-rank test. Cox proportional hazard regression analyses evaluated the relation of sex with survival. At index visit, women were older (59 ± 16 vs. 52 ± 15 years, P < 0.0001) had more symptoms [New York Heart Association (NYHA) Class III-IV 45.0% vs. 35.3%, P < 0.0001], more obstructive physiology (77.4% vs. 71.8%, P = 0.0001), more mitral regurgitation (moderate or greater in 56.1% vs. 43.9%, P < 0.0001), higher E/e' ratio (n = 1649, 20.6 vs. 15.6, P < 0.0001), higher estimated pulmonary artery systolic pressure (n = 1783, 40.8 ± 15.4 vs. 34.8 ± 10.8 mmHg, P < 0.0001), worse cardiopulmonary exercise performance (n = 1267; percent VO2 predicted 62.8 ± 20% vs. 65.8 ± 19.2%, P = 0.007), and underwent more frequent alcohol septal ablation (4.9% vs. 3.0%, P = 0.004) but similar frequency of myectomy (28% vs. 30%, P = 0.24). Median follow-up was 10.9 (IQR 7.4-16.2) years. Kaplan-Meier analysis demonstrated lower survival in women compared with men (P < 0.0001). In multivariable modelling, female sex remained independently associated with mortality (HR 1.13 [1.03-1.22], P = 0.01) when adjusted for age, NYHA Class III-IV symptoms, and cardiovascular comorbidities. Women with HCM present at more advanced age, with more symptoms, worse cardiopulmonary exercise tolerance, and different haemodynamics than men. Sex is an important determinant in HCM management as women with HCM have worse survival. Women may require more aggressive diagnostic and therapeutic approaches. Published on behalf of the European Society of Cardiology. All

  10. Unsteady numerical simulation of the flow in the U9 Kaplan turbine model

    NASA Astrophysics Data System (ADS)

    Javadi, Ardalan; Nilsson, Håkan

    2014-03-01

    The Reynolds-averaged Navier-Stokes equations with the RNG k-ε turbulence model closure are utilized to simulate the unsteady turbulent flow throughout the whole flow passage of the U9 Kaplan turbine model. The U9 Kaplan turbine model comprises 20 stationary guide vanes and 6 rotating blades (696.3 RPM), working at best efficiency load (0.71 m3/s). The computations are conducted using a general finite volume method, using the OpenFOAM CFD code. A dynamic mesh is used together with a sliding GGI interface to include the effect of the rotating runner. The clearance is included in the guide vane. The hub and tip clearances are also included in the runner. An analysis is conducted of the unsteady behavior of the flow field, the pressure fluctuation in the draft tube, and the coherent structures of the flow. The tangential and axial velocity distributions at three sections in the draft tube are compared against LDV measurements. The numerical result is in reasonable agreement with the experimental data, and the important flow physics close to the hub in the draft tube is captured. The hub and tip vortices and an on-axis forced vortex are captured. The numerical results show that the frequency of the forced vortex in 1/5 of the runner rotation.

  11. Symmetry Properties of Potentiometric Titration Curves.

    ERIC Educational Resources Information Center

    Macca, Carlo; Bombi, G. Giorgio

    1983-01-01

    Demonstrates how the symmetry properties of titration curves can be efficiently and rigorously treated by means of a simple method, assisted by the use of logarithmic diagrams. Discusses the symmetry properties of several typical titration curves, comparing the graphical approach and an explicit mathematical treatment. (Author/JM)

  12. Lymphopenia predicts poor prognosis in patients with esophageal squamous cell carcinoma.

    PubMed

    Feng, Ji-Feng; Liu, Jin-Shi; Huang, Ying

    2014-12-01

    Lymphopenia is a useful predictive factor in several cancers. The aim of this study was to determine the prognostic value of lymphopenia in patients with esophageal squamous cell carcinoma (ESCC).A retrospective analysis of 307 consecutive patients who had undergone esophagectomy for ESCC was conducted. In our study, a lymphocyte count (LC) of fewer than 1.0 Giga/L was defined as lymphopenia. Kaplan-Meier method was used to calculate the cancer-specific survival (CSS). Cox regression analyses were performed to evaluate the prognostic factors. Receiver operating characteristic (ROC) curve was also plotted to verify the accuracy of LC for CSS prediction.The mean LC was 1.55 ± 0.64 Giga/L (range 0.4-3.7 Giga/L). The incidence of lymphopenia (LC < 1.0 Giga/L) was 16.6% (51/307). Patients with lymphopenia (LC < 1.0 Giga/L) had a significantly shorter 5-year CSS (21.6% vs 43.8%, P = 0.004). On multivariate analysis, lymphopenia (LC < 1.0 Giga/L) was an independent prognostic factor in patients with ESCC (P = 0.013). Lymphopenia had a hazard ratio (HR) of 1.579 [95% confidence interval (CI): 1.100-2.265] for CSS. ROC curve demonstrated that lymphopenia (LC < 1.0 Giga/L) predicts survival with a sensitivity of 86.2% and a specificity of 27.2%. Lymphopenia (LC < 1.0 Giga/L) is still an independent predictive factor for long-term survival in patients with ESCC.

  13. A Meier-Gorlin syndrome mutation in a conserved C-terminal helix of Orc6 impedes origin recognition complex formation.

    PubMed

    Bleichert, Franziska; Balasov, Maxim; Chesnokov, Igor; Nogales, Eva; Botchan, Michael R; Berger, James M

    2013-10-08

    In eukaryotes, DNA replication requires the origin recognition complex (ORC), a six-subunit assembly that promotes replisome formation on chromosomal origins. Despite extant homology between certain subunits, the degree of structural and organizational overlap between budding yeast and metazoan ORC has been unclear. Using 3D electron microscopy, we determined the subunit organization of metazoan ORC, revealing that it adopts a global architecture very similar to the budding yeast complex. Bioinformatic analysis extends this conservation to Orc6, a subunit of somewhat enigmatic function. Unexpectedly, a mutation in the Orc6 C-terminus linked to Meier-Gorlin syndrome, a dwarfism disorder, impedes proper recruitment of Orc6 into ORC; biochemical studies reveal that this region of Orc6 associates with a previously uncharacterized domain of Orc3 and is required for ORC function and MCM2-7 loading in vivo. Together, our results suggest that Meier-Gorlin syndrome mutations in Orc6 impair the formation of ORC hexamers, interfering with appropriate ORC functions. DOI:http://dx.doi.org/10.7554/eLife.00882.001.

  14. The risk of revision in total knee arthroplasty is not affected by previous high tibial osteotomy

    PubMed Central

    Badawy, Mona; Fenstad, Anne M; Indrekvam, Kari; Havelin, Leif I; Furnes, Ove

    2015-01-01

    Background and purpose — Previous studies have found different outcomes after revision of knee arthroplasties performed after high tibial osteotomy (HTO). We evaluated the risk of revision of total knee arthroplasty with or without previous HTO in a large registry material. Patients and methods — 31,077 primary TKAs were compared with 1,399 TKAs after HTO, using Kaplan-Meier 10-year survival percentages and adjusted Cox regression analysis. Results — The adjusted survival analyses showed similar survival in the 2 groups. The Kaplan-Meier 10-year survival was 93.8% in the primary TKA group and 92.6% in the TKA-post-HTO group. Adjusted RR was 0.97 (95% CI: 0.77–1.21; p = 0.8). Interpretation — In this registry-based study, previous high tibial osteotomy did not appear to compromise the results regarding risk of revision after total knee arthroplasty compared to primary knee arthroplasty. PMID:26058747

  15. Survival Analysis of Patients with End Stage Renal Disease

    NASA Astrophysics Data System (ADS)

    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.

  16. Clinical and Economic Evaluation of Treatment Strategies for T1N0 Anal Canal Cancer.

    PubMed

    Deshmukh, Ashish A; Zhao, Hui; Das, Prajnan; Chiao, Elizabeth Y; You, Yi-Qian Nancy; Franzini, Luisa; Lairson, David R; Swartz, Michael D; Giordano, Sharon H; Cantor, Scott B

    2018-07-01

    A comparative assessment of treatment alternatives for T1N0 anal canal cancer has never been conducted. We compared the outcomes associated with the treatment alternatives-chemoradiotherapy (CRT), radiotherapy (RT), and surgery or ablation techniques (surgery/ablation)-for T1N0 anal canal cancer. This retrospective cohort study was conducted using the Surveillance, Epidemiology and End Results (SEER) registries linked with Medicare longitudinal data (SEER-Medicare database). Analysis included 190 patients who were treated for T1N0 anal canal cancer using surgery/ablation (n=44), RT (n=50), or CRT (n=96). The outcomes were reported in terms of survival and hazards ratios using Kaplan-Meier and Cox proportional hazards modeling, respectively; lifetime costs; and cost-effectiveness measured in terms of incremental cost-effectiveness ratio, that is, the ratio of the difference in costs between the 2 alternatives to the difference in effectiveness between the same 2 alternatives. There was no significant difference in the survival duration between the treatment groups as predicted by the Kaplan-Meier curves. After adjusting for patient characteristics and propensity score, the hazard ratio of death for the patients who received CRT compared with surgery/ablation was 1.742 (95% confidence interval, 0.793-3.829) and RT was 2.170 (95% confidence interval, 0.923-5.101); however, the relationship did not reach statistical significance. Surgery/ablation resulted in lower lifetime cost than RT or CRT. The incremental cost-effectiveness ratio associated with CRT compared with surgery/ablation was $142,883 per life year gained. There was no statistically significant difference in survival among the treatment alternatives for T1N0 anal canal cancer. Given that surgery/ablation costs less than RT or CRT and might be cost-effective compared with RT and CRT, it is crucial to explore this finding further in this era of limited health care resources.

  17. Different electrophysiological profiles and treatment response in 'typical' and 'atypical' chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Kuwabara, Satoshi; Isose, Sagiri; Mori, Masahiro; Mitsuma, Satsuki; Sawai, Setsu; Beppu, Minako; Sekiguchi, Yukari; Misawa, Sonoko

    2015-10-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is currently classified into 'typical' CIDP and 'atypical' subtypes such as multifocal acquired demyelinating sensory and motor neuropathy (MADSAM). To assess the frequency of CIDP subtypes, and to elucidate clinical and electrophysiological features, and treatment response in each subtype. We reviewed data from 100 consecutive patients fulfilling criteria for CIDP proposed by the European Federation of Neurological Societies and the Peripheral Nerve Society. The Kaplan-Meier curve was used to estimate long-term outcome. Patients were classified as having typical CIDP (60%), MADSAM (34%), demyelinating acquired distal symmetric neuropathy (8%) or pure sensory CIDP (1%). Compared with patients with MADSAM, patients with typical CIDP showed more rapid progression and severe disability, and demyelination predominant in the distal nerve segments. MADSAM was characterised by multifocal demyelination in the nerve trunks. Abnormal median-normal sural sensory responses were more frequently found for typical CIDP (53% vs 13%). Patients with typical CIDP invariably responded to corticosteroids, immunoglobulin or plasmapheresis, whereas patients with MADSAM were more refractory to these treatments. The Kaplan-Meier analyses showed that 64% of patients with typical CIDP and 41% of patients with MADSAM had a clinical remission 5 years later (p=0.02). Among the CIDP spectrum, typical CIDP and MADSAM are the major subtypes, and their pathophysiology appears to be distinct. In typical CIDP, the distal nerve terminals and possibly the nerve roots, where the blood-nerve barrier is anatomically deficient, are preferentially affected, raising the possibility of antibody-mediated demyelination, whereas cellular immunity with breakdown of the barrier may be important in MADSAM neuropathy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  18. Prevalence and mortality of cancer among HIV-infected inpatients in Beijing, China.

    PubMed

    Yang, Jun; Su, Shu; Zhao, Hongxin; Wang, Dennis; Wang, Jiali; Zhang, Fujie; Zhao, Yan

    2016-02-16

    Cancer is responsible for elevated HIV-related morbidity and mortality. Research on HIV-infected patients with concurrent cancer is rare in China. The purpose of our study was to investigate the prevalence and risk factors associated with cancer among HIV-infected inpatients in Beijing, and to investigate the mortality and risk factors among HIV-infected inpatients with cancer. Hospital records from a total of 1946 HIV-infected patients were collected from the Beijing Ditan Hospital. The data, from 2008 to 2013, were collected retrospectively. The cancer diagnoses included AIDS-defining cancers (ADC) and non-AIDS defining cancers (NADC). Logistic regression was used to identify risk factors predicting the concurrence of cancer with HIV. Mortality was examined using Kaplan-Meier estimates and Cox proportional hazards models. 7.7 % (149 cases) of all HIV-infected inpatients had concurrent cancer at their first hospital admission; of those, 33.6 % (50 cases) had ADCs, and 66.4 % (99 cases) had NADCs. The most prevalent NADCs were Hodgkin's lymphoma, gastrointestinal cancer, liver cancer, and lung cancer. Patients who did not accept antiretroviral therapy (ART) were more likely to suffer from cancer [AOR = 2.07 (1.42-3.01), p = 0.001]. Kaplan-Meier curves indicated that the survival probability of HIV-positive cancer patients was significantly lower than that of HIV-positive cancer-free patients (log-rank test, p < 0.001). For patients diagnosed with cancer, the mortality was also higher among those who did not receive ART [AHR = 2.19 (1.84-2.61), p < 0.001]. The prevalence of cancer concurrence among hospitalized HIV-infected patients was 7.7 %. Concurrent cancer also increased mortality among HIV-infected patients. ART was protective against concurrent cancer as well as mortality among HIV-infected cancer patients. These results highlight the importance of promoting cancer screening and early ART initiation among HIV-infected patients.

  19. Statins Reduces the Risk of Dementia in Patients with Late-Onset Depression: A Retrospective Cohort Study.

    PubMed

    Yang, Ya-Hsu; Teng, Hao-Wei; Lai, Yen-Ting; Li, Szu-Yuan; Lin, Chih-Ching; Yang, Albert C; Chan, Hsiang-Lin; Hsieh, Yi-Hsuan; Lin, Chiao-Fan; Hsu, Fu-Ying; Liu, Chih-Kuang; Liu, Wen-Sheng

    2015-01-01

    Patients with late-onset depression (LOD) have been reported to run a higher risk of subsequent dementia. The present study was conducted to assess whether statins can reduce the risk of dementia in these patients. We used the data from National Health Insurance of Taiwan during 1996-2009. Standardized Incidence Ratios (SIRs) were calculated for LOD and subsequent dementia. The criteria for LOD diagnoses included age ≥65 years, diagnosis of depression after 65 years of age, at least three service claims, and treatment with antidepressants. The time-dependent Cox proportional hazards model was applied for multivariate analyses. Propensity scores with the one-to-one nearest-neighbor matching model were used to select matching patients for validation studies. Kaplan-Meier curve estimate was used to measure the group of patients with dementia living after diagnosis of LOD. Totally 45,973 patients aged ≥65 years were enrolled. The prevalence of LOD was 12.9% (5,952/45,973). Patients with LOD showed to have a higher incidence of subsequent dementia compared with those without LOD (Odds Ratio: 2.785; 95% CI 2.619-2.958). Among patients with LOD, lipid lowering agent (LLA) users (for at least 3 months) had lower incidence of subsequent dementia than non-users (Hazard Ratio = 0.781, 95% CI 0.685-0.891). Nevertheless, only statins users showed to have reduced risk of dementia (Hazard Ratio = 0.674, 95% CI 0.547-0.832) while other LLAs did not, which was further validated by Kaplan-Meier estimates after we used the propensity scores with the one-to-one nearest-neighbor matching model to control the confounding factors. Statins may reduce the risk of subsequent dementia in patients with LOD.

  20. Heart transplant outcomes in recipients of Centers for Disease Control (CDC) high risk donors.

    PubMed

    Tsiouris, Athanasios; Wilson, Lynn; Sekar, Rajesh B; Mangi, Abeel A; Yun, James J

    2016-12-01

    A lack of donor hearts remains a major limitation of heart transplantation. Hearts from Centers for Disease Control (CDC) high-risk donors can be utilized with specific recipient consent. However, outcomes of heart transplantation with CDC high-risk donors are not well known. We sought to define outcomes, including posttransplant hepatitis and human immunodeficiency virus (HIV) status, in recipients of CDC high-risk donor hearts at our institution. All heart transplant recipients from August 2010 to December 2014 (n = 74) were reviewed. Comparison of 1) CDC high-risk donor (HRD) versus 2) standard-risk donor (SRD) groups were performed using chi-squared tests for nominal data and Wilcoxon two-sample tests for continuous variables. Survival was estimated with Kaplan-Meier curves. Of 74 heart transplant recipients reviewed, 66 (89%) received a SRD heart and eight (11%) received a CDC HRD heart. We found no significant differences in recipient age, sex, waiting list 1A status, pretransplant left ventricular assist device (LVAD) support, cytomegalovirus (CMV) status, and graft ischemia times (p = NS) between the HRD and SRD groups. All of the eight HRD were seronegative at the time of transplant. Postoperatively, there was no significant difference in rejection rates at six and 12 months posttransplant. Importantly, no HRD recipients acquired hepatitis or HIV. Survival in HRD versus SRD recipients was not significantly different by Kaplan-Meier analysis (log rank p = 0.644) at five years posttransplant. Heart transplants that were seronegative at the time of transplant had similar posttransplant graft function, rejection rates, and five-year posttransplant survival versus recipients of SRD hearts. At our institution, no cases of hepatitis or HIV occurred in HRD recipients in early follow-up. © 2016 Wiley Periodicals, Inc.

  1. Lymph node density as a prognostic predictor in patients with betel nut-related oral squamous cell carcinoma.

    PubMed

    Chang, Wei-Chin; Lin, Chun-Shu; Yang, Cheng-Yu; Lin, Chih-Kung; Chen, Yuan-Wu

    2018-04-01

    Lymph node metastasis in oral squamous cell carcinoma (OSCC) is a poor prognostic factor. The histopathologic stage (e.g., pN) is used to evaluate the severity of lymph node metastasis; however, the current staging system insufficiently predicts survival and recurrence. We investigated clinical outcomes and lymph node density (LND) in betel nut-chewing individuals. We retrospectively analyzed 389 betel nut-exposed patients with primary OSCC who underwent surgical resection in 2002-2015. The prognostic significance of LND was evaluated by overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method. Kaplan-Meier analyses showed that the 5-year OS and DFS rates in all patients were 60.9 and 48.9%, respectively. Multivariate analysis showed that variables independently prognostic for OS were aged population (hazard ratio [HR] = 1.6, 95% confidence interval [95% CI] = 1.1-2.5; P = .025), and cell differentiation classification (HR = 2.4, 95% CI = 1.4-4.2; P = .002). In pathologic N-positive patients, a receiver operating characteristic (ROC) curve for OS was used and indicated the best cutoff of 0.05, and the multivariate analysis showed that LND was an independent predictor of OS (HR = 2.2, 95% CI = 1.3-3.7; P = .004). Lymph node density, at a cutoff of 0.05, was an independent predictor of OS and DFS. OS and DFS underwent multiple analyses, and LND remained significant. The pathologic N stage had no influence in the OS analysis. LND is a more reliable predictor of survival in betel nut-chewing patients for further post operation adjuvant treatment, such as reoperation or adjuvant radiotherapy.

  2. A prospective observational study comparing a physiological scoring system with time-based discharge criteria in pediatric ambulatory surgical patients.

    PubMed

    Armstrong, James; Forrest, Helen; Crawford, Mark W

    2015-10-01

    Discharge criteria based on physiological scoring systems can be used in the postanesthesia care unit (PACU) to fast-track patients after ambulatory surgery; however, studies comparing physiological scoring systems with traditional time-based discharge criteria are lacking. The purpose of this study was to compare PACU discharge readiness times using physiological vs time-based discharge criteria in pediatric ambulatory surgical patients. We recorded physiological observations from consecutive American Society of Anesthesiologists physical status I-III patients aged 1-18 yr who were admitted to the PACU after undergoing ambulatory surgery in a tertiary academic pediatric hospital. The physiological score was a combination of the Aldrete and Chung systems. Scores were recorded every 15 min starting upon arrival in the PACU. Patients were considered fit for discharge once they attained a score ≥12 (maximum score, 14), provided no score was zero, with the time to achieve a score ≥12 defining the criteria-based discharge (CBD) time. Patients were discharged from the PACU when both the CBD and the existing time-based discharge (TBD) criteria were met. The CBD and TBD data were compared using Kaplan-Meier and log-rank analysis. Observations from 506 children are presented. Median (interquartile range [IQR]) age was 5.5 [2.8-9.9] yr. Median [IQR] CBD and TBD PACU discharge readiness times were 30 [15-45] min and 60 [45-60] min, respectively. Analysis of Kaplan-Meier curves indicated a significant difference in discharge times using the different criteria (hazard ratio, 5.43; 95% confidence interval, 4.51 to 6.53; P < 0.001). All patients were discharged home without incident. This prospective study suggests that discharge decisions based on physiological criteria have the potential for significantly speeding the transit of children through the PACU, thereby enhancing PACU efficiency and resource utilization.

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

    PubMed

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

    2013-01-01

    There are numerous unanswered questions in the application of artificial neural network models for analysis of survival data. In most studies, independent variables have been studied as qualitative dichotomous variables, and results of using discrete and continuous quantitative, ordinal, or multinomial categorical predictive variables in these models are not well understood in comparison to conventional models. This study was designed and conducted to examine the application of these models in order to determine the survival of gastric cancer patients, in comparison to the Cox proportional hazards model. We studied the postoperative survival of 330 gastric cancer patients who suffered surgery at a surgical unit of the Iran Cancer Institute over a five-year period. Covariates of age, gender, history of substance abuse, cancer site, type of pathology, presence of metastasis, stage, and number of complementary treatments were entered in the models, and survival probabilities were calculated at 6, 12, 18, 24, 36, 48, and 60 months using the Cox proportional hazards and neural network models. We estimated coefficients of the Cox model and the weights in the neural network (with 3, 5, and 7 nodes in the hidden layer) in the training group, and used them to derive predictions in the study group. Predictions with these two methods were compared with those of the Kaplan-Meier product limit estimator as the gold standard. Comparisons were performed with the Friedman and Kruskal-Wallis tests. Survival probabilities at different times were determined using the Cox proportional hazards and a neural network with three nodes in the hidden layer; the ratios of standard errors with these two methods to the Kaplan-Meier method were 1.1593 and 1.0071, respectively, revealed a significant difference between Cox and Kaplan-Meier (P < 0.05) and no significant difference between Cox and the neural network, and the neural network and the standard (Kaplan-Meier), as well as better accuracy

  4. [Estimation of survival rates: technics used (author's transl)].

    PubMed

    Rodary, C; Laplanche, A; Comnougue, C; Flamant, R

    1979-01-01

    The direct method and life-table methods (actuarial and Kaplan-Meier) for estimating survival rates are described here. The difference between direct method and lifetable method is the use of information about the patients who are still alive. Practical examples of calculation are given with recommandations for graphical displays.

  5. Differential Expression and Clinical Significance of Transforming Growth Factor-Beta Isoforms in GBM Tumors.

    PubMed

    Roy, Laurent-Olivier; Poirier, Marie-Belle; Fortin, David

    2018-04-08

    Glioblastoma (GBM) represents the most common and aggressive malignant primary brain tumors in adults. Response to standard treatment is transitory and the survival of clinical trial cohorts are little more than 14 months. GBM are characterized by excessive proliferation, invasiveness, and radio-/chemoresistance features; which are strongly upregulated by transforming growth factor-beta (TGF-β). We hypothesized that TGF-β gene expression could correlate with overall survival (OS) and serve as a prognostic biomarker. TGF-β₁ and -β₂ expression were analyzed by qPCR in 159 GBM tumor specimens. Kaplan-Meier and multivariate analyses were used to correlate expression with OS and progression-free survival (PFS). In GBM, TGF-β₁ and -β₂ levels were 33- and 11-fold higher respectively than in non-tumoral samples. Kaplan-Meier and multivariate analyses revealed that high to moderate expressions of TGF-β₁ significantly conferred a strikingly poorer OS and PFS in newly diagnosed patients. Interestingly, at relapse, neither isoforms had meaningful impact on clinical evolution. We demonstrate that TGF-β₁ is the dominant isoform in newly diagnosed GBM rather than the previously acknowledged TGF-β₂. We believe our study is the first to unveil a significant relationship between TGF-β₁ expression and OS or PFS in newly diagnosed GBM. TGF-β₁ could serve as a prognostic biomarker or target affecting treatment planning and patient follow-up.

  6. Community Music during the New Deal: The Contributions of Willem Van de Wall and Max Kaplan

    ERIC Educational Resources Information Center

    Krikun, Andrew

    2010-01-01

    Willem Van de Wall (1887-1953) and Max Kaplan (1911-98) built careers spanning music performance, music education, adult education, sociology, social work, music therapy and community music. Willem Van de Wall was a seminal influence on the development of the fields of music therapy and adult education--researching the role of music in…

  7. Initial high anti-emetic efficacy of granisetron with dexamethasone is not maintained over repeated cycles.

    PubMed Central

    de Wit, R.; van den Berg, H.; Burghouts, J.; Nortier, J.; Slee, P.; Rodenburg, C.; Keizer, J.; Fonteyn, M.; Verweij, J.; Wils, J.

    1998-01-01

    We have reported previously that the anti-emetic efficacy of single agent 5HT3 antagonists is not maintained when analysed with the measurement of cumulative probabilities. Presently, the most effective anti-emetic regimen is a combination of a 5HT3 antagonist plus dexamethasone. We, therefore, assessed the sustainment of efficacy of such a combination in 125 patients, scheduled to receive cisplatin > or = 70 mg m(-2) either alone or in combination with other cytotoxic drugs. Anti-emetic therapy was initiated with 10 mg of dexamethasone and 3 mg of granisetron intravenously, before cisplatin. On days 1-6, patients received 8 mg of dexamethasone and 1 mg of granisetron twice daily by oral administration. Protection was assessed during all cycles and calculated based on cumulative probability analyses using the method of Kaplan-Meier and a model for transitional probabilities. Irrespective of the type of analysis used, the anti-emetic efficacy of granisetron/dexamethasone decreased over cycles. The initial complete acute emesis protection rate of 66% decreased to 30% according to the method of Kaplan-Meier and to 39% using the model for transitional probabilities. For delayed emesis, the initial complete protection rate of 52% decreased to 21% (Kaplan-Meier) and to 43% (transitional probabilities). In addition, we observed that protection failure in the delayed emesis period adversely influenced the acute emesis protection in the next cycle. We conclude that the anti-emetic efficacy of a 5HT3 antagonist plus dexamethasone is not maintained over multiple cycles of highly emetogenic chemotherapy, and that the acute emesis protection is adversely influenced by protection failure in the delayed emesis phase. PMID:9652766

  8. Intraocular pressure control after the implantation of a second Ahmed glaucoma valve.

    PubMed

    Jiménez-Román, Jesús; Gil-Carrasco, Félix; Costa, Vital Paulino; Schimiti, Rui Barroso; Lerner, Fabián; Santana, Priscila Rezende; Vascocellos, Jose Paulo Cabral; Castillejos-Chévez, Armando; Turati, Mauricio; Fabre-Miranda, Karina

    2016-06-01

    The objective of this study is to evaluate the efficacy and safety of a second Ahmed glaucoma valve (AGV) in eyes with refractory glaucoma that had undergone prior Ahmed device implantation. This multicenter, retrospective study evaluated 58 eyes (58 patients) that underwent a second AGV (model S2-n = 50, model FP7-n = 8) due to uncontrolled IOP under maximal medical therapy. Outcome measures included IOP, visual acuity, number of glaucoma medications, and postoperative complications. Success was defined as IOP <21 mmHg (criterion 1) or 30 % reduction of IOP (criterion 2) with or without hypotensive medications. Persistent hypotony (IOP <5 mmHg after 3 months of follow-up), loss of light perception, and reintervention for IOP control were defined as failure. Mean preoperative IOP and mean IOPs at 12 and 30 months were 27.55 ± 1.16 mmHg (n = 58), 14.45 ± 0.83 mmHg (n = 42), and 14.81 ± 0.87 mmHg (n = 16), respectively. The mean numbers of glaucoma medications preoperatively at 12 and 30 months were 3.17 ± 0.16 (n = 58), 1.81 ± 0.2 (n = 42), and 1.83 ± 0.35 (n = 18), respectively. The reductions in mean IOP and number of medications were statistically significant at all time intervals (P < 0.001). According to criterion 1, Kaplan-Meier survival curves disclosed success rates of 62.9 % at 12 months and 56.6 % at 30 months. According to criterion 2, Kaplan-Meier survival curves disclosed success rates of 43.9 % at 12 months and 32.9 % at 30 months. The most frequent early complication was hypertensive phase (10.3 %) and the most frequent late complication was corneal edema (17.2 %). Second AGV implantation may effectively reduce IOP in eyes with uncontrolled glaucoma, and is associated with relatively few complications.

  9. Loss of PTEN Expression Is Associated With High MicroRNA 24 Level and Poor Prognosis in Patients With Tongue Squamous Cell Carcinoma.

    PubMed

    Zhao, Jingzhu; Chi, Jiadong; Gao, Ming; Zhi, Jingtai; Li, Yigong; Zheng, Xiangqian

    2017-07-01

    The aim of this study was to detect the relationship between phosphatase and tensin homolog deletion on chromosome 10 (PTEN) and microRNA 24 (miR-24) and correlate PTEN expression with important clinical parameters of patients with tongue squamous cell carcinoma (TSCC). In this retrospective case series, all TSCC patients treated at Tianjin Medical University Cancer Institute and Hospital between March 2005 and October 2011 were retrospectively reviewed. Demographic information and clinical data (histologic type, clinical stage, tumor differentiation, and so on) were collected. The miR-24 level was detected by quantitative reverse transcription-polymerase chain reaction. The PTEN level was analyzed by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction. Data analyses were performed by Spearman correlation analysis, Pearson χ 2 test, and paired t test. Kaplan-Meier curves, log-rank analyses, and a Cox proportional hazards model were used to evaluate the prognostic value of PTEN. A total of 90 patients (aged 59.4 ± 9.5 years, 53 men and 37 women) were identified. Loss of PTEN expression was detected in 28 of 90 tumors (31.1%). The PTEN messenger RNA level was negatively correlated with the miR-24 level (r = -0.569, P < .01). PTEN expression also was negatively correlated with the miR-24 level (r = -0.621, P < .01). Furthermore, PTEN expression was significantly lower in cancer tissues than in adjacent normal tissues, and its expression was negatively correlated with clinical stage (P < .01) and positively correlated with differentiation (P < .05) in TSCC patients. In addition, the Kaplan-Meier curve indicated that loss of PTEN expression resulted in poor survival of TSCC patients (P < .01). Multivariate analysis indicated that PTEN expression level and clinical stage may be independent prognostic factors for TSCC patients. This study suggested that PTEN expression was negatively correlated with the miR-24 level in

  10. Cofilin-1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patients

    PubMed Central

    Bracalente, Candelaria; Rinflerch, Adriana R.; Ibañez, Irene L.; García, Francisco M.; Volonteri, Victoria; Galimberti, Gastón N.; Klamt, Fabio; Durán, Hebe

    2018-01-01

    Melanoma is an aggressive cancer with highly metastatic ability. We propose cofilin-1, a key protein in the regulation of actin dynamics and migration, as a prognostic marker. We determined cofilin-1 levels in a retrospective cohort of patients with melanomas and benign lesions of melanocytes (nevi) by immunohistochemistry. Higher cofilin-1 levels were found in malignant melanoma (MM) with Breslow Index (BI)>2 vs MM with BI<2, melanoma in situ (MIS) and nevi and also in MM with metastasis vs MM without detected metastasis. Kaplan-Meier survival curves were performed, clustering patients according to either the type of melanocytic lesions or cofilin-1 level. Survival curves demonstrated worse prognosis of patients with high vs low cofilin-1 levels. TCGA database analysis of melanoma also showed low survival in patients with upregulated cofilin-1 mRNA vs patients without alteration in CFL1 mRNA expression. As cofilin-1 has a dual function depending on its intracellular localization, we evaluated nuclear and cytoplasmic levels of cofilin-1 in melanoma and nevi samples by immunofluorescence. MM with high Breslow index and metastatic cells not only presented cytoplasmic cofilin-1, but also showed this protein at the nucleus. An increase in nuclear/cytoplasmic cofilin-1 mean fluorescence ratio was observed in MM with BI>2 vs MM with BI<2, MIS and nevi. In conclusion, an association of cofilin-1 levels with malignant features and an inverse correlation with survival were demonstrated. Moreover, this study suggests that not only the higher levels of cofilin-1, but also its nuclear localization can be proposed as marker of worse outcome of patients with melanoma. PMID:29844875

  11. Cofilin-1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patients.

    PubMed

    Bracalente, Candelaria; Rinflerch, Adriana R; Ibañez, Irene L; García, Francisco M; Volonteri, Victoria; Galimberti, Gastón N; Klamt, Fabio; Durán, Hebe

    2018-05-08

    Melanoma is an aggressive cancer with highly metastatic ability. We propose cofilin-1, a key protein in the regulation of actin dynamics and migration, as a prognostic marker. We determined cofilin-1 levels in a retrospective cohort of patients with melanomas and benign lesions of melanocytes (nevi) by immunohistochemistry. Higher cofilin-1 levels were found in malignant melanoma (MM) with Breslow Index (BI)>2 vs MM with BI<2, melanoma in situ (MIS) and nevi and also in MM with metastasis vs MM without detected metastasis. Kaplan-Meier survival curves were performed, clustering patients according to either the type of melanocytic lesions or cofilin-1 level. Survival curves demonstrated worse prognosis of patients with high vs low cofilin-1 levels. TCGA database analysis of melanoma also showed low survival in patients with upregulated cofilin-1 mRNA vs patients without alteration in CFL1 mRNA expression. As cofilin-1 has a dual function depending on its intracellular localization, we evaluated nuclear and cytoplasmic levels of cofilin-1 in melanoma and nevi samples by immunofluorescence. MM with high Breslow index and metastatic cells not only presented cytoplasmic cofilin-1, but also showed this protein at the nucleus. An increase in nuclear/cytoplasmic cofilin-1 mean fluorescence ratio was observed in MM with BI>2 vs MM with BI<2, MIS and nevi. In conclusion, an association of cofilin-1 levels with malignant features and an inverse correlation with survival were demonstrated. Moreover, this study suggests that not only the higher levels of cofilin-1, but also its nuclear localization can be proposed as marker of worse outcome of patients with melanoma.

  12. Formation of curved micrometer-sized single crystals.

    PubMed

    Koifman Khristosov, Maria; Kabalah-Amitai, Lee; Burghammer, Manfred; Katsman, Alex; Pokroy, Boaz

    2014-05-27

    Crystals in nature often demonstrate curved morphologies rather than classical faceted surfaces. Inspired by biogenic curved single crystals, we demonstrate that gold single crystals exhibiting curved surfaces can be grown with no need of any fabrication steps. These single crystals grow from the confined volume of a droplet of a eutectic composition melt that forms via the dewetting of nanometric thin films. We can control their curvature by controlling the environment in which the process is carried out, including several parameters, such as the contact angle and the curvature of the drops, by changing the surface tension of the liquid drop during crystal growth. Here we present an energetic model that explains this phenomenon and predicts why and under what conditions crystals will be forced to grow with the curvature of the microdroplet even though the energetic state of a curved single crystal is very high.

  13. A crowdsourced nickel-and-dime approach to analog OBM research: A behavioral economic framework for understanding workforce attrition.

    PubMed

    Henley, Amy J; DiGennaro Reed, Florence D; Reed, Derek D; Kaplan, Brent A

    2016-09-01

    Incentives are a popular method to achieve desired employee performance; however, research on optimal incentive magnitude is lacking. Behavioral economic demand curves model persistence of responding in the face of increasing cost and may be suitable to examine the reinforcing value of incentives on work performance. The present use-inspired basic study integrated an experiential human operant task within a crowdsourcing platform to evaluate the applicability of behavioral economics for quantifying changes in workforce attrition. Participants included 88 Amazon Mechanical Turk Workers who earned either a $0.05 or $0.10 incentive for completing a progressively increasing response requirement. Analyses revealed statistically significant differences in breakpoint between the two groups. Additionally, a novel translation of the Kaplan-Meier survival-curve analyses for use within a demand curve framework allowed for examination of elasticity of workforce attrition. Results indicate greater inelastic attrition in the $0.05 group. We discuss the benefits of a behavioral economic approach to modeling employee behavior, how the metrics obtained from the elasticity of workforce attrition analyses (e.g., P max ) may be used to set goals for employee behavior while balancing organizational costs, and how economy type may have influenced observed outcomes. © 2016 Society for the Experimental Analysis of Behavior.

  14. Survival and mortality among users and non-users of hydroxyurea with sickle cell disease

    PubMed Central

    de Araujo, Olinda Maria Rodrigues; Ivo, Maria Lúcia; Ferreira, Marcos Antonio; Pontes, Elenir Rose Jardim Cury; Bispo, Ieda Maria Gonçalves Pacce; de Oliveira, Eveny Cristine Luna

    2015-01-01

    OBJECTIVE: to estimate survival, mortality and cause of death among users or not of hydroxyurea with sickle cell disease. METHOD: cohort study with retrospective data collection, from 1980 to 2010 of patients receiving inpatient treatment in two Brazilian public hospitals. The survival probability was determined using the Kaplan-Meier estimator, survival calculations (SPSS version 10.0), comparison between survival curves, using the log rank method. The level of significance was p=0.05. RESULTS: of 63 patients, 87% had sickle cell anemia, with 39 using hydroxyurea, with a mean time of use of the drug of 20.0±10.0 years and a mean dose of 17.37±5.4 to 20.94±7.2 mg/kg/day, raising the fetal hemoglobin. In the comparison between those using hydroxyurea and those not, the survival curve was greater among the users (p=0.014). A total of 10 deaths occurred, with a mean age of 28.1 years old, and with Acute Respiratory Failure as the main cause. CONCLUSION: the survival curve is greater among the users of hydroxyurea. The results indicate the importance of the nurse incorporating therapeutic advances of hydroxyurea in her care actions. PMID:25806633

  15. Indirect Treatment Comparison of Talimogene Laherparepvec Compared with Ipilimumab and Vemurafenib for the Treatment of Patients with Metastatic Melanoma.

    PubMed

    Quinn, Casey; Ma, Qiufei; Kudlac, Amber; Palmer, Stephen; Barber, Beth; Zhao, Zhongyun

    2016-04-01

    Few randomized controlled trials have compared new treatments for metastatic melanoma. We sought to examine the relative treatment effect of talimogene laherparepvec compared with ipilimumab and vemurafenib. A systematic literature review of treatments for metastatic melanoma was undertaken but a valid network of evidence could not be established because of a lack of comparative data or studies with sufficient common comparators. A conventional adjusted indirect treatment comparison via network meta-analysis was, therefore, not feasible. Instead, a meta-analysis of absolute efficacy was undertaken, adjusting overall survival (OS) data for differences in prognostic factors between studies using a published algorithm. Four trials were included in the final indirect treatment comparison: two of ipilimumab, one of vemurafenib, and one of talimogene laherparepvec. Median OS for ipilimumab and vemurafenib increased significantly when adjustment was applied, demonstrating that variation in disease and patient characteristics was biasing OS estimates; adjusting for this made the survival data more comparable. For both ipilimumab and vemurafenib, the adjustments improved Kaplan-Meier OS curves; the observed talimogene laherparepvec OS curve remained above the adjusted OS curves for ipilimumab and vemurafenib, showing that long-term survival could differ from the observed medians. Even with limited data, talimogene laherparepvec, ipilimumab, and vemurafenib could be compared following adjustments, thereby providing a more reliable understanding of the relative effect of treatment on survival in a more comparable patient population. The results of this analysis suggest that OS with talimogene laherparepvec is at least as good as with ipilimumab and vemurafenib and improvement was more pronounced in patients with no bone, brain, lung or other visceral metastases. Amgen Inc.

  16. [Prognostic value of three different staging schemes based on pN, MLR and LODDS in patients with T3 esophageal cancer].

    PubMed

    Wang, L; Cai, L; Chen, Q; Jiang, Y H

    2017-10-23

    Objective: To evaluate the prognostic value of three different staging schemes based on positive lymph nodes (pN), metastatic lymph nodes ratio (MLR) and log odds of positive lymph nodes (LODDS) in patients with T3 esophageal cancer. Methods: From 2007 to 2014, clinicopathological characteristics of 905 patients who were pathologically diagnosed as T3 esophageal cancer and underwent radical esophagectomy in Zhejiang Cancer Hospital were retrospectively analyzed. Kaplan-Meier curves and Multivariate Cox proportional hazards models were used to evaluate the independent prognostic factors. The values of three lymph node staging schemes for predicting 5-year survival were analyzed by using receiver operating characteristic (ROC) curves. Results: The 1-, 3- and 5-year overall survival rates of patients with T3 esophageal cancer were 80.9%, 50.0% and 38.4%, respectively. Multivariate analysis showed that MLR stage, LODDS stage and differentiation were independent prognostic survival factors ( P <0.05 for all). ROC curves showed that the area under the curve of pN stage, MLR stage, LODDS stage was 0.607, 0.613 and 0.618, respectively. However, the differences were not statistically significant ( P >0.05). Conclusions: LODDS is an independent prognostic factor for patients with T3 esophageal cancer. The value of LODDS staging system may be superior to pN staging system for evaluating the prognosis of these patients.

  17. An artificial neural network improves prediction of observed survival in patients with laryngeal squamous carcinoma.

    PubMed

    Jones, Andrew S; Taktak, Azzam G F; Helliwell, Timothy R; Fenton, John E; Birchall, Martin A; Husband, David J; Fisher, Anthony C

    2006-06-01

    The accepted method of modelling and predicting failure/survival, Cox's proportional hazards model, is theoretically inferior to neural network derived models for analysing highly complex systems with large datasets. A blinded comparison of the neural network versus the Cox's model in predicting survival utilising data from 873 treated patients with laryngeal cancer. These were divided randomly and equally into a training set and a study set and Cox's and neural network models applied in turn. Data were then divided into seven sets of binary covariates and the analysis repeated. Overall survival was not significantly different on Kaplan-Meier plot, or with either test model. Although the network produced qualitatively similar results to Cox's model it was significantly more sensitive to differences in survival curves for age and N stage. We propose that neural networks are capable of prediction in systems involving complex interactions between variables and non-linearity.

  18. Internal Migration and Sexual Initiation among Never Married Youths in Nigeria

    PubMed Central

    Mberu, Blessing Uchenna; White, Michael J

    2013-01-01

    The high rates of youth migration to urban and economic centers, in the context of persistent poverty and devastating HIV/AIDS burden, raises intricate social policy challenges in developing countries. This study examines patterns of internal migration and sexual initiation among Nigerian youths, using the 2003 Nigeria DHS data, descriptive statistics, Kaplan-Meier survival curves and discrete-time hazard regression models. Migrants generally show stronger association than non-migrants, and urban-urban migrants show the strongest independent association to early sexual initiation. These outcomes underscore that loss of social capital and exposure to sexually lenient urban environment increase youth's propensity to sexual engagement. Other significant covariates are age, gender, ethnic origin, education, independent living arrangement and formal employment. The findings highlight the inadequacy of policy perspectives that neglect complex contextual nuances across groups and the need to address limited livelihood opportunities that fuel youth migration to urban destinations. PMID:21435767

  19. Results of Casting in Severe Curves in Infantile Scoliosis.

    PubMed

    Stasikelis, Peter J; Carpenter, Ashley M

    2018-04-01

    Previous work has demonstrated best results for casting in infantile scoliosis when the curves are small and the child begins casting under 2 years of age. This study examines if casting can delay the need for growth friendly instrumentation in severe curves (50 to 106 degrees) and how the comorbidities of syrinx or genetic syndromes affected outcomes. All children undergoing casting for scoliosis at a single institution over an 8-year period were examined. Inclusion criteria included initial curve at first casting of ≥50 degrees, age ≤3 years at the start of casting, and a minimum follow-up of 3 years. Of 148 children undergoing casting during this period, 44 met our inclusion criteria. All children underwent magnetic resonance imaging. Ten children with a syrinx were identified. Ten children had known genetic syndromes (2 who also had a syrinx). The 26 children without these comorbidities were considered idiopathic. Curve magnitude ranged from 50 to 106 degrees. Nine of the 26 (35%) children in the children with idiopathic curves demonstrated resolution of their curves, while only 3 of the remaining 18 (17%) did. Of the children that did not have resolution of their curves, 14 were maintained over the entire follow-up period to within 15 degrees of their initial curve and 13 were improved 15 degrees or more. Only 5 children had an increase of 15 degrees or more over the follow-up period and 4 of these have undergone growth friendly instrumentation after a mean delay from initial cast of 71 months (range, 18 to 100 mo). This study demonstrates that even in severe curves, casting was effective in delaying instrumentation in all cases, and led to curve resolution of the curves in 12 of 44 children. Level III-case control study.

  20. ASURV: Astronomical SURVival Statistics

    NASA Astrophysics Data System (ADS)

    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.

  1. M1 macrophage recruitment correlates with worse outcome in SHH Medulloblastomas.

    PubMed

    Lee, Chanhee; Lee, Joongyub; Choi, Seung Ah; Kim, Seung-Ki; Wang, Kyu-Chang; Park, Sung-Hye; Kim, Se Hoon; Lee, Ji Yeoun; Phi, Ji Hoon

    2018-05-08

    Recent progress in molecular analysis has advanced the understanding of medulloblastoma (MB) and is anticipated to facilitate management of the disease. MB is composed of 4 molecular subgroups: WNT, SHH, Group 3, and Group 4. Macrophages play a crucial role in the tumor microenvironment; however, the functional role of their activated phenotype (M1/M2) remains controversial. Herein, we investigate the correlation between tumor-associated macrophage (TAM) recruitment within the MB subgroups and prognosis. Molecular subgrouping was performed by a nanoString-based RNA assay on retrieved snap-frozen tissue samples. Immunohistochemistry (IHC) and immunofluorescence (IF) assays were performed on subgroup identified samples, and the number of polarized macrophages was quantified from IHC. Survival analyses were conducted on collected clinical data and quantified macrophage data. TAM (M1/M2) recruitment in SHH MB was significantly higher compared to that in other subgroups. A Kaplan-Meier survival curve and multivariate Cox regression demonstrated that high M1 expressers showed worse overall survival (OS) and progression-free survival (PFS) than low M1 expressers in SHH MB, with relative risk (RR) values of 11.918 and 6.022, respectively. M1 rather than M2 correlates more strongly with worse outcome in SHH medulloblastoma.

  2. Clinical implication of elevated human cervical cancer oncogene-1 expression in esophageal squamous cell carcinoma.

    PubMed

    Liu, Ying; Li, Ke; Ren, Zhonghai; Li, Shenglei; Zhang, Hongyan; Fan, Qingxia

    2012-07-01

    The human cervical cancer oncogene 1 (HCCR-1), a novel human oncoprotein, has been shown to be upregulated in various human tumors and plays a critical role in tumorigenesis and tumor progression. Here, the authors investigated HCCR-1 level in esophageal squamous cell carcinoma (ESCC) tissues and assessed the correlation between HCCR-1 level and prognosis of the patients with ESCC. HCCR-1 levels were investigated by immunohistochemistry, in situ hybridization, real-time quantitative RT-PCR and Western blotting methods; Kaplan-Meier curve was used to evaluate the prognostic value of HCCR-1 level in patients with ESCC using log-rank test. HCCR-1 displayed high levels in ESCC tissues compared to squamous dysplasia tissues and normal esophageal epithelial tissues. No significant correlation was observed between the levels of HCCR-1 mRNA and protein and gender and age (all p>0.05) but obviously related to histological grade, clinical stage, and lymph node metastasis (all p<0.001). Moreover, the survival rate of the patients with low HCCR-1 levels was higher than that of the patients with high HCCR-1 levels (both p<0.05). These data demonstrate that HCCR-1 may be used as a novel predictor for the prognosis of the patients with ESCC.

  3. Longevity of anterior resin-bonded bridges: survival rates of two tooth preparation designs.

    PubMed

    Abuzar, M; Locke, J; Burt, G; Clausen, G; Escobar, K

    2018-04-16

    Significant developments have occurred in the design of resin-bonded bridges (RBB) over the past two decades. They are commonly used as an alternative treatment option for a single missing tooth. The longevity of these bridges needs to be further investigated to evaluate long-term outcomes for this option to remain relevant. A cohort of patients who received anterior resin-bonded bridges (ARBB) over two decades was studied retrospectively. Longevity of 206 ARBB was assessed using Kaplan-Meier probability estimates. The two modified tooth preparation designs investigated were: (A) mesial and distal vertical grooves only; and (B) one proximal groove adjacent to the pontic and two palatal grooves. Age and gender of the patient cohort were also recorded. Overall survival rate of ARBB was 98% at 5 years, 97.2% at 10 years, and 95.1% from 12 years till 21 years. Survival curves showed minor differences when compared for the two designs, age groups and gender of ARBB recipients. Differences in the proportion of surviving bridges for design A (95.96%) and design B (98.13%) were not statistically significant (Fisher's exact test). Anterior RBB with described tooth preparation designs demonstrate a high survival rate. © 2018 Australian Dental Association.

  4. Natural history definition and a suggested clinical approach to Buerger's disease: a case-control study with survival analysis.

    PubMed

    Fazeli, Bahare; Ravari, Hassan; Assadi, Reza

    2012-08-01

    The aim of this study was first to describe the natural history of Buerger's disease (BD) and then to discuss a clinical approach to this disease based on multivariate analysis. One hundred eight patients who corresponded with Shionoya's criteria were selected from 2000 to 2007 for this study. Major amputation was considered the ultimate adverse event. Survival analyses were performed by Kaplan-Meier curves. Independent variables including gender, duration of smoking, number of cigarettes smoked per day, minor amputation events and type of treatments, were determined by multivariate Cox regression analysis. The recorded data demonstrated that BD may present in four forms, including relapsing-remitting (75%), secondary progressive (4.6%), primary progressive (14.2%) and benign BD (6.2%). Most of the amputations occurred due to relapses within the six years after diagnosis of BD. In multivariate analysis, duration of smoking of more than 20 years had a significant relationship with further major amputation among patients with BD. Smoking cessation programs with experienced psychotherapists are strongly recommended for those areas in which Buerger's disease is common. Patients who have smoked for more than 20 years should be encouraged to quit smoking, but should also be recommended for more advanced treatment for limb salvage.

  5. ZEB1 expression is correlated with tumor metastasis and reduced prognosis of breast carcinoma in Asian patients.

    PubMed

    Xiang, Shuai; Liu, Ya-Min; Chen, Xu; Wang, Ya-Wen; Ma, Ran-Ran; Wu, Xiao-Juan; Gao, Peng

    2015-07-01

    Tumor metastasis is one of the key events leading to tumor relapse and poor prognosis. Nowadays, increasing evidences demonstrated that ZEB1 was implicated in human carcinogenesis. However, involvement of ZEB1 deregulation in tumorigenesis in Asian patients with breast carcinoma remains elusive. The present study included 102 Asian patients with breast carcinoma treated by surgery from January of 2005 to December of 2006, and the expression of ZEB1 was evaluated by immunohistochemistry. To further assess the prognostic value of ZEB1, Kaplan-Meier curves were constructed. In this study, elevated levels of ZEB1 expression was found in carcinomas with higher aggressive potential. We also correlated expression of ZEB1 with lymph node metastasis (P = 0.021), advanced clinical stage (P = 0.012) in all cases, and high tumor grade (P = 0.047) in invasive ductal carcinoma. Furthermore, our data suggested an elevated level of Ki-67 expression in cases with positive expression of ZEB1. Clinically, reduced overall survival and disease-free survival were observed in cases with positive ZEB1 expression than that in negative cases. Our results correlated ZEB1 with aggressive potentials of breast carcinoma and revealed a possibility for ZEB1 as a prognostic marker in breast carcinoma.

  6. TGFBI expression is an independent predictor of survival in adjuvant-treated lung squamous cell carcinoma patients.

    PubMed

    Pajares, M J; Agorreta, J; Salvo, E; Behrens, C; Wistuba, I I; Montuenga, L M; Pio, R; Rouzaut, A

    2014-03-18

    Transforming growth factor β-induced protein (TGFBI) is a secreted protein that mediates cell anchoring to the extracellular matrix. This protein is downregulated in lung cancer, and when overexpressed, contributes to apoptotic cell death. Using a small series of stage IV non-small cell lung cancer (NSCLC) patients, we previously suggested the usefulness of TGFBI as a prognostic and predictive factor in chemotherapy-treated late-stage NSCLC. In order to validate and extend these results, we broaden the analysis and studied TGFBI expression in a large series of samples obtained from stage I-IV NSCLC patients. TGFBI expression was assessed by immunohistochemistry in 364 completely resected primary NSCLC samples: 242 adenocarcinomas (ADCs) and 122 squamous cell carcinomas (SCCs). Kaplan-Meier curves, log-rank tests and the Cox proportional hazards model were used to analyse the association between TGFBI expression and survival. High TGFBI levels were associated with longer overall survival (OS, P<0.001) and progression-free survival (PFS, P<0.001) in SCC patients who received adjuvant platinium-based chemotherapy. Moreover, multivariate analysis demonstrated that high TGFBI expression is an independent predictor of better survival in patients (OS: P=0.030 and PFS: P=0.026). TGFBI may be useful for the identification of a subset of NSCLC who may benefit from adjuvant therapy.

  7. Double demonstration of oncogenic high risk human papilloma virus DNA and HPV-E7 protein in oral cancers.

    PubMed

    Pannone, G; Santoro, A; Carinci, F; Bufo, P; Papagerakis, S M; Rubini, C; Campisi, G; Giovannelli, L; Contaldo, M; Serpico, R; Mazzotta, M; Lo Muzio, L

    2011-01-01

    Oncogenic HPVs are necessarily involved in cervical cancer but their role in oral carcinogenesis is debated. To detect HPV in oral cancer, 38 cases of formalin fixed-paraffin embedded OSCC were studied by both DNA genotyping (MY09/11 L1 consensus primers in combination with GP5-GP6 primer pair followed by sequencing) and immunohistochemistry (monoclonal Abs against capsid protein and HPV-E7 protein, K1H8 DAKO and clone 8C9 INVITROGEN, respectively). HPV-16 tonsil cancer was used as positive control. The overall prevalence of HPV infection in OSCCs was 10.5%. Amplification of DNA samples showed single HPV DNA infection in 3 cases (HPV16; HPV53; HPV70) and double infection in one case of cheek cancer (HPV31/HPV44). The overall HR-HPV prevalence was 7.5%. E-7 antigen was immunohistochemically detected in all HPV-positive cases. HPV+ OSCC cases showed an overall better outcome than HPV negative oral cancers, as evaluated by Kaplan-Meier curves. HPVs exert their oncogenic role after DNA integration, gene expression of E5, E6 and E7 loci and p53/pRb host proteins suppression. This study showed that HPV-E7 protein inactivating pRb is expressed in oral cancer cells infected by oncogenic HPV other than classical HR-HPV-16/18. Interestingly HPV-70, considered a low risk virus with no definite collocation in oncogenic type category, gives rise to the expression of HPV-E7 protein and inactivate pRb in oral cancer. HPV-70, as proved in current literature, is able to inactivates also p53 protein, promoting cell immortalization. HPV-53, classified as a possible high risk virus, expresses E7 protein in OSCC, contributing to oral carcinogenesis. We have identified among OSCCs, a subgroup characterized by HPV infection (10.5%). Finally, we have proved the oncogenic potential of some HPV virus types, not well known in literature.

  8. Axial U(1) current in Grabowska and Kaplan's formulation

    NASA Astrophysics Data System (ADS)

    Hamada, Yu; Kawai, Hikaru

    2017-06-01

    Recently, Grabowska and Kaplan [Phys. Rev. Lett. 116, 211602 (2016); Phys. Rev. D 94, 114504 (2016)] suggested a nonperturbative formulation of a chiral gauge theory, which consists of the conventional domain-wall fermion and a gauge field that evolves by gradient flow from one domain wall to the other. We introduce two sets of domain-wall fermions belonging to complex conjugate representations so that the effective theory is a 4D vector-like gauge theory. Then, as a natural definition of the axial-vector current, we consider a current that generates simultaneous phase transformations for the massless modes in 4 dimensions. However, this current is exactly conserved and does not reproduce the correct anomaly. In order to investigate this point precisely, we consider the mechanism of the conservation. We find that this current includes not only the axial current on the domain wall but also a contribution from the bulk, which is nonlocal in the sense of 4D fields. Therefore, the local current is obtained by subtracting the bulk contribution from it.

  9. Coupled skinny baker's maps and the Kaplan-Yorke conjecture

    NASA Astrophysics Data System (ADS)

    Gröger, Maik; Hunt, Brian R.

    2013-09-01

    The Kaplan-Yorke conjecture states that for ‘typical’ dynamical systems with a physical measure, the information dimension and the Lyapunov dimension coincide. We explore this conjecture in a neighborhood of a system for which the two dimensions do not coincide because the system consists of two uncoupled subsystems. We are interested in whether coupling ‘typically’ restores the equality of the dimensions. The particular subsystems we consider are skinny baker's maps, and we consider uni-directional coupling. For coupling in one of the possible directions, we prove that the dimensions coincide for a prevalent set of coupling functions, but for coupling in the other direction we show that the dimensions remain unequal for all coupling functions. We conjecture that the dimensions prevalently coincide for bi-directional coupling. On the other hand, we conjecture that the phenomenon we observe for a particular class of systems with uni-directional coupling, where the information and Lyapunov dimensions differ robustly, occurs more generally for many classes of uni-directionally coupled systems (also called skew-product systems) in higher dimensions.

  10. The Factor Structure and Age-Related Factorial Invariance of the Delis-Kaplan Executive Function System (D-KEFS)

    ERIC Educational Resources Information Center

    Latzman, Robert D.; Markon, Kristian E.

    2010-01-01

    There has been an increased interest in the structure of and relations among executive functions.The present study examined the factor structure as well as age-related factorial invariance of the Delis-Kaplan Executive Function System (D-KEFS), a widely used inventory aimed at assessing executive functions. Analyses were first conducted using data…

  11. 4 out of 5 Students Surveyed Would Recommend this Activity (Comparing Chewing Gum Flavor Durations)

    ERIC Educational Resources Information Center

    Richardson, Mary; Rogness, Neal; Gajewski, Byron

    2005-01-01

    This paper describes an interactive activity developed for illustrating hypothesis tests on the mean for paired or matched samples. The activity is extended to illustrate assessing normality, the Wilcoxon signed rank test, Kaplan-Meier survival functions, two-way analysis of variance, and the randomized block design. (Contains 6 tables and 13…

  12. Pressure pulsation in Kaplan turbines: Prototype-CFD comparison

    NASA Astrophysics Data System (ADS)

    Rivetti, A.; Lucino1, C.; Liscia, S.; Muguerza, D.; Avellan, F.

    2012-11-01

    Pressure pulsation phenomena in a large Kaplan turbine are investigated by means of numerical simulations (CFD) and prototype measurements in order to study the dynamic behavior of flow due to the blade passage and its interaction with other components of the turbine. Numerical simulations are performed with the commercial software Ansys CFX code, solving the incompressible Unsteady Reynolds-Averaged-Navier Stokes equations under a finite volume scheme. The computational domain involves the entire machine at prototype scale. Special care is taken in the discretization of the wicket gate overhang and runner blade gap. Prototype measurements are performed using pressure transducers at different locations among the wicket gate outlet and the draft tube inlet. Then, CFD results are compared with temporary signals of prototype measurements at identical locations to validate the numerical model. A detailed analysis was focused on the tip gap flow and the pressure field at the discharge ring. From a rotating reference frame perspective, it is found that the mean pressure fluctuates accordingly the wicket gate passage. Moreover, in prototype measurements the pressure frequency that reveals the presence of modulated cavitation at the discharge ring is distinguished, as also verified from the shape of erosion patches in concordance with the number of wicket gates.

  13. Socialization into a Civilization: The Dewey-Kaplan Synthesis in American Jewish Schooling in the Early 20th Century

    ERIC Educational Resources Information Center

    Jacobs, Benjamin M.

    2009-01-01

    This historical study focuses on how John Dewey's theory of education as socialization and Mordecai Kaplan's theory of Judaism as a civilization together served as an ideological base and pedagogical framework for the creation of "progressive," "reconstructed" American Jewish school programs in the early 20th century…

  14. The value of molecular expression of KIT and KIT ligand analysed using real-time polymerase chain reaction and immunohistochemistry as a prognostic indicator for canine cutaneous mast cell tumours.

    PubMed

    Costa Casagrande, T A; de Oliveira Barros, L M; Fukumasu, H; Cogliati, B; Chaible, L M; Dagli, M L Z; Matera, J M

    2015-03-01

    This study investigated the correlation between KIT gene expression determined by immunohistochemistry and real-time polymerase chain reaction (RT-PCR) and the rate of tumour recurrence and tumour-related deaths in dogs affected with mast cell tumour (MCT). Kaplan-Meier curves were constructed to compare tumour recurrence and tumour-related death between patients. The log-rank test was used to check for significant differences between curves. KIT-I, KIT-II and KIT-III staining patterns were observed in 9 (11.11%), 50 (61.73%) and 22 (27.16%) tumours, respectively. Tumour recurrence rates and tumour-related deaths were not associated with KIT staining patterns (P = 0278, P > 0.05), KIT (P = 0.289, P > 0.05) or KIT ligand (P = 0.106, P > 0.05) gene expression. Despite the lack of association between KIT staining pattern and patient survival time, the results suggest a correlation between aberrant KIT localization and increased proliferative activity of MCTs. RT-PCR seems to be a sensible method for quantitative detection of KIT gene expression in canine MCT, although expressions levels are not correlated with prognosis. © 2013 Blackwell Publishing Ltd.

  15. The expression ratio of Map7/B2M is prognostic for survival in patients with stage II colon cancer.

    PubMed

    Blum, Craig; Graham, Amanda; Yousefzadeh, Matt; Shrout, Jessica; Benjamin, Katie; Krishna, Murli; Hoda, Raza; Hoda, Rana; Cole, David J; Garrett-Mayer, Elizabeth; Reed, Carolyn; Wallace, Michael; Mitas, Michael

    2008-09-01

    Colorectal cancer (CRC) is the second most frequent cause of cancer-related death in the United States. To determine whether certain molecular markers might be prognostic for survival, we measured by quantitative real-time RT-PCR the expression levels of 15 previously studied genes that are known to be up-regulated or down-regulated in the progression of epithelial cancers. The tumor samples were extracted from formalin-fixed paraffin-embedded primary tissues derived from patients with Stage II CRC who developed disease recurrence within two years (n=10), or were disease-free for at least 4 years (n=12). We were able to determine, by AUC curve analysis, that the ratio of microtubule associated protein 7 (Map7)/B2M was predictive of outcome in our sample set. Further, using Kaplan-Meier survival analysis, we observed significantly different curves as a function of marker positivity for the Map7/B2M (p=0.0001; HR=11) expression ratio. This suggests that the expression ratio of Map7/B2M may serve as a valuable prognostic marker in patients with Stage II colon cancer, and potentially guide therapeutic decision making.

  16. The expression ratio of Map7/B2M is prognostic for survival in patients with stage II colon cancer

    PubMed Central

    BLUM, CRAIG; GRAHAM, AMANDA; YOUSEFZADEH, MATT; SHROUT, JESSICA; BENJAMIN, KATIE; KRISHNA, MURLI; HODA, RAZA; HODA, RANA; COLE, DAVID J.; GARRETT-MAYER, ELIZABETH; REED, CAROLYN; WALLACE, MICHAEL; MITAS, MICHAEL

    2012-01-01

    Colorectal cancer (CRC) is the second most frequent cause of cancer-related death in the United States. To determine whether certain molecular markers might be prognostic for survival, we measured by quantitative real-time RT-PCR the expression levels of 15 previously studied genes that are known to be up-regulated or down-regulated in the progression of epithelial cancers. The tumor samples were extracted from formalin-fixed paraffin-embedded primary tissues derived from patients with Stage II CRC who developed disease recurrence within two years (n=10), or were disease-free for at least 4 years (n=12). We were able to determine, by AUC curve analysis, that the ratio of microtubule associated protein 7 (Map7)/B2M was predictive of outcome in our sample set. Further, using Kaplan-Meier survival analysis, we observed significantly different curves as a function of marker positivity for the Map7/B2M (p=0.0001; HR=11) expression ratio. This suggests that the expression ratio of Map7/B2M may serve as a valuable prognostic marker in patients with Stage II colon cancer, and potentially guide therapeutic decision making. PMID:18695889

  17. Predictors of Perinatal Mortality Associated with Placenta Previa and Placental Abruption: An Experience from a Low Income Country

    PubMed Central

    Berhan, Yifru

    2014-01-01

    A retrospective cohort study design was used to assess predictors of perinatal mortality in women with placenta previa and abruption between January 2006 and December 2011. Four hundred thirty-two women (253 with placenta previa and 179 with placental abruption) were eligible for analysis. Binary logistic regression, Kaplan-Meier survival curve, and receiver operating characteristic (ROC) curve were used. On admission, 77% of the women were anaemic (<12 gm/dL) with mean haemoglobin level of 9.0 ± 3.0 gm/dL. The proportion of overall severe anaemia increased from about 28% on admission to 41% at discharge. There were 50% perinatal deaths (neonatal deaths of less than seven days of age and fetal deaths after 28 weeks of gestation). In the adjusted odds ratios, lengthy delay in accessing hospital care, prematurity, anaemia in the mothers, and male foetuses were independent predictors of perinatal mortality. The haemoglobin level at admission was more sensitive and more specific than prematurity in the prediction of perinatal mortality. The proportion of severe anaemia and perinatal mortality was probably one of the highest in the world. PMID:25002975

  18. Lymphovascular invasion in clear cell renal cell carcinoma--association with disease-free and cancer-specific survival.

    PubMed

    Belsante, Michael; Darwish, Oussama; Youssef, Ramy; Bagrodia, Aditya; Kapur, Payal; Sagalowsky, Arthur I; Lotan, Yair; Margulis, Vitaly

    2014-01-01

    The objective is to evaluate the effect of lymphovascular invasion (LVI) on disease-free survival (DFS) and cancer-specific survival (CSS) in patients with clinically localized clear cell renal cell carcinoma (ccRCC). Patients with ccRCC who were treated surgically in 1997 to 2010 were identified. Retrospective chart review was performed to identify clinical outcomes. Independent pathologic re-review was performed by a single pathologist to confirm LVI status. Pathologic features were correlated with clinical outcomes using Kaplan-Meier and Cox regression analyses. Four hundred and nineteen patients with nonmetastatic ccRCC comprised the study cohort. Three hundred and thirty-three of these patients had an organ-confined (pT1-2, N any, and M0) disease. LVI was present in 14.3% of all nonmetastatic patients. In all patients with nonmetastatic ccRCC, presence of LVI was correlated with significantly shorter DFS (P <0.001) and CSS (P = 0.001) on Kaplan-Meier analysis. In cases of organ-confined, nonmetastatic ccRCC, presence of LVI was a significant predictor of DFS (hazard ratio = 4.0, P = 0.026) and CSS (hazard ratio = 12.7, P = 0.01) on multivariate analysis. Patients with organ-confined RCC who were LVI positive had similar DFS (P = 0.957) and CSS (P = 0.799) to patients with locally advanced tumors (pT3-pT4, N any, and M0) on Kaplan-Meier analysis. The presence of LVI is an independent predictor of both DFS and CSS in organ-confined, nonmetastatic ccRCC. LVI positivity in patients with otherwise pathologically organ-confined ccRCC confers oncologic outcomes similar to those of patients with locally advanced disease. If confirmed by others, future revisions to the tumor-node-metastasis staging system may incorporate LVI status into the prognostic algorithm of patients with RCC. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Defibrotide for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome following nontransplant-associated chemotherapy: Final results from a post hoc analysis of data from an expanded-access program.

    PubMed

    Kernan, Nancy A; Richardson, Paul G; Smith, Angela R; Triplett, Brandon M; Antin, Joseph H; Lehmann, Leslie; Messinger, Yoav; Liang, Wei; Hume, Robin; Tappe, William; Soiffer, Robert J; Grupp, Stephan A

    2018-06-06

    Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially fatal complication of conditioning for hematopoietic stem cell transplantation (HSCT) but can occur after nontransplant-associated chemotherapy. Following HSCT, VOD/SOS with multi-organ dysfunction (MOD) may be associated with >80% mortality. Defibrotide is approved to treat severe hepatic VOD/SOS post-HSCT in patients aged >1 month in the European Union and hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the United States. Prior to US approval, defibrotide was available to treat VOD/SOS through an expanded-access treatment (T-IND) program. A post hoc analysis of nontransplant-associated VOD/SOS patients treated with defibrotide initiated within 30 days of starting chemotherapy and followed for 70 days is presented. Patients were diagnosed by Baltimore or modified Seattle criteria or biopsy, and received defibrotide 25 mg/kg/day in four divided doses (≥21 days recommended). Of the 1,154 patients in the T-IND, 137 had nontransplant-associated VOD/SOS, 82 of whom developed VOD/SOS within 30 days of starting chemotherapy. Of them, 66 (80.5%) were aged ≤16 years. Across all the 82 patients, Kaplan-Meier estimated day +70 survival was 74.1%, 65.8% in patients with MOD (n = 38), and 81.3% in patients without MOD (n = 44). By age group, Kaplan-Meier estimated day +70 survival was 80.1% in pediatric patients (n = 66) and 50.0% in adults (n = 16). Treatment-related adverse events occurred in 26.8%. In this post hoc analysis of 82 patients initiating defibrotide within 30 days of starting chemotherapy, Kaplan-Meier estimated survival was 74.1% at 70 days after defibrotide initiation. Safety profile was consistent with prior defibrotide studies. © 2018 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.

  20. Long-Term Survivors Using Intraoperative Radiotherapy for Recurrent Gynecologic Malignancies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tran, Phuoc T.; Su Zheng; Hara, Wendy

    2007-10-01

    Purpose: To analyze the outcomes of therapy and identify prognostic factors for patients treated with surgery followed by intraoperative radiotherapy (IORT) for gynecologic malignancies at a single institution. Methods and Materials: We performed a retrospective review of 36 consecutive patients treated with IORT to 44 sites with mean follow-up of 50 months. The primary site was the cervix in 47%, endometrium in 31%, vulva in 14%, vagina in 6%, and fallopian tubes in 3%. Previous RT had failed in 72% of patients, and 89% had recurrent disease. Of 38 IORT sessions, 84% included maximal cytoreductive surgery, including 18% exenterations. Themore » mean age was 52 years (range, 30-74), mean tumor size was 5 cm (range, 0.5-12), previous disease-free interval was 32 months (range, 0-177), and mean IORT dose was 1,152 cGy (range, 600-1,750). RT and systemic therapy after IORT were given to 53% and 24% of the cohort, respectively. The outcomes measured were locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and treatment-related complications. Results: The Kaplan-Meier 5-year LRC, DMFS, and DSS probability for the whole group was 44%, 51%, and 47%, respectively. For cervical cancer patients, the Kaplan-Meier 5-year LRC, DMFS, and DSS estimate was 45%, 60%, and 46%, respectively. The prognostic factors found on multivariate analysis (p {<=} 0.05) were the disease-free interval for LRC, tumor size for DMFS, and cervical primary, previous surgery, and locoregional relapse for DSS. Our cohort had 10 Grade 3-4 complications associated with treatment (surgery and IORT) and a Kaplan-Meier 5-year Grade 3-4 complication-free survival rate of 72%. Conclusions: Survival for pelvic recurrence of gynecologic cancer is poor (range, 0-25%). IORT after surgery seems to confer long-term local control in carefully selected patients.« less

  1. Simplified tools for measuring retention in care in antiretroviral treatment program in Ethiopia: cohort and current retention in care.

    PubMed

    Assefa, Yibeltal; Worku, Alemayehu; Wouters, Edwin; Koole, Olivier; Haile Mariam, Damen; Van Damme, Wim

    2012-01-01

    Patient retention in care is a critical challenge for antiretroviral treatment programs. This is mainly because retention in care is related to adherence to treatment and patient survival. It is therefore imperative that health facilities and programs measure patient retention in care. However, the currently available tools, such as Kaplan Meier, for measuring retention in care have a lot of practical limitations. The objective of this study was to develop simplified tools for measuring retention in care. Retrospective cohort data were collected from patient registers in nine health facilities in Ethiopia. Retention in care was the primary outcome for the study. Tools were developed to measure "current retention" in care during a specific period of time for a specific "ART-age group" and "cohort retention" in care among patients who were followed for the last "Y" number of years on ART. "Probability of retention" based on the tool for "cohort retention" in care was compared with "probability of retention" based on Kaplan Meier. We found that the new tools enable to measure "current retention" and "cohort retention" in care. We also found that the tools were easy to use and did not require advanced statistical skills. Both "current retention" and "cohort retention" are lower among patients in the first two "ART-age groups" and "ART-age cohorts" than in subsequent "ART-age groups" and "ART-age cohorts". The "probability of retention" based on the new tools were found to be similar to the "probability of retention" based on Kaplan Meier. The simplified tools for "current retention" and "cohort retention" will enable practitioners and program managers to measure and monitor rates of retention in care easily and appropriately. We therefore recommend that health facilities and programs start to use these tools in their efforts to improve retention in care and patient outcomes.

  2. The number of seizures needed in the EMU

    PubMed Central

    Struck, Aaron F.; Cole, Andrew J.; Cash, Sydney S.; Westover, M. Brandon

    2016-01-01

    Summary Objective The purpose of this study was to develop a quantitative framework to estimate the likelihood of multifocal epilepsy based on the number of unifocal seizures observed in the epilepsy monitoring unit (EMU). Methods Patient records from the EMU at Massachusetts General Hospital (MGH) from 2012 to 2014 were assessed for the presence of multifocal seizures as well the presence of multifocal interictal discharges and multifocal structural imaging abnormalities during the course of the EMU admission. Risk factors for multifocal seizures were assessed using sensitivity and specificity analysis. A Kaplan-Meier survival analysis was used to estimate the risk of multifocal epilepsy for a given number of consecutive seizures. To overcome the limits of the Kaplan-Meier analysis, a parametric survival function was fit to the EMU subjects with multifocal seizures and this was used to develop a Bayesian model to estimate the risk of multifocal seizures during an EMU admission. Results Multifocal interictal discharges were a significant predictor of multifocal seizures within an EMU admission with a p < 0.01, albeit with only modest sensitivity 0.74 and specificity 0.69. Multifocal potentially epileptogenic lesions on MRI were not a significant predictor p = 0.44. Kaplan-Meier analysis was limited by wide confidence intervals secondary to significant patient dropout and concern for informative censoring. The Bayesian framework provided estimates for the number of unifocal seizures needed to predict absence of multifocal seizures. To achieve 90% confidence for the absence of multifocal seizure, three seizures are needed when the pretest probability for multifocal epilepsy is 20%, seven seizures for a pretest probability of 50%, and nine seizures for a pretest probability of 80%. Significance These results provide a framework to assist clinicians in determining the utility of trying to capture a specific number of seizures in EMU evaluations of candidates for

  3. An identifiable model for informative censoring

    USGS Publications Warehouse

    Link, W.A.; Wegman, E.J.; Gantz, D.T.; Miller, J.J.

    1988-01-01

    The usual model for censored survival analysis requires the assumption that censoring of observations arises only due to causes unrelated to the lifetime under consideration. It is easy to envision situations in which this assumption is unwarranted, and in which use of the Kaplan-Meier estimator and associated techniques will lead to unreliable analyses.

  4. [Application of Competing Risks Model in Predicting Smoking Relapse Following Ischemic Stroke].

    PubMed

    Hou, Li-Sha; Li, Ji-Jie; Du, Xu-Dong; Yan, Pei-Jing; Zhu, Cai-Rong

    2017-07-01

    To determine factors associated with smoking relapse in men who survived from their first stroke. Data were collected through face to face interviews with stroke patients in the hospital, and then repeated every three months via telephone over the period from 2010 to 2014. Kaplan-Meier method and competing risk model were adopted to estimate and predict smoking relapse rates. The Kaplan-Meier method estimated a higher relapse rate than the competing risk model. The four-year relapse rate was 43.1% after adjustment of competing risk. Exposure to environmental tobacco smoking outside of home and workplace (such as bars and restaurants) ( P =0.01), single ( P <0.01), and prior history of smoking at least 20 cigarettes per day ( P =0.02) were significant predictors of smoking relapse. When competing risks exist, competing risks model should be used in data analyses. Smoking interventions should give priorities to those without a spouse and those with a heavy smoking history. Smoking ban in public settings can reduce smoking relapse in stroke patients.

  5. Fitting the curve in Excel®: Systematic curve fitting of laboratory and remotely sensed planetary spectra

    NASA Astrophysics Data System (ADS)

    McCraig, Michael A.; Osinski, Gordon R.; Cloutis, Edward A.; Flemming, Roberta L.; Izawa, Matthew R. M.; Reddy, Vishnu; Fieber-Beyer, Sherry K.; Pompilio, Loredana; van der Meer, Freek; Berger, Jeffrey A.; Bramble, Michael S.; Applin, Daniel M.

    2017-03-01

    Spectroscopy in planetary science often provides the only information regarding the compositional and mineralogical make up of planetary surfaces. The methods employed when curve fitting and modelling spectra can be confusing and difficult to visualize and comprehend. Researchers who are new to working with spectra may find inadequate help or documentation in the scientific literature or in the software packages available for curve fitting. This problem also extends to the parameterization of spectra and the dissemination of derived metrics. Often, when derived metrics are reported, such as band centres, the discussion of exactly how the metrics were derived, or if there was any systematic curve fitting performed, is not included. Herein we provide both recommendations and methods for curve fitting and explanations of the terms and methods used. Techniques to curve fit spectral data of various types are demonstrated using simple-to-understand mathematics and equations written to be used in Microsoft Excel® software, free of macros, in a cut-and-paste fashion that allows one to curve fit spectra in a reasonably user-friendly manner. The procedures use empirical curve fitting, include visualizations, and ameliorates many of the unknowns one may encounter when using black-box commercial software. The provided framework is a comprehensive record of the curve fitting parameters used, the derived metrics, and is intended to be an example of a format for dissemination when curve fitting data.

  6. Vasodilator-Stimulated Phosphoprotein (VASP) depletion from breast cancer MDA-MB-231 cells inhibits tumor spheroid invasion through downregulation of Migfilin, β-catenin and urokinase-plasminogen activator (uPA)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gkretsi, Vasiliki; Stylianou, Andreas; Stylianopoulos, Triantafyllos, E-mail: tstylian@ucy.ac.cy

    A hallmark of cancer cells is their ability to invade surrounding tissues and form metastases. Cell-extracellular matrix (ECM)-adhesion proteins are crucial in metastasis, connecting tumor ECM with actin cytoskeleton thus enabling cells to respond to mechanical cues. Vasodilator-stimulated phosphoprotein (VASP) is an actin-polymerization regulator which interacts with cell-ECM adhesion protein Migfilin, and regulates cell migration. We compared VASP expression in MCF-7 and MDA-MB-231 breast cancer (BC) cells and found that more invasive MDA-MB-231 cells overexpress VASP. We then utilized a 3-dimensional (3D) approach to study metastasis in MDA-MB-231 cells using a system that considers mechanical forces exerted by the ECM.more » We prepared 3D collagen I gels of increasing concentration, imaged them by atomic force microscopy, and used them to either embed cells or tumor spheroids, in the presence or absence of VASP. We show, for the first time, that VASP silencing downregulated Migfilin, β-catenin and urokinase plasminogen activator both in 2D and 3D, suggesting a matrix-independent mechanism. Tumor spheroids lacking VASP demonstrated impaired invasion, indicating VASP’s involvement in metastasis, which was corroborated by Kaplan-Meier plotter showing high VASP expression to be associated with poor remission-free survival in lymph node-positive BC patients. Hence, VASP may be a novel BC metastasis biomarker. - Highlights: • More invasive MDA-MB-231 overexpress VASP compared to MCF-7 breast cancer cells. • We prepared 3D collagen I gels of increasing concentration and characterized them. • VASP silencing downregulated Migfilin, β-catenin and uPA both in 2D and 3D culture. • Tumor spheroids lacking VASP demonstrated impaired invasion. • Kaplan-Meier plotter shows association of high VASP expression with poor survival.« less

  7. Survivorship Analysis and Clinical Outcomes of Transtibial Pullout Repair for Medial Meniscus Posterior Root Tears: A 5- to 10-Year Follow-up Study.

    PubMed

    Chung, Kyu Sung; Noh, June Mo; Ha, Jeong Ku; Ra, Ho Jong; Park, Sung Bae; Kim, Hyung Kook; Kim, Jin Goo

    2018-02-01

    This study investigated the clinical outcomes and mid- to long-term survival rates in patients undergoing transtibial pullout repair of medial meniscus posterior root tears (MMPRTs) after a minimum follow-up of 5 years. Between 2005 and 2011, patients with MMPRTs who had been followed for at least 5 years after undergoing transtibial pullout repair were recruited. Participants were identified using medical records and information in a prospectively collected database. Clinical outcomes were assessed based on a comparison of patient preoperative Lysholm scores and their scores at the final follow-up. A Kaplan-Meier survival analysis was used to investigate the survival rates of repair procedures. Clinical failures were defined as cases requiring conversion to total knee arthroplasty (TKA) or having final Lysholm score <65 or less than their preoperative scores. Overall, 91 patients (mean age, 58.7 ± 9.7 years) were included: the mean follow-up duration was 84.8 ± 13.8 months. Among these patients, the mean Lysholm score improved significantly from 51.8 ± 7.9 preoperatively to 83.0 ± 11.1 at the final follow-up (P < .001). Overall, 4 patients failed due to conversion to TKA (n = 1) or having final Lysholm scores <65 or less than the preoperative scores (n = 3). The overall Kaplan-Meier probabilities of survival after repair were 99% at 5 years, 98% at 6 years, 95% at 7 years, and 92% at 8 years. Among patients with MMPRTs, transtibial pullout repair demonstrated a high clinical survival rate and the patients demonstrated clinical improvement, based on mid- and long-term follow-up examinations. Level IV, retrospective uncontrolled case series. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  8. Satisfactory Results of the Exeter Revision Femoral Stem Used for Primary Total Hip Arthroplasty.

    PubMed

    Desy, Nicholas M; Johnson, Joshua D; Sierra, Rafael J

    2017-02-01

    The Exeter cemented femoral stem has demonstrated excellent clinical and radiographic outcomes as well as long-term survivorship free from aseptic loosening. A shorter revision stem (125 mm) with a 44 offset became available for the purpose of cement-in-cement revision situations. In certain cases, this shorter revision stem may be used for various primary total hip arthroplasties (THAs) where the standard length stem would require distally reaming the femoral canal. We sought to report on the early to midterm results of this specific stem when used for primary THA regarding (1) clinical and radiographic outcomes, (2) complications, and (3) survivorship. Twenty-nine patients (33 hips) underwent a hybrid THA using the smaller revision Exeter cemented femoral stem. Twenty-five patients (28 hips) had at least 2 years of follow-up and were assessed for clinical and radiographic outcomes. All 33 hips were included in the analysis of complications and survivorship. The Kaplan-Meier survivorship was performed using revision for all causes and for aseptic loosening as the end points. The average clinical follow-up was 4 years (range, 2-7). Harris Hip Scores improved from a mean preoperative value of 56 (range, 23-96) to 90 (range, 51-100) at the latest follow-up. All patients demonstrated superior cement mantles with no signs of loosening. One patient suffered a B2 periprosthetic fracture and 1 patient experienced 2 episodes of instability. The 5-year Kaplan-Meier survivorship was 96.7% for all causes of revision and was 100% using aseptic loosening as the end point. The shorter Exeter revision cemented femoral stem has favorable early to midterm clinical and radiographic outcomes when used for primary THA with a low complication rate and is a viable option in patients with narrow femoral canals where uncemented stem fixation is not desired. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. MALAT1 predicts poor survival in osteosarcoma patients and promotes cell metastasis through associating with EZH2

    PubMed Central

    Huo, Yanqing; Li, Qingbo; Wang, Xiqian; Jiao, Xiejia; Zheng, Jiachun; Li, Zhiqiang; Pan, Xiaohan

    2017-01-01

    Osteosarcoma is the most common type of bone cancer, especially in children and young adults. Recently, long noncoding RNAs (lncRNAs) have emerged as new prognostic markers and gene regulators in several cancers, including osteosarcoma. In this study, we investigated the contributions of the lncRNA MALAT1 in osteosarcoma with a specific focus on its transcriptional regulation and its interaction with EZH2. Our results showed that MALAT1 was significantly increased in osteosarcoma specimens and cell lines. ROC curve analysis showed that MALAT1 had a higher area under the curve than alkaline phosphatase, and Kaplan-Meier survival analysis indicated that patients with high serum levels of MALAT1 showed reduced survival rate. Knockdown of MALAT1 decreased osteosarcoma cell invasion and promoted E-cadherin expression. Mechanistic investigations showed that MALAT1 was transcriptionally activated by TGF-β. Additionally, EZH2 is highly expressed and associated with the 3’ end region of lncRNA MALAT1 in osteosarcoma, and this association finally suppressed the expression of E-cadherin. Subsequently, our gain and loss function assay showed that MALAT1 overexpression promoted cell metastasis and decreased E-cadherin level, however, this effect was partially reversed by EZH2 knockdown. In conclusion, our work illuminates that lncRNA MALAT1 is a potential diagnostic and prognostic factor in osteosarcoma and further demonstrates how MALAT1 confers an oncogenic function. Thus, lncRNA MALAT1 may serve as a promising prognostic and therapeutic target for osteosarcoma patients. PMID:28388584

  10. Protein-coding genes combined with long noncoding RNA as a novel transcriptome molecular staging model to predict the survival of patients with esophageal squamous cell carcinoma.

    PubMed

    Guo, Jin-Cheng; Wu, Yang; Chen, Yang; Pan, Feng; Wu, Zhi-Yong; Zhang, Jia-Sheng; Wu, Jian-Yi; Xu, Xiu-E; Zhao, Jian-Mei; Li, En-Min; Zhao, Yi; Xu, Li-Yan

    2018-04-09

    Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal carcinoma in China. This study was to develop a staging model to predict outcomes of patients with ESCC. Using Cox regression analysis, principal component analysis (PCA), partitioning clustering, Kaplan-Meier analysis, receiver operating characteristic (ROC) curve analysis, and classification and regression tree (CART) analysis, we mined the Gene Expression Omnibus database to determine the expression profiles of genes in 179 patients with ESCC from GSE63624 and GSE63622 dataset. Univariate cox regression analysis of the GSE63624 dataset revealed that 2404 protein-coding genes (PCGs) and 635 long non-coding RNAs (lncRNAs) were associated with the survival of patients with ESCC. PCA categorized these PCGs and lncRNAs into three principal components (PCs), which were used to cluster the patients into three groups. ROC analysis demonstrated that the predictive ability of PCG-lncRNA PCs when applied to new patients was better than that of the tumor-node-metastasis staging (area under ROC curve [AUC]: 0.69 vs. 0.65, P < 0.05). Accordingly, we constructed a molecular disaggregated model comprising one lncRNA and two PCGs, which we designated as the LSB staging model using CART analysis in the GSE63624 dataset. This LSB staging model classified the GSE63622 dataset of patients into three different groups, and its effectiveness was validated by analysis of another cohort of 105 patients. The LSB staging model has clinical significance for the prognosis prediction of patients with ESCC and may serve as a three-gene staging microarray.

  11. External validation of the diffuse intrinsic pontine glioma survival prediction model: a collaborative report from the International DIPG Registry and the SIOPE DIPG Registry.

    PubMed

    Veldhuijzen van Zanten, Sophie E M; Lane, Adam; Heymans, Martijn W; Baugh, Joshua; Chaney, Brooklyn; Hoffman, Lindsey M; Doughman, Renee; Jansen, Marc H A; Sanchez, Esther; Vandertop, William P; Kaspers, Gertjan J L; van Vuurden, Dannis G; Fouladi, Maryam; Jones, Blaise V; Leach, James

    2017-08-01

    We aimed to perform external validation of the recently developed survival prediction model for diffuse intrinsic pontine glioma (DIPG), and discuss its utility. The DIPG survival prediction model was developed in a cohort of patients from the Netherlands, United Kingdom and Germany, registered in the SIOPE DIPG Registry, and includes age <3 years, longer symptom duration and receipt of chemotherapy as favorable predictors, and presence of ring-enhancement on MRI as unfavorable predictor. Model performance was evaluated by analyzing the discrimination and calibration abilities. External validation was performed using an unselected cohort from the International DIPG Registry, including patients from United States, Canada, Australia and New Zealand. Basic comparison with the results of the original study was performed using descriptive statistics, and univariate- and multivariable regression analyses in the validation cohort. External validation was assessed following a variety of analyses described previously. Baseline patient characteristics and results from the regression analyses were largely comparable. Kaplan-Meier curves of the validation cohort reproduced separated groups of standard (n = 39), intermediate (n = 125), and high-risk (n = 78) patients. This discriminative ability was confirmed by similar values for the hazard ratios across these risk groups. The calibration curve in the validation cohort showed a symmetric underestimation of the predicted survival probabilities. In this external validation study, we demonstrate that the DIPG survival prediction model has acceptable cross-cohort calibration and is able to discriminate patients with short, average, and increased survival. We discuss how this clinico-radiological model may serve a useful role in current clinical practice.

  12. Decreased expression of FOXF2 as new predictor of poor prognosis in stage I non-small cell lung cancer.

    PubMed

    Kong, Peng-Zhou; Li, Guang-Ming; Tian, Yin; Song, Bin; Shi, RuYi

    2016-08-23

    Forkhead box F2 (FOXF2) is relatively limited to the adult lung, but its contribution to non-small cell lung cancer (NSCLC) prognosis is unclear. FOXF2 mRNA levels in NSCLC were lower than that in paired normal lung tissues (P = 0.012). The FOXF2low patients had shorter survival time than the FOXF2high patients (P = 0.024) especially in stage I (P = 0.002), chemotherapy (P = 0.018) and < 60 age groups (P = 0.002). Lower FOXF2 mRNA levels could independently predict poorer survival for patients with NSCLC (HR = 2.384, 95% CI = 1.241-4.577; P = 0.009), especially in stage I (HR =4.367, 95% CI =1.599-11.925; P = 0.004). The two independent datasets confirmed our findings. We examined FOXF2 mRNA levels in 84 primary NSCLC and 8 normal lung tissues using qRT-PCR. Rank-sum tests and chi-square tests were used to assess the differences among groups with various clinicopathological factors. Kaplan-Meier tests were used to compare survival status in patients with different FOXF2 mRNA levels. Cox proportional hazards regression model was used to evaluate the predictive value of FOXF2 mRNA level in NSCLC patients. Independent validation was performed using an independent dataset (98 samples) and an online survival analysis software Kaplan-Meier plotter (1928 samples). Our results demonstrated that decreased FOXF2 expression is an independent predictive factor for poor prognosis of patients with NSCLC, especially in stage I NSCLC.

  13. Up-Regulation of Angiotensin-Converting Enzyme (ACE) Enhances Cell Proliferation and Predicts Poor Prognosis in Laryngeal Cancer.

    PubMed

    Han, Chao-Dong; Ge, Wen-Sheng

    2016-11-01

    BACKGROUND The angiotensin-converting enzyme (ACE, CD143) gene plays a crucial role in the pathology of many cancers. Previous studies mostly focused on the gene polymorphism, but the other functions of ACE have rarely been reported. The purpose of this study was to investigate the expression of ACE and its biological function, as well as its prognostic value, in laryngeal cancer. MATERIAL AND METHODS The expression of ACE was detected by quantitative real-time polymerase chain reaction (qRT-PCR) analysis in 106 patients with laryngeal cancer and 85 healthy people. Then the cell proliferation was estimated after the cell lines Hep-2 were transfected with pGL3-ACE and empty vector, respectively. In addition, the relationship between ACE expression and clinicopathologic characteristics was analyzed. Finally, Kaplan-Meier analysis was used to evaluate the overall survival of patients with different ACE expression, while Cox regression analysis was conducted to reveal the prognostic value of ACE in laryngeal cancer. RESULTS Our results demonstrate that ACE is over-expressed in laryngeal cancer and thus promotes cell proliferation. The up-regulation of ACE was significantly influenced by tumor stage and lymph node metastasis. Patients with high ACE expression had a shorter overall survival compared with those with low ACE expression according to Kaplan-Meier analysis. The ACE gene was also found to be an important factor in the prognosis of laryngeal cancer. CONCLUSIONS Our study shows that the ACE gene was up-regulated, which promoted the cell proliferation, and it could be an independent prognostic marker in laryngeal cancer.

  14. Long noncoding RNA SNHG5 is up-regulated and serves as a potential prognostic biomarker in acute myeloid leukemia.

    PubMed

    Li, J; Sun, C-K

    2018-06-01

    Growing evidence has demonstrated that the dysregulation of long non-coding RNAs (lncRNAs) may act as an important role in human tumorigenesis. Our present study aimed to explore the expression pattern and prognostic value of a newly discovered lncRNA small nucleolar RNA host gene 5 (SNHG5) in acute myeloid leukemia (AML). The expression of SNHG5 was determined using Real-time reverse transcription-polymerase chain reaction (qRT-PCR) in bone marrow and plasma obtained from AML patients and healthy controls. The correlation between SNHG5 expression and clinical features were statistically analyzed. The association between SNHG5 expression and overall survival was estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed to analyze the prognostic significance of SNHG5 expression. SNHG5 expression levels were consistently higher in the bone marrow and plasma of AML patients than those in the healthy controls (p<0.01). Furthermore, SNHG5 upregulation more frequently occurred in AML patients with advanced FAB classification (p<0.005) and unfavorable cytogenetics (p=0.001). In addition, the data of Kaplan-Meier method revealed that overall patient survival for those with high plasma SNHG5 expression was significantly shorter than those patients with low SNHG5 expression (p<0.0070). Importantly, univariate and multivariate Cox regression analysis identified increased SNHG5 expression as an independent factor predicting poor prognosis for AML patients. Our findings provide evidence that plasma SNHG5 is an independent biomarker for patients with AML, suggesting the potential role of SNHG5 as a highly specific and sensitive biomarker.

  15. Retinoblastoma Vitreous Seed Clouds (Class 3): A Comparison of Treatment with Ophthalmic Artery Chemosurgery with or without Intravitreous and Periocular Chemotherapy.

    PubMed

    Francis, Jasmine H; Iyer, Saipriya; Gobin, Y Pierre; Brodie, Scott E; Abramson, David H

    2017-10-01

    To compare the efficacy and toxicity of treating class 3 retinoblastoma vitreous seeds with ophthalmic artery chemosurgery (OAC) alone versus OAC with intravitreous chemotherapy. Retrospective cohort study. Forty eyes containing clouds (class 3 vitreous seeds) of 40 retinoblastoma patients (19 treated with OAC alone and 21 treated with OAC plus intravitreous and periocular chemotherapy). Ocular survival, disease-free survival and time to regression of seeds were estimated with Kaplan-Meier estimates. Ocular toxicity was evaluated by clinical findings and electroretinography: 30-Hz flicker responses were compared at baseline and last follow-up visit. Continuous variables were compared with Student t test, and categorical variables were compared with the Fisher exact test. Ocular survival, disease-free survival, and time to regression of seeds. There were no disease- or treatment-related deaths and no patient demonstrated externalization of tumor or metastatic disease. There was no significant difference in the age, laterality, disease, or disease status (treatment naïve vs. previously treated) between the 2 groups. The time to regression of seeds was significantly shorter for eyes treated with OAC plus intravitreous chemotherapy (5.7 months) compared with eyes treated with OAC alone (14.6 months; P < 0.001). The 18-month Kaplan-Meier estimates of disease-free survival were significantly worse for the OAC alone group: 67.1% (95% confidence interval, 40.9%-83.6%) versus 94.1% (95% confidence interval, 65%-99.1%) for the OAC plus intravitreous chemotherapy group (P = 0.05). The 36-month Kaplan-Meier estimates of ocular survival were 83.3% (95% confidence interval, 56.7%-94.3%) for the OAC alone group and 100% for the OAC plus intravitreous chemotherapy group (P = 0.16). The mean change in electroretinography responses was not significantly different between groups, decreasing by 11 μV for the OAC alone group and 22 μV for the OAC plus intravitreous chemotherapy

  16. Statistical methods for astronomical data with upper limits. II - Correlation and regression

    NASA Technical Reports Server (NTRS)

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

    1986-01-01

    Statistical methods for calculating correlations and regressions in bivariate censored data where the dependent variable can have upper or lower limits are presented. Cox's regression and the generalization of Kendall's rank correlation coefficient provide significant levels of correlations, and the EM algorithm, under the assumption of normally distributed errors, and its nonparametric analog using the Kaplan-Meier estimator, give estimates for the slope of a regression line. Monte Carlo simulations demonstrate that survival analysis is reliable in determining correlations between luminosities at different bands. Survival analysis is applied to CO emission in infrared galaxies, X-ray emission in radio galaxies, H-alpha emission in cooling cluster cores, and radio emission in Seyfert galaxies.

  17. Lenalidomide-induced myelosuppression is associated with renal dysfunction: adverse events evaluation of treatment-naïve patients undergoing front-line lenalidomide and dexamethasone therapy.

    PubMed

    Niesvizky, Ruben; Naib, Tara; Christos, Paul J; Jayabalan, David; Furst, Jessica R; Jalbrzikowski, Jessica; Zafar, Faiza; Mark, Tomer; Lent, Richard; Pearse, Roger N; Ely, Scott; Leonard, John P; Mazumdar, Madhu; Chen-Kiang, Selina; Coleman, Morton

    2007-09-01

    Data on 72 patients receiving lenalidomide/dexamethasone for multiple myeloma (MM) was used to determine the factors that are associated with lenalidomide-induced myelosuppression. Eight of 14 patients with grade > or =3 myelosuppression had baseline creatinine clearance (CrCl) < or =0.67 ml/s. Kaplan-Meier analysis by log-rank test demonstrated a significant association (P < 0.0001) between renal insufficiency and time to myelosuppression (hazard ratio = 8.4; 95% confidence interval 2.9-24.7, P = 0.0001). Therefore, CrCl is inversely associated with significant myelosuppression. Caution should be exercised when lenalidomide therapy is commenced and CrCl should be incorporated as a determinant of the initial dosing of lenalidomide in MM patients.

  18. Prognostic predictors of patients with carcinoma of the gastric cardia.

    PubMed

    Zhang, Ming; Li, Zhigao; Ma, Yan; Zhu, Guanyu; Zhang, Hongfeng; Xue, Yingwei

    2012-05-01

    This study gives insight into survival predictors and clinicopathological features of carcinoma of the gastric cardia. The study included 233 patients who underwent operation for carcinoma of the gastric cardia. Clinicopathological prognostic variables were evaluated as predictors of long-term survival by univariate and multivariate analysis. Cox regression was used for multivariate analysis and survival curves were drawn by the Kaplan- Meier method. Carcinoma of the gastric cardia was characterized by positive lymph node metastasis (77.3%), serosal invasion (83.3%) and more stage III or IV tumors (72.5%). Overall 5-year survival rate was 21.9% and median survival period was 24 months. The 5-year survival rate was influenced by tumor size, depth on invasion, lymph node metastasis, extent of lymph node dissection, disease stage, operation methods and resection margin. The absent of serosal invasion and lymph node metastasis, curative resection should be considered to be the favourable predictors of long-term survival of patients with carcinoma of the gastric cardia.

  19. Association of the AA genotype of the BCL2 (-938C>A) promoter polymorphism with better survival in ovarian cancer.

    PubMed

    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.

  20. Risk of Falls in Parkinson's Disease: A Cross-Sectional Study of 160 Patients

    PubMed Central

    Contreras, Ana; Grandas, Francisco

    2012-01-01

    Falls are a major source of disability in Parkinson's disease. Risk factors for falling in Parkinson's disease remain unclear. To determine the relevant risk factors for falling in Parkinson's disease, we screened 160 consecutive patients with Parkinson's disease for falls and assessed 40 variables. A comparison between fallers and nonfallers was performed using statistical univariate analyses, followed by bivariate and multivariate logistic regression, receiver-operating characteristics analysis, and Kaplan-Meier curves. 38.8% of patients experienced falls since the onset of Parkinson's disease (recurrent in 67%). Tinetti Balance score and Hoehn and Yahr staging were the best independent variables associated with falls. The Tinetti Balance test predicted falls with 71% sensitivity and 79% specificity and Hoehn and Yahr staging with 77% sensitivity and 71% specificity. The risk of falls increased exponentially with age, especially from 70 years onward. Patients aged >70 years at the onset of Parkinson's disease experienced falls significantly earlier than younger patients. PMID:22292126

  1. Colistin-resistant Enterobacteriaceae infections: clinical and molecular characterization and analysis of in vitro synergy.

    PubMed

    de Maio Carrillho, Claudia M D; Gaudereto, Juliana J; Martins, Roberta Cristina Ruedas; de Castro Lima, Victor Augusto Camarinha; de Oliveira, Larissa M; Urbano, Mariana R; Perozin, Jamile S; Levin, Anna Sara; Costa, Silvia F

    2017-03-01

    We described 27 polyclonal colistin-resistant Enterobacteriaceae (MIC 4-16 μg/mL) infections (12 pneumonia, 12 urinary tract infection (UTI), two Bacteremia, and one skin/soft tissue infection) in which 74% harbored KPC. The isolates were polyclonal, 6 STs were identified and the colistin resistance was due to chromosome mutations. Eight patients with UTI received monotherapy, and combination therapy was given to 19 patients. Overall mortality was 37%. In vitro synergy using time-kill assay was observed in 14 of 19 (74%) isolates tested; the synergistic effect was observed for almost all isolates for the combination of three drugs: colistin, amikacin, and tigecycline. The Kaplan-Meier survival curve showed no significant difference comparing combination therapy with 2, 3, or more drugs and risk factors associated with death were dialysis and shock. These findings reinforce the fact that colistin in combination with other classes of drugs can be useful in treating infections caused by colistin-resistant CRE. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Effects of marital status on survival of hepatocellular carcinoma by race/ethnicity and gender.

    PubMed

    Wu, Wenrui; Fang, Daiqiong; Shi, Ding; Bian, Xiaoyuan; Li, Lanjuan

    2018-01-01

    It is well demonstrated that being married is associated with a better prognosis in multiple types of cancer. However, whether the protective effect of marital status varied across race/ethnicity and gender in patients with hepatocellular carcinoma remains unclear. Therefore, we aimed to evaluate the roles of race/ethnicity and gender in this relationship. We identified eligible patients from Surveillance, Epidemiology and End Results (SEER) database during 2004-2012. Overall and cancer-specific survival differences across marital status were compared by Kaplan-Meier curves. We also estimated crude hazard ratios (CHRs) and adjusted hazard ratios (AHRs) with 95% confidence intervals (CIs) for marital status associated with survival by race/ethnicity and gender in Cox proportional hazard models. A total of 12,168 eligible patients diagnosed with hepatocellular carcinoma were included. We observed that married status was an independent protective prognostic factor for overall and cancer-specific survival. In stratified analyses by race/ethnicity, the AHR of overall mortality (unmarried vs married) was highest for Hispanic (AHR =1.25, 95% CI, 1.13-1.39; P <0.001) and lowest for Asian or Pacific Islander (AHR =1.13; 95% CI, 1.00-1.28; P =0.042). Stratified by gender, the AHR was higher in males (AHR =1.27; 95% CI, 1.20-1.33; P <0.001). Conclusion: We demonstrated that married patients obtained better survival advantages. Race/ethnicity and gender could influence the magnitude of associations between marital status and risk of mortality.

  3. Tumour heterogeneity in glioblastoma assessed by MRI texture analysis: a potential marker of survival.

    PubMed

    Molina, David; Pérez-Beteta, Julián; Luque, Belén; Arregui, Elena; Calvo, Manuel; Borrás, José M; López, Carlos; Martino, Juan; Velasquez, Carlos; Asenjo, Beatriz; Benavides, Manuel; Herruzo, Ismael; Martínez-González, Alicia; Pérez-Romasanta, Luis; Arana, Estanislao; Pérez-García, Víctor M

    2016-07-04

    The main objective of this retrospective work was the study of three-dimensional (3D) heterogeneity measures of post-contrast pre-operative MR images acquired with T 1 weighted sequences of patients with glioblastoma (GBM) as predictors of clinical outcome. 79 patients from 3 hospitals were included in the study. 16 3D textural heterogeneity measures were computed including run-length matrix (RLM) features (regional heterogeneity) and co-occurrence matrix (CM) features (local heterogeneity). The significance of the results was studied using Kaplan-Meier curves and Cox proportional hazards analysis. Correlation between the variables of the study was assessed using the Spearman's correlation coefficient. Kaplan-Meyer survival analysis showed that 4 of the 11 RLM features and 4 of the 5 CM features considered were robust predictors of survival. The median survival differences in the most significant cases were of over 6 months. Heterogeneity measures computed on the post-contrast pre-operative T 1 weighted MR images of patients with GBM are predictors of survival. Texture analysis to assess tumour heterogeneity has been widely studied. However, most works develop a two-dimensional analysis, focusing only on one MRI slice to state tumour heterogeneity. The study of fully 3D heterogeneity textural features as predictors of clinical outcome is more robust and is not dependent on the selected slice of the tumour.

  4. A conversation with Drs. Kaplan and Moser about conflicting data, confusing results, and some recent treatment recommendations for the management of hypertension.

    PubMed

    Post, Wendy; Moser, Marvin; Kaplan, Norman

    2005-10-01

    Following a hypertension symposium in Baltimore, MD, on June 1, 2005, Dr. Wendy Post from the Johns Hopkins University School of Medicine, Baltimore, MD, had the opportunity to interview two of the outstanding hypertension experts in the United States on several controversial issues in hypertension management. Dr. Norman Kaplan is Clinical Professor of Medicine at the Southwestern Health Science Center in Dallas, TX, and Dr. Marvin Moser is Clinical Professor of Medicine at the Yale University School of Medicine, New Haven, CT. Both have been leaders in the field of hypertension treatment and education for more than 40 years. Dr. Kaplan's book Clinical Hypertension has been a standard textbook since 1973 and is now in its ninth edition. Dr. Marvin Moser was the Senior Medical Consultant to the National High Blood Pressure Education Program from 1974 to 2002 and was Chairman of the first Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure and a member of the six subsequent committees. His book Clinical Management of Hypertension is in its seventh edition. Drs. Moser and Kaplan were corecipients of the 2004 International Society of Hypertension Award for Outstanding Contributions to Hypertension Treatment and Education and have lectured extensively throughout the United States and overseas.

  5. Contribution of serum FGF21 level to the identification of left ventricular systolic dysfunction and cardiac death.

    PubMed

    Shen, Yun; Zhang, Xueli; Pan, Xiaoping; Xu, Yiting; Xiong, Qin; Lu, Zhigang; Ma, Xiaojing; Bao, Yuqian; Jia, Weiping

    2017-08-18

    The relationship between fibroblast growth factor 21 (FGF21) and cardiovascular disease has been well established in recent studies. This study aimed to investigate the relationship between FGF21 and left ventricular systolic dysfunction and cardiac death. Two-dimensional echocardiography was used to measure the left ventricular ejection fraction (LVEF) to estimate left ventricular systolic function. The optimal cutoff of FGF21 for identifying left ventricular systolic dysfunction at baseline was analyzed via receiver operating characteristic (ROC) curves. The identification of different serum levels of FGF21 and their association with cardiac death was analyzed via Kaplan-Meier survival curves. Serum FGF21 level was measured by an enzyme-linked immunosorbent assay kit, and serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level was determined by a chemiluminescent immunoassay. A total of 253 patients were recruited for this study at baseline. Patients were excluded if they lacked echocardiography or laboratory measurement data, and there were 218 patients enrolled in the final analysis. The average age was 66.32 ± 10.10 years. The optimal cutoff values of FGF21 and NT-pro-BNP for identifying left ventricular systolic dysfunction at baseline were 321.5 pg/mL and 131.3 ng/L, respectively, determined separately via ROC analysis. The areas under the curves were non-significant among FGF21, NT-pro-BNP and FGF21 + NT-pro-BNP as determined by pairwise comparisons. Both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP were independent risk factors for left ventricular systolic dysfunction at baseline (odd ratio (OR) 3.138 [1.037-9.500], P = 0.043, OR 9.207 [2.036-41.643], P = 0.004, separately). Further Kaplan-Meier survival analysis indicated an association between both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP with cardiac death in 5 years [RR 5.000 (1.326-18.861), P = 0.026; RR 9.643 (2

  6. Controlling Nutritional Status (CONUT) score as a predictor of all-cause mortality in elderly hypertensive patients: a prospective follow-up study

    PubMed Central

    Sun, Xiaonan; Luo, Leiming; Zhao, Xiaoqian; Ye, Ping

    2017-01-01

    Objectives The aim of this study was to elucidate the impact of nutritional status on survival per Controlling Nutritional Status (CONUT) score and Geriatric Nutritional Risk Index (GNRI) in patients with hypertension over 80 years of age. Design Prospective follow-up study. Participants A total of 336 hypertensive patients over 80 years old were included in this study. Outcome measures All-cause deaths were recorded as Kaplan-Meier curves to evaluate the association between CONUT and all-cause mortality at follow-up. Cox regression models were used to investigate the prognostic value of CONUT and GNRI for all-cause mortality in the 90-day period after admission. Results Hypertensive patients with higher CONUT scores exhibited higher mortality within 90 days after admission (1.49%, 6.74%, 15.38%, respectively, χ2=30.92, p=0.000). Surviving patients had higher body mass index (24.25±3.05 vs 24.25±3.05, p=0.012), haemoglobin (123.78±17.05 vs 115.07±20.42, p=0.040) and albumin levels, as well as lower fasting blood glucose (6.90±2.48 vs 8.24±3.51, p=0.010). Higher GRNI score (99.42±6.55 vs 95.69±7.77, p=0.002) and lower CONUT (3.13±1.98 vs 5.14±2.32) both indicated better nutritional status. Kaplan-Meier curves indicated that survival rates were significantly worse in the high-CONUT group compared with the low-CONUT group (χ1 =13.372, p=0.001). Cox regression indicated an increase in HR with increasing CONUT risk (from normal to moderate to severe). HRs (95% CI) for 3-month mortality was 1.458 (95% CI 1.102 to 1.911). In both respiratory tract infection and ‘other reason’ groups, only CONUT was a sufficiently predictor for all-cause mortality (HR=1.284, 95% CI 1.013 to 1.740, p=0.020 and HR=1.841, 95% CI 1.117 to 4.518, p=0.011). Receiver operating characteristic showed that CONUT higher than 3.0 was found to predict all-cause mortality with a sensitivity of 77.8% and a specificity of 64.7% (area under the curve=0.778, p<0.001). Conclusion

  7. Controlling Nutritional Status (CONUT) score as a predictor of all-cause mortality in elderly hypertensive patients: a prospective follow-up study.

    PubMed

    Sun, Xiaonan; Luo, Leiming; Zhao, Xiaoqian; Ye, Ping

    2017-09-18

    The aim of this study was to elucidate the impact of nutritional status on survival per Controlling Nutritional Status (CONUT) score and Geriatric Nutritional Risk Index (GNRI) in patients with hypertension over 80 years of age. Prospective follow-up study. A total of 336 hypertensive patients over 80 years old were included in this study. All-cause deaths were recorded as Kaplan-Meier curves to evaluate the association between CONUT and all-cause mortality at follow-up. Cox regression models were used to investigate the prognostic value of CONUT and GNRI for all-cause mortality in the 90-day period after admission. Hypertensive patients with higher CONUT scores exhibited higher mortality within 90 days after admission (1.49%, 6.74%, 15.38%, respectively, χ 2 =30.92, p=0.000). Surviving patients had higher body mass index (24.25±3.05 vs 24.25±3.05, p=0.012), haemoglobin (123.78±17.05 vs 115.07±20.42, p=0.040) and albumin levels, as well as lower fasting blood glucose (6.90±2.48 vs 8.24±3.51, p=0.010). Higher GRNI score (99.42±6.55 vs 95.69±7.77, p=0.002) and lower CONUT (3.13±1.98 vs 5.14±2.32) both indicated better nutritional status. Kaplan-Meier curves indicated that survival rates were significantly worse in the high-CONUT group compared with the low-CONUT group (χ 1 =13.372, p=0.001). Cox regression indicated an increase in HR with increasing CONUT risk (from normal to moderate to severe). HRs (95% CI) for 3-month mortality was 1.458 (95% CI 1.102 to 1.911). In both respiratory tract infection and 'other reason' groups, only CONUT was a sufficiently predictor for all-cause mortality (HR=1.284, 95% CI 1.013 to 1.740, p=0.020 and HR=1.841, 95% CI 1.117 to 4.518, p=0.011). Receiver operating characteristic showed that CONUT higher than 3.0 was found to predict all-cause mortality with a sensitivity of 77.8% and a specificity of 64.7% (area under the curve=0.778, p<0.001). Nutritional status assessed via CONUT is an accurate predictor of all

  8. Development of low head Kaplan turbine for power station rehabilitation project

    NASA Astrophysics Data System (ADS)

    Lim, S. M.; Ohtake, N.; Kurosawa, S.; Suzuki, T.; Yamasaki, T.; Nishi, H.

    2012-11-01

    This paper presents the latest Kaplan turbine rehabilitation project for Funagira Power Station in Japan completed by J-POWER Group in collaboration with Toshiba Corporation. Area of rehabilitation was restricted to guide vane and runner. The main goal of the rehabilitation project was to expand the operating range of the existing turbine in terms of discharge and power with high operational stability, low noise as well as high cavitation performance. Computational Fluids Dynamics and model test were used to optimize the shape of guide vane and runner in development stage. Finally, field tests and runner inspection were carried out to confirm the performance of the new turbine. It was found that the new turbine has excellent performance in efficiency, power output, operational stability compared with existing turbine. Moreover, no sign of cavitation on the runner blade surface was observed after 5078 hours of operation near 100% load.

  9. Implementation of pressurized air injection system in a Kaplan prototype for the reduction of vibration caused by tip vortex cavitation

    NASA Astrophysics Data System (ADS)

    Rivetti, A.; Angulo, M.; Lucino, C.; Hene, M.; Capezio, O.; Liscia, S.

    2016-11-01

    Blade tip cavitation is a well-known phenomenon that affects the performance of large-diameter Kaplan turbines and induces structural vibration. Injection of pressurized air has been found to yield promising results in reducing those damaging effects. In this work, the results of an experimental test of air injection on a 9.5-m-diameter Kaplan turbine are reported. Experiments were performed for several load conditions and for two different net heads. Accelerations, pressure pulsation and noise emission were monitored for every tested condition. Results show that, at the expense of a maximum efficiency drop of 0.2%, air injection induces a decrease on the level of vibration from 57% up to 84%, depending on the load condition. Such decrease is seen to be proportional to the air flow rate, in the range from 0.06 to 0.8‰ (respect to the discharge at the best efficiency point).

  10. Modeling Patterns of Activities using Activity Curves

    PubMed Central

    Dawadi, Prafulla N.; Cook, Diane J.; Schmitter-Edgecombe, Maureen

    2016-01-01

    Pervasive computing offers an unprecedented opportunity to unobtrusively monitor behavior and use the large amount of collected data to perform analysis of activity-based behavioral patterns. In this paper, we introduce the notion of an activity curve, which represents an abstraction of an individual’s normal daily routine based on automatically-recognized activities. We propose methods to detect changes in behavioral routines by comparing activity curves and use these changes to analyze the possibility of changes in cognitive or physical health. We demonstrate our model and evaluate our change detection approach using a longitudinal smart home sensor dataset collected from 18 smart homes with older adult residents. Finally, we demonstrate how big data-based pervasive analytics such as activity curve-based change detection can be used to perform functional health assessment. Our evaluation indicates that correlations do exist between behavior and health changes and that these changes can be automatically detected using smart homes, machine learning, and big data-based pervasive analytics. PMID:27346990

  11. Modeling Patterns of Activities using Activity Curves.

    PubMed

    Dawadi, Prafulla N; Cook, Diane J; Schmitter-Edgecombe, Maureen

    2016-06-01

    Pervasive computing offers an unprecedented opportunity to unobtrusively monitor behavior and use the large amount of collected data to perform analysis of activity-based behavioral patterns. In this paper, we introduce the notion of an activity curve , which represents an abstraction of an individual's normal daily routine based on automatically-recognized activities. We propose methods to detect changes in behavioral routines by comparing activity curves and use these changes to analyze the possibility of changes in cognitive or physical health. We demonstrate our model and evaluate our change detection approach using a longitudinal smart home sensor dataset collected from 18 smart homes with older adult residents. Finally, we demonstrate how big data-based pervasive analytics such as activity curve-based change detection can be used to perform functional health assessment. Our evaluation indicates that correlations do exist between behavior and health changes and that these changes can be automatically detected using smart homes, machine learning, and big data-based pervasive analytics.

  12. Section Curve Reconstruction and Mean-Camber Curve Extraction of a Point-Sampled Blade Surface

    PubMed Central

    Li, Wen-long; Xie, He; Li, Qi-dong; Zhou, Li-ping; Yin, Zhou-ping

    2014-01-01

    The blade is one of the most critical parts of an aviation engine, and a small change in the blade geometry may significantly affect the dynamics performance of the aviation engine. Rapid advancements in 3D scanning techniques have enabled the inspection of the blade shape using a dense and accurate point cloud. This paper proposes a new method to achieving two common tasks in blade inspection: section curve reconstruction and mean-camber curve extraction with the representation of a point cloud. The mathematical morphology is expanded and applied to restrain the effect of the measuring defects and generate an ordered sequence of 2D measured points in the section plane. Then, the energy and distance are minimized to iteratively smoothen the measured points, approximate the section curve and extract the mean-camber curve. In addition, a turbine blade is machined and scanned to observe the curvature variation, energy variation and approximation error, which demonstrates the availability of the proposed method. The proposed method is simple to implement and can be applied in aviation casting-blade finish inspection, large forging-blade allowance inspection and visual-guided robot grinding localization. PMID:25551467

  13. Section curve reconstruction and mean-camber curve extraction of a point-sampled blade surface.

    PubMed

    Li, Wen-long; Xie, He; Li, Qi-dong; Zhou, Li-ping; Yin, Zhou-ping

    2014-01-01

    The blade is one of the most critical parts of an aviation engine, and a small change in the blade geometry may significantly affect the dynamics performance of the aviation engine. Rapid advancements in 3D scanning techniques have enabled the inspection of the blade shape using a dense and accurate point cloud. This paper proposes a new method to achieving two common tasks in blade inspection: section curve reconstruction and mean-camber curve extraction with the representation of a point cloud. The mathematical morphology is expanded and applied to restrain the effect of the measuring defects and generate an ordered sequence of 2D measured points in the section plane. Then, the energy and distance are minimized to iteratively smoothen the measured points, approximate the section curve and extract the mean-camber curve. In addition, a turbine blade is machined and scanned to observe the curvature variation, energy variation and approximation error, which demonstrates the availability of the proposed method. The proposed method is simple to implement and can be applied in aviation casting-blade finish inspection, large forging-blade allowance inspection and visual-guided robot grinding localization.

  14. Survivorship of standard versus modified posterior surgical approaches in metal-on-metal hip resurfacing.

    PubMed

    M Takamura, K; Maher, P; Nath, T; Su, E P

    2014-05-01

    Metal-on-metal hip resurfacing (MOMHR) is available as an alternative option for younger, more active patients. There are failure modes that are unique to MOMHR, which include loosening of the femoral head and fractures of the femoral neck. Previous studies have speculated that changes in the vascularity of the femoral head may contribute to these failure modes. This study compares the survivorship between the standard posterior approach (SPA) and modified posterior approach (MPA) in MOMHR. A retrospective clinical outcomes study was performed examining 351 hips (279 male, 72 female) replaced with Birmingham Hip Resurfacing (BHR, Smith and Nephew, Memphis, Tennessee) in 313 patients with a pre-operative diagnosis of osteoarthritis. The mean follow-up period for the SPA group was 2.8 years (0.1 to 6.1) and for the MPA, 2.2 years (0.03 to 5.2); this difference in follow-up period was statistically significant (p < 0.01). Survival analysis was completed using the Kaplan-Meier method. At four years, the Kaplan-Meier survival curve for the SPA was 97.2% and 99.4% for the MPA; this was statistically significant (log-rank; p = 0.036). There were eight failures in the SPA and two in the MPA. There was a 3.5% incidence of femoral head collapse or loosening in the SPA and 0.4% in the MPA, which represented a significant difference (p = 0.041). There was a 1.7% incidence of fractures of the femoral neck in the SPA and none in the MPA (p = 0.108). This study found a significant difference in survivorship at four years between the SPA and the MPA (p = 0.036). The clinical outcomes of this study suggest that preserving the vascularity of the femoral neck by using the MPA results in fewer vascular-related failures in MOMHRs. Cite this article: Bone Joint Res 2014;3:150-4. ©2014 The British Editorial Society of Bone & Joint Surgery.

  15. Outcome of Acute Prosthetic Joint Infections Due to Gram-Negative Bacilli Treated with Open Debridement and Retention of the Prosthesis▿

    PubMed Central

    Martínez-Pastor, Juan C.; Muñoz-Mahamud, Ernesto; Vilchez, Félix; García-Ramiro, Sebastián; Bori, Guillem; Sierra, Josep; Martínez, José A.; Font, Lluis; Mensa, Josep; Soriano, Alex

    2009-01-01

    The aim of our study was to evaluate the outcome of acute prosthetic joint infections (PJIs) due to gram-negative bacilli (GNB) treated without implant removal. Patients with an acute PJI due to GNB diagnosed from 2000 to 2007 were prospectively registered. Demographics, comorbidity, type of implant, microbiology data, surgical treatment, antimicrobial therapy, and outcome were recorded. Classification and regression tree analysis, the Kaplan-Meier survival method, and the Cox regression model were applied. Forty-seven patients were included. The mean age was 70.7 years, and there were 15 hip prostheses and 32 knee prostheses. The median number of days from the time of arthroplasty was 20. The most frequent pathogens were members of the Enterobacteriaceae family in 41 cases and Pseudomonas spp. in 20 cases. Among the Enterobacteriaceae, 14 were resistant to ciprofloxacin, while all Pseudomonas aeruginosa isolates were susceptible to ciprofloxacin. The median durations of intravenous and oral antibiotic treatment were 14 and 64 days, respectively. A total of 35 (74.5%) patients were in remission after a median follow-up of 463 days (interquartile range, 344 to 704) days. By use of the Kaplan-Meier survival curve, a C-reactive protein (CRP) concentration of ≤15 mg/dl (P = 0.03) and receipt of a fluoroquinolone, when all GNB isolated were susceptible (P = 0.0009), were associated with a better outcome. By use of a Cox regression model, a CRP concentration of ≤15 mg/dl (odds ratio [OR], 3.57; 95% confidence interval [CI], 1.05 to 12.5; P = 0.043) and receipt of a fluoroquinolone (OR, 9.09; 95% CI, 1.96 to 50; P = 0.005) were independently associated with better outcomes. Open debridement without removal of the implant had a success rate of 74.5%, and the factors associated with good prognosis were a CRP concentration at the time of diagnosis ≤15 mg/dl and treatment with a fluoroquinolone. PMID:19687237

  16. Outcome of acute prosthetic joint infections due to gram-negative bacilli treated with open debridement and retention of the prosthesis.

    PubMed

    Martínez-Pastor, Juan C; Muñoz-Mahamud, Ernesto; Vilchez, Félix; García-Ramiro, Sebastián; Bori, Guillem; Sierra, Josep; Martínez, José A; Font, Lluis; Mensa, Josep; Soriano, Alex

    2009-11-01

    The aim of our study was to evaluate the outcome of acute prosthetic joint infections (PJIs) due to gram-negative bacilli (GNB) treated without implant removal. Patients with an acute PJI due to GNB diagnosed from 2000 to 2007 were prospectively registered. Demographics, comorbidity, type of implant, microbiology data, surgical treatment, antimicrobial therapy, and outcome were recorded. Classification and regression tree analysis, the Kaplan-Meier survival method, and the Cox regression model were applied. Forty-seven patients were included. The mean age was 70.7 years, and there were 15 hip prostheses and 32 knee prostheses. The median number of days from the time of arthroplasty was 20. The most frequent pathogens were members of the Enterobacteriaceae family in 41 cases and Pseudomonas spp. in 20 cases. Among the Enterobacteriaceae, 14 were resistant to ciprofloxacin, while all Pseudomonas aeruginosa isolates were susceptible to ciprofloxacin. The median durations of intravenous and oral antibiotic treatment were 14 and 64 days, respectively. A total of 35 (74.5%) patients were in remission after a median follow-up of 463 days (interquartile range, 344 to 704) days. By use of the Kaplan-Meier survival curve, a C-reactive protein (CRP) concentration of < or = 15 mg/dl (P = 0.03) and receipt of a fluoroquinolone, when all GNB isolated were susceptible (P = 0.0009), were associated with a better outcome. By use of a Cox regression model, a CRP concentration of < or = 15 mg/dl (odds ratio [OR], 3.57; 95% confidence interval [CI], 1.05 to 12.5; P = 0.043) and receipt of a fluoroquinolone (OR, 9.09; 95% CI, 1.96 to 50; P = 0.005) were independently associated with better outcomes. Open debridement without removal of the implant had a success rate of 74.5%, and the factors associated with good prognosis were a CRP concentration at the time of diagnosis < or = 15 mg/dl and treatment with a fluoroquinolone.

  17. Evaluation of the 7(th) edition of the UICC-AJCC tumor, node, metastasis classification for esophageal cancer in a Chinese cohort.

    PubMed

    Huang, Yan; Guo, Weigang; Shi, Shiming; He, Jian

    2016-07-01

    To assess and evaluate the prognostic value of the 7(th) edition of the Union for International Cancer Control-American Joint Committee on Cancer (UICC-AJCC) tumor, node, metastasis (TNM) staging system for Chinese patients with esophageal cancer in comparison with the 6(th) edition. A retrospective review was performed on 766 consecutive esophageal cancer patients treated with esophagectomy between 2008 and 2012. Patients were staged according to the 6(th) and 7(th) editions for esophageal cancer respectively. Survival was calculated by the Kaplan-Meier method, and multivariate analysis was performed using Cox regression model. Overall 3-year survival rate was 59.5%. There were significant differences in 3-year survival rates among T stages both according to the 6(th) edition and the 7(th) edition (P<0.001). According to the 7(th) edition, the 3-year survival rates of N0 (75.4%), N1 (65.2%), N2 (39.7%) and N3 (27.3%) patients were significant differences (P<0.001). Kaplan-Meier curve revealed a good discriminatory ability from stage I to IV, except for stage IB, IIA and IIB in the 7(th) edition staging system. Based on the 7(th) edition, the degree of differentiation, tumor length and tumor location were not independent prognostic factors on multivariate analysis. The multivariate analyses suggested that pT-, pN-, pTNM-category were all the independent prognostic factors based on the 6(th) and 7(th) edition staging system. The 7(th) edition of AJCC TNM staging system of esophageal cancer should discriminate pT2-3N0M0 (stage IB, IIA and IIB) better when considering the esophageal squamous cell cancer patients. Therefore, to improve and optimize the AJCC TNM classification for Chinese patients with esophageal cancer, more considerations about the value of tumor grade and tumor location in pT2-3N0M0 esophageal squamous cell cancer should be taken in the next new TNM staging system.

  18. Copy number gain of MYCN gene is a recurrent genetic aberration and favorable prognostic factor in Chinese pediatric neuroblastoma patients

    PubMed Central

    2013-01-01

    Background Amplification of MYCN oncogene is an established marker indicating aggressive tumor progression of neuroblastoma (NBL). But copy number analyses of MYCN gene in ganglioneuroblastoma (GNBL) and ganglioneuroma(GN) is poorly described in the literature. In the study, we evaluated the copy number aberrations of MYCN gene in clinical samples of NBLs, GNBLs and GNs and analyzed their association with clinical outcome of the patients. Methods In this study, we analyzed MYCN gene and chromosome 2 aneusomy by using fluorescence in situ hybridization (FISH) method in a total of 220 patients with NBL, GNBL and GN cases. Kaplan-Meier curves were generated by using SPSS 12.0 software. Results Of 220 patients, 178 (81.0%) were NBLs, 32 (14.5%) were GNBLs and 10 (4.5%) were GNs. MYCN gain is a recurrent genetic aberration of neuroblastic tumors (71.8%, 158/220), which was found in 129 NBLs (58.6%, 129/220), 25 GNBLs (11.4%, 25/220) and 4 GN cases (1.8%, 4/220). However, MYCN amplification was only present in 24 NBL tumors (13.5%, 24/178) and 1 GNBL case (3.1%, 1/32). Kaplan-Meier survival analysis indicated that MYCN amplification is significantly correlated with decreased overall survival in NBLs (P=0.017). Furthermore, a better prognosis trend was observed in patients with MYCN gain tumors compared with those with MYCN gene normal copy number tumors and MYCN amplification tumors (P=0.012). Conclusions In summary, the frequency of MYCN amplification in NBLs is high and is rarely observed in GNBLs and GNs, which suggest MYCN plays an important role in neuroblastic tumors differentiation. MYCN gain appeared to define a subgroup of NBLs with much better outcome and classification of MYCN gene copy number alteration as three groups (amplification, gain and normal) can provide a powerful prognostic indicator in NBLs. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6417541528559124 PMID:23320395

  19. Glaucoma Progression and its Relationship with Corrected and Uncorrected Intraocular Pressure in Eyes with History of Refractive Corneal Surgery.

    PubMed

    Kwon, Junki; Sung, Kyung Rim; Jo, Jaehyuck; Yang, Sung Ho

    2018-04-20

    To investigate glaucoma progression and its relationship with corrected and uncorrected intraocular pressure (IOP) in patients with a history of refractive corneal surgery (RCS). Totally, 56 eyes of 56 primary open-angle glaucoma patients who had a history of RCS were included. Mean keratometry and central corneal thickness were measured at the time of glaucoma diagnosis. Three IOP measurements, i.e., uncorrected IOP ( UC IOP) and corrected IOP calculated by applying the Kohlhaas ( CK IOP) and Ehlers ( CE IOP) formulas, were used. Participants were categorized into two groups (low-teen [<15 mmHg] and high-teen [≥15 mmHg] groups) according to the mean follow-up IOP, in each of the three IOP measurements. Glaucoma progression was determined based on either structurally or functionally by stereoscopic optic disc/retinal nerve fiber layer photographs or visual field tests. Kaplan-Meier survival curves were compared between the low-teens group and high-teens group for each IOP measurement. Risk factors for glaucoma progression, including uncorrected and corrected IOP measurements, were analyzed using a Cox proportional-hazards model. Among total eyes, glaucoma progression was found in 19 (34%) eyes during 4.3 years of mean follow-up period. Individual values of uncorrected IOP and corrected IOP showed significant differences (p < 0.001). Incidence of glaucoma progression was higher in high-teens group than in low-teens group by corrected IOP values (both Kohlhaas and Ehlers, p = 0.006, 0.003), but not by uncorrected IOP values (p = 0.749). The cumulative probability of glaucoma progression was significantly greater in the high-teens group than in the low-teens group using the Elhers formula determined by Kaplan-Meier analysis (p = 0.030). For glaucoma eyes with history of RCS, high-teen group by corrected mean follow-up IOP showed more glaucoma progression than low-teen group. More intensive IOP-lowering treatment will be required for patient with high

  20. Previous Bladder Cancer History in Patients with High-Risk, Non-muscle-invasive Bladder Cancer Correlates with Recurrence and Progression: Implications of Natural History.

    PubMed

    Mitrakas, Lampros P; Zachos, Ioannis V; Tzortzis, Vassileios P; Gravas, Stavros A; Rouka, Erasmia C; Dimitropoulos, Konstantinos I; Vandoros, Gerasimos P; Karatzas, Anastasios D; Melekos, Michael D; Papavassiliou, Athanasios G

    2015-07-01

    The purpose of this study was to assess the correlation of previous bladder cancer history with the recurrence and progression of patients with high-risk non-muscle-invasive bladder cancer treated with adjuvant Bacillus Calmette-Guérin (BCG) and to evaluate their natural history. Patients were divided into two groups based on the existence of previous bladder cancer (primary, non-primary). A logistic regression analysis was used to identify the possible differences in the probabilities of recurrence and progression with respect to tumor history, while potential differences due to gender, tumor size (> 3 cm, < 3 cm), stage (pTa, T1), concomitant carcinoma in situ (pTis) and number of tumors (single, multiple) were also assessed. Univariate and multivariate models were employed. In addition, Kaplan-Meier survival analysis was used to compare recurrence- and progression-free survival between the groups. A total of 192 patients were included (144 with primary and 48 with non-primary tumors). The rates of recurrence and progression for patients with primary tumors were 27.8% and 12.5%, respectively. The corresponding percentages for patients with non-primary tumors were 77.1% and 33.3%, respectively. The latter group of patients displayed significantly higher probabilities of recurrence (p=0.000; 95% confidence interval [CI], 4.067 to 18.804) and progression (p=0.002; 95% CI, 1.609 to 7.614) in a univariate logistic regression analysis. Previous bladder cancer history remained significant in the multivariate model accounting for history, age, gender, tumor size , number of tumors, stage and concomitant pTis (p=0.000; 95% CI, 4.367 to 21.924 and p=0.002; 95% CI, 1.611 to 8.182 for recurrence and progression respectively). Kaplan-Meier curves revealed that the non-primary group hadreduced progression- and recurrence-free survival. Previous non-muscle-invasive bladder cancer history correlates significantly with recurrence and progression in patients with high-risk non

  1. Short- and long-term survival after open versus endovascular repair of abdominal aortic aneurysm-Polish population analysis.

    PubMed

    Symonides, Bartosz; Śliwczyński, Andrzej; Gałązka, Zbigniew; Pinkas, Jarosław; Gaciong, Zbigniew

    2018-01-01

    The aim of the study was to compare short and long-term mortality and readmissions in patients with non-ruptured abdominal aortic aneurysm (AAA) treated with endovascular aortic repair (EVAR) or open aneurysm repair (OAR). Retrospective survival analysis based on prospectively collected medical records of the national Polish public health insurer. In the National Health Fund database we identified all patients who underwent elective open or endovascular treatment of AAA between January 1st 2011 and March 22nd 2016. The data on mortality, selected concomitant diseases and readmissions were collected. A total of 7805 patients (mean age 70.9±8.1 yrs, 85.8% males) underwent OAR (n = 2336) or EVAR (n = 5469). A median follow up was 27.5 months (IQR range 10.0-38.4 months). The primary outcome variable was all-cause mortality, secondary outcomes included 30-day mortality and readmissions. Kaplan-Meier (K-M), Cox proportional-hazards and propensity score analyses were performed for primary and secondary outcomes adjusting for repair type of AAA (OAR vs. EVAR), age, sex and concomitant diseases. EVAR patients had higher all-cause mortality (6.4% vs. 4.6% P = 0.002, adjHR 1.34, 95%CI 1.07-1.67, P = 0.010) compared with OAR. The mortality risks for OAR patients decreased below those for EVAR patients after 9.9 months. Of all the tested confounding factors only age independently and significantly influenced long-term mortality. Readmissions occurred more often in EVAR than in OAR (16.5% vs. 8.4% P<0.001, adjHR 2.15, 95%CI 1.84-2.52, P<0.001) independently from other covariants. Survival and readmissions Kaplan-Meier curves remained statistically different between OAR and EVAR patients after propensity score matching. Survival benefit of EVAR over OAR disappeared early during the first year after procedure, particularly in patients below 70 years of age, accompanied by an increased frequency of readmissions of EVAR patients. Our data suggest re-evaluation of the strategy for

  2. Up-regulation of miR-9 expression predicate advanced clinicopathological features and poor prognosis in patients with hepatocellular carcinoma.

    PubMed

    Cai, Lizhi; Cai, Xi

    2014-12-31

    MicroRNAs (miRNAs) are endogenous small (19-24 nt long) noncoding RNAs that regulate gene expression in a sequence specific manner. An increasing association between miRNA and cancer has been recently reported. Hepatocellular carcinoma (HCC), as the fifth most common cancer and the most common cause of death in men, has become the third leading cause of cancer-related deaths globally. In this study, we investigated the miR-9 expression in HCC to evaluate their value in prognosis of this tumor. The expression of miR-9 in matched normal and tumor tissues of HCC was evaluated using a quantitative real-time RT-PCR. A Kaplan-Meier survival curve was generated following a log-rank test. It was observed that miR-9 expression was upregulated in HCC tissues compared with noncancerous liver tissues (7.26 ± 1.30 vs. 3.14 ± 1.08, P < 0.001). The up-regulation of miR-9 in HCC cancer tissues was also significantly correlated with aggressive clinicopathological features. We found that the patients with high miR-9 expression have a higher tumor staging (P = 0.0389) and are in higher risk of venous infiltration (P < 0.0001). Moreover, the results of Kaplan-Meier analyses showed that HCC patients with the high miR-9 expression tend to have shorter overall survival (P < 0.0001). The multivariate analysis clearly indicated that the high miR-9 expression in biopsy samples may be considered as an independent prognostic factor in HCC for decreased survival (4.28; 95%CI, 2.77-7.23, P < 0.001). Our data indicate the potential of miR-9 as a novel prognostic biomarker for HCC. Large well-designed studies with diverse populations and functional evaluations are warranted to confirm and extend our findings. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_228.

  3. The Fate of Primary Nonrefluxing Megaureter: A Prospective Outcome Analysis of the Rate of Urinary Tract Infections, Surgical Indications and Time to Resolution.

    PubMed

    Braga, Luis H; D'Cruz, Jennifer; Rickard, Mandy; Jegatheeswaran, Kizanee; Lorenzo, Armando J

    2016-04-01

    We examined data on a cohort of patients with primary nonrefluxing megaureter to determine risk factors for febrile urinary tract infection, indications for surgery and time to resolution. The records of patients younger than 24 months with primary nonrefluxing megaureter were prospectively captured from 2008 to 2015. Six a priori defined variables were studied, including gender, circumcision status, hydronephrosis SFU (Society for Fetal Urology) grade (low--1 and 2 vs high--3 and 4), continuous antibiotic prophylaxis use, ureteral dilatation (greater than 11 mm) and tortuosity. Univariate analyses and Cox hazard regression were done for febrile urinary tract infection risk factors. Resolution trends were analyzed using Kaplan-Meier curves. Mean ± SD age at the first clinic visit was 3.7 ± 4 months and mean followup was 26.3 ± 16.6 months. Of 80 patients with primary megaureter 66 (83%) had high grade hydronephrosis, 72 (90%) were male, 21 (26%) were circumcised and 40 (50%) had ureteral dilatation greater than 11 mm at baseline. Overall continuous antibiotic prophylaxis was prescribed to 34 patients (43%) and febrile urinary tract developed infection in 27 (34%) at a mean age of 5.8 months (median 3, range 1 to 24). Cox regression identified uncircumcised male gender (HR 3.4, 95% CI 1.1-10.7, p = 0.04) and lack of continuous antibiotic prophylaxis (HR 4.1, 95% CI 1.3-12.7, p = 0.01) as independent risk factors for febrile urinary tract infection. The 19 surgical patients (24%) had a larger mean ureteral diameter immediately preoperatively than those who did not require surgery (17 ± 5 vs 12 ± 4 mm, p <0.01). Kaplan-Meier curves showed that 85% of primary nonrefluxing megaureters that did not require surgery resolved in a median of 17 months. Febrile urinary tract infection developed in 34% of patients with primary nonrefluxing megaureter within the first 6 months of life. Circumcision and continuous antibiotic prophylaxis significantly decreased febrile

  4. Comparison of power curve monitoring methods

    NASA Astrophysics Data System (ADS)

    Cambron, Philippe; Masson, Christian; Tahan, Antoine; Torres, David; Pelletier, Francis

    2017-11-01

    Performance monitoring is an important aspect of operating wind farms. This can be done through the power curve monitoring (PCM) of wind turbines (WT). In the past years, important work has been conducted on PCM. Various methodologies have been proposed, each one with interesting results. However, it is difficult to compare these methods because they have been developed using their respective data sets. The objective of this actual work is to compare some of the proposed PCM methods using common data sets. The metric used to compare the PCM methods is the time needed to detect a change in the power curve. Two power curve models will be covered to establish the effect the model type has on the monitoring outcomes. Each model was tested with two control charts. Other methodologies and metrics proposed in the literature for power curve monitoring such as areas under the power curve and the use of statistical copulas have also been covered. Results demonstrate that model-based PCM methods are more reliable at the detecting a performance change than other methodologies and that the effectiveness of the control chart depends on the types of shift observed.

  5. Beta-Catenin and Epithelial Tumors: A Study Based on 374 Oropharyngeal Cancers

    PubMed Central

    Santoro, Angela; Pannone, Giuseppe; Papagerakis, Silvana; McGuff, H. Stan; Cafarelli, Barbara; Lepore, Silvia; De Maria, Salvatore; Rubini, Corrado; Mattoni, Marilena; Staibano, Stefania; Mezza, Ernesto; De Rosa, Gaetano; Aquino, Gabriella; Losito, Simona; Loreto, Carla; Crimi, Salvatore; Bufo, Pantaleo

    2014-01-01

    Introduction. Although altered regulation of the Wnt pathway via beta-catenin is a frequent event in several human cancers, its potential implications in oral/oropharyngeal squamous cell carcinomas (OSCC/OPSCC) are largely unexplored. Work purpose was to define association between beta-catenin expression and clinical-pathological parameters in 374 OSCCs/OP-SCCs by immunohistochemistry (IHC). Materials and Methods. Association between IHC detected patterns of protein expression and clinical-pathological parameters was assessed by statistical analysis and survival rates by Kaplan-Meier curves. Beta-catenin expression was also investigated in OSCC cell lines by Real-Time PCR. An additional analysis of the DNA content was performed on 22 representative OSCCs/OPSCCs by DNA-image-cytometric analysis. Results and Discussion. All carcinomas exhibited significant alterations of beta-catenin expression (P < 0.05). Beta-catenin protein was mainly detected in the cytoplasm of cancerous cells and only focal nuclear positivity was observed. Higher cytoplasmic expression correlated significantly with poor histological differentiation, advanced stage, and worst patient outcome (P < 0.05). By Real-Time PCR significant increase of beta-catenin mRNA was detected in OSCC cell lines and in 45% of surgical specimens. DNA ploidy study demonstrated high levels of aneuploidy in beta-catenin overexpressing carcinomas. Conclusions. This is the largest study reporting significant association between beta-catenin expression and clinical-pathological factors in patients with OSCCs/OPSCCs. PMID:24511551

  6. Urine Trefoil Factors as Prognostic Biomarkers in Chronic Kidney Disease.

    PubMed

    Yamanari, Toshio; Sugiyama, Hitoshi; Tanaka, Keiko; Morinaga, Hiroshi; Kitagawa, Masashi; Onishi, Akifumi; Ogawa-Akiyama, Ayu; Kano, Yuzuki; Mise, Koki; Ohmoto, Yasukazu; Shikata, Kenichi; Wada, Jun

    2018-01-01

    Trefoil factor family (TFF) peptides are increased in serum and urine in patients with chronic kidney disease (CKD). However, whether the levels of TFF predict the progression of CKD remains to be elucidated. We determined the TFF levels using peptide-specific ELISA in spot urine samples and performed a prospective cohort study. The association between the levels of urine TFFs and other urine biomarkers as well as the renal prognosis was analyzed in 216 CKD patients (mean age: 53.7 years, 47.7% female, 56.9% with chronic glomerulonephritis, and mean eGFR: 58.5 ml/min/1.73 m 2 ). The urine TFF1 and TFF3 levels significantly increased with the progression of CKD stages, but not the urine TFF2 levels. The TFF1 and TFF3 peptide levels predicted the progression of CKD ≥ stage 3b by ROC analysis (AUC 0.750 and 0.879, resp.); however, TFF3 alone predicted CKD progression in a multivariate logistic regression analysis (odds ratio 3.854, 95% confidence interval 1.316-11.55). The Kaplan-Meier survival curves demonstrated that patients with a higher TFF1 and TFF3 alone, or in combination with macroalbuminuria, had a significantly worse renal prognosis. The data suggested that urine TFF peptides are associated with renal progression and the outcomes in patients with CKD.

  7. Urine Trefoil Factors as Prognostic Biomarkers in Chronic Kidney Disease

    PubMed Central

    Yamanari, Toshio; Tanaka, Keiko; Morinaga, Hiroshi; Kitagawa, Masashi; Onishi, Akifumi; Ogawa-Akiyama, Ayu; Kano, Yuzuki; Mise, Koki; Ohmoto, Yasukazu; Shikata, Kenichi

    2018-01-01

    Introduction Trefoil factor family (TFF) peptides are increased in serum and urine in patients with chronic kidney disease (CKD). However, whether the levels of TFF predict the progression of CKD remains to be elucidated. Methods We determined the TFF levels using peptide-specific ELISA in spot urine samples and performed a prospective cohort study. The association between the levels of urine TFFs and other urine biomarkers as well as the renal prognosis was analyzed in 216 CKD patients (mean age: 53.7 years, 47.7% female, 56.9% with chronic glomerulonephritis, and mean eGFR: 58.5 ml/min/1.73 m2). Results The urine TFF1 and TFF3 levels significantly increased with the progression of CKD stages, but not the urine TFF2 levels. The TFF1 and TFF3 peptide levels predicted the progression of CKD ≥ stage 3b by ROC analysis (AUC 0.750 and 0.879, resp.); however, TFF3 alone predicted CKD progression in a multivariate logistic regression analysis (odds ratio 3.854, 95% confidence interval 1.316–11.55). The Kaplan-Meier survival curves demonstrated that patients with a higher TFF1 and TFF3 alone, or in combination with macroalbuminuria, had a significantly worse renal prognosis. Conclusion The data suggested that urine TFF peptides are associated with renal progression and the outcomes in patients with CKD. PMID:29850501

  8. Development of ipilimumab: contribution to a new paradigm for cancer immunotherapy.

    PubMed

    Hoos, Axel; Ibrahim, Ramy; Korman, Alan; Abdallah, Kald; Berman, David; Shahabi, Vafa; Chin, Kevin; Canetta, Renzo; Humphrey, Rachel

    2010-10-01

    Identification of cytotoxic T-lymphocyte antigen-4 (CTLA-4) as a key negative regulator of T-cell activity led to development of the fully human, monoclonal antibody ipilimumab to block CTLA-4 and potentiate antitumor T-cell responses. Animal studies first provided insight into the ability of an anti-CTLA-4 antibody to cause tumor regression, particularly in combination regimens. Early clinical studies defined ipilimumab pharmacokinetics and possibilities for combinability. Phase II trials of ipilimumab in advanced melanoma showed objective responses, but a greater number of patients had disease stabilization. In a phase III trial, ipilimumab was the first agent to demonstrate an improvement in overall survival in patients with previously treated, advanced melanoma. The adverse event profile associated with ipilimumab was primarily immune-related. Adverse events can be severe and life-threatening, but most were reversible using treatment guidelines. Ipilimumab monotherapy exhibits conventional and new patterns of activity in advanced melanoma, with a delayed separation of Kaplan-Meier survival curves. The observation of some new response patterns with ipilimumab, which are not captured by standard response criteria, led to novel criteria for the evaluation of immunotherapy in solid tumors. Overall, lessons from the development of ipilimumab contributed to a new clinical paradigm for cancer immunotherapy evolved by the Cancer Immunotherapy Consortium. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. Relationship between admission blood glucose level and prognosis in elderly patients without previously known diabetes who undergo emergency non-cardiac surgery.

    PubMed

    Ma, Jinling; He, Lei; Wang, Xiujie; Gao, Meng; Zhao, Yuexiang; Liu, Jie

    2015-08-01

    Elevated blood glucose levels on admission are important as a marker for adverse events in patients who undergo surgery. This study aims to evaluate the relationship between admission glucose level and adverse outcome during the 30-day follow-up period in elderly patients without previously known diabetes who undergo emergency non-cardiac surgery. The primary and secondary end points were all-cause and major adverse cardiac event (MACE) mortalities, respectively, during the 30-day postoperative follow-up period. Higher 30-day all-cause (24.1 %) and MACE (13.7 %) mortalities were observed in patients with an admission glucose ≥ 11.1 mmol/L than in patients with admission glucose <11.1 mmol/L (p < 0.001). Multivariate logistic regression analysis shows that an higher admission blood glucose level is an independent predictor for the development of the 30-day all-cause mortality [odds ratio (OR), 1.91; 95 % confidence interval (CI), 1.746-2.082; p < 0.001) and cardiac mortality (OR 1.97, 95 % CI 1.774-2.191; p < 0.001] after adjusting for age, gender, body mass index, comorbidities, and medication before admission. Kaplan-Meier event-free survival curves demonstrate that an admission blood glucose level ≥ 11.1 mmol/L has worse event-free survival than an admission blood glucose level <11.1 mmol/L.

  10. High dose hypofractionated frameless volumetric modulated arc radiotherapy is a feasible method for treating canine trigeminal nerve sheath tumors.

    PubMed

    Dolera, Mario; Malfassi, Luca; Marcarini, Silvia; Mazza, Giovanni; Carrara, Nancy; Pavesi, Simone; Sala, Massimo; Finesso, Sara; Urso, Gaetano

    2018-06-08

    The aim of this prospective pilot study was to evaluate the feasibility and effectiveness of curative intent high dose hypofractionated frameless volumetric modulated arc radiotherapy for treatment of canine trigeminal peripheral nerve sheath tumors. Client-owned dogs with a presumptive imaging-based diagnosis of trigeminal peripheral nerve sheath tumor were recruited for the study during the period of February 2010 to December 2013. Seven dogs were enrolled and treated with high dose hypofractionated volumetric modulated arc radiotherapy delivered by a 6 MV linear accelerator equipped with a micro-multileaf beam collimator. The plans were computed using a Monte Carlo algorithm with a prescription dose of 37 Gy delivered in five fractions on alternate days. Overall survival was estimated using a Kaplan-Meier curve analysis. Magnetic resonance imaging (MRI) follow-up examinations revealed complete response in one dog, partial response in four dogs, and stable disease in two dogs. Median overall survival was 952 days with a 95% confidence interval of 543-1361 days. Volumetric modulated arc radiotherapy was demonstrated to be feasible and effective for trigeminal peripheral nerve sheath tumor treatment in this sample of dogs. The technique required few sedations and spared organs at risk. Even though larger studies are required, these preliminary results supported the use of high dose hypofractionated volumetric modulated arc radiotherapy as an alternative to other treatment modalities. © 2018 American College of Veterinary Radiology.

  11. Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in oligodendroglial tumors.

    PubMed

    Kuo, Lu-Ting; Lu, Hsueh-Yi; Lee, Chien-Chang; Tsai, Jui-Chang; Lai, Hong-Shiee; Tseng, Ham-Min; Kuo, Meng-Fai; Tu, Yong-Kwang

    2016-08-01

    Aberrant methylation has been associated with transcriptional inactivation of tumor-related genes in a wide spectrum of human neoplasms. The influence of DNA methylation in oligodendroglial tumors is not fully understood. Genomic DNA was isolated from 61 oligodendroglial tumors for analysis of methylation using methylation-specific multiplex ligation-dependent probe amplification assay (MS-MLPA). We correlated methylation status with clinicopathological findings and outcome. The genes found to be most frequently methylated in oligodendroglial tumors were RASSF1A (80.3%), CASP8 (70.5%), and CDKN2A (52.5%). Kaplan-Meier survival curve analysis demonstrated longer duration of progression-free survival in patients with 19q loss, aged less than 38 years, and with a proliferative index of less than 5%. Methylation of the ESR1 promoter is significantly associated with shorter duration of overall survival and progression-free survival, and that methylation of IGSF4 and RASSF1A is significantly associated with shorter duration of progression-free survival. However, none of the methylation status of ESR1, IGSF4, and RASSF1A was of prognostic value for survival in a multivariate Cox model. A number of novel and interesting epigenetic alterations were identified in this study. The findings highlight the importance of methylation profiles in oligodendroglial tumors and their possible involvement in tumorigenesis. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  12. Principal Curves on Riemannian Manifolds.

    PubMed

    Hauberg, Soren

    2016-09-01

    Euclidean statistics are often generalized to Riemannian manifolds by replacing straight-line interpolations with geodesic ones. While these Riemannian models are familiar-looking, they are restricted by the inflexibility of geodesics, and they rely on constructions which are optimal only in Euclidean domains. We consider extensions of Principal Component Analysis (PCA) to Riemannian manifolds. Classic Riemannian approaches seek a geodesic curve passing through the mean that optimizes a criteria of interest. The requirements that the solution both is geodesic and must pass through the mean tend to imply that the methods only work well when the manifold is mostly flat within the support of the generating distribution. We argue that instead of generalizing linear Euclidean models, it is more fruitful to generalize non-linear Euclidean models. Specifically, we extend the classic Principal Curves from Hastie & Stuetzle to data residing on a complete Riemannian manifold. We show that for elliptical distributions in the tangent of spaces of constant curvature, the standard principal geodesic is a principal curve. The proposed model is simple to compute and avoids many of the pitfalls of traditional geodesic approaches. We empirically demonstrate the effectiveness of the Riemannian principal curves on several manifolds and datasets.

  13. Laplacian scale-space behavior of planar curve corners.

    PubMed

    Zhang, Xiaohong; Qu, Ying; Yang, Dan; Wang, Hongxing; Kymer, Jeff

    2015-11-01

    Scale-space behavior of corners is important for developing an efficient corner detection algorithm. In this paper, we analyze the scale-space behavior with the Laplacian of Gaussian (LoG) operator on a planar curve which constructs Laplacian Scale Space (LSS). The analytical expression of a Laplacian Scale-Space map (LSS map) is obtained, demonstrating the Laplacian Scale-Space behavior of the planar curve corners, based on a newly defined unified corner model. With this formula, some Laplacian Scale-Space behavior is summarized. Although LSS demonstrates some similarities to Curvature Scale Space (CSS), there are still some differences. First, no new extreme points are generated in the LSS. Second, the behavior of different cases of a corner model is consistent and simple. This makes it easy to trace the corner in a scale space. At last, the behavior of LSS is verified in an experiment on a digital curve.

  14. Cochlear microphonic broad tuning curves

    NASA Astrophysics Data System (ADS)

    Ayat, Mohammad; Teal, Paul D.; Searchfield, Grant D.; Razali, Najwani

    2015-12-01

    It is known that the cochlear microphonic voltage exhibits much broader tuning than does the basilar membrane motion. The most commonly used explanation for this is that when an electrode is inserted at a particular point inside the scala media, the microphonic potentials of neighbouring hair cells have different phases, leading to cancelation at the electrodes location. In situ recording of functioning outer hair cells (OHCs) for investigating this hypothesis is exceptionally difficult. Therefore, to investigate the discrepancy between the tuning curves of the basilar membrane and those of the cochlear microphonic, and the effect of phase cancellation of adjacent hair cells on the broadness of the cochlear microphonic tuning curves, we use an electromechanical model of the cochlea to devise an experiment. We explore the effect of adjacent hair cells (i.e., longitudinal phase cancellation) on the broadness of the cochlear microphonic tuning curves in different locations. The results of the experiment indicate that active longitudinal coupling (i.e., coupling with active adjacent outer hair cells) only slightly changes the broadness of the CM tuning curves. The results also demonstrate that there is a π phase difference between the potentials produced by the hair bundle and the soma near the place associated with the characteristic frequency based on place-frequency maps (i.e., the best place). We suggest that the transversal phase cancellation (caused by the phase difference between the hair bundle and the soma) plays a far more important role than longitudinal phase cancellation in the broadness of the cochlear microphonic tuning curves. Moreover, by increasing the modelled longitudinal resistance resulting the cochlear microphonic curves exhibiting sharper tuning. The results of the simulations suggest that the passive network of the organ of Corti determines the phase difference between the hair bundle and soma, and hence determines the sharpness of the

  15. Smooth conditional distribution function and quantiles under random censorship.

    PubMed

    Leconte, Eve; Poiraud-Casanova, Sandrine; Thomas-Agnan, Christine

    2002-09-01

    We consider a nonparametric random design regression model in which the response variable is possibly right censored. The aim of this paper is to estimate the conditional distribution function and the conditional alpha-quantile of the response variable. We restrict attention to the case where the response variable as well as the explanatory variable are unidimensional and continuous. We propose and discuss two classes of estimators which are smooth with respect to the response variable as well as to the covariate. Some simulations demonstrate that the new methods have better mean square error performances than the generalized Kaplan-Meier estimator introduced by Beran (1981) and considered in the literature by Dabrowska (1989, 1992) and Gonzalez-Manteiga and Cadarso-Suarez (1994).

  16. A Point System to Forecast Hepatocellular Carcinoma Risk Before and After Treatment Among Persons with Chronic Hepatitis C.

    PubMed

    Xing, Jian; Spradling, Philip R; Moorman, Anne C; Holmberg, Scott D; Teshale, Eyasu H; Rupp, Loralee B; Gordon, Stuart C; Lu, Mei; Boscarino, Joseph A; Schmidt, Mark A; Trinacty, Connie M; Xu, Fujie

    2017-11-01

    Risk of hepatocellular carcinoma (HCC) may be difficult to determine in the clinical setting. Develop a scoring system to forecast HCC risk among patients with chronic hepatitis C. Using data from the Chronic Hepatitis Cohort Study collected during 2005-2014, we derived HCC risk scores for males and females using an extended Cox model with aspartate aminotransferase-to-platelet ratio index (APRI) as a time-dependent variables and mean Kaplan-Meier survival functions from patient data at two study sites, and used data collected at two separate sites for external validation. For model calibration, we used the Greenwood-Nam-D'Agostino goodness-of-fit statistic to examine differences between predicted and observed risk. Of 12,469 patients (1628 with a history of sustained viral response [SVR]), 504 developed HCC; median follow-up was 6 years. Final predictors in the model included age, alcohol abuse, interferon-based treatment response, and APRI. Point values, ranging from -3 to 14 (males) and -3 to 12 (females), were established using hazard ratios of the predictors aligned with 1-, 3-, and 5-year Kaplan-Meier survival probabilities of HCC. Discriminatory capacity was high (c-index 0.82 males and 0.84 females) and external calibration demonstrated no differences between predicted and observed HCC risk for 1-, 3-, and 5-year forecasts among males (all p values >0.97) and for 3- and 5-year risk among females (all p values >0.87). This scoring system, based on age, alcohol abuse history, treatment response, and APRI, can be used to forecast up to a 5-year risk of HCC among hepatitis C patients before and after SVR.

  17. Long non-coding RNA PVT1 as a novel potential biomarker for predicting the prognosis of colorectal cancer.

    PubMed

    Fan, Heng; Zhu, Jian-Hua; Yao, Xue-Qing

    2018-05-01

    Long non-coding RNA (lncRNA) plays a very important role in the occurrence and development of various tumors, and is a potential biomarker for cancer diagnosis and prognosis. The purpose of this study was to investigate the relationship between the expression of lncRNA plasmacytoma variant translocation 1 (PVT1) and the prognostic significance in patients with colorectal cancer. The expression of PVT1 was measured by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in cancerous and adjacent tissues of 210 colorectal cancer patients. The disease-free survival and overall survival of colorectal cancer patients were evaluated by Kaplan-Meier analysis, and univariate and multivariate analysis were performed by Cox proportional-hazards model. Our results revealed that PVT1 expression in cancer tissues of colorectal cancer was significantly higher than that of adjacent tissues ( P<0.001). High PVT1 expression was increased by 51.4% (108/210), which was significantly correlated with the tumor differentiation, the depth of invasion, the stage of tumor, node, metastasis (TNM), and lymphatic metastasis. The Kaplan-Meier analysis showed that high PVT1 expression resulted in a shorter disease-free survival (Log-rank test P<0.001) and overall survival (Log-rank test P<0.001) compared with the low PVT1 expression group in colorectal cancer patients, whether at TNM I/II stage or at TNM III/IV stage. A multivariate Cox regression analysis demonstrated that high PVT1 expression was an independent predictor of poor prognosis in colorectal cancer patients. Our results suggest that high PVT1 expression might be a potential biomarker for assessing tumor recurrence and prognosis in colorectal cancer patients.

  18. Glioblastoma: Vascular Habitats Detected at Preoperative Dynamic Susceptibility-weighted Contrast-enhanced Perfusion MR Imaging Predict Survival.

    PubMed

    Juan-Albarracín, Javier; Fuster-Garcia, Elies; Pérez-Girbés, Alexandre; Aparici-Robles, Fernando; Alberich-Bayarri, Ángel; Revert-Ventura, Antonio; Martí-Bonmatí, Luis; García-Gómez, Juan M

    2018-06-01

    Purpose To determine if preoperative vascular heterogeneity of glioblastoma is predictive of overall survival of patients undergoing standard-of-care treatment by using an unsupervised multiparametric perfusion-based habitat-discovery algorithm. Materials and Methods Preoperative magnetic resonance (MR) imaging including dynamic susceptibility-weighted contrast material-enhanced perfusion studies in 50 consecutive patients with glioblastoma were retrieved. Perfusion parameters of glioblastoma were analyzed and used to automatically draw four reproducible habitats that describe the tumor vascular heterogeneity: high-angiogenic and low-angiogenic regions of the enhancing tumor, potentially tumor-infiltrated peripheral edema, and vasogenic edema. Kaplan-Meier and Cox proportional hazard analyses were conducted to assess the prognostic potential of the hemodynamic tissue signature to predict patient survival. Results Cox regression analysis yielded a significant correlation between patients' survival and maximum relative cerebral blood volume (rCBV max ) and maximum relative cerebral blood flow (rCBF max ) in high-angiogenic and low-angiogenic habitats (P < .01, false discovery rate-corrected P < .05). Moreover, rCBF max in the potentially tumor-infiltrated peripheral edema habitat was also significantly correlated (P < .05, false discovery rate-corrected P < .05). Kaplan-Meier analysis demonstrated significant differences between the observed survival of populations divided according to the median of the rCBV max or rCBF max at the high-angiogenic and low-angiogenic habitats (log-rank test P < .05, false discovery rate-corrected P < .05), with an average survival increase of 230 days. Conclusion Preoperative perfusion heterogeneity contains relevant information about overall survival in patients who undergo standard-of-care treatment. The hemodynamic tissue signature method automatically describes this heterogeneity, providing a set of vascular habitats with high

  19. Patency of the Internal Iliac Artery after Placement of Common and External Iliac Artery Stents.

    PubMed

    Vinogradova, Margie; Lee, Hye Joon; Armstrong, Ehrin J; Laird, John; Humphries, Misty D

    2017-01-01

    Treatment of severe aortoiliac occlusive disease (AIOD) frequently requires long-segment stenting of the common and external iliac arteries (CIA and EIA, respectively). This study aims to analyze the patency of the internal iliac artery (IIA) after placement of a CIA and EIA stents across the orifice. A retrospective analysis of all patients who underwent de novo ipsilateral stent placement in the CIA and EIA between 2006 and 2013 was performed. Kaplan-Meier analysis was used to analyze patency of the IIA, and Cox proportional hazard models were used to identify characteristics associated with occlusion. We identified 77 patients and 93 limbs where ipsilateral CIA and EIA stents were placed. Preintervention angiographic review found 52 cases of a patent ipsilateral IIA where stents were placed across the origin of the IIA in 31 cases and staggered across the orifice in 20 limbs. Kaplan-Meier analysis demonstrated a 37% patency in limbs where the stent covered the IIA orifice compared to 78% patency in uncovered arteries (P = 0.04). New-onset buttock claudication developed in 4 patients, 2 with patent IIAs and 2 with occluded. New-onset impotence also developed in 3 patients with occluded IIA and 5 patients with patent IIAs. Placement of stents across the origin of the IIA may not result in immediate occlusion, but long-term patency of covered IIAs is decreased compared to uncovered IIAs. This study is limited by a small sample size, but when treating AIOD, coverage of the internal iliac origin should be avoided to maintain patency of the pelvic circulation. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Clinical outcomes of patients treated with a second course of stereotactic radiosurgery for locally or regionally recurrent brain metastases after prior stereotactic radiosurgery.

    PubMed

    Kim, Daniel H; Schultheiss, Timothy E; Radany, Eric H; Badie, Behnam; Pezner, Richard D

    2013-10-01

    Patients with metastatic disease are living longer and may be confronted with locally or regionally recurrent brain metastases (BM) after prior stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT). This study analyzes outcomes in patients without prior whole brain radiotherapy (WBRT) who were treated with a second course of SRS/FSRT for locally or regionally recurrent BM. We identified 32 patients at our institution who were treated with a second course of SRS/FSRT after initial SRS/FSRT for newly diagnosed BM. We report clinical outcomes including local control, survival, and toxicities. Control rates and survival were calculated using Kaplan-Meier analysis and the multivariate proportional hazards model. The Kaplan-Meier estimate of local control at 6 months was 77 % for targets treated by a second course of SRS/FSRT with 11/71 (15 %) targets experiencing local failure. Multivariate analysis shows that upon re-treatment, local recurrences were more likely to fail than regional recurrences (OR 8.8, p = 0.02). Median survival for all patients from first SRS/FSRT was 14.6 months (5.3-72.2 months) and 7.9 months (0.7-61.1 months) from second SRS/FSRT. Thirty-eight percent of patients ultimately received WBRT as salvage therapy after the second SRS/FSRT. Seventy-one percent of patients died without active neurologic symptoms. The present study demonstrates that the majority of patients who progress after SRS/FSRT for newly diagnosed BM are candidates for salvage SRS/FSRT. By reserving WBRT for later salvage, we believe that a significant proportion of patients can avoid WBRT all together, thus putting fewer patients at risk for neurocognitive toxicity.

  1. Prospective Randomized Trial Comparing Efficacy of Topical Loteprednol Etabonate 0.5% Versus Cyclosporine-A 0.05% for Treatment of Dry Eye Syndrome Following Hematopoietic Stem Cell Transplantation.

    PubMed

    Boynton, Grace E; Raoof, Duna; Niziol, Leslie M; Hussain, Munira; Mian, Shahzad I

    2015-07-01

    To evaluate the safety and efficacy of topical loteprednol etabonate (LE) 0.5% compared with cyclosporine A (CsA) 0.05% for the prophylaxis and treatment of dry eye syndrome (DES) after hematopoietic stem cell transplantation (HSCT). Seventy-five patients were randomized to LE (n = 76 eyes of 38 patients) or CsA (n = 74 eyes of 37 patients) pre-HSCT. Lissamine green and fluorescein staining, tear break-up time, tear osmolarity (Osm), Schirmer score (Sch), intraocular pressure, visual acuity, and Ocular Surface Disease Index were assessed pre-HSCT, 3, 6, 9, and 12 months post-HSCT. There were no differences in DES incidence (P = 0.22; log-rank test) or progression (P = 0.41; log-rank test) between the 2 treatment arms during the course of the study. Among eyes with no DES at enrollment, the Kaplan-Meier analysis yielded a 90% rate of DES development in cyclosporine-treated eyes and a 79% rate of DES development in LE-treated eyes by 12 months post-HSCT. The Kaplan-Meier analysis of eyes with DES at enrollment demonstrated a 38% rate of disease progression among cyclosporine-treated eyes and a 26% rate of disease progression among loteprednol-treated eyes by 12 months. No patient in either group had an elevation of 10 mm Hg or greater from baseline at any study visit, and no patients had their treatment discontinued for elevation in intraocular pressure. Pre-HSCT initiation of LE 0.5% appears to be safe and may be as effective as CsA 0.5% for the treatment and prophylaxis of DES following HSCT.

  2. Safety and efficacy of high-dose chemotherapy with autologous stem cell transplantation for patients with malignant astrocytomas.

    PubMed

    Chen, Benjamin; Ahmed, Tauseef; Mannancheril, Anney; Gruber, Michael; Benzil, Deborah L

    2004-05-15

    Malignant astrocytomas are among the most resistant tumors to curative treatments. Mean survival without treatment is measured in weeks, and even with maximal surgery and radiation, the mean reported survival is < 1 year. The advent of supportive treatments and newer agents has resulted in benefits for many patients with cancer. The authors investigated the safety and effect on survival of a high-dose thiotepa and carboplatin regimen with autologous stem cell transplantation (ASCT) in patients with malignant astrocytomas who were enrolled in a prospective trial approved by an institutional review board (IRB). Twenty-one patients were enrolled in an IRB-approved, prospective trial. After baseline testing was completed, patients underwent peripheral stem cell mobilization with cyclophosphamide (4 g/m2) and etoposide (450 mg/m2) followed by granulocyte-colony-stimulating factor (10 microg/kg). Peripheral stem cells were harvested when leukocyte counts recovered. Patients received 2 cycles of thiotepa (750 mg/m2) and carboplatin (1600 mg/m2) followed by infusion of the preserved stem cells. The cycles were administered 6-10 weeks apart. Primary outcome measures were patient survival (Kaplan-Meier analysis) and treatment toxicity (using National Cancer Institute common toxicity criteria). Autologous stem cells were harvested effectively and transfused in all patients. Kaplan-Meier survival analysis demonstrated a survival time of 34.3 +/- 5.5 months (range, 9-94 months). Despite significant myelosuppression, only three patients experienced Grade 4 complications and eight experienced Grade 3 complications. High-dose chemotherapy with thiotepa and carboplatin with concomitant ASCT was used safely to treat patients with malignant astrocytomas and may provide a survival advantage. Copyright 2004 American Cancer Society.

  3. Efficacy of a recombinant endotoxin neutralizing protein in rabbits with Escherichia coli sepsis.

    PubMed

    Saladino, R; Garcia, C; Thompson, C; Hammer, B; Parsonnet, J; Novitsky, T; Siber, G; Fleisher, G

    1994-02-01

    Gram-negative bacterial sepsis is associated with endotoxemia and a high mortality rate. In previous studies, we demonstrated the therapeutic benefit of an anti-lipopolysaccharide factor isolated from amebocytes of Limulus polyphemus, and of a recombinant version of this protein, termed endotoxin neutralizing protein (ENP), in rabbits challenged with purified lipopolysaccharides. To assess the benefit of ENP in treating a live bacterial infection, we established a rabbit model of Escherichia coli (E. coli) peritonitis and bacteremia with high mortality despite gentamicin treatment. Twenty-four pairs of New Zealand white rabbits were challenged intraperitoneally (IP) with E. coli O18ac K1 in 5% porcine mucin (mean bacteria per dose = 2.5 x 10(8)). The animals were treated with intravenous (i.v.) gentamicin (2.5 mg/kg), and with either ENP (5 mg/kg) or saline i.v. at 1 hr after E. coli challenge. All rabbits were bacteremic 1 hr after challenge (geometric mean 4.1 +/- 1.2 x 10(4) cfu/mL). Peak geometric mean serum endotoxin (2.62 v 10.54 EU/mL, P = .013) and tumor necrosis factor (TNF) (2540 v 6438 TNF units/mL, P = .046) concentrations were lower in ENP-treated animals as compared to control animals. Seven of 24 animals treated with ENP survived 24 hr compared with 4 of 24 controls (Kaplan-Meier analysis, P = .19). However, in the subgroup of 13 paired animals in whom bacteremia was eliminated by gentamicin treatment, 5 of 13 ENP-treated animals survived 24 hr, compared with 1 of 13 controls (Kaplan-Meier analysis, P = .032).(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Prognostic value of inflammation-based scores in patients with osteosarcoma

    PubMed Central

    Liu, Bangjian; Huang, Yujing; Sun, Yuanjue; Zhang, Jianjun; Yao, Yang; Shen, Zan; Xiang, Dongxi; He, Aina

    2016-01-01

    Systemic inflammation responses have been associated with cancer development and progression. C-reactive protein (CRP), Glasgow prognostic score (GPS), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and neutrophil-platelet score (NPS) have been shown to be independent risk factors in various types of malignant tumors. This retrospective analysis of 162 osteosarcoma cases was performed to estimate their predictive value of survival in osteosarcoma. All statistical analyses were performed by SPSS statistical software. Receiver operating characteristic (ROC) analysis was generated to set optimal thresholds; area under the curve (AUC) was used to show the discriminatory abilities of inflammation-based scores; Kaplan-Meier analysis was performed to plot the survival curve; cox regression models were employed to determine the independent prognostic factors. The optimal cut-off points of NLR, PLR, and LMR were 2.57, 123.5 and 4.73, respectively. GPS and NLR had a markedly larger AUC than CRP, PLR and LMR. High levels of CRP, GPS, NLR, PLR, and low level of LMR were significantly associated with adverse prognosis (P < 0.05). Multivariate Cox regression analyses revealed that GPS, NLR, and occurrence of metastasis were top risk factors associated with death of osteosarcoma patients. PMID:28008988

  5. Identification of Serum Periostin as a Potential Diagnostic and Prognostic Marker for Colorectal Cancer.

    PubMed

    Dong, Dong; Zhang, Lufang; Jia, Li; Ji, Wei; Wang, Zhiyong; Ren, Li; Niu, Ruifang; Zhou, Yunli

    2018-06-01

    Periostin (POSTN) plays an important role in numerous cancers, especially in gastrointestinal malignancy. The objective of this study was to investigate the diagnostic and prognostic role of serum POSTN in colorectal cancer (CRC). Serum periostin, together with CEA, CA19.9, CA72.4, and CA242 levels were measured in samples from 108 patients with CRC and 56 healthy controls, and their correlation with clinical characteristics was further analyzed. Receiver operating curves (ROC), Kaplan-Meier curves, and log-rank analyses were used to evaluate diagnostic and prognostic significance. Serum POSTN levels were significantly higher in patients with CRC compared with healthy controls (p < 0.0001) and associated with clinical stages (p < 0.001). ROC analysis revealed that POSTN was a biomarker comparable to CEA, CA19.9, and CA72.4 to distinguish all CRC from healthy controls (AUC = 0.75). Moreover, POSTN retained its diagnostic ability for CEA-negative (AUC = 0.69) and CA19.9-negative CRC patients (AUC = 0.71). Survival analysis revealed that patients with lower serum POSTN had longer overall survival than those with high serum POSTN (p = 0.0146). Serum POSTN might be a novel diagnostic and prognostic biomarker for patients with CRC.

  6. Lipoprotein(a) levels predict adverse vascular events after acute myocardial infarction.

    PubMed

    Mitsuda, Takayuki; Uemura, Yusuke; Ishii, Hideki; Takemoto, Kenji; Uchikawa, Tomohiro; Koyasu, Masayoshi; Ishikawa, Shinji; Miura, Ayako; Imai, Ryo; Iwamiya, Satoshi; Ozaki, Yuta; Kato, Tomohiro; Shibata, Rei; Watarai, Masato; Murohara, Toyoaki

    2016-12-01

    Lipoprotein(a) [Lp(a)], which is genetically determined, has been reported as an independent risk factor for atherosclerotic vascular disease. However, the prognostic value of Lp(a) for secondary vascular events in patients after coronary artery disease has not been fully elucidated. This 3-year observational study included a total of 176 patients with ST-elevated myocardial infarction (STEMI), whose Lp(a) levels were measured within 24 h after primary percutaneous coronary intervention. We divided enrolled patients into two groups according to Lp(a) level and investigated the association between Lp(a) and the incidence of major adverse cardiac and cerebrovascular events (MACCE). A Kaplan-Meier analysis demonstrated that patients with higher Lp(a) levels had a higher incidence of MACCE than those with lower Lp(a) levels (log-rank P = 0.034). A multivariate Cox regression analysis revealed that Lp(a) levels were independently correlated with the occurrence of MACCE after adjusting for other classical risk factors of atherosclerotic vascular diseases (hazard ratio 1.030, 95 % confidence interval: 1.011-1.048, P = 0.002). In receiver-operating curve analysis, the cutoff value to maximize the predictive power of Lp(a) was 19.0 mg/dl (area under the curve = 0.674, sensitivity 69.2 %, specificity 62.0 %). Evaluation of Lp(a) in addition to the established coronary risk factors improved their predictive value for the occurrence of MACCE. In conclusion, Lp(a) levels at admission independently predict secondary vascular events in patients with STEMI. Lp(a) might provide useful information for the development of secondary prevention strategies in patients with myocardial infarction.

  7. Methylation of S100A8 is a promising diagnosis and prognostic marker in hepatocellular carcinoma.

    PubMed

    Liu, Kun; Zhang, Yuening; Zhang, Chengdong; Zhang, Qinle; Li, Jiatong; Xiao, Feifan; Li, Yingfang; Zhang, Ruoheng; Dou, Dongwei; Liang, Jiezhen; Qin, Jian; Lin, Zhidi; Zhao, Dong; Jiang, Min; Liang, Zhenxin; Su, Jie; Gupta, Vanaparthy Pranay; He, Min; Yang, Xiaoli

    2016-08-30

    The abnormality of DNA methylation is one of the major epigenetic alterations in the human hepatocellular carcinoma (HCC). We have assessed the global genomic DNA methylation profiles in human HCC patients by using the Infinium Human Methylation27 BeadChip. A CpG loci of S100A8 was found to be significantly hypomethylated in HCC.Pooled meta-analysis of five validation public datasets demonstrated its methylation level was significantly lower for HCC compared to paired adjacent normal tissues. Quantitative pyrosequencing analysis also showed that the S100A8 methylation level was decreased in cancer tissues (31.90%±13.31%) than that in the paired adjacent normal tissues (65.33%±3.64%, p<0.01). The area under the ROC curve (AUC) value was 0.950 (p<0.01). Kaplan-Meier survival curves revealed that hypomethylation of S100A8 was associated with shortened overall survival (OS) and progression-free survival (PFS) (log rank p<0.05). Multivariate Cox proportional hazards model also indicated significantly shorter OS (HR, 1.709; 95 % CI, 1.127-2.591) and PFS (HR, 1.767; 95 % CI, 1.168-2.974) were observed in the low-methylation-level group compared to the high-methylation-level group. Furthermore, S100A8 overexpression in Huh7 and MHCC-97H hepatoma cell lines led to increased cell proliferation, migration, invasion, and tumor growth. These findings suggested S100A8 methylation to be served as potential diagnosis and prognosis marker for HCC. S100A8 also may play as a tumor promoter in HCC.

  8. Methylation of S100A8 is a promising diagnosis and prognostic marker in hepatocellular carcinoma

    PubMed Central

    Xiao, Feifan; Li, Yingfang; Zhang, Ruoheng; Dou, Dongwei; Liang, Jiezhen; Qin, Jian; Lin, Zhidi; Zhao, Dong; Jiang, Min; Liang, Zhenxin; Su, Jie; Gupta, Vanaparthy Pranay; He, Min; Yang, Xiaoli

    2016-01-01

    The abnormality of DNA methylation is one of the major epigenetic alterations in the human hepatocellular carcinoma (HCC). We have assessed the global genomic DNA methylation profiles in human HCC patients by using the Infinium Human Methylation27 BeadChip. A CpG loci of S100A8 was found to be significantly hypomethylated in HCC. Pooled meta-analysis of five validation public datasets demonstrated its methylation level was significantly lower for HCC compared to paired adjacent normal tissues. Quantitative pyrosequencing analysis also showed that the S100A8 methylation level was decreased in cancer tissues (31.90%±13.31%) than that in the paired adjacent normal tissues (65.33%±3.64%, p<0.01). The area under the ROC curve (AUC) value was 0.950 (p<0.01). Kaplan-Meier survival curves revealed that hypomethylation of S100A8 was associated with shortened overall survival (OS) and progression-free survival (PFS) (log rank p<0.05). Multivariate Cox proportional hazards model also indicated significantly shorter OS (HR, 1.709; 95 % CI, 1.127–2.591) and PFS (HR, 1.767; 95 % CI, 1.168–2.974) were observed in the low-methylation-level group compared to the high-methylation-level group. Furthermore, S100A8 overexpression in Huh7 and MHCC-97H hepatoma cell lines led to increased cell proliferation, migration, invasion, and tumor growth. These findings suggested S100A8 methylation to be served as potential diagnosis and prognosis marker for HCC. S100A8 also may play as a tumor promoter in HCC. PMID:27462864

  9. MEKK1 is a Novel Regulator of the Dmp1-Arf-p53 Pathway and Prognostic Indicator in Breast Cancer

    DTIC Science & Technology

    2012-12-01

    hDMP1, INK4a/ARF, p53 or Hdm2 amplification. Kaplan -Meier analyses have been conducted to study the impact for the impact of loss or gain of each locus on...Palma P, Pellegrini S, Fina P et al. Mdm2 gene alterations and mdm2 protein expression in breast carcinomas. J Pathol 1995; 175: 31–38. 21 Turbin DA

  10. Survival analysis: Part I — analysis of time-to-event

    PubMed Central

    2018-01-01

    Length of time is a variable often encountered during data analysis. Survival analysis provides simple, intuitive results concerning time-to-event for events of interest, which are not confined to death. This review introduces methods of analyzing time-to-event. The Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazards regression modeling method are described with examples of hypothetical data. PMID:29768911

  11. One-Carbon Metabolism and Breast Cancer Survival in a Population-Based Study

    DTIC Science & Technology

    2008-06-01

    the dietary intake of one- carbon-related micronutrients /compounds (e.g. folate, methionine, chioline, B vitamins, alcohol, etc) in relation to...examine the dietary intake of one-carbon-related micronutrients /compounds (e.g. folate, methionine, chioline, B vitamins, alcohol, etc) in relation to...of dietary methyl content and overall survival. Some descriptive statistical analysis has been reported in previous annual report. The Kaplan-Meier

  12. Median nitrate concentrations in groundwater in the New Jersey Highlands Region estimated using regression models and land-surface characteristics

    USGS Publications Warehouse

    Baker, Ronald J.; Chepiga, Mary M.; Cauller, Stephen J.

    2015-01-01

    The Kaplan-Meier method of estimating summary statistics from left-censored data was applied in order to include nondetects (left-censored data) in median nitrate-concentration calculations. Median concentrations also were determined using three alternative methods of handling nondetects. Treatment of the 23 percent of samples that were nondetects had little effect on estimated median nitrate concentrations because method detection limits were mostly less than median values.

  13. Diagnostic and prognostic value of cardiac troponin I assays in patients admitted with symptoms suggestive of acute coronary syndrome.

    PubMed

    Apple, Fred S; Quist, Heidi E; Murakami, MaryAnn M

    2004-04-01

    Increasing numbers of patients are presenting to emergency departments with symptoms suggestive of an acute myocardial infarction. To demonstrate the comparative performance of the Ortho Vitros Troponin I and Beckman Access AccuTnI assays used to detect myocardial infarction and to develop risk stratification schemes for all-cause death in patients who presented with myocardial ischemia symptoms that were suggestive of acute coronary syndrome (ACS). The prospective enrollment of patients with ACS and the measurement of serial plasma samples by 2 commercial cardiac troponin I (cTnI) assays. A metropolitan medical center that admitted patients with ACS during a 2-month period. The study population consisted of 200 consecutively admitted patients who presented with symptoms that were suggestive of ACS. Correlation scatterplots showed no significant bias between cTnI assays based on 659 specimens across the dynamic range of each assay. Only minor differences in slopes and intercepts were observed between assays when correlations were based across selected concentration ranges. The receiver operating characteristic curve areas for the detection of myocardial infarction were not significantly different (Ortho,.991; Beckman,.995). At the 99th percentile (Beckman, 0.04 microg/L; Ortho, 0.08 microg/L), each assay demonstrated 100% sensitivity with 78% and 80% specificity, respectively. Kaplan-Meier survival curves and the log-rank test were used to compare time-to-event data. Patients with increased baseline cTnI values had higher odds ratios of death than did those with normal concentrations. For Ortho, the 99th percentile cutoff was 5.9, and the 10% coefficient of variation cutoff was 10.3; for Beckman, the 99th percentile cutoff was 31.4, and the 10% coefficient of variation cutoff was 15.3. Comparable diagnostic and risk stratification abilities were demonstrated in patients with ACS by the Ortho Vitros and Beckman Access cTnI assays, with no significant analytic bias

  14. Predictive value of initial FDG-PET features for treatment response and survival in esophageal cancer patients treated with chemo-radiation therapy using a random forest classifier.

    PubMed

    Desbordes, Paul; Ruan, Su; Modzelewski, Romain; Pineau, Pascal; Vauclin, Sébastien; Gouel, Pierrick; Michel, Pierre; Di Fiore, Frédéric; Vera, Pierre; Gardin, Isabelle

    2017-01-01

    In oncology, texture features extracted from positron emission tomography with 18-fluorodeoxyglucose images (FDG-PET) are of increasing interest for predictive and prognostic studies, leading to several tens of features per tumor. To select the best features, the use of a random forest (RF) classifier was investigated. Sixty-five patients with an esophageal cancer treated with a combined chemo-radiation therapy were retrospectively included. All patients underwent a pretreatment whole-body FDG-PET. The patients were followed for 3 years after the end of the treatment. The response assessment was performed 1 month after the end of the therapy. Patients were classified as complete responders and non-complete responders. Sixty-one features were extracted from medical records and PET images. First, Spearman's analysis was performed to eliminate correlated features. Then, the best predictive and prognostic subsets of features were selected using a RF algorithm. These results were compared to those obtained by a Mann-Whitney U test (predictive study) and a univariate Kaplan-Meier analysis (prognostic study). Among the 61 initial features, 28 were not correlated. From these 28 features, the best subset of complementary features found using the RF classifier to predict response was composed of 2 features: metabolic tumor volume (MTV) and homogeneity from the co-occurrence matrix. The corresponding predictive value (AUC = 0.836 ± 0.105, Se = 82 ± 9%, Sp = 91 ± 12%) was higher than the best predictive results found using the Mann-Whitney test: busyness from the gray level difference matrix (P < 0.0001, AUC = 0.810, Se = 66%, Sp = 88%). The best prognostic subset found using RF was composed of 3 features: MTV and 2 clinical features (WHO status and nutritional risk index) (AUC = 0.822 ± 0.059, Se = 79 ± 9%, Sp = 95 ± 6%), while no feature was significantly prognostic according to the Kaplan-Meier analysis. The RF classifier can improve predictive and prognostic values

  15. The prognostic value of tumor-infiltrating neutrophils in gastric adenocarcinoma after resection.

    PubMed

    Zhao, Jing-jing; Pan, Ke; Wang, Wei; Chen, Ju-gao; Wu, Yan-heng; Lv, Lin; Li, Jian-jun; Chen, Yi-bing; Wang, Dan-dan; Pan, Qiu-zhong; Li, Xiao-dong; Xia, Jian-chuan

    2012-01-01

    Several pieces of evidence indicate that tumor-infiltrating neutrophils (TINs) are correlated to tumor progression. In the current study, we explore the relationship between TINs and clinicopathological features of gastric adenocarcinoma patients. Furthermore, we investigated the prognostic value of TINs. The study was comprised of two groups, training group (115 patients) and test group (97 patients). Biomarkers (intratumoral CD15+ neutrophils) were assessed by immunohistochemistry. The relationship between clinicopathological features and patient outcome were evaluated using Cox regression and Kaplan-Meier analysis. Immunohistochemical detection showed that the tumor-infiltrating neutrophils (TINs) in the training group ranged from 0.00-115.70 cells/high-power microscopic field (HPF) and the median number was 21.60 cells/HPF. Based on the median number, the patients were divided into high and low TINs groups. Chi-square test analysis revealed that the density of CD15+ TINs was positively associated with lymph node metastasis (p = 0.024), distance metastasis (p = 0.004) and UICC (International Union Against Cancer) staging (p = 0.028). Kaplan-Meier analysis showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.002). Multivariate Cox's analysis showed that the density of CD15+ TINs was an independent prognostic factor for overall survival of gastric adenocarcinoma patients. Using another 97 patients as a test group and basing on the median number of TINs (21.60 cells/HPF) coming from the training group, Kaplan-Meier analysis also showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.032). The results verify that the number of CD15+ TINs can predict the survival of gastric adenocarcinoma surgical patients. The presence of CD15+ TINs is an independent and unfavorable factor in the prognosis of gastric

  16. The Prognostic Value of Tumor-Infiltrating Neutrophils in Gastric Adenocarcinoma after Resection

    PubMed Central

    Wang, Wei; Chen, Ju-gao; Wu, Yan-heng; Lv, Lin; Li, Jian-jun; Chen, Yi-bing; Wang, Dan-dan; Pan, Qiu-zhong; Li, Xiao-dong; Xia, Jian-chuan

    2012-01-01

    Background Several pieces of evidence indicate that tumor-infiltrating neutrophils (TINs) are correlated to tumor progression. In the current study, we explore the relationship between TINs and clinicopathological features of gastric adenocarcinoma patients. Furthermore, we investigated the prognostic value of TINs. Patients and Methods The study was comprised of two groups, training group (115 patients) and test group (97 patients). Biomarkers (intratumoral CD15+ neutrophils) were assessed by immunohistochemistry. The relationship between clinicopathological features and patient outcome were evaluated using Cox regression and Kaplan-Meier analysis. Results Immunohistochemical detection showed that the tumor-infiltrating neutrophils (TINs) in the training group ranged from 0.00–115.70 cells/high-power microscopic field (HPF) and the median number was 21.60 cells/HPF. Based on the median number, the patients were divided into high and low TINs groups. Chi-square test analysis revealed that the density of CD15+ TINs was positively associated with lymph node metastasis (p = 0.024), distance metastasis (p = 0.004) and UICC (International Union Against Cancer) staging (p = 0.028). Kaplan-Meier analysis showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.002). Multivariate Cox's analysis showed that the density of CD15+ TINs was an independent prognostic factor for overall survival of gastric adenocarcinoma patients. Using another 97 patients as a test group and basing on the median number of TINs (21.60 cells/HPF) coming from the training group, Kaplan-Meier analysis also showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.032). The results verify that the number of CD15+ TINs can predict the survival of gastric adenocarcinoma surgical patients. Conclusions The presence of CD15+ TINs is an independent and

  17. Evaluation of Revascularization Subtypes in Octogenarians Undergoing Coronary Artery Bypass Grafting

    PubMed Central

    Aziz, Abdulhameed; Lee, Anson M.; Pasque, Michael K.; Lawton, Jennifer S.; Moazami, Nader; Damiano, Ralph J.; Moon, Marc R.

    2009-01-01

    Background Recent data suggest that octogenarians’ long-term survival after complete CABG revascularization is superior to incomplete revascularization. Discriminating between variable definitions of “complete” complicates interpretation of survival data. We aimed to clarify octogenarian long-term survival rates by stratifying revascularization subtypes. Methods and Results From 1986 to 2007, 580 patients 80 to 94 years of age underwent CABG. Functional complete revascularization was defined as at least one graft to all diseased coronary vessels with greater than 50% stenosis. Traditional complete revascularization was defined as one graft to each major arterial system with at least 50% stenosis. Incomplete revascularization was defined as leaving diseased, ungrafted regions. Revascularization was functional in 279 (48%), traditional in 181 (31%), and incomplete in 120 (21%). Long-term survival was evaluated by Kaplan-Meier analysis. Of 537 operative survivors, there were 402 late deaths. Cumulative long-term survival totaled 2,890 patient-years. Late survival (Kaplan-Meier) was similar between functional (6.8 years, mean) and traditional (6.7 years) groups (p=0.51), but diminished with incomplete (4.2 years) revascularization (p=0.007). Survival by group at 5 years was: 59±3% functional, 57±4% traditional, and 45±5% incomplete. Survival at 8 years was: 40±3% functional, 37±4% traditional, and 26±5% incomplete. To minimize selection bias in patients with limited life expectancy, Kaplan-Meier analysis was repeated including only patients with survival greater than 12 months. Survival was again impaired with incomplete revascularization (p=0.04), and there was no difference between functional and traditional complete revascularization (p=0.73). Conclusions Bypassing all diseased arterial vessels after revascularization does not afford significant long-term survival advantage compared to a traditional approach. Incomplete revascularization, related to more

  18. Pesticide mixtures in the Swedish streams: Environmental risks, contributions of individual compounds and consequences of single-substance oriented risk mitigation.

    PubMed

    Gustavsson, Mikael; Kreuger, Jenny; Bundschuh, Mirco; Backhaus, Thomas

    2017-11-15

    This paper presents the ecotoxicological assessment and environmental risk evaluation of complex pesticide mixtures occurring in freshwater ecosystems in southern Sweden. The evaluation is based on exposure data collected between 2002 and 2013 by the Swedish pesticide monitoring program and includes 1308 individual samples, detecting mixtures of up to 53 pesticides (modal=8). Pesticide mixture risks were evaluated using three different scenarios for non-detects (best-case, worst-case and using the Kaplan-Meier method). The risk of each scenario was analyzed using Swedish Water Quality Objectives (WQO) and trophic-level specific environmental thresholds. Using the Kaplan-Meier method the environmental risk of 73% of the samples exceeded acceptable levels, based on an assessment using Concentration-Addition and WQOs for the individual pesticides. Algae were the most sensitive organism group. However, analytical detection limits, especially for insecticides, were insufficient to analyze concentrations at or near their WQO's. Thus, the risk of the analyzed pesticide mixtures to crustaceans and fish is systematically underestimated. Treating non-detects as being present at their individual limit of detection increased the estimated risk by a factor 100 or more, compared to the best-case or the Kaplan-Meier scenario. Pesticide mixture risks are often driven by only 1-3 compounds. However, the risk-drivers (i.e., individual pesticides explaining the largest share of potential effects) differ substantially between sites and samples, and 83 of the 141 monitored pesticides need to be included in the assessment to account for 95% of the risk at all sites and years. Single-substance oriented risk mitigation measures that would ensure that each individual pesticide is present at a maximum of 95% of its individual WQO, would also reduce the mixture risk, but only from a median risk quotient of 2.1 to a median risk quotient of 1.8. Also, acceptable total risk levels would still

  19. The number of seizures needed in the EMU.

    PubMed

    Struck, Aaron F; Cole, Andrew J; Cash, Sydney S; Westover, M Brandon

    2015-11-01

    The purpose of this study was to develop a quantitative framework to estimate the likelihood of multifocal epilepsy based on the number of unifocal seizures observed in the epilepsy monitoring unit (EMU). Patient records from the EMU at Massachusetts General Hospital (MGH) from 2012 to 2014 were assessed for the presence of multifocal seizures as well the presence of multifocal interictal discharges and multifocal structural imaging abnormalities during the course of the EMU admission. Risk factors for multifocal seizures were assessed using sensitivity and specificity analysis. A Kaplan-Meier survival analysis was used to estimate the risk of multifocal epilepsy for a given number of consecutive seizures. To overcome the limits of the Kaplan-Meier analysis, a parametric survival function was fit to the EMU subjects with multifocal seizures and this was used to develop a Bayesian model to estimate the risk of multifocal seizures during an EMU admission. Multifocal interictal discharges were a significant predictor of multifocal seizures within an EMU admission with a p < 0.01, albeit with only modest sensitivity 0.74 and specificity 0.69. Multifocal potentially epileptogenic lesions on MRI were not a significant predictor p = 0.44. Kaplan-Meier analysis was limited by wide confidence intervals secondary to significant patient dropout and concern for informative censoring. The Bayesian framework provided estimates for the number of unifocal seizures needed to predict absence of multifocal seizures. To achieve 90% confidence for the absence of multifocal seizure, three seizures are needed when the pretest probability for multifocal epilepsy is 20%, seven seizures for a pretest probability of 50%, and nine seizures for a pretest probability of 80%. These results provide a framework to assist clinicians in determining the utility of trying to capture a specific number of seizures in EMU evaluations of candidates for epilepsy surgery. Wiley Periodicals, Inc. © 2015

  20. The influence of cardiac rhythm type and frequency on the prognosis of severe heart failure patients initially qualified for heart transplantation.

    PubMed

    Sobieszczańska-Małek, Małgorzata; Zieliński, Tomasz; Rywik, Tomasz; Piotrowska, Małgorzata; Religa, Grzegorz; Przybyłowski, Piotr; Rózański, Jacek; Korewicki, Jerzy

    2010-01-01

    Atrial fibrillation (AF) is the most common arrhythmia among patients (pts) with heart failure and has significant influence on survival. to assess prognosis of pts with refractory heart failure (HF) qualified for heart transplantation (HTX). 872 pts (107 W and 765 M) were qualified for HTX between Dec 2003 and Oct 2007. Patient's death or super urgent heart transplantation were considered the end point in Kaplan-Meier survival curves. 680 pts were on sinus rhythm (SR) and 192(22.0%) had atrial fibrillation (AF). During follow-up (1-1464 days, mean 550 days) 155 pts (17.7%) died, 17.65% with SR and 18.23% with AF (ns). EF - mean 21,6 (SR) and 21,8 (FA), NYHA 3,1 (SR), NTproBNP- mean 3635, 4 (SR) and 4349,4 (FA), Arronson - mean 7,8 (SR) and 7,7 (FA). There were no significant differences between groups. We analyzed influence of heart rate (Kaplan-Maier method) on survival. The pts were divided according to HR: gr.I <70/min, gr II 71-89/min, gr III >90/min. The shortest survival rate was noticed in group III. There was no difference in survival between group I and II. The prognosis for patients qualified for heart transplant does not depend on the type of the dominant cardiac rhythm (atrial fibrillation or sinus rhythm). The prognosis is significantly better for those patients whose basic, resting heart rate does not exceed 90 bpm regardless of the rhythm type.

  1. Resistance within hemodialysis shunts predicts patency.

    PubMed

    Bui, Trung D; Gordon, Ian L; Parashar, Amish; Vo, David; Wilson, Samuel E

    2006-01-01

    The authors examined the relationship between patency after thrombectomy of clotted dialysis grafts and intraoperative measurements of flow (Q), pressure gradient (PGR), and longitudinal resistance (RL). Eighteen thrombosed arteriovenous (AV) grafts underwent 21 thrombectomies. Pressures at arterial (P1) and venous (P2) ends of the AV grafts were determined with 22-gauge catheters and standard transducers; flow was measured with transit-time probes; arithmetic averaging of waveforms was used to compute mean Q, PGR, and RL. Kaplan-Meier patency curves were analyzed by using log rank methods. Mean patency for all grafts was 164 +/-152 days. For each variable, the 21 measurements were split and the patency curve for the grafts with the 11 lowest value grafts was compared to the curve representing the 10 highest value grafts. The difference between high RL versus low RL patency curves was significant with high-resistance grafts having a median patency of 55 days and low-resistance grafts having a median patency greater than 151 days (p = 0.0089). In contrast, the high Q group median patency was 151 days versus 174 days for the low Q group (p = 0.86). Median patency for the low PGR group was 115 days compared to 62 days for the high PGR group (p = 0.162). Longitudinal resistance within AV grafts, but not flow or pressure gradient, showed a significant correlation with patency after thrombectomy. Increased resistance to flow within AV grafts appears to be an important factor affecting the propensity of dialysis grafts to thrombose.

  2. Ciprofloxacin during upper respiratory tract infections to reduce Pseudomonas aeruginosa infection in paediatric cystic fibrosis: a pilot study.

    PubMed

    Connett, Gary J; Pike, Katharine C; Legg, Julian P; Cathie, Katrina; Dewar, Ann; Foote, Keith; Harris, Amanda; Faust, Saul N

    2015-12-01

    Acute viral respiratory illnesses are associated with acquisition of Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients. This study aimed to pilot a protocol for a randomized controlled trial to determine whether oral antipseudomonal antibiotics used at the onset of such episodes might delay onset of infection with this organism. A total of 41 children with CF aged 2-14 years, without chronic Pseudomonas infection, were randomized to receive ciprofloxacin (n = 28) or placebo (n = 13) at the onset of acute viral respiratory infections on an intention to treat basis, during a study period of up to 32 months. There were no unexpected adverse events believed related to the use of the study medication. The rate of withdrawal from the study was low (approximately 7%) and did not differ between groups. Randomization was effective and acceptable to participants. Primary and secondary outcome measures all favoured active treatment, but there were no significant between group differences. The median rate of Pseudomonas isolates was 0/patient/year (interquartile range 0-0.38) in both the active and placebo groups. Kaplan-Meier survival curves showed no significant difference in time to first Pseudomonas isolate between groups. This study demonstrated the clinical feasibility of using oral ciprofloxacin in CF patients at times of viral infection. Within this sample size, no significant association was found between active treatment and decreased growth of Pseudomonas in follow-up microbiological samples. A definitive study would require at least 320 children to demonstrate significant differences in the rate of pseudomonal isolates. © The Author(s), 2015.

  3. Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death.

    PubMed

    Fischer, D; Rossa, S; Landmesser, U; Spiekermann, S; Engberding, N; Hornig, B; Drexler, H

    2005-01-01

    Endothelial dysfunction of coronary and peripheral arteries has been demonstrated in patients with chronic heart failure (CHF) and appears to be associated with functional implications. However, it is unknown whether endothelial dysfunction in CHF is independently associated with impaired outcome or progression of the disease. We assessed the follow-up of 67 consecutive patients with CHF [New York Heart Association (NYHA) functional class II-III] in which flow-dependent, endothelium-mediated vasodilation (FDD) of the radial artery was assessed by high resolution ultrasound. The primary endpoint was defined by cardiac death, hospitalization due to worsening of heart failure (NYHA class IV, pulmonary oedema), or heart transplantation. Cox regression analysis was used to determine whether FDD was associated with these heart failure-related events. During a median follow-up of 45.7 months 24 patients had an event: 18 patients were hospitalized due to worsening of heart failure or heart transplantation, six patients died for cardiac reasons. Cox regression analysis demonstrated that FDD (P<0.01), diabetes mellitus (P<0.01), and ejection fraction (P<0.01) were independent predictive factors for the occurrence of the primary endpoint. The Kaplan-Meier survival curve revealed a significantly better clinical outcome in patients with FDD above the median (6.2%) compared with those with FDD below the median (P<0.013). These observations suggest that endothelium-mediated vasodilation represents an independent predictor of cardiac death and hospitalization in patients with CHF, consistent with the notion that endothelium-derived nitric oxide may play a protective role in heart failure.

  4. Compression of contour data through exploiting curve-to-curve dependence

    NASA Technical Reports Server (NTRS)

    Yalabik, N.; Cooper, D. B.

    1975-01-01

    An approach to exploiting curve-to-curve dependencies in order to achieve high data compression is presented. One of the approaches to date of along curve compression through use of cubic spline approximation is taken and extended by investigating the additional compressibility achievable through curve-to-curve structure exploitation. One of the models under investigation is reported on.

  5. Abnormal glucose tolerance post-gestational diabetes mellitus as defined by the International Association of Diabetes and Pregnancy Study Groups criteria.

    PubMed

    Noctor, Eoin; Crowe, Catherine; Carmody, Louise A; Saunders, Jean A; Kirwan, Breda; O'Dea, Angela; Gillespie, Paddy; Glynn, Liam G; McGuire, Brian E; O'Neill, Ciarán; O'Shea, P M; Dunne, F P

    2016-10-01

    An increase in gestational diabetes mellitus (GDM) prevalence has been demonstrated across many countries with adoption of the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) diagnostic criteria. Here, we determine the cumulative incidence of abnormal glucose tolerance among women with previous GDM, and identify clinical risk factors predicting this. Two hundred and seventy women with previous IADPSG-defined GDM were prospectively followed up for 5years (mean 2.6) post-index pregnancy, and compared with 388 women with normal glucose tolerance (NGT) in pregnancy. Cumulative incidence of abnormal glucose tolerance (using American Diabetes Association criteria for impaired fasting glucose, impaired glucose tolerance and diabetes) was determined using the Kaplan-Meier method of survival analysis. Cox regression models were constructed to test for factors predicting abnormal glucose tolerance. Twenty-six percent of women with previous GDM had abnormal glucose tolerance vs 4% with NGT, with the log-rank test demonstrating significantly different survival curves (P<0.001). Women meeting IADPSG, but not the World Health Organization (WHO) 1999 criteria, had a lower cumulative incidence than women meeting both sets of criteria, both in the early post-partum period (4.2% vs 21.7%, P<0.001) and at longer-term follow-up (13.7% vs 32.6%, P<0.001). Predictive factors were glucose levels on the pregnancy oral glucose tolerance test, family history of diabetes, gestational week at testing, and BMI at follow-up. The proportion of women developing abnormal glucose tolerance remains high among those with IADPSG-defined GDM. This demonstrates the need for continued close follow-up, although the optimal frequency and method needs further study. © 2016 European Society of Endocrinology.

  6. How Do We Defend Democratic Education? Lois Weiner and Andy Kaplan Respond to Diane Ravitch's "The Reign of Error"

    ERIC Educational Resources Information Center

    Weiner, Lois; Kaplan, Andy

    2014-01-01

    In this commentary, Andy Kaplan discusses with Lois Weiner, Diane Ravitch's latest book "The Reign of Error," which combines scholarly argument and scrupulous research in defense of democratic education. Weiner notes, the book will prove an important resource in the ongoing struggle for the survival of public schooling. Weiner adds,…

  7. Zebrafish cdc6 hypomorphic mutation causes Meier-Gorlin syndrome-like phenotype.

    PubMed

    Yao, Likun; Chen, Jing; Wu, Xiaotong; Jia, Shunji; Meng, Anming

    2017-11-01

    Cell Division Cycle 6 (Cdc6) is a component of pre-replicative complex (preRC) forming on DNA replication origins in eukaryotes. Recessive mutations in ORC1, ORC4, ORC6, CDT1 or CDC6 of the preRC in human cause Meier-Gorlin syndrome (MGS) that is characterized by impaired post-natal growth, short stature and microcephaly. However, vertebrate models of MGS have not been reported. Through N-ethyl-N-nitrosourea mutagenesis and Cas9 knockout, we generate several cdc6 mutant lines in zebrafish. Loss-of-function mutations of cdc6, as manifested by cdc6tsu4305 and cdc6tsu7cd mutants, lead to embryonic lethality due to cell cycle arrest at the S phase and extensive apoptosis. Embryos homozygous for a cdc6 hypomorphic mutation, cdc6tsu21cd, develop normally during embryogenesis. Later on, compared with their wild-type (WT) siblings, cdc6tsu21cd mutant fish show growth retardation, and their body weight and length in adulthood are greatly reduced, which resemble human MGS. Surprisingly, cdc6tsu21cd mutant fish become males with a short life and fail to mate with WT females, suggesting defective reproduction. Overexpression of Cdc6 mutant forms, which mimic human CDC6(T323R) mutation found in a MGS patient, in zebrafish cdc6tsu4305 mutant embryos partially represses cell death phenotype, suggesting that the human CDC6(T323R) mutation is a hypomorph. cdc6tsu21cd mutant fish will be useful to detect more tissue defects and develop medical treatment strategies for MGS patients. © The Author 2017. Published by Oxford University Press.

  8. Zebrafish cdc6 hypomorphic mutation causes Meier-Gorlin syndrome-like phenotype

    PubMed Central

    Yao, Likun; Chen, Jing; Wu, Xiaotong; Jia, Shunji; Meng, Anming

    2017-01-01

    Abstract Cell Division Cycle 6 (Cdc6) is a component of pre-replicative complex (preRC) forming on DNA replication origins in eukaryotes. Recessive mutations in ORC1, ORC4, ORC6, CDT1 or CDC6 of the preRC in human cause Meier-Gorlin syndrome (MGS) that is characterized by impaired post-natal growth, short stature and microcephaly. However, vertebrate models of MGS have not been reported. Through N-ethyl-N-nitrosourea mutagenesis and Cas9 knockout, we generate several cdc6 mutant lines in zebrafish. Loss-of-function mutations of cdc6, as manifested by cdc6tsu4305 and cdc6tsu7cd mutants, lead to embryonic lethality due to cell cycle arrest at the S phase and extensive apoptosis. Embryos homozygous for a cdc6 hypomorphic mutation, cdc6tsu21cd, develop normally during embryogenesis. Later on, compared with their wild-type (WT) siblings, cdc6tsu21cd mutant fish show growth retardation, and their body weight and length in adulthood are greatly reduced, which resemble human MGS. Surprisingly, cdc6tsu21cd mutant fish become males with a short life and fail to mate with WT females, suggesting defective reproduction. Overexpression of Cdc6 mutant forms, which mimic human CDC6(T323R) mutation found in a MGS patient, in zebrafish cdc6tsu4305 mutant embryos partially represses cell death phenotype, suggesting that the human CDC6(T323R) mutation is a hypomorph. cdc6tsu21cd mutant fish will be useful to detect more tissue defects and develop medical treatment strategies for MGS patients. PMID:28985365

  9. p-Curve and p-Hacking in Observational Research.

    PubMed

    Bruns, Stephan B; Ioannidis, John P A

    2016-01-01

    The p-curve, the distribution of statistically significant p-values of published studies, has been used to make inferences on the proportion of true effects and on the presence of p-hacking in the published literature. We analyze the p-curve for observational research in the presence of p-hacking. We show by means of simulations that even with minimal omitted-variable bias (e.g., unaccounted confounding) p-curves based on true effects and p-curves based on null-effects with p-hacking cannot be reliably distinguished. We also demonstrate this problem using as practical example the evaluation of the effect of malaria prevalence on economic growth between 1960 and 1996. These findings call recent studies into question that use the p-curve to infer that most published research findings are based on true effects in the medical literature and in a wide range of disciplines. p-values in observational research may need to be empirically calibrated to be interpretable with respect to the commonly used significance threshold of 0.05. Violations of randomization in experimental studies may also result in situations where the use of p-curves is similarly unreliable.

  10. p-Curve and p-Hacking in Observational Research

    PubMed Central

    Bruns, Stephan B.; Ioannidis, John P. A.

    2016-01-01

    The p-curve, the distribution of statistically significant p-values of published studies, has been used to make inferences on the proportion of true effects and on the presence of p-hacking in the published literature. We analyze the p-curve for observational research in the presence of p-hacking. We show by means of simulations that even with minimal omitted-variable bias (e.g., unaccounted confounding) p-curves based on true effects and p-curves based on null-effects with p-hacking cannot be reliably distinguished. We also demonstrate this problem using as practical example the evaluation of the effect of malaria prevalence on economic growth between 1960 and 1996. These findings call recent studies into question that use the p-curve to infer that most published research findings are based on true effects in the medical literature and in a wide range of disciplines. p-values in observational research may need to be empirically calibrated to be interpretable with respect to the commonly used significance threshold of 0.05. Violations of randomization in experimental studies may also result in situations where the use of p-curves is similarly unreliable. PMID:26886098

  11. The impact of non-fatal workplace injuries and illnesses on mortality.

    PubMed

    Boden, Leslie I; O'Leary, Paul K; Applebaum, Katie M; Tripodis, Yorghos

    2016-12-01

    Little research has examined the relationship between non-fatal workplace injuries and illnesses, and long-term mortality. We linked non-fatal injury cases reported to the New Mexico workers' compensation system for 1994-2000 with Social Security Administration data on individual earnings and mortality through 2014. We then derived sex-specific Kaplan-Meier curves to show time to death for workers with lost-time injuries (n = 36,377) and comparison workers (n = 70,951). We fit multivariable Cox survival models to estimate the hazard ratio separately for male and female workers with lost-time injuries. The estimated hazard ratio for lost-time injuries is 1.24 for women and 1.21 for men. Ninety-five percent confidence intervals were 1.15, 1.35 and 1.15, 1.27, respectively. Lost-time occupational injuries are associated with a substantially elevated mortality hazard. This implies an important formerly unmeasured cost of these injuries and a further reason to focus on preventing them. Am. J. Ind. Med. 59:1061-1069, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. [Correlations between OCT4 expression and clinicopathological factors and prognosis of patients with lung adenocarcinoma].

    PubMed

    Zhang, Xueyan; Wang, Huimin; Jin, Bo; Dong, Qianggang; Huang, Jinsu; Han, Baohui

    2013-04-01

    In recent years, cases of lung adenocarcinoma morbidity have consistently grown. OCT4 is the key gene that controls the automatic renewal of stem cells, and regulates the proliferation and differentiation of cancer stem cells. The aim of this study is to detect OCT4 expression in lung adenocarcinoma tissues, and to evaluate its relevance in the metastasis, chemotherapeutic effect, and prognosis in lung adenocarcinoma patients. Immunofluorescence method was employed to detect OCT4 expression in lung adenocarcinoma tissues. The relationship between OCT4 expression and clinical pathological indicators is examined through chi-square test. Moreover, the survival rate is calculated through the Kaplan-Meier survivorship curve. Finally, the relevance between the indicators and patient survival is estimated using Cox analysis. Among the 126 tissue samples of lung adenocarcinoma, 91 showed OCT4 positive cells. OCT4 expression is closely related to metastasis and chemoresistance in lung adenocarcinoma patients, and negatively corresponds to the patients' disease-free survival and survival periods. OCT4 expression is related to metastasis and chemoresistance in lung adenocarcinoma patients, and thus indicates poor prognosis.

  13. Diagnostic and prognostic significance of receptor-binding cancer antigen expressed on SiSo cells in lung-cancer-associated pleural effusion.

    PubMed

    Yang, Jian; Zhu, Ying; Wu, Liangquan; Zhu, Wenyan; Zhang, Xiuwei; Yang, Yang; Xu, Chunhua

    2018-01-01

    This study aimed to evaluate the diagnostic and prognostic value of pleural effusion levels of soluble receptor-binding cancer antigen expressed on SiSo cells (sRCAS1) in lung cancer patients with malignant pleural effusion (MPE). Pleural effusion samples were collected from 78 patients with MPE, and from 48 patients with benign pleural effusion (BPE). Pleural effusion sRCAS1 concentrations were measured by enzyme-linked immunosorbent assay. MPE has significantly higher sRCAS1 levels than that of BPE (P < .01). With a cutoff value of 18.7 U/mL, sRCAS1 showed a good diagnostic performance for MPE. Univariate and multivariate analysis indicated that elevated sRCAS1 levels were an independent predictor of overall survival (OS) and disease-free survival (DFS). Kaplan-Meier survival curves further confirmed that patients with high sRCAS1 have shorter DFS and OS (P = .026 and P = .032, respectively). In conclusion, measurement of sRCAS1 might be a useful diagnostic and prognostic marker for MPE. © 2016 John Wiley & Sons Ltd.

  14. Cytologic regression in women with atypical squamous cells of unknown significance and negative human papillomavirus test.

    PubMed

    Wang, Shu; Lang, Jing He; Cheng, Xue Mei

    2009-12-01

    The aim of this study was to investigate the cytologic regression in women with atypical squamous cells of unknown significance and negative high-risk human papillomavirus test. The 45 women with atypical squamous cells of unknown significance and negative high-risk human papillomavirus at baseline were analyzed about the cytologic regression during 2 years of follow-up. The cumulative rate of cytologic regression was calculated by Kaplan-Meier curves. Of 45 women, the cumulative rates were as follows: 55.6% obtained cytologic regression before 6 months, 84.4% by 1 year, and 95.6% at 2 years. Cytologic regression was not influenced by age, menopausal status, and baseline human papillomavirus load. However, the 1-year cumulative regression rate in women with previous cervical lesions was significantly lower than those without (P=.02), even much lower in women with high-grade intraepithelial neoplasia or worse (P=.008). Most women with atypical squamous cells of unknown significance and negative high-risk human papillomavirus could obtain cytologic regression within 2 years. Women with antecedent cervical lesions need longer time to reach this regression.

  15. Necrosis of the femoral head after kidney transplantation.

    PubMed

    Lausten, G S; Lemser, T; Jensen, P K; Egfjord, M

    1998-12-01

    We reviewed the medical records of 750 patients (445 men, 305 women), who had received a kidney transplant during the period 1968-1995, for any sign of necrosis of the femoral head. For post-operative immunosuppression, 374 patients had received high-dose corticosteroids (average 12.5 g during the first year post-operatively), while 376 patients had received low-dose corticosteroids (average 6.5 g during the first year post-operatively) and cyclosporin A. Survival curves according to Kaplan and Meier (J Am Stat Ass 1958: 53: 457-481) were constructed. In the high-dose steroid group, 42/374 patients (11.2%) developed femoral head necrosis, at an average of 26.2 months post-transplantation. In the low-dose steroid group, only 19/376 (5.1%) patients developed this complication, at an average of 20.5 months post-transplantation. This difference in numbers of femoral head necroses was highly significant (p < 0.005). We conclude that steroid doses should be minimized whenever feasible in post-transplant immunosuppression therapy.

  16. Impact of pre-operative body mass index in head and neck cancer patients undergoing microvascular reconstruction.

    PubMed

    Hyun, D-J; Joo, Y-H; Kim, M-S

    2017-11-01

    To analyse the relationship of pre-operative body mass index with surgical complications and oncological outcomes in patients undergoing microvascular reconstruction for head and neck squamous cell cancer. A retrospective review was conducted of 259 patients who underwent microvascular free flap reconstruction after head and neck ablative surgery. Mean body mass index was 22.48 kg/m2. There were no correlations between body mass index and: flap failure (p = 0.739), flap ischaemia (p = 0.644), pharyngocutaneous fistula (p = 0.141) or wound infection (p = 0.224). The five-year disease-specific survival rate was 63 per cent. On univariate analysis, the five-year disease-specific survival rate was significantly correlated with pre-operative body mass index, based on Kaplan-Meier survival curves (p = 0.028). The five-year disease-specific survival rates in underweight, normal weight, overweight and obese groups were 47 per cent, 55 per cent, 65 per cent and 80 per cent, respectively. Pre-operative body mass index was a useful predictor for recurrence and survival in patients who underwent microvascular reconstruction for head and neck squamous cell cancer.

  17. Different clinical response to interferon beta and glatiramer acetate related to the presence of oligoclonal IgM bands in CSF in multiple sclerosis patients.

    PubMed

    Casanova, Bonaventura; Lacruz, Laura; Villar, María Luisa; Domínguez, José Andrés; Gadea, María Carcelén; Gascón, Francisco; Mallada, Javier; Hervás, David; Simó-Castelló, María; Álvarez-Cermeño, José Carlos; Calles, Carmen; Olascoaga, Javier; Ramió-Torrentà, Lluís; Alcalá, Carmen; Cervelló, Angeles; Boscá, Isabel; Pérez-Mirallles, Francisco Carlos; Coret, Francisco

    2018-06-07

    To study the efficacy of interferon beta (IFNβ) and glatiramer acetate (GA) related to the presence of oligoclonal M bands (OCMB) in the cerebrospinal fluid in relapsing-remitting multiple sclerosis (RRMS). This is an observational, multicenter and retrospective study with prospectively collected data of patients that started treatment with IFNβ or GA. Treatment decision was made blinded to the OCMB status. Time to first attack after starting therapy was compared by using Kaplan-Meier curves, and adjustment by Cox regression analysis was performed. Two hundred and fifty-six patients entered in the study (141-55% received IFNβ; 115-45% received GA). After a mean follow-up of 41 and 65 months, 54.7% of patients remained free from further attacks (RF). The proportion of RF patients was higher in the GA group than in the IFNβ group (72.2 vs. 40.4%, p < 0.001). The IFNβ patients with OCMB+ presented the poorest response, 31.3% RF vs. 48.1% in IFNβ without OCMB, p = 0.03. OCMB in CSF could be a biomarker of treatment response in multiple sclerosis.

  18. Runaway transient simulation of a model Kaplan turbine

    NASA Astrophysics Data System (ADS)

    Liu, S.; Zhou, D.; Liu, D.; Wu, Y.; Nishi, M.

    2010-08-01

    The runaway transient is a typical transient process of a hydro power unit, where the rotational speed of a turbine runner rapidly increases up to the runaway speed under a working head as the guide vanes cannot be closed due to some reason at the load rejection. In the present paper, the characteristics of the runaway transient of a model Kaplan turbine having ns = 479(m-kW) is simulated by using a time-dependent CFD technique where equation of rotational motion of runner, continuity equation and unsteady RANS equations with RNG k-epsilon turbulence model are solved iteratively. In the calculation, unstructured mesh is used to the whole flow passage, which consists of several sub-domains: entrance, casing, stay vanes + guide vanes, guide section, runner and draft tube. And variable speed sliding mesh technique is used to exchange interface flow information between moving part and stationary part, and three-dimensional unstructured dynamic mesh technique is also adopted to ensure mesh quality. Two cases were treated in the simulation of runaway transient characteristics after load rejection: one is the rated operating condition as the initial condition, and the other is the condition at the maximum head. Regarding the runaway speed, the experimental speed is 1.45 times the initial speed and the calculation is 1.47 times the initial for the former case. In the latter case, the experiment and the calculation are 1.67 times and 1.69 times respectively. From these results, it is recognized that satisfactorily prediction will be possible by using the present numerical method. Further, numerical results show that the swirl in the draft-tube flow becomes stronger in the latter part of the transient process so that a vortex rope will occur in the draft tube and its precession will cause the pressure fluctuations which sometimes affect the stability of hydro power system considerably.

  19. An Unified Multiscale Framework for Planar, Surface, and Curve Skeletonization.

    PubMed

    Jalba, Andrei C; Sobiecki, Andre; Telea, Alexandru C

    2016-01-01

    Computing skeletons of 2D shapes, and medial surface and curve skeletons of 3D shapes, is a challenging task. In particular, there is no unified framework that detects all types of skeletons using a single model, and also produces a multiscale representation which allows to progressively simplify, or regularize, all skeleton types. In this paper, we present such a framework. We model skeleton detection and regularization by a conservative mass transport process from a shape's boundary to its surface skeleton, next to its curve skeleton, and finally to the shape center. The resulting density field can be thresholded to obtain a multiscale representation of progressively simplified surface, or curve, skeletons. We detail a numerical implementation of our framework which is demonstrably stable and has high computational efficiency. We demonstrate our framework on several complex 2D and 3D shapes.

  20. Hsp-27 levels and thrombus burden relate to clinical outcomes in patients with ST-segment elevation myocardial infarction

    PubMed Central

    Tian, Maozhou; Zhu, Lingmin; Lin, Hongyang; Lin, Qiaoyan; Huang, Peng; Yu, Xiao; Jing, Yanyan

    2017-01-01

    High thrombus burden, subsequent distal embolization, and myocardial no-reflow remain a large obstacle that may negate the benefits of urgent coronary revascularization in patients with ST-segment elevation myocardial infarction (STEMI). However, the biological function and clinical association of Hsp-27 with thrombus burden and clinical outcomes in patients with STEMI is not clear. Consecutive patients (n = 146) having STEMI undergoing primary percutaneous coronary intervention (pPCI) within 12 hours from the onset of symptoms were enrolled in this prospective study in the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shangdong, P.R. China. Patients were divided into low thrombus burden and high thrombus burden groups. The present study demonstrated that patients with high-thrombus burden had higher plasma Hsp-27 levels ([32.0 ± 8.6 vs. 58.0 ± 12.3] ng/mL, P < 0.001). The median value of Hsp-27 levels in all patients with STEMI was 45 ng/mL. Using the receiver operating characteristic (ROC) curve analysis, plasma Hsp-27 levels were of significant diagnostic value for high thrombus burden (AUC, 0.847; 95% CI, 0.775–0.918; P < 0.01). The multivariate cox regression analysis demonstrated that Hsp-27 > 45 ng/mL (HR 2.801, 95% CI 1.296–4.789, P = 0.001), were positively correlated with the incidence of major adverse cardiovascular events (MACE). Kaplan-Meier survival analysis demonstrated that MACE-free survival at 180-day follow-up was significantly lower in patients with Hsp-27 > 45 ng/mL (log rank = 10.28, P < 0.001). Our data demonstrate that plasma Hsp-27 was positively correlated with high thrombus burden and the incidence of MACE in patients with STEMI who underwent pPCI. PMID:29088740

  1. Research on conformal dome of Karman-curve shape

    NASA Astrophysics Data System (ADS)

    Zhang, Yunqiang; Chang, Jun; Niu, Yajun

    2018-01-01

    Because the conformal optical technology can obviously improve the aerodynamic performance of the infrared guidance missile, it has been studied deeply in recent years. By comparing the performance of the missiles with conformal dome and conventional missiles, the advantages of the conformal optical technology are demonstrated in the maneuverability and stealth of the missile. At present, the study of conformal optical systems focuses on ellipsoid or quadratic curve types. But in actual use, the dome using these curves is not the best choice. In this paper, the influence of different shape of the dome on aerodynamic performance, aerodynamic heating, internal space volume and other properties is discussed. The result shows infrared optical system with conformal dome of Karman-curve shape has a good application prospect, is the future direction of development. Finally, the difficult problems of conformal dome of Karman-curve shape are discussed.

  2. Low-pass filtering of noisy field Schlumberger sounding curves. Part II: Application

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ghosh, N.; Wadhwa, R.S.; Shrotri, B.S.

    1986-02-01

    The basic principles of the application of the linear system theory for smoothing noise-degraded d.c. geoelectrical sounding curves were recently established by Patella. A field Schlumberger sounding is presented to demonstrate first their application and validity. To achieve this purpose, firstly it is pointed out that the required smoothing or low-pass filtering can be considered as an intrinsic property of the transformation of original Schlumberger sounding curves into pole-pole (two-electrode) curves. Then the authors sketch a numerical algorithm to perform the transformation, opportunely modified from a known procedure for transforming dipole diagrams into Schlumberger ones. Finally they show a fieldmore » example with the double aim of demonstrating (i) the high quality of the low-pass filtering, and (ii) the reliability of the transformed pole-pole curve as far as quantitative interpretation is concerned.« less

  3. Small artery elasticity predicts future cardiovascular events in chinese patients with angiographic coronary artery disease.

    PubMed

    Wan, Zhaofei; Liu, Xiaojun; Wang, Xinhong; Liu, Fuqiang; Liu, Weimin; Wu, Yue; Pei, Leilei; Yuan, Zuyi

    2014-04-01

    Arterial elasticity has been shown to predict cardiovascular disease (CVD) in apparently healthy populations. The present study aimed to explore whether arterial elasticity could predict CVD events in Chinese patients with angiographic coronary artery disease (CAD). Arterial elasticity of 365 patients with angiographic CAD was measured. During follow-up (48 months; range 6-65), 140 CVD events occurred (including 34 deaths). Univariate Cox analysis demonstrated that both large arterial elasticity and small arterial elasticity were significant predictors of CVD events. Multivariate Cox analysis indicated that small arterial elasticity remained significant. Kaplan-Meier analysis showed that the probability of having a CVD event/CVD death increased with a decrease of small arterial elasticity (P < .001, respectively). Decreased small arterial elasticity independently predicts the risk of CVD events in Chinese patients with angiographic CAD.

  4. Surface growth kinematics via local curve evolution.

    PubMed

    Moulton, Derek E; Goriely, Alain

    2014-01-01

    A mathematical framework is developed to model the kinematics of surface growth for objects that can be generated by evolving a curve in space, such as seashells and horns. Growth is dictated by a growth velocity vector field defined at every point on a generating curve. A local orthonormal basis is attached to each point of the generating curve and the velocity field is given in terms of the local coordinate directions, leading to a fully local and elegant mathematical structure. Several examples of increasing complexity are provided, and we demonstrate how biologically relevant structures such as logarithmic shells and horns emerge as analytical solutions of the kinematics equations with a small number of parameters that can be linked to the underlying growth process. Direct access to cell tracks and local orientation enables for connections to be made to the underlying growth process.

  5. A Tangent Bundle Theory for Visual Curve Completion.

    PubMed

    Ben-Yosef, Guy; Ben-Shahar, Ohad

    2012-07-01

    Visual curve completion is a fundamental perceptual mechanism that completes the missing parts (e.g., due to occlusion) between observed contour fragments. Previous research into the shape of completed curves has generally followed an "axiomatic" approach, where desired perceptual/geometrical properties are first defined as axioms, followed by mathematical investigation into curves that satisfy them. However, determining psychophysically such desired properties is difficult and researchers still debate what they should be in the first place. Instead, here we exploit the observation that curve completion is an early visual process to formalize the problem in the unit tangent bundle R(2) × S(1), which abstracts the primary visual cortex (V1) and facilitates exploration of basic principles from which perceptual properties are later derived rather than imposed. Exploring here the elementary principle of least action in V1, we show how the problem becomes one of finding minimum-length admissible curves in R(2) × S(1). We formalize the problem in variational terms, we analyze it theoretically, and we formulate practical algorithms for the reconstruction of these completed curves. We then explore their induced visual properties vis-à-vis popular perceptual axioms and show how our theory predicts many perceptual properties reported in the corresponding perceptual literature. Finally, we demonstrate a variety of curve completions and report comparisons to psychophysical data and other completion models.

  6. Mutations in CDC45, Encoding an Essential Component of the Pre-initiation Complex, Cause Meier-Gorlin Syndrome and Craniosynostosis.

    PubMed

    Fenwick, Aimee L; Kliszczak, Maciej; Cooper, Fay; Murray, Jennie; Sanchez-Pulido, Luis; Twigg, Stephen R F; Goriely, Anne; McGowan, Simon J; Miller, Kerry A; Taylor, Indira B; Logan, Clare; Bozdogan, Sevcan; Danda, Sumita; Dixon, Joanne; Elsayed, Solaf M; Elsobky, Ezzat; Gardham, Alice; Hoffer, Mariette J V; Koopmans, Marije; McDonald-McGinn, Donna M; Santen, Gijs W E; Savarirayan, Ravi; de Silva, Deepthi; Vanakker, Olivier; Wall, Steven A; Wilson, Louise C; Yuregir, Ozge Ozalp; Zackai, Elaine H; Ponting, Chris P; Jackson, Andrew P; Wilkie, Andrew O M; Niedzwiedz, Wojciech; Bicknell, Louise S

    2016-07-07

    DNA replication precisely duplicates the genome to ensure stable inheritance of genetic information. Impaired licensing of origins of replication during the G1 phase of the cell cycle has been implicated in Meier-Gorlin syndrome (MGS), a disorder defined by the triad of short stature, microtia, and a/hypoplastic patellae. Biallelic partial loss-of-function mutations in multiple components of the pre-replication complex (preRC; ORC1, ORC4, ORC6, CDT1, or CDC6) as well as de novo stabilizing mutations in the licensing inhibitor, GMNN, cause MGS. Here we report the identification of mutations in CDC45 in 15 affected individuals from 12 families with MGS and/or craniosynostosis. CDC45 encodes a component of both the pre-initiation (preIC) and CMG helicase complexes, required for initiation of DNA replication origin firing and ongoing DNA synthesis during S-phase itself, respectively, and hence is functionally distinct from previously identified MGS-associated genes. The phenotypes of affected individuals range from syndromic coronal craniosynostosis to severe growth restriction, fulfilling diagnostic criteria for Meier-Gorlin syndrome. All mutations identified were biallelic and included synonymous mutations altering splicing of physiological CDC45 transcripts, as well as amino acid substitutions expected to result in partial loss of function. Functionally, mutations reduce levels of full-length transcripts and protein in subject cells, consistent with partial loss of CDC45 function and a predicted limited rate of DNA replication and cell proliferation. Our findings therefore implicate the preIC as an additional protein complex involved in the etiology of MGS and connect the core cellular machinery of genome replication with growth, chondrogenesis, and cranial suture homeostasis. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  7. Retrospective clinical evaluation of ceramic onlays placed by dental students.

    PubMed

    Archibald, Jennifer J; Santos, Gildo Coelho; Moraes Coelho Santos, Maria Jacinta

    2017-09-16

    Indirect restorations with partial or complete occlusal surface coverage have been recommended to restore teeth with weakened walls in order to prevent cusp fracture. The success of these restorations when performed by dental students is unknown. The purpose of this retrospective study was to evaluate the clinical performance of adhesively bonded ceramic onlay restorations placed by third- and fourth-year dental students. Sixty-five ceramic onlays were placed in patients between 2009 and 2015. The onlays were laboratory or chairside fabricated with a computer-aided design and computer-aided manufacturing (CAD-CAM) system, using either IPS e.max Press or IPS e.max CAD. An adhesive technique and luting composite resin agent were used to cement the restorations. Thirty-seven onlays were evaluated clinically using the modified United States Public Health Service (USPHS) criteria. Data were statistically analyzed using the Cox proportional hazards model to compare tooth type and failures and the Fisher exact and McNemar tests to compare the USPHS criteria for significant differences (α=.05). Survival probability was calculated using the Kaplan-Meier algorithm. Five onlays were considered to be failures and needed replacement. According to the Kaplan-Meier analysis, the estimated survival rate was 96.3% after 2 years and 91.5% at 4 years. All 5 of the failures occurred on molars (13.5%) and none on premolars (P=.025). A statistically significant difference was found for marginal discoloration between onlays placed within 0 to 3 years and 3 to 6 years (P<.05) but no differences between any other criteria. Ceramic onlays placed by dental students demonstrated acceptable long-term clinical performance. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  8. Three- to nine-year survival estimates and fracture mechanisms of zirconia- and alumina-based restorations using standardized criteria to distinguish the severity of ceramic fractures.

    PubMed

    Moráguez, Osvaldo D; Wiskott, H W Anselm; Scherrer, Susanne S

    2015-12-01

    The aims of this study were set as follows: 1. To provide verifiable criteria to categorize the ceramic fractures into non-critical (i.e., amenable to polishing) or critical (i.e., in need of replacement) 2. To establish the corresponding survival rates for alumina and zirconia restorations 3. To establish the mechanism of fracture using fractography Fifty-eight patients restored with 115 alumina-/zirconia-based crowns and 26 zirconia-based fixed dental prostheses (FDPs) were included. Ceramic fractures were classified into four types and further subclassified into "critical" or "non-critical." Kaplan-Meier survival estimates were calculated for "critical fractures only" and "all fractures." Intra-oral replicas were taken for fractographic analyses. Kaplan-Meier survival estimates for "critical fractures only" and "all fractures" were respectively: Alumina single crowns: 90.9 and 68.3 % after 9.5 years (mean 5.71 ± 2.6 years). Zirconia single crowns: 89.4 and 80.9 % after 6.3 years (mean 3.88 ± 1.2 years). Zirconia FDPs: 68.6 % (critical fractures) and 24.6 % (all fractures) after 7.2 and 4.6 years respectively (FDP mean observation time 3.02 ± 1.4 years). No core/framework fractures were detected. Survival estimates varied significantly depending on whether "all" fractures were considered as failures or only those deemed as "critical". For all restorations, fractographic analyses of failed veneering ceramics systematically demonstrated heavy occlusal wear at the failure origin. Therefore, the relief of local contact pressures on unsupported ceramic is recommended. Occlusal contacts on mesial or distal ridges should systematically be eliminated. A classification standard for ceramic fractures into four categories with subtypes "critical" and "non-critical" provides a differentiated view of the survival of ceramic restorations.

  9. CHIP involves in non-small cell lung cancer prognosis through VEGF pathway.

    PubMed

    Tingting, Qian; Jiao, Wang; Qingfeng, Wang; Yancheng, Liu; Shijun, Y U; Zhaoqi, Wang; Dongmei, Sun; ShiLong, Wang

    2016-10-01

    CHIP (c-terminal Hsp70-interacting protein) is an E3 ligase playing vital roles in various cancers. The VEGF pathway has become an important therapeutic target in non-small cell lung cancer (NSCLC). However, little is known about the role of CHIP and the relationship between CHIP and VEGF-VEGFR2 (VEGF receptor 2) pathway in NSCLC. In this study we aimed to investigate the clinical function of CHIP in NSCLC and explore the relevant regulatory mechanism. QRT-PCR was performed to detect CHIP expression in NSCLC tissues. The association of CHIP expression and clinical parameters was analyzed using the Chi-square test. Kaplan- Meier and Cox analyses were performed to identify the role of CHIP in the prognosis of NSCLC patients. ELISA test was used to detect the VEGF secretion of NSCLC cells and western blot were used to detected the protein expression of VEGFR2 in NSCLC cells. and the results revealed that CHIP expression was decreased in NSCLC tissues and significantly correlated with clinical stages, lymph node metastasis and distant metastasis (P<0.05). Moreover, Kaplan-Meier and Cox regression analyses showed that patients with negative expression of CHIP had a shorter survival time and CHIP could be an independent prognostic biomarker. In addition, ELISA tests showed that CHIP negatively regulated the secretion level of VEGF. Furthermore, western blot assay indicated that the VEGFR2 protein level was reduced after CHIP over-expression. Taken together, our findings demonstrate for the first time that CHIP may serve as a promising prognostic biomarker for NSCLC patients and it may be involved in NSCLC angiogenesis through regulating VEGF secretion and expression of VEGFR2. Copyright © 2016. Published by Elsevier Masson SAS.

  10. Impact of Age on the Prognosis of Operable Gastric Cancer Patients: An Analysis Based on SEER Database.

    PubMed

    Chen, Jie; Chen, Jinggui; Xu, Yu; Long, Ziwen; Zhou, Ye; Zhu, Huiyan; Wang, Yanong; Shi, Yingqiang

    2016-06-01

    To investigate the impact of age on the clinicopathological features and survival of patients with gastric cancer (GC), and hope to better define age-specific patterns of GC and possible associated risk factors.Using the surveillance, epidemiology, and end results (SEER) database to search the patients who diagnosed GC between 2007 and 2011 with a known age. The overall and 5-year gastric cancer specific survival (CSS) data were obtained using Kaplan-Meier plots. Multivariable Cox regression models were built for the analysis of long-term survival outcomes and risk factors.A total of 7762 GC patients treated with surgery during the 4-year study period were included in the final study cohort. We divided into five subgroups according to the different age ranges. The overall 5-year cause-specific survival (CSS) was 60.3% in Group 1 (below 45 years), 60.3% in the Group 2 (45-55 years), 61.2% in Group 3 (56-65 years), 59.2% in Group 4 (66-75 years), and 59.2% in Group 5 (older than 76 years). Kaplan-Meier plots showed that patients older than 76 years had the worst 5-year CSS of 56.0% rate in all the subgroups. Age, tumor size, primary site, histological type, and Tumor Node Metastasis stage were identified as significant risk factors for poor survival on univariate analysis (all P < 0.001, log-rank test). Additionally, as the age increased, the risk of death for GC demonstrated a significant increase.In conclusion, our analysis of the SEER database revealed that the prognosis of GC varies with age. Patients at age 56 to 65 group have more favorable clinicopathologic characteristics and better CSS than other groups.

  11. Statistical evaluation of a project to estimate fish trajectories through the intakes of Kaplan hydropower turbines

    NASA Astrophysics Data System (ADS)

    Sutton, Virginia Kay

    This paper examines statistical issues associated with estimating paths of juvenile salmon through the intakes of Kaplan turbines. Passive sensors, hydrophones, detecting signals from ultrasonic transmitters implanted in individual fish released into the preturbine region were used to obtain the information to estimate fish paths through the intake. Aim and location of the sensors affects the spatial region in which the transmitters can be detected, and formulas relating this region to sensor aiming directions are derived. Cramer-Rao lower bounds for the variance of estimators of fish location are used to optimize placement of each sensor. Finally, a statistical methodology is developed for analyzing angular data collected from optimally placed sensors.

  12. Demonstrating Optical Aberration Correction With a Mems Micro-Mirror Device

    DTIC Science & Technology

    1996-12-01

    intensity distributions for a corrected and uncorrected MEMS reflection. The curves have been nor- malized to the peak value of the corrected wave front...demonstration: A = 632.8 mn, f = 7 mm, and L = 203 ym. For the solid curve , s = 0, while the dashed curve shows s = 7r/L, so that the change in phase...specified for Figure 8 (see page 29), so that the figures are directly comparable. The solid curve shows an intensity distribution for 01 = 0 (no

  13. Correcting for dependent censoring in routine outcome monitoring data by applying the inverse probability censoring weighted estimator.

    PubMed

    Willems, Sjw; Schat, A; van Noorden, M S; Fiocco, M

    2018-02-01

    Censored data make survival analysis more complicated because exact event times are not observed. Statistical methodology developed to account for censored observations assumes that patients' withdrawal from a study is independent of the event of interest. However, in practice, some covariates might be associated to both lifetime and censoring mechanism, inducing dependent censoring. In this case, standard survival techniques, like Kaplan-Meier estimator, give biased results. The inverse probability censoring weighted estimator was developed to correct for bias due to dependent censoring. In this article, we explore the use of inverse probability censoring weighting methodology and describe why it is effective in removing the bias. Since implementing this method is highly time consuming and requires programming and mathematical skills, we propose a user friendly algorithm in R. Applications to a toy example and to a medical data set illustrate how the algorithm works. A simulation study was carried out to investigate the performance of the inverse probability censoring weighted estimators in situations where dependent censoring is present in the data. In the simulation process, different sample sizes, strengths of the censoring model, and percentages of censored individuals were chosen. Results show that in each scenario inverse probability censoring weighting reduces the bias induced in the traditional Kaplan-Meier approach where dependent censoring is ignored.

  14. [Expression and clinical significance of 5hmC in bladder urothelial carcinoma].

    PubMed

    Li, Jie; Xu, Yuqiao; Zhang, Zhiwen; Zhang, Ming; Zhang, Zhekai; Zhang, Feng; Li, Qing

    2016-02-01

    To investigate the expression of 5-hydroxymethylcytosine (5hmC) in bladder urothelial carcinoma (UC) and its clinical significance. The expression of 5hmC in 21 cases of UC tissues and pericarcinous urinary tract epithelium was detected by immunohistochemical staining. Then the expression of 5hmC in the surgical resection of UC tissues in 92 cases was also surveyed. Non parametric U Mann-Whitney test was used to analyze the correlation between 5hmC expression and clinical data. Single factor survival analysis was performed by Kaplan-Meier test. The expression of 5hmC in normal urinary tract epithelium and UC tissues was significantly different, but there was no significant difference in the expression of 5hmC between low and high grades of UC tissues as well as between different TNM grades. Kaplan-Meier single factor survival analysis showed that there was no significant correlation between the 5hmC expression level and the survival rate or the recurrence-free survival of UC patients. The expression level of 5hmC in UC tissues is significantly lower than that in pericarcinous urinary tract epithelium. There is no correlation between the 5hmC expression and the progression, prognosis and recurrence of UC.

  15. High serum uric acid concentration predicts poor survival in patients with breast cancer.

    PubMed

    Yue, Cai-Feng; Feng, Pin-Ning; Yao, Zhen-Rong; Yu, Xue-Gao; Lin, Wen-Bin; Qian, Yuan-Min; Guo, Yun-Miao; Li, Lai-Sheng; Liu, Min

    2017-10-01

    Uric acid is a product of purine metabolism. Recently, uric acid has gained much attraction in cancer. In this study, we aim to investigate the clinicopathological and prognostic significance of serum uric acid concentration in breast cancer patients. A total of 443 female patients with histopathologically diagnosed breast cancer were included. After a mean follow-up time of 56months, survival was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of uric acid concentrations, univariate and multivariate Cox regression analyses were applied. Of the clinicopathological parameters, uric acid concentration was associated with age, body mass index, ER status and PR status. Univariate analysis identified that patients with increased uric acid concentration had a significantly inferior overall survival (HR 2.13, 95% CI 1.15-3.94, p=0.016). In multivariate analysis, we found that high uric acid concentration is an independent prognostic factor predicting death, but insufficient to predict local relapse or distant metastasis. Kaplan-Meier analysis indicated that high uric acid concentration is related to the poor overall survival (p=0.013). High uric acid concentration predicts poor survival in patients with breast cancer, and might serve as a potential marker for appropriate management of breast cancer patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Evaluation of the TRPM2 channel as a biomarker in breast cancer using public databases analysis.

    PubMed

    Sumoza-Toledo, Adriana; Espinoza-Gabriel, Mario Iván; Montiel-Condado, Dvorak

    Breast cancer is one of the most common malignancies affecting women. Recent investigations have revealed a major role of ion channels in cancer. The transient receptor potential melastatin-2 (TRPM2) is a plasma membrane and lysosomal channel with important roles in cell migration and cell death in immune cells and tumor cells. In this study, we investigated the prognostic value of TRPM2 channel in breast cancer, analyzing public databases compiled in Oncomine™ (Thermo Fisher, Ann Arbor, MI) and online Kaplan-Meier Plotter platforms. The results revealed that TRPM2 mRNA overexpression is significant in situ and invasive breast carcinoma compared to normal breast tissue. Furthermore, multi-gene validation using Oncomine™ showed that this channel is coexpressed with proteins related to cellular migration, transformation, and apoptosis. On the other hand, Kaplan-Meier analysis exhibited that low expression of TRPM2 could be used to predict poor outcome in ER- and HER2+ breast carcinoma patients. TRPM2 is a promising biomarker for aggressiveness of breast cancer, and a potential target for the development of new therapies. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

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

    PubMed

    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.

  18. Some insight on censored cost estimators.

    PubMed

    Zhao, H; Cheng, Y; Bang, H

    2011-08-30

    Censored survival data analysis has been studied for many years. Yet, the analysis of censored mark variables, such as medical cost, quality-adjusted lifetime, and repeated events, faces a unique challenge that makes standard survival analysis techniques invalid. Because of the 'informative' censorship imbedded in censored mark variables, the use of the Kaplan-Meier (Journal of the American Statistical Association 1958; 53:457-481) estimator, as an example, will produce biased estimates. Innovative estimators have been developed in the past decade in order to handle this issue. Even though consistent estimators have been proposed, the formulations and interpretations of some estimators are less intuitive to practitioners. On the other hand, more intuitive estimators have been proposed, but their mathematical properties have not been established. In this paper, we prove the analytic identity between some estimators (a statistically motivated estimator and an intuitive estimator) for censored cost data. Efron (1967) made similar investigation for censored survival data (between the Kaplan-Meier estimator and the redistribute-to-the-right algorithm). Therefore, we view our study as an extension of Efron's work to informatively censored data so that our findings could be applied to other marked variables. Copyright © 2011 John Wiley & Sons, Ltd.

  19. Measuring Systematic Error with Curve Fits

    ERIC Educational Resources Information Center

    Rupright, Mark E.

    2011-01-01

    Systematic errors are often unavoidable in the introductory physics laboratory. As has been demonstrated in many papers in this journal, such errors can present a fundamental problem for data analysis, particularly when comparing the data to a given model. In this paper I give three examples in which my students use popular curve-fitting software…

  20. Evaluation of blade-strike models for estimating the biological performance of large Kaplan hydro turbines

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Deng, Z.; Carlson, T. J.; Ploskey, G. R.

    2005-11-01

    Bio-indexing of hydro turbines has been identified as an important means to optimize passage conditions for fish by identifying operations for existing and new design turbines that minimize the probability of injury. Cost-effective implementation of bio-indexing requires the use of tools such as numerical and physical turbine models to generate hypotheses for turbine operations that can be tested at prototype scales using live fish. Blade strike has been proposed as an index variable for the biological performance of turbines. Report reviews an evaluation of the use of numerical blade-strike models as a means with which to predict the probability ofmore » blade strike and injury of juvenile salmon smolt passing through large Kaplan turbines on the mainstem Columbia River.« less

  1. Deregulation of DNA-dependent protein kinase catalytic subunit contributes to human hepatocarcinogenesis development and has a putative prognostic value.

    PubMed

    Evert, M; Frau, M; Tomasi, M L; Latte, G; Simile, M M; Seddaiu, M A; Zimmermann, A; Ladu, S; Staniscia, T; Brozzetti, S; Solinas, G; Dombrowski, F; Feo, F; Pascale, R M; Calvisi, D F

    2013-11-12

    The DNA-repair gene DNA-dependent kinase catalytic subunit (DNA-PKcs) favours or inhibits carcinogenesis, depending on the cancer type. Its role in human hepatocellular carcinoma (HCC) is unknown. DNA-dependent protein kinase catalytic subunit, H2A histone family member X (H2AFX) and heat shock transcription factor-1 (HSF1) levels were assessed by immunohistochemistry and/or immunoblotting and qRT-PCR in a collection of human HCC. Rates of proliferation, apoptosis, microvessel density and genomic instability were also determined. Heat shock factor-1 cDNA or DNA-PKcs-specific siRNA were used to explore the role of both genes in HCC. Activator protein 1 (AP-1) binding to DNA-PKcs promoter was evaluated by chromatin immunoprecipitation. Kaplan-Meier curves and multivariate Cox model were used to study the impact on clinical outcome. Total and phosphorylated DNA-PKcs and H2AFX were upregulated in HCC. Activated DNA-PKcs positively correlated with HCC proliferation, genomic instability and microvessel density, and negatively with apoptosis and patient's survival. Proliferation decline and massive apoptosis followed DNA-PKcs silencing in HCC cell lines. Total and phosphorylated HSF1 protein, mRNA and activity were upregulated in HCC. Mechanistically, we demonstrated that HSF1 induces DNA-PKcs upregulation through the activation of the MAPK/JNK/AP-1 axis. DNA-dependent protein kinase catalytic subunit transduces HSF1 effects in HCC cells, and might represent a novel target and prognostic factor in human HCC.

  2. Kasai hepatoportoenterostomy in South Australia: a case for 'centralized decentralization'.

    PubMed

    Tu, Chen Gang; Khurana, Sanjeev; Couper, Richard; Ford, Andrew W D

    2015-11-01

    Recent follow-up studies have demonstrated significant improvement in overall survival as well as survival with native liver following geographic centralization of services to three centres in the UK. However, this model has not been replicated in countries with relatively low population density such as Australia and Canada. Retrospective evaluation of all patients born with biliary atresia (BA) in South Australia from 1989 to 2010 was performed. Thirty-one patients with BA were discovered. Two patients were excluded because the initial Kasai procedure (KP) was performed interstate. Outcome parameters measured were (i) clearance of jaundice (bilirubin of less than 20 μmol/L, by 6 months); (ii) survival with native liver; and (iii) overall survival. Kaplan-Meier survival curves were plotted for both survival with native liver and overall survival. The incidence of BA in South Australia between 1989 and 2010 was 7.48 per 100,000 live births. Following KP, clearance of jaundice was achieved in 42.9% of patients. Five-year actuarial survival with native liver was 55.2%, and overall 5-year actuarial survival was 89.3%. The results of KP performed at Women's and Children's Hospital from 1989 to 2010 can be considered comparable with international benchmarks. Based on these results, we propose the creation of a 'centralized' pool of surgeons in Australia to help continue providing 'decentralized' care of BA. © 2014 Royal Australasian College of Surgeons.

  3. Levels of serum uric acid at admission for hypoglycaemia predict 1-year mortality.

    PubMed

    Bonaventura, Aldo; Gallo, Fiorenza; Carbone, Federico; Liberale, Luca; Maggi, Davide; Sacchi, Giovanni; Dallegri, Franco; Montecucco, Fabrizio; Cordera, Renzo

    2018-04-01

    Hypoglycaemia represents a critical burden with clinical and social consequences in the management of diabetes. Serum uric acid (SUA) has been associated with cardiovascular diseases (CVD), but no conclusive findings are available nowadays in patients suffering from hypoglycaemia. We investigated whether SUA levels at the time of hypoglycaemia could predict all-cause mortality after 1-year follow-up. In total, 219 patients admitted to the Emergency Department (ED) of Ospedale Policlinico S. Martino of Genoa (Italy) have been enrolled between January 2011 and December 2014. The primary endpoint of the study consisted in determining whether SUA levels at the time of ED admission could predict the occurrence of death after 1 year. The majority of patients were diabetic, especially type 2. CVD and chronic kidney disease were prevalent comorbidities. By a cut-off value obtained by the receiver operating characteristic curve analysis, a Kaplan-Meier analysis demonstrated that patients with SUA levels > 5.43 mg/dL were more prone to death after 1 year compared to those with lower SUA levels. The risk of death increased with high SUA levels both in the univariate and the multivariate models including estimated glomerular filtration rate, C-reactive protein, type of diabetes, and age-adjusted Charlson comorbidity index. SUA could be useful as a predictor of 1-year mortality in hypoglycaemic patients, irrespective of severe comorbidities notably increasing the risk of death in these frail patients.

  4. Postoperative course of Crohn disease according to timing of bowel resection: Results from the CONNECT Study.

    PubMed

    Lee, Ji Min; Lee, Kang-Moon; Kim, Joo Sung; Kim, You Sun; Cheon, Jae Hee; Ye, Byong Duk; Kim, Young-Ho; Han, Dong Soo; Lee, Chang Kyun; Park, Hyun-Ju

    2018-04-01

    Previous studies have demonstrated that early surgery in Crohn disease (CD) can result in a better clinical course than late surgery. The aim of this study was to compare the clinical course of CD following bowel resection performed at the time of diagnosis (early surgery) and during the course of the disease (late surgery).We reviewed medical records from a hospital-based cohort database that includes Korean CD patients diagnosed before 2009. Patients who underwent bowel resection were included. Age, sex, disease phenotype, time of surgery, medication history including use of corticosteroids, immunomodulators, and biologics, and further surgical history were assessed.In all, 243 CD patients who had undergone bowel resection were included, and 120 patients underwent surgery at the time of diagnosis, while 123 underwent surgery after diagnosis (median 105 months, range 2-277). The use of biologics was significantly higher in the late surgery group than in the early surgery group (P = .020). The use of immunomodulators and reoperation rates did not differ between the groups. Early surgery was associated with less use of biologics (Kaplan-Meier curve analysis P = .015). Multivariate analysis indicated that early surgery and old age at surgery were independent variables associated with less use of biologics.CD patients who underwent bowel resection at the time of diagnosis have a more favorable disease course, represented by less use of biologics. Early surgery might be a treatment option in a subset of CD patients.

  5. Association of donor and recipient SUMO4 rs237025 genetic variant with new-onset diabetes mellitus after liver transplantation in a Chinese population.

    PubMed

    Zhang, Tao; Liu, Yuan; Hu, Yibo; Zhang, Xiaoqing; Zhong, Lin; Fan, Junwei; Peng, Zhihai

    2017-09-05

    New-onset diabetes mellitus (NODM) is a common complication after liver transplantation (LT). The small ubiquitin-like modifier 4 (SUMO4) rs237025 polymorphism has been reported to be associated with type 2 diabetes mellitus (T2DM). In this study, we aimed to evaluate the association of donor and recipient SUMO4 rs237025 polymorphisms with NODM and the long-term consequences of NODM after LT. A total of 126 liver transplant patients were enrolled in the study. One single nucleotide polymorphism, SUMO4 rs237025, was genotyped in both donors and recipients. Both donor and recipient SUMO4 rs237025 polymorphisms were found to be significantly associated with NODM after LT. In multivariate analysis, recipient age>50 years, tacrolimus trough concentrations>10ng/mL at 1month after LT, donor and recipient rs237025 genetic variant, and the combined donor and recipient rs237025 genetic variant were independent predictive factors of NODM. Area under the receiver operating characteristic curve (AUROC) analysis indicated the higher predictive ability of the model containing combined donor and recipient rs237025 polymorphisms than the clinical model (p=0.046). Furthermore, Kaplan-Meier survival analysis demonstrated that NODM was related to significantly poorer patient survival in comparison with non-NODM patients (p=0.041). Both donor and recipient SUMO4 rs237025 polymorphisms contribute to the development of NODM after LT and NODM is a frequent complication that negatively affects patient survival. Copyright © 2017. Published by Elsevier B.V.

  6. Upregulation of nuclear transporter, Kpnβ1, contributes to accelerated cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) in diffuse large B-cell lymphoma.

    PubMed

    He, Song; Miao, Xiaobing; Wu, Yaxun; Zhu, Xinghua; Miao, Xianjing; Yin, Haibing; He, Yunhua; Li, Chunsun; Liu, Yushan; Lu, Xiaoyun; Chen, Yali; Wang, Yuchan; Xu, Xiaohong

    2016-03-01

    The Karyopherin proteins are involved in the shuttling of cargo proteins, and certain RNAs, across the nuclear pore complex into and out of the cell nucleus. Karyopherin β1 (Kpnβ1) is a member of the Karyopherin β superfamily of nuclear transport proteins. In addition to the nuclear import function, Kpnβ1 is associated with the occurrence of tumors. This study investigated the expression and biologic function of Kpnβ1 in diffuse large B-cell lymphoma (DLBCL). The prognostic value of Kpnβ1 expression was evaluated using immunohistochemical staining. The role of Kpnβ1 on cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) was also determined. We demonstrated that Kpnβ1 mRNA and protein expression levels were significantly higher in DLBCL B-cells and DLBCL cell lines than in normal CD19 purified B-cells. Immunohistochemical analysis suggested that the expression of Kpnβ1 was correlated with Ki-67 (P < 0.001). Kaplan-Meier curve showed that high expression of Kpnβ1 was significantly associated with shorter overall survival. In addition, Kpnβ1 was associated with the proliferation of DLBCL cells. Importantly, we found that Kpnβ1 could interact with p65 and promote CAM-DR via accelerating NF-κB activation in DLBCL. Patients with tumors highly expressing Kpnβ1 have poorer overall survivals. Kpnβ1 interacts with p65 and enhances CAM-DR.

  7. The regulatory BCL2 promoter polymorphism (-938C>A) is associated with relapse and survival of patients with oropharyngeal squamous cell carcinoma.

    PubMed

    Lehnerdt, G F; Franz, P; Bankfalvi, A; Grehl, S; Kelava, A; Nückel, H; Lang, S; Schmid, K W; Siffert, W; Bachmann, H S

    2009-06-01

    Expression of the antiapoptotic and antiproliferative protein B-cell lymphoma 2 (Bcl-2) has been repeatedly shown to be associated with better locoregional control and patients' survival in oropharyngeal squamous cell carcinoma (OSCC). A regulatory (-938C>A) single-nucleotide polymorphism (SNP) in the inhibitory P2 BCL2 gene promoter generates significantly different BCL2 promoter activities and has been associated with outcome in different malignancies. The aim of the present study was to analyze the possible influence of the (-938C>A) SNP on survival of patients suffering from OSCC. One hundred and thirty-three patients with primary OSCC were retrospectively investigated. Bcl-2 expression of tumor cells was demonstrated by means of immunohistochemistry. Both the Bcl-2 expression and the (-938C>A) genotypes were correlated with the patients' survival. The (-938C>A) SNP was significantly related to Bcl-2 expression (P = 0.008). Kaplan-Meier curves revealed a significant association of the -938 SNP with relapse-free (P = 0.0283) and overall survival (P = 0.0247). Multiple Cox regression identified the BCL2 (-938CC) genotype as an independent prognostic factor for relapse [hazard ratio (HR) 1.898, P = 0.021] as well as for death in OSCC patients (HR 1.897, P = 0.013). The (-938C>A) SNP represents a potential novel prognostic marker in patients with OSCC that could help to identify a group of patients at high risk for relapse and death.

  8. Do older people benefit from having a confidant? An Oklahoma Physicians Resource/Research Network (OKPRN) study.

    PubMed

    Lawler, Frank H; Mold, James W; McCarthy, Laine H

    2013-01-01

    The objective was to determine whether having a confidant was associated with improved health-related quality of life (HRQoL) or survival in older, community-dwelling individuals. This prospective cohort study included 23 family physician members of the Oklahoma Physicians Research/Resource Network in 9 practices and 852 community-dwelling adults 65 or older participating in the Oklahoma Longitudinal Assessment of Health Outcomes of Mature Adults Studies. Longitudinal models analyzed changes in self-administered Quality of Well-Being (QWB-SA) scores over an average (S.D.) of 2.51 (1.28) years. Cox proportional hazards models assessed variables possibly associated with mortality over an average survival time (+/-S.D.) of 9.22 (3.24) years. We controlled for chronic illnesses, baseline age, gender, marital status, income, race, BMI, education and specified Medical Outcomes Study Short Form-36 (SF-36) domain scores. Initially, 740 participants (87%) had a confidant. Being married was strongly associated with having a confidant (91.9% vs. 77.8%, p<0.0001). A confidant was associated with better SF-36 domain scores (p<0.0001), less morbidity, higher baseline QWB-SA scores and favorable changes in QWB-SA (p<0.0001). Unadjusted risk of death (37.8% vs 46.4%, p=0.08) was not lower. Kaplan-Meier confidant status survival curves were not statistically different (p=0.16). Older people with a confidant demonstrated enhanced HRQoL maintenance over the short term, but not greater survival.

  9. The prognostic value of a seven-microRNA classifier as a novel biomarker for the prediction and detection of recurrence in glioma patients.

    PubMed

    Chen, Wanghao; Yu, Qiang; Chen, Bo; Lu, Xingyu; Li, Qiaoyu

    2016-08-16

    Glioma is often diagnosed at a later stage, and the high risk of recurrence remains a major challenge. We hypothesized that the microRNA expression profile may serve as a biomarker for the prognosis and prediction of glioblastoma recurrence. We defined microRNAs that were associated with good and poor prognosis in 300 specimens of glioblastoma from the Cancer Genome Atlas. By analyzing microarray gene expression data and clinical information from three random groups, we identified 7 microRNAs that have prognostic and prognostic accuracy: microRNA-124a, microRNA-129, microRNA-139, microRNA-15b, microRNA-21, microRNA-218 and microRNA-7. The differential expression of these miRNAs was verified using an independent set of glioma samples from the Affiliated People's Hospital of Jiangsu University. We used the log-rank test and the Kaplan-Meier method to estimate correlations between the miRNA signature and disease-free survival/overall survival. Using the LASSO model, we observed a uniform significant difference in disease-free survival and overall survival between patients with high-risk and low-risk miRNA signature scores. Furthermore, the prognostic capability of the seven-miRNA signature was demonstrated by receiver operator characteristic curve analysis. A Circos plot was generated to examine the network of genes and pathways predicted to be targeted by the seven-miRNA signature. The seven-miRNA-based classifier should be useful in the stratification and individualized management of patients with glioma.

  10. The flaws in the detail of an observational study on transcatheter aortic valve implantation versus surgical aortic valve replacement in intermediate-risks patients.

    PubMed

    Barili, Fabio; Freemantle, Nick; Folliguet, Thierry; Muneretto, Claudio; De Bonis, Michele; Czerny, Martin; Obadia, Jean Francois; Al-Attar, Nawwar; Bonaros, Nikolaos; Kluin, Jolanda; Lorusso, Roberto; Punjabi, Prakash; Sadaba, Rafael; Suwalski, Piotr; Benedetto, Umberto; Böning, Andreas; Falk, Volkmar; Sousa-Uva, Miguel; Kappetein, Pieter A; Menicanti, Lorenzo

    2017-06-01

    The PARTNER group recently published a comparison between the latest generation SAPIEN 3 transcatheter aortic valve implantation (TAVI) system (Edwards Lifesciences, Irvine, CA, USA) and surgical aortic valve replacement (SAVR) in intermediate-risk patients, apparently demonstrating superiority of the TAVI and suggesting that TAVI might be the preferred treatment method in this risk class of patients. Nonetheless, assessment of the non-randomized methodology used in this comparison reveals challenges that should be addressed in order to elucidate the validity of the results. The study by Thourani and colleagues showed several major methodological concerns: suboptimal methods in propensity score analysis with evident misspecification of the propensity scores (PS; no adjustment for the most significantly different covariates: left ventricular ejection fraction, moderate-severe mitral regurgitation and associated procedures); use of PS quintiles rather than matching; inference on not-adjusted Kaplan-Meier curves, although the authors correctly claimed for the need of balancing score adjusting for confounding factors in order to have unbiased estimates of the treatment effect; evidence of poor fit; lack of data on valve-related death.These methodological flaws invalidate direct comparison between treatments and cannot support authors' conclusions that TAVI with SAPIEN 3 in intermediate-risk patients is superior to surgery and might be the preferred treatment alternative to surgery. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  11. Oxygen uptake efficiency slope and peak oxygen consumption predict prognosis in children with tetralogy of Fallot.

    PubMed

    Tsai, Yun-Jeng; Li, Min-Hui; Tsai, Wan-Jung; Tuan, Sheng-Hui; Liao, Tin-Yun; Lin, Ko-Long

    2016-07-01

    Oxygen uptake efficiency slope (OUES) and peak oxygen consumption (VO2peak) are exercise parameters that can predict cardiac morbidity in patients with numerous heart diseases. But the predictive value in patients with tetralogy of Fallot is still undetermined, especially in children. We evaluated the prognostic value of OUES and VO2peak in children with total repair of tetralogy of Fallot. Retrospective cohort study. Forty tetralogy of Fallot patients younger than 12 years old were recruited. They underwent a cardiopulmonary exercise test during the follow-up period after total repair surgery. The results of the cardiopulmonary exercise test were used to predict the cardiac related hospitalization in the following two years after the test. OUES normalized by body surface area (OUES/BSA) and the percentage of predicted VO2peak appeared to be predictive for two-year cardiac related hospitalization. Receiver operating characteristic curve analysis demonstrated that the best threshold value for OUES/BSA was 1.029 (area under the curve = 0.70, p = 0.03), and for VO2peak was 74% of age prediction (area under the curve = 0.72, p = 0.02). The aforementioned findings were confirmed by Kaplan-Meier plots and log-rank test. OUES/BSA and VO2peak are useful predictors of cardiac-related hospitalization in children with total repair of tetralogy of Fallot. © The European Society of Cardiology 2015.

  12. Decision curve analysis revisited: overall net benefit, relationships to ROC curve analysis, and application to case-control studies.

    PubMed

    Rousson, Valentin; Zumbrunn, Thomas

    2011-06-22

    Decision curve analysis has been introduced as a method to evaluate prediction models in terms of their clinical consequences if used for a binary classification of subjects into a group who should and into a group who should not be treated. The key concept for this type of evaluation is the "net benefit", a concept borrowed from utility theory. We recall the foundations of decision curve analysis and discuss some new aspects. First, we stress the formal distinction between the net benefit for the treated and for the untreated and define the concept of the "overall net benefit". Next, we revisit the important distinction between the concept of accuracy, as typically assessed using the Youden index and a receiver operating characteristic (ROC) analysis, and the concept of utility of a prediction model, as assessed using decision curve analysis. Finally, we provide an explicit implementation of decision curve analysis to be applied in the context of case-control studies. We show that the overall net benefit, which combines the net benefit for the treated and the untreated, is a natural alternative to the benefit achieved by a model, being invariant with respect to the coding of the outcome, and conveying a more comprehensive picture of the situation. Further, within the framework of decision curve analysis, we illustrate the important difference between the accuracy and the utility of a model, demonstrating how poor an accurate model may be in terms of its net benefit. Eventually, we expose that the application of decision curve analysis to case-control studies, where an accurate estimate of the true prevalence of a disease cannot be obtained from the data, is achieved with a few modifications to the original calculation procedure. We present several interrelated extensions to decision curve analysis that will both facilitate its interpretation and broaden its potential area of application.

  13. Metabolic disturbances identified in plasma are associated with outcomes in patients with heart failure: diagnostic and prognostic value of metabolomics.

    PubMed

    Cheng, Mei-Ling; Wang, Chao-Hung; Shiao, Ming-Shi; Liu, Min-Hui; Huang, Yu-Yen; Huang, Cheng-Yu; Mao, Chun-Tai; Lin, Jui-Fen; Ho, Hung-Yao; Yang, Ning-I

    2015-04-21

    Identification of novel biomarkers is needed to improve the diagnosis and prognosis of heart failure (HF). Metabolic disturbance is remarkable in patients with HF. This study sought to assess the diagnostic and prognostic values of metabolomics in HF. Mass spectrometry-based profiling of plasma metabolites was performed in 515 participants; the discovery phase study enrolled 51 normal control subjects and 183 HF patients, and the validation study enrolled 63 control subjects and 218 patients with stage C HF. Another independent group of 32 patients with stage C HF who recovered to New York Heart Association functional class I at 6 and 12 months was profiled as the "recovery" group. A panel of metabolites, including histidine, phenylalanine, spermidine, and phosphatidylcholine C34:4, has a diagnostic value similar to B-type natriuretic peptide (BNP). In the recovery group, the values of this panel significantly improved at 6 and 12 months. To evaluate the prognostic values, events were defined as the combined endpoints of death or HF-related re-hospitalization. A metabolite panel, which consisted of the asymmetric methylarginine/arginine ratio, butyrylcarnitine, spermidine, and the total amount of essential amino acids, provided significant prognostic values (p < 0.0001) independent of BNP and traditional risk factors. The prognostic value of the metabolite panel was better than that of BNP (area under the curve of 0.85 vs. 0.74 for BNP) and Kaplan-Meier curves (log rank: 17.5 vs. 9.95). These findings were corroborated in the validation study. Metabolomics demonstrate powerful diagnostic value in estimating HF-related metabolic disturbance. The profile of metabolites provides better prognostic value versus conventional biomarkers. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  14. Early Right Ventricular Assist Device Use in Patients Undergoing Continuous-Flow Left Ventricular Assist Device Implantation: Incidence and Risk Factors From the Interagency Registry for Mechanically Assisted Circulatory Support.

    PubMed

    Kiernan, Michael S; Grandin, E Wilson; Brinkley, Marshall; Kapur, Navin K; Pham, Duc Thinh; Ruthazer, Robin; Rame, J Eduardo; Atluri, Pavan; Birati, Edo Y; Oliveira, Guilherme H; Pagani, Francis D; Kirklin, James K; Naftel, David; Kormos, Robert L; Teuteberg, Jeffrey J; DeNofrio, David

    2017-10-01

    To investigate preimplant risk factors associated with early right ventricular assist device (RVAD) use in patients undergoing continuous-flow left ventricular assist device (LVAD) surgery. Patients in the Interagency Registry for Mechanically Assisted Circulatory Support who underwent primary continuous-flow-LVAD surgery were examined for concurrent or subsequent RVAD implantation within 14 days of LVAD. Risk factors for RVAD implantation and the combined end point of RVAD or death within 14 days of LVAD were assessed with stepwise logistic regression. We compared survival between patients with and without RVAD using Kaplan-Meier method and Cox proportional hazards modeling. Of 9976 patients undergoing continuous-flow-LVAD implantation, 386 patients (3.9%) required an RVAD within 14 days of LVAD surgery. Preimplant characteristics associated with RVAD use included interagency registry for mechanically assisted circulatory support patient profiles 1 and 2, the need for preoperative extracorporeal membrane oxygenation or renal replacement therapy, severe preimplant tricuspid regurgitation, history of cardiac surgery, and concomitant procedures other than tricuspid valve repair at the time of LVAD. Hemodynamic determinants included elevated right atrial pressure, reduced pulmonary artery pulse pressure, and reduced stroke volume. The final model demonstrated good performance for both RVAD implant (area under the curve, 0.78) and the combined end point of RVAD or death within 14 days (area under the curve, 0.73). Compared with patients receiving an isolated LVAD, patients requiring RVAD had decreased 1- and 6-month survival: 78.1% versus 95.8% and 63.6% versus 87.9%, respectively ( P <0.0001 for both). The need for RVAD implantation after LVAD is associated with indices of global illness severity, markers of end-organ dysfunction, and profiles of hemodynamic instability. © 2017 American Heart Association, Inc.

  15. Combinations of elevated tissue miRNA-17-92 cluster expression and serum prostate-specific antigen as potential diagnostic biomarkers for prostate cancer.

    PubMed

    Feng, Sujuan; Qian, Xiaosong; Li, Han; Zhang, Xiaodong

    2017-12-01

    The aim of the present study was to investigate the effectiveness of the miR-17-92 cluster as a disease progression marker in prostate cancer (PCa). Reverse transcription-quantitative polymerase chain reaction analysis was used to detect the microRNA (miR)-17-92 cluster expression levels in tissues from patients with PCa or benign prostatic hyperplasia (BPH), in addition to in PCa and BPH cell lines. Spearman correlation was used for comparison and estimation of correlations between miRNA expression levels and clinicopathological characteristics such as the Gleason score and prostate-specific antigen (PSA). Receiver operating curve (ROC) analysis was performed for evaluation of specificity and sensitivity of miR-17-92 cluster expression levels for discriminating patients with PCa from patients with BPH. Kaplan-Meier analysis was plotted to investigate the predictive potential of miR-17-92 cluster for PCa biochemical recurrence. Expression of the majority of miRNAs in the miR-17-92 cluster was identified to be significantly increased in PCa tissues and cell lines. Bivariate correlation analysis indicated that the high expression of unregulated miRNAs was positively correlated with Gleason grade, but had no significant association with PSA. ROC curves demonstrated that high expression of miR-17-92 cluster predicted a higher diagnostic accuracy compared with PSA. Improved discriminating quotients were observed when combinations of unregulated miRNAs with PSA were used. Survival analysis confirmed a high combined miRNA score of miR-17-92 cluster was associated with shorter biochemical recurrence interval. miR-17-92 cluster could be a potential diagnostic and prognostic biomarker for PCa, and the combination of the miR-17-92 cluster and serum PSA may enhance the accuracy for diagnosis of PCa.

  16. Metabolic tumour volume and total lesion glycolysis, measured using preoperative 18F-FDG PET/CT, predict the recurrence of endometrial cancer.

    PubMed

    Shim, S-H; Kim, D-Y; Lee, D-Y; Lee, S-W; Park, J-Y; Lee, J J; Kim, J-H; Kim, Y-M; Kim, Y-T; Nam, J-H

    2014-08-01

    To investigate the prognostic value of metabolic tumour volume (MTV) and total lesion glycolysis (TLG), measured by preoperative positron emission tomography and computerised tomography (PET/CT), in women with endometrial cancer. Retrospective cohort study. A tertiary referral centre. Women with endometrial cancer who underwent preoperative (18)F-FDG PET/CT in the period 2004-2009. Clinicopathological data for 84 women with endometrial cancer were reviewed from medical records. Cox proportional hazards modelling identified recurrence predictors. The receiver operating characteristic (ROC) curve was used to determine the cut-off value for predicting recurrence. Disease-free survival (DFS). The number of patients with International Federation of Gynecology and Obstetrics (FIGO) stages were: I (58); II (11); III (13); and IV (2). The median DFS was 48 (1-85) months. By univariate analysis, DFS was significantly associated with FIGO stage, histology, peritoneal cytology, myometrial invasion, nodal metastasis, serum CA-125, MTV, and TLG. Using multivariate analysis, the MTV (P = 0.010; hazard ratio, HR = 1.010; 95% confidence interval, 95% CI = 1.002-1.018) and TLG (P = 0.024; HR = 1.001; 95% CI = 1.000-1.002) were associated with DFS. The area under the ROC curve was 0.679 (95% CI = 0.505-0.836) after discriminating for recurrence using an MTV cut-off value of 17.15 ml. Regarding TLG, the cut-off value was 56.43 g and the area under the ROC plot was 0.661 (95% CI = 0.501-0.827). Kaplan-Meier survival graphs demonstrated a significant difference in DFS between groups categorised using the cut-off values for MTV and TLG (P < 0.022 for MTV and P < 0.047 for TLG, by log-rank test). Preoperative MTV and TLG could be independent prognostic factors predicting the recurrence of endometrial cancer. © 2014 Royal College of Obstetricians and Gynaecologists.

  17. Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy.

    PubMed

    Sales-Marques, Carolinne; Cardoso, Cynthia Chester; Alvarado-Arnez, Lucia Elena; Illaramendi, Ximena; Sales, Anna Maria; Hacker, Mariana de Andréa; Barbosa, Mayara Garcia de Mattos; Nery, José Augusto da Costa; Pinheiro, Roberta Olmo; Sarno, Euzenir Nunes; Pacheco, Antonio Guilherme; Moraes, Milton Ozório

    2017-07-01

    The pathways that trigger exacerbated immune reactions in leprosy could be determined by genetic variations. Here, in a prospective approach, both genetic and non-genetic variables influencing the amount of time before the development of reactional episodes were studied using Kaplan-Meier survival curves, and the genetic effect was estimated by the Cox proportional-hazards regression model. In a sample including 447 leprosy patients, we confirmed that gender (male), and high bacillary clinical forms are risk factors for leprosy reactions. From the 15 single nucleotide polymorphisms (SNPs) at the 8 candidate genes genotyped (TNF/LTA, IFNG, IL10, TLR1, NOD2, SOD2, and IL6) we observed statistically different survival curves for rs751271 at the NOD2 and rs2069845 at the IL6 genes (log-rank p-values = 0.002 and 0.023, respectively), suggesting an influence on the amount of time before developing leprosy reactions. Cox models showed associations between the SNPs rs751271 at NOD2 and rs2069845 at IL6 with leprosy reactions (HRGT = 0.45, p = 0.002; HRAG = 1.88, p = 0.0008, respectively). Finally, IL-6 and IFN-γ levels were confirmed as high, while IL-10 titers were low in the sera of reactional patients. Rs751271-GT genotype-bearing individuals correlated (p = 0.05) with lower levels of IL-6 in sera samples, corroborating the genetic results. Although the experimental size may be considered a limitation of the study, the findings confirm the association of classical variables such as sex and clinical forms with leprosy, demonstrating the consistency of the results. From the results, we conclude that SNPs at the NOD2 and IL6 genes are associated with leprosy reactions as an outcome. NOD2 also has a clear functional pro-inflammatory link that is coherent with the exacerbated responses observed in these patients.

  18. Propagating Cell-Membrane Waves Driven by Curved Activators of Actin Polymerization

    PubMed Central

    Peleg, Barak; Disanza, Andrea; Scita, Giorgio; Gov, Nir

    2011-01-01

    Cells exhibit propagating membrane waves which involve the actin cytoskeleton. One type of such membranal waves are Circular Dorsal Ruffles (CDR) which are related to endocytosis and receptor internalization. Experimentally, CDRs have been associated with membrane bound activators of actin polymerization of concave shape. We present experimental evidence for the localization of convex membrane proteins in these structures, and their insensitivity to inhibition of myosin II contractility in immortalized mouse embryo fibroblasts cell cultures. These observations lead us to propose a theoretical model which explains the formation of these waves due to the interplay between complexes that contain activators of actin polymerization and membrane-bound curved proteins of both types of curvature (concave and convex). Our model predicts that the activity of both types of curved proteins is essential for sustaining propagating waves, which are abolished when one type of curved activator is removed. Within this model waves are initiated when the level of actin polymerization induced by the curved activators is higher than some threshold value, which allows the cell to control CDR formation. We demonstrate that the model can explain many features of CDRs, and give several testable predictions. This work demonstrates the importance of curved membrane proteins in organizing the actin cytoskeleton and cell shape. PMID:21533032

  19. Long-term prognosis in patients continuing taking antithrombotics after peptic ulcer bleeding.

    PubMed

    Wang, Xi-Xu; Dong, Bo; Hong, Biao; Gong, Yi-Qun; Wang, Wei; Wang, Jue; Zhou, Zhen-Yu; Jiang, Wei-Jun

    2017-01-28

    To investigate the long-term prognosis in peptic ulcer patients continuing taking antithrombotics after ulcer bleeding, and to determine the risk factors that influence the prognosis. All clinical data of peptic ulcer patients treated from January 1, 2009 to January 1, 2014 were retrospectively collected and analyzed. Patients were divided into either a continuing group to continue taking antithrombotic drugs after ulcer bleeding or a discontinuing group to discontinue antithrombotic drugs. The primary outcome of follow-up in peptic ulcer bleeding patients was recurrent bleeding, and secondary outcome was death or acute cardiovascular disease occurrence. The final date of follow-up was December 31, 2014. Basic demographic data, complications, and disease classifications were analyzed and compared by t - or χ 2 -test. The number of patients that achieved various outcomes was counted and analyzed statistically. A survival curve was drawn using the Kaplan-Meier method, and the difference was compared using the log-rank test. COX regression multivariate analysis was applied to analyze risk factors for the prognosis of peptic ulcer patients. A total of 167 patients were enrolled into this study. As for the baseline information, differences in age, smoking, alcohol abuse, and acute cardiovascular diseases were statistically significant between the continuing and discontinuing groups (70.8 ± 11.4 vs 62.4 ± 12.0, P < 0.001; 8 (8.2%) vs 15 (21.7%), P < 0.05; 65 (66.3%) vs 13 (18.8%), P < 0.001). At the end of the study, 18 patients had recurrent bleeding and three patients died or had acute cardiovascular disease in the continuing group, while four patients had recurrent bleeding and 15 patients died or had acute cardiovascular disease in the discontinuing group. The differences in these results were statistically significant ( P = 0.022, P = 0.000). The Kaplan-Meier survival curve indicated that the incidence of recurrent bleeding was higher in patients in the

  20. Age at diagnosis and prognosis of oral cancer in relation to the patient's residential area: experience from a medical center in Taiwan.

    PubMed

    Su, Che-Chun; Chung, Jian-An; Hsu, Yun-Ying; Huang, Su-Ju; Lian, Ie-Bin

    2008-11-01

    Smoking and betel quid chewing are established risk factors for oral cancer in Taiwan. The prevalence of these risk factors in the central county of Changhua falls within the middle range nationally, yet the county has the highest incidence of oral cancer in Taiwan. The purpose of this study, therefore, was to identify if patients' ages and prognoses at diagnosis were related to their place of residence and, if so, to explore environmental and geographical factors which might explain local variance in the incidence of oral cancers within Changhua and their prevalence in the county as a whole. The paper contains results from a retrospective review of medical records for patients diagnosed with oral cancer in Changhua County who were treated at the Changhua Christian Hospital (CCH) between 1994 and 2005. The Wilcoxon signed rank test, ANOVA, t-test, Kaplan-Meier curve and log-rank tests were carried out to examine the association between patients' places of residence, their ages at diagnosis, and their overall prognoses. A total of 1363 oral cancer cases were diagnosed in the study period. These consisted of 1272 males and 91 females. A steady increase in the number of patients diagnosed with oral cancer annually was noted. The tongue and buccal mucosa were the two most frequently affected sites constituting 56% of cases, while squamous cell carcinoma was diagnosed in nearly 80% of the study population. The mean ages at diagnosis were 53.1 and 52.8 years for patients living in the northern and central areas of Changhua, and 55.1 years for those living in the south. Patients living in the northern and central areas of Changhua had poorer long-term prognoses as indicated by Kaplan-Meier survival curves and the log-rank test, and it appears that differences in the level, type and distribution of industry in these areas distinguish these patients from those living in the south of the county. In particular, the density of electroplating factories in northern and central

  1. Survival analysis using inverse probability of treatment weighted methods based on the generalized propensity score.

    PubMed

    Sugihara, Masahiro

    2010-01-01

    In survival analysis, treatment effects are commonly evaluated based on survival curves and hazard ratios as causal treatment effects. In observational studies, these estimates may be biased due to confounding factors. The inverse probability of treatment weighted (IPTW) method based on the propensity score is one of the approaches utilized to adjust for confounding factors between binary treatment groups. As a generalization of this methodology, we developed an exact formula for an IPTW log-rank test based on the generalized propensity score for survival data. This makes it possible to compare the group differences of IPTW Kaplan-Meier estimators of survival curves using an IPTW log-rank test for multi-valued treatments. As causal treatment effects, the hazard ratio can be estimated using the IPTW approach. If the treatments correspond to ordered levels of a treatment, the proposed method can be easily extended to the analysis of treatment effect patterns with contrast statistics. In this paper, the proposed method is illustrated with data from the Kyushu Lipid Intervention Study (KLIS), which investigated the primary preventive effects of pravastatin on coronary heart disease (CHD). The results of the proposed method suggested that pravastatin treatment reduces the risk of CHD and that compliance to pravastatin treatment is important for the prevention of CHD. (c) 2009 John Wiley & Sons, Ltd.

  2. In vitro culture increases mechanical stability of human tissue engineered cartilage constructs by prevention of microscale scaffold buckling.

    PubMed

    Middendorf, Jill M; Shortkroff, Sonya; Dugopolski, Caroline; Kennedy, Stephen; Siemiatkoski, Joseph; Bartell, Lena R; Cohen, Itai; Bonassar, Lawrence J

    2017-11-07

    Many studies have measured the global compressive properties of tissue engineered (TE) cartilage grown on porous scaffolds. Such scaffolds are known to exhibit strain softening due to local buckling under loading. As matrix is deposited onto these scaffolds, the global compressive properties increase. However the relationship between the amount and distribution of matrix in the scaffold and local buckling is unknown. To address this knowledge gap, we studied how local strain and construct buckling in human TE constructs changes over culture times and GAG content. Confocal elastography techniques and digital image correlation (DIC) were used to measure and record buckling modes and local strains. Receiver operating characteristic (ROC) curves were used to quantify construct buckling. The results from the ROC analysis were placed into Kaplan-Meier survival function curves to establish the probability that any point in a construct buckled. These analysis techniques revealed the presence of buckling at early time points, but bending at later time points. An inverse correlation was observed between the probability of buckling and the total GAG content of each construct. This data suggests that increased GAG content prevents the onset of construct buckling and improves the microscale compressive tissue properties. This increase in GAG deposition leads to enhanced global compressive properties by prevention of microscale buckling. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. PARP-1 serves as a novel molecular marker for hepatocellular carcinoma in a Southern Chinese Zhuang population.

    PubMed

    Li, Jiatong; Dou, Dongwei; Li, Ping; Luo, Wenqi; Lv, Wenxin; Zhang, Chengdong; Song, Xiaowei; Yang, Yuan; Zhang, Yuening; Xu, Yanzhen; Xiao, Feifan; Wei, Yan; Qin, Jian; Li, Hongtao; Yang, Xiaoli

    2017-07-01

    PARP-1 (poly(ADP-ribose) polymerase-1) plays an important role in tumorigenesis. Since its effects on different populations are varied, this study investigated the impact of PARP-1 on primary hepatocellular carcinoma in a Southern Chinese Zhuang population. We assessed the global PARP-1 messenger RNA expression in patients with hepatocellular carcinoma using The Cancer Genome Atlas dataset. Increased PARP-1 expression, related to alpha-fetoprotein level, was observed. The area under the receiver operating characteristic curve value was 0.833. Kaplan-Meier survival curves indicated that higher PARP-1 expression was not correlated with poorer overall survival and recurrence-free survival. In a Zhuang population, PARP-1 messenger RNA and protein levels were increased in the hepatocellular carcinoma tissue and its adjacent liver tissues as assessed by quantitative polymerase chain reaction, immunohistochemistry, and western blotting. Higher PARP-1 level was associated with a higher tumor stage (p < 0.05), without correlation with age, gender, smoking, drinking, tumor size, serum alpha-fetoprotein level, hepatitis B virus infection, metastasis, and invasion (p > 0.05). Further analysis suggested that H2AX, a PARP-1 protein interaction partner, was coordinated with PARP-1 in hepatocellular carcinoma tumorigenesis. Overall, some new characteristics of PARP-1 expression were noted in the Zhuang population. PARP-1 is a novel promising diagnostic marker for hepatocellular carcinoma in the Southern Chinese Zhuang population.

  4. Albumin-Bilirubin and Platelet-Albumin-Bilirubin Grades Accurately Predict Overall Survival in High-Risk Patients Undergoing Conventional Transarterial Chemoembolization for Hepatocellular Carcinoma.

    PubMed

    Hansmann, Jan; Evers, Maximilian J; Bui, James T; Lokken, R Peter; Lipnik, Andrew J; Gaba, Ron C; Ray, Charles E

    2017-09-01

    To evaluate albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (PALBI) grades in predicting overall survival in high-risk patients undergoing conventional transarterial chemoembolization for hepatocellular carcinoma (HCC). This single-center retrospective study included 180 high-risk patients (142 men, 59 y ± 9) between April 2007 and January 2015. Patients were considered high-risk based on laboratory abnormalities before the procedure (bilirubin > 2.0 mg/dL, albumin < 3.5 mg/dL, platelet count < 60,000/mL, creatinine > 1.2 mg/dL); presence of ascites, encephalopathy, portal vein thrombus, or transjugular intrahepatic portosystemic shunt; or Model for End-Stage Liver Disease score > 15. Serum albumin, bilirubin, and platelet values were used to determine ALBI and PALBI grades. Overall survival was stratified by ALBI and PALBI grades with substratification by Child-Pugh class (CPC) and Barcelona Liver Clinic Cancer (BCLC) stage using Kaplan-Meier analysis. C-index was used to determine discriminatory ability and survival prediction accuracy. Median survival for 79 ALBI grade 2 patients and 101 ALBI grade 3 patients was 20.3 and 10.7 months, respectively (P < .0001). Median survival for 30 PALBI grade 2 and 144 PALBI grade 3 patients was 20.3 and 12.9 months, respectively (P = .0667). Substratification yielded distinct ALBI grade survival curves for CPC B (P = .0022, C-index 0.892), BCLC A (P = .0308, C-index 0.887), and BCLC C (P = .0287, C-index 0.839). PALBI grade demonstrated distinct survival curves for BCLC A (P = 0.0229, C-index 0.869). CPC yielded distinct survival curves for the entire cohort (P = .0019) but not when substratified by BCLC stage (all P > .05). ALBI and PALBI grades are accurate survival metrics in high-risk patients undergoing conventional transarterial chemoembolization for HCC. Use of these scores allows for more refined survival stratification within CPC and BCLC stage. Copyright © 2017 SIR. Published by Elsevier Inc. All

  5. Establishment and Validation of GV-SAPS II Scoring System for Non-Diabetic Critically Ill Patients

    PubMed Central

    Liu, Wen-Yue; Lin, Shi-Gang; Zhu, Gui-Qi; Poucke, Sven Van; Braddock, Martin; Zhang, Zhongheng; Mao, Zhi; Shen, Fei-Xia

    2016-01-01

    Background and Aims Recently, glucose variability (GV) has been reported as an independent risk factor for mortality in non-diabetic critically ill patients. However, GV is not incorporated in any severity scoring system for critically ill patients currently. The aim of this study was to establish and validate a modified Simplified Acute Physiology Score II scoring system (SAPS II), integrated with GV parameters and named GV-SAPS II, specifically for non-diabetic critically ill patients to predict short-term and long-term mortality. Methods Training and validation cohorts were exacted from the Multiparameter Intelligent Monitoring in Intensive Care database III version 1.3 (MIMIC-III v1.3). The GV-SAPS II score was constructed by Cox proportional hazard regression analysis and compared with the original SAPS II, Sepsis-related Organ Failure Assessment Score (SOFA) and Elixhauser scoring systems using area under the curve of the receiver operator characteristic (auROC) curve. Results 4,895 and 5,048 eligible individuals were included in the training and validation cohorts, respectively. The GV-SAPS II score was established with four independent risk factors, including hyperglycemia, hypoglycemia, standard deviation of blood glucose levels (GluSD), and SAPS II score. In the validation cohort, the auROC values of the new scoring system were 0.824 (95% CI: 0.813–0.834, P< 0.001) and 0.738 (95% CI: 0.725–0.750, P< 0.001), respectively for 30 days and 9 months, which were significantly higher than other models used in our study (all P < 0.001). Moreover, Kaplan-Meier plots demonstrated significantly worse outcomes in higher GV-SAPS II score groups both for 30-day and 9-month mortality endpoints (all P< 0.001). Conclusions We established and validated a modified prognostic scoring system that integrated glucose variability for non-diabetic critically ill patients, named GV-SAPS II. It demonstrated a superior prognostic capability and may be an optimal scoring system

  6. Establishment and Validation of GV-SAPS II Scoring System for Non-Diabetic Critically Ill Patients.

    PubMed

    Liu, Wen-Yue; Lin, Shi-Gang; Zhu, Gui-Qi; Poucke, Sven Van; Braddock, Martin; Zhang, Zhongheng; Mao, Zhi; Shen, Fei-Xia; Zheng, Ming-Hua

    2016-01-01

    Recently, glucose variability (GV) has been reported as an independent risk factor for mortality in non-diabetic critically ill patients. However, GV is not incorporated in any severity scoring system for critically ill patients currently. The aim of this study was to establish and validate a modified Simplified Acute Physiology Score II scoring system (SAPS II), integrated with GV parameters and named GV-SAPS II, specifically for non-diabetic critically ill patients to predict short-term and long-term mortality. Training and validation cohorts were exacted from the Multiparameter Intelligent Monitoring in Intensive Care database III version 1.3 (MIMIC-III v1.3). The GV-SAPS II score was constructed by Cox proportional hazard regression analysis and compared with the original SAPS II, Sepsis-related Organ Failure Assessment Score (SOFA) and Elixhauser scoring systems using area under the curve of the receiver operator characteristic (auROC) curve. 4,895 and 5,048 eligible individuals were included in the training and validation cohorts, respectively. The GV-SAPS II score was established with four independent risk factors, including hyperglycemia, hypoglycemia, standard deviation of blood glucose levels (GluSD), and SAPS II score. In the validation cohort, the auROC values of the new scoring system were 0.824 (95% CI: 0.813-0.834, P< 0.001) and 0.738 (95% CI: 0.725-0.750, P< 0.001), respectively for 30 days and 9 months, which were significantly higher than other models used in our study (all P < 0.001). Moreover, Kaplan-Meier plots demonstrated significantly worse outcomes in higher GV-SAPS II score groups both for 30-day and 9-month mortality endpoints (all P< 0.001). We established and validated a modified prognostic scoring system that integrated glucose variability for non-diabetic critically ill patients, named GV-SAPS II. It demonstrated a superior prognostic capability and may be an optimal scoring system for prognostic evaluation in this patient group.

  7. Influence of Media on Seasonal Influenza Epidemic Curves.

    PubMed

    Saito, Satoshi; Saito, Norihiro; Itoga, Masamichi; Ozaki, Hiromi; Kimura, Toshiyuki; Okamura, Yuji; Murakami, Hiroshi; Kayaba, Hiroyuki

    2016-09-01

    Theoretical investigations predicting the epidemic curves of seasonal influenza have been demonstrated so far; however, there is little empirical research using ever accumulated epidemic curves. The effects of vaccine coverage and information distribution on influenza epidemics were evaluated. Four indices for epidemics (i.e., onset-peak duration, onset-end duration, ratio of the onset-peak duration to onset-end duration and steepness of epidemic curves) were defined, and the correlations between these indices and anti-flu drug prescription dose, vaccine coverage, the volume of media and search trend on influenza through internet were analyzed. Epidemiological data on seasonal influenza epidemics from 2002/2003 to 2013/2014 excluding 2009/2010 season were collected from National Institute of Infectious Diseases of Japan. The onset-peak duration and its ratio to onset-end duration correlated inversely with the volume of anti-flu drug prescription. Onset-peak duration correlated positively with media information volume on influenza. The steepness of the epidemic curve, and anti-flu drug prescription dose inversely correlated with the volume of media information. Pre-epidemic search trend and media volume on influenza correlated with the vaccine coverage in the season. Vaccine coverage had no strong effect on epidemic curve. Education through media has an effect on the epidemic curve of seasonal influenza. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  8. Movement Distribution: A New Measure of Sleep Fragmentation in Children with Upper Airway Obstruction

    PubMed Central

    Coussens, Scott; Baumert, Mathias; Kohler, Mark; Martin, James; Kennedy, Declan; Lushington, Kurt; Saint, David; Pamula, Yvonne

    2014-01-01

    Study Objectives: To develop a measure of sleep fragmentation in children with upper airway obstruction based on survival curve analysis of sleep continuity. Design: Prospective repeated measures. Setting: Hospital sleep laboratory. Participants: 92 children aged 3.0 to 12.9 years undergoing 2 overnight polysomnographic (PSG) sleep studies, 6 months apart. Subjects were divided into 3 groups based on their obstructive apnea and hypopnea index (OAHI) and other upper airway obstruction (UAO) symptoms: primary snorers (PS; n = 24, OAHI < 1), those with obstructive sleep apnea syndrome (OSAS; n = 20, OAHI ≥ 1) and non-snoring controls (C; n = 48, OAHI < 1). Interventions: Subjects in the PS and OSAS groups underwent tonsillectomy and adenoidectomy between PSG assessments. Measurements and Results: Post hoc measures of movement and contiguous sleep epochs were exported and analyzed using Kaplan-Meier estimates of survival to generate survival curves for the 3 groups. Statistically significant differences were found between these group curves for sleep continuity (P < 0.05) when using movement events as the sleep fragmenting event, but not if stage 1 NREM sleep or awakenings were used. Conclusion: Using conventional indices of sleep fragmentation in survival curve analysis of sleep continuity does not provide a useful measure of sleep fragmentation in children with upper airway obstruction. However, when sleep continuity is defined as the time between gross body movements, a potentially useful clinical measure is produced. Citation: Coussens S, Baumert M, Kohler M, Martin J, Kennedy D, Lushington K, Saint D, Pamula Y. Movement distribution: a new measure of sleep fragmentation in children with upper airway obstruction. SLEEP 2014;37(12):2025-2034. PMID:25325486

  9. A Note on Comparing the Elasticities of Demand Curves.

    ERIC Educational Resources Information Center

    Nieswiadomy, Michael

    1986-01-01

    Demonstrates a simple and useful way to compare the elasticity of demand at each price (or quantity) for different demand curves. The technique is particularly useful for the intermediate microeconomic course. (Author)

  10. Area under precision-recall curves for weighted and unweighted data.

    PubMed

    Keilwagen, Jens; Grosse, Ivo; Grau, Jan

    2014-01-01

    Precision-recall curves are highly informative about the performance of binary classifiers, and the area under these curves is a popular scalar performance measure for comparing different classifiers. However, for many applications class labels are not provided with absolute certainty, but with some degree of confidence, often reflected by weights or soft labels assigned to data points. Computing the area under the precision-recall curve requires interpolating between adjacent supporting points, but previous interpolation schemes are not directly applicable to weighted data. Hence, even in cases where weights were available, they had to be neglected for assessing classifiers using precision-recall curves. Here, we propose an interpolation for precision-recall curves that can also be used for weighted data, and we derive conditions for classification scores yielding the maximum and minimum area under the precision-recall curve. We investigate accordances and differences of the proposed interpolation and previous ones, and we demonstrate that taking into account existing weights of test data is important for the comparison of classifiers.

  11. Area under Precision-Recall Curves for Weighted and Unweighted Data

    PubMed Central

    Grosse, Ivo

    2014-01-01

    Precision-recall curves are highly informative about the performance of binary classifiers, and the area under these curves is a popular scalar performance measure for comparing different classifiers. However, for many applications class labels are not provided with absolute certainty, but with some degree of confidence, often reflected by weights or soft labels assigned to data points. Computing the area under the precision-recall curve requires interpolating between adjacent supporting points, but previous interpolation schemes are not directly applicable to weighted data. Hence, even in cases where weights were available, they had to be neglected for assessing classifiers using precision-recall curves. Here, we propose an interpolation for precision-recall curves that can also be used for weighted data, and we derive conditions for classification scores yielding the maximum and minimum area under the precision-recall curve. We investigate accordances and differences of the proposed interpolation and previous ones, and we demonstrate that taking into account existing weights of test data is important for the comparison of classifiers. PMID:24651729

  12. Comparison of transmission dynamics between Streptococcus uberis and Streptococcus agalactiae intramammary infections.

    PubMed

    Leelahapongsathon, Kansuda; Schukken, Ynte Hein; Pinyopummintr, Tanu; Suriyasathaporn, Witaya

    2016-02-01

    The objectives of study were to determine the transmission parameters (β), durations of infection, and basic reproductive numbers (R0) of both Streptococcus agalactiae and Streptococcus uberis as pathogens causing mastitis outbreaks in dairy herds. A 10-mo longitudinal study was performed using 2 smallholder dairy herds with mastitis outbreaks caused by Strep. agalactiae and Strep. uberis, respectively. Both herds had poor mastitis control management and did not change their milking management during the entire study period. Quarter milk samples were collected at monthly intervals from all lactating animals in each herd for bacteriological identification. The durations of infection for Strep. uberis intramammary infection (IMI) and Strep. agalactiae IMI were examined using Kaplan-Meier survival curves, and the Kaplan-Meier survival functions for Strep. uberis IMI and Strep. agalactiae IMI were compared using log rank survival-test. The spread of Strep. uberis and Strep. agalactiae through the population was determined by transmission parameter, β, the probability per unit of time that one infectious quarter will infect another quarter, assuming that all other quarters are susceptible. For the Strep. uberis outbreak herd (31 cows), 56 new infections and 28 quarters with spontaneous cure were observed. For the Strep. agalactiae outbreak herd (19 cows), 26 new infections and 9 quarters with spontaneous cure were observed. The duration of infection for Strep. agalactiae (mean=270.84 d) was significantly longer than the duration of infection for Strep. uberis (mean=187.88 d). The transmission parameters (β) estimated (including 95% confidence interval) for Strep. uberis IMI and Strep. agalactiae IMI were 0.0155 (0.0035-0.0693) and 0.0068 (0.0008-0.0606), respectively. The R0 (including 95% confidence interval) during the study were 2.91 (0.63-13.47) and 1.86 (0.21-16.61) for Strep. uberis IMI and Strep. agalactiae IMI, respectively. In conclusion, the transmission

  13. Repair of Kaplan turbine shaft sealing based on evaluation of hydraulic conditions

    NASA Astrophysics Data System (ADS)

    Lakatos, K.; Szamosi, Z.; Bereczkei, S.

    2012-11-01

    This paper has been written to call attention to a potential danger what may occur in Kaplan turbine refurbishments. In Tiszalök hydropower plant, Hungary, the shaft sealing of the refurbished turbine was damaged. In searching for the reasons it was assumed that due to increased internal velocities in the turbine, the pressure at the hub clearance became lower than the atmospheric pressure, and therefore the sealing, which always operated satisfactorily before the refurbishment, had uncertain water supply, dry-running occurred, and after some time the sealing was burnt. First the flow conditions in the turbine and the pressure at the hub clearance were calculated by a one-dimensional flow model. Later this was refined by a two-dimensional approach. The above conclusion was also justified by the data acquisition system and by observing the operation of the small dewatering pump. When the turbine operated at a larger discharge than a certain limit value, then the dewatering pump remained standstill, indicating that no water passed through the shaft sealing. External water supply was then applied, and after this the turbine operated all right.

  14. Overexpression of Pofut1 and activated Notch1 may be associated with poor prognosis in breast cancer.

    PubMed

    Wan, Guoxing; Tian, Lin; Yu, Yuandong; Li, Fang; Wang, Xuanbin; Li, Chen; Deng, Shouheng; Yu, Xiongjie; Cai, Xiaojun; Zuo, Zhigang; Cao, Fengjun

    2017-09-09

    The present study was to evaluate the prognostic value of protein expression of Pofut1 and Notch1 signaling in breast cancer. Formalin-fixed paraffin-embedded 314 breast specimens including 174 infiltrating ductal carcinoma(IDC), 50 ductal carcinoma in situ(DCIS) and 90 adjacent normal tissue(ANT) were immunohistochemically examined to evaluate the protein expression of Pofut1, activated Notch1(N1IC) and Slug on specimens. Survival analysis was performed by Kaplan-Meier method and Cox's proportional-hazards model. A online database was computationally used to further explore the prognostic role of Pofut1 and Notch1 mRNA expression by Kaplan-Meier Plotter. Pofut1, Slug and N1IC expression were significantly increased in IDC compared to ANT(all p < 0.05). High expression of Pofut1, Slug and N1IC were associated with tumor aggressiveness including lymph node metastasis (LNM: p = 0.005 for Pofut1, p < 0.001 for N1IC, p = 0.017 for Slug), advanced stage(p = 0.039 for Pofut1, p = 0.025 for N1IC) and higher histological grade(p = 0.001 for N1IC). Additionally, high expression of Pofut1 was found to be significantly associated with high expressions of N1IC and Slug in IDC(r = 0.244, p = 0.001; r = 0.374, p < 0.001, respectively), similar correlation was also observed between high N1IC and Slug expression(r = 0.496, p < 0.001). Moreover, Kaplan-Meier and Cox's regression analysis indicated the significant prognostic value of elevated Pofut1, N1IC, Slug expressions, positive LNM and advanced tumor stage for the prediction of a shorter disease-free survival (DFS) and overall survival(OS). The web-based analysis also suggested a significant association of high Pofut1 and Notch1 mRNA expression with worse survival outcome. Our findings suggested that overexpression of Pofut1 and activated Notch1 signaling may be associated with a poor prognosis in breast cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. The Short-Term and Intermediate-Term Risk of Second Neoplasms After Diagnosis and Treatment of Unilateral Vestibular Schwannoma: Analysis of 9460 Cases

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Carlson, Matthew L., E-mail: carlson.matthew@mayo.edu; Department of Neurologic Surgery, Mayo Clinic School of Medicine, Rochester, Minnesota; Glasgow, Amy E.

    Purpose: To determine the incidence of second intracranial neoplasms after the diagnosis and treatment of sporadic vestibular schwannoma (VS). Methods and Materials: Analysis of the Surveillance, Epidemiology, and End Results (SEER) database including all patients identified with a diagnosis of VS and a second intracranial tumor. The Kaplan-Meier method was used to determine the incidence of second tumors while allowing for censoring at loss to follow-up or death. Multivariable associations between treatment modality and second tumor formation were explored using Cox proportional hazards regression analysis. Two illustrative cases are also presented. Results: In all, 9460 patients with unilateral VS weremore » identified between 2004 and 2012. Overall, 66 (0.7%) patients experienced a separate intracranial tumor, benign or malignant, after treatment of VS. Kaplan-Meier estimates for time to second neoplasm at 1, 3, and 5 years were 0.3%, 0.7%, and 0.8%, respectively. Multivariable comparison between VS treatment modalities revealed that the risk of second tumor formation was similar between radiation and surgery (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.36-1.51; P=.93) but greater for tumors managed with observation alone compared with radiation (HR 2.48; 95% CI 1.31-4.71; P<.01). A total of 6 (0.06%) intracranial malignancies were diagnosed after VS treatment. Kaplan-Meier estimates for time to malignancy at 1, 3, and 5 years were 0%, 0.1%, and 0.1%, respectively. After adjustment for age at diagnosis, sex, and treatment modality, the probability of malignancy after radiation was not greater than after observation alone or microsurgery (HR 4.88; 95% CI 0.85-28.14; P=.08) during the study period. Conclusions: The risk for the development of a second intracranial neoplasm, benign or malignant, at 5 years after treatment of unilateral VS is approximately 0.8%, whereas the risk of acquiring a separate malignancy is 0.1%, or approximately 1 per 1000

  16. The Impact of Polymorphic Variations in the 5p15, 6p12, 6p21 and 15q25 Loci on the Risk and Prognosis of Portuguese Patients with Non-Small Cell Lung Cancer

    PubMed Central

    de Mello, Ramon Andrade; Ferreira, Mónica; Soares-Pires, Filipa; Costa, Sandra; Cunha, João; Oliveira, Pedro; Hespanhol, Venceslau; Reis, Rui Manuel

    2013-01-01

    Introduction Polymorphic variants in the 5p15, 6p12, 6p21, and 15q25 loci were demonstrated to potentially contribute to lung cancer carcinogenesis. Therefore, this study was performed to assess the role of those variants in non-small cell lung cancer (NSCLC) risk and prognosis in a Portuguese population. Materials and Methods Blood from patients with NSCLC was prospectively collected. To perform an association study, DNA from these patients and healthy controls were genotyped for a panel of 19 SNPs using a Sequenom® MassARRAY platform. Kaplan-Meier curves were used to assess the overall survival (OS) and progression-free survival (PFS). Results One hundred and forty-four patients with NSCLC were successfully consecutively genotyped for the 19 SNPs. One SNP was associated with NSCLC risk: rs9295740 G/A. Two SNPs were associated with non-squamous histology: rs3024994 (VEGF intron 2) T/C and rs401681 C/T. Three SNPs were associated with response rate: rs3025035 (VEGF intron 7) C/T, rs833061 (VEGF –460) C/T and rs9295740 G/A. One SNP demonstrated an influence on PFS: rs401681 C/T at 5p15, p = 0.021. Four SNPs demonstrated an influence on OS: rs2010963 (VEGF +405 G/C), p = 0.042; rs3025010 (VEGF intron 5 C/T), p = 0.047; rs401681 C/T at 5p15, p = 0.046; and rs31489 C/A at 5p15, p = 0.029. Conclusions Our study suggests that SNPs in the 6p12, 6p21, and 5p15 loci may serve as risk, predictive and prognostic NSCLC biomarkers. In the future, SNPs identified in the genomes of patients may improve NSCLC screening strategies and therapeutic management as well. PMID:24039754

  17. Catmull-Rom Curve Fitting and Interpolation Equations

    ERIC Educational Resources Information Center

    Jerome, Lawrence

    2010-01-01

    Computer graphics and animation experts have been using the Catmull-Rom smooth curve interpolation equations since 1974, but the vector and matrix equations can be derived and simplified using basic algebra, resulting in a simple set of linear equations with constant coefficients. A variety of uses of Catmull-Rom interpolation are demonstrated,…

  18. Treatment Planning and Volumetric Response Assessment for Yttrium-90 Radioembolization: Semiautomated Determination of Liver Volume and Volume of Tumor Necrosis in Patients with Hepatic Malignancy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Monsky, Wayne L., E-mail: wayne.monsky@ucdmc.ucdavis.edu; Garza, Armando S.; Kim, Isaac

    Purpose: The primary purpose of this study was to demonstrate intraobserver/interobserver reproducibility for novel semiautomated measurements of hepatic volume used for Yttrium-90 dose calculations as well as whole-liver and necrotic-liver (hypodense/nonenhancing) tumor volume after radioembolization. The secondary aim was to provide initial comparisons of tumor volumetric measurements with linear measurements, as defined by Response Evaluation Criteria in Solid Tumors criteria, and survival outcomes. Methods: Between 2006 and 2009, 23 consecutive radioembolization procedures were performed for 14 cases of hepatocellular carcinoma and 9 cases of hepatic metastases. Baseline and follow-up computed tomography obtained 1 month after treatment were retrospectively analyzed. Threemore » observers measured liver, whole-tumor, and tumor-necrosis volumes twice using semiautomated software. Results: Good intraobserver/interobserver reproducibility was demonstrated (intraclass correlation [ICC] > 0.9) for tumor and liver volumes. Semiautomated measurements of liver volumes were statistically similar to those obtained with manual tracing (ICC = 0.868), but they required significantly less time to perform (p < 0.0001, ICC = 0.088). There was a positive association between change in linear tumor measurements and whole-tumor volume (p < 0.0001). However, linear measurements did not correlate with volume of necrosis (p > 0.05). Dose, change in tumor diameters, tumor volume, and necrotic volume did not correlate with survival (p > 0.05 in all instances). However, Kaplan-Meier curves suggest that a >10% increase in necrotic volume correlated with survival (p = 0.0472). Conclusion: Semiautomated volumetric analysis of liver, whole-tumor, and tumor-necrosis volume can be performed with good intraobserver/interobserver reproducibility. In this small retrospective study, measurements of tumor necrosis were suggested to correlate with survival.« less

  19. Age-stratified outcomes after robotic-assisted laparoscopic radical prostatectomy.

    PubMed

    Zorn, Kevin C; Mendiola, Frederick P; Rapp, David E; Mikhail, Albert A; Lin, Shang; Orvieto, Marcelo A; Zagaja, Gregory P; Shalhav, Arieh L

    2007-01-01

    We sought to evaluate post-operative return of urinary and sexual function in men undergoing robotic-assisted laparoscopic radical prostatectomy (RLRP). Prospective assessment of urinary continence and sexual function was performed in patients undergoing RLRP. Subjective assessment involved the use of the validated RAND-36 Item Health Survey/UCLA Prostate Cancer Index questionnaire. Questionnaires were completed pre-operatively and at 1, 3, 6 and 12 months post-operatively. Subset analyses were performed to assess the effect of age on functional outcomes. A total of 338 consecutive patients underwent RLRP between February 2003 and August 2005. Included patients for evaluation comprised of 21, 129, and 150 patients, aged <50, 50-59, and ≥60 years old, respectively. Kaplan-Meier curve analysis demonstrated that younger men (<60 years) achieved subjective continence significantly earlier than older age group (≥60 years) (P = 0.02). Continence rates, however, equalized among all age groups at 1 year follow-up. Younger men (<50 years) also demonstrated a quicker and greater return of sexual function (P = 0.01), which persisted through assessment at 1 year post-operatively. Our results suggest that younger men may have an earlier return of continence and potency when compared to men > 60 years. Despite this finding, continence outcomes appear to be equal among age groups after 1 year of follow-up. Moreover, men < 60 years continue to report superior potency outcomes compared to men > 60 years at 1 year post-operatively. Such findings are valuable in counseling patients undergoing RLRP.

  20. AMP kinase-related kinase NUAK2 affects tumor growth, migration, and clinical outcome of human melanoma.

    PubMed

    Namiki, Takeshi; Tanemura, Atsushi; Valencia, Julio C; Coelho, Sergio G; Passeron, Thierry; Kawaguchi, Masakazu; Vieira, Wilfred D; Ishikawa, Masashi; Nishijima, Wataru; Izumo, Toshiyuki; Kaneko, Yasuhiko; Katayama, Ichiro; Yamaguchi, Yuji; Yin, Lanlan; Polley, Eric C; Liu, Hongfang; Kawakami, Yutaka; Eishi, Yoshinobu; Takahashi, Eishi; Yokozeki, Hiroo; Hearing, Vincent J

    2011-04-19

    The identification of genes that participate in melanomagenesis should suggest strategies for developing therapeutic modalities. We used a public array comparative genomic hybridization (CGH) database and real-time quantitative PCR (qPCR) analyses to identify the AMP kinase (AMPK)-related kinase NUAK2 as a candidate gene for melanomagenesis, and we analyzed its functions in melanoma cells. Our analyses had identified a locus at 1q32 where genomic gain is strongly associated with tumor thickness, and we used real-time qPCR analyses and regression analyses to identify NUAK2 as a candidate gene at that locus. Associations of relapse-free survival and overall survival of 92 primary melanoma patients with NUAK2 expression measured using immunohistochemistry were investigated using Kaplan-Meier curves, log rank tests, and Cox regression models. Knockdown of NUAK2 induces senescence and reduces S-phase, decreases migration, and down-regulates expression of mammalian target of rapamycin (mTOR). In vivo analysis demonstrated that knockdown of NUAK2 suppresses melanoma tumor growth in mice. Survival analysis showed that the risk of relapse is greater in acral melanoma patients with high levels of NUAK2 expression than in acral melanoma patients with low levels of NUAK2 expression (hazard ratio = 3.88; 95% confidence interval = 1.44-10.50; P = 0.0075). These data demonstrate that NUAK2 expression is significantly associated with the oncogenic features of melanoma cells and with the survival of acral melanoma patients. NUAK2 may provide a drug target to suppress melanoma progression. This study further supports the importance of NUAK2 in cancer development and tumor progression, while AMPK has antioncogenic properties.

  1. Proton Pump Inhibitors Independently Protect Against Early Allograft Injury or Chronic Rejection After Lung Transplantation.

    PubMed

    Lo, Wai-Kit; Goldberg, Hilary J; Boukedes, Steve; Burakoff, Robert; Chan, Walter W

    2018-02-01

    Acid reflux has been associated with poor outcomes following lung transplantation. Unlike surgical fundoplication, the role of noninvasive, pharmacologic acid suppression remains uncertain. To assess the relationship between post-transplant acid suppression with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) and onset of early allograft injury or chronic rejection following lung transplantation. This was a retrospective cohort study of lung transplant recipients at a tertiary center in 2007-2014. Patients with pre-transplant antireflux surgery were excluded. Time-to-event analysis using the Cox proportional hazards model was applied to assess acid suppression therapy and onset of acute or chronic rejection, defined histologically and clinically. Subgroup analyses were performed to assess PPI versus H2RA use. A total of 188 subjects (60% men, mean age 54, follow-up 554 person-years) met inclusion criteria. During follow-up, 115 subjects (61.5%) developed rejection, with all-cause mortality of 27.6%. On univariate analyses, acid suppression and BMI, but not other patient demographics, were associated with rejection. The Kaplan-Meier curve demonstrated decreased rejection with use of acid suppression therapy (log-rank p = 0.03). On multivariate analyses, acid suppression (HR 0.39, p = 0.04) and lower BMI (HR 0.67, p = 0.04) were independently predicted against rejection. Subgroup analyses demonstrated that persistent PPI use was more protective than H2RA or no antireflux medications. Post-lung transplant exposure to persistent PPI therapy results in the greatest protection against rejection in lung transplant recipients, independent of other clinical predictors including BMI, suggesting that PPI may have antireflux or anti-inflammatory effects in enhancing allograft protection.

  2. Usefulness of morning home blood pressure measurements in patients with type 2 diabetes mellitus: results of a 10-year, prospective, longitudinal study.

    PubMed

    Kamoi, Kyuzi

    2015-01-01

    Previous cross-sectional studies and 6-year longitudinal study have demonstrated that home blood pressure (HBP) measurements upon awakening have a stronger predictive power for death, micro- and macrovascular complications than clinic blood pressure (CBP) measurements in patients with type 2 diabetes (T2DM). This study investigated which of these measurements offers stronger predictive power for outcomes over 10 years. At baseline, 400 Japanese patients with T2DM were classified as having hypertension (HT) or normotension (NT) based on HBP and CBP. The mean survey duration was 95 months. Primary and secondary end-points were death and new or worsened micro- and macrovascular complications, respectively. Differences in outcomes for each end-point between HT and NT patients were analyzed using Kaplan-Meier survival curves and log-rank testing. Associated risk factors were assessed using Cox proportional hazards analysis. Based on HBP, death and micro- and macrovascular complications were significantly higher in patients with HT than with NT at baseline and end-point. Based on CBP, there were no significant differences in incidence of death, micro- or macrovascular complications between patients with HT and NT at baseline and end-point, although a significant difference in incidence of death was observed between the HT and NT groups at end-point. However, the significance was significantly lower in CBP than in HBP. One risk factor associated with micro- and macrovascular complications in patients with HBP was therapy for HT. This 10-year longitudinal study of patients with T2DM demonstrated that elevated HBP upon awakening is predictive of death, and micro- and macrovascular complications.

  3. Three-dimensional spatially curved local Bessel beams generated by metasurface

    NASA Astrophysics Data System (ADS)

    Liu, Dawei; Wu, Jiawen; Cheng, Bo; Li, Hongliang

    2018-03-01

    We propose a reflective metasurface based on an artificial admittance modulation surface to generate three-dimensional spatially curved beams. The phase acquisition utilized to modulate this sinusoidally varying surface admittance combines the enveloping theory of differential geometry and the method for producing two-dimensional Bessel beams. The metasurface is fabricated, and the comparison between the full-wave simulations and experimental results demonstrates good performance of three-dimensional spatially curved beams generated by the metasurface.

  4. Targeting the Prometastatic Microenvironment of the Involuting Mammary Gland

    DTIC Science & Technology

    2014-09-01

    analyses. To assess expression of Ltbp1 in breast cancer we began by mining in silico data using database available online specifically Kaplan-Meier... Dermatology , New York University School of Medicine, 550 First Ave, New York, NY 10016, USA Full list of author information is available at the end of the...1Department of Cell Biology, New York University School of Medicine, New York, NY, USA. 2The Ronald O Perelman Department of Dermatology , New York

  5. Aldo-keto Reductase Family 1 B10 as a Novel Target for Breast Cancer Treatment

    DTIC Science & Technology

    2010-08-01

    overexpressed in tested human breast cancer tissues and mediates acetyl-CoA carboxylase-α ( ACCA ) stability, affecting fatty acid de novo synthesis and...9703; Fax. 217-545-3227; E-mail: dcao@siumed.edu Running title: AKR1B10 as a new risk factor for breast cancer Abbreviations used: ACCA , acetyl...The effect of AKR1B10 expression in cancer tissue on patient survival was evaluated with Kaplan - Meier plots, and results showed that AKR1B10

  6. Improve T Cell Therapy in Neuroblastoma

    DTIC Science & Technology

    2015-09-01

    bioluminescence was then measured overtime. The graph is representative of one of 4 experiments using CMV-CTLs from 4 donors. Panel E. Kaplan-Meier...whole-cell vaccine expressing the iC9 gene and labeled with an enhanced firefly luciferase. Tumor growth was measured by in vivo imaging. Panel E...down regulation in LTE -T cells is not caused by specific culture conditions. T lymphocytes were activated with immobilized OKT3 (1 μg ml) and

  7. Measuring survival time: a probability-based approach useful in healthcare decision-making.

    PubMed

    2011-01-01

    In some clinical situations, the choice between treatment options takes into account their impact on patient survival time. Due to practical constraints (such as loss to follow-up), survival time is usually estimated using a probability calculation based on data obtained in clinical studies or trials. The two techniques most commonly used to estimate survival times are the Kaplan-Meier method and the actuarial method. Despite their limitations, they provide useful information when choosing between treatment options.

  8. The Oxford unicompartmental knee fails at a high rate in a high-volume knee practice.

    PubMed

    Schroer, William C; Barnes, C Lowry; Diesfeld, Paul; LeMarr, Angela; Ingrassia, Rachel; Morton, Diane J; Reedy, Mary

    2013-11-01

    The Oxford knee is a unicompartmental implant featuring a mobile-bearing polyethylene component with excellent long-term survivorship results reported by the implant developers and early adopters. By contrast, other studies have reported higher revision rates in large academic practices and in national registries. Registry data have shown increased failure with this implant especially by lower-volume surgeons and institutions. In the setting of a high-volume knee arthroplasty practice, we sought to determine (1) the failure rate of the Oxford unicompartmental knee implant using a failure definition for aseptic loosening that combined clinical features, plain radiographs, and scintigraphy, and (2) whether increased experience with this implant would decrease failure rate, if there is a learning curve effect. Eighty-three Oxford knee prostheses were implanted between September 2005 and July 2008 by the principal investigator. Radiographic and clinical data were available for review for all cases. A failed knee was defined as having recurrent pain after an earlier period of recovery from surgery, progressive radiolucent lines compared with initial postoperative radiographs, and a bone scan showing an isolated area of uptake limited to the area of the replaced compartment. Eleven knees in this series failed (13%); Kaplan-Meier survivorship was 86.5% (95% CI, 78.0%-95.0%) at 5 years. Failure occurrences were distributed evenly over the course of the study period. No learning curve effect was identified. Based on these findings, including a high failure rate of the Oxford knee implant and the absence of any discernible learning curve effect, the principal investigator no longer uses this implant.

  9. Experience in the management of ECMO therapy as a mortality risk factor.

    PubMed

    Guilló Moreno, V; Gutiérrez Martínez, A; Romero Berrocal, A; Sánchez Castilla, M; García-Fernández, J

    2018-02-01

    The extracorporeal oxygenation membrane (ECMO) is a system that provides circulatory and respiratory assistance to patients in cardiac or respiratory failure refractory to conventional treatment. It is a therapy with numerous associated complications and high mortality. Multidisciplinary management and experienced teams increase survival. Our purpose is to evaluate and analyse the effect of the learning curve on mortality. Retrospective and observational study of 31 patients, from January 2012 to December 2015. Patients were separated into 2periods. These periods were divided by the establishment of an ECMO protocol. We compared the quantitative variables by performing the Mann-Whitney U test. For the categorical qualitative variables we performed the chi-square test or Fisher exact statistic as appropriate. The survival curve was computed using the Kaplan-Meier method, and the analysis of statistical significance using the Log-rank test. Data analysis was performed with the STATA programme 14. Survival curves show the tendency to lower mortality in the subsequent period (P=0.0601). The overall mortality rate in the initial period was higher than in the subsequent period (P=0.042). In another analysis, we compared the characteristics of the 2groups and concluded that they were homogeneous. The degree of experience is an independent factor for mortality. The application of a care protocol is fundamental to facilitate the management of ECMO therapy. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Demonstrating Fermat's Principle in Optics

    ERIC Educational Resources Information Center

    Paleiov, Orr; Pupko, Ofir; Lipson, S. G.

    2011-01-01

    We demonstrate Fermat's principle in optics by a simple experiment using reflection from an arbitrarily shaped one-dimensional reflector. We investigated a range of possible light paths from a lamp to a fixed slit by reflection in a curved reflector and showed by direct measurement that the paths along which light is concentrated have either…

  11. Characterization of time series via Rényi complexity-entropy curves

    NASA Astrophysics Data System (ADS)

    Jauregui, M.; Zunino, L.; Lenzi, E. K.; Mendes, R. S.; Ribeiro, H. V.

    2018-05-01

    One of the most useful tools for distinguishing between chaotic and stochastic time series is the so-called complexity-entropy causality plane. This diagram involves two complexity measures: the Shannon entropy and the statistical complexity. Recently, this idea has been generalized by considering the Tsallis monoparametric generalization of the Shannon entropy, yielding complexity-entropy curves. These curves have proven to enhance the discrimination among different time series related to stochastic and chaotic processes of numerical and experimental nature. Here we further explore these complexity-entropy curves in the context of the Rényi entropy, which is another monoparametric generalization of the Shannon entropy. By combining the Rényi entropy with the proper generalization of the statistical complexity, we associate a parametric curve (the Rényi complexity-entropy curve) with a given time series. We explore this approach in a series of numerical and experimental applications, demonstrating the usefulness of this new technique for time series analysis. We show that the Rényi complexity-entropy curves enable the differentiation among time series of chaotic, stochastic, and periodic nature. In particular, time series of stochastic nature are associated with curves displaying positive curvature in a neighborhood of their initial points, whereas curves related to chaotic phenomena have a negative curvature; finally, periodic time series are represented by vertical straight lines.

  12. Measurement of M²-Curve for Asymmetric Beams by Self-Referencing Interferometer Wavefront Sensor.

    PubMed

    Du, Yongzhao

    2016-11-29

    For asymmetric laser beams, the values of beam quality factor M x 2 and M y 2 are inconsistent if one selects a different coordinate system or measures beam quality with different experimental conditionals, even when analyzing the same beam. To overcome this non-uniqueness, a new beam quality characterization method named as M²-curve is developed. The M²-curve not only contains the beam quality factor M x 2 and M y 2 in the x -direction and y -direction, respectively; but also introduces a curve of M x α 2 versus rotation angle α of coordinate axis. Moreover, we also present a real-time measurement method to demonstrate beam propagation factor M²-curve with a modified self-referencing Mach-Zehnder interferometer based-wavefront sensor (henceforth SRI-WFS). The feasibility of the proposed method is demonstrated with the theoretical analysis and experiment in multimode beams. The experimental results showed that the proposed measurement method is simple, fast, and a single-shot measurement procedure without movable parts.

  13. Decision curve analysis revisited: overall net benefit, relationships to ROC curve analysis, and application to case-control studies

    PubMed Central

    2011-01-01

    Background Decision curve analysis has been introduced as a method to evaluate prediction models in terms of their clinical consequences if used for a binary classification of subjects into a group who should and into a group who should not be treated. The key concept for this type of evaluation is the "net benefit", a concept borrowed from utility theory. Methods We recall the foundations of decision curve analysis and discuss some new aspects. First, we stress the formal distinction between the net benefit for the treated and for the untreated and define the concept of the "overall net benefit". Next, we revisit the important distinction between the concept of accuracy, as typically assessed using the Youden index and a receiver operating characteristic (ROC) analysis, and the concept of utility of a prediction model, as assessed using decision curve analysis. Finally, we provide an explicit implementation of decision curve analysis to be applied in the context of case-control studies. Results We show that the overall net benefit, which combines the net benefit for the treated and the untreated, is a natural alternative to the benefit achieved by a model, being invariant with respect to the coding of the outcome, and conveying a more comprehensive picture of the situation. Further, within the framework of decision curve analysis, we illustrate the important difference between the accuracy and the utility of a model, demonstrating how poor an accurate model may be in terms of its net benefit. Eventually, we expose that the application of decision curve analysis to case-control studies, where an accurate estimate of the true prevalence of a disease cannot be obtained from the data, is achieved with a few modifications to the original calculation procedure. Conclusions We present several interrelated extensions to decision curve analysis that will both facilitate its interpretation and broaden its potential area of application. PMID:21696604

  14. Numerical integration techniques for curved-element discretizations of molecule-solvent interfaces.

    PubMed

    Bardhan, Jaydeep P; Altman, Michael D; Willis, David J; Lippow, Shaun M; Tidor, Bruce; White, Jacob K

    2007-07-07

    Surface formulations of biophysical modeling problems offer attractive theoretical and computational properties. Numerical simulations based on these formulations usually begin with discretization of the surface under consideration; often, the surface is curved, possessing complicated structure and possibly singularities. Numerical simulations commonly are based on approximate, rather than exact, discretizations of these surfaces. To assess the strength of the dependence of simulation accuracy on the fidelity of surface representation, here methods were developed to model several important surface formulations using exact surface discretizations. Following and refining Zauhar's work [J. Comput.-Aided Mol. Des. 9, 149 (1995)], two classes of curved elements were defined that can exactly discretize the van der Waals, solvent-accessible, and solvent-excluded (molecular) surfaces. Numerical integration techniques are presented that can accurately evaluate nonsingular and singular integrals over these curved surfaces. After validating the exactness of the surface discretizations and demonstrating the correctness of the presented integration methods, a set of calculations are presented that compare the accuracy of approximate, planar-triangle-based discretizations and exact, curved-element-based simulations of surface-generalized-Born (sGB), surface-continuum van der Waals (scvdW), and boundary-element method (BEM) electrostatics problems. Results demonstrate that continuum electrostatic calculations with BEM using curved elements, piecewise-constant basis functions, and centroid collocation are nearly ten times more accurate than planar-triangle BEM for basis sets of comparable size. The sGB and scvdW calculations give exceptional accuracy even for the coarsest obtainable discretized surfaces. The extra accuracy is attributed to the exact representation of the solute-solvent interface; in contrast, commonly used planar-triangle discretizations can only offer improved

  15. Numerical Integration Techniques for Curved-Element Discretizations of Molecule–Solvent Interfaces

    PubMed Central

    Bardhan, Jaydeep P.; Altman, Michael D.; Willis, David J.; Lippow, Shaun M.; Tidor, Bruce; White, Jacob K.

    2012-01-01

    Surface formulations of biophysical modeling problems offer attractive theoretical and computational properties. Numerical simulations based on these formulations usually begin with discretization of the surface under consideration; often, the surface is curved, possessing complicated structure and possibly singularities. Numerical simulations commonly are based on approximate, rather than exact, discretizations of these surfaces. To assess the strength of the dependence of simulation accuracy on the fidelity of surface representation, we have developed methods to model several important surface formulations using exact surface discretizations. Following and refining Zauhar’s work (J. Comp.-Aid. Mol. Des. 9:149-159, 1995), we define two classes of curved elements that can exactly discretize the van der Waals, solvent-accessible, and solvent-excluded (molecular) surfaces. We then present numerical integration techniques that can accurately evaluate nonsingular and singular integrals over these curved surfaces. After validating the exactness of the surface discretizations and demonstrating the correctness of the presented integration methods, we present a set of calculations that compare the accuracy of approximate, planar-triangle-based discretizations and exact, curved-element-based simulations of surface-generalized-Born (sGB), surface-continuum van der Waals (scvdW), and boundary-element method (BEM) electrostatics problems. Results demonstrate that continuum electrostatic calculations with BEM using curved elements, piecewise-constant basis functions, and centroid collocation are nearly ten times more accurate than planartriangle BEM for basis sets of comparable size. The sGB and scvdW calculations give exceptional accuracy even for the coarsest obtainable discretized surfaces. The extra accuracy is attributed to the exact representation of the solute–solvent interface; in contrast, commonly used planar-triangle discretizations can only offer improved

  16. Stenting for curved lesions using a novel curved balloon: Preliminary experimental study.

    PubMed

    Tomita, Hideshi; Higaki, Takashi; Kobayashi, Toshiki; Fujii, Takanari; Fujimoto, Kazuto

    2015-08-01

    Stenting may be a compelling approach to dilating curved lesions in congenital heart diseases. However, balloon-expandable stents, which are commonly used for congenital heart diseases, are usually deployed in a straight orientation. In this study, we evaluated the effect of stenting with a novel curved balloon considered to provide better conformability to the curved-angled lesion. In vitro experiments: A Palmaz Genesis(®) stent (Johnson & Johnson, Cordis Co, Bridgewater, NJ, USA) mounted on the Goku(®) curve (Tokai Medical Co. Nagoya, Japan) was dilated in vitro to observe directly the behavior of the stent and balloon assembly during expansion. Animal experiment: A short Express(®) Vascular SD (Boston Scientific Co, Marlborough, MA, USA) stent and a long Express(®) Vascular LD stent (Boston Scientific) mounted on the curved balloon were deployed in the curved vessel of a pig to observe the effect of stenting in vivo. In vitro experiments: Although the stent was dilated in a curved fashion, stent and balloon assembly also rotated conjointly during expansion of its curved portion. In the primary stenting of the short stent, the stent was dilated with rotation of the curved portion. The excised stent conformed to the curved vessel. As the long stent could not be negotiated across the mid-portion with the balloon in expansion when it started curving, the mid-portion of the stent failed to expand fully. Furthermore, the balloon, which became entangled with the stent strut, could not be retrieved even after complete deflation. This novel curved balloon catheter might be used for implantation of the short stent in a curved lesion; however, it should not be used for primary stenting of the long stent. Post-dilation to conform the stent to the angled vessel would be safer than primary stenting irrespective of stent length. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  17. Are driving and overtaking on right curves more dangerous than on left curves?

    PubMed

    Othman, Sarbaz; Thomson, Robert; Lannér, Gunnar

    2010-01-01

    It is well known that crashes on horizontal curves are a cause for concern in all countries due to the frequency and severity of crashes at curves compared to road tangents. A recent study of crashes in western Sweden reported a higher rate of crashes in right curves than left curves. To further understand this result, this paper reports the results of novel analyses of the responses of vehicles and drivers during negotiating and overtaking maneuvers on curves for right hand traffic. The overall objectives of the study were to find road parameters for curves that affect vehicle dynamic responses, to analyze these responses during overtaking maneuvers on curves, and to link the results with driver behavior for different curve directions. The studied road features were speed, super-elevation, radius and friction including their interactions, while the analyzed vehicle dynamic factors were lateral acceleration and yaw angular velocity. A simulation program, PC-Crash, has been used to simulate road parameters and vehicle response interaction in curves. Overtaking maneuvers have been simulated for all road feature combinations in a total of 108 runs. Analysis of variances (ANOVA) was performed, using two sided randomized block design, to find differences in vehicle responses for the curve parameters. To study driver response, a field test using an instrumented vehicle and 32 participants was reviewed as it contained longitudinal speed and acceleration data for analysis. The simulation results showed that road features affect overtaking performance in right and left curves differently. Overtaking on right curves was sensitive to radius and the interaction of radius with road condition; while overtaking on left curves was more sensitive to super-elevation. Comparisons of lateral acceleration and yaw angular velocity during these maneuvers showed different vehicle response configurations depending on curve direction and maneuver path. The field test experiments also showed

  18. Numerical Investigation of the Flow Structure in a Kaplan Draft Tube at Part Load

    NASA Astrophysics Data System (ADS)

    Maddahian, R.; Cervantes, M. J.; Sotoudeh, N.

    2016-11-01

    This research presents numerical simulation of the unsteady flow field inside the draft tube of a Kaplan turbine at part load condition. Due to curvature of streamlines, the ordinary two-equations turbulence models fail to predict the flow features. Therefore, a modification of the Shear Stress Transport (SST-SAS) model is utilized to approximate the turbulent stresses. A guide vane, complete runner and draft tube are considered to insure the real boundary conditions at the draft tube inlet. The outlet boundary is assumed to discharge into the atmosphere. The obtained pressure fluctuations inside the draft tube are in good agreement with available experimental data. In order to further investigate the RVR formation and its movement, the λ2 criterion, relating the position of the vortex core and strength to the second largest Eigen value of the velocity gradient tensor, is employed. The method used for vortex identification shows the flow structure and vortex motion inside the draft tube accurately.

  19. Light curves and spectra from a thermonuclear explosion of a white dwarf merger

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    van Rossum, Daniel R.; Kashyap, Rahul; Fisher, Robert

    Double-degenerate (DD) mergers of carbon–oxygen white dwarfs have recently emerged as a leading candidate for normal Type Ia supernovae (SNe Ia). But, many outstanding questions surround DD mergers, including the characteristics of their light curves and spectra. We have recently identified a spiral instability in the post-merger phase of DD mergers and demonstrated that this instability self-consistently leads to detonation in some cases. We call this the spiral merger SN Ia model. We utilize the SuperNu radiative transfer software to calculate three-dimensional synthetic light curves and spectra of the spiral merger simulation with a system mass of 2.1more » $${M}_{\\odot }$$ from Kashyap et al. Because of their large system masses, both violent and spiral merger light curves are slowly declining. The spiral merger resembles very slowly declining SNe Ia, including SN 2001ay, and provides a more natural explanation for its observed properties than other SN Ia explosion models. Previous synthetic light curves and spectra of violent DD mergers demonstrate a strong dependence on viewing angle, which is in conflict with observations. Here, we demonstrate that the light curves and spectra of the spiral merger are less sensitive to the viewing angle than violent mergers, in closer agreement with observation. We find that the spatial distribution of 56Ni and IMEs follows a characteristic hourglass shape. Finally, we discuss the implications of the asymmetric distribution of 56Ni for the early-time gamma-ray observations of 56Ni from SN 2014J. We suggest that DD mergers that agree with the light curves and spectra of normal SNe Ia will likely require a lower system mass.« less

  20. Light curves and spectra from a thermonuclear explosion of a white dwarf merger

    DOE PAGES

    van Rossum, Daniel R.; Kashyap, Rahul; Fisher, Robert; ...

    2016-08-15

    Double-degenerate (DD) mergers of carbon–oxygen white dwarfs have recently emerged as a leading candidate for normal Type Ia supernovae (SNe Ia). But, many outstanding questions surround DD mergers, including the characteristics of their light curves and spectra. We have recently identified a spiral instability in the post-merger phase of DD mergers and demonstrated that this instability self-consistently leads to detonation in some cases. We call this the spiral merger SN Ia model. We utilize the SuperNu radiative transfer software to calculate three-dimensional synthetic light curves and spectra of the spiral merger simulation with a system mass of 2.1more » $${M}_{\\odot }$$ from Kashyap et al. Because of their large system masses, both violent and spiral merger light curves are slowly declining. The spiral merger resembles very slowly declining SNe Ia, including SN 2001ay, and provides a more natural explanation for its observed properties than other SN Ia explosion models. Previous synthetic light curves and spectra of violent DD mergers demonstrate a strong dependence on viewing angle, which is in conflict with observations. Here, we demonstrate that the light curves and spectra of the spiral merger are less sensitive to the viewing angle than violent mergers, in closer agreement with observation. We find that the spatial distribution of 56Ni and IMEs follows a characteristic hourglass shape. Finally, we discuss the implications of the asymmetric distribution of 56Ni for the early-time gamma-ray observations of 56Ni from SN 2014J. We suggest that DD mergers that agree with the light curves and spectra of normal SNe Ia will likely require a lower system mass.« less

  1. CRITICAL CURVES AND CAUSTICS OF TRIPLE-LENS MODELS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Daněk, Kamil; Heyrovský, David, E-mail: kamil.danek@utf.mff.cuni.cz, E-mail: heyrovsky@utf.mff.cuni.cz

    2015-06-10

    Among the 25 planetary systems detected up to now by gravitational microlensing, there are two cases of a star with two planets, and two cases of a binary star with a planet. Other, yet undetected types of triple lenses include triple stars or stars with a planet with a moon. The analysis and interpretation of such events is hindered by the lack of understanding of essential characteristics of triple lenses, such as their critical curves and caustics. We present here analytical and numerical methods for mapping the critical-curve topology and caustic cusp number in the parameter space of n-point-mass lenses.more » We apply the methods to the analysis of four symmetric triple-lens models, and obtain altogether 9 different critical-curve topologies and 32 caustic structures. While these results include various generic types, they represent just a subset of all possible triple-lens critical curves and caustics. Using the analyzed models, we demonstrate interesting features of triple lenses that do not occur in two-point-mass lenses. We show an example of a lens that cannot be described by the Chang–Refsdal model in the wide limit. In the close limit we demonstrate unusual structures of primary and secondary caustic loops, and explain the conditions for their occurrence. In the planetary limit we find that the presence of a planet may lead to a whole sequence of additional caustic metamorphoses. We show that a pair of planets may change the structure of the primary caustic even when placed far from their resonant position at the Einstein radius.« less

  2. Results of press-fit stems in revision knee arthroplasties.

    PubMed

    Wood, Gavin C; Naudie, Douglas D R; MacDonald, Steven J; McCalden, Richard W; Bourne, Robert B

    2009-03-01

    The ideal method of stem fixation in revision knee arthroplasty is controversial with advantages and disadvantages for cemented and press-fit designs. Studies have suggested cemented revision knee stems may provide better long-term survival. The aim of this study was to report our experience with press-fit uncemented stems and metaphyseal cement fixation in a selected series of patients undergoing revision total knee arthroplasty. One hundred twenty-seven patients (135 knees) who underwent revision total knee arthroplasty using a press-fit technique (press-fit diaphyseal fixation and cemented metaphyseal fixation) were reviewed. Minimum followup was 2 years (mean, 5 years; range, 2-12 years). A Kaplan-Meier survivorship analysis using an end point of revision surgery or radiographic loosening was used to determine probability of survival at 5 and 10 years. Of the 127 patients (135 knees), 31 patients (36 knees) died and two patients (two knees) were lost to followup. Six patients (six knees) had revisions at a mean of 3.5 years (range, 1-8 years). Kaplan-Meier survivorship analysis revealed a probability of survival free of revision for aseptic loosening of 98% at 12 years. Survivorship of press-fit stems for revision knee arthroplasty is comparable to reported survivorship of cemented stem revision knee arthroplasty. Radiographic analysis has shown continued satisfactory appearances regardless of constraint, stem size, and augmentations.

  3. Prognostic significance of hemoglobin level in patients with congestive heart failure and normal ejection fraction.

    PubMed

    Varadarajan, Padmini; Gandhi, Siddharth; Sharma, Sanjay; Umakanthan, Branavan; Pai, Ramdas G

    2006-10-01

    Previous studies have shown low hemoglobin (Hb) to have an adverse effect on survival in patients with congestive heart failure (CHF) and reduced left ventricular (LV) ejection fraction (EF); but its effect on survival in patients with CHF and normal EF is not known. This study sought to determine whether low Hb has an effect on survival in patients with both CHF and normal EF. Detailed chart reviews were performed by medical residents on 2,246 patients (48% with normal EF) with a discharge diagnosis of CHF in a large tertiary care hospital from 1990 to 1999. The CHF diagnosis was validated using the Framingham criteria. Mortality data were obtained from the National Death Index. Survival analysis was performed using Kaplan-Meier and Cox regression models. By Kaplan-Meier analysis, low Hb (< 12 gm/dl) compared with normal hemoglobin was associated with a lower 5-year survival in patients with CHF and both normal (38 vs. 50%, p = 0.0008) and reduced (35 vs. 48%, p = 0.0009) EF. Using the Cox regression model, low Hb was an independent predictor of mortality after adjusting for age, gender, renal dysfunction, diabetes mellitus, hypertension, and EF in both groups of patients. Low Hb has an independent adverse effect on survival in patients with CHF and both normal and reduced EF in both groups of patients.

  4. Incident and prevalent cohorts with pulmonary arterial hypertension: insight from SERAPHIN.

    PubMed

    Simonneau, Gérald; Channick, Richard N; Delcroix, Marion; Galiè, Nazzareno; Ghofrani, Hossein-Ardeschir; Jansa, Pavel; Le Brun, Franck-Olivier; Mehta, Sanjay; Perchenet, Loic; Pulido, Tomás; Sastry, B K S; Sitbon, Olivier; Souza, Rogério; Torbicki, Adam; Rubin, Lewis J

    2015-12-01

    In SERAPHIN, a long-term, randomised, controlled trial (NCT00660179) in pulmonary arterial hypertension (PAH), macitentan significantly reduced the risk of morbidity/mortality and PAH-related death/hospitalisation. We evaluated disease progression and the effect of macitentan in treatment-naïve incident and prevalent cohorts.Patients allocated to placebo, or macitentan 3 mg or 10 mg were classified by time from diagnosis to enrolment as incident (≤6 months; n=110) or prevalent (>6 months; n=157). The risk of morbidity/mortality and PAH-related death/hospitalisation was determined using Cox regression.The risk of morbidity/mortality (Kaplan-Meier estimates at month 12: 54.4% versus 26.7%; p=0.006) and PAH-related death/hospitalisation (Kaplan-Meier estimates at month 12: 47.3% versus 19.9%; p=0.006) were significantly higher for incident versus prevalent patients receiving placebo, respectively. There was no significant difference in the risk of all-cause death between incident and prevalent cohorts (p=0.587). Macitentan 10 mg significantly reduced the risk of morbidity/mortality and PAH-related death/hospitalisation versus placebo in incident and prevalent cohorts.Incident patients had a higher risk for PAH progression compared with prevalent patients but not a higher risk of death. Macitentan delayed disease progression in both incident and prevalent PAH patients. Copyright ©ERS 2015.

  5. The effect of preoperative serum triglycerides and high-density lipoprotein-cholesterol levels on the prognosis of breast cancer.

    PubMed

    Li, Xing; Tang, Hailin; Wang, Jin; Xie, Xinhua; Liu, Peng; Kong, Yanan; Ye, Feng; Shuang, Zeyu; Xie, Zeming; Xie, Xiaoming

    2017-04-01

    Although dyslipidemia has been documented to be associated with several types of cancer including breast cancer, it remains uncertainty the prognostic value of serum lipid in breast cancer. The purpose of this study is to evaluate the association between the preoperative plasma lipid profile and the prognostic of breast cancer patients. The levels of preoperative serum lipid profile (including cholesterol [CHO], Triglycerides [TG], high-density lipoprotein-cholesterol [HDL-C], low-density lipoprotein-cholesterol [LDL-C], apolipoprotein A-I [ApoAI], and apolipoprotein B [ApoB]) and the clinical data were retrospectively collected and reviewed in 1044 breast cancer patients undergoing operation. Kaplan-Meier method and the Cox proportional hazards regression model were used in analyzing the overall survival [OS] and disease-free survival [DFS]. Combining the receiver-operating characteristic and Kaplan-Meier analysis, we found that preoperative lower TG and HDL-C level were risk factors of breast cancer patients. In multivariate analyses, a decreased HDL-C level showed significant association with worse OS (HR: 0.528; 95% CI: 0.302-0.923; P = 0.025), whereas a decreased TG level showed significant association with worse DFS (HR: 0.569; 95% CI: 0.370-0.873; P = 0.010). Preoperative serum levels of TG and HDL-C may be independent factor to predict outcome in breast cancer patient. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Heparin for clearance of peripherally inserted central venous catheter in newborns: an in vitro study

    PubMed Central

    Balaminut, Talita; Venturini, Danielle; da Silva, Valéria Costa Evangelista; Rossetto, Edilaine Giovanini; Zani, Adriana Valongo

    2015-01-01

    Objective: To compare the efficacy of two concentrations of heparin to clear the lumen of in vitro clotted neonatal peripherally inserted central catheters (PICCs). Methods: This is an in vitro, experimental quantitative study of 76 neonatal 2.0-Fr PICCs coagulated in vitro. The catheters were divided into two groups of 38 PICCs each. In both groups an infusion of low molecular weight heparin was administered with a dose of 25IU/mL for Group 1 and 50IU/mL for Group 2. The negative pressure technique was applied to the catheters of both groups at 5, 15 and 30min and at 4h to test their permeability. Kaplan-Meier survival analysis was used to verify the outcome of the groups according to time intervals. Results: The comparison between both groups in the first 5min showed that more catheters from Group 2 were cleared compared to Group 1 (57.9 vs. 21.1%, respectively). Kaplan-Meier survival analysis showed that less time was needed to clear catheters treated with 50IU/mL of heparin (p<0.001). Conclusions: The use of low molecular weight heparin at a concentration of 50IU/mL was more effective in restoring the permeability of neonatal PICCs occluded in vitro by a clot, and the use of this concentration is within the safety margin indicated by scientific literature. PMID:26116325

  7. Gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy.

    PubMed

    Gerami, Pedram; Cook, Robert W; Russell, Maria C; Wilkinson, Jeff; Amaria, Rodabe N; Gonzalez, Rene; Lyle, Stephen; Jackson, Gilchrist L; Greisinger, Anthony J; Johnson, Clare E; Oelschlager, Kristen M; Stone, John F; Maetzold, Derek J; Ferris, Laura K; Wayne, Jeffrey D; Cooper, Chelsea; Obregon, Roxana; Delman, Keith A; Lawson, David

    2015-05-01

    A gene expression profile (GEP) test able to accurately identify risk of metastasis for patients with cutaneous melanoma has been clinically validated. We aimed for assessment of the prognostic accuracy of GEP and sentinel lymph node biopsy (SLNB) tests, independently and in combination, in a multicenter cohort of 217 patients. Reverse transcription polymerase chain reaction (RT-PCR) was performed to assess the expression of 31 genes from primary melanoma tumors, and SLNB outcome was determined from clinical data. Prognostic accuracy of each test was determined using Kaplan-Meier and Cox regression analysis of disease-free, distant metastasis-free, and overall survivals. GEP outcome was a more significant and better predictor of each end point in univariate and multivariate regression analysis, compared with SLNB (P < .0001 for all). In combination with SLNB, GEP improved prognostication. For patients with a GEP high-risk outcome and a negative SLNB result, Kaplan-Meier 5-year disease-free, distant metastasis-free, and overall survivals were 35%, 49%, and 54%, respectively. Within the SLNB-negative cohort of patients, overall risk of metastatic events was higher (∼30%) than commonly found in the general population of patients with melanoma. In this study cohort, GEP was an objective tool that accurately predicted metastatic risk in SLNB-eligible patients. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  8. Clinical Significance of SASH1 Expression in Glioma

    PubMed Central

    Yang, Liu; Zhang, Haitao; Yao, Qi; Yan, Yingying; Wu, Ronghua; Liu, Mei

    2015-01-01

    Objective. SAM and SH3 domain containing 1 (SASH1) is a recently discovered tumor suppressor gene. The role of SASH1 in glioma has not yet been described. We investigated SASH1 expression in glioma cases to determine its clinical significance on glioma pathogenesis and prognosis. Methods. We produced tissue microarrays using 121 patient-derived glioma samples and 30 patient-derived nontumor cerebral samples. Immunohistochemistry and Western blotting were used to evaluate SASH1 expression. We used Fisher's exact tests to determine relationships between SASH1 expression and clinicopathological characteristics; Cox regression analysis to evaluate the independency of different SASH1 expression; Kaplan-Meier analysis to determine any correlation of SASH1 expression with survival rate. Results. SASH1 expression was closely correlated with the WHO glioma grade. Of the 121 cases, 66.9% with low SASH1 expression were mostly grade III-IV cases, whereas 33.1% with high SASH1 expression were mostly grades I-II. Kaplan-Meier analysis revealed a significant positive correlation between SASH1 expression and postoperative survival. Conclusions. SASH1 was widely expressed in normal and low-grade glioma tissues. SASH1 expression strongly correlated with glioma grades, showing higher expression at a lower grade, which decreased significantly as grade increased. Furthermore, SASH1 expression was positively correlated with better postoperative survival in patients with glioma. PMID:26424902

  9. Clinical Significance of SASH1 Expression in Glioma.

    PubMed

    Yang, Liu; Zhang, Haitao; Yao, Qi; Yan, Yingying; Wu, Ronghua; Liu, Mei

    2015-01-01

    SAM and SH3 domain containing 1 (SASH1) is a recently discovered tumor suppressor gene. The role of SASH1 in glioma has not yet been described. We investigated SASH1 expression in glioma cases to determine its clinical significance on glioma pathogenesis and prognosis. We produced tissue microarrays using 121 patient-derived glioma samples and 30 patient-derived nontumor cerebral samples. Immunohistochemistry and Western blotting were used to evaluate SASH1 expression. We used Fisher's exact tests to determine relationships between SASH1 expression and clinicopathological characteristics; Cox regression analysis to evaluate the independency of different SASH1 expression; Kaplan-Meier analysis to determine any correlation of SASH1 expression with survival rate. SASH1 expression was closely correlated with the WHO glioma grade. Of the 121 cases, 66.9% with low SASH1 expression were mostly grade III-IV cases, whereas 33.1% with high SASH1 expression were mostly grades I-II. Kaplan-Meier analysis revealed a significant positive correlation between SASH1 expression and postoperative survival. SASH1 was widely expressed in normal and low-grade glioma tissues. SASH1 expression strongly correlated with glioma grades, showing higher expression at a lower grade, which decreased significantly as grade increased. Furthermore, SASH1 expression was positively correlated with better postoperative survival in patients with glioma.

  10. Decreased graft survival in liver transplant recipients of donors with positive blood cultures: a review of the United Network for Organ Sharing dataset.

    PubMed

    Huaman, Moises A; Vilchez, Valery; Mei, Xiaonan; Shah, Malay B; Daily, Michael F; Berger, Jonathan; Gedaly, Roberto

    2017-06-01

    Liver transplantation using blood culture positive donors (BCPD) has allowed a significant expansion of the donor pool. We aimed to characterize BCPD and assess the outcomes of BCPD liver transplant recipients. We retrieved data from the United Network for Organ Sharing (UNOS) registry on all adults who underwent primary, single-organ deceased-donor liver transplantation in the USA between 2008 and 2013. Patients were classified into two cohorts: the BCPD cohort and the non-BCPD cohort. One-year graft and patient survival were compared between cohorts using Kaplan-Meier estimates and Cox models. A total of 28 961 patients were included. There were 2316 (8.0%) recipients of BCPD. BCPD were more likely to be older, female, black, diabetic, hypertensive, and obese compared to non-BCPD. Graft survival was significantly lower in BCPD recipients compared to non-BCPD recipients (Kaplan-Meier, 0.85 vs. 0.87; P = 0.009). Results remained significant in propensity-matched analysis (P = 0.038). BCPD was independently associated with decreased graft survival (adjusted HR; 1.10, 95% CI 1.01-1.20; P = 0.04). There were no significant differences in patient survival between study groups. BCPD was associated with decreased graft survival in liver transplant recipients. Studies are needed to identify subgroups of BCPD with the highest risk of graft failure and characterize the underlying pathogenic mechanisms. © 2016 Steunstichting ESOT.

  11. Stent placement with the monorail technique for treatment of mesenteric artery stenosis.

    PubMed

    Schaefer, Philipp J; Schaefer, Fritz K W; Hinrichsen, Holger; Jahnke, Thomas; Charalambous, Nikolas; Heller, Martin; Mueller-Huelsbeck, Stefan

    2006-04-01

    To analyze the immediate and midterm success of stenting of mesenteric arteries by a monorail technique in patients with chronic mesenteric ischemia. In this prospective case series, 19 patients (11 male, 8 female; mean age, 62.9 +/- 10.4 y; range, 36-82 y) with 23 symptomatic stenoses of mesenteric arteries were treated with stent placement by a monorail technique in a radiologic intervention center over a period of 4.5 years. Clinical examinations and duplex sonography were used to evaluate the stents' patency and clinical success. Kaplan-Meier graphs were calculated to analyze the patency and freedom-from-symptom rate. Initial technical success rate was 22/23 (96%). Mean follow-up was 17 months (range, 1-58 mo). Primary patency and primary clinical success rates were 82% and 78%, respectively. According to Kaplan-Meier tables, the patency rates were 96%, 87%, 76%, and 61% at 0, 1, 15, and 24 months, respectively, and the freedom-from-symptom rates were 95%, 90%, 72%, and 54% at 0, 1, 24, and 30 months, respectively. No peri-interventional complications occurred. Two patients died of cardiac failure in the hospital within 30 days after intervention; deaths were not related to the intervention. Stent placement by a monorail technique in mesenteric arteries is an effective and safe treatment for symptomatic stenoses in patients with chronic mesenteric ischemia after a mean follow-up of 17 months.

  12. Validation of long-term survival prediction for scheduled abdominal aortic aneurysm repair with an independent calculator using only pre-operative variables.

    PubMed

    Carlisle, J B; Danjoux, G; Kerr, K; Snowden, C; Swart, M

    2015-06-01

    We observed survival after scheduled repair of abdominal aortic aneurysm in 1096 patients for a median (IQR [range]) of 3.0 (1.5-5.8 [0-15]) years: 943 patients had complete data, 250 of whom died. We compared discrimination and calibration of an external model with the Kaplan-Meier model generated from the study data. Integrated Brier misclassification scores for both models at 1-5 postoperative years were 0.04, 0.08, 0.11, 0.13 and 0.16, respectively. Harrel's concordance index at 1-5 postoperative years was 0.73, 0.71, 0.68, 0.67 and 0.66, respectively. Groups with median 5-year predicted mortality of 40% (n = 251), 18% (n = 414) and 8% (n = 164) had lower observed mortality than 114 patients with 70% predicted mortality, hazard ratio (95% CI): 0.58 (0.37-0.76), p = 0.0031; 0.30 (0.19-0.48), p = 1.7 × 10(-12) and 0.19 (0.13-0.27), p = 1.3 × 10(-10) , respectively, test for trend p = 5.6 × 10(-15) . Survival predicted by the external calculator was similar to the Kaplan-Meier estimate. © 2015 The Association of Anaesthetists of Great Britain and Ireland.

  13. PRIMARY ACQUIRED MELANOSIS OF THE CONJUNCTIVA: EXPERIENCE WITH 311 EYES

    PubMed Central

    Shields, Jerry A.; Shields, Carol L.; Mashayekhi, Arman; Marr, Brian P.; Benavides, Raquel; Thangappan, Archana; Phan, Laura; Eagle, Ralph C.

    2007-01-01

    Purpose To evaluate clinical features and risks for transformation of conjunctival primary acquired melanosis (PAM) into melanoma. Methods Retrospective chart review and Kaplan-Meier estimates of times to PAM enlargement, recurrence, and transformation into melanoma. Main outcome measures: PAM enlargement, recurrence, and transformation into melanoma. Results The mean patient age at diagnosis of PAM was 56 years; 62% were female and 96% Caucasian. The conjunctival quadrant(s) affected by PAM and its extent in clock hours were recorded. Initial management included observation in 62%, biopsy combined with cryotherapy in 34%, and other methods in 4%. Of PAM that was observed, Kaplan-Meier estimates at 10 years revealed PAM enlargement in 35% and transformation into melanoma in 12%. Of those that underwent incisional or excisional biopsy, 10-year estimates of PAM recurrence and transformation into melanoma were 58% and 11%, respectively. Progression to melanoma occurred in 0% of PAM without atypia, 0% of PAM with mild atypia, and 13% of PAM with severe atypia. Multivariable analysis revealed that the most significant factor for both PAM recurrence and progression to melanoma was extent of PAM in clock hours. Conclusion PAM without atypia or with mild atypia shows 0% progression into melanoma, whereas PAM with severe atypia shows progression into melanoma in 13%. The greater the extent of PAM in clock hours, the greater the risk for transformation into melanoma. PMID:18427595

  14. Curved-line search algorithm for ab initio atomic structure relaxation

    NASA Astrophysics Data System (ADS)

    Chen, Zhanghui; Li, Jingbo; Li, Shushen; Wang, Lin-Wang

    2017-09-01

    Ab initio atomic relaxations often take large numbers of steps and long times to converge, especially when the initial atomic configurations are far from the local minimum or there are curved and narrow valleys in the multidimensional potentials. An atomic relaxation method based on on-the-flight force learning and a corresponding curved-line search algorithm is presented to accelerate this process. Results demonstrate the superior performance of this method for metal and magnetic clusters when compared with the conventional conjugate-gradient method.

  15. Observable Zitterbewegung in curved spacetimes

    NASA Astrophysics Data System (ADS)

    Kobakhidze, Archil; Manning, Adrian; Tureanu, Anca

    2016-06-01

    Zitterbewegung, as it was originally described by Schrödinger, is an unphysical, non-observable effect. We verify whether the effect can be observed in non-inertial reference frames/curved spacetimes, where the ambiguity in defining particle states results in a mixing of positive and negative frequency modes. We explicitly demonstrate that such a mixing is in fact necessary to obtain the correct classical value for a particle's velocity in a uniformly accelerated reference frame, whereas in cosmological spacetime a particle does indeed exhibit Zitterbewegung.

  16. Digital Humanitarians: How Big Data Is Changing the Face of Humanitarian Response : Patrick Meier, 2015, CRC Press (Boca Raton, FL, 978-1-4822-4839-5, 259 pp.).

    PubMed

    Dave, Anushree

    2017-12-01

    This is a review of Patrick Meier's 2015 book, Digital Humanitarians: How Big Data Is Changing the Face of Humanitarian Response. The book explores the role of technologies such as high-resolution satellite imagery, online social media, drones, and artificial intelligence in humanitarian responses during disasters such as the 2010 Haiti earthquake. In this analysis, the book is examined using a humanitarian health ethics perspective.

  17. X-ray light curves of active galactic nuclei are phase incoherent

    NASA Technical Reports Server (NTRS)

    Krolik, Julian; Done, Chris; Madejski, Grzegorz

    1993-01-01

    We compute the Fourier phase spectra for the light curves of five low-luminosity active galactic nuclei observed by EXOSAT. There is no statistically significant phase coherence in any of them. This statement is equivalent, subject to a technical caveat, to a demonstration that their fluctuation statistics are Gaussian. Models in which the X-ray output is controlled wholly by a unitary process undergoing a nonlinear limit cycle are therefore ruled out, while models with either a large number of randomly excited independent oscillation modes or nonlinearly interacting spatially dependent oscillations are favored. We also demonstrate how the degree of phase coherence in light curve fluctuations influences the application of causality bounds on internal length scales.

  18. Estimation of the Ratio of Scale Parameters in the Two Sample Problem with Arbitrary Right Censorship.

    DTIC Science & Technology

    1980-06-01

    70. AWST RC 7 Coeittu an rewwase ati of nee*aa.ean mimDdentify by black n,.mboJ T two-sample version of the Cram~ r -von Mines statistic for right...estimator for exponential distributions. KEY WORDS: Cram~ r -von Mtses distance; Kaplan-Meier estimators; Right censorship; Scale parameter; lodgea and...suppose that two positive random variables ’i 2 S0 and ’ r differ in distribution only by their scale parameters. That is, there exists a positive

  19. Survival and movements of molting male black ducks in Labrador

    USGS Publications Warehouse

    Bowman, Timothy D.; Longcore, J.R.

    1989-01-01

    We marked 26 flightless male American black ducks with transmitters during the post-nuptial molt in northern Labrabor to determine survival and movements. Twelve ducks remained in the watershed where marked and 11 ducks moved to different watersheds. The period survival rate (PSR) for these flightless males was 0.89 using the Kaplan-Meier estimator. Only 2 ducks were killed by predators. Death of these 2 ducks might have been influenced by our disturbance, thus we considered the PSR minimal.

  20. Cytoreductive Nephrectomy in Elderly Patients with Metastatic Renal Cell Carcinoma in the Targeted Therapy Era.

    PubMed

    Uprety, Dipesh; Bista, Amir; Smith, Angela L; Vallatharasu, Yazhini; Marinier, David E

    2018-05-01

    The role of cytoreductive nephrectomy (CN) for metastatic renal cell cancer (mRCC) is not clearly understood after the approval of targeted therapies, particularly in the elderly population. The aim of this study was to compare survivals between patients who did and did not receive CN. The SEER-18 database was utilized in order to identify elderly patients with mRCC to compare overall survival (OS) and cancer-specific survival (CSS) between patients who did or did not receive CN between February 2006 and 2012. Kaplan-Meier curve and log rank test were used to compare OS and CSS between these two arms. Cox proportional hazard model was used for multivariate analysis and statistical significance was defined as p≤0.05. There was a significant survival benefit for those who received CN compared to those who did not receive CN (median OS: 18 months vs. 4 months, p<0.001; median CSS: 21 months vs. 5 months, p<0.001). CN offered significant survival benefit, even in elderly patients with metastatic renal cell cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. Validation of the revised International Prognostic Scoring System in patients with myelodysplastic syndrome in Japan: results from a prospective multicenter registry.

    PubMed

    Kawabata, Hiroshi; Tohyama, Kaoru; Matsuda, Akira; Araseki, Kayano; Hata, Tomoko; Suzuki, Takahiro; Kayano, Hidekazu; Shimbo, Kei; Zaike, Yuji; Usuki, Kensuke; Chiba, Shigeru; Ishikawa, Takayuki; Arima, Nobuyoshi; Nogawa, Masaharu; Ohta, Akiko; Miyazaki, Yasushi; Mitani, Kinuko; Ozawa, Keiya; Arai, Shunya; Kurokawa, Mineo; Takaori-Kondo, Akifumi

    2017-09-01

    The Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes has been conducting prospective registration, central review, and follow-up study for patients with aplastic anemia and myelodysplastic syndrome (MDS) since 2006. Using this database, we retrospectively analyzed the prognosis of patients with MDS. As of May 2016, 351 cases were registered in this database, 186 of which were eligible for the present study. Kaplan-Meier analysis showed that overall survival (OS) curves of the five risk categories stipulated by the revised international prognostic scoring system (IPSS-R) were reasonably separated. 2-year OS rates for the very low-, low-, intermediate-, high-, and very high-risk categories were 95, 89, 79, 35, and 12%, respectively. In the same categories, incidence of leukemic transformation at 2 years was 0, 10, 8, 56, and 40%, respectively. Multivariate analysis revealed that male sex, low platelet counts, increased blast percentage (>2%), and high-risk karyotype abnormalities were independent risk factors for poor OS. Based on these data, we classified Japanese MDS patients who were classified as intermediate-risk in IPSS-R, into the lower risk MDS category, highlighting the need for careful assessment of treatments within low- and high-risk treatment protocols.

  2. The use of a water seal to manage air leaks after a pulmonary lobectomy: a retrospective study.

    PubMed

    Okamoto, Junichi; Okamoto, Tatsuro; Fukuyama, Yasuro; Ushijima, Chie; Yamaguchi, Masafumi; Ichinose, Yukito

    2006-08-01

    The methods for managing chest drainage tubes during the postoperative period differ among thoracic surgeons and, as a result, the optimal method remains controversial. We reviewed 170 consecutive patients undergoing a pulmonary lobectomy for either primary lung cancer or metastatic lung cancer from January 1998 to December 2002. After the operation, the chest drainage tube was placed on a suction pump with a negative pressure of -10 cmH(2)O in 120 patients before 2001, while such drainage tubes were kept on water seal in 47 cases mainly since 2001. Regarding the preoperative and postoperative variables, postoperative air leak as well as the video-assisted thoracic surgery (VATS) procedure were more frequently observed in the water seal group than in the suction group (p=0.01580, p<0.001, respectively). In comparing these different populations, each Kaplan-Meier curve, which presented the duration of the postoperative air leak seemed to be similar between the two methods. These observations suggest that applying chest tubes on water seal seems to be an effective method for preventing postoperative air leak in clinical practice. However, a prospective randomized trial using a larger series of patients is warranted for this subject.

  3. CXCR4 expression varies significantly among different subtypes of glioblastoma multiforme (GBM) and its low expression or hypermethylation might predict favorable overall survival.

    PubMed

    Ma, Xinlong; Shang, Feng; Zhu, Weidong; Lin, Qingtang

    2017-09-01

    CXCR4 is an oncogene in glioblastoma multiforme (GBM) but the mechanism of its dysregulation and its prognostic value in GBM have not been fully understood. Bioinformatic analysis was performed by using R2 and the UCSC Xena browser based on data from GSE16011 in GEO datasets and in GBM cohort in TCGA database (TCGA-GBM). Kaplan Meier curves of overall survival (OS) were generated to assess the association between CXCR4 expression/methylation and OS in patients with GBM. GBM patients with high CXCR4 expression had significantly worse 5 and 10 yrs OS (p < 0.05). Across different GBM subtypes, there was an inverse relationship between overall DNA methylation and CXCR4 expression. CXCR4 expression was significantly lower in CpG island methylation phenotype (CIMP) group than in non CIMP group. Log rank test results showed that patients with high CXCR4 methylation (first tertile) had significantly better 5 yrs OS (p = 0.038). CXCR4 expression is regulated by DNA methylation in GBM and its low expression or hypermethylation might indicate favorable OS in GBM patients.

  4. The impact of socioeconomic status on the association between biomedical and psychosocial well-being and all-cause mortality in older Spanish adults.

    PubMed

    Doménech-Abella, Joan; Mundó, Jordi; Moneta, Maria Victoria; Perales, Jaime; Ayuso-Mateos, José Luis; Miret, Marta; Haro, Josep Maria; Olaya, Beatriz

    2018-03-01

    The aim of this paper was to analyze the effect of biomedical and psychosocial well-being, based on distinct successful aging models (SA), on time to mortality, and determine whether this effect was modified by socioeconomic status (SES) in a nationally representative sample of older Spanish adults. Data were taken from a 3-year follow-up study with 2783 participants aged 50 or over. Vital status was ascertained using national registers or asking participants' relatives. Kaplan-Meier curves were used to estimate the time to death by SES, and levels of biomedical and psychosocial SA. Cox proportional hazard regression models were conducted to explore interactions between SES and SA models while adjusting for gender, age, and marital status. Lower levels of SES and biomedical and psychosocial SA were associated with low probability of survival. Only the interaction between SES and biomedical SA was significant. Biomedical SA impacted on mortality rates among individuals with low SES but not on those with medium or high SES, whereas psychosocial SA affected mortality regardless of SES. Promoting equal access to health care system and improved psychosocial well-being could be a protective factor against premature mortality in older Spanish adults with low SES.

  5. Predictors of adalimumab drug survival in psoriasis differ by reason for discontinuation: long-term results from the Bio-CAPTURE registry.

    PubMed

    van den Reek, J M P A; Tummers, M; Zweegers, J; Seyger, M M B; van Lümig, P P M; Driessen, R J B; van de Kerkhof, P C M; Kievit, W; de Jong, E M G J

    2015-03-01

    Drug survival is an indicator for treatment success; insight in predictors associated with drug survival is important. To analyse the long-term drug survival for adalimumab in patients with psoriasis treated in daily practice and (II) to identify predictors of prolonged drug survival for adalimumab split for different reasons of discontinuation. Data were extracted from a prospective psoriasis cohort and analysed using Kaplan-Meier survival curves split for reasons of discontinuation. Baseline predictors associated with longer drug survival were identified using multivariate Cox-regression analysis. One hundred and sixteen patients were included with a total of 208 patient-years. Overall drug survival was 76% after 1 year and 52% after 4.5 years. In patients who stopped due to ineffectiveness, longer drug survival was associated with the absence of specific comorbidities (P = 0.03). In patients who stopped due to side-effects, longer drug survival was associated with male gender (P = 0.02). Predictors of adalimumab drug survival in psoriasis differ by reason for discontinuation. Strong, specific predictors can lead to patient-tailored treatment. © 2014 European Academy of Dermatology and Venereology.

  6. [Duration of breastfeeding and its relevant influencing factors on under 2-years-old in rural areas of 10 provinces in China].

    PubMed

    Wang, Jian-min; Li, Neng; Xie, Sheng-nan; Yang, Sen-bei; Zheng, Xiao-xuan; Zhang, Jing

    2013-07-01

    To understand the current status and relevant factors influencing the duration of breastfeeding in rural areas in China. Children under two years old were selected as subjects from the study on "Physical growth among the under 7-years-old children from the rural areas of ten provinces in China in 2006". Kaplan-Meier method was used to estimate the survival curves and Cox multivariate stepwise regression was used to identify the relevant factors on the duration of breastfeeding. Median of the duration for breastfeeding was 12 months in rural areas of 10 provinces in China. Results of this study suggested that factors as sex, birth order, areas of residency, nationality, initiation of formula, parents' education levels, maternal services and family income were correlated with the duration of breastfeeding. Duration of breastfeeding among rural children under 2-years of age was short in the 10 provinces of China. Factors as level of education, residential areas and family income of the parents as well as sex of the children were correlated with the duration of breastfeeding. Intervention program should be implemented to improve the current status on breastfeeding.

  7. Predicting risk of nonmelanoma skin cancer and premalignant skin lesions in renal transplant recipients.

    PubMed

    Urwin, Helen R; Jones, Peter W; Harden, Paul N; Ramsay, Helen M; Hawley, Carmel M; Nicol, David L; Fryer, Anthony A

    2009-06-15

    Nonmelanoma skin cancer (NMSC) and associated premalignant lesions represent a major complication after transplantation, particularly in areas with high ultraviolet radiation (UVR) exposure. The American Society of Transplantation has proposed annual NMSC screening for all renal transplant recipients. The aim of this study was to develop a predictive index (PI) that could be used in targeted screening. Data on patient demographics, UVR exposure, and other clinical parameters were collected on 398 adult recipients recruited from the Princess Alexandra Hospital, Brisbane. Structured interview, skin examination, biopsy of lesions, and review of medical/pathologic records were performed. Time to presentation with the first NMSC was assessed using Cox's regression models and Kaplan-Meier estimates used to assess detection of NMSC during screening. Stepwise selection identified age, outdoor UVR exposure, living in a hot climate, pretransplant NMSC, childhood sunburning, and skin type as predictors. The PI generated was used to allocate patients into three screening groups (6 months, 2 years, and 5 years). The survival curves of these groups were significantly different (P<0.0001). Jack-knife validation correctly allocated all patients into the appropriate group. We have developed a simple PI to enable development of targeted NMSC surveillance strategies.

  8. Prognostic significance of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with stage III and IV colorectal cancer

    PubMed Central

    Kim, Jae Hyun; Lee, Jun Yeop; Kim, Hae Koo; Lee, Jin Wook; Jung, Sung Gyu; Jung, Kyoungwon; Kim, Sung Eun; Moon, Won; Park, Moo In; Park, Seun Ja

    2017-01-01

    AIM To evaluate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with colorectal cancer (CRC). METHODS Between April 1996 and December 2010, medical records from a total of 1868 patients with CRC were retrospectively reviewed. The values of simple inflammatory markers including NLR and PLR in predicting the long-term outcomes of these patients were evaluated using Kaplan-Meier curves and Cox regression models. RESULTS The median follow-up duration was 46 mo (interquartile range, 22-73). The estimation of NLR and PLR was based on the time of diagnosis. In multivariate Cox regression analysis, high NLR (≥ 3.0) and high PLR (≥ 160) were independent risk factors predicting poor long-term outcomes in patients with stage III and IV CRC. However, high NLR and high PLR were not prognostic factors in patients with stage I and II CRC. CONCLUSION In this study, we identified that high NLR (≥ 3.0) and high PLR (≥ 160) are useful prognostic factors to predict long-term outcomes in patients with stage III and IV CRC. PMID:28210087

  9. Increased expression of progesterone receptor membrane component 1 is associated with aggressive phenotype and poor prognosis in ER-positive and negative breast cancer.

    PubMed

    Ruan, Xiangyan; Zhang, Ying; Mueck, Alfred O; Willibald, Marina; Seeger, Harald; Fehm, Tanja; Brucker, Sara; Neubauer, Hans

    2017-02-01

    Expression of progesterone receptor membrane component 1 (PGRMC1) has been shown to be higher in breast cancer than normal tissue. We have previously shown that certain progestogens strongly stimulate proliferation of breast cancer cells overexpressing PGRMC1, and therefore hypothesize that PGRMC1 may play a critical role in breast cancer progression. Because little information is available if expression of PGRMC1 is also associated with worse prognosis for breast cancer patients, in this study we investigated the clinicopathologic significance of PGRMC1 expression in breast cancer tissue. Expression of PGRMC1 was analyzed by immunohistochemical staining of primary tumor tissues obtained from 69 breast cancer patients. A labeling score was developed, and results were correlated with tumor size, lymph node metastasis, and clinical outcome. Overexpression of PGRMC1 is correlating with larger tumor size and lymph node metastasis. Kaplan-Meier survival curves indicate that patients with PGRMC1 tumors have poorer disease-free and overall survival independent from the estrogen receptor status than breast cancer patients with PGRMC1 tumors. Our findings suggest that the expression of PGRMC1 might be useful for predicting prognosis in patients with breast cancer.

  10. Parametric regression model for survival data: Weibull regression model as an example

    PubMed Central

    2016-01-01

    Weibull regression model is one of the most popular forms of parametric regression model that it provides estimate of baseline hazard function, as well as coefficients for covariates. Because of technical difficulties, Weibull regression model is seldom used in medical literature as compared to the semi-parametric proportional hazard model. To make clinical investigators familiar with Weibull regression model, this article introduces some basic knowledge on Weibull regression model and then illustrates how to fit the model with R software. The SurvRegCensCov package is useful in converting estimated coefficients to clinical relevant statistics such as hazard ratio (HR) and event time ratio (ETR). Model adequacy can be assessed by inspecting Kaplan-Meier curves stratified by categorical variable. The eha package provides an alternative method to model Weibull regression model. The check.dist() function helps to assess goodness-of-fit of the model. Variable selection is based on the importance of a covariate, which can be tested using anova() function. Alternatively, backward elimination starting from a full model is an efficient way for model development. Visualization of Weibull regression model after model development is interesting that it provides another way to report your findings. PMID:28149846

  11. External validation of sTWEAK as a prognostic noninvasive biomarker for head and neck squamous cell carcinoma.

    PubMed

    Terra, Ximena; Gómez, David; García-Lorenzo, Jacinto; Flores, Joan Carles; Figuerola, Enric; Mora, Josefina; Chacón, Matilde R; Quer, Miquel; Camacho, Mercedes; León, Xavier; Avilés-Jurado, Francesc Xavier

    2016-04-01

    The main purpose of this study was to validate the prognostic significance of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) in head and neck squamous cell carcinoma (HNSCC) using an independent cohort. Data were evaluated from 153 patients with HNSCC in stages III to IV, who received radiotherapy (RT) or chemoradiotherapy. We quantified soluble TWEAK (sTWEAK) in pretreatment samples using enzyme-linked immunosorbent assay. The classification tree revealed a cutoff value of 322 pg/mL for sTWEAK to be ideal for discriminating between patients' disease control. Kaplan-Meier curves indicate that the disease-free survival rate in patients with high sTWEAK was significantly higher than in patients with low levels (p = .006, log-rank test). An independent link was identified between low sTWEAK and poor clinical outcome in Cox regression multivariate analysis (hazard ratio = 1.866; 95% confidence interval [CI] = 1.114-3.125; p = .001). Our study highlights the significance of this noninvasive biomarker in the discrimination according to the disease control achieved by patients who received a nonsurgical organ-preservation treatment. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1358-E1363, 2016. © 2015 Wiley Periodicals, Inc.

  12. Clinicopathological Correlations of Autophagy-related Proteins LC3, Beclin 1 and p62 in Gastric Cancer.

    PubMed

    Masuda, G O; Yashiro, Masakazu; Kitayama, Kishu; Miki, Yuichiro; Kasashima, Hiroaki; Kinoshita, Haruhito; Morisaki, Tamami; Fukuoka, Tatshunari; Hasegawa, Tsuyoshi; Sakurai, Katsunobu; Toyokawa, Takahiro; Kubo, Naoshi; Tanaka, Hiroaki; Muguruma, Kazuya; Masaichi, Ohira; Hirakawa, Kosei

    2016-01-01

    This study evaluated the clinicopathological significance of autophagy, an intracellular degradation system, in gastric cancer. The expression levels of three autophagy-related proteins, namely light chain 3 (LC3), Beclin 1 and p62, were analyzed by immunohistochemistry using samples from 510 patients with primary gastric cancer. LC3, Beclin 1, and p62 expression was positive in 79 (15.5%), 126 (24.7%) and 251 (49.2%) out of 510 carcinomas, respectively. Autophagy was defined when samples were positive for at least two out of the three proteins. Autophagy-positive cases were 113 (22.1%) out of the 510. Autophagy determined by LC3, Beclin 1, and p62 significantly correlated with lymph node metastasis, vessel invasion, and hepatic metastasis. A Kaplan-Meier survival curve showed that autophagy was significantly associated with poor survival of patients with gastric cancer, especially for those with disease at stage I. Multivariate analysis indicated that autophagy was an independent prognostic factor. Autophagy promotes the progression of gastric cancer at an early clinical stage. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  13. Lymphocyte-to-monocyte ratio is associated with survival in pembrolizumab-treated metastatic melanoma patients.

    PubMed

    Failing, Jarrett J; Yan, Yiyi; Porrata, Luis F; Markovic, Svetomir N

    2017-12-01

    The peripheral blood lymphocyte-to-monocyte ratio (LMR) has been associated with prognosis in many malignancies including metastatic melanoma. However, it has not been studied in patients treated with immune checkpoint inhibitors. In this study, we analyzed the baseline LMR with progression-free survival (PFS) and overall survival (OS) in metastatic melanoma patients treated with pembrolizumab. A total of 133 patients with metastatic melanoma treated with pembrolizumab were included in this retrospective study. LMR was calculated from pretherapy peripheral blood counts and the optimal cutoff value was determined by a receiver operator characteristic curve. PFS and OS were evaluated using the Kaplan-Meier method and multivariate Cox proportional hazard modeling. Patients with an LMR of at least 1.7 showed improved PFS (hazard ratio=0.55; 95% confidence interval: 0.34-0.92; P=0.024) and OS (hazard ratio=0.29; 95% confidence interval: 0.15-0.59; P=0.0007). The baseline LMR is associated with PFS and OS in metastatic melanoma patients treated with pembrolizumab, and could represent a convenient and cost-effective prognostic biomarker. Validation of these findings in an independent cohort is needed.

  14. Novel nitric oxide producing probiotic wound healing patch: preparation and in vivo analysis in a New Zealand white rabbit model of ischaemic and infected wounds.

    PubMed

    Jones, Mitchell; Ganopolsky, Jorge G; Labbé, Alain; Gilardino, Mirko; Wahl, Christopher; Martoni, Christopher; Prakash, Satya

    2012-06-01

    The treatment of chronic wounds poses a significant challenge for clinicians and patients alike. Here we report design and preclinical efficacy of a novel nitric oxide gas (gNO)-producing probiotic patch for wound healing. Specifically, a wound healing patch using lactic acid bacteria in an adhesive gas permeable membrane has been designed and investigated for treating ischaemic and infected full-thickness dermal wounds in a New Zealand white rabbit model for ischaemic wound healing. Kaplan-Meier survival curves showed increased wound closure with gNO-producing patch-treated wounds over 21 days of therapy (log-rank P = 0·0225 and Wilcoxon P = 0·0113). Cox proportional hazard regression showed that gNO-producing patch-treated wounds were 2·52 times more likely to close compared with control patches (hazard P = 0·0375, score P = 0·032 and likelihood ratio P = 0·0355), and histological analysis showed improved wound healing in gNO-producing patch-treated animals. This study may provide an effective, safe and less costly alternative for treating chronic wounds. © 2012 The Authors. © 2012 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

  15. Prognostic significance of epidermal growth factor receptor (EGFR) over expression in urothelial carcinoma of urinary bladder.

    PubMed

    Hashmi, Atif Ali; Hussain, Zubaida Fida; Irfan, Muhammad; Khan, Erum Yousuf; Faridi, Naveen; Naqvi, Hanna; Khan, Amir; Edhi, Muhammad Muzzammil

    2018-06-07

    Epidermal growth factor receptor (EGFR) has been shown to have abnormal expression in many human cancers and is considered as a marker of poor prognosis. Frequency of over expression in bladder cancer has not been studied in our population; therefore we aimed to evaluate the frequency and prognostic significance of EGFR immunohistochemical expression in locoregional population. We performed EGFR immunohistochemistry on 126 cases of bladder cancer and association of EGFR expression with tumor grade, lamina propria invasion, deep muscle invasion and recurrence of disease was evaluated. High EGFR expression was noted in 26.2% (33 cases), 15.1% (19 cases) and 58.7% (74 cases) revealed low and no EGFR expression respectively. Significant association of EGFR expression was noted with tumor grade, lamina propria invasion, deep muscle invasion and recurrence status while no significant association was seen with age, gender and overall survival. Kaplan- Meier curves revealed significant association of EGFR expression with recurrence while no significant association was seen with overall survival. Significant association of EGFR overexpression with tumor grade, muscularis propria invasion and recurrence signifies its prognostic value; therefore EGFR can be used as a prognostic biomarker in Urothelial bladder carcinoma.

  16. [A boy with Meier-Gorlin syndrome carrying a novel ORC6 mutation and uniparental disomy of chromosome 16].

    PubMed

    Li, Juan; Ding, Yu; Chang, Guoying; Cheng, Qing; Li, Xin; Wang, Jian; Wang, Xiumin; Shen, Yiping

    2017-02-10

    To identify the genetic cause for a 11-year-old Chinese boy with Meier-Gorlin syndrome (MGS). Chromosomal microarray analysis (CMA) was used to detect potential variations, while whole exome sequencing (WES) was used to identify sequence variants. Sanger sequencing was used to confirm the suspected variants. The boy has featured short stature, microtia, small patella, slender body build, craniofacial anomalies, and small testes with normal gonadotropin. A complete uniparental disomy of chromosome 16 was revealed by CMA. WES has identified a novel homozygous mutation c.67A>G (p.Lys23Glu) in ORC6 gene mapped to chromosome 16. As predicted by Alamut functional software, the mutation may affect the function of structural domain of the ORC6 protein. The patient is probably the first diagnosed MGS case in China, who carried a novel homozygous mutation of the ORC6 gene and uniparental disomy of chromosome 16. The effect of this novel mutation on the growth and development needs to be further investigated.

  17. Meier-Gorlin syndrome: growth and secondary sexual development of a microcephalic primordial dwarfism disorder.

    PubMed

    de Munnik, Sonja A; Otten, Barto J; Schoots, Jeroen; Bicknell, Louise S; Aftimos, Salim; Al-Aama, Jumana Y; van Bever, Yolande; Bober, Michael B; Borm, George F; Clayton-Smith, Jill; Deal, Cheri L; Edrees, Alaa Y; Feingold, Murray; Fryer, Alan; van Hagen, Johanna M; Hennekam, Raoul C; Jansweijer, Maaike C E; Johnson, Diana; Kant, Sarina G; Opitz, John M; Ramadevi, A Radha; Reardon, Willie; Ross, Alison; Sarda, Pierre; Schrander-Stumpel, Constance T R M; Sluiter, A Erik; Temple, I Karen; Terhal, Paulien A; Toutain, Annick; Wise, Carol A; Wright, Michael; Skidmore, David L; Samuels, Mark E; Hoefsloot, Lies H; Knoers, Nine V A M; Brunner, Han G; Jackson, Andrew P; Bongers, Ernie M H F

    2012-11-01

    Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by primordial dwarfism, microtia, and patellar aplasia/hypoplasia. Recently, mutations in the ORC1, ORC4, ORC6, CDT1, and CDC6 genes, encoding components of the pre-replication complex, have been identified. This complex is essential for DNA replication and therefore mutations are expected to impair cell proliferation and consequently could globally reduce growth. However, detailed growth characteristics of MGS patients have not been reported, and so this is addressed here through study of 45 MGS patients, the largest cohort worldwide. Here, we report that growth velocity (length) is impaired in MGS during pregnancy and first year of life, but, thereafter, height increases in paralleled normal reference centiles, resulting in a mean adult height of -4.5 standard deviations (SD). Height is dependent on ethnic background and underlying molecular cause, with ORC1 and ORC4 mutations causing more severe short stature and microcephaly. Growth hormone therapy (n = 9) was generally ineffective, though in two patients with significantly reduced IGF1 levels, growth was substantially improved by GH treatment, with 2SD and 3.8 SD improvement in height. Growth parameters for monitoring growth in future MGS patients are provided and as well we highlight that growth is disproportionately affected in certain structures, with growth related minor genital abnormalities (42%) and mammary hypoplasia (100%) frequently present, in addition to established effects on ears and patellar growth. Copyright © 2012 Wiley Periodicals, Inc.

  18. Long-Term Outcomes of Anterior Cruciate Ligament Reconstruction Using Either Synthetics With Remnant Preservation or Hamstring Autografts: A 10-Year Longitudinal Study.

    PubMed

    Chen, Tianwu; Zhang, Peng; Chen, Jiwu; Hua, Yinghui; Chen, Shiyi

    2017-10-01

    The optimal graft choice of anterior cruciate ligament (ACL) reconstruction remains controversial. To compare the outcomes, especially the long-term cumulative failure rate, of ACL reconstruction using either synthetics with remnant preservation or hamstring autografts (4-strand semitendinosus and gracilis tendons). Cohort study; Level of evidence, 2. A total of 133 patients who underwent ACL reconstruction (synthetics: n = 43; hamstring autografts: n = 90) between July 2004 and December 2007 were included. Questionnaires (Tegner activity scale, Lysholm knee scale, and International Knee Documentation Committee [IKDC] subjective form) were completed preoperatively and at 6 months, 1 year, 5 years, and 10 years postoperatively. The Knee injury and Osteoarthritis Outcome Score (KOOS) was additionally applied at 10 years' follow-up. The physical examination was based on the 2000 IKDC form. The manual maximum side-to-side difference (KT-1000 arthrometer), single-hop test, thigh muscle atrophy, and joint degeneration (Kellgren and Lawrence classification) were evaluated. The Kaplan-Meier curve and log-rank test (Mantel-Cox, 95% CI) were used to compare graft survivorship. Ten years postoperatively, 111 patients were available, with 38 (88.4%) patients (mean age, 27.6 ± 9.3 years; 28 men) with synthetics and 73 (81.1%) patients (mean age, 28.6 ± 8.8 years; 64 men) with hamstring autografts. Among them, 104 patients (synthetics: n = 35 [81.4%]; hamstring autografts: n = 69 [76.7%]) completed subjective evaluations, and 89 patients (synthetics: n = 30 [69.8%]; hamstring autografts: n = 59 [65.6%]) completed objective evaluations. For hamstring autografts and synthetics, the cumulative failure rates were 8.2% and 7.9%, respectively, and the log-rank test demonstrated no significant difference between the 2 Kaplan-Meier survival curves ( P = .910). At 6 months postoperatively, for hamstring autografts and synthetics, the mean Lysholm score was 83.0 ± 7.8 and 88.1 ± 7

  19. Measurement of M2-Curve for Asymmetric Beams by Self-Referencing Interferometer Wavefront Sensor

    PubMed Central

    Du, Yongzhao

    2016-01-01

    For asymmetric laser beams, the values of beam quality factor Mx2 and My2 are inconsistent if one selects a different coordinate system or measures beam quality with different experimental conditionals, even when analyzing the same beam. To overcome this non-uniqueness, a new beam quality characterization method named as M2-curve is developed. The M2-curve not only contains the beam quality factor Mx2 and My2 in the x-direction and y-direction, respectively; but also introduces a curve of Mxα2 versus rotation angle α of coordinate axis. Moreover, we also present a real-time measurement method to demonstrate beam propagation factor M2-curve with a modified self-referencing Mach-Zehnder interferometer based-wavefront sensor (henceforth SRI-WFS). The feasibility of the proposed method is demonstrated with the theoretical analysis and experiment in multimode beams. The experimental results showed that the proposed measurement method is simple, fast, and a single-shot measurement procedure without movable parts. PMID:27916845

  20. Developing Novel Reservoir Rule Curves Using Seasonal Inflow Projections

    NASA Astrophysics Data System (ADS)

    Tseng, Hsin-yi; Tung, Ching-pin

    2015-04-01

    Due to significant seasonal rainfall variations, reservoirs and their flexible operational rules are indispensable to Taiwan. Furthermore, with the intensifying impacts of climate change on extreme climate, the frequency of droughts in Taiwan has been increasing in recent years. Drought is a creeping phenomenon, the slow onset character of drought makes it difficult to detect at an early stage, and causes delays on making the best decision of allocating water. For these reasons, novel reservoir rule curves using projected seasonal streamflow are proposed in this study, which can potentially reduce the adverse effects of drought. This study dedicated establishing new rule curves which consider both current available storage and anticipated monthly inflows with leading time of two months to reduce the risk of water shortage. The monthly inflows are projected based on the seasonal climate forecasts from Central Weather Bureau (CWB), which a weather generation model is used to produce daily weather data for the hydrological component of the GWLF. To incorporate future monthly inflow projections into rule curves, this study designs a decision flow index which is a linear combination of current available storage and inflow projections with leading time of 2 months. By optimizing linear relationship coefficients of decision flow index, the shape of rule curves and the percent of water supply in each zone, the best rule curves to decrease water shortage risk and impacts can be developed. The Shimen Reservoir in the northern Taiwan is used as a case study to demonstrate the proposed method. Existing rule curves (M5 curves) of Shimen Reservoir are compared with two cases of new rule curves, including hindcast simulations and historic seasonal forecasts. The results show new rule curves can decrease the total water shortage ratio, and in addition, it can also allocate shortage amount to preceding months to avoid extreme shortage events. Even though some uncertainties in

  1. Computerised curve deconvolution of TL/OSL curves using a popular spreadsheet program.

    PubMed

    Afouxenidis, D; Polymeris, G S; Tsirliganis, N C; Kitis, G

    2012-05-01

    This paper exploits the possibility of using commercial software for thermoluminescence and optically stimulated luminescence curve deconvolution analysis. The widely used software package Microsoft Excel, with the Solver utility has been used to perform deconvolution analysis to both experimental and reference glow curves resulted from the GLOw Curve ANalysis INtercomparison project. The simple interface of this programme combined with the powerful Solver utility, allows the analysis of complex stimulated luminescence curves into their components and the evaluation of the associated luminescence parameters.

  2. Design curves for circular and annular duct silencers

    NASA Technical Reports Server (NTRS)

    Watson, Willie R.; Ramakrishnan, R.

    1989-01-01

    Conventional models of sound propagation between porous walls (Scott, 1946) are adapted in order to calculate design curves for the lined circular and annular-duct silencers used in HVAC systems. The derivation of the governing equations is outlined, and results for two typical cases are presented graphically. Good agreement with published experimental data is demonstrated.

  3. Jackknife variance of the partial area under the empirical receiver operating characteristic curve.

    PubMed

    Bandos, Andriy I; Guo, Ben; Gur, David

    2017-04-01

    Receiver operating characteristic analysis provides an important methodology for assessing traditional (e.g., imaging technologies and clinical practices) and new (e.g., genomic studies, biomarker development) diagnostic problems. The area under the clinically/practically relevant part of the receiver operating characteristic curve (partial area or partial area under the receiver operating characteristic curve) is an important performance index summarizing diagnostic accuracy at multiple operating points (decision thresholds) that are relevant to actual clinical practice. A robust estimate of the partial area under the receiver operating characteristic curve is provided by the area under the corresponding part of the empirical receiver operating characteristic curve. We derive a closed-form expression for the jackknife variance of the partial area under the empirical receiver operating characteristic curve. Using the derived analytical expression, we investigate the differences between the jackknife variance and a conventional variance estimator. The relative properties in finite samples are demonstrated in a simulation study. The developed formula enables an easy way to estimate the variance of the empirical partial area under the receiver operating characteristic curve, thereby substantially reducing the computation burden, and provides important insight into the structure of the variability. We demonstrate that when compared with the conventional approach, the jackknife variance has substantially smaller bias, and leads to a more appropriate type I error rate of the Wald-type test. The use of the jackknife variance is illustrated in the analysis of a data set from a diagnostic imaging study.

  4. Functional polymorphisms of circadian negative feedback regulation genes are associated with clinical outcome in hepatocellular carcinoma patients receiving radical resection.

    PubMed

    Zhang, Zhaohui; Ma, Fei; Zhou, Feng; Chen, Yibing; Wang, Xiaoyan; Zhang, Hongxin; Zhu, Yong; Bi, Jianwei; Zhang, Yiguan

    2014-12-01

    Previous studies have demonstrated that circadian negative feedback loop genes play an important role in the development and progression of many cancers. However, the associations between single-nucleotide polymorphisms (SNPs) in these genes and the clinical outcomes of hepatocellular carcinoma (HCC) after surgical resection have not been studied so far. Thirteen functional SNPs in circadian genes were genotyped using the Sequenom iPLEX genotyping system in a cohort of 489 Chinese HCC patients who received radical resection. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognosis analysis. Cumulative effect analysis and survival tree analysis were used for the multiple SNPs analysis. Four individual SNPs, including rs3027178 in PER1, rs228669 and rs2640908 in PER3 and rs3809236 in CRY1, were significantly associated with overall survival (OS) of HCC patients, and three SNPs, including rs3027178 in PER1, rs228729 in PER3 and rs3809236 in CRY1, were significantly associated with recurrence-free survival (RFS). Moreover, we observed a cumulative effect of significant SNPs on OS and RFS (P for trend < 0.001 for both). Survival tree analysis indicated that wild genotype of rs228729 in PER3 was the primary risk factor contributing to HCC patients' RFS. Our study suggests that the polymorphisms in circadian negative feedback loop genes may serve as independent prognostic biomarkers in predicting clinical outcomes for HCC patients who received radical resection. Further studies with different ethnicities are needed to validate our findings and generalize its clinical utility.

  5. A Pessimistic Explanatory Style is Prognostic for Poor Lung Cancer Survival

    PubMed Central

    Novotny, Paul; Colligan, Robert C.; Szydlo, Daniel W.; Clark, Matthew M.; Rausch, Sarah; Wampfler, Jason; Sloan, Jeff A.; Yang, Ping

    2010-01-01

    Background Several studies have demonstrated the importance of personality constructs on health behaviors and health status. Having a pessimistic outlook has been related to negative health behaviors and higher mortality. However, the construct has not been well explored in cancer populations. Methods Survival time of 534 adults, who were diagnosed with lung cancer and had a pessimistic explanatory style, was examined. The patients had completed the Minnesota Multiphasic Personality Inventory (MMPI) approximately 18.2 years prior to receiving their lung cancer diagnosis. MMPI Optimism-Pessimism (PSM) scores were divided into high (60 or more) and low scores (less than 60), and log-rank tests and Kaplan-Meier curves were used to determine survival differences. Multivariate Cox models were used for assessing prognostic values of pessimism along with other known predictors for lung cancer survival outcome. Booting strapping of the survival models was used as a sensitivity analysis. Results At the time of lung cancer diagnosis, patients were on average 67 years old; 48% were female; 85% had non-small cell lung cancer (NSCLC); 15% had small cell lung cancer (SCLC); 30% were stage I; 4% were stage II; 31% were stage III/limited; and 35% were stage IV/extensive. Patients who exhibited a non-pessimistic explanatory style survived approximately six months longer than patients classified as having a pessimistic explanatory style. Conclusion Among lung cancer patients, those having a pessimistic explanatory style experienced less favorable survival outcome, which may be related to cancer treatment decisions. Further research in this area is warranted. PMID:20139778

  6. Survivorship of the native hip joint after percutaneous repair of acetabular fractures in the elderly.

    PubMed

    Gary, Joshua L; Lefaivre, Kelly A; Gerold, Frank; Hay, Michael T; Reinert, Charles M; Starr, Adam J

    2011-10-01

    Our purpose was to examine survivorship of the native hip joint in patients ages 60 and over who underwent percutaneous reduction and fixation of acetabular fractures. A retrospective review at a University Level I Trauma Center was performed. Our institutional trauma database was reviewed. Patients aged 60 or older treated with percutaneous reduction and fixation of acetabular fractures between 1994 and 2007 were selected. 79 consecutive patients with 80 fractures were identified. Rate of conversion to total hip arthroplasty were used to construct a Kaplan-Meier curve showing survivorship of the native hip joint after treatment. 75 fractures had adequate clinical follow-up with a mean of 3.9 years (range 0.5-11.9 years). Average blood loss was 69 cc and there were no postoperative infections. 19/75 (25%) were converted to total hip arthroplasty at a mean time of 1.4 years after the index procedure. Survivorship analysis demonstrated a cumulative survival of 65% at 11.9 years of follow-up. There were no conversions to arthroplasty beyond 4.7 years postoperatively. There were no statistically significant associations between conversion to arthroplasty and age, sex, closed vs. limited open reduction, and simple vs. complex fracture pattern. Percutaneous fixation is a viable treatment option for patients age 60 or greater with acetabular fractures. Rates of conversion to total hip arthroplasty are comparable to open treatment methods and if conversion is required, soft tissues are preserved for future surgery. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Cathepsin B Expression and the Correlation with Clinical Aspects of Oral Squamous Cell Carcinoma.

    PubMed

    Yang, Wei-En; Ho, Chuan-Chen; Yang, Shun-Fa; Lin, Shu-Hui; Yeh, Kun-Tu; Lin, Chiao-Wen; Chen, Mu-Kuan

    2016-01-01

    Cathepsin B (CTSB), a member of the cathepsin family, is a cysteine protease that is widely distributed in the lysosomes of cells in various tissues. It is overexpressed in several human cancers and may be related to tumorigenesis. The main purpose of this study was to analyze CTSB expression in oral squamous cell carcinoma (OSCC) and its correlation with patient prognosis. Tissue microarrays were used to detect CTSB expression in 280 patients and to examine the association between CTSB expression and clinicopathological parameters. In addition, the metastatic effects of the CTSB knockdown on two oral cancer cell lines were investigated by transwell migration assay. Cytoplasmic CTSB expression was detected in 34.6% (97/280) of patients. CTSB expression was correlated with positive lymph node metastasis (p = 0.007) and higher tumor grade (p = 0.008) but not with tumor size and distant metastasis. In addition, multivariate analysis using a Cox proportional hazards model revealed a higher hazard ratio, demonstrating that CTSB expression was an independent unfavorable prognostic factor in buccal mucosa carcinoma patients. Furthermore, the Kaplan-Meier curve revealed that buccal mucosa OSCC patients with positive CTSB expression had significantly shorter overall survival. Moreover, treatment with the CTSB siRNA exerted an inhibitory effect on migration in OC2 and CAL27 oral cancer cells. We conclude that CTSB expression may be useful for determining OSCC prognosis, particularly for patients with lymph node metastasis, and may function as a biomarker of the survival of OSCC patients in Taiwan.

  8. Is multifocality a prognostic factor in childhood hepatoblastoma?

    PubMed

    Saettini, Francesco; Conter, Valentino; Provenzi, Massimo; Rota, Matteo; Giraldi, Eugenia; Foglia, Carlo; Cavalleri, Laura; D'Antiga, Lorenzo

    2014-09-01

    The aim of this study was to assess the prognostic value of multifocality and the effectiveness of two different therapeutic strategies in patients with newly diagnosed hepatoblastoma. Between 1998 and 2011, 31 patients diagnosed with hepatoblastoma were referred to Ospedale Papa Giovanni XXIII, Bergamo, Italy. Patients were stratified according to SIOPEL protocols into high-risk (HR if AFP <100 ng/mL and/or PRETEXT IV and/or vascular invasion and/or extra-hepatic intra-abdominal disease and/or metastases) and standard-risk (SR, all others). The patient data we evaluated were: multifocality; patient age; gender; platelet count; AFP level at diagnosis, during treatment and follow-up; histotype; gestational age; birth weight; surgery (either resection or transplantation) and chemotherapy regimen adopted before and after surgery. The outcome measures were event free survival (EFS) and overall survival (OS); survival curves were estimated according to Kaplan-Meier. EFS and OS were associated significantly with multifocality (3-year EFS 40% vs. 95%, P = 0.006; 3-year OS 42% vs. 95%, P = 0.004). Multivariate analysis demonstrated that multifocality predicts lower EFS (hazard ratio 10.01, P = 0.007). Other factors at diagnosis did not reach statistical significance. A marked treatment dependent improvement was associated with intensive chemotherapy given both before and after liver transplantation (P = 0.06). Patients diagnosed with multifocal tumors had lower EFS levels. Multifocality should be taken into account for future stratification and further studied to assess genetic profile, immunochemistry and prognostic role. © 2014 Wiley Periodicals, Inc.

  9. Do BRCA1/2 mutation carriers have an earlier onset of natural menopause?

    PubMed

    van Tilborg, Theodora C; Broekmans, Frank J; Pijpe, Anouk; Schrijver, Lieske H; Mooij, Thea M; Oosterwijk, Jan C; Verhoef, Senno; Gómez Garcia, Encarna B; van Zelst-Stams, Wendy A; Adank, Muriel A; van Asperen, Christi J; van Doorn, Helena C; van Os, Theo A; Bos, Anna M; Rookus, Matti A; Ausems, Margreet G

    2016-08-01

    It has been hypothesized that BRCA1/2 mutation carriers have an earlier age at natural menopause (ANM), although to date findings are inconclusive. This study assessed the influence of BRCA mutation status on ANM, and aimed to explore the reasons of inconsistency in the literature. Cross-sectional assessment from an ongoing nationwide cohort study among members of BRCA1/2 mutated families. Information was obtained by a standardized questionnaire. Kaplan-Meier curves were constructed, and Cox regression was used to assess the association between BRCA1/2 mutation status and ANM. Adjustments were made for birth cohort, family, smoking, use of hormonal contraceptives, and parity. A total of 1,208 BRCA1/2 mutation carriers and 2,211 proven noncarriers were included. Overall, no association was found between BRCA1/2 mutation status and ANM (adjusted hazard ratio [HR] = 1.06 [95% CI, 0.87-1.30]). We examined if the null finding was due to informative censoring by uptake of risk-reducing salpingo-oophorectomy. Indeed, within the oldest birth cohort, in which the percentage of surgical menopause events was lowest and comparable between carriers and noncarriers, the HR for earlier natural menopause in carriers was 1.45 (95% CI, 1.09-1.94). The second oldest birth cohort, however, demonstrated a decreased HR (0.67 [95% CI, 0.46-0.98]), and thus no trend over birth cohorts was found. Various types of selection bias hamper the comparison of ANM between BRCA1/2 mutation carriers and noncarriers, genetically tested in the clinic.

  10. An analysis of the gene interaction networks identifying the role of PARP1 in metastasis of non-small cell lung cancer.

    PubMed

    Chen, Kai; Li, Yajie; Xu, Hui; Zhang, Chunfeng; Li, Zhiqiang; Wang, Wei; Wang, Baofeng

    2017-10-20

    Though there were many researches about the effects of cancer cells on non-small cell lung cancer (NSCLC) currently, it has been rarely reported completed oncogene and its mechanism in tumors by far. Here, we used biological methods with known oncogene of NSCLC to find new oncogene and explore its functionary mechanism in NSCLC. The study firstly built NSCLC genetic interaction network based on bioinformatics methods and then combined shortest path algorithm with significance test to confirmed core genes that were closely involved with given genes; real-time qPCR was conducted to detect expression levels between patients with NSCLC and normal people; additionally, detection of PARP1's role in migration and invasion was performed by trans-well assays and wound-healing. Through gene interaction network, it was found that, core genes like PARP1, EGFR and ALK had a direct interaction. TCGA database showed that PARP1 presented strong expression in NSCLC and the expression level of metastatic NSCLC was significantly higher than that of non-metastatic NSCLC. Cell migration of NSCLC in accordance to the scratch test was suppressed by PARP1 silence but stimulated noticeably by PARP1 overexpression. According to Kaplan-meier survival curve, the higher PARP1 expression, the poorer patient survival rate and prognosis. Thus, PARP1 expression had a negative correction with patient survival rate and prognosis. New oncogene PARP1 was found from known NSCLC oncogene in terms of gene interaction network, demonstrating PARP1's impact on NSCLC cell migration.

  11. Cut-point for Ki-67 proliferation index as a prognostic marker for glioblastoma.

    PubMed

    Wong, Eugene; Nahar, Najmun; Hau, Eric; Varikatt, Winny; Gebski, Val; Ng, Thomas; Jayamohan, Jayasingham; Sundaresan, Puma

    2018-01-16

    Ki-67 proliferation index (Ki-67 index) is used to quantify cell proliferation during histopathological assessment of various tumors including glioblastoma (GB). We aimed to assess correlation between Ki-67 index and overall survival in patients with GB and determine a cut-point for Ki-67 index that predicts for poorer survival. Records of adult patients diagnosed with GB on histopathological specimens at a tertiary cancer center in Sydney between 1 January 2002 and 30 July 2012 were retrieved. Specimens of these patients were examined for quantification of Ki-67 staining by two independent pathologists. Patient, disease, treatment, and survival data were collected from hospital and cancer care service records. Statistical analysis was performed using proportional hazards models, Kaplan-Meier curves, and the minimum P-value approach. Of the eligible 71 patients, 58% were males with median age of 58 (range 18-87). Seventy-three percent of patients were of ECOG performance status 0-1. There was a statistically significant correlation between Ki-67 index and overall survival. In patients with Ki-67 > 22% (n = 36), 5-year survival was approximately 30% compared to 5% in those with Ki-67 ≤ 22% (n = 35; log-rank P-value = 0.04; hazard ratio (HR) = 0.53; 95% confidence intervals (CI), 0.29-0.97). This study demonstrates a positive correlation between Ki-67 index and overall survival in patients with GB. Percentage staining of Ki-67 < 22% appears to predict for poorer survival in GB. © 2018 John Wiley & Sons Australia, Ltd.

  12. l-DOPA Decarboxylase (DDC) Expression Status as a Novel Molecular Tumor Marker for Diagnostic and Prognostic Purposes in Laryngeal Cancer.

    PubMed

    Patsis, Christos; Glyka, Vasiliki; Yiotakis, Ioannis; Fragoulis, Emmanuel G; Scorilas, Andreas

    2012-08-01

    l-DOPA decarboxylase (DDC) plays an essential role in the enzymatic synthesis of dopamine and alterations in its gene expression have been reported in several malignancies. Our objective was to analyze DDC messenger RNA (mRNA) and protein expression in laryngeal tissues and to evaluate the clinical implication of this molecule in laryngeal cancer. In this study, total RNA was isolated from 157 tissue samples surgically removed from 100 laryngeal cancer patients. A highly sensitive real-time polymerase chain reaction methodology based on SYBR Green I fluorescent dye was developed for the quantification of DDC mRNA levels. In addition, Western blot analysis was performed for the detection of DDC protein. DDC mRNA expression was revealed to be significantly downregulated in primary laryngeal cancer samples compared with their nonmalignant counterparts (P = .001). A significant negative association was also disclosed between DDC mRNA levels and TNM staging (P = .034). Univariate analysis showed that patients bearing DDC-positive tumors had a significantly decreased risk of death (hazard ratio = 0.23, P = .012) and local recurrence (hazard ratio = 0.32, P =.006), whereas DDC expression retained its favorable prognostic significance in the multivariate analysis. Kaplan-Meier curves further demonstrated that DDC-positive patients experienced longer overall and disease-free survival periods (P = .006 and P = .004, respectively). Moreover, DDC protein was detected in both neoplastic and noncancerous tissues. Therefore, our results suggest that DDC expression status could qualify as a promising biomarker for the future clinical management of laryngeal cancer patients.

  13. l-DOPA Decarboxylase (DDC) Expression Status as a Novel Molecular Tumor Marker for Diagnostic and Prognostic Purposes in Laryngeal Cancer1

    PubMed Central

    Patsis, Christos; Glyka, Vasiliki; Yiotakis, Ioannis; Fragoulis, Emmanuel G; Scorilas, Andreas

    2012-01-01

    l-DOPA decarboxylase (DDC) plays an essential role in the enzymatic synthesis of dopamine and alterations in its gene expression have been reported in several malignancies. Our objective was to analyze DDC messenger RNA (mRNA) and protein expression in laryngeal tissues and to evaluate the clinical implication of this molecule in laryngeal cancer. In this study, total RNA was isolated from 157 tissue samples surgically removed from 100 laryngeal cancer patients. A highly sensitive real-time polymerase chain reaction methodology based on SYBR Green I fluorescent dye was developed for the quantification of DDC mRNA levels. In addition, Western blot analysis was performed for the detection of DDC protein. DDC mRNA expression was revealed to be significantly downregulated in primary laryngeal cancer samples compared with their nonmalignant counterparts (P = .001). A significant negative association was also disclosed between DDC mRNA levels and TNM staging (P = .034). Univariate analysis showed that patients bearing DDC-positive tumors had a significantly decreased risk of death (hazard ratio = 0.23, P = .012) and local recurrence (hazard ratio = 0.32, P =.006), whereas DDC expression retained its favorable prognostic significance in the multivariate analysis. Kaplan-Meier curves further demonstrated that DDC-positive patients experienced longer overall and disease-free survival periods (P = .006 and P = .004, respectively). Moreover, DDC protein was detected in both neoplastic and noncancerous tissues. Therefore, our results suggest that DDC expression status could qualify as a promising biomarker for the future clinical management of laryngeal cancer patients. PMID:22937181

  14. Stromal mast cells in invasive breast cancer are a marker of favourable prognosis: a study of 4,444 cases.

    PubMed

    Rajput, Ashish B; Turbin, Dmitry A; Cheang, Maggie Cu; Voduc, David K; Leung, Sam; Gelmon, Karen A; Gilks, C Blake; Huntsman, David G

    2008-01-01

    We have previously demonstrated in a pilot study of 348 invasive breast cancers that mast cell (MC) infiltrates within primary breast cancers are associated with a good prognosis. Our aim was to verify this finding in a larger cohort of invasive breast cancer patients and examine the relationship between the presence of MCs and other clinical and pathological features. Clinically annotated tissue microarrays (TMAs) containing 4,444 cases were constructed and stained with c-Kit (CD-117) using standard immunoperoxidase techniques to identify and quantify MCs. For statistical analysis, we applied a split-sample validation technique. Breast cancer specific survival was analyzed by Kaplan-Meier [KM] method and log rank test was used to compare survival curves. Survival analysis by KM method showed that the presence of stromal MCs was a favourable prognostic factor in the training set (P = 0.001), and the validation set group (P = 0.006). X-tile plot generated to define the optimal number of MCs showed that the presence of any number of stromal MCs predicted good prognosis. Multivariate analysis showed that the MC effect in the training set (Hazard ratio [HR] = 0.804, 95% Confidence interval [CI], 0.653-0.991, P = 0.041) and validation set analysis (HR = 0.846, 95% CI, 0.683-1.049, P = 0.128) was independent of age, tumor grade, tumor size, lymph node, ER and Her2 status. This study concludes that stromal MC infiltration in invasive breast cancer is an independent good prognostic marker and reiterates the critical role of local inflammatory responses in breast cancer progression.

  15. Clinical Usefulness of Measuring Red Blood Cell Distribution Width in Patients with Hepatitis B Virus-Related Acute-On-Chronic Liver Failure.

    PubMed

    Jin, Lei; Gao, Yufeng; Ye, Jun; Zou, Guizhou; Li, Xu

    2017-09-01

    The red blood cell distribution width (RDW) is increased in chronic liver disease, but its clinical significance in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is still unclear. The aim of the present study was to investigate the clinical significance of RDW in HBV-ACLF patients. The medical records of HBV-ACLF patients who were admitted to The Second Affiliated Hospital of Anhui Medical University between April 2012 and December 2015 were retrospectively reviewed. Correlations between RDW, neutrophil lymphocyte ratio (NLR), and the model for end-stage liver disease (MELD) scores were analyzed using the Spearman's approach. Multivariable stepwise logistic regression test was used to evaluate independent clinical parameters predicting 3-month mortality of HBV-ACLF patients. The association between RDW and hospitalization outcome was estimated by receiver operating curve (ROC) analysis. Patient survival was estimated by Kaplan-Meier analysis and subsequently compared by log-rank test. Sixty-two HBV-ACLF patients and sixty CHB patients were enrolled. RDW were increased in HBVACLF patients and positively correlated with the NLR as well as MELD scores. Multivariate analysis demonstrated that RDW value was an independent predictor for mortality. RDW had an area under the ROC of 0.799 in predicting 3-month mortality of HBV-ACLF patients. Patients with HBV-ACLF who had RDW > 17% showed significantly poorer survival than those who had RDW ≤ 17%. RDW values are significantly increased in patients with HBV-ACLF. Moreover, RDW values are an independent predicting factor for an in-hospital mortality in patients with HBV-ACLF.

  16. Development and Assessment of a New Empirical Model for Predicting Full Creep Curves

    PubMed Central

    Gray, Veronica; Whittaker, Mark

    2015-01-01

    This paper details the development and assessment of a new empirical creep model that belongs to the limited ranks of models reproducing full creep curves. The important features of the model are that it is fully standardised and is universally applicable. By standardising, the user no longer chooses functions but rather fits one set of constants only. Testing it on 7 contrasting materials, reproducing 181 creep curves we demonstrate its universality. New model and Theta Projection curves are compared to one another using an assessment tool developed within this paper. PMID:28793458

  17. Multiple Optical Traps with a Single-Beam Optical Tweezer Utilizing Surface Micromachined Planar Curved Grating

    NASA Astrophysics Data System (ADS)

    Kuo, Ju-Nan; Chen, Kuan-Yu

    2010-11-01

    In this paper, we present a single-beam optical tweezer integrated with a planar curved diffraction grating for microbead manipulation. Various curvatures of the surface micromachined planar curved grating are systematically investigated. The planar curved grating was fabricated using multiuser micro-electro-mechanical-system (MEMS) processes (MUMPs). The angular separation and the number of diffracted orders were determined. Experimental results indicate that the diffraction patterns and curvature of the planar curved grating are closely related. As the curvature of the planar curved grating increases, the vertical diffraction angle increases, resulting in the strip patterns of the planar curved grating. A single-beam optical tweezer integrated with a planar curved diffraction grating was developed. We demonstrate a technique for creating multiple optical traps from a single laser beam using the developed planar curved grating. The strip patterns of the planar curved grating that resulted from diffraction were used to trap one row of polystyrene beads.

  18. How long will I have my ACE? The natural history of the antegrade continence enema stoma in idiopathic constipation.

    PubMed

    Khoo, A Kate; Askouni, Evita; Basson, Sonia; Ng, Jessica; Cleeve, Stewart

    2017-11-01

    We aim to determine the natural history of the ACE in idiopathic constipation and factors predictive of closure. A retrospective case-note review of all patients undergo ACE formation for idiopathic constipation Jan 2003-Mar 2016. Kaplan-Meier analysis was used to determine ACE survival and Cox's proportional hazard models to examine potential predictors of closure. 29/84 (35%) ACEs were closed: 21/84 due to success and 8/84 due to failure. Median age of closure was 15.5 years (3.5-23.6). Median ACE survival was 77.0 months (95% CI 58.0-96.0). An ACE survival curve was derived from which we estimate that 5-year post-ACE, one-third of patients can expect to have had their ACE closed. Younger age at ACE was predictive of earlier closure (p = 0.023) and closure for success (p < 0.001). Neither patient sex (p = 0.546) nor presence of psychological comorbidities (p = 0.769) predicted likelihood of closure. Incontinence 6-week post-ACE was also associated with increased likelihood of closure (p = 0.042). The ACE survival curve estimates the proportion of patients with idiopathic constipation who can expect closure (either due to success or failure) at certain timepoints. This may be useful for patient counseling. Younger age at ACE was associated with earlier closure (for success).

  19. Technique-associated outcomes in horses following large colon resection.

    PubMed

    Pezzanite, Lynn M; Hackett, Eileen S

    2017-11-01

    To compare survival and complications in horses undergoing large colon resection with either sutured end-to-end or stapled functional end-to-end anastomoses. Retrospective cohort study. Twenty-six client-owned horses with gastrointestinal disease. Retrospective data were retrieved from the medical records of 26 horses undergoing colectomy, including 14 horses with sutured end-to-end and 12 horses with stapled functional end-to-end anastomoses, between 2003 and 2016. Records were evaluated for signalment, medical and surgical treatments, and survival to hospital discharge. Long-term follow-up was obtained through owner contact. Continuous variables were compared with Mann-Whitney tests. Fisher's exact testing was used to compare survival to hospital discharge. Survival time was compared by constructing Kaplan-Meier survival curves and performing log-rank curve comparison testing. Mean age of horses undergoing colectomy was 13 years. Reason for colectomy was prophylaxis (12) or salvage (14). Mean surgical time was 169 minutes. Mean hospitalization time was 9 days, which did not differ with anastomosis type (P = .62). Nine of 12 horses undergoing stapled functional end-to-end anastomosis and 12 of 14 horses undergoing sutured end-to-end anastomosis survived to hospital discharge (P = .63). Survival time did not differ with anastomosis technique (P = .35). Short- and long-term survival outcomes are not different between sutured end-to-end or stapled functional end-to-end anastomoses in horses undergoing colectomy. © 2017 The American College of Veterinary Surgeons.

  20. Soluble ST2 and N-terminal pro-brain natriuretic peptide combination. Useful biomarker for predicting outcome of childhoodpulmonary arterial hypertension.

    PubMed

    Chida, Ayako; Sato, Hiroki; Shintani, Masaki; Nakayama, Tomotaka; Kawamura, Yoichi; Furutani, Yoshiyuki; Inai, Kei; Saji, Tsutomu; Matsuoka, Rumiko; Nonoyama, Shigeaki; Nakanishi, Toshio

    2014-01-01

    Some potential biomarkers have been reported recently in patients with pulmonary arterial hypertension (PAH), but the most clinically useful among these potential biomarkers, especially in childhood PAH, has not been identified. Therefore, this study investigated which biomarker is useful in assessing severity of and patient prognosis in childhood idiopathic PAH (IPAH)/heritable PAH (HPAH). Fifty-nine patients who were younger than 16 years at onset of IPAH/HPAH were selected. The following 10 biomarker candidates were quantified: high-sensitivity troponin T, human heart fatty acid-binding protein, N-terminal pro-brain natriuretic peptide (NT-proBNP), pentraxin-3, soluble ST2 (sST2), angiopoietin-2 (Ang-2), matrix metalloproteinase 2, tenascin C, endostatin (ES), and thymidine kinase. Functional characteristics and clinical outcomes were analyzed retrospectively. NT-proBNP, sST2, Ang-2, and ES correlated well with New York Heart Association class. On area under the receiver operating characteristic curve analysis, sST2 had a significantly good relationship with prognosis. On Kaplan-Meier curve and univariate Cox regression analyses, elevated sST2 and NT-proBNP level predicted poor outcome of the present patients with childhood IPAH/HPAH. Furthermore, patients with elevated sST2 had significantly worse prognosis among those with high NT-proBNP. The sST2 and NT-proBNP combination is a useful biomarker to predict clinical condition and outcome in patients with childhood IPAH/HPAH.  

  1. Impact of comorbidity on survival by tumour location: Breast, colorectal and lung cancer (2000-2014).

    PubMed

    Parés-Badell, Oleguer; Banqué, Marta; Macià, Francesc; Castells, Xavier; Sala, Maria

    2017-08-01

    To assess the impact of comorbidity, measured by the Charlson Comorbidity Index (CCI), on survival in breast, colorectal and lung cancer. We identified 3455 breast cancer, 3336 colorectal cancer and 2654 lung cancer patients through the Hospital del Mar cancer registry. The prevalence of comorbidities according to the CCI was calculated. Kaplan-Meier curves and the log-rank test were used to compare survival curves for each cancer location. Cox regression was used to calculate survival hazard ratios and 1-, 3- and 5-year mortality rate ratios adjusted by age, sex, CCI, place of first consultation, stage, treatment and period of diagnosis. The overall unadjusted 5-year follow-up survival proportion was 82.6% for breast cancer, 55.7% for colorectal cancer, and 16.3% for lung cancer. Overall survival was associated with CCI≥3 in breast cancer (HR: 2.33 95%CI: 1.76-3.08), colorectal cancer (HR: 1.39; 95%CI: 1.13-1.70) and lung cancer (HR: 1.22; 95%CI: 1.06-1.40). In breast cancer, the higher the CCI, the higher the adjusted mortality rate ratio and differences were greater in 5-year than in 1-year follow-up survival. Comorbidity is a significant predictor of overall survival in cancer patients; however, it has a stronger impact on survival in breast cancer than in colorectal and lung cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Estimating survival of radio-tagged birds

    USGS Publications Warehouse

    Bunck, C.M.; Pollock, K.H.; Lebreton, J.-D.; North, P.M.

    1993-01-01

    Parametric and nonparametric methods for estimating survival of radio-tagged birds are described. The general assumptions of these methods are reviewed. An estimate based on the assumption of constant survival throughout the period is emphasized in the overview of parametric methods. Two nonparametric methods, the Kaplan-Meier estimate of the survival funcrion and the log rank test, are explained in detail The link between these nonparametric methods and traditional capture-recapture models is discussed aloag with considerations in designing studies that use telemetry techniques to estimate survival.

  3. Description of a Heart Team approach to coronary revascularization and its beneficial long-term effect on clinical events after PCI.

    PubMed

    Bonzel, Tassilo; Schächinger, Volker; Dörge, Hilmar

    2016-05-01

    MVD (p < 0.001). Beyond 2 years, Kaplan-Meier curves were linear. The structured Heart Team approach is an effective tool for ad hoc and conference-based clinical decision-making with a sustained clinical benefit. This is demonstrated in low late CABG (and PCI) rates after a 1.PCI, without elevated mortality. The all-comer population supports the universal value of these data. Stable annual event rates late after PCI suggest a conversion to stable CAD. Heart Team conferences are also important tools in cases of valvular and end-stage heart disease.

  4. Pitfalls of inferring annual mortality from inspection of published survival curves.

    PubMed

    Singer, R B

    1994-01-01

    In many FU articles currently published, results are given primarily in the form of graphs of survival curves, rather than in the form of life table data. Sometimes the authors may comment on the slope of the survival curve as though it were equal to the annual mortality rate (after reversal of the minus sign to a plus sign). Even if no comment of this sort is made, medical directors and underwriters may be tempted to think along similar lines in trying to interpret the significance of the survival curve in terms of mortality. However it is a very serious error of life table methodology to conceive of mortality rate as equal to the negative slope of the survival curve. The nature of the error is demonstrated in this article. An annual mortality rate derived from the survival curve actually depends on two variables: a quotient with the negative slope (sign reversed), delta P/ delta as the numerator, and the survival rate, P, itself as the denominator. The implications of this relationship are discussed. If there are two "parallel" survival curves with the same slope at a given time duration, the lower curve will have a higher mortality rate than the upper curve. A constant slope with increasing duration means that the annual mortality rate also increases with duration. Some characteristics of high initial mortality are also discussed and their relation to different units of FU time.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. The Emission, Lifetimes, and Formation Threshold of the Vegard-Kaplan Transition of Solid Nitrogen Exposed to Far-ultraviolet Radiation

    NASA Astrophysics Data System (ADS)

    Lu, Hsiao-Chi; Lo, Jen-Iu; Peng, Yu-Chain; Chou, Sheng-Lung; Lin, Meng-Yeh; Cheng, Bing-Ming

    2016-11-01

    Irradiation of solid nitrogen at 4 K with far-ultraviolet light from a synchrotron caused excitation to the upper state of the Vegard-Kaplan (VK) system; the emission in that system was simultaneously recorded in wavelength region 200-440 nm. The lifetimes of emission lines for VK (0, 1) to (0, 12) transitions were measured in the range of 2.12 ˜ 2.65 s. The threshold wavelength to observe the VK emission was 175.0 ± 3.5 nm, corresponding to energy 7.08 ± 0.14 eV. This investigation of the generation of icy VK nitrogen enhances our understanding of its photochemistry in space.

  6. Disease risk curves.

    PubMed

    Hughes, G; Burnett, F J; Havis, N D

    2013-11-01

    Disease risk curves are simple graphical relationships between the probability of need for treatment and evidence related to risk factors. In the context of the present article, our focus is on factors related to the occurrence of disease in crops. Risk is the probability of adverse consequences; specifically in the present context it denotes the chance that disease will reach a threshold level at which crop protection measures can be justified. This article describes disease risk curves that arise when risk is modeled as a function of more than one risk factor, and when risk is modeled as a function of a single factor (specifically the level of disease at an early disease assessment). In both cases, disease risk curves serve as calibration curves that allow the accumulated evidence related to risk to be expressed on a probability scale. When risk is modeled as a function of the level of disease at an early disease assessment, the resulting disease risk curve provides a crop loss assessment model in which the downside is denominated in terms of risk rather than in terms of yield loss.

  7. The learning curve in robotic distal pancreatectomy.

    PubMed

    Napoli, Niccolò; Kauffmann, Emanuele F; Perrone, Vittorio Grazio; Miccoli, Mario; Brozzetti, Stefania; Boggi, Ugo

    2015-09-01

    No data are available on the learning curve in robotic distal pancreatectomy (RADP). The learning curve in RADP was assessed in 55 consecutive patients using the cumulative sum method, based on operative time. Data were extracted from a prospectively maintained database and analyzed retrospectively considering all events occurring within 90 days of surgery. No operation was converted to laparoscopic or open surgery and no patient died. Post-operative complications occurred in 34 patients (61.8%), being of Clavien-Dindo grade I-II in 32 patients (58.1%), including pancreatic fistula in 29 patients (52.7%). No grade C pancreatic fistula occurred. Four patients received blood transfusions (7.2%), three were readmitted (5.4%) and one required repeat surgery (1.8%). Based on the reduction of operative times (421.1 ± 20.5 vs 248.9 ± 9.3 min; p < 0.0001), completion of the learning curve was achieved after ten operations. Operative time of the first 10 operations was associated with a positive slope (0.47 + 1.78* case number; R (2) 0.97; p < 0.0001*), while that of the following 45 procedures showed a negative slope (23.52 - 0.39* case number; R (2) 0.97; p < 0.0001*). After completion of the learning curve, more patients had a malignant histology (0 vs 35.6%; p = 0.002), accounting for both higher lymph node yields (11.1 ± 12.2 vs 20.9 ± 18.5) (p = 0.04) and lower rate of spleen preservation (90 vs 55.6%) (p = 0.04). RADP was safely feasible in selected patients and the learning curve was completed after ten operations. Improvement in clinical outcome was not demonstrated, probably because of the limited occurrence of outcome comparators.

  8. Transient Elastography is Superior to FIB-4 in Assessing the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B.

    PubMed

    Kim, Seung Up; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Song, Kijun; Han, Kwang-Hyub

    2016-05-01

    Liver stiffness (LS), assessed using transient elastography (TE), and (FIB-4) can both estimate the risk of developing hepatocellular carcinoma (HCC). We compared prognostic performances of LS and FIB-4 to predict HCC development in patients with chronic hepatitis B (CHB).Data from 1308 patients with CHB, who underwent TE, were retrospectively analyzed. FIB-4 was calculated for all patients. The cumulative rate of HCC development was assessed using Kaplan-Meier curves. The predictive performances of LS and FIB-4 were evaluated using time-dependent receiver-operating characteristic (ROC) curves.The mean age (883 men) was 50 years. During follow-up (median 6.1 years), 119 patients developed HCC. The areas under the ROC curves (AUROCs) predicting HCC risk at 3, 5, and 7 years were consistently greater for LS than for FIB-4 (0.791-0.807 vs 0.691-0.725; all P < 0.05). Similarly, when the respective AUROCs for LS and FIB-4 at every time point during the 7-year follow-up were plotted, LS also showed consistently better performance than FIB-4 after 1 year of enrollment. The combined use of LS and FIB-4 significantly enhanced the prognostic performance compared with the use of FIB-4 alone (P < 0.05), but the performance of the combined scores was statistically similar to that of LS alone (P > 0.05).LS showed significantly better performance than FIB-4 in assessing the risk of HCC development, and the combined use of LS and FIB-4 did not provide additional benefit compared with the use of LS alone. Hence, LS assessed using TE might be helpful for optimizing HCC surveillance strategies.

  9. Increasing time to postoperative stereotactic radiation therapy for patients with resected brain metastases: investigating clinical outcomes and identifying predictors associated with time to initiation.

    PubMed

    Yusuf, Mehran B; Amsbaugh, Mark J; Burton, Eric; Nelson, Megan; Williams, Brian; Koutourousiou, Maria; Nauta, Haring; Woo, Shiao

    2018-02-01

    We sought to determine the impact of time to initiation (TTI) of post-operative radiosurgery on clinical outcomes for patients with resected brain metastases and to identify predictors associated with TTI. All patients with resected brain metastases treated with postoperative SRS or fractionated stereotactic radiation therapy (fSRT) from 2012 to 2016 at a single institution were reviewed. TTI was defined as the interval from resection to first day of radiosurgery. Receiver operating characteristic (ROC) curves were used to identify an optimal threshold for TTI with respect to local failure (LF). Survival outcomes were estimated using the Kaplan-Meier method and analyzed using the log-rank test and Cox proportional hazards models. Logistic regression models were used to identify factors associated with ROC-determined TTI covariates. A total of 79 resected lesions from 73 patients were evaluated. An ROC curve of LF and TTI identified an optimal threshold for TTI of 30.5 days, with an area under the curve of 0.637. TTI > 30 days was associated with an increased hazard of LF (HR 4.525, CI 1.239-16.527) but was not significantly associated with survival (HR 1.002, CI 0.547-1.823) or distant brain failure (DBF, HR 1.943, CI 0.989-3.816). Fifteen patients (20.5%) required post-operative inpatient rehabilitation. Post-operative rehabilitation was associated with TTI > 30 days (OR 1.48, CI 1.142-1.922). In our study of resected brain metastases, longer time to initiation of post-operative radiosurgery was associated with increased local failure. Ideally, post-op SRS should be initiated within 30 days of resection if feasible.

  10. The long-term outcomes of epilepsy surgery

    PubMed Central

    Keller, Simon; Nicolson, Andrew; Biswas, Shubhabrata; Smith, David; Osman Farah, Jibril; Eldridge, Paul; Wieshmann, Udo

    2018-01-01

    Objective Despite modern anti-epileptic drug treatment, approximately 30% of epilepsies remain medically refractory and for these patients, epilepsy surgery may be a treatment option. There have been numerous studies demonstrating good outcome of epilepsy surgery in the short to median term however, there are a limited number of studies looking at the long-term outcomes. The aim of this study was to ascertain the long-term outcome of resective epilepsy surgery in a large neurosurgery hospital in the U.K. Methods This a retrospective analysis of prospectively collected data. We used the 2001 International League Against Epilepsy (ILAE) classification system to classify seizure freedom and Kaplan-Meier survival analysis to estimate the probability of seizure freedom. Results We included 284 patients who underwent epilepsy surgery (178 anterior temporal lobe resections, 37 selective amygdalohippocampectomies, 33 temporal lesionectomies, 36 extratemporal lesionectomies), and had a prospective median follow-up of 5 years (range 1–27). Kaplan-Meier estimates showed that 47% (95% CI 40–58) remained seizure free (apart from simple partial seizures) at 5 years and 38% (95% CI 31–45) at 10 years after surgery. 74% (95% CI 69–80) had a greater than 50% seizure reduction at 5 years and 70% (95% CI 64–77) at 10 years. Patients who had an amygdalohippocampectomy were more likely to have seizure recurrence than patients who had an anterior temporal lobe resection (p = 0.006) and temporal lesionectomy (p = 0.029). There was no significant difference between extra temporal and temporal lesionectomies. Hippocampal sclerosis was associated with a good outcome but declined in relative frequency over the years. Conclusion The vast majority of patients who were not seizure free experienced at least a substantial and long-lasting reduction in seizure frequency. A positive long-term outcome after epilepsy surgery is possible for many patients and especially those with

  11. Prognosis Related to Metastatic Burden Measured by 18F-Fluorocholine PET/CT in Castrate Resistant Prostate Cancer

    PubMed Central

    Kwee, Sandi A.; Lim, John; Watanabe, Alex; Kromer-Baker, Kathleen; Coel, Marc N.

    2015-01-01

    This study investigates the prognostic significance of metabolically active tumor volume (MATV) measurements applied to fluorine-18 fluorocholine (FC) PET/CT in castrate-resistant prostate cancer (CRPC). Methods FC PET/CT imaging was performed in 30 patients with CRPC. Metastatic disease was quantified on the basis of maximum standardized uptake value (SUVmax), MATV, and total lesion activity (TLA = MATV × mean SUV). Tumor burden indices derived from whole-body summation of PET tumor volume measurements (ie. net MATV and net TLA) were evaluated as variables in Cox regression and Kaplan-Meier survival analyses. Results Net MATV ranged from 0.12 cm3 to 1543.9 cm3 (median 52.6 cm3). Net TLA ranged from 0.40g to 6688.7g (median 225.1g). PSA level at the time of PET correlated significantly with net MATV (Pearson r = 0.65, p = 0.0001) and net TLA (r = 0.60, p = 0.0005) but not highest lesional SUVmax of each scan. Survivors were followed for a median 23 months (range 6 – 38 months). On Cox regression analyses, overall survival was significantly associated with net MATV (p = 0.0068), net TLA (p = 0.0072), and highest lesion SUVmax (p = 0.0173), and borderline associated with PSA level (p = 0.0458). Only net MATV and net TLA remained significant in univariate-adjusted survival analyses. Kaplan-Meier analysis demonstrated significant differences in survival between groups stratified by median net MATV (log-rank P = 0.0371), net TLA (log-rank P = 0.0371), and highest lesion SUVmax (log-rank P = 0.0223). Conclusions Metastatic prostate cancer detected by FC PET/CT can be quantified based on volumetric measurements of tumor metabolic activity. The prognostic value of FC PET/CT may stem from this capacity to assess whole-body tumor burden. With further clinical validation, FC PET-based indices of global disease activity and mortality risk could prove useful in patient-individualized treatment of CRPC. PMID:24676753

  12. The long-term outcomes of epilepsy surgery.

    PubMed

    Mohan, Midhun; Keller, Simon; Nicolson, Andrew; Biswas, Shubhabrata; Smith, David; Osman Farah, Jibril; Eldridge, Paul; Wieshmann, Udo

    2018-01-01

    Despite modern anti-epileptic drug treatment, approximately 30% of epilepsies remain medically refractory and for these patients, epilepsy surgery may be a treatment option. There have been numerous studies demonstrating good outcome of epilepsy surgery in the short to median term however, there are a limited number of studies looking at the long-term outcomes. The aim of this study was to ascertain the long-term outcome of resective epilepsy surgery in a large neurosurgery hospital in the U.K. This a retrospective analysis of prospectively collected data. We used the 2001 International League Against Epilepsy (ILAE) classification system to classify seizure freedom and Kaplan-Meier survival analysis to estimate the probability of seizure freedom. We included 284 patients who underwent epilepsy surgery (178 anterior temporal lobe resections, 37 selective amygdalohippocampectomies, 33 temporal lesionectomies, 36 extratemporal lesionectomies), and had a prospective median follow-up of 5 years (range 1-27). Kaplan-Meier estimates showed that 47% (95% CI 40-58) remained seizure free (apart from simple partial seizures) at 5 years and 38% (95% CI 31-45) at 10 years after surgery. 74% (95% CI 69-80) had a greater than 50% seizure reduction at 5 years and 70% (95% CI 64-77) at 10 years. Patients who had an amygdalohippocampectomy were more likely to have seizure recurrence than patients who had an anterior temporal lobe resection (p = 0.006) and temporal lesionectomy (p = 0.029). There was no significant difference between extra temporal and temporal lesionectomies. Hippocampal sclerosis was associated with a good outcome but declined in relative frequency over the years. The vast majority of patients who were not seizure free experienced at least a substantial and long-lasting reduction in seizure frequency. A positive long-term outcome after epilepsy surgery is possible for many patients and especially those with hippocampal sclerosis or those who had anterior temporal

  13. Decreased expression of dual specificity phosphatase 22 in colorectal cancer and its potential prognostic relevance for stage IV CRC patients.

    PubMed

    Yu, Dan; Li, Zhenli; Gan, Meifu; Zhang, Hanyun; Yin, Xiaoyang; Tang, Shunli; Wan, Ledong; Tian, Yiping; Zhang, Shuai; Zhu, Yimin; Lai, Maode; Zhang, Dandan

    2015-11-01

    Dual specificity phosphatase 22 (DUSP22) is a novel dual specificity phosphatase that has been demonstrated to be a cancer suppressor gene associated with numerous biological and pathological processes. However, little is known of DUSP22 expression profiling in colorectal cancer and its prognostic value. Our study aims to investigate the role of DUSP22 expression in the prognosis of colorectal cancer. We detected the mRNA expression in 92 paired primary colorectal cancer tissues and the corresponding adjacent normal tissues by using QuantiGenePlex assay. The Friedman test was used to determine the statistical difference of gene expression. Kaplan-Meier survival analysis was performed. Mann-Whitney test and Kruskal-Wallis test were used to conduct data analyses to determine the prognostic value. Statistical significance was set at P < 0.05. In 74 of 92 cases, DUSP22 mRNA was reduced in primary colorectal cancer tissues, compared to the adjacent normal tissues. The mRNA levels of DUSP22 were significantly lower in colorectal cancer tissues than in adjacent normal tissues (0.0290 vs. 0.0658; P < 0.001). Low expression of DUSP22 correlated significantly with large tumor size (P = 0.013). No association was observed between DUSP22 mRNA expression and differentiation, histopathological type, tumor invasion, lymph node metastases, metastases, TNM stage, and Duke's phase (all P > 0.05). Kaplan-Meier analysis indicated that DUSP22 expression had no significant relationship with overall survival in all patients (P > 0.05). Interestingly, low expression level of DUSP22 in stage IV patients had a poor survival measures with a marginal P value (P = 0.07). Reduced DUSP22 expression was found in colorectal cancer specimens. Low expression level of DUSP22 in stage IV patients had a poor survival outcome. Further study is required for the investigation of the role of DUSP22 in colorectal cancer.

  14. Phase II Study of Paclitaxel Given Once per Week Along With Trastuzumab and Pertuzumab in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer

    PubMed Central

    Dang, Chau; Iyengar, Neil; Datko, Farrah; D'Andrea, Gabriella; Theodoulou, Maria; Dickler, Maura; Goldfarb, Shari; Lake, Diana; Fasano, Julie; Fornier, Monica; Gilewski, Theresa; Modi, Shanu; Gajria, Devika; Moynahan, Mary Ellen; Hamilton, Nicola; Patil, Sujata; Jochelson, Maxine; Norton, Larry; Baselga, Jose; Hudis, Clifford

    2015-01-01

    Purpose The CLEOPATRA (Clinical Evaluation of Trastuzumab and Pertuzumab) study demonstrated superior progression-free survival (PFS) and overall survival when pertuzumab was added to trastuzumab and docetaxel. Paclitaxel given once per week is effective and less toxic than docetaxel. We performed a phase II study to evaluate the efficacy and safety of pertuzumab and trastuzumab with paclitaxel given once per week. Patients and Methods Patients with metastatic human epidermal growth factor receptor 2–positive breast cancer with zero to one prior therapy were enrolled. Treatment consisted of paclitaxel 80 mg/m2 once per week plus trastuzumab (8 mg/kg loading dose → 6 mg/kg) once every 3 weeks plus pertuzumab (840 mg loading dose → 420 mg) once every 3 weeks, all given intravenously. The primary end point was 6-month PFS assessed by Kaplan-Meier methods. Results From January 2011 to December 2013, we enrolled 69 patients: 51 (74%) and 18 (26%) treated in first- and second-line metastatic settings, respectively. At a median follow-up of 21 months (range, 3 to 38 months), 6-month PFS was 86% (95% CI, 75% to 92%). The median PFS was 19.5 months (95% CI, 14 to 26 months) overall. PFS was 24.2 months (95% CI, 14 months to not reached [NR]) and 16.4 months (95% CI, 8.5 months to NR) for those without and with prior treatment, respectively. At 1 year, Kaplan-Meier PFS was 70% (95% CI, 56% to 79%) overall, 71% (95% CI, 55% to 82%) for those without prior therapy, and 66% (95% CI, 40% to 83%) for those with prior therapy. Treatment was well-tolerated; there was no febrile neutropenia or symptomatic left ventricular systolic dysfunction. Conclusion Paclitaxel given once per week with trastuzumab and pertuzumab is highly active and well tolerated and seems to be an effective alternative to docetaxel-based combination therapy. PMID:25547504

  15. Phase II study of paclitaxel given once per week along with trastuzumab and pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer.

    PubMed

    Dang, Chau; Iyengar, Neil; Datko, Farrah; D'Andrea, Gabriella; Theodoulou, Maria; Dickler, Maura; Goldfarb, Shari; Lake, Diana; Fasano, Julie; Fornier, Monica; Gilewski, Theresa; Modi, Shanu; Gajria, Devika; Moynahan, Mary Ellen; Hamilton, Nicola; Patil, Sujata; Jochelson, Maxine; Norton, Larry; Baselga, Jose; Hudis, Clifford

    2015-02-10

    The CLEOPATRA (Clinical Evaluation of Trastuzumab and Pertuzumab) study demonstrated superior progression-free survival (PFS) and overall survival when pertuzumab was added to trastuzumab and docetaxel. Paclitaxel given once per week is effective and less toxic than docetaxel. We performed a phase II study to evaluate the efficacy and safety of pertuzumab and trastuzumab with paclitaxel given once per week. Patients with metastatic human epidermal growth factor receptor 2-positive breast cancer with zero to one prior therapy were enrolled. Treatment consisted of paclitaxel 80 mg/m(2) once per week plus trastuzumab (8 mg/kg loading dose → 6 mg/kg) once every 3 weeks plus pertuzumab (840 mg loading dose → 420 mg) once every 3 weeks, all given intravenously. The primary end point was 6-month PFS assessed by Kaplan-Meier methods. From January 2011 to December 2013, we enrolled 69 patients: 51 (74%) and 18 (26%) treated in first- and second-line metastatic settings, respectively. At a median follow-up of 21 months (range, 3 to 38 months), 6-month PFS was 86% (95% CI, 75% to 92%). The median PFS was 19.5 months (95% CI, 14 to 26 months) overall. PFS was 24.2 months (95% CI, 14 months to not reached [NR]) and 16.4 months (95% CI, 8.5 months to NR) for those without and with prior treatment, respectively. At 1 year, Kaplan-Meier PFS was 70% (95% CI, 56% to 79%) overall, 71% (95% CI, 55% to 82%) for those without prior therapy, and 66% (95% CI, 40% to 83%) for those with prior therapy. Treatment was well-tolerated; there was no febrile neutropenia or symptomatic left ventricular systolic dysfunction. Paclitaxel given once per week with trastuzumab and pertuzumab is highly active and well tolerated and seems to be an effective alternative to docetaxel-based combination therapy. © 2014 by American Society of Clinical Oncology.

  16. Self-Interacting Dark Matter Can Explain Diverse Galactic Rotation Curves

    NASA Astrophysics Data System (ADS)

    Kamada, Ayuki; Kaplinghat, Manoj; Pace, Andrew B.; Yu, Hai-Bo

    2017-09-01

    The rotation curves of spiral galaxies exhibit a diversity that has been difficult to understand in the cold dark matter (CDM) paradigm. We show that the self-interacting dark matter (SIDM) model provides excellent fits to the rotation curves of a sample of galaxies with asymptotic velocities in the 25 - 300 km /s range that exemplify the full range of diversity. We assume only the halo concentration-mass relation predicted by the CDM model and a fixed value of the self-interaction cross section. In dark-matter-dominated galaxies, thermalization due to self-interactions creates large cores and reduces dark matter densities. In contrast, thermalization leads to denser and smaller cores in more luminous galaxies and naturally explains the flatness of rotation curves of the highly luminous galaxies at small radii. Our results demonstrate that the impact of the baryons on the SIDM halo profile and the scatter from the assembly history of halos as encoded in the concentration-mass relation can explain the diverse rotation curves of spiral galaxies.

  17. Self-Interacting Dark Matter Can Explain Diverse Galactic Rotation Curves.

    PubMed

    Kamada, Ayuki; Kaplinghat, Manoj; Pace, Andrew B; Yu, Hai-Bo

    2017-09-15

    The rotation curves of spiral galaxies exhibit a diversity that has been difficult to understand in the cold dark matter (CDM) paradigm. We show that the self-interacting dark matter (SIDM) model provides excellent fits to the rotation curves of a sample of galaxies with asymptotic velocities in the 25-300  km/s range that exemplify the full range of diversity. We assume only the halo concentration-mass relation predicted by the CDM model and a fixed value of the self-interaction cross section. In dark-matter-dominated galaxies, thermalization due to self-interactions creates large cores and reduces dark matter densities. In contrast, thermalization leads to denser and smaller cores in more luminous galaxies and naturally explains the flatness of rotation curves of the highly luminous galaxies at small radii. Our results demonstrate that the impact of the baryons on the SIDM halo profile and the scatter from the assembly history of halos as encoded in the concentration-mass relation can explain the diverse rotation curves of spiral galaxies.

  18. Stroke prediction with CHA2DS2-VASc score in patients with mesenteric ischemia without atrial fibrillation-insights from a nationwide cohort.

    PubMed

    Hu, Wei-Syun; Lin, Cheng-Li

    2017-11-01

    The current study sought to evaluate the accuracy of CHA 2 DS 2 -VASc score for ischemic stroke prediction in patients with mesenteric ischemia without atrial fibrillation (AF). The study participants included patients aged ≥18years with a new diagnosis of mesenteric ischemia during hospitalization between January 1, 2000 and December 31, 2011. Individuals with atrial fibrillation (AF) or atrial flutter during the study period were excluded. The study participants were followed up until the ischemic stroke appeared or they were censored due to withdrawal from this program, mortality, or the end of the study period, whichever came first. Cox proportional hazards regression models were applied for ischemic stroke risk stratification in the study participants by CHA 2 DS 2 -VASc score. The c-statistic based on the receiver operating characteristic (ROC) analysis was applied to investigate the accuracy of CHA 2 DS 2 -VASc score for ischemic stroke risk discrimination. A total of 24039 study participants were enrolled. Ischemic stroke incidence increased from 1.54% in CHA 2 DS 2 -VASc score of 0 to 9.23% in CHA 2 DS 2 -VASc score of 6 or more. Moreover, the Kaplan-Meier curve with a log rank test demonstrated that patients with a higher CHA 2 DS 2 -VASc score were associated with an increased cumulative incidence rate of ischemic stroke during the follow-up period (p<0.001). The discriminatory performance of the CHA2DS2-VASc score resulted in C-statistics of 0.65(95% CI=0.63-0.66) for predicting ischemic stroke risk among patients with mesenteric ischemia without AF. A higher CHA 2 DS 2 -VASc score is demonstrated to be associated with an increased risk of ischemic stroke among patients with mesenteric ischemia without comorbid AF. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Prevalence, Predictors and Clinical Outcome of Residual Pulmonary Hypertension Following Tricuspid Annuloplasty.

    PubMed

    Chen, Yan; Liu, Ju-Hua; Chan, Daniel; Sit, Ko-Yung; Wong, Chun-Ka; Ho, Kar-Lai; Ho, Lai-Ming; Zhen, Zhe; Lam, Yui-Ming; Lau, Chu-Pak; Au, Wing-Kok; Tse, Hung-Fat; Yiu, Kai-Hang

    2016-07-22

    Tricuspid annuloplasty is increasingly performed during left heart valve surgery, but the long-term clinical outcome postoperatively is not satisfactory. The aim of this study was to determine whether residual pulmonary hypertension (PHT) contributes to the adverse outcome. One-hundred thirty-seven patients (age 61±11 years; men, 30%) who underwent tricuspid annuloplasty during left-side valve surgery were enrolled. The mean pulmonary artery systolic pressure before surgery was 49±13 mm Hg and 32±15 mm Hg following surgery. Patients were divided into 3 groups according to postoperative pulmonary artery systolic pressure: no residual PHT (n=78, 57%), mild residual PHT (n=43, 31%), or significant residual PHT (n=16, 12%). A preoperative larger right ventricular (RV) geometry and tricuspid valve tethering area were associated with mild or significant residual PHT. A total of 24 adverse events (20 heart failures and 4 cardiovascular deaths) occurred during a median follow-up of 25 months. Kaplan-Meier survival curve demonstrated that patients with significant residual PHT had the highest percentage of adverse events followed by those with mild residual PHT. Patients with no residual PHT had a very low risk of adverse events. Multivariable Cox regression analysis revealed that both mild (hazard ratio=4.94; 95% CI =1.34-18.16; P=0.02) and significant residual PHT (hazard ratio=8.67; 95% CI =2.43-30.98; P<0.01) were independent factors associated with adverse events. The present study demonstrated that 43% of patients who underwent tricuspid annuloplasty had residual PHT. The presence of mild or significant residual PHT was associated with adverse events in these patients. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  20. Marital status as a predictor of survival in patients with human papilloma virus-positive oropharyngeal cancer.

    PubMed

    Rubin, Samuel J; Kirke, Diana N; Ezzat, Waleed H; Truong, Minh T; Salama, Andrew R; Jalisi, Scharukh

    Determine whether marital status is a significant predictor of survival in human papillomavirus-positive oropharyngeal cancer. A single center retrospective study included patients diagnosed with human papilloma virus-positive oropharyngeal cancer at Boston Medical Center between January 1, 2010 and December 30, 2015, and initiated treatment with curative intent at Boston Medical Center. Demographic data and tumor-related variables were recorded. Univariate analysis was performed using a two-sample t-test, chi-squared test, Fisher's exact test, and Kaplan Meier curves with a log rank test. Multivariate survival analysis was performed using a Cox regression model. A total of 65 patients were included in the study with 24 patients described as married and 41 patients described as single. There was no significant difference in most demographic variables or tumor related variables between the two study groups, except single patients were significantly more likely to have government insurance (p=0.0431). Furthermore, there was no significant difference in 3-year overall survival between married patients and single patients (married=91.67% vs single=87.80%; p=0.6532) or 3-year progression free survival (married=79.17% vs single=85.37%; p=0.8136). After adjusting for confounders including age, sex, race, insurance type, smoking status, treatment, and AJCC combined pathologic stage, marital status was not a significant predictor of survival [HR=0.903; 95% CI (0.126,6.489); p=0.9192]. Although previous literature has demonstrated that married patients with head and neck cancer have a survival benefit compared to single patients with head and neck cancer, we were unable to demonstrate the same survival benefit in a cohort of patients with human papilloma virus-positive oropharyngeal cancer. Copyright © 2017 Elsevier Inc. All rights reserved.