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Sample records for actuarial progression-free survival

  1. Sorafenib Improves Progression-Free Survival in Some Patients with Metastatic Thyroid Cancer

    MedlinePlus

    ... of Endocrine & Neuroendocrine Neoplasias Research Sorafenib Improves Progression-Free Survival in Some Patients with Metastatic Thyroid Cancer ... starting treatment without their disease getting worse ( progression-free survival ), as assessed by independent review. Secondary endpoints ...

  2. Crizotinib Improves Progression-Free Survival in Some Patients with Advanced Lung Cancer

    MedlinePlus

    ... Prevention Lung Cancer Screening Research Crizotinib Improves Progression-Free Survival in Some Patients with Advanced Lung Cancer ( ... starting treatment without their disease getting worse (progression-free survival), as assessed by radiologic review. Results Progression- ...

  3. Actuarial survival of a large Canadian cohort of preterm infants

    PubMed Central

    Jones, Huw P; Karuri, Stella; Cronin, Catherine MG; Ohlsson, Arne; Peliowski, Abraham; Synnes, Anne; Lee, Shoo K

    2005-01-01

    Background The increased survival of preterm and very low birth weight infants in recent years has been well documented but continued surveillance is required in order to monitor the effects of new therapeutic interventions. Gestation and birth weight specific survival rates most accurately reflect the outcome of perinatal care. Our aims were to determine survival to discharge for a large Canadian cohort of preterm infants admitted to the neonatal intensive care unit (NICU), and to examine the effect of gender on survival and the effect of increasing postnatal age on predicted survival. Methods Outcomes for all 19,507 infants admitted to 17 NICUs throughout Canada between January 1996 and October 1997 were collected prospectively. Babies with congenital anomalies were excluded from the study population. Gestation and birth weight specific survival for all infants with birth weight <1,500 g (n = 3419) or gestation ≤30 weeks (n = 3119) were recorded. Actuarial survival curves were constructed to show changes in expected survival with increasing postnatal age. Results Survival to discharge at 24 weeks gestation was 54%, compared to 82% at 26 weeks and 95% at 30 weeks. In infants with birth weights 600–699, survival to discharge was 62%, compared to 79% at 700–799 g and 96% at 1,000–1,099 g. In infants born at 24 weeks gestational age, survival was higher in females but there were no significant gender differences above 24 weeks gestation. Actuarial analysis showed that risk of death was highest in the first 5 days. For infants born at 24 weeks gestation, estimated survival probability to 48 hours, 7 days and 4 weeks were 88 (CI 84,92)%, 70 (CI 64, 76)% and 60 (CI 53,66)% respectively. For smaller birth weights, female survival probabilities were higher than males for the first 40 days of life. Conclusion Actuarial analysis provides useful information when counseling parents and highlights the importance of frequently revising the prediction for long term

  4. Combining progression-free survival and overall survival as a novel composite endpoint for glioblastoma trials

    PubMed Central

    Trippa, Lorenzo; Wen, Patrick Y.; Parmigiani, Giovanni; Berry, Donald A.; Alexander, Brian M.

    2015-01-01

    Background The use of auxiliary endpoints may provide efficiencies for clinical trial design, but such endpoints may not have intrinsic clinical relevance or clear linkage to more meaningful endpoints. The purpose of this study was to generate a novel endpoint that considers both overall survival (OS) and earlier events such as progression-free survival (PFS) and determine whether such an endpoint could increase efficiency in the design of glioblastoma clinical trials. Methods Recognizing that the association between PFS and OS varies depending on therapy and tumor type, we developed a statistical model to predict OS based on PFS as the trial progresses. We then evaluated the efficiency of our model using simulations of adaptively randomized trials incorporating PFS and OS distributions from prior published trials in neuro-oncology. Results When treatment effects on PFS and OS are concordant, our proposed approach results in efficiency gains compared with randomization based on OS alone while sacrificing minimal efficiency compared with using PFS as the primary endpoint. When treatment effects are limited to PFS, our approach provides randomization probabilities that are close to those based on OS alone. Conclusion Use of OS as the primary endpoint, combined with statistical modeling of the relationship between OS and PFS during the course of the trial, results in more robust and efficient trial designs than using either endpoint alone. PMID:25568226

  5. Testing of evaluation bias for progression free survival endpoint in oncology clinical trials.

    PubMed

    Sun, Yan; Wu, Wenting; Sargent, Daniel

    2016-09-30

    Progression-free survival is an increasingly popular end point in oncology clinical trials. A complete blinded independent central review (BICR) is often required by regulators in an attempt to reduce the bias in progression-free survival (PFS) assessment. In this paper, we propose a new methodology that uses a sample-based BICR as an audit tool to decide whether a complete BICR is needed. More specifically, we propose a new index, the differential risk, to measure the reading discordance pattern, and develop a corresponding hypothesis testing procedure to decide whether the bias in local evaluation is acceptable. Simulation results demonstrate that our new index is sensitive to the change of discordance pattern; type I error is well controlled in the hypothesis testing procedure, and the calculated sample size provides the desired power. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27089832

  6. Association between progression-free survival and health-related quality of life in oncology: a systematic review protocol

    PubMed Central

    Kovic, Bruno; Guyatt, Gordon; Brundage, Michael; Thabane, Lehana; Bhatnagar, Neera; Xie, Feng

    2016-01-01

    Introduction There is an increasing number of new oncology drugs being studied, approved and put into clinical practice based on improvement in progression-free survival, when no overall survival benefits exist. In oncology, the association between progression-free survival and health-related quality of life is currently unknown, despite its importance for patients with cancer, and the unverified assumption that longer progression-free survival indicates improved health-related quality of life. Thus far, only 1 study has investigated this association, providing insufficient evidence and inconclusive results. The objective of this study protocol is to provide increased transparency in supporting a systematic summary of the evidence bearing on this association in oncology. Methods and analysis Using the OVID platform in MEDLINE, Embase and Cochrane databases, we will conduct a systematic review of randomised controlled human trials addressing oncology issues published starting in 2000. A team of reviewers will, in pairs, independently screen and abstract data using standardised, pilot-tested forms. We will employ numerical integration to calculate mean incremental area under the curve between treatment groups in studies for health-related quality of life, along with total related error estimates, and a 95% CI around incremental area. To describe the progression-free survival to health-related quality of life association, we will construct a scatterplot for incremental health-related quality of life versus incremental progression-free survival. To estimate the association, we will use a weighted simple regression approach, comparing mean incremental health-related quality of life with either median incremental progression-free survival time or the progression-free survival HR, in the absence of overall survival benefit. Discussion Identifying direction and magnitude of association between progression-free survival and health-related quality of life is critically

  7. Gain of chromosome arm 1q in atypical meningioma correlates with shorter progression-free survival

    PubMed Central

    Jansen, M.; Mohapatra, G.; Betensky, R.A.; Keohane, C.; Louis, D.N.

    2013-01-01

    Aims Atypical (WHO grade II) meningiomas have moderately high recurrence rates; even for completely resected tumours, approximately one-third will recur. Postoperative radiotherapy (RT) may aid local control and improve survival, but carries the risk of side effects. More accurate prediction of recurrence risk is therefore needed for patients with atypical meningioma. Previously, we used high-resolution array CGH to identify genetic variations in 47 primary atypical meningiomas and found that approximately 60% of tumors show gain of 1q at 1q25.1 and 1q25.3 to 1q32.1 and that 1q gain appeared to correlate with shorter progression-free survival. This study aimed to validate and extend these findings in an independent sample. Methods 86 completely resected atypical meningiomas (with 25 recurrences) from two neurosurgical centres in Ireland were identified and clinical follow up was obtained. Utilizing a dual-colour interphase FISH assay, 1q gain was assessed using BAC probes directed against 1q25.1 and 1q32.1. Results The results confirm the high prevalence of 1q gain at these loci in atypical meningiomas. We further show that gain at 1q32.1 and age each correlate with progression-free survival in patients who have undergone complete surgical resection of atypical meningiomas. Conclusions These independent findings suggest that assessment of 1q copy number status can add clinically useful information for the management of patients with atypical meningiomas. PMID:21988727

  8. Estimating progression-free survival in paediatric brain tumour patients when some progression statuses are unknown

    PubMed Central

    Yuan, Ying; Thall, Peter F.; Wolff, Johannes E.

    2012-01-01

    Summary In oncology, progression-free survival time, which is defined as the minimum of the times to disease progression or death, often is used to characterize treatment and covariate effects. We are motivated by the desire to estimate the progression time distribution on the basis of data from 780 paediatric patients with choroid plexus tumours, which are a rare brain cancer where disease progression always precedes death. In retrospective data on 674 patients, the times to death or censoring were recorded but progression times were missing. In a prospective study of 106 patients, both times were recorded but there were only 20 non-censored progression times and 10 non-censored survival times. Consequently, estimating the progression time distribution is complicated by the problems that, for most of the patients, either the survival time is known but the progression time is not known, or the survival time is right censored and it is not known whether the patient’s disease progressed before censoring. For data with these missingness structures, we formulate a family of Bayesian parametric likelihoods and present methods for estimating the progression time distribution. The underlying idea is that estimating the association between the time to progression and subsequent survival time from patients having complete data provides a basis for utilizing covariates and partial event time data of other patients to infer their missing progression times. We illustrate the methodology by analysing the brain tumour data, and we also present a simulation study. PMID:22408277

  9. The role of censoring on progression free survival: oncologist discretion advised.

    PubMed

    Prasad, Vinay; Bilal, Usama

    2015-11-01

    Censoring is increasingly appreciated as a potential bias affecting estimates of progression free survival (PFS) in randomised trials. In this commentary, we explore the central assumption of censoring. Censored patients are considered no more or less likely to undergo the event of interest than those who remain in the analysis. Instead however, if one makes alternate assumptions, that censored patients are different than those who remain on the trial, estimates of PFS change. Using the example of the recent BOLERO-2 trial of exemestane and everolimus, we show that by altering the assumptions for censoring, the major conclusions of clinical trials may change. As such, the number of censored patients at each time interval should be routinely reported in randomised trials to better understand the implications of censoring. PMID:26259493

  10. Progression free survival and functional outcome after surgical resection of intramedullary ependymomas.

    PubMed

    Abdullah, Kalil G; Lubelski, Daniel; Miller, Jacob; Steinmetz, Michael P; Shin, John H; Krishnaney, Ajit; Mroz, Thomas E; Benzel, Edward C

    2015-12-01

    We present a 15 year institutional analysis of the factors affecting progression free survival (PFS) and overall survival (OS) in patients undergoing attempted resection of adult intramedullary spinal cord ependymomas. Intramedullary spinal cord tumors are rare but important clinical entities, and ependymomas are the most commonly encountered intramedullary tumor. In total, 53 adult patients over the span of 15 years were analyzed for OS, PFS, and the effects of plane of dissection (POD) and gross total resection (GTR) on functional and long term outcomes. The mean age was 45 years and median follow-up was 54 months. The follow-up neurological outcome and modified McCormick scale were used to determine the functional outcome. Kaplan-Meier curves were used to calculate progression and survival. The overall ability to achieve GTR was significantly correlated to identification of an intraoperative POD (p<0.001). There was a trend towards increased PFS with the ability to achieve a GTR. There was no significant difference in the pre- and postoperative functional outcome scores. The ability to achieve a GTR is strongly correlated to the identification of a POD in ependymomas. There is a trend towards an increased probability of PFS in intramedullary spinal cord tumors when GTR is achieved. The resection of these tumors is likely to halt, but not reverse, neurological deterioration. PMID:26234635

  11. Levels of uninvolved immunoglobulins predict clinical status and progression-free survival for multiple myeloma patients.

    PubMed

    Harutyunyan, Nika M; Vardanyan, Suzie; Ghermezi, Michael; Gottlieb, Jillian; Berenson, Ariana; Andreu-Vieyra, Claudia; Berenson, James R

    2016-07-01

    Multiple myeloma (MM) is characterized by the enhanced production of the same monoclonal immunoglobulin (M-Ig or M protein). Techniques such as serum protein electrophoresis and nephelometry are routinely used to quantify levels of this protein in the serum of MM patients. However, these methods are not without their shortcomings and problems accurately quantifying M proteins remain. Precise quantification of the types and levels of M-Ig present is critical to monitoring patient response to therapy. In this study, we investigated the ability of the HevyLite (HLC) immunoassay to correlate with clinical status based on levels of involved and uninvolved antibodies. In our cohort of MM patients, we observed that significantly higher ratios and greater differences of involved HLC levels compared to uninvolved HLC levels correlated with a worse clinical status. Similarly, higher absolute levels of involved HLC antibodies and lower levels of uninvolved HLC antibodies also correlated with a worse clinical status and a shorter progression-free survival. These findings suggest that the HLC assay is a useful and a promising tool for determining the clinical status and survival time for patients with multiple myeloma.

  12. A Weibull multi-state model for the dependence of progression-free survival and overall survival.

    PubMed

    Li, Yimei; Zhang, Qiang

    2015-07-30

    In oncology clinical trials, overall survival, time to progression, and progression-free survival are three commonly used endpoints. Empirical correlations among them have been published for different cancers, but statistical models describing the dependence structures are limited. Recently, Fleischer et al. proposed a statistical model that is mathematically tractable and shows some flexibility to describe the dependencies in a realistic way, based on the assumption of exponential distributions. This paper aims to extend their model to the more flexible Weibull distribution. We derived theoretical correlations among different survival outcomes, as well as the distribution of overall survival induced by the model. Model parameters were estimated by the maximum likelihood method and the goodness of fit was assessed by plotting estimated versus observed survival curves for overall survival. We applied the method to three cancer clinical trials. In the non-small-cell lung cancer trial, both the exponential and the Weibull models provided an adequate fit to the data, and the estimated correlations were very similar under both models. In the prostate cancer trial and the laryngeal cancer trial, the Weibull model exhibited advantages over the exponential model and yielded larger estimated correlations. Simulations suggested that the proposed Weibull model is robust for data generated from a range of distributions.

  13. Pretreatment Immune Status Correlates with Progression-Free Survival in Chemotherapy-Treated Metastatic Colorectal Cancer Patients.

    PubMed

    Tada, Kohei; Kitano, Shigehisa; Shoji, Hirokazu; Nishimura, Takashi; Shimada, Yasuhiro; Nagashima, Kengo; Aoki, Kazunori; Hiraoka, Nobuyoshi; Honma, Yoshitaka; Iwasa, Satoru; Okita, Natsuko; Takashima, Atsuo; Kato, Ken; Yamada, Yasuhide; Katayama, Naoyuki; Boku, Narikazu; Heike, Yuji; Hamaguchi, Tetsuya

    2016-07-01

    It remains unclear whether the immunologic status of cells in peripheral blood can be used as a prognostic indicator of response to treatment for patients with unresectable metastatic colorectal cancer (MCRC). We therefore investigated the relationship between the pretreatment immunologic status of 40 patients with MCRC who planned to receive the first-line chemotherapy and their progression-free survival. Twenty-five immune cell subsets, including monocytic myeloid-derived suppressor cells (M-MDSC) and effector memory T cells (TEM), were measured by multicolor-flow cytometry. We divided patients into high and low (above and below the median, respectively) groups based on the median value for each immune cell subset and compared progression-free survival of the two groups. Patients with high M-MDSC, low CD4(+) TEM, or low CD8(+) TEM quantities had significantly shorter progression-free survival (P = 0.004, 0.005, and 0.002, respectively). Patients were classified into two prognostic groups based on numbers of adverse factors; having two or three adverse factors (n = 21, 52.5%) was correlated with significantly shorter progression-free survival compared with none or one (n = 19, 47.5%; P < 0.001). The presence of two or three adverse factors was an independent poor prognostic factor for progression-free survival (HR, 9.2; 95% confidence interval, 2.5-34.2; P < 0.001). These results provide evidence that pretreatment peripheral immune status can inform the outcome of patients with MCRC treated with first-line chemotherapy. Cancer Immunol Res; 4(7); 592-9. ©2016 AACR. PMID:27197061

  14. Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma

    PubMed Central

    Fonseca, Rafael; Siegel, David; Dimopoulos, Meletios A.; Špička, Ivan; Masszi, Tamás; Hájek, Roman; Rosiñol, Laura; Goranova-Marinova, Vesselina; Mihaylov, Georgi; Maisnar, Vladimír; Mateos, Maria-Victoria; Wang, Michael; Niesvizky, Ruben; Oriol, Albert; Jakubowiak, Andrzej; Minarik, Jiri; Palumbo, Antonio; Bensinger, William; Kukreti, Vishal; Ben-Yehuda, Dina; Stewart, A. Keith; Obreja, Mihaela; Moreau, Philippe

    2016-01-01

    The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n = 48; Rd, n = 52) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standard-risk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01080391. PMID:27439911

  15. Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma.

    PubMed

    Avet-Loiseau, Hervé; Fonseca, Rafael; Siegel, David; Dimopoulos, Meletios A; Špička, Ivan; Masszi, Tamás; Hájek, Roman; Rosiñol, Laura; Goranova-Marinova, Vesselina; Mihaylov, Georgi; Maisnar, Vladimír; Mateos, Maria-Victoria; Wang, Michael; Niesvizky, Ruben; Oriol, Albert; Jakubowiak, Andrzej; Minarik, Jiri; Palumbo, Antonio; Bensinger, William; Kukreti, Vishal; Ben-Yehuda, Dina; Stewart, A Keith; Obreja, Mihaela; Moreau, Philippe

    2016-09-01

    The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n = 48; Rd, n = 52) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standard-risk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01080391. PMID:27439911

  16. Macrocytosis during sunitinib treatment predicts progression-free survival in patients with metastatic renal cell carcinoma.

    PubMed

    Kucharz, Jakub; Giza, Agnieszka; Dumnicka, Paulina; Kuzniewski, Marek; Kusnierz-Cabala, Beata; Bryniarski, Pawel; Herman, Roma; Zygulska, Aneta Lidia; Krzemieniecki, Krzysztof

    2016-10-01

    Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, is a first-line treatment for metastatic renal cell carcinoma (mRCC) in patients in 'low' and 'intermediate' Memorial Sloan Kettering Cancer Center and Heng risk groups. Disruptions of hematopoiesis, such as anemia, neutropenia, and thrombocytopenia, are typically observed during sunitinib treatment. When it comes to RBC parameters, an increase in mean cell volume (MCV) tends to occur, meeting the criteria for macrocytosis in some patients (MCV > 100 fL). We examined changes in RBC parameters of 27 mRCC patients treated with sunitinib (initial dose of 50 mg/day, 6-week treatment: 4 weeks on, 2 weeks off) and correlated them with progression-free survival time (PFS). Patients who had macrocytosis after 3 treatment cycles had significantly longer PFS than those whose MCV stayed less than 100 fL (not reached vs. 11.2 months, p < 0.001). We also found a correlation between MCV values after the first and third treatment cycles and the risk of progression: HR of 0.9 (0.81-0.99) and 0.76 (0.65-0.90) per 1 fL increase in MCV, respectively. The mechanism of MCV elevation during sunitinib treatment has not yet been fully explained. One of the probable causes is sunitinib's inhibitory influence on c-Kit kinase, as is the case with imatinib. For mRCC patients, this phenomenon could help predict PFS, but since our sample was small, further studies are essential. PMID:27573381

  17. Intermediate clinical endpoints: a bridge between progression-free survival and overall survival in ovarian cancer trials.

    PubMed

    Matulonis, Ursula A; Oza, Amit M; Ho, Tony W; Ledermann, Jonathan A

    2015-06-01

    Ovarian cancer patients are usually diagnosed at an advanced stage, experience recurrence after platinum-based chemotherapy, and eventually develop resistance to chemotherapy. Overall survival (OS), which has improved in recent years as more active treatments have been incorporated into patient care, is regarded as the most clinically relevant endpoint in ovarian cancer trials. However, although there remains a significant need for new treatments that prolong OS further without compromising quality of life, it has become increasingly difficult to detect an OS benefit for investigational treatments because of the use of multiple lines of chemotherapy to treat ovarian cancer. Progression-free survival (PFS), which measures the time to disease progression or death, is unaffected by postprogression therapies but does not evaluate the long-term impact of investigational treatments on tumor biology and responses to future therapies. Recent clinical trials of targeted agents in relapsed ovarian cancer have shown improvements in PFS but not OS, and this is possibly reflective of the long postprogression survival (PPS) period associated with this disease. Intermediate endpoints such as the time to second disease progression or death and the time to second subsequent therapy or death may provide supportive evidence for clinically meaningful PFS improvements and may be used to determine whether these improvements persist beyond the first disease progression and throughout subsequent lines of therapy. For clinical trials that have settings with a long PPS duration and/or involve multiple rounds of postprogression therapy, a primary endpoint of PFS supported by intermediate clinical endpoints and OS may provide a more comprehensive approach for evaluating efficacy.

  18. Methylation status at HYAL2 predicts overall and progression-free survival of colon cancer patients under 5-FU chemotherapy.

    PubMed

    Pfütze, Katrin; Benner, Axel; Hoffmeister, Michael; Jansen, Lina; Yang, Rongxi; Bläker, Hendrik; Herpel, Esther; Ulrich, Alexis; Ulrich, Cornelia M; Chang-Claude, Jenny; Brenner, Hermann; Burwinkel, Barbara

    2015-12-01

    DNA methylation variations in gene promoter regions are well documented tumor-specific alterations in human malignancies including colon cancer, which may influence tumor behavior and clinical outcome. As a subset of colon cancer patients does not benefit from adjuvant chemotherapy, predictive biomarkers are desirable. Here, we describe that DNA methylation levels at CpG loci of hyaluronoglucosaminidase 2 (HYLA2) could be used to identify stage II and III colon cancer patients who are most likely to benefit from 5-flourouracil (5-FU) chemotherapy with respect to overall survival and progression-free survival. PMID:26453961

  19. Progression-free survival: an important end point in evaluating therapy for recurrent high-grade gliomas.

    PubMed

    Lamborn, Kathleen R; Yung, W K Alfred; Chang, Susan M; Wen, Patrick Y; Cloughesy, Timothy F; DeAngelis, Lisa M; Robins, H Ian; Lieberman, Frank S; Fine, Howard A; Fink, Karen L; Junck, Larry; Abrey, Lauren; Gilbert, Mark R; Mehta, Minesh; Kuhn, John G; Aldape, Kenneth D; Hibberts, Janelle; Peterson, Pamela M; Prados, Michael D

    2008-04-01

    The North American Brain Tumor Consortium (NABTC) uses 6-month progression-free survival (6moPFS) as the efficacy end point of therapy trials for adult patients with recurrent high-grade gliomas. In this study, we investigated whether progression status at 6 months predicts survival from that time, implying the potential for prolonged survival if progression could be delayed. We also evaluated earlier time points to determine whether the time of progression assessment alters the strength of the prediction. Data were from 596 patient enrollments (159 with grade III gliomas and 437 with grade IV tumors) in NABTC phase II protocols between February 1998 and December 2002. Outcome was assessed statistically using Kaplan-Meier curves and Cox proportional hazards models. Median survivals were 39 and 30 weeks for patients with grade III and grade IV tumors, respectively. Twenty-eight percent of patients with grade III and 16% of patients with grade IV tumors had progression-free survival of >26 weeks. Progression status at 9, 18, and 26 weeks predicted survival from those times for patients with grade III or grade IV tumors (p < 0.001 and hazard ratios < 0.5 in all cases). Including KPS, age, number of prior chemotherapies, and response in a multivariate model did not substantively change the results. Progression status at 6 months is a strong predictor of survival, and 6moPFS is a valid end point for trials of therapy for recurrent malignant glioma. Earlier assessments of progression status also predicted survival and may be incorporated in the design of future clinical trials.

  20. [Bevacizumab as first-line therapy in metastatic renal cell carcinoma: Progression-free survival for 3 years].

    PubMed

    Pichler, R; Horninger, W; Aigner, F; Heidegger, I

    2016-03-01

    We report the case of a 72-year-old woman who was diagnosed in 2006 with renal cell cancer (RCC) and had undergone consecutive tumor nephrectomy (clear-cell RCC, Fuhrmann grade II, stage pT3a, R0). Over the years, the patient underwent several surgical and radiological interventions due to various metastatic lesions. This case report describes the 3-year progression-free survival in a patient who underwent first-line therapy with the monoclonal antibody bevacizumab. Except for hypertension, the patient does not suffer currently from any other side effects of bevacizumab therapy.

  1. Cyproheptadine significantly improves the overall and progression-free survival of sorafenib-treated advanced HCC patients

    PubMed Central

    Feng, Yu-Min; Feng, Chin-Wen; Lu, Chin-Li; Lee, Ming-Yang; Chen, Chi-Yi; Chen, Solomon Chih-Cheng

    2015-01-01

    Objective Sorafenib is a recommended treatment for advanced hepatocellular carcinoma. The study is to evaluate the efficacy of sorafenib plus cyproheptadine compared with sorafenib alone in patients with advanced hepatocellular carcinoma. Methods A retrospective cohort study reviewed all consecutive advanced hepatocellular carcinoma cases with Child-Pugh Class A disease starting sorafenib treatment at our hospital from August 2012 to March 2013. They were followed up until 31 December 2013. A total of 52 patients were enrolled: 32 patients in the combination (sorafenib–cyproheptadine) group and 20 patients in the control (sorafenib alone) group. The response to treatment, overall survival and progression-free survival were compared. Results The median overall survival was 11.0 months (95% confidence interval: 6.8–15.1 months) in the combination group compared with 4.8 months (95% confidence interval: 3.1–6.6 months) in the control group (crude hazard ratio = 0.45, 95% confidence interval: 0.22–0.82). The median progression-free survival time was 7.5 months (95% confidence interval: 5.1–10.0 months) in the combination group compared with 1.7 months (95% confidence interval: 1.4–2.1 months) in the control group (crude hazard ratio = 0.43, 95% confidence interval: 0.22–0.86). Kaplan–Meier survival analysis revealed that both overall survival and progression-free survival in the combination group were significantly longer than that in the control group. The multivariate model found patients in the combination group were 76% less likely to die (adjusted hazard ratio = 0.24, 95% confidence interval: 0.10–0.58) and 82% less likely to have progression (adjusted hazard ratio = 0.18, 95% confidence interval: 0.08–0.44) during the 17 months of follow-up. Conclusion Cyproheptadine may significantly improve survival outcomes of sorafenib-treated advanced hepatocellular carcinoma patients. PMID:25646358

  2. Effects of Concurrent Topotecan and Radiation on 6-Month Progression-Free Survival in the Primary Treatment of Glioblastoma Multiforme

    SciTech Connect

    Grabenbauer, Gerhard G. Gerber, Klaus-Dieter; Ganslandt, Oliver; Richter, Andrea M.S.; Klautke, Gunther; Birkmann, Josef; Meyer, Martin

    2009-09-01

    Purpose: To report a prospective, randomized, Phase II trial of radiotherapy with and without topotecan for the treatment of glioblastoma. Patients and Methods: Inclusion criteria were histology of glioblastoma, age <60 years, and Eastern Cooperative Oncology Group status 0-2. Patients were stratified according to recursive partitioning analysis class, center, and enzyme-inducing antiepileptic medication. Magnetic resonance imaging scans, neurologic examinations, and quality of life assessments were done every 3 months. The primary endpoint was the progression-free survival rate at 6 months (6-m-PFS). This trial was designed as an exploratory, randomized, Phase II trial with an accrual of 140 patients to detect a difference of 15-20% in 6-m-PFS. An interim analysis was scheduled after 60 patients. Median follow-up was 14 months (range, 1-50 months). Results: The 6-m-PFS was 56% and 40% for patients with and without topotecan, respectively. This benefit disappeared within 2 months. Mean (range) progression-free survival time was 8 (5-10.9) months and 6.7 (4-9.5) months for patients with and without topotecan, respectively. The corresponding 2-year-overall survival rates were 28% vs. 22% (nonsignificant difference), and mean (range) survival time was 20.7 (13.9-27.5) months vs. 18.9 (13.5-24.4) months (nonsignificant difference). Conclusions: A slight but measurable increase of 16% was detected in 6-m-PFS for patients receiving topotecan with radiation as compared with patients having radiotherapy alone. These data might support further investigations into topotecan for the treatment of glioblastoma.

  3. Determinants of Overall and Progression-Free Survival of Nigerian Patients with Philadelphia-Positive Chronic Myeloid Leukemia

    PubMed Central

    Oyekunle, Anthony A.; Bolarinwa, Rahman A.; Oyelese, Adesola T.; Salawu, Lateef; Durosinmi, Muheez A.

    2015-01-01

    Objective. The tyrosine kinase inhibitors have markedly changed the disease course for patients with Ph+ and/or BCR-ABL1+ chronic myeloid leukemia (CML). This study was embarked upon to assess the long-term effects of imatinib therapy on survival in adult Nigerian patients with CML. Methods. All adult patients on imatinib (400–600 mg) seen from July 2003 to December 2010 were assessed. Male/female distribution was 171/101, with a median age of 38 (range, 20–75) years. Overall survival (OS) and progression-free survival (PFS) were determined using the Kaplan-Meier techniques. Results. Of all the 272 patients, 205 were in chronic phase, 54 in accelerated phase, and five in blastic phase, at commencement of imatinib. As at December 2010, 222 were alive. OS at 1 and 5 years was 94% and 63%, while PFS was 89% and 54%, respectively. Similarly, amongst the 205 patients in chronic phase, OS at 1 and 5 years was 97% and 68%, while PFS was 92% and 57%. Conclusion. Imatinib's place as first-line therapy in the treatment of CML has further been reinforced in our patients, with improved survival and reduced morbidity, comparable with outcomes in other populations. PMID:26435715

  4. Donor KIR B Genotype Improves Progression Free Survival of Non-Hodgkin lymphoma Patients Receiving Unrelated Donor Transplantation

    PubMed Central

    Bachanova, Veronika; Weisdorf, Daniel J.; Wang, Tao; Marsh, Steven G.E.; Trachtenberg, Elizabeth; Haagenson, Michael D; Spellman, Stephen R.; Ladner, Martha; Guethlein, Lisbeth A.; Parham, Peter; Miller, Jeffrey S.; Cooley, Sarah A.

    2016-01-01

    Donor killer immunoglobulin-like receptor (KIR) genotypes associate with relapse protection and survival after allotransplantation for acute myelogenous leukemia. We examined the possibility of a similar effect in a cohort of 614 non-Hodgkin lymphoma (NHL) patients receiving unrelated donor (URD) T-cell replete marrow or peripheral blood grafts. Sixty four percent (n=396) of donor-recipient pairs were 10/10 allele HLA-matched; 26% were 9/10 allele matched. Seventy percent of donors had KIR B/x genotype; the others had KIR A/A genotype. NHL patients receiving 10/10 HLA-matched URD grafts with KIR B/x donors experienced significantly lower relapse at 5 years (26%; CI 21–32% vs. 37%; CI 27–46%, p=0.05) compared with KIR A/A donors, resulting in improved 5 year progression-free survival (PFS) (35%; CI 26–44% vs. 22%; CI 11–35%; p=0.007). In multivariate analysis, use of KIR B/x donors associated with significantly reduced relapse risk (RR 0.63, p=0.02) and improved PFS (RR 0.71, p=0.008). The relapse protection afforded by KIR B/x donors was not observed in HLA-mismatched transplants, and was not specific to any particular KIR-B gene. Selecting 10/10 HLA-matched and KIR B/x donors should benefit patients with NHL receiving URD allogeneic transplantation. PMID:27220262

  5. Detection of Critical Genes Associated with Overall Survival (OS) and Progression-Free Survival (PFS) in Reconstructed Canine B-Cell Lymphoma Gene Regulatory Network (GRN).

    PubMed

    Zamani-Ahmadmahmudi, Mohamad; Najafi, Ali; Nassiri, Seyed Mahdi

    2016-01-01

    Canine B-cell lymphoma GRN was reconstructed from gene expression data in the STRING and MiMI databases. Critical genes of networks were identified and correlations of critical genes with overall survival (OS) and progression-free survival (PFS) were evaluated. Significant changes were detected in the expressions of GLUL, CD44, CD79A, ARF3, FOS, BLOC1S1, FYN, GZMB, GALNT3, IFI44, CD3G, GNG2, ESRP1, and CCND1 in the STRING network and of PECAM1, GLUL, CD44, GDI1, E2F4, TLE1, CD79A, UCP2, CCND1, FYN, RHOQ, BIN1, and A2M in the MiMI network. Final survival analysis highlighted CCND1 and FOS as genes with significant correlations with OS and PFS.

  6. Germline polymorphisms in an enhancer of PSIP1 are associated with progression-free survival in epithelial ovarian cancer

    PubMed Central

    French, Juliet D.; Johnatty, Sharon E.; Lu, Yi; Beesley, Jonathan; Gao, Bo; Kalimutho, Murugan; Henderson, Michelle J.; Russell, Amanda J.; Kar, Siddhartha; Chen, Xiaoqing; Hillman, Kristine M.; Kaufmann, Susanne; Sivakumaran, Haran; O'Reilly, Martin; Wang, Chen; Korbie, Darren J.; Lambrechts, Diether; Despierre, Evelyn; Van Nieuwenhuysen, Els; Lambrechts, Sandrina; Vergote, Ignace; Karlan, Beth; Lester, Jenny; Orsulic, Sandra; Walsh, Christine; Fasching, Peter A.; Beckmann, Matthias W.; Ekici, Arif B.; Hein, Alexander; Matsuo, Keitaro; Hosono, Satoyo; Pisterer, Jacobus; Hillemanns, Peter; Nakanishi, Toru; Yatabe, Yasushi; Goodman, Marc T.; Lurie, Galina; Matsuno, Rayna K.; Thompson, Pamela J.; Pejovic, Tanja; Bean, Yukie; Heitz, Florian; Harter, Philipp; du Bois, Andreas; Schwaab, Ira; Hogdall, Estrid; Kjaer, Susanne K.; Jensen, Allan; Hogdall, Claus; Lundvall, Lene; Engelholm, Svend Aage; Brown, Bob; Flanagan, James M.; Metcalf, Michelle D.; Siddiqui, Nadeem; Sellers, Thomas; Fridley, Brooke; Cunningham, Julie; Schildkraut, Joellen M.; Iversen, Ed; Weber, Rachel Palmieri; Brennan, Donal; Berchuck, Andrew; Pharoah, Paul; Harnett, Paul; Norris, Murray D.; Haber, Michelle; Goode, Ellen L.; Lee, Jason S.; Khanna, Kum Kum; Meyer, Kerstin B.; Chenevix-Trench, Georgia; deFazio, Anna; Edwards, Stacey L.; MacGregor, Stuart

    2016-01-01

    Women with epithelial ovarian cancer (EOC) are usually treated with platinum/taxane therapy after cytoreductive surgery but there is considerable inter-individual variation in response. To identify germline single-nucleotide polymorphisms (SNPs) that contribute to variations in individual responses to chemotherapy, we carried out a multi-phase genome-wide association study (GWAS) in 1,244 women diagnosed with serous EOC who were treated with the same first-line chemotherapy, carboplatin and paclitaxel. We identified two SNPs (rs7874043 and rs72700653) in TTC39B (best P=7×10−5, HR=1.90, for rs7874043) associated with progression-free survival (PFS). Functional analyses show that both SNPs lie in a putative regulatory element (PRE) that physically interacts with the promoters of PSIP1, CCDC171 and an alternative promoter of TTC39B. The C allele of rs7874043 is associated with poor PFS and showed increased binding of the Sp1 transcription factor, which is critical for chromatin interactions with PSIP1. Silencing of PSIP1 significantly impaired DNA damage-induced Rad51 nuclear foci and reduced cell viability in ovarian cancer lines. PSIP1 (PC4 and SFRS1 Interacting Protein 1) is known to protect cells from stress-induced apoptosis, and high expression is associated with poor PFS in EOC patients. We therefore suggest that the minor allele of rs7874043 confers poor PFS by increasing PSIP1 expression. PMID:26840454

  7. Prognostic nomogram to predict progression-free survival in patients with platinum-sensitive recurrent ovarian cancer

    PubMed Central

    Lee, C K; Simes, R J; Brown, C; Lord, S; Wagner, U; Plante, M; Vergote, I; Pisano, C; Parma, G; Burges, A; Bourgeois, H; Högberg, T; Bentley, J; Angleitner-Boubenizek, L; Ferrero, A; Richter, B; Hirte, H; Gebski, V; Pfisterer, J; Pujade-Lauraine, E; Friedlander, M

    2011-01-01

    Background: Patients with platinum-sensitive recurrent ovarian cancer are a heterogeneous group, and it is not possible to accurately predict the progression-free survival (PFS) in these patients. We developed and validated a nomogram to help improve prediction of PFS in patients treated with platinum-based chemotherapy. Methods: The nomogram was developed in a training cohort (n=955) from the CALYPSO trial and validated in the AGO-OVAR 2.5 Study (n=340). The proportional-hazards model (nomogram) was based on pre-treatment characteristics. Results: The nomogram had a concordance index (C-index) of 0.645. Significant predictors were tumour size platinum-chemotherapy-free interval, CA-125, number of organ metastatic sites and white blood count. When the nomogram was applied without CA-125 (CA-125 was not available in validation cohort), the C-indices were 0.624 (training) and 0.594 (validation). When classification was based only on the platinum-chemotherapy-free interval, the indices were 0.571 (training) and 0.560 (validation). The calibration plot in the validation cohort based on four predictors (without CA-125) suggested good agreement between actual and nomogram-predicted 12-month PFS probabilities. Conclusion: This nomogram, using five pre-treatment characteristics, improves prediction of PFS in patients with platinum-sensitive ovarian cancer having platinum-based chemotherapy. It will be useful for the design and stratification of patients in clinical trials and also for counselling patients. PMID:21915127

  8. Anemia before and during concurrent chemoradiotherapy in patients with cervical carcinoma: Effect on progression-free survival.

    PubMed

    Obermair, A; Cheuk, R; Horwood, K; Neudorfer, M; Janda, M; Giannis, G; Nicklin, J L; Perrin, L C; Crandon, A J

    2003-01-01

    To determine the impact of anemia before and during chemoradiation in patients with cervical cancer, we collected data on hemoglobin (Hb) levels before and during treatment from 60 unselected patients with cervical carcinoma. All patients had FIGO stage IB to IVA disease and were treated with concurrent chemoradiation for the aim of cure. Patients with an Hb value below or equal to the lower 25th quartile were considered anemic. Progression-free survival (PFS) was evaluated by univariate and multivariate analyses. After a median follow-up of 26.3 months, 20 patients developed disease progression. The lowest Hb during chemoradiation (nadir Hb), the stage of disease, and parametrial involvement were correlated significantly with PFS. On multivariate analysis, the nadir Hb (relative risk [RR] 0.29) and tumor stage (RR 3.4) remained the only prognostically relevant factors predicting PFS. At 60 months the PFS was 39.1% for anemic patients and 48.0% for nonanemic patients (P < 0.0002). In patients undergoing chemoradiation for cervical carcinoma, a low nadir Hb is highly predictive of shortened PFS, whereas the Hb before treatment is prognostically not significant. PMID:14675347

  9. Cytokine gene polymorphisms and progression-free survival in classical Hodgkin lymphoma by EBV status: Results from two independent cohorts

    PubMed Central

    Ghesquières, Hervé; Maurer, Matthew J.; Casasnovas, Olivier; Ansell, Stephen M.; Larrabee, Beth R.; Lech-Maranda, Eva; Novak, Anne J.; Borrel, Anne-Laure; Slager, Susan L.; Brice, Pauline; Allmer, Cristine; Brion, Annie; Ziesmer, Steven C.; Morschhauser, Franck; Habermann, Thomas M.; Gaillard, Isabelle; Link, Brian K.; Stamatoullas, Aspasia; Fermé, Christophe; Dogan, Ahmet; Macon, William R.; Audouin, Josée; Cerhan, James R.; Salles, Gilles

    2014-01-01

    Background Cytokines are important immune mediators of classical Hodgkin lymphoma (CHL) pathogenesis, and circulating levels at diagnosis may help predict prognosis. Germline single nucleotide polymorphisms (SNPs) in immune genes have been correlated with cytokine production and function. Methods We investigated whether selected germline SNPs in IL10 (rs1800890, rs1800896, rs1800871, rs1800872), TNFA (rs1800629), IL6 (rs1800795), ILRN (rs419598), INFG (rs2430561) and CCL17 (rs223828) were associated with circulating levels of related cytokines at diagnosis and progression-free survival (PFS) in CHL. Patients were from France (GELA, N = 464; median age = 32 years) and the United States (Iowa/Mayo Specialized Program Of Research Excellence [SPORE], N = 239; median age = 38 years); 22% of 346 CHL cases with EBV tumor status were positive. Results There was no association with any of the SNPs with cytokine levels. Overall, there was no association of any of the SNPs with PFS. In exploratory analyses by EBV status, TNFA rs1800629 (HRAA/AG = 2.41; 95%CI, 1.17–4.94) was associated with PFS in EBV-negative GELA patients, with similar trends in the SPORE patients (HRAA/AG = 1.63; 95%CI, 0.61–4.40). In a meta-analysis of the two studies, TNFA (HRAA/AG = 2.11; 95%CI, 1.18–3.77; P = 0.01) was statistically significant, and further adjustment for the international prognostic system did not alter this result. Conclusions This study showed that germline variation in TNFA was associated with CHL prognosis for EBV-negative patients, which will require confirmation. These results support broader studies on the differential impact of genetic variation in immune genes on EBV-positive vs. EBV-negative CHL pathogenesis. PMID:24008079

  10. Long‐Term Post‐CABG Survival: Performance of Clinical Risk Models Versus Actuarial Predictions

    PubMed Central

    Carr, Brendan M.; Romeiser, Jamie; Ruan, Joyce; Gupta, Sandeep; Seifert, Frank C.; Zhu, Wei

    2015-01-01

    Abstract Background/aim Clinical risk models are commonly used to predict short‐term coronary artery bypass grafting (CABG) mortality but are less commonly used to predict long‐term mortality. The added value of long‐term mortality clinical risk models over traditional actuarial models has not been evaluated. To address this, the predictive performance of a long‐term clinical risk model was compared with that of an actuarial model to identify the clinical variable(s) most responsible for any differences observed. Methods Long‐term mortality for 1028 CABG patients was estimated using the Hannan New York State clinical risk model and an actuarial model (based on age, gender, and race/ethnicity). Vital status was assessed using the Social Security Death Index. Observed/expected (O/E) ratios were calculated, and the models' predictive performances were compared using a nested c‐index approach. Linear regression analyses identified the subgroup of risk factors driving the differences observed. Results Mortality rates were 3%, 9%, and 17% at one‐, three‐, and five years, respectively (median follow‐up: five years). The clinical risk model provided more accurate predictions. Greater divergence between model estimates occurred with increasing long‐term mortality risk, with baseline renal dysfunction identified as a particularly important driver of these differences. Conclusions Long‐term mortality clinical risk models provide enhanced predictive power compared to actuarial models. Using the Hannan risk model, a patient's long‐term mortality risk can be accurately assessed and subgroups of higher‐risk patients can be identified for enhanced follow‐up care. More research appears warranted to refine long‐term CABG clinical risk models. doi: 10.1111/jocs.12665 (J Card Surg 2016;31:23–30) PMID:26543019

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

    PubMed Central

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

    2014-01-01

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

  12. Six-month progression-free survival as an alternative primary efficacy endpoint to overall survival in newly diagnosed glioblastoma patients receiving temozolomide

    PubMed Central

    Polley, Mei-Yin C.; Lamborn, Kathleen R.; Chang, Susan M.; Butowski, Nicholas; Clarke, Jennifer L.; Prados, Michael

    2010-01-01

    We assessed six-month progression-free survival (PFS) as an alternative primary efficacy endpoint to overall survival in newly diagnosed glioblastoma multiforme (GBM) patients receiving temozolomide (TMZ). A total of 183 patients with newly diagnosed GBM enrolled in 3 phase II protocols at the University of California–San Francisco were included. Patients were treated with interventions based on the Stupp regimen, each with the added component of a second oral agent given concurrently with radiotherapy and TMZ, followed by its coadministration with adjuvant TMZ. We examined whether progression status at 2, 4, and 6 months predicted subsequent survival using the landmark analysis. The hazard ratios of death as a function of progression status were estimated based on the Cox proportional hazards model after adjustment for putative prognostic factors. Progression status at 2, 4, and 6 months were all consistently found to be strong predictors of subsequent survival in all studies. The study-specific hazard ratios associated with progression status at 6 months ranged from 2.03 to 3.39. The hazard ratios associated with the earlier time points (2- and 4-month progression) all exceeded 2 in magnitude, ranging from 2.29 to 4.73. P-values were statistically significant for all time points. In this report, we demonstrated a strong association between the endpoints of PFS at 2, 4, and 6 months and survival. Patients who showed the signs of early progression were at significantly higher risk of earlier death. Our analysis suggests that 6-month PFS may be an appropriate primary endpoint in the context of phase II upfront GBM trials in the TMZ era. PMID:20167815

  13. Is surgery at progression a prognostic marker for improved 6-month progression-free survival or overall survival for patients with recurrent glioblastoma?

    PubMed

    Clarke, Jennifer L; Ennis, Michele M; Yung, W K Alfred; Chang, Susan M; Wen, Patrick Y; Cloughesy, Timothy F; Deangelis, Lisa M; Robins, H Ian; Lieberman, Frank S; Fine, Howard A; Abrey, Lauren; Gilbert, Mark R; Mehta, Minesh; Kuhn, John G; Aldape, Kenneth D; Lamborn, Kathleen R; Prados, Michael D

    2011-10-01

    Historically, the North American Brain Tumor Consortium used 6-month progression-free survival (PFS6) as the primary outcome for recurrent glioma phase II clinical trials. In some trials, a subset of patients received the trial treatment before surgery to assess tumor uptake and biological activity. We compared PFS6 and overall survival (OS) for patients with glioblastoma undergoing surgery at progression to results for those without surgery to evaluate the impact of surgical intervention on these outcomes. Two data sets were analyzed. The first included 511 patients enrolled during the period 1998-2005, 105 of whom had surgery (excluding biopsies) during the study or ≤ 30 days prior to registration. Analysis was stratified on the basis of whether temozolomide was part of the protocol treatment regimen. The second data set included 247 patients enrolled during 2005-2008, 103 of whom underwent surgery during the clinical trial or immediately prior to study registration. A combined data set consisting of all patients who did not receive temozolomide was also compiled. No statistically significant difference in PFS6 or OS was found between the surgery and nonsurgery groups in either data set alone or in the combined data set (P > .45). We conclude that PFS6 and OS results for patients with and without surgical intervention at the time of progression are similar, allowing data from these patients to be combined in assessing the benefit of new treatments without the need for stratification or other statistical adjustment.

  14. Is surgery at progression a prognostic marker for improved 6-month progression-free survival or overall survival for patients with recurrent glioblastoma?

    PubMed Central

    Clarke†, Jennifer L.; Ennis†, Michele M.; Yung, W. K. Alfred; Chang, Susan M.; Wen, Patrick Y.; Cloughesy, Timothy F.; DeAngelis, Lisa M.; Robins, H. Ian; Lieberman, Frank S.; Fine, Howard A.; Abrey, Lauren; Gilbert, Mark R.; Mehta, Minesh; Kuhn, John G.; Aldape, Kenneth D.; Lamborn, Kathleen R.; Prados, Michael D.

    2011-01-01

    Historically, the North American Brain Tumor Consortium used 6-month progression-free survival (PFS6) as the primary outcome for recurrent glioma phase II clinical trials. In some trials, a subset of patients received the trial treatment before surgery to assess tumor uptake and biological activity. We compared PFS6 and overall survival (OS) for patients with glioblastoma undergoing surgery at progression to results for those without surgery to evaluate the impact of surgical intervention on these outcomes. Two data sets were analyzed. The first included 511 patients enrolled during the period 1998–2005, 105 of whom had surgery (excluding biopsies) during the study or ≤30 days prior to registration. Analysis was stratified on the basis of whether temozolomide was part of the protocol treatment regimen. The second data set included 247 patients enrolled during 2005–2008, 103 of whom underwent surgery during the clinical trial or immediately prior to study registration. A combined data set consisting of all patients who did not receive temozolomide was also compiled. No statistically significant difference in PFS6 or OS was found between the surgery and nonsurgery groups in either data set alone or in the combined data set (P > .45). We conclude that PFS6 and OS results for patients with and without surgical intervention at the time of progression are similar, allowing data from these patients to be combined in assessing the benefit of new treatments without the need for stratification or other statistical adjustment. PMID:21813511

  15. Contemporary phase III clinical trial endpoints in advanced ovarian cancer: assessing the pros and cons of objective response rate, progression-free survival, and overall survival.

    PubMed

    Tate Thigpen, J

    2015-01-01

    Among gynecologic cancers, ovarian cancer provides the greatest challenge because 75% to 80% of patients present with stage III/IV disease. Over the last 40 years, a series of large trials conducted by the Gynecologic Oncology Group and other cooperative groups has produced striking improvements in patient outcome; but the majority still dies of their disease. Further research in both the laboratory and the clinic is essential to continued improvement in patient management. Clinical trials, however, have become a major challenge because of issues with trial endpoints. Historically, overall survival (OS) has been regarded as the "gold standard" of endpoints. Lack of effective treatment for patients who progressed on or recurred after front-line therapy allowed trials to avoid obfuscation of OS by post-progression therapy. More recently, studies have identified over 20 agents active against ovarian cancer. Reasonable evidence shows that effective post-progression therapy with multiple lines of active agents can render the survival endpoint uninterpretable. Two other endpoints avoid this problem. The objective response rate, assessed by the Response Evaluation Criteria in Solid Tumors (RECIST), is an accepted endpoint for accelerated approval in ovarian cancer. More importantly, progression-free survival (PFS), measured from study entry to progression of disease, avoids post-progression therapy completely. Without effective post-progression therapy (prior to 1990), data show that PFS is a surrogate for OS. Recent experience with 4 large trials of bevacizumab shows that PFS can be accurately assessed if progression is clearly defined and if timing of assessments is consistent in all study arms. Acceptance of PFS as the optimal endpoint for ovarian cancer trials by investigators and regulatory agencies is crucial to further advances in management because effective post-progression therapy has rendered differences in OS virtually impossible to assess reliably.

  16. Actuarial Valuation.

    ERIC Educational Resources Information Center

    Teachers Retirement System of Louisiana, Baton Rouge.

    This report presents the results of the actuarial valuation of assets and liabilities as well as funding requirements for the Teachers Retirement System of Louisiana as of June 30, 1996. Data reported include current funding, actuarial assets and valuation assets. These include the Louisiana State University Agriculture and Extension Service Fund,…

  17. Progression-free survival of two cases of high-risk neuroblastoma with refractory/relapsed disease following surgery alone.

    PubMed

    Sokol, Elizabeth; Haut, Paul R; Gosiengfiao, Yasmin; Feinstein, Kate; Pytel, Peter; Cohn, Susan L

    2013-03-01

    Outcome for the vast majority of high-risk neuroblastoma patients with refractory or relapsed disease is dismal. We report two high-risk patients who remain progression-free for more than 113 and 18 months following the diagnosis of refractory/relapsed disease who were treated with surgery alone. Complete resolution of a refractory thoracic mass and relapsed liver nodules was observed in one patient. The refractory/relapsed disease in the second patient has remained stable. In both cases, the tumor showed histologic evidence of neuroblastoma maturation. These cases demonstrate that refractory/relapsed neuroblastoma is clinically heterogeneous and highlight the need for better biomarkers to optimize patient care.

  18. Active Smoking May Negatively Affect Response Rate, Progression-Free Survival, and Overall Survival of Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib

    PubMed Central

    Keizman, Daniel; Gottfried, Maya; Ish-Shalom, Maya; Maimon, Natalie; Peer, Avivit; Neumann, Avivit; Hammers, Hans; Eisenberger, Mario A.; Sinibaldi, Victoria; Pili, Roberto; Hayat, Henry; Kovel, Svetlana; Sella, Avishay; Boursi, Ben; Weitzen, Rony; Mermershtain, Wilmosh; Rouvinov, Keren; Berger, Raanan; Carducci, Michael A.

    2014-01-01

    Background. Obesity, smoking, hypertension, and diabetes are risk factors for renal cell carcinoma development. Their presence has been associated with a worse outcome in various cancers. We sought to determine their association with outcome of sunitinib treatment in metastatic renal cell carcinoma (mRCC). Methods. An international multicenter retrospective study of sunitinib-treated mRCC patients was performed. Multivariate analyses were performed to determine the association between outcome and the pretreatment status of smoking, body mass index, hypertension, diabetes, and other known prognostic factors. Results. Between 2004 and 2013, 278 mRCC patients were treated with sunitinib: 59 were active smokers, 67 were obese, 73 were diabetic, and 165 had pretreatment hypertension. Median progression-free survival (PFS) was 9 months, and overall survival (OS) was 22 months. Factors associated with PFS were smoking status (past and active smokers: hazard ratio [HR]: 1.17, p = .39; never smokers: HR: 2.94, p < .0001), non-clear cell histology (HR: 1.62, p = .011), pretreatment neutrophil-to-lymphocyte ratio >3 (HR: 3.51, p < .0001), use of angiotensin system inhibitors (HR: 0.63, p = .01), sunitinib dose reduction or treatment interruption (HR: 0.72, p = .045), and Heng risk (good and intermediate risk: HR: 1.07, p = .77; poor risk: HR: 1.87, p = .046). Factors associated with OS were smoking status (past and active smokers: HR: 1.25, p = .29; never smokers: HR: 2.7, p < .0001), pretreatment neutrophil-to-lymphocyte ratio >3 (HR: 2.95, p < .0001), and sunitinib-induced hypertension (HR: 0.57, p = .002). Conclusion. Active smoking may negatively affect the PFS and OS of sunitinib-treated mRCC. Clinicians should consider advising patients to quit smoking at initiation of sunitinib treatment for mRCC. PMID:24309979

  19. Correlation between progression-free survival and overall survival in metastatic breast cancer patients receiving anthracyclines, taxanes, or targeted therapies: a trial-level meta-analysis

    PubMed Central

    Adunlin, George; Cyrus, John W. W.; Dranitsaris, George

    2016-01-01

    Over the past decade, several new drugs have received regulatory approval for metastatic breast cancer (MBC). However, some of these approvals were based on improvement in progression-free survival (PFS), without a concomitant increase in overall survival (OS). This has led some to question the utility of using PFS as a measure for drug approval. To address the uncertainty of using PFS as a surrogate for OS in MBC, a systematic literature review followed by a trial-level correlative analysis was conducted in patients receiving anthracyclines, taxanes, or targeted therapies. Electronic databases were searched to identify randomized trials published between January 1990 and August 2015. Data extraction included hazard ratios for PFS (HRPFS) and OS (HROS) between comparative arms as well as trial-level parameters. Weighted multivariate regression analysis was then used to test the strength of the association between HRPFS and HROS. 72 trials providing 84 comparative arms met the inclusion criteria. HRPFS was a significant predictor of HROS (model coefficient = 0.18, p = 0.04). However, only 31 % (i.e., model R2) of the variability between the PFS–OS association was accounted for. When trials were limited to ≥2nd-line setting, the strength of the association improved (model coefficient = 0.40, p < 0.001) and the model R2 increased to 55 %. However, the HRPFS–HROS association was no longer significant when only 1st-line trials were considered (p = 0.90). HRPFS is a predictor for HROS in MBC randomized trials. However, the effect was driven by trials in the ≥2nd-line setting. Therefore, PFS can be a suitable surrogate for OS in trials evaluating new treatments in the 2nd setting and beyond. The use of PFS alone as a primary trial endpoint in the 1st-line setting is not recommended. PMID:26596731

  20. Intra-Arterial Delivery of Bevacizumab after Blood-Brain Barrier Disruption for the Treatment of Recurrent Glioblastoma: Progression-Free Survival and Overall Survival

    PubMed Central

    Burkhardt, Jan-Karl; Riina, Howard; Shin, Benjamin J.; Christos, Paul; Kesavabhotla, Kartik; Hofstetter, Christoph P.; Tsiouris, Apostolos John; Boockvar, John A.

    2013-01-01

    BACKGROUND This prospective, single-center study assesses progression-free survival (PFS) and overall survival (OS) in patients with recurrent glioblastoma multiforme (GBM) treated with a single dose of superselective intra-arterial cerebral infusion (SIACI) of bevacizumab (BV) after blood-brain barrier disruption (BBBD). Patients were initially enrolled in our phase I study, for which the primary end point was to determine the safety and maximum tolerated dose of SIACI BV. METHODS Fourteen patients with recurrent GBM were recruited between August 2009 and November 2010 after failing the standard treatment with radiation therapy and temozolomide. None of these patients were previously treated with BV. After receiving a single dose of IA BV (2 to 15 mg/kg), standard IV BV chemotherapy was continued in 12 of 14 patients (86%). The recently updated Response Assessment in Neuro-Oncology Working Group (RANO) criteria were used to evaluate PFS, and the Kaplan-Meier estimator was used to evaluate PFS and OS. RESULTS Using RANO criteria, the median PFS in these patients was 10 months. The median OS estimation for this cohort was 8.8 months. The OS was less than the PFS because 4 patients died without progressing. Toxicity attributed to the IA BV treatment was present in 2 patients (wound dehiscence and rash). Another patient suffered from seizures 1 week after the SIACI procedure; however, this patient had epilepsy before and seizure type/frequency were similar before and after therapy. CONCLUSIONS Our study shows that for patients naïve to BV, a single dose of SIACI BV after BBBD followed by IV BV offers an encouraging outcome in terms of PFS when compared with previous trials using IV BV with and without concomitant irinotecan (CPT-11). Larger phase II trials are warranted to determine whether repeated IA BV alone is superior to IV BV for recurrent GBM. PMID:22405392

  1. Association of Drug Transporter Expression with Mortality and Progression-Free Survival in Stage IV Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Mogler, Carolin; Herpel, Esther; Grabe, Niels; Lahrmann, Bernd; Plinkert, Peter K.; Herold-Mende, Christel; Weiss, Johanna; Dyckhoff, Gerhard

    2014-01-01

    Drug transporters such as P-glycoprotein (ABCB1) have been associated with chemotherapy resistance and are considered unfavorable prognostic factors for survival of cancer patients. Analyzing mRNA expression levels of a subset of drug transporters by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or protein expression by tissue microarray (TMA) in tumor samples of therapy naïve stage IV head and neck squamous cell carcinoma (HNSCC) (qRT-PCR, n = 40; TMA, n = 61), this in situ study re-examined the significance of transporter expression for progression-free survival (PFS) and overall survival (OS). Data from The Cancer Genome Atlas database was used to externally validate the respective findings (n = 317). In general, HNSCC tended to lower expression of drug transporters compared to normal epithelium. High ABCB1 mRNA tumor expression was associated with both favorable progression-free survival (PFS, p = 0.0357) and overall survival (OS, p = 0.0535). Similar results were obtained for the mRNA of ABCC1 (MRP1, multidrug resistance-associated protein 1; PFS, p = 0.0183; OS, p = 0.038). In contrast, protein expression of ATP7b (copper transporter ATP7b), mRNA expression of ABCG2 (BCRP, breast cancer resistance protein), ABCC2 (MRP2), and SLC31A1 (hCTR1, human copper transporter 1) did not correlate with survival. Cluster analysis however revealed that simultaneous high expression of SLC31A1, ABCC2, and ABCG2 indicates poor survival of HNSCC patients. In conclusion, this study militates against the intuitive dogma where high expression of drug efflux transporters indicates poor survival, but demonstrates that expression of single drug transporters might indicate even improved survival. Prospectively, combined analysis of the ‘transportome’ should rather be performed as it likely unravels meaningful data on the impact of drug transporters on survival of patients with HNSCC. PMID:25275603

  2. {sup 18}Fluorodeoxyglucose PET Is Prognostic of Progression-Free and Overall Survival in Locally Advanced Pancreas Cancer Treated With Stereotactic Radiotherapy

    SciTech Connect

    Schellenberg, Devin; Quon, Andy; Minn, A. Yuriko; Graves, Edward E.; Kunz, Pamela; Ford, James M.; Fisher, George A.; Goodman, Karyn A.; Koong, Albert C.; Chang, Daniel T.

    2010-08-01

    Purpose: This study analyzed the prognostic value of positron emission tomography (PET) for locally advanced pancreas cancer patients undergoing stereotactic body radiotherapy (SBRT). Patients and Methods: Fifty-five previously untreated, unresectable pancreas cancer patients received a single fraction of 25-Gy SBRT sequentially with gemcitabine-based chemotherapy. On the preradiation PET-CT, the tumor was contoured and the maximum standardized uptake value (SUVmax) and metabolic tumor burden (MTB) were calculated using an in-house software application. High-SUVmax and low-SUVmax subgroups were created by categorizing patients above or below the median SUVmax. The analysis was repeated to form high-MTB and low-MTB subgroups as well as clinically relevant subgroups with SUVmax values of <5, 5-10, or >10. Multivariate analysis analyzing SUVmax, MTB, age, chemotherapy cycles, and pretreatment carbohydrate antigen (CA)19-9 was performed. Results: For the entire population, median survival was 12.7 months. Median survival was 9.8 vs.15.3 months for the high- and low- SUVmax subgroups (p <0.01). Similarly, median survival was 10.1 vs. 18.0 months for the high MTB and low MTB subgroups (p <0.01). When clinical SUVmax cutoffs were used, median survival was 6.4 months in those with SUVmax >10, 9.5 months with SUVmax 5.0-10.0, and 17.7 months in those with SUVmax <5 (p <0.01). On multivariate analysis, clinical SUVmax was an independent predictor for overall survival (p = 0.03) and progression-free survival (p = 0.03). Conclusion: PET scan parameters can predict for length of survival in locally advanced pancreas cancer patients.

  3. Treatment with Hypomethylating Agents before Allogeneic Stem Cell Transplant Improves Progression-Free Survival for Patients with Chronic Myelomonocytic Leukemia.

    PubMed

    Kongtim, Piyanuch; Popat, Uday; Jimenez, Antonio; Gaballa, Sameh; El Fakih, Riad; Rondon, Gabriela; Chen, Julianne; Bueso-Ramos, Carlos; Borthakur, Gautam; Pemmaraju, Naveen; Garcia-Manero, Guillermo; Kantarjian, Hagop; Alousi, Amin; Hosing, Chitra; Anderlini, Paolo; Khouri, Issa F; Kebriaei, Partow; Andersson, Borje S; Oran, Betul; Rezvani, Katayoun; Marin, David; Shpall, Elizabeth J; Champlin, Richard E; Ciurea, Stefan O

    2016-01-01

    The treatment of patients with chronic myelomonocytic leukemia (CMML) with transplant has not been optimized. We retrospectively reviewed the data for 83 consecutive patients with CMML (47 with CMML-1/2 and 36 with CMML progressed to acute myeloid leukemia) who received an allogeneic stem cell transplant (allo-SCT) at our institution between April 1991 and December 2013 to identify factors associated with improved survival and determine whether treatment with hypomethylating agents before transplant improves progression-free survival (PFS). The median age of the cohort was 57 years. Seventy-eight patients received induction treatment before transplant, with 37 receiving hypomethylating agents and 41 receiving cytotoxic chemotherapy. Patients treated with a hypomethylating agent had a significantly lower cumulative incidence of relapse at 3 years post-transplant (22%) than those treated with other agents (35%; P = .03), whereas treatment-related mortality at 1 year post-transplant did not significantly differ between the groups (27% and 30%, respectively; P = .84). The lower relapse rate resulted in a significantly higher 3-year PFS rate in patients treated with a hypomethylating agent (43%) than in those treated with other agents (27%; P = .04). Our data support the use of hypomethylating agents before allo-SCT for patients with CMML to achieve morphologic remission and improve PFS of these patients. Future studies are needed to confirm these findings.

  4. Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML).

    PubMed

    Hanfstein, B; Müller, M C; Hehlmann, R; Erben, P; Lauseker, M; Fabarius, A; Schnittger, S; Haferlach, C; Göhring, G; Proetel, U; Kolb, H-J; Krause, S W; Hofmann, W-K; Schubert, J; Einsele, H; Dengler, J; Hänel, M; Falge, C; Kanz, L; Neubauer, A; Kneba, M; Stegelmann, F; Pfreundschuh, M; Waller, C F; Branford, S; Hughes, T P; Spiekermann, K; Baerlocher, G M; Pfirrmann, M; Hasford, J; Saußele, S; Hochhaus, A

    2012-09-01

    In the face of competing first-line treatment options for CML, early prediction of prognosis on imatinib is desirable to assure favorable survival or otherwise consider the use of a second-generation tyrosine kinase inhibitor (TKI). A total of 1303 newly diagnosed imatinib-treated patients (pts) were investigated to correlate molecular and cytogenetic response at 3 and 6 months with progression-free and overall survival (PFS, OS). The persistence of BCR-ABL transcript levels >10% according to the international scale (BCR-ABL(IS)) at 3 months separated a high-risk group (28% of pts; 5-year OS: 87%) from a group with >1-10% BCR-ABL(IS) (41% of pts; 5-year OS: 94%; P=0.012) and from a group with ≤1% BCR-ABL(IS) (31% of pts; 5-year OS: 97%; P=0.004). Cytogenetics identified high-risk pts by >35% Philadelphia chromosome-positive metaphases (Ph+, 27% of pts; 5-year OS: 87%) compared with ≤35% Ph+ (73% of pts; 5-year OS: 95%; P=0.036). At 6 months, >1% BCR-ABL(IS) (37% of pts; 5-year OS: 89%) was associated with inferior survival compared with ≤1% (63% of pts; 5-year OS: 97%; P<0.001) and correspondingly >0% Ph+ (34% of pts; 5-year OS: 91%) compared with 0% Ph+ (66% of pts; 5-year OS: 97%; P=0.015). Treatment optimization is recommended for pts missing these landmarks. PMID:22446502

  5. Progression-free and overall survival in metastatic castration-resistant prostate cancer treated with abiraterone acetate can be predicted with serial C11-acetate PET/CT

    PubMed Central

    Farnebo, Jacob; Wadelius, Agnes; Sandström, Per; Nilsson, Sten; Jacobsson, Hans; Blomqvist, Lennart; Ullén, Anders

    2016-01-01

    Abstract In this retrospective study, we evaluated the benefit of repeated carbon 11 (C11)-acetate positron emission tomography/computed tomography (PET/CT) to assess response in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA). A total of 30 patients with mCRPC were monitored with C11-acetate PET/CT and PSA levels during their treatment with AA. Retrospective evaluation of their response was made after 102 days (median; range 70–155) of treatment. Statistical analyses were employed to detect predictors of progression-free survival (PFS) and overall survival (OS), and potential correlation between serum levels of PSA, standardized uptake values (SUVpeak), and bone lesion index measured from PET were investigated. At follow-up 10 patients exhibited partial response (PR), 10 progressive disease (PD), and 10 stable disease (SD), as assessed by PET/CT. In survival analysis, both PR and PD were significantly associated with PFS and OS. CT response was also associated with OS, but only 19/30 patients demonstrated a lesion meeting target lesion criteria according to RECIST 1.1. No PET/CT baseline characteristic was significantly associated with PFS or OS. A PSA response (reduction in the level by >50%) could also predict PFS and OS. In the subgroup lacking a PSA response, those with PD had significantly shorter OS than those with PR or SD. PFS and OS in patients with mCRPC treated with AA can be predicted from repeated C11-acetate PET/CT. This may be of particular clinical value in patients who do not exhibit a PSA response to treatment. PMID:27495034

  6. Progression-free and overall survival in metastatic castration-resistant prostate cancer treated with abiraterone acetate can be predicted with serial C11-acetate PET/CT.

    PubMed

    Farnebo, Jacob; Wadelius, Agnes; Sandström, Per; Nilsson, Sten; Jacobsson, Hans; Blomqvist, Lennart; Ullén, Anders

    2016-08-01

    In this retrospective study, we evaluated the benefit of repeated carbon 11 (C11)-acetate positron emission tomography/computed tomography (PET/CT) to assess response in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA).A total of 30 patients with mCRPC were monitored with C11-acetate PET/CT and PSA levels during their treatment with AA. Retrospective evaluation of their response was made after 102 days (median; range 70-155) of treatment. Statistical analyses were employed to detect predictors of progression-free survival (PFS) and overall survival (OS), and potential correlation between serum levels of PSA, standardized uptake values (SUVpeak), and bone lesion index measured from PET were investigated.At follow-up 10 patients exhibited partial response (PR), 10 progressive disease (PD), and 10 stable disease (SD), as assessed by PET/CT. In survival analysis, both PR and PD were significantly associated with PFS and OS. CT response was also associated with OS, but only 19/30 patients demonstrated a lesion meeting target lesion criteria according to RECIST 1.1. No PET/CT baseline characteristic was significantly associated with PFS or OS. A PSA response (reduction in the level by >50%) could also predict PFS and OS. In the subgroup lacking a PSA response, those with PD had significantly shorter OS than those with PR or SD.PFS and OS in patients with mCRPC treated with AA can be predicted from repeated C11-acetate PET/CT. This may be of particular clinical value in patients who do not exhibit a PSA response to treatment. PMID:27495034

  7. Progression-free and overall survival in patients with recurrent Glioblastoma multiforme treated with last-line bevacizumab versus bevacizumab/lomustine.

    PubMed

    Heiland, D H; Masalha, W; Franco, P; Machein, M R; Weyerbrock, A

    2016-02-01

    Bevacizumab (BEV) is widely used for treatment of patients with recurrent glioblastoma multiforme (GBM). 1-(2-Chlorethyl)-cyclohexyl-nitrosourea (CCNU, lomustine) monotherapy is an approved chemotherapeutical option for recurrent GBM. Recent evidence demonstrated a survival benefit of combined treatment with BEV and CCNU in patients with a first recurrence of GBM. We examined the outcome of recurrent GBM patients with BEV monotherapy versus BEV/CCNU therapy when used as last-line therapy. 35 patients with recurrent GBM treated between 2010 and 2014 were included in this retrospective study. Progression-free and overall survival was determined with reference to the beginning of BEV or BEV/CCNU therapy and initial diagnosis. 17 patients received BEV monotherapy, 18 patients received combined BEV and CCNU therapy. The impact of parameters such as IDH mutation, MGMT promoter methylation, tumor localization, histology and the number of surgeries were included in a multivariate ANOVA analysis. Furthermore, Karnofsky performance score (KPS), neurological function and toxicity were assessed. BEV/CCNU treatment led to an extension of PFS (6.11 months; 95% CL 3.41-12.98 months; log-rank p = 0.00241) and OS (6.59 months; 95% CL 5.51-16.3 months; log-rank p = 0.0238) of 2 months compared to BEV monotherapy. This survival advantage was independent of histology, IDH mutation status or the number of previous surgeries. Neurological function, KPS and toxicity were not significantly different between both treatment groups. Last-line therapy with BEV/CCNU results in a longer PFS and OS compared to BEV monotherapy and is well-tolerated. These findings confirm the role of these agents in the treatment of recurrent GBM and are in line with other studies. PMID:26614518

  8. Larger number of invariant natural killer T cells in PBSC allografts correlates with improved GVHD-free and progression-free survival.

    PubMed

    Malard, Florent; Labopin, Myriam; Chevallier, Patrice; Guillaume, Thierry; Duquesne, Alix; Rialland, Fanny; Derenne, Sophie; Peterlin, Pierre; Leauté, Anne-Gaelle; Brissot, Eolia; Gregoire, Marc; Moreau, Philippe; Saas, Philippe; Gaugler, Béatrice; Mohty, Mohamad

    2016-04-01

    We studied the impact of a set of immune cells contained within granulocyte colony-stimulating factor-mobilized peripheral blood stem cell grafts (naïve and memory T-cell subsets, B cells, regulatory T cells, invariant natural killer T cells [iNKTs], NK cells, and dendritic cell subsets) in patients (n = 80) undergoing allogeneic stem cell transplantation (SCT), using the composite end point of graft-versus-host disease (GVHD)-free and progression-free survival (GPFS) as the primary end point. We observed that GPFS incidences in patients receiving iNKT doses above and below the median were 49% vs 22%, respectively (P= .007). In multivariate analysis, the iNKT dose was the only parameter with a significant impact on GPFS (hazard ratio = 0.48; 95% confidence interval, 0.27-0.85;P= .01). The incidences of severe grade III to IV acute GVHD and National Institutes of Health grade 2 to 3 chronic GVHD (12% and 16%, respectively) were low and associated with the use of antithymocyte globulin in 91% of patients. No difference in GVHD incidence was reported according to the iNKT dose. In conclusion, a higher dose of iNKTs within the graft is associated with an improved GPFS. These data may pave the way for prospective and active interventions aiming to manipulate the graft content to improve allo-SCT outcome.

  9. Prediction of biomarkers of therapeutic effects of patients with lung adenocarcinoma treated with gefitinib based on progression-free-survival by metabolomic fingerprinting.

    PubMed

    Zhuang, Jingcong; Tang, Xiaohu; Du, Zhenxia; Yang, Ming; Zhou, Ying

    2016-11-01

    Lung carcinoma is one of the most frequently diagnosed malignancy and threats human life and health. In clinical practice, gefitinib, one of the most well-known epidermal growth factor receptor tyrosine kinase inhibitors, was frequently used in the treatment of non-small cell lung carcinoma. However, this drug is not useful for all non-small cell patients. In this study, the biomarkers were found out to predict the therapeutic effects of gefitinib for lung carcinoma patients. Serum samples were collected from patients with advanced lung adenocarcinoma. The ultra-high performance liquid chromatography (UHPLC)-quadrupole-time of flight mass spectrometry (Q-TOF MS) was conducted to obtain the metabolic data for each patient. Partial least squares-discriminate analysis (PLS-DA) was performed to indicate the differences between metabolites of patients, and Cox proportional hazards regression analysis was used to eliminate the interference of the patient's gender, age, smoking history and disease stage. Thus, differential biomarkers were found. The combination of these biomarkers was statistically significant predictors based on progression-free survival. If these biomarkers can be further confirmed by the clinic, it could suggest the proper therapeutic schedule, and help to reduce patients' economic burden and medication side effects. PMID:27591660

  10. Lower expression of activating transcription factors 3 and 4 correlates with shorter progression-free survival in multiple myeloma patients receiving bortezomib plus dexamethasone therapy.

    PubMed

    Narita, T; Ri, M; Masaki, A; Mori, F; Ito, A; Kusumoto, S; Ishida, T; Komatsu, H; Iida, S

    2015-12-04

    Bortezomib (BTZ), a proteasome inhibitor, is widely used in the treatment of multiple myeloma (MM), but a fraction of patients respond poorly to this agent. To identify factors predicting the duration of progression-free survival (PFS) of MM patients on BTZ treatment, the expression of proteasome and endoplasmic reticulum (ER) stress-related genes was quantified in primary samples from patients receiving a combination of BTZ and dexamethasone (BD). Fifty-six MM patients were stratified into a group with PFS<6 months (n=33) and a second group with PFS⩾6 months (n=23). Of the 15 genes analyzed, the expression of activating transcription factor 3 (ATF3) and ATF4 was significantly lower in patients with shorter PFS (P=0.0157 and P=0.0085, respectively). Chromatin immunoprecipitation analysis showed that these ATFs bind each other and transactivate genes encoding the pro-apoptotic transcription factors, CHOP and Noxa, which promote ER stress-associated apoptosis. When either ATF3 or ATF4 expression was silenced, MM cells partially lost sensitivity to BTZ treatment. This was accompanied by lower levels of Noxa, CHOP and DR5. Thus low basal expression of ATF3 and ATF4 may attenuate BTZ-induced apoptosis. Hence, ATF3 and ATF4 could potentially be used as biomarkers to predict efficacy of BD therapy in patients with MM.

  11. Genome Wide Association Study for Predictors of Progression Free Survival in Patients on Capecitabine, Oxaliplatin, Bevacizumab and Cetuximab in First-Line Therapy of Metastatic Colorectal Cancer

    PubMed Central

    Böhringer, Stefan; van der Straaten, Tahar; Gelderblom, Hans; Punt, Cornelis; Guchelaar, Henk-Jan

    2015-01-01

    Purpose Despite expanding options for systemic treatment, survival for metastatic colorectal cancer (mCRC) remains limited and individual response is difficult to predict. In search of pre-treatment predictors, pharmacogenetic research has mainly used a candidate gene approach. Genome wide association (GWA) studies offer the benefit of simultaneously analyzing a large number of SNPs, in both known and still unidentified functional regions. Using a GWA approach, we searched for genetic markers affecting progression free survival (PFS) in mCRC patients treated with first-line capecitabine, oxaliplatin and bevacizumab (CAPOX-B), with or without cetuximab. Patients and Methods 755 patients were included in the CAIRO2-trial, a multicenter phase III trial, randomizing between first-line treatment with CAPOX-B versus CAPOX-B plus cetuximab. Germline DNA and complete clinical information was available from 553 patients and genome wide genotyping was performed, using Illumina’s OmniExpress beadchip arrays, with 647,550 markers passing all quality checks. Another 2,202,473 markers were imputated by using HapMap2. Association with PFS was analysed using a Cox proportional hazards model. Results One marker, rs885036, associated significantly with PFS (P = 2.17x10-8) showing opposite effects on PFS depending on treatment arm. The minor allele was associated with increased PFS in patients receiving cetuximab. A cluster of markers located on chromosome 8 associated with PFS, irrespective of treatment arm (P-values of 2.30x10-7 to 1.04x10-6). Conclusion This is the first GWA study to find SNPs affecting PFS in mCRC patients treated with CAPOX-B, either with or without cetuximab. Rs885036 is a potential predictive marker for cetuximab efficacy. These markers need to be validated in independent treatment cohorts. PMID:26222057

  12. Consolidation chemotherapy improves progression-free survival in stage III small-cell lung cancer following concurrent chemoradiotherapy: a retrospective study

    PubMed Central

    Chen, Xin-Ru; Liang, Jian-Zhong; Ma, Shu-Xiang; Fang, Wen-Feng; Zhou, Ning-Ning; Liao, Hai; Li, De-Lan; Chen, Li-Kun

    2016-01-01

    Background Concurrent chemoradiotherapy (CCRT) is the standard treatment for limited-stage small-cell lung cancer (LD-SCLC). However, the efficacy of consolidation chemotherapy (CCT) in LD-SCLC remains controversial despite several studies that were performed in the early years of CCT use. The aim of this study was to reevaluate the effectiveness and toxicities associated with CCT. Methods This retrospective analysis evaluated 177 patients with stage IIIA and IIIB small-cell lung cancer (SCLC) who underwent CCRT from January 2001 to December 2013 at Sun Yat-Sen University Cancer Center (SYSUCC). Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier methods. Univariate and multivariate analyses were performed to analyze patient prognosis factors. Results Among the 177 patients, 72 (41%) received CCT and 105 (59%) did not receive CCT. PFS was significantly better for patients in the CCT group compared to that for patients in the non-CCT group (median PFS: 17.0 vs 12.9 months, respectively, P=0.031), whereas the differences in OS were not statistically significant (median OS: 31.6 vs 24.8 months, respectively, P=0.118). The 3- and 5-year OS rates were 33.3% and 20.8% for patients in the CCT group and 27.6% and 6.7% for patients in the non-CCT group, respectively. Multivariate analysis revealed that having a pretreatment carcinoembryonic antigen level <5 ng/mL (P=0.035), having undergone prophylactic cranial irradiation (P<0.001), and having received CCT (P=0.002) could serve as favorable independent prognostic factors for PFS. Multivariate analysis for OS also showed that having undergone PCI (P<0.001) and having received CCT (P=0.006) were independent significant prognostic factors. Conclusion CCT can improve PFS for patients with stage IIIA and IIIB SCLC following CCRT without significantly increasing treatment-related toxicities. PMID:27703372

  13. Immunologic Escape After Prolonged Progression-Free Survival With Epidermal Growth Factor Receptor Variant III Peptide Vaccination in Patients With Newly Diagnosed Glioblastoma

    PubMed Central

    Sampson, John H.; Heimberger, Amy B.; Archer, Gary E.; Aldape, Kenneth D.; Friedman, Allan H.; Friedman, Henry S.; Gilbert, Mark R.; Herndon, James E.; McLendon, Roger E.; Mitchell, Duane A.; Reardon, David A.; Sawaya, Raymond; Schmittling, Robert J.; Shi, Weiming; Vredenburgh, James J.; Bigner, Darell D.

    2010-01-01

    Purpose Immunologic targeting of tumor-specific gene mutations may allow precise eradication of neoplastic cells without toxicity. Epidermal growth factor receptor variant III (EGFRvIII) is a constitutively activated and immunogenic mutation not expressed in normal tissues but widely expressed in glioblastoma multiforme (GBM) and other neoplasms. Patients and Methods A phase II, multicenter trial was undertaken to assess the immunogenicity of an EGFRvIII-targeted peptide vaccine and to estimate the progression-free survival (PFS) and overall survival (OS) of vaccinated patients with newly diagnosed EGFRvIII-expressing GBM with minimal residual disease. Intradermal vaccinations were given until toxicity or tumor progression was observed. Sample size was calculated to differentiate between PFS rates of 20% and 40% 6 months after vaccination. Results There were no symptomatic autoimmune reactions. The 6-month PFS rate after vaccination was 67% (95% CI, 40% to 83%) and after diagnosis was 94% (95% CI, 67% to 99%; n = 18). The median OS was 26.0 months (95% CI, 21.0 to 47.7 months). After adjustment for age and Karnofsky performance status, the OS of vaccinated patients was greater than that observed in a control group matched for eligibility criteria, prognostic factors, and temozolomide treatment (hazard ratio, 5.3; P = .0013; n = 17). The development of specific antibody (P = .025) or delayed-type hypersensitivity (P = .03) responses to EGFRvIII had a significant effect on OS. At recurrence, 82% (95% CI, 48% to 97%) of patients had lost EGFRvIII expression (P < .001). Conclusion EGFRvIII-targeted vaccination in patients with GBM warrants investigation in a phase III, randomized trial. PMID:20921459

  14. Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

    PubMed Central

    2010-01-01

    Background Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs. Methods 55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated. Results Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact. Conclusions Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs. PMID:20663133

  15. EGFR mutations are associated with favorable intracranial response and progression-free survival following brain irradiation in non-small cell lung cancer patients with brain metastases

    PubMed Central

    2012-01-01

    Background The presence of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) is associated with increased radiosensitivity in vitro. However, the results from clinical studies regarding the radiosensitivity in NSCLC with mutant EGFR are inconclusive. We retrospectively analyzed our NSCLC patients who had been regularly followed up by imaging studies after irradiation for brain metastases, and investigated the impact of EGFR mutations on radiotherapy (RT). Methods Forty-three patients with brain metastases treated with RT, together with EGFR mutation status, demographics, smoking history, performance status, recursive partitioning analysis (RPA) class, tumor characteristics, and treatment modalities, were included. Radiological images were taken at 1 to 3 months after RT, and 3 to 6 months thereafter. Radiographic response was evaluated by RECIST criteria version 1.1 according to the intracranial images before and after RT. Log-rank test and Cox regression model were used to correlate EGFR mutation status and other clinical features with intracranial radiological progression-free survival (RPFS) and overall survival (OS). Results The median follow-up duration was 15 months. Patients with mutant EGFR had higher response rates to brain RT than those with wild-type EGFR (80% vs. 46%; p = 0.037). Logistic regression analysis showed that EGFR mutation status is the only predictor for treatment response (p = 0.032). The median intracranial RPFS was 18 months (95% CI = 8.33-27.68 months). In Cox regression analysis, mutant EGFR (p = 0.025) and lower RPA class (p = 0.026) were associated with longer intracranial RPFS. EGFR mutation status (p = 0.061) and performance status (p = 0.076) had a trend to predict OS. Conclusions Mutant EGFR in NSCLC patients is an independent prognostic factor for better treatment response and longer intracranial RPFS following RT for brain metastases. PMID:23110940

  16. Quantitative Targeted Proteomics of Pancreatic Cancer: Deoxycytidine Kinase Protein Level Correlates to Progression-Free Survival of Patients Receiving Gemcitabine Treatment.

    PubMed

    Ohmine, Ken; Kawaguchi, Kei; Ohtsuki, Sumio; Motoi, Fuyuhiko; Ohtsuka, Hideo; Kamiie, Junichi; Abe, Takaaki; Unno, Michiaki; Terasaki, Tetsuya

    2015-09-01

    The purpose of the present study is to identify the determinant(s) of gemcitabine (dFdC)-sensitivity in pancreatic cancer tissues of patients treated with dFdC alone and in pancreatic cancer cell lines exposed to dFdC in vitro. Protein expression levels of 12 enzymes and 13 transporters potentially involved in transport and metabolism of dFdC in pancreatic cancer cell lines and tissues were quantified by means of our LC-MS/MS-based quantitative targeted proteomics technology. Protein expression levels of deoxycytidine kinase (dCK), uridine monophosphate-cytidine monophosphate (UMP-CMP) kinase, cytosolic nucleotidase III (cN-III), and equilibrative nucleoside transporter 1 (ENT1) were significantly correlated with IC50 or 1/IC50 in five cell lines with different sensitivities to dFdC (p < 0.05). Expression levels of the selected proteins in pancreatic cancer tissues of 10 patients with different progression-free survival (PFS) (49-955 days) were quantified, and their relationship with PFS was examined. Only the protein expression level of dCK was significantly correlated with PFS (p < 0.05). Multiple regression analysis was also performed, and combinations of ENT1, UMP-CMP kinase, CTPS1, and dCK were highly correlated with PFS. Our results indicate that the protein expression level of dCK in pancreatic cancer tissue is a good predictor of PFS, and thus dCK may be the best biomarker of dFdC sensitivity in pancreatic cancer patients treated with dFdC, although other proteins would also contribute to dFdC-sensitivity at the cellular level in vivo and in vitro.

  17. The Prognostic Value of the Tumor Shrinkage Rate for Progression-Free Survival in Patients with Non-Small Cell Lung Cancer Receiving Gefitinib

    PubMed Central

    Park, Dong Il; Kim, Sun Young; Kim, Ju Ock; Jung, Sung Soo; Park, Hee Sun; Moon, Jae Young; Chung, Chae Uk; Kim, Song Soo; Seo, Jae Hee

    2015-01-01

    Background The efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy can be measured based on the rate of treatment response, based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria or progression-free survival (PFS). However, there are some patients harboring sensitive EGFR mutations who responded poorly to EGFR-TKI therapy. In addition, there is variability in the PFS after EGFR-TKI treatment. Methods We performed a retrospective analysis of the medical records of 85 patients with non-small cell lung cancer, who had achieved a stable disease or better response at the first evaluation of treatment response, after receiving a 2-month course of gefitinib. We calculated the tumor shrinkage rate (TSR) by measuring the longest and perpendicular diameter of the main mass on computed tomography before, and 2 months after, gefitinib therapy. Results There was a significant positive correlation between the TSR and PFS (R=0.373, p=0.010). In addition, a simple linear regression analysis showed that the TSR might be an indicator for the PFS (B±standard error, 244.54±66.79; p=0.001). On univariate analysis, the sex, histologic type, smoking history and the number of prior chemotherapy regimens, were significant prognostic factors. On multivariate regression analysis, both the TSR (β=0.257, p=0.029) and adenocarcinoma (β=0.323, p=0.005) were independent prognostic factors for PFS. Conclusion Our results showed that the TSR might be an early prognostic indicator for PFS in patients receiving EGFR-TKI therapy. PMID:26508917

  18. Establishing the Quantitative Relationship Between Lanreotide Autogel®, Chromogranin A, and Progression-Free Survival in Patients with Nonfunctioning Gastroenteropancreatic Neuroendocrine Tumors.

    PubMed

    Buil-Bruna, Núria; Dehez, Marion; Manon, Amandine; Nguyen, Thi Xuan Quyen; Trocóniz, Iñaki F

    2016-05-01

    The objective of this work was to establish the quantitative relationship between Lanreotide Autogel® (LAN) on serum chromogranin A (CgA) and progression-free survival (PFS) in patients with nonfunctioning gastroenteropancreatic neuroendocrine tumors (GEP-NETs) through an integrated pharmacokinetic/pharmacodynamic (PK/PD) model. In CLARINET, a phase III, randomized, double-blind, placebo-controlled study, 204 patients received deep subcutaneous injections of LAN 120 mg (n = 101) or placebo (n = 103) every 4 weeks for 96 weeks. Data for 810 LAN and 1298 CgA serum samples (n = 632 placebo and n = 666 LAN) were used to develop a parametric time-to-event model to relate CgA levels and PFS (76 patients experienced disease progression: n = 49 placebo and n = 27 LAN). LAN serum profiles were described by a one-compartment disposition model. Absorption was characterized by two parallel pathways following first- and zero-order kinetics. As PFS data were considered informative dropouts, CgA and PFS responses were modeled jointly. The LAN-induced decrease in CgA levels was described by an inhibitory E MAX model. Patient age and target lesions at baseline were associated with an increment in baseline CgA. Weibull model distribution showed that decreases in CgA from baseline reduced the hazard of disease progression significantly (P < 0.001). Covariates of tumor location in the pancreas and tumor hepatic tumor load were associated with worse prognosis (P < 0.001). We established a semimechanistic PK/PD model to better understand the effect of LAN on a surrogate endpoint (serum CgA) and ultimately the clinical endpoint (PFS) in treatment-naive patients with nonfunctioning GEP-NETs. PMID:26908127

  19. Use of Matched Unrelated Donors Compared with Matched Related Donors is Associated with Lower Relapse and Superior Progression Free Survival after Reduced Intensity Conditioning Hematopoietic Stem Cell Transplantation

    PubMed Central

    Ho, Vincent T.; Kim, Haesook T.; Aldridge, Julie; Liney, Deborah; Kao, Grace; Armand, Philippe; Koreth, John; Cutler, Corey; Ritz, Jerome; Antin, Joseph H.; Soiffer, Robert J.; Alyea, Edwin P.

    2011-01-01

    As success of reduced intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) relies primarily on graft-versus-leukemia (GVL) activity, increased minor HLA disparity in unrelated compared to related donors could have a significant impact on transplant outcomes. To assess whether use of unrelated donors (URD) engenders more potent GVL in RIC HSCT compared to matched related donors (MRD), we retrospectively studied 433 consecutive T-replete 6/6 HLA matched URD (n= 246) and MRD (n=187) RIC HSCT for hematologic malignancies at our institution. Diseases included: AML(127), NHL(71), CLL (68), MDS (64), HD(40), CML (25), MM(23), MPD (12), ALL(7), other leukemia (1). All received uniform fludarabine and intravenous busulfan conditioning, and GVHD prophylaxis with tacrolimus/mini-MTX or tacrolimus/sirolimus +/− mini-MTX. Unrelated donors were younger compared to MRD (median age: 33 yrs vs. 52 yrs, p<0.0001), and provided larger CD34+ products (median CD34+ cells infused: 8.7 × 106/kg vs. 7.5 × 106/kg, p=0.002). Distribution of diseases, disease risk, prior transplant, and CMV status was similar in both cohorts. Cumulative incidence of grade II–IV acute GVHD (at day+180), 2 year-chronic GVHD, and 2-year non-relapse mortality (NRM) were 20% vs. 16%, 55% vs. 50%, and 8% vs. 6% in URD and MRD, respectively (p=NS). Cumulative incidence of relapse at 2 years was lower in URD, 52% vs. 65% (p=0.005). With median follow-up of 26.5 and 35.8 months, 2-yr progression free survival (PFS) was significantly better in unrelated donor transplants, 39.5% for URD and 29% for MRD (p= 0.01). Overall survival at 2 years were 56% for URD vs. 50% for MRD (p=0.53). In multivariable analysis, URD was associated with a lower risk of relapse (HR 0.67, p =0.002) and superior PFS (HR 0.69, p=0.002). These results suggest that URD is associated with greater GVL activity than MRD, and could have practice changing impact on future donor selection in RIC HSCT. PMID:21193054

  20. Loss of aquaporin 3 protein expression constitutes an independent prognostic factor for progression-free survival: an immunohistochemical study on stage pT1 urothelial bladder cancer

    PubMed Central

    2012-01-01

    Background Treatment of patients with stage pT1 urothelial bladder cancer (UBC) continues to be a challenge due to its unpredictable clinical course. Reliable molecular markers that help to determine appropriate individual treatment are still lacking. Loss of aquaporin (AQP) 3 protein expression has previously been shown in muscle-invasive UBC. The aim of the present study was to investigate the prognostic value of AQP3 protein expression with regard to the prognosis of stage pT1 UBC. Method AQP 3 protein expression was investigated by immunohistochemistry in specimens of 87 stage T1 UBC patients, who were diagnosed by transurethral resection of the bladder (TURB) and subsequent second resection at a high-volume urological centre between 2002 and 2009. Patients underwent adjuvant instillation therapy with Bacillus Calmette-Guérin (BCG). Loss of AQP3 protein expression was defined as complete absence of the protein within the whole tumour. Expression status was correlated retrospectively with clinicopathological and follow-up data (median: 31 months). Multivariate Cox regression analysis was used to assess the value of AQP3 tumour expression with regard to recurrence-free (RFS), progression-free (PFS) and cancer-specific survival (CSS). RFS, PFS and CSS were calculated by Kaplan-Meier analysis and Log rank test. Results 59% of patients were shown to exhibit AQP3-positive tumours, whereas 41% of tumours did not express the marker. Loss of AQP3 protein expression was associated with a statistically significantly worse PFS (20% vs. 72%, p=0.020). This finding was confirmed by multivariate Cox regression analysis (HR 7.58, CI 1.29 – 44.68; p=0.025). Conclusions Loss of AQP3 protein expression in pT1 UBC appears to play a key role in disease progression and is associated with worse PFS. Considering its potential prognostic value, assessment of AQP3 protein expression could be used to help stratify the behavior of patients with pT1 UBC. PMID:23043286

  1. Adding Erlotinib to Chemoradiation Improves Overall Survival but Not Progression-Free Survival in Stage III Non-Small Cell Lung Cancer

    SciTech Connect

    Komaki, Ritsuko; Allen, Pamela K.; Wei, Xiong; Blumenschein, George R.; Tang, Ximing; Lee, J. Jack; Welsh, James W.; Wistuba, Ignacio I.; Liu, Diane D.; Hong, Waun Ki

    2015-06-01

    Purpose: To test, in a single-arm, prospective, phase 2 trial, whether adding the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to concurrent chemoradiotherapy for previously untreated, locally advanced, inoperable non-small cell lung cancer would improve survival and disease control without increasing toxicity. Methods and Materials: Forty-eight patients with previously untreated non-small cell lung cancer received intensity modulated radiation therapy (63 Gy/35 fractions) on Monday through Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin area under the curve [AUC] = 2) on Mondays, for 7 weeks. All patients also received the EGFR tyrosine kinase inhibitor erlotinib (150 mg orally 1/d) on Tuesday-Sunday for 7 weeks, followed by consolidation paclitaxel–carboplatin. The primary endpoint was time to progression; secondary endpoints were overall survival (OS), toxicity, response, and disease control and whether any endpoint differed by EGFR mutation status. Results: Of 46 patients evaluable for response, 40 were former or never-smokers, and 41 were evaluable for EGFR mutations (37 wild-type [WT] and 4 mutated [all adenocarcinoma]). Median time to progression was 14.0 months and did not differ by EGFR status. Toxicity was acceptable (no grade 5, 1 grade 4, 11 grade 3). Twelve patients (26%) had complete responses (10 WT, 2 mutated), 27 (59%) partial (21 WT, 2 mutated, 4 unknown), and 7 (15%) none (6 WT, 2 mutated, 1 unknown) (P=.610). At 37.0 months' follow-up (range, 3.6-76.5 months) for all patients, median OS time was 36.5 months, and 1-, 2-, and 5-year OS rates were 82.6%, 67.4%, and 35.9%, respectively; none differed by mutation status. Twelve patients had no progression, and 34 had local and/or distant failure. Eleven of 27 distant failures were in the brain (7 WT, 3 mutated, 1 unknown). Conclusions: Toxicity and OS were promising, but time to progression did not meet expectations. The prevalence of distant

  2. Nomograms Predicting Progression-Free Survival, Overall Survival, and Pelvic Recurrence in Locally Advanced Cervical Cancer Developed From an Analysis of Identifiable Prognostic Factors in Patients From NRG Oncology/Gynecologic Oncology Group Randomized Trials of Chemoradiotherapy

    PubMed Central

    Rose, Peter G.; Java, James; Whitney, Charles W.; Stehman, Frederick B.; Lanciano, Rachelle; Thomas, Gillian M.; DiSilvestro, Paul A.

    2015-01-01

    Purpose To evaluate the prognostic factors in locally advanced cervical cancer limited to the pelvis and develop nomograms for 2-year progression-free survival (PFS), 5-year overall survival (OS), and pelvic recurrence. Patients and Methods We retrospectively reviewed 2,042 patients with locally advanced cervical carcinoma enrolled onto Gynecologic Oncology Group clinical trials of concurrent cisplatin-based chemotherapy and radiotherapy. Nomograms for 2-year PFS, five-year OS, and pelvic recurrence were created as visualizations of Cox proportional hazards regression models. The models were validated by bootstrap-corrected, relatively unbiased estimates of discrimination and calibration. Results Multivariable analysis identified prognostic factors including histology, race/ethnicity, performance status, tumor size, International Federation of Gynecology and Obstetrics stage, tumor grade, pelvic node status, and treatment with concurrent cisplatin-based chemotherapy. PFS, OS, and pelvic recurrence nomograms had bootstrap-corrected concordance indices of 0.62, 0.64, and 0.73, respectively, and were well calibrated. Conclusion Prognostic factors were used to develop nomograms for 2-year PFS, 5-year OS, and pelvic recurrence for locally advanced cervical cancer clinically limited to the pelvis treated with concurrent cisplatin-based chemotherapy and radiotherapy. These nomograms can be used to better estimate individual and collective outcomes. PMID:25732170

  3. Correlations of survival with progression-free survival, response rate, and disease control rate in advanced biliary tract cancer: a meta-analysis of randomised trials of first-line chemotherapy

    PubMed Central

    Moriwaki, Toshikazu; Yamamoto, Yoshiyuki; Gosho, Masahiko; Kobayashi, Mariko; Sugaya, Akinori; Yamada, Takeshi; Endo, Shinji; Hyodo, Ichinosuke

    2016-01-01

    Background: The need to promote novel drug development for advanced biliary tract cancer (ABTC) has emphasised the importance of determining whether various efficacy end points can act as surrogates for overall survival (OS). Methods: We conducted a literature search of randomised trials of first-line chemotherapy for ABTC and investigated correlations between efficacy end points and OS using weighted linear regression analysis. The ratios of the median OS, median progression-free survival (PFS), response rate, and disease control rate in each trial were used to summarise treatment effects. The surrogate threshold effect (STE), which was the minimum treatment effect on PFS required to predict a non-zero treatment effect on OS, was calculated. Results: Seventeen randomised trials with 36 treatment arms were identified, and a sample size of 2148 patients with 19 paired arms was analysed. The strongest correlation between all evaluated efficacy end points was observed between median OS and median PFS ratios (r2=0.66). In trials with gemcitabine-containing therapies and targeted agents, the r2-values were 0.78. The STE was estimated at 0.83 for all trials and 0.81 for trials with gemcitabine-containing therapies, and was not calculated for trials with targeted agents. Conclusions: The median PFS ratio correlated well with the median OS ratio, and may be useful for planning a clinical trial for novel drug development. PMID:27031848

  4. Overall Response Rate, Progression-Free Survival, and Overall Survival With Targeted and Standard Therapies in Advanced Non–Small-Cell Lung Cancer: US Food and Drug Administration Trial-Level and Patient-Level Analyses

    PubMed Central

    Blumenthal, Gideon M.; Karuri, Stella W.; Zhang, Hui; Zhang, Lijun; Khozin, Sean; Kazandjian, Dickran; Tang, Shenghui; Sridhara, Rajeshwari; Keegan, Patricia; Pazdur, Richard

    2015-01-01

    Purpose To conduct analyses exploring trial-level and patient-level associations between overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in advanced non–small-cell lung cancer (NSCLC) trials. Methods We identified 14 trials (N = 12,567) submitted to US Food and Drug Administration since 2003 of treatments for advanced NSCLC. Only randomized, active-controlled trials with more than 150 patients were included. Associations between trial-level PFS hazard ratio (HR), OS HR, and ORR odds ratio were analyzed using a weighted linear regression model. Patient-level responder analyses comparing PFS and OS between patients with and without an objective response were performed using pooled data from all studies. Results In the trial-level analysis, the association between PFS and ORR was strong (R2 = 0.89; 95% CI, 0.80 to 0.98). There was no association between OS and ORR (R2 = 0.09; 95% CI, 0 to 0.33) and OS and PFS (R2 = 0.08; 95% CI, 0 to 0.31). In the patient-level responder analyses, patients who achieved a response had better PFS and OS compared with nonresponders (PFS: HR, 0.40; 95% CI, 0.38 to 0.42; OS: HR, 0.40; 95% CI, 0.38 to 0.43). Conclusion On a trial level, there is a strong association between ORR and PFS. An association between ORR and OS and between PFS and OS was not established, possibly because of cross-over and longer survival after progression in the targeted therapy and first-line trials. The patient-level analysis showed that responders have a better PFS and OS compared with nonresponders. A therapy in advanced NSCLC with a large magnitude of effect on ORR may have a large PFS effect. PMID:25667291

  5. Individual Patient Data Analysis of Progression-Free Survival Versus Overall Survival As a First-Line End Point for Metastatic Colorectal Cancer in Modern Randomized Trials: Findings From the Analysis and Research in Cancers of the Digestive System Database

    PubMed Central

    Shi, Qian; de Gramont, Aimery; Grothey, Axel; Zalcberg, John; Chibaudel, Benoist; Schmoll, Hans-Joachim; Seymour, Matthew T.; Adams, Richard; Saltz, Leonard; Goldberg, Richard M.; Punt, Cornelis J.A.; Douillard, Jean-Yves; Hoff, Paulo M.; Hecht, Joel Randolph; Hurwitz, Herbert; Díaz-Rubio, Eduardo; Porschen, Rainer; Tebbutt, Niall C.; Fuchs, Charles; Souglakos, John; Falcone, Alfredo; Tournigand, Christophe; Kabbinavar, Fairooz F.; Heinemann, Volker; Van Cutsem, Eric; Bokemeyer, Carsten; Buyse, Marc; Sargent, Daniel J.

    2015-01-01

    Purpose Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Methods Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti–epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R2 statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models. Results Forty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R2, 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy. Conclusion In modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents. PMID:25385741

  6. Weekly paclitaxel with trastuzumab and pertuzumab in patients with HER2-overexpressing metastatic breast cancer: overall survival and updated progression-free survival results from a phase II study.

    PubMed

    Smyth, L M; Iyengar, N M; Chen, M F; Popper, S M; Patil, S; Wasserheit-Lieblich, C; Argolo, D F; Singh, J C; Chandarlapaty, S; Sugarman, S M; Comen, E A; Drullinsky, P R; Traina, T A; Troso-Sandoval, T; Baselga, J; Norton, L; Hudis, C A; Dang, C T

    2016-07-01

    We previously reported progression-free survival (PFS) results on a phase II trial of weekly paclitaxel, trastuzumab, and pertuzumab in patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer (MBC) treated in the first- and second-line setting. Here, we report results for overall survival (OS) and updated PFS after an additional year of follow-up. Patients with HER2-positive MBC with 0-1 prior treatment were eligible. Treatment consisted of paclitaxel (80 mg/m(2)) weekly, and trastuzumab (loading dose 8 mg/kg → 6 mg/kg) and pertuzumab (loading dose 840 mg → 420 mg) every 3 weeks, all given intravenously. Primary endpoint was 6-month PFS. Secondary endpoints included median PFS, 6-month and median OS. Evaluable patients received at least one full dose of treatment. From January 2011 to December 2013, 69 patients were enrolled: 51 (74 %) and 18 (26 %) treated in first- and second-line metastatic settings, respectively. As of July 1, 2015, the median follow-up was 33 months (range 3-49 months; 67 patients were evaluable for efficacy). The median OS was 44 months (95 % CI 37.5-NR) overall and 44 months (95 % CI 38.3-NR) and 37.5 months (95 % CI 30.3-NR) for patients with 0 and 1 prior metastatic treatment, respectively; 6-month OS was 98 % (95 % CI 90-1). The 6-month PFS was 86 % (95 % CI 75-93) overall and 89 % (95 % CI 76-95) and 78 % (95 % CI 51-91) for patients with 0 and 1 prior therapy, respectively; and median PFS was 21.4 months (95 % CI 14.1-NR) overall and 25.7 months (95 % CI 14.1-NR) and 16.9 months (95 % CI 8.5-NR) for patients with 0-1 prior treatment, respectively. Treatment was well tolerated. Updated analysis demonstrates that weekly paclitaxel, when added to trastuzumab and pertuzumab, is associated with a favorable OS and PFS and offers an alternative to docetaxel-based therapy. http://www.ClinicalTrials.gov NCT0127604.

  7. Using quality-adjusted progression-free survival as an outcome measure to assess the benefits of cancer drugs in randomized-controlled trials: case of the BOLERO-2 trial.

    PubMed

    Diaby, Vakaramoko; Adunlin, Georges; Ali, Askal Ayalew; Tawk, Rima

    2014-08-01

    The aim of this study is to estimate the quality-adjusted progression-free survival (QAPFS) as an effectiveness measure for the treatment arms of the BOLERO-2 trial. For each treatment arm of the trial, QAPFS was estimated by multiplying the overall health utility weights associated with progression-free survival (PFS) (accounting for utility decrements associated with the adverse events of treatments) by the corresponding mean PFS time. Health utility data were obtained from the literature, while mean PFS times were estimated through a survival analysis of the reconstructed individual patient data of the BOLERO-2 trial. PFS (robust mean, (95 % robust confidence interval)) was 44.73 weeks (41.03; 48.43) for Everolimus + Exemestane and 22.98 weeks (19.88; 26.08) for Placebo + Exemestane. The QAPFS (robust mean, (95 % robust confidence interval)) for the treatment arms of the trial was 30.09 (27.60; 32.58) for Everolimus + Exemestane and 16.27 (14.07; 18.46) for Placebo + Exemestane, respectively. Using QAPFS as an outcome measure provides a complete picture of the benefit induced by the treatment arms of the BOLERO-2 trial. The benefit of Everolimus + Exemestane over Placebo + Exemestane observed in the trial is maintained in this analysis. The approach and estimates obtained as part of our analysis can serve as a basis for cost effectiveness analyses of the treatment arms of the BOLERO-2 trial.

  8. The Casualty Actuarial Society: Helping Universities Train Future Actuaries

    ERIC Educational Resources Information Center

    Boa, J. Michael; Gorvett, Rick

    2014-01-01

    The Casualty Actuarial Society (CAS) believes that the most effective way to advance the actuarial profession is to work in partnership with universities. The CAS stands ready to assist universities in creating or enhancing courses and curricula associated with property/casualty actuarial science. CAS resources for university actuarial science…

  9. Preoperative Radiation Therapy Followed by Reexcision May Improve Local Control and Progression-Free Survival in Unplanned Excisions of Soft Tissue Sarcomas of the Extremity and Chest-Wall

    PubMed Central

    Saeed, Hina; Johnstone, Candice A.; Charlson, John A.; Hackbarth, Donald A.; Neilson, John C.

    2016-01-01

    Background. The management for unplanned excision (UE) of soft tissue sarcomas (STS) has not been established. In this study, we compare outcomes of UE versus planned excision (PE) and determine an optimal treatment for UE in STS. Methods. From 2000 to 2014 a review was performed on all patients treated with localized STS. Clinical outcomes including local recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) were evaluated using the Kaplan-Meier estimate. Univariate (UVA) and multivariate (MVA) analyses were performed to determine prognostic variables. For MVA, Cox proportional hazards model was used. Results. 245 patients were included in the analysis. 14% underwent UE. Median follow-up was 2.8 years. The LR rate was 8.6%. The LR rate in UE was 35% versus 4.2% in PE patients (p < 0.0001). 2-year PFS in UE versus PE patients was 4.2 years and 9.3 years, respectively (p = 0.08). Preoperative radiation (RT) (p = 0.01) and use of any RT for UE (p = 0.003) led to improved PFS. On MVA, preoperative RT (p = 0.04) and performance status (p = 0.01) led to improved PFS. Conclusions. UEs led to decreased LC and PFS versus PE in patients with STS. The use of preoperative RT followed by reexcision improved LC and PFS in patients who had UE of their STS. PMID:27803813

  10. Rituximab plus a CHOP-like regimen, central nervous system prophylaxis, and contralateral testicular irradiation for localized primary testicular diffuse large B-cell lymphoma lead to prolonged progression-free survival.

    PubMed

    Ichikawa, Kunimoto; Noguchi, Masaaki; Koike, Michiaki; Aritaka, Nanae; Sekiguchi, Yasunobu; Sunami, Yoshitaka; Tsutsui, Miyuki; Hosone, Masaru; Hirano, Takao; Gotoh, Akihiko; Komatsu, Norio

    2014-10-01

    We retrospectively evaluated the clinical features, management, and survival of 12 patients (age 51-84 years) with localized primary testicular diffuse large B-cell lymphoma (PTL). All 12 PTL patients underwent orchiectomy. Seven of the 12 patients were treated with strategy A, which consisted of at least six cycles of rituximab (R) plus a CHOP-like regimen, central nervous system (CNS) prophylaxis involving intrathecal chemotherapy (IT) and/or high-dose intravenous methotrexate, and contralateral scrotal irradiation (cRT). The other five patients were treated with strategy B, which included three regimens: orchiectomy alone, orchiectomy plus cRT and IT, and orchiectomy plus 3-4 cycles of R-CHOP plus cRT with or without IT. The median follow-up period was 48 months (range 19-123 months). The 4-year progression-free survival (PFS) rate for the seven patients treated with strategy A was 85.7 %, whereas that for the five patients treated with strategy B was 20 %. The patients treated with strategy A exhibited a significantly higher 4-year PFS rate than those treated with strategy B (P = 0.017). These results confirmed that the administration of a sufficient number of cycles of an R-containing chemotherapy regimen plus cRT plus CNS prophylaxis should be considered as a treatment for localized PTL. PMID:25085255

  11. Plasma miR-200b in ovarian carcinoma patients: distinct pattern of pre/post-treatment variation compared to CA-125 and potential for prediction of progression-free survival

    PubMed Central

    Kapetanakis, Nikiforos-Ioannis; Uzan, Catherine; Jimenez-Pailhes, Anne-Sophie; Gouy, Sébastien; Bentivegna, Enrica; Morice, Philippe; Caron, Olivier; Gourzones-Dmitriev, Claire; Le Teuff, Gwénaël; Busson, Pierre

    2015-01-01

    Ovarian carcinomas (OvCa) are highly heterogeneous malignancies. We investigated four circulating plasma microRNAs (miR-21, miR-34a, miR-200b and miR-205) as candidate biomarkers. Using qPCR, we assessed the plasma concentration of these markers in 101 women, including 51 previously untreated OvCa patients, 25 healthy women and 25 patients bearing benign pelvic lesions. For a subset of 33 OvCa patients, the assay was repeated at the end of the primary treatment. The pattern of variations (post- minus pre-treatment) of concentration was compared to that of CA-125. A Cox regression model was used to study the association between variations and the progression-free survival (PFS). Plasma miR-200b proved to have a greater average concentration in OvCa samples (median 2−ΔΔCt = 15.18) than in samples linked to non-malignant lesions (median 2−ΔΔCt = 1.26, p-value = 0.0004). Its concentration was highly heterogeneous among OvCa patients, without any correlations with the FIGO stage and the pre-treatment CA-125 level. The decrease in CA-125 concentration was constant and often dramatic, while the variations of miR-200b concentration were much more diverse. The variation of miR-200b was marginally associated with the PFS (hazard ratio=2.95 95%CI=[0.94; 9.28], p=0.06) while miR-200b as a continuous time-dependent variable was significantly associated (HR=1.06 [1.02; 1.10], p=0.003). This study is the first direct empirical evidence that miR-200b can provide additional information, independent of CA-125 in OvCa patients. PMID:26416421

  12. Prospective validation of a risk score based on biological markers for predicting progression free survival in Binet stage A chronic lymphocytic leukemia patients: results of the multicenter O-CLL1-GISL study.

    PubMed

    Gentile, Massimo; Cutrona, Giovanna; Mosca, Laura; Matis, Serena; Fabris, Sonia; Lionetti, Marta; Ilariucci, Fiorella; Zupo, Simona; Musolino, Caterina; Levato, Luciano; Molica, Stefano; Di Raimondo, Francesco; Vincelli, Iolanda; Di Rienzo, Nicola; Pesce, Emanuela Anna; Angrilli, Francesco; Federico, Massimo; Neri, Antonino; Ferrarini, Manlio; Morabito, Fortunato

    2014-07-01

    A risk score based on three biological features (CD38, ZAP-70, and IGHV mutational status) was previously developed to predict progression-free survival (PFS) in untreated Binet A CLL patients. Here we perform a score validation analysis in a prospective and independent cohort of patients. Biological markers (CD38, ZAP-70, and IGHV mutational status) and gene expression profiles (GEP) of leukemic cells from CLL patients included in a prospective multicenter observational study (O-CLL1-GISL protocol, clinicaltrial.gov ID:NCT00917549) were used to assess the value and reproducibility of this score. To date, 468 Binet A patients were classified as low- (0 positive marker), intermediate- (1 positive marker), or high-risk (2 or 3 positive markers) using the progression risk score. The 3-year PFS probability was 91.7%, 82.9%, and 57.4% for low-, intermediate-, and high-risk (P < 0.0001) cases, respectively. These values were similar to those found in the original cohort. At Cox multivariate analysis, Rai stage, absolute lymphocyte count, progression risk score, and β-2 microglobulin maintained an independent prognostic impact on PFS. This score remained a predictor of progression when analysis was limited to 371 Rai 0 cases (P < 0.0001). Finally, the cells from the different CLL risk groups showed differences in their gene expression patterns. These results confirm the ability of this progression risk score to predict PFS among Binet A patients. The utility of the score was also extended by demonstrating that it retains prognostic value when applied exclusively to Rai 0 patients. Specific transcriptional patterns were significantly associated with risk groups.

  13. Interim fluorine-18 fluorodeoxyglucose PET-computed tomography and cell of origin by immunohistochemistry predicts progression-free and overall survival in diffuse large B-cell lymphoma patients in the rituximab era

    PubMed Central

    Hallack Neto, Abrahão; Siqueira, Sheila; Lage, Luis Alberto de Padua Covas; de Paula, Henrique M.; Coutinho, Arthur M.; Pereira, Juliana

    2016-01-01

    Objective The aim of this study was to analyze the prognostic value of the interim PET (iPET)-computed tomography (CT) (iPET-CT) after two cycles of immunochemotherapy with the R-CHOP protocol in patients with diffuse large B-cell non-Hodgkin lymphoma (DLBCL) treated with a curative intent in combination with the neoplastic cell origin defined by Hans’s immunohistochemstry algorithm followed in a reference center for cancer treatment in Brazil. Materials and methods We prospectively evaluated 147 DLBCL patients treated with R-CHOP-21 to assess the value of the International Prognostic Index, iPET-CT, and cell of origin by immunohistochemistry as prognostic markers in the rituximab era. Fluorine-18 fluorodeoxyglucose PET-CT was performed after two cycles (iPET-CT) and at the end of treatment in 111 patients. Lymphoma cases were categorized into germinal center (GC) and nongerminal center subtypes by immunohistochemistry according to Hans’s algorithm. Results The median age of GC-DLBCL patients (52.7 years) was lower than that of nongerminal center-DLBCL patients (59.4 years) (P=0.021); in addition, it was lower in patients with negative iPET-CT findings (52.7 years) versus positive findings (59.4 years) (P=0.031). The overall survival at 48 months was 100% for iPET-CT-negative GC-DLBCL patients and 61.2% for iPET-CT-positive GC-DLBCL patients (P=0.002). Progression-free survival at 30 months was 100% for iPET-CT-negative GC-DLBCL patients and 60.3% for iPET-CT-positive GC-DLBCL patients (P=0.001). Conclusion We conclude that iPET-CT associated with cell origin identified a very good prognostic group in DLBCL patients treated with R-CHOP. Video Abstract: http://links.lww.com/NMC/A59 PMID:27281359

  14. SU-E-J-254: Evaluating the Role of Mid-Treatment and Post-Treatment FDG-PET/CT in Predicting Progression-Free Survival and Distant Metastasis of Anal Cancer Patients Treated with Chemoradiotherapy

    SciTech Connect

    Zhang, H; Wang, J; Chuong, M; D’Souza, W; Choi, W; Lu, W; Latifi, K; Hoffe, S; Moros, E; Saeed, Nadia; Tan, S; Shridhar, R

    2015-06-15

    Purpose: To evaluate the role of mid-treatment and post-treatment FDG-PET/CT in predicting progression-free survival (PFS) and distant metastasis (DM) of anal cancer patients treated with chemoradiotherapy (CRT). Methods: 17 anal cancer patients treated with CRT were retrospectively studied. The median prescription dose was 56 Gy (range, 50–62.5 Gy). All patients underwent FDG-PET/CT scans before and after CRT. 16 of the 17 patients had an additional FDG-PET/CT image at 3–5 weeks into the treatment (denoted as mid-treatment FDG-PET/CT). 750 features were extracted from these three sets of scans, which included both traditional PET/CT measures (SUVmax, SUVpeak, tumor diameters, etc.) and spatialtemporal PET/CT features (comprehensively quantify a tumor’s FDG uptake intensity and distribution, spatial variation (texture), geometric property and their temporal changes relative to baseline). 26 clinical parameters (age, gender, TNM stage, histology, GTV dose, etc.) were also analyzed. Advanced analytics including methods to select an optimal set of predictors and a model selection engine, which identifies the most accurate machine learning algorithm for predictive analysis was developed. Results: Comparing baseline + mid-treatment PET/CT set to baseline + posttreatment PET/CT set, 14 predictors were selected from each feature group. Same three clinical parameters (tumor size, T stage and whether 5-FU was held during any cycle of chemotherapy) and two traditional measures (pre- CRT SUVmin and SUVmedian) were selected by both predictor groups. Different mix of spatial-temporal PET/CT features was selected. Using the 14 predictors and Naive Bayes, mid-treatment PET/CT set achieved 87.5% accuracy (2 PFS patients misclassified, all local recurrence and DM patients correctly classified). Post-treatment PET/CT set achieved 94.0% accuracy (all PFS and DM patients correctly predicted, 1 local recurrence patient misclassified) with logistic regression, neural network or

  15. Developing an Actuarial Track Utilizing Existing Resources

    ERIC Educational Resources Information Center

    Rodgers, Kathy V.; Sarol, Yalçin

    2014-01-01

    Students earning a degree in mathematics often seek information on how to apply their mathematical knowledge. One option is to follow a curriculum with an actuarial emphasis designed to prepare students as an applied mathematician in the actuarial field. By developing only two new courses and utilizing existing courses for Validation by…

  16. 42 CFR 403.258 - Statement of actuarial opinion.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... actuarial opinion means a signed declaration in which a qualified actuary states that the assumptions used... policy experience, if any, and reasonable expectations. (b) Qualified actuary means— (1) A member in...

  17. Classification of progression free survival with nasopharyngeal carcinoma tumors

    NASA Astrophysics Data System (ADS)

    Farhidzadeh, Hamidreza; Kim, Joo Y.; Scott, Jacob G.; Goldgof, Dmitry B.; Hall, Lawrence O.; Harrison, Louis B.

    2016-03-01

    Nasopharyngeal carcinoma (NPC) is an abnormal growth of tissue which arises from the back of the nose. At the time of diagnosis, detection of tumor features with prognostic significance, including patient demographics, imaging characteristics and molecular characteristics, can enable the treating clinician to select a treatment that is optimized for the individual patient. At present, the analysis of tumor imaging features is limited to size criteria and macroscopic textural semantic descriptors, but computerized quantification of intratumoral heterogeneity and their temporal evolution may provide another metric for predicting prognosis. We propose medical imaging feature analysis methods and radiomics machine learning methods to predict failure of treatment. NPC tumors on contrast-enhanced T1 (T1Gd) sequences of 25 NPC patients' diagnostic magnetic resonance images (MRI) were manually contoured. Otsu segmentation was applied to segment the tumor into highly enhancing vs. weakly enhancing signal intensity subregions. Within these subregions, texture features were extracted to numerically quantify the intraregional heterogeneity. Patients were divided into two prognostic groups; a progression-freesurvival group (those without locoregional recurrence or distant metastases), and the disease progression group (those with locoregional recurrence or distant metastases). We used Support Vector Machines (SVM) to perform classification (prediction of prognosis). The features from the highly enhancing subregion classify prognosis with 80% predictive accuracy with AUC=0.60, while the captured features from the weakly enhancing subregion classify prognosis with 76% accuracy with AUC= 0.76.

  18. Increasing Tumor Volume is Predictive of Poor Overall and Progression-Free Survival: Secondary Analysis of the Radiation Therapy Oncology Group 93-11 Phase I-II Radiation Dose-Escalation Study in Patients with Inoperable Non-Small-Cell Lung Cancer

    SciTech Connect

    Werner-Wasik, Maria Swann, R. Suzanne; Bradley, Jeffrey; Graham, Mary; Emami, Bahman; Purdy, James; Sause, William

    2008-02-01

    Purpose: Patients with non-small-cell lung cancer (NSCLC) in the Radiation Therapy Oncology Group (RTOG) 93-11 trial received radiation doses of 70.9, 77.4, 83.8, or 90.3 Gy. The locoregional control and survival rates were similar among the various dose levels. We investigated the effect of the gross tumor volume (GTV) on the outcome. Methods and Materials: The GTV was defined as the sum of the volumes of the primary tumor and involved lymph nodes. The tumor response, median survival time (MST), and progression-free survival (PFS) were analyzed separately for smaller ({<=}45 cm{sup 3}) vs. larger (>45 cm{sup 3}) tumors. Results: The distribution of the GTV was as follows: {<=}45 cm{sup 3} in 79 (49%) and >45 cm{sup 3} in 82 (51%) of 161 patients. The median GTV was 47.3 cm{sup 3}. N0 status and female gender were associated with better tumor responses. Patients with smaller ({<=}45 cm{sup 3}) tumors achieved a longer MST and better PFS than did patients with larger (>45 cm{sup 3}) tumors (29.7 vs. 13.3 months, p < 0.0001; and 15.8 vs. 8.3 months, p < 0.0001, respectively). Increasing the radiation dose had no effect on the MST or PFS. On multivariate analysis, only a smaller GTV was a significant prognostic factor for improved MST and PFS (hazard ratio [HR], 2.12, p = 0.0002; and HR, 2.0, p = 0.0002, respectively). The GTV as a continuous variable was also significantly associated with the MST and PFS (HR, 1.59, p < 0.0001; and HR, 1.39, p < 0.0001, respectively). Conclusions: Radiation dose escalation up to 90.3 Gy did not result in improved MST or PFS. The tumor responses were greater in node-negative patients and women. An increasing GTV was strongly associated with decreased MST and PFS. Future radiotherapy trials patients might need to use stratification by tumor volume.

  19. Starting an Actuarial Program with Existing Resources

    ERIC Educational Resources Information Center

    Taylor, Paul T.

    2014-01-01

    Many institutions wish to offer a path for students pursuing actuarial careers but lack the student demand to offer new courses or hire additional faculty. Fortunately, a program training students to enter the profession can often be constructed using existing courses and well-informed advising.

  20. Recruiting and Advising Challenges in Actuarial Science

    ERIC Educational Resources Information Center

    Case, Bettye Anne; Guan, Yuanying Michelle; Paris, Stephen

    2014-01-01

    Some challenges to increasing actuarial science program size through recruiting broadly among potential students are identified. Possible solutions depend on the structures and culture of the school. Up to three student cohorts may result from partition of potential students by the levels of academic progress before program entry: students…

  1. 29 CFR 4231.10 - Actuarial calculations and assumptions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... MULTIEMPLOYER PLANS § 4231.10 Actuarial calculations and assumptions. (a) Most recent valuation. All calculations required by this part must be based on the most recent actuarial valuation as of the date...

  2. 29 CFR 4010.8 - Plan actuarial information.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... knowledge and belief, the actuarial information submitted is true, correct, and complete and conforms to all... 29 Labor 9 2010-07-01 2010-07-01 false Plan actuarial information. 4010.8 Section 4010.8 Labor... DISCLOSURE REQUIREMENTS ANNUAL FINANCIAL AND ACTUARIAL INFORMATION REPORTING § 4010.8 Plan...

  3. Actuarial considerations of medical malpractice evaluations in M&As.

    PubMed

    Frese, Richard C

    2014-11-01

    To best project an actuarial estimate for medical malpractice exposure for a merger and acquisition, a organization's leaders should consider the following factors, among others: How to support an unbiased actuarial estimation. Experience of the actuary. The full picture of the organization's malpractice coverage. The potential for future loss development. Frequency and severity trends.

  4. 20 CFR 901.20 - Standards of performance of actuarial services.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... designation. An enrolled actuary shall not advertise his/her status as an enrolled actuary in any solicitation... ethics. (2) An enrolled actuary shall not perform actuarial services for any person or organization...

  5. 42 CFR 403.258 - Statement of actuarial opinion.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Statement of actuarial opinion. 403.258 Section 403.258 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Program: Loss Ratio Provisions § 403.258 Statement of actuarial opinion. (a) For purposes of...

  6. Development of an Actuarial Science Program at Salisbury University

    ERIC Educational Resources Information Center

    Wainwright, Barbara A.

    2014-01-01

    This paper focuses on the development of an actuarial science track for the mathematics major at Salisbury University (SU). A timeline from the initial investigation into such a program through the proposal and approval processes is shared for those who might be interested in developing a new actuarial program. It is wise to start small and take…

  7. 26 CFR 301.6059-1 - Periodic report of actuary.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .... The actuarial report must be filed by the plan administrator (within the meaning of section 414(g)) on... purposes of this section, “plan year” means the plan year as determined for purposes of the minimum funding... required to be made), (2) A description of the funding method and actuarial assumptions used to...

  8. 26 CFR 301.6059-1 - Periodic report of actuary.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... The actuarial report must be filed by the plan administrator (within the meaning of section 414(g)) on... purposes of this section, “plan year” means the plan year as determined for purposes of the minimum funding... required to be made), (2) A description of the funding method and actuarial assumptions used to...

  9. Actuarial models of life insurance with stochastic interest rate

    NASA Astrophysics Data System (ADS)

    Wei, Xiang; Hu, Ping

    2009-07-01

    On the basis of general actuarial model of life insurance, this article has carried on research to continuous life insurance actuarial models under the stochastic interest rate separately. And it provide net single premium for life insurance and life annuity due over a period based on that de Moivre law of mortality and Makeham's law of mortality separately.

  10. Starting an Actuarial Science Major at a Liberal Arts College

    ERIC Educational Resources Information Center

    Mills, Mark A.

    2014-01-01

    The article provides details of the process of starting an actuarial science major at a small, liberal arts college. Some critique of the major is included, as well as some challenges that may be faced by others wanting to start such a major at their institution.

  11. Actuarial Science at One Four-Year Comprehensive University

    ERIC Educational Resources Information Center

    Charlwood, Kevin E.

    2014-01-01

    Building an Actuarial Science program designated as advanced requires dedicated faculty, support from the administration, and a core group of strong students. Washburn University may serve as a model for those wishing to start or enhance such a program at their institution. We face three main ongoing challenges: first, the hiring and retention of…

  12. Predicting Success for Actuarial Students in Undergraduate Mathematics Courses

    ERIC Educational Resources Information Center

    Smith, Richard Manning; Schumacher, Phyllis A.

    2005-01-01

    A study of undergraduate actuarial graduates found that math SAT scores, verbal SAT scores, percentile rank in high school graduating class, and percentage score on a college mathematics placement exam had some relevance to forecasting the students' grade point averages in their major. For both males and females, percentile rank in high school…

  13. An Overview of the Society of Actuaries and Its Education Programs

    ERIC Educational Resources Information Center

    Klugman, Stuart; Long, Gena

    2014-01-01

    The Society of Actuaries (SOA) is the world's largest actuarial organization. This article describes the SOA with particular attention paid to its education and qualification processes and resources available for university and college programs.

  14. 20 CFR 901.20 - Standards of performance of actuarial services.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... person or organization which he/she believes or has reasonable grounds for believing may utilize his/her... of actuarial services, of which the enrolled actuary has knowledge, he/she shall not perform...

  15. 20 CFR 901.20 - Standards of performance of actuarial services.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... exercise due care, skill, prudence and diligence when performing actuarial services under ERISA and the... actuary may not in any way use or participate in the use of any form of public communication or...

  16. 20 CFR 901.20 - Standards of performance of actuarial services.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... exercise due care, skill, prudence and diligence when performing actuarial services under ERISA and the... actuary may not in any way use or participate in the use of any form of public communication or...

  17. The Role of an Actuarial Director in the Development of an Introductory Program

    ERIC Educational Resources Information Center

    Staples, Susan G.

    2014-01-01

    We describe the roles and duties of a director in developing an introductory actuarial program. Degree plan design, specialized exam courses, internship classes, coordination of efforts with Economics and Finance Departments, opportunities for creating a minor in actuarial mathematics, actuarial clubs, career advice, and interaction with actuarial…

  18. 26 CFR 301.6692-1 - Failure to file actuarial report.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... the actuarial report described in section 6059 and § 301.6059-1 within the time prescribed, the plan...)(9) and the regulations thereunder prescribe the time for making an actuarial valuation of a defined... report upon an actuarial valuation of the plan which is made within the time prescribed by section...

  19. Including an Exam P/1 Prep Course in a Growing Actuarial Science Program

    ERIC Educational Resources Information Center

    Wakefield, Thomas P.

    2014-01-01

    The purpose of this article is to describe the actuarial science program at our university and the development of a course to enhance students' problem solving skills while preparing them for Exam P/1 of the Society of Actuaries (SOA) and the Casualty Actuary Society (CAS). The Exam P/1 prep course, formally titled Mathematical Foundations of…

  20. 77 FR 63337 - Renewal of Charter of Advisory Committee on Actuarial Examinations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-16

    ... Joint Board for the Enrollment of Actuaries announces the renewal of the charter of the Advisory... From the Federal Register Online via the Government Publishing Office JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES Renewal of Charter of Advisory Committee on Actuarial Examinations AGENCY:...

  1. Actuarial analysis of the occurrence of remissions following thymectomy for myasthenia gravis in 400 patients.

    PubMed Central

    Durelli, L; Maggi, G; Casadio, C; Ferri, R; Rendine, S; Bergamini, L

    1991-01-01

    The role of thymectomy in the treatment of myasthenia gravis (MG) was analysed in 400 patients affected with generalised MG operated on between 1974-83, and prospectively followed up for five years after surgery. The occurrence of stable remission (SR) (that is, complete clinical drug-free remission that remains stable for all the subsequent follow up) was the endpoint of survival analyses and the distribution of SR time (SRT, that is, the interval from thymectomy to the occurrence of SR) was assessed by actuarial and Cox multivariate analyses. SRT distribution after surgery showed a slow progressive increase of cumulative SR rate that could both be ascribed to a delayed effect of thymectomy as well as reflect the natural history of MG, itself characterised by an increasing probability of spontaneous remission with time. SRT distribution was similar after stratification for all variables studied except when patients without thymoma were stratified for the need for immunosuppressive treatment in addition to thymectomy. Patients without thymoma who did not require additional immunosuppressive therapy (n = 130) had the highest SR rate occurring in the two years after thymectomy, and differed from patients treated with immunosuppressive drugs who showed the highest SR rate five years after surgery. Actuarial analysis has therefore identified a subgroup of patients where SR, occurring in the first years after surgery, is more likely to be ascribed to thymectomy than merely reflect the natural course of the disease. PMID:1865202

  2. Brentuximab vedotin is associated with improved progression-free survival after allogeneic transplantation for Hodgkin lymphoma

    PubMed Central

    Chen, Robert; Palmer, Joycelynne M.; Tsai, Ni-Chun; Thomas, Sandra H.; Siddiqi, Tanya; Popplewell, Leslie; Farol, Len; Nademanee, Auayporn; Forman, Stephen J.

    2014-01-01

    We previously reported that BV enabled successful reduced-intensity allogeneic hematopoietic cell transplantation (RIC-alloHCT) in patients with relapsed Hodgkin lymphoma, after a median follow-up of 14.4 months. We now provide an updated report on 21 patients who were treated from 2009–2012 with BV prior to RIC-alloHCT with a uniform fludarabine/melphalan conditioning regimen and donor source after a median follow-up of 29.9 months. We have also retrospectively compared the patient characteristics and outcomes of these BV pre-treated patients to 23 patients who received fludarabine/melphalan RIC-alloHCT without prior BV, in the time period before the drug was available (2003–2009, pre-BV era). Patients who were treated with BV prior to RIC-alloHCT had a lower median HCT-specific comorbidity index (HCT-CI) and a reduced number of peri-transplant toxicities. There were also improvements in 2-year PFS (59.3% versus 26.1%) and cumulative incidence of relapse/progression (23.8% versus 56.5%). PMID:25008328

  3. Of pacemakers and statistics: the actuarial method extended.

    PubMed

    Dussel, J; Wolbarst, A B; Scott-Millar, R N; Obel, I W

    1980-01-01

    Pacemakers cease functioning because of either natural battery exhaustion (nbe) or component failure (cf). A study of four series of pacemakers shows that a simple extension of the actuarial method, so as to incorporate Normal statistics, makes possible a quantitative differentiation between the two modes of failure. This involves the separation of the overall failure probability density function PDF(t) into constituent parts pdfnbe(t) and pdfcf(t). The approach should allow a meaningful comparison of the characteristics of different pacemaker types.

  4. An actuarial approach to retrofit savings in buildings

    SciTech Connect

    Subbarao, Krishnappa; Etingov, Pavel V.; Reddy, T. A.

    2014-01-01

    An actuarial method has been developed for determining energy savings from retrofits from energy use data for a number of buildings. This method should be contrasted with the traditional method of using pre- and post-retrofit data on the same building. This method supports the U.S. Department of Energy Building Performance Database of real building performance data and related tools that enable engineering and financial practitioners to evaluate retrofits. The actuarial approach derives, from the database, probability density functions (PDFs) for energy savings from retrofits by creating peer groups for the user’s pre post buildings. From the energy use distribution of the two groups, the savings PDF is derived. This provides the basis for engineering analysis as well as financial risk analysis leading to investment decisions. Several technical issues are addressed: The savings PDF is obtained from the pre- and post-PDF through a convolution. Smoothing using kernel density estimation is applied to make the PDF more realistic. The low data density problem can be mitigated through a neighborhood methodology. Correlations between pre and post buildings are addressed to improve the savings PDF. Sample size effects are addressed through the Kolmogorov--Smirnov tests and quantile-quantile plots.

  5. 77 FR 24233 - Actuarial Advisory Committee With Respect to the Railroad Retirement Account; Notice of Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-23

    ... From the Federal Register Online via the Government Publishing Office RAILROAD RETIREMENT BOARD Actuarial Advisory Committee With Respect to the Railroad Retirement Account; Notice of Public Meeting Notice is hereby given in accordance with Public Law 92-463 that the Actuarial Advisory Committee...

  6. 76 FR 67774 - Actuarial Advisory Committee With Respect to the Railroad Retirement Account; Notice of Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-02

    ... From the Federal Register Online via the Government Publishing Office RAILROAD RETIREMENT BOARD Actuarial Advisory Committee With Respect to the Railroad Retirement Account; Notice of Public Meeting Notice is hereby given in accordance with Public Law 92-463 that the Actuarial Advisory Committee...

  7. 75 FR 47650 - Actuarial Advisory Committee With Respect to the Railroad Retirement Account; Notice of Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-06

    ... From the Federal Register Online via the Government Publishing Office RAILROAD RETIREMENT BOARD Actuarial Advisory Committee With Respect to the Railroad Retirement Account; Notice of Public Meeting Notice is hereby given in accordance with Public Law 92-463 that the Actuarial Advisory Committee...

  8. 75 FR 22754 - Federal Advisory Committee; Department of Defense Board of Actuaries; Charter Renewal

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-30

    ... of the Secretary Federal Advisory Committee; Department of Defense Board of Actuaries; Charter... Defense gives notice that it is renewing the charter for the Department of Defense Board of Actuaries (hereafter referred to as the Board). FOR FURTHER INFORMATION CONTACT: Jim Freeman, Deputy Advisory...

  9. 5 CFR 839.1119 - How is the actuarial reduction for TSP computed?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false How is the actuarial reduction for TSP computed? 839.1119 Section 839.1119 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED... actuarial reduction for TSP computed? (a) The part of your TSP account on the date you retired that...

  10. 5 CFR 839.1119 - How is the actuarial reduction for TSP computed?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false How is the actuarial reduction for TSP computed? 839.1119 Section 839.1119 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED... actuarial reduction for TSP computed? (a) The part of your TSP account on the date you retired that...

  11. 42 CFR 440.340 - Actuarial report for benchmark-equivalent coverage.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false Actuarial report for benchmark-equivalent coverage... AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS SERVICES: GENERAL PROVISIONS Benchmark Benefit and Benchmark-Equivalent Coverage § 440.340 Actuarial report for benchmark-equivalent coverage....

  12. 42 CFR 457.431 - Actuarial report for benchmark-equivalent coverage.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Actuarial report for benchmark-equivalent coverage... GRANTS TO STATES State Plan Requirements: Coverage and Benefits § 457.431 Actuarial report for benchmark-equivalent coverage. (a) To obtain approval for benchmark-equivalent health benefits coverage described...

  13. 42 CFR 457.431 - Actuarial report for benchmark-equivalent coverage.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Actuarial report for benchmark-equivalent coverage... GRANTS TO STATES State Plan Requirements: Coverage and Benefits § 457.431 Actuarial report for benchmark-equivalent coverage. (a) To obtain approval for benchmark-equivalent health benefits coverage described...

  14. 42 CFR 440.340 - Actuarial report for benchmark-equivalent coverage.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Actuarial report for benchmark-equivalent coverage... AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS SERVICES: GENERAL PROVISIONS Benchmark Benefit and Benchmark-Equivalent Coverage § 440.340 Actuarial report for benchmark-equivalent coverage....

  15. 42 CFR 457.431 - Actuarial report for benchmark-equivalent coverage.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false Actuarial report for benchmark-equivalent coverage... GRANTS TO STATES State Plan Requirements: Coverage and Benefits § 457.431 Actuarial report for benchmark-equivalent coverage. (a) To obtain approval for benchmark-equivalent health benefits coverage described...

  16. 42 CFR 440.340 - Actuarial report for benchmark-equivalent coverage.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Actuarial report for benchmark-equivalent coverage... AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS SERVICES: GENERAL PROVISIONS Benchmark Benefit and Benchmark-Equivalent Coverage § 440.340 Actuarial report for benchmark-equivalent coverage....

  17. 42 CFR 440.340 - Actuarial report for benchmark-equivalent coverage.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Actuarial report for benchmark-equivalent coverage... AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS SERVICES: GENERAL PROVISIONS Benchmark Benefit and Benchmark-Equivalent Coverage § 440.340 Actuarial report for benchmark-equivalent coverage....

  18. 75 FR 68790 - Medicare Program; Medicare Part B Monthly Actuarial Rates, Premium Rate, and Annual Deductible...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-09

    ... actuarial rates for aged and disabled enrollees are used to determine the correct amount of general revenue... used each year is the annual percentage increase in the Part B actuarial rate for enrollees age 65 and... enrollees, or the current monthly premium rate increased by the ] same percentage as the most recent...

  19. 76 FR 67572 - Medicare Program; Medicare Part B Monthly Actuarial Rates, Premium Rate, and Annual Deductible...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-01

    ... actuarial rates for aged and disabled enrollees are used to determine the correct amount of general revenue... inflation factor to be used each year is the annual percentage increase in the Part B actuarial rate for... for aged enrollees, or the current monthly premium rate increased by the same percentage as the...

  20. A Comparison of Logistic Regression, Neural Networks, and Classification Trees Predicting Success of Actuarial Students

    ERIC Educational Resources Information Center

    Schumacher, Phyllis; Olinsky, Alan; Quinn, John; Smith, Richard

    2010-01-01

    The authors extended previous research by 2 of the authors who conducted a study designed to predict the successful completion of students enrolled in an actuarial program. They used logistic regression to determine the probability of an actuarial student graduating in the major or dropping out. They compared the results of this study with those…

  1. Actuarial senescence can increase the risk of extinction of mammal populations.

    PubMed

    Robert, Alexandre; Chantepie, Stéphane; Pavard, Samuel; Sarrazin, François; Teplitsky, Céline

    2015-01-01

    Despite recent acknowledgement that senescence can have negative impact on survival and fertility in natural environments across a wide range of animal species, we still do not know if it can reduce the viability of wild endangered populations. Focusing on actuarial senescence (i.e., the decline of survival probabilities at old ages), we use species-specific demographic information to project the extinction risk of wild populations of 58 species of mammals, accounting (or not) for senescence. Our projections reveal potential negative effects of aging on population viability, with an average decrease of 27% of the time to extinction and a potential deterioration of the population-level projected conservation status in 10% of the species. Senescence is associated with particularly strong increases of the extinction risk in species with low mortality rates and long intervals between litters, independently of their place in the phylogeny, indicating that the pace of life history can be used to forecast the detrimental effects of aging on the viability of species. The aim of the various existing systems of classification of threatened species is to set conservation priorities based on assessments of extinction risk. Our results indicate that the quantitative effects of senescence on extinction are highly heterogeneous, which can affect the ranking of species and populations when setting conservation, priorities. In mammals, based on life history traits of a few species, generic patterns of senescence can be incorporated into projection population models to minimize these biases in viability assessments.

  2. Mating Reverses Actuarial Aging in Female Queensland Fruit Flies

    PubMed Central

    Yap, Sarsha; Fanson, Benjamin G.; Taylor, Phillip W.

    2015-01-01

    Animals that have a long pre-reproductive adult stage often employ mechanisms that minimize aging over this period in order to preserve reproductive lifespan. In a remarkable exception, one tephritid fruit fly exhibits substantial pre-reproductive aging but then mitigates this aging during a diet-dependent transition to the reproductive stage, after which life expectancy matches that of newly emerged flies. Here, we ascertain the role of nutrients, sexual maturation and mating in mitigation of previous aging in female Queensland fruit flies. Flies were provided one of three diets: ‘sugar’, ‘essential’, or ‘yeast-sugar’. Essential diet contained sugar and micronutrients found in yeast but lacked maturation-enabling protein. At days 20 and 30, a subset of flies on the sugar diet were switched to essential or yeast-sugar diet, and some yeast-sugar fed flies were mated 10 days later. Complete mitigation of actuarial aging was only observed in flies that were switched to a yeast-sugar diet and mated, indicating that mating is key. Identifying the physiological processes associated with mating promise novel insights into repair mechanisms for aging. PMID:26147734

  3. The influence of actuarial risk assessment in clinical judgments and tribunal decisions about mentally disordered offenders in maximum security.

    PubMed

    Hilton, N Z; Simmons, J L

    2001-08-01

    Research has shown that actuarial assessments of violence risk are consistently more accurate than unaided judgments by clinicians, and it has been suggested that the availability of actuarial instruments will improve forensic decision making. This study examined clinical judgments and autonomous review tribunal decisions to detain forensic patients in maximum security. Variables included the availability of an actuarial risk report at the time of decision making, patient characteristics and history, and clinical presentation over the previous year. Detained and transferred patients did not differ in their actuarial risk of violent recidivism. The best predictor of tribunal decision was the senior clinician's testimony. There was also no significant association between the actuarial risk score and clinicians' opinions. Whether the actuarial report was available at the time of decision making did not alter the statistical model of either clinical judgments or tribunal decisions. Implications for the use of actuarial risk assessment in forensic decision making are discussed.

  4. Monitoring Actuarial Present Values of Term Life Insurance By a Statistical Process Control Chart

    NASA Astrophysics Data System (ADS)

    Hafidz Omar, M.

    2015-06-01

    Tracking performance of life insurance or similar insurance policy using standard statistical process control chart is complex because of many factors. In this work, we present the difficulty in doing so. However, with some modifications of the SPC charting framework, the difficulty can be manageable to the actuaries. So, we propose monitoring a simpler but natural actuarial quantity that is typically found in recursion formulas of reserves, profit testing, as well as present values. We shared some simulation results for the monitoring process. Additionally, some advantages of doing so is discussed.

  5. Predictors for resectability and survival in locally advanced pancreatic cancer after gemcitabine-based neoadjuvant therapy

    PubMed Central

    2014-01-01

    Background To evaluate the predictors for resectability and survival of patients with locally advanced pancreatic cancer (LAPC) treated with gemcitabine-based neoadjuvant therapy (GBNAT). Methods Between May 2003 and Dec 2009, 41 tissue-proved LAPC were treated with GBNAT. The location of pancreatic cancer in the head, body and tail was 17, 18 and 6 patients respectively. The treatment response was evaluated by RECIST criteria. Surgical exploration was based on the response and the clear plan between tumor and celiac artery/superior mesentery artery. Kaplan–Meier analysis and Cox Model were used to calculate the resectability and survival rates. Results Finally, 25 patients received chemotherapy (CT) and 16 patients received concurrent chemoradiation therapy (CRT). The response rate was 51% (21 patients), 2 CR (1 in CT and 1 in CRT) and 19 PR (10 in CT and 9 in CRT). 20 patients (48.8%) were assessed as surgically resectable, in which 17 (41.5%) underwent successful resection with a 17.6% positive-margin rate and 3 failed explorations were pancreatic head cancer for dense adhesion. Two pancreatic neck cancer turned fibrosis only. Patients with surgical intervention had significant actuarial overall survival. Tumor location and post-GBNAT CA199 < 152 were predictors for resectability. Post-GBNAT CA-199 < 152 and post-GBNAT CA-125 < 32.8 were predictors for longer disease progression-free survival. Pre-GBNAT CA-199 < 294, post-GBNAT CA-125 < 32.8, and post-op CEA < 6 were predictors for longer overall survival. Conclusion Tumor location and post-GBNAT CA199 < 152 are predictors for resectability while pre-GBNAT CA-199 < 294, post-GBNAT CA-125 < 32.8, post-GBNAT CA-199 < 152 and post-op CEA < 6 are survival predictors in LAPC patients with GBNAT. PMID:25258022

  6. 77 FR 12577 - Department of Defense (DoD) Medicare-Eligible Retiree Health Care Board of Actuaries; Federal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-01

    ... of the Secretary Department of Defense (DoD) Medicare-Eligible Retiree Health Care Board of Actuaries... that the following Federal advisory committee meeting of the DoD Medicare-Eligible Retiree Health Care... Medicare- Eligible Retiree Health Care Board of Actuaries meeting or make an oral presentation or submit...

  7. Choosing the 'best' plan in a health insurance exchange: actuarial value tells only part of the story.

    PubMed

    Lore, Ryan; Gabel, Jon R; McDevitt, Roland; Slover, Michael

    2012-08-01

    In the health insurance exchanges that will come online in 2014, consumers will be able to compare health plans with respect to actuarial value, or the percentage of health care costs that a plan would pay for a standard population. This analysis illustrates the out-of-pocket costs that might result from plans with various plan designs and actuarial values. We find that average out-of-pocket expense declines as actuarial values rise, but two plans with similar actuarial values can produce very different outcomes for a given person. The overall affordability of a plan also will be influenced by age rating, income-related premium subsidies, and out-of-pocket subsidies. Actuarial value is a useful starting point for selecting a plan, but it does not pinpoint which plan will produce the best overall value for a particular person. PMID:22946140

  8. 78 FR 8596 - Hartford Financial Services Group, Inc., Commercial/Actuarial/ Information Delivery Services (IDS...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-06

    ... was published in the Federal Register on January 4, 2013 (78 FR 773). The Hartford-IDS Group is.../ Information Delivery Services (IDS)/Corporate & Financial Reporting Group, Hartford, CT; Notice of Negative... Services Group, Inc., Commercial/Actuarial/Information Delivery Services (IDS)/Corporate &...

  9. 42 CFR 457.431 - Actuarial report for benchmark-equivalent coverage.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Actuarial report for benchmark-equivalent coverage. 457.431 Section 457.431 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STATE CHILDREN'S HEALTH INSURANCE PROGRAMS (SCHIPs) ALLOTMENTS...

  10. 42 CFR 457.431 - Actuarial report for benchmark-equivalent coverage.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Actuarial report for benchmark-equivalent coverage. 457.431 Section 457.431 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STATE CHILDREN'S HEALTH INSURANCE PROGRAMS (SCHIPs) ALLOTMENTS...

  11. 76 FR 17762 - Regulations Governing the Performance of Actuarial Services Under the Employee Retirement Income...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-31

    ... comprehensive amendments to the regulations regarding section 3042 in 1988 (53 FR 34484). In anticipation of... published in the Federal Register on June 30, 2004 (69 FR 39376). On December 21, 2007, the Joint Board... actuary in the Federal Register (72 FR 72606). On September 21, 2009, the Joint Board issued...

  12. 77 FR 69850 - Medicare Program; Medicare Part B Monthly Actuarial Rates, Premium Rate, and Annual Deductible...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-21

    ... because of entitlement to Medicare under the end-stage renal disease (ESRD) program. Projected monthly costs for disabled enrollees (other than those with ESRD) are prepared in a fashion parallel to the projection for the aged using appropriate actuarial assumptions (see Table 2). Costs for the ESRD program...

  13. Academic Attributes of College Freshmen that Lead to Success in Actuarial Studies in a Business College

    ERIC Educational Resources Information Center

    Smith, Richard Manning; Schumacher, Phyllis

    2006-01-01

    The authors studied beginning undergraduate actuarial concentrators in a business college. They identified four variables (math Scholastic Aptitude Test [SAT] score, verbal SAT score, percentile rank in high school graduating class, and percentage score on a college mathematics placement exam) that were available for entering college students that…

  14. Applying a Forensic Actuarial Assessment (the Violence Risk Appraisal Guide) to Nonforensic Patients

    ERIC Educational Resources Information Center

    Harris, Grant T.; Rice, Marnie E.; Camilleri, Joseph A..

    2004-01-01

    The actuarial Violence Risk Appraisal Guide (VRAG) was developed for male offenders where it has shown excellent replicability in many new forensic samples using officially recorded outcomes. Clinicians also make decisions, however, about the risk of interpersonal violence posed by nonforensic psychiatric patients of both sexes. Could an actuarial…

  15. Actuarial calculation for PSAK-24 purposes post-employment benefit using market-consistent approach

    NASA Astrophysics Data System (ADS)

    Effendie, Adhitya Ronnie

    2015-12-01

    In this paper we use a market-consistent approach to calculate present value of obligation of a companies' post-employment benefit in accordance with PSAK-24 (the Indonesian accounting standard). We set some actuarial assumption such as Indonesian TMI 2011 mortality tables for mortality assumptions, accumulated salary function for wages assumption, a scaled (to mortality) disability assumption and a pre-defined turnover rate for termination assumption. For economic assumption, we use binomial tree method with estimated discount rate as its average movement. In accordance with PSAK-24, the Projected Unit Credit method has been adapted to determine the present value of obligation (actuarial liability), so we use this method with a modification in its discount function.

  16. Valuing structured professional judgment: predictive validity, decision-making, and the clinical-actuarial conflict.

    PubMed

    Falzer, Paul R

    2013-01-01

    Structured professional judgment (SPJ) has received considerable attention as an alternative to unstructured clinical judgment and actuarial assessment, and as a means of resolving their ongoing conflict. However, predictive validity studies have typically relied on receiver operating characteristic (ROC) analysis, the same technique commonly used to validate actuarial assessment tools. This paper presents SPJ as distinct from both unstructured clinical judgment and actuarial assessment. A key distinguishing feature of SPJ is the contribution of modifiable factors, either dynamic or protective, to summary risk ratings. With modifiable factors, the summary rating scheme serves as a prognostic model rather than a classification procedure. However, prognostic models require more extensive and thorough predictive validity testing than can be provided by ROC analysis. It is proposed that validation should include calibration and reclassification techniques, as well as additional measures of discrimination. Several techniques and measures are described and illustrated. The paper concludes by tracing the limitations of ROC analysis to its philosophical foundation and its origin as a statistical theory of decision-making. This foundation inhibits the performance of crucial tasks, such as determining the sufficiency of a risk assessment and examining the evidentiary value of statistical findings. The paper closes by noting a current effort to establish a viable and complementary relationship between SPJ and decision-making theory.

  17. Androgen-deprivation therapy does not impact cause-specific or overall survival after permanent prostate brachytherapy

    SciTech Connect

    Merrick, Gregory S. . E-mail: gmerrick@wheelinghospital.com; Butler, Wayne M.; Wallner, Kent E.; Galbreath, Robert W.; Allen, Zachariah A. M.S.; Adamovich, Edward

    2006-07-01

    Purpose: To determine if androgen-deprivation therapy (ADT) has an impact on cause-specific, biochemical progression-free, or overall survival after prostate brachytherapy. Methods and Materials: From April 1995 through June 2002, 938 consecutive patients underwent brachytherapy for clinical Stage T1b to T3a (2002 AJCC) prostate cancer. All patients underwent brachytherapy more than 3 years before analysis. A total of 382 patients (40.7%) received ADT with a duration of 6 months or less in 277 and more than 6 months in 105. The median follow-up was 5.4 years. Multiple clinical, treatment, and dosimetric parameters were evaluated as predictors of cause-specific, biochemical progression-free, and overall survival. Results: The 10-year cause-specific, biochemical progression-free, and overall survival rates for the entire cohort were 96.4%, 95.9%, and 78.1%, respectively. Except for biochemical progression-free survival in high-risk patients, ADT did not statistically impact any of the three survival categories. A Cox linear-regression analysis demonstrated that Gleason score was the best predictor of cause-specific survival, whereas percent-positive biopsies, prostate volume, and risk group predicted for biochemical progression-free survival. Patient age and tobacco use were the strongest predictors of overall survival. One hundred two patients have died, with 80 of the deaths a result of cardiovascular disease (54) and second malignancies (26). To date, only 12 patients have died of metastatic prostate cancer. Conclusions: After brachytherapy, androgen-deprivation therapy did not have an impact on cause-specific or overall survival for any risk group; however, ADT had a beneficial effect on biochemical progression-free survival in high-risk patients. Cardiovascular disease and second malignancies far outweighed prostate cancer as competing causes of death.

  18. Ethical practice in sex offender assessment: consideration of actuarial and polygraph methods.

    PubMed

    Vess, James

    2011-09-01

    The current generation of community protection laws represents a shift in priorities that may see the individual rights of sex offenders compromised for the goal of public safety. At the center of many judicial decisions under these laws are the risk assessment reports provided by mental health practitioners. The widespread enactment of laws allowing for additional sanctions for sex offenders, and a burgeoning research literature regarding the methods used to assess risk have served to heighten rather than resolve the ethical concerns associated with professional practice in this area. This article examines ethical issues inherent in the use of two assessment methods commonly used with sex offenders in the correctional context, focusing on actuarial measures and polygraph tests. Properly conducted and adequately reported actuarial findings are considered to provide useful information of sufficient accuracy to inform rather than mislead judicial decision makers, although careful consideration must be given to the limitations of current measures in each individual case. Despite its increasing use, polygraph testing is considered controversial, with little consensus regarding its accuracy or appropriate applications. On the basis of the current state of the professional literature regarding the polygraph, its use with sex offenders raises unresolved ethical concerns.

  19. Ethical practice in sex offender assessment: consideration of actuarial and polygraph methods.

    PubMed

    Vess, James

    2011-09-01

    The current generation of community protection laws represents a shift in priorities that may see the individual rights of sex offenders compromised for the goal of public safety. At the center of many judicial decisions under these laws are the risk assessment reports provided by mental health practitioners. The widespread enactment of laws allowing for additional sanctions for sex offenders, and a burgeoning research literature regarding the methods used to assess risk have served to heighten rather than resolve the ethical concerns associated with professional practice in this area. This article examines ethical issues inherent in the use of two assessment methods commonly used with sex offenders in the correctional context, focusing on actuarial measures and polygraph tests. Properly conducted and adequately reported actuarial findings are considered to provide useful information of sufficient accuracy to inform rather than mislead judicial decision makers, although careful consideration must be given to the limitations of current measures in each individual case. Despite its increasing use, polygraph testing is considered controversial, with little consensus regarding its accuracy or appropriate applications. On the basis of the current state of the professional literature regarding the polygraph, its use with sex offenders raises unresolved ethical concerns. PMID:20944058

  20. The factor structure of static actuarial items: its relation to prediction.

    PubMed

    Barbaree, Howard E; Langton, Calvin M; Peacock, Edward J

    2006-04-01

    Principal components analysis was conducted on items contained in actuarial instruments used with adult sex offenders, including: the Rapid Assessment of Sex Offender Risk for Recidivism (RASORR), the Static-99, the Violence Risk Appraisal Guide (VRAG), the Sex Offender Risk Appraisal Guide (SORAG), and the Minnesota Sex Offender Screening Tool-Revised (MnSOST-R). In a data set that included child molesters and rapists (N = 311), six interpretable components were identified: Antisocial Behavior, Child Sexual Abuse, Persistence, Detached Predatory Behavior, Young and Single, and Male Victim(s). The RRASOR was highly correlated with Persistence, and the VRAG and SORAG were highly correlated with Antisocial Behavior. Antisocial Behavior was a significant predictor of violent recidivism, while Persistence and Child Sexual Abuse were significant predictors of sexual recidivism. PMID:16937082

  1. Projections of health care expenditures as a share of the GDP: actuarial and macroeconomic approaches.

    PubMed Central

    Warshawsky, M J

    1994-01-01

    STUDY QUESTION. Can the steady increases in health care expenditures as a share of GDP projected by widely cited actuarial models be rationalized by a macroeconomic model with sensible parameters and specification? DATA SOURCES. National Income and Product Accounts, and Social Security and Health Care Financing Administration are the data sources used in parameters estimates. STUDY DESIGN. Health care expenditures as a share of gross domestic product (GDP) are projected using two methodological approaches--actuarial and macroeconomic--and under various assumptions. The general equilibrium macroeconomic approach has the advantage of allowing an investigation of the causes of growth in the health care sector and its consequences for the overall economy. DATA COLLECTION METHODS. Simulations are used. PRINCIPAL FINDINGS. Both models unanimously project a continued increase in the ratio of health care expenditures to GDP. Under the most conservative assumptions, that is, robust economic growth, improved demographic trends, or a significant moderation in the rate of health care price inflation, the health care sector will consume more than a quarter of national output by 2065. Under other (perhaps more realistic) assumptions, including a continuation of current trends, both approaches predict that health care expenditures will comprise between a third and a half of national output. In the macroeconomic model, the increasing use of capital goods in the health care sector explains the observed rise in relative prices. Moreover, this "capital deepening" implies that a relatively modest fraction of the labor force is employed in health care and that the rest of the economy is increasingly starved for capital, resulting in a declining standard of living. PMID:8063567

  2. Competence in Mathematics and Academic Achievement: An Analysis of Enrollees in the Bachelor of Science in Actuarial Science Program

    ERIC Educational Resources Information Center

    Wamala, Robert; Maswere, Dyson W.; Mwanga, Yeko

    2013-01-01

    This study investigates the role of prior grounding attained in mathematics in predicting the academic achievement of enrollees in Bachelor of Science in Actuarial Science (BSAS). The investigation is based on administrative records of 240 BSAS enrollees at Makerere University, School of Statistics and Planning in the 2007-2009 cohorts. Students'…

  3. 78 FR 9890 - DoD Medicare-Eligible Retiree Health Care Board of Actuaries; Notice of Federal Advisory...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ... of the Secretary DoD Medicare-Eligible Retiree Health Care Board of Actuaries; Notice of Federal... that the following Federal Advisory Committee meeting of the DoD Medicare-Eligible Retiree Health Care... in the valuation of benefits under DoD retiree health care programs for...

  4. 75 FR 6360 - Federal Advisory Committee; DoD Medicare-Eligible Retiree Health Care Board of Actuaries

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-09

    ... of the Secretary Federal Advisory Committee; DoD Medicare-Eligible Retiree Health Care Board of... that the DoD Medicare-Eligible Retiree Health Care Board of Actuaries will meet on August 18, 2010... used in the valuation of benefits under DoD retiree health care programs for...

  5. A Brief Actuarial Assessment for the Prediction of Wife Assault Recidivism: The Ontario Domestic Assault Risk Assessment

    ERIC Educational Resources Information Center

    Hilton, N. Zoe; Harris, Grant T.; Rice, Marnie E.; Lang, Carol; Cormier, Catherine A.; Lines, Kathryn J.

    2004-01-01

    An actuarial assessment to predict male-to-female marital violence was constructed from a pool of potential predictors in a sample of 589 offenders identified in police records and followed up for an average of almost 5 years. Archival information in several domains (offender characteristics, domestic violence history, nondomestic criminal…

  6. 5 CFR 839.1121 - What is the Actuarial Reduction for the Basic Employee Death Benefit (BEDB)?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Basic Employee Death Benefit (BEDB)? 839.1121 Section 839.1121 Administrative Personnel OFFICE OF... Benefits § 839.1121 What is the Actuarial Reduction for the Basic Employee Death Benefit (BEDB)? If you... will be the amount of the BEDB divided by the present value factor for your age at the time of...

  7. Actuarial Models for Assessing Prison Violence Risk: Revisions and Extensions of the Risk Assessment Scale for Prison (RASP)

    ERIC Educational Resources Information Center

    Cunningham, Mark D.; Sorensen, Jon R.

    2006-01-01

    An investigation and extension of the Risk Assessment Scale for Prison (RASP-Potosi), an actuarially derived scale for the assessment of prison violence, was undertaken through a retrospective review of the disciplinary records of the first 12 months of confinement of a cohort of inmates entering the Florida Department of Corrections in 2002 and…

  8. 76 FR 18649 - Technical Revisions to Actuarial Information on Form 5500 Annual Return/Report for Pension Plans...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-05

    ... MB (Multiemployer Defined Benefit Plan and Certain Money Purchase Plan Actuarial Information) and the.../Report of Employee Benefit Plan have been adopted in IRS Notice 2010-83 (2010-51 I.R.B. 862) and IRS Notice 2011-3 (2011-2 I.R.B. 263) to reflect funding relief alternatives retroactively available...

  9. If You Build It, Will They Come? Tales of Developing a New Degree Program in Actuarial Science

    ERIC Educational Resources Information Center

    Marano, Lisa E.

    2014-01-01

    In 2007, the B.S. in Applied Mathematics program consisting of five concentrations, including Actuarial Science, began at West Chester University of Pennsylvania, and we graduated our first class (of one) that December. We describe our program, some ideas to consider when planning your own program, and share some of the successes of our program…

  10. A theoretical model of the evolution of actuarial senescence under environmental stress

    PubMed Central

    Watson, H.; Cohen, A.A.; Isaksson, C.

    2015-01-01

    Free-living organisms are exposed to a wide range of stressors, all of which can disrupt components of stress-related and detoxification physiology. The subsequent accumulation of somatic damage is widely believed to play a major role in the evolution of senescence. Organisms have evolved sophisticated physiological regulatory mechanisms to maintain homeostasis in response to environmental perturbations, but these systems are likely to be constrained in their ability to optimise robustness to multiple stressors due to functional correlations among related traits. While evolutionary change can accelerate due to human ecological impacts, it remains to be understood how exposure to multiple environmental stressors could affect senescence rates and subsequently population dynamics and fitness. We used a theoretical evolutionary framework to quantify the potential consequences for the evolution of actuarial senescence in response to exposure to simultaneous physiological stressors – one versus multiple and additive versus synergistic – in a hypothetical population of avian “urban adapters”. In a model in which multiple stressors have additive effects on physiology, species may retain greater capacity to recover, or respond adaptively, to environmental challenges. However, in the presence of high synergy, physiological dysregulation suddenly occurs, leading to a rapid increase in age-dependent mortality and subsequent population collapse. Our results suggest that, if the synergistic model is correct, population crashes in environmentally-stressed species could happen quickly and with little warning, as physiological thresholds of stress resistance are overcome. PMID:26335620

  11. Pertuzumab in Combination with Trastuzumab and Chemotherapy in the Treatment of HER2-Positive Metastatic Breast Cancer: Safety, Efficacy, and Progression Free Survival

    PubMed Central

    Maly, Joseph J; Macrae, Erin R

    2014-01-01

    Tyrosine kinase inhibitors have revolutionized the oncology community and were pioneered by the use in HER2-targeted therapies. Improved outcomes were seen with the advent of trastuzumab, leading investigators to develop newer agents to target the HER2 pathway such as the novel monoclonal antibody pertuzumab. In this paper, we describe the attributes of pertuzumab including: mechanism of action, pharmacokinetics and metabolism, safety/cardiotoxicity, drug interactions, efficacy, and role in HER2-positive breast cancer management. Newly reviewed here versus previously published reviews on pertuzumab oriented therapy are data of pertuzumab monotherapy as it is used in combination with other anti-HER2 agents derived from preclinical research and ongoing clinical trials. MATERIALS AND METHODS A computer based literature search was carried out using PubMed data reported at international meetings (ASCO) up to September 2013 were included. PMID:24855372

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

    SciTech Connect

    Herbert, Christopher; Liu, Mitchell; Tyldesley, Scott; Morris, W. James; Joffres, Michel; Khaira, Mandip; Kwan, Winkle; Moiseenko, Vitali; Pickles, Thomas

    2012-05-01

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

  13. Properties of actuarially fair and pay-as-you-go health insurance schemes for the elderly. An OLG model approach.

    PubMed

    Johansson, P O

    2000-07-01

    The aged dependency ratio or ADR is growing at a fast pace in many countries. This fact causes stress to the economy and might create conflicts of interest between young and old. In this paper the properties of different health insurance systems for the elderly are analysed within an overlapping generations (OLG) model. The properties of actuarial health insurance and different variations of pay-as-you-go (PAYG) health insurance are compared. It turns out that the welfare properties of these contracts are heavily dependent on the economy's dynamic properties. Of particular importance is the magnitude of the rate of population growth relative to the interest rate. In addition, it is shown that public health insurance is associated with an inherent externality resulting in a second-best solution.

  14. Substance Abuse among High-Risk Sexual Offenders: Do Measures of Lifetime History of Substance Abuse Add to the Prediction of Recidivism over Actuarial Risk Assessment Instruments?

    ERIC Educational Resources Information Center

    Looman, Jan; Abracen, Jeffrey

    2011-01-01

    There has been relatively little research on the degree to which measures of lifetime history of substance abuse add to the prediction of risk based on actuarial measures alone among sexual offenders. This issue is of relevance in that a history of substance abuse is related to relapse to substance using behavior. Furthermore, substance use has…

  15. Survival of breast cancer patients. Our experience.

    PubMed

    Marrazzoa, Antonio; Taormina, Pietra; David, Massimo; Riili, Ignazio; Casà, Luigi; Catalano, Filippo; Lo Gerfo, Domenico; Noto, Antonio

    2007-01-01

    Life expectancy for patients with breast carcinoma has changed in Europe over the last two decades. In Italy, the overall survival rate is about 77% at 5 years. When considering the situation in Sicily, the EUROCARE 2 study examined survival data from the Ragusa Cancer Registry, showing that the curves are worse than in other regions of Italy. Starting from these considerations we decide to evaluate whether these data from the Ragusa Cancer Registry corresponded to Palermo data. So we analysed data from 575 consecutive patients with breast cancer, treated in our Breast Unit from 1990 to 2003 according to the St. Gallen Recommendations and followed for a median period of 5 years. The prognostic role of age, tumour size, nodal status, TNM, stage, grading and hormonal receptors (OR, PR) were analysed and survival curves at 5 and 10 years were produced using the actuarial survival methods. All causes of death were considered. The median follow-up was 33 months. The Log rank test and univariate cox proportional model were used to demonstrate the association between prognostic factors and outcome. When considering T and N status, the curves showed an inverse correlation between survival and increases in these parameters. Overall survival was 92.9% at 5 years and 81.4% at 10 years for T1, 78.4% at 5 years and 61.4% at 10 years for T2 and 40.8% for T3-T4 at 5 and 10 years. Overall survival for NO was 92.1% and 78.2%, respectively, at 5 and 10 years, but decreased to 72.0% and 59.9% at 5 and 10 years for N1. In N2 patients we found that only about 50% of patients were still alive at 5 and 10 years, while for N3 patients the figures were 57.2% and 40%, respectively. PMID:17663369

  16. Unguided clinical and actuarial assessment of re-offending risk: a direct comparison with sex offenders in Denmark.

    PubMed

    Bengtson, Susanne; Långström, Niklas

    2007-06-01

    Meta-analyses suggest that actuarial risk assessments outperform unguided clinical judgment for prediction of recidivism in criminal offenders. However, there is a lack of direct comparisons of the predictive accuracy of clinical judgment and actuarial risk scales for sexual offenders. We followed up 121 male sex offenders (> or =18 years) subjected to pre-trial forensic psychiatric assessment in Denmark in 1978-1992 (mean post-detainment time = 16.4 years) to compare the predictive validity of unstructured clinical judgment of recidivism risk with that of the well-established Static-99 (Hanson and Thornton, Law and Human Behavior 24:119-136, 2000) and an extension of the Static-99, the Static-2002 (Hanson and Thornton, Notes on the development of Static-2002 (Rep. No. 2003-01), Public Safety and Emergency Preparedness Canada, Ottawa, Canada, 2003). The predictive accuracy of unguided judgment did not exceed chance for any sexual, severe sexual or any violent (sexual or non-sexual) reconviction (AUCs of the ROC curve = 0.52, 95%CI = 0.41-0.63; 0.50, 95%CI = 0.34-0.67; and 0.57, 95%CI = 0.40-0.73, respectively). In contrast, all three outcomes were predicted significantly better than chance by the Static-99 (AUC = 0.62, 95%CI = 0.52-0.72; 0.72, 95%CI = 0.59-0.84; and 0.71, 95%CI = 0.56-0.86) and the Static-2002 (AUC = 0.67, 95%CI = 0.57-0.77; 0.69, 95%CI = 0.56-0.83; and 0.70, 95%CI = 0.55-0.86). Static-99 outperformed clinical judgment for sexual recidivision (chi(2) = 5.11, df = 1, p < .05). The Static-2002 was significantly more accurate for the prediction of any sexual recidivism as compared to unguided clinical judgment but its advantage fell just short of statistical significance for severe sexual recidivism (chi(2) = 3.56, df = 1, p = 0.06). When tested for recidivism within 2 years, none of the three prediction methods yielded results significantly better than chance for any outcome. This direct trial of the unguided clinical method argues against its

  17. An actuarial analysis shows that offering lung cancer screening as an insurance benefit would save lives at relatively low cost.

    PubMed

    Pyenson, Bruce S; Sander, Marcia S; Jiang, Yiding; Kahn, Howard; Mulshine, James L

    2012-04-01

    Lung cancer screening is not established as a public health practice, yet the results of a recent large randomized controlled trial showed that screening with low-dose spiral computed tomography reduces lung cancer mortality. Using actuarial models, this study estimated the costs and benefits of annual lung cancer screening offered as a commercial insurance benefit in the high-risk US population ages 50-64. Assuming current commercial reimbursement rates for treatment, we found that screening would cost about $1 per insured member per month in 2012 dollars. The cost per life-year saved would be below $19,000, an amount that compares favorably with screening for cervical, breast, and colorectal cancers. Our results suggest that commercial insurers should consider lung cancer screening of high-risk individuals to be high-value coverage and provide it as a benefit to people who are at least fifty years old and have a smoking history of thirty pack-years or more. We also believe that payers and patients should demand screening from high-quality, low-cost providers, thus helping set an example of efficient system innovation.

  18. Beyond Survival

    ERIC Educational Resources Information Center

    Steffenson, Dave

    1975-01-01

    The author argues that environmentalists need to realize that the present ecological crisis is essentially a value crisis, not merely a fight for survival alone. He envisions a complete value change for the human population and advocates the incorporation of value strategies into all environmental education programs immediately. (MA)

  19. Tumor Response and Survival Predicted by Post-Therapy FDG-PET/CT in Anal Cancer

    SciTech Connect

    Schwarz, Julie K.; Siegel, Barry A.; Dehdashti, Farrokh; Myerson, Robert J.; Fleshman, James W.; Grigsby, Perry W.

    2008-05-01

    Purpose: To evaluate the response to therapy for anal carcinoma using post-therapy imaging with positron emission tomography (PET)/computed tomography and F-18 fluorodeoxyglucose (FDG) and to compare the metabolic response with patient outcome. Patients and Methods: This was a prospective cohort study of 53 consecutive patients with anal cancer. All patients underwent pre- and post-treatment whole-body FDG-PET/computed tomography. Patients had been treated with external beam radiotherapy and concurrent chemotherapy. Whole-body FDG-PET was performed 0.9-5.4 months (mean, 2.1) after therapy completion. Results: The post-therapy PET scan did not show any abnormal FDG uptake (complete metabolic response) in 44 patients. Persistent abnormal FDG uptake (partial metabolic response) was found in the anal tumor in 9 patients. The 2-year cause-specific survival rate was 94% for patients with a complete vs. 39% for patients with a partial metabolic response in the anal tumor (p = 0.0008). The 2-year progression-free survival rate was 95% for patients with a complete vs. 22% for patients with a partial metabolic response in the anal tumor (p < 0.0001). A Cox proportional hazards model of survival outcome indicated that a complete metabolic response was the most significant predictor of progression-free survival in our patient population (p = 0.0003). Conclusions: A partial metabolic response in the anal tumor as determined by post-therapy FDG-PET is predictive of significantly decreased progression-free and cause-specific survival after chemoradiotherapy for anal cancer.

  20. Metformin Use and Endometrial Cancer Survival

    PubMed Central

    Nevadunsky, Nicole S.; Van Arsdale, Anne; Strickler, Howard D.; Moadel, Alyson; Kaur, Gurpreet; Frimer, Marina; Conroy, Erin; Goldberg, Gary L.; Einstein, Mark H.

    2013-01-01

    Objective Impaired glucose tolerance and diabetes are risk factors for the development of uterine cancer. Although greater progression free survival among diabetic patients with ovarian and breast cancer using metformin have been reported, no studies have assessed the association of metformin use with survival in women with endometrial cancer (EC). Methods We conducted a single-institution retrospective cohort study of all patients treated for uterine cancer from January 1999 through December 2009. Demographic, medical, social, and survival data were abstracted from medical records and the national death registry. Overall survival (OS) was estimated using Kaplan-Meier methods. Cox models were utilized for multivariate analysis. All statistical tests were two-sided. Results Of 985 patients, 114 (12%) had diabetes and were treated with metformin, 136 (14%) were diabetic but did not use metformin, and 735 (74%) had not been diagnosed with diabetes. Greater OS was observed in diabetics with non-endometrioid EC who used metformin than in diabetic cases not using metformin and non-endometrioid EC cases without diabetes (log rank test (p=0.02)). This association remained significant (hazard ratio = 0.54, 95% CI: 0.30–0.97, p<0.04) after adjusting for age, clinical stage, grade, chemotherapy treatment, radiation treatment and presence of hyperlipidemia in multivariate analysis. No association between metformin use and OS in diabetics with endometrioid histology was observed. Conclusion Diabetic EC patients with non-endometrioid tumors who used metformin had lower risk of death than women with EC who did not use metformin. These data suggest that metformin might be useful as adjuvant therapy for non-endometrioid EC. PMID:24189334

  1. Diet and Physical Activity Change or Usual Care in Improving Progression-Free Survival in Patients With Previously Treated Stage II, III, or IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-02-09

    Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Brenner Tumor; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  2. Blood neutrophil-lymphocyte ratio predicts survival in locally advanced cancer stomach treated with neoadjuvant chemotherapy FOLFOX 4.

    PubMed

    el Aziz, Lamiss Mohamed Abd

    2014-12-01

    Accurate predictors of survival for patients with advanced gastric cancer treated with neoadjuvant chemotherapy are currently lacking. In this study, we aimed to evaluate the prognostic significance of the neutrophil-lymphocyte ratio (NLR) in patients with stage III-IV gastric cancer who received neoadjuvant chemotherapy FOLFOX 4 as neoadjuvant chemotherapy. We enrolled 70 patients with stage III-IV cancer stomach in this study. Patients received FOLFOX 4 as neoadjuvant chemotherapy. Blood sample was collected before chemotherapy. The NLR was divided into two groups: high (>3) and low (≤ 3). Univariate analysis on progression-free survival (PFS) and overall survival (OS) was performed using the Kaplan-Meier and log-rank tests, and multivariate analysis was conducted using the Cox proportional hazards regression model. The toxicity was evaluated according to National Cancer Institute Common Toxicity Criteria. The univariate analysis showed that PFS and OS were both worse for patients with high NLR than for those with low NLR before chemotherapy (median PFS 28 and 44 months, respectively, P = 0.001; median OS 30 and 48 months, P = 0.001). Multivariate analysis showed that NLRs before chemotherapy were independent prognostic factors of OS but not for progression-free survival. NLR may serve as a potential biomarker for survival prognosis in patients with stage III-IV gastric cancer receiving neoadjuvant chemotherapy. The FOLFOX 4 demonstrated an acceptable toxicity.

  3. Usefulness of a normal coronary angiogram in patients aged ≥65 years to foretell survival.

    PubMed

    Moreyra, Abel E; Charalambous, Marinos; Cosgrove, Nora M; Rajaei, Sheeva; Cullen, Kathryn; Cheng, Jerry Q; David, Alice; Kostis, William J; Kostis, John B

    2015-11-15

    A normal coronary angiogram (CA) has been reported to confer a good prognosis. However, how this applies to patients aged ≥65 years is not well known. From 1986 to 1996, 11,625 patients aged ≥65 underwent coronary angiography. We identified 271 patients with either normal (NORM, n = 160) CA or <30% diameter stenosis disease (NEAR-NORM, n = 111). Using the Myocardial Infarction Data Acquisition System, we examined the probability of survival and the risk of developing an ischemic event or undergoing a revascularization procedure during an average of 15.1 ± 6.2 years (range 0.5 to 25.8 years). Matched actuarial subjects were used to compare survival to the general population. The incidence of an ischemic event was low (2.0 events per 100 persons/year for the NORM and 2.8 patients per 100 persons/year for the NEAR-NORM group, p = NS). Rates of revascularization were higher in the NEAR-NORM group compared to the NORM group (1 per 100 persons/year vs 0.5 per 100 persons/year, p = 0.04). During the 25.8-year follow-up, there were 77 deaths (48.4%) for the NORM and 64 (57.1%) for the NEAR-NORM group (χ2 = 1.7, NS). The NORM group survived 6,789 days, 1,517 more days than the actuarial subjects (95% confidence interval [CI] 1,072 to 1,956; p <0.0001) and the NEAR-NORM group survived 5,922 days, 875 more days (95% CI 368 to 1,376; p <0.005). In conclusion, patients with normal or near-normal CA at age ≥65 years have a low rate of myocardial ischemic events and have significantly longer survival than matched subjects from the general population. PMID:26411358

  4. Comparison of Risk Factors and survival of Type 1 and Type II Endometrial Cancers

    PubMed Central

    Malik, Tahira Y.; Chishti, Uzma; Aziz, Aliya B.; Sheikh, Irfan

    2016-01-01

    Objective: To compare risk factors and progression free survival of type 1 & 2 endometrial cancers. Methods: A retrospective analysis of 149 patients with early stage endometrial carcinoma treated between 1997 and 2012 in Aga Khan University Hospital, Karachi was performed. Results: A total of 149 patients were analyzed. Type I tumors accounted for 92% of cases in the study while 8% were type II tumors. The mean age, BMI, parity, co-morbidities (hypertension & Diabetes), family history and history of polycystic disease were comparable in both groups. Overall better survival (113 Vs 24 months) was observed for type I endometrial cancer. Conclusion: Both types of endometrial cancer may share common etiologic factors. Despite the limitation of small numbers in one group this study confirms better survival in type 1 endometrial cancer. PMID:27648033

  5. Comparison of Risk Factors and survival of Type 1 and Type II Endometrial Cancers

    PubMed Central

    Malik, Tahira Y.; Chishti, Uzma; Aziz, Aliya B.; Sheikh, Irfan

    2016-01-01

    Objective: To compare risk factors and progression free survival of type 1 & 2 endometrial cancers. Methods: A retrospective analysis of 149 patients with early stage endometrial carcinoma treated between 1997 and 2012 in Aga Khan University Hospital, Karachi was performed. Results: A total of 149 patients were analyzed. Type I tumors accounted for 92% of cases in the study while 8% were type II tumors. The mean age, BMI, parity, co-morbidities (hypertension & Diabetes), family history and history of polycystic disease were comparable in both groups. Overall better survival (113 Vs 24 months) was observed for type I endometrial cancer. Conclusion: Both types of endometrial cancer may share common etiologic factors. Despite the limitation of small numbers in one group this study confirms better survival in type 1 endometrial cancer.

  6. Bevacizumab Combined with Chemotherapy Improves Survival for Patients with Metastatic Colorectal Cancer: Evidence from Meta Analysis

    PubMed Central

    Jankovic, Slobodan

    2016-01-01

    Background Colorectal cancer is one of the leading causes of cancer deaths in both sexes in the world. Improvement of existing therapy modalities and implementing new ones in order to improve survival of patients with colorectal cancer represents a great challenge for medicine. The aim of this paper was to assess the impact that adding bevacizumab to chemotherapy has on survival in patients with metastatic colorectal cancer, compared to the use of chemotherapy alone. Methods Hazard ratios (HRs) with their 95% confidence intervals (CI) were determined from the studies and pooled. Two-sided p values were reported and considered to indicate statistical significance if less than 0.05. Results A total of 12 studies that meet the inclusion criteria were identified in the literature search, 3 phase II studies and 9 phase III studies. Based on the random effects meta-analysis, a statistically significant improvement was identified for both overall survival (HR = 0.84; 95% CI: 0.74–0.94; p = 0.003) and progression free survival (HR = 0.64; 95% CI: 0.55–0.73; p<0.00001) in patients with metastatic colorectal cancer when bevacizumab was added to chemotherapy, compared to chemotherapy treatment alone. Conclusion The findings of this meta analysis confirm the benefit of adding bevacizumab to chemotherapy in terms of survival and progression free survival, but the magnitude of this effect is not consistent throughout the included studies. This suggests the need for further research of interaction of bevacizumab with chemotherapeutic agents as well as recognition of patients’ characteristics important for the treatment selection criteria. PMID:27579775

  7. On the Survival Stage.

    ERIC Educational Resources Information Center

    Callahan, Steven

    1997-01-01

    Presents a survival expert's model of survival. Characterizes survival in terms of being prepared for a crisis, escaping the immediate threat, avoiding disorientation and fear, and the survival routine, which includes hope, flexibility, and humor. Notes the impact of posttrauma situations and the need for continued vigilance. (RJM)

  8. Immunoparesis status in immunoglobulin light chain amyloidosis at diagnosis affects response and survival by regimen type

    PubMed Central

    Muchtar, Eli; Dispenzieri, Angela; Kumar, Shaji K.; Dingli, David; Lacy, Martha Q.; Buadi, Francis K.; Hayman, Suzanne R.; Kapoor, Prashant; Leung, Nelson; Chakraborty, Rajshekhar; Russell, Stephen; Lust, John A.; Lin, Yi; Go, Ronald S.; Zeldenrust, Steven; Kyle, Robert A.; Rajkumar, S. Vincent; Gertz, Morie A.

    2016-01-01

    Clinical tools to guide in the appropriate treatment selection in immunoglobulin light chain (AL) amyloidosis are not well developed. We evaluated the response and outcome for various regimens at first-line treatment (n=681) and first progression (n=240) stratified by the immunoparesis status at diagnosis. Immunoparesis was assessed by the average relative difference of the uninvolved immunoglobulins, classifying patients into a negative average relative difference (i.e. significant immunoparesis) or a positive average relative difference (no/modest immunoparesis). Treatment was categorized as autologous stem cell transplant and four non-transplant regimens (melphalan-based; bortezomib-based, immunomodulatory drug-based and dexamethasone alone). Patients with significant immunoparesis who underwent stem cell transplant had a significantly lower rate of very good partial response or better response (58%), progression-free survival (median 30 months) and overall survival (108 months), compared to those without significant immunoparesis (80%, 127 months, median not reached, respectively; P<0.001 for all comparisons). Among the non-transplant regimens, melphalan resulted in an unfavorable progression-free survival (11 vs. 27 months; P<0.001) and overall survival (30 vs. 74 months; P=0.001) in patients with significant immunoparesis compared to those without significant immunoparesis. In contrast, no significant difference in outcomes between the immunoparesis groups was seen for those treated with bortezomib or immunomodulatory drugs. At first progression, immunoparesis status did not impact response or survival of any regimen. Melphalan at first-line provided poorer outcomes for patients with significant immunoparesis, while bortezomib or immunomodulatory drugs were more likely to overcome the adverse prognosis associated with significant immunoparesis. PMID:27479823

  9. Treatment Factors Associated With Long-Term Survival Following Cytoreductive Surgery and Regional Chemotherapy for Patients with Malignant Peritoneal Mesothelioma

    PubMed Central

    Alexander, H. Richard; Bartlett, David L.; Pingpank, James F.; Libutti, Steven K.; Royal, Richard; Hughes, Marybeth S.; Holtzman, Matthew; Hanna, Nader; Turner, Keli; Beresneva, Tatiana; Zhu, Yue

    2013-01-01

    OBJECTIVES Malignant peritoneal mesothelioma (MPM) is a primary cancer that arises diffusely from the serosa of the peritoneum. Morbidity and mortality are almost invariably due to loco-regional progression; cytoreduction with intra-operative or peri-operative high dose regional chemotherapy has been established as the preferred approach in selected patients. This study was performed to identify factors associated with long-term outcome. METHODS Between January, 1992 and 2010, 211 patients with MPM treated at three major referral centers with operative cytoreduction and hyperthermic intra-operative peritoneal chemotherapy (HIPEC) were analyzed. RESULTS The median actuarial overall survival was 38.4 months; the actuarial 5 and 10 year survivals were 41% and 26%, respectively. On multivariate analysis, factors independently associated with favorable outcome were age less than 60 years (p< 0.01), complete or near complete (R0–1) versus incomplete (R2–3) resection (p< 0.02), low versus high histologic grade (P< 0.01), and the use of cisplatin versus mitomycin-C during HIPEC (p< 0.01). There was an insignificant trend towards female gender and improved survival (male Hazard Ratio: 1.46, 95% CI: 0.89–2.41, p=0.13). CONCUSIONS Operative cytoreduction with HIPEC is associated with long term survival in patients with MPM. Factors associated with survival include age, complete or near complete gross tumor resection, histologic tumor grade, and HIPEC with cisplatin. The fact that cisplatin versus mitomycin-c was independently associated with improved survival demonstrates a salutary effect for HIPEC with cisplatin in the management of patients with MPM. PMID:23489943

  10. Upregulation of chemokine receptor CCR10 is essential for glioma proliferation, invasion and patient survival

    PubMed Central

    Chen, Lingchao; Liu, Xing; Zhang, Hai-Yan; Du, Wenzong; Qin, Zhiyong; Yao, Yu; Mao, Ying; Zhou, Liangfu

    2014-01-01

    Human gliomas are characterized by their invasion of normal brain structures irrespective of their grade of malignancy. Tumor cell invasion share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptor CCR10 is highly expressed in human glioblastoma compared with control brain tissue. In vitro, signaling through CCL27-CCR10 mediates activation of p-Akt, and subsequently induces proliferation and invasive responses. Cell proliferation and invasion promoted by CCL27 were blocked by inhibition of p-Akt or CCR10. In vivo, down-regulation of CCR10 significantly impairs growth of glioma. Clinically, High CCR10 expression in GBM correlated with p-Akt, shorter overall survival and progression-free survival (P < 0.05). Together, these findings suggest that elevated CCR10 is a critical molecular event associated with gliomagenesis. PMID:25149529

  11. A Winter Survival Unit.

    ERIC Educational Resources Information Center

    Phillips, Ronald E.

    1979-01-01

    The article is a condensation of materials from the winter survival unit of a Canadian snow ecology course. The unit covers: cold physiology, frostbite, snowblindness, hypothermia, winter campout, and survival strategies. (SB)

  12. Survivability Versus Time

    NASA Technical Reports Server (NTRS)

    Joyner, James J., Sr.

    2014-01-01

    Develop Survivability vs Time Model as a decision-evaluation tool to assess various emergency egress methods used at Launch Complex 39B (LC 39B) and in the Vehicle Assembly Building (VAB) on NASAs Kennedy Space Center. For each hazard scenario, develop probability distributions to address statistical uncertainty resulting in survivability plots over time and composite survivability plots encompassing multiple hazard scenarios.

  13. Improved survival with neoadjuvant therapy and resection for adenocarcinoma of the esophagus.

    PubMed Central

    Stewart, J R; Hoff, S J; Johnson, D H; Murray, M J; Butler, D R; Elkins, C C; Sharp, K W; Merrill, W H; Sawyers, J L

    1993-01-01

    OBJECTIVE: This study sought to determine the impact of preoperative chemotherapy and radiation therapy (neoadjuvant therapy) followed by resection in patients with adenocarcinoma of the esophagus. SUMMARY BACKGROUND DATA: Long-term survival in patients with carcinoma of the esophagus has been poor. An increase in the incidence of adenocarcinoma of the esophagus has been reported recently. METHODS: Fifty-eight patients with biopsy-proven adenocarcinoma of the esophagus treated at this institution from January 1951 through February 1993 were studied. Since 1989, 24 patients were entered prospectively into a multimodality treatment protocol consisting of preoperative cisplatin, 5-fluorouracil (5-FU), and leucovorin with or without etoposide, and concomitant mediastinal radiation (30 Gy). Patients were re-evaluated and offered resection. RESULTS: There were no deaths related to neoadjuvant therapy and toxicity was minimal. Before multimodality therapy was used, the operative mortality rate was 19% (3 of 16 patients). With multimodality therapy, there have been no operative deaths (0 of 23 patients). The median survival time in patients treated before multimodality therapy was 8 months and has yet to be reached for those treated with the neoadjuvant regimen (> 26 months, p < 0.0001). The actuarial survival rate at 24 months was 15% before multimodality therapy and 76% with multimodality therapy. No difference in survival was noted in neoadjuvant protocols with or without etoposide (p = 0.827). CONCLUSIONS: Multimodality therapy with preoperative chemotherapy and radiation therapy followed by resection appears to offer a survival advantage to patients with adenocarcinoma of the esophagus. PMID:8215648

  14. Primary Tumor Resection and Survival in Patients with Stage IV Gastric Cancer

    PubMed Central

    Mutlu, Hasan; Karaağaç, Mustafa; Eryilmaz, Melek Karakurt; Gündüz, Şeyda; Artaç, Mehmet

    2016-01-01

    Purpose The aim of this study was to determine whether surgical resection of the primary tumor contributes to survival in patients with metastatic gastric cancer. Materials and Methods A total of 288 patients with metastatic gastric cancer from the Akdeniz University, Antalya Training and Research Hospital, and the Meram University of Konya database were retrospectively analyzed. The effect of primary tumor resection on survival of patients with metastatic gastric cancer was investigated using the log-rank test. Kaplan-Meier survival estimates were calculated. Multivariate analysis was performed using Cox proportional hazards regression modeling. Results The median overall survival was 12.0 months (95% confidence intewrval [CI], 10.4~13.6 months) and 7.8 months (95% CI, 5.5~10.0 months) for patients with and without primary tumor resection, respectively (P<0.001). The median progression-free survival was 8.3 months (95% CI, 7.1~9.5 months) and 6.2 months (95% CI, 5.8~6.7 months) for patients with and without primary tumor resection, respectively (P=0.002). Conclusions Non-curative gastrectomy in patients with metastatic gastric cancer might increase their survival rate regardless of the occurrence of life-threatening tumor-related complications. PMID:27433392

  15. Mesothelioma patients with germline BAP1 mutations have 7-fold improved long-term survival.

    PubMed

    Baumann, Francine; Flores, Erin; Napolitano, Andrea; Kanodia, Shreya; Taioli, Emanuela; Pass, Harvey; Yang, Haining; Carbone, Michele

    2015-01-01

    BRCA1-associated protein-1 (BAP1) mutations cause a new cancer syndrome, with a high rate of malignant mesothelioma (MM). Here, we tested the hypothesis that MM associated with germline BAP1 mutations has a better prognosis compared with sporadic MM. We compared survival among germline BAP1 mutation MM patients with that of all MM (N = 10 556) recorded in the United States Surveillance, Epidemiology, and End Results (SEER) data from 1973 to 2010. We identified 23 MM patients--11 alive--with germline BAP1 mutations and available data on survival. Ten patients had peritoneal MM, ten pleural MM and three MM in both locations. Thirteen patients had one or more malignancies in addition to MM. Actuarial median survival for the MM patients with germline BAP1 mutations was 5 years, as compared with <1 year for the median survival in the United States SEER MM group. Five-year survival was 47%, 95% confidence interval (24-67%), as compared with 6.7% (6.2-7.3%) in the control SEER group. Analysis of the pooled cohort of germline BAP1 mutation MM showed that patients with peritoneal MM (median survival of 10 years, P = 0.0571), or with a second malignancy in addition to MM (median survival of 10 years, P = 0.0716), survived for a longer time compared with patients who only had pleural MM, or MM patients without a second malignancy, respectively. In conclusion, we found that MM patients with germline BAP1 mutations have an overall 7-fold increased long-term survival, independently of sex and age. Appropriate genetic counseling and clinical management should be considered for MM patients who are also BAP1 mutation carriers.

  16. Surviving Atmospheric Spacecraft Breakup

    NASA Technical Reports Server (NTRS)

    Szewczyk, Nathaniel J.; Conley, Catharine A.

    2003-01-01

    In essence, to survival a spacecraft breakup an animal must not experience a lethal event. Much as with surviving aircraft breakup, dissipation of lethal forces via breakup of the craft around the organism is likely to greatly increase the odds of survival. As spacecraft can travel higher and faster than aircraft, it is often assumed that spacecraft breakup is not a survivable event. Similarly, the belief that aircraft breakup or crashes are not survivable events is still prevalent in the general population. As those of us involved in search and rescue know, it is possible to survive both aircraft breakup and crashes. Here we make the first report of an animal, C. elegans, surviving atmospheric breakup of the spacecraft supporting it and discuss both the lethal events these animals had to escape and the implications implied for search and rescue following spacecraft breakup.

  17. Survival of patients with structurally-grouped TP53 mutations in ovarian and breast cancers

    PubMed Central

    Seagle, Brandon-Luke L.; Eng, Kevin H.; Dandapani, Monica; Yeh, Judy Y.; Odunsi, Kunle; Shahabi, Shohreh

    2015-01-01

    The objective of this study was to determine if ovarian cancer patients with a TP53 mutation grouped by location of the mutation within the p53 protein structure exhibit differential survival outcomes. Data from patients with high grade serous ovarian cancer (HGS OvCa) (N = 316) or breast cancer (BrCa) (N = 981) sequenced by The Cancer Genome Atlas (TCGA) was studied by Kaplan-Meier and Cox proportional hazards survival analysis. A TP53 DNA binding domain (BD) missense mutation (MM) occurred in 58.5% (185/316) of HGS OvCas and 16.8% (165/981) of BrCas. Patients with a TP53 DNA BD MM grouped by structural location had significantly different overall survival (OS) and progression free survival (PFS). Median OS (months) of HGS OvCa patients by structural group were: Sheet-loop-helix stabilizers, 31.1; DNA minor groove residue R248, 33.6; Wild-type, 34.2; all other MMs, 44.5; DNA major groove residues, 84.1, and zinc ion coordinating residues, 87.0 (log-rank p = 0.006). PFS of DNA major groove MM cases was longer than TP53 wild-type cases (19.1 versus 10.1 months, log-rank p = 0.038). HGS OvCa and BrCa patients with structurally-grouped TP53 DNA BD MMs have different survival outcomes. PMID:26215675

  18. Long-Term Survival in Patients with Metastatic Melanoma Treated with DTIC or Temozolomide

    PubMed Central

    Kim, Christina; Lee, Christopher W.; Kovacic, Laurel; Shah, Amil; Klasa, Richard

    2010-01-01

    Background. Patients with metastatic melanoma typically have a poor outcome; however, a small proportion of patients achieve long-term survival (LTS). It is unclear how often LTS is related to sensitivity to chemotherapy. Methods. All patients with metastatic melanoma treated with either dacarbazine (DTIC) or temozolomide (TMZ) at the British Columbia Cancer Agency (BCCA) from January 1, 1988 to February 1, 2006 were identified through the BCCA pharmacy electronic database, which was then linked to the surveillance and outcomes unit to identify patients with LTS, defined as survival ≥18 months following chemotherapy. Results. In total, 397 patients were treated with either DTIC (n = 349) or TMZ (n = 48) and 43 patients (10.8%) were identified with LTS. Two additional patients with LTS were added prior to 1988 for a total of 45 patients. The 5-year overall and progression-free survival rates for patients with LTS were 33% and 16%, respectively. In total, 16% had a complete response (CR) to chemotherapy, which was the only factor identified that correlated with survival in the multivariate analysis. However, most patients with LTS had an incomplete response to chemotherapy. Conclusions. LTS occurs in select patients who achieve a CR to chemotherapy. However, this occurs in only a minority of patients and, in most cases, the longer survival is likely the result of indolent disease biology or host factors. PMID:20538743

  19. Factors Predictive of Improved Survival in Patients With Brain Metastases From Gynecologic Cancer

    PubMed Central

    Gressel, Gregory M.; Lundsberg, Lisbet S.; Altwerger, Gary; Katchi, Tasleem; Azodi, Masoud; Schwartz, Peter E.; Ratner, Elena S.

    2015-01-01

    Objective The reported incidence of brain metastasis from epithelial ovarian cancer (EOC), endometrial cancer (EC), and cervical cancer (CC) is exceedingly rare. As the long-term survival for patients with gynecologic cancer increases, there has been a corresponding increase in the number of diagnosed intracranial metastases. We seek to report our experience with managing brain metastatic disease (BMD) in patients with gynecologic cancer. Methods A retrospective review of all patients with EOC, EC, and CC at our institution revealed 47 patients with concurrent BMD between 2000 and 2013. Demographic data, risk factors, treatment modalities, progression-free data, and overall survival data were collected. Results Median survival time in patients with brain metastasis from EOC, EC, and CC was 9.0, 4.5, and 3.0 months, respectively. Two-year overall survival rates were 31.6%, 13.6%, and 0%, respectively. Patients received surgery, radiation therapy alone, palliative care, or radiation plus surgery. Radiation combined with surgical resection resulted in a significant hazards ratio of 0.36 (95% confidence interval, 0.15–0.86), compared with radiation alone. Conclusions Our report provides a large single-institution experience of brain metastases from gynecologic cancer. Patients with BMD have poor prognoses; however, treatment with multimodal therapy including surgical resection and radiation may prolong overall survival. PMID:26332394

  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. Improved Posttreatment Functional Outcome is Associated with Better Survival in Patients Irradiated for Metastatic Spinal Cord Compression

    SciTech Connect

    Rades, Dirk . E-mail: Rades.Dirk@gmx.net; Veninga, Theo; Stalpers, Lukas J.A.; Basic, Hiba; Hoskin, Peter J.; Karstens, Johann H.; Schild, Steven E.; Dunst, Juergen

    2007-04-01

    Purpose: To evaluate the potential prognostic impact of the effect of radiotherapy (RT) on motor function and of the post-RT ambulatory status on survival in metastatic spinal cord compression (MSCC) patients. Methods and Materials: Of 1,852 patients irradiated for MSCC, 778 patients (42%) received short-course RT and 1,074 (58%) received long-course RT. The effect of RT on motor function (improvement vs. no change vs. deterioration) and the ambulatory status after RT (ambulatory vs. nonambulatory) were evaluated with respect to survival. Results: The actuarial survival rate of the entire cohort was 56% at 6 months, 43% at 12 months, and 32% at 24 months. The patients in whom motor function improved after RT had a significantly better 1-year survival rate than those who had no change or deterioration of motor function (75% vs. 40% and 3%, p < 0.001). The 1-year survival rate of the patients who were ambulatory after RT was significantly better than for those who were not ambulatory (63% vs. 4%, p < 0.001). The results were confirmed in multivariate analysis. Conclusions: The response to RT and the post-RT ambulatory status are important predictors for survival in MSCC patients. This finding can be used by physicians to stratify future studies, plan further therapy, and improve follow-up strategy in these patients.

  2. Actuarial considerations on genetic testing.

    PubMed

    Le Grys, D J

    1997-08-29

    In the UK the majority of life insurers employ relatively liberal underwriting standards so that people can easily gain access to life assurance cover. Up to 95% of applicants are accepted at standard terms. If genetic testing becomes widespread then the buying habits of the public may change. Proportionately more people with a predisposition to major types of disease may take life assurance cover while people with no predisposition may take proportionately less. A model is used to show the possible effect. However, the time-scales are long and the mortality of assured people is steadily improving. The change in buying habits may result in the rate of improvement slowing down. In the whole population, the improvement in mortality is likely to continue and could improve faster if widespread genetic testing results in earlier diagnosis and treatment. Life insurers would not call for genetic tests and need not see the results of previous tests except for very large sums assured. In the UK, life insurers are unlikely to change their underwriting standards, and are extremely unlikely to bring in basic premium rating systems that give discounts on the premium or penalty points according to peoples genetic profile. The implications of widespread genetic testing on medical insurance and some health insurance covers may be more extreme.

  3. Survival impact of rituximab combined with ACVBP and upfront consolidation autotransplantation in high-risk diffuse large B-cell lymphoma for GELA

    PubMed Central

    Fitoussi, Olivier; Belhadj, Karim; Mounier, Nicolas; Parrens, Marie; Tilly, Hervé; Salles, Gilles; Feugier, Pierre; Ferme, Christophe; Ysebaert, Loic; Gabarre, Jean; Herbrecht, Raoul; Janvier, Maud; Van Den Neste, Eric; Morschhauser, Franck; Casasnovas, Olivier; Ghesquieres, Hervé; Anglaret, Bruno; Brechignac, Sabine; Haioun, Corinne; Gisselbrecht, Christian

    2011-01-01

    Background As rituximab combined with CHOP improves complete remission and overall survival in diffuse large B-cell lymphoma, intensified chemotherapy followed by autologous stem-cell transplantation has also been advocated for high-risk patients. The aim of this study was to establish whether or not combining rituximab with high-dose chemotherapy and auto-transplantation also benefits patient survival. Design and Methods The LNH2003-3 study was a phase II trial including diffuse large B-cell lymphoma patients with 2 or 3 International Prognostic Index factors. They received four cycles of intensive biweekly chemotherapy with rituximab, doxorubicine, cyclophosphamide, vindesine, bleomycine, prednisolone (R-ACVBP) followed by auto-transplantation in responding patients. Two hundred and nine patients under 60 years of age were included in the study and 155 responding patients underwent auto-transplantation. In addition, a case-control study was performed by matching (1:1) 181 patients treated with R-ACVBP with ACVBP patients not given rituximab but submitted to auto-transplantation from the previous LNH1998-3 trial. Results With a median follow up of 45 months, 4-year progression-free survival and overall survival were estimated at 76% (CI: 69–81) and 78% (CI: 72–83), respectively. There was no difference between patients with 2 or 3 International Prognostic Index factors. Four year progression-free survival was significantly higher in R-ACVBP than ACVBP patients (74% vs. 58%; P=0.0005). There was also a significant increase in 4-year overall survival (76% vs. 68%; P=0.0494). Conclusions In high-risk diffuse large B-cell lymphoma patients, treatment with R-ACVBP followed by auto-transplantation results in a 78% 4-year overall survival which should be compared to other approaches. (Clinicaltrials.gov identifier: NCT00144807) PMID:21546499

  4. Reentry survivability modeling

    NASA Astrophysics Data System (ADS)

    Fudge, Michael L.; Maher, Robert L.

    1997-10-01

    Statistical methods for expressing the impact risk posed to space systems in general [and the International Space Station (ISS) in particular] by other resident space objects have been examined. One of the findings of this investigation is that there are legitimate physical modeling reasons for the common statistical expression of the collision risk. A combination of statistical methods and physical modeling is also used to express the impact risk posed by re-entering space systems to objects of interest (e.g., people and property) on Earth. One of the largest uncertainties in the expressing of this risk is the estimation of survivable material which survives reentry to impact Earth's surface. This point was recently demonstrated in dramatic fashion by the impact of an intact expendable launch vehicle (ELV) upper stage near a private residence in the continental United States. Since approximately half of the missions supporting ISS will utilize ELVs, it is appropriate to examine the methods used to estimate the amount and physical characteristics of ELV debris surviving reentry to impact Earth's surface. This paper examines reentry survivability estimation methodology, including the specific methodology used by Caiman Sciences' 'Survive' model. Comparison between empirical results (observations of objects which have been recovered on Earth after surviving reentry) and Survive estimates are presented for selected upper stage or spacecraft components and a Delta launch vehicle second stage.

  5. Response as a predictor of survival in patients with recurrent glioblastoma treated with bevacizumab

    PubMed Central

    Prados, Michael; Cloughesy, Timothy; Samant, Meghna; Fang, Liang; Wen, Patrick Y.; Mikkelsen, Tom; Schiff, David; Abrey, Lauren E.; Yung, W.K. Alfred; Paleologos, Nina; Nicholas, Martin K.; Jensen, Randy; Vredenburgh, James; Das, Asha; Friedman, Henry S.

    2011-01-01

    Development of effective therapies for recurrent glioblastoma multiforme (GBM) and reliable, timely evaluation of their benefit are needed. Understanding the relationship between objective response (OR) and survival is important for determining whether OR can provide an early signal of treatment activity in clinical trials. We performed a landmark analysis to evaluate the association between OR and survival at 9, 18, and 26 weeks for 167 patients with recurrent GBM who participated in BRAIN, a phase II trial that evaluated efficacy of bevacizumab alone or in combination with irinotecan, using the Cox regression models adjusted for age, baseline Karnofsky performance score, first vs second relapse, and treatment arm. Hazard ratios (HRs) and P-values for survival between responders and nonresponders were calculated. Additional analyses were performed to test robustness, validity, fit, and accuracy of the models. The relationships between progression-free survival (PFS) and survival and between OR and PFS were also explored. There were 55 responders and 112 nonresponders across the 2 treatment arms in BRAIN. OR status at 9, 18, and 26 weeks was a statistically significant predictor of survival (HR ≤ 0.52, P < .01). PFS was also a statistically significant predictor of survival at each landmark (HR ≤ 0.25, P < .0001). The association between OR and PFS was not statistically significant, likely due to inadequate statistical power for the analysis. Clarifying the relationship of OR and survival is important for determining whether OR can be a reliable predictor of the benefit of a therapeutic agent in patients with recurrent GBM. PMID:21084434

  6. Supratentorial hemispheric ependymomas: an analysis of 109 adults for survival and prognostic factors.

    PubMed

    Hollon, Todd; Nguyen, Vincent; Smith, Brandon W; Lewis, Spencer; Junck, Larry; Orringer, Daniel A

    2016-08-01

    OBJECTIVE Survival rates and prognostic factors for supratentorial hemispheric ependymomas have not been determined. The authors therefore designed a retrospective study to determine progression-free survival (PFS), overall survival (OS), and prognostic factors for hemispheric ependymomas. METHODS The study population consisted of 8 patients from our institution and 101 patients from the literature with disaggregated survival information (n = 109). Patient age, sex, tumor side, tumor location, extent of resection (EOR), tumor grade, postoperative chemotherapy, radiation, time to recurrence, and survival were recorded. Kaplan-Meier survival analyses and Cox proportional hazard models were completed to determine survival rates and prognostic factors. RESULTS Anaplastic histology/WHO Grade III tumors were identified in 62% of cases and correlated with older age. Three-, 5-, and 10-year PFS rates were 57%, 51%, and 42%, respectively. Three-, 5-, and 10-year OS rates were 77%, 71%, and 58%, respectively. EOR and tumor grade were identified on both Kaplan-Meier log-rank testing and univariate Cox proportional hazard models as prognostic for PFS and OS. Both EOR and tumor grade remained prognostic on multivariate analysis. Subtotal resection (STR) predicted a worse PFS (hazard ratio [HR] 4.764, p = 0.001) and OS (HR 4.216, p = 0.008). Subgroup survival analysis of patients with STR demonstrated a 5- and 10-year OS of 28% and 0%, respectively. WHO Grade III tumors also had worse PFS (HR 10.2, p = 0.004) and OS (HR 9.1, p = 0.035). Patients with WHO Grade III tumors demonstrated 5- and 10-year OS of 61% and 46%, respectively. Postoperative radiation was not prognostic for PFS or OS. CONCLUSIONS A high incidence of anaplastic histology was found in hemispheric ependymomas and was associated with older age. EOR and tumor grade were prognostic factors for PFS and OS on multivariate analysis. STR or WHO Grade III pathology, or both, predicted worse overall prognosis in patients

  7. Extended Survival and Prognostic Factors for Patients With ALK-Rearranged Non–Small-Cell Lung Cancer and Brain Metastasis

    PubMed Central

    Johung, Kimberly L.; Yeh, Norman; Desai, Neil B.; Williams, Terence M.; Lautenschlaeger, Tim; Arvold, Nils D.; Ning, Matthew S.; Attia, Albert; Lovly, Christine M.; Goldberg, Sarah; Beal, Kathryn; Yu, James B.; Kavanagh, Brian D.; Chiang, Veronica L.; Camidge, D. Ross

    2016-01-01

    Purpose We performed a multi-institutional study to identify prognostic factors and determine outcomes for patients with ALK-rearranged non–small-cell lung cancer (NSCLC) and brain metastasis. Patients and Methods A total of 90 patients with brain metastases from ALK-rearranged NSCLC were identified from six institutions; 84 of 90 patients received radiotherapy to the brain (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]), and 86 of 90 received tyrosine kinase inhibitor (TKI) therapy. Estimates for overall (OS) and intracranial progression-free survival were determined and clinical prognostic factors were identified by Cox proportional hazards modeling. Results Median OS after development of brain metastases was 49.5 months (95% CI, 29.0 months to not reached), and median intracranial progression-free survival was 11.9 months (95% CI, 10.1 to 18.2 months). Forty-five percent of patients with follow-up had progressive brain metastases at death, and repeated interventions for brain metastases were common. Absence of extracranial metastases, Karnofsky performance score ≥ 90, and no history of TKIs before development of brain metastases were associated with improved survival (P = .003, < .001, and < .001, respectively), whereas a single brain metastasis or initial treatment with SRS versus WBRT were not (P = .633 and .666, respectively). Prognostic factors significant by multivariable analysis were used to describe four patient groups with 2-year OS estimates of 33%, 59%, 76%, and 100%, respectively (P < .001). Conclusion Patients with brain metastases from ALK-rearranged NSCLC treated with radiotherapy (SRS and/or WBRT) and TKIs have prolonged survival, suggesting that interventions to control intracranial disease are critical. The refinement of prognosis for this molecular subtype of NSCLC identifies a population of patients likely to benefit from first-line SRS, close CNS observation, and treatment of emergent CNS disease. PMID:26438117

  8. Surviving at extremes

    NASA Astrophysics Data System (ADS)

    Dougan, Lorna

    2015-11-01

    Wherever we look on Earth - even in the most inhospitable places - we find life. But how do organisms manage to survive such difficult conditions? Lorna Dougan explains how physicists are helping to unravel the properties of “extremophile” life.

  9. Survival of falling robots

    NASA Astrophysics Data System (ADS)

    Cameron, Jonathan M.; Arkin, Ronald C.

    1992-02-01

    As mobile robots are used in more uncertain and dangerous environments, it will become important to design them so that they can survive falls. In this paper, we examine a number of mechanisms and strategies that animals use to withstand these potentially catastrophic events and extend them to the design of robots. A brief survey of several aspects of how common cats survive falls provides an understanding of the issues involved in preventing traumatic injury during a falling event. After outlining situations in which robots might fall, a number of factors affecting their survival are described. From this background, several robot design guidelines are derived. These include recommendations for the physical structure of the robot as well as requirements for the robot control architecture. A control architecture is proposed based on reactive control techniques and action-oriented perception that is geared to support this form of survival behavior.

  10. Survival of falling robots

    NASA Technical Reports Server (NTRS)

    Cameron, Jonathan M.; Arkin, Ronald C.

    1992-01-01

    As mobile robots are used in more uncertain and dangerous environments, it will become important to design them so that they can survive falls. In this paper, we examine a number of mechanisms and strategies that animals use to withstand these potentially catastrophic events and extend them to the design of robots. A brief survey of several aspects of how common cats survive falls provides an understanding of the issues involved in preventing traumatic injury during a falling event. After outlining situations in which robots might fall, a number of factors affecting their survival are described. From this background, several robot design guidelines are derived. These include recommendations for the physical structure of the robot as well as requirements for the robot control architecture. A control architecture is proposed based on reactive control techniques and action-oriented perception that is geared to support this form of survival behavior.

  11. Mathematical Modeling of Therapy-induced Cancer Drug Resistance: Connecting Cancer Mechanisms to Population Survival Rates

    PubMed Central

    Sun, Xiaoqiang; Bao, Jiguang; Shao, Yongzhao

    2016-01-01

    Drug resistance significantly limits the long-term effectiveness of targeted therapeutics for cancer patients. Recent experimental studies have demonstrated that cancer cell heterogeneity and microenvironment adaptations to targeted therapy play important roles in promoting the rapid acquisition of drug resistance and in increasing cancer metastasis. The systematic development of effective therapeutics to overcome drug resistance mechanisms poses a major challenge. In this study, we used a modeling approach to connect cellular mechanisms underlying cancer drug resistance to population-level patient survival. To predict progression-free survival in cancer patients with metastatic melanoma, we developed a set of stochastic differential equations to describe the dynamics of heterogeneous cell populations while taking into account micro-environment adaptations. Clinical data on survival and circulating tumor cell DNA (ctDNA) concentrations were used to confirm the effectiveness of our model. Moreover, our model predicted distinct patterns of dose-dependent synergy when evaluating a combination of BRAF and MEK inhibitors versus a combination of BRAF and PI3K inhibitors. These predictions were consistent with the findings in previously reported studies. The impact of the drug metabolism rate on patient survival was also discussed. The proposed model might facilitate the quantitative evaluation and optimization of combination therapeutics and cancer clinical trial design. PMID:26928089

  12. Limited survival in patients with carcinomatosis from foregut malignancies after cytoreduction and continuous hyperthermic peritoneal perfusion.

    PubMed

    Farma, Jeffrey M; Pingpank, James F; Libutti, Steven K; Bartlett, David L; Ohl, Susan; Beresneva, Tatiana; Alexander, H Richard

    2005-12-01

    Peritoneal carcinomatosis is a frequent mode of metastasis in patients with gastric, duodenal, or pancreatic cancer. Survival in this setting is short and therapeutic options are limited. This analysis examines the outcomes of 18 patients treated with operative cytoreduction and continuous hyperthermic peritoneal perfusion. Eighteen patients (6 males and 12 females) with gastric (n = 9), pancreatic (n = 7), or duodenal (n = 2) cancer were treated on protocol. Patients underwent optimal cytoreduction (complete gross resection, 11; minimal residual disease, 7) and a 90-minute perfusion with cisplatin. Clinical parameters and tumor and treatment characteristics were analyzed. Survival curves were estimated using the Kaplan-Meier method. Procedures included gastrectomy (n = 8), pancreaticoduodenectomy (n = 3), and hemicolectomy (n = 2). After cytoreduction, patients had no evidence of residual disease (n = 11), fewer than 100 implants less than 5 mm (n = 1), more than 100 implants between 5-10 mm (n = 3), or multiple implants with greater than 1 cm (n = 3). Five patients received a postoperative intraperitoneal dwell with 5-fluorouracil and paclitaxel. There was one perioperative mortality, and complications occurred in 10 patients. The median progression-free survival was 8 months (mean, 10 months; range, 1-47 months) with a median overall survival of 8 months (mean, 18 months; range, 1-74 months). In this cohort, peritoneal perfusion with cisplatin used to treat foregut malignancies has a high incidence of complications and does not significantly alter the natural history of the disease. Investigation of novel therapeutic approaches should be considered.

  13. Total peroxiredoxin expression is associated with survival in patients with follicular lymphoma.

    PubMed

    Peroja, Pekka; Haapasaari, Kirsi-Maria; Mannisto, Susanna; Miinalainen, Ilkka; Koivunen, Petri; Leppä, Sirpa; Karjalainen-Lindsberg, Marja-Liisa; Kuusisto, Milla Elvi Linnea; Turpeenniemi-Hujanen, Taina; Kuittinen, Outi; Karihtala, Peeter

    2016-05-01

    Redox state-regulating enzymes may have roles in chemoresistance and also in lymphomagenesis, but there have been only a limited number of studies on this topic in lymphomas. Our aim was to assess expression of the redox state-regulating enzymes peroxiredoxins (Prxs) I-VI and thioredoxin (Trx) and the oxidative stress marker nitrotyrosine in follicular lymphomas (FLs). We immunohistochemically assessed Prxs I-VI, Trx and nitrotyrosine in a cohort of 76 histologically confirmed, untreated FLs. We also studied the localisation of Prxs I, II, III, V and VI by means of immunoelectron microscopy (IEM). Immunohistochemistry results were correlated with disease-specific survival (DSS), progression-free survival (PFS), overall survival (OS) and clinical prognostic factors. When all Prx expression intensities were grouped as a single variable, we discovered that high total Prx intensity correlated with favourable DSS (p = 0.024) and OS (p = 0.035) but not with PFS. No deaths due to lymphoma were recorded amongst patients with high total Prx expression during the median follow-up period of 7.6 years. IEM results were in line with earlier ones demonstrating wide subcellular localisation of Prx isoenzymes. In conclusion, our results demonstrate an association between high total Prx expression and prolonged survival and suggest that Prxs may have a protective role in FL that cannot be compensated by other antioxidant mechanisms. PMID:26983700

  14. Survival outcomes after stereotactic body radiotherapy for 79 Japanese patients with hepatocellular carcinoma.

    PubMed

    Yamashita, Hideomi; Onishi, Hiroshi; Murakami, Naoya; Matsumoto, Yasuo; Matsuo, Yukinori; Nomiya, Takuma; Nakagawa, Keiichi

    2015-05-01

    Stereotactic body radiotherapy (SBRT) is a relatively new treatment for liver tumor. Outcomes of SBRT for liver tumors unsuitable for ablation or surgical resection were evaluated. A total of 79 patients treated with SBRT for primary hepatocellular carcinoma (HCC) between 2004 and 2012 in six Japanese institutions were studied retrospectively. Patients treated with SBRT preceded by trans-arterial chemoembolization were eligible. Their median age was 73 years, 76% were males, and their Child-Pugh scores were Grades A (85%) and B (11%) before SBRT. The median biologically effective dose (α/β = 10 Gy) was 96.3 Gy. The median follow-up time was 21.0 months for surviving patients. The 2-year overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival were 53%, 40% and 76%, respectively. Sex and serum PIVKA-II values were significant predictive factors for OS. Hypovascular or hypervascular types of HCC, sex and clinical stage were significant predictive factors for PFS. The 2-year PFS was 66% in Stage I vs 18% in Stages II-III. Multivariate analysis indicated that clinical stage was the only significant predictive factor for PFS. No Grade 3 laboratory toxicities in the acute, sub-acute, and chronic phases were observed. PFS after SBRT for liver tumor was satisfactory, especially for Stage I HCC, even though these patients were unsuitable for resection and ablation. SBRT is safe and might be an alternative to resection and ablation. PMID:25691453

  15. Effect of nifedipine on renal allograft function and survival beyond one year.

    PubMed

    Shin, G T; Cheigh, J S; Riggio, R R; Suthanthiran, M; Stubenbord, W T; Serur, D; Wang, J C; Rubin, A L; Stenzel, K H

    1997-01-01

    We previously reported that a calcium channel blocker supplemented immunosuppression produced excellent patient and graft survival rates in cadaveric kidney transplantation. We report here the long term outcome of patients treated with nifedipine-supplemented triple immunosuppression as compared with those of historical controls who were treated similarly without nifedipine. Study subjects included 111 patients transplanted in 1990-1994, treated with nifedipine and triple immunosuppression and with functioning grafts for more than one year (Nifedipine group). The results of cyclosporine (CyA) dose, blood pressure (BP), serum creatinine (Cr), and actuarial graft survival rate (GSR) up to 5 years posttransplant in these patients were compared with those of 52 patients transplanted in 1985-1990, treated similarly without calcium channel blockers (Control group). Donor sources, gender ratio, age distribution, causes of end stage renal disease, incidence of hypertension prior to transplantation and incidence of rejection in the first year between the groups were comparable. Throughout the study period the Nifedipine group had significantly lower serum Cr (1.5 +/- 0.7 vs. 1.8 +/- 0.7 mg/dl) and higher GSR (93.8% vs. 88% at 5 years) than the Control group. BP was comparable despite higher CyA doses in the Nifedipine group (4.3 +/- 1.1 vs. 3.3 +/- 1.1 mg/kg/day). We conclude that nifedipine is beneficial in improving long-term graft function and survival in kidney transplant recipients by mitigating CyA associated renal injury.

  16. Comparison of long-term survival between temozolomide-based chemoradiotherapy and radiotherapy alone for patients with low-grade gliomas after surgical resection

    PubMed Central

    Gai, Xiu-juan; Wei, Yu-mei; Tao, Heng-min; An, Dian-zheng; Sun, Jia-teng; Li, Bao-sheng

    2016-01-01

    Purpose This study was designed to compare the survival outcomes of temozolomide-based chemoradiotherapy (TMZ + RT) vs radiotherapy alone (RT-alone) for low-grade gliomas (LGGs) after surgical resection. Patients and methods In this retrospective analysis, we reviewed postoperative records of 69 patients with LGGs treated with TMZ + RT (n=31) and RT-alone (n=38) at the Shandong Cancer Hospital Affiliated to Shandong University between June 2011 and December 2013. Patients in the TMZ + RT group were administered 50–100 mg oral TMZ every day until the radiotherapy regimen was completed. Results The median follow-up since surgery was 33 months and showed no significant intergroup differences (P=0.06). There were statistically significant intergroup differences in the progression-free survival rate (P=0.037), with 83.9% for TMZ-RT group and 60.5% for RT-alone group. The overall 2-year overall survival (OS) rate was 89.86%. Age distribution (≥45 years and <45 years) and resection margin (complete resection or not) were significantly associated with OS (P=0.03 and P=0.004, respectively). Conclusion Although no differences were found in the 2-year OS between the TMZ + RT and RT-alone groups, there was a trend toward increased 2-year progression-free survival in the TMZ + RT group. With better tolerability, concurrent TMZ chemoradiotherapy may be beneficial for postoperative patients with LGGs. Age distribution and surgical margin are likely potential indicators of disease prognosis. The possible differences in long-term survival between the two groups and the links between prognostic factors and long-term survival may be worthy of further investigation. PMID:27574452

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

    SciTech Connect

    Du, Zhongli; Zhang, Wencheng; Zhou, Yuling; Yu, Dianke; Chen, Xiabin; Chang, Jiang; Qiao, Yan; Zhang, Meng; Huang, Ying; Wu, Chen; Xiao, Zefen; Tan, Wen; and others

    2015-09-01

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

  18. Influence of intravenous amifostine on xerostomia, tumor control, and survival after radiotherapy for head-and- neck cancer: 2-year follow-up of a prospective, randomized, phase III trial

    SciTech Connect

    Wasserman, Todd H. . E-mail: twasserman@bellsouth.net; Brizel, David M.; Henke, Michael; Monnier, Alain; Eschwege, Francois; Sauer, Rolf; Strnad, Vratislav

    2005-11-15

    Purpose: To evaluate chronic xerostomia and tumor control 18 and 24 months after initial treatment with amifostine in a randomized controlled trial of patients with head-and-neck cancer; at 12 months after radiotherapy (RT), amifostine had been shown to reduce xerostomia without changing tumor control. Methods and Materials: Adults with head-and-neck cancer who underwent once-daily RT for 5-7 weeks (total dose, 50-70 Gy) received either open-label amifostine (200 mg/m{sup 2} i.v.) 15-30 min before each fraction of radiation (n = 150) or RT alone (control; n = 153). Results: Amifostine administration was associated with a reduced incidence of Grade {>=}2 xerostomia over 2 years of follow-up (p = 0.002), an increase in the proportion of patients with meaningful (>0.1 g) unstimulated saliva production at 24 months (p = 0.011), and reduced mouth dryness scores on a patient benefit questionnaire at 24 months (p < 0.001). Locoregional control rate, progression-free survival, and overall survival were not significantly different between the amifostine group and the control group. Conclusions: Amifostine administration during head-and-neck RT reduces the severity and duration of xerostomia 2 years after treatment and does not seem to compromise locoregional control rates, progression-free survival, or overall survival.

  19. Surviving atmospheric spacecraft breakup.

    PubMed

    Szewczyk, Nathaniel J; McLamb, William

    2005-01-01

    Spacecraft travel higher and faster than aircraft, making breakup potentially less survivable. As with aircraft breakup, the dissipation of lethal forces via spacecraft breakup around an organism is likely to greatly increase the odds of survival. By employing a knowledge of space and aviation physiology, comparative physiology, and search-and-rescue techniques, we were able to correctly predict and execute the recovery of live animals following the breakup of the space shuttle Columbia. In this study, we make what is, to our knowledge, the first report of an animal, Caenorhabditis elegans, surviving the atmospheric breakup of the spacecraft that was supporting it and discuss both the lethal events these animals had to escape and the implications for search and rescue following spacecraft breakup.

  20. Surviving atmospheric spacecraft breakup

    NASA Technical Reports Server (NTRS)

    Szewczyk, Nathaniel J.; McLamb, William

    2005-01-01

    Spacecraft travel higher and faster than aircraft, making breakup potentially less survivable. As with aircraft breakup, the dissipation of lethal forces via spacecraft breakup around an organism is likely to greatly increase the odds of survival. By employing a knowledge of space and aviation physiology, comparative physiology, and search-and-rescue techniques, we were able to correctly predict and execute the recovery of live animals following the breakup of the space shuttle Columbia. In this study, we make what is, to our knowledge, the first report of an animal, Caenorhabditis elegans, surviving the atmospheric breakup of the spacecraft that was supporting it and discuss both the lethal events these animals had to escape and the implications for search and rescue following spacecraft breakup.

  1. Survival after judicial hanging.

    PubMed

    Sabermoghaddam, Mohsen; Abad, Mohsen; Golmakani, Ebrahim; Mozaffari, Nasrollah

    2015-06-01

    Hanging is known not only as a common method of suicide but also as a capital punishment method in some countries. Although several cases have been reported to survive after the attempted suicidal/accidental hanging, to the extent of our knowledge, no modern case of survival after judicial hanging exists. We reported a case of an individual who revived after modern judicial hanging despite being declared dead. The case was admitted with poor clinical presentations and the Glasgow Coma Scale of 6/15. The victim received all the standard supportive intensive care and gained complete clinical recovery.

  2. Survival after judicial hanging.

    PubMed

    Sabermoghaddam, Mohsen; Abad, Mohsen; Golmakani, Ebrahim; Mozaffari, Nasrollah

    2015-06-01

    Hanging is known not only as a common method of suicide but also as a capital punishment method in some countries. Although several cases have been reported to survive after the attempted suicidal/accidental hanging, to the extent of our knowledge, no modern case of survival after judicial hanging exists. We reported a case of an individual who revived after modern judicial hanging despite being declared dead. The case was admitted with poor clinical presentations and the Glasgow Coma Scale of 6/15. The victim received all the standard supportive intensive care and gained complete clinical recovery. PMID:25747958

  3. Education for Survival.

    ERIC Educational Resources Information Center

    Allen, James E., Jr.

    In this address, James E. Allen, Jr., Assistant Secretary for Education and U.S. Commissioner of Education, discusses the relationship of education to the problem of ecological destruction. He states that the solutions to the problems of air, water, and soil pollution may be found in redirected education. This "education for survival" can serve to…

  4. Communications Survival Kit.

    ERIC Educational Resources Information Center

    Williamson, Shirley Porter; Braden, Bill

    The purpose of the Communications Survival Kit is to serve as a guide for counselors to assist in planning, developing and implementing a public relations program for the guidance department at the local school level. The kit contains practical information in three categories. First is a rationale for a public relations (PR) program, what PR is…

  5. Unix survival guide.

    PubMed

    Stein, Lincoln D

    2007-01-01

    For a mixture of historical and practical reasons, much of the bioinformatics software discussed in this series runs on Linux, Mac OSX, Solaris, or one of the many other Unix variants. This appendix provides the novice with easy-to-understand information needed to survive in the Unix environment.

  6. Independence and Survival.

    ERIC Educational Resources Information Center

    James, H. Thomas

    Independent schools that are of viable size, well managed, and strategically located to meet competition will survive and prosper past the current financial crisis. We live in a complex technological society with insatiable demands for knowledgeable people to keep it running. The future will be marked by the orderly selection of qualified people,…

  7. Survivability via Control Objectives

    SciTech Connect

    CAMPBELL,PHILIP L.

    2000-08-11

    Control objectives open an additional front in the survivability battle. A given set of control objectives is valuable if it represents good practices, it is complete (it covers all the necessary areas), and it is auditable. CobiT and BS 7799 are two examples of control objective sets.

  8. The Option for Survival

    ERIC Educational Resources Information Center

    Berry, R. Stephen

    1971-01-01

    Suggests formula for survival that takes a thermodynamic view which holds that we must recycle waste while the thermodynamic potential still is moderately high. Otherwise they are lost, as helium is lost when it leaves Earth's atmosphere and goes into space. The idea that the Earth is a closed system is a myth; it collapses each time we put our…

  9. Education for Survival

    ERIC Educational Resources Information Center

    Aldrich, Richard

    2010-01-01

    This article provides a brief overview of current approaches to education and concludes that none of these is sufficient to meet the challenges that now face the human race. It argues instead for a new concept of education for survival. (Contains 1 note.)

  10. Surviving Tight Times.

    ERIC Educational Resources Information Center

    Neugebauer, Roger

    2002-01-01

    Discusses several strategies recommended by small business experts to help for-profit and non-profit child care centers survive a financial crisis. Strategies include: identifying the source of the problem, monitoring cash flow, reducing or deferring expenditures, expediting regular income and exploring new sources of income, patiently working…

  11. Chemotherapy response as a prognosticator for survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy

    SciTech Connect

    Eagan, R.T.; Fleming, T.R.; Lee, R.E.; Ingle, J.N.; Frytak, S.; Creagan, E.T.

    1980-07-01

    Twenty-two patients with limited unresectable squamous cell lung cancer were treated with 6 courses of combination chemotherapy consisting of cyclophosphamide, adriamycin, cisplatin, and bleomycin (CAP-Bleo) and short-course thoracic irradiation started after the first 4 weeks of chemotherapy. Of 20 patients with visible tumor who were treated with 4 weeks of chemotherapy alone, 10 (50%) had a tumor regression in that 4 week period and 10 did not. Those patients with tumor regression had significantly better progression free and overall survivals than did patients with no chemotherapy regressions (medians of 258 days vs. 136 days and 356 days vs. 150 days respectively). The original bleomycin dose had to be reduced by 50% primarily because of excessive radiation esophagitis that has not been reported with use of either the CAP regimen or bleomycin along in conjunction with thoracic irradiation. An initial chemotherapy regression seems to be a good prognosticator for progression-free and overall survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy.

  12. Five-year survival in EGFR-mutant metastatic lung adenocarcinoma treated with EGFR-TKIs

    PubMed Central

    Lin, Jessica J.; Cardarella, Stephanie; Lydon, Christine A.; Dahlberg, Suzanne E.; Jackman, David M.; Jänne, Pasi A.; Johnson, Bruce E.

    2016-01-01

    Introduction Activating mutations in the epidermal growth factor receptor (EGFR) predict for prolonged progression-free survival in patients with advanced non-small cell lung cancer (NSCLC) treated with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) versus chemotherapy. Long-term survival outcomes, however, remain undefined. The objective of this study was to determine the 5-year survival in these patients, and identify clinical factors associated with overall survival (OS). Methods Patients with EGFR-mutant metastatic lung adenocarcinoma treated with erlotinib or gefitinib at Dana-Farber Cancer Institute between 2002 and 2009 were included. OS was analyzed. Results Among 137 patients, median PFS and OS were 12.1 months (95% CI, 10.2-13.5 months) and 30.9 months (95% CI, 28.2-35.7 months), respectively. Twenty patients (14.6%) were 5-year survivors. In multivariate analysis, exon 19 deletions (hazard ratio [HR], 0.63; 95% CI, 0.44-0.91; P = 0.01), absence of extrathoracic (HR 0.62; 95% CI, 0.41-0.93; P = 0.02) or brain metastasis (HR 0.48; 95% CI, 0.30-0.77, P = 0.002), and not a current smoker (HR 0.23; 95% CI, 0.09-0.59; P = 0.002) were associated with prolonged OS. Age, gender, stage at diagnosis, liver or bone or adrenal metastasis, specific TKI, and line of TKI therapy were not associated with OS. Conclusions Our data suggest that the prevalence of 5-year survival among EGFR-mutant metastatic lung adenocarcinoma patients treated with erlotinib or gefitinib is 14.6%. Exon 19 deletions and absence of extrathoracic or brain metastasis are associated with prolonged survival. Based on our findings, clinicians can gain an enhanced estimation of long-term outcomes in this population. PMID:26724471

  13. Obesity and survival among women with ovarian cancer: results from the Ovarian Cancer Association Consortium

    PubMed Central

    Nagle, C M; Dixon, S C; Jensen, A; Kjaer, S K; Modugno, F; deFazio, A; Fereday, S; Hung, J; Johnatty, S E; Fasching, P A; Beckmann, M W; Lambrechts, D; Vergote, I; Van Nieuwenhuysen, E; Lambrechts, S; Risch, H A; Rossing, M A; Doherty, J A; Wicklund, K G; Chang-Claude, J; Goodman, M T; Ness, R B; Moysich, K; Heitz, F; du Bois, A; Harter, P; Schwaab, I; Matsuo, K; Hosono, S; Goode, E L; Vierkant, R A; Larson, M C; Fridley, B L; Høgdall, C; Schildkraut, J M; Weber, R P; Cramer, D W; Terry, K L; Bandera, E V; Paddock, L; Rodriguez-Rodriguez, L; Wentzensen, N; Yang, H P; Brinton, L A; Lissowska, J; Høgdall, E; Lundvall, L; Whittemore, A; McGuire, V; Sieh, W; Rothstein, J; Sutphen, R; Anton-Culver, H; Ziogas, A; Pearce, C L; Wu, A H; Webb, P M

    2015-01-01

    Background: Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer. Methods: We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype. Results: Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30–34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99–1.23); BMI: ⩾35, pHR: 1.12 (95% CI: 1.01–1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m−2) and endometrioid subtypes (pHR: 1.08 per 5 kg m−2), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m−2) subtype, but only the association with high-grade serous cancers was significant. Conclusions: Higher BMI is associated with adverse survival among the majority of women with ovarian cancer. PMID:26151456

  14. LYMPHOPENIA AS A PROGNOSTIC FACTOR FOR OVERALL SURVIVAL IN ADVANCED CARCINOMAS, SARCOMAS AND LYMPHOMAS

    PubMed Central

    Ray-Coquard, Isabelle; Cropet, Claire; Van Glabbeke, Martine; Sebban, Catherine; Le Cesne, Axel; Judson, Ian; Tredan, Olivier; Verweij, Jaap; Biron, Pierre; Labidi, Inthidar; Guastalla, Jean-Paul; Bachelot, Thomas; Perol, David; Chabaud, Sylvie; Hogendoorn, Pancras C.W.; Cassier, Philippe; Dufresne, Armelle; Blay, Jean-Yves

    2009-01-01

    Lymphopenia is frequent in advanced cancers and predicts the toxicity of chemotherapy. Its impact on relapse and survival is uncertain. Its prognostic value for survival was analyzed in 3 databases of previously reported prospective multicenter studies: 1) FEC chemotherapy in metastatic breast carcinoma; 2) CYVADIC in advanced soft-tissue sarcoma (EORTC-STBSG 62791); 3) prospective, consecutive phase III studies of aggressive diffuse large-cell non-Hodgkin’s lymphomas conducted at Bérard center between 1987 and 1993. Univariate and multivariate analyses of prognostic factors for survival were performed. The incidence of lymphopenia <1000/μL before treatment was constant among series: 25%, 24%, 27% respectively. Lymphopenia was significantly more frequent (p<0.05) in metastatic breast cancer patients with performance status (PS)>1, non-Hodgkin’s lymphoma patients with international prognostic index (IPI)>0, and advanced soft-tissue sarcoma and metastatic breast cancer patients with bone metastases. In univariate analysis, lymphopenia <1000/μL significantly correlated to overall survival in patients with metastatic breast cancer (median 10 vs. 14 months, p <0.0001), advanced soft-tissue sarcoma (median 5 vs. 10 months, p <0.01), and non-Hodgkin lymphoma (median 11 vs. 94 months, p <0.0001). In multivariate analysis (Cox model), lymphopenia was an independent prognostic factor for overall survival in metastatic breast cancer (RR: 1.8; 95%CI 1.3–2.4) along with liver metastases and PS; in advanced soft-tissue sarcoma (RR: 1.46; 95%CI 1.0–2.1) along with liver metastases, lung metastases and PS; and in non-Hodgkin’s lymphoma (RR: 1.48; 95%CI 1.03–2.1) along with IPI. Our findings demonstrate that lymphopenia is an independent prognostic factor for overall and progression-free survival in several cancers. PMID:19549917

  15. The pretreatment albumin to globulin ratio predicts survival in patients with natural killer/T-cell lymphoma

    PubMed Central

    Bi, Xi-wen; Wang, Liang; Zhang, Wen-wen; Yan, Shu-mei; Sun, Peng; Xia, Yi; Li, Zhi-ming

    2016-01-01

    Background. The pretreatment albumin to globulin ratio (AGR) has been reported to be a predictor of survival in several types of cancer. The aim of this study was to evaluate the prognostic impact of AGR in patients with natural killer/T-cell lymphoma (NKTCL). Methods. We retrospectively reviewed the available serum biochemistry results for 331 NKTCL patients before treatment. AGR was calculated as albumin/(total protein—albumin), and a cut-off value of 1.3 was used to define AGR as low or high. Survival analysis was used to assess the prognostic value of AGR. Results. A low AGR (<1.3) was associated with significantly more adverse clinical features, including old age, poor performance status, advanced stage, elevated lactate dehydrogenase, B symptoms, and high International Prognostic Index (IPI) and natural killer/T-cell lymphoma prognostic index (NKPI) scores. Patients with a low AGR had a significantly lower 5-year overall survival (44.5 vs. 65.2%, P < 0.001) and progression-free survival (33.1 vs. 57.4%, P < 0.001). In the multivariate analysis, a low AGR remained an independent predictor of poorer survival. Additionally, AGR distinguished patients with different outcomes in the IPI low-risk group and in the NKPI high-risk group. Discussion. Pretreatment AGR may serve as a simple and effective predictor of prognosis in patients with NKTCL. PMID:26966671

  16. The pretreatment albumin to globulin ratio predicts survival in patients with natural killer/T-cell lymphoma.

    PubMed

    Bi, Xi-Wen; Wang, Liang; Zhang, Wen-Wen; Yan, Shu-Mei; Sun, Peng; Xia, Yi; Li, Zhi-Ming; Jiang, Wen-Qi

    2016-01-01

    Background. The pretreatment albumin to globulin ratio (AGR) has been reported to be a predictor of survival in several types of cancer. The aim of this study was to evaluate the prognostic impact of AGR in patients with natural killer/T-cell lymphoma (NKTCL). Methods. We retrospectively reviewed the available serum biochemistry results for 331 NKTCL patients before treatment. AGR was calculated as albumin/(total protein-albumin), and a cut-off value of 1.3 was used to define AGR as low or high. Survival analysis was used to assess the prognostic value of AGR. Results. A low AGR (<1.3) was associated with significantly more adverse clinical features, including old age, poor performance status, advanced stage, elevated lactate dehydrogenase, B symptoms, and high International Prognostic Index (IPI) and natural killer/T-cell lymphoma prognostic index (NKPI) scores. Patients with a low AGR had a significantly lower 5-year overall survival (44.5 vs. 65.2%, P < 0.001) and progression-free survival (33.1 vs. 57.4%, P < 0.001). In the multivariate analysis, a low AGR remained an independent predictor of poorer survival. Additionally, AGR distinguished patients with different outcomes in the IPI low-risk group and in the NKPI high-risk group. Discussion. Pretreatment AGR may serve as a simple and effective predictor of prognosis in patients with NKTCL.

  17. The tumour microenvironment influences survival and time to transformation in follicular lymphoma in the rituximab era.

    PubMed

    Blaker, Yngvild Nuvin; Spetalen, Signe; Brodtkorb, Marianne; Lingjaerde, Ole Christian; Beiske, Klaus; Østenstad, Bjørn; Sander, Birgitta; Wahlin, Björn Engelbrekt; Melen, Christopher Michael; Myklebust, June Helen; Holte, Harald; Delabie, Jan; Smeland, Erlend Bremertun

    2016-10-01

    The tumour microenvironment influences outcome in patients with follicular lymphoma (FL), but its impact on transformation is less studied. We investigated the prognostic significance of the tumour microenvironment on transformation and survival in FL patients treated in the rituximab era. We examined diagnostic and transformed biopsies from 52 FL patients using antibodies against CD3, CD4, CD8, CD21 (CR2), CD57 (B3GAT1), CD68, FOXP3, TIA1, PD-1 (PDCD1), PD-L1 (CD274) and PAX5. Results were compared with a second cohort of 40 FL patients without signs of transformation during a minimum of five years observation time. Cell numbers and localization were semi-quantitatively assessed. Better developed CD21+  follicular dendritic cell (FDC) meshworks at diagnosis was a negative prognostic factor for overall survival (OS), progression-free survival (PFS) and time to transformation (TTT) in patients with subsequently transformed FL. Remnants of FDC meshworks at transformation were associated with shorter OS and PFS from transformation. High degrees of intrafollicular CD68+ and PD-L1+  macrophage infiltration, high total area scores and an extrafollicular/diffuse pattern of FOXP3+  T cells and high intrafollicular scores of CD4+  T cells at diagnosis were associated with shorter TTT. Scores of several T-cell subset markers from the combined patient cohorts were predictive for transformation, especially CD4 and CD57. PMID:27341313

  18. Hypertabastic survival model.

    PubMed

    Tabatabai, Mohammad A; Bursac, Zoran; Williams, David K; Singh, Karan P

    2007-10-26

    A new two-parameter probability distribution called hypertabastic is introduced to model the survival or time-to-event data. A simulation study was carried out to evaluate the performance of the hypertabastic distribution in comparison with popular distributions. We then demonstrate the application of the hypertabastic survival model by applying it to data from two motivating studies. The first one demonstrates the proportional hazards version of the model by applying it to a data set from multiple myeloma study. The second one demonstrates an accelerated failure time version of the model by applying it to data from a randomized study of glioma patients who underwent radiotherapy treatment with and without radiosensitizer misonidazole. Based on the results from the simulation study and two applications, the proposed model shows to be a flexible and promising alternative to practitioners in this field.

  19. Survival of extreme opinions

    NASA Astrophysics Data System (ADS)

    Hsu, Jiann-wien; Huang, Ding-wei

    2009-12-01

    We study the survival of extreme opinions in various processes of consensus formation. All the opinions are treated equally and subjected to the same rules of changing. We investigate three typical models to reach a consensus in each case: (A) personal influence, (B) influence from surroundings, and (C) influence to surroundings. Starting with uniformly distributed random opinions, our calculated results show that the extreme opinions can survive in both models (A) and (B), but not in model (C). We obtain a conclusion that both personal influence and passive adaptation to the environment are not sufficient enough to eradicate all the extreme opinions. Only the active persuasion to change the surroundings eliminates the extreme opinions completely.

  20. Doubly robust survival trees.

    PubMed

    Steingrimsson, Jon Arni; Diao, Liqun; Molinaro, Annette M; Strawderman, Robert L

    2016-09-10

    Estimating a patient's mortality risk is important in making treatment decisions. Survival trees are a useful tool and employ recursive partitioning to separate patients into different risk groups. Existing 'loss based' recursive partitioning procedures that would be used in the absence of censoring have previously been extended to the setting of right censored outcomes using inverse probability censoring weighted estimators of loss functions. In this paper, we propose new 'doubly robust' extensions of these loss estimators motivated by semiparametric efficiency theory for missing data that better utilize available data. Simulations and a data analysis demonstrate strong performance of the doubly robust survival trees compared with previously used methods. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27037609

  1. How worms survive desiccation

    PubMed Central

    Erkut, Cihan; Penkov, Sider; Fahmy, Karim; Kurzchalia, Teymuras V.

    2012-01-01

    While life requires water, many organisms, known as anhydrobiotes, can survive in the absence of water for extended periods of time. Although discovered 300 years ago, we know very little about the fascinating phenomenon of anhydrobiosis. In this paper, we summarize our previous findings on the desiccation tolerance of the Caenorhabditis elegans dauer larva. A special emphasis is given to the role of trehalose in protecting membranes against desiccation. We also propose a simple mechanism for this process. PMID:24058825

  2. Carbonaceous Survivability on Impact

    NASA Technical Reports Server (NTRS)

    Bunch, T. E.; Becker, Luann; Morrison, David (Technical Monitor)

    1994-01-01

    In order to gain knowledge about the potential contributions of comets and cosmic dust to the origin of life on Earth, we need to explore the survivability of their potential organic compounds on impact and the formation of secondary products that may have arisen from the chaotic events sustained by the carriers as they fell to Earth. We have performed a series of hypervelocity impact experiments using carbon-bearing impactors (diamond, graphite, kerogens, PAH crystals, and Murchison and Nogoya meteorites) into Al plate targets at velocities - 6 km/s. Estimated peak shock pressures probably did not exceed 120 GPa and peak shock temperatures were probably less than 4000 K for times of nano- to microsecs. Nominal crater dia. are less than one mm. The most significant results of these experiments are the preservation of the higher mass PAHs (e. g., pyrene relative to napthalene) and the formation of additional alkylated PAHs. We have also examined the residues of polystyrene projectiles impacted by a microparticle accelerator into targets at velocities up to 15 km/s. This talk will discuss the results of these experiments and their implications with respect to the survival of carbonaceous deliverables to early Earth. The prospects of survivability of organic molecules on "intact" capture of cosmic dust in space via soft: and hard cosmic dust collectors will also be discussed.

  3. Impact of short course hormonal therapy on overall and cancer specific survival after permanent prostate brachytherapy

    SciTech Connect

    Beyer, David C. . E-mail: dbeyer@azoncology.com; McKeough, Timothy; Thomas, Theresa

    2005-04-01

    Purpose: To review the impact of prior hormonal therapy on 10-year overall and prostate cancer specific survival after primary brachytherapy. Methods and Materials: A retrospective review was performed on the Arizona Oncology Services tumor registry for 2,378 consecutive permanent prostate brachytherapy cases from 1988 through 2001. Hormonal therapy was administered before the implant in 464 patients for downsizing of the prostate or at the discretion of the referring physician. All deceased patients with known clinical recurrence were considered to have died of prostate cancer, irrespective of the immediate cause of death. Risk groups were defined, with 1,135 favorable (prostate-specific antigen [PSA] < 10, Gleason < 7, Stage T1-T2a), 787 intermediate (single adverse feature), and 456 unfavorable (two or more adverse features) patients. Kaplan-Meier actuarial survival curves were generated for both overall and cause-specific survival from the time of treatment. Multivariate analysis was performed to assess the impact of hormonal intervention in comparison with known risk factors of grade, PSA, and age. Results: With follow-up ranging up to 12.6 years and a median of 4.1 year, a total of 474 patients died, with 67 recorded as due to prostate cancer. Overall and cause-specific 10-year survival rates are 43% and 88%, respectively. Overall survival is 44% for the hormone naive patients, compared with 20% for the hormone-treated cohort (p = 0.02). The cancer-specific survival is 89% vs. 81% for the same groups (p = 0.133). Multivariate analysis confirms the significance of age > 70 years (p = 0.0013), Gleason score {>=} 7 (p = 0.0005), and prior hormone use (p = 0.0065) on overall survival. Conclusions: At 10 years, in prostate cancer patients receiving brachytherapy, overall survival is worse in men receiving neoadjuvant hormonal therapy, compared with hormone naive patients. This does not appear to be due to other known risk factors for survival (i.e., stage, grade

  4. Test for age-specificity in survival of the common tern

    USGS Publications Warehouse

    Nisbet, I.C.T.; Cam, E.

    2002-01-01

    study meant that a decline in survival probability within individuals (actuarial senescence) could have been masked by heterogeneity in survival probability among individuals (mortality selection). This emphasizes the need for the development of modelling tools permitting separation of these two phenomena, valid under field conditions in which the recapture probabilities are less than one.

  5. BCR-ABL mutations in chronic myeloid leukemia treated with tyrosine kinase inhibitors and impact on survival.

    PubMed

    Pagnano, Katia Borgia Barbosa; Bendit, Israel; Boquimpani, Carla; De Souza, Carmino Antonio; Miranda, Eliana C M; Zalcberg, Ilana; Larripa, Irene; Nardinelli, Luciana; Silveira, Rosana Antunes; Fogliatto, Laura; Spector, Nelson; Funke, Vaneuza; Pasquini, Ricardo; Hungria, Vania; Chiattone, Carlos Sérgio; Clementino, Nelma; Conchon, Monika; Moiraghi, Elena Beatriz; Lopez, Jose Luis; Pavlovsky, Carolina; Pavlovsky, Miguel A; Cervera, Eduardo E; Meillon, Luis Antonio; Simões, Belinda; Hamerschlak, Nelson; Bozzano, Alicia Helena Magarinos; Mayta, Ernesto; Cortes, Jorge; Bengió, Raquel M

    2015-01-01

    This is the largest Latin American study of BCR-ABL mutations in chronic myeloid leukemia (CML) patients, resistant to imatinib (IM). In 195/467 (41%) patients, mutations were detected. The most frequent mutation was T315I (n = 31, 16%). Progression-free (PFS) and overall survival (OS) at 5 years were lower in patients with BCR-ABL mutations (43% vs. 65%, p = 0.07 and 47% vs. 72%, p = 0.03, respectively) and in those with the T315I mutation (p = 0.003 and p = 0.03). OS and PFS were superior in subgroup who switched to second generation inhibitors (SGIs) after IM failure (OS: 50% vs. 39% p = 0.01; PFS: 48% vs. 30% p = 0.02). BCR-ABL mutations conferred a significant poor prognosis in CML patients. PMID:26288116

  6. BCR-ABL mutations in chronic myeloid leukemia treated with tyrosine kinase inhibitors and impact on survival.

    PubMed

    Pagnano, Katia Borgia Barbosa; Bendit, Israel; Boquimpani, Carla; De Souza, Carmino Antonio; Miranda, Eliana C M; Zalcberg, Ilana; Larripa, Irene; Nardinelli, Luciana; Silveira, Rosana Antunes; Fogliatto, Laura; Spector, Nelson; Funke, Vaneuza; Pasquini, Ricardo; Hungria, Vania; Chiattone, Carlos Sérgio; Clementino, Nelma; Conchon, Monika; Moiraghi, Elena Beatriz; Lopez, Jose Luis; Pavlovsky, Carolina; Pavlovsky, Miguel A; Cervera, Eduardo E; Meillon, Luis Antonio; Simões, Belinda; Hamerschlak, Nelson; Bozzano, Alicia Helena Magarinos; Mayta, Ernesto; Cortes, Jorge; Bengió, Raquel M

    2015-01-01

    This is the largest Latin American study of BCR-ABL mutations in chronic myeloid leukemia (CML) patients, resistant to imatinib (IM). In 195/467 (41%) patients, mutations were detected. The most frequent mutation was T315I (n = 31, 16%). Progression-free (PFS) and overall survival (OS) at 5 years were lower in patients with BCR-ABL mutations (43% vs. 65%, p = 0.07 and 47% vs. 72%, p = 0.03, respectively) and in those with the T315I mutation (p = 0.003 and p = 0.03). OS and PFS were superior in subgroup who switched to second generation inhibitors (SGIs) after IM failure (OS: 50% vs. 39% p = 0.01; PFS: 48% vs. 30% p = 0.02). BCR-ABL mutations conferred a significant poor prognosis in CML patients.

  7. Modern treatment in chronic lymphocytic leukemia: impact on survival and efficacy in high-risk subgroups

    PubMed Central

    Cuneo, Antonio; Cavazzini, Francesco; Ciccone, Maria; Daghia, Giulia; Sofritti, Olga; Saccenti, Elena; Negrini, Massimo; Rigolin, Gian Matteo

    2014-01-01

    Treatment of chronic lymphocytic leukemia (CLL) has dramatically changed over the last years, with significant improvement in overall survival (OS) and increased efficacy in genetically defined “high-risk” disease. Besides prospective clinical trials usually enrolling young and fit patients, retrospective studies were performed comparing the outcome of patients belonging to different age groups and showing longer survival in patients diagnosed in the most recent periods. In patients younger than 70 years the 10-year relative survival was 43–53% in the 1980s as compared with 59–63% in the 2000s. Likewise, the 10-year relative survival in patients >70 years was 22–42% in the 1980s and 46–55% in the 2000s. Improved outcome derived in part by the introduction of effective regimens in genetically defined “high-risk” disease (i.e., 17p−, 11q−, TP53, NOTCH1, SF3B1 mutations), especially in the younger and/or fit patients. The unfavorable prognostic significance of 11q− was overcome by chemoimmunotherapy. High-dose steroids with anti-CD52 appeared to improve the response rate in 17p-/TP53 mutated cases and allogeneic transplantation achieved prolonged disease control irrespective of high-risk disease. Further improvement is being generated by the new anti-CD20 obinutuzumab in the elderly and by mechanism-based treatment using kinase-targeting agents or anti-BCL2 molecules yielding high-response rate and impressive progression-free survival in the chemorefractory setting as well as in previously untreated patients. PMID:24648042

  8. Interactive effects of senescence and natural disturbance on the annual survival probabilities of snail kites

    USGS Publications Warehouse

    Reichert, Brian E.; Martin, J.; Kendall, William L.; Cattau, Christopher E.; Kitchens, Wiley M.

    2010-01-01

    Individuals in wild populations face risks associated with both intrinsic (i.e. aging) and external (i.e. environmental) sources of mortality. Condition-dependent mortality occurs when there is an interaction between such factors; however, few studies have clearly demonstrated condition-dependent mortality and some have even argued that condition-dependent mortality does not occur in wild avian populations. Using large sample sizes (2084 individuals, 3746 re-sights) of individual-based longitudinal data collected over a 33 year period (1976-2008) on multiple cohorts, we used a capture-mark-recapture framework to model age-dependent survival in the snail kite Rostrhamus sociabilis plumbeus population in Florida. Adding to the growing amount of evidence for actuarial senescence in wild populations, we found evidence of senescent declines in survival probabilities in adult kites. We also tested the hypothesis that older kites experienced condition-dependent mortality during a range-wide drought event (2000-2002). The results provide convincing evidence that the annual survival probability of senescent kites was disproportionately affected by the drought relative to the survival probability of prime-aged adults. To our knowledge, this is the first evidence of condition-dependent mortality to be demonstrated in a wild avian population, a finding which challenges recent conclusions drawn in the literature. Our study suggests that senescence and condition-dependent mortality can affect the demography of wild avian populations. Accounting for these sources of variation may be particularly important to appropriately compute estimates of population growth rate, and probabilities of quasi-extinctions.

  9. Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

    SciTech Connect

    McMillan, Matthew T.; Ojerholm, Eric; Roses, Robert E.; Plastaras, John P.; Metz, James M.; Mamtani, Ronac; Stripp, Diana; Ben-Josef, Edgar; Datta, Jashodeep

    2015-10-01

    Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiation therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered.

  10. Survival in patients with oral and maxillofacial diffuse large B-cell lymphoma.

    PubMed

    Guevara-Canales, Janet Ofelia; Morales-Vadillo, Rafael; Cava-Vergiú, Carlos Enrique; Leite, Fabiola Pessoa Pereira; Miranda Chaves Netto, Henrique Duque de; Soares, Fernando Augusto; Chaves, Maria das Graças Afonso Miranda

    2013-01-01

    The purpose of this study was to determine the survival and prognostic factors of patients with diffuse large B-cell lymphoma (DLBCL) of the oral cavity and maxillofacial region. Retrospectively, the clinical records of patients with a primary diagnosis of DLBCL of the oral cavity and maxillofacial region treated at the A.C. Camargo Hospital for Cancer, São Paulo, Brazil, between January 1980 and December 2005 were evaluated to determine (A) overall survival (OS) at 2 and 5 years and the individual survival percentage for each possible prognostic factor by means of the actuarial technique (also known as mortality tables), and the Kaplan Meier product limit method (which provided the survival value curves for each possible prognostic factor); (B) prognostic factors subject to univariate evaluation with the log-rank test (also known as Mantel-Cox), and multivariate analysis with Cox's regression model (all the variables together). The data were considered significant at p≤0.05. From 1980 to 2005, 3513 new cases of lymphomas were treated, of which 151 (4.3%) occurred in the oral cavity and maxillofacial region. Of these 151 lesions, 48 were diffuse large B-cell lymphoma, with 64% for OS at 2 years and 45% for OS at 5 years. Of the variables studied as possible prognostic factors, multivariate analysis found the following variables have statistically significant values: age (p=0.042), clinical stage (p=0.007) and performance status (p=0.031). These data suggest that patients have a higher risk of mortality if they are older, at a later clinical stage, and have a higher performance status.

  11. Nuclear War Survival Skills

    SciTech Connect

    Kearny, C.H.

    2002-06-24

    The purpose of this book is to provide Americans with information and instructions that will significantly increase their chances of surviving a possible nuclear attack. It brings together field-tested instructions that, if followed by a large fraction of Americans during a crisis that preceded an attack, could save millions of lives. The author is convinced that the vulnerability of our country to nuclear threat or attack must be reduced and that the wide dissemination of the information contained in this book would help achieve that objective of our overall defense strategy.

  12. Survival of the strategist

    SciTech Connect

    Burr, M.T.

    1994-10-01

    Competition and privatization are two significant trends in the global power market. Surviving in this competitive environment will require developers to maximize their strategic advantages. The logjam in project development is caused by a variety of market factors. Political, regulatory and financing barriers combine to impede the development flow in many countries. Also, a lack of expertise in dealing with the unfamiliar business and cultural environments of developing markets is frustrating developers efforts to break through barriers. In response, many companies are reexamining markets and formulating new approaches to international development.

  13. Proposal for a Novel Methodology to Screen And Score Cost Versus Survival for Anticancer Drugs in Metastatic Disease: Could Cost Weigh in Evaluation?

    PubMed Central

    Guirgis, Helmy M.

    2012-01-01

    Purpose: Rising costs of anticancer drugs prompt concerns about their approval, use, and affordability. A methodology was developed to evaluate cost versus survival for anticancer drugs in metastatic breast cancer and non–small-cell lung cancer (NSCLC). Methods: Costs of evaluated drugs were calculated by using average wholesale prices in US dollars. Ratios of cost to day of survival (cost/survival/d) were obtained by dividing costs of the entire treatment by reported median survival gain in days. A crude score of 100% was assigned to a cost/survival/d of less than $25, and 0% to a cost/survival/d of more than $750. A strategy was designed to correct for overall survival (OS) versus progression-free survival (PFS), adverse effects, and quality of life. Results: In breast cancer, PFS scores of bevacizumab varied between 0% and 60%. In NSCLC, OS scores of bevacizumab improved from 0% to 50%, as a result of histology, lower prices, and extended therapy. Gefitinib and erlotinib PFS scores were 80% and 70%, respectively. Correction for longer survival with erlotinib resulted in similar scores. In maintenance therapy, the OS score for pemetrexed was 70% as compared with 25% for erlotinib. Generic drugs scored 70% to 90%. Conclusion: Cost/survival varied with the number of cycles. In breast cancer, bevacizumab scores failed to justify its use. In NSCLC, 10 cycles of bevacizumab scored 0%. Scores improved with extended treatment and lower prices. Scores for gefitinib and erlotinib would support their approval. Erlotinib was preferred because of longer PFS. Results tended to endorse maintenance pemetrexed but not erlotinib. Generic drugs demonstrated high scores. Cost/survival could weigh in drug evaluation. PMID:23180986

  14. SurvNet: a web server for identifying network-based biomarkers that most correlate with patient survival data.

    PubMed

    Li, Jun; Roebuck, Paul; Grünewald, Stefan; Liang, Han

    2012-07-01

    An important task in biomedical research is identifying biomarkers that correlate with patient clinical data, and these biomarkers then provide a critical foundation for the diagnosis and treatment of disease. Conventionally, such an analysis is based on individual genes, but the results are often noisy and difficult to interpret. Using a biological network as the searching platform, network-based biomarkers are expected to be more robust and provide deep insights into the molecular mechanisms of disease. We have developed a novel bioinformatics web server for identifying network-based biomarkers that most correlate with patient survival data, SurvNet. The web server takes three input files: one biological network file, representing a gene regulatory or protein interaction network; one molecular profiling file, containing any type of gene- or protein-centred high-throughput biological data (e.g. microarray expression data or DNA methylation data); and one patient survival data file (e.g. patients' progression-free survival data). Given user-defined parameters, SurvNet will automatically search for subnetworks that most correlate with the observed patient survival data. As the output, SurvNet will generate a list of network biomarkers and display them through a user-friendly interface. SurvNet can be accessed at http://bioinformatics.mdanderson.org/main/SurvNet.

  15. SURVIV for survival analysis of mRNA isoform variation

    PubMed Central

    Shen, Shihao; Wang, Yuanyuan; Wang, Chengyang; Wu, Ying Nian; Xing, Yi

    2016-01-01

    The rapid accumulation of clinical RNA-seq data sets has provided the opportunity to associate mRNA isoform variations to clinical outcomes. Here we report a statistical method SURVIV (Survival analysis of mRNA Isoform Variation), designed for identifying mRNA isoform variation associated with patient survival time. A unique feature and major strength of SURVIV is that it models the measurement uncertainty of mRNA isoform ratio in RNA-seq data. Simulation studies suggest that SURVIV outperforms the conventional Cox regression survival analysis, especially for data sets with modest sequencing depth. We applied SURVIV to TCGA RNA-seq data of invasive ductal carcinoma as well as five additional cancer types. Alternative splicing-based survival predictors consistently outperform gene expression-based survival predictors, and the integration of clinical, gene expression and alternative splicing profiles leads to the best survival prediction. We anticipate that SURVIV will have broad utilities for analysing diverse types of mRNA isoform variation in large-scale clinical RNA-seq projects. PMID:27279334

  16. Global real-time quantitative reverse transcription-polymerase chain reaction detecting proto-oncogenes associated with 14q32 chromosomal translocation as a valuable marker for predicting survival in multiple myeloma.

    PubMed

    Inagaki, Atsushi; Tajima, Emi; Uranishi, Miyuki; Totani, Haruhito; Asao, Yu; Ogura, Hiroka; Masaki, Ayako; Yoshida, Tatsuya; Mori, Fumiko; Ito, Asahi; Yano, Hiroki; Ri, Masaki; Kayukawa, Satoshi; Kataoka, Takae; Kusumoto, Shigeru; Ishida, Takashi; Hayami, Yoshihito; Hanamura, Ichiro; Komatsu, Hirokazu; Inagaki, Hiroshi; Matsuda, Yasufumi; Ueda, Ryuzo; Iida, Shinsuke

    2013-12-01

    CCND1, FGFR3 and c-MAF mRNA expression of tumor samples from 123 multiple myeloma patients were analyzed by global RQ/RT-PCR. CCND1, FGFR3 and c-MAF were positive in 44 (36%), 28 (23%) and 16 (13%) of patients, respectively. In 7 patients, both FGFR3 and c-MAF were positive. The expression of c-MAF was independent unfavorable prognostic factors for overall survival (OS). Autologous stem cell transplantation improved progression-free survival of CCND1-positive patients. Bortezomib, thalidomide or lenalidomide extended OS of FGFR3 and/or c-MAF-positive patients. Thus, CCND1, FGFR3 and c-MAF mRNA expression can predict survival and is useful for planning stratified treatment strategies for myeloma patients.

  17. Monitoring changes in circulating tumour cells as a prognostic indicator of overall survival and treatment response in patients with metastatic melanoma

    PubMed Central

    2014-01-01

    Background New effective treatments for metastatic melanoma greatly improve survival in a proportion of patients. However biomarkers to identify patients that are more likely to benefit from a particular treatment are needed. We previously reported on a multimarker approach for the detection of heterogenous melanoma circulating tumour cells (CTCs). Here we evaluated the prognostic value of this multimarker quantification of CTCs and investigated whether changes in CTC levels during therapy can be used as a biomarker of treatment response and survival outcomes. Methods CTCs were captured by targeting the melanoma associated markers MCSP and MCAM as well as the melanoma stem cell markers ABCB5 and CD271. CTCs were quantified in 27 metastatic melanoma patients treated by surgery or with vemurafenib, ipilimumab or dacarbazine. Patients were enrolled prospectively and CTC counts performed at baseline (prior to treatment), during and after treatment. Results Baseline CTC numbers were not found to be prognostic of overall survival nor of progression free survival. However, a low baseline CTC number was associated with a rapid response to vemurafenib therapy. A decrease in CTCs after treatment initiation was associated with response to treatment and prolonged overall survival in vemurafenib treated patients. Conclusions Measuring changes in CTC numbers during treatment is useful for monitoring therapy response in melanoma patients and for providing prognostic information relating to overall survival. Further studies with larger sample sizes are required to confirm the utility of CTC quantification as a companion diagnostic for metastatic melanoma treatment. PMID:24915896

  18. Surrogate endpoints for overall survival in metastatic melanoma: a meta-analysis of randomised controlled trials

    PubMed Central

    Flaherty, Keith T; Hennig, Michael; Lee, Sandra J; Ascierto, Paolo A; Dummer, Reinhard; Eggermont, Alexander M M; Hauschild, Axel; Kefford, Richard; Kirkwood, John M; Long, Georgina V; Lorigan, Paul; Mackensen, Andreas; McArthur, Grant; O'Day, Steven; Patel, Poulam M; Robert, Caroline; Schadendorf, Dirk

    2015-01-01

    Summary Background Recent phase 3 trials have shown an overall survival benefit in metastatic melanoma. We aimed to assess whether progression-free survival (PFS) could be regarded as a reliable surrogate for overall survival through a meta-analysis of randomised trials. Methods We systematically reviewed randomised trials comparing treatment regimens in metastatic melanoma that included dacarbazine as the control arm, and which reported both PFS and overall survival with a standard hazard ratio (HR). We correlated HRs for overall survival and PFS, weighted by sample size or by precision of the HR estimate, assuming fixed and random effects. We did sensitivity analyses according to presence of crossover, trial size, and dacarbazine dose. Findings After screening 1649 reports and meeting abstracts published before Sept 8, 2013, we identified 12 eligible randomised trials that enrolled 4416 patients with metastatic melanoma. Irrespective of weighting strategy, we noted a strong correlation between the treatment effects for PFS and overall survival, which seemed independent of treatment type. Pearson correlation coefficients were 0.71 (95% CI 0.29–0.90) with a random-effects assumption, 0.85 (0.59–0.95) with a fixed-effects assumption, and 0.89 (0.68–0.97) with sample-size weighting. For nine trials without crossover, the correlation coefficient was 0.96 (0.81–0.99), which decreased to 0.93 (0.74–0.98) when two additional trials with less than 50% crossover were included. Inclusion of mature follow-up data after at least 50% crossover (in vemurafenib and dabrafenib phase 3 trials) weakened the PFS to overall survival correlation (0.55, 0.03–0.84). Inclusion of trials with no or little crossover with the random-effects assumption yielded a conservative statement of the PFS to overall survival correlation of 0.85 (0.51–0.96). Interpretation PFS can be regarded as a robust surrogate for overall survival in dacarbazine-controlled randomised trials of

  19. Mechanisms of Fat Graft Survival.

    PubMed

    Pu, Lee L Q

    2016-02-01

    Although more fat grafting procedures have been performed by plastic surgeons with the primary goal to restore soft tissue loss, the actual mechanism on how fat graft survives remains less completely understood. An established old theory on fat graft survival is still based on the cell survival theory proposed by Peer in the early 1950s. On the basis of his preliminary experimental study, he proposed that the mechanism of fat graft survival is based on established early blood circulation through anastomosis of the fat graft and host blood vessels. Recently, several investigators have demonstrated new concepts of the fat graft survival: One further advanced the old Peer cell survival theory and another based on new discovery and understanding of adipose-derived stem cells. This article serves as a scientific review on how fat graft survives after in vivo transplantation based on a number of well-conducted experimental studies. Both the graft survival and graft replacement theories on how fat graft survives are true based on the previously mentioned well-conducted experimental studies. Each theory may play a role in fat graft survival. It is possible that graft survival may be more dominant in some patients but the graft replacement may be more dominant in other patients.

  20. Postfledging survival of European starlings

    USGS Publications Warehouse

    Krementz, D.G.; Nichols, J.D.; Hines, J.E.

    1989-01-01

    We tested the hypotheses that mass at fledging and fledge date within the breeding season affect postfledging survival in European Starlings (Sturnus vulgaris). Nestlings were weighed on day 18 after hatch and tagged with individually identifiable patagial tags. Fledge date was recorded. Marked fledglings were resighted during weekly two-day intensive observation periods for 9 weeks postfledging. Post-fledging survival and sighting probabilities were estimated for each of four groups (early or late fledging by heavy or light fledging mass). Body mass was related to post-fledging survival for birds that fledged early. Results were not clear-cut for relative fledge date, although there was weak evidence that this also influenced survival. Highest survival probability estimates occurred in the EARLY-HEAVY group, while the lowest survival estimate occurred in the LATE-LIGHT group. Sighting probabilities differed significantly among groups, emphasizing the need to estimate and compare survival using models which explicitly incorporate sighting probabilities.

  1. Survival benefit and safety of the combinations of FOLFOXIRI ± bevacizumab versus the combinations of FOLFIRI ± bevacizumab as first-line treatment for unresectable metastatic colorectal cancer: a meta-analysis

    PubMed Central

    Xu, Wei; Kuang, Meng; Gong, Yang; Cao, Chunxiang; Chen, Jinfei; Tang, Cuiju

    2016-01-01

    Background The survival of patients with metastatic colorectal cancer (mCRC) could be improved with exposure to three active drugs, irinotecan, fluorouracil/leucovorin, and oxaliplatin, irrespective of their sequence. However, only 50%–80% of patients can be exposed to all the three drugs in a sequential strategy with two-drug combinations. We carried out this systematic assessment to compare the survival benefit and safety of FOLFOXIRI (irinotecan, fluorouracil/leucovorin, and oxaliplatin) ± bevacizumab (with or without bevacizumab) versus FOLFIRI (irinotecan and fluorouracil/leucovorin) ± bevacizumab (with or without bevacizumab) as first-line treatment for unresectable mCRC. Methods PubMed and EMBASE were searched for original articles written in English and published before December 2015. A total of 1,035 patients from three randomized controlled trials were included. Results Our results demonstrated that overall survival (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.73–0.97), progression-free survival (HR, 0.69; 95% CI, 0.59–0.81), and overall response rate (odds ratio, 1.96; 95% CI, 1.28–2.98) were significantly improved in the FOLFOXIRI ± bevacizumab arm compared to the FOLFIRI ± bevacizumab arm. Significantly higher incidences of neutropenia, anemia, diarrhea, stomatitis, and neuropathy were observed in the FOLFOXIRI ± bevacizumab arm. Conclusion Current evidence shows that the combination of FOLFOXIRI ± bevacizumab significantly improves the overall survival, progression-free survival, and overall response rate of patients with mCRC, with an increased but manageable toxicity, compared with the combinations of FOLFIRI ± bevacizumab. The combination of FOLFOXIRI ± bevacizumab should be considered as a treatment option for these patients under the premise of reasonable selection of target population. PMID:27536147

  2. Cold sea survival.

    NASA Technical Reports Server (NTRS)

    Veghte, J. H.

    1972-01-01

    Two prototype three-man life rafts were evaluated during the winter months in Arctic waters off Kodiak Island, Alaska, to assess potential survival problems and determine tolerance limits. Each raft incorporated thermal characteristics specifically designed for cold water. Water and air temperatures varied from 0 to +2 C and -5 to +4 C respectively. All subjects were removed upon reaching subjective tolerance. The results showed that none of the clothing assemblies was adequate to maintain a person in comfort even with dry boarding. No significant biochemical shifts in the blood or urine were found. The TUL raft was found to be superior in its thermal characteristics and afforded better subject protection. General tolerance for cold water immersion, wet and dry, and cold water raft exposures are depicted graphically, based on previously reported data.

  3. Process control for survival

    SciTech Connect

    Yocom, J.A.

    1991-06-01

    Increasing competition for a decreasing market mandates that the success of a company be determined by the manner in which it embraces quality. Statistical Process Control (SPC) is the most efficient means of dramatically improving quality and is essential to survival in the emerging electronic marketplace. During the three years that industry practitioners assembled to write IPC-PC-90, General Requirements for the Implementation of statistical Process Control, many heated discussions ensued about the actual definition of SPC. Some people view SPC as the application of Control Chart methods, others view it as the use of Statistical Experimental Design. Both are in some ways wrong and are limiting the scope of application. Those companies that have successfully applied SPC view it as a philosophy of statistical principles that will reduce variation in every phase of their business. 2 figs.

  4. Clinical impact of post-progression survival on overall survival in patients with limited-stage disease small cell lung cancer after first-line chemoradiotherapy

    PubMed Central

    Kasahara, Norimitsu; Imai, Hisao; Kaira, Kyoichi; Mori, Keita; Wakuda, Kazushige; Ono, Akira; Taira, Tetsuhiko; Kenmotsu, Hirotsugu; Harada, Hideyuki; Naito, Tateaki; Murakami, Haruyasu; Endo, Masahiro; Nakajima, Takashi; Yamada, Masanobu; Takahashi, Toshiaki

    2015-01-01

    Background The effects of first-line chemoradiotherapy on overall survival (OS) may be confounded by subsequent lines of therapy in patients with limited-stage disease small cell lung cancer (LD-SCLC). Therefore, we aimed to determine the relationships between progression-free survival (PFS), post-progression survival (PPS) and OS after first-line chemoradiotherapy in LD-SCLC patients. Patients and methods. We retrospectively analyzed 71 LD-SCLC patients with performance status (PS) 0–2 who received first-line chemoradiotherapy and had disease recurrence between September 2002 and March 2013 at Shizuoka Cancer Center (Shizuoka, Japan). We determined the correlation between PFS and OS and between PPS and OS at the individual level. In addition, we performed univariate and multivariate analyses to identify significant prognostic factors of PPS. Results OS is more strongly correlated with PPS (Spearman’s r = 0.86, R2 = 0.72, p < 0.05) than PFS (Spearman’s r = 0.46, R2 = 0.38, p < 0.05). In addition, the response to second-line treatments, the presence of distant metastases at recurrence and the number of additional regimens after first-line chemoradiotherapy were significant independent prognostic factors for PPS. Conclusions PPS has more impact on OS than PFS in recurrent LD-SCLC patients with good PS at beginning of the treatment. Moreover, treatments administered after first-line chemoradiotherapy may affect their OS. However, larger multicenter studies are needed to validate these findings. PMID:26834529

  5. A Histomorphologic Grading System That Predicts Overall Survival in Diffuse Malignant Peritoneal Mesothelioma With Epithelioid Subtype

    PubMed Central

    Blackham, Aaron U.; Levine, Edward; Russell, Greg; Votanopoulos, Konstantinos I.; Stewart, John H.; Shen, Perry; Geisinger, Kim R.; Sirintrapun, Sahussapont J.

    2016-01-01

    Diffuse malignant peritoneal mesothelioma (MPeM) is rare and arises from peritoneal serosal surfaces. Although it shares similar histomorphology with its counterpart, malignant pleural mesothelioma, etiologies, clinical courses, and therapies differ. Nuclear grading and level of mitoses have been correlated with prognosis in malignant pleural mesothelioma with epithelioid subtype. Whether nuclear grading and level of mitoses correlate with prognosis in MPeM is still unknown. Our study utilizes a 2 tier system incorporating nuclear features and level of the mitoses to stratify cases of MPeM with epithelioid subtype. Fifty-one cases of MPeM with clinical follow-up underwent retrospective microscopic review. From that subset, 46 cases were of epithelioid subtype, which were then stratified into a low-grade or high-grade tier. Survival times were calculated on the basis of Kaplan-Meier analysis. The low-grade tier had higher overall survival with a median of 11.9 years and 57% at 5 years when compared with the high-grade tier with a median of 3.3 years and 21% at 5 years (P=0.002). Although not statistically significant, the low-grade tier had higher progression-free survival with a median of 4.7 years and 65% at 5 years when compared with the high-grade tier with a median of 1.9 years and 35% at 5 years (P=0.089). Our study is first to specifically evaluate and correlate nuclear features and level of mitoses with overall survival in MPeM with epithelioid subtype. PMID:27438989

  6. Circulating tumor cells, disease recurrence and survival in newly diagnosed breast cancer

    PubMed Central

    2012-01-01

    Introduction The presence of circulating tumor cells (CTC) is an independent prognostic factor for progression-free survival and breast cancer-related death (BRD) for patients with metastatic breast cancer beginning a new line of systemic therapy. The current study was undertaken to explore whether the presence of CTC at the time of diagnosis was associated with recurrence-free survival (RFS) and BRD. Methods In a prospective single center study, CTC were enumerated with the CellSearch system in 30 ml of peripheral blood of 602 patients before undergoing surgery for breast cancer. There were 97 patients with a benign tumor, 101 did not meet the inclusion criteria of which there were 48 patients with DCIS, leaving 404 stage I to III patients. Patients were stratified into unfavorable (CTC ≥1) and favorable (CTC = 0) prognostic groups. Results ≥1 CTC in 30 ml blood was detected in 15 (15%) benign tumors, in 9 DCIS (19%), in 28 (16%) stage I, 32 (18%) stage II and in 16 (31%) patients with stage III. In stage I to III patients 76 (19%) had ≥1 CTC of whom 16 (21.1%) developed a recurrence. In 328 patients with 0 CTC 38 (11.6%) developed a recurrence. Four-year RFS was 88.4% for favorable CTC and 78.9% for unfavorable CTC (P = 0.038). A total of 25 patients died of breast cancer-related causes and 11 (44%) had ≥1 CTC. BRD was 4.3% for favorable and 14.5% for unfavorable CTC (P = 0.001). In multivariate analysis ≥1 CTC was associated with distant disease-free survival, but not for overall recurrence-free survival. CTC, progesterone receptor and N-stage were independent predictors of BRD in multivariate analysis. Conclusions Presence of CTC in breast cancer patients before undergoing surgery with curative intent is associated with an increased risk for breast cancer-related death. PMID:23088337

  7. Do Increased Doses to Stem-Cell Niches during Radiation Therapy Improve Glioblastoma Survival?

    PubMed Central

    Adeberg, Sebastian; Harrabi, Semi Ben; Mohr, Angela; Rieber, Juliane; Rieken, Stefan; Debus, Juergen

    2016-01-01

    Background and Purpose. The reasons for the inevitable glioblastoma recurrence are yet understood. However, recent data suggest that tumor cancer stem cells (CSCs) in the stem-cell niches, with self-renewing capacities, might be responsible for tumor initiation, propagation, and recurrence. We aimed to analyze the effect of higher radiation doses to the stem-cell niches on progression-free survival (PFS) and overall survival (OS) in glioblastoma patients. Materials and Methods. Sixty-five patients with primary glioblastoma treated with radiation therapy were included in this retrospective analysis. The SVZ and DG were segmented on treatment planning magnetic resonance imaging, and the dose distributions to the structures were calculated. The relationship of dosimetry data and survival was evaluated using the Cox regression analysis. Results. Conventionally fractionated patients (n = 54) who received higher doses (Dmean ≥ 40 Gy) to the IL SVZ showed improved PFS (8.5 versus 5.2 months; p = 0.013). Furthermore, higher doses (Dmean ≥ 30 Gy) to the CL SVZ were associated with increased PFS (10.1 versus 6.9 months; p = 0.025). Conclusion. Moderate higher IL SVZ doses (≥40 Gy) and CL SVZ doses (≥30 Gy) are associated with improved PFS. Higher doses to the DG, the second stem-cell niche, did not influence the survival. Targeting the potential cancer stem cells in the SVZ might be a promising treatment approach for glioblastoma and should be addressed in a prospective randomized trial. PMID:27429623

  8. Long-Term Survival in Patients With Synchronous, Solitary Brain Metastasis From Non-Small-Cell Lung Cancer Treated With Radiosurgery

    SciTech Connect

    Flannery, Todd W.; Suntharalingam, Mohan; Regine, William F.; Chin, Lawrence S.; Krasna, Mark J.; Shehata, Michael K.; Edelman, Martin J.; Kremer, Marnie; Patchell, Roy A.; Kwok, Young

    2008-09-01

    Purpose: To report the outcome of patients with synchronous, solitary brain metastasis from non-small-cell lung cancer (NSCLC) treated with gamma knife stereotactic radiosurgery (GKSRS). Patients and Methods: Forty-two patients diagnosed with synchronous, solitary brain metastasis from NSCLC were treated with GKSRS between 1993 and 2006. The median Karnofsky performance status (KPS) was 90. Patients had thoracic Stage I-III disease (American Joint Committee on Cancer 2002 guidelines). Definitive thoracic therapy was delivered to 26/42 (62%) patients; 9 patients underwent chemotherapy and radiation, 12 patients had surgical resection, and 5 patients underwent preoperative chemoradiation and surgical resection. Results: The median overall survival (OS) was 18 months. The 1-, 2-, and 5-year actuarial OS rates were 71.3%, 34.1%, and 21%, respectively. For patients who underwent definitive thoracic therapy, the median OS was 26.4 months compared with 13.1 months for those who had nondefinitive therapy, and the 5-year actuarial OS was 34.6% vs. 0% (p < 0.0001). Median OS was significantly longer for patients with a KPS {>=}90 vs. KPS < 90 (27.8 months vs. 13.1 months, p < 0.0001). The prognostic factors significant on multivariate analysis were definitive thoracic therapy (p = 0.020) and KPS (p = 0.001). Conclusions: This is one of the largest series of patients diagnosed with synchronous, solitary brain metastasis from NSCLC treated with GKSRS. Definitive thoracic therapy and KPS significantly impacted OS. The 5-year OS of 21% demonstrates the potential for long-term survival in patients treated with GKSRS; therefore, patients with good KPS should be considered for definitive thoracic therapy.

  9. Results of radiation therapy in stage 1B cervical carcinoma at King Chulalongkorn Memorial Hospital: fifteen-year experience.

    PubMed

    Lertbutsayanukul, C; Lertsanguansinchai, P; Shotelersuk, K; Khorprasert, C; Rojpornpradit, P; Asavametha, N; Pataramontree, J; Suriyapee, S; Tresukosol, D; Termrungruanglert, W

    2001-06-01

    A retrospective study was performed on 131 patients with stage 1B cervical carcinoma who were referred and treated with external beam radiation and intracavitary brachytherapy at the Division of Radiation Therapy, Department of Radiology, King Chulalongkorn Memorial Hospital between February 1985 and February 2000. Primary outcomes were overall survival rate, progression free survival rate, recurrence, and treatment-related complications. The treatment results from different sources of intracavitary radiation therapy were secondary endpoints. The number of patients treated with Ra-226, Cs-137, and Ir-192 intracavitary irradiation were 12, 84, and 35 patients respectively. The median follow-up times were 69, 59, and 21 months for Ra-226, Cs-137, and Ir-192, respectively. Actuarial 5-year overall survival rate was 89 per cent. The 5-year progression free survival rate was 80 per cent. Actuarial 5-year survival and progression free survival rate were comparable among different sources of intracavitary brachytherapy (p = 0.553 and p=0.793, respectively). The overall recurrent rate was 16.8 per cent. Of the recurrence; 40.9 per cent was locoregional, 54.6 per cent was distant failure, and 4.5 per cent was combined locoregional and distant failure. The overall complication rate was 25.95 per cent. The severe complication rates (Grade III-V) from treatment occurred in the urinary bladder (0.76%) and in the small bowel (0.76%.) These results suggest that radiation therapy alone is an effective treatment for stage 1B cervical carcinoma. Additionally, all types of intracavitary brachytherapy provide comparable clinical results.

  10. Will the olympics survive?.

    PubMed Central

    Khosla, T.

    1977-01-01

    The United States of America dominated 58 events in athletics, field and swimming, which between them accounted for 35 per cent of all events in the Munich Olympiad. 1972; these events favour taller individuals. But, in 25 per cent of other events (1) cycling, (2) fencing, (3) gymnastics, (4) judo, (5) weightlifting and (6) Graeco Roman wrestling the U.S.A. did not win a single medal. The failure of the U.S.A. to maintain her lead in Munich was largely due to weaknesses in these other events in many of which the potential medallists can be derived from the lower half of the height distribution (events 3 to 6). These weaknesses are Russia's strength and they continued to remain unstrengthened at Montreal. Also, the domination held by the U.S.A. in swimming was seriously challenged by East Germany. The present trends indicate that the U.S.A.'s ranking is likely to slip further to the third position in Moscow 1980. Factors inhibiting the survival of the Olympics are pointed. PMID:861436

  11. Surviving a Suicide Attempt

    PubMed Central

    Al-Harrasi, Ahmed; Al Maqbali, Mandhar; Al-Sinawi, Hamed

    2016-01-01

    Suicide is a global phenomenon in all regions of the world affecting people of all age groups. It has detrimental consequences on patients, their families, and the community as a whole. There have been numerous risk factors described for suicide including mental illness, stressful life situations, loss of social support, and general despair. The association of suicide with Islam has not been extensively studied. The common impression from clinical practice is that being a practicing Muslim reduces the risk of suicide. Another factor associated with suicide is starting a patient on antidepressants. However, this has been questioned recently. This report describes a middle-aged man with depression and multiple social stressors who survived a serious suicide attempt. The discussion will focus on the factors that lead him to want to end his life and the impact of the assumed protective factors such as religious belief and family support on this act of self-harm. Such patients can be on the edge when there is an imbalance between risk factors (such as depression, insomnia, and psychosocial stressors) and protective factors (like religious affiliation and family support). All physicians are advised to assess the suicide risk thoroughly in patients with depression regardless of any presumed protective factor. PMID:27602193

  12. Surviving a Suicide Attempt

    PubMed Central

    Al-Harrasi, Ahmed; Al Maqbali, Mandhar; Al-Sinawi, Hamed

    2016-01-01

    Suicide is a global phenomenon in all regions of the world affecting people of all age groups. It has detrimental consequences on patients, their families, and the community as a whole. There have been numerous risk factors described for suicide including mental illness, stressful life situations, loss of social support, and general despair. The association of suicide with Islam has not been extensively studied. The common impression from clinical practice is that being a practicing Muslim reduces the risk of suicide. Another factor associated with suicide is starting a patient on antidepressants. However, this has been questioned recently. This report describes a middle-aged man with depression and multiple social stressors who survived a serious suicide attempt. The discussion will focus on the factors that lead him to want to end his life and the impact of the assumed protective factors such as religious belief and family support on this act of self-harm. Such patients can be on the edge when there is an imbalance between risk factors (such as depression, insomnia, and psychosocial stressors) and protective factors (like religious affiliation and family support). All physicians are advised to assess the suicide risk thoroughly in patients with depression regardless of any presumed protective factor.

  13. Surviving a Suicide Attempt.

    PubMed

    Al-Harrasi, Ahmed; Al Maqbali, Mandhar; Al-Sinawi, Hamed

    2016-09-01

    Suicide is a global phenomenon in all regions of the world affecting people of all age groups. It has detrimental consequences on patients, their families, and the community as a whole. There have been numerous risk factors described for suicide including mental illness, stressful life situations, loss of social support, and general despair. The association of suicide with Islam has not been extensively studied. The common impression from clinical practice is that being a practicing Muslim reduces the risk of suicide. Another factor associated with suicide is starting a patient on antidepressants. However, this has been questioned recently. This report describes a middle-aged man with depression and multiple social stressors who survived a serious suicide attempt. The discussion will focus on the factors that lead him to want to end his life and the impact of the assumed protective factors such as religious belief and family support on this act of self-harm. Such patients can be on the edge when there is an imbalance between risk factors (such as depression, insomnia, and psychosocial stressors) and protective factors (like religious affiliation and family support). All physicians are advised to assess the suicide risk thoroughly in patients with depression regardless of any presumed protective factor. PMID:27602193

  14. Determination of Survivable Fires

    NASA Technical Reports Server (NTRS)

    Dietrich, D. L.; Niehaus, J. E.; Ruff, G. A.; Urban, D. L.; Takahashi, F.; Easton, J. W.; Abbott, A. A.; Graf, J. C.

    2012-01-01

    At NASA, there exists no standardized design or testing protocol for spacecraft fire suppression systems (either handheld or total flooding designs). An extinguisher's efficacy in safely suppressing any reasonable or conceivable fire is the primary benchmark. That concept, however, leads to the question of what a reasonable or conceivable fire is. While there exists the temptation to over-size' the fire extinguisher, weight and volume considerations on spacecraft will always (justifiably) push for the minimum size extinguisher required. This paper attempts to address the question of extinguisher size by examining how large a fire a crew member could successfully survive and extinguish in the confines of a spacecraft. The hazards to the crew and equipment during an accidental fire include excessive pressure rise resulting in a catastrophic rupture of the vehicle skin, excessive temperatures that burn or incapacitate the crew (due to hyperthermia), carbon dioxide build-up or other accumulation of other combustion products (e.g. carbon monoxide). Estimates of these quantities are determined as a function of fire size and mass of material burned. This then becomes the basis for determining the maximum size of a target fire for future fire extinguisher testing.

  15. The effect of the UGT1A1*28 allele on survival after irinotecan-based chemotherapy: a collaborative meta-analysis.

    PubMed

    Dias, M M; Pignon, J-P; Karapetis, C S; Boige, V; Glimelius, B; Kweekel, D M; Lara, P N; Laurent-Puig, P; Martinez-Balibrea, E; Páez, D; Punt, C J A; Redman, M W; Toffoli, G; Wadelius, M; McKinnon, R A; Sorich, M J

    2014-10-01

    To date, studies of irinotecan pharmacogenetics have mostly focused on the effect of the UGT1A1*28 allele on irinotecan-related toxicity. However, the clinical utility of routine UGT1A1*28 genotyping to pre-emptively adjust irinotecan dosage is dependent upon whether UGT1A1*28 also affects patient survival following irinotecan therapy. Previous observational studies evaluating the influence of UGT1A1*28 on survival have shown contradictory results. A systematic review and meta-analysis of both published and unpublished data were performed to summarize the available evidence of the relationship between the UGT1A1*28 allele and patient survival related to irinotecan therapy. Overall and progression-free survival meta-analysis data were available for 1524 patients and 1494 patients, respectively. The difference in the survival between patients of different UGT1A1*28 genotypes (homozygous, heterozygous or wild-type) who had received irinotecan was not found to be statistically significant. There was also no evidence of irinotecan dose, regimen or line of therapy having an impact on this association. PMID:24709690

  16. A retrospective review of outcome and survival following surgery and adjuvant xenogeneic DNA vaccination in 32 dogs with oral malignant melanoma

    PubMed Central

    TREGGIARI, Elisabetta; GRANT, Jessica Pauline; NORTH, Susan Margaret

    2016-01-01

    A xenogeneic DNA vaccination has been licensed for use in dogs with locally controlled stage II and III oral malignant melanoma (OMM). At present, there are limited outcome data for dogs with OMM treated with surgery and immunotherapy. The aim of this study is to retrospectively review the outcome and survival of 32 dogs affected by OMM that were treated with a combination of surgery and the xenogeneic DNA vaccination (with the addition of radiotherapy in some cases) and to determine the influence of surgical margins and delay in receiving vaccination. The overall median survival time (MST) was 335 days (95% CI: 301–540 days), and the overall median progression-free survival (PFS) was 160 days (mean 182 days, 95% CI: 132–232 days). Stage, completeness of surgical margins and delay in administration of the vaccine did not appear to statistically influence survival or PFS, although these results may reflect the low statistical power of the study due to small numbers. Further studies are required to assess whether the addition of any adjuvant treatment to surgery, including immunotherapy, is able to significantly prolong survival in cases of canine oral melanoma. PMID:26781703

  17. Time-course pattern of blood 25-hydroxycholecalciferol is a significant predictor of survival outcome in metastatic colorectal cancer: a clinical practice-based study.

    PubMed

    Obermannova, R; Dusek, L; Greplova, K; Jarkovsky, J; Sterba, J; Vyzula, R; Demlova, R; Zdrazilova-Dubska, L; Valik, D

    2015-01-01

    Vitamin D deficiency has been implicated in the epidemiology of common malignancies including colorectal cancer. We studied consecutive blood levels of 25-hydroxycholecalciferol (25-OHD) in relation to other clinical and laboratory variables in metastatic colorectal cancer patients to ascertain whether their variations may be prognostic or predictive parameters of survival outcomes. Eighty four patients treated with first-line oxaliplatin-based chemotherapy with or without bevacizumab were included. The patients were enrolled on the intent-to-treat basis considering their performance status, comorbidities and laboratory parameters to be medically apt for intensive chemotherapy. Overall survival and progression-free survival were selected as the primary outcomes. Progression free survival and overall survival medians were 15.4 months and 41.2 months, respectively. The cut-off levels of 40 nmol/l for 25-OHD and 11 µg/l for first CEA were identified to be clinical decision levels stratifying patients to the respective prognostic groups. We found that the most consistent outcome predictors were i) any patient surgery, ii) CEA and, independently, iii) time-related blood levels of 25-OHD. We confirmed fundamental and consistent vitamin D deficiency in metastatic colorectal cancer. We demonstrated that all patients with at least one blood level above 40 nmol/l versus all below this cut-off showed profound differences in their disease outcomes. The primary disease stage or time to metastatic stage did not influence the predictive power of blood 25-OHD levels, implying that the time-course pattern of 25-OHD but not the first single measurement may be an independent prognostic factor. PMID:26458311

  18. Surviving your new CEO.

    PubMed

    Coyne, Kevin P; Coyne, Edward J

    2007-05-01

    Almost 50% of the largest American firms will have a new CEO within the next four years; your company could very well be next. Senior executives know that a CEO transition means they're in for a round of firings, organizational reshuffles, and other unwelcome career changes. When your career suddenly depends on the views of a person you may not know, how worried should you be? According to the authors--very. They investigated the 2002-2004 CEO turnover rates of the top 1,000 U.S. companies and interviewed more than a dozen CEOs, each of whom had taken over at least one very large organization. Their study reveals that when a new CEO takes charge, remaining top managers are more likely than not to be shown the door. Those who leave often land in a lower position at a new company, work in a much smaller firm, or retire altogether. The news is not all grim, however. The interviewees offer some pointers on how to create a good impression and maximize your chances of survival and success under the new regime. Some of that advice may surprise you. One CEO pointed out, for instance, that "managers do not realize how much the CEO is looking for teammates on day one. I am amazed at how few people come through the door and say, 'I want to help. I may not be perfect, but I buy into your vision:" Other recommendations are more intuitive, such as learning the new CEO's working style, understanding her agenda, and helping her look good in her new position by achieving positive operating results--and soon. Along with the inevitable stresses, the authors point out, CEO transitions can provide opportunities. Whether you reinvigorate your career within your company or find fulfillment elsewhere, the key lies in deciding what you want to do--and then doing it right.

  19. Predicting Survival in ARDS.

    PubMed

    Karnik, Niteen D; Gupta, Anish V

    2015-11-01

    Acute respiratory distress syndrome (ARDS) is a fulminant clinical disorder of varied etiology, characterized by diffuse lung injury and severe hypoxemia. It is a leading cause of ICU admission and the associated high mortality has sparked a lot of research on etiology, outcome, scoring systems, mortality predictors, biomarkers including inflammatory cytokines and even genomics in ARDS. The previously used AECC (American European Consensus Conference) definition (1994) of ARDS was replaced by the recent Berlin definition (2012) so as to improve its validity and reliability.1,2 This would not only standardize patient enrollment into clinical trials but also help implement the results of these trials into clinical practice. Although various studies have shown a reduction in mortality due to ARDS, it has been largely attributed to the general improvement in critical care and the use of lung protection ventilation strategies.3-6 Hence focus on the etiology, co-morbidities, risk factors, complications and mortality predictors, is the need of the hour so as to improve survival. ARDS can occur secondary to multiple causes i.e. either due to direct lung involvement (pneumonia, lung contusion etc) or indirect alveolar damage by inflammatory cytokines (sepsis, trauma, burns, pancreatitis etc.). The causes of ARDS in tropical countries are varied with seasonal variation. Acute febrile illnesses (AFI) like malaria, leptospirosis and dengue usually predominate in the monsoons while H1N1 infection and pneumonias typically peak in the colder winter months. However, malaria, dengue and H1N1 have a potential to be perennial. PMID:27608777

  20. Infant survival in prematurity.

    PubMed

    CARTWRIGHT, E W

    1954-05-01

    Reduction of neonatal mortality and the rate of stillbirth may be expected from improved management of spontaneous labor and delivery.Neither roentgenographic measurement nor the inception of fetal movement or heartbeat nor any other single test is an index of fetal maturity; all must be considered together. Prenatal care, particularly supplemented diet, will help to avoid premature delivery, or at least to prolong pregnancy; since the fetus undergoes accelerated growth during the last weeks of pregnancy, even slight extension of gestation increases the chances for survival. Analgesia in the first stage of premature labor is contraindicated. Only low spinal anesthesia and other types of conduction anesthesia should be employed for later stages. The fetal membranes should be preserved as long as possible, but premature rupture does not call for immediate termination of pregnancy. Deep episiotomy and prophylactic outlet forceps are routinely employed to hasten the second stage of premature delivery and to protect the immature fetus. Breech presentation is managed by unassisted expulsion or by forceps extraction of the head. The umbilical cord is not immediately severed on delivery; administration of oxytocic drugs after the second stage of labor, combined with gentle stripping of the cord, results in rapid transfer of increased amount of placental blood. The airways of the infant should be immediately cleared. Artificial respiration may be necessary and it must be gentle.All premature infants should receive supplementary oxygen to render breathing regular and more efficient. They should be insulated immediately in controlled temperature and humidity, and they should be handled little.

  1. Presidential Survival in Tough Times.

    ERIC Educational Resources Information Center

    Bowen, Raymond C.

    Surviving the position of college president requires the development of a presidential survival kit filled with idiosyncratic items not normally associated with formal educational training. Strength, agility, control, and the ability to improvise are some of the talents required of a college president. In addition, the longevity and success of a…

  2. A prospective study of the survival of chemically activated anterior resin composite restorations in general dental practice: 5-year results.

    PubMed

    van Noort, R; Davis, L G

    1993-08-01

    The principals of 26 general dental practices agreed to use six chemically activated resin composite restorative materials to restore Class III and Class V lesions and record information concerning their performance over a period of 5 years. The information collected was analysed by actuarial methods to assess the clinical longevity and reasons for replacement as perceived by the dentists operating in the General Dental Service in England. At the end of 5 years, 14 dentists provided sufficient returns for their data to be considered suitable for analysis. The database consisted of 2399 Class III and 1093 Class V restorations. The overall probability of survival at 5 years of Class III and Class V restorations was 62.9% and 71.8% respectively. The difference in performance between the six restorative materials was small, with the probability of survival varying from 70.4 +/- 2.9% to 56.3 +/- 2.9% for the Class III restorations and 78.6 +/- 3.7% to 67.7 +/- 4.2% for the Class V restorations. The main reasons for replacement were general surface discoloration, secondary caries and fracture. The chemically activated composite restorative materials available at the time of initiating this study produced comparable performances in general dental practice when used without enamel and dentine bonding techniques. This suggests that more general practice-based clinical studies are needed to determine whether or not improvements in materials and techniques are effectively transferred to the general practice situation.

  3. Marketing child survival.

    PubMed

    Grant, J P

    1984-01-01

    Growth monitoring charts, packets of oral rehydration salts (ORS), and vaccines, are inexpensive, life-saving, growth-protecting technologies which can enable parents to protect their children against the worst effects of poverty. Similarly, a matrix of current and easily understandable information about pregnancy, breast feeding, weaning, feeding during and immediately after illness, child spacing, and preparing and using home-made oral rehydration solutions, also could empower parents to protect the lives and the health of their children. The question arises as to how can these technologies and this information be put at the disposal of millions of families in the low-income world. The initial task of the Child Survival and Development Revolution is the communication of what is now possible, yet little is known about how to communicate information whose principal value is to the poor. There are 2 large-scale precedents: the Green Revolution, which in many instances succeeded in putting into the hands of thousands of small and large farmers the techniques and the knowledge which enabled them to double and treble the yields from their lands; and the campaign to put the knowledge and the means of family planning at the disposal of many millions of people. There are 2 lessons to be learned from these precedents: they have shown that the way to promote a people's technology and to put information at the disposal of the majority is by mobilizing all possible resources and working through all possible channels both to create the demand and to meet it; and neither the Green Revolution nor the family planning movement rally took off until they were viewed as political and economic priorities and given the full support of the nation's political leadership. Nowhere are these 2 lessons more clearly illustrated than in present-day Indonesia. Because the campaign for family planning was given high personal and political priority by the President, and because 85% of all family

  4. Donor Chimerism Early after Reduced-intensity Conditioning Hematopoietic Stem Cell Transplantation Predicts Relapse and Survival

    PubMed Central

    Koreth, John; Kim, Haesook T.; Nikiforow, Sarah; Milford, Edgar L.; Armand, Philippe; Cutler, Corey; Glotzbecker, Brett; Ho, Vincent T.; Antin, Joseph H.; Soiffer, Robert J.; Ritz, Jerome; Alyea, Edwin P.

    2015-01-01

    The impact of early donor cell chimerism on outcomes of T-replete reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) is ill-defined. We evaluated day 30 (D30) and 100 (D100) total donor cell chimerism after RIC HSCT undertaken between 2002 and 2010 at our institution, excluding patients who died or relapsed before D30. When available, donor T-cell chimerism was also assessed. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), relapse and non-relapse mortality (NRM). 688 patients with hematologic malignancies (48% myeloid; 52% lymphoid) and a median age of 57 years (range, 18-74) undergoing RIC HSCT with T-replete donor grafts (97% peripheral blood; 92% HLA-matched) and median follow-up of 58.2 months (range, 12.6-120.7) were evaluated. In multivariable analysis total donor cell and T-cell chimerism at D30 and D100 each predicted RIC HSCT outcomes, with D100 total donor cell chimerism most predictive. D100 total donor cell chimerism <90% was associated with increased relapse (HR 2.54, 95% CI 1.83-3.51, p<0.0001), impaired PFS (HR 2.01, 95% CI 1.53-2.65, p<0.0001) and worse OS (1.50, 95% CI 1.11-2.04, p=0.009), but not NRM (HR 0.76; 95% CI 0.44-2.27, p=0.33). There was no additional utility of incorporating sustained D30-D100 total donor cell chimerism, or T-cell chimerism. Low donor chimerism early after RIC HSCT is an independent risk factor for relapse and impaired survival. Donor chimerism assessment early after RIC HSCT can prognosticate for long-term outcomes and help identify high-risk patient cohorts that may benefit from additional therapeutic interventions. PMID:24907627

  5. Impact of Screening and Risk Factors for Local Recurrence and Survival After Conservative Surgery and Radiotherapy for Early Breast Cancer: Results From a Large Series With Long-Term Follow-Up

    SciTech Connect

    Kunkler, Ian H.; Kerr, Gillian R.; Thomas, Jeremy S.; Jack, Wilma J.L.; Bartlett, John M.S.; Pedersen, Hans C.; Cameron, David A.; Dixon, J. Michael; Chetty, Udi

    2012-07-01

    Purpose: To investigate conventional prognostic factors for ipsilateral breast tumor recurrence (IBTR), distant metastasis (DM), and survival after breast-conserving therapy (BCT) in screen-detected and symptomatic cases on surveillance up to 25 years. Patients and Methods: A total of 1812 consecutive patients in three cohorts (1981-1989, 1990-1992, and 1993-1998) with T12N01M0 invasive breast cancer were treated with BCT (median follow-up, 14 years). Tumor type and grade were reviewed by a single pathologist. Hormone receptor status was measured by immunohistochemistry on tissue microarrays. A Cox proportional hazards model was used to assess independent prognostic variables for relapse and survival. Results: A total of 205 IBTR occurred, with 5-, 10-, 15-, and 20-year actuarial relapse rates of 4.5% (95% confidence interval [CI] 3.35-5.5%), 8.4% (95% CI 7.1-9.8%), 14.1% (95% CI 12.0-16%), and 17.4% (95% CI 14.5-20.2%). Number of nodes, young age, pathologic tumor size, and multifocality were significant factors for IBTR. Three hundred seventy-eight patients developed DM. The actuarial metastatic rate was 12% at 5 years and 17.9% at 10 years. Young age, number of positive nodes, pathologic tumor size, and tumor grade were significant factors for DM relapse. When conventional prognostic indices were taken into account screen-detected cancers showed no improvement in overall relapse or survival rate compared with symptomatic cases but did show a reduced risk of DM after IBTR. After 10 years IBTR relapse continued at a constant rate of 0.87% per annum. Conclusions: The Edinburgh BCT series has shown that screen-detected invasive breast cancers do not have significantly different clinical outcomes compared with symptomatic cases when pathologic risk factors are taken into account. This suggests that these patients be managed in a similar way.

  6. Influence of Statins on Survival Outcome in Patients with Metastatic Castration Resistant Prostate Cancer Treated with Abiraterone Acetate

    PubMed Central

    Boegemann, Martin; Schlack, Katrin; Fischer, Ann-Kathrin; Gerß, Joachim; Steinestel, Julie; Semjonow, Axel; Schrader, Andres Jan; Krabbe, Laura-Maria

    2016-01-01

    Objective Even though the exact mechanism is largely unknown until now, statins are supposed to improve survival outcomes in various malignancies. For prostate cancer however, statins are known to compete with dehydroepiandrosterone (DHEAS) for the transport into the cytosol both using the cell by the Solute Carrier Transporter and thus diminish the cellular uptake of DHEAS as a precursor of androgens. Abiraterone inhibits CYP17A1 and thus effectively decreases the production of all relevant androgens including DHEAS. In this study we examined whether statins still affect survival outcome in patients with metastatic castration resistant prostate cancer (mCRPC) when treated with Abiraterone. Patients and Methods 108 men with mCRPC treated with Abiraterone from 02/2010 to 07/2015 with (n = 21) or without (n = 87) concomitant treatment with statins were investigated. Progression free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier-estimates and univariate Cox-regression analysis. The influence on best clinical benefit under Abiraterone treatment was analyzed with bivariate and multivariate logistic regression analysis. Results PSA-decline ≥ 50% was not significantly different in both groups (57 vs. 53%; p = 0.73). The median PFS (9 vs. 10 months; p = 0.97) and OS (14 vs. 18 months; p = 0.77) did not differ significantly between those men treated with and without concomitant statin therapy, respectively. Accordingly, there was no improvement for best clinical benefit in patients using statins (odds ratio: 1.2 (CI: 0.4–4.2); p = 0.76). Conclusion Use of statins as concomitant medication did not improve survival outcomes or best clinical benefit in men with mCRPC treated with Abiraterone. PMID:27583544

  7. Coronary artery bypass grafting associated to aortic valve replacement in the elderly: survival and quality of life

    PubMed Central

    2012-01-01

    Myocardial ischemia is often associated to aortic valve stenosis in the elderly. Aim of this study was to evaluate the impact on survival and quality of life of CABG associated to aortic valve replacement in the septuagenarians and octogenarians. Between January 1991 and January 2010, 520 patients ageing > 70 years underwent aortic valve replacement with a mechanical prosthesis in two Institutions. They were divided into 2 groups: Group A included 406 patients undergoing isolated aortic valve replacement; Group B 114 patients receiving aortic valve replacement and CABG. A comparative analysis of long-term survival and quality of life (SF-36 test) was performed. Mean age was 74.2 ± 3.6 years (74.3 ± 3.6 in Group A, 74 ± 3.3 in Group B; p = 0.33). Hospital mortality was 9.5% (46 patients). Twenty-nine (7.8%) in Group A and 17 in Group B (15.2%)(p = 0.019). Actuarial survival was 88.5% ± 0.015 at 1 year, 81.9% ± 0.02 at 5 years, 76.6% ± 0.032 at 10 and 57.3 ± 0.1 at 15 years. Ten-year survival was 77% ± 0.034 in Group A and 77.8% ± 0.045 in Group B (p = 0.2). Multivariate analysis did not reveal associated CABG as a predictor of long term mortality. The scores obtained in the SF-36 test were similar in the two groups and significantly higher than those of the general population matched for country, age and sex (p < 0.001 in all domains). Associated CABG determines a significant increase of hospital mortality in the elderly undergoing aortic valve replacement. Survivors did not show differences in long-term outcome and quality of life according to the presence of associated CABG. PMID:22309837

  8. Survival in BRAF V600–Mutant Advanced Melanoma Treated with Vemurafenib

    PubMed Central

    Sosman, Jeffrey A.; Kim, Kevin B.; Schuchter, Lynn; Gonzalez, Rene; Pavlick, Anna C.; Weber, Jeffrey S.; McArthur, Grant A.; Hutson, Thomas E.; Moschos, Stergios J.; Flaherty, Keith T.; Hersey, Peter; Kefford, Richard; Lawrence, Donald; Puzanov, Igor; Lewis, Karl D.; Amaravadi, Ravi K.; Chmielowski, Bartosz; Lawrence, H. Jeffrey; Shyr, Yu; Ye, Fei; Li, Jiang; Nolop, Keith B.; Lee, Richard J.; Joe, Andrew K.; Ribas, Antoni

    2013-01-01

    BACKGROUND Approximately 50% of melanomas harbor activating (V600) mutations in the serine–threonine protein kinase B-RAF (BRAF). The oral BRAF inhibitor vemurafenib (PLX4032) frequently produced tumor regressions in patients with BRAF V600–mutant metastatic melanoma in a phase 1 trial and improved overall survival in a phase 3 trial. METHODS We designed a multicenter phase 2 trial of vemurafenib in patients with previously treated BRAF V600–mutant metastatic melanoma to investigate the efficacy of vemurafenib with respect to overall response rate (percentage of treated patients with a tumor response), duration of response, and overall survival. The primary end point was the overall response rate as ascertained by the independent review committee; overall survival was a secondary end point. RESULTS A total of 132 patients had a median follow-up of 12.9 months (range, 0.6 to 20.1). The confirmed overall response rate was 53% (95% confidence interval [CI], 44 to 62; 6% with a complete response and 47% with a partial response), the median duration of response was 6.7 months (95% CI, 5.6 to 8.6), and the median progression-free survival was 6.8 months (95% CI, 5.6 to 8.1). Primary progression was observed in only 14% of patients. Some patients had a response after receiving vemurafenib for more than 6 months. The median overall survival was 15.9 months (95% CI, 11.6 to 18.3). The most common adverse events were grade 1 or 2 arthralgia, rash, photosensitivity, fatigue, and alopecia. Cutaneous squamous-cell carcinomas (the majority, keratoacanthoma type) were diagnosed in 26% of patients. CONCLUSIONS Vemurafenib induces clinical responses in more than half of patients with previously treated BRAF V600–mutant metastatic melanoma. In this study with a long follow-up, the median overall survival was approximately 16 months. (Funded by Hoffmann–La Roche; ClinicalTrials.gov number, NCT00949702.) PMID:22356324

  9. Accuracy of Life Tables in Predicting Overall Survival in Candidates for Radiotherapy for Prostate Cancer

    SciTech Connect

    Walz, Jochen; Gallina, Andrea; Hutterer, Georg; Perrotte, Paul; Shariat, Shahrokh F.; Graefen, Markus; McCormack, Michael; Benard, Francois; Valiquette, Luc; Saad, Fred; Karakiewicz, Pierre I.

    2007-09-01

    Purpose: To test the accuracy of life tables (LTs) in predicting survival in men treated with radiotherapy for localized prostate cancer. Methods and Materials: We selected the records of 3,176 patients treated with radiotherapy and who had no clinical evidence of disease relapse. Life table-derived life expectancy (LE) was defined for every individual using a population-specific LT. Age, Charlson Comorbidity Index (CCI), and LT-derived LE were then used as predictors of overall mortality in Cox regression models. Predictive accuracy (PA) was estimated with the Harrell's concordance index and was internally validated with 200 bootstrap resamples. Results: The actuarial median survival was 4.7 years (mean, 6.4 years). At radiotherapy, median age was 70.6 years, median CCI was 2, and median LT-derived LE was 12 years. All variables were statistically significant predictors of overall mortality (all p values <0.001). Age (PA, 60.2%), CCI (PA, 60.1%), and LT-derived LE (PA, 60.2%) were equally accurate. Finally, when age and CCI were combined (PA, 63.2%), both variables provided more accurate mortality predictions than either variable alone (all p values = 0.01). Conclusions: Life tables have a limited ability to predict LE in patients treated with radiotherapy for prostate cancer. We, therefore, recommend the use of multivariate prognostic models that integrate several variables, such as at least age and comorbidities, to estimate LE. This might help to improve LE estimation during prostate cancer treatment decision making.

  10. Survivability of Deterministic Dynamical Systems

    NASA Astrophysics Data System (ADS)

    Hellmann, Frank; Schultz, Paul; Grabow, Carsten; Heitzig, Jobst; Kurths, Jürgen

    2016-07-01

    The notion of a part of phase space containing desired (or allowed) states of a dynamical system is important in a wide range of complex systems research. It has been called the safe operating space, the viability kernel or the sunny region. In this paper we define the notion of survivability: Given a random initial condition, what is the likelihood that the transient behaviour of a deterministic system does not leave a region of desirable states. We demonstrate the utility of this novel stability measure by considering models from climate science, neuronal networks and power grids. We also show that a semi-analytic lower bound for the survivability of linear systems allows a numerically very efficient survivability analysis in realistic models of power grids. Our numerical and semi-analytic work underlines that the type of stability measured by survivability is not captured by common asymptotic stability measures.

  11. [Physical activity and cancer survival].

    PubMed

    Romieu, Isabelle; Touillaud, Marina; Ferrari, Pietro; Bignon, Yves-Jean; Antoun, Sami; Berthouze-Aranda, Sophie; Bachmann, Patrick; Duclos, Martine; Ninot, Grégory; Romieu, Gilles; Sénesse, Pierre; Behrendt, Jan; Balosso, Jacques; Pavic, Michel; Kerbrat, Pierre; Serin, Daniel; Trédan, Olivier; Fervers, Béatrice

    2012-10-01

    Physical activity has been shown in large cohort studies to positively impact survival in cancer survivors. Existing randomized controlled trials showed a beneficial effect of physical activity on physical fitness, quality of life, anxiety and self-esteem; however, the small sample size, the short follow-up and the lack of standardization of physical activity intervention across studies impaired definite conclusion in terms of survival. Physical activity reduces adiposity and circulating estrogen levels and increases insulin sensitivity among other effects. A workshop was conducted at the International Agency for Research on Cancer in April 2011 to discuss the role of physical activity on cancer survival and the methodology to develop multicentre randomized intervention trials, including the type of physical activity to implement and its association with nutritional recommendations. The authors discuss the beneficial effect of physical activity on cancer survival with a main focus on breast cancer and report the conclusions from this workshop. PMID:24007856

  12. Survivability of Deterministic Dynamical Systems.

    PubMed

    Hellmann, Frank; Schultz, Paul; Grabow, Carsten; Heitzig, Jobst; Kurths, Jürgen

    2016-01-01

    The notion of a part of phase space containing desired (or allowed) states of a dynamical system is important in a wide range of complex systems research. It has been called the safe operating space, the viability kernel or the sunny region. In this paper we define the notion of survivability: Given a random initial condition, what is the likelihood that the transient behaviour of a deterministic system does not leave a region of desirable states. We demonstrate the utility of this novel stability measure by considering models from climate science, neuronal networks and power grids. We also show that a semi-analytic lower bound for the survivability of linear systems allows a numerically very efficient survivability analysis in realistic models of power grids. Our numerical and semi-analytic work underlines that the type of stability measured by survivability is not captured by common asymptotic stability measures. PMID:27405955

  13. The Survival of the Wisest

    ERIC Educational Resources Information Center

    Salk, Jonas

    1975-01-01

    Suggests that humans differ from other living organisms in the ability to exercise learned behavior and the individual will, which may allow people to make the changes in values necessary to survive on this planet. (DW)

  14. Natural Freedom and Wilderness Survival

    ERIC Educational Resources Information Center

    Welton, George E.

    1978-01-01

    The "naturalism" of Jean Jacques Rousseau offers a philosophical base for wilderness survival: the renewal of participants in nature so that they can reenter civilization with a proper balance of natural and civil liberty. (MJB)

  15. Staying Alive: Problems of Survival.

    ERIC Educational Resources Information Center

    Stalheim, Bill

    1990-01-01

    Presented is an approach to the teaching of biological diversity using the theme of survival. Teaching methods for this approach and the advantages of its use are discussed. A suggested course outline is included. (CW)

  16. Survivability of Deterministic Dynamical Systems

    PubMed Central

    Hellmann, Frank; Schultz, Paul; Grabow, Carsten; Heitzig, Jobst; Kurths, Jürgen

    2016-01-01

    The notion of a part of phase space containing desired (or allowed) states of a dynamical system is important in a wide range of complex systems research. It has been called the safe operating space, the viability kernel or the sunny region. In this paper we define the notion of survivability: Given a random initial condition, what is the likelihood that the transient behaviour of a deterministic system does not leave a region of desirable states. We demonstrate the utility of this novel stability measure by considering models from climate science, neuronal networks and power grids. We also show that a semi-analytic lower bound for the survivability of linear systems allows a numerically very efficient survivability analysis in realistic models of power grids. Our numerical and semi-analytic work underlines that the type of stability measured by survivability is not captured by common asymptotic stability measures. PMID:27405955

  17. [Physical activity and cancer survival].

    PubMed

    Romieu, Isabelle; Touillaud, Marina; Ferrari, Pietro; Bignon, Yves-Jean; Antoun, Sami; Berthouze-Aranda, Sophie; Bachmann, Patrick; Duclos, Martine; Ninot, Grégory; Romieu, Gilles; Sénesse, Pierre; Behrendt, Jan; Balosso, Jacques; Pavic, Michel; Kerbrat, Pierre; Serin, Daniel; Trédan, Olivier; Fervers, Béatrice

    2012-10-01

    Physical activity has been shown in large cohort studies to positively impact survival in cancer survivors. Existing randomized controlled trials showed a beneficial effect of physical activity on physical fitness, quality of life, anxiety and self-esteem; however, the small sample size, the short follow-up and the lack of standardization of physical activity intervention across studies impaired definite conclusion in terms of survival. Physical activity reduces adiposity and circulating estrogen levels and increases insulin sensitivity among other effects. A workshop was conducted at the International Agency for Research on Cancer in April 2011 to discuss the role of physical activity on cancer survival and the methodology to develop multicentre randomized intervention trials, including the type of physical activity to implement and its association with nutritional recommendations. The authors discuss the beneficial effect of physical activity on cancer survival with a main focus on breast cancer and report the conclusions from this workshop.

  18. Customer service skills for survival.

    PubMed

    McAtee, L F

    1999-11-01

    As APICS practitioners, we all must share a common goal. How can we contribute to our company's success? Success can be measured in positive terms of market share, growth, profitability, return on investment, or some combination thereof. Each company must establish its own definition of success. For the purposes of this article, success will be equated to one word that we can all readily identify with: survival. What skills do we need to survive in the marketplace of the next millennium?

  19. Long-term haemodialysis survival

    PubMed Central

    Nielsen, Arne Høj; Hansen, Henrik Post

    2012-01-01

    Haemodialysis (HD) treatment for end-stage renal disease bears a poor prognosis. We present a case of a patient who, apart from two transplant periods lasting 8 months in all, was treated with conventional in-centre HD three times a week and who survived for 41 years. Patients should be aware that there is no theoretical upper limit for patient survival on HD. PMID:22833810

  20. Youth Offender Care Needs Assessment Tool (YO-CNAT): an actuarial risk assessment tool for predicting problematic child-rearing situations in juvenile offenders on the basis of police records.

    PubMed

    van der Put, Claudia E; Stams, Geert Jan J M

    2013-12-01

    In the juvenile justice system, much attention is paid to estimating the risk for recidivism among juvenile offenders. However, it is also important to estimate the risk for problematic child-rearing situations (care needs) in juvenile offenders, because these problems are not always related to recidivism. In the present study, an actuarial care needs assessment tool for juvenile offenders, the Youth Offender Care Needs Assessment Tool (YO-CNAT), was developed to predict the probability of (a) a future supervision order imposed by the child welfare agency, (b) a future entitlement to care indicated by the youth care agency, and (c) future incidents involving child abuse, domestic violence, and/or sexual norm trespassing behavior at the juvenile's address. The YO-CNAT has been developed for use by the police and is based solely on information available in police registration systems. It is designed to assist a police officer without clinical expertise in making a quick assessment of the risk for problematic child-rearing situations. The YO-CNAT was developed on a sample of 1,955 juvenile offenders and was validated on another sample of 2,045 juvenile offenders. The predictive validity (area under the receiver-operating-characteristic curve) scores ranged between .70 (for predicting future entitlement to care) and .75 (for predicting future worrisome incidents at the juvenile's address); therefore, the predictive accuracy of the test scores of the YO-CNAT was sufficient to justify its use as a screening instrument for the police in deciding to refer a juvenile offender to the youth care agency for further assessment into care needs.

  1. Youth Offender Care Needs Assessment Tool (YO-CNAT): an actuarial risk assessment tool for predicting problematic child-rearing situations in juvenile offenders on the basis of police records.

    PubMed

    van der Put, Claudia E; Stams, Geert Jan J M

    2013-12-01

    In the juvenile justice system, much attention is paid to estimating the risk for recidivism among juvenile offenders. However, it is also important to estimate the risk for problematic child-rearing situations (care needs) in juvenile offenders, because these problems are not always related to recidivism. In the present study, an actuarial care needs assessment tool for juvenile offenders, the Youth Offender Care Needs Assessment Tool (YO-CNAT), was developed to predict the probability of (a) a future supervision order imposed by the child welfare agency, (b) a future entitlement to care indicated by the youth care agency, and (c) future incidents involving child abuse, domestic violence, and/or sexual norm trespassing behavior at the juvenile's address. The YO-CNAT has been developed for use by the police and is based solely on information available in police registration systems. It is designed to assist a police officer without clinical expertise in making a quick assessment of the risk for problematic child-rearing situations. The YO-CNAT was developed on a sample of 1,955 juvenile offenders and was validated on another sample of 2,045 juvenile offenders. The predictive validity (area under the receiver-operating-characteristic curve) scores ranged between .70 (for predicting future entitlement to care) and .75 (for predicting future worrisome incidents at the juvenile's address); therefore, the predictive accuracy of the test scores of the YO-CNAT was sufficient to justify its use as a screening instrument for the police in deciding to refer a juvenile offender to the youth care agency for further assessment into care needs. PMID:23815118

  2. Probabilistic Survivability Versus Time Modeling

    NASA Technical Reports Server (NTRS)

    Joyner, James J., Sr.

    2015-01-01

    This technical paper documents Kennedy Space Centers Independent Assessment team work completed on three assessments for the Ground Systems Development and Operations (GSDO) Program to assist the Chief Safety and Mission Assurance Officer (CSO) and GSDO management during key programmatic reviews. The assessments provided the GSDO Program with an analysis of how egress time affects the likelihood of astronaut and worker survival during an emergency. For each assessment, the team developed probability distributions for hazard scenarios to address statistical uncertainty, resulting in survivability plots over time. The first assessment developed a mathematical model of probabilistic survivability versus time to reach a safe location using an ideal Emergency Egress System at Launch Complex 39B (LC-39B); the second used the first model to evaluate and compare various egress systems under consideration at LC-39B. The third used a modified LC-39B model to determine if a specific hazard decreased survivability more rapidly than other events during flight hardware processing in Kennedys Vehicle Assembly Building (VAB).Based on the composite survivability versus time graphs from the first two assessments, there was a soft knee in the Figure of Merit graphs at eight minutes (ten minutes after egress ordered). Thus, the graphs illustrated to the decision makers that the final emergency egress design selected should have the capability of transporting the flight crew from the top of LC 39B to a safe location in eight minutes or less. Results for the third assessment were dominated by hazards that were classified as instantaneous in nature (e.g. stacking mishaps) and therefore had no effect on survivability vs time to egress the VAB. VAB emergency scenarios that degraded over time (e.g. fire) produced survivability vs time graphs that were line with aerospace industry norms.

  3. Multiple tumours in survival estimates.

    PubMed

    Rosso, Stefano; De Angelis, Roberta; Ciccolallo, Laura; Carrani, Eugenio; Soerjomataram, Isabelle; Grande, Enrico; Zigon, Giulia; Brenner, Hermann

    2009-04-01

    In international comparisons of cancer registry based survival it is common practice to restrict the analysis to first primary tumours and exclude multiple cancers. The probability of correctly detecting subsequent cancers depends on the registry's running time, which results in different proportions of excluded patients and may lead to biased comparisons. We evaluated the impact on the age-standardised relative survival estimates of also including multiple primary tumours. Data from 2,919,023 malignant cancers from 69 European cancer registries participating in the EUROCARE-4 collaborative study were used. A total of 183,683 multiple primary tumours were found, with an overall proportion of 6.3% over all the considered cancers, ranging from 0.4% (Naples, Italy) to 12.9% (Iceland). The proportion of multiple tumours varied greatly by type of tumour, being higher for those with high incidence and long survival (breast, prostate and colon-rectum). Five-year relative survival was lower when including patients with multiple cancers. For all cancers combined the average difference was -0.4 percentage points in women and -0.7 percentage points in men, and was greater for older registries. Inclusion of multiple tumours led to lower survival in 44 out of 45 cancer sites analysed, with the greatest differences found for larynx (-1.9%), oropharynx (-1.5%), and penis (-1.3%). Including multiple primary tumours in survival estimates for international comparison is advisable because it reduces the bias due to different observation periods, age, registration quality and completeness of registration. The general effect of inclusion is to reduce survival estimates by a variable amount depending on the proportion of multiple primaries and cancer site.

  4. CYR61/CCN1 overexpression in the myeloma microenvironment is associated with superior survival and reduced bone disease

    PubMed Central

    Stewart, James P.; Bam, Rakesh; Qu, Pingping; Barlogie, Bart; van Rhee, Frits; Shaughnessy, John D.; Epstein, Joshua; Yaccoby, Shmuel

    2014-01-01

    Secreted protein CCN1, encoded by CYR61, is involved in wound healing, angiogenesis, and osteoblast differentiation. We identified CCN1 as a microenvironmental factor produced by mesenchymal cells and overexpressed in bones of a subset of patients with monoclonal gammopathy of undetermined significance (MGUS), asymptomatic myeloma (AMM), and multiple myeloma (MM). Our analysis showed that overexpression of CYR61 was independently associated with superior overall survival of MM patients enrolled in our Total Therapy 3 protocol. Moreover, elevated CCN1 was associated with a longer time for MGUS/AMM to progress to overt MM. During remission from MM, high levels of CCN1 were associated with superior progression-free and overall survival and stratified patients with molecularly defined high-risk MM. Recombinant CCN1 directly inhibited in vitro growth of MM cells, and overexpression of CYR61 in MM cells reduced tumor growth and prevented bone destruction in vivo in severe combined immunodeficiency-hu mice. Signaling through αvβ3 was required for CCN1 prevention of bone disease. CYR61 expression may signify early perturbation of the microenvironment before conversion to overt MM and may be a compensatory mechanism to control MM progression. Therapeutics that upregulate CYR61 should be investigated for treating MM bone disease. PMID:25061178

  5. Pretransplantation Minimal Residual Disease Predicts Survival in Patients with Mantle Cell Lymphoma Undergoing Autologous Stem Cell Transplantation in Complete Remission.

    PubMed

    Cowan, Andrew J; Stevenson, Philip A; Cassaday, Ryan D; Graf, Solomon A; Fromm, Jonathan R; Wu, David; Holmberg, Leona A; Till, Brian G; Chauncey, Thomas R; Smith, Stephen D; Philip, Mary; Orozco, Johnnie J; Shustov, Andrei R; Green, Damian J; Libby, Edward N; Bensinger, William I; Shadman, Mazyar; Maloney, David G; Press, Oliver W; Gopal, Ajay K

    2016-02-01

    Autologous stem cell transplantation (ASCT) is standard therapy for mantle cell lymphoma (MCL) in remission after induction chemotherapy, with the best results for patients in complete remission (CR). We hypothesized that evaluation of minimal residual disease (MRD) before ASCT could further stratify outcomes for these patients. Patients with MCL who underwent ASCT in clinical CR between 1996 and 2011 with pretransplantation MRD testing were eligible. Presence of a clonal IgH rearrangement, t(11; 14) by PCR or positive flow cytometry from blood or bone marrow, was considered positive. An adjusted proportional hazards model for associations with progression-free (PFS) and overall survival (OS) was performed. Of 75 MCL patients in CR, 8 (11%) were MRD positive. MRD positivity was associated with shorter OS and PFS. The median OS for MRD-negative patients was not reached, with 82% survival at 5 years, whereas for the MRD-positive patients, median OS was 3.01 years (hazard ratio [HR], 4.04; P = .009), with a median follow-up of 5.1 years. The median PFS for MRD-negative patients was not reached with 75% PFS at 5 years, whereas for MRD-positive patients, it was 2.38 years (HR, 3.69; P = .002). MRD positivity is independently associated with poor outcomes after ASCT for MCL patients in CR.

  6. Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma

    PubMed Central

    Gopal, Ajay K.; Smith, Scott E.; Ansell, Stephen M.; Rosenblatt, Joseph D.; Savage, Kerry J.; Connors, Joseph M.; Engert, Andreas; Larsen, Emily K.; Huebner, Dirk; Fong, Abraham; Younes, Anas

    2016-01-01

    Presented here are the 5-year end-of-study results from the pivotal phase 2 trial of brentuximab vedotin in patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) after failed hematopoietic autologous stem cell transplantation. At 5 years, the overall patient population (N = 102) had an estimated overall survival (OS) rate of 41% (95% confidence interval [CI]: 31-51) and progression-free survival (PFS) rate of 22% (95% CI: 13-31). Patients who achieved a complete response (CR) to brentuximab vedotin (N = 34) had estimated OS and PFS rates of 64% (95% CI: 48-80%) and 52% (95% CI: 34-69%), respectively. The median OS and PFS were not reached in CR patients, with 13 patients (38% of all CR patients) remaining in follow-up and in remission at study closure. Of the 13 patients, 4 received consolidative hematopoietic allogeneic stem cell transplant, and 9 (9% of all enrolled patients) remain in sustained CR without receiving any further anticancer therapy after treatment with brentuximab vedotin. Of the patients who experienced treatment-emergent peripheral neuropathy, 88% experienced either resolution (73%) or improvement (14%) in symptoms. These 5-year follow-up data demonstrate that a subset of patients with R/R HL who obtained CR with single-agent brentuximab vedotin achieved long-term disease control and may potentially be cured. The trial was registered at www.clinicaltrials.gov as #NCT00848926. PMID:27432875

  7. TP53 and MDM2 single nucleotide polymorphisms influence survival in non-del(5q) myelodysplastic syndromes

    PubMed Central

    Sallman, David A.; Basiorka, Ashley A.; Irvine, Brittany A.; Zhang, Ling; Epling-Burnette, P.K.; Rollison, Dana E.; Mallo, Mar; Sokol, Lubomir; Solé, Francesc; Maciejewski, Jaroslaw; List, Alan F.

    2015-01-01

    P53 is a key regulator of many cellular processes and is negatively regulated by the human homolog of murine double minute-2 (MDM2) E3 ubiquitin ligase. Single nucleotide polymorphisms (SNPs) of either gene alone, and in combination, are linked to cancer susceptibility, disease progression, and therapy response. We analyzed the interaction of TP53 R72P and MDM2 SNP309 SNPs in relationship to outcome in patients with myelodysplastic syndromes (MDS). Sanger sequencing was performed on DNA isolated from 208 MDS cases. Utilizing a novel functional SNP scoring system ranging from +2 to −2 based on predicted p53 activity, we found statistically significant differences in overall survival (OS) (p = 0.02) and progression-free survival (PFS) (p = 0.02) in non-del(5q) MDS patients with low functional scores. In univariate analysis, only IPSS and the functional SNP score predicted OS and PFS in non-del(5q) patients. In multivariate analysis, the functional SNP score was independent of IPSS for OS and PFS. These data underscore the importance of TP53 R72P and MDM2 SNP309 SNPs in MDS, and provide a novel scoring system independent of IPSS that is predictive for disease outcome. PMID:26416416

  8. TP53 and MDM2 single nucleotide polymorphisms influence survival in non-del(5q) myelodysplastic syndromes.

    PubMed

    McGraw, Kathy L; Cluzeau, Thomas; Sallman, David A; Basiorka, Ashley A; Irvine, Brittany A; Zhang, Ling; Epling-Burnette, P K; Rollison, Dana E; Mallo, Mar; Sokol, Lubomir; Solé, Francesc; Maciejewski, Jaroslaw; List, Alan F

    2015-10-27

    P53 is a key regulator of many cellular processes and is negatively regulated by the human homolog of murine double minute-2 (MDM2) E3 ubiquitin ligase. Single nucleotide polymorphisms (SNPs) of either gene alone, and in combination, are linked to cancer susceptibility, disease progression, and therapy response. We analyzed the interaction of TP53 R72P and MDM2 SNP309 SNPs in relationship to outcome in patients with myelodysplastic syndromes (MDS). Sanger sequencing was performed on DNA isolated from 208 MDS cases. Utilizing a novel functional SNP scoring system ranging from +2 to -2 based on predicted p53 activity, we found statistically significant differences in overall survival (OS) (p = 0.02) and progression-free survival (PFS) (p = 0.02) in non-del(5q) MDS patients with low functional scores. In univariate analysis, only IPSS and the functional SNP score predicted OS and PFS in non-del(5q) patients. In multivariate analysis, the functional SNP score was independent of IPSS for OS and PFS. These data underscore the importance of TP53 R72P and MDM2 SNP309 SNPs in MDS, and provide a novel scoring system independent of IPSS that is predictive for disease outcome. PMID:26416416

  9. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial

    PubMed Central

    Oza, Amit M; Cook, Adrian D; Pfisterer, Jacobus; Embleton, Andrew; Ledermann, Jonathan A; Pujade-Lauraine, Eric; Kristensen, Gunnar; Carey, Mark S; Beale, Philip; Cervantes, Andrés; Park-Simon, Tjoung-Won; Rustin, Gordon; Joly, Florence; Mirza, Mansoor R; Plante, Marie; Quinn, Michael; Poveda, Andrés; Jayson, Gordon C; Stark, Dan; Swart, Ann Marie; Farrelly, Laura; Kaplan, Richard; Parmar, Mahesh K B; Perren, Timothy J

    2015-01-01

    Summary Background The ICON7 trial previously reported improved progression-free survival in women with ovarian cancer with the addition of bevacizumab to standard chemotherapy, with the greatest effect in patients at high risk of disease progression. We report the final overall survival results of the trial. Methods ICON7 was an international, phase 3, open-label, randomised trial undertaken at 263 centres in 11 countries across Europe, Canada, Australia and New Zealand. Eligible adult women with newly diagnosed ovarian cancer that was either high-risk early-stage disease (International Federation of Gynecology and Obstetrics [FIGO] stage I–IIa, grade 3 or clear cell histology) or more advanced disease (FIGO stage IIb–IV), with an Eastern Cooperative Oncology Group performance status of 0–2, were enrolled and randomly assigned in a 1:1 ratio to standard chemotherapy (six 3-weekly cycles of intravenous carboplatin [AUC 5 or 6] and paclitaxel 175 mg/m2 of body surface area) or the same chemotherapy regimen plus bevacizumab 7·5 mg per kg bodyweight intravenously every 3 weeks, given concurrently and continued with up to 12 further 3-weekly cycles of maintenance therapy. Randomisation was done by a minimisation algorithm stratified by FIGO stage, residual disease, interval between surgery and chemotherapy, and Gynecologic Cancer InterGroup group. The primary endpoint was progression-free survival; the study was also powered to detect a difference in overall survival. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN91273375. Findings Between Dec 18, 2006, and Feb 16, 2009, 1528 women were enrolled and randomly assigned to receive chemotherapy (n=764) or chemotherapy plus bevacizumab (n=764). Median follow-up at the end of the trial on March 31, 2013, was 48·9 months (IQR 26·6–56·2), at which point 714 patients had died (352 in the chemotherapy group and 362 in the

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

    PubMed Central

    Xiao, Yao; Tang, Jie; OuYang, Pu-Yun; Su, Zhen; Xie, Fang-Yun

    2016-01-01

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

  11. IMRT for Sinonasal Tumors Minimizes Severe Late Ocular Toxicity and Preserves Disease Control and Survival

    SciTech Connect

    Duprez, Frederic; Madani, Indira; Morbee, Lieve; Bonte, Katrien; Deron, Philippe; Domjan, Vilmos; Boterberg, Tom; De Gersem, Werner; De Neve, Wilfried

    2012-05-01

    Purpose: To report late ocular (primary endpoint) and other toxicity, disease control, and survival (secondary endpoints) after intensity-modulated radiotherapy (IMRT) for sinonasal tumors. Methods and Materials: Between 1998 and 2009, 130 patients with nonmetastatic sinonasal tumors were treated with IMRT at Ghent University Hospital. Prescription doses were 70 Gy (n = 117) and 60-66 Gy (n = 13) at 2 Gy per fraction over 6-7 weeks. Most patients had adenocarcinoma (n = 82) and squamous cell carcinoma (n = 23). One hundred and one (101) patients were treated postoperatively. Of 17 patients with recurrent tumors, 9 were reirradiated. T-stages were T1-2 (n = 39), T3 (n = 21), T4a (n = 38), and T4b (n = 22). Esthesioneuroblastoma was staged as Kadish A, B, and C in 1, 3, and 6 cases, respectively. Results: Median follow-up was 52, range 15-121 months. There was no radiation-induced blindness in 86 patients available for late toxicity assessment ({>=}6 month follow-up). We observed late Grade 3 tearing in 10 patients, which reduced to Grade 1-2 in 5 patients and Grade 3 visual impairment because of radiation-induced ipsilateral retinopathy and neovascular glaucoma in 1 patient. There was no severe dry eye syndrome. The worst grade of late ocular toxicity was Grade 3 (n = 11), Grade 2 (n = 31), Grade 1 (n = 33), and Grade 0 (n = 11). Brain necrosis and osteoradionecrosis occurred in 6 and 1 patients, respectively. Actuarial 5-year local control and overall survival were 59% and 52%, respectively. On multivariate analysis local control was negatively affected by cribriform plate and brain invasion (p = 0.044 and 0.029, respectively) and absence of surgery (p = 0.009); overall survival was negatively affected by cribriform plate and orbit invasion (p = 0.04 and <0.001, respectively) and absence of surgery (p = 0.001). Conclusions: IMRT for sinonasal tumors allowed delivering high doses to targets at minimized ocular toxicity, while maintaining disease control and survival

  12. Pretreatment Serum Testosterone and Androgen Deprivation: Effect on Disease Recurrence and Overall Survival in Prostate Cancer Patients Treated With Brachytherapy

    SciTech Connect

    Taira, Al V.; Merrick, Gregory S. Galbreath, Robert W.; Butler, Wayne M.; Wallner, Kent E.; Allen, Zachariah A.; Lief, Jonathan H.; Adamovich, Edward

    2009-07-15

    Purpose: Low testosterone has been implicated as a possible adverse prognostic factor in patients with newly diagnosed prostate cancer. We evaluated the impact of pretreatment serum testosterone on survival after prostate brachytherapy. Methods and Materials: From October 2001 to November 2004, 619 patients underwent brachytherapy and 546 had a pretreatment serum testosterone level measured. Pretreatment serum testosterone levels were assigned by the following criteria: below-normal (n = 105), low normal (n = 246), mid normal (n = 132), high normal (n = 50), and above normal (n = 13). Median follow-up was 5.2 years. Cause of death was determined for each deceased patient. Results: Six-year biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) were 97.7%, 99.8%, and 89.2%. When comparing patients with low or low normal testosterone with those with average or higher testosterone, there was no significant difference in bPFS (97.6% vs. 98.4%; p = 0.72), CSS (99.8% vs. 100%; p = 0.72), or OS (88.9% vs. 90.8%; p = 0.73). Among patients with average and higher pretreatment testosterone, there was no significant difference in outcomes when comparing patients who did and did not receive androgen deprivation therapy (ADT). For patients with low or low normal testosterone levels, there was no significant difference in bPFS or CSS when comparing patients who did and did not receive ADT. However, there was a trend toward lower OS in patients with baseline lower testosterone levels who also received ADT (83.9% vs. 91.3%, p = 0.075). Conclusions: Low pretreatment testosterone levels alone did not affect disease recurrence or OS. Patients with baseline low testosterone who also were treated with ADT had a trend toward decreased OS.

  13. Surviving cancer without compromising aspirations.

    PubMed

    McGregor, Sandra

    2011-07-01

    This short paper is a reflection of how one person coped, survived and grew following numerous metastatic incidences over a 20 year period. Surviving cancer is a complex process but coping with the threat of regular recurrence has required a coping strategy that embraced the disease, set it aside and refused to compromise hopes, dreams and future life. Central to this personal journey has been the need to redefine normality, live with and set aside the fear of future metastases and death and find an answer and meaning in a changing biology, increased morbidity and possible mortality. This paper contends that not compromising the direction of travel and being able to focus on a career has ensured that survival was valuable and valued. A working environment in which students' problems have been immediate has produced different stressors. These have ultimately forced personal worries to be set aside, while living with cancer has become normal and accepted. PMID:21514884

  14. Surviving cancer without compromising aspirations.

    PubMed

    McGregor, Sandra

    2011-07-01

    This short paper is a reflection of how one person coped, survived and grew following numerous metastatic incidences over a 20 year period. Surviving cancer is a complex process but coping with the threat of regular recurrence has required a coping strategy that embraced the disease, set it aside and refused to compromise hopes, dreams and future life. Central to this personal journey has been the need to redefine normality, live with and set aside the fear of future metastases and death and find an answer and meaning in a changing biology, increased morbidity and possible mortality. This paper contends that not compromising the direction of travel and being able to focus on a career has ensured that survival was valuable and valued. A working environment in which students' problems have been immediate has produced different stressors. These have ultimately forced personal worries to be set aside, while living with cancer has become normal and accepted.

  15. Survival of Sami cancer patients

    PubMed Central

    Soininen, Leena; Pokhrel, Arun; Dyba, Tadek; Pukkala, Eero; Hakulinen, Timo

    2012-01-01

    Objectives The incidence of cancer among the indigenous Sami people of Northern Finland is lower than among the Finnish general population. The survival of Sami cancer patients is not known, and therefore it is the object of this study. Study design The cohort consisted of 2,091 Sami and 4,161 non-Sami who lived on 31 December 1978 in the two Sami municipalities of Inari and Utsjoki, which are located in Northern Finland and are 300–500 km away from the nearest central hospital. The survival experience of Sami and non-Sami cancer patients diagnosed in this cohort during 1979–2009 was compared with that of the Finnish patients outside the cohort. Methods The Sami and non-Sami cancer patients were matched to other Finnish cancer patients for gender, age and year of diagnosis and for the site of cancer. An additional matching was done for the stage at diagnosis. Cancer-specific survival analyses were made using the Kaplan–Meier method and Cox regression modelling. Results There were 204 Sami and 391 non-Sami cancer cases in the cohort, 20,181 matched controls without matching with stage, and 7,874 stage-matched controls. In the cancer-specific analysis without stage variable, the hazard ratio for Sami was 1.05 (95% confidence interval 0.85–1.30) and for non-Sami 1.02 (0.86–1.20), indicating no difference between the survival of those groups and other patients in Finland. Likewise, when the same was done by also matching the stage, there was no difference in cancer survival. Conclusion Long distances to medical care or Sami ethnicity have no influence on the cancer patient survival in Northern Finland. PMID:22765936

  16. Survival Benefit for Pediatric Patients With Recurrent Ependymoma Treated With Reirradiation

    SciTech Connect

    Bouffet, Eric; Ballourah, Walid; Bartels, Ute K.; Tsangaris, Elena; Huang, Annie; Mabbot, Donald J.; Laperriere, Normand; Tabori, Uri

    2012-08-01

    Purpose: The outcome of recurrent ependymoma in children is dismal. Reirradiation has been proposed as an effective modality for ependymoma at relapse. However, the toxicity and outcome benefits of this approach have not been well established. Methods and Materials: We conducted a retrospective population-based study of all patients with recurrent ependymoma treated between 1986 and 2010 in our institution. Demographic, treatment, and outcome data were analyzed for the entire cohort. Results: Of 113 patients with intracranial ependymoma, 47 patients relapsed. At the time of relapse, 29 patients were treated with surgical resection and/or chemotherapy, and 18 patients received full-dose ({>=}54 Gy focal and/or craniospinal) reirradiation with or without surgery at recurrence. Reirradiation was tolerated well with no severe acute complications noticed. Three-year overall survival was 7% {+-} 6% and 81% {+-} 12% for nonreirradiated and reirradiated patients, respectively (p < 0.0001). Time to second progression after reirradiation was significantly longer than time to first progression. This surprising phenomenon was associated with improved progression-free survival for tumors with evidence of DNA damage (n = 15; p = 0.002). At a mean follow-up of 3.73 years, only 2/18 patients had endocrine dysfunction, and 1 patient required special education support. However, a decline in intellectual function from pre- to postreirradiation assessment was observed. Conclusions: Reirradiation is an effective treatment that may change the natural history of recurrent ependymoma in children. However, this change may be associated with increased neurocognitive toxicity. Additional follow-up is needed to determine the risk of late recurrence, secondary radiation-induced tumors, and long-term functional outcome of these patients.

  17. Survival analysis in patients with newly diagnosed glioblastoma using pre- and postradiotherapy MR spectroscopic imaging†

    PubMed Central

    Li, Yan; Lupo, Janine M.; Parvataneni, Rupa; Lamborn, Kathleen R.; Cha, Soonmee; Chang, Susan M.; Nelson, Sarah J.

    2013-01-01

    Background The objective of this study was to examine the predictive value of parameters of 3D 1H magnetic resonance spectroscopic imaging (MRSI) prior to treatment with radiation/chemotherapy (baseline) and at a postradiation 2-month follow-up (F2mo) in relationship to 6-month progression-free survival (PFS6) and overall survival (OS). Methods Sixty-four patients with newly diagnosed glioblastoma multiforme (GBM) being treated with radiation and concurrent chemotherapy were involved in this study. Evaluated were metabolite indices and metabolite ratios. Logistic linear regression and Cox proportional hazards models were utilized to evaluate PFS6 and OS, respectively. These analyses were adjusted by age and MR scanner field strength (1.5 T or 3 T). Stepwise regression was performed to determine a subset of the most relevant variables. Results Associated with shorter PFS6 were a decrease in the ratio of N-acetyl aspartate to choline-containing compounds (NAA/Cho) in the region with a Cho-to-NAA index (CNI) >3 at baseline and an increase of the CNI within elevated CNI regions (>2) at F2mo. Patients with higher normalized lipid and lactate at either time point had significantly worse OS. Patients who had larger volumes with abnormal CNI at F2mo had worse PFS6 and OS. Conclusions Our study found more 3D MRSI parameters that predicted PFS6 and OS for patients with GBM than did anatomic, diffusion, or perfusion imaging, which were previously evaluated in the same population of patients. PMID:23393206

  18. Pretreatment neutrophil-to-lymphocyte ratio as a survival predictor for small-cell lung cancer

    PubMed Central

    Wang, Xin; Teng, Feifei; Kong, Li; Yu, Jinming

    2016-01-01

    Background The inflammatory response indexes, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have prognostic value for a variety of cancers. However, their prognostic value for small-cell lung cancer (SCLC) has been rarely reported. In this study, we monitored changes of NLR and PLR along with the clinical outcomes in patients with limited-stage and extensive-stage SCLC who received standard treatments. Materials and methods We retrospectively reviewed the records of 153 patients who were pathologically diagnosed with SCLC and collected their hematological data at different time points during disease and treatment process. Kaplan–Meier analysis and Cox proportional hazards models were used to determine the prognostic significance of NLR and PLR for overall survival (OS) and progression-free survival (PFS). Results The median OS and PFS for all patients were 23.3 months and 11.0 months, respectively. After applying cutoffs of 3.2 for NLR and 122.7 for PLR, NLR, but not PLR, showed independent prognostic significance. High-NLR group was associated with shorter median OS (high vs low, 18.0 months vs 31.0 months, P<0.01) and shorter PFS (high vs low, 9.3 months vs 13.0 months, P=0.006). The cumulative 3-year OS rate and 3-year PFS rate of high-NLR group versus low-NLR group were 14.3% versus 37.3% and 8.6% versus 22.9%, respectively. In the multivariate analysis, both disease stage and NLR at diagnosis were independent prognostic factors for OS and PFS. Conclusion The NLR at diagnosis showed significant prognostic value for clinical outcomes in SCLC patients treated with chemoradiotherapy. As an effective biomarker of host immune status, NLR could potentially help monitoring disease progression and adjusting treatment plans. PMID:27703374

  19. Quantification of mutant alleles in circulating tumor DNA can predict survival in lung cancer

    PubMed Central

    Ye, Xin; Bai, Hua; Wang, Zhijie; Sun, Yun; Zhao, Jun; An, Tongtong; Duan, Jianchun; Wu, Meina; Wang, Jie

    2016-01-01

    Purpose We aimed to investigate the feasibility of droplet digital PCR (ddPCR) for the quantitative and dynamic detection of EGFR mutations and next generation sequencing (NGS) for screening EGFR-tyrosine kinase inhibitors (EGFR-TKIs) resistance-relevant mutations in circulating tumor DNA (ctDNA) from advanced lung adenocarcinoma (ADC) patients. Results Detection limit of EGFR mutation in ctDNA by ddPCR was 0.04%. Taking the EGFR mutation in tumor tissue as the golden standard, the concordance of EGFR mutations detected in ctDNA was 74% (54/73). Patients with EGFR mutation in ctDNA (n = 54) superior progression-free survival (PFS, median, 12.6 vs. 6.7 months, P < 0.001) and overall survival (OS, median, 35.6 vs. 23.8 months, P = 0.028) compared to those with EGFR wild type in ctDNA (n = 19). Patients with high EGFR-mutated abundance in ctDNA (> 5.15%) showed better PFS compared to those with low EGFR mutated abundance (≤ 5.15%) (PFS, median, 15.4 vs. 11.1 months, P = 0.021). NGS results showed that 66.6% (8/12) total mutational copy number were elevated and 76.5% (26/34) mutual mutation frequency increased after disease progression. Methods Seventy-three advanced ADC patients with tumor tissues carrying EGFR mutations and their matched pre- and post-EGFR-TKIs plasma samples were enrolled in this study. Absolute quantities of plasma EGFR mutant and wild-type alleles were measured by ddPCR. Multi-genes testing was performed using NGS in 12 patients. Conclusions Dynamic and quantitative analysis of EGFR mutation in ctDNA could guide personalized therapy for advanced ADC. NGS shows good performance in multiple genes testing especially novel and uncommon genes. PMID:26989078

  20. The Women's Guide to Surviving Graduate School. Graduate Survival Skills.

    ERIC Educational Resources Information Center

    Rittner, Barbara; Trudeau, Patricia

    This guidebook offers advice to women students on surviving and thriving in graduate school. It takes the reader from the graduate school selection process to completing the program successfully. Written in a informal style, the 11 chapters include: (1) "Should You Go to Graduate School?" (pros and cons of attending graduate school, deciding what…

  1. Survival analysis and neural nets.

    PubMed

    Liestøl, K; Andersen, P K; Andersen, U

    1994-06-30

    We consider feed-forward neural nets and their relation to regression models for survival data. We show how the back-propagation algorithm may be used to obtain maximum likelihood estimates in certain standard regression models for survival data, as well as in various generalizations of these. Examples concerning malignant melanoma and post-partum amenorrhoea during lactation are used as illustration. We conclude that although problems with the substantial number of parameters and their interpretation remain, the feed-forward neural network models are flexible extensions to the standard regression models and thereby candidates for use in prediction and exploratory analyses in larger data sets.

  2. Campylobacter virulence and survival factors.

    PubMed

    Bolton, Declan J

    2015-06-01

    Despite over 30 years of research, campylobacteriosis is the most prevalent foodborne bacterial infection in many countries including in the European Union and the United States of America. However, relatively little is known about the virulence factors in Campylobacter or how an apparently fragile organism can survive in the food chain, often with enhanced pathogenicity. This review collates information on the virulence and survival determinants including motility, chemotaxis, adhesion, invasion, multidrug resistance, bile resistance and stress response factors. It discusses their function in transition through the food processing environment and human infection. In doing so it provides a fundamental understanding of Campylobacter, critical for improved diagnosis, surveillance and control.

  3. A Quasi Actuarial Prospect for Individual Assessment.

    ERIC Educational Resources Information Center

    Owens, William A.

    A conceptual model of individual assessment through the use of biodata responses with minimal input information is outlined. The process is considered especially applicable to industrial psychology. A scored autobiographical data form, which measures the individual's past behavior and experiences, provides for assignment to a specific subgroup…

  4. The addition of rituximab to fludarabine and cyclophosphamide chemotherapy results in a significant improvement in overall survival in patients with newly diagnosed mantle cell lymphoma: results of a randomized UK National Cancer Research Institute trial

    PubMed Central

    Rule, Simon; Smith, Paul; Johnson, Peter W.M.; Bolam, Simon; Follows, George; Gambell, Joanne; Hillmen, Peter; Jack, Andrew; Johnson, Stephen; Kirkwood, Amy A; Kruger, Anton; Pocock, Christopher; Seymour, John F.; Toncheva, Milena; Walewski, Jan; Linch, David

    2016-01-01

    Mantle cell lymphoma is an incurable and generally aggressive lymphoma that is more common in elderly patients. Whilst a number of different chemotherapeutic regimens are active in this disease, there is no established gold standard therapy. Rituximab has been used widely to good effect in B-cell malignancies but there is no evidence that it improves outcomes when added to chemotherapy in this disease. We performed a randomized, open-label, multicenter study looking at the addition of rituximab to the standard chemotherapy regimen of fludarabine and cyclophosphamide in patients with newly diagnosed mantle cell lymphoma. A total of 370 patients were randomized. With a median follow up of six years, rituximab improved the median progression-free survival from 14.9 to 29.8 months (P<0.001) and overall survival from 37.0 to 44.5 months (P=0.005). This equates to absolute differences of 9.0% and 22.1% for overall and progression-free survival, respectively, at two years. Overall response rates were similar, but complete response rates were significantly higher in the rituximab arm: 52.7% vs. 39.9% (P=0.014). There was no clinically significant additional toxicity observed with the addition of rituximab. Overall, approximately 18% of patients died of non-lymphomatous causes, most commonly infections. The addition of rituximab to fludarabine and cyclophosphamide chemotherapy significantly improves outcomes in patients with mantle cell lymphoma. However, these regimens have significant late toxicity and should be used with caution. This trial has been registered (ISRCTN81133184 and clinicaltrials.gov:00641095) and is supported by the UK National Cancer Research Network. PMID:26611473

  5. Reading As a Survival Skill.

    ERIC Educational Resources Information Center

    Blosser, Patricia E.

    1980-01-01

    Described is a technique for the development of survival reading activity packets for the science classroom. The reading packets described include labels from different food and medicine products and from magazine and newspaper articles. Three types of questions were used with each packet: factual, interpretive, and application. (DS)

  6. Wilderness Emergency: Surviving the Unexpected.

    ERIC Educational Resources Information Center

    Fear, Gene

    In any unexpected survival experience, one must accept the situation with just what one has at the moment it happens, where it happens, and how it happens. Problem solving must be based on known body enemies that threaten life, their priority of influence, and their severity of threat to life. Solutions will depend on the body's energy supply,…

  7. Wilderness Survival and Outdoor Education.

    ERIC Educational Resources Information Center

    Ball, Matt

    Outdoor education is often delivered through games and activities such as nature hikes or observing an ecosystem within a 1-foot circle on the ground. Often, participants look closely at the earth only for that brief moment. Wilderness survival is another way to teach about the outdoors. It offers skills that encourage participants to become more…

  8. Cool echidnas survive the fire.

    PubMed

    Nowack, Julia; Cooper, Christine Elizabeth; Geiser, Fritz

    2016-04-13

    Fires have occurred throughout history, including those associated with the meteoroid impact at the Cretaceous-Palaeogene (K-Pg) boundary that eliminated many vertebrate species. To evaluate the recent hypothesis that the survival of the K-Pg fires by ancestral mammals was dependent on their ability to use energy-conserving torpor, we studied body temperature fluctuations and activity of an egg-laying mammal, the echidna (Tachyglossus aculeatus), often considered to be a 'living fossil', before, during and after a prescribed burn. All but one study animal survived the fire in the prescribed burn area and echidnas remained inactive during the day(s) following the fire and substantially reduced body temperature during bouts of torpor. For weeks after the fire, all individuals remained in their original territories and compensated for changes in their habitat with a decrease in mean body temperature and activity. Our data suggest that heterothermy enables mammals to outlast the conditions during and after a fire by reducing energy expenditure, permitting periods of extended inactivity. Therefore, torpor facilitates survival in a fire-scorched landscape and consequently may have been of functional significance for mammalian survival at the K-Pg boundary. PMID:27075255

  9. Top 10 Staff Survival Tips.

    ERIC Educational Resources Information Center

    O'Brien, Laurie

    1995-01-01

    Tips for camp staff on how to survive summer camp include not giving campers sugary drinks before bedtime, setting behavior limits with campers, setting an example by following camp rules, getting enough rest, being fair and consistent, controlling anger, being accountable for actions, asking questions, and being flexible. (LP)

  10. Corticosteroids compromise survival in glioblastoma.

    PubMed

    Pitter, Kenneth L; Tamagno, Ilaria; Alikhanyan, Kristina; Hosni-Ahmed, Amira; Pattwell, Siobhan S; Donnola, Shannon; Dai, Charles; Ozawa, Tatsuya; Chang, Maria; Chan, Timothy A; Beal, Kathryn; Bishop, Andrew J; Barker, Christopher A; Jones, Terreia S; Hentschel, Bettina; Gorlia, Thierry; Schlegel, Uwe; Stupp, Roger; Weller, Michael; Holland, Eric C; Hambardzumyan, Dolores

    2016-05-01

    Glioblastoma is the most common and most aggressive primary brain tumour. Standard of care consists of surgical resection followed by radiotherapy and concomitant and maintenance temozolomide (temozolomide/radiotherapy→temozolomide). Corticosteroids are commonly used perioperatively to control cerebral oedema and are frequently continued throughout subsequent treatment, notably radiotherapy, for amelioration of side effects. The effects of corticosteroids such as dexamethasone on cell growth in glioma models and on patient survival have remained controversial. We performed a retrospective analysis of glioblastoma patient cohorts to determine the prognostic role of steroid administration. A disease-relevant mouse model of glioblastoma was used to characterize the effects of dexamethasone on tumour cell proliferation and death, and to identify gene signatures associated with these effects. A murine anti-VEGFA antibody was used in parallel as an alternative for oedema control. We applied the dexamethasone-induced gene signature to The Cancer Genome Atlas glioblastoma dataset to explore the association of dexamethasone exposure with outcome. Mouse experiments were used to validate the effects of dexamethasone on survival in vivo Retrospective clinical analyses identified corticosteroid use during radiotherapy as an independent indicator of shorter survival in three independent patient cohorts. A dexamethasone-associated gene expression signature correlated with shorter survival in The Cancer Genome Atlas patient dataset. In glioma-bearing mice, dexamethasone pretreatment decreased tumour cell proliferation without affecting tumour cell viability, but reduced survival when combined with radiotherapy. Conversely, anti-VEGFA antibody decreased proliferation and increased tumour cell death, but did not affect survival when combined with radiotherapy. Clinical and mouse experimental data suggest that corticosteroids may decrease the effectiveness of treatment and shorten

  11. Plasticity and rectangularity in survival curves

    PubMed Central

    Weon, Byung Mook; Je, Jung Ho

    2011-01-01

    Living systems inevitably undergo a progressive deterioration of physiological function with age and an increase of vulnerability to disease and death. To maintain health and survival, living systems should optimize survival strategies with adaptive interactions among molecules, cells, organs, individuals, and environments, which arises plasticity in survival curves of living systems. In general, survival dynamics in a population is mathematically depicted by a survival rate, which monotonically changes from 1 to 0 with age. It would be then useful to find an adequate function to describe complicated survival dynamics. Here we describe a flexible survival function, derived from the stretched exponential function by adopting an age-dependent shaping exponent. We note that the exponent is associated with the fractal-like scaling in cumulative mortality rate. The survival function well depicts general features in survival curves; healthy populations exhibit plasticity and evolve towards rectangular-like survival curves, as examples in humans or laboratory animals. PMID:22355622

  12. AIAA Survivability Technical Committee Draft

    NASA Technical Reports Server (NTRS)

    Shipman, Jim; Williamson, Joel

    1997-01-01

    A relatively new area of interest in aerospace systems survivability is the growing threat of spacecraft penetration by orbital debris. Orbital debris, or "space junk", is composed of the man-made remnants of non-functioning spacecraft still orbiting the Earth. NASA estimates that there are currently over 100,000 orbital debris particles 1 centimeter in diameter or larger that cannot be tracked by existing radar, with the population growing at approximately 4% per year in low earth orbits. With an average velocity of over 8.7 km/sec, these projectiles can penetrate and disable many vulnerable spacecraft systems. Since the likelihood of spacecraft penetration increases with spacecraft surface area, large spacecraft (such as the International Space Station) and communication satellite fleets (such as Iridium) have begun to adopt survivability enhancement strategies similar to those employed by combat aircraft. Collision avoidance maneuvers are commonly practiced by the Space Shuttle and are planned by the International Space Station to decrease their susceptibility to impact by trackable orbital debris; likewise, improved shielding, internal equipment placement, and improved crew operations following penetration can reduce the vulnerability of spacecraft to loss following orbital debris impact. Computer simulations such as the Manned Spacecraft and Crew Survivability (MSCSurv) program at the NASA-Marshall Space Flight Center have recently been developed to quantify and reduce the likelihood of crew or spacecraft loss following orbital debris penetration. The AIAA Survivability Technical Committee is working to enable the transfer of military-developed survivability technologies to help the aerospace industry cope with this growing threat.

  13. Prediction of survival prognosis of non-small cell lung cancer by APE1 through regulation of epithelial-mesenchymal transition

    PubMed Central

    Duan, Wei; Huang, Chongbiao; Zheng, Xiangqian; Sun, Lei; Luo, Jingtao; Wang, Dong; Zhang, Sheng; Xin, Xiaojie; Gao, Ming

    2016-01-01

    The DNA base excision repair gene APE1 involves in DNA damage repair pathway and overexpression in a variety of human cancers. Analyses of patients with non-small cell lung cancer (NSCLC) suggested that multiple factors associated with prognosis of NSCLC patients. Further investigation showed that APE1 expression was able to predict the progression-free survival and overall survival in patients with NSCLC and correlated with lymph node metastasis. Intriguingly, as a stratification of APE1-141 SNPs in APE1 positive expression, we also found APE1-141 GT/GG was identified as a marker for prediction of poor survival in NSCLC patients. In the in vitro experiments, the results showed that when APE1 expression was inhibited by siRNA or AT101 (an APE1 inhibitor), the migration and invasion of NSCLC cells were suppressed. Furthermore, epithelial-mesenchymal transition (EMT) markers was tested to provide evidence that APE1 promoted NSCLC EMT through interaction with SirT1. Using NSCLC xenograft models, we confirmed that AT101 shrank tumor volumes and inhibited lymph node metastasis. In conclusion, APE1 could be a potential target for patients with NSCLC metastasis and AT101 is a potent inhibitor in further treatment of NSCLC patients. PMID:27074577

  14. Survival Advantage With the Addition of Radiation Therapy to Chemotherapy in Early Stage Peripheral T-Cell Lymphoma, Not Otherwise Specified

    SciTech Connect

    Zhang, Xi-Mei; Li, Ye-Xiong; Wang, Wei-Hu; Jin, Jing; Wang, Shu-Lian; Liu, Yue-Ping; Song, Yong-Wen; Fang, Hui; Ren, Hua; Zhou, Li-Qiang; Liu, Xin-Fan; Yu, Zi-Hao

    2013-03-15

    Purpose: Early stage peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is rare. The purpose of this study was to evaluate the outcome of treatment as well as the potential role of radiation therapy in PTCL-NOS. Methods and Materials: Thirty-five patients with early stage PTCL-NOS were included. There were 13 patients with stage I disease and 22 with stage II. All patients except 1 received doxorubicin-based chemotherapy alone (n=13) or a combination of chemotherapy and radiation therapy (CMT) (n=21). Results: The 3-year overall survival (OS) and progression-free survival (PFS) rates for the entire group were 41.3% and 25.7%, respectively. The addition of radiation therapy to chemotherapy significantly improved OS and PFS in early stage PTCL-NOS. The 3-year OS and PFS rates were 49.7% and 33.3% for CMT, compared with 23.1% (P=.042) and 15.4% (P=.035) for chemotherapy alone, respectively. The prognosis for patients who achieved a complete response (CR) was significantly better than that observed in those who did not achieve a CR. Conclusions: Despite the aggressive clinical course of early stage PTCL-NOS, additional radiation therapy has a significant impact on outcome. The integration of local radiation therapy into more effective systemic therapies may further improve survival.

  15. Circulating microRNAs in esophageal squamous cell carcinoma: association with locoregional staging and survival

    PubMed Central

    Li, Bing-Xin; Yu, Qi; Shi, Ze-Liang; Li, Ping; Fu, Shen

    2015-01-01

    Locoregional staging and prognostic information play a critical role in esophageal squamous cell carcinoma (ESCC) treatment strategies. Although microRNA (miRNA) is a promising marker for cancer detection, the relationship between circulating plasma miRNAs and ESCC remains unclear. Our study aims to investigate the association between circulating plasma miRNAs and tumor diagnosis or prognosis in ESCC patients. Plasma levels of miR-16, miR-21, miR-22, miR-126, miR-148b, miR-185, miR-221, miR-223, and miR-375 were evaluated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays from 38 ESCC patients prior to treatment and 19 healthy subjects. Differences in selected miRNAs and their diagnostic and prognostic value were examined. Levels of four of the selected miRNAs were found to be significantly higher in ESCC patients than in controls; namely, miR-16, miR-21, miR-185, and miR-375 (P < 0.050). In addition, the area under the receiver operating characteristic (ROC) curve (AUC) for miR-375 was 0.921 (95% confidence interval [CI] 0.817-0.976). Moreover, the expression levels of miR-16 were higher in patients with T3-4 tumors than in patients with T1-2 tumors (P = 0.020). Kaplan-Meier survival analysis showed that high expression levels of miR-16 and miR-21 in the plasma correlated significantly with shortened progression-free survival (PFS; P = 0.031 and P = 0.038, respectively) and overall survival (OS; P = 0.022 and P = 0.041, respectively) in ESCC patients. Four plasma miRNAs were identified that could potentially serve as novel diagnostic biomarkers for ESCC. Moreover, specific miRNAs, such as miR-16 and miR-21, can predict poor survival in ESCC. PMID:26221263

  16. Survival of auditory hair cells.

    PubMed

    Seymour, Michelle L; Pereira, Fred A

    2015-07-01

    The inability of mammals to regenerate auditory hair cells creates a pressing need to understand the means of enhancing hair cell survival following insult or injury. Hair cells are easily damaged by noise exposure, by ototoxic medications and as a consequence of aging processes, all of which lead to progressive and permanent hearing impairment as hair cells are lost. Significant efforts have been invested in designing strategies to prevent this damage from occurring since permanent hearing loss has a profound impact on communication and quality of life for patients. In this mini-review, we discuss recent progress in the use of antioxidants, anti-inflammatories and apoptosis inhibitors to enhance hair cell survival. We conclude by clarifying the distinction between protection and rescue strategies and by highlighting important areas of future research.

  17. Impact of immunosuppression treatment on the improvement in graft survival after deceased donor renal transplantation: a long-term cohort study.

    PubMed

    González-Molina, Miguel; Burgos, Dolores; Cabello, Mercedes; Ruiz-Esteban, Pedro; Rodríguez, Manuel A; Gutiérrez, Cristina; López, Verónica; Baena, Víctor; Hernández, Domingo

    2014-01-01

    We analyzed graft half-life and attrition rates in 1045 adult deceased donor kidney transplants from 1986-2001, with follow-up to 2011, grouped in two periods (1986-95 vs. 1996-01) according to immunosuppression. The Kaplan-Meier curve showed a significant increase in graft survival during 1996-2001. The uncensored real graft half-life was 10.25 years in 1986-95 and the actuarial was 14.58 years in 1996-2001 (P<0.001). The attrition rates showed a significantly greater graft loss in 1986-95, even excluding the first year from the analysis. The decline in renal function was significantly less pronounced in 1996-2001, indicating better preservation of renal function, despite the increase in donor age and stroke as the cause of donor death. The parsimonious Cox multivariate model showed donor age, acute rejection, panel reactive antibody, cold ischemia time and delayed graft function were significantly associated with a higher risk of graft loss. In contrast, the risk of graft loss fell by 21% in 1996-2001 compared with 1986-95. A similar reduction (25%) was observed when MMF treatment was entered into the multivariate model instead of study period. Long-term graft survival improved significantly in 1996-2001 compared to 1986-1995 despite older donor age. Modern immunosuppression could have contributed to the improved kidney transplant outcome.

  18. Does Random Dispersion Help Survival?

    NASA Astrophysics Data System (ADS)

    Schinazi, Rinaldo B.

    2015-04-01

    Many species live in colonies that prosper for a while and then collapse. After the collapse the colony survivors disperse randomly and found new colonies that may or may not make it depending on the new environment they find. We use birth and death chains in random environments to model such a population and to argue that random dispersion is a superior strategy for survival.

  19. Dispersion as a Survival Strategy

    NASA Astrophysics Data System (ADS)

    Junior, Valdivino Vargas; Machado, Fábio Prates; Roldán-Correa, Alejandro

    2016-08-01

    We consider stochastic growth models to represent population subject to catastrophes. We analyze the subject from different set ups considering or not spatial restrictions, whether dispersion is a good strategy to increase the population viability. We find out it strongly depends on the effect of a catastrophic event, the spatial constraints of the environment and the probability that each exposed individual survives when a disaster strikes.

  20. Relative survival multistate Markov model.

    PubMed

    Huszti, Ella; Abrahamowicz, Michal; Alioum, Ahmadou; Binquet, Christine; Quantin, Catherine

    2012-02-10

    Prognostic studies often have to deal with two important challenges: (i) separating effects of predictions on different 'competing' events and (ii) uncertainty about cause of death. Multistate Markov models permit multivariable analyses of competing risks of, for example, mortality versus disease recurrence. On the other hand, relative survival methods help estimate disease-specific mortality risks even in the absence of data on causes of death. In this paper, we propose a new Markov relative survival (MRS) model that attempts to combine these two methodologies. Our MRS model extends the existing multistate Markov piecewise constant intensities model to relative survival modeling. The intensity of transitions leading to death in the MRS model is modeled as the sum of an estimable excess hazard of mortality from the disease of interest and an 'offset' defined as the expected hazard of all-cause 'natural' mortality obtained from relevant life-tables. We evaluate the new MRS model through simulations, with a design based on registry-based prognostic studies of colon cancer. Simulation results show almost unbiased estimates of prognostic factor effects for the MRS model. We also applied the new MRS model to reassess the role of prognostic factors for mortality in a study of colorectal cancer. The MRS model considerably reduces the bias observed with the conventional Markov model that does not permit accounting for unknown causes of death, especially if the 'true' effects of a prognostic factor on the two types of mortality differ substantially.

  1. Proline Mechanisms of Stress Survival

    PubMed Central

    Liang, Xinwen; Zhang, Lu; Natarajan, Sathish Kumar

    2013-01-01

    Abstract Significance: The imino acid proline is utilized by different organisms to offset cellular imbalances caused by environmental stress. The wide use in nature of proline as a stress adaptor molecule indicates that proline has a fundamental biological role in stress response. Understanding the mechanisms by which proline enhances abiotic/biotic stress response will facilitate agricultural crop research and improve human health. Recent Advances: It is now recognized that proline metabolism propels cellular signaling processes that promote cellular apoptosis or survival. Studies have shown that proline metabolism influences signaling pathways by increasing reactive oxygen species (ROS) formation in the mitochondria via the electron transport chain. Enhanced ROS production due to proline metabolism has been implicated in the hypersensitive response in plants, lifespan extension in worms, and apoptosis, tumor suppression, and cell survival in animals. Critical Issues: The ability of proline to influence disparate cellular outcomes may be governed by ROS levels generated in the mitochondria. Defining the threshold at which proline metabolic enzyme expression switches from inducing survival pathways to cellular apoptosis would provide molecular insights into cellular redox regulation by proline. Are ROS the only mediators of proline metabolic signaling or are other factors involved? Future Directions: New evidence suggests that proline biosynthesis enzymes interact with redox proteins such as thioredoxin. An important future pursuit will be to identify other interacting partners of proline metabolic enzymes to uncover novel regulatory and signaling networks of cellular stress response. Antioxid. Redox Signal. 19, 998–1011. PMID:23581681

  2. Yolk androgens reduce offspring survival.

    PubMed

    Sockman, K W; Schwabl, H

    2000-07-22

    Females may favour some offspring over others by differential deposition of yolk hormones. In American kestrels (Falco sparverius), we found that yolks of eggs laid late in the sequence of a clutch had more testosterone (T) and androstenedione (A4) than yolks of first-laid eggs. To investigate the effects of these yolk androgens on nestling 'fitness', we injected both T and A4 into the yolks of first-laid eggs and compared their hatching time, nestling growth and nestling survival with those of first-laid eggs in which we injected vehicle as a control. Compared to controls, injection of T and A4 at a dose intended to increase their levels to those of later-laid eggs delayed hatching and reduced nestling growth and survival rates. Yolk androgen treatment of egg 1 had no effect on survival of siblings hatching from subsequently laid eggs. The adverse actions of yolk androgen treatment in the kestrel are in contrast to the favourable actions of yolk T treatment found previously in canaries (Serinus canaria). Additional studies are necessary in order to determine whether the deposition of yolk androgens is an adaptive form of parental favouritism or an adverse by-product of endocrine processes during egg formation. Despite its adaptive significance, such 'transgenerational' effects of steroid hormones may have helped to evolutionarily shape the hormonal mechanisms regulating reproduction. PMID:10983830

  3. Illusory contour formation survives crowding.

    PubMed

    Lau, Jonathan Siu Fung; Cheung, Sing-Hang

    2012-06-12

    Flanked objects are difficult to identify using peripheral vision due to visual crowding, which limits conscious access to target identity. Nonetheless, certain types of visual information have been shown to survive crowding. Such resilience to crowding provides valuable information about the underlying neural mechanism of crowding. Here we ask whether illusory contour formation survives crowding of the inducers. We manipulated the presence of illusory contours through the (mis)alignment of the four inducers of a Kanizsa square. In the inducer-aligned condition, the observers judged the perceived shape (thin vs. fat) of the illusory Kanizsa square, manipulated by small rotations of the inducers. In the inducer-misaligned condition, three of the four inducers (all except the upper-left) were rotated 90°. The observers judged the orientation of the upper-left inducer. Crowding of the inducers worsened observers' performance significantly only in the inducer-misaligned condition. Our findings suggest that information for illusory contour formation survives crowding of the inducers. Crowding happens at a stage where the low-level featural information is integrated for inducer orientation discrimination, but not at a stage where the same information is used for illusory contour formation.

  4. Yolk androgens reduce offspring survival.

    PubMed Central

    Sockman, K W; Schwabl, H

    2000-01-01

    Females may favour some offspring over others by differential deposition of yolk hormones. In American kestrels (Falco sparverius), we found that yolks of eggs laid late in the sequence of a clutch had more testosterone (T) and androstenedione (A4) than yolks of first-laid eggs. To investigate the effects of these yolk androgens on nestling 'fitness', we injected both T and A4 into the yolks of first-laid eggs and compared their hatching time, nestling growth and nestling survival with those of first-laid eggs in which we injected vehicle as a control. Compared to controls, injection of T and A4 at a dose intended to increase their levels to those of later-laid eggs delayed hatching and reduced nestling growth and survival rates. Yolk androgen treatment of egg 1 had no effect on survival of siblings hatching from subsequently laid eggs. The adverse actions of yolk androgen treatment in the kestrel are in contrast to the favourable actions of yolk T treatment found previously in canaries (Serinus canaria). Additional studies are necessary in order to determine whether the deposition of yolk androgens is an adaptive form of parental favouritism or an adverse by-product of endocrine processes during egg formation. Despite its adaptive significance, such 'transgenerational' effects of steroid hormones may have helped to evolutionarily shape the hormonal mechanisms regulating reproduction. PMID:10983830

  5. Survival benefit from S-1 as compared to Fluorouracil in Asian patients with advanced gastrointestinal cancer: a meta-analysis.

    PubMed

    Cao, Chunxiang; Zhang, Xunlei; Kuang, Meng; Gu, Dongying; He, Mingliang; Chen, Jinfei; Tang, Cuiju

    2014-08-01

    Whether S-1 could replace 5-Fluorouracil (5-Fu) or not in the treatment of advanced gastrointestinal (GI) cancer (including advanced gastric cancer [AGS] and metastatic colorectal cancer [mCRC]) in Asian patients has been controversial. This meta-analysis was performed to compare the activity, efficacy and toxicity of S-1-based versus 5-Fu-based chemotherapy in those Asian patients. Randomized controlled trials (RCTs) were identified by electronic search of Pubmed. Relevant abstracts were manually searched to identify relevant trials. A total of 2182 patients from eight RCTs were included, and our results demonstrated that S-1-based chemotherapy significantly improved overall survival (OS) (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.77-1.00) and overall response rate (ORR) (odds ratio [OR], 1.72; 95% CI, 1.09-2.70), but no significant progression-free survival (PFS) benefit was found between arms (HR, 0.87; 95% CI, 0.72-1.06). Subgroup analyses revealed that S-1-based chemotherapy significantly improved OS and ORR in subgroups of patients with non-platinum containing regimens (P = 0.041; P = 0.034) and patients with no prior chemotherapy history (P = 0.025; P = 0.016). Statistically significant improvements of PFS and ORR in the S-1-based chemotherapy were observed in the subgroup of patients with AGC (P < 0.001; P = 0.005). S-1-based chemotherapy was characterized by significantly higher incidences of diarrhea, fatigue and thrombocytopenia, and a lower incidence of nausea. This analysis provided strong evidence for survival benefits of S-1, and S-1-based chemotherapy could be considered to replace 5-Fu-based therapy for the treatment of advanced GI cancer in Asian patients.

  6. Visceral adipose tissue is prognostic for survival of diffuse large B cell lymphoma treated with frontline R-CHOP.

    PubMed

    Shin, Dong-Yeop; Kim, Areumnuri; Byun, Byung Hyun; Moon, Hansol; Kim, Soyeun; Ko, Young-Jin; Kim, Min-Jung; Lee, Hyo-Rak; Kang, Hye-Jin; Na, Im Il; Park, Sunhoo; Lee, Seung Sook; Yang, Sung-Hyun

    2016-02-01

    The potential role of visceral adipose tissue (VAT) as a prognostic factor in patients with diffuse large B cell lymphoma (DLBCL) treated with frontline rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) immunochemotherapy was explored. Total adipose tissue and VAT were measured by analyzing positron emission tomography (PET)/computed tomography (CT) images obtained during the initial staging of patients with DLBCL. The VAT ratio was calculated as follows: VAT ratio = VAT area/total adipose tissue area. Body mass index (BMI), sex, and International Prognostic Index (IPI) were also incorporated as co-variates in the final model of multivariate Cox regression analysis for survival. A total of 156 patients with DLBCL, who were treated with frontline R-CHOP, were enrolled in our study. The median patient age was 61 years, and 81 patients were male (51.9 %). The median cycle of R-CHOP was six. The IPI risk group was a strong prognostic factor for progression-free survival (PFS) and overall survival (OS) (p < 0.001). Obese BMIs were an independent prognostic factor for PFS, but not for OS in multivariate analyses, compared to patients with normal BMIs (HR = 0.43, 95 % CI = 0.19-0.98, and p = 0.046 for PFS). A high VAT ratio (third tertile) was an independent adverse prognostic factor for PFS and OS in multivariate analyses (HR = 2.87 and 2.66, 95 % CI = 1.30-6.32 and 1.30-5.44, and p = 0.009 and 0.007 for PFS and OS, respectively). VAT ratio was an independent prognostic factor for patients with DLBCL treated with first-line R-CHOP; thus, additional large prospective studies are warranted. PMID:26658607

  7. Matched Survival Analysis in Patients With Locoregionally Advanced Resectable Oropharyngeal Carcinoma: Platinum-Based Induction and Concurrent Chemoradiotherapy Versus Primary Surgical Resection

    SciTech Connect

    Boscolo-Rizzo, Paolo; Gava, Alessandro; Baggio, Vittorio; Marchiori, Carlo; Stellin, Marco; Fuson, Roberto; Lamon, Stefano; Da Mosto, Maria Cristina

    2011-05-01

    Purpose: The outcome of a prospective case series of 47 patients with newly diagnosed resectable locoregionally advanced oropharyngeal squamous cell carcinoma treated with platinum-based induction-concurrent chemoradiotherapy (IC/CCRT) was compared with the outcome of 47 matched historical control patients treated with surgery and postoperative RT. Methods and Materials: A total of 47 control patients with locoregionally advanced oropharyngeal squamous cell carcinoma were identified from review of a prospectively compiled comprehensive computerized head-and-neck cancer database and were matched with a prospective case series of patients undergoing IC/CCRT by disease stage, nodal status, gender, and age ({+-}5 years). The IC/CCRT regimen consisted of one cycle of induction chemotherapy followed by conventionally fractionated RT to a total dose of 66-70 Gy concomitantly with two cycles of chemotherapy. Each cycle of chemotherapy consisted of cisplatinum, 100 mg/m{sup 2}, and a continuous infusion of 5-fluorouracil, 1,000 mg/m{sup 2}/d for 5 days. The survival analysis was performed using Kaplan-Meier estimates. Matched-pair survival was compared using the Cox proportional hazards model. Results: No significant difference was found in the overall survival or progression-free survival rates between the two groups. The matched analysis of survival did not show a statistically significant greater hazard ratio for overall death (hazard ratio, 1.35; 95% confidence interval, 0.65-2.80; p = .415) or progression (hazard ratio, 1.44; 95% confidence interval, 0.72-2.87; p = .301) for patients undergoing IC/CCRT. Conclusion: Although the sample size was small and not randomized, this matched-pair comparison between a prospective case series and a historical cohort treated at the same institution showed that the efficacy of IC/CCRT with salvage surgery is as good as primary surgical resection and postoperative RT.

  8. Peptide receptor radionuclide therapy of treatment-refractory metastatic thyroid cancer using 90Yttrium and 177Lutetium labeled somatostatin analogs: toxicity, response and survival analysis

    PubMed Central

    Budiawan, Hendra; Salavati, Ali; Kulkarni, Harshad R; Baum, Richard P

    2014-01-01

    The overall survival rate of non-radioiodine avid differentiated (follicular, papillary, medullary) thyroid carcinoma is significantly lower than for patients with iodine-avid lesions. The purpose of this study was to evaluate toxicity and efficacy (response and survival) of peptide receptor radionuclide therapy (PRRT) in non-radioiodine-avid or radioiodine therapy refractory thyroid cancer patients. Sixteen non-radioiodine-avid and/or radioiodine therapy refractory thyroid cancer patients, including follicular thyroid carcinoma (n = 4), medullary thyroid carcinoma (n = 8), Hürthle cell thyroid carcinoma (n = 3), and mixed carcinoma (n = 1) were treated with PRRT by using 90Yttrium and/or 177Lutetium labeled somatostatin analogs. 68Ga somatostatin receptor PET/CT was used to determine the somatostatin receptor density in the residual tumor/metastatic lesions and to assess the treatment response. Hematological profiles and renal function were periodically examined after treatment. By using fractionated regimen, only mild, reversible hematological toxicity (grade 1) or nephrotoxicity (grade 1) were seen. Response assessment (using EORTC criteria) was performed in 11 patients treated with 2 or more (maximum 5) cycles of PRRT and showed disease stabilization in 4 (36.4%) patients. Two patients (18.2%) showed partial remission, in the remaining 5 patients (45.5%) disease remained progressive. Kaplan-Meier analysis resulted in a mean survival after the first PRRT of 4.2 years (95% CI, range 2.9-5.5) and median progression free survival of 25 months (inter-quartiles: 12-43). In non-radioiodine-avid/radioiodine therapy refractory thyroid cancer patients, PRRT is a promising therapeutic option with minimal toxicity, good response rate and excellent survival benefits. PMID:24380044

  9. Declining Use of Radiotherapy in Stage I and II Hodgkin's Disease and Its Effect on Survival and Secondary Malignancies

    SciTech Connect

    Koshy, Matthew; Rich, Shayna E.; Mahmood, Usama; Kwok, Young

    2012-02-01

    Purpose: Concerns regarding long-term toxicities have led some to withhold radiotherapy (RT) for the treatment of Stage I and II Hodgkin's disease (HD). The present study was undertaken to assess the use of RT for HD and its effect on overall survival and the development of secondary malignancies. Methods and Materials: The present study included data from the Surveillance, Epidemiology, and End Results database from patients aged {>=}20 years who had been diagnosed with Stage I or II HD between 1988 and 2006. Overall survival was estimated using the Kaplan-Meier method, and the Cox multivariate regression model was used to analyze trends. Results: A total of 12,247 patients were selected, and 51.5% had received RT. The median follow-up for the present cohort was 4.9 years, with 21% of the cohort having >10 years of follow-up. Between 1988 and 1991, 62.9% had undergone RT, but between 2004 and 2006, only 43.7% had undergone RT (p < .001). The 5-year overall survival rate was 76% for patients who had not received RT and 87% for those who had (p < .001). The hazard ratio adjusted for other variables in the regression model showed that patients who had not undergone RT (hazard ratio, 1.72; 95% confidence interval, 1.72-2.02) was associated with significantly worse survival compared with patients who had received RT. The actuarial rate of developing a second malignancy was 14.6% vs. 15.0% at 15 years for those who had and had not undergone RT, respectively (p = .089). Conclusions: The present study is one of the largest studies to examine the role of RT for Stage I and II HD. Our results revealed a survival benefit with the addition of RT with no increase in the development of secondary malignancies compared with patients who had not received RT. Furthermore, the present nationwide study revealed a >20% absolute decrease in the use of RT from 1988 to 2006.

  10. Surviving the Sudden Death of a Baby

    MedlinePlus

    ... Funds Request Information Get Involved Surviving the Sudden Death of a Baby Home Grieving Families Surviving the ... Candle on For Families Who Have Experienced the Death of a Baby The numbers are staggering. Every ...

  11. 46 CFR 172.195 - Survival conditions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Under Subchapter O of This Chapter § 172.195 Survival conditions. A vessel is presumed to survive... that is closed by means of a weathertight door or hatch cover. This opening does not include an...

  12. Starvation-Survival in Haloarchaea

    PubMed Central

    Winters, Yaicha D.; Lowenstein, Tim K.; Timofeeff, Michael N.

    2015-01-01

    Recent studies claiming to revive ancient microorganisms trapped in fluid inclusions in halite have warranted an investigation of long-term microbial persistence. While starvation-survival is widely reported for bacteria, it is less well known for halophilic archaea—microorganisms likely to be trapped in ancient salt crystals. To better understand microbial survival in fluid inclusions in ancient evaporites, laboratory experiments were designed to simulate growth of halophilic archaea under media-rich conditions, complete nutrient deprivation, and a controlled substrate condition (glycerol-rich) and record their responses. Haloarchaea used for this work included Hbt. salinarum and isolate DV582A-1 (genus Haloterrigena) sub-cultured from 34 kyear Death Valley salt. Hbt. salinarum and DV582A-1 reacted to nutrient limitation with morphological and population changes. Starved populations increased and most cells converted from rods to small cocci within 56 days of nutrient deprivation. The exact timing of starvation adaptations and the physical transformations differed between species, populations of the same species, and cells of the same population. This is the first study to report the timing of starvation strategies for Hbt. salinarum and DV582A-1. The morphological states in these experiments may allow differentiation between cells trapped with adequate nutrients (represented here by early stages in nutrient-rich media) from cells trapped without nutrients (represented here by experimental starvation) in ancient salt. The hypothesis that glycerol, leaked from Dunaliella, provides nutrients for the survival of haloarchaea trapped in fluid inclusions in ancient halite, is also tested. Hbt. salinarum and DV582A-1 were exposed to a mixture of lysed and intact Dunaliella for 56 days. The ability of these organisms to utilize glycerol from Dunaliella cells was assessed by documenting population growth, cell length, and cell morphology. Hbt. salinarum and DV582A-1

  13. Starvation-Survival in Haloarchaea.

    PubMed

    Winters, Yaicha D; Lowenstein, Tim K; Timofeeff, Michael N

    2015-01-01

    Recent studies claiming to revive ancient microorganisms trapped in fluid inclusions in halite have warranted an investigation of long-term microbial persistence. While starvation-survival is widely reported for bacteria, it is less well known for halophilic archaea-microorganisms likely to be trapped in ancient salt crystals. To better understand microbial survival in fluid inclusions in ancient evaporites, laboratory experiments were designed to simulate growth of halophilic archaea under media-rich conditions, complete nutrient deprivation, and a controlled substrate condition (glycerol-rich) and record their responses. Haloarchaea used for this work included Hbt. salinarum and isolate DV582A-1 (genus Haloterrigena) sub-cultured from 34 kyear Death Valley salt. Hbt. salinarum and DV582A-1 reacted to nutrient limitation with morphological and population changes. Starved populations increased and most cells converted from rods to small cocci within 56 days of nutrient deprivation. The exact timing of starvation adaptations and the physical transformations differed between species, populations of the same species, and cells of the same population. This is the first study to report the timing of starvation strategies for Hbt. salinarum and DV582A-1. The morphological states in these experiments may allow differentiation between cells trapped with adequate nutrients (represented here by early stages in nutrient-rich media) from cells trapped without nutrients (represented here by experimental starvation) in ancient salt. The hypothesis that glycerol, leaked from Dunaliella, provides nutrients for the survival of haloarchaea trapped in fluid inclusions in ancient halite, is also tested. Hbt. salinarum and DV582A-1 were exposed to a mixture of lysed and intact Dunaliella for 56 days. The ability of these organisms to utilize glycerol from Dunaliella cells was assessed by documenting population growth, cell length, and cell morphology. Hbt. salinarum and DV582A-1

  14. Starvation-Survival in Haloarchaea.

    PubMed

    Winters, Yaicha D; Lowenstein, Tim K; Timofeeff, Michael N

    2015-01-01

    Recent studies claiming to revive ancient microorganisms trapped in fluid inclusions in halite have warranted an investigation of long-term microbial persistence. While starvation-survival is widely reported for bacteria, it is less well known for halophilic archaea-microorganisms likely to be trapped in ancient salt crystals. To better understand microbial survival in fluid inclusions in ancient evaporites, laboratory experiments were designed to simulate growth of halophilic archaea under media-rich conditions, complete nutrient deprivation, and a controlled substrate condition (glycerol-rich) and record their responses. Haloarchaea used for this work included Hbt. salinarum and isolate DV582A-1 (genus Haloterrigena) sub-cultured from 34 kyear Death Valley salt. Hbt. salinarum and DV582A-1 reacted to nutrient limitation with morphological and population changes. Starved populations increased and most cells converted from rods to small cocci within 56 days of nutrient deprivation. The exact timing of starvation adaptations and the physical transformations differed between species, populations of the same species, and cells of the same population. This is the first study to report the timing of starvation strategies for Hbt. salinarum and DV582A-1. The morphological states in these experiments may allow differentiation between cells trapped with adequate nutrients (represented here by early stages in nutrient-rich media) from cells trapped without nutrients (represented here by experimental starvation) in ancient salt. The hypothesis that glycerol, leaked from Dunaliella, provides nutrients for the survival of haloarchaea trapped in fluid inclusions in ancient halite, is also tested. Hbt. salinarum and DV582A-1 were exposed to a mixture of lysed and intact Dunaliella for 56 days. The ability of these organisms to utilize glycerol from Dunaliella cells was assessed by documenting population growth, cell length, and cell morphology. Hbt. salinarum and DV582A-1

  15. Liposomal Nanoparticles of a Spleen Tyrosine Kinase P-Site Inhibitor Amplify the Potency of Low Dose Total Body Irradiation Against Aggressive B-Precursor Leukemia and Yield Superior Survival Outcomes in Mice.

    PubMed

    Uckun, Fatih M; Myers, Dorothea E; Cheng, Jianjun; Qazi, Sanjive

    2015-06-01

    This study was designed to improve the efficacy of radiation therapy against radiation-resistant leukemia. We report that the potency of low dose radiation therapy against B-precursor acute lymphoblastic leukemia (BPL) can be markedly enhanced by combining radiation with a liposomal nanoparticle (LNP) formulation of the SYK-P-site inhibitor C61 ("C61-LNP"). C61-LNP plus low dose total body irradiation (TBI) was substantially more effective than TBI alone or C61-LNP alone in improving the event-free survival outcome NOD/SCID mice challenged with an otherwise invariably fatal dose of human ALL xenograft cells derived from relapsed BPL patients. C61-LNP plus low dose TBI also yielded progression-free survival, tumor-free survival and overall survival outcomes in CD22ΔE12 × BCR-ABL double transgenic mice with advanced stage, radiation-resistant BPL with lymphomatous features that were significantly superior to those of mice treated with TBI alone or C61-LNP alone.

  16. Long-term survival in an advanced gastric cancer patient treated with cetuximab in association with FOLFIRI: a case report

    PubMed Central

    Adua, Daniela; Di Fabio, Francesca; Rojas Llimpe, Fabiola Lorena; Pini, Sara

    2014-01-01

    In December 2004, a 52-year-old woman with metastatic gastric cancer was enrolled in the phase II clinical trial FOLCETUX, receiving cetuximab at an initial dose of 400 mg/m2 i.v. followed by weekly doses of 250 mg/m2, irinotecan 180 mg/m2 i.v. on day 1, LFA 100 mg/m2 i.v. followed by 5-FU 400 mg/m2 i.v. bolus and 600 mg/m2 i.v. 22-h continuous infusion on days 1 and 2 every two weeks, to a total of 17 cycles. CT and PET-CT performed after six weeks treatment failed to show any residual disease, with complete radiological response in accord to RECIST criteria and complete metabolic response. A total of 24 maintenance administrations with cetuximab alone (250 mg/m2 weekly) were performed, as foreseen by the protocol in responders. In November 2012 a clinical, radiological (CT) and metabolic (PET-CT) patient examination proved negative for recurrent disease, signifying 95 months’ progression free survival. PMID:24490046

  17. 38 CFR 3.402 - Surviving spouse.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Surviving spouse. 3.402..., Compensation, and Dependency and Indemnity Compensation Effective Dates § 3.402 Surviving spouse. Awards of pension, compensation, or dependency and indemnity compensation to or for a surviving spouse will...

  18. Sequencing of Local Therapy Affects the Pattern of Treatment Failure and Survival in Children With Atypical Teratoid Rhabdoid Tumors of the Central Nervous System

    SciTech Connect

    Pai Panandiker, Atmaram S.; Merchant, Thomas E.; Beltran, Chris; Wu, Shengjie; Sharma, Shelly; Boop, Frederick A.; Jenkins, Jesse J.; Helton, Kathleen J.; Wright, Karen D.; Broniscer, Alberto; Kun, Larry E.; Gajjar, Amar

    2012-04-01

    Purpose: To assess the pattern of treatment failure associated with current therapeutic paradigms for childhood atypical teratoid rhabdoid tumors (AT/RT). Methods and Materials: Pediatric patients with AT/RT of the central nervous system treated at our institution between 1987 and 2007 were retrospectively evaluated. Overall survival (OS), progression-free survival, and cumulative incidence of local failure were correlated with age, sex, tumor location, extent of disease, and extent of surgical resection. Radiotherapy (RT) sequencing, chemotherapy, dose, timing, and volume administered after resection were also evaluated. Results: Thirty-one patients at a median age of 2.3 years at diagnosis (range, 0.45-16.87 years) were enrolled into protocols that included risk- and age-stratified RT. Craniospinal irradiation with focal tumor bed boost (median dose, 54 Gy) was administered to 18 patients. Gross total resection was achieved in 16. Ten patients presented with metastases at diagnosis. RT was delayed more than 3 months in 20 patients and between 1 and 3 months in 4; 7 patients received immediate postoperative irradiation preceding high-dose alkylator-based chemotherapy. At a median follow-up of 48 months, the cumulative incidence of local treatment failure was 37.5% {+-} 9%; progression-free survival was 33.2% {+-} 10%; and OS was 53.5% {+-} 10%. Children receiving delayed RT ({>=}1 month postoperatively) were more likely to experience local failure (hazard ratio [HR] 1.23, p = 0.007); the development of distant metastases before RT increased the risk of progression (HR 3.49, p = 0.006); and any evidence of disease progressionbefore RT decreased OS (HR 20.78, p = 0.004). Disease progression occurred in 52% (11/21) of children with initially localized tumors who underwent gross total resection, and the progression rate increased proportionally with increasing delay from surgery to RT. Conclusions: Delayed RT is associated with a higher rate of local and metastatic

  19. Donor chimerism early after reduced-intensity conditioning hematopoietic stem cell transplantation predicts relapse and survival.

    PubMed

    Koreth, John; Kim, Haesook T; Nikiforow, Sarah; Milford, Edgar L; Armand, Philippe; Cutler, Corey; Glotzbecker, Brett; Ho, Vincent T; Antin, Joseph H; Soiffer, Robert J; Ritz, Jerome; Alyea, Edwin P

    2014-10-01

    The impact of early donor cell chimerism on outcomes of T cell-replete reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) is ill defined. We evaluated day 30 (D30) and 100 (D100) total donor cell chimerism after RIC HSCT undertaken between 2002 and 2010 at our institution, excluding patients who died or relapsed before D30. When available, donor T cell chimerism was also assessed. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), relapse, and nonrelapse mortality (NRM). We evaluated 688 patients with hematologic malignancies (48% myeloid and 52% lymphoid) and a median age of 57 years (range, 18 to 74) undergoing RIC HSCT with T cell-replete donor grafts (97% peripheral blood; 92% HLA-matched), with a median follow-up of 58.2 months (range, 12.6 to 120.7). In multivariable analysis, total donor cell and T cell chimerism at D30 and D100 each predicted RIC HSCT outcomes, with D100 total donor cell chimerism most predictive. D100 total donor cell chimerism <90% was associated with increased relapse (hazard ratio [HR], 2.54; 95% confidence interval [CI], 1.83 to 3.51; P < .0001), impaired PFS (HR, 2.01; 95% CI, 1.53 to 2.65; P < .0001), and worse OS (HR, 1.50; 95% CI, 1.11 to 2.04, P = .009), but not with NRM (HR, .76; 95% CI, .44 to 2.27; P = .33). There was no additional utility of incorporating sustained D30 to D100 total donor cell chimerism or T cell chimerism. Low donor chimerism early after RIC HSCT is an independent risk factor for relapse and impaired survival. Donor chimerism assessment early after RIC HSCT can prognosticate for long-term outcomes and help identify high-risk patient cohorts who may benefit from additional therapeutic interventions.

  20. Personalized Circulating Tumor DNA Biomarkers Dynamically Predict Treatment Response and Survival In Gynecologic Cancers

    PubMed Central

    Anand, Sanya; Sebra, Robert; Catalina Camacho, Sandra; Garnar-Wortzel, Leopold; Nair, Navya; Moshier, Erin; Wooten, Melissa; Uzilov, Andrew; Chen, Rong; Prasad-Hayes, Monica; Zakashansky, Konstantin; Beddoe, Ann Marie; Schadt, Eric; Dottino, Peter; Martignetti, John A.

    2015-01-01

    Background High-grade serous ovarian and endometrial cancers are the most lethal female reproductive tract malignancies worldwide. In part, failure to treat these two aggressive cancers successfully centers on the fact that while the majority of patients are diagnosed based on current surveillance strategies as having a complete clinical response to their primary therapy, nearly half will develop disease recurrence within 18 months and the majority will die from disease recurrence within 5 years. Moreover, no currently used biomarkers or imaging studies can predict outcome following initial treatment. Circulating tumor DNA (ctDNA) represents a theoretically powerful biomarker for detecting otherwise occult disease. We therefore explored the use of personalized ctDNA markers as both a surveillance and prognostic biomarker in gynecologic cancers and compared this to current FDA-approved surveillance tools. Methods and Findings Tumor and serum samples were collected at time of surgery and then throughout treatment course for 44 patients with gynecologic cancers, representing 22 ovarian cancer cases, 17 uterine cancer cases, one peritoneal, three fallopian tube, and one patient with synchronous fallopian tube and uterine cancer. Patient/tumor-specific mutations were identified using whole-exome and targeted gene sequencing and ctDNA levels quantified using droplet digital PCR. CtDNA was detected in 93.8% of patients for whom probes were designed and levels were highly correlated with CA-125 serum and computed tomography (CT) scanning results. In six patients, ctDNA detected the presence of cancer even when CT scanning was negative and, on average, had a predictive lead time of seven months over CT imaging. Most notably, undetectable levels of ctDNA at six months following initial treatment was associated with markedly improved progression free and overall survival. Conclusions Detection of residual disease in gynecologic, and indeed all cancers, represents a diagnostic

  1. Functional impairment of activated protein C in breast cancer - relationship to survival outcomes

    PubMed Central

    Roselli, Mario; Ferroni, Patrizia; Riondino, Silvia; Mariotti, Sabrina; Portarena, Ilaria; Alessandroni, Jhessica; Ialongo, Cristiano; Massoud, Renato; Costarelli, Leopoldo; Cavaliere, Francesco; Bernardini, Sergio; Guadagni, Fiorella

    2016-01-01

    An impairment of the activated protein C (APC) system has been occasionally reported in breast cancer (BC). However, the clinical significance and prognostic value of an impaired APC functionality in BC patients is still poorly understood. Thus, the present study was aimed at investigating the prognostic value of altered APC functionality for progression-free (PFS) and overall survival (OS) in a cohort study of BC patients. APC functionality was retrospectively analyzed by a coagulation inhibition assay (ThromboPath) in 290 consecutive patients with primary (n=246) or relapsing/recurrent (n=44) BC. All patients were prospectively followed for a median time of 3.5 years (14% recurrence rate). As control group, 145 age-matched healthy women were also investigated. The results obtained demonstrated that APC function was impaired in roughly 20% of all BC at baseline. BC women with stage I/II had a significantly lower rate of APC impairment (13%) than women with stage III (22%) or distant metastases (44%, p=0.001). At univariate analyses, an impairment of APC function had a negative prognostic impact in terms of PFS (5-year PFS rates 53% vs. 70%; HR=2.5; p<0.001) and OS (5-year OS rates 79% vs. 93%; HR=3.9; p=0.005). However, prognostic significance was retained in multivariate models only for PFS (HR=2.0; p=0.017). We may, thus, conclude that BC patients are in a prothrombotic condition, which could play a role in the progression of the disease. Monitoring coagulation changes in BC women could provide important prognostic information especially in patients with advanced stages. PMID:27429857

  2. Functional impairment of activated protein C in breast cancer - relationship to survival outcomes.

    PubMed

    Roselli, Mario; Ferroni, Patrizia; Riondino, Silvia; Mariotti, Sabrina; Portarena, Ilaria; Alessandroni, Jhessica; Ialongo, Cristiano; Massoud, Renato; Costarelli, Leopoldo; Cavaliere, Francesco; Bernardini, Sergio; Guadagni, Fiorella

    2016-01-01

    An impairment of the activated protein C (APC) system has been occasionally reported in breast cancer (BC). However, the clinical significance and prognostic value of an impaired APC functionality in BC patients is still poorly understood. Thus, the present study was aimed at investigating the prognostic value of altered APC functionality for progression-free (PFS) and overall survival (OS) in a cohort study of BC patients. APC functionality was retrospectively analyzed by a coagulation inhibition assay (ThromboPath) in 290 consecutive patients with primary (n=246) or relapsing/recurrent (n=44) BC. All patients were prospectively followed for a median time of 3.5 years (14% recurrence rate). As control group, 145 age-matched healthy women were also investigated. The results obtained demonstrated that APC function was impaired in roughly 20% of all BC at baseline. BC women with stage I/II had a significantly lower rate of APC impairment (13%) than women with stage III (22%) or distant metastases (44%, p=0.001). At univariate analyses, an impairment of APC function had a negative prognostic impact in terms of PFS (5-year PFS rates 53% vs. 70%; HR=2.5; p<0.001) and OS (5-year OS rates 79% vs. 93%; HR=3.9; p=0.005). However, prognostic significance was retained in multivariate models only for PFS (HR=2.0; p=0.017). We may, thus, conclude that BC patients are in a prothrombotic condition, which could play a role in the progression of the disease. Monitoring coagulation changes in BC women could provide important prognostic information especially in patients with advanced stages. PMID:27429857

  3. Crossover studies with survival outcomes.

    PubMed

    Buyze, Jozefien; Goetghebeur, Els

    2013-12-01

    Crossover designs are well known to have major advantages when comparing the effect of two treatments which do not interact. With a right-censored survival endpoint, however, this design is quickly abandoned in favour of the more costly parallel design. Motivated by human immunodeficiency virus (HIV) prevention studies which lacked power, we evaluate what may be gained in this setting and compare parallel with crossover designs. In a heterogeneous population, we find and explain a substantial increase in power for the crossover study using a non-parametric logrank test. With frailties in a proportional hazards model, crossover designs equally lead to substantially smaller variance for the subject-specific hazard ratio (HR), while the population-averaged HR sees negligible gain. Its efficiency benefit is recovered when the population-averaged HR is reconstructed from estimated subject-specific hazard rates. We derive the time point for treatment crossover that optimizes efficiency and end with the analysis of two recent HIV prevention trials. We find that a Cellulose sulphate trial could have hardly gained efficiency from a crossover design, while a Nonoxynol-9 trial stood to gain substantial power. We conclude that there is a role for effective crossover designs in important classes of survival problems. PMID:21715438

  4. Survival analysis of aging aircraft

    NASA Astrophysics Data System (ADS)

    Benavides, Samuel

    This study pushes systems engineering of aging aircraft beyond the boundaries of empirical and deterministic modeling by making a sharp break with the traditional laboratory-derived corrosion prediction algorithms that have shrouded real-world failures of aircraft structure. At the heart of this problem is the aeronautical industry's inability to be forthcoming in an accurate model that predicts corrosion failures in aircraft in spite of advances in corrosion algorithms or improvements in simulation and modeling. The struggle to develop accurate corrosion probabilistic models stems from a multitude of real-world interacting variables that synergistically influence corrosion in convoluted and complex ways. This dissertation, in essence, offers a statistical framework for the analysis of structural airframe corrosion failure by utilizing real-world data while considering the effects of interacting corrosion variables. This study injects realism into corrosion failures of aging aircraft systems by accomplishing four major goals related to the conceptual and methodological framework of corrosion modeling. First, this work connects corrosion modeling from the traditional, laboratory derived algorithms to corrosion failures in actual operating aircraft. This work augments physics-based modeling by examining the many confounding and interacting variables, such as environmental, geographical and operational, that impact failure of airframe structure. Examined through the lens of censored failure data from aircraft flying in a maritime environment, this study enhances the understanding between the triad of the theoretical, laboratory and real-world corrosion. Secondly, this study explores the importation and successful application of an advanced biomedical statistical tool---survival analysis---to model censored corrosion failure data. This well-grounded statistical methodology is inverted from a methodology that analyzes survival to one that examines failures. Third, this

  5. Impact of metformin use on survival in locally-advanced, inoperable non-small cell lung cancer treated with definitive chemoradiation

    PubMed Central

    Ahmed, Inaya; Ferro, Adam; Cohler, Alan; Langenfeld, John; Surakanti, Sujani G.; Aisner, Joseph; Zou, Wei; Haffty, Bruce G.

    2015-01-01

    Background We investigated survival outcomes in diabetic patients with non-small cell lung cancer (NSCLC) treated with concurrent metformin and definitive chemoradiation. Methods This single-institution, retrospective cohort study included 166 patients with NSCLC who were treated definitively with chemoradiation between 1999 and 2013. Of 40 patients who had type II diabetes, 20 (50%) were on metformin, and 20 (50%) were not on metformin. The primary outcome was overall survival (OS), and secondary outcomes included progression-free survival (PFS), locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS). Kaplan Meier method and log-rank test were performed in survival analysis. Cox regression was utilized in univariate analysis of potential confounders. Results Median follow-up was 17.0 months. Compared with non-diabetic patients, diabetic patients on metformin demonstrated similar OS (16.3 vs. 14.3 mo, P=0.23), PFS (11.6 vs. 9.7 mo, P=0.26), LRRFS (14.1 vs. 11.9 mo, P=0.78), and DMFS (13.4 vs. 10.0 mo, P=0.69). Compared with diabetic patients not on metformin, diabetic patients on metformin also exhibited similar OS (14.3 vs. 19.2 mo, P=0.18), PFS (19.7 vs. 10.1 mo, P=0.38), LRRFS (11.9 vs. 15.5 mo, P=0.69), and DMFS (10.0 vs. 17.4 mo, P=0.12). Identified negative prognostic factors on included squamous cell histology, lower performance status, higher T stage, and non-caucasian ethnicity. Conclusions No statistically significant differences in survival or patterns of failure were found among the three cohorts in this small set of patients. No statistically significant differences in survival or patterns of failure were found between the three cohorts in this small set of patients. Though it is possible that metformin use may in fact have no effect on survival in NSCLC patients treated with definitive RT, larger-scale retrospective and prospective studies are implicated for clarification. PMID:25922712

  6. Postoperative Treatment of Primary Glioblastoma Multiforme With Radiation and Concomitant Temozolomide in Elderly Patients

    SciTech Connect

    Combs, Stephanie E. Wagner, Johanna; Bischof, Marc; Welzel, Thomas; Wagner, Florian; Debus, Juergen; Schulz-Ertner, Daniela

    2008-03-15

    Purpose: To evaluate efficacy and toxicity in elderly patients with glioblastoma multiforme (GBM) treated with postoperative radiochemotherapy with temozolomide (TMZ). Patients and Methods: Forty-three patients aged 65 years or older were treated with postoperative with radiochemotherapy using TMZ for primary GBM. Median age at primary diagnosis was 67 years; 14 patients were female, 29 were male. A complete surgical resection was performed in 12 patients, subtotal resection in 17 patients, and biopsy only in 14 patients. Radiotherapy was applied with a median dose of 60 Gy, in a median fractionation of 5 x 2 Gy/wk. Thirty-five patients received concomitant TMZ at 50 mg/m{sup 2}, and in 8 patients 75 mg/m{sup 2} of TMZ was applied. Adjuvant cycles of TMZ were prescribed in 5 patients only. Results: Median overall survival was 11 months in all patients; the actuarial overall survival rate was 48% at 1 year and 8% at 2 years. Median overall survival was 18 months after complete resection, 16 months after subtotal resection, and 6 months after biopsy only. Median progression-free survival was 4 months; the actuarial progression-free survival rate was 41% at 6 months and 18% at 12 months. Radiochemotherapy was well tolerated in most patients and could be completed without interruption in 38 of 43 patients. Four patients developed hematologic side effects greater than Common Terminology Criteria Grade 2, which led to early discontinuation of TMZ in 1 patient. Conclusions: Radiochemotherapy is safe and effective in a subgroup of elderly patients with GBM and should be considered in patients without major comorbidities.

  7. Prognostic factors for long term survival in patients with advanced non-small cell lung cancer

    PubMed Central

    Moumtzi, Despoina; Lampaki, Sofia; Porpodis, Konstantinos; Lagoudi, Kalliopi; Hohenforst-Schmidt, Wolfgang; Pataka, Athanasia; Tsiouda, Theodora; Zissimopoulos, Athanasios; Lazaridis, George; Karavasilis, Vasilis; Timotheadou, Helen; Barbetakis, Nikolaos; Pavlidis, Pavlos; Kontakiotis, Theodoros; Zarogoulidis, Konstantinos

    2016-01-01

    Background Non-small cell lung cancer (NSCLC) represents 85% of all lung cancers. It is estimated that 60% of patients with NSCLC at time of diagnosis have advanced disease. The aim of this study was to investigate clinical and demographic prognostic factors of long term survival in patients with unresectable NSCLC. Methods We retrospectively reviewed data of 1,156 patients with NSCLC stage IIIB or IV who survived more than 60 days from the time of diagnosis and treated from August 1987 until March 2013 in the Oncology Department of Pulmonary Clinic of the General Hospital Papanikolaou. Initially univariate analysis using the log-rank test was conducted and then multivariate analysis using the proportional hazards model of Cox. Also Kaplan Meier curves were used to describe the distribution of survival times of patients. The level of significance was set at 0.05. Results The mean age at diagnosis was 62 years. About 11.9% of patients were women and 88.1% were male. The majority of cases were adenocarcinomas (42.2%), followed squamous (33%) and finally the large cell (6%). Unlike men, most common histological type among women was adenocarcinoma rather than squamous (63% vs. 10.9%). In univariate analysis statistically significant factors in the progression free survival (PFS) and overall survival (OS) were: weight loss ≥5%, histological type, line 1 drugs, line 1 combination, line 1 cycles and radio lung. Specifically radio lung gives clear survival benefit in the PFS and OS in stage IIIB (P=0.002) and IV (P<0.001). On the other hand, the number of distant metastases in stage IV patients did not affect OS, neither PFS. In addition patients who received platinum and taxane had better PFS (P=0.001) and OS (P<0.001) than those who received platinum without taxane. Also the third drug administration proved futile, since survival (682.06±34.9) (P=0.023) and PFS (434.93±26.93) (P=0.012) of patients who received less than three drugs was significantly larger. Finally

  8. 20 CFR 725.213 - Duration of entitlement; surviving spouse or surviving divorced spouse.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Duration of entitlement; surviving spouse or surviving divorced spouse. 725.213 Section 725.213 Employees' Benefits EMPLOYMENT STANDARDS ADMINISTRATION... Benefits) § 725.213 Duration of entitlement; surviving spouse or surviving divorced spouse. (a)...

  9. 20 CFR 725.212 - Conditions of entitlement; surviving spouse or surviving divorced spouse.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Conditions of entitlement; surviving spouse or surviving divorced spouse. 725.212 Section 725.212 Employees' Benefits EMPLOYMENT STANDARDS... Dependents (augmented Benefits) § 725.212 Conditions of entitlement; surviving spouse or surviving...

  10. Delayed Complications in Patients Surviving at Least 3 Years After Stereotactic Radiosurgery for Brain Metastases

    SciTech Connect

    Yamamoto, Masaaki; Kawabe, Takuya; Higuchi, Yoshinori; Sato, Yasunori; Nariai, Tadashi; Barfod, Bierta E.; Kasuya, Hidetoshi; Urakawa, Yoichi

    2013-01-01

    Purpose: Little is known about delayed complications after stereotactic radiosurgery in long-surviving patients with brain metastases. We studied the actual incidence and predictors of delayed complications. Patients and Methods: This was an institutional review board-approved, retrospective cohort study that used our database. Among our consecutive series of 2000 patients with brain metastases who underwent Gamma Knife radiosurgery (GKRS) from 1991-2008, 167 patients (8.4%, 89 women, 78 men, mean age 62 years [range, 19-88 years]) who survived at least 3 years after GKRS were studied. Results: Among the 167 patients, 17 (10.2%, 18 lesions) experienced delayed complications (mass lesions with or without cyst in 8, cyst alone in 8, edema in 2) occurring 24.0-121.0 months (median, 57.5 months) after GKRS. The actuarial incidences of delayed complications estimated by competing risk analysis were 4.2% and 21.2% at the 60th month and 120th month, respectively, after GKRS. Among various pre-GKRS clinical factors, univariate analysis demonstrated tumor volume-related factors: largest tumor volume (hazard ratio [HR], 1.091; 95% confidence interval [CI], 1.018-1.154; P=.0174) and tumor volume {<=}10 cc vs >10 cc (HR, 4.343; 95% CI, 1.444-12.14; P=.0108) to be the only significant predictors of delayed complications. Univariate analysis revealed no correlations between delayed complications and radiosurgical parameters (ie, radiosurgical doses, conformity and gradient indexes, and brain volumes receiving >5 Gy and >12 Gy). After GKRS, an area of prolonged enhancement at the irradiated lesion was shown to be a possible risk factor for the development of delayed complications (HR, 8.751; 95% CI, 1.785-157.9; P=.0037). Neurosurgical interventions were performed in 13 patients (14 lesions) and mass removal for 6 lesions and Ommaya reservoir placement for the other 8. The results were favorable. Conclusions: Long-term follow-up is crucial for patients with brain metastases

  11. Updated survival analysis of two sequential prospective trials of R-MACLO-IVAM followed by maintenance for newly diagnosed mantle cell lymphoma

    PubMed Central

    Hosein, Peter J.; Sandoval-Sus, Jose D.; Goodman, Deborah; Arteaga, Alexandra Gomez; Reis, Isildinha; Hoffman, James; Stefanovic, Alexandra; Rosenblatt, Joseph D.; Lossos, Izidore S.

    2015-01-01

    A phase II trial of R-MACLO-IVAM followed by thalidomide maintenance for mantle cell lymphoma (MCL) demonstrated promising progression-free survival (PFS) and overall survival (OS) rates. Thalidomide maintenance was associated with significant toxicity and was subsequently modified to rituximab maintenance. Herein we present updated results and follow-up. Two sequential phase II trials included chemotherapy-naïve patients with MCL up to 75 years old. Four cycles of R-MACLO-IVAM chemotherapy were delivered as previously described. Patients who achieved complete responses (CR) were eligible for thalidomide or rituximab maintenance therapy. Among 36 patients enrolled, the mantle cell lymphoma International Prognostic Index (MIPI) was low in 53%, intermediate in 36% and high in 11%. Thirty-five patients completed at least 2 cycles of chemotherapy; 34 (94%) achieved a CR. After a median follow-up of 74.4 months, the 5-year PFS was 51% (95% CI 33% – 68%) and the 5-year OS was 85% (95% CI 73% – 97%). Two deaths occurred during the chemotherapy phase due to disease progression and neutropenic sepsis respectively. One patient developed secondary acute myeloid leukemia after 7 years. R-MACLO-IVAM chemotherapy is effective for patients with newly diagnosed MCL. PMID:25737247

  12. Clinical value of morphometric and DNA flow cytometric variables as independent predictors of survival in epithelial ovarian carcinoma: a 5-year follow-up study.

    PubMed

    Veerman, Margot M; van der Wurff, Anneke A M; van de Water, Marije; Kruitwagen, Roy F P M; Feijen, Harrie W H; Vos, Maria Caroline

    2009-09-01

    The aim of this follow-up study is to validate the clinical significance of quantitative morphometric and DNA flow cytometric variables as independent prognostic factors of overall survival and progression-free survival in epithelial ovarian carcinoma. Tumor samples were collected from 135 patients with epithelial ovarian carcinoma at 3 hospitals in the Netherlands. Evaluated clinico-pathologic variables were age, histologic subtype, differentiation grade, clinical stage [International Federation of Gynecology and Obstetrics (FIGO)], presence of ascites, serum CA-125, and the completeness of debulking surgery. Morphometry and DNA flow cytometric techniques were assessed on each tumor sample to determine the mitotic activity index (MAI), volume percentage epithelium, mean nuclear area (MNA), standard deviation of MNA (SD MNA), nuclear perimeter (NP), and DNA ploidy. Univariate analysis showed that differentiation grade, FIGO stage, presence of ascites, preoperative CA-125 levels, DNA ploidy, and MAI, NP, and MNA were of significant prognostic value. After multivariate analysis (using forward Cox proportional hazard analysis), only differentiation grade and FIGO stage remained significant. From this study, we can conclude that morphometry and DNA flow cytometry are not independent prognosticators and therefore have no clinical value in predicting prognosis in ovarian carcinoma.

  13. Genitourinary mast cells and survival.

    PubMed

    Theoharides, Theoharis C; Stewart, Julia M

    2015-10-01

    Mast cells (MCs) are ubiquitous in the body, but they have historically been associated with allergies, and most recently with regulation of immunity and inflammation. However, it remains a puzzle why so many MCs are located in the diencephalon, which regulates emotions and in the genitourinary tract, including the bladder, prostate, penis, vagina and uterus that hardly ever get allergic reactions. A number of papers have reported that MCs have estrogen, gonadotropin and corticotropin-releasing hormone (CRH) receptors. Moreover, animal experiments have shown that diencephalic MCs increase in number during courting in doves. We had reported that allergic stimulation of nasal MCs leads to hypothalamic-pituitary adrenal (HPA) activation. Interestingly, anecdotal information indicates that female patients with mastocytosis or mast cell activation syndrome may have increased libido. Preliminary evidence also suggests that MCs may have olfactory receptors. MCs may, therefore, have been retained phylogenetically not only to "smell danger", but to promote survival and procreation. PMID:26813805

  14. Survivable pulse power space radiator

    DOEpatents

    Mims, J.; Buden, D.; Williams, K.

    1988-03-11

    A thermal radiator system is described for use on an outer space vehicle, which must survive a long period of nonuse and then radiate large amounts of heat for a limited period of time. The radiator includes groups of radiator panels that are pivotally connected in tandem, so that they can be moved to deployed configuration wherein the panels lie largely coplanar, and to a stowed configuration wherein the panels lie in a stack to resist micrometerorite damage. The panels are mounted on a boom which separates a hot power source from a payload. While the panels are stowed, warm fluid passes through their arteries to keep them warm enough to maintain the coolant in a liquid state and avoid embrittlement of material. The panels can be stored in a largely cylindrical shell, with panels progressively further from the boom being of progressively shorter length. 5 figs.

  15. Genitourinary mast cells and survival

    PubMed Central

    Stewart, Julia M.

    2015-01-01

    Mast cells (MCs) are ubiquitous in the body, but they have historically been associated with allergies, and most recently with regulation of immunity and inflammation. However, it remains a puzzle why so many MCs are located in the diencephalon, which regulates emotions and in the genitourinary tract, including the bladder, prostate, penis, vagina and uterus that hardly ever get allergic reactions. A number of papers have reported that MCs have estrogen, gonadotropin and corticotropin-releasing hormone (CRH) receptors. Moreover, animal experiments have shown that diencephalic MCs increase in number during courting in doves. We had reported that allergic stimulation of nasal MCs leads to hypothalamic-pituitary adrenal (HPA) activation. Interestingly, anecdotal information indicates that female patients with mastocytosis or mast cell activation syndrome may have increased libido. Preliminary evidence also suggests that MCs may have olfactory receptors. MCs may, therefore, have been retained phylogenetically not only to “smell danger”, but to promote survival and procreation. PMID:26813805

  16. Survival Data and Regression Models

    NASA Astrophysics Data System (ADS)

    Grégoire, G.

    2014-12-01

    We start this chapter by introducing some basic elements for the analysis of censored survival data. Then we focus on right censored data and develop two types of regression models. The first one concerns the so-called accelerated failure time models (AFT), which are parametric models where a function of a parameter depends linearly on the covariables. The second one is a semiparametric model, where the covariables enter in a multiplicative form in the expression of the hazard rate function. The main statistical tool for analysing these regression models is the maximum likelihood methodology and, in spite we recall some essential results about the ML theory, we refer to the chapter "Logistic Regression" for a more detailed presentation.

  17. [Circulatory survival of irreversible comas].

    PubMed

    Cartier, F; Chevet, D; Garré, M; Launois, B; Thomas, R; Le Pollès, R

    1975-01-18

    On the basis of a series of 53 cases of irreversible coma maintained in circulatory survival with the aim of removing the kidneys, the authors discuss the mode of treatment, with particular reference to the intravenous fluids used and the use of medications influencing the circulation. Fluid and electrolytes given must be adjusted hourly to ensure the exact replacement of urinary losses. Isoprotenerol is the only medication usually necessary. In the event of circulatory insufficiency, which is difficult to foresee and hence prevent, immediate volume expansion in a short a time as possible and isoprotenerol most frequently correct the situation (14 out of 17 cases). Thus effective circulation may be maintained until the kidneys are removed (48 out of 53 cases). 92 p.cent of the grafted kidneys functioned from the first day onwards. PMID:1093120

  18. Bacterial survival in laundered fabrics.

    PubMed

    Walter, W G; Schillinger, J E

    1975-03-01

    Bacterial survival was determined in linens (i) inoculated with Staphylococcus auerus (ii), taken from hospital isolation patients' beds, and (iii) used by students in their homes. Two different washers using temperatures of 38, 49, 54 and 60 C, respectively, for different times were empolyed along with a commercial tumbler dryer. Findings, after macerating the linens in Waring blender and enumerating on nonselective media, indicate that acceptable levels of survivors can be acheived in motel and hotel linens by an 8- to 10-min wash cycle at 54 C followed by adequate drying. However, it is recommended that a wash cycle with 60 C for 10 to 13 min be employed for linens in health care factilities. The microbial significance of various laundering practices is discussed. PMID:1090256

  19. Bacterial Survival in Laundered Fabrics

    PubMed Central

    Walter, William G.; Schillinger, John E.

    1975-01-01

    Bacterial survival was determined in linens (i) inoculated with Staphylococcus aureus (ii), taken from hospital isolation patients' beds, and (iii) used by students in their homes. Two different washers using temperatures of 38, 49, 54 and 60 C, respectively, for different times were employed along with a commercial tumbler dryer. Findings, after macerating the linens in a Waring blender and enumerating on nonselective media, indicate that acceptable levels of survivors can be achieved in motel and hotel linens by an 8- to 10-min wash cycle at 54 C followed by adequate drying. However, it is recommended that a wash cycle with 60 C for 10 to 13 min be employed for linens in health care factilities. The microbial significance of various laundering practices is discussed. PMID:1090256

  20. Survivable pulse power space radiator

    DOEpatents

    Mims, James; Buden, David; Williams, Kenneth

    1989-01-01

    A thermal radiator system is described for use on an outer space vehicle, which must survive a long period of nonuse and then radiate large amounts of heat for a limited period of time. The radiator includes groups of radiator panels that are pivotally connected in tandem, so that they can be moved to deployed configuration wherein the panels lie largely coplanar, and to a stowed configuration wherein the panels lie in a stack to resist micrometeorite damage. The panels are mounted on a boom which separates a hot power source from a payload. While the panels are stowed, warm fluid passes through their arteries to keep them warm enough to maintain the coolant in a liquid state and avoid embrittlement of material. The panels can be stored in a largely cylindrical shell, with panels progressively further from the boom being of progressively shorter length.

  1. Optics survivability support, volume 2

    NASA Astrophysics Data System (ADS)

    Wild, N.; Simpson, T.; Busdeker, A.; Doft, F.

    1993-01-01

    This volume of the Optics Survivability Support Final Report contains plots of all the data contained in the computerized Optical Glasses Database. All of these plots are accessible through the Database, but are included here as a convenient reference. The first three pages summarize the types of glass included with a description of the radiation source, test date, and the original data reference. This information is included in the database as a macro button labeled 'LLNL DATABASE'. Following this summary is an Abbe chart showing which glasses are included and where they lie as a function of nu(sub d) and n(sub d). This chart is also callable through the database as a macro button labeled 'ABBEC'.

  2. Maternal nutrition, health, and survival.

    PubMed

    Christian, Parul

    2002-05-01

    The burden of maternal morbidity and mortality in developing countries is high. Each year, 600,000 women die from pregnancy-related causes and 62 million women suffer from morbidity and complications of pregnancy. The extent to which maternal nutrition can improve maternal health and survival is not well understood. Excluding deaths due to induced abortions, the other four main causes of maternal mortality (preeclampsia, hemorrhage, obstructed labor, and infection) may be amenable to nutrition interventions. The role of calcium in reducing the incidence of preeclampsia and hypertension is promising, but more research in deficient populations is urgently needed. Antenatal iron supplementation, although frequently recommended to prevent anemia during pregnancy, has had little program success. Severe anemia may be an important cause of maternal mortality, but convincing evidence is lacking on the health consequences of mild-to-moderate maternal anemia. Knowledge of the etiology of anemia is important in identifying effective strategies for combating it. Other vitamins such as folate, B12, and vitamin A may enhance the effect of iron supplementation in populations where multiple nutrition deficiencies exist. Maternal night blindness is widespread in South Asian women. In Nepal, this condition is associated with markedly increased risks of vitamin A deficiency, anemia, morbidity, and maternal and infant mortality. These findings need to be replicated elsewhere in South Asia. One study has shown vitamin A and beta carotene supplementation to reduce maternal mortality and morbidity. These findings need testing in different settings with emphasis on investigating the mechanisms of the effect. The area of prepregnancy nutrition and its influence on prolonged and obstructed labor is wide open for investigation. The scope for research in the area of maternal nutrition and health is large and the onus is on nutritionists to bring to the forefront the role of nutrition in

  3. A tumor DNA complex aberration index is an independent predictor of survival in breast and ovarian cancer.

    PubMed

    Vollan, Hans Kristian Moen; Rueda, Oscar M; Chin, Suet-Feung; Curtis, Christina; Turashvili, Gulisa; Shah, Sohrab; Lingjærde, Ole Christian; Yuan, Yinyin; Ng, Charlotte K; Dunning, Mark J; Dicks, Ed; Provenzano, Elena; Sammut, Stephen; McKinney, Steven; Ellis, Ian O; Pinder, Sarah; Purushotham, Arnie; Murphy, Leigh C; Kristensen, Vessela N; Brenton, James D; Pharoah, Paul D P; Børresen-Dale, Anne-Lise; Aparicio, Samuel; Caldas, Carlos

    2015-01-01

    Complex focal chromosomal rearrangements in cancer genomes, also called "firestorms", can be scored from DNA copy number data. The complex arm-wise aberration index (CAAI) is a score that captures DNA copy number alterations that appear as focal complex events in tumors, and has potential prognostic value in breast cancer. This study aimed to validate this DNA-based prognostic index in breast cancer and test for the first time its potential prognostic value in ovarian cancer. Copy number alteration (CNA) data from 1950 breast carcinomas (METABRIC cohort) and 508 high-grade serous ovarian carcinomas (TCGA dataset) were analyzed. Cases were classified as CAAI positive if at least one complex focal event was scored. Complex alterations were frequently localized on chromosome 8p (n = 159), 17q (n = 176) and 11q (n = 251). CAAI events on 11q were most frequent in estrogen receptor positive (ER+) cases and on 17q in estrogen receptor negative (ER-) cases. We found only a modest correlation between CAAI and the overall rate of genomic instability (GII) and number of breakpoints (r = 0.27 and r = 0.42, p < 0.001). Breast cancer specific survival (BCSS), overall survival (OS) and ovarian cancer progression free survival (PFS) were used as clinical end points in Cox proportional hazard model survival analyses. CAAI positive breast cancers (43%) had higher mortality: hazard ratio (HR) of 1.94 (95%CI, 1.62-2.32) for BCSS, and of 1.49 (95%CI, 1.30-1.71) for OS. Representations of the 70-gene and the 21-gene predictors were compared with CAAI in multivariable models and CAAI was independently significant with a Cox adjusted HR of 1.56 (95%CI, 1.23-1.99) for ER+ and 1.55 (95%CI, 1.11-2.18) for ER- disease. None of the expression-based predictors were prognostic in the ER- subset. We found that a model including CAAI and the two expression-based prognostic signatures outperformed a model including the 21-gene and 70-gene signatures but excluding CAAI. Inclusion of CAAI in the

  4. Bone Marrow Minimal Residual Disease Was an Early Response Marker and a Consistent Independent Predictor of Survival After Anti-GD2 Immunotherapy

    PubMed Central

    Cheung, Nai-Kong V.; Ostrovnaya, Irina; Kuk, Deborah; Cheung, Irene Y.

    2015-01-01

    Purpose Immunotherapy is a standard of care for children with high-risk neuroblastoma, where bone marrow (BM) is the predominant metastatic site. Early response markers of minimal residual disease (MRD) in the BM that are also predictive of survival could help individualize patient therapies. Patients and Methods After achieving first remission (n = 163), primary refractory disease (n = 102), or second remission (n = 95), children with stage 4 neuroblastoma received anti-GD2 3F8 antibody immunotherapy. BM MRD before 3F8 treatment and after cycle 2 (postMRD) was measured using a four-marker panel (B4GALNT1, PHOX2B, CCND1, and ISL1) by quantitative reverse transcription polymerase chain reaction. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Prognostic variables were tested in both univariable and multivariable analyses, and MRD markers were further assessed individually and in combination as binary composite (postMRD: 0 and 1) and as equal sum (postMRDSum: 0 to 4) using the Cox regression models, and their predictive accuracy was determined by the concordance index. Results When BM was evaluated after cycle 2, individual markers were highly predictive of PFS and OS. The prediction accuracy improved when they were combined in postMRDSum. A multivariable model taking into account all the variables significant in the univariable analyses identified postMRDSum to be independently predictive of PFS and OS. When the model for OS also included missing killer immunoglobulin-like receptor ligand, human antimouse antibody response, and the enrollment disease status, the concordance index was 0.704. Conclusion BM MRD after two cycles of immunotherapy was confirmed as an early response marker and a consistent independent predictor of survival. PMID:25559819

  5. Androgen Deprivation Therapy Does Not Impact Cause-Specific or Overall Survival in High-Risk Prostate Cancer Managed With Brachytherapy and Supplemental External Beam

    SciTech Connect

    Merrick, Gregory S. . E-mail: gmerrick@urologicresearchinstitute.org; Butler, Wayne M.; Wallner, Kent E.; Galbreath, Robert W.; Allen, Zachariah A.; Adamovich, Edward; Lief, Jonathan

    2007-05-01

    Purpose: To determine cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) in high-risk prostate cancer patients undergoing brachytherapy with or without supplemental therapies. Methods and Materials: Between April 1995 and July 2002, 204 patients with high-risk prostate cancer (Gleason score {>=}8 or prostate-specific antigen [PSA] >20 ng/mL or clinical stage {>=}T2c) underwent brachytherapy. Median follow-up was 7.0 years. The bPFS was defined by a PSA {<=}0.40 ng/mL after nadir. Multiple clinical, treatment, and dosimetric parameters were evaluated for the impact on survival. Results: The 10-year CSS, bPFS, and OS were 88.9%, 86.6%, and 68.6%, respectively. A statistically significant difference in bPFS was discerned between hormone naive, ADT {<=}6 months, and ADT >6 month cohorts (79.7% vs. 95.% vs. 89.9%, p = 0.032). Androgen deprivation therapy (ADT) did not impact CSS or OS. For bPFS patients, the median posttreatment PSA was <0.04 ng/mL. A Cox linear regression analysis demonstrated that Gleason score was the best predictor of CSS, whereas percent positive biopsies and duration of ADT best predicted for bPFS. The OS was best predicted by Gleason score and diabetes. Thirty-eight patients have died, with 26 of the deaths from cardiovascular/pulmonary disease or second malignancy. Eleven patients have died of metastatic prostate cancer. Conclusions: The ADT improved 10-year bPFS without statistical impact on CSS or OS. Death as a result of cardiovascular/pulmonary disease and second malignancies were more than twice as common as prostate cancer deaths. Strategies to improve cardiovascular health should positively impact OS.

  6. Low HIP1R mRNA and protein expression are associated with worse survival in diffuse large B-cell lymphoma patients treated with R-CHOP.

    PubMed

    Wong, Kah Keng; Ch'ng, Ewe Seng; Loo, Suet Kee; Husin, Azlan; Muruzabal, María Arestin; Møller, Michael B; Pedersen, Lars M; Pomposo, María Puente; Gaafar, Ayman; Banham, Alison H; Green, Tina M; Lawrie, Charles H

    2015-12-01

    Huntingtin-interacting protein 1-related (HIP1R) is an endocytic protein involved in receptor trafficking, including regulating cell surface expression of receptor tyrosine kinases. We have previously shown that low HIP1R protein expression was associated with poorer survival in diffuse large B-cell lymphoma (DLBCL) patients from Denmark treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). In this multicenter study, we extend these findings and validate the prognostic and subtyping utility of HIP1R expression at both transcript and protein level. Using data mining on three independent transcriptomic datasets of DLBCL, HIP1R transcript was preferentially expressed in germinal center B-cell (GCB)-like DLBCL subtype (P<0.01 in all three datasets), and lower expression was correlated with worse overall survival (OS; P<0.01) and progression-free survival (PFS; P<0.05) in a microarray-profiled DLBCL dataset. At the protein level examined by immunohistochemistry, HIP1R expression at 30% cut-off was associated with GCB-DLBCL molecular subtype (P=0.0004; n=42), and predictive of OS (P=0.0006) and PFS (P=0.0230) in de novo DLBCL patients treated with R-CHOP (n=73). Cases with high FOXP1 and low HIP1R expression frequency (FOXP1(hi)/HIP1R(lo) phenotype) exhibited poorer OS (P=0.0038) and PFS (P=0.0134). Multivariate analysis showed that HIP1R<30% or FOXP1(hi)/HIP1R(lo) subgroup of patients exhibited inferior OS and PFS (P<0.05) independently of the International Prognostic Index. We conclude that HIP1R expression is strongly indicative of survival when utilized on its own or in combination with FOXP1, and the molecule is potentially applicable for subtyping of DLBCL cases. PMID:26341140

  7. 10-Year Survival and Quality of Life in Patients With High-Risk {sub P}N{sub 0} Prostate Cancer Following Definitive Radiotherapy

    SciTech Connect

    Berg, Arne Lilleby, Wolfgang; Bruland, Oyvind Sverre; Fossa, Sophie Dorothea

    2007-11-15

    Purpose: To evaluate long-term overall survival (OS), cancer-specific survival (CSS), clinical progression-free survival (cPFS), and health-related quality of life (HRQoL) following definitive radiotherapy (RT) given to T{sub 1-4p}N{sub 0}M{sub 0} prostate cancer patients provided by a single institution between 1989 and 1996. Methods and Materials: We assessed outcome among 203 patients who had completed three-dimensional conformal RT (66 Gy) without hormone treatment and in whom staging by lymphadenectomy had been performed. OS was compared with an age-matched control group from the general population. A cross-sectional, self-report survey of HRQoL was performed among surviving patients. Results: Median observation time was 10 years (range, 1-16 years). Eighty-one percent had high-risk tumors defined as T{sub 3-4} or Gleason score (GS) {>=}7B (4+3). Among these, 10-year OS, CSS, and cPFS rates were 52%, 66%, and 39%, respectively. The corresponding fractions in low-risk patients (T{sub 1-2} and GS {<=}7A [3+4]) were 79%, 95%, and 73%, respectively. Both CSS and cPFS were predicted by GS and T-classification; OS was associated with GS only. High-risk, but not low-risk, patients had reduced OS compared with the general population (p < 0.0005). When pelvis-related side effects were included in multivariate analyzes together with physical function and pain, sexual, urinary, and bowel function were not independently associated with self-reported global quality of life. Conclusions: Despite surgically proven {sub p}N{sub 0}, RT with dosage <70 Gy as monotherapy does not give satisfactory CSS rates after 10 years in patients with T{sub 3-4} or GS {>=}7B.

  8. Survival analysis of pelvic lymphadenectomy alone versus combined pelvic and para-aortic lymphadenectomy in patients exhibiting endometrioid type endometrial cancer

    PubMed Central

    TOPTAS, TAYFUN; SIMSEK, TAYUP

    2015-01-01

    The therapeutic benefit of lymphadenectomy in patients exhibiting endometrial cancer (EC) remains controversial. The aim of the present study was to determine whether the addition of para-aortic lymphadenectomy to pelvic lymphadenectomy (PLND) improves survival in patients with endometrioid type EC. A single tertiary-center, retrospective analysis was conducted in a total of 186 patients who were surgically treated with either PLND alone (n=97) or combined pelvic and para-aortic lymphadenectomy (PPaLND; n=89). Adjuvant treatments were assigned according to the Gynecologic Oncology Group (GOG) risk of recurrence analysis. The primary endpoint of the present study was progression-free survival (PFS). The median follow-up time was 38 months (95% confidence interval, 36.47–42.90) for all patients. No statistically significant differences were identified between the two groups in terms of overall survival (OS), PFS or time to progression (TTP). Kaplan-Meier estimates of three-year OS, PFS and TTP for patients with low or low-intermediate risk were as follows: PLND, 100, 98.7 and 98.7%, respectively; and PPaLND, all 100%. The estimated three-year OS, PFS and TTP for patients with high or high-intermediate risk were as follows: PLND, 92.3, 81.3 and 81.3%; and PPaLND, 90.7, 77.1 and 80.9%, respectively. No statistically significant differences were detected in the three-year OS, PFS and TTP between the lymphadenectomy groups, regardless of the GOG risk of recurrence (PLND, 98.4, 95.3 and 95.3%; and PPaLND, 94.9, 87.1 and 89.4%). Therefore, the combination treatment, PPaLND did not provide any survival advantage over pelvic lymphadenectomy alone. PMID:25435992

  9. Hypoxia-inducible factor-1 {alpha} expression predicts superior survival in patients with diffuse large B-cell lymphoma treated with R-CHOP.

    PubMed

    Evens, Andrew M; Sehn, Laurie H; Farinha, Pedro; Nelson, Beverly P; Raji, Adekunle; Lu, Yi; Brakman, Adam; Parimi, Vamsi; Winter, Jane N; Schumacker, Paul T; Gascoyne, Randy D; Gordon, Leo I

    2010-02-20

    PURPOSE Hypoxia-inducible factor (HIF) controls the expression of genes in response to hypoxia, as well as a wide range of other cellular processes. We previously showed constitutive stabilization of HIF-1alpha in the majority of patients with diffuse large B-cell lymphoma (DLBCL). To our knowledge, the prognostic significance of HIF in lymphoma has never been investigated. PATIENTS AND METHODS We studied the immunohistochemical protein expression of HIF-1alpha on tissue microarrays from 153 patients with DLBCL treated in sequential cohorts with cyclophosphamide, doxorubicin, oncovin, and prednisone (CHOP) or rituximab-CHOP (R-CHOP) from 1999 to 2002. Results were correlated with patient outcome. Results Median follow-up for all patients was 80 months. Among all patients, HIF-1alpha was expressed in 62% of germinal center and 59% of non-germinal center patients. With HIF-1alpha analyzed as a dependent variable, there were no survival differences in CHOP-treated patients. In the R-CHOP group, however, HIF-1alpha protein expression correlated with significantly improved progression-free survival (PFS) and overall survival (OS). Five-year PFS for HIF-1alpha-positive patients was 71% v 43% for HIF-1alpha-negative patients (P = .0187), whereas 5-year OS was 75% and 54%, respectively (P = .025). In multivariate analysis with International Prognostic Index criteria, HIF-1alpha remained a significant predictor for PFS (P = .026) and OS (P = .043). Compared with other biomarkers, HIF-1alpha correlated only with BCL6 (P = .004). In terms of gene expression, we found several common gene associations of HIF-1alpha and the stromal-1 signature with genes predominantly involved in regulation of the extracellular matrix (eg, BGN, COL1A2, COL5A1, and PLOD2). CONCLUSION The expression of HIF-1alpha protein is an important independent favorable prognostic factor for survival in patients with DLBCL treated with R-CHOP. PMID:20048181

  10. Local Response and Impact on Survival After Local Ablation of Liver Metastases From Colorectal Carcinoma by Computed Tomography-Guided High-Dose-Rate Brachytherapy

    SciTech Connect

    Ricke, Jens; Mohnike, Konrad; Pech, Maciej; Seidensticker, Max; Ruehl, Ricarda; Wieners, Gero; Gaffke, Gunnar; Kropf, Siegfried; Felix, Roland; Wust, Peter

    2010-10-01

    Purpose: To determine local tumor control after CT-guided brachytherapy at various dose levels and the prognostic impact of extensive cytoreduction in colorectal liver metastases. Methods and Materials: Seventy-three patients were treated on a single-center prospective trial that was initially designed to be randomized to three dose levels of 15 Gy, 20 Gy, or 25 Gy per lesion, delivered in a single fraction. However, because there was a high rate of cross-over of subjects from higher to lower dose levels, this study is better understood as a prospective trial with three dose levels. No upper size limit for the metastases was applied. We assessed time to local progression, progression-free survival, and overall survival. Results: According to safety constraints cross-over was performed. The final assignment was n = 98, n = 68, and n = 33 in the 15-Gy, 20-Gy, and 25-Gy groups, respectively. Median diameter of the largest tumor lesion in each patient was 5 cm (range, 1-13.5 cm). Estimated mean local recurrence-free survival for all lesions was 34 months (median not reached). The group assigned to 15 Gy after cross-over displayed 34 local recurrences out of 98 lesions; 20 Gy, 15 out of 68 lesions; 25 Gy, 1 out of 33 lesions. The difference between the 25-Gy and the 20-Gy or 15-Gy group was significant (p < 0.05). Repeated local tumor ablations were the most prominent factor for increased survival and dominated additional systemic antitumor treatments. Conclusions: Local tumor control after CT-guided brachytherapy of colorectal liver metastases demonstrated a strong dose dependency. The role of extensive minimally invasive tumor ablation in metastatic colorectal cancer needs to be further established.

  11. Improved Survival of HER2+ Breast Cancer Patients Treated with Trastuzumab and Chemotherapy Is Associated with Host Antibody Immunity against the HER2 Intracellular Domain.

    PubMed

    Knutson, Keith L; Clynes, Raphael; Shreeder, Barath; Yeramian, Patrick; Kemp, Kathleen P; Ballman, Karla; Tenner, Kathleen S; Erskine, Courtney L; Norton, Nadine; Northfelt, Donald; Tan, Winston; Calfa, Carmen; Pegram, Mark; Mittendorf, Elizabeth A; Perez, Edith A

    2016-07-01

    The addition of trastuzumab to chemotherapy extends survival among patients with HER2(+) breast cancer. Prior work showed that trastuzumab and chemotherapy augments HER2 extracellular domain (ECD)-specific antibodies. The current study investigated whether combination therapy induced immune responses beyond HER2-ECD and, importantly, whether those immune responses were associated with survival. Pretreatment and posttreatment sera were obtained from 48 women with metastatic HER2(+) breast cancer on NCCTG (now Alliance for Clinical Trials in Oncology) studies, N0337 and N983252. IgG to HER2 intracellular domain (ICD), HER2-ECD, p53, IGFBP2, CEA, and tetanus toxoid were examined. Sera from 25 age-matched controls and 26 surgically resected HER2(+) patients were also examined. Prior to therapy, some patients with metastatic disease had elevated antibodies to IGFBP2, p53, HER2-ICD, HER2-ECD, and CEA, but not to tetanus toxin, relative to controls and surgically resected patients. Treatment augmented antibody responses to HER2-ICD in 69% of metastatic patients, which was highly associated with improved progression-free survival (PFS; HR = 0.5, P = 0.0042) and overall survival (OS; HR = 0.7, P = 0.038). Augmented antibody responses to HER2-ICD also correlated (P = 0.03) with increased antibody responses to CEA, IGFBP2, and p53, indicating that treatment induces epitope spreading. Paradoxically, patients who already had high preexisting immunity to HER2-ICD did not respond to therapy with increased antibodies to HER2-ICD and demonstrated poorer PFS (HR = 1.6, P < 0.0001) and OS (HR = 1.4, P = 0.0006). Overall, the findings further demonstrate the importance of the adaptive immune system in the efficacy of trastuzumab-containing regimens. Cancer Res; 76(13); 3702-10. ©2016 AACR. PMID:27197192

  12. Long-term survival outcomes of reduced-intensity allogeneic or autologous transplantation in relapsed grade 3 follicular lymphoma

    PubMed Central

    Klyuchnikov, Evgeny; Bacher, Ulrike; Ahn, Kwang Woo; Carreras, Jeanette; Kröger, Nicolaus M.; Hari, Parameswaran N.; Ku, Grace H.; Ayala, Ernesto; Chen, Andy I.; Chen, Yi-Bin; Cohen, Jonathon B.; Freytes, César O.; Gale, Robert Peter; Kamble, Rammurti T.; Kharfan-Dabaja, Mohamed A.; Lazarus, Hillard M.; Martino, Rodrigo; Mussetti, Alberto; Savani, Bipin N.; Schouten, Harry C.; Usmani, Saad Z.; Wiernik, Peter H.; Wirk, Baldeep; Smith, Sonali M.; Sureda, Anna; Hamadani, Mehdi

    2015-01-01

    Grade-3 follicular lymphoma (FL) has aggressive clinical behavior. To evaluate the optimal first transplantation approach in relapsed/refractory grade-3 FL patients, we compared the long-term outcomes after allogeneic (allo-) vs. autologous hematopoietic cell transplantation (auto-HCT) in the rituximab-era. A total of 197 patients undergoing first RIC allo-HCT or first auto-HCT during 2000-2012 were included. Rituximab-naïve patients were excluded. Allo-HCT recipients were younger; more heavily pretreated, and had a longer interval between diagnosis and HCT. The 5-year probabilities of non-relapse mortality (NRM), relapse/progression, progression-free survival (PFS) and overall survival (OS) for auto-HCT vs. allo-HCT groups were 4% vs. 27% (p<0.001); 61% vs. 20% (p<0.001); 36% vs. 51% (p=0.07) and 59% vs. 54% (p=0.7), respectively. On multivariate analysis auto-HCT was associated with reduced risk of NRM (RR=0.20; p=0.001). Within the first 11months post-HCT auto- and allo-HCT had similar risks of relapse/progression and PFS. Beyond 11months, auto-HCT was associated with higher risk of relapse/progression (RR=21.3; p=0.003) and inferior PFS (RR=3.2; p=0.005). In the first 24 months post-HCT, auto-HCT was associated with improved OS (RR=0.42; p=0.005), but in long-time survivors (beyond 24 months) it was associated with inferior OS (RR=3.6; p=0.04). RIC allo-HCT as the first transplant approach can provide improved PFS and OS, in long-term survivors. PMID:26437062

  13. Markers of Epithelial to Mesenchymal Transition in Association with Survival in Head and Neck Squamous Cell Carcinoma (HNSCC)

    PubMed Central

    Pectasides, Eirini; Rampias, Theodoros; Sasaki, Clarence; Perisanidis, Christos; Kouloulias, Vassilis; Burtness, Barbara; Zaramboukas, Thomas; Rimm, David; Fountzilas, George; Psyrri, Amanda

    2014-01-01

    Background Elucidating the molecular phenotype of cancers with high metastatic potential will facilitate the development of novel therapeutic approaches to the disease. Gene expression profiles link epithelial to mesenchymal transition (EMT) phenotype with high-risk HNSCC. We sought to determine the role of protein biomarkers of EMT in head and neck squamous carcinoma (HNSC) prognosis. Methods Protein expression analysis of EGFR, β-catenin and E-cadherin was performed on a cohort of 102 patients with HNSCC recruited between 1992 and 2005 using automated quantitative protein analysis (AQUA). We evaluated associations with clinicopathological parameters and prognosis. Results There were 67 patients with primary squamous cell carcinoma of the head and neck in this cohort who met inclusion criteria and for whom we had complete E-cadherin, beta-catenin and EGFR expression data. High E-cadherin expressers had longer 5-year progression-free survival (PFS) compared to those with low E-cadherin (59.7% versus 40.6%, p = 0.04) and overall survival (OS) (69.6% versus 44.3%, p  = 0.05). Kaplan-Meier analysis showed that patients with low beta-catenin-expressing tumors trended toward worse 5-year PFS (p = 0.057). High EGFR expressers had inferior OS compared to low EGFR expressers (27.7% vs. 54%, p = 0.029). In the multivariable analysis context, E-cadherin remained an independent predictor of improved OS (HR = 0.204, 95% CI 0.043 to 0.972, p = 0.046) while EGFR trended towards significance for OS. Conclusions The putative markers of EMT defined within a panel of HNSCC using AQUA are associated with tumors of poor prognosis. PMID:24722213

  14. Addition of bortezomib to standard dose chop chemotherapy improves response and survival in relapsed mantle cell lymphoma.

    PubMed

    Furtado, Michelle; Johnson, Rod; Kruger, Anton; Turner, Deborah; Rule, Simon

    2015-01-01

    The proteasome inhibitor, bortezomib, potentially increases cell sensitivity to chemotherapy. This study was performed to determine the overall response rate (ORR), overall survival (OS), progression-free survival (PFS) and toxicity of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) compared to CHOP + bortezomib chemotherapy in mantle cell lymphoma (MCL) patients at first relapse. Forty-six patients were randomly assigned to standard dose CHOP ± bortezomib 1·6 mg/m(2) given on a 21-d cycle for up to eight cycles of treatment. Median age was 71 years (CHOP arm) and 69 years (CHOP-bortezomib arm). Median Eastern Cooperative Oncology Group performance status was 1 (CHOP) and 0 (CHOP-bortezomib) with 65% and 52%, respectively, having a disease stage of IV. ORR was 47·8% (CHOP) and 82·6% (CHOP-bortezomib). Complete response rate was 21·7% (CHOP) vs. 34·8% (CHOP-bortezomib); partial response rate was 26·1% (CHOP) vs. 47·8% (CHOP-bortezomib). Median OS was 11·8 months (CHOP) and 35·6 months (CHOP-bortezomib) (P = 0·01, Hazard ratio [HR] 0·37 [95% confidence interval (CI) 0·16-0·83)] and there was a non-significant improvement in PFS: 8·1 months (CHOP) and 16·5 months (CHOP-bortezomib) [P = 0·12, HR 0·60 (95% CI 0·31-1·15)]. Severe (≥grade 3) sensory neuropathy was similar in both arms (4·3% CHOP vs. 6·5% CHOP-bortezomib). We conclude that the addition of bortezomib to CHOP chemotherapy for relapsed MCL significantly improves outcome with a manageable increase in toxicity.

  15. Improved survival of poor prognosis diffuse histiocytic (large cell) lymphoma managed with sequential induction chemotherapy, "boost" radiation therapy, and autologous bone marrow transplantation.

    PubMed

    Chadha, M; Shank, B; Fuks, Z; Clarkson, B D; Bonfiglio, P; Gnecco, C; Gulati, S

    1988-03-01

    From 1981 to 1985, 33 patients with the diagnosis of diffuse histiocytic (large cell) lymphoma (DHL) with a poor prognosis received induction multi-drug chemotherapy followed by autologous marrow cryopreservation. Thirty patients who had residual disease after chemotherapy were given "boost" irradiation to these sites, followed immediately by hyperfractionated total body irradiation, 1320 to 1375 cGy in 11 fractions over 4 days, then cyclophosphamide (60 mg/kg/d) for 2 days. All patients received an autologous bone marrow transplant (ABMT), with 15 patients receiving marrow purged with 4-hydroperoxycyclophosphamide. Patients were transplanted either as part of a planned induction-transplant approach (Group I), or as salvage after relapse on the same induction regimen (Group II), or other conventional chemotherapy regimens (Group III). In the entire group, 16 of 33 patients (48%) are alive free of lymphoma with a median follow-up of 32 months (11 to 53 mo). Actuarial (Kaplan-Meier) survival is 51% at 2 years and 46% at 3 years, with only 1 patient dying after 2 years out of 11 at risk. Eight patients (24%) succumbed to early treatment related complications. Nine patients (27%) died from relapse. Patients receiving ABMT as planned sequential therapy post-induction (Group I) did significantly better than patients given ABMT as salvage therapy after relapse on prior chemotherapy (Groups II and III) and better than the historical group of patients treated with chemotherapy alone. At 2 years, the survival in Group I is 79% versus 0% for Group II versus 48% for Group III. Historically, this group of high risk patients had a 2-year disease-free survival of 20% or less with chemotherapy alone. PMID:3277931

  16. Aggressive Therapy for Patients with Non-small Cell Lung Carcinoma and Synchronous Brain-only Oligometastatic Disease is Associated with Long-term Survival

    PubMed Central

    Gray, Phillip J.; Mak, Raymond H.; Yeap, Beow Y.; Cryer, Sarah K.; Pinnell, Nancy E.; Christianson, Laura W.; Sher, David J.; Arvold, Nils D.; Baldini, Elizabeth H.; Chen, Aileen B.; Kozono, David E.; Swanson, Scott J.; Jackman, David M.; Alexander, Brian M.

    2015-01-01

    Objectives Optimal therapy for patients with non-small cell lung carcinoma (NSCLC) presenting with synchronous brain-only oligometastases (SBO) is not well defined. We sought to analyze the effect of differing therapeutic paradigms in this subpopulation. Materials and Methods We retrospectively analyzed NSCLC patients with 1-4 SBO diagnosed between 1/2000 and 1/2011 at our institution. Patients with T0 tumors or documented Karnofsky Performance Status <70 were excluded. Aggressive thoracic therapy (ATT) was defined as resection of the primary disease or chemoradiotherapy whose total radiation dose exceeded 45 Gy. Cox proportional hazards and competing risks models were used to analyze factors affecting survival and first recurrence in the brain. Results Sixty-six patients were included. Median follow-up was 31.9 months. Intrathoracic disease extent included 9 stage I, 10 stage II and 47 stage III patients. Thirty-eight patients received ATT, 28 did not. Patients receiving ATT were younger (median age 55 vs. 60.5 years, p=0.027) but were otherwise similar to those who did not. Receipt of ATT was associated with prolonged median overall survival (OS) (26.4 vs. 10.5 months; p<0.001) with actuarial 2-year rates of 54% vs. 26%. ATT remained associated with OS after controlling for age, thoracic stage, performance status and initial brain therapy (HR 0.40, p=0.009). On multivariate analysis, the risk of first failure in the brain was associated with receipt of ATT (HR 3.62, p=0.032) and initial combined modality brain therapy (HR 0.34, p=0.046). Conclusion Aggressive management of thoracic disease in NSCLC patients with SBO is associated with improved survival. Careful management of brain disease remains important, especially for those treated aggressively. PMID:24974152

  17. Split-Course, High-Dose Palliative Pelvic Radiotherapy for Locally Progressive Hormone-Refractory Prostate Cancer

    SciTech Connect

    Gogna, Nirdosh Kumar; Baxi, Siddhartha; Hickey, Brigid; Baumann, Kathryn; Burmeister, Elizabeth; Holt, Tanya

    2012-06-01

    Purpose: Local progression, in patients with hormone-refractory prostate cancer, often causes significant morbidity. Pelvic radiotherapy (RT) provides effective palliation in this setting, with most published studies supporting the use of high-dose regimens. The aim of the present study was to examine the role of split-course hypofractionated RT used at our institution in treating this group of patients. Methods and Materials: A total of 34 men with locoregionally progressive hormone-refractory prostate cancer, treated with a split course of pelvic RT (45-60 Gy in 18-24 fractions) between 2000 and 2008 were analyzed. The primary endpoints were the response rate and actuarial locoregional progression-free survival. Secondary endpoints included overall survival, compliance, and acute and late toxicity. Results: The median age was 71 years (range, 53-88). Treatment resulted in an overall initial response rate of 91%, a median locoregional progression-free survival of 43 months, and median overall survival of 28 months. Compliance was excellent and no significant late toxicity was reported. Conclusions: The split course pelvic RT described has an acceptable toxicity profile, is effective, and compares well with other high-dose palliative regimens that have been previously reported.

  18. Lesotho: the politics of survival.

    PubMed

    Lye, W F

    1982-01-01

    In this discussion of the politics of survival in Lesotho, attention is directed to the historical foundations; the road to dependency, the emergence of a political economy; and political transitions. The 1.25 million citizens of Lesotho enjoy a precarious independence. In November 1981, the government welcomed Russian military advisers. Presumably the reason for this was to help defend itself against the Republic of South Africa. This action was only the most recent of a series of increasingly hostile acts and verbal barrages which confirm the persistent aversion of Lesotho toward South Africa. The behavior contrasts markedly with an equally persistent pattern, that of continuous consultations between the Prime Minister of Lesotho since independence in 1966 and every leader of South Africa. The fact that some 200,000 Sotho workers, almost 1/6 of the nation's populaton, cross annually into South Africa to earn their only possible means of income lends a special character to this relationship. It reveals both the depth of Lesotho's aversion while equally affirming its reluctant dependence. It also illuminates a reciprocal need on the part of South Africa, which causes them to tolerate the irritant. The key to understanding the recent history of Lesotho lies with this fundamental interdependence and aversion. In the context of declining living standards at home and the demand for labor by South Africa, at first on the nearby farms and after 1867 in the mines and cities, Lesotho's economy became increasingly subject to political forces beyond its control. During even the early days of Moshoeshoe's reign, he encouraged youths to leave their families to obtain work among the aliens. His original objective was to have the youths learn useful new techniques which could be applied to enrich Lesotho beyond the few coins they might earn. The central focus of foreign employment before long became routine jobs in the mines. By the last decade of the 19th century, Lesotho

  19. Lesotho: the politics of survival.

    PubMed

    Lye, W F

    1982-01-01

    In this discussion of the politics of survival in Lesotho, attention is directed to the historical foundations; the road to dependency, the emergence of a political economy; and political transitions. The 1.25 million citizens of Lesotho enjoy a precarious independence. In November 1981, the government welcomed Russian military advisers. Presumably the reason for this was to help defend itself against the Republic of South Africa. This action was only the most recent of a series of increasingly hostile acts and verbal barrages which confirm the persistent aversion of Lesotho toward South Africa. The behavior contrasts markedly with an equally persistent pattern, that of continuous consultations between the Prime Minister of Lesotho since independence in 1966 and every leader of South Africa. The fact that some 200,000 Sotho workers, almost 1/6 of the nation's populaton, cross annually into South Africa to earn their only possible means of income lends a special character to this relationship. It reveals both the depth of Lesotho's aversion while equally affirming its reluctant dependence. It also illuminates a reciprocal need on the part of South Africa, which causes them to tolerate the irritant. The key to understanding the recent history of Lesotho lies with this fundamental interdependence and aversion. In the context of declining living standards at home and the demand for labor by South Africa, at first on the nearby farms and after 1867 in the mines and cities, Lesotho's economy became increasingly subject to political forces beyond its control. During even the early days of Moshoeshoe's reign, he encouraged youths to leave their families to obtain work among the aliens. His original objective was to have the youths learn useful new techniques which could be applied to enrich Lesotho beyond the few coins they might earn. The central focus of foreign employment before long became routine jobs in the mines. By the last decade of the 19th century, Lesotho

  20. 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.

  1. Astrovirus survival in drinking water.

    PubMed

    Abad, F X; Pintó, R M; Villena, C; Gajardo, R; Bosch, A

    1997-08-01

    A method based on infection of CaCo-2 cultured cell monolayers (CC) and reverse transcription-PCR (RT-PCR) was developed for the specific detection of infectious astrovirus. The procedure was validated by titrating poliovirus stocks in parallel in CaCo-2 cells by determining the most probable number of cytopathogenic units and by cell culture and subsequent RT-PCR (CC-RT-PCR). CC-RT-PCR was then employed to measure the persistence of astrovirus suspended in dechlorinated tap water. After 60 days, the decay of astrovirus infectivity was 2 log units at 4 +/- 1 degrees C and 3.2 log units at 20 +/- 1 degrees C, while after 90 days, the titer reduction was 3.3 and 5 log units at 4 +/- 1 degrees C and 20 +/- 1 degrees C, respectively. Astrovirus decay in the presence of free chlorine (FC) was monitored by CC-RT-PCR. Residual infectivity was found after 2 h in the presence of 1 mg of FC/liter. Under these conditions, astrovirus shows a log titer reduction (LTR) or 4, while 0.5 mg of FC/liter induced an LTR of 2.4. The possibility of acquiring data on the survival of fastidious viruses in the environment opens new perspectives on the epidemiology of some significant infections transmitted by the fecal-oral route. PMID:9251198

  2. Overall survival in non-small cell lung cancer—what is clinically meaningful?

    PubMed Central

    Fenchel, Klaus; Sellmann, Ludger

    2016-01-01

    The development of molecularly targeted therapies [tyrosine kinase inhibitors (TKIs) and monoclonal antibodies] has significantly improved outcomes for patients with advanced or metastatic non-small cell lung cancer (NSCLC) resulting in improved progression-free survival (PFS), overall survival (OS) and quality of life (QoL). In addition, targeting the immune axis (CTLA-4, PD-1/PD-L1) has also shown promising results. Major goals of almost all clinical trials based on histology and molecular markers for NSCLC patients are improvements of OS and QoL. However, in the majority of these trials only small incremental improvements in OS were seen. Food and Drug Administration (FDA) and other health authorities have recommended to consider OS to be the standard clinical benefit endpoint that should be used to establish the efficacy of a treatment for NSCLC patients, however, the question remains what is clinically meaningful and how can this outcome be measured. According to suggestions of the American Society of Clinical Oncology (ASCO) Cancer Research Committee a relative improvement in median OS of at least 20% (3–4 months) is regarded to define a clinically meaningful improvement in outcome of NSCLC patients. However, this should not diminish PFS as a valid endpoint since a PFS improvement can also result in a meaningful palliation (e.g., painful bone metastases). Other factors (e.g., QoL) may also be involved to measure and to define the clinical importance of a given trial result. Using the “Quality-adjusted Time Without Symptoms of Toxicity” (Q-TWiST) analysis method it has been demonstrated that a clinically important and meaningful difference for Q-TWiST is 10–15% of OS in a study. Trials that are designed with less ambitious goals, however, may still be of benefit to individual NSCLC patients if the trial endpoints are met. Since there is no single factor which will make a trial clinically meaningful, these recommendations, however, are not intended to

  3. Prognostic factors and survival in late adolescent and adult patients with small round cell tumors.

    PubMed

    Eralp, Yeşim; Bavbek, Sevil; Başaran, Mert; Kaytan, Esra; Yaman, Fulya; Bilgiç, Bilge; Darendeliler, Emin; Onat, Haluk

    2002-08-01

    The primary objective of this study is to review the clinical characteristics of 25 patients in the adult and late adolescent age group, diagnosed and treated with small round cell tumors involving soft tissues (extraosseous Ewing sarcoma, rhabdo-myosarcoma, primitive neuroectodermal tumor, and undiffer-entiated small round cell tumors). Additionally, survival and prognostic factors influencing the outcome with multimodality treatment are evaluated. There were 19 males (76%) and 6 females (24%). The median age was 26 years (range: 15-56 years). In 9 patients (36%), the tumor was located at an extremity, whereas 16 patients (64%) had central localizations. Tumor size was larger than 10 cm in 7 patients (29.2%). Six patients (24%) had metastatic disease. Twelve patients (48%) received radiation and 16 patients (64%) underwent surgery. Among the resected tumors, 2 were resected with contaminated margins (12.5%), whereas 2 were radically resected and 12 (75%) were resected with wide margins. All patients were given a median of 4 cycles of multiagent chemotherapy (1-14 cycles). With preoperative chemotherapy, complete regression (CR) of the tumor was achieved in 6 patients (24%). In 4 patients (16%), a partial response was obtained. After the completion of multimodality treatment, 12 patients (48%) had a CR. Progression-free (PFS) and overall survival (OS) for the entire group was 25.0 +/- 10.8% at 1 year and 30.5 +/- 15.5% at 3 years, respectively. Nonmetastatic disease, wide and radical resection, and presence of CR to multimodality treatment were associated with a significantly longer PFS and OS by univariate analysis. By multivariate analysis, CR to multimodality treat-ment was the only independent predictive factor for a longer OS (p: 0.0036, relative risk [RR]: 23.6, 95% CI: 2.8; 198.7) and metastatic presentation was the only independent factor predic-tive for a shorter PFS (p: 0.017, RR. 15, 95% CI: 1.6; 141.2). Large-scale, multicenter studies are required for

  4. Failure to Achieve a PSA Level {<=}1 ng/mL After Neoadjuvant LHRHA Therapy Predicts for Lower Biochemical Control Rate and Overall Survival in Localized Prostate Cancer Treated With Radiotherapy

    SciTech Connect

    Mitchell, Darren M. McAleese, Jonathan; Park, Richard M.; Stewart, David P.; Stranex, Stephen; Eakin, Ruth L.; Houston, Russell F.; O'Sullivan, Joe M.

    2007-12-01

    Purpose: To investigate whether failure to suppress the prostate-specific antigen (PSA) level to {<=}1 ng/mL after {>=}2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy in patients scheduled to undergo external beam radiotherapy for localized prostate carcinoma is associated with reduced biochemical failure-free survival. Methods and Materials: A retrospective case note review of consecutive patients with intermediate- or high-risk localized prostate cancer treated between January 2001 and December 2002 with neoadjuvant hormonal deprivation therapy, followed by concurrent hormonal therapy and radiotherapy was performed. Patient data were divided for analysis according to whether the PSA level in Week 1 of radiotherapy was {<=}1.0 ng/mL. Biochemical failure was determined using the American Society for Therapeutic Radiology and Oncology (Phoenix) definition. Results: A total of 119 patients were identified. The PSA level after neoadjuvant hormonal deprivation therapy was {<=}1 ng/mL in 67 patients and >1 ng/mL in 52. At a median follow-up of 49 months, the 4-year actuarial biochemical failure-free survival rate was 84% vs. 60% (p = 0.0016) in favor of the patients with a PSA level after neoadjuvant hormonal deprivation therapy of {<=}1 ng/mL. The overall survival rate was 94% vs. 77.5% (p = 0.0045), and the disease-specific survival rate at 4 years was 98.5% vs. 82.5%. Conclusions: The results of our study have shown that patients with a PSA level >1 ng/mL at the beginning of external beam radiotherapy after {>=}2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy have a significantly greater rate of biochemical failure and lower survival rate compared with those with a PSA level of {<=}1 ng/mL. Patients without adequate PSA suppression should be considered a higher risk group and considered for dose escalation or the use of novel treatments.

  5. Tumor Volume Decrease at 8 weeks is Associated with Longer Survival in EGFR-mutant Advanced Non-Small-Cell Lung Cancer Patients treated with EGFR Tyrosine Kinase Inhibitor

    PubMed Central

    Nishino, Mizuki; Dahlberg, Suzanne E.; Cardarella, Stephanie; Jackman, David M.; Rabin, Michael S.; Hatabu, Hiroto; Jänne, Pasi A.; Johnson, Bruce E.

    2013-01-01

    Background The study investigated if tumor volume changes at 8 weeks of therapy are associated with outcomes in advanced NSCLC patients with sensitizing EGFR mutations treated with EGFR tyrosine kinase inhibitors (TKIs). Patients and methods In 56 advanced NSCLC patients with sensitizing EGFR mutations treated with first-line erlotinib or gefitinib, tumor volumes of dominant lung lesions were measured on baseline and follow-up CT and were analyzed for association with survival. Results Among 56 eligible patients, the median tumor volume was 17.8 cm3 (range: 1.3-172.7 cm3) on the baseline scans. 49 patients had follow-up CT at approximately 8 weeks; the median tumor volume at 8 weeks was 7.1 cm3 (range: 0.4-62.3 cm3), with the median proportional volume change of -59% (range: -90% to +91%) from baseline. The proportional volume change at 8 weeks was associated with survival (p=0.02). Using the cut-off value of 38% volume decrease (75th percentile) at 8 weeks, patients with volume decrease >38% (n=37) had a median overall survival of 43.5 months compared to 16.3 months among those with volume decrease ≤38% (n=12) (p=0.01). The median progression-free survival for patients with >38% volume decrease was 12.6 months, compared to 5.5 months for those with ≤38% volume decrease (p=0.2). Conclusions The proportional volume change at 8 weeks is associated with overall survival in EGFR-mutant advanced NSCLC patients treated with first-line EGFR-TKIs. The observation of the study, if confirmed in larger study cohorts, indicates that tumor volume analysis at 8 weeks may provide an early marker for survival, and contribute to therapeutic decision making by identifying patients who may benefit from additional anti-cancer therapy after 8 weeks of EGFR-TKI therapy. PMID:23787800

  6. Survival of multiple myeloma patients aged 65-70 years in the era of novel agents and autologous stem cell transplantation. A multicenter retrospective collaborative study of the Japanese Society of Myeloma and the European Myeloma Network.

    PubMed

    Ozaki, Shuji; Harada, Takeshi; Saitoh, Takayuki; Shimazaki, Chihiro; Itagaki, Mitsuhiro; Asaoku, Hideki; Kuroda, Yoshiaki; Chou, Takaaki; Yoshiki, Yumiko; Suzuki, Kenshi; Murakami, Hirokazu; Hayashi, Kunihiko; Mina, Roberto; Palumbo, Antonio; Shimizu, Kazuyuki

    2014-01-01

    Novel agents such as thalidomide, lenalidomide and bortezomib have dramatically changed the treatment paradigm of multiple myeloma (MM). However, it is not clear whether these agents improve the prognosis of elderly patients who have undergone autologous stem cell transplantation (auto-SCT). We retrospectively analyzed the outcome of 318 newly diagnosed patients aged 65–70 years who were treated between January 1, 2004, and December 31, 2009. As initial therapy, 192 patients were treated with conventional chemotherapy,88 with novel agent-containing regimens, 21 with conventional chemotherapy plus auto-SCT and the remaining 17 with novel agents plus auto-SCT. The median progression-free survival was 19.1, 24.5, 26.8 and 35.2 months, respectively, and the 5-year overall survival (OS) was 40, 62, 63 and 87%, respectively. Initial therapy with novel agents (p < 0.001) or auto-SCT (p < 0.02) significantly improved OS compared with the group without these treatment modalities. Salvage therapy with novel agents also significantly improved survival after relapse compared with conventional chemotherapy alone (p < 0.04). In a multivariate analysis, the use of novel agents was an independent prognostic factor significantly associated with extended OS(p < 0.003). These results indicate that novel agents and auto-SCT had a major impact on OS in eligible patients in this subgroup of MM.

  7. Differential Survival in Europe and the United States: Estimates Based on Subjective Probabilities of Survival

    PubMed Central

    Delavande, Adeline; Rohwedder, Susann

    2013-01-01

    Cross-country comparisons of differential survival by socioeconomic status (SES) are useful in many domains. Yet, to date, such studies have been rare. Reliably estimating differential survival in a single country has been challenging because it requires rich panel data with a large sample size. Cross-country estimates have proven even more difficult because the measures of SES need to be comparable internationally. We present an alternative method for acquiring information on differential survival by SES. Rather than using observations of actual survival, we relate individuals’ subjective probabilities of survival to SES variables in cross section. To show that subjective survival probabilities are informative proxies for actual survival when estimating differential survival, we compare estimates of differential survival based on actual survival with estimates based on subjective probabilities of survival for the same sample. The results are remarkably similar. We then use this approach to compare differential survival by SES for 10 European countries and the United States. Wealthier people have higher survival probabilities than those who are less wealthy, but the strength of the association differs across countries. Nations with a smaller gradient appear to be Belgium, France, and Italy, while the United States, England, and Sweden appear to have a larger gradient. PMID:22042664

  8. Survival of Hepatocellular Carcinoma in Puerto Rico

    PubMed Central

    MARRERO, CARLOS ROMERO; ORTIZ, ANA P.; PÉREZ, CYNTHIA M.; PÉREZ, JAVIER; TORRES, ESTHER A.

    2013-01-01

    Background Blacks and Hispanics in the United States (US) have the lowest survival rates of hepatocellular carcinoma (HCC), mainly associated to the presence of advanced disease at diagnosis when intervention is least beneficial. This study compared the survival distribution and relative survival of HCC in Puerto Rico (PR) during 1988-1992 and 1998-2002. Methods All HCC cases in the PR Central Cancer Registry database for 1988-1992 (n=306) and 1998-2002 (n=333) were identified. Patient characteristics and clinical variables were compared between study periods. Survival by age at diagnosis, sex, tumor stage and treatment was estimated using the Kaplan-Meier method, and survival curves were compared using the Wilcoxon test. A Cox proportional hazards model was employed to assess the effect of period of diagnosis on survival, after adjusting for confounders. One- and three-year survival rates were also calculated. Results Patients diagnosed during 1998-2002 (median: 3.08 months, 95% CI: 2.30-4.16) had a longer observed survival than those diagnosed from 1988-1992 (median: 1.80 months, 95% CI: 1.44-2.52). A significant interaction was observed between the variables age and period of diagnosis, where only among persons aged ≥ 60 years the risk of HCC death was lower (sex-adjusted HR=O.72; 95%CI: 0.59-0.88) in patients diagnosed during 1998-2002 as compared to those diagnosed during 1988-1992. The overall one- and three-year relative survival during 1998-2002 was approximately 6% (22.4% vs.16.6%) and 2% higher (9.0% vs. 6.7%) respectively, as compared to 1988-1992. Conclusion We observed a temporal improvement in the survival of HCC in PR during the last decade. However, this survival is inferior to the one observed in the US population. Further studies are needed to identify factors that explain these disparities. PMID:19530551

  9. How can tropical cyclones survive?

    NASA Astrophysics Data System (ADS)

    Smedman, Ann-Sofi

    2013-04-01

    How can tropical cyclones survive? It is important for understanding the development of tropical cyclones to be able to quantify the exchange of enthalpy and momentum between air and water. Air-sea fluxes are often formulated as drag CD and enthalpy CK exchange coefficients. Emanuel, 1986, derived an expression for potential intensity that depends on local environment parameters and is proportional to the ratio of enthalpy and drag coefficients. This ratio should be larger than 0.75 for a cyclone to develop. There are no direct surface measurements of CK/ CD under hurricane conditions and extrapolation from most open-ocean measurements at 25 m/s gives values of CK/ CD< 0.75 and in that case no cyclone could survive and Emanuel's theory must be wrong. However there are measurements of CK taken over the Baltic Sea and Lake Ontario showing increasing values of CK up to 2.5 for wind speeds around 12 m/s. If this can be implemented for hurricane conditions the ratio CK/ CD>0.75 is in accordance with Emanuel's prediction. The high CK values are observed during situations when there is a regime shift of the structure of turbulence in the boundary layer. From spectral analysis it was found that as the boundary layer approaches neutral stratification, smaller-scale eddies become increasingly important in the turbulent transport of humidity and sensible heat and thus enhance the exchange coefficient CK. This turbulence regime is called the UVCN regime and require high wind speed, small temperature difference between air and water, sufficiently strong wind gradients and growing sea condition ( Smedman et al., 2007, Sahlee et al., 2008). What is the difference between world oceans and enclosed seas? The answer is the waves. The wave field over the open oceans is swell dominated but in enclosed seas and coastal areas swell is restricted mainly to low wind speed conditions, and swell is short lived because of short distances to the shores. When swell is present the MABL will be

  10. SURVIVAL OF CENTENARIANS IN JAPAN.

    PubMed

    Murotani, Kenta; Zhou, Bin; Kaneda, Hideaki; Nakatani, Eiji; Kojima, Shinsuke; Nagai, Yoji; Fukushima, Masanori

    2015-11-01

    The objective of the study was to explore the survival trends of centenarians in Japan. A cohort of centenarians born between 1881 and 1900 was analysed based on national census data, and the average life expectancy at 100 years of age, risk of death and maximum age were estimated. An analysis of covariance and a Cox regression analysis were performed to explore the factors associated with life expectancy and risk of death. The death rates in centenarians tended to decrease with birth year, and the average life expectancy from the age of 100 slightly increased at a rate of 0.013 years (95% CI: 0.007-0.019) by birth year in men and 0.026 in women. Women had a longer life expectancy than men, with a difference of 0.174 years (95% CI: 0.071-0.277) at birth year 1881 and increasing by 0.013 years per year thereafter. The risk of death in both sexes decreased significantly by birth year over the course of the period analysed, and the risk of death in men was 1.16 (95% CI: 1.14-1.19) times that of women. In women, death rates at every age significantly decreased with birth year over the course of the period analysed until age 104. However, this trend did not hold true for ages 105 and older. The average life expectancy of centenarians at the age of 100 in Japan increased by birth year in the 1881-1900 birth cohort. In addition, Japanese centenarians had the lowest death rates among several countries.

  11. Strategies for surviving a shakeout.

    PubMed

    Day, G S

    1997-01-01

    Shakeouts are a fact of life in almost every industry-witness the shrinking number of players in areas as diverse as banking, software, and hospital supply distribution. The key to survival is sensing your industry's shakeout before the competition does. And the first hurdle for managers to overcome is the belief that it can't happen to them. It can and it probably will. George Day describes two shakeout syndromes that affect different types of industries. A boom-and-bust shakeout afflicts hot emerging markets or highly cyclical businesses. A glut of competitors enter the market during boom times, but many of them fail when growth slows or a dominant design emerges. A seismic-shift shakeout strikes mature industries that have enjoyed years of protected prosperity as a result of, for example, local regulations or import barriers. But deregulation, globalization, or technological change can pull the rug out from under them. Day outlines how companies can detect the early warning signs of a shakeout. He explains how adaptive survivors, such as Dell Computer, successfully adjust their businesses in the midst of a bust, and how aggressive amalgamators, such as Arrow Electronics, cut costs and acquire smaller rivals in order to remain standing after a seismic shift. But the fact remains that most companies will get squeezed out during a consolidation. Although it is enormously difficult for executives to come to terms with the grim news, the sooner they do so, the better. And, as Day points out, all is not necessarily lost: with the right timing, also-rans can make a profitable exit from an industry. PMID:10165451

  12. Does Valproic Acid or Levetiracetam Improve Survival in Glioblastoma? A Pooled Analysis of Prospective Clinical Trials in Newly Diagnosed Glioblastoma

    PubMed Central

    Happold, Caroline; Gorlia, Thierry; Chinot, Olivier; Gilbert, Mark R.; Nabors, L. Burt; Wick, Wolfgang; Pugh, Stephanie L.; Hegi, Monika; Cloughesy, Timothy; Roth, Patrick; Reardon, David A.; Perry, James R.; Mehta, Minesh P.; Stupp, Roger

    2016-01-01

    Purpose Symptomatic epilepsy is a common complication of glioblastoma and requires pharmacotherapy. Several uncontrolled retrospective case series and a post hoc analysis of the registration trial for temozolomide indicated an association between valproic acid (VPA) use and improved survival outcomes in patients with newly diagnosed glioblastoma. Patients and Methods To confirm the hypothesis suggested above, a combined analysis of survival association of antiepileptic drug use at the start of chemoradiotherapy with temozolomide was performed in the pooled patient cohort (n = 1,869) of four contemporary randomized clinical trials in newly diagnosed glioblastoma: AVAGlio (Avastin in Glioblastoma; NCT00943826), CENTRIC (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status; NCT00689221), CORE (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Unmethylated Gene Promoter Status; NCT00813943), and Radiation Therapy Oncology Group 0825 (NCT00884741). Progression-free survival (PFS) and overall survival (OS) were compared between: (1) any VPA use and no VPA use at baseline or (2) VPA use both at start of and still after chemoradiotherapy. Results of Cox regression models stratified by trial and adjusted for baseline prognostic factors were analyzed. The same analyses were performed with levetiracetam (LEV). Results VPA use at start of chemoradiotherapy was not associated with improved PFS or OS compared with all other patients pooled (PFS: hazard ratio [HR], 0.91; 95% CI, 0.77 to 1.07; P = .241; OS: HR, 0.96; 95% CI, 0.80 to 1.15; P = .633). Furthermore, PFS and OS of patients taking VPA both at start of and still after chemoradiotherapy were not different from those without antiepileptic drug use at both time points (PFS: HR, 0.92; 95% CI, 0.74 to 1.15; P = .467; OS: HR, 1.10; 95% CI, 0.86 to 1.40; P = .440). Similarly, no

  13. Analysis of survival data from telemetry projects

    USGS Publications Warehouse

    Bunck, C.M.

    1987-01-01

    Telemetry is an increasingly popular method for studying animal movements and habitat use. Telemetry provides a means for studying survival and causes of mortality. This paper describes some statistical techniques which can provide valid estimates of survival rates based on data from telemetry studies.

  14. Improving the Odds of Surviving Sepsis

    MedlinePlus

    ... Improving the Odds of Surviving Sepsis Inside Life Science View All Articles | Inside Life Science Home Page Improving the Odds of Surviving Sepsis ... Threatening Bacterial Infection Remains Mysterious This Inside Life Science article also appears on LiveScience . Learn about related ...

  15. 46 CFR 28.120 - Survival craft.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 1 2014-10-01 2014-10-01 false Survival craft. 28.120 Section 28.120 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY UNINSPECTED VESSELS REQUIREMENTS FOR COMMERCIAL FISHING INDUSTRY VESSELS Requirements for All Vessels § 28.120 Survival craft. (a) Except as provided in paragraphs (b) through (h) of this section and 28.305,...

  16. Benefits of a Cohort Survival Projection Model

    ERIC Educational Resources Information Center

    Suslow, Sidney

    1977-01-01

    A cohort survival model of student attendance provides primary and secondary benefits in accurate student information not before available. At Berkeley the computerized Cohort Survival History File, in use for two years, has been successful in assessing various aspects of students' academic behavior and student flow problems. (Editor/LBH)

  17. Survival of postfledging female American black ducks

    USGS Publications Warehouse

    Longcore, J.R.; McAuley, D.G.; Frazer, C.

    1991-01-01

    We equipped 106 hatching-year (HY), female, black ducks (Anas rubripes) with transmitters during 1985-87 and monitored survival from late August to mid-December on a lightly hunted area on the Maine-New Brunswick border. The 1985-87 estimate of survival (hunting losses included) was 0.593, and when losses from hunting were censored it was 0.694. Survival in August-September was 0.987; by 31 October survival declined to 0.885, and by 30 November it was 0.718. Most nonhunting mortality was caused by predators (21/41, 53.2%); there were 14 deaths (34.1%) from mammals or unknown predators and 7 (17.1%) from raptors. Hunting caused 13 (31. 7%) deaths. Ducks with lowest mass had the lowest survival. The estimate of survival for postfledging female black ducks, when multiplied with interval survival rates for hunting, winter, and breeding periods, produced an annual survival estimate of 0.262, about 12% lower than that (0.38) based on analysis of banding data.

  18. Factors predictive of survival in ampullary carcinoma.

    PubMed Central

    Howe, J R; Klimstra, D S; Moccia, R D; Conlon, K C; Brennan, M F

    1998-01-01

    OBJECTIVE: To review the recent Memorial Sloan-Kettering Cancer Center experience with adenocarcinoma of the ampulla of Vater and to identify clinicopathologic factors that have an impact on patient survival. SUMMARY BACKGROUND DATA: The prognosis for patients with tumors of the ampulla of Vater is improved relative to other periampullary neoplasms. Identification of independent prognostic factors in ampullary tumors has been limited by small numbers of tumors and a lack of pathologic review. METHODS: Data were collected prospectively for patients presenting with periampullary carcinomas to the Memorial Sloan-Kettering Cancer Center between October 15, 1983 and June 30, 1995. The correlation between clinicopathologic variables and survival of ampullary carcinoma was tested by the Kaplan-Meier method and log-rank test, and Cox proportional hazards regression. Survival of patients with periampullary adenocarcinomas was compared by the Kaplan-Meier method. RESULTS: In 123 patients presenting with ampullary carcinoma, 101 tumors (82.1%) were resected. Factors significantly correlated with improved survival were resection (p < 0.01), and in resected tumors, negative nodes (p = 0.04) and margins (p = 0.02) independently predicted for improved survival. In periampullary tumors, the highest rates of resection and overall survival (median, 43.6 months) were found in ampullary carcinomas. CONCLUSIONS: Factors predictive of improved survival in ampullary carcinoma include resection, negative margins, and negative nodes. Improved overall survival in ampullary relative to periampullary adenocarcinoma is due in part to a significantly higher rate of resection. Images Figure 1. PMID:9671071

  19. Adaptive Memory: Survival Processing Enhances Retention

    ERIC Educational Resources Information Center

    Nairne, James S.; Thompson, Sarah R.; Pandeirada, Josefa N. S.

    2007-01-01

    The authors investigated the idea that memory systems might have evolved to help us remember fitness-relevant information--specifically, information relevant to survival. In 4 incidental learning experiments, people were asked to rate common nouns for their survival relevance (e.g., in securing food, water, or protection from predators); in…

  20. Temperature mediated moose survival in Northeastern Minnesota

    USGS Publications Warehouse

    Lenarz, M.S.; Nelson, M.E.; Schrage, M.W.; Edwards, A.J.

    2009-01-01

    The earth is in the midst of a pronounced warming trend and temperatures in Minnesota, USA, as elsewhere, are projected to increase. Northern Minnesota represents the southern edge to the circumpolar distribution of moose (Alces alces), a species intolerant of heat. Moose increase their metabolic rate to regulate their core body temperature as temperatures rise. We hypothesized that moose survival rates would be a function of the frequency and magnitude that ambient temperatures exceeded the upper critical temperature of moose. We compared annual and seasonal moose survival in northeastern Minnesota between 2002 and 2008 with a temperature metric. We found that models based on January temperatures above the critical threshold were inversely correlated with subsequent survival and explained >78 of variability in spring, fall, and annual survival. Models based on late-spring temperatures also explained a high proportion of survival during the subsequent fall. A model based on warm-season temperatures was important in explaining survival during the subsequent winter. Our analyses suggest that temperatures may have a cumulative influence on survival. We expect that continuation or acceleration of current climate trends will result in decreased survival, a decrease in moose density, and ultimately, a retreat of moose northward from their current distribution.

  1. Adaptive Memory: Is Survival Processing Special?

    ERIC Educational Resources Information Center

    Nairne, James S.; Pandeirada, Josefa N. S.

    2008-01-01

    Do the operating characteristics of memory continue to bear the imprints of ancestral selection pressures? Previous work in our laboratory has shown that human memory may be specially tuned to retain information processed in terms of its survival relevance. A few seconds of survival processing in an incidental learning context can produce recall…

  2. Escherichia coli survival in waters: Temperature dependence

    EPA Science Inventory

    Knowing the survival rates of water-borne Escherichia coli is important in evaluating microbial contamination and making appropriate management decisions. E. coli survival rates are dependent on temperature, a dependency that is routinely expressed using an analogue of the Q10 mo...

  3. Survival of Escherichia coli in stormwater biofilters.

    PubMed

    Chandrasena, G I; Deletic, A; McCarthy, D T

    2014-04-01

    Biofilters are widely adopted in Australia for stormwater treatment, but the reported removal of common faecal indicators (such as Escherichia coli (E. coli)) varies from net removal to net leaching. Currently, the underlying mechanisms that govern the faecal microbial removal in the biofilters are poorly understood. Therefore, it is important to study retention and subsequent survival of faecal microorganisms in the biofilters under different biofilter designs and operational characteristics. The current study investigates how E. coli survival is influenced by temperature, moisture content, sunlight exposure and presence of other microorganisms in filter media and top surface sediment. Soil samples were taken from two different biofilters to investigate E. coli survival under controlled laboratory conditions. Results revealed that the presence of other microorganisms and temperature are vital stressors which govern the survival of E. coli captured either in the top surface sediment or filter media, while sunlight exposure and moisture content are important for the survival of E. coli captured in the top surface sediment compared to that of the filter media. Moreover, increased survival was found in the filter media compared to the top sediment, and sand filter media was found be more hostile than loamy sand filter media towards E. coli survival. Results also suggest that the contribution from the tested environmental stressors on E. coli survival in biofilters will be greatly affected by the seasonality and may vary from one site to another.

  4. Congruity Effects in the Survival Processing Paradigm

    ERIC Educational Resources Information Center

    Nairne, James S.; Pandeirada, Josefa N. S.

    2011-01-01

    Five experiments were conducted to investigate a proposal by Butler, Kang, and Roediger (2009) that congruity (or fit) between target items and processing tasks might contribute, at least partly, to the mnemonic advantages typically produced by survival processing. In their research, no significant survival advantages were found when words were…

  5. Public Perception of Cancer Survival Rankings

    ERIC Educational Resources Information Center

    Jensen, Jakob D.; Scherr, Courtney L.; Brown, Natasha; Jones, Christina; Christy, Katheryn

    2013-01-01

    Past research has observed that certain subgroups (e.g., individuals who are overweight/obese) have inaccurate estimates of survival rates for particular cancers (e.g., colon cancer). However, no study has examined whether the lay public can accurately rank cancer survival rates in comparison with one another (i.e., rank cancers from most deadly…

  6. Public perception of cancer survival rankings.

    PubMed

    Jensen, Jakob D; Scherr, Courtney L; Brown, Natasha; Jones, Christina; Christy, Katheryn

    2013-12-01

    Past research has observed that certain subgroups (e.g., individuals who are overweight/obese) have inaccurate estimates of survival rates for particular cancers (e.g., colon cancer). However, no study has examined whether the lay public can accurately rank cancer survival rates in comparison with one another (i.e., rank cancers from most deadly to least deadly). A sample of 400 Indiana adults aged 18 to 89 years (M = 33.88 years) completed a survey with questions regarding perceived cancer survival rates. Most cancers were ranked accurately; however, breast and stomach cancer survival rankings were highly distorted such that breast cancer was perceived to be significantly more deadly and stomach cancer significantly less deadly than reality. Younger participants also overestimated the survival rate for pancreatic cancer. These distortions mirror past content analytic work demonstrating that breast, stomach, and pancreatic cancers are misrepresented in the news. PMID:23463791

  7. Prognostic Indicators for Ebola Patient Survival.

    PubMed

    Crowe, Samuel J; Maenner, Matthew J; Kuah, Solomon; Erickson, Bobbie Rae; Coffee, Megan; Knust, Barbara; Klena, John; Foday, Joyce; Hertz, Darren; Hermans, Veerle; Achar, Jay; Caleo, Grazia M; Van Herp, Michel; Albariño, César G; Amman, Brian; Basile, Alison Jane; Bearden, Scott; Belser, Jessica A; Bergeron, Eric; Blau, Dianna; Brault, Aaron C; Campbell, Shelley; Flint, Mike; Gibbons, Aridth; Goodman, Christin; McMullan, Laura; Paddock, Christopher; Russell, Brandy; Salzer, Johanna S; Sanchez, Angela; Sealy, Tara; Wang, David; Saffa, Gbessay; Turay, Alhajie; Nichol, Stuart T; Towner, Jonathan S

    2016-02-01

    To determine whether 2 readily available indicators predicted survival among patients with Ebola virus disease in Sierra Leone, we evaluated information for 216 of the 227 patients in Bo District during a 4-month period. The indicators were time from symptom onset to healthcare facility admission and quantitative real-time reverse transcription PCR cycle threshold (Ct), a surrogate for viral load, in first Ebola virus-positive blood sample tested. Of these patients, 151 were alive when detected and had reported healthcare facility admission dates and Ct values available. Time from symptom onset to healthcare facility admission was not associated with survival, but viral load in the first Ebola virus-positive blood sample was inversely associated with survival: 52 (87%) of 60 patients with a Ct of >24 survived and 20 (22%) of 91 with a Ct of <24 survived. Ct values may be useful for clinicians making treatment decisions or managing patient or family expectations.

  8. Prognostic Indicators for Ebola Patient Survival.

    PubMed

    Crowe, Samuel J; Maenner, Matthew J; Kuah, Solomon; Erickson, Bobbie Rae; Coffee, Megan; Knust, Barbara; Klena, John; Foday, Joyce; Hertz, Darren; Hermans, Veerle; Achar, Jay; Caleo, Grazia M; Van Herp, Michel; Albariño, César G; Amman, Brian; Basile, Alison Jane; Bearden, Scott; Belser, Jessica A; Bergeron, Eric; Blau, Dianna; Brault, Aaron C; Campbell, Shelley; Flint, Mike; Gibbons, Aridth; Goodman, Christin; McMullan, Laura; Paddock, Christopher; Russell, Brandy; Salzer, Johanna S; Sanchez, Angela; Sealy, Tara; Wang, David; Saffa, Gbessay; Turay, Alhajie; Nichol, Stuart T; Towner, Jonathan S

    2016-02-01

    To determine whether 2 readily available indicators predicted survival among patients with Ebola virus disease in Sierra Leone, we evaluated information for 216 of the 227 patients in Bo District during a 4-month period. The indicators were time from symptom onset to healthcare facility admission and quantitative real-time reverse transcription PCR cycle threshold (Ct), a surrogate for viral load, in first Ebola virus-positive blood sample tested. Of these patients, 151 were alive when detected and had reported healthcare facility admission dates and Ct values available. Time from symptom onset to healthcare facility admission was not associated with survival, but viral load in the first Ebola virus-positive blood sample was inversely associated with survival: 52 (87%) of 60 patients with a Ct of >24 survived and 20 (22%) of 91 with a Ct of <24 survived. Ct values may be useful for clinicians making treatment decisions or managing patient or family expectations. PMID:26812579

  9. Prognostic Indicators for Ebola Patient Survival

    PubMed Central

    Kuah, Solomon; Erickson, Bobbie Rae; Coffee, Megan; Knust, Barbara; Klena, John; Foday, Joyce; Hertz, Darren; Hermans, Veerle; Achar, Jay; Caleo, Grazia M.; Van Herp, Michel; Albariño, César G.; Amman, Brian; Basile, Alison Jane; Bearden, Scott; Belser, Jessica A.; Bergeron, Eric; Blau, Dianna; Brault, Aaron C.; Campbell, Shelley; Flint, Mike; Gibbons, Aridth; Goodman, Christin; McMullan, Laura; Paddock, Christopher; Russell, Brandy; Salzer, Johanna S.; Sanchez, Angela; Sealy, Tara; Wang, David; Saffa, Gbessay; Turay, Alhajie; Nichol, Stuart T.; Towner, Jonathan S.

    2016-01-01

    To determine whether 2 readily available indicators predicted survival among patients with Ebola virus disease in Sierra Leone, we evaluated information for 216 of the 227 patients in Bo District during a 4-month period. The indicators were time from symptom onset to healthcare facility admission and quantitative real-time reverse transcription PCR cycle threshold (Ct), a surrogate for viral load, in first Ebola virus–positive blood sample tested. Of these patients, 151 were alive when detected and had reported healthcare facility admission dates and Ct values available. Time from symptom onset to healthcare facility admission was not associated with survival, but viral load in the first Ebola virus–positive blood sample was inversely associated with survival: 52 (87%) of 60 patients with a Ct of >24 survived and 20 (22%) of 91 with a Ct of <24 survived. Ct values may be useful for clinicians making treatment decisions or managing patient or family expectations. PMID:26812579

  10. Wild turkey poult survival in southcentral Iowa

    USGS Publications Warehouse

    Hubbard, M.W.; Garner, D.L.; Klaas, E.E.

    1999-01-01

    Poult survival is key to understanding annual change in wild turkey (Meleagris gallopavo) populations. Survival of eastern wild turkey poults (M. g. silvestris) 0-4 weeks posthatch was studied in southcentral Iowa during 1994-97. Survival estimates of poults were calculated based on biweekly flush counts and daily locations acquired via radiotelemetry. Poult survival averaged 0.52 ?? 0.14% (?? ?? SE) for telemetry counts and 0.40 ?? 0.15 for flush counts. No within-year or across-year differences were detected between estimation techniques. More than 72% (n = 32) of documented poult mortality occurred ???14 days posthatch, and mammalian predation accounted for 92.9% of documented mortality. If mortality agents are not of concern, we suggest biologists conduct 4-week flush counts to obtain poult survival estimates for use in population models and development of harvest recommendations.

  11. Mitochondrial and Postmitochondrial Survival Signaling in Cancer

    PubMed Central

    Yadav, Neelu; Chandra, Dhyan

    2014-01-01

    Cancer cells are resistant to conventional chemotherapy and radiotherapy, however, the molecular mechanisms of resistance to therapy remain unclear. Cellular survival machinery protects mitochondrial integrity against endogenous or exogenous stresses. Prodeath molecules orchestrate around mitochondria to initiate and execute cell death in cancer, and also play an under appreciated role in survival of cancer cells. Prosurvival mechanisms can operate at mitochondrial and postmitochondrial levels to attenuate core apoptotic death program. It is intriguing to explore how prosurvival and prodeath molecules crosstalk to regulate mitochondrial functions leading to increased cancer cell survival. This review describes some putative survival mechanisms at mitochondria, which may play significant role in designing effective agents for cancer prevention and therapy. These survival pathways may also have significance in understanding other human pathophysiological conditions including diabetes, cardiovascular, autoimmune, and neurodegenerative diseases. PMID:24333692

  12. Bacterial spores survive electrospray charging and desolvation.

    PubMed

    Pratt, Sara N; Austin, Daniel E

    2014-05-01

    The survivability of Bacillus subtilis spores and vegetative Escherichia coli cells after electrospray from aqueous suspension was tested using mobility experiments at atmospheric pressure. E. coli did not survive electrospray charging and desolvation, but B. subtilis did. Experimental conditions ensured that any surviving bacteria were de-agglomerated, desolvated, and electrically charged. Based on mobility measurements, B. subtilis spores survived even with 2,000-20,000 positive charges. B. subtilis was also found to survive introduction into vacuum after either positive or negative electrospray. Attempts to measure the charge distribution of viable B. subtilis spores using electrostatic deflection in vacuum were inconclusive; however, viable spores with low charge states (less than 42 positive or less than 26 negative charges) were observed.

  13. Stereotactic Body Radiation Therapy for Patients With Lung Cancer Previously Treated With Thoracic Radiation

    SciTech Connect

    Kelly, Patrick; Balter, Peter A.; Rebueno, Neal; Sharp, Hadley J.; Liao Zhongxing; Komaki, Ritsuko; Chang, Joe Y.

    2010-12-01

    Purpose: Stereotactic body radiation therapy (SBRT) provides excellent local control with acceptable toxicity for patients with early-stage non-small cell lung cancer. However, the efficacy and safety of SBRT for patients previously given thoracic radiation therapy is not known. In this study, we retrospectively reviewed outcomes after SBRT for recurrent disease among patients previously given radiation therapy to the chest. Materials and Methods: A search of medical records for patients treated with SBRT to the thorax after prior fractionated radiation therapy to the chest at The University of Texas M. D. Anderson Cancer Center revealed 36 such cases. The median follow-up time after SBRT was 15 months. The endpoints analyzed were overall survival, local control, and the incidence and severity of treatment-related toxicity. Results: SBRT provided in-field local control for 92% of patients; at 2 years, the actuarial overall survival rate was 59%, and the actuarial progression-free survival rate was 26%, with the primary site of failure being intrathoracic relapse. Fifty percent of patients experienced worsening of dyspnea after SBRT, with 19% requiring oxygen supplementation; 30% of patients experienced chest wall pain and 8% Grade 3 esophagitis. No Grade 4 or 5 toxic effects were noted. Conclusions: SBRT can provide excellent in-field tumor control in patients who have received prior radiation therapy. Toxicity was significant but manageable. The high rate of intrathoracic failure indicates the need for further study to identify patients who would derive the most benefit from SBRT for this purpose.

  14. Hepatic Angiosarcoma May Have Fair Survival Nowadays

    PubMed Central

    Huang, Neng-Chyan; Kuo, Yau-Chang; Chiang, Jui-Chin; Hung, Shih-Yuan; Wang, Huay-Min; Hung, Yao-Min; Chang, Yun-Te; Wann, Shue-Ren; Chang, Hong-Tai; Wang, Jyh-Seng; Ho, Sheng-Yow; Guo, How-Ran

    2015-01-01

    Abstract Hepatic angiosarcoma (HAS) is rare but often fatal. A review of literature in 1979 found that only 3% of the 70 patients lived for more than 2 years, but the survival might have been improved over the years. We conducted a retrospective study and reviewed the medical records of patients who visited a teaching hospital in Taiwan from January 2000 to August 2010 and had pathological proof of HAS. In addition, we conducted a review of literature and compared those who survived for 2 years or more to those who did not. Of the 3503 patients with primary liver cancer we identified, 9 had HAS, of whom 3 (33.3%) survived for 2 years or more. One survived for 24 months without surgical resection, and the other two received surgery with postoperative chemotherapy and were still alive 32 and 37 months later, respectively. Through reviewing literature, we identified 3 more patients in Taiwan who had survived for 2 years or more. One survived for 42 months without surgical resection, the other two received segmentectomy with postoperative chemotherapy or radiotherapy. We also identified 8 such cases outside Taiwan, including 1 who received chemotherapy without surgery and survived for 53 months. None of the differences in the clinical characteristics between those who had and had not survived for 2 years or more reached statistical significance. In conclusion, we believe the combination of surgery and adjuvant chemotherapy may be able to achieve long-term survival in some HAS patients nowadays, and it is even possible to achieve fair survival using chemotherapy alone. PMID:25984668

  15. Racial Disparities in Survival Among Injured Drivers

    PubMed Central

    Haskins, Amy E.; Clark, David E.; Travis, Lori L.

    2013-01-01

    Prior studies on racial and ethnic disparities in survival after motor vehicle crashes have examined only population-based death rates or have been restricted to hospitalized patients. In the current study, we examined 3 components of crash survival by race/ethnicity: survival overall, survival to reach a hospital, and survival among those hospitalized. Nine years of data (from 2000 through 2008) from the National Automotive Sampling System Crashworthiness Data System were used to examine white non-Hispanic, black non-Hispanic, and Hispanic drivers aged ≥15 years with serious injuries (injury severity scores of ≥9). By using multivariable logistic regression, we found that a driver's race/ethnicity was not significantly associated with overall survival after being injured in a crash (for blacks, odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.36, 1.32; for Hispanics, OR = 1.00, 95% CI: 0.59, 1.72), and blacks and Hispanics were equally likely to survive to be treated at a hospital compared with whites (for blacks, OR = 1.00, 95% CI: 0.52, 1.93; for Hispanics, OR = 1.13, 95% CI: 0.71, 1.79). However, among patients who were treated at a hospital, blacks were 50% less likely to survive 30 days compared with whites (OR = 0.50, 95% CI: 0.33, 0.76). The disparity in survival after serious traffic injuries among blacks appears to occur after hospitalization, not in prehospital survival. PMID:23371352

  16. Impact of Pretransplantation (18)F-Fluorodeoxyglucose-Positron Emission Tomography on Survival Outcomes after T Cell-Depleted Allogeneic Transplantation for Hodgkin Lymphoma.

    PubMed

    Reyal, Yasmin; Kayani, Irfan; Bloor, Adrian J C; Fox, Christopher P; Chakraverty, Ronjon; Sjursen, Ann-Marie; Fielding, Adele K; Ben Taylor, Marcus; Bishton, Mark J; Morris, Emma C; Thomson, Kirsty J; Russell, Nigel; Mackinnon, Stephen; Peggs, Karl S

    2016-07-01

    Pretransplant (18)F-fluorodeoxyglucose (FDG) positron emission tomography status is an important prognostic factor for outcomes after autologous stem cell transplantation (SCT) in Hodgkin lymphoma (HL), but its impact on outcomes after allogeneic SCT remains unclear. We retrospectively evaluated outcomes after T cell-depleted allogeneic SCT of 116 patients with nonprogressive HL according to pretransplant Deauville scores. Endpoints were overall survival (OS), progression-free survival (PFS), relapse rate (RR), and nonrelapse-related mortality (NRM). OS, PFS, and RR did not differ significantly between the Deauville 1 to 2 and Deauville 3 to 5 cohorts (OS: 77.5% versus 67.3%, P = .49; PFS: 59.4% versus 55.7%, P = .43; RR: 20.9% versus 22.6%, P = .28 at 4 years). Differences in PFS remained statistically nonsignificant when comparisons were made between Deauville 1 to 3 and Deauville 4 to 5 cohorts (60.9% versus 51.4%, P = .10), and RR remained very similar (21.5% versus 23.8%, P = .42). Multivariate analyses demonstrated trends toward significance for an effect of Deauville score on PFS (hazard ratio 1.82 for Deauville 4 to 5, P = .06) and for number of lines of prior therapy on OS (hazard ratio 2.34 for >5 lines, P = .10). The latter effect appeared to be driven by higher NRM rather than increased RR. Our findings suggest that Deauville score before allogeneic SCT in patients with nonprogressive HL has a relatively modest impact on survival outcomes in comparison with the impact in autologous SCT and that predictive values for the individual patient remain low, indicating that residual FDG-avid disease should not preclude allogeneic SCT. Furthermore, our findings bring into question the importance of attainment of metabolic complete response in this setting if it is at the expense of increasing NRM risk. PMID:27095691

  17. Overall Survival Analysis of a Phase II Randomized Controlled Trial of a Poxviral-Based PSA-Targeted Immunotherapy in Metastatic Castration-Resistant Prostate Cancer

    PubMed Central

    Kantoff, Philip W.; Schuetz, Thomas J.; Blumenstein, Brent A.; Glode, L. Michael; Bilhartz, David L.; Wyand, Michael; Manson, Kelledy; Panicali, Dennis L.; Laus, Reiner; Schlom, Jeffrey; Dahut, William L.; Arlen, Philip M.; Gulley, James L.; Godfrey, Wayne R.

    2010-01-01

    Purpose Therapeutic prostate-specific antigen (PSA) –targeted poxviral vaccines for prostate cancer have been well tolerated. PROSTVAC-VF treatment was evaluated for safety and for prolongation of progression-free survival (PFS) and overall survival (OS) in a randomized, controlled, and blinded phase II study. Patients and Methods In total, 125 patients were randomly assigned in a multicenter trial of vaccination series. Eligible patients had minimally symptomatic castration-resistant metastatic prostate cancer (mCRPC). PROSTVAC-VF comprises two recombinant viral vectors, each encoding transgenes for PSA, and three immune costimulatory molecules (B7.1, ICAM-1, and LFA-3). Vaccinia-based vector was used for priming followed by six planned fowlpox-based vector boosts. Patients were allocated (2:1) to PROSTVAC-VF plus granulocyte-macrophage colony-stimulating factor or to control empty vectors plus saline injections. Results Eighty-two patients received PROSTVAC-VF and 40 received control vectors. Patient characteristics were similar in both groups. The primary end point was PFS, which was similar in the two groups (P = .6). However, at 3 years post study, PROSTVAC-VF patients had a better OS with 25 (30%) of 82 alive versus 7 (17%) of 40 controls, longer median survival by 8.5 months (25.1 v 16.6 months for controls), an estimated hazard ratio of 0.56 (95% CI, 0.37 to 0.85), and stratified log-rank P = .0061. Conclusion PROSTVAC-VF immunotherapy was well tolerated and associated with a 44% reduction in the death rate and an 8.5-month improvement in median OS in men with mCRPC. These provocative data provide preliminary evidence of clinically meaningful benefit but need to be confirmed in a larger phase III study. PMID:20100959

  18. Survival Outcome Assessed According to Tumor Response and Shrinkage Pattern in Patients with EGFR Mutation–Positive Non–Small-Cell Lung Cancer Treated with Gefitinib or Erlotinib

    PubMed Central

    Takeda, Masayuki; Nakagawa, Kazuhiko

    2014-01-01

    Introduction: Somatic mutations in the epidermal growth factor receptor gene (EGFR) are associated with a marked therapeutic response to EGFR–tyrosine kinase inhibitors (TKIs) in patients with advanced non–small cell lung cancer (NSCLC). Clinical indicators of the likely survival benefit of EGFR-TKI treatment in NSCLC patients with EGFR mutations have not been identified, however. We therefore evaluated progression-free survival (PFS) and overall survival (OS) according to tumor response and tumor shrinkage pattern in such patients. Methods: Among 145 EGFR mutation–positive NSCLC patients treated with EGFR-TKIs, 68 individuals were selected for analysis. Results: Of the 68 selected patients, 6 achieved a complete response (CR), 42 a partial response (PR), and 14 stable disease (SD). Both PFS and OS were significantly longer in patients who achieved a CR or PR than in those who experienced SD. Multivariate analysis showed that a response (CR or PR) to EGFR-TKIs was significantly associated with both PFS and OS. Among the CR/PR group, the median maximal tumor shrinkage relative to baseline was 56%, and the median time to response (TTR) was 4.2 weeks. The subsets of these patients who experienced rapid tumor regression (TTR of ≤4.2 weeks) or a high degree of tumor shrinkage (≥56%) did not show a more favorable PFS or OS compared with those who experienced slow tumor regression or a low degree of tumor shrinkage. Conclusion: Response (CR or PR) may represent the optimal surrogate for efficacy among EGFR mutation–positive NSCLC patients treated with EGFR-TKIs. PMID:24419417

  19. Systematic review and meta-analysis of phase I/II targeted therapy combined with radiotherapy in patients with glioblastoma multiforme: quality of report, toxicity, and survival.

    PubMed

    dos Santos, Marcos A; Pignon, Jean-Pierre; Blanchard, Pierre; Lefeuvre, Delphine; Levy, Antonin; Touat, Mehdi; Louvel, Guillaume; Dhermain, Frédéric; Soria, Jean-Charles; Deutsch, Eric; Le Teuff, Gwénaël

    2015-06-01

    To perform a systematic review and meta-analysis of severe adverse events (SAE) reported in early trials combining molecularly targeted therapies (MTT) with radiotherapy (RT), and to compare them to standard therapy. A summary data meta-analysis was performed and compared to the historical standard. Inclusion criteria were phase I and/or II trials published between 2000 and 2011, with glioblastoma multiforme patients treated with RT and MTT. Pooled incidence rates (IR) of SAE were estimated as well as the pooled median progression-free survival (PFS) and overall survival (OS). Nineteen prospective trials (9 phase I, 1 phase I/II and 9 phase II) out of 29 initially selected were included (n = 755 patients). The exact number of patients who had experienced SAE was mentioned in 37 % of the trials, concerning only 17 % of the patients. Information such as the period during which adverse events were monitored, the planned treatment duration, and late toxicity were not reported in the trials. The pooled IR of overall SAE was 131.2 (95 % CI 88.8-193.7) per 1000 person-months compared to 74.7 (63.6-87.8) for standard therapy (p < 0.01). Significant differences were observed for gastrointestinal events (p = 0.05) and treatment-related deaths (p = 0.02), in favour of standard therapy. No significant difference was observed in PFS and OS. Reporting a summary of toxicity data in early clinical trials should be stringently standardized. The use of MTT with RT compared to standard therapy increased SAE while yielded comparable survival in glioblastoma multiforme patients.

  20. Triple-Negative Subtype Predicts Poor Overall Survival and High Locoregional Relapse in Inflammatory Breast Cancer

    PubMed Central

    Li, Jing; Gonzalez-Angulo, Ana M.; Allen, Pamela K.; Yu, Tse K.; Woodward, Wendy A.; Ueno, Naoto T.; Lucci, Anthony; Krishnamurthy, Savitri; Gong, Yun; Bondy, Melissa L.; Yang, Wei; Willey, Jie S.; Cristofanilli, Massimo; Valero, Vicente

    2011-01-01

    Background. Numerous studies have demonstrated that expression of estrogen/progesterone receptor (ER/PR) and human epidermal growth factor receptor (HER)-2 is important for predicting overall survival (OS), distant relapse (DR), and locoregional relapse (LRR) in early and advanced breast cancer patients. However, these findings have not been confirmed for inflammatory breast cancer (IBC), which has different biological features than non-IBC. Methods. We retrospectively analyzed the records of 316 women who presented to MD Anderson Cancer Center in 1989–2008 with newly diagnosed IBC without distant metastases. Most patients received neoadjuvant chemotherapy, mastectomy, and postmastectomy radiation. Patients were grouped according to receptor status: ER+ (ER+/PR+ and HER-2−; n = 105), ER+HER-2+ (ER+/PR+ and HER-2+; n = 37), HER-2+ (ER−/PR− and HER-2+; n = 83), or triple-negative (TN) (ER−PR−HER-2−; n = 91). Kaplan–Meier and Cox proportional hazards methods were used to assess LRR, DR, and OS rates and their associations with prognostic factors. Results. The median age was 50 years (range, 24–83 years). The median follow-up time and median OS time for all patients were both 33 months. The 5-year actuarial OS rates were 58.7% for the entire cohort, 69.7% for ER+ patients, 73.5% for ER+HER-2+ patients, 54.0% for HER=2+ patients, and 42.7% for TN patients (p < .0001); 5-year LRR rates were 20.3%, 8.0%, 12.6%, 22.6%, and 38.6%, respectively, for the four subgroups (p < .0001); and 5-year DR rates were 45.5%, 28.8%, 50.1%, 52.1%, and 56.7%, respectively (p < .001). OS and LRR rates were worse for TN patients than for any other subgroup (p < .0001–.03). Conclusions. TN disease is associated with worse OS, DR, and LRR outcomes in IBC patients, indicating the need for developing new locoregional and systemic treatment strategies for patients with this aggressive subtype. PMID:22147002

  1. Cancer survival disparities by health insurance status.

    PubMed

    Niu, Xiaoling; Roche, Lisa M; Pawlish, Karen S; Henry, Kevin A

    2013-06-01

    Previous studies found that uninsured and Medicaid insured cancer patients have poorer outcomes than cancer patients with private insurance. We examined the association between health insurance status and survival of New Jersey patients 18-64 diagnosed with seven common cancers during 1999-2004. Hazard ratios (HRs) with 95% confidence intervals for 5-year cause-specific survival were calculated from Cox proportional hazards regression models; health insurance status was the primary predictor with adjustment for other significant factors in univariate chi-square or Kaplan-Meier survival log-rank tests. Two diagnosis periods by health insurance status were compared using Kaplan-Meier survival log-rank tests. For breast, colorectal, lung, non-Hodgkin lymphoma (NHL), and prostate cancer, uninsured and Medicaid insured patients had significantly higher risks of death than privately insured patients. For bladder cancer, uninsured patients had a significantly higher risk of death than privately insured patients. Survival improved between the two diagnosis periods for privately insured patients with breast, colorectal, or lung cancer and NHL, for Medicaid insured patients with NHL, and not at all for uninsured patients. Survival from cancer appears to be related to a complex set of demographic and clinical factors of which insurance status is a part. While ensuring that everyone has adequate health insurance is an important step, additional measures must be taken to address cancer survival disparities.

  2. Linking age, survival, and transit time distributions

    NASA Astrophysics Data System (ADS)

    Calabrese, Salvatore; Porporato, Amilcare

    2015-10-01

    Although the concepts of age, survival, and transit time have been widely used in many fields, including population dynamics, chemical engineering, and hydrology, a comprehensive mathematical framework is still missing. Here we discuss several relationships among these quantities by starting from the evolution equation for the joint distribution of age and survival, from which the equations for age and survival time readily follow. It also becomes apparent how the statistical dependence between age and survival is directly related to either the age dependence of the loss function or the survival-time dependence of the input function. The solution of the joint distribution equation also allows us to obtain the relationships between the age at exit (or death) and the survival time at input (or birth), as well as to stress the symmetries of the various distributions under time reversal. The transit time is then obtained as a sum of the age and survival time, and its properties are discussed along with the general relationships between their mean values. The special case of steady state case is analyzed in detail. Some examples, inspired by hydrologic applications, are presented to illustrate the theory with the specific results. This article was corrected on 11 Nov 2015. See the end of the full text for details.

  3. Rigid shells enhance survival of gekkotan eggs.

    PubMed

    Andrews, Robin M

    2015-11-01

    The majority of lizards and snakes produce permeable parchment-shelled eggs that require high moisture conditions for successful embryonic development. One clade of gekkotan lizards is an exception; females produce relatively impermeable rigid-shelled eggs that normally incubate successfully under low moisture conditions. I tested the hypothesis that the rigid-shell increases egg survival during incubation, but only under low moisture conditions. To test this hypothesis, I incubated rigid-shelled eggs of Chondrodactylus turneri under low and under high moisture conditions. Eggs were incubated with parchment-shelled eggs of Eublepharis macularius to insure that incubation conditions were suitable for parchment-shelled eggs. Chondrodactylus turneri eggs had very high survival (>90%) when they were incubated under low moisture conditions. In contrast, eggs incubated under high moisture conditions had low survival overall, and lower survival than those of the parchment-shelled eggs of E. macularius. Mortality of C. turneri and E. macularius eggs incubated under high moisture conditions was the result of fungal infection, a common source of egg mortality for squamates under laboratory and field conditions. These observations document high survival of rigid-shelled eggs under low moisture conditions because eggs escape from fungal infection. Highly mineralized rigid shells also make egg survival independent of moisture availability and may also provide protection from small invertebrates in nature. Enhanced egg survival could thus compensate for the low reproductive output of gekkotans that produce rigid-shelled eggs.

  4. Sources of variation in waterfowl survival rates

    USGS Publications Warehouse

    Krementz, D.G.; Barker, R.J.; Nichols, J.D.

    1997-01-01

    Because of the need to manage hunted populations of waterfowl (Anatidae), biologists have studied many demographic traits of waterfowl by analyzing band recoveries. These analyses have produced the most extensive and best estimates of survival available for any group of birds. Using these data, we examined several factors that might explain variation among annual survival rates to explore large-scale patterns that might be useful in understanding waterfowl population dynamics. We found that geography, body mass, and tribe (i.e. phylogeny) were important in explaining variation in average waterfowl survival rates.

  5. Survival and severity in dominant cerebellar ataxias

    PubMed Central

    Monin, Marie-Lorraine; Tezenas du Montcel, Sophie; Marelli, Cecilia; Cazeneuve, Cecile; Charles, Perrine; Tallaksen, Chantal; Forlani, Sylvie; Stevanin, Giovanni; Brice, Alexis; Durr, Alexandra

    2015-01-01

    Inherited spinocerebellar ataxias (SCAs) are known to be genetically and clinically heterogeneous. Whether severity and survival are variable, however, is not known. We, therefore, studied survival and severity in 446 cases and 509 relatives with known mutations. Survival was 68 years [95% CI: 65–70] in 223 patients with polyglutamine expansions versus 80 years [73–84] in 23 with other mutations (P < 0.0001). Disability was also more severe in the former: at age 60, 30% were wheelchair users versus 3% with other SCAs (P < 0.001). This has implications for genetic counseling and the design of therapeutic trials. PMID:25750924

  6. Survival probability for the stadium billiard

    NASA Astrophysics Data System (ADS)

    Dettmann, Carl P.; Georgiou, Orestis

    2009-12-01

    We consider the open stadium billiard, consisting of two semicircles joined by parallel straight sides with one hole situated somewhere on one of the sides. Due to the hyperbolic nature of the stadium billiard, the initial decay of trajectories, due to loss through the hole, appears exponential. However, some trajectories (bouncing ball orbits) persist and survive for long times and therefore form the main contribution to the survival probability function at long times. Using both numerical and analytical methods, we concur with previous studies that the long-time survival probability for a reasonably small hole drops like Constant×(; here we obtain an explicit expression for the Constant.

  7. Factors affecting survival following radical mastectomy.

    PubMed

    Freund, H; Grover, N B; Durst, A L

    1978-01-01

    Data on 17 potentially useful factors from 152 women undergoing radical mastectomy for operable breast cancer were analyzed in order to determine the effect of each on survival and their relative importance. Only four, clinical stage, clinical and pathological lymph node involvement, and appearance of recurrence and metastases, proved to be of significant prognostic value. Axillary nodal involvement was the main single determinant of survival. Multiple regression analysis, based on factor analysis of the original input variables, was able to account for 34% of the variance in survival and is thus of only very limited use as a predictive instrument in the clinical management of prospective patients. PMID:651367

  8. Correlation of PD-L1 Expression of Tumor Cells with Survival Outcomes after Radical Intensity-Modulated Radiation Therapy for Non-Metastatic Nasopharyngeal Carcinoma

    PubMed Central

    Lee, Victor H. F.; Lo, Anthony W. I.; Leung, Chun-Yin; Shek, Wai-Hung; Kwong, Dora L. W.; Lam, Ka-On; Tong, Chi-Chung; Sze, Chun-Kin; Leung, To-Wai

    2016-01-01

    Purpose We investigated if programmed death-ligand 1 (PD-L1) expression levels were prognostic of survival outcomes after intensity-modulated radiation therapy (IMRT) for non-metastatic nasopharyngeal carcinoma (NPC). Methods and Materials 104 patients with non-metastatic NPC treated with radical IMRT were investigated for their PD-L1 expression by immunohistochemistry (IHC) which were correlated with survival endpoints including locoregional failure-free survival (LRFFS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and overall survival (OS). Results After a median follow-up of 7.6 years, 21 (20.2%), 19 (18.3%) and 31 (29.8%) patients suffered from locoregional failure, distant metastases and overall disease progression, respectively, and 31 (29.8%) patients died. Patients whose tumors had PD-L1 IHC 2+ (moderate to strong membrane staining in ≥ 25% of tumor cells) enjoyed longer LRFFS (5-year 100% vs. 74.4%, Hazard ratio [HR], 0.159, 95% confidence interval [CI], 0.021–0.988; P = 0.042) and marginally longer PFS (5-year 95.0% vs. 65.2%, HR, 0.351, 95% CI, 0.08–0.999, P = 0.067) compared to those whose tumors had PD-L1 IHC 0 (minimal membrane staining with PD-L1 in < 5% tumor cells or no staining with PD-L1) or 1+ (minimal to moderate membrane staining with PD-L1 in between 5–24% tumor cells). PD-L1 IHC 2+ was independently prognostic of both LRFFS (P = 0.014) and PFS (P = 0.045) in multivariable analyses. Only induction chemotherapy followed by concurrent chemoradiation was prognostic of DMFS (P = 0.003) and no prognostic factor for OS was identified. Conclusion PD-L1 expression levels correlated with LRRFS and PFS in non-metastatic NPC treated with radical IMRT. It may play a role in radiosensitivity for NPC, which should be further confirmed in prospective studies using immunotherapy together with IMRT. PMID:27341634

  9. Characteristics and overall survival of EGFR mutation-positive non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors: a retrospective analysis for 1660 Japanese patients

    PubMed Central

    Inoue, Akira; Yoshida, Kazushi; Morita, Satoshi; Imamura, Fumio; Seto, Takashi; Okamoto, Isamu; Nakagawa, Kazuhiko; Yamamoto, Nobuyuki; Muto, Satoshi; Fukuoka, Masahiro

    2016-01-01

    Background The Japan Guidelines of Lung Cancer Therapy recommend epidermal growth factor receptor-tyrosine kinase inhibitors as a first-line therapy for advanced/recurrent non-small cell lung cancer patients with epidermal growth factor receptor mutation. Although survival periods in recent reports of epidermal growth factor receptor-tyrosine kinase inhibitor treatment have been getting longer, the reasons why are unclear. We investigated the survival, prognostic factors and real-world treatment of non-small cell lung cancer patients with epidermal growth factor receptor mutation in clinical practice. Methods Non-small cell lung cancer patients (n = 1660) who started first-line treatment from January 2008 to December 2012 were enrolled. Patients were diagnosed with epidermal growth factor receptor mutation-positive advanced/recurrent non-small cell lung cancer by histology or cytology samples. The primary objective was to estimate overall survival. The secondary objectives were to determine prognostic factors, real-world treatment patterns and efficacy of gefitinib treatment. We calculated the treatment exposure rate for each treatment category using the following formula: exposure rate = person-years for the treatment category/total person-years × 100. Results The median overall survival was 30.8 months. Sex, age, histology, epidermal growth factor receptor mutation type, clinical stage and performance status affected overall survival. The exposure rates for all epidermal growth factor receptor-tyrosine kinase inhibitors, gefitinib and platinum-doublet chemotherapy were 62.1, 46.4 and 8.5% respectively. Overall 56.1% of patients were administered gefitinib as first-line therapy, and 39.0% were treated with ≥2 epidermal growth factor receptor-tyrosine kinase inhibitor regimens. The median progression-free survival in the first-line gefitinib group was 11.4 months. Factors affecting prognosis were sex, histology, clinical stage and performance status. Conclusion

  10. Pre-radiotherapy plasma carotenoids and markers of oxidative stress are associated with survival in head and neck squamous cell carcinoma patients: a prospective study

    PubMed Central

    2009-01-01

    Background The purpose of this study was to compare plasma levels of antioxidants and oxidative stress biomarkers in head and neck squamous cell carcinoma (HNSCC) patients with healthy controls. Furthermore, the effect of radiotherapy on these biomarkers and their association with survival in HNSCC patients were investigated. Methods Seventy-eight HNSCC patients and 100 healthy controls were included in this study. Follow-up samples at the end of radiotherapy were obtained in 60 patients. Fifteen antioxidant biomarkers (6 carotenoids, 4 tocopherols, ascorbic acid, total antioxidant capacity, glutathione redox potential, total glutathione and total cysteine) and four oxidative stress biomarkers (total hydroperoxides, γ-glutamyl transpeptidase, 8-isoprostagladin F2α and ratio of oxidized/total ascorbic acid) were measured in plasma samples. Analysis of Covariance was used to compare biomarkers between patients and healthy controls. Kaplan-Meier plots and Cox' proportional hazards models were used to study survival among patients. Results Dietary antioxidants (carotenoids, tocopherols and ascorbic acid), ferric reducing antioxidant power (FRAP) and modified FRAP were lower in HNSCC patients compared to controls and dietary antioxidants decreased during radiotherapy. Total hydroperoxides (d-ROMs), a marker for oxidative stress, were higher in HNSCC patients compared to controls and increased during radiotherapy. Among the biomarkers analyzed, high levels of plasma carotenoids before radiotherapy are associated with a prolonged progression-free survival (hazard rate ratio: 0.42, 95% CI: 0.20-0.91, p = 0.03). Additionally, high relative increase in plasma levels of d-ROMs (hazard rate ratio: 0.31, 95% CI: 0.13-0.76, p = 0.01) and high relative decrease in FRAP (hazard rate ratio: 0.42, 95% CI: 0.17-0.998, p = 0.05) during radiotherapy are also positively associated with survival. Conclusions Biomarkers of antioxidants and oxidative stress are unfavourable in HNSCC

  11. Homeless Women, Street Smarts, and Their Survival.

    ERIC Educational Resources Information Center

    Pearce, Carole

    2001-01-01

    A qualitative study of four homeless women depicted their self-perceptions, instability of relationships, decision-making processes, and resourcefulness. Their informal learning included situational and intentional learning applied to survival. (SK)

  12. Does cancer survival differ for older patients?

    PubMed

    Kant, A K; Glover, C; Horm, J; Schatzkin, A; Harris, T B

    1992-12-01

    The relation of age to 5-year relative survival rates was examined for leading sites of cancer resulting in death among 127,554 patients; data from 1978 to 1982 were studied for four areas of the Surveillance, Epidemiology and End Results program of the National Cancer Institute. Overall and stage-stratified relative survival rates declined with advancing patient age for cancer of the lung, prostate, pancreas, bladder, oral cavity, uterus, cervix, ovary, and large bowel (women only). In men, this trend was not explained by age differences in stage of diagnosis, whereas, among women, age was associated with more advanced disease for most sites examined. Although overall survival rates were lower in black patients compared with white patients, the age-survival and age-stage trends were similar in the two racial groups.

  13. A relative survival model for clustered responses.

    PubMed

    Kuss, Oliver; Blankenburg, Thomas; Haerting, Johannes

    2008-06-01

    Relative Survival is the ratio of the overall survival of a group of patients to the expected survival for a demographically similar group. It is commonly used in disease registries to estimate the effect of a particular disease when the true cause of death is not reliably known. Regression models for relative survival have been described and we extend these models to allow for clustered responses by embedding them into the class of Generalized linear mixed models (GLMM). The method is motivated and demonstrated by a data set from the HALLUCA study, an epidemiological study which investigated provision of medical care to lung cancer patients in the region of Halle in the eastern part of Germany.

  14. Biological variability model of cell survival curves

    SciTech Connect

    Domon, M.

    1980-06-01

    The radiation sensitivity of a mammalian cell population has been conventionally characterized by the survival curve parameters, n and D/sub 0/. The present correspondence concerns the interpretation of these parameters when there is biological variability in the radiation sensitivity of a cell population. To derive a relationship between the survival curve parameters and the biological variability, a log-normal distribution was assumed for the sensitivity variability. For a given spread of the distribution, a survival curve on a semilogarithmic scale was obtained graphically. Analysis of such survival curves led to the conclusion that n is inversely related to the spread and the D/sub 0/ is determined by both the LD/sub 50/ and the spread of the log-normal distribution.

  15. 46 CFR 172.245 - Survival conditions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... conditions. A vessel is presumed to survive assumed damage if it meets the following conditions in the final..., such as an air pipe, or an opening that is closed by means of a weathertight door or hatch cover....

  16. SURVIVAL OF SALMONELLA SPECIES IN RIVER WATER

    EPA Science Inventory

    The survival of four Salmonella strains in river water microcosms was monitored by culturing techniques, direct counts, whole-cell hybridization, scanning electron microscopy, and resuscitation techniques via the direct viable count method and flow cytometry. Plate counts of bact...

  17. SURVIVAL OF SALMONELLA SPECIES IN RIVER WATER.

    EPA Science Inventory

    The survival of four Salmonella strains in river water microcosms was monitored using culturing techniques, direct counts, whole cell hybridization, scanning electron microscopy, and resuscitation techniques via the direct viable count method and flow cytrometry. Plate counts of...

  18. Abiraterone Improves Survival in Metastatic Prostate Cancer

    Cancer.gov

    A multinational phase III trial found that the drug abiraterone acetate prolonged the median survival of patients with metastatic castration-resistant prostate cancer by 4 months compared with patients who received a placebo.

  19. Surviving Sepsis: Taming a Deadly Immune Response

    MedlinePlus

    ... disclaimer . Subscribe Surviving Sepsis Taming a Deadly Immune Response Many people have never heard of sepsis, or ... tract infection) and then a powerful and harmful response by your body’s own immune system . “With sepsis, ...

  20. Survival of asbestos insulation workers with mesothelioma.

    PubMed Central

    Ribak, J; Selikoff, I J

    1992-01-01

    Malignant mesothelioma is a lethal disease. It is rare in the general population; however, workers exposed to asbestos suffer significant burdens of the neoplasm. The survival time of 457 consecutive fatal cases of pleural and peritoneal mesothelioma that occurred among 17,800 asbestos insulation workers observed prospectively from 1 January 1967 to 1 January 1987 was studied. Mean survival time from initial presentation of the disease to death was 11.4 months for the pleural mesothelioma patients compared with 7.4 months for the peritoneal group. This difference was statistically significant. Mean survival time from diagnosis to death was shorter for both groups of patients: 8.4 months for pleural mesothelioma v 5.8 months for the peritoneal cases. In conclusion, survival time in mesothelioma patients is short; most die within a year from the onset of the initial symptoms. No effective therapy is yet available. PMID:1419863

  1. Survivable Authentication for Health Information Systems

    PubMed Central

    Bicakci, Kemal; Baykal, Nazife

    2003-01-01

    Possible solutions to establish a survivable authentication framework in a health information system including the one based on one-time passwords (OTPs) are discussed. A new convenient method to generate OTPs is proposed. PMID:14728296

  2. Retrofiting survivability of military vehicles

    SciTech Connect

    Canavan, Gregory H

    2009-01-01

    .5. Over the range from 0.5 to 4.5 cm the shock KE is attenuated by a factor of {approx}70, while its momentum is changed little. The shock and particle velocity falls by a factor of 200 while the mass increases by a factor of 730. In the limit of very porous media u {approx} 1/M, so KE {approx} 1/M, which falls by a factor of {approx}600, while momentum Mu does not change at all. Figure 2 shows the KE, Mu, u, and M for a material with a porosity of 1.05, for which the KE changes little. In the limit of media of very low porosity, u {approx} 1/{radical}M, so KE is constant while Mu {approx} {radical}M, which increases by a factor of 15. Thus, if the goal is to reduce the peak pressure from strong explosions below, very porous materials, which strongly reduce pressure but do not increase momentum, are preferred to non-porous materials, which amplify momentum but do not decrease pressure. These predictions are in qualitative accord with the results of experiments at Los Alamos in which projectiles from high velocity, large caliber cannons were stopped by one to two sandbags. The studies were performed primarily to determine the effectiveness of sand in stopping fragments of various sizes, but could be extended to study sand's effectiveness in attenuating blast pressure. It would also be useful to test the above predictions on the effectiveness of media with higher porosity. Water barriers have been discussed but not deployed in previous retrofit survivability studies for overseas embassies. They would detect the flash from the mine detonation below, trigger a thin layer of explosive above a layer of water, and drive water droplets into the approaching blast wave. The blast loses energy in evaporating the droplets and loses momentum in slowing them. Under favorable conditions that could attenuate the pressure in the blast enough to prevent the penetration or disruption of the vehicle. However, such barriers would depend on prompt and reliable detonation detection and water

  3. Monte Carlo simulation of Alaska wolf survival

    NASA Astrophysics Data System (ADS)

    Feingold, S. J.

    1996-02-01

    Alaskan wolves live in a harsh climate and are hunted intensively. Penna's biological aging code, using Monte Carlo methods, has been adapted to simulate wolf survival. It was run on the case in which hunting causes the disruption of wolves' social structure. Social disruption was shown to increase the number of deaths occurring at a given level of hunting. For high levels of social disruption, the population did not survive.

  4. Upregulation of Dicer is more frequent in monoclonal gammopathies of undetermined significance than in multiple myeloma patients and is associated with longer survival in symptomatic myeloma patients

    PubMed Central

    Sarasquete, María E.; Gutiérrez, Norma C.; Misiewicz-Krzeminska, Irena; Paiva, Bruno; Chillón, María C.; Alcoceba, Miguel; García-Sanz, Ramón; Hernández, Jesús M.; González, Marcos; San-Miguel, Jesús F.

    2011-01-01

    Dicer and Drosha are key enzymes in the miRNA-processing pathway which is altered in many human cancers. We analyzed Dicer and Drosha expression levels by quantitative PCR in 151 patients with monoclonal gammopathies: 102 symptomatic myeloma patients, 23 smoldering myelomas and 26 monoclonal gammopathy of undetermined significance. We found that Dicer expression values were significantly higher in monoclonal gammopathy of undetermined significance than in smoldering myelomas and symptomatic myeloma (mean ± SD, 0.84±0.36 vs. 0.60±0.23 and 0.62±0.51; P<0.01). Moreover, the median progression-free survival was significantly longer in symptomatic myeloma patients with high expression of Dicer (not reached vs. 23.6 months; P=0.02). By contrast, no differences in the expression of Drosha among these groups of patients were observed. Our data suggest that Dicer expression may play an important role in the progression and prognosis of monoclonal gammopathies. (Clinicaltrials.gov identifier: NCT00461747 for MM patients under 65 years of age and NCT00443235 for MM patients over 65 years of age) PMID:21160068

  5. Association of Somatic Mutations of ADAMTS Genes With Chemotherapy Sensitivity and Survival in High-Grade Serous Ovarian Carcinoma

    PubMed Central

    Liu, Yuexin; Yasukawa, Maya; Chen, Kexin; Hu, Limei; Broaddus, Russell R.; Ding, Li; Mardis, Elaine R.; Spellman, Paul; Levine, Douglas A.; Mills, Gordon B.; Shmulevich, Ilya; Sood, Anil K.; Zhang, Wei

    2015-01-01

    IMPORTANCE Chemotherapy response in the majority of patients with ovarian cancer remains unpredictable. OBJECTIVE To identify novel molecular markers for predicting chemotherapy response in patients with ovarian cancer. DESIGN, SETTING, AND PARTICIPANTS Observational study of genomics and clinical data of high-grade serous ovarian cancer cases with genomic and clinical data made public between 2009 and 2014 via the Cancer Genome Atlas project. MAIN OUTCOMES AND MEASURES Chemotherapy response (primary outcome) and overall survival (OS), progression-free survival (PFS), and platinum-free duration (secondary outcome). RESULTS In 512 patients with ovarian cancer with available whole-exome sequencing data, mutations from 8 members of the ADAMTS family (ADAMTS mutations) with an overall mutation rate of approximately 10.4% were associated with a significantly higher chemotherapy sensitivity (100% for ADAMTS-mutated vs 64% for ADAMTS wild-type cases; P < .001) and longer platinum-free duration (median platinum-free duration, 21.7 months for ADAMTS-mutated vs 10.1 months for ADAMTS wild-type cases; P = .001). Moreover, ADAMTS mutations were associated with significantly better OS (hazard ratio [HR], 0.54 [95% CI, 0.42–0.89]; P = .01 and median OS, 58.0 months for ADAMTS-mutated vs 41.3 months for ADAMTS wild-type cases) and PFS (HR, 0.42 [95% CI, 0.38–0.70]; P < .001 and median PFS, 31.8 for ADAMTS-mutated vs 15.3 months for ADAMTS wild-type cases). After adjustment by BRCA1 or BRCA2 mutation, surgical stage, residual tumor, and patient age, ADAMTS mutations were significantly associated with better OS (HR, 0.53 [95% CI, 0.32–0.87]; P = .01), PFS (HR, 0.40 [95% CI, 0.25–0.62]; P < .001), and platinum-free survival (HR, 0.45 [95% CI, 0.28–0.73]; P = .001). ADAMTS-mutated cases exhibited a distinct mutation spectrum and were significantly associated with tumors with a higher genome-wide mutation rate than ADAMTS wild-type cases across the whole exome (median

  6. Survival probability in patients with liver trauma.

    PubMed

    Buci, Skender; Kukeli, Agim

    2016-08-01

    Purpose - The purpose of this paper is to assess the survival probability among patients with liver trauma injury using the anatomical and psychological scores of conditions, characteristics and treatment modes. Design/methodology/approach - A logistic model is used to estimate 173 patients' survival probability. Data are taken from patient records. Only emergency room patients admitted to University Hospital of Trauma (former Military Hospital) in Tirana are included. Data are recorded anonymously, preserving the patients' privacy. Findings - When correctly predicted, the logistic models show that survival probability varies from 70.5 percent up to 95.4 percent. The degree of trauma injury, trauma with liver and other organs, total days the patient was hospitalized, and treatment method (conservative vs intervention) are statistically important in explaining survival probability. Practical implications - The study gives patients, their relatives and physicians ample and sound information they can use to predict survival chances, the best treatment and resource management. Originality/value - This study, which has not been done previously, explores survival probability, success probability for conservative and non-conservative treatment, and success probability for single vs multiple injuries from liver trauma.

  7. Creating a drowning chain of survival.

    PubMed

    Szpilman, David; Webber, Jonathon; Quan, Linda; Bierens, Joost; Morizot-Leite, Luiz; Langendorfer, Stephen John; Beerman, Steve; Løfgren, Bo

    2014-09-01

    All nations would benefit from a simple, clear Drowning Chain of Survival. In high income nations this tool will refine prevention and the call for action. In low and middle income nations this tool is a guide for policy making, resource allocation and priority setting in drowning prevention. A best evidence approach was utilized to create a universal Drowning Chain of Survival. Education on how to prevent drowning and to how react when a drowning incident occurs has not always been guided by good levels of evidence, or high levels of specialized training in drowning process recognition and management. The Drowning Chain of Survival refers to a series of steps that when enacted, attempts to reduce mortality associated with drowning and attempted aquatic rescue. The term "chain of survival" has provided a useful metaphor for the elements of the emergency cardiac care system for sudden cardiac arrest, however interventions and patient management in drowning involves principles and actions that are specific to these situations. The result is a unique and universal Drowning Chain of Survival comprised of five links guiding the important life-saving steps for lay and professional rescuers. This may significantly improve chances of prevention, survival and recovery from drowning. The steps of the chain are: Prevent drowning, Recognize distress, Provide flotation, Remove from water, and Provide care as needed.

  8. Survival probability in patients with liver trauma.

    PubMed

    Buci, Skender; Kukeli, Agim

    2016-08-01

    Purpose - The purpose of this paper is to assess the survival probability among patients with liver trauma injury using the anatomical and psychological scores of conditions, characteristics and treatment modes. Design/methodology/approach - A logistic model is used to estimate 173 patients' survival probability. Data are taken from patient records. Only emergency room patients admitted to University Hospital of Trauma (former Military Hospital) in Tirana are included. Data are recorded anonymously, preserving the patients' privacy. Findings - When correctly predicted, the logistic models show that survival probability varies from 70.5 percent up to 95.4 percent. The degree of trauma injury, trauma with liver and other organs, total days the patient was hospitalized, and treatment method (conservative vs intervention) are statistically important in explaining survival probability. Practical implications - The study gives patients, their relatives and physicians ample and sound information they can use to predict survival chances, the best treatment and resource management. Originality/value - This study, which has not been done previously, explores survival probability, success probability for conservative and non-conservative treatment, and success probability for single vs multiple injuries from liver trauma. PMID:27477933

  9. The survival of Coxiella burnetii in soils

    NASA Astrophysics Data System (ADS)

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

    2007-05-01

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

  10. Adolescent and Young Adult Cancer Survival

    PubMed Central

    Seibel, Nita L.; Smith, Ashley Wilder; Stedman, Margaret R.

    2014-01-01

    Adolescent and young adults (AYAs) face challenges in having their cancers recognized, diagnosed, treated, and monitored. Monitoring AYA cancer survival is of interest because of the lack of improvement in outcome previously documented for these patients as compared with younger and older patient outcomes. AYA patients 15–39 years old, diagnosed during 2000–2008 with malignant cancers were selected from the SEER 17 registries data. Selected cancers were analyzed for incidence and five-year relative survival by histology, stage, and receptor subtypes. Hazard ratios were estimated for cancer death risk among younger and older ages relative to the AYA group. AYA survival was worse for female breast cancer (regardless of estrogen receptor status), acute lymphoid leukemia (ALL), and acute myeloid leukemia (AML). AYA survival for AML was lowest for a subtype associated with a mutation of the nucleophosmin 1 gene (NPM1). AYA survival for breast cancer and leukemia remain poor as compared with younger and older survivors. Research is needed to address disparities and improve survival in this age group. PMID:25417236

  11. OATP1B1 and tumour OATP1B3 modulate exposure, toxicity, and survival after irinotecan-based chemotherapy

    PubMed Central

    Teft, W A; Welch, S; Lenehan, J; Parfitt, J; Choi, Y-H; Winquist, E; Kim, R B

    2015-01-01

    Background: Treatment of advanced and metastatic colorectal cancer with irinotecan is hampered by severe toxicities. The active metabolite of irinotecan, SN-38, is a known substrate of drug-metabolising enzymes, including UGT1A1, as well as OATP and ABC drug transporters. Methods: Blood samples (n=127) and tumour tissue (n=30) were obtained from advanced cancer patients treated with irinotecan-based regimens for pharmacogenetic and drug level analysis and transporter expression. Clinical variables, toxicity, and outcomes data were collected. Results: SLCO1B1 521C was significantly associated with increased SN-38 exposure (P<0.001), which was additive with UGT1A1*28. ABCC5 (rs562) carriers had significantly reduced SN-38 glucuronide and APC metabolite levels. Reduced risk of neutropenia and diarrhoea was associated with ABCC2–24C/T (odds ratio (OR)=0.22, 0.06–0.85) and CES1 (rs2244613; OR=0.29, 0.09–0.89), respectively. Progression-free survival (PFS) was significantly longer in SLCO1B1 388G/G patients and reduced in ABCC2–24T/T and UGT1A1*28 carriers. Notably, higher OATP1B3 tumour expression was associated with reduced PFS. Conclusions: Clarifying the association of host genetic variation in OATP and ABC transporters to SN-38 exposure, toxicity and PFS provides rationale for personalising irinotecan-based chemotherapy. Our findings suggest that OATP polymorphisms and expression in tumour tissue may serve as important new biomarkers. PMID:25611302

  12. 46 CFR 180.130 - Stowage of survival craft.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... assist in launching a survival craft must be provided if: (1) The survival craft weights more than 90.7 kilograms (200 pounds); and (2) The survival craft requires lifting more than 300 vertical millimeters...

  13. 46 CFR 180.130 - Stowage of survival craft.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... assist in launching a survival craft must be provided if: (1) The survival craft weights more than 90.7 kilograms (200 pounds); and (2) The survival craft requires lifting more than 300 vertical millimeters...

  14. Survivability Is More Fundamental Than Evolvability

    PubMed Central

    Palmer, Michael E.; Feldman, Marcus W.

    2012-01-01

    For a lineage to survive over long time periods, it must sometimes change. This has given rise to the term evolvability, meaning the tendency to produce adaptive variation. One lineage may be superior to another in terms of its current standing variation, or it may tend to produce more adaptive variation. However, evolutionary outcomes depend on more than standing variation and produced adaptive variation: deleterious variation also matters. Evolvability, as most commonly interpreted, is not predictive of evolutionary outcomes. Here, we define a predictive measure of the evolutionary success of a lineage that we call the k-survivability, defined as the probability that the lineage avoids extinction for k generations. We estimate the k-survivability using multiple experimental replicates. Because we measure evolutionary outcomes, the initial standing variation, the full spectrum of generated variation, and the heritability of that variation are all incorporated. Survivability also accounts for the decreased joint likelihood of extinction of sub-lineages when they 1) disperse in space, or 2) diversify in lifestyle. We illustrate measurement of survivability with in silico models, and suggest that it may also be measured in vivo using multiple longitudinal replicates. The k-survivability is a metric that enables the quantitative study of, for example, the evolution of 1) mutation rates, 2) dispersal mechanisms, 3) the genotype-phenotype map, and 4) sexual reproduction, in temporally and spatially fluctuating environments. Although these disparate phenomena evolve by well-understood microevolutionary rules, they are also subject to the macroevolutionary constraint of long-term survivability. PMID:22723844

  15. Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Is Separated into Two Subgroups Associated with Survival by BCR-ABL Fluorescence in situ Hybridization of Segmented Cell Nuclei: Report from a Single Institution.

    PubMed

    Kamoda, Yoshimasa; Izumi, Kiyotaka; Iioka, Futoshi; Akasaka, Takashi; Nakamura, Fumihiko; Kishimori, Chiyuki; Tsuda, Katsuyo; Fukutsuka, Katsuhiro; Okumura, Atsuko; Hayashida, Masahiko; Ohno, Hitoshi

    2016-01-01

    Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) may include the lymphoid blast crisis of chronic myeloid leukemia (CML-BC). We applied fluorescence in situ hybridization (FISH) of the BCR-ABL fusion gene to peripheral blood and/or bone marrow smears to determine whether the fusion was restricted to mononuclear cell nuclei or if segmented cell nuclei representing mature neutrophils also carried the fusion (Seg-FISH). Among 20 patients with Ph+ ALL without a prior diagnosis of CML, 9 were Seg-FISH+ and 11 were Seg-FISH-. Seg-FISH+ cases were characterized by a higher rate of p210-type BCR-ABL transcripts, higher white cell and blast counts, and a higher rate of myeloid and T-lymphoid antigen expression than Seg-FISH- cases, in addition to 'major route' cytogenetic abnormalities associated with CML-BC. Eighteen patients were treated with tyrosine kinase inhibitors (TKIs) either alone or in combination with multiagent chemotherapy, and 7 underwent allogeneic hematopoietic stem cell transplantation. Progression-free and overall survivals were greater in the Seg-FISH+ group than in the Seg-FISH- group. These results suggest that the Seg-FISH+ group represents lymphoid CML-BC that occurs de novo, while the Seg-FISH- represents Ph+ ALL in the strict sense, and the two groups are associated with survival when treated with TKIs or TKI-combined therapy. PMID:27537935

  16. The expression of 16 genes related to the cell of origin and immune response predicts survival in elderly patients with diffuse large B-cell lymphoma treated with CHOP and rituximab

    PubMed Central

    Jais, Jean-Philippe; Haioun, Corine; Molina, Thierry J; Rickman, David S.; De Reynies, Aurélien; Berger, Françoise; Gisselbrecht, Christian; Brière, Josette; Reyes, Félix; Gaulard, Philippe; Feugier, Pierre; Labouyrie, Eric; Tilly, Hervé; Bastard, Christian; Coiffier, Bertrand; Salles, Gilles; Leroy, Karen

    2008-01-01

    Gene expression profiles have been associated with clinical outcome in patients with Diffuse Large B-Cell Lymphoma (DLBCL) treated with anthracycline containing chemotherapy. Using Affymetrix HU133A microarrays, we analyzed the lymphoma transcriptional profile of 30 patients treated with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and 23 patients treated with Ritxumab (R)-CHOP in the Groupe d’Etude des Lymphomes de l’Adulte clinical centers. We used this data set to select transcripts showing an association with progression free survival in all patients or showing a differential effect in the two treatment groups. We performed real-time quantitative RT-PCR in the 23 R-CHOP samples of the screening set and 44 R-CHOP additional samples to evaluate the prognostic significance of these transcripts. In these 67 patients, the level of expression of 16 genes and the cell of origin classification were significantly associated with overall survival, independently of the International Prognostic Index. A multivariate model comprising 4 genes of the cell of origin signature (LMO2, MME, LPP and FOXP1) and 2 genes related to immune response, identified for their differential effects in R-CHOP patients (APOBEC3G and RAB33A), demonstrated a high predictive efficiency in this set of patients, suggesting that both features affect outcome in DLBCL patients receiving immunochemotherapy. PMID:18615101

  17. In vivo orthodontic retainer survival - a review

    PubMed Central

    LABUNET, ANCA VICTORIA; BADEA, MÎNDRA

    2015-01-01

    Background Relapse following orthodontic treatment is a constant concern of orthodontists. Fixed retention is preferred especially for the lower arch by most orthodontists. Objectives This review focuses on in vivo studies. The main objective is to determine the survival rates of different types of retainer: glass-fiber reinforced composite resin, polyethylene or multistrand stainless steel wire bonded to each tooth from canine to canine in the mandibular arch. A second objective is to assess which of these types is less likely to cause additional problems and the third objective is to evaluate the factors that may influence retainer survival. Results and conclusions There were 8 studies identified that matched the objectives stated. Current in vivo studies on survival rate take little notice of the role of the material used for bonding of the fixed retainer. It is not possible to draw a conclusion on reliability of new types of retainers glass fiber reinforced composite resin or polyethylene compared to multistrand stainless steel wire. The multistrand wire remains the gold standard for fixed retention. Although it is a logical outcome that retainer survival is dependent on the application technique, there seems to be no research outcome proving that operator experience, moisture control are essential, nor does patient age or sex have statistically proven effects on survival rates. Adequate studies that involve such aspects should be performed. PMID:26609260

  18. The survival of platypuses in captivity.

    PubMed

    Whittington, R J

    1991-01-01

    Data are presented on the duration of survival of 228 platypuses at six Australian zoos between 1934 and 1988. Only 22.4% of all platypuses survived more than 1 year in captivity. Of 15 living platypuses, 3 had been held in captivity for less than 1 year, 5 for between 1 and 5 years, 6 for between 5 and 10 years and 1 for 21 years. Of 213 platypuses that died in captivity, 81.7% had died within 1 year; most within the first month. The duration of survival was unrelated to the age of animals at acquisition or to sex. The survival rate of animals donated to zoos, including "refugees", was similar to that of purpose-caught animals. Clearly, only a small proportion of platypuses adapted to captive husbandry. The cause of death of most platypuses was not established. However, infectious disease did not appear to be significant. Approximately 28% of deaths were related to inadequate husbandry. Recommendations are made to improve the survival of platypuses in captivity. Research has commenced in zoos to facilitate this goal.

  19. Bacteria survival probability in bactericidal filter paper.

    PubMed

    Mansur-Azzam, Nura; Hosseinidoust, Zeinab; Woo, Su Gyeong; Vyhnalkova, Renata; Eisenberg, Adi; van de Ven, Theo G M

    2014-05-01

    Bactericidal filter papers offer the simplicity of gravity filtration to simultaneously eradicate microbial contaminants and particulates. We previously detailed the development of biocidal block copolymer micelles that could be immobilized on a filter paper to actively eradicate bacteria. Despite the many advantages offered by this system, its widespread use is hindered by its unknown mechanism of action which can result in non-reproducible outcomes. In this work, we sought to investigate the mechanism by which a certain percentage of Escherichia coli cells survived when passing through the bactericidal filter paper. Through the process of elimination, the possibility that the bacterial survival probability was controlled by the initial bacterial load or the existence of resistant sub-populations of E. coli was dismissed. It was observed that increasing the thickness or the number of layers of the filter significantly decreased bacterial survival probability for the biocidal filter paper but did not affect the efficiency of the blank filter paper (no biocide). The survival probability of bacteria passing through the antibacterial filter paper appeared to depend strongly on the number of collision between each bacterium and the biocide-loaded micelles. It was thus hypothesized that during each collision a certain number of biocide molecules were directly transferred from the hydrophobic core of the micelle to the bacterial lipid bilayer membrane. Therefore, each bacterium must encounter a certain number of collisions to take up enough biocide to kill the cell and cells that do not undergo the threshold number of collisions are expected to survive.

  20. Autophagy supports Candida glabrata survival during phagocytosis

    PubMed Central

    Roetzer, Andreas; Gratz, Nina; Kovarik, Pavel; Schüller, Christoph

    2010-01-01

    The opportunistic human fungal pathogen Candida glabrata is confronted with phagocytic cells of the host defence system. Survival of internalized cells is thought to contribute to successful dissemination. We investigated the reaction of engulfed C. glabrata cells using fluorescent protein fusions of the transcription factors CgYap1 and CgMig1 and catalase CgCta1. The expression level and peroxisomal localization of catalase was used to monitor the metabolic and stress status of internalized C. glabrata cells. These reporters revealed that the phagocytosed C. glabrata cells were exposed to transient oxidative stress and starved for carbon source. Cells trapped within macrophages increased their peroxisome numbers indicating a metabolic switch. Prolonged phagocytosis caused a pexophagy-mediated decline in peroxisome numbers. Autophagy, and in particular pexophagy, contributed to survival of C. glabrata during engulfment. Mutants lacking CgATG11 or CgATG17, genes required for pexophagy and non-selective autophagy, respectively, displayed reduced survival rates. Furthermore, both CgAtg11 and CgAtg17 contribute to survival, since the double mutant was highly sensitive to engulfment. Inhibition of peroxisome formation by deletion of CgPEX3 partially restored viability of CgATG11 deletion mutants during engulfment. This suggests that peroxisome formation and maintenance might sequester resources required for optimal survival. Mobilization of intracellular resources via autophagy is an important virulence factor that supports the viability of C. glabrata in the phagosomal compartment of infected innate immune cells. PMID:19811500

  1. Starvation-survival of subsurface bacteria

    SciTech Connect

    Magill, N.G.

    1988-01-01

    The ability of four subsurface isolates to survive starvation was examined and the results were compared to survival curves obtained for Escherichia coli B and Serratia marcescens. To examine the starvation-survival phenomenon further, several experimental parameters including nutritional history, initial cell density, growth phase, temperature of growth and starvation, and aeration. Nutritional history, initial cell density, and growth phases of the cells had some effect on the ability of these bacteria to survive whereas temperature and limited aeration had no effect under the conditions tested. No conditions were found where E. coli B or Serratia marcescens died rapidly or where less than 10% of the original cell number of viable cells remained. Because the apparent survival of these bacteria may be due to cryptic growth, cross-feeding experiments with {sup 14}C-labeled cells and unlabeled cells were carried out with E. coli B and Pseudomonas Lula V. Leaked extracellular {sup 14}C-compounds were not used for growth or maintenance energy, and were not taken up by either bacterium. Cryptic growth did not occur; the cells were truly starving under the experimental conditions used.

  2. Analysis of survival data from telemetry projects

    USGS Publications Warehouse

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

    1985-01-01

    Telemetry techniques can be used to study the survival rates of animal populations and are particularly suitable for species or settings for which band recovery models are not. Statistical methods for estimating survival rates and parameters of survival distributions from observations of radio-tagged animals will be described. These methods have been applied to medical and engineering studies and to the study of nest success. Estimates and tests based on discrete models, originally introduced by Mayfield, and on continuous models, both parametric and nonparametric, will be described. Generalizations, including staggered entry of subjects into the study and identification of mortality factors will be considered. Additional discussion topics will include sample size considerations, relocation frequency for subjects, and use of covariates.

  3. Seniors' survival trajectories and the illness connection.

    PubMed

    Montbriand, Muriel J

    2004-04-01

    In a recent life history research, 100 out of 190 randomly selected seniors from a Canadian prairie city determined that their lives were survival trajectories, many with connections to their present illnesses. Seniors told of surviving the Great Depression and World War II, making hard decisions, and experiencing adversities that changed their life courses and perceptions. Completed in 2003, this 5-year study consisted of two phases. The first phase, an ethnomethod, sought the meaning seniors ascribe to illness and healing. The second phase was a reentry of the initial data. Highlighting seniors' stories shows how hard decisions evolved and contrasts can be made in seniors' narratives. Through seniors' analyses of their own lives, findings in this inquiry demonstrate how the price of survival is embedded in ways of perceiving adverse experiences. Those who avoided facing adversities in making difficult decisions were those who now blame illnesses on life experiences. PMID:15068573

  4. Quantum zeno paradox: Survival and decay

    NASA Astrophysics Data System (ADS)

    Chiu, Charles B.

    2009-11-01

    Quantum mechanics enables the calculation of the time evolution of a dynamical system provided the Hamiltonian is defined and the initial state is specified. Due to the time reversal invariance, the time evolution of a given initial state at t=0 does not have a time-arrow. These problems have been extensively studied by E. C. G. Sudarshan and collaborators, including myself. Here the survival probability, which is the square of the survival amplitude, is an even function of t. Using the survival amplitude as a common framework, we discuss Zeno effects in several processes: the decay of an unstable particle, pion productions in proton-nucleus collisions and the Aharonov-Vardi effect which is another manifestation of the Zeno effect.

  5. Seniors' survival trajectories and the illness connection.

    PubMed

    Montbriand, Muriel J

    2004-04-01

    In a recent life history research, 100 out of 190 randomly selected seniors from a Canadian prairie city determined that their lives were survival trajectories, many with connections to their present illnesses. Seniors told of surviving the Great Depression and World War II, making hard decisions, and experiencing adversities that changed their life courses and perceptions. Completed in 2003, this 5-year study consisted of two phases. The first phase, an ethnomethod, sought the meaning seniors ascribe to illness and healing. The second phase was a reentry of the initial data. Highlighting seniors' stories shows how hard decisions evolved and contrasts can be made in seniors' narratives. Through seniors' analyses of their own lives, findings in this inquiry demonstrate how the price of survival is embedded in ways of perceiving adverse experiences. Those who avoided facing adversities in making difficult decisions were those who now blame illnesses on life experiences.

  6. Panspermia Survival Scenarios for Organisms that Survive Typical Hypervelocity Solar System Impact Events.

    NASA Astrophysics Data System (ADS)

    Pasini, D.

    2014-04-01

    Previous experimental studies have demonstrated the survivability of living cells during hypervelocity impact events, testing the panspermia and litho-panspermia hypotheses [1]. It has been demonstrated by the authors that Nannochloropsis Oculata Phytoplankton, a eukaryotic photosynthesizing autotroph found in the 'euphotic zone' (sunlit surface layers of oceans [2]), survive impacts up to 6.93 km s-1 (approx. shock pressure 40 GPa) [3, 4]. Also shown to survive impacts up to 5.49 km s-1 is the tardigrade species Hypsibius dujardini (a complex micro-animal consisting of 40,000 cells) [5, 6]. It has also been shown that they can survive sustained pressures up to 600 MPa using a water filled pressure capsule [7]. Additionally bacteria can survive impacts up to 5.4 km s-1 (~30 GPa) - albeit with a low probability of survival [1], and the survivability of yeast spores in impacts up to 7.4 km s-1 (~30 GPa) has also recently been demonstrated [8]. Other groups have also reported that the lichen Xanthoria elegans is able to survive shocks in similar pressure ranges (~40 GPa) [9]. Here we present various simulated impact regimes to show which scenarios are condusive to the panspermia hypothesis of the natural transfer of life (via an icy body) through space to an extraterrestrial environment.

  7. Dispersal and survival of a polygynandrous passerine

    USGS Publications Warehouse

    Craig, Heather R.; Kendall, Steve J.; Wild, Teri C.; Powell, Abby N.

    2015-01-01

    Although sex biases in survival and dispersal are thought to be linked to avian mating systems, little is known about these demographic patterns in less common mating strategies such as polygynandry. We investigated breeding-site fidelity, natal philopatry, and apparent survival of the polygynandrous Smith's Longspur (Calcarius pictus) over a 7-yr period at 2 areas in Alaska's Brooks Range. We used capture–recapture histories of 243 color-banded adults and 431 juveniles to estimate annual survival and determined dispersal patterns from 34 adults that were found breeding within the study areas over multiple years. Most adults (88%) returned to nest in the same breeding neighborhood as in previous years; mean dispersal distance was 300.9 ± 74.2 m and did not differ between sexes. Juveniles exhibited low natal philopatry; only 4% of banded hatch-year birds were resighted as adults during subsequent years. Those that did return dispersed, on average, 1,674.4 ± 465.8 m from their natal nests (n = 6). Model-averaged survival estimates indicated that annual survival of adult females (50–58%) was only slightly lower than that of males (60–63%); juvenile survival was 41% but was paired with a low (13%) encounter probability. We attribute the lack of sex bias in adult dispersal to this species' polygynandrous mating strategy. Within this system, there are multiple mates within a breeding neighborhood. We argue that natural selection may favor females that remain on the same, familiar breeding site, because they do not have to disperse to a new area to find a suitable mate. Dispersal among breeding populations most likely occurs by juveniles returning as adults. Our findings support hypotheses that suggest a relationship between dispersal and mating strategy and provide some of the first insight into the demographic patterns of a polygynandrous passerine.

  8. Evaluating Additive Interaction Using Survival Percentiles.

    PubMed

    Bellavia, Andrea; Bottai, Matteo; Orsini, Nicola

    2016-05-01

    Evaluation of statistical interaction in time-to-event analysis is usually limited to the study of multiplicative interaction, via inclusion of a product term in a Cox proportional-hazard model. Measures of additive interaction are available but seldom used. All measures of interaction in survival analysis, whether additive or multiplicative, are in the metric of hazard, usually assuming that the interaction between two predictors of interest is constant during the follow-up period. We introduce a measure to evaluate additive interaction in survival analysis in the metric of time. This measure can be calculated by evaluating survival percentiles, defined as the time points by which different subpopulations reach the same incidence proportion. Using this approach, the probability of the outcome is fixed and the time variable is estimated. We also show that by using a regression model for the evaluation of conditional survival percentiles, including a product term between the two exposures in the model, interaction is evaluated as a deviation from additivity of the effects. In the simple case of two binary exposures, the product term is interpreted as excess/decrease in survival time (i.e., years, months, days) due to the presence of both exposures. This measure of interaction is dependent on the fraction of events being considered, thus allowing evaluation of how interaction changes during the observed follow-up. Evaluation of interaction in the context of survival percentiles allows deriving a measure of additive interaction without assuming a constant effect over time, overcoming two main limitations of commonly used approaches.

  9. Growth and survival of Mountain Plovers

    USGS Publications Warehouse

    Miller, Brian J.; Knopf, Fritz L.

    1993-01-01

    Growth and survival rates of Mountain Plovers (Charadrius montanus) were monitored using radiotelemetry from hatching until birds left the breeding grounds on the Pawnee National Grassland, Weld County, Colorado. Chick weights increased logarithmically (r) = 0.961) and tarsus length linearly (r = 0.948) with age. Using the average fledgling weight of 69.8 g and an age/weight regression we predicted that the average age at fledging was 36 d. Fourteen Mountain Plover nests each had three effs; an average of 2.6 eggs hatched in seven nests, whereas remaining nests were lost to predation, storms, or trampling by a cow. Twenty-four adult Mountain Plovers were monitored for 275 telemetry days with no mortalities. Twenty flightless chicks had a calculated daily survival rate of 0.979 for 233 telemetry-days. Mortalities of flightless chicks were due to predation or unknown causes. The daily survival rate predicted that 1.2 of the 2.6 chicks hatched per nest lived to fly. Eight fledged chicks were monitored for 74 telemetry-days, with a daily survival rate of 0.974. Mortalities of fledglings were all attributed to predation. The combined survival rates predicted that 0.7 or the 2.6 hatched chicks lived to leave the nesting area. Survival rates of flightless chicks were similar to those reported 20 yr ago, implying that recent declines in Mountain Plover numbers on the continent are not attributable to either longer-term declines in nesting productivity or phenomena occurring at non-breeding locales.

  10. 10-year survival of total ankle arthroplasties

    PubMed Central

    2011-01-01

    Background and purpose There is an ongoing need to review large series of total ankle replacements (TARs) for monitoring of changes in practice and their outcome. 4 national registries, including the Swedish Ankle Register, have previously reported their 5-year results. We now present an extended series with a longer follow-up, and with a 10-year survival analysis. Patients and methods Records of uncemented 3-component TARs were retrospectively reviewed, determining risk factors such as age, sex, and diagnosis. Prosthetic survival rates were calculated with exchange or removal of components as endpoint—excluding incidental exchange of the polyethylene meniscus. Results Of the 780 prostheses implanted since 1993, 168 (22%) had been revised by June 15, 2010. The overall survival rate fell from 0.81 (95% CI: 0.79–0.83) at 5 years to 0.69 (95% CI: 0.67–0.71) at 10 years. The survival rate was higher, although not statistically significantly so, during the latter part of the period investigated. Excluding the STAR prosthesis, the survival rate for all the remaining designs was 0.78 at 10 years. Women below the age of 60 with osteoarthritis were at a higher risk of revision, but age did not influence the outcome in men or women with rheumatoid arthritis. Revisions due to technical mistakes at the index surgery and instability were undertaken earlier than revisions for other reasons. Interpretation The results have slowly improved during the 18-year period investigated. However, we do not believe that the survival rates of ankle replacements in the near future will approach those of hip and knee replacements—even though improved instrumentation and design of the prostheses, together with better patient selection, will presumably give better results. PMID:22066551

  11. Hypervelocity impact survivability experiments for carbonaceous impactors

    NASA Technical Reports Server (NTRS)

    Bunch, T. E.; Becker, Luann; Bada, Jeffrey; Macklin, John; Radicatidibrozolo, Filippo; Fleming, R. H.; Erlichman, Jozef

    1993-01-01

    We performed a series of hypervelocity impact experiments using carbon-bearing impactors (diamond, graphite, fullerenes, phthalic acid crystals, and Murchison meteorite) into Al plate at velocities between 4.2 and 6.1 km/s. These tests were made to do the following: (1) determine the survivability of carbon forms and organize molecules in low hypervelocity impact; (2) characterize carbonaceous impactor residues; and (3) determine whether or not fullerenes could form from carbonaceous impactors, under our experimental conditions, or survive as impactors. An analytical protocol of field emission SEM imagery, SEM-EDX, laser Raman spectroscopy, single and 2-stage laser mass spectrometry, and laser induced fluorescence (LIF) found the following: (1) diamonds did not survive impact at 4.8 km/s, but were transformed into various forms of disordered graphite; (2) intact, well-ordered graphite impactors did survive impact at 5.9 km/sec, but were only found in the crater bottom centers; the degree of impact-induced disorder in the graphite increases outward (walls, rims, ejecta); (3) phthalic acid crystals were destroyed on impact (at 4.2 km/s, although a large proportion of phthalic acid molecules did survive impact); (4) fullerenes did not form as products of carbonaceous impactors (5.9 - 6.1 km/s, fullerene impactor molecules mostly survived impact at 5.9 km/s; and (5) two Murchison meteorite samples (launched at 4.8 and 5.9 km/s) show preservation of some higher mass polycyclic aromatic hydrocarbons (PAHs) compared with the non-impacted sample. Each impactor type shows unique impactor residue morphologies produced at a given impact velocity. An expanded methodology is presented to announce relatively new analytical techniques together with innovative modifications to other methods that can be used to characterize small impact residues in LDEF craters, in addition to other acquired extraterrestrial samples.

  12. Discriminant Analysis of 18F-Fluoro-Thymidine Kinetic Parameters to Predict Survival in Patients with Recurrent High-Grade Glioma

    PubMed Central

    Wardak, Mirwais; Schiepers, Christiaan; Dahlbom, Magnus; Cloughesy, Timothy; Chen, Wei; Satyamurthy, Nagichettiar; Czernin, Johannes; Phelps, Michael E.; Huang, Sung-Cheng

    2011-01-01

    Purpose The primary objective of this study was to investigate if changes in 18F-FLT kinetic parameters, taken at an early stage after start of therapy, could predict overall survival (OS) and progression-free survival (PFS) in patients with recurrent malignant glioma undergoing treatment with bevacizumab and irinotecan. Experimental Design High-grade recurrent brain tumors were investigated in 18 patients (8M, 10F), 26-76 yr. Each had 3 dynamic PET studies: at baseline, and after 2 weeks, and 6 weeks from the start of treatment. 2.0 MBq/kg of 18F-FLT was injected intravenously and dynamic PET images acquired for 1 hr. Factor analysis generated factor images from which blood and tumor uptake curves were derived. A 3-compartment, 2-tissue model was applied to estimate the tumor 18F-FLT kinetic rate constants using a metabolite and partial volume corrected input function. Different combinations of predictor variables were exhaustively searched in a discriminant function to accurately classify patients into their known OS and PFS groups. A leave-one-out cross-validation technique was used to assess the generalizability of the model predictions. Results In this study population, changes in single parameters such as standardized uptake value or influx rate constant did not accurately classify patients into their respective OS groups (<1yr and ≥1yr) [hit-ratios ≤ 78%]. However, changes in a set of 18F-FLT kinetic parameters could perfectly separate these two groups of patients [hit-ratio=100%] and were also able to correctly classify patients into their respective PFS groups (<100 days and ≥100 days) [hit-ratio=88%]. Conclusions Discriminant analysis using changes in 18F-FLT kinetic parameters early during treatment appears to be a powerful method for evaluating the efficacy of therapeutic regimens. PMID:21868765

  13. Can an IL13 -1112 C/T (rs1800925) polymorphism predict responsiveness to neoadjuvant chemoradiotherapy and survival of Chinese Han patients with locally advanced rectal cancer?

    PubMed Central

    Chang, Hui; Xi, Shaoyan; Xiao, Weiwei; Zeng, Zhifan; Zhang, Huizhong; Xu, Ruihua; Gao, Yuanhong

    2016-01-01

    We sought to determine whether a polymorphism in the Interleukin 13 gene (IL13), 1112 C/T (rs1800925) predicts responsiveness to neoadjuvant chemoradiotherapy (neoCRT) and prognosis in Chinese Han patients with locally advanced rectal cancer (LARC). Pre-treatment biopsies of primary rectal lesion and surgical specimens were collected from 58 patients with LARC, who were treated with neoCRT and surgery. Tumor DNA was extracted from these biopsies and sequenced to analyze the rs1800925 polymorphism. The tumor response to neoCRT was categorized using a tumor regression grade (TRG, 0-2 were poor responders; 3-4 were good responders). Analyses of progression free survival (PFS) and overall survival (OS) were carried out using the Kaplan-Meier method. Of the forty-six patients for whom tumor DNA was successfully sequenced, 23 were good responders to neoCRT (11 patients with a pathological complete response, i.e. pCR) and the other 23 were poor responders. Good and poor responders were equally likely to have a C/C genotype at rs1800925 (73.9%) as a T/T or C/T genotype (26.1%). There were no differences between the C/C and T/T+C/T genotypes with respect to the ypT0-2 ratio (38.2% vs. 41.7%, P = 1.0), ypN0 nodal status (67.6% vs. 50.0%, P= 0.314), 6-year PFS (67.6% vs. 50%, P=0.274), or 6-year OS (76.5% vs. 66.7%, P=0.441). Thus, the IL13-1112 C/T (rs1800925) polymorphism does not predict responsiveness to neoCRT or prognosis of Chinese Han patients with LARC. PMID:27167201

  14. Additional Survival Benefit of Involved-Lesion Radiation Therapy After R-CHOP Chemotherapy in Limited Stage Diffuse Large B-Cell Lymphoma

    SciTech Connect

    Kwon, Jeanny; Kim, Il Han; Kim, Byoung Hyuck; Kim, Tae Min; Heo, Dae Seog

    2015-05-01

    Purpose: The purpose of this study was to evaluate the role of involved-lesion radiation therapy (ILRT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in limited stage diffuse large B-cell lymphoma (DLBCL) by comparing outcomes of R-CHOP therapy alone with R-CHOP followed by ILRT. Methods and Materials: We identified 198 patients treated with R-CHOP (median, 6 cycles) for pathologically confirmed DLBCL of limited stage from July 2004 to December 2012. Clinical characteristics of these patients were 33% with stage I and 66.7% with stage II; 79.8% were in the low or low-intermediate risk group; 13.6% had B symptoms; 29.8% had bulky tumors (≥7 cm); and 75.3% underwent ≥6 cycles of R-CHOP therapy. RT was given to 43 patients (21.7%) using ILRT technique, which included the prechemotherapy tumor volume with a median margin of 2 cm (median RT dose: 36 Gy). Results: After a median follow-up of 40 months, 3-year progression-free survival (PFS) and overall survival (OS) were 85.8% and 88.9%, respectively. Multivariate analysis showed ≥6 cycles of R-CHOP (PFS, P=.004; OS, P=.004) and ILRT (PFS, P=.021; OS, P=.014) were favorable prognosticators of PFS and OS. A bulky tumor (P=.027) and response to R-CHOP (P=.012) were also found to be independent factors of OS. In subgroup analysis, the effect of ILRT was prominent in patients with a bulky tumor (PFS, P=.014; OS, P=.030) or an elevated level of serum lactate dehydrogenase (LDH; PFS, P=.004; OS, P=.012). Conclusions: Our results suggest that ILRT after R-CHOP therapy improves PFS and OS in patients with limited stage DLBCL, especially in those with bulky disease or an elevated serum LDH level.

  15. Does immunohistochemistry affect response to therapy and survival of inoperable non-small cell lung carcinoma patients? A survey of 145 stage III-IV consecutive cases.

    PubMed

    Pelosi, Giuseppe; Haspinger, Eva Regina; Bimbatti, Manuela; Leone, Giorgia; Paolini, Biagio; Fabbri, Alessandra; Tamborini, Elena; Perrone, Federica; Testi, Adele; Garassino, Marina; Maisonneuve, Patrick; de Braud, Filippo; Pilotti, Silvana; Pastorino, Ugo

    2014-04-01

    Whether non-small cell lung carcinoma (NSCLC) unveiled by immunohistochemistry (IHC) has the same clinical outcome as those typed by morphology is still matter of debate. A total of 145 stage III-IV, consecutive inoperable NSCLC patients treated by chemotherapy (133 cases) or EGFR tyrosine kinase inhibitor (12 cases) and including 100 biopsies, 11 surgical specimens, and 34 cytological samples had originally accounted for 120 adenocarcinomas (ADs), 19 squamous cell carcinomas (SQCs), and 6 adenosquamous carcinomas (ADSQCs) by integrating morphology and thyroid transcription factor-1 (TTF1)/p40 IHC. Thirty-two NSCLC-not otherwise specified (NSCLC-NOS) cases were identified by morphology revision of the original diagnoses, which showed solid growth pattern (P < .001), 22 ADs, 5 SQCs, and 5 ADSQCs by IHC profiling (P < .001), and 10 gene-altered tumors (3 EGFR, 5 KRAS, and 2 ALK). While no significant relationships were observed between response to therapy and original, morphology or IHC diagnoses, driver mutations and tumor differentiation by TTF1 expression, AD run better progression-free survival (PFS) or overall survival (OS) than other tumor types by morphology (P = .010 and P = .047) and IHC (P = .033 and P = .046), respectively. Furthermore, patients with NSCLC-NOS confirmed as AD by IHC tended to have poorer OS (P = .179) and PFS (P = .193) similar to that of ADSQC and SQC (P = .702 and P = .540, respectively). A category of less differentiated AD with poorer prognosis on therapy could be identified by IHC, while there were no differences for SQC or ADSQC. The terminology of "NSCLC-NOS, favor by IHC" is appropriate to alert clinicians toward more aggressive tumors. PMID:24326823

  16. Patients With Proneural Glioblastoma May Derive Overall Survival Benefit From the Addition of Bevacizumab to First-Line Radiotherapy and Temozolomide: Retrospective Analysis of the AVAglio Trial

    PubMed Central

    Sandmann, Thomas; Bourgon, Richard; Garcia, Josep; Li, Congfen; Cloughesy, Timothy; Chinot, Olivier L.; Wick, Wolfgang; Nishikawa, Ryo; Mason, Warren; Henriksson, Roger; Saran, Frank; Lai, Albert; Moore, Nicola; Kharbanda, Samir; Peale, Franklin; Hegde, Priti; Abrey, Lauren E.; Phillips, Heidi S.; Bais, Carlos

    2015-01-01

    Purpose The AVAglio (Avastin in Glioblastoma) and RTOG-0825 randomized, placebo-controlled phase III trials in newly diagnosed glioblastoma reported prolonged progression-free survival (PFS), but not overall survival (OS), with the addition of bevacizumab to radiotherapy plus temozolomide. To establish whether certain patient subgroups derived an OS benefit from the addition of bevacizumab to first-line standard-of-care therapy, AVAglio patients were retrospectively evaluated for molecular subtype, and bevacizumab efficacy was assessed for each patient subgroup. Patients and Methods A total of 349 pretreatment specimens (bevacizumab arm, n = 171; placebo arm, n = 178) from AVAglio patients (total, N = 921) were available for biomarker analysis. Samples were profiled for gene expression and isocitrate dehydrogenase 1 (IDH1) mutation status and classified into previously identified molecular subtypes. PFS and OS were assessed within each subtype. Results A multivariable analysis accounting for prognostic covariates revealed that bevacizumab conferred a significant OS advantage versus placebo for patients with proneural IDH1 wild-type tumors (17.1 v 12.8 months, respectively; hazard ratio, 0.43; 95% CI, 0.26 to 0.73; P = .002). This analysis also revealed an interaction between the proneural subtype biomarker and treatment arm (P = .023). The group of patients with mesenchymal and proneural tumors derived a PFS benefit from bevacizumab compared with placebo; however, this translated to an OS benefit in the proneural subset only. Conclusion Retrospective analysis of AVAglio data suggests that patients with IDH1 wild-type proneural glioblastoma may derive an OS benefit from first-line bevacizumab treatment. The predictive value of the proneural subtype observed in AVAglio should be validated in an independent data set. PMID:26124478

  17. Survival outcomes of bevacizumab in first-line metastatic colorectal cancer in a real-life setting: results of the ETNA cohort.

    PubMed

    Fourrier-Réglat, Annie; Smith, Denis; Rouyer, Magali; Bénichou, Jacques; Guimbaud, Rosine; Bécouarn, Yves; Bernard, Olivier; Noize, Pernelle; Moore, Nicholas; Ravaud, Alain

    2014-12-01

    Although the real-life benefits of bevacizumab may differ from clinical trials, observational data are rare. In this cohort study, the effectiveness of bevacizumab in first-line treatment of metastatic colorectal cancer was investigated. Patients initiating bevacizumab between January 2006 and December 2007 were identified in 28 French centres. Outcomes were investigated in the whole cohort and in those with irinotecan-based treatment that was used in the pivotal clinical trial; patients were stratified using inclusion/exclusion criteria of the pivotal clinical trial (PCT) (eligible for the PCT, not eligible or unclassifiable). The Kaplan-Meier method estimated progression-free survival (PFS) and overall survival (OS). A total of 411 patients were included: 57 % male, median age 65.1 years, 78 % Eastern Cooperative Oncology Group performance status ≤1, 88 % irinotecan-based regimen, median duration of bevacizumab use 5.5 months, median OS = 25.3 months (95 % confidence interval, CI [23.3; 27.0]) and median PFS = 10.1 months (95 % CI [9.5; 11.0]). Among the 360 patients who received irinotecan-based chemotherapy, 144 would have been eligible for the PCT, 194 not eligible and 22 unclassifiable. Median OS in those considered eligible was 29.1 (95 % CI [25.4; 33.6]) and in those considered not eligible this was 24.9 months (95 % CI [21.3; 26.9]); median PFS was respectively 11.5 months (95 % CI [10.3; 12.0]) and 9.4 months (95 % CI [8.8; 10.3]). The effectiveness of bevacizumab was found to be similar to that found in other studies including clinical trials which is reassuring.

  18. Evaluating survival model performance: a graphical approach.

    PubMed

    Mandel, M; Galai, N; Simchen, E

    2005-06-30

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

  19. Surviving sepsis in the critical care environment.

    PubMed

    Benedict, Lara

    2015-01-01

    The management of sepsis and septic shock in the intensive care environment is a complex task requiring the cooperation of a multidisciplinary team. The Surviving Sepsis Campaign provides systematic guidelines for the recognition, early intervention, and supportive management of sepsis. Critical care nurses are instrumental in ensuring that these guidelines and other sources of evidence-based practice are used for patients with severe sepsis or septic shock. This article discusses the pathophysiologic processes in severe sepsis and septic shock and discusses the appropriate interventions as recommended by the Surviving Sepsis Campaign. Recommended early treatments are reviewed along with interventions related to hemodynamics, perfusion, and supportive care in the critical care environment.

  20. Predicting survival and morbidity-free survival to very old age

    PubMed Central

    Witteman, Jacqueline C. M.; Franco, Oscar H.; Stricker, Bruno H. C.; Breteler, Monique M. B.; Hofman, Albert; Tiemeier, Henning

    2010-01-01

    As life expectancy continually increases, it is imperative to identify determinants of survival to the extreme end of the lifespan and more importantly to identify factors that increase the chance of survival free of major morbidities. As such, the current study assessed 45 common disease factors as predictors of survival and morbidity-free survival to age 85 years. Within the Rotterdam Study, a population-based cohort, we evaluated morbidity-free participants who were able to attain age 85 within the study duration (n = 2,008). Risk factors were assessed at baseline (1990–1993), and mortality and morbidities were then collected continuously until mortality or the occurrence of their 85th birthday (average time of 7.9 years). Risk factors included demographic and lifestyle variables, health and morbidity indicators and physiological makers. Major morbidities examined included dementia, cancer, cerebrovascular accident, heart failure and myocardial infarction. Logistic regression analyses demonstrated that many of the variables were independently predictive for survival and for morbidity-free ageing to 85 years. These included being female, absence of left ventricular abnormalities, stable body weight, unimpaired instrumental activities of daily living, lower C-RP levels and higher levels of femoral neck bone mineral density and albumin. Relative to non-survival, predictors were stronger for morbidity-free survival than for total survival or survival with morbidity. This suggests that lifespan and healthy survival to older age can be relatively well predicted. Understanding predictors of a long and healthy lifespan is vital for developing primary and secondary preventions to help improve the quality of life of older adults and for reducing the financial burden of the rapidly escalating ageing population. PMID:20514522

  1. Survival during the Breeding Season: Nest Stage, Parental Sex, and Season Advancement Affect Reed Warbler Survival

    PubMed Central

    Wierucka, Kaja; Halupka, Lucyna; Klimczuk, Ewelina; Sztwiertnia, Hanna

    2016-01-01

    Avian annual survival has received much attention, yet little is known about seasonal patterns in survival, especially of migratory passerines. In order to evaluate survival rates and timing of mortality within the breeding season of adult reed warblers (Acrocephalus scirpaceus), mark-recapture data were collected in southwest Poland, between 2006 and 2012. A total of 612 individuals (304 females and 308 males) were monitored throughout the entire breeding season, and their capture-recapture histories were used to model survival rates. Males showed higher survival during the breeding season (0.985, 95% CI: 0.941–0.996) than females (0.869, 95% CI: 0.727–0.937). Survival rates of females declined with the progression of the breeding season (from May to August), while males showed constant survival during this period. We also found a clear pattern within the female (but not male) nesting cycle: survival was significantly lower during the laying, incubation, and nestling periods (0.934, 95% CI: 0.898–0.958), when birds spent much time on the nest, compared to the nest building and fledgling periods (1.000, 95% CI: 1.00–1.000), when we did not record any female mortality. These data (coupled with some direct evidence, like bird corpses or blood remains found next to/on the nest) may suggest that the main cause of adult mortality was on-nest predation. The calculated survival rates for both sexes during the breeding season were high compared to annual rates reported for this species, suggesting that a majority of mortality occurs at other times of the year, during migration or wintering. These results have implications for understanding survival variation within the reproductive period as well as general trends of avian mortality. PMID:26934086

  2. 38 CFR 3.257 - Children; no surviving spouse entitled.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Children; no surviving... and Estate § 3.257 Children; no surviving spouse entitled. Where pension is not payable to a surviving... worth, payments will be made to or for the child or children as if there were no surviving spouse....

  3. 20 CFR 234.44 - Payment to surviving relatives.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Payment to surviving relatives. 234.44... LUMP-SUM PAYMENTS Residual Lump-Sum Payment § 234.44 Payment to surviving relatives. (a) How surviving relatives are paid. If the employee either did not designate a beneficiary or was not survived by...

  4. 38 CFR 3.257 - Children; no surviving spouse entitled.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Children; no surviving... and Estate § 3.257 Children; no surviving spouse entitled. Where pension is not payable to a surviving... worth, payments will be made to or for the child or children as if there were no surviving spouse....

  5. 38 CFR 3.257 - Children; no surviving spouse entitled.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Children; no surviving... and Estate § 3.257 Children; no surviving spouse entitled. Where pension is not payable to a surviving... worth, payments will be made to or for the child or children as if there were no surviving spouse....

  6. 38 CFR 3.257 - Children; no surviving spouse entitled.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Children; no surviving... and Estate § 3.257 Children; no surviving spouse entitled. Where pension is not payable to a surviving... worth, payments will be made to or for the child or children as if there were no surviving spouse....

  7. 46 CFR 117.150 - Survival craft embarkation arrangements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Survival craft embarkation arrangements. 117.150 Section... EQUIPMENT AND ARRANGEMENTS Survival Craft Arrangements and Equipment § 117.150 Survival craft embarkation... apparatus when either— (1) The embarkation station for the survival craft is on a deck more than 4.5...

  8. 1992 ASCAN wilderness survival training school view

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Astronaut candidates Chris A. Hadfield, Jerry M. Linenger and Koichi Wakata (left to right in foreground) are issued gear for a survival school hosted by Fairchild Air Force Base. Hadfield, from Canada, and Wakata, from Japan, are among the five international candidates in the group of astronaut candidates involved in a year-long training and evaluation program.

  9. Black Colleges: An Alternative Strategy for Survival.

    ERIC Educational Resources Information Center

    Whiting, Albert N.

    1988-01-01

    Joseph Perkins argued in the "Wall Street Journal" that one-third of the 100 traditionally Black colleges should become two-year institutions. This rebuttal suggests that Black institutions' survival involves planning for new and broader missions in an unsheltered, integrated, competitive environment. (MLW)

  10. Microbial survival in space shuttle crash.

    PubMed

    McLean, Robert J C; Welsh, Allana K; Casasanto, Valerie A

    2006-03-01

    A slow growing, heat resistant bacterium, identified by 16S rRNA gene sequencing as Microbispora sp., was recovered from the wreckage of the ill-fated space shuttle Columbia (STS-107). As this organism survived disintegration of the space craft, heat of reentry, and impact, it supports the possibility of a natural mechanism for the interplanetary spread of life by meteorites.

  11. Survival by Dialysis Modality-Who Cares?

    PubMed

    Lee, Martin B; Bargman, Joanne M

    2016-06-01

    In light of the recent emphasis on patient-centered outcomes and quality of life for patients with kidney disease, we contend that the nephrology community should no longer fund, perform, or publish studies that compare survival by dialysis modality. These studies have become redundant; they are methodologically limited, unhelpful in practice, and therefore a waste of resources. More than two decades of these publications show similar survival between patients undergoing peritoneal dialysis and those receiving thrice-weekly conventional hemodialysis, with differences only for specific subgroups. In clinical practice, modality choice should be individualized with the aim of maximizing quality of life, patient-reported outcomes, and achieving patient-centered goals. Expected survival is often irrelevant to modality choice. Even for the younger and fitter home hemodialysis population, quality of life, not just duration of survival, is a major priority. On the other hand, increasing evidence suggests that patients with ESRD continue to experience poor quality of life because of high symptom burden, unsolved clinical problems, and unmet needs. Patients care more about how they will live instead of how long. It is our responsibility to align our research with their needs. Only by doing so can we meet the challenges of ESRD patient care in the coming decades.

  12. The Jicarilla Apaches. A Study in Survival.

    ERIC Educational Resources Information Center

    Gunnerson, Dolores A.

    Focusing on the ultimate fate of the Cuartelejo and/or Paloma Apaches known in archaeological terms as the Dismal River people of the Central Plains, this book is divided into 2 parts. The early Apache (1525-1700) and the Jicarilla Apache (1700-1800) tribes are studied in terms of their: persistent cultural survival, social/political adaptability,…

  13. The Kendrick Battery: Sensitivity to Survival Effects.

    ERIC Educational Resources Information Center

    Hayslip, Bert, Jr.; And Others

    1989-01-01

    Compared residualized Kendrick Battery scores, measures of affect, and measures of organicity among 53 elderly persons to determine measures' ability to differentiate elderly persons who survived and those who did not. Results suggest that Kendrick Battery subtests, measures of depression and organicity, in combination with length of…

  14. Survival Strategies for Successful Learning Lab Management.

    ERIC Educational Resources Information Center

    Shelton, Dick

    Information in this two-part report is provided to help directors of college reading and study skills centers plan for survival in an era of declining enrollment. After introductory material noting the need for such centers as colleges increase student retention efforts, Part I of the report examines six administrative factors that affect a…

  15. Dark survival in a warming world

    PubMed Central

    McMinn, A.; Martin, A.

    2013-01-01

    Most algae regularly experience periods of darkness ranging from a few hours to a few days. During this time, they are unable to photosynthesize, and so must consume stored energy products. However, some organisms such as polar algae and some microalgal cysts and spores are exposed to darkness for months to years, and these must use alternative strategies to survive. Some taxa, such as dinoflagellates, form cysts and become dormant. Others use physiological methods or adopt mixotrophy. The longest documented survival of more than a century was for dinoflagellates buried in sediments in a Norwegian fjord. Seasonal changes in daylight hours are naturally unaffected by climate change. This means that polar microalgae will in the future need to survive the same period of seasonal darkness but at higher temperatures, and this will require a greater drawdown of stored energy. Recent experimental work has shown that both Arctic and Antarctic phytoplankton are able to survive increases of up to 6°C in the dark. PMID:23345578

  16. Vulnerability/survivability of the GPS system

    NASA Astrophysics Data System (ADS)

    Burgess, Alan

    This paper considers some of the features that contribute to the military survivability of GPS in times of crisis. It discusses each segment in turn and addresses the potential threats and the counter measures applicable thus enabling GPS to provide a continuing service. The design aspects primarily protect military applications, but the benefits apply equally to the civil community.

  17. 46 CFR 28.120 - Survival craft.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... operate within 12 miles of the coastline. (c) A buoyant apparatus may be substituted instead of the... on board which operate within 12 miles of the coastline. (d) Each survival craft installed on board a... than 10.97 meters (36 feet) in length that meets the flotation provisions of 33 CFR part 183 is...

  18. Movements and survival of lark bunting fledglings

    USGS Publications Warehouse

    Yackel Adams, A.A.; Skagen, S.K.; Adams, R.D.

    2001-01-01

    We quantified post-fledging pre-independence behavior and survival in Lark Buntings (Calamospiza melanocorys) using radio-telemetry. Brood division was recorded in six broods and was maintained throughout the observed fledgling care period. Chicks were capable of short flights (up to 25 m) by fledgling day 6 and longer flights (to 100 m) by fledgling day 13. During the first three weeks after fledging, juveniles moved as far as 800 m from nests. Nine of 23 (39%) monitored fledglings died within 15 days of fledging, primarily due to predation by raptors. Daily survival rates were 0.953 +/- 0.019 for fledgling days 0a??9, 0.955 +/- 0.038 for fledgling days 10a??20, and 0.953 +/- 0.015 for fledgling days 0a??20. The probability of surviving fledgling days 0a??20 was 0.367. More quantification of juvenile survival is clearly needed to understand the role of post-fledging mortality in source-sink dynamics.

  19. Surviving the War--And the Peace

    ERIC Educational Resources Information Center

    Thompson, Doug

    2012-01-01

    This article presents the author's response to "Surviving the War: A College Counselor's Journal" by Philip Clinton. He argues that Clinton's engrossing account of the 1990-91 school year at Cairo American College (CAC) gives individuals wonderful insights into the unusual challenges occasionally encountered by an international counselor. The year…

  20. Survival Strategies of Older Homeless Men.

    ERIC Educational Resources Information Center

    Cohen, Carl I.; And Others

    1988-01-01

    Examined how 281 homeless men aged 50 and older living on skid row were able to procure basic necessities such as money, food, shelter, and health care. Found men had and used informal supports to survive. Inability to fulfill needs was primarily associated with physical health, depression, lack of contacts with institutions and agencies, and…