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Sample records for 2-year progression-free survival

  1. 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- ...

  2. Progression-Free Survival: An Important Prognostic Marker for Long-Term Survival of Small Cell Lung Cancer

    PubMed Central

    Park, Myoung-Rin; Park, Yeon-Hee; Choi, Jae-Woo; Park, Dong-Il; Chung, Chae-Uk; Moon, Jae-Young; Park, Hee-Sun; Jung, Sung-Soo; Kim, Ju-Ock; Kim, Sun-Young

    2014-01-01

    Background Small cell lung cancer (SCLC) is an extremely aggressive tumor with a poor clinical course. Although many efforts have been made to improve patients' survival rates, patients who survive longer than 2 years after chemotherapy are still very rare. We examined the baseline characteristics of patients with long-term survival rates in order to identify the prognostic factors for overall survivals. Methods A total of 242 patients with cytologically or histologically diagnosed SCLC were enrolled into this study. The patients were categorized into long- and short-term survival groups by using a survival cut-off of 2 years after diagnosis. Cox's analyses were performed to identify the independent factors. Results The mean patient age was 65.66 years, and 85.5% were males; among the patients, 61 of them (25.2%) survived longer than 2 years. In the multivariate analyses, CRP (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.25-6.06; p=0.012), TNM staging (HR, 3.29; 95% CI, 1.59-6.80; p=0.001), and progression-free survival (PFS) (HR, 11.14; 95% CI, 2.98-41.73; p<0.001) were independent prognostic markers for poor survival rates. Conclusion In addition to other well-known prognostic factors, this study discovered relationships between the long-term survival rates and serum CRP levels, TNM staging, and PFS. In situations with unfavorable conditions, the PFS would be particularly helpful for managing SCLC patients. PMID:24920948

  3. 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

  4. Progression-free survival as a potential surrogate for overall survival in metastatic breast cancer

    PubMed Central

    Beauchemin, Catherine; Cooper, Dan; Lapierre, Marie-Ève; Yelle, Louise; Lachaine, Jean

    2014-01-01

    Background Progression-free survival (PFS) and time to progression (TTP) are frequently used to establish the clinical efficacy of anti-cancer drugs. However, the surrogacy of PFS/TTP for overall survival (OS) remains a matter of uncertainty in metastatic breast cancer (mBC). This study assessed the relationship between PFS/TTP and OS in mBC using a trial-based approach. Methods We conducted a systematic literature review according to the PICO method: ‘Population’ consisted of women with mBC; ‘Interventions’ and ‘Comparators’ were standard treatments for mBC or best supportive care; ‘Outcomes’ of interest were median PFS/TTP and OS. We first performed a correlation analysis between median PFS/TTP and OS, and then conducted subgroup analyses to explore possible reasons for heterogeneity. Then, we assessed the relationship between the treatment effect on PFS/TTP and OS. The treatment effect on PFS/TTP and OS was quantified by the absolute difference of median values. We also conducted linear regression analysis to predict the effects of a new anti-cancer drug on OS on the basis of its effects on PFS/TTP. Results A total of 5,041 studies were identified, and 144 fulfilled the eligibility criteria. There was a statistically significant relationship between median PFS/TTP and OS across included trials (r=0.428; P<0.01). Correlation coefficient for the treatment effect on PFS/TTP and OS was estimated at 0.427 (P<0.01). The obtained linear regression equation was ΔOS =−0.088 (95% confidence interval [CI] −1.347–1.172) + 1.753 (95% CI 1.307–2.198) × ΔPFS (R2=0.86). Conclusion Results of this study indicate a significant association between PFS/TTP and OS in mBC, which may justify the use of PFS/TTP in the approval for commercialization and reimbursement of new anti-cancer drugs in this cancer setting. PMID:24971020

  5. 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.

  6. Overview: Progression-Free Survival as an Endpoint in Clinical Trials with Solid Tumors

    PubMed Central

    Korn, Ronald L.; Crowley, John J.

    2013-01-01

    Progression-free survival (PFS) is increasingly used as an important and even a primary endpoint in randomized cancer clinical trials in the evaluation of patients with solid tumors, because of both practical and clinical considerations. Although in its simplest form PFS is the time from randomization to a pre-defined endpoint, there are many factors that can influence the exact moment of when disease progression is recorded. In this overview, we review the circumstances that can devalue the use of PFS as a primary endpoint, and attempt to provide a pathway for a future desired state when PFS will become not just a secondary alternative to overall survival but rather an endpoint of choice. PMID:23669420

  7. Joint modeling of progression-free survival and death in advanced cancer clinical trials.

    PubMed

    Dejardin, David; Lesaffre, Emmanuel; Verbeke, Geert

    2010-07-20

    Progression-related endpoints (such as time to progression or progression-free survival) and time to death are common endpoints in cancer clinical trials. It is of interest to study the link between progression-related endpoints and time to death (e.g. to evaluate the degree of surrogacy). However, current methods ignore some aspects of the definitions of progression-related endpoints. We review those definitions and investigate their impact on modeling the joint distribution. Further, we propose a multi-state model in which the association between the endpoints is modeled through a frailty term. We also argue that interval-censoring needs to be taken into account to more closely match the latent disease evolution. The joint distribution and an expression for Kendall's tau are derived. The model is applied to data from a clinical trial in advanced metastatic ovarian cancer. PMID:20572123

  8. 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

  9. 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

  10. 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. PMID:27017948

  11. Estimation of Progression-Free Survival for All Treated Patients in the Randomized Discontinuation Trial Design

    PubMed Central

    Karrison, Theodore G.; Ratain, Mark J.; Stadler, Walter M.; Rosner, Gary L.

    2013-01-01

    The randomized discontinuation trial (RDT) design is an enrichment-type design that has been used in a variety of diseases to evaluate the efficacy of new treatments. The RDT design seeks to select a more homogeneous group of patients, consisting of those who are more likely to show a treatment benefit if one exists. In oncology, the RDT design has been applied to evaluate the effects of cytostatic agents, that is, drugs that act primarily by slowing tumor growth rather than shrinking tumors. In the RDT design, all patients receive treatment during an initial, open-label run-in period of duration T. Patients with objective response (substantial tumor shrinkage) remain on therapy while those with early progressive disease are removed from the trial. Patients with stable disease (SD) are then randomized to either continue active treatment or switched to placebo. The main analysis compares outcomes, for example, progression-free survival (PFS), between the two randomized arms. As a secondary objective, investigators may seek to estimate PFS for all treated patients, measured from the time of entry into the study, by combining information from the run-in and post run-in periods. For t ≤ T, PFS is estimated by the observed proportion of patients who are progression-free among all patients enrolled. For t > T, the estimate can be expressed as Ŝ(t) = p̂OR × ŜOR(t − T) + p̂SD × ŜSD(t − T), where p̂OR is the estimated probability of response during the run-in period, p̂SD is the estimated probability of SD, and ŜOR(t − T) and ŜSD(t − T) are the Kaplan–Meier estimates of subsequent PFS in the responders and patients with SD randomized to continue treatment, respectively. In this article, we derive the variance of Ŝ(t), enabling the construction of confidence intervals for both S(t) and the median survival time. Simulation results indicate that the method provides accurate coverage rates. An interesting aspect of the design is that outcomes during the

  12. The imaging viewpoint: how imaging affects determination of progression-free survival.

    PubMed

    Sullivan, Daniel Carl; Schwartz, Lawrence H; Zhao, Binsheng

    2013-05-15

    Tumor measurements on computed tomgoraphic or MRI scans and/or the appearance of new lesions on any of a variety of imaging studies including positron emission tomographic scans are key determinants for assessing progression-free survival as an endpoint in many clinical trials of therapies for solid tumors. Test-retest tumor measurement reproducibility may vary considerably across serial scans on the same patient unless rigorous attention is paid to standardization of image acquisition parameters and unless measurements are made by trained, experienced observers using validated objective methods. Target lesion selection also must be done with care to choose lesions that are or will be reproducibly measurable. Likewise, new lesions will be missed or misinterpreted on follow-up imaging studies unless those imaging studies are obtained using techniques suitable for detecting early, small lesions. Reader variability is clearly a major component of the problem. The increasing availability of semiautomatic image processing algorithms will help ameliorate that issue. In addition, an array of internationally accepted guidelines, standards, and accreditation programs now exist to help address these problems. PMID:23669422

  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. 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

  16. Carboplatin–paclitaxel-induced leukopenia and neuropathy predict progression-free survival in recurrent ovarian cancer

    PubMed Central

    Lee, C K; Gurney, H; Brown, C; Sorio, R; Donadello, N; Tulunay, G; Meier, W; Bacon, M; Maenpaa, J; Petru, E; Reed, N; Gebski, V; Pujade-Lauraine, E; Lord, S; Simes, R J; Friedlander, M

    2011-01-01

    Background: We assess the prognostic value of chemotherapy-induced leukopenia and sensory neuropathy in the CALYPSO trial patients treated with carboplatin–paclitaxel (CP) or carboplatin–liposomal doxorubicin (CPLD). Methods: We performed a landmark analysis at first month after randomisation to correlate leukopenia (nadir white blood cell <4.0 × 109 per litre or severe infection) during cycle 1 of chemotherapy with progression-free survival (PFS). Using time-dependent proportional-hazards models, we also investigated the association between neuropathy and PFS. Results: Of 608 patients with nadir blood and did not receive growth factors, 72% (CP=70%, CPLD=73%) had leukopenia. Leukopenia was prognostic for PFS in those receiving CP (adjusted hazard ratio (aHR) 0.66, P=0.01). Carboplatin–liposomal doxorubicin was more effective than CP in patients without leukopenia (aHR 0.51, P=0.001), but not those experiencing leukopenia (aHR 0.93, P=0.54; interaction P=0.008). Of 949 patients, 32% (CP=62%, CPLD=28%) reported neuropathy during landmark. Neuropathy was prognostic for PFS in the CP group only (aHR 0.77, P=0.02). Carboplatin–liposomal doxorubicin appeared to be more effective than CP among patients without neuropathy (aHR 0.70, P<0.0001), but not those with neuropathy (aHR 0.96, P=0.81; interaction P=0.15). Conclusion: First-cycle leukopenia and neuropathy were prognostic for patients treated with CP. Efficacy of CP treatment was similar to CPLD in patients who developed leukopenia. These findings support further research to understand the mechanisms of treatment-related toxicity. PMID:21750553

  17. 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

  18. Relationship between progression-free survival and overall survival in chronic lymphocytic leukemia: a literature-based analysis

    PubMed Central

    Beauchemin, C.; Johnston, J.B.; Lapierre, M.È.; Aissa, F.; Lachaine, J.

    2015-01-01

    Background The endpoints of progression-free survival (pfs) and time-to-progression (ttp) are frequently used to evaluate the clinical benefit of anticancer drugs. However, the surrogacy of those endpoints for overall survival (os) is not validated in all cancer settings. In the present study, we used a trial-based approach to assess the relationship between median pfs or ttp and median os in chronic lymphocytic leukemia (cll). Methods The pico (population, interventions, comparators, outcomes) method was used to conduct a systematic review of the literature. The population consisted of patients with cll; the interventions and comparators were standard therapies for cll; and the outcomes were median pfs, ttp, and os. Two independent reviewers screened titles, abstracts, and full papers for eligibility and then extracted data from selected studies. Correlation coefficients were calculated to assess the relationship between median pfs or ttp and median os. Subgroup correlation analyses were also conducted according to the characteristics of the selected studies (such as line of treatment and type of treatment under investigation). Results Of the 1263 potentially relevant articles identified during the literature search, twenty-three were included. On average, median pfs or ttp was 16.0 months (standard deviation: 12.4 months) and median os was 43.5 months (standard deviation: 31.2 months). Results of the correlation analysis indicated that median pfs or ttp is highly correlated with median os (Spearman correlation coefficient: 0.813; p ≤ 0.001). A significant correlation between median pfs or ttp and median os was observed in second- and subsequent-line therapies, but not in the first-line setting. Conclusions Our study demonstrates a strong correlation between median pfs or ttp and median os in previously treated cll, which reinforce the hypothesis that pfs and ttp could be adequate surrogate endpoints for os in this cancer setting. PMID:26089725

  19. Progression-Free Survival Remains Poor Over Sequential Lines of Systemic Therapy in Patients with BRAF-mutated Colorectal Cancer

    PubMed Central

    Morris, Van K.; Overman, Michael J.; Jiang, Zhi-Qin; Garrett, Chris; Agarwal, Shweta; Eng, Cathy; Kee, Bryan; Fogelman, David; Dasari, Arvind; Wolff, Robert; Maru, Dipen; Kopetz, Scott

    2014-01-01

    Background BRAF mutations occur in 5–10% of metastatic colorectal cancers and are biomarkers associated with a poor prognosis. However, the outcomes with standard chemotherapy over sequential lines of therapy in a large cohort of patients with BRAF-mutant tumors have not been described. Methods We searched the MD Anderson Cancer Center databases for patients with colorectal cancer patients and identified BRAF mutations between December 2003 and May 2012. Patients were analyzed for clinical characteristics, progression-free survival (PFS), overall survival (OS), and chemotherapeutic agents used. Survival was estimated according to the Kaplan-Meier method. Results Among the 1567 patients tested for BRAF mutations at our institution, 127 (8.1%) had tumors with BRAF mutations. The 71 patients who presented with metastatic disease received a median of 2 lines of chemotherapy. For the first three lines of chemotherapy, median progression-free survivals were 6.3 months (n=69 patients, 95% confidence interval (CI) of 4.9–7.7 months), 2.5 months (n=58, 95% CI of 1.8–3.0 months), and 2.6 months (n=31, 95% CI of 1.0–4.2 months), respectively. Median PFS was not affected by the backbone chemotherapeutic agent in the first-line setting, whether oxaliplatin-based or irinotecan-based (6.4 months vs. 5.4 months, respectively, p-value = 0.99). Conclusions Progression-free survival is expectedly poor for patients with BRAF-mutated metastatic colorectal cancer. Despite the ascertainment bias present (with testing preferentially performed in patients suitable for clinical trials in refractory disease), these data provide historic controls suitable for future study design and support the idea that novel therapeutic options are essential in this population. PMID:25069797

  20. Estimating quality adjusted progression free survival of first-line treatments for EGFR mutation positive non small cell lung cancer patients in The Netherlands

    PubMed Central

    2012-01-01

    Background Gefitinib, a tyrosine kinase inhibitor, is an effective treatment in advanced non-small cell lung cancer (NSCLC) patients with an activating mutation in the epidermal growth factor receptor (EGFR). Randomised clinical trials showed a benefit in progression free survival for gefitinib versus doublet chemotherapy regimens in patients with an activated EGFR mutation (EGFR M+). From a patient perspective, progression free survival is important, but so is health-related quality of life. Therefore, this analysis evaluates the Quality Adjusted progression free survival of gefitinib versus three relevant doublet chemotherapies (gemcitabine/cisplatin (Gem/Cis); pemetrexed/cisplatin (Pem/Cis); paclitaxel/carboplatin (Pac/Carb)) in a Dutch health care setting in patients with EGFR M+ stage IIIB/IV NSCLC. This study uses progression free survival rather than overall survival for its time frame in order to better compare the treatments and to account for the influence that subsequent treatment lines would have on overall survival analysis. Methods Mean progression free survival for Pac/Carb was obtained by extrapolating the median progression free survival as reported in the Iressa-Pan-Asia Study (IPASS). Data from a network meta-analysis was used to estimate the mean progression free survival for therapies of interest relative to Pac/Carb. Adjustment for health-related quality of life was done by incorporating utilities for the Dutch population, obtained by converting FACT-L data (from IPASS) to utility values and multiplying these with the mean progression free survival for each treatment arm to determine the Quality Adjusted progression free survival. Probabilistic sensitivity analysis was carried out to determine 95% credibility intervals. Results The Quality Adjusted progression free survival (PFS) (mean, (95% credibility interval)) was 5.2 months (4.5; 5.8) for Gem/Cis, 5.3 months (4.6; 6.1) for Pem/Cis; 4.9 months (4.4; 5.5) for Pac/Carb and 8.3 (7.0; 9.9) for

  1. 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. PMID:18356283

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

    PubMed Central

    Lamborn, Kathleen R.; Alfred Yung, W. K.; 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.

    2008-01-01

    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. PMID:18356283

  3. [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. PMID:26471795

  4. Long-Term Progression-Free Survival in a Patient with Locally Advanced, Unresectable Pancreatic Adenocarcinoma

    PubMed Central

    Kahn, Leonel A; Matin, Mahan; Bold, Richard J; Tanaka, Michael I; Monjazeb, Arta M

    2015-01-01

    Pancreatic adenocarcinoma is amongst the most lethal malignancies with dismal five-year survival rates. Surgical excision is the mainstay of therapy and unresectable disease is considered incurable. Herein, we describe a patient with unresectable, advanced stage pancreatic adenocarcinoma with a remarkable clinical course following definitive chemoradiotherapy. PMID:26824007

  5. Low expression of ARHI is associated with shorter progression-free survival in pancreatic endocrine tumors.

    PubMed

    Dalai, Irene; Missiaglia, Edoardo; Barbi, Stefano; Butturini, Giovanni; Doglioni, Claudio; Falconi, Massimo; Scarpa, Aldo

    2007-03-01

    Little is known about the molecular anomalies involved in the development and progression of malignancy of pancreatic endocrine tumors (PETs). A recently identified member of the Ras family, Ras homologue member I (ARHI), has been shown to be involved in breast, ovary, and thyroid carcinogenesis. Unlike other members, it acts as a tumor suppressor gene that inhibits cell growth. Here we analyzed the mRNA expression of ARHI in 52 primary PETs and 16 normal pancreata using quantitative reverse transcription-polymerase chain reaction. ARHI expression showed a statistically significant difference between either normal pancreas or well-differentiated endocrine tumors (WDET) and poorly differentiated endocrine carcinomas (PDECs) (P < .001 and P < .001, respectively). Moreover, ARHI expression among WDEC samples was more heterogeneous than in WDET, with several tumors showing level of expression analogous to that observed in PDECs. A significant correlation between lower ARHI expression and shorter survival (P = .020) was identified, and a low ARHI expression was associated to a shorter time to progression (P < .001), even considering the proliferation index Ki67 in the multivariate analysis. ARHI is involved in PET progression. Its mRNA expression seemed to be a prognostic factor for disease outcome and, in association with the proliferative index Ki67, a predictor for a rapid tumor relapse. PMID:17401457

  6. 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. PMID:26818715

  7. Allotransplantation for patients age 40 years and greater with non-Hodgkin Lymphoma (NHL): encouraging progression-free survival

    PubMed Central

    McClune, Brian L.; Ahn, Kwang Woo; Wang, Hai-Lin; Antin, Joseph H.; Artz, Andrew S.; Cahn, Jean-Yves; Deol, Abhinav; Freytes, César O.; Hamadani, Mehdi; Holmberg, Leona A.; Jagasia, Madan H.; Jakubowski, Ann A.; Kharfan-Dabaja, Mohamed A.; Lazarus, Hillard M.; Miller, Alan M.; Olsson, Richard; Pedersen, Tanya L.; Pidala, Joseph; Pulsipher, Michael A.; Rowe, Jacob M.; Saber, Wael; van Besien, Koen W.; Waller, Edmund K.; Aljurf, Mahmoud D.; Akpek, Görgun; Bacher, Ulrike; Chao, Nelson J.; Chen, Yi-Bin; Cooper, Brenda W.; Dehn, Jason; de Lima, Marcos J.; Hsu, Jack W.; Lewis, Ian D.; Marks, David I.; McGuirk, Joseph; Cairo, Mitchell S.; Schouten, Harry C.; Szer, Jeffrey; Ramanathan, Muthalagu; Savani, Bipin N.; Seftel, Matthew; Socie, Gérard; Vij, Ravi; Warlick, Erica D.; Weisdorf, Daniel J.

    2014-01-01

    Non-Hodgkin lymphomas (NHL) disproportionately affect older patients who uncommonly receive allogeneic hematopoietic cell transplantation (HCT). We analyzed CIBMTR data on 1248 patients ≥40 years receiving reduced-intensity conditioning (RIC) or non-myeloablative (NMA) HCT for aggressive (n=668) and indolent (n=580) NHL. Aggressive lymphoma was more frequent in the oldest cohort [(age 40–54) 49% vs. (55–64) 57% vs. (≥65) 67% p=0.0008]; fewer patients ≥65 had prior autografting [26% vs. 24% vs. 9%; p=0.002)]. Rates of relapse, acute and chronic GVHD and non-relapse mortality (NRM) at one year were similar [22%, 95% confidence interval (CI) 19–26%; 27%, 95% CI 23–31%; 34%, 95% CI 24–44%]. Progression-free (PFS) and overall (OS) survival at 3 years was slightly lower in older cohorts [OS:54%, 95% CI 50–58%; 40%, 95% CI 36–44%; 39%, 95% CI 28–50%; p<0.0001]. Multivariate analysis revealed no significant effect of age on acute or chronic GVHD or relapse. Age ≥55 years, Karnofsky performance status <80, and HLA-mismatch adversely impacted NRM, PFS, and OS. Disease status at HCT, but not histologic subtype, worsened NRM, relapse, PFS and OS. Even for patients ≥55 years, OS still approached 40% at 3 years suggesting HCT effects long-term remissions and remains underutilized in qualified older patients with NHL. PMID:24641829

  8. 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

  9. 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

  10. 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

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

    PubMed

    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; On Behalf Of The Ovarian Cancer Association Consortium

    2016-02-01

    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=7x10-5, 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

  12. Autologous stem cell transplantation in first complete remission may not extend progression-free survival in patients with peripheral T cell lymphomas.

    PubMed

    Yam, Clinton; Landsburg, Daniel J; Nead, Kevin T; Lin, Xinyi; Mato, Anthony R; Svoboda, Jakub; Loren, Alison W; Frey, Noelle V; Stadtmauer, Edward A; Porter, David L; Schuster, Stephen J; Nasta, Sunita D

    2016-07-01

    Patients with peripheral T cell lymphomas (PTCL) generally have a poor prognosis when treated with conventional chemotherapy. Consolidation with autologous stem cell transplantation (ASCT) has been reported to improve progression-free survival. However, these studies have not compared consolidative ASCT with active observation in patients with PTCL achieving first complete remission (CR1) following induction chemotherapy. We conducted a retrospective analysis of PTCL patients treated at the University of Pennsylvania between 1/1/2007 and 12/31/2014. Patients with cutaneous T cell lymphoma, concurrent B cell lymphomas, and anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK-positive ALCL) were excluded from the study. We compared progression-free survival for patients who underwent ASCT in CR1 following CHOP-like induction regimens and patients who underwent active observation during CR1. 48 patients met all inclusion and exclusion criteria and underwent either active observation (28 patients) or consolidative ASCT (20 patients) in CR1. The 1-year cumulative incidence of relapse in the observation and ASCT groups was 50% (95% confidence interval [CI]: 30-67%) and 46% (95% CI: 23-67%), respectively (P = 0.55). Median progression-free survival in the observation and ASCT groups was 15.8 and 12.8 months, respectively (log rank, P = 0.79). Estimated 3-year progression-free survival in the observation and ASCT groups was 37 and 41%, respectively. In conclusion, for PTCL patients achieving CR1 following CHOP-like induction chemotherapy, ASCT does not appear to improve progression-free survival compared to active observation. This finding should be confirmed in a larger, prospective study. Am. J. Hematol. 91:672-676, 2016. © 2016 Wiley Periodicals, Inc. PMID:27012928

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

    PubMed

    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

    2016-09-01

    Donor killer immunoglobulin-like receptor (KIR) genotypes are associated 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 and 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%; 95% confidence interval [CI], 21% to 32% versus 37%; 95% CI, 27% to 46%; P = .05) compared with KIR A/A donors, resulting in improved 5-year progression-free survival (PFS) (35%; 95% CI, 26% to 44% versus 22%; 95% CI, 11% to 35%; P = .007). In multivariate analysis, use of KIR B/x donors was associated with significantly reduced relapse risk (relative risk [RR], .63, P = .02) and improved PFS (RR, .71, P = .008). The relapse protection afforded by KIR B/x donors was not observed in HLA-mismatched transplantations 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

  14. Allotransplantation for patients age ≥40 years with non-Hodgkin lymphoma: encouraging progression-free survival.

    PubMed

    McClune, Brian L; Ahn, Kwang Woo; Wang, Hai-Lin; Antin, Joseph H; Artz, Andrew S; Cahn, Jean-Yves; Deol, Abhinav; Freytes, César O; Hamadani, Mehdi; Holmberg, Leona A; Jagasia, Madan H; Jakubowski, Ann A; Kharfan-Dabaja, Mohamed A; Lazarus, Hillard M; Miller, Alan M; Olsson, Richard; Pedersen, Tanya L; Pidala, Joseph; Pulsipher, Michael A; Rowe, Jacob M; Saber, Wael; van Besien, Koen W; Waller, Edmund K; Aljurf, Mahmoud D; Akpek, Görgun; Bacher, Ulrike; Chao, Nelson J; Chen, Yi-Bin; Cooper, Brenda W; Dehn, Jason; de Lima, Marcos J; Hsu, Jack W; Lewis, Ian D; Marks, David I; McGuirk, Joseph; Cairo, Mitchell S; Schouten, Harry C; Szer, Jeffrey; Ramanathan, Muthalagu; Savani, Bipin N; Seftel, Matthew; Socie, Gérard; Vij, Ravi; Warlick, Erica D; Weisdorf, Daniel J

    2014-07-01

    Non-Hodgkin lymphoma (NHL) disproportionately affects older patients, who do not often undergo allogeneic hematopoietic cell transplantation (HCT). We analyzed Center for International Blood and Marrow Transplant Research data on 1248 patients age ≥40 years receiving reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning HCT for aggressive (n = 668) or indolent (n = 580) NHL. Aggressive lymphoma was more frequent in the oldest cohort 49% for age 40 to 54 versus 57% for age 55 to 64 versus 67% for age ≥65; P = .0008). Fewer patients aged ≥65 had previous autografting (26% versus 24% versus 9%; P = .002). Rates of relapse, acute and chronic GVHD, and nonrelapse mortality (NRM) at 1 year post-HCT were similar in the 3 age cohorts (22% [95% confidence interval (CI), 19% to 26%] for age 40 to 54, 27% [95% CI, 23% to 31%] for age 55 to 64, and 34% [95% CI, 24% to 44%] for age ≥65. Progression-free survival (PFS) and overall survival (OS) at 3 years was slightly lower in the older cohorts (OS: 54% [95% CI, 50% to 58%] for age 40 to 54; 40% [95% CI, 36% to 44%] for age 55 to 64, and 39% [95% CI, 28% to 50%] for age ≥65; P < .0001). Multivariate analysis revealed no significant effect of age on the incidence of acute or chronic GVHD or relapse. Age ≥55 years, Karnofsky Performance Status <80, and HLA mismatch adversely affected NRM, PFS, and OS. Disease status at HCT, but not histological subtype, was associated with worse NRM, relapse, PFS, and OS. Even for patients age ≥55 years, OS still approached 40% at 3 years, suggesting that HCT affects long-term remission and remains underused in qualified older patients with NHL. PMID:24641829

  15. MGMT promoter methylation is associated with temozolomide response and prolonged progression-free survival in disseminated cutaneous melanoma.

    PubMed

    Tuominen, Rainer; Jewell, Rosalyn; van den Oord, Joost J; Wolter, Pascal; Stierner, Ulrika; Lindholm, Christer; Hertzman Johansson, Carolina; Lindén, Diana; Johansson, Hemming; Frostvik Stolt, Marianne; Walker, Christy; Snowden, Helen; Newton-Bishop, Julia; Hansson, Johan; Egyházi Brage, Suzanne

    2015-06-15

    To investigate the predictive and prognostic value of O(6) -methylguanine DNA methyltransferase (MGMT) inactivation by analyses of promoter methylation in pretreatment tumor biopsies from patients with cutaneous melanoma treated with dacarbazine (DTIC) or temozolomide (TMZ) were performed. The patient cohorts consisted of Belgian and Swedish disseminated melanoma patients. Patients were subdivided into those receiving single-agent treatment with DTIC/TMZ (cohort S, n = 74) and those treated with combination chemotherapy including DTIC/TMZ (cohort C, n = 79). Median follow-up was 248 and 336 days for cohort S and cohort C, respectively. MGMT promoter methylation was assessed by three methods. The methylation-related transcriptional silencing of MGMT mRNA expression was assessed by real-time RT-PCR. Response to chemotherapy and progression-free survival (PFS) and overall survival were correlated to MGMT promoter methylation status. MGMT promoter methylation was detected in tumor biopsies from 21.5 % of the patients. MGMT mRNA was found to be significantly lower in tumors positive for MGMT promoter methylation compared to tumors without methylation in both treatment cohorts (p < 0.005). DTIC/TMZ therapy response rate was found to be significantly associated with MGMT promoter methylation in cohort S (p = 0.0005), but did not reach significance in cohort C (p = 0.16). Significantly longer PFS was observed among patients with MGMT promoter-methylated tumors (p = 0.002). Multivariate Cox regression analysis identified presence of MGMT promoter methylation as an independent variable associated with longer PFS. Together, this implies that MGMT promoter methylation is associated with response to single-agent DTIC/TMZ and longer PFS in disseminated cutaneous melanoma. PMID:25400033

  16. 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

  17. Diffusion MR Characteristics Following Concurrent Radiochemotherapy Predicts Progression-Free and Overall Survival in Newly Diagnosed Glioblastoma

    PubMed Central

    Chang, Warren; Pope, Whitney B.; Harris, Robert J.; Hardy, Anthony J.; Leu, Kevin; Mody, Reema R.; Nghiemphu, Phioanh L.; Lai, Albert; Cloughesy, Timothy F.; Ellingson, Benjamin M.

    2015-01-01

    The standard of care for newly diagnosed glioblastoma (GBM) is surgery, then radiotherapy (RT) with concurrent temozolomide (TMZ), followed by adjuvant TMZ. We hypothesized patients with low diffusivity measured using apparent diffusion coefficient (ADC) histogram analysis evaluated after RT+TMZ, prior to adjuvant TMZ, would have a significantly shorter progression-free (PFS) and overall survival (OS). To test this hypothesis we evaluated 120 patients with newly diagnosed GBM receiving RT+TMZ followed by adjuvant TMZ. MRI was performed after completion of RT+TMZ, prior to initiation of adjuvant TMZ. A double Gaussian mixed model was used to describe the ADC histograms within the enhancing tumor, where ADCL and ADCH were defined as the mean ADC value of the lower and higher Gaussian distribution, respectively. An ADCL value of 1.0 um2/ms and ADCH value of 1.6 um2/ms were used to stratify patients into high and low risk categories. Results suggest patients with low ADCL had significantly shorter PFS (Cox Hazard Ratio = 0.12, P = 0.0006). OS was significantly shorter with low ADCL tumors, showing a median OS of 407 vs. 644 days (Cox Hazard Ratio = 0.31, P = 0.047). ADCH was not predictive of PFS or OS when accounting for age and ADCL. In summary, newly diagnosed glioblastoma patients with low ADCL after completion of RT+TMZ are likely to progress and die earlier than patients with higher ADCL. Results suggest ADC histogram analysis may be useful for patient risk stratification following completion of RT+TMZ. PMID:26740971

  18. Connexin 43 expression predicts poor progression-free survival in patients with non-muscle invasive urothelial bladder cancer

    PubMed Central

    Poyet, Cédric; Buser, Lorenz; Roudnicky, Filip; Detmar, Michael; Hermanns, Thomas; Mannhard, Doris; Höhn, Andrej; Rüschoff, Jan; Zhong, Qing; Sulser, Tullio; Moch, Holger; Wild, Peter J

    2015-01-01

    Objectives To evaluate the protein expression of connexin 43 (Cx43) in primary urothelial bladder cancer and test its association with the histopathological characteristics and clinical outcome. Methods A tissue microarray containing 348 tissue samples from 174 patients with primary urothelial carcinomas of the bladder was immunohistochemically stained for Cx43. The intensity of staining was semiquantitatively evaluated (score 0, 1+, 2+), and the association with clinicopathological features was assessed. Univariable and multivariable analyses were performed to identify predictors for progression-free survival (PFS). Results Membranous Cx43 immunoreactivity was detected in 118 (67.8%) of 174 analysable urothelial carcinomas, of which 31 (17.8%) showed even a strong (score 2+) and mainly homogeneous staining. Strong expression levels of Cx43 (score 2+) were associated with higher tumour grade, multiplicity and increased proliferation (all p<0.05). In the subgroup of patients with stage pTa and pT1 bladder tumours (n=158), strong Cx43 expression (p<0.001), solid growth pattern (p<0.001) and increased Ki-67 proliferation fraction (p<0.05) were significantly associated with shorter PFS in an univariable Cox regression analysis. In multivariable Cox regression models, Cx43 immunoreactivity and histological growth pattern remained highly significant and adverse risk factors for PFS. Conclusions The expression levels of Cx43 are frequent in non-muscle invasive bladder cancer (NMIBC), with high expression levels being associated with poor prognosis. Routine assessment of Cx43 expression may improve the identification of high-risk NMIBC. PMID:26251520

  19. 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

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

    PubMed

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

    2010-03-01

    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

  1. 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

  2. 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

  3. 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. PMID:21813511

  4. Progression-Free Survival as a Surrogate for Overall Survival in Advanced/Recurrent Gastric Cancer Trials: A Meta-Analysis

    PubMed Central

    Oba, Koji; Bang, Yung-Jue; Bleiberg, Harry; Boku, Narikazu; Bouché, Olivier; Catalano, Paul; Fuse, Nozomu; Michiels, Stefan; Moehler, Markus; Morita, Satoshi; Ohashi, Yasuo; Ohtsu, Atsushi; Roth, Arnaud; Rougier, Philippe; Sakamoto, Junichi; Sargent, Daniel; Sasako, Mitsuru; Shitara, Kohei; Thuss-Patience, Peter; Van Cutsem, Eric; Burzykowski, Tomasz; Buyse, Marc

    2013-01-01

    The traditional endpoint for assessing efficacy of chemotherapies for advanced/recurrent gastric cancer is overall survival (OS), but OS requires prolonged follow-up. We investigated whether progression-free survival (PFS) is a valid surrogate for OS. Using individual patient data from the GASTRIC meta-analysis, surrogacy of PFS was assessed through the correlation between the endpoints and through the correlation between the treatment effects on the endpoints. External validation of the prediction based on PFS was also evaluated. Individual data from 4069 patients in 20 randomized trials were analyzed. The rank correlation coefficient between PFS and OS was 0.853 (95% confidence interval [CI] = 0.852 to 0.854). The R 2 between treatment effects on PFS and on OS was 0.61 (95% CI = 0.04 to 1.00). Treatment effects on PFS and on OS were only moderately correlated, and we could not confirm the validity of PFS as a surrogate endpoint for OS in advanced/recurrent gastric cancer. PMID:24108811

  5. Cetuximab treatment for metastatic colorectal cancer with KRAS p.G13D mutations improves progression-free survival

    PubMed Central

    OSUMI, HIROKI; SHINOZAKI, EIJI; OSAKO, MASAHIKO; KAWAZOE, YOSHIMASA; OBA, MASARU; MISAKA, TAKAHARU; GOTO, TAKASHI; KAMO, HITOMI; SUENAGA, MITSUKUNI; KUMEKAWA, YOSUKE; OGURA, MARIKO; OZAKA, MASATO; MATSUSAKA, SATOSHI; CHIN, KEISHO; HATAKE, KIYOHIKO; MIZUNUMA, NOBUYUKI

    2015-01-01

    A number of previous studies have reported that 30–50% of patients with colorectal cancer (CRC) harbor Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, which is a major predictive biomarker of resistance to epidermal growth factor (EGFR)-targeted therapy. Treatment with an anti-EGFR inhibitor is recommended for patients with KRAS wild-type metastatic colorectal cancer (mCRC). A recent retrospective study of cetuximab reported that patients with KRAS p.G13D mutations had better outcomes compared with those with other mutations. The aim of this retrospective study was to assess the prevalence of KRAS p.G13D mutations and evaluate the effectiveness of cetuximab in mCRC patients with KRAS p.G13D or other KRAS mutations. We reviewed the clinical records of 98 mCRC patients with KRAS mutations who were treated between August, 2004 and January, 2011 in four hospitals located in Tokyo and Kyushu Island. We also investigated KRAS mutation subtypes and patient characteristics. In the patients who received cetuximab, univariate and multivariate analyses were performed to assess the effect of KRAS p.G13D mutations on progression-free survival (PFS) and overall survival (OS). Of the 98 patients, 23 (23.5%) had KRAS p.G13D-mutated tumors, whereas 75 (76.5%) had tumors harboring other mutations. Of the 31 patients who received cetuximab, 9 (29.0%) had KRAS p.G13D mutations and 22 (71.0%) had other mutations. There were no significant differences in age, gender, primary site, pathological type, history of chemotherapy, or the combined use of irinotecan between either of the patient subgroups. The univariate analysis revealed no significant difference in PFS or OS between the patients with KRAS p.G13D mutations and those with other mutations (median PFS, 4.5 vs. 2.8 months, respectively; P=0.65; and median OS, 15.3 vs. 8.9 months, respectively; P=0.51). However, the multivariate analysis revealed a trend toward better PFS among patients harboring p.G13D mutations (PFS

  6. Six-Month Progression-Free Survival as the Primary Endpoint to Evaluate the Activity of New Agents as Second-line Therapy for Advanced Urothelial Carcinoma

    PubMed Central

    Agarwal, Neeraj; Bellmunt, Joaquim; Maughan, Benjamin L.; Boucher, Kenneth M.; Choueiri, Toni K.; Qu, Angela Q.; Vogelzang, Nicholas J.; Fougeray, Ronan; Niegisch, Guenter; Albers, Peter; Wong, Yu-Ning; Ko, Yoo-Joung; Sridhar, Srikala S.; Tantravahi, Srinivas K.; Galsky, Matthew D.; Petrylak, Daniel P.; Vaishampayan, Ulka N.; Mehta, Amitkumar N.; Beer, Tomasz M.; Sternberg, Cora. N.; Rosenberg, Jonathan E.; Sonpavde, Guru

    2014-01-01

    This study examined the association of progression-free survival at 6 months with overall survival in the context of second-line therapy of advanced urothelial carcinoma in pooled patient-level data from 10 phase II trials and then externally validated in a large phase III trial. Progression-free survival at 6 months was significantly correlated with overall survival and is an innovative primary endpoint to evaluate new agents in this setting. Objective Second-line systemic therapy for advanced urothelial carcinoma (UC) has substantial unmet needs, and current agents show dismal activity. Second-line trials of metastatic UC have used response rate (RR) and median progression-free survival (PFS) as primary endpoints, which may not reflect durable benefits. A more robust endpoint to identify signals of durable benefits when investigating new agents in second-line trials may expedite drug development. PFS at 6 months (PFS6) is a candidate endpoint, which may correlate with overall survival (OS) at 12 months (OS12) and may be applicable across cytostatic and cytotoxic agents. Methods Ten second-line phase II trials with individual patient outcomes data evaluating chemotherapy or biologics were combined for discovery, followed by external validation in a phase III trial. The relationship between PFS6/RR and OS12 was assessed at the trial level using Pearson correlation and weighted linear regression, and at the individual level using Pearson chi-square test with Yates continuity correction. Results In the discovery dataset, a significant correlation was observed between PFS6 and OS12 at the trial (R2 = 0.55, Pearson correlation = 0.66) and individual levels (82%, Қ = 0.45). Response correlated with OS12 at the individual level less robustly (78%, Қ = 0.36), and the trial level association was not statistically significant (R2 = 0.16, Pearson correlation = 0.37). The correlation of PFS6 (81%, Қ = 0.44) appeared PMID:24220220

  7. Interpreting overall survival results when progression-free survival benefits exist in today’s oncology landscape: a metastatic renal cell carcinoma case study

    PubMed Central

    Tang, Yiyun; Bycott, Paul; Åkerborg, Örjan; Jönsson, Linus; Negrier, Sylvie; Chen, Connie

    2014-01-01

    Background The debate surrounding the acceptance of progression-free survival (PFS) as an intermediate endpoint to overall survival (OS) has grown in recent years, due to the challenges in demonstrating an OS benefit within clinical trials today. PFS is generally a good predictor of OS for cases where survival post-progression (SPP) is short, and less so when SPP is long. SPP depends on multiple factors, including residual effect from experimental treatment and effect from crossover or other subsequent therapies, posing unique challenges into the translation of PFS benefit into OS. Methods The objective of this analysis was to conduct simulations investigating how increasing SPP impacts PFS translation to OS, utilizing data from the AXIS (axitinib versus sorafenib in advanced metastatic renal cell carcinoma) trial. The underlying assumption was a treatment benefit in PFS (the PFS distribution parameters were chosen to be equal to median PFS in the AXIS trial) but no treatment effect on SPP, implying that PFS improvement is directly reflected in OS improvement. Results The probability of a statistically significant difference between arms for OS decreased from 54.7% to 6.1% when median SPP was increased from one to 20 months. The probability of the hazard ratio of OS being ≥0.9 was similarly increased from 24.3% to 72.6%, even though the hazard ratio for PFS was 0.69. Conclusion The present study shows that when simulated SPP is added to trial PFS data, the existing PFS benefit is diluted. Knowing that the AXIS treatment arms are well balanced with respect to post-trial treatments, we conclude that the PFS to OS benefit translation is primarily obscured by random variability largely unrelated to the true outcomes. The implications for drug development are not insignificant, as there would be a need to include more patients in studies or utilize a longer follow-up time to overcome the SPP variability issue. PMID:25278784

  8. Evaluation of progression-free survival as a surrogate endpoint for survival in chemotherapy and targeted agent metastatic colorectal cancer trials.

    PubMed

    Sidhu, Roger; Rong, Alan; Dahlberg, Steve

    2013-03-01

    Pooled analyses of chemotherapy trials in metastatic colorectal cancer (mCRC) have suggested that progression-free survival (PFS) is a surrogate endpoint for overall survival (OS). However, this has not been evaluated under current standard-of-care regimens of chemotherapy in combination with targeted therapies. We conducted an analysis of published mCRC trials of chemotherapy and targeted therapies from 2000 to evaluate the surrogacy of PFS and response rate (RR) for OS. Study-level data was pooled from 24 randomized mCRC trials that evaluated fluoropyrimidine-based regimens and included trials conducted with targeted agents (panitumumab, cetuximab, bevacizumab, and aflibercept). A total of 69 treatment arms with a sample size of 20,438 patients was included. Linear regression analysis was carried out to estimate the correlation of PFS and RR with OS. The correlation coefficient between PFS HRs and OS HRs was 0.86 for all trials, 0.89 for 12 phase III trials of targeted agents in combination with chemotherapy, 0.95 for 8 first-line phase III trials of targeted agents, and 0.83 for 9 trials of anti-EGFR-targeted agents. In all cases, correlation coefficients between RR and OS HRs were lower than those between PFS HRs and OS HRs (range, 0.42-0.81). In this study-level analysis of randomized mCRC trials of chemotherapy and targeted agents, improvements in PFS are strongly correlated with improvements in OS. This suggests that PFS remains a valid surrogate endpoint for OS with current treatment regimens in the mCRC setting. PMID:23303214

  9. Progression-free survival as a surrogate endpoint for overall survival in patients with third-line or later-line chemotherapy for advanced gastric cancer

    PubMed Central

    Liu, Liya; Yu, Hao; Huang, Lihong; Shao, Fang; Bai, Jianling; Lou, Donghua; Chen, Feng

    2015-01-01

    Background The correlation between overall survival (OS) and progression-free survival (PFS) has been evaluated in patients with metastatic or advanced gastric cancer who have received first-line and/or second-line chemotherapy. However, no corresponding analysis has been done for patients who have undergone third-line or later-line chemotherapy. Methods A total of 303 patients from the Phase II/III studies of apatinib were pooled (the Phase II study as a training data set, the Phase III study as a testing data set). Landmark analyses of PFS at 2 months from randomization were performed to minimize lead time bias. The Cox proportional hazard model was used to test for the significance effect of PFS rate at 2 months in predicting OS. Additionally, the PFS/OS correlations were evaluated by the normal induced copula (National Institute for Health and Care Excellence) estimation model. Results The median OS was 3.37 months (95% confidence interval 2.63–3.80) in patients who experienced progression at 2 months and 5.67 months in patients who did not (95% confidence interval 4.83–6.67; P<0.0001). Compared with patients who did not progress at 2 months, the adjusted hazard ratio for death was 3.39 (95% confidence interval 1.79–6.41; P<0.0001) for patients who experienced progression at 2 months. Moreover, the correlation of PFS/OS was 0.84 (95% confidence interval 0.74–0.90). Similar results were found in the testing data set. Conclusion These results indicate that PFS correlates strongly with OS, suggesting PFS may be a useful early endpoint for patients with advanced gastric cancer who have undergone third-line or later-line chemotherapy. These observations require prospective validation. PMID:25960663

  10. Increased C-kit intensity is a poor prognostic factor for progression-free and overall survival in patients with newly diagnosed AML.

    PubMed

    Advani, Anjali S; Rodriguez, Cristina; Jin, Tao; Jawde, Rony Abou; Saber, Wael; Baz, Rachid; Kalaycio, Matt; Sobecks, Ronald; Sekeres, Mikkael; Tripp, Barbara; Hsi, Eric

    2008-06-01

    C-kit, a tyrosine kinase receptor, is expressed on most myeloid blasts and is thought to be important in the pathogenesis of AML. Activation of the c-kit receptor leads to phosphorylation and activation of downstream signaling proteins, which are important for cell survival and proliferation. Here, we discuss the prognostic impact of c-kit intensity, measured using the mean fluorescent index (MFI) in patients with newly diagnosed AML. On multivariate analysis, c-kit MFI>20.3 correlated with a decreased progression-free survival and overall survival, independent of known prognostic factors (age, white blood count at diagnosis and cytogenetics). Whether inhibiting c-kit in patients with AML will alter prognosis is the basis of ongoing clinical trials. PMID:17928050

  11. Systematic CpG Islands Methylation Profiling of Genes in the Wnt Pathway in Epithelial Ovarian Cancer Identifies Biomarkers of Progression-Free Survival

    PubMed Central

    Dai, Wei; Teodoridis, Jens M.; Zeller, Constanze; Graham, Janet; Hersey, Jenny; Flanagan, James M.; Stronach, Euan; Millan, David W.; Siddiqui, Nadeem; Paul, Jim; Brown, Robert

    2011-01-01

    Purpose Wnt pathways control key biological processes that potentially impact on tumour progression and patient survival. We aimed to evaluate DNA methylation at promoter CpG islands (CGIs) of Wnt pathway genes in ovarian tumours at presentation and identify biomarkers of patient progression-free survival (PFS). Experimental Design Epithelial ovarian tumours (screening study n=120, validation study n=61) prospectively collected through a cohort study, were analysed by differential methylation hybridisation (DMH) at 302 loci spanning 189 promoter CGIs at 137 genes in Wnt pathways. The association of methylation and progression free survival was examined by Cox proportional hazards model. Results DNA methylation is associated with PFS at 20/302 loci (p<0.05, n=111), with 5 loci significant at FDR<10%. 11/20 loci retain significance in an independent validation cohort (n=48,p≤0.05,FDR≤10%), and 7 of these loci, at FZD4, DVL1, NFATC3, ROCK1, LRP5, AXIN1 and NKD1 genes, are independent from clinical parameters (adjusted p<0.05). Increased methylation at these loci associates with increased hazard of disease progression. A multivariate Cox model incorporates only NKD1 and DVL1, identifying two groups differing in PFS (HR=2.09; 95%CI (1.39, 3.15); permutation test p<0.005). Methylation at DVL1 and NFATC3 show significant association with response. Consistent with their epigenetic regulation, reduced expression of FZD4, DVL1 and ROCK1 is an indicator of early disease relapse in an independent ovarian tumour cohort (n=311, adjusted p<0.05). Conclusions The data highlights the importance of epigenetic regulation of multiple promoter CGIs of Wnt pathway genes in ovarian cancer and identifies methylation at NKD1 and DVL1 as independent predictors of PFS. PMID:21459799

  12. Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-GD2 immunotherapy and isotretinoin: a prospective Phase II study

    PubMed Central

    Kushner, Brian H; Ostrovnaya, Irina; Cheung, Irene Y; Kuk, Deborah; Kramer, Kim; Modak, Shakeel; Yataghene, Karima; Cheung, Nai-Kong V

    2015-01-01

    Relapse of high-risk neuroblastoma (HR-NB) is deemed invariably fatal yet increasing numbers of HR-NB patients achieve a second complete/very good partial remission (CR/VGPR), hence the urgency to find a successful consolidative therapy. Identifying efficacy in patients without assessable disease, however, is problematic. We report the first study providing outcome data for this group of patients with poor prognosis. To prevent another relapse, HR-NB patients in second or later CR/VGPR received the anti-GD2 murine antibody 3F8 plus granulocyte-macrophage colony-stimulating factor plus isotretinoin in a Phase II trial. Upon meeting the target aim for progression-free survival (PFS) in the initial cohort of 33 patients, the trial was amended to allow patients who developed human anti-mouse antibody (HAMA) to receive rituximab to ablate HAMA with or without low-dose maintenance chemotherapy until immunotherapy could resume. For the total of 101 study patients, 5-year PFS and overall survival (OS) rates were 33% ± 5% and 48% ± 5%, respectively. Among the 33 long-term progression-free survivors, 19 had MYCN amplification, 19 had previously received anti-GD2 immunotherapy plus isotretinoin (as first-line therapy), and 15 never received maintenance chemotherapy. In a multivariate analysis of prognostic factors, only absence of minimal residual disease in bone marrow after 2 cycles of immunotherapy and before initiation of isotretinoin or anti-HAMA therapy was significantly favorable for both PFS and OS. Therefore, long-term PFS is possible for HR-NB patients who achieve at least a second CR/VGPR and receive consolidation that includes anti-GD2 immunotherapy plus isotretinoin, even if the patients received these biological treatments before relapse. Results from this prospective study will aid in the development of future Phase II studies for this growing ultra high-risk patient population. PMID:26140243

  13. {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.

  14. Treatment of Metastatic Breast Cancer in a Real-World Scenario: Is Progression-Free Survival With First Line Predictive of Benefit From Second and Later Lines?

    PubMed Central

    Bonotto, Marta; Gerratana, Lorenzo; Iacono, Donatella; Minisini, Alessandro Marco; Rihawi, Karim; Fasola, Gianpiero

    2015-01-01

    Introduction. Despite the availability of several therapeutic options for metastatic breast cancer (MBC), no robust predictive factors are available to help clinical decision making. Nevertheless, a decreasing benefit from first line to subsequent lines of treatment is commonly observed. The aim of this study was to assess the impact of benefit from first-line therapy on outcome with subsequent lines. Methods. We analyzed a consecutive series of 472 MBC patients treated with chemotherapy (CT) and/or endocrine therapy (ET) between 2004 and 2012. We evaluated progression-free survival (PFS) at first (PFS1), second, third, and fourth therapeutic lines, according to treatment (ET and/or CT) and tumor subtypes. Results. In the whole cohort, median overall survival was 34 months, and median PFS1 was 9 months. A 6-month benefit was shown by 289 patients (63.5%) at first line, 128 (40.5%) at second line, 76 (33.8%) at third line, and 34 (23.3%) at fourth line. Not having a 6-month benefit at PFS1 was associated with less chance of benefit at second line (odds ratio [OR]: 0.48; 95% confidence interval [CI]: 0.29–0.77, p = .0026) and at any line beyond first (OR: 0.39; 95% CI: 0.24–0.62, p < .0001). In the total series, after stratification for tumor subtypes, a strong predictive effect was observed among HER2-positive tumors (OR: 0.2; 95% CI: 0.05–0.73, p = .0152). Conclusion. Our results suggest that the absence of at least a 6-month benefit in terms of PFS with first-line therapy predicts a reduced probability of benefit from subsequent therapeutic lines, especially in HER2-positive disease. Implications for Practice: This study supports evidence showing that the absence of a 6-month benefit in terms of progression-free survival with first-line therapy predicts a lack of benefit from subsequent therapeutic lines in metastatic breast cancer. The random distribution of benefit experienced by a subset of the cohort further spurs an interest in identifying predictive

  15. Clinical Significance of the Relationship between Progression-Free Survival or Postprogression Survival and Overall Survival in Patients with Extensive Disease-Small-Cell Lung Cancer Treated with Carboplatin plus Etoposide

    PubMed Central

    Imai, Hisao; Mori, Keita; Watase, Nodoka; Fujimoto, Sakae; Kaira, Kyoichi; Yamada, Masanobu; Minato, Koichi

    2016-01-01

    Background. The effects of first-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies in patients with small-cell lung cancer (SCLC). Therefore, by using individual-level data, we aimed to determine the relationships between progression-free survival (PFS) or postprogression survival (PPS) and OS after first-line chemotherapies in patients with extensive disease-SCLC (ED-SCLC) treated with carboplatin plus etoposide. Methods. Between July 1998 and December 2014, we analyzed 63 cases of patients with ED-SCLC who were treated with carboplatin and etoposide as first-line chemotherapy. The relationships of PFS and PPS with OS were analyzed at the individual level. Results. Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.90, p < 0.05, and R2 = 0.71) and PFS was moderately correlated with OS (r = 0.72, p < 0.05, and R2 = 0.62). Type of relapse (refractory/sensitive) and the number of regimens administered after disease progression after the first-line chemotherapy were both significantly associated with PPS (p < 0.05). Conclusions. PPS has a stronger relationship with OS than does PFS in ED-SCLC patients who have received first-line chemotherapy. These results suggest that treatments administered after first-line chemotherapy affect the OS of ED-SCLC patients treated with carboplatin plus etoposide. PMID:27445549

  16. 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

  17. 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

  18. Factors that predict progression-free survival in Chinese lung adenocarcinoma patients treated with epidermal growth factor receptor tyrosine kinase inhibitors

    PubMed Central

    Cui, Shaohua; Xiong, Liwen; Lou, Yuqing; Shi, Huangping; Gu, Aiqin; Zhao, Yizhuo; Chu, Tianqing; Wang, Huimin; Zhang, Wei; Dong, Lili

    2016-01-01

    Background Although first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have shown efficacy in patients with advanced lung cancers, survival predictors with these drugs have not been extensively investigated. This study was performed to explore factors that may predict progression-free survival (PFS) in Chinese lung adenocarcinoma patients treated with EGFR-TKIs. Methods We retrospectively collected clinicopathologic data on 208 patients who received either gefitinib, erlotinib or icotinib, including the patients’ EGFR mutation status and levels of six serum tumor markers [carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cancer antigen 125 (CA125), squamous cell carcinoma antigen (SCC), cytokeratin-19 fragments (CYFRA21-1) and lactate dehydrogenase (LDH)]. Univariate and multivariate survival analyses were performed to identify independent prognostic factors associated with PFS. Results At the study cutoff date, 189 (90.9%) of the patients met the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 criteria for progressive disease (PD), while 19 (9.1%) had stable disease (SD). The median PFS of the 208 patients was 12.4 months (95% CI, 11.0–13.8 months). In the multivariate analysis using a Cox proportional hazard model, a non-smoking history [hazard ratio (HR) =2.460; 95% CI, 1.484–4.079; P<0.001], first-line treatment (HR =1.500; 95% CI, 1.062–2.119; P=0.021), and a high pretreatment serum level of CEA (HR =1.424; 95% CI 1.026–1.977; P=0.035) were found to be significant predictors of a longer PFS. Conclusions In Chinese lung adenocarcinoma patients treated with EGFR-TKIs, a non-smoking history, first-line EGFR-TKIs treatment and a high serum level of CEA were independent predictors of a longer PFS along with an EGFR-activating mutation. PMID:26904214

  19. GSTP1 Ile105Val polymorphism correlates with progression-free survival in MCRC patients treated with or without irinotecan: a study of the Dutch Colorectal Cancer Group

    PubMed Central

    Kweekel, D M; Koopman, M; Antonini, N F; Van der Straaten, T; Nortier, J W R; Gelderblom, H; Punt, C J A; Guchelaar, H-J

    2008-01-01

    A Valine residue at position 105 of the GSTP1 protein results in decreased enzyme activity. As nuclear GSTP1 activity decreases irinotecan cytotoxicity, Val-allele carriers may benefit more from irinotecan chemotherapy. Our aim was to investigate the association of GSTP1 genotype with treatment outcome of irinotecan. Progression-free survival (PFS) and toxicity were determined in 267 metastatic colorectal cancer (MCRC) patients who were treated with first-line capecitabine (CAP) plus irinotecan (CAPIRI), or CAP single agent in a prospective randomised phase III trial (CAIRO). GSTP1 genotype was determined by Pyrosequencing. Patients receiving CAP showed a PFS of 6.6 (Ile/Ile), 6.0 (Ile/Val) and 6.5 months (Val/Val); compared to 7.0 (Ile/Ile), 8.8 (Ile/Val) and 9.2 months (Val/Val) with CAPIRI. Median PFS was 2.7 months longer in Val-allele carriers treated with CAPIRI compared to CAP (P=0.005). Patients with the Ile/Ile genotype showed similar PFS with CAPIRI and CAP (7.0 compared to 6.6 months, P=0.972). Toxicity did not differ significantly among genotypes. GSTP1 codon 105 polymorphism may be predictive for the response to irinotecan-based chemotherapy in patients with MCRC, with the Val-allele being associated with a better outcome. Ile/Ile genotype patients do not appear to benefit from the addition of irinotecan to CAP. PMID:18797455

  20. 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 Central

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

    2015-01-01

    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. PMID:26636288

  1. 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

  2. Expression signature distinguishing two tumour transcriptome classes associated with progression-free survival among rare histological types of epithelial ovarian cancer

    PubMed Central

    Wang, Chen; Winterhoff, Boris J; Kalli, Kimberly R; Block, Matthew S; Armasu, Sebastian M; Larson, Melissa C; Chen, Hsiao-Wang; Keeney, Gary L; Hartmann, Lynn C; Shridhar, Viji; Konecny, Gottfried E; Goode, Ellen L; Fridley, Brooke L

    2016-01-01

    Background: The mechanisms of recurrence have been under-studied in rare histologies of invasive epithelial ovarian cancer (EOC) (endometrioid, clear cell, mucinous, and low-grade serous). We hypothesised the existence of an expression signature predictive of outcome in the rarer histologies. Methods: In split discovery and validation analysis of 131 Mayo Clinic EOC cases, we used clustering to determine clinically relevant transcriptome classes using microarray gene expression measurements. The signature was validated in 967 EOC tumours (91 rare histological subtypes) with recurrence information. Results: We found two validated transcriptome classes associated with progression-free survival (PFS) in the Mayo Clinic EOC cases (P=8.24 × 10−3). This signature was further validated in the public expression data sets involving the rare EOC histologies, where these two classes were also predictive of PFS (P=1.43 × 10−3). In contrast, the signatures were not predictive of PFS in the high-grade serous EOC cases. Moreover, genes upregulated in Class-1 (with better outcome) were showed enrichment in steroid hormone biosynthesis (false discovery rate, FDR=0.005%) and WNT signalling pathway (FDR=1.46%); genes upregulated in Class-2 were enriched in cell cycle (FDR=0.86%) and toll-like receptor pathways (FDR=2.37%). Conclusions: These findings provide important biological insights into the rarer EOC histologies that may aid in the development of targeted treatment options for the rarer histologies. PMID:27253175

  3. Radiographic Progression-Free Survival As a Response Biomarker in Metastatic Castration-Resistant Prostate Cancer: COU-AA-302 Results

    PubMed Central

    Morris, Michael J.; Molina, Arturo; Small, Eric J.; de Bono, Johann S.; Logothetis, Christopher J.; Fizazi, Karim; de Souza, Paul; Kantoff, Philip W.; Higano, Celestia S.; Li, Jinhui; Kheoh, Thian; Larson, Steven M.; Matheny, Shannon L.; Naini, Vahid; Burzykowski, Tomasz; Griffin, Thomas W.; Scher, Howard I.; Ryan, Charles J.

    2015-01-01

    Purpose Progression-free survival (PFS) in metastatic castration-resistant prostate cancer (mCRPC) trials has been inconsistently defined and poorly associated with overall survival (OS). A reproducible quantitative definition of radiographic PFS (rPFS) was tested for association with a coprimary end point of OS in a randomized trial of abiraterone in patients with mCRPC. Patients and Methods rPFS was defined as ≥ two new lesions on an 8-week bone scan plus two additional lesions on a confirmatory scan, ≥ two new confirmed lesions on any scan ≥ 12 weeks after random assignment, and/or progression in nodes or viscera on cross-sectional imaging, or death. rPFS was assessed by independent review at 15% of deaths and by investigator review at 15% and 40% of deaths. rPFS and OS association was evaluated by Spearman's correlation. Results A total of 1,088 patients were randomly assigned to abiraterone plus prednisone or prednisone alone. At first interim analysis, the hazard ratio (HR) by independent review was 0.43 (95% CI, 0.35 to 0.52; P < .001; abiraterone plus prednisone: median rPFS, not estimable; prednisone: median rPFS, 8.3 months). Similar HRs were obtained by investigator review at the first two interim analyses (HR, 0.49; 95% CI, 0.41 to 0.60; P < .001 and HR, 0.53; 95% CI, 0.45 to 0.62; P < .001, respectively), validating the imaging data assay used. Spearman's correlation coefficient between rPFS and OS was 0.72. Conclusion rPFS was highly consistent and highly associated with OS, providing initial prospective evidence on further developing rPFS as an intermediate end point in mCRPC trials. PMID:25624432

  4. Bortezomib-based induction improves progression-free survival of myeloma patients harboring 17p deletion and/or t(4;14) and overcomes their adverse prognosis.

    PubMed

    El-Ghammaz, Amro M S; Abdelwahed, Essam

    2016-08-01

    Providing a risk-adapted treatment strategy has been a key goal in the ongoing research efforts aimed at providing treatment tailored to the individual genetic make-up. Eighty myeloma patients have been tested for presence of 17p deletion and/or t(4;14) by fluorescent in situ hybridization (FISH). Based on FISH results, they have been categorized into patients lacking them (standard risk) and those harboring them (high risk). Patients in each category were randomly assigned 1:1 to induction treatment by either vincristine, adriamycin and dexamethasone (VAD), or bortezomib and dexamethasone (VD) followed by autologous stem cell transplantation and thalidomide maintenance and were followed up for 32 months. 32.5 % of patients were high risk. Following induction, there were significantly higher rates of at least very good partial response achievement in VD arms in standard- and high-risk patients. Regarding complete response achievement, there were insignificant differences between VAD and VD arms in standard and high-risk patients. After a median follow-up of 17.5 months, there was insignificant difference in overall survival (OS) between VAD and VD arms in standard and high-risk patients. There was superior progression-free survival (PFS) in VD arms in standard- and high-risk patients. Among patients who received VD, those belonging to standard and high-risk groups had similar PFS. In conclusion, bortezomib-based induction is superior to non-bortezomib-based one in patients harboring 17p deletion and/or t(4;14) in terms of improving PFS but not OS. Also, it reduces progression risk in patients harboring these high risk cytogenetics. PMID:27184486

  5. Microwave ablation plus chemotherapy improved progression-free survival of advanced non-small cell lung cancer compared to chemotherapy alone.

    PubMed

    Wei, Zhigang; Ye, Xin; Yang, Xia; Huang, Guanghui; Li, Wenhong; Wang, Jiao; Han, Xiaoying

    2015-02-01

    The aim of the study was to determine survival benefit of the microwave ablation (MWA)/chemotherapy combination compared with chemotherapy alone. Patients with untreated, stage IIIB or IV NSCLC and at least one additional measurable site other than the ablative site were enrolled. They were divided into MWA/chemotherapy group and chemotherapy group. The primary endpoint was progression-free survival (PFS); secondary endpoints included response, time to local progression (TTLP), overall survival (OS), and adverse events (AEs). Forty-six and twenty-eight patients were enrolled in the MWA/chemotherapy group and chemotherapy group, respectively. Complete ablation was observed in 84.8 % patients in the MWA/chemotherapy group. Median TTLP was 27.0 months. Objective response rate and disease control rate in MWA/chemotherapy group were 21.7 and 76.1 %, and in the chemotherapy group were 32.1 % (p = 0.320) and 75.0 % (p = 0.916), respectively. MWA/chemotherapy combination prolonged PFS [MWA/chemotherapy group 10.9 (95 % CI 5.1-16.7) ms vs. chemotherapy group 4.8 (95 % CI 3.9-5.8) ms, p = 0.001] and tended to improve OS [MWA/chemotherapy group 23.9 (95 % CI 15.2-32.6) ms vs. chemotherapy group 17.3 (95 % CI 15.2-19.3) ms, p = 0.140]. Multivariate analyses showed that MWA was an independent prognostic factor of PFS and primary tumor size was an independent prognostic factor of OS. AEs of MWA were observed in 67.4 % patients. Chemotherapy-associated AEs were observed in 39.1 and 53.6 % of patients in the MWA/chemotherapy and chemotherapy group, respectively. MWA/chemotherapy combination improved PFS of advanced NSCLC compared to chemotherapy alone, and the combination did not increase the adverse events of chemotherapy. PMID:25572816

  6. Piwil 2 Expression Is Correlated with Disease-Specific and Progression-Free Survival of Chemotherapy-Treated Bladder Cancer Patients

    PubMed Central

    Taubert, Helge; Wach, Sven; Jung, Rudolf; Pugia, Michael; Keck, Bastian; Bertz, Simone; Nolte, Elke; Stoehr, Robert; Lehmann, Jan; Ohlmann, Carsten-H; Stöckle, Michael; Wullich, Bernd; Hartmann, Arndt

    2015-01-01

    Piwi-like 2 (Piwil 2) belongs to the family of Argonaute genes/proteins. The expression of Piwil 2 is associated with stem cells. A role in tumorigenesis and/or tumor progression is proposed for different cancers but not yet for bladder cancer (BCa). We investigated Piwil 2 expression by immunohistochemistry in a cohort of 202 BCa patients treated by cystectomy and adjuvant chemotherapy. The association between Piwil 2 expression and disease-specific (DSS) or progression-free survival (PFS) was calculated using Kaplan-Meier analyses and univariate/multivariate Cox regression hazard models. In a multivariate Cox regression analysis, Piwil 2 expression, either in the cytoplasm or the nucleus, was significantly associated with DSS and PFS. A weak cytoplasmic staining pattern was associated with poor DSS and tumor progression (relative risk [RR] = 2.7, P = 0.004, and RR = 2.4, P = 0.027). Likewise, absent nuclear Piwil 2 immunoreactivity was associated with poor DSS and tumor progression (RR = 2.3, P = 0.023, and RR = 2.2, P = 0.022). BCa patients whose tumors exhibited a combination of weak cytoplasmic and absent nuclear immunoreactivity had a 6-fold increased risk of tumor-related death (P = 0.005) compared with patients with strong expression. Considering only patients with high-grade G3 tumors, a 7.8-fold risk of tumor-associated death and a 3.6-fold risk of tumor progression were detected independently of the histologic tumor subtype or the chemotherapy regimen. In summary, a combination of weak cytoplasmic and absent nuclear expression of Piwil 2 is significantly associated with an increased risk of DSS and tumor progression. This indicates that Piwil 2 could be a valuable prognostic marker for high-risk BCa patients. PMID:25998509

  7. 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

  8. 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

  9. 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. PMID:26280109

  10. 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

  11. Low MAD2 expression levels associate with reduced progression-free survival in patients with high-grade serous epithelial ovarian cancer

    PubMed Central

    Furlong, Fiona; Fitzpatrick, Patricia; O'Toole, Sharon; Phelan, Sine; McGrogan, Barbara; Maguire, Aoife; O'Grady, Anthony; Gallagher, Michael; Prencipe, Maria; McGoldrick, Aloysius; McGettigan, Paul; Brennan, Donal; Sheils, Orla; Martin, Cara; W Kay, Elaine; O'Leary, John; McCann, Amanda

    2012-01-01

    Epithelial ovarian cancer (EOC) has an innate susceptibility to become chemoresistant. Up to 30% of patients do not respond to conventional chemotherapy [paclitaxel (Taxol®) in combination with carboplatin] and, of those who have an initial response, many patients relapse. Therefore, an understanding of the molecular mechanisms that regulate cellular chemotherapeutic responses in EOC cells has the potential to impact significantly on patient outcome. The mitotic arrest deficiency protein 2 (MAD2), is a centrally important mediator of the cellular response to paclitaxel. MAD2 immunohistochemical analysis was performed on 82 high-grade serous EOC samples. A multivariate Cox regression analysis of nuclear MAD2 IHC intensity adjusting for stage, tumour grade and optimum surgical debulking revealed that low MAD2 IHC staining intensity was significantly associated with reduced progression-free survival (PFS) (p = 0.0003), with a hazard ratio of 4.689. The in vitro analyses of five ovarian cancer cell lines demonstrated that cells with low MAD2 expression were less sensitive to paclitaxel. Furthermore, paclitaxel-induced activation of the spindle assembly checkpoint (SAC) and apoptotic cell death was abrogated in cells transfected with MAD2 siRNA. In silico analysis identified a miR-433 binding domain in the MAD2 3′ UTR, which was verified in a series of experiments. Firstly, MAD2 protein expression levels were down-regulated in pre-miR-433 transfected A2780 cells. Secondly, pre-miR-433 suppressed the activity of a reporter construct containing the 3′-UTR of MAD2. Thirdly, blocking miR-433 binding to the MAD2 3′ UTR protected MAD2 from miR-433 induced protein down-regulation. Importantly, reduced MAD2 protein expression in pre-miR-433-transfected A2780 cells rendered these cells less sensitive to paclitaxel. In conclusion, loss of MAD2 protein expression results in increased resistance to paclitaxel in EOC cells. Measuring MAD2 IHC staining intensity may predict

  12. 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

  13. 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

  14. Tumor Response and Progression-Free Survival as Potential Surrogate Endpoints for Overall Survival in Extensive-Stage Small Cell Lung Cancer (ES-SCLC): Findings Based on North Central Cancer Treatment Group (NCCTG) Trials

    PubMed Central

    Foster, Nathan R.; Qi, Yingwei; Shi, Qian; Krook, James E.; Kugler, John W.; Jett, James R.; Molina, Julian R.; Schild, Steven E.; Adjei, Alex A.; Mandrekar, Sumithra J.

    2010-01-01

    Purpose We investigated the putative surrogate endpoints (PSEs) of best response (BR), complete response (CR), confirmed response (CoR), and progression-free survival (PFS) for associations with Overall Survival (OS), and as possible surrogate endpoints for OS. Methods Individual patient (pt) data from 870 untreated ES-SCLC pts participating in 6 single-arm (274 pts) and 3 randomized trials (596 pts) were pooled. Patient-level associations between PSEs and OS were assessed by Cox models using landmark analyses. Trial-level surrogacy of PSEs assessed by the association of treatment effects on OS and individual PSEs. Trial-level surrogacy measures included: R2 from weighted least squares regression model (WLS R2), Spearman's correlation coefficient, and R2 from bivariate survival model (Copula R2). Results Median OS and PFS were 9.6 (95% CI: 9.1-10.0) and 5.5 (95% CI: 5.2-5.9) months, respectively; BR, CR, and CoR rates were 44%, 22%, and 34%, respectively. Patient-level associations showed that PFS status at 4 months was a strong predictor of subsequent survival (HR=0.42 (95% CI: 0.35-0.51); concordance index=0.63; p<0.01), with 6-month PFS being the strongest (HR=0.41 (95% CI: 0.35-0.49); concordance index=0.66; p<0.01). At the trial-level, PFS showed the highest level of surrogacy for OS (WLS R2=0.79; Copula R2=0.80), explaining 79% of the variance in OS. Tumor response endpoints showed lower surrogacy levels (WLS R2≤0.48). Conclusion PFS was strongly associated with OS at both the patient and trial-level. PFS also shows promise as a potential surrogate for OS, but further validation is needed using data from a larger number of randomized phase III trials. PMID:20960500

  15. 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.

  16. Survival in a 2-year-old boy with hemorrhage secondary to an aortoesophageal fistula.

    PubMed

    Coates, Laura J; McNally, Janet; Caputo, Massimo; Cusick, Eleri

    2011-12-01

    Aortoesophageal fistula (AOF) in children with no history of cardiac disease or trauma is extremely rare, and survival is even rarer. We present a case of a 2-year-old boy who presented with massive hematemesis secondary to a primary aortoesophageal fistula and was found at endoscopy to have a submucosal hematoma. He then suffered a cardiac arrest with further catastrophic bleeding only controlled by a Sengstaken-Blakemore tube. Subsequent cardiopulmonary bypass was instituted and allowed direct repair of the fistula. He was discharged home 4 weeks later. The etiology of the fistula remains unknown. PMID:22152890

  17. 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

  18. 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

  19. 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. PMID:27306421

  20. 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. PMID:25017612

  1. Valproic acid, compared to other antiepileptic drugs, is associated with improved overall and progression-free survival in glioblastoma but worse outcome in grade II/III gliomas treated with temozolomide.

    PubMed

    Redjal, Navid; Reinshagen, Clemens; Le, Andrew; Walcott, Brian P; McDonnell, Erin; Dietrich, Jorg; Nahed, Brian V

    2016-05-01

    Valproic acid (VPA) is an anti-epileptic drug with properties of a histone deacetylase inhibitor (HDACi). HDACi play a key role in epigenetic regulation of gene expression and have been increasingly used as anticancer agents. Recent studies suggest that VPA is associated with improved survival in high-grade gliomas. However, effects on lower grade gliomas have not been examined. This study investigates whether use of VPA correlates with tumor grade, histological progression, progression-free and overall survival (OS) in grade II, III, and IV glioma patients. Data from 359 glioma patients (WHO II-IV) treated with temozolomide plus an antiepileptic drug (VPA or another antiepileptic drug) between January 1997 and June 2013 at the Massachusetts General Hospital was analyzed retrospectively. After confounder adjustment, VPA was associated with a 28 % decrease in hazard of death (p = 0.031) and a 28 % decrease in the hazard of progression or death (p = 0.015) in glioblastoma. Additionally, VPA dose correlated with reduced hazard of death by 7 % (p = 0.002) and reduced hazard of progression or death by 5 % (p < 0.001) with each 100 g increase in total dose. Conversely, in grade II and III gliomas VPA was associated with a 118 % increased risk of tumor progression or death (p = 0.014), and every additional 100 g of VPA raised the hazard of progression or death by 4 %, although not statistically significant (p = 0.064). Moreover, grade II and III glioma patients taking VPA had 2.17 times the risk of histological progression (p = 0.020), although this effect was no longer significant after confounder adjustment. In conclusion, VPA was associated with improved survival in glioblastoma in a dose-dependent manner. However, in grade II and III gliomas, VPA was linked to histological progression and decrease in progression-free survival. Prospective evaluation of VPA treatment for glioma patients is warranted to confirm these findings. PMID:26830093

  2. 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

  3. GATA3 mRNA expression, but not mutation, associates with longer progression-free survival in ER-positive breast cancer patients treated with first-line tamoxifen for recurrent disease.

    PubMed

    Liu, Jingjing; Prager-van der Smissen, Wendy J C; Look, Maxime P; Sieuwerts, Anieta M; Smid, Marcel; Meijer-van Gelder, Marion E; Foekens, John A; Hollestelle, Antoinette; Martens, John W M

    2016-06-28

    In breast cancer, GATA3 mutations have been associated with a favorable prognosis and the response to neoadjuvant aromatase inhibitor treatment. Therefore, we investigated whether GATA3 mutations predict the outcome of tamoxifen treatment in the advanced setting. In a retrospective study consisting of 235 hormone-naive patients with ER-positive breast cancer who received tamoxifen as first-line treatment for recurrent disease, GATA3 mutations (in 14.0% of patients) did not significantly associate with either the overall response rate (ORR) or with the length of progression-free survival (PFS) after the start of tamoxifen therapy. Interestingly, among 148 patients for whom both mutation and mRNA expression data were available, GATA3 mutations associated with an increased expression of GATA3. However, only 23.7% of GATA3 high tumors had a mutation. Evaluation of the clinical significance of GATA3 mRNA revealed that it was associated with prolonged PFS, but not with the ORR, also in multivariate analysis. Thus, GATA3 mRNA expression, but not GATA3 mutation, is an independent predictor of prolonged PFS in ER-positive breast cancer patients who received first-line tamoxifen for recurrent disease. Besides GATA3 mutation, other mechanisms must exist that underlie increased GATA3 levels. PMID:27018307

  4. Magnitude of the Benefit of Progression-Free Survival as a Potential Surrogate Marker in Phase 3 Trials Assessing Targeted Agents in Molecularly Selected Patients with Advanced Non-Small Cell Lung Cancer: Systematic Review

    PubMed Central

    Hotta, Katsuyuki; Kato, Yuka; Leighl, Natasha; Takigawa, Nagio; Gaafar, Rabab Mohamed; Kayatani, Hiroe; Hirata, Taizo; Ohashi, Kadoaki; Kubo, Toshio; Tabata, Masahiro; Tanimoto, Mitsune; Kiura, Katsuyuki

    2015-01-01

    Background In evaluation of the clinical benefit of a new targeted agent in a phase 3 trial enrolling molecularly selected patients with advanced non-small cell lung cancer (NSCLC), overall survival (OS) as an endpoint seems to be of limited use because of a high level of treatment crossover for ethical reasons. A more efficient and useful indicator for assessing efficacy is needed. Methods and Findings We identified 18 phase 3 trials in the literature investigating EGFR-tyrosine kinase inhibitor (TKIs) or ALK-TKIs, now approved for use to treat NSCLC, compared with standard cytotoxic chemotherapy (eight trials were performed in molecularly selected patients and ten using an “all-comer” design). Receiver operating characteristic analysis was used to identify the best threshold by which to divide the groups. Although trials enrolling molecularly selected patients and all-comer trials had similar OS-hazard ratios (OS-HRs) (0.99 vs. 1.04), the former exhibited greater progression-free survival-hazard ratios (PFS-HR) (mean, 0.40 vs. 1.01; P<0.01). A PFS-HR of 0.60 successfully distinguished between the two types of trials (sensitivity 100%, specificity 100%). The odds ratio for overall response was higher in trials with molecularly selected patients than in all-comer trials (mean: 6.10 vs. 1.64; P<0.01). An odds ratio of 3.40 for response afforded a sensitivity of 88% and a specificity of 90%. Conclusion The notably enhanced PFS benefit was quite specific to trials with molecularly selected patients. A PFS-HR cutoff of ∼0.6 may help detect clinical benefit of molecular targeted agents in which OS is of limited use, although desired threshold might differ in an individual trial. PMID:25775395

  5. Prenatal Diagnosis of Atrial Restriction in Hypoplastic Left Heart Syndrome is Associated with Decreased 2-Year Survival

    PubMed Central

    Lowenthal, Alexander; Kipps, Alaina K.; Brook, Michael M.; Meadows, Jeffery; Azakie, Anthony; Moon-Grady, Anita J.

    2012-01-01

    Objective To compare the course of HLHS patients diagnosed prenatally with any degree of atrial restriction with those without evidence of atrial restriction. Design Retrospective, cohort. Methods Prenatally diagnosed HLHS patients from 8/1999–1/2009 were categorized as non-restrictive versus restrictive, defined by left atrial hypertension on pulmonary venous Doppler and/or an interatrial septum. Results Of 73 total fetal patients identified, 49 were liveborn. Survival at 2 years was 29/35 (83% CI: 59.5%–88.9%) for the non-restrictive group and 6/14 (43% CI:17.7%–66.0%) for the restrictive group (p<0.0001). Of those who underwent stage 1 palliation (35 with nonrestrictive and 10 with restrictive atrial septa) both groups had a similar incidence of preoperative acidosis and need for ventilation and inotropic support. Postoperatively, there was no difference between groups in ventilator days, length of stay, or survival to discharge. There was decreased survival at 2 years in the restrictive group, 60% (CI: 26.2%–87.8%) versus 83% (CI: 66.4%–93.4%) in the non-restrictive group. Furthermore, a disproportionate number of interstage deaths was evident in the restrictive group. Conclusion Prenatal presence of any degree of atrial septal restriction in the setting of HLHS confers a significant survival disadvantage, with increases in both early and late mortality. PMID:22511219

  6. Decitabine improves progression-free survival in older high-risk MDS patients with multiple autosomal monosomies: results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group.

    PubMed

    Lübbert, Michael; Suciu, Stefan; Hagemeijer, Anne; Rüter, Björn; Platzbecker, Uwe; Giagounidis, Aristoteles; Selleslag, Dominik; Labar, Boris; Germing, Ulrich; Salih, Helmut R; Muus, Petra; Pflüger, Karl-Heinz; Schaefer, Hans-Eckart; Bogatyreva, Lioudmila; Aul, Carlo; de Witte, Theo; Ganser, Arnold; Becker, Heiko; Huls, Gerwin; van der Helm, Lieke; Vellenga, Edo; Baron, Frédéric; Marie, Jean-Pierre; Wijermans, Pierre W

    2016-01-01

    In a study of elderly AML patients treated with the hypomethylating agent decitabine (DAC), we noted a surprisingly favorable outcome in the (usually very unfavorable) subgroup with two or more autosomal monosomies (MK2+) within a complex karyotype (Lübbert et al., Haematologica 97:393-401, 2012). We now analyzed 206 myelodysplastic syndrome (MDS) patients (88 % of 233 patients randomized in the EORTC/GMDSSG phase III trial 06011, 61 of them with RAEBt, i.e. AML by WHO) with cytogenetics informative for MK status.. Endpoints are the following: complete/partial (CR/PR) and overall response rate (ORR) and progression-free (PFS) and overall survival (OS). Cytogenetic subgroups are the following: 63 cytogenetically normal (CN) patients, 143 with cytogenetic abnormalities, 73 of them MK-negative (MK-), and 70 MK-positive (MK+). These MK+ patients could be divided into 17 with a single autosomal monosomy (MK1) and 53 with at least two monosomies (MK2+). ORR with DAC in CN patients: 36.1 %, in MK- patients: 16.7 %, in MK+ patients: 43.6 % (MK1: 44.4 %, MK2+ 43.3 %). PFS was prolonged by DAC compared to best supportive care (BSC) in the CN (hazard ratio (HR) 0.55, 99 % confidence interval (CI), 0.26; 1.15, p = 0.03) and MK2+ (HR 0.50; 99 % CI, 0.23; 1.06, p = 0.016) but not in the MK-, MK+, and MK1 subgroups. OS was not improved by DAC in any subgroup. In conclusion, we demonstrate for the first time in a randomized phase III trial that high-risk MDS patients with complex karyotypes harboring two or more autosomal monosomies attain encouraging responses and have improved PFS with DAC treatment compared to BSC. PMID:26596971

  7. Patients with Exon 19 Deletion Were Associated with Longer Progression-Free Survival Compared to Those with L858R Mutation after First-Line EGFR-TKIs for Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

    PubMed Central

    Fang, Wenfeng; Yan, Yue; Hu, Zhihuang; Hong, Shaodong; Wu, Xuan; Qin, Tao; Liang, Wenhua; Zhang, Li

    2014-01-01

    Backgrounds It has been extensively proved that the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is superior to that of cytotoxic chemotherapy in advanced non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, the question of whether the efficacy of EGFR-TKIs differs between exon 19 deletion and exon 21 L858R mutation has not been yet statistically answered. Methods Subgroup data on hazard ratio (HR) for progression-free survival (PFS) of correlative studies were extracted and synthesized based on random-effect model. Comparison of outcomes between specific mutations was estimated through indirect and direct methods, respectively. Results A total of 13 studies of advanced NSCLC patients with either 19 or 21 exon alteration receiving first-line EGFR-TKIs were included. Based on the data from six clinical trials for indirect meta-analysis, the pooled HRTKI/chemotherapy for PFS were 0.28 (95% CI 0.20–0.38, P<0.001) in patients with 19 exon deletion and 0.47 (95% CI 0.35–0.64, P<0.001) in those with exon 21 L858R mutation. Indirect comparison revealed that the patients with exon 19 deletion had longer PFS than those with exon 21 L858R mutation (HR19 exon deletion/exon 21 L858R mutation  = 0.59, 95% CI 0.38–0.92; P = 0.019). Additionally, direct meta-analysis showed similar result (HR19 exon deletion/exon 21 L858R mutation  = 0.75, 95% CI 0.65 to 0.85; P<0.001) by incorporating another seven studies. Conclusions For advanced NSCLC patients, exon 19 deletion might be associated with longer PFS compared to L858 mutation at exon 21 after first-line EGFR-TKIs. PMID:25222496

  8. 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

  9. 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

  10. Multi-Trial Evaluation of Progression-Free Survival (PFS) as a Surrogate Endpoint for Overall Survival (OS) in First-Line Extensive-Stage Small Cell Lung Cancer (ES-SCLC)

    PubMed Central

    Foster, Nathan R.; Renfro, Lindsay A.; Schild, Steven E.; Redman, Mary W.; Wang, Xiaofei F.; Dahlberg, Suzanne E.; Ding, Keyue; Bradbury, Penelope A.; Ramalingam, Suresh S.; Gandara, David R.; Shibata, Taro; Saijo, Nagahiro; Vokes, Everett E.; Adjei, Alex A.; Mandrekar, Sumithra J.

    2015-01-01

    Introduction We previously reported that PFS may be a candidate surrogate endpoint for OS in first-line ES-SCLC using data from 3 randomized trials (Foster, Cancer 2011). In this validation study (N0424-Alliance), we assessed the patient- and trial-level surrogacy of PFS using data from 7 new first-line phase II/III ES-SCLC trials and across all 10 trials as well (7 new, 3 previous). Methods Individual patient data were utilized across the 7 new trials (2259 patients) and all 10 trials (2855 patients). Patient-level surrogacy (Kendall’s τ) was assessed using the Clayton copula bivariate survival model. Trial-level surrogacy was assessed via association of the log hazard ratios on OS and PFS across trials, including weighted (by trial size) least squares regression of Cox model effects (WLS R2) and correlation of the copula effects (Copula R2). The minimum effect on the surrogate (MES) needed to detect a non-zero treatment effect on OS was also calculated. Results The median OS and PFS across all 10 trials were 9.8 and 5.9 months, respectively. PFS showed strong surrogacy within the 7 new trials (Copula R2 = 0.90 (SE=0.27); WLS R2 = 0.83 (95% CI: 0.43, 0.95); MES=0.67; Kendall’s τ = 0.58) and across all 10 trials (Copula R2 =0.81 (SE=0.25); WLS R2=0.77 (95% CI: 0.47–0.91); MES=0.70; Kendall’s τ =0.57). Conclusions PFS demonstrated strong surrogacy for OS in first-line ES-SCLC based on this external validation study of individual patient data. PFS is a good alternative endpoint to OS and should be considered when resource constraints (time or patient) might make it useful or desirable in place of OS. Additional analyses are needed to assess its appropriateness for targeted agents in this disease setting. PMID:26134227

  11. HIGH PROBABILITY OF LONG-TERM SURVIVAL IN 2-YEAR SURVIVORS OF AUTOLOGOUS HEMATOPOIETIC CELL TRANSPLANTATION FOR ACUTE MYELOID LEUKEMIA IN FIRST OR SECOND COMPLETE REMISSION

    PubMed Central

    Majhail, Navneet S.; Bajorunaite, Ruta; Lazarus, Hillard M.; Wang, Zhiwei; Klein, John P.; Zhang, Mei-Jie; Rizzo, J. Douglas

    2010-01-01

    We describe long-term outcomes of autologous hematopoietic-cell transplantation (HCT) for 315 acute myeloid leukemia (AML) patients in first or second complete remission (CR). All patients were in continuous CR for ≥2-years post-HCT. Patients were predominantly transplanted in CR1 (78%) and had good or intermediate cytogenetic risk disease (74%). Median followup of survivors was 106 (range, 24-192) months. Overall survival at 10-years post-HCT was 94% (95% confidence intervals, 89-97%) and 80% (67-91%) for patients receiving HCT in CR1 and CR2, respectively. The cumulative incidence of relapse at 10-years post-HCT was 6% (3-10%) and 10% (3-20%) and that of non-relapse mortality was 5% (2-9%) and 11% (4-21%), respectively. On multivariate analysis, HCT in CR2 (vs. CR1), older age at transplantation and poor cytogenetic risk disease were independent predictors of late mortality and adverse disease-free survival. The use of growth factors to promote engraftment following HCT was the only risk factor for relapse. Relative-mortality of these 2-year survivors was comparable to that of age-, race- and gender-matched normal population. Patients who receive an autologous HCT for AML in CR1 or CR2 and remain in remission for ≥2-years have very favorable long-term survival. Their mortality rates are similar to that of the general population. PMID:20479710

  12. Development and External Validation of Prognostic Model for 2-Year Survival of Non-Small-Cell Lung Cancer Patients Treated With Chemoradiotherapy

    SciTech Connect

    Dehing-Oberije, Cary Yu Shipeng; De Ruysscher, Dirk; Meersschout, Sabine; Van Beek, Karen; Lievens, Yolande; Van Meerbeeck, Jan; De Neve, Wilfried; Rao, Bharat Ph.D.; Weide, Hiska van der; Lambin, Philippe

    2009-06-01

    Purpose: Radiotherapy, combined with chemotherapy, is the treatment of choice for a large group of non-small-cell lung cancer (NSCLC) patients. Recent developments in the treatment of these patients have led to improved survival. However, the clinical TNM stage is highly inaccurate for the prediction of survival, and alternatives are lacking. The objective of this study was to develop and validate a prediction model for survival of NSCLC patients, treated with chemoradiotherapy. Patients and Methods: The clinical data from 377 consecutive inoperable NSCLC patients, Stage I-IIIB, treated radically with chemoradiotherapy were collected. A prognostic model for 2-year survival was developed, using 2-norm support vector machines. The performance of the model was expressed as the area under the curve of the receiver operating characteristic and assessed using leave-one-out cross-validation, as well as two external data sets. Results: The final multivariate model consisted of gender, World Health Organization performance status, forced expiratory volume in 1 s, number of positive lymph node stations, and gross tumor volume. The area under the curve, assessed by leave-one-out cross-validation, was 0.74, and application of the model to the external data sets yielded an area under the curve of 0.75 and 0.76. A high- and low-risk group could be clearly identified using a risk score based on the model. Conclusion: The multivariate model performed very well and was able to accurately predict the 2-year survival of NSCLC patients treated with chemoradiotherapy. The model could support clinicians in the treatment decision-making process.

  13. Long-Term Survival And Late Relapse In 2-Year Survivors Of Autologous Hematopoietic Cell Transplantation For Hodgkin And Non-Hodgkin Lymphoma

    PubMed Central

    Majhail, Navneet S.; Bajorunaite, Ruta; Lazarus, Hillard M.; Wang, Zhiwei; Klein, John P.; Zhang, Mei-Jie; Rizzo, J. Douglas

    2009-01-01

    Summary This study described long-term outcomes of autologous hematopoietic-cell transplantation (HCT) for advanced Hodgkin (HL) and non-Hodgkin lymphoma (NHL). The study included recipients of autologous HCT for HL (N=407) and NHL (N=960) from 1990–98 who were in continuous complete remission for at least 2 years post-HCT. Median follow-up was 104 months for HL and 107 months for NHL. Overall survival at 10-years was 77% (72–82%) for HL, 78% (73–82%) for diffuse large-cell NHL, 77% (71–83%) for follicular NHL, 85% (75–93%) for lymphoblastic/Burkitt NHL, 52% (37–67%) for mantle-cell NHL and 77% (67–85%) for other NHL. On multivariate analysis, mantle-cell NHL had the highest relative-risk for late mortality (2.87 (1.70–4.87)), while the risks of death for other histologies were comparable. Relapse was the most common cause of death. Relative mortality compared to age, race and gender adjusted normal population remained significantly elevated and was 14.8 (6.3–23.3) for HL and 5.9 (3.6–8.2) for NHL at 10-years post-HCT. Recipients of autologous HCT for HL and NHL who remain in remission for at least 2-years have favorable subsequent long-term survival but remain at risk for late relapse. Compared to the general population, mortality rates continue to remain elevated at 10-years post-transplantation. PMID:19573079

  14. 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.

  15. Developmental milestones record - 2 years

    MedlinePlus

    Growth milestones for children - 2 years; Normal childhood growth milestones - 2 years; Childhood growth milestones - 2 years ... a cause for concern if not seen by 2 years.) Can run with better coordination . (May still ...

  16. Developmental milestones record - 2 years

    MedlinePlus

    Growth milestones for children - 2 years; Normal childhood growth milestones - 2 years; Childhood growth milestones - 2 years ... cause for concern if not seen by 2 years.) Can run with better coordination. (May still have ...

  17. 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.

  18. Long-term survival and functional status of patients with low-grade astrocytoma of spinal cord

    SciTech Connect

    Robinson, Clifford G.; Prayson, Richard A.; Hahn, Joseph F.; Kalfas, Iain H.; Whitfield, Melvin D.; Lee, S.-Y.; Suh, John H. . E-mail: suhj@ccf.org

    2005-09-01

    Purpose: To determine survival and changes in neurologic function and Karnofsky performance status (KPS) in a series of patients treated for low-grade astrocytoma of the spinal cord during the past two decades. Methods: This study consisted of 14 patients with pathologically confirmed low-grade astrocytoma of the spinal cord who were treated between 1980 and 2003. All patients underwent decompressive laminectomy followed by biopsy (n = 7), subtotal resection (n = 6), or gross total resection (n = 1). Ten patients underwent postoperative radiotherapy (median total dose 50 Gy in 28 fractions). The overall survival, progression-free survival, and changes in neurologic function and KPS were measured. Results: The overall survival rate at 5, 10, and 20 years was 100%, 75%, and 60%, respectively. The progression-free survival rate at 5, 10, and 20 years was 93%, 80%, and 60%, respectively. Neither overall survival nor progression-free survival was clearly correlated with any patient, tumor, or treatment factors. Neurologic function and KPS worsened after surgery in 8 (57%) of 14 and 9 (69%) of 13 patients, respectively. At a mean follow-up of 10.2 years, neurologic function had stabilized or improved in 8 (73%) of 11 remaining patients, but the KPS had worsened in 5 (50%) of 10. Most patients who were employed before surgery were working at last follow-up. Conclusion: Patients who undergo gross total resection of their tumor may be followed closely. Patients who undergo limited resection should continue to receive postoperative RT (50.4 Gy in 1.8-Gy fractions). The functional measures should be routinely evaluated to appreciate the treatment outcomes.

  19. Social Development:: 2 Year Olds

    MedlinePlus

    ... Español Text Size Email Print Share Social Development: 2 Year Olds Page Content Article Body By nature, ... probably are acting the same way. At age two, children view the world almost exclusively through their ...

  20. Language Development: 2 Year Olds

    MedlinePlus

    ... Stages Listen Español Text Size Email Print Share Language Development: 2 Year Olds Page Content Article Body ... Pay attention to how he also is using language to describe ideas and information and to express ...

  1. Postradiotherapy 2-Year Prostate-Specific Antigen Nadir as a Predictor of Long-Term Prostate Cancer Mortality

    SciTech Connect

    Zelefsky, Michael J.; Shi Weiji; Yamada, Yoshiya; Kollmeier, Marisa A.; Cox, Brett; Park, Jessica; Seshan, Venkatraman E.

    2009-12-01

    Purpose: To report the influence of posttreatment prostate-specific antigen (PSA) nadir response at 2 years after external beam radiotherapy (RT) on distant metastases (DM) and cause-specific mortality (CSM). Methods and Materials: Eight hundred forty-four patients with localized prostate cancer were treated with conformal RT. The median duration of follow-up was 9.1 years. A fixed landmark time point at 2 years was used to assess the influence of nadir PSA value as a time-dependent variable on long-term outcomes. Results: Multivariate analysis demonstrated that nadir PSA <=1.5 ng/mL at the landmark was an independent predictor of progression-free survival after adjusting for T stage, Gleason score, pre-RT PSA value, and RT dose (p = 0.03). The 5- and 10-year cumulative incidences of DM were 2.4% and 7.9%, respectively, in those with nadir PSA levels <=1.5 ng/mL at the 2-year landmark, and were 10.3% and 17.5%, respectively, in patients with higher nadir values. Multivariate analysis showed that the higher nadir PSA value at the 2-year landmark (p = 0.002), higher Gleason scores (p < 0.001), and increasing T stage (p = 0.03) were predictors of DM after adjusting for pre-RT PSA values and RT dose. Multivariate analysis also showed that higher Gleason scores (p = 0.002), and higher nadir PSA values at the 2-year landmark (p = 0.03) were risk factors associated with CSM after adjusting for T stage and pre-RT PSA value. Conclusions: Nadir PSA values of <=1.5 ng/mL at 2 years after RT for prostate cancer predict for long-term DM and CSM outcomes. Patients with higher absolute nadir levels at 2 years after treatment should be evaluated for the presence of nonresponding disease, and earlier salvage treatment interventions should be considered.

  2. Emotional Development: 2 Year Olds

    MedlinePlus

    ... Español Text Size Email Print Share Emotional Development: 2 Year Olds Page Content Article Body It’s so ... to follow the ups and downs of a two-year-old. One moment he’s beaming and friendly; ...

  3. 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

  4. [A case of total intestinal aganglionosis. 2 years of survival].

    PubMed

    López Gútiérrez, J C; de Agustín, J C; Murcia, J; Carrero, C; Muguerza, R; Soto, C; Utrilla, J G; Lassaletta, L

    1991-10-01

    A two-year-old male is presented. Small bowel aganglionosis was proved to extend to 3 cm below ligament of Treitz. Gastrostomy and ileostomy was done. He received his caloric intake by cyclic home parenteral nutrition trough implantable venous system. At eighteen months of age, intestinal transplantation was refused and reoperation was done. The child underwent Ziegler's miotomymiectomy on 60 cm of aganglionic jejunum. Now at twenty seven months of age he receives cyclic parenteral nutrition, and enteral feedings are being increased slowly. The weight/height was at 91 per 100 standard, intestinal motility appears much better on contrast study and he is developmentally a normal child. PMID:1760266

  5. Childhood Bereavement: Psychopathology in the 2 Years Postparental Death

    ERIC Educational Resources Information Center

    Cerel, Julie; Fristad, Mary A.; Verducci, Joseph; Weller, Ronald A.; Weller, Elizabeth B.

    2006-01-01

    Objective: Although the death of a parent is one of the most significant stressors a child can experience, the psychiatric sequelae of parental death are not fully understood. Method: A total of 360 parent-bereaved children (ages 6-17) and their surviving parents were directly interviewed four times during the first 2 years following the death (at…

  6. 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

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

    PubMed Central

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

    2015-01-01

    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

  8. [A case of ampullary carcinoma progression-free for four years after treatment with TS-1].

    PubMed

    Mori, Naoki; Sakurai, Naoki; Iizawa, Hajime

    2015-03-01

    A 63-year old man was referred to our hospital because of fever, appetite loss, and increased biliary enzyme levels. Upper gastrointestinal endoscopy revealed a tumor in the duodenal papilla, diagnosed as an adenocarcinoma via biopsy, and computed tomography (CT) revealed multiple tumors in the liver. Chemotherapy with TS-1 was initiated based on a diagnosis of ampullary cancer with multiple liver metastases. After TS-1 treatment, the multiple tumors were no longer detectable, and the primary tumor did not increase in size for 4 years. At this time, however, the patient experienced fever, jaundice, and appetite loss. The hepatic mass was not detected via CT or MRI. The primary tumor was determined to be resectable; therefore, we performed subtotal stomach preserving pancreatoduodenectomy. The patient was discharged 55 days after surgery and is alive without recurrence 2 years after surgery. PMID:25812510

  9. 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.

  10. Survival outcome according to KRAS mutation status in newly diagnosed patients with stage IV non-small cell lung cancer treated with platinum doublet chemotherapy

    PubMed Central

    Brady, Anna K.; McNeill, Jonathan D.; Judy, Brendan; Bauml, Joshua; Evans, Tracey L.; Cohen, Roger B.; Langer, Corey; Vachani, Anil; Aggarwal, Charu

    2015-01-01

    Introduction Mutations (MT) of the KRAS gene are the most common mutation in non-small cell lung cancer (NSCLC), seen in about 20–25% of all adenocarcinomas. Effect of KRAS MT on response to cytotoxic chemotherapy is unclear. Methods We undertook a single-institution retrospective analysis of 93 consecutive patients with stage IV NSCLC adenocarcinoma with known KRAS and EGFR MT status to determine the association of KRAS MT with survival. All patients were treated between January 1, 2008 and December 31, 2011 with standard platinum based chemotherapy at the University of Pennsylvania. Overall and progression free survival were analyzed using Kaplan-Meier and Cox proportional hazard methods. Results All patients in this series received platinum doublet chemotherapy, and 42 (45%) received bevacizumab. Overall survival and progression free survival for patients with KRAS MT was no worse than for patients with wild type KRAS. Median overall survival for patients with KRAS MT was 19 months (mo) vs. 15.6 mo for KRAS WT, p = 0.34, and progression-free survival was 6.2 mo in patients with KRAS MT vs. 7mo in patients with KRAS WT, p = 0.51. In multivariable analysis including age, race, gender, and ECOG PS, KRAS MT was not associated with overall survival (HR 1.12, 95% CI 0.58–2.16, p = 0.74) or progression free survival (HR 0.80, 95% CI 0.48–1.34, p = 41). Of note, receipt of bevacizumab was associated with improved overall survival only in KRAS WT patients (HR 0.34, p = 0.01). Conclusions KRAS MT are not associated with inferior progression-free and overall survival in advanced NSCLC patients treated with standard first-line platinum-based chemotherapy. PMID:26471290

  11. 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.

  12. 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

  13. A Higher Cardiothoracic Ratio Is Associated with 2-Year Mortality after Hemodialysis Initiation

    PubMed Central

    Ito, Kiyonori; Ookawara, Susumu; Ueda, Yuichiro; Miyazawa, Haruhisa; Yamada, Hodaka; Goto, Sawako; Ishii, Hiroki; Shindo, Mitsutoshi; Kitano, Taisuke; Hirai, Keiji; Yoshida, Masashi; Kaku, Yoshio; Hoshino, Taro; Nabata, Aoi; Mori, Honami; Yoshida, Izumi; Kakei, Masafumi; Morishita, Yoshiyuki; Tabei, Kaoru

    2015-01-01

    A high cardiothoracic ratio (CTR) is indicative of a cardiac disorder. However, few reports have revealed an association between the CTR and mortality in patients starting hemodialysis (HD). Methods Patients with HD initiation (n = 387; mean age, 66.7 ± 12.7 years) were divided into the following three groups according to their CTR at HD initiation: CTR <50%, 50% ≤ CTR < 55%, and CTR ≥55%. Kaplan-Meier analysis was performed to compare 2-year all-cause mortality among these groups. Furthermore, we investigated the factors affecting their 2-year mortality using a Cox proportional hazard regression analysis. Results Sixty-five patients (17%) died within 2 years after HD initiation. Kaplan-Meier analysis showed that patients with CTR ≥55% had a higher mortality rate than those in the other groups. Cox proportional hazard regression analysis was performed using parameters with p values <0.1 among these three groups [sex, age, presence or absence of ischemic heart disease, hemoglobin levels, serum albumin levels, CTR, body mass index (BMI)] and confounding factors [presence or absence of diabetes mellitus, and estimated glomerular filtration rate (eGFR)]. Age, eGFR, BMI, and CTR ≥55% at HD initiation were identified as factors influencing 2-year mortality. Conclusion CTR >55% is one of the most important independent factors to affect 2-year all-cause mortality. Thus, confirming the cardiac condition of patients at HD initiation with a CTR >55% may improve their survival. PMID:26951636

  14. Medical Care and Your 1- to 2-Year-Old

    MedlinePlus

    ... Zika & Pregnancy Medical Care and Your 1- to 2-Year-Old KidsHealth > For Parents > Medical Care and Your 1- to 2-Year-Old Print A A A Text Size ... Following simple instructions? Saying a few words? Combining two words by age 2? The doctor may ask ...

  15. Motor Testing at 1 Year Improves the Prediction of Motor and Mental Outcome at 2 Years after Perinatal Hypoxic-Ischaemic Encephalopathy

    ERIC Educational Resources Information Center

    van Schie, Petra Em; Becher, Jules G.; Dallmeijer, Annet J.; Barkhof, Frederik; van Weissenbruch, Mirjam M.; Vermeulen, R. Jeroen

    2010-01-01

    Aim: To investigate the predictive value of motor testing at 1 year for motor and mental outcome at 2 years after perinatal hypoxic-ischaemic encephalopathy (HIE) in term neonates. Method: Motor and mental outcome at 2 years was assessed with the Bayley Scales of Infant Development, 2nd edition (BSID-II) in 32 surviving children (20 males, 12…

  16. Predicting School Readiness from Neurodevelopmental Assessments at Age 2 Years after Respiratory Distress Syndrome in Infants Born Preterm

    ERIC Educational Resources Information Center

    Patrianakos-Hoobler, Athena I.; Msall, Michael E.; Huo, Dezheng; Marks, Jeremy D.; Plesha-Troyke, Susan; Schreiber, Michael D.

    2010-01-01

    Aim: To determine whether neurodevelopmental outcomes at the age of 2 years accurately predict school readiness in children who survived respiratory distress syndrome after preterm birth. Method: Our cohort included 121 preterm infants who received surfactant and ventilation and were enrolled in a randomized controlled study of inhaled nitric…

  17. Efficacy of Salvage Radiotherapy Plus 2-Year Androgen Suppression for Postradical Prostatectomy Patients With PSA Relapse

    SciTech Connect

    Choo, Richard; Danjoux, Cyril; Gardner, Sandra; Morton, Gerard; Szumacher, Ewa; Loblaw, D. Andrew; Cheung, Patrick; Pearse, Maria

    2009-11-15

    Purpose: To determine the efficacy of a combined approach of radiotherapy (RT) plus 2-year androgen suppression (AS) as salvage treatment for prostate-specific antigen (PSA) relapse after radical prostatectomy (RP). Methods and Materials: Seventy-five patients with PSA relapse after RP were treated with salvage RT plus 2-year AS, as per a pilot, prospective study. AS started within 1 month after completion of salvage RT and consisted of nilutamide for 4 weeks and buserelin acetate depot subcutaneously every 2 months for 2 years. Relapse-free rate including freedom from PSA relapse was estimated using the Kaplan-Meier method. PSA relapse was defined as a PSA rise above 0.2 ng/mL with two consecutive increases over a minimum of 3 months. A Cox regression analysis was performed to evaluate prognostic factors for relapse. Results: Median age of the cohort was 63 years at the time of salvage RT. Median follow-up from salvage RT was 6.4 years. All achieved initially complete PSA response (< 0.2) with the protocol treatment. Relapse-free rate including the freedom from PSA relapse was 91.5% at 5 years and 78.6% at 7 years. Overall survival rate was 93.2% at both 5 and 7 years. On Cox regression analysis, pT3 stage and PSA relapse less than 2 years after RP were significant prognostic factors for relapse. Conclusion: The combined treatment of salvage RT plus 2-year AS yielded an encouraging result for patients with PSA relapse after RP and needs a confirmatory study.

  18. Media use by children younger than 2 years.

    PubMed

    Brown, Ari

    2011-11-01

    In 1999, the American Academy of Pediatrics (AAP) issued a policy statement addressing media use in children. The purpose of that statement was to educate parents about the effects that media--both the amount and the content--may have on children. In one part of that statement, the AAP recommended that "pediatricians should urge parents to avoid television viewing for children under the age of two years." The wording of the policy specifically discouraged media use in this age group, although it is frequently misquoted by media outlets as no media exposure in this age group. The AAP believed that there were significantly more potential negative effects of media than positive ones for this age group and, thus, advised families to thoughtfully consider media use for infants. This policy statement reaffirms the 1999 statement with respect to media use in infants and children younger than 2 years and provides updated research findings to support it. This statement addresses (1) the lack of evidence supporting educational or developmental benefits for media use by children younger than 2 years, (2) the potential adverse health and developmental effects of media use by children younger than 2 years, and (3) adverse effects of parental media use (background media) on children younger than 2 years. PMID:22007002

  19. Triadic Interaction among Newly Acquainted 2-Year-Olds

    ERIC Educational Resources Information Center

    Ishikawa, Fumiko; Hay, Dale F.

    2006-01-01

    Are children as young as 2 years old able to interact in groups of three? The study applied the family triad model first introduced by Parke, Power, and Gottman (1979) to the case of peer interaction. In Experiment 1, the model was refined for use in studies of peer interaction and applied to an existing dataset of 16 triads of newly acquainted…

  20. 75 FR 77958 - Gravesite Reservation Survey (2 Year); Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-14

    ...-461-7485. Correction In FR Doc. 2010-30554, published on December 7, 2010, at 75 FR 76082, make the... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF VETERANS AFFAIRS Gravesite Reservation Survey (2 Year); Correction AGENCY: National Cemetery...

  1. Detection of Flare Stars in TAOS 2-year Data

    NASA Astrophysics Data System (ADS)

    Kim, D.-W.; Protopapas, P.; Alcock, C.; Byun, Y.-I.; Zhang, Z.-W.; Wang, J.-H.; King, S.-K.; Wen, C. Y.; Lehner, M. J.; Bianco, F. B.; Coehlo, N. K.; Mondal, S.; Axelrod, T.; Chen, W. P.; Cook, K. H.; Dave, R.; de Pater, I.; Porrata, R.; Lee, T.; Lin, H.-C.; Lissauer, J. J.; Marshall, S. L.; Rice, J. A.; Schwamb, M. E.; Wang, S. Y.

    2009-04-01

    We analyzed 2 years of data from the Taiwan-American Occultation Survey (TAOS, Lehner et al. 2009), accumulated during 2005 and 2006, and found 3 flare stars. All of them are known x-ray sources. Among the detected flare stars, 1RXS J044712.8+203809 shows three recurrences of flare events within a month.

  2. Intensity Accents in French 2 Year Olds' Speech.

    ERIC Educational Resources Information Center

    Allen, George D.

    The acoustic features and functions of accentuation in French are discussed, and features of accentuation in the speech of French 2-year-olds are explored. The four major acoustic features used to signal accentual distinctions are fundamental frequency of voicing, duration of segments and syllables, intensity of segments and syllables, and…

  3. 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

  4. TERT promoter mutations in melanoma survival.

    PubMed

    Nagore, Eduardo; Heidenreich, Barbara; Rachakonda, Sívaramakrishna; Garcia-Casado, Zaida; Requena, Celia; Soriano, Virtudes; Frank, Christoph; Traves, Victor; Quecedo, Esther; Sanjuan-Gimenez, Josefa; Hemminki, Kari; Landi, Maria Teresa; Kumar, Rajiv

    2016-07-01

    Despite advances in targeted therapies, the treatment of advanced melanoma remains an exercise in disease management, hence a need for biomarkers for identification of at-risk primary melanoma patients. In this study, we aimed to assess the prognostic value of TERT promoter mutations in primary melanomas. Tumors from 300 patients with stage I/II melanoma were sequenced for TERT promoter and BRAF/NRAS mutations. Cumulative curves were drawn for patients with and without mutations with progression-free and melanoma-specific survival as outcomes. Cox proportional hazard regression models were used to determine the effect of the mutations on survivals. Individually, presence of TERT promoter and BRAF/NRAS mutations associated with poor disease-free and melanoma-specific survival with modification of the effect by the rs2853669 polymorphism within the TERT promoter. Hazard ratio (HR) for simultaneous occurrence of TERT promoter and BRAF/NRAS mutations for disease-free survival was 2.3 (95% CI 1.2-4.4) and for melanoma-specific survival 5.8 (95% CI 1.9-18.3). The effect of the mutations on melanoma-specific survival in noncarriers of variant allele of the polymorphism was significant (HR 4.5, 95% CI 1.4-15.2) but could not be calculated for the carriers due to low number of events. The variant allele per se showed association with increased survival (HR 0.3, 95% CI 0.1-0.9). The data in this study provide preliminary evidence that TERT promoter mutations in combination with BRAF/NRAS mutations can be used to identify patients at risk of aggressive disease and the possibility of refinement of the classification with inclusion of the rs2853669 polymorphism within TERT promoter. PMID:26875008

  5. The predictive value of 2-year posttreatment biopsy after prostate cancer radiotherapy for eventual biochemical outcome

    SciTech Connect

    Vance, Waseet; Tucker, Susan L.; Crevoisier, Renaud de; Kuban, Deborah A.; Cheung, M. Rex . E-mail: mrcheung@mdanderson.org

    2007-03-01

    Purpose: To determine the value of a 2-year post-radiotherapy (RT) prostate biopsy for predicting eventual biochemical failure in patients who were treated for localized prostate cancer. Methods and Materials: This study comprised 164 patients who underwent a planned 2-year post-RT prostate biopsy. The independent prognostic value of the biopsy results for forecasting eventual biochemical outcome and overall survival was tested with other factors (the Gleason score, 1992 American Joint Committee on Cancer tumor stage, pretreatment prostate-specific antigen level, risk group, and RT dose) in a multivariate analysis. The current nadir + 2 (CN + 2) definition of biochemical failure was used. Patients with rising prostate-specific antigen (PSA) or suspicious digital rectal examination before the biopsy were excluded. Results: The biopsy results were normal in 78 patients, scant atypical and malignant cells in 30, carcinoma with treatment effect in 43, and carcinoma without treatment effect in 13. Using the CN + 2 definition, we found a significant association between biopsy results and eventual biochemical failure. We also found that the biopsy status provides predictive information independent of the PSA status at the time of biopsy. Conclusion: A 2-year post-RT prostate biopsy may be useful for forecasting CN + 2 biochemical failure. Posttreatment prostate biopsy may be useful for identifying patients for aggressive salvage therapy.

  6. 2-year outcomes in Initial survivors with Acute Liver failure: Results from a Prospective, Multicenter Study

    PubMed Central

    Fontana, Robert J.; Ellerbe, Caitlyn; Durkalski, Valerie E.; Rangnekar, Amol; Reddy, K. Rajender; Stravitz, Todd; McGuire, Brendan; Davern, Timothy; Reuben, Adrian; Liou, Iris; Fix, Oren; Ganger, Daniel R; Chung, Raymond T.; Schilsky, Mike; Han, Steven; Hynan, Linda S.; Sanders, Corron; Lee, William M.

    2014-01-01

    BACKGROUND The long-term clinical outcomes in initial survivors with acute liver failure (ALF) are not well known. AIMS The aim of the current study is to provide an overview of the 2 year clinical outcomes amongst initial survivors and liver transplant (LT) recipients that were alive 3 weeks after enrollment in the Acute Liver Failure Study Group (ALFSG). METHODS Outcomes in adult ALFSG patients that were enrolled between 1998 and 2010 were reviewed. RESULTS 2-year patient survival was significantly higher in the 262 LT recipients (92.4%) compared to the 306 acetaminophen (APAP) spontaneous survivors (SS) (89.5%) and 200 non-APAP SS (75.5%) (p < 0.0001). The causes of death were similar in the 3 groups but the time to death was significantly longer in the LT recipients (p< 0.0001). Independent predictors of 2-year mortality in the APAP group were a high serum phosphate level and patient age (c-statistic = 0.65 (0.54, 0.76)), patient age and days from jaundice to ALF onset in the non-APAP group (c-statistic =0.69 (0.60, 0.78)), and patient age, days from jaundice, and higher coma grade in the LT recipients (c-statistic=0.74 (0.61, 0.87)). The LT recipients were significantly more likely to be employed and have a higher educational level (p < 0.05). CONCLUSIONS Two-year outcomes in initial survivors of ALF are generally good but non-APAP patients have a significantly lower survival which may relate to pre-existing medical co-morbidities. Spontaneous survivors with APAP overdose experience substantial morbidity during follow-up from ongoing psychiatric and substance abuse issues. PMID:25039930

  7. High levels of genomic aberrations in serous ovarian cancers are associated with better survival.

    PubMed

    Baumbusch, Lars O; Helland, Åslaug; Wang, Yun; Liestøl, Knut; Schaner, Marci E; Holm, Ruth; Etemadmoghadam, Dariush; Alsop, Kathryn; Brown, Pat; Mitchell, Gillian; Fereday, Sian; DeFazio, Anna; Bowtell, David D L; Kristensen, Gunnar B; Lingjærde, Ole Christian; Børresen-Dale, Anne-Lise

    2013-01-01

    Genomic instability and copy number alterations in cancer are generally associated with poor prognosis; however, recent studies have suggested that extreme levels of genomic aberrations may be beneficial for the survival outcome for patients with specific tumour types. We investigated the extent of genomic instability in predominantly high-grade serous ovarian cancers (SOC) using two independent datasets, generated in Norway (n = 74) and Australia (n = 70), respectively. Genomic instability was quantified by the Total Aberration Index (TAI), a measure of the abundance and genomic size of copy number changes in a tumour. In the Norwegian cohort, patients with TAI above the median revealed significantly prolonged overall survival (p<0.001) and progression-free survival (p<0.05). In the Australian cohort, patients with above median TAI showed prolonged overall survival (p<0.05) and moderately, but not significantly, prolonged progression-free survival. Results were confirmed by univariate and multivariate Cox regression analyses with TAI as a continuous variable. Our results provide further evidence supporting an association between high level of genomic instability and prolonged survival of high-grade SOC patients, possibly as disturbed genome integrity may lead to increased sensitivity to chemotherapeutic agents. PMID:23372714

  8. Surviving Cancer

    MedlinePlus

    ... Watch the video to learn more about these breast cancer survivors. To enlarge the video, click the brackets in the lower right-hand corner. To reduce the video, press the Escape (Esc) button on your keyboard.) Age and Health May Affect Survival A person's age, and more importantly his or ...

  9. 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)

  10. Evidence for a time-dependent association between FOLR1 expression and survival from ovarian carcinoma: implications for clinical testing. An Ovarian Tumour Tissue Analysis consortium study

    PubMed Central

    Köbel, M; Madore, J; Ramus, S J; Clarke, B A; Pharoah, P D P; Deen, S; Bowtell, D D; Odunsi, K; Menon, U; Morrison, C; Lele, S; Bshara, W; Sucheston, L; Beckmann, M W; Hein, A; Thiel, F C; Hartmann, A; Wachter, D L; Anglesio, M S; Høgdall, E; Jensen, A; Høgdall, C; Kalli, K R; Fridley, B L; Keeney, G L; Fogarty, Z C; Vierkant, R A; Liu, S; Cho, S; Nelson, G; Ghatage, P; Gentry-Maharaj, A; Gayther, S A; Benjamin, E; Widschwendter, M; Intermaggio, M P; Rosen, B; Bernardini, M Q; Mackay, H; Oza, A; Shaw, P; Jimenez-Linan, M; Driver, K E; Alsop, J; Mack, M; Koziak, J M; Steed, H; Ewanowich, C; DeFazio, A; Chenevix-Trench, G; Fereday, S; Gao, B; Johnatty, S E; George, J; Galletta, L; Goode, E L; Kjær, S K; Huntsman, D G; Fasching, P A; Moysich, K B; Brenton, J D; Kelemen, L E

    2014-01-01

    Background: Folate receptor 1 (FOLR1) is expressed in the majority of ovarian carcinomas (OvCa), making it an attractive target for therapy. However, clinical trials testing anti-FOLR1 therapies in OvCa show mixed results and require better understanding of the prognostic relevance of FOLR1 expression. We conducted a large study evaluating FOLR1 expression with survival in different histological types of OvCa. Methods: Tissue microarrays composed of tumour samples from 2801 patients in the Ovarian Tumour Tissue Analysis (OTTA) consortium were assessed for FOLR1 expression by centralised immunohistochemistry. We estimated associations for overall (OS) and progression-free (PFS) survival using adjusted Cox regression models. High-grade serous ovarian carcinomas (HGSC) from The Cancer Genome Atlas (TCGA) were evaluated independently for association between FOLR1 mRNA upregulation and survival. Results: FOLR1 expression ranged from 76% in HGSC to 11% in mucinous carcinomas in OTTA. For HGSC, the association between FOLR1 expression and OS changed significantly during the years following diagnosis in OTTA (Pinteraction=0.01, N=1422) and TCGA (Pinteraction=0.01, N=485). In OTTA, particularly for FIGO stage I/II tumours, patients with FOLR1-positive HGSC showed increased OS during the first 2 years only (hazard ratio=0.44, 95% confidence interval=0.20–0.96) and patients with FOLR1-positive clear cell carcinomas (CCC) showed decreased PFS independent of follow-up time (HR=1.89, 95% CI=1.10–3.25, N=259). In TCGA, FOLR1 mRNA upregulation in HGSC was also associated with increased OS during the first 2 years following diagnosis irrespective of tumour stage (HR: 0.48, 95% CI: 0.25–0.94). Conclusions: FOLR1-positive HGSC tumours were associated with an increased OS in the first 2 years following diagnosis. Patients with FOLR1-negative, poor prognosis HGSC would be unlikely to benefit from anti-FOLR1 therapies. In contrast, a decreased PFS interval was observed for FOLR1

  11. Improvement in High-Grade Osteosarcoma Survival

    PubMed Central

    Hung, Giun-Yi; Yen, Hsiu-Ju; Yen, Chueh-Chuan; Wu, Po-Kuei; Chen, Cheng-Fong; Chen, Paul C-H; Wu, Hung-Ta H.; Chiou, Hong-Jen; Chen, Wei-Ming

    2016-01-01

    Abstract The aim of this study was to compare survival before and after 2004 and define the prognostic factors for high-grade osteosarcomas beyond those of typical young patients with localized extremity disease. Few studies have reported the long-term treatment outcomes of high-grade osteosarcoma in Taiwan. A total of 202 patients with primary high-grade osteosarcoma who received primary chemotherapy at Taipei Veterans General Hospital between January 1995 and December 2011 were retrospectively evaluated and compared by period (1995–2003 vs 2004–2011). Patients of all ages and tumor sites and those following or not following controlled protocols were included in analysis of demographic, tumor-related, and treatment-related variables and survival. Overall survival and progression-free survival at 5 years were, respectively, 67.7% and 48% for all patients (n = 202), 77.3% and 57.1% for patients without metastasis (n = 157), and 33.9% and 14.8% for patients with metastasis (n = 45). The survival rates of patients treated after 2004 were significantly higher (by 13%–16%) compared with those of patients treated before 2004, with an accompanying 30% increase in histological good response rate (P = .002). Factors significantly contributing to inferior survival in univariate and multivariate analyses were diagnosis before 2004, metastasis at diagnosis, and being a noncandidate for a controlled treatment protocol. By comparison with the regimens used at our institution before 2004, the current results support the effectiveness of the post-2004 regimens, which consisted of substantially reduced cycles of high-dose methotrexate and a higher dosage of ifosfamide per cycle, cisplatin, and doxorubicin, for treating high-grade osteosarcoma in Asian patients. PMID:27082623

  12. Clinical outcomes of pars plicata anterior vitrectomy: 2-year results

    PubMed Central

    Narang, Priya; Agarwal, Amar

    2015-01-01

    Purpose: To demonstrate the safety and outcome of a surgical approach that uses pars plicata site for anterior vitrectomy during phacoemulsification procedure complicated by posterior capsule rupture and residual cortical matter. Design: Single center, retrospective, interventional, noncomparative study. Materials and Methods: Medical records of a consecutive series of 35 eyes of 35 patients who underwent pars plicata anterior vitrectomy (PPAV) were reviewed. The main outcome measures were corrected and uncorrected distance visual acuity (CDVA, UDVA), early and late postoperative complications and intraocular pressure (IOP). Ultrasound biomicroscopic (UBM) evaluation of sclerotomy site and spectral domain optical coherence tomography analysis for central macular thickness (CMT) was performed. The final visual outcome at 2 years was evaluated. Results: At 2 years follow-up, the mean postoperative UDVA (logarithm of the minimum angle of resolution [logMAR]) and CDVA (logMAR) was 0.49 ± 0.26 and 0.19 ± 0.14, respectively. There was no significant change in the IOP (P = 0.061) and the mean CMT at 2 years was 192.5 ± 5.54 μm. The postoperative UBM image of the sclerotomy site at 8 weeks demonstrated a clear wound without any vitreous adhesion or incarceration. Intraoperative hyphema was seen in 1 (2.8%) case and postoperative uveitis was seen in 2 (5.7%) cases, which resolved with medications. No case of an iatrogenic retinal break or retinal detachment was reported. Conclusions: PPAV enables a closed chamber approach, allows thorough cleanup of vitreous in the pupillary plane and anterior chamber and affords better access to the subincisional and retropupillary cortical remnant with a significant visual outcome and an acceptable complication rate. PMID:26632124

  13. Multidrug-resistant tuberculosis that required 2 years for diagnosis.

    PubMed

    Yano, Shuichi; Kobayashi, Kanako; Ikeda, Toshikazu

    2012-01-01

    Isoniazid (H) or rifampicin (R) mono-resistant disease can be treated easily and effectively with first-line drugs, while combined H and R resistance (ie, multidrug-resistant tuberculosis (MDRTB)) requires treatment with at least four agents, including a quinolone and an injectable agent. Drug-resistant Mycobacterium tuberculosis strains are reported to be extremely difficult to cultivate invitro. The authors report a case of MDRTB that required 2 years for diagnosis, and was detected only in sputum culture on solid medium. Physicians should consider MDRTB if TB is suspected but pathogens are not detected. PMID:22605803

  14. Clinical neuroprediction: Amygdala reactivity predicts depressive symptoms 2 years later.

    PubMed

    Mattson, Whitney I; Hyde, Luke W; Shaw, Daniel S; Forbes, Erika E; Monk, Christopher S

    2016-06-01

    Depression is linked to increased amygdala activation to neutral and negatively valenced facial expressions. Amygdala activation may be predictive of changes in depressive symptoms over time. However, most studies in this area have focused on small, predominantly female and homogenous clinical samples. Studies are needed to examine how amygdala reactivity relates to the course of depressive symptoms dimensionally, prospectively and in populations diverse in gender, race and socioeconomic status. A total of 156 men from predominately low-income backgrounds completed an fMRI task where they viewed emotional facial expressions. Left and right amygdala reactivity to neutral, but not angry or fearful, facial expressions relative to a non-face baseline at age 20 predicted greater depressive symptoms 2 years later, controlling for age 20 depressive symptoms. Heightened bilateral amygdala reactivity to neutral facial expressions predicted increases in depressive symptoms 2 years later in a large community sample. Neutral facial expressions are affectively ambiguous and a tendency to interpret these stimuli negatively may reflect to cognitive biases that lead to increases in depressive symptoms over time. Individual differences in amygdala reactivity to neutral facial expressions appear to identify those at most risk for a more problematic course of depressive symptoms across time. PMID:26865423

  15. Role Modeling in the First 2 Years of Medical School.

    PubMed

    Obadia, Sharon J

    2015-08-01

    Role modeling opportunities for osteopathic physician teachers during a student's first 2 years of medical school are emerging as more colleges of osteopathic medicine strive to connect basic science didactics with clinically based learning activities. Examples of positive modeling by physician teachers during the first years of medical school are illustrated by 10 vignettes that can be incorporated into faculty development programs to increase awareness of such opportunities. The physician teacher in each vignette interacts with the student demonstrating desired professional behaviors. These vignettes also illustrate the effect of a positive "hidden curriculum" on a student's professional development. By recognizing these valuable teachable moments, teachers can incorporate role modeling into their daily practice. PMID:26214824

  16. A phonological system at 2 years after cochlear implantation

    PubMed Central

    CHIN, STEVEN B.; PISONI, DAVID B.

    2011-01-01

    This report is a description of a developing phonological system as manifested in the productions of a prelingually deafened child approximately 2 years after fitting with a Nucleus 22-Channel Multi-Electrode Cochlear Implant. A probe list consisting of 23 proper nouns familiar to the child was used to elicit samples of her speech; stimulus materials consisted of photographs of those persons (friends and family members) whose names were included in the probe list. Analysis of the child's productions addressed the composition of the phonetic inventory of consonants and vowels and the presence of syllable structure and other phonotactic constraints. Results indicated a rich inventory of speech sound segments (among both consonants and vowels) and a lack of stringent constraints on syllable structure and consonants permitted in specified word positions. A further comparative analysis of correspondences with the ambient language showed a number of patterns that are also common in the speech of children with normal hearing. PMID:22091697

  17. Rapid fast-mapping abilities in 2-year-olds.

    PubMed

    Spiegel, Chad; Halberda, Justin

    2011-05-01

    Learning a new word consists of two primary tasks that have often been conflated into a single process: referent selection, in which a child must determine the correct referent of a novel label, and referent retention, which is the ability to store this newly formed label-object mapping in memory for later use. In addition, children must be capable of performing these tasks rapidly and repeatedly as they are frequently exposed to novel words during the course of natural conversation. Here we used a preferential pointing task to investigate 2-year-olds' (N=72) ability to infer the referent of a novel noun from a single ambiguous exposure and their ability to retain this mapping over time. Children were asked to identify the referent of a novel label on six critical trials distributed throughout the course of a 10-min study involving many familiar and novel objects. On these critical trials, images of a known object and a novel object (e.g., a ball and a nameless artifact constructed in the laboratory) appeared on two computer screens and a voice asked children to "point at the _____ [e.g., glark]." Following label onset, children were allowed only 3s during which to infer the correct referent, point at it, and potentially store this new word-object mapping. In a final posttest trial, all previously labeled novel objects appeared and children were asked to point to one of them (e.g., "Can you find the glark?"). To succeed, children needed to have initially mapped the novel labels correctly and retained these mappings over the course of the study. Despite the difficult demands of the current task, children successfully identified the target object on the retention trial. We conclude that 2-year-olds are able to fast map novel nouns during a brief single exposure under ambiguous labeling conditions. PMID:21145067

  18. Effects of cognitive rehabilitation training on schizophrenia: 2 years of follow-up

    PubMed Central

    Tao, Jianqing; Zeng, Qiang; Liang, Jia; Zhou, Aihua; Yin, Xuebing; Xu, Ai

    2015-01-01

    Objective: Schizophrenia is a mental disorder and characterized by abnormal social behavior and failure to recognize what is real. The current study was to explore the long-term effects of cognitive rehabilitation training on schizophrenia. Methods: Eighty six cases of hospitalized patients with schizophrenia were randomly divided into study group and control group. The relapse and employment (attending school) rates were used as indicators to assess the treatment effect. All patients were followed up by 2 years. Kaplan-Meier survival analysis was conducted with relapse and employment (attending school) rates. Results: The rates of relapse in the study group and the control group were 18% and 41%, and relapse free survival time was 22.22 months and 18.55 months; the rates of employment (attending school) were 64% and 43%, and not employment (attending school) time were 10.68 months and 15.74 months, respectively. There was significant difference between the two groups (P<0.05). Conclusions: We found that the cognitive rehabilitation training could significantly reduce schizophrenic relapse rate, prolong the time of patients without relapse, improve the employment (attending school) rate, and shorten the discharged time, which is a powerful treatment method to improve social competence in schizophrenia patients. PMID:26629117

  19. Cost and Schedule Analytical Techniques Development: Option 2 Year

    NASA Technical Reports Server (NTRS)

    1997-01-01

    This Final Report summarizes the activities performed by Science Applications International Corporation (SAIC) for the Option 2 Year from December 1, 1996 through November 30, 1997. The Final Report is in compliance with Paragraph 5 of Section F of the contract. This CSATD contract provides products and deliverable in the form of models, data bases, methodologies, studies and analyses for the NASA Marshall Space Flight Center's (MSFC) Engineering Cost Office (PPO3) the Program Plans and Requirements Officer (PP02), and other user organizations. Detailed Monthly Progress reports were submitted to MSFC in accordance with the contract's Statement of Work, Section TV "Reporting and Documentation". These reports spelled out each month's specific work accomplishments, deliverables submitted, major meetings held, and other pertinent information. This Final Report will summarize these activities at higher level. During this contract Option Year, SAIC expended 29,830 man-hours in tile performance of tasks called out in the Statement of Work and reported oil in this yearly Final Report. This represents approximately 16 full-time EPs. Included are the basis Huntsville-based team, plus SAIC specialists in San Diego, Ames Research Center, Chicago, and Colorado Springs performing specific tasks for which they are uniquely qualified.

  20. New geoscience teachers division for 2-year colleges

    NASA Astrophysics Data System (ADS)

    Krumm, Debra; Granshaw, Frank

    2011-11-01

    The role of 2-year colleges (2YCs) in geoscience education is growing as the number of students enrolled in Earth and space science courses increases and as these institutions—which include community colleges and junior colleges—provide more students majoring in geoscience at public universities. In recognition of the increasing role of 2YCs in geoscience education, the National Association of Geoscience Teachers (NAGT) recently created a Geo2YC division for faculty, administrators, graduate students, and other geoscience professionals who share a professional interest in geoscience education at 2YCs. The mission of the new division, which is NAGT's first national division, is to serve as a forum for exchanging curricular ideas, concerns, and resources; establish a network of geoscience educators at 2YCs and other institutions with shared interests; sponsor NAGT 2YC activities and make recommendations to the NAGT Council in support of 2YC geoscience education; support and coordinate research on 2YC geoscience education; and advocate for 2YC geoscience education within NAGT and with other organizations.

  1. Interstitial Lung Disease in Children Younger Than 2 Years.

    PubMed

    Spagnolo, Paolo; Bush, Andrew

    2016-06-01

    Childhood interstitial lung disease (chILD) represents a highly heterogeneous group of rare disorders associated with substantial morbidity and mortality. Although our understanding of chILD remains limited, important advances have recently been made, the most important being probably the appreciation that disorders that present in early life are distinct from those occurring in older children and adults, albeit with some overlap. chILD manifests with diffuse pulmonary infiltrates and nonspecific respiratory signs and symptoms, making exclusion of common conditions presenting in a similar fashion an essential preliminary step. Subsequently, a systematic approach to diagnosis includes a careful history and physical examination, computed tomography of the chest, and some or all of bronchoscopy with bronchoalveolar lavage, genetic testing, and if diagnostic uncertainty persists, lung biopsy. This review focuses on chILD presenting in infants younger than 2 years of age and discusses recent advances in the classification, diagnostic approach, and management of chILD in this age range. We describe novel genetic entities, along with initiatives that aim at collecting clinical data and biologic samples from carefully characterized patients in a prospective and standardized fashion. Early referral to expert centers and timely diagnosis may have important implications for patient management and prognosis, but effective therapies are often lacking. Following massive efforts, international collaborations among the key stakeholders are finally starting to be in place. These have allowed the setting up and conducting of the first randomized controlled trial of therapeutic interventions in patients with chILD. PMID:27245831

  2. Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years

    PubMed Central

    McKinlay, Christopher J.D.; Alsweiler, Jane M.; Ansell, Judith M.; Anstice, Nicola S.; Chase, J. Geoffrey; Gamble, Gregory D.; Harris, Deborah L.; Jacobs, Robert J.; Jiang, Yannan; Paudel, Nabin; Signal, Matthew; Thompson, Benjamin; Wouldes, Trecia A.; Yu, Tzu-Ying; Harding, Jane E.

    2015-01-01

    Background Neonatal hypoglycemia is common and can cause neurologic impairment, but evidence supporting thresholds for intervention is limited. Methods We performed a prospective cohort study involving 528 neonates with a gestational age of at least 35 weeks who were considered to be at risk for hypoglycemia; all were treated to maintain a blood glucose concentration of at least 47 mg per deciliter (2.6 mmol per liter). We intermittently measured blood glucose for up to 7 days. We continuously monitored interstitial glucose concentrations, which were masked to clinical staff. Assessment at 2 years included Bayley Scales of Infant Development III and tests of executive and visual function. Results Of 614 children, 528 were eligible, and 404 (77% of eligible children) were assessed; 216 children (53%) had neonatal hypoglycemia (blood glucose concentration, <47 mg per deciliter). Hypoglycemia, when treated to maintain a blood glucose concentration of at least 47 mg per deciliter, was not associated with an increased risk of the primary outcomes of neurosensory impairment (risk ratio, 0.95; 95% confidence interval [CI], 0.75 to 1.20; P = 0.67) and processing difficulty, defined as an executive-function score or motion coherence threshold that was more than 1.5 SD from the mean (risk ratio, 0.92; 95% CI, 0.56 to 1.51; P = 0.74). Risks were not increased among children with unrecognized hypoglycemia (a low interstitial glucose concentration only). The lowest blood glucose concentration, number of hypoglycemic episodes and events, and negative interstitial increment (area above the interstitial glucose concentration curve and below 47 mg per deciliter) also did not predict the outcome. Conclusions In this cohort, neonatal hypoglycemia was not associated with an adverse neurologic outcome when treatment was provided to maintain a blood glucose concentration of at least 47 mg per deciliter. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human

  3. Predicting school readiness from neurodevelopmental assessments at age 2 years after respiratory distress syndrome in infants born preterm

    PubMed Central

    PATRIANAKOS-HOOBLER, ATHENA I; MSALL, MICHAEL E; HUO, DEZHENG; MARKS, JEREMY D; PLESHA-TROYKE, SUSAN; SCHREIBER, MICHAEL D

    2010-01-01

    AIM To determine whether neurodevelopmental outcomes at the age of 2 years accurately predict school readiness in children who survived respiratory distress syndrome after preterm birth. METHOD Our cohort included 121 preterm infants who received surfactant and ventilation and were enrolled in a randomized controlled study of inhaled nitric oxide for respiratory distress syndrome. Abnormal outcomes at the age of 2 years were defined as neurosensory disability (cerebral palsy, blindness, or bilateral hearing loss) or delay (no neurosensory disability but Bayley Scales of Infant Development mental or performance developmental index scores <70). School readiness (assessed at a mean age of 5y 6mo, SD 1y) was determined using neurodevelopmental assessments of motor, sensory, receptive vocabulary, perceptual, conceptual, and adaptive skills. RESULTS The mean birthweight of the cohort (57 males, 64 females) was 987g (SD 374), and the mean gestational age was 27.3 weeks (SD 2.6). At the age of 2 years, the neurodevelopmental classification was ‘disabled’ in 11% and ‘delayed’ in 23%. At the age of 5 years 6 months, intensive special education was required for 11% and some special education for 21%. Disability and delay at the age of 2 years were 92% and 50% predictive of lack of school readiness respectively, whereas only 15% of children who were normal at the age of 2 years were not school ready at the later assessment. Children with delay at 2 years were more likely to need special education if they were socially disadvantaged. INTERPRETATION Without preschool developmental supports, preterm survivors living in poverty will require more special education services. PMID:20002128

  4. 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

  5. Radical irradiation and misonidazole for T2 grade III and T3 bladder cancer: 2 year follow-up

    SciTech Connect

    Abratt, R.P.; Barnes, D.R.; Hammond, J.A.; Sarembok, L.A.; Tucker, R.D.; Williams, A.M.

    1984-09-01

    Patients with T2 grade III and T3 bladder cancer were treated in a Phase II trial of radical irradiation plus Misonidazole (MISO). Twenty-two patients were treated and the results compared with historical controls. The cystoscopic complete tumor response between 6 and 12 months post therapy were 73 and 43%, respectively. The patient two year survival was 81 and 51%, respectively, and the patient 2 year survival with bladder preservation was 61 and 48%, respectively - 4 patients in the MISO study having undergone salvage cystectomy. Complications that may be radiation related in the MISO study are would sepsis after salvage cystectomy in 2 patients, rectal stenosis requiriing colostomy 16 months after salvage cystecomy in 1 patient and the development of a contracted bladder in 1 patient with a history of prior extensive endoscopic therapy. No misonidazole neurotoxicity seen. These findings are being further evaluated in a prospective radomized trial.

  6. Review of meta-analyses evaluating surrogate endpoints for overall survival in oncology

    PubMed Central

    Sherrill, Beth; Kaye, James A; Sandin, Rickard; Cappelleri, Joseph C; Chen, Connie

    2012-01-01

    Overall survival (OS) is the gold standard in measuring the treatment effect of new drug therapies for cancer. However, practical factors may preclude the collection of unconfounded OS data, and surrogate endpoints are often used instead. Meta-analyses have been widely used for the validation of surrogate endpoints, specifically in oncology. This research reviewed published meta-analyses on the types of surrogate measures used in oncology studies and examined the extent of correlation between surrogate endpoints and OS for different cancer types. A search was conducted in October 2010 to compile available published evidence in the English language for the validation of disease progression-related endpoints as surrogates of OS, based on meta-analyses. We summarize published meta-analyses that quantified the correlation between progression-based endpoints and OS for multiple advanced solid-tumor types. We also discuss issues that affect the interpretation of these findings. Progression-free survival is the most commonly used surrogate measure in studies of advanced solid tumors, and correlation with OS is reported for a limited number of cancer types. Given the increased use of crossover in trials and the availability of second-/third-line treatment options available to patients after progression, it will become increasingly more difficult to establish correlation between effects on progression-free survival and OS in additional tumor types. PMID:23109809

  7. [Retroperitoneal lymphadenectomy and survival of patients treated for an advanced ovarian cancer: the CARACO trial].

    PubMed

    Classe, J-M; Cerato, E; Boursier, C; Dauplat, J; Pomel, C; Villet, R; Cuisenier, J; Lorimier, G; Rodier, J-F; Mathevet, P; Houvenaeghel, G; Leveque, J; Lécuru, F

    2011-05-01

    The standard management for advanced-stage epithelial ovarian cancer is optimum cytoreductive surgery followed by platinum based chemotherapy. However, retroperitoneal lymph node resection remains controversial. The multiple directions of the lymph drainage pathway in ovarian cancer have been recognized. The incidence and pattern of lymph node involvement depends on the extent of the disease and the histological type. Several published cohorts suggest the survival benefit of pelvic and para-aortic lymphadenectomy. A recent large randomized trial have demonstrated the potential benefit for surgical removal of bulky lymph nodes in term of progression-free survival but failed to show any overall survival benefit because of a critical methodology. Further randomised trials are needed to balance risks and benefits of systematic lymphadenectomy in advanced-stage disease. CARACO is a French ongoing trial, built to bring a reply to this important question. A huge effort for inclusion of the patients, and involving new teams, are mandatory. PMID:21482037

  8. 75 FR 76082 - Agency Information Collection; Gravesite Reservation Survey (2-Year) Activity Under OMB Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-07

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF VETERANS AFFAIRS Agency Information Collection; Gravesite Reservation Survey (2- Year) Activity Under OMB Review... correspondence. SUPPLEMENTAL INFORMATION: Title: Gravesite Reservation Survey (2-Year), VA Form 40-40....

  9. 7 CFR 25.403. - Ongoing 2-year work plan requirement.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 1 2012-01-01 2012-01-01 false Ongoing 2-year work plan requirement. 25.403. Section... COMMUNITIES Post-Designation Requirements § 25.403. Ongoing 2-year work plan requirement. (a) Each Empowerment... interval of the designation period. (b) The 2-year work plan shall be submitted to USDA 45 days prior...

  10. 7 CFR 25.403. - Ongoing 2-year work plan requirement.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 1 2013-01-01 2013-01-01 false Ongoing 2-year work plan requirement. 25.403. Section... COMMUNITIES Post-Designation Requirements § 25.403. Ongoing 2-year work plan requirement. (a) Each Empowerment... interval of the designation period. (b) The 2-year work plan shall be submitted to USDA 45 days prior...

  11. 7 CFR 25.403. - Ongoing 2-year work plan requirement.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 1 2014-01-01 2014-01-01 false Ongoing 2-year work plan requirement. 25.403. Section... COMMUNITIES Post-Designation Requirements § 25.403. Ongoing 2-year work plan requirement. (a) Each Empowerment... interval of the designation period. (b) The 2-year work plan shall be submitted to USDA 45 days prior...

  12. 7 CFR 25.403. - Ongoing 2-year work plan requirement.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 1 2011-01-01 2011-01-01 false Ongoing 2-year work plan requirement. 25.403. Section... COMMUNITIES Post-Designation Requirements § 25.403. Ongoing 2-year work plan requirement. (a) Each Empowerment... interval of the designation period. (b) The 2-year work plan shall be submitted to USDA 45 days prior...

  13. Smoking Patterns, Attitudes and Motives: Unique Characteristics among 2-Year versus 4-Year College Students

    ERIC Educational Resources Information Center

    Berg, C. J.; An, L. C.; Thomas, J. L.; Lust, K. A.; Sanem, J. R.; Swan, D. W.; Ahluwalia, J. S.

    2011-01-01

    Given the previously documented higher rates of smoking among 2-year college students in comparison with 4-year university students, this study compares smoking patterns, attitudes and motives among 2-year and 4-year college students. Two thousand two hundred and sixty-five undergraduate students aged 18-25 years at a 2-year college and a 4-year…

  14. A randomised trial of granulocyte-macrophage colony-stimulating factor for neonatal sepsis: outcomes at 2 years

    PubMed Central

    Marlow, Neil; Morris, Timothy; Brocklehurst, Peter; Carr, Robert; Cowan, Frances M; Patel, Nishma; Petrou, Stavros; Redshaw, Maggie E; Modi, Neena; Dore, Caroline

    2013-01-01

    Objective The authors performed a randomised trial in very preterm small-for-gestational age (SGA) babies to determine if prophylaxis with granulocyte-macrophage colony-stimulating factor (GM-CSF) improves outcomes (the PROGRAMS trial). Despite increased neutrophil counts following GM-CSF, the authors reported no significant difference in neonatal sepsis-free survival. Patients and methods 280 babies born <31 weeks of gestation and SGA were entered into the trial. Outcome was determined at 2 years to determine neurodevelopmental and general health outcomes, including economic costs. Results The authors found no significant differences in health outcomes or health and social care costs between the trial groups. In the GM-CSF arm, 87 of 134 (65%) babies survived to 2 years without severe disability compared with 87 of 131 (66%) controls (RR: 1·0, 95% CI 0·8 to 1·2). Marginally, more children receiving GM-CSF were reported to have cough (RR 1·7, 95% CI 1·1 to 2·6) and had signs of chronic respiratory disease (Harrison's sulcus; RR 2·0, 95% CI 1·0 to 3·9) though this was not reflected in bronchodilator use or need for hospitalisation for respiratory disease. Overall, the rate of neurologic abnormality (7%–9%) was similar but mean overall developmental scores were lower than expected for gestational age. Conclusions The administration of GM-CSF to very preterm SGA babies is not associated with improved or more adverse outcomes at 2 years of age. The apparent excess of developmental impairment in the entire PROGRAMS cohort, without corresponding increase in neurological abnormality, may represent diffuse brain injury attributable to intrauterine growth restriction. PMID:22542709

  15. Prognostic factors and survival in patients with metastatic or recurrent carcinoma of the uterine cervix.

    PubMed

    Eralp, Y; Saip, P; Sakar, B; Kucucuk, S; Aydiner, A; Dincer, M; Aslay, I; Topuz, E

    2003-01-01

    The aim of this study is to identify the impact of various prognostic factors on survival in patients with recurrent carcinoma of the uterine cervix. Fifty-two patients who were treated with platinum-based chemotherapy for recurrent or metastatic disease were retrospectively evaluated. Twenty-seven patients (90%) had received pelvic radiation as primary treatment. Out of 45 evaluable patients, two (4.4%) had complete response (CR), three (6.7%) had a continuous CR after additional surgical treatment and irradiation. Five patients (11.1%) had partial response (PR). The majority of patients had progressive response to treatment (22 patients, 48.9%). After a median follow-up period of 19 months, 31 patients (60%) had died. Progression-free survival after initial diagnosis was observed to have a significant association with response to chemotherapy for recurrent disease (Fisher two-sided P = 0.027). The median survival duration for relapsed disease was 11.8 months. Those with a longer disease-free interval ( 8 months vs. survival duration after relapse by univariate analysis. Multivariate analysis revealed that progressive response to chemotherapy (P = 0.002, HR = 4.6) and recurrence within the previously irradiated field (P = 0.04, HR = 2.7) were significant independent prognostic factors for a shorter time to progression after recurrence. Furthermore, advanced stage at presentation (P = 0.001, HR = 3.0) and a short disease-free interval after primary treatment (<8 months, P = 0.003, HR = 3.4) were determined as independent prognostic factors with a significant negative influence on progression-free survival and overall survival from initial diagnosis, respectively. The use of toxic and expensive combinations for the treatment of recurrent cervical cancer patients should be well balanced against potential hazards. Based on our data, less toxic regimens

  16. IMPACT OF PRE-TRANSPLANT RITUXIMAB ON SURVIVAL AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR DIFFUSE LARGE B-CELL LYMPHOMA

    PubMed Central

    Fenske, Timothy S.; Hari, Parameswaran N.; Carreras, Jeanette; Zhang, Mei-Jie; Kamble, Rammurti T.; Bolwell, Brian J.; Cairo, Mitchell S.; Champlin, Richard E.; Chen, Yi-Bin; Freytes, César O.; Gale, Robert Peter; Hale, Gregory A.; Ilhan, Osman; Khoury, H. Jean; Lister, John; Maharaj, Dipnarine; Marks, David I.; Munker, Reinhold; Pecora, Andrew L.; Rowlings, Philip A.; Shea, Thomas C.; Stiff, Patrick; Wiernik, Peter H.; Winter, Jane N.; Rizzo, J. Douglas; van Besien, Koen; Lazarus, Hillard M.; Vose, Julie M.

    2010-01-01

    Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens for diffuse large B-cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, many patients develop refractory or recurrent DLBCL and then receive autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes following AuHCT. Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n=176, “+R” group) or was not (n=818, “ −R” group) administered with front-line or salvage therapy prior to AuHCT. The +R group had superior progression-free survival (50% versus 38%, p=0.008) and overall survival (57% versus 45%, p=0.006) at 3 years. Platelet and neutrophil engraftment were not affected by exposure to rituximab. Non-relapse mortality (NRM) did not differ significantly between the +R and −R groups. In multivariate analysis, the +R group had improved progression-free survival (relative risk of relapse/progression or death 0.64, p<0.001) and improved overall survival (relative risk of death of 0.74, p=0.039). We conclude that pre-transplant rituximab is associated with a lower rate of progression and improved survival following AuHCT for DLBCL, with no evidence of impaired engraftment or increased NRM. PMID:19822306

  17. Neoadjuvant chemotherapy in advanced epithelial ovarian cancer: A survival study

    PubMed Central

    Baruah, Upasana; Barmon, Debabrata; Kataki, Amal Chandra; Deka, Pankaj; Hazarika, Munlima; Saikia, Bhargab J.

    2015-01-01

    Context: Patients with advanced ovarian cancer have a poor prognosis in spite of the best possible care. Primary debulking surgery has been the standard of care in advanced ovarian cancer; however, it is associated with high mortality and morbidity rates as shown in various studies. Several studies have discussed the benefit of neoadjuvant chemotherapy in patients with advanced ovarian cancer. Aims: This study aims to evaluate the survival statistics of the patients who have been managed with interval debulking surgery (IDS) from January 2007 to December 2009. Materials and Methods: During the period from January 2007 to December 2009, a retrospective analysis of 104 patients who underwent IDS for stage IIIC or IV advanced epithelial ovarian cancer at our institute were selected for the study. IDS was attempted after three to five courses of chemotherapy with paclitaxal (175 mg/m2 ) and carboplatin (5-6 of area under curve). Overall survival (OS) and progression free survival (PFS) were compared with results of primary debulking study from existing literature. OS and PFS rates were estimated by means of the Kaplan-Meier method. Results were statistically analyzed by IBM SPSS Statistics 19. Results: The median OS was 26 months and the median PFS was 18 months. In multivariate analysis it was found that both OS and PFS was affected by the stage, and extent of debulking. Conclusions: Neoadjuvant chemotherapy, followed by surgical cytoreduction is a promising treatment strategy for the management of advanced epithelial ovarian cancers. PMID:25810573

  18. Defensive platform size and survivability. [Platform survivability

    SciTech Connect

    Canavan, Gregory H.

    1988-06-01

    This report discusses the survivability of space platforms, concentrating on space based kinetic energy interceptors. It evaluates the efficacy of hardening, maneuver, self-defense, and deception in extending the survivability of platforms of varying sizes to expected threats, concluding that they should be adequate in the near and mid terms.

  19. 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

  20. Association of response endpoints with survival outcomes in multiple myeloma

    PubMed Central

    Lonial, S; Anderson, K C

    2014-01-01

    Since the introduction of the proteasome inhibitor bortezomib and the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, more patients with multiple myeloma are achieving deep, durable responses and disease control, and are living longer. These improvements have afforded more robust analyses of the relationship between response and survival. Generally, these studies have demonstrated that improvements in the quality of response across all stages of treatment are associated with better disease control and longer survival. Thus, achievement of maximal response should be strongly considered, particularly in the frontline setting, but must also be balanced with tolerability, quality of life and patient preferences. In select patients, achievement of a lesser response may be adequate to prolong survival, and attempts to treat these patients to a deeper response may place them at unnecessary risk without significant benefit. Maintenance therapy has been shown to improve the quality of response and disease control and, in some studies, survival. Studies support maintenance therapy for high-risk patients as a standard of care, and there are emerging data supporting maintenance therapy in standard-risk patients to improve progression-free and possibly overall survival. Multidrug regimens combining a proteasome inhibitor and an IMiD have shown exceptional response outcomes with acceptable increases in toxicity in both the frontline and salvage settings, and are becoming a standard treatment approach. Moving forward, the use of immunophenotypic and molecular response criteria will be essential in better understanding the impact of highly active and continuous treatment regimens across myeloma patient populations. Future translational studies will help to develop antimyeloma agents to their fullest potential. The introduction of novel targeted therapies, including the IMiD pomalidomide and the proteasome inhibitors carfilzomib and ixazomib (MLN9708), will provide

  1. Association of response endpoints with survival outcomes in multiple myeloma.

    PubMed

    Lonial, S; Anderson, K C

    2014-02-01

    Since the introduction of the proteasome inhibitor bortezomib and the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, more patients with multiple myeloma are achieving deep, durable responses and disease control, and are living longer. These improvements have afforded more robust analyses of the relationship between response and survival. Generally, these studies have demonstrated that improvements in the quality of response across all stages of treatment are associated with better disease control and longer survival. Thus, achievement of maximal response should be strongly considered, particularly in the frontline setting, but must also be balanced with tolerability, quality of life and patient preferences. In select patients, achievement of a lesser response may be adequate to prolong survival, and attempts to treat these patients to a deeper response may place them at unnecessary risk without significant benefit. Maintenance therapy has been shown to improve the quality of response and disease control and, in some studies, survival. Studies support maintenance therapy for high-risk patients as a standard of care, and there are emerging data supporting maintenance therapy in standard-risk patients to improve progression-free and possibly overall survival. Multidrug regimens combining a proteasome inhibitor and an IMiD have shown exceptional response outcomes with acceptable increases in toxicity in both the frontline and salvage settings, and are becoming a standard treatment approach. Moving forward, the use of immunophenotypic and molecular response criteria will be essential in better understanding the impact of highly active and continuous treatment regimens across myeloma patient populations. Future translational studies will help to develop antimyeloma agents to their fullest potential. The introduction of novel targeted therapies, including the IMiD pomalidomide and the proteasome inhibitors carfilzomib and ixazomib (MLN9708), will provide

  2. 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.

  3. Preoperative statin use is not associated with improvement in survival after glioblastoma surgery.

    PubMed

    Bhavsar, S; Hagan, K; Arunkumar, R; Potylchansky, Y; Grasu, R; Dang, A; Carlson, R; Cowels, C; Arnold, B; Rahlfs, T F; Lipski, I; Walsh, C; Nguyen, A T; Feng, L; Cata, J P

    2016-09-01

    Cohort studies have suggested that the use of statins is associated with decreased risk of glioma formation and mortality. Here, a cohort of patients with glioblastoma multiforme (GBM) was analyzed to further investigate associations between preoperative use of statins and recurrence, and progression free and overall survival. Patients who had surgery for GBM (N=284) were followed up for a median of 18.1months. Seventy-eight patients were taking statins preoperatively while the rest were not. Cox proportional hazards models adjusted for several covariates of interest were applied before and after propensity score matching. Compared with statin users, those not taking the lipid-lowering drugs had similar progression free survival before (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.70-1.26; p=0.68) and after propensity score matching (HR 0.95, 95% CI 0.67-1.35; p=0.68). Mortality was similar between both groups of patients before (HR 0.94, 95% CI 0.70-1.22; p= 0.73) and after propensity score matching (HR 1.13, 95% CI 0.78-1.64; p=0.49). Age and dexamethasone use were independent prognostic factors of survival. Contrary to previously published evidence, this study could not find an association between preoperative statin use and longer survival in GBM patients. Due to the small number of patients and retrospective nature of the study, further work is needed to understand the role of perioperative statins in GBM patients. PMID:27396375

  4. Infantile Amnesia across the Years: A 2-Year Follow-Up of Children's Earliest Memories

    ERIC Educational Resources Information Center

    Peterson, Carole; Warren, Kelly L.; Short, Megan M.

    2011-01-01

    Although infantile amnesia has been investigated for many years in adults, only recently has it been investigated in children. This study was a 2-year follow-up and extension of an earlier study. Children (4-13 years old) were asked initially and 2 years later for their earliest 3 memories. At follow-up, their age at the time of these memories…

  5. Chief Student Affairs Officers in 2-Year Colleges: Their Demographics and Educational Backgrounds

    ERIC Educational Resources Information Center

    Keim, Marybelle C.

    2008-01-01

    The purpose of this study was to determine demographics and educational backgrounds of chief student affairs officers (CSAOs) in public 2-year colleges. Using systematic sampling techniques, 300 2-year colleges were selected from the AACC Membership Directory for inclusion in the study. Each college's website was visited to determine the name of…

  6. The Role of 2-Year Colleges in the Improving Situation of Hispanic Postsecondary Education

    ERIC Educational Resources Information Center

    Gonzalez, Arturo; Hilmer, Michael J.

    2006-01-01

    During the past two decades 2-year colleges have become an increasingly important part of the American higher education system, especially for Hispanics who are disproportionately likely to start their careers in 2-year colleges. Given that today's economy rewards college attendance more than every before [Bound & Johnson (1992). "The…

  7. 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

  8. Adverse Events during 2 Years of Daily Wear of Silicone Hydrogels in Children

    PubMed Central

    Sankaridurg, Padmaja; Chen, Xiang; Naduvilath, Thomas; de la Jara, Percy Lazon; Lin, Zhi; Li, Li; Smith, Earl L.; Ge, Jian; Holden, Brien A.

    2015-01-01

    Purpose Type and incidence of adverse events and rate of discontinuations for 2 years of daily wear with silicone hydrogel contact lenses in Chinese children with myopia. Methods Two hundred forty children aged 7 to 14 years were enrolled in a prospective randomized clinical trial from November 2008 to April 2009. Children with myopia of up to −3.50 diopters (D) spherical equivalent with astigmatism less than or equal to −0.75 D were randomized to one commercial and three experimental lens designs of Lotrafilcon B silicone hydrogel lenses (four groups) used bilaterally on a daily wear, monthly replacement schedule. The main outcome measures were incidence per 100 patient-years (incidence, in percentage) of adverse events and rate of discontinuations. Results There were no events of microbial keratitis. Fifty-five adverse events (incidence, 14.2%) were seen. There were also 12 recurrent events. The type and incidence percentage were contact lens papillary conjunctivitis (16 events, 4.1%), superior epithelial arcuate lesions (SEALs, six events, 1.5%), corneal erosions (eight events, 2.1%), infiltrative keratitis (five events, 1.3%), asymptomatic infiltrative keratitis (seven events, 1.8%), and asymptomatic infiltrates (13 events, 3.42%). There were differences in the incidence of SEALs between groups (p = 0.023), with the incidence of SEALs being greater with one of the experimental designs. No event resulted in any vision loss. Seventy participants (29.2%) discontinued, with one-third (26 participants, 10.8%) occurring in the first month of lens wear. Discomfort and non–lens-related reasons such as safety concern and disinterest were frequently cited reasons for discontinuations. Conclusions Adverse events with daily wear of silicone hydrogels in children were mainly mechanical in nature, and significant infiltrative events were few. The large number of dropouts in the early days of lens wear and their reasons for discontinuation suggest that adaptation and

  9. 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.

  10. Patterns of fatigue and its correlates over the first 2 years after traumatic brain injury.

    PubMed

    Bushnik, Tamara; Englander, Jeffrey; Wright, Jerry

    2008-01-01

    This study used a prospective longitudinal design to quantify fatigue and associated factors during the first 2 years after traumatic brain injury (TBI). Fifty-one individuals were assessed at 3 time points: within the first 6, 12, and 18-24 months after TBI. Self-reported fatigue improved during the first year, as did pain, sleep quality, cognitive independence, and involvement in productive activity. Further changes up to 2 years after TBI were not observed. The subset of individuals who reported significant increases in fatigue over the first 2 years demonstrated poorer outcomes in cognition, motor symptoms, and general functioning than those with decreased or stable fatigue. PMID:18219232

  11. Enhancing tumor apparent diffusion coefficient histogram skewness stratifies the postoperative survival in recurrent glioblastoma multiforme patients undergoing salvage surgery.

    PubMed

    Zolal, Amir; Juratli, Tareq A; Linn, Jennifer; Podlesek, Dino; Sitoci Ficici, Kerim Hakan; Kitzler, Hagen H; Schackert, Gabriele; Sobottka, Stephan B; Rieger, Bernhard; Krex, Dietmar

    2016-05-01

    Objective To determine the value of apparent diffusion coefficient (ADC) histogram parameters for the prediction of individual survival in patients undergoing surgery for recurrent glioblastoma (GBM) in a retrospective cohort study. Methods Thirty-one patients who underwent surgery for first recurrence of a known GBM between 2008 and 2012 were included. The following parameters were collected: age, sex, enhancing tumor size, mean ADC, median ADC, ADC skewness, ADC kurtosis and fifth percentile of the ADC histogram, initial progression free survival (PFS), extent of second resection and further adjuvant treatment. The association of these parameters with survival and PFS after second surgery was analyzed using log-rank test and Cox regression. Results Using log-rank test, ADC histogram skewness of the enhancing tumor was significantly associated with both survival (p = 0.001) and PFS after second surgery (p = 0.005). Further parameters associated with prolonged survival after second surgery were: gross total resection at second surgery (p = 0.026), tumor size (0.040) and third surgery (p = 0.003). In the multivariate Cox analysis, ADC histogram skewness was shown to be an independent prognostic factor for survival after second surgery. Conclusion ADC histogram skewness of the enhancing lesion, enhancing lesion size, third surgery, as well as gross total resection have been shown to be associated with survival following the second surgery. ADC histogram skewness was an independent prognostic factor for survival in the multivariate analysis. PMID:26830088

  12. Double half-cone flap umbilicoplasty for proboscoid umbilical hernia in a 2 years old child with satisfactory results 2 years later

    PubMed Central

    Ashu, Eseme Ebai; Leroy, Guifo Marc; Aristide, Bang Guy; Joss, Bitang Mafok Louis; Bonaventure, Jemea; Patrick, Savom Eric; Myriam, Fotso Guegne

    2015-01-01

    Surgical repair of large umbilical hernias may present a challenging surgical problem; standard surgical techniques have proven to be inadequate for both closing the fascial defect of the umbilicus and providing a satisfactory cosmetic result. We describe here a case of double half-cone flap umbilicoplasty that was performed in a 2 years old boy. The case of a 2 years old child with proboscoid umbilical hernia. The protruding umbilical skin was excised sharply by two V-shaped cuts leaving two half cones, a short cephalic (0.5cm) and a long caudal (1cm). A classic herniotomy was carried out, with repair of the facial defect. The caudal half cone was sutured from its apex till half it's length upon itself with interrupted sutures and it was anchored deeply to the fascia. Then we inverted the cephalic half cone which was sutured to the caudal cone to form the new umbilicus. The early result was excellent with no complications and the result after 2years revealed a cosmetically satisfactory shape of the umbilicus. this technique provides a good solution for reconstruction of the protruding umbilical skin and it is easy to learn, easy to be taught and perform in surgical environments and may be applicable for any kind of umbilical reconstruction. PMID:26664545

  13. Reactions Following Completion of 1 and 2 Year Multidrug Therapy (MDT)

    PubMed Central

    Balagon, Ma. Victoria F.; Gelber, Robert H.; Abalos, Rodolfo M.; Cellona, Roland V.

    2010-01-01

    We evaluated the incidence, severity, and duration of reactional states in 139 multibacillary (MB) leprosy patients in the first 2 years after the completion of the 1 year regimen of multidrug therapy (MDT) currently recommended by the World Health Organization (WHO) and compared those findings with 295 MB leprosy patients treated with the same regimen previously recommended for 2 years. During the first year after the completion of 1 year MDT, patients experienced 1 or more reactional states 27% of the time, the vast majority being lepra type 1 reactions (reversal reactions, RR), whereas patients who received 2 year MDT experienced a reactional state during that time period only 8% of the time (P < 0.001). Furthermore, during the first year after the completion of therapy, and during the first 2 years, both the number of reactional states and reversal reactions were significantly (P ≤ 0.004) more frequent, severe, of longer duration, and more commonly associated with neuritis. PMID:20810832

  14. 75 FR 60172 - Proposed Information Collection (Gravesite Reservation Survey (2 Year)) Activity: Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-29

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF VETERANS AFFAIRS Proposed Information Collection (Gravesite Reservation Survey (2 Year)) Activity: Comment Request... Paperwork Reduction Act (PRA) of 1995, Federal agencies are required to publish notice in the...

  15. 78 FR 68909 - Proposed Information Collection (Gravesite Reservation Survey (2 Year)) Activity: Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-15

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF VETERANS AFFAIRS Proposed Information Collection (Gravesite Reservation Survey (2 Year)) Activity: Comment Request... Paperwork Reduction Act (PRA) of 1995, Federal agencies are required to publish notice in the...

  16. Treatment of a Circadian Rhythm Disturbance in a 2-Year-Old Blind Child.

    ERIC Educational Resources Information Center

    Mindell, J. A.; And Others

    1996-01-01

    The use of sleep scheduling and a daytime routine for the treatment of circadian rhythm disorder was found helpful in decreasing a blind 2-year old's nighttime wake periods and daytime sleepiness. (DB)

  17. Many Kidney Transplant Patients Land in ER Within 2 Years: Study

    MedlinePlus

    ... news/fullstory_157959.html Many Kidney Transplant Patients Land in ER Within 2 Years: Study Findings show need to coordinate care after organ transplant, researcher says To use the sharing features on this page, please enable ...

  18. Survival analysis of patients on maintenance hemodialysis.

    PubMed

    Chandrashekar, A; Ramakrishnan, S; Rangarajan, D

    2014-07-01

    Despite the continuous improvement of dialysis technology and pharmacological treatment, mortality rates for dialysis patients are still high. A 2-year prospective study was conducted at a tertiary care hospital to determine the factors influencing survival among patients on maintenance hemodialysis. 96 patients with end-stage renal disease surviving more than 3 months on hemodialysis (8-12 h/week) were studied. Follow-up was censored at the time of death or at the end of 2-year study period, whichever occurred first. Of the 96 patients studied (mean age 49.74 ± 14.55 years, 75% male and 44.7% diabetics), 19 died with an estimated mortality rate of 19.8%. On an age-adjusted multivariate analysis, female gender and hypokalemia independently predicted mortality. In Cox analyses, patient survival was associated with delivered dialysis dose (single pool Kt/V, hazard ratio [HR] =0.01, P = 0.016), frequency of hemodialysis (HR = 3.81, P = 0.05) and serum albumin (HR = 0.24, P = 0.005). There was no significant difference between diabetes and non-diabetes in relation to death (Relative Risk = 1.109; 95% CI = 0.49-2.48, P = 0.803). This study revealed that mortality among hemodialysis patients remained high, mostly due to sepsis and ischemic heart disease. Patient survival was better with higher dialysis dose, increased frequency of dialysis and adequate serum albumin level. Efforts at minimizing infectious complications, preventing cardiovascular events and improving nutrition should increase survival among hemodialysis patients. PMID:25097332

  19. Survival analysis of patients on maintenance hemodialysis

    PubMed Central

    Chandrashekar, A.; Ramakrishnan, S.; Rangarajan, D.

    2014-01-01

    Despite the continuous improvement of dialysis technology and pharmacological treatment, mortality rates for dialysis patients are still high. A 2-year prospective study was conducted at a tertiary care hospital to determine the factors influencing survival among patients on maintenance hemodialysis. 96 patients with end-stage renal disease surviving more than 3 months on hemodialysis (8-12 h/week) were studied. Follow-up was censored at the time of death or at the end of 2-year study period, whichever occurred first. Of the 96 patients studied (mean age 49.74 ± 14.55 years, 75% male and 44.7% diabetics), 19 died with an estimated mortality rate of 19.8%. On an age-adjusted multivariate analysis, female gender and hypokalemia independently predicted mortality. In Cox analyses, patient survival was associated with delivered dialysis dose (single pool Kt/V, hazard ratio [HR] =0.01, P = 0.016), frequency of hemodialysis (HR = 3.81, P = 0.05) and serum albumin (HR = 0.24, P = 0.005). There was no significant difference between diabetes and non-diabetes in relation to death (Relative Risk = 1.109; 95% CI = 0.49-2.48, P = 0.803). This study revealed that mortality among hemodialysis patients remained high, mostly due to sepsis and ischemic heart disease. Patient survival was better with higher dialysis dose, increased frequency of dialysis and adequate serum albumin level. Efforts at minimizing infectious complications, preventing cardiovascular events and improving nutrition should increase survival among hemodialysis patients. PMID:25097332

  20. Clinicopathologic and Survival Characteristics of Malignant Pleural Mesothelioma Registered in Hospital Cancer Registry

    PubMed Central

    Najmi, Kosar; Khosravi, Adnan; Seifi, Sharare; Chaibakhsh, Samira; Radmand, Golnar; Khodadad, Kian

    2014-01-01

    Background Malignant pleural mesothelioma (MPM) is a rare but fatal thoracic tumor, which in the majority of patients is caused by prolonged exposure to asbestos fibers. We aimed at presenting clinicopathological and treatment outcomes of 60 patients of MPM registered in our hospital cancer registry. Materials and Methods Demographic characteristics of patients, exposure to asbestos, smoking habit, their clinicopathologic characteristics and survival analysis were described. Results Sixty patients had MPM. Forty patients (66.7%) were men. The mean age of patients was 55.8±11 years. Chest pain and dyspnea were the most prevalent symptoms (31.7%, and 30%, respectively). Thirty-six (61.7%) patients reported asbestos exposure. The median survival and Progression free survival (PFS) were 10.5 months (0.95CI=9.22-11.78) and 7.57 months (0.95CI=5.68-9.45), respectively. In multivariate analysis, exposure to asbestos and epithelioid subtype significantly extended the survival time. Bilateral involvement, high blood level of LDH and platelet count ≥400,000 significantly shortened the overall survival. Conclusion MPM is still an important health problem in Iran. Given the aforementioned results, developing a national program to eliminate asbestos-related diseases according to the world health organization (WHO) recommendation is necessary. PMID:25506370

  1. Long-Term Outcome of a Hepatocellular Carcinoma 71/2 Years After Surgery and Repeated Radiofrequency Ablation: Case Report and Review of the Literature

    SciTech Connect

    Thanos, L. Mylona, S.; Nikita, A.; Ptohis, N.; Kelekis, D.A.

    2007-04-15

    An interesting case is presented of a 78-year-old patient with cirrhosis who was managed with combined treatment (surgery and radiofrequency (RF) ablation) for hepatocellular carcinoma (HCC) and has survived for 71/2 years. Elevation of the {alpha}-FP (alpha-fetoprotein) levels was noted 2 years after surgery. CT demonstrated two lesions: one central at the remaining right liver lobe, and the other at the excision site. Biopsy of the lesions confirmed the diagnosis of HCC for both of them. RF ablation of these two lesions was performed in one session with technical success. Four and a half years after the first RF ablation a new recurrence was demonstrated at the CT follow-up control. RF ablation was again applied successfully. The imaging findings and the therapeutic percutaneous management of this patient along with the natural course of HCC and its recurrence are discussed, and the literature concerning risk factors is reviewed.

  2. Occupational Survival Skills

    ERIC Educational Resources Information Center

    Leach, James A.; Nelson, Robert E.

    1978-01-01

    The author describes a set of twelve curriculum modules called "Occupational Survival Skills" relating to the "human" aspects of work organizations. The modules were based on information from opinion surveys of workers, students, parents, and teachers on what occupational survival skills are and how to teach them. (MF)

  3. Prospective study of cognitive function in children receiving whole-brain radiotherapy and chemotherapy: 2-year results

    SciTech Connect

    Packer, R.J.; Sutton, L.N.; Atkins, T.E.; Radcliffe, J.; Bunin, G.R.; D'Angio, G.; Siegel, K.R.; Schut, L. )

    1989-05-01

    As survival rates have risen for children with malignant primary brain tumors, so has the concern that many survivors have significant permanent cognitive deficits. Cranial irradiation (CRT) has been implicated as the major cause for cognitive dysfunction. To clarify the etiology, incidence, and severity of intellectual compromise in children with brain tumors after CRT, a prospective study was undertaken comparing the neuropsychological outcome in 18 consecutive children with malignant brain tumors treated with CRT to outcome in 14 children harboring brain tumors in similar sites in the nervous system who had not received CRT. Children with cortical or subcortical brain tumors were not eligible for study. Neuropsychological testing was performed after surgery prior to radiotherapy, after radiotherapy, and at 1- and 2-year intervals thereafter. Children who had received CRT had a mean full-scale intelligence quotient (FSIQ) of 105 at diagnosis which fell to 91 by Year 2. Similar declines were noted in their performance intelligence quotient (IQ) and verbal IQ. After CRT, patients demonstrated a statistically significant decline from baseline in FSIQ (p less than 0.02) and verbal IQ (p less than 0.04). Children who had not received CRT did not demonstrate a fall in any cognitive parameter over time. The decline between baseline testing and testing performed at Year 2 in patients who had CRT was inversely correlated with age (p less than 0.02), as younger children demonstrated the greatest loss of intelligence. Children less than 7 years of age at diagnosis had a mean decline in FSIQ of 25 points 2 years posttreatment. No other clinical parameter correlated with the overall IQ or decline in IQ. After CRT, children demonstrated a wide range of dysfunction including deficits in fine motor, visual-motor, and visual-spatial skills and memory difficulties.

  4. Survival of young American alligators on a Florida lake

    USGS Publications Warehouse

    Woodward, A.R.; Hines, T.C.; Abercrombie, C.L.; Nichols, J.D.

    1987-01-01

    A capture-recapture study was conducted on Orange Lake, Florida, from 1979 through 1984 to estimate survival rates of young in an American alligator (Alligator mississippiensis) populations. Hatchlings remained together in sibling groups (pods) for at least their 1st year and then began to disperse during their 2nd spring and summer. Mortality through mid-November of their 1st year was negligible. Jolly-Seber (JS) survival estimates of hatchlings for 6 and 12 months were 76 and 41%, respectively. The 2-year JS estimate for the 1980 cohort was 8%. Minimum-Known-Alive (MKA) survival values were 72 and 46% of JS estimates for 6 months and 1 year of age. Survival during the 2nd 6 months of life (spring-summer) tended to be lower than survival during the 1st 6 months (fall-winter).

  5. Association of clinical and pathological variables with survival in thymoma.

    PubMed

    Aydiner, Adnan; Toker, Alper; Sen, Fatma; Bicakci, Ercan; Saglam, Esra Kaytan; Erus, Suat; Eralp, Yesim; Tas, Faruk; Oral, Ethem Nezih; Topuz, Erkan; Dilege, Sukru

    2012-09-01

    Our aim was to evaluate clinical and pathological features in prognosis of thymoma patients with particular emphasis on patients with myasthenia gravis (MG). From 1995 to 2010, 140 thymoma patients (women/men: 63/77) with a median age of 46 years (11-80 years) were admitted to our institution. According to World Health Organization (WHO), there were 23 (17%) type A, 12 (9%) type AB, 24 (17%) type B1, 42 (31%) type B2 and 36 (26%) type B3. The distribution of Masaoka stages I, II, III and IV was 24 (17%), 71 (51%), 18 (13%) and 27 (19%), respectively. MG coexisted in 61% of patients. After a mean follow-up of 34 months (1-158 months), 102 (73%) patients are alive and well while 14 (10%) are alive with disease. Twenty-three patients (16%) have died, only 9 died of thymoma. In univariate analyses, completeness of resection (P < .001), WHO histology (P = .008), Masaoka stage (P < .001) and MG (P = .002) were significant prognostic factors for progression-free survival (PFS). Young age (P = .008); Masaoka stages 1 and 2 (P = .039); WHO types A, AB and B1 (P = .031); complete resection (P = .024) and presence of MG (P = .05) significantly correlated with overall survival (OS). In multivariate analysis, Masaoka stages 1 and 2 (P = .038) and presence of MG (P = .01) were significantly correlated with a longer PFS; MG (P = .021) and WHO subtype (P = .022) were found to be significant prognostic factors for OS. Adjuvant radiotherapy improved neither OS nor PFS in completely resected stage 2 thymoma. Masaoka staging, WHO and MG are major determinants of prognosis in Turkish thymoma patients. Additionally, radiotherapy did not provide survival advantage to stage 2 patients with complete resection. PMID:22057358

  6. Sex Steroid Hormone Receptor Expression Affects Ovarian Cancer Survival12

    PubMed Central

    Jönsson, Jenny-Maria; Skovbjerg Arildsen, Nicolai; Malander, Susanne; Måsbäck, Anna; Hartman, Linda; Nilbert, Mef; Hedenfalk, Ingrid

    2015-01-01

    Background and Aims: Although most ovarian cancers express estrogen (ER), progesterone (PR), and androgen (AR) receptors, they are currently not applied in clinical decision making. We explored the prognostic impact of sex steroid hormone receptor protein and mRNA expression on survival in epithelial ovarian cancer. Methods: Immunohistochemical stainings for ERα, ERβ, PR, and AR were assessed in relation to survival in 118 serous and endometrioid ovarian cancers. Expression of the genes encoding the four receptors was studied in relation to prognosis in the molecular subtypes of ovarian cancer in an independent data set, hypothesizing that the expression levels and prognostic impact may differ between the subtypes. Results: Expression of PR or AR protein was associated with improved 5-year progression-free (P = .001 for both) and overall survival (P < .001 for both, log-rank test). ERα and ERβ did not provide prognostic information. Patients whose tumors coexpressed PR and AR had the most favorable prognosis, and this effect was retained in multivariable analyses. Analyses of the corresponding genes using an independent data set revealed differences among the molecular subtypes, but no clear relationship between high coexpression of PGR and AR and prognosis. Conclusions: A favorable outcome was seen for patients whose tumors coexpressed PR and AR. Gene expression data suggested variable effects in the different molecular subtypes. These findings demonstrate a prognostic role for PR and AR in ovarian cancer and support that tumors should be stratified based on molecular as well as histological subtypes in future studies investigating the role of endocrine treatment in ovarian cancer. PMID:26500033

  7. Immunologic Autograft Engineering and Survival in Non-Hodgkin Lymphoma.

    PubMed

    Porrata, Luis F; Burgstaler, Edwin A; Winters, Jeffrey L; Jacob, Eapen K; Gastineau, Dennis A; Suman, Vera J; Inwards, David J; Ansell, Stephen M; Micallef, Ivana N; Johnston, Patrick B; Nevala, Wendy; Markovic, Svetomir N

    2016-06-01

    Retrospective studies have reported that the collected and infused autograft absolute lymphocyte count (A-ALC) affects clinical outcomes after autologous peripheral hematopoietic stem cell transplantation (APHSCT). We hypothesized that manipulation of the apheresis machine to target a higher A-ALC dose would translate into prolonged progression-free survival (PFS) in patients with non-Hodgkin lymphoma (NHL) undergoing APHSCT. Between December 2007 and October 2010, we performed a double-blind, phase III, randomized study randomly assigning 122 patients with NHL to undergo collection with the Fenwal Amicus Apheresis system with our standard settings (mononuclear cells offset of 1.5 and RBC offset of 5.0) or at modified settings (mononuclear cells offset of 1.5 and RBC of 6.0). The primary endpoint was PFS. Neither PFS (hazard ratio [HR] of modified to standard, 1.13; 95% confidence interval [CI], .62 to 2.08; P = .70) nor overall survival (OS) (HR modified to standard, .85; 95% CI, .39 to 1.86; P = .68) were found to differ by collection method. Collection of A-ALC between both methods was similar. Both PFS (P = .0025; HR, 2.77; 95% CI, 1.39 to 5.52) and OS (P = .004; HR, 3.38; 95% CI, 1.27 to 9.01) were inferior in patients infused with an A-ALC < .5 × 10(9) lymphocytes/kg compared with patients infused with an A-ALC ≥ .5 × 10(9) lymphocytes/kg, regardless of the method of collection. We did not detect significant differences in clinical outcomes or in the A-ALC collection between the modified and the standard Fenwal Amicus settings; however, despite physician discretion on primary number of collections and range of cells infused, higher A-ALC infused dose were associated with better survival after APHSCT. PMID:26826432

  8. Impact of Living Environment on 2-Year Mortality in Elderly Maintenance Hemodialysis Patients

    PubMed Central

    Huang, Wen-Hung; Lin, Ja-Liang; Lin-Tan, Dan-Tzu; Chen, Kuan-Hsing; Hsu, Ching-Wei; Yen, Tzung-Hai

    2013-01-01

    Background Studies on risk factors of mortality in elderly patients with hemodialysis usually focus on comorbidities, nutrition, and inflammation. Discussion on the correlation between living environment and mortality of these patients is limited. Methods A total of 256 elderly hemodialysis patients participated in this 2-year prospective observational study. The subjects were divided into 2 subgroups based on whether they were living in Taipei Basin (n = 63) or not (n = 193). Demographic, hematological, nutritional, inflammatory, biochemical, and dialysis-related data were obtained for cross-sectional analysis. Causes of death and mortality rates were also analyzed for each subgroup. Results Patients in the basin group had a higher incidence of combined protein-energy wasting and inflammation than those in the around basin group. At the end of the 2-year follow-up, 68 patients had died. Univariate binary logistic regression analysis revealed that a very advanced age, basin group, serum albumin levels, serum creatinine levels, non-anuria, and the complications of stroke and CAD were associated with 2-year mortality. Meanwhile, log high-sensitivity C-reactive protein (hs-CRP) levels were not associated with 2-year mortality. Multivariate Cox regression analysis revealed that basin group, serum albumin levels, and the complications of stroke and CAD were significant risk factors for 2-year mortality in these patients. Conclusion The results of this study indicate that factors such as living in the Taipei Basin with higher air pollutant levels in elderly hemodialysis patients is associated with protein-energy wasting and inflammation, as well as 2-year mortality. These findings suggest that among this population, living environment is as important as comorbidities and nutrition. Furthermore, air pollution should be getting more attention especially in the overcrowding Basin topography. PMID:24058552

  9. 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

  10. 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

  11. Cell cycle and aging, morphogenesis, and response to stimuli genes are individualized biomarkers of glioblastoma progression and survival

    PubMed Central

    2011-01-01

    Background Glioblastoma is a complex multifactorial disorder that has swift and devastating consequences. Few genes have been consistently identified as prognostic biomarkers of glioblastoma survival. The goal of this study was to identify general and clinical-dependent biomarker genes and biological processes of three complementary events: lifetime, overall and progression-free glioblastoma survival. Methods A novel analytical strategy was developed to identify general associations between the biomarkers and glioblastoma, and associations that depend on cohort groups, such as race, gender, and therapy. Gene network inference, cross-validation and functional analyses further supported the identified biomarkers. Results A total of 61, 47 and 60 gene expression profiles were significantly associated with lifetime, overall, and progression-free survival, respectively. The vast majority of these genes have been previously reported to be associated with glioblastoma (35, 24, and 35 genes, respectively) or with other cancers (10, 19, and 15 genes, respectively) and the rest (16, 4, and 10 genes, respectively) are novel associations. Pik3r1, E2f3, Akr1c3, Csf1, Jag2, Plcg1, Rpl37a, Sod2, Topors, Hras, Mdm2, Camk2g, Fstl1, Il13ra1, Mtap and Tp53 were associated with multiple survival events. Most genes (from 90 to 96%) were associated with survival in a general or cohort-independent manner and thus the same trend is observed across all clinical levels studied. The most extreme associations between profiles and survival were observed for Syne1, Pdcd4, Ighg1, Tgfa, Pla2g7, and Paics. Several genes were found to have a cohort-dependent association with survival and these associations are the basis for individualized prognostic and gene-based therapies. C2, Egfr, Prkcb, Igf2bp3, and Gdf10 had gender-dependent associations; Sox10, Rps20, Rab31, and Vav3 had race-dependent associations; Chi3l1, Prkcb, Polr2d, and Apool had therapy-dependent associations. Biological processes

  12. 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.

  13. Survival Skills: Secondary.

    ERIC Educational Resources Information Center

    Curriculum Review, 1979

    1979-01-01

    Reviewed are five programs (textbooks, audiovisual materials, workbooks, video-cassettes) designed to improve academic survival skills in secondary students. Content emphasis, reading level, rationale, objectives, organization, instructional method, student evaluation, physical features, and recommendations are listed for each. (KC)

  14. Survival at Isle Royale.

    ERIC Educational Resources Information Center

    Ballone, Lena M.

    2001-01-01

    Describes a simulation based on the popular television show "Survivor" in which students work in groups and study physiological needs for human survival. Focuses on communication skills, problem solving, and cooperative learning. (YDS)

  15. 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.

  16. 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.

  17. Surviving Operation Desert Storm

    SciTech Connect

    Vice, J. )

    1992-08-01

    The importance of aircraft survivability during the invasion of Iraq is examined detailing anecdotal evidence of susceptibility and vulnerability reduction. Among the aircraft used that were designed to be more survivable than their predecessors were the F-117, A-10, F/A-18, and the AH-64. Reduced vulnerability is incorporated into the aircraft designs in the form of damage tolerant components, redundancy, self-sealing fluid systems, and miniaturization.

  18. Survival analysis of cancer patients with multiple endpoints using global score test methodology

    NASA Astrophysics Data System (ADS)

    Zain, Zakiyah; Whitehead, John

    2014-06-01

    Progression-free survival (PFS), time-to-progression (TTP) and overall survival (OS) are examples of multiple endpoints commonly used in clinical trials of cancer patients. PFS is increasingly used as a primary endpoint in evaluation of patients with solid tumors, while multiple endpoints are often analysed independently. These endpoints are indeed correlated and it is desirable to evaluate effectiveness of treatments by means of a single parameter. In this paper, a single overall treatment effect is provided by combining the univariate score statistics for comparing treatments with respect to each survival endpoint. This global score test methodology was applied in analysis of 330 patients with an aggressive cancer, each with two endpoints recorded, T1 and T2, relating to disease progression and death respectively. The values of score statistics obtained from the proposed method matched closely those from the logrank test. Meanwhile, the correlations between the two score test statistics were found to be similar to those computed using the established Wei, Lin and Weissfeld method. Simulations further confirmed the consistent performance of this new method in analysis of bivariate survival data.

  19. 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

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

    PubMed

    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

  1. 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

  2. From Genesis to Infinity or from 0 to 50,000 Online Students in 2 Years.

    ERIC Educational Resources Information Center

    Weiss, April; Kennedy, Paul

    In 2 years, RMIT University (Melbourne, Australia) set up an online learning system for 50,000 students. The development of the RMIT Distributed Learning System has taken the University from a cottage industry model to a fully fledged enterprise system for flexible online learning, integrated with the University's student administration system and…

  3. Behavior Predictors of Language Development over 2 Years in Children with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Bopp, Karen D.; Mirenda, Pat; Zumbo, Bruno D.

    2009-01-01

    Purpose: This exploratory study examined predictive relationships between 5 types of behaviors and the trajectories of vocabulary and language development in young children with autism over 2 years. Method: Participants were 69 children with autism assessed using standardized measures prior to the initiation of early intervention (T1) and 6 months…

  4. Weight and Weight-Related Behaviors among 2-Year College Students

    ERIC Educational Resources Information Center

    Nanney, Marilyn S.; Lytle, Leslie A.; Farbakhsh, Kian; Moe, Stacey G.; Linde, Jennifer A.; Gardner, Jolynn K.; Laska, Melissa N.

    2015-01-01

    Objectives and Participants: The purpose of this article is to describe weight indicators and weight-related behaviors of students enrolled in 2-year colleges, including sex differences. Methods: During Fall 2011 and Spring 2012, 441 students from 3 Minnesota community colleges enrolled in the Choosing Healthy Options in College Environments and…

  5. Sexual Identity, Attractions, and Behavior among Young Sexual-Minority Women over a 2-Year Period.

    ERIC Educational Resources Information Center

    Diamond, Lisa M.

    2000-01-01

    Examined sexual identities, attractions, and behaviors of sexual-minority women in 2-year follow-up of women first interviewed at 16-23 years. Found half the participants had changed sexual-minority orientations more than once; one- third changed identities since the first interview. Found changes in sexual attractions were larger among bisexuals…

  6. Slowly but Surely: Adverbs Support Verb Learning in 2-Year-Olds

    ERIC Educational Resources Information Center

    Syrett, Kristen; Arunachalam, Sudha; Waxman, Sandra R.

    2014-01-01

    To acquire the meanings of verbs, toddlers make use of the surrounding linguistic information. For example, 2-year-olds successfully acquire novel transitive verbs that appear in semantically rich frames containing content nouns ("The boy is gonna pilk a balloon"), but they have difficulty with pronominal frames ("He is gonna pilk…

  7. THE PSYCHOLOGICAL IMPACT OF THE PUBLIC 2-YEAR COLLEGE ON CERTAIN NONINTELLECTUAL FUNCTIONS.

    ERIC Educational Resources Information Center

    PLANT, WALTER T.; TELFORD, CHARLES W.

    THIS STUDY SOUGHT TO DETERMINE IF THERE ARE SIGNIFICANT CHANGES IN SELECTED PERSONALITY TRAITS, IDEOLOGIES, AND VALUES OF STUDENTS WHO ATTEND A 2-YEAR PUBLIC JUNIOR COLLEGE. A BATTERY OF PSYCHOLOGICAL TESTS WAS ADMINISTERED TO ALL PERSONS APPLYING FOR ADMISSION AS COLLEGE FRESHMEN FOR THE FALL SEMESTER OF 1960 AT ONE OF SIX CALIFORNIA PUBLIC…

  8. Emotionally Focused Interventions for Couples with Chronically Ill Children: A 2-Year Follow-Up

    ERIC Educational Resources Information Center

    Cloutier, Paula F.; Manion, Ian G.; Walker, Jan Gordon; Johnson, Susan M.

    2002-01-01

    Couples with chronically ill children are particularly at risk for experiencing marital distress. The study presented here is a 2-year follow-up of a randomized control trial that assessed the efficacy of Emotionally Focused Therapy (EFT) in decreasing marital distress in a sample of couples with a chronically ill child. Thirteen couples with…

  9. Prenatal Cocaine Exposure: A Comparison of 2-Year-Old Children in Parental and Nonparental Care

    ERIC Educational Resources Information Center

    Brown, Josephine V.; Bakeman, Roger; Coles, Claire D.; Platzman, Kathleen A.; Lynch, Mary Ellen

    2004-01-01

    Effects of prenatal cocaine exposure and parental versus nonparental care on outcome at 2 years of age were examined. The sample included 83 cocaine-exposed and 63 nonexposed children and their caregivers; 49 and 34 of the cocaine-exposed children experienced parental and nonparental care, respectively. Prenatal drug exposure was not related…

  10. Phonetic Modification of Vowel Space in Storybook Speech to Infants up to 2 Years of Age

    ERIC Educational Resources Information Center

    Burnham, Evamarie B.; Wieland, Elizabeth A.; Kondaurova, Maria V.; McAuley, J. Devin; Bergeson, Tonya R.; Dilley, Laura C.

    2015-01-01

    Purpose: A large body of literature has indicated vowel space area expansion in infant-directed (ID) speech compared with adult-directed (AD) speech, which may promote language acquisition. The current study tested whether this expansion occurs in storybook speech read to infants at various points during their first 2 years of life. Method: In 2…

  11. AGU awarded grant to establish program on engaging 2-year-college students in research

    NASA Astrophysics Data System (ADS)

    Asher, Pranoti; Adamec, Bethany Holm

    2012-03-01

    Students at 2-year colleges are a critical part of the future Earth and space science workforce, and undergraduate research experiences provide a hook to retain and ultimately to graduate students in the field. AGU was awarded a planning grant by the U.S. National Science Foundation Directorate for Geosciences (Opportunities for Enhancing Diversity in the Geosciences award 1201578) to help launch a new initiative concerning these issues; education and public outreach staff are the principal investigators. This new initiative, titled Unique Research Experiences for Two-Year College Faculty and Students (URECAS), will begin with a planning workshop this summer (11-13 July). The workshop will bring together faculty from 2-year colleges, 4-year colleges and universities, and representatives from professional societies and federal organizations to learn more about how to support 2-year-college faculty and students engaged in Earth and space science research and to discuss the development of a program to strengthen the role of 2-year-college Earth and space science students in the future workforce

  12. Administration of high-dose interleukin-2 in a 2-year-old with metastatic melanoma.

    PubMed

    Bernhardt, M Brooke; Hicks, M John; Pappo, Alberto S

    2009-12-15

    Malignant melanoma is rare in pediatrics, and therapies for patients with disseminated disease have not been well studied. This report describes our experience with the use of high-dose interleukin 2 (aldesleukin, IL-2) in a 2-year-old child with metastatic melanoma and describes our approach for the administration of this agent to young patients. PMID:19731326

  13. Antecedents of Compliance in 2-Year-Olds From a High-Risk Sample.

    ERIC Educational Resources Information Center

    Erickson, Martha Farrell; Crichton, Leslie

    In order to identify antecedents of infant's compliance with mothers' directions on how to solve four tasks (graded in terms of stressfulness to the infant), 194 high-risk mothers and their 2-year-old children were observed on videotape and assessed with a six-point rating scale. Data collected prenatally and postnatally at 3, 6, 12 and 18 months…

  14. How Are 2-Year US Colleges Addressing Student Alcohol Use and Related Problems?

    ERIC Educational Resources Information Center

    Lenk, Kathleen M.; Nelson, Toben F.; Erickson, Darin J.; Toomey, Traci L.

    2015-01-01

    A considerable amount of attention and research has been dedicated to addressing alcohol use and related problems among students at 4-year colleges; however, less attention has been given to alcohol-related issues among students at 2-year technical/community colleges. This article describes research that expands on a study by Chiauzzi and…

  15. How Joint Attention Relates to Cooperation in 1- and 2-Year-Olds

    ERIC Educational Resources Information Center

    Wu, Zhen; Pan, Jingtong; Su, Yanjie; Gros-Louis, Julie

    2013-01-01

    Joint attention has been suggested to contribute to children's development of cooperation; however, few empirical studies have directly tested this hypothesis. Children aged 1 and 2 years participated in two joint action activities to assess their cooperation with an adult partner, who stopped participating at a specific moment during the…

  16. Students with Disabilities at 2-Year Institutions in the United States: Factors Related to Success

    ERIC Educational Resources Information Center

    Mamiseishvili, Ketevan; Koch, Lynn C.

    2012-01-01

    This study used data from the Beginning Postsecondary Students Longitudinal Study to examine the demographic and in-college characteristics of students with disabilities at 2-year institutions, identify the types of educational services available to them, and determine how students' disability conditions and their selected demographic and…

  17. MST with Conduct Disordered Youth in Sweden: Costs and Benefits after 2 Years

    ERIC Educational Resources Information Center

    Olsson, Tina M.

    2010-01-01

    Objectives: The purpose of this study was to investigate the costs and benefits associated with multisystemic therapy (MST) for conduct disordered youth, 2 years following intake. Methods: The study employed a secondary analysis of 156 youth enrolled in a randomized trial assessing the psychosocial and behavioral outcomes of MST. Results: MST cost…

  18. Improving Social Competence through Emotion Knowledge in 2-Year-Old Children: A Pilot Study

    ERIC Educational Resources Information Center

    Giménez-Dasí, Marta; Fernández-Sánchez, Marta; Quintanilla, Laura

    2015-01-01

    Research Findings: The goal of this study was to determine the efficacy of an educational intervention program to improve emotion knowledge, emotion regulation, and social competence in 2-year-old Spanish children. This study makes two original contributions because there are no validated education programs for such young children and because it…

  19. Attitudes of College Students Enrolled in 2-Year Health Care Programs towards Online Learning

    ERIC Educational Resources Information Center

    Abdulla, Dalya

    2012-01-01

    Colleges offering 2-year diplomas to high-school graduates were among the forefront leaders in online learning however studies illustrating appropriate course construction for such student populations are scarce. Pharmacy Math (MATH16532) is a core course for students enrolled in the Practical Nursing (PN) and Pharmacy Technician (PT) programs at…

  20. Cervical necrotizing fasciitis caused by Serratia marcescens in a 2 year old.

    PubMed

    Newton, Christopher L; deLEMOS, David; Abramo, Thomas J; Murrey, Allen; Noell, Courtney

    2002-12-01

    We report an unusual, life-threatening complication of producing fulminant cervical necrotizing fasciitis in a previously healthy 2-year-old girl. We reviewed the literature for necrotizing fasciitis in children and its morbidity, mortality, and treatment. This case illustrates the necessity of prompt recognition and aggressive management in patients presenting with cervical necrotizing fasciitis. PMID:12488837

  1. Myopia Control with a Novel Peripheral Gradient Soft Lens and Orthokeratology: A 2-Year Clinical Trial

    PubMed Central

    Pauné, Jaime; Morales, Hari; Armengol, Jesús; Quevedo, Lluisa; Faria-Ribeiro, Miguel; González-Méijome, José M.

    2015-01-01

    Objective. To evaluate the degree of axial elongation with soft radial refractive gradient (SRRG) contact lenses, orthokeratology (OK), and single vision (SV) spectacle lenses (control) during a period of 1 year before treatment and 2 years after treatment. Methods. This was a prospective, longitudinal, nonrandomized study. The study groups consisted of 30, 29, and 41 children, respectively. The axial length (AL) was measured during 2 years after recruitment and lens fitting. Results. The baseline refractive sphere was correlated significantly (Spearman's Rho (ρ) correlation = 0.542; P < 0.0001) with the amount of myopia progression before baseline. After 2 years, the mean myopia progression values for the SRRG, OK, and SV groups were −0.56 ± 0.51, −0.32 ± 0.53, and −0.98 ± 0.58 diopter, respectively. The results represent reductions in myopic progression of 43% and 67% for the SRRG and OK groups, respectively, compared to the SV group. The AL increased 27% and 38% less in the SRRG and OK groups, respectively compared with the SV group at the 2-year visit (P < 0.05). Axial elongation was not significantly different between SRRG and OK (P = 0.430). Conclusion. The SRRG lens significantly decreased AL elongation compared to the SV control group. The SRRG lens was similarly effective to OK in preventing myopia progression in myopic children and adolescent. PMID:26605331

  2. Generacion 1.5: A Cultural Historical Agenda for Research at the 2-Year College

    ERIC Educational Resources Information Center

    Salas, Spencer; Portes, Pedro R.; D'Amico, Mark M.; Rios-Aguilar, Cecilia

    2011-01-01

    In this article, we employ a cultural historical theoretical framework to extend understandings of how widespread 2-year college placement policies concerning English remediation potentially locate and retain U.S.-educated Latino adolescents at the margins of higher education through well-intentioned yet deficit-driven postsecondary cultural…

  3. Word Learning from Videos: More Evidence from 2-Year-Olds

    ERIC Educational Resources Information Center

    Allen, Rebekah; Scofield, Jason

    2010-01-01

    Young children are frequently exposed to examples of screen media like videos. The current studies asked whether videos would support word learning and whether word learning from videos might resemble word learning from a live speaker. In Study 1, 2-year-olds saw a video of a target image being labelled with a novel word and were later asked to…

  4. Developmental Assessment of Preterm Infants at 2 Years: Validity of Parent Reports

    ERIC Educational Resources Information Center

    Johnson, Samantha; Wolke, Dieter; Marlow, Neil

    2008-01-01

    Parental questionnaires are inexpensive alternatives to standardized testing for outcome measurement. The Parent Report of Children's Abilities has previously been revised (PARCA-R) and validated for use with very-preterm infants at 2 years of age. This study revalidated the PARCA-R for assessing cognition in a larger and more inclusive sample of…

  5. Environmental NO2 Level is Associated with 2-Year Mortality in Patients Undergoing Peritoneal Dialysis

    PubMed Central

    Lin, Jui-Hsiang; Yen, Tzung-Hai; Weng, Cheng-Hao; Huang, Wen-Hung

    2015-01-01

    Abstract An ongoing issue related to global urbanization is the association of air pollution with increased incidences of morbidity and mortality. However, no in-depth study has investigated this issue focusing on peritoneal dialysis (PD) patients. Therefore, this study assessed the effects of traffic-related air pollutants and other important mortality-associated factors on 2-year mortality in PD patients. A total of 160 PD patients were recruited in this 2-year retrospective observational study. Differences in air quality were analyzed with respect to the patients’ living areas. The PD patients were categorized into 2 groups according to high (n = 65) and low (n = 95) nitrogen dioxide (NO2) exposure. Demographic, hematological, nutritional, inflammatory, biochemical, air pollutants, and dialysis-related data were analyzed. Univariate and multivariate Cox regression analyses were used for 2-year mortality analysis. A total of 160 PD patients (38 men and 122 women) were enrolled. Fourteen patients (8.8%) died within 2 years; among them, the causes of death were infection (n = 10), malignancy (n = 1), and cardiovascular events (n = 3). Among the 10 patients who died from infection, 5, 4, and 1 died from pneumonia, PD-related peritonitis, and sepsis of unknown origin, respectively. All patients who died from pneumonia were living in high environmental NO2 exposure areas. Multivariate Cox regression analysis showed that age (hazard ratio [HR] 1.073, 95% confidence interval [CI] [1.013–1.137]; P = 0.017), white blood cell count (HR 1.41, 95% CI [1.116–1.781]; P = 0.004), log normalized protein nitrogen appearance (HR 0.0001, 95% CI [0–0.073]; P = 0.005), high cardiothoracic ratio (HR 14.28, 95% CI [1.778–114.706]; P = 0.012), and high environmental NO2 exposure (HR 3.776, 95% CI [1.143–12.47]; P = 0.029) were significantly associated with 2-year mortality. PD patients with high environmental NO2 exposure had a higher

  6. Environmental NO2 level is associated with 2-year mortality in patients undergoing peritoneal dialysis.

    PubMed

    Lin, Jui-Hsiang; Yen, Tzung-Hai; Weng, Cheng-Hao; Huang, Wen-Hung

    2015-01-01

    An ongoing issue related to global urbanization is the association of air pollution with increased incidences of morbidity and mortality. However, no in-depth study has investigated this issue focusing on peritoneal dialysis (PD) patients. Therefore, this study assessed the effects of traffic-related air pollutants and other important mortality-associated factors on 2-year mortality in PD patients.A total of 160 PD patients were recruited in this 2-year retrospective observational study. Differences in air quality were analyzed with respect to the patients' living areas. The PD patients were categorized into 2 groups according to high (n = 65) and low (n = 95) nitrogen dioxide (NO2) exposure. Demographic, hematological, nutritional, inflammatory, biochemical, air pollutants, and dialysis-related data were analyzed. Univariate and multivariate Cox regression analyses were used for 2-year mortality analysis.A total of 160 PD patients (38 men and 122 women) were enrolled. Fourteen patients (8.8%) died within 2 years; among them, the causes of death were infection (n = 10), malignancy (n = 1), and cardiovascular events (n = 3). Among the 10 patients who died from infection, 5, 4, and 1 died from pneumonia, PD-related peritonitis, and sepsis of unknown origin, respectively. All patients who died from pneumonia were living in high environmental NO2 exposure areas. Multivariate Cox regression analysis showed that age (hazard ratio [HR] 1.073, 95% confidence interval [CI] [1.013-1.137]; P = 0.017), white blood cell count (HR 1.41, 95% CI [1.116-1.781]; P = 0.004), log normalized protein nitrogen appearance (HR 0.0001, 95% CI [0-0.073]; P = 0.005), high cardiothoracic ratio (HR 14.28, 95% CI [1.778-114.706]; P = 0.012), and high environmental NO2 exposure (HR 3.776, 95% CI [1.143-12.47]; P = 0.029) were significantly associated with 2-year mortality.PD patients with high environmental NO2 exposure had a higher 2-year mortality rate

  7. Mapping Longitudinal Development of Local Cortical Gyrification in Infants from Birth to 2 Years of Age

    PubMed Central

    Li, Gang; Wang, Li; Shi, Feng; Lyall, Amanda E.; Lin, Weili; Gilmore, John H.

    2014-01-01

    Human cortical folding is believed to correlate with cognitive functions. This likely correlation may have something to do with why abnormalities of cortical folding have been found in many neurodevelopmental disorders. However, little is known about how cortical gyrification, the cortical folding process, develops in the first 2 years of life, a period of dynamic and regionally heterogeneous cortex growth. In this article, we show how we developed a novel infant-specific method for mapping longitudinal development of local cortical gyrification in infants. By using this method, via 219 longitudinal 3T magnetic resonance imaging scans from 73 healthy infants, we systemically and quantitatively characterized for the first time the longitudinal cortical global gyrification index (GI) and local GI (LGI) development in the first 2 years of life. We found that the cortical GI had age-related and marked development, with 16.1% increase in the first year and 6.6% increase in the second year. We also found marked and regionally heterogeneous cortical LGI development in the first 2 years of life, with the high-growth regions located in the association cortex, whereas the low-growth regions located in sensorimotor, auditory, and visual cortices. Meanwhile, we also showed that LGI growth in most cortical regions was positively correlated with the brain volume growth, which is particularly significant in the prefrontal cortex in the first year. In addition, we observed gender differences in both cortical GIs and LGIs in the first 2 years, with the males having larger GIs than females at 2 years of age. This study provides valuable information on normal cortical folding development in infancy and early childhood. PMID:24647943

  8. Cytokines as a predictor of clinical response following hip arthroscopy: minimum 2-year follow-up.

    PubMed

    Shapiro, Lauren M; Safran, Marc R; Maloney, William J; Goodman, Stuart B; Huddleston, James I; Bellino, Michael J; Scuderi, Gaetano J; Abrams, Geoffrey D

    2016-08-01

    Hip arthroscopy in patients with osteoarthritis has been shown to have suboptimal outcomes. Elevated cytokine concentrations in hip synovial fluid have previously been shown to be associated with cartilage pathology. The purpose of this study was to determine whether a relationship exists between hip synovial fluid cytokine concentration and clinical outcomes at a minimum of 2 years following hip arthroscopy. Seventeen patients without radiographic evidence of osteoarthritis had synovial fluid aspirated at time of portal establishment during hip arthroscopy. Analytes included fibronectin-aggrecan complex as well as a multiplex cytokine array. Patients completed the modified Harris Hip Score, Western Ontario and McMaster Universities Arthritis Index and the International Hip Outcomes Tool pre-operatively and at a minimum of 2 years following surgery. Pre and post-operative scores were compared with a paired t-test, and the association between cytokine values and clinical outcome scores was performed with Pearson's correlation coefficient with an alpha value of 0.05 set as significant. Sixteen of seventeen patients completed 2-year follow-up questionnaires (94%). There was a significant increase in pre-operative to post-operative score for each clinical outcome measure. No statistically significant correlation was seen between any of the intra-operative cytokine values and either the 2-year follow-up scores or the change from pre-operative to final follow-up outcome values. No statistically significant associations were seen between hip synovial fluid cytokine concentrations and 2-year follow-up clinical outcome assessment scores for those undergoing hip arthroscopy. PMID:27583163

  9. Increased Food Insecurity Among Mothers of 2 Year Olds with Special Health Care Needs.

    PubMed

    Adams, Elizabeth J; Hoffmann, Laurel M; Rosenberg, Kenneth D; Peters, Dawn; Pennise, Melissa

    2015-10-01

    The objective of this study is to explore the association between having a child with special health care needs (CSHCN) and food insecurity when the child is 2 years old. We studied women who had a live birth in 2004-2005 and responded to Oregon's Pregnancy Risk Assessment Monitoring System (PRAMS) survey 3 months postpartum (Time 1) and the follow-up survey (PRAMS-2), when the child was 2 years old (Time 2). Women answering affirmatively to the PRAMS-2 question, "In the last 12 months, did you ever eat less than you felt you should because there was not enough money for food?" were considered food insecure. CSHCN status was identified by affirmative responses to questions about needs for ongoing services (Time 2). PRAMS and PRAMS-2 responses were weighted for study design and non-response. Results report weighted analyses, unless noted. Among 1812 mothers completing PRAMS-2, 13.6 % (unweighted) had a 2-year-old CSHCN and 11.9 % (unweighted) were food insecure at Time 2. The estimated prevalence of food insecurity at 2-year follow-up was 20.7 % among families of CSHCN and 9.7 % for others. After adjustment for Time 2 marital status, education, lifetime U.S. residence, income and health conditions, multivariable logistic regression revealed that odds of food insecurity were more than two times as great for CSHCN mothers 2 years post-partum compared to non-CSHCN mothers (adjusted odds ratio 2.6, 95 % confidence interval 1.3, 4.6). Families of CSHCN face increased risk for food insecurity. Improved understanding of causal determinants of food insecurity among households of CSHCN is needed. PMID:25682114

  10. Cytokines as a predictor of clinical response following hip arthroscopy: minimum 2-year follow-up

    PubMed Central

    Shapiro, Lauren M.; Safran, Marc R.; Maloney, William J.; Goodman, Stuart B.; Huddleston, James I.; Bellino, Michael J.; Scuderi, Gaetano J.; Abrams, Geoffrey D.

    2016-01-01

    Hip arthroscopy in patients with osteoarthritis has been shown to have suboptimal outcomes. Elevated cytokine concentrations in hip synovial fluid have previously been shown to be associated with cartilage pathology. The purpose of this study was to determine whether a relationship exists between hip synovial fluid cytokine concentration and clinical outcomes at a minimum of 2 years following hip arthroscopy. Seventeen patients without radiographic evidence of osteoarthritis had synovial fluid aspirated at time of portal establishment during hip arthroscopy. Analytes included fibronectin–aggrecan complex as well as a multiplex cytokine array. Patients completed the modified Harris Hip Score, Western Ontario and McMaster Universities Arthritis Index and the International Hip Outcomes Tool pre-operatively and at a minimum of 2 years following surgery. Pre and post-operative scores were compared with a paired t-test, and the association between cytokine values and clinical outcome scores was performed with Pearson’s correlation coefficient with an alpha value of 0.05 set as significant. Sixteen of seventeen patients completed 2-year follow-up questionnaires (94%). There was a significant increase in pre-operative to post-operative score for each clinical outcome measure. No statistically significant correlation was seen between any of the intra-operative cytokine values and either the 2-year follow-up scores or the change from pre-operative to final follow-up outcome values. No statistically significant associations were seen between hip synovial fluid cytokine concentrations and 2-year follow-up clinical outcome assessment scores for those undergoing hip arthroscopy. PMID:27583163

  11. Potential surrogate endpoints for overall survival in locoregionally advanced nasopharyngeal carcinoma: an analysis of a phase III randomized trial

    PubMed Central

    Chen, Yu-Pei; Chen, Yong; Zhang, Wen-Na; Liang, Shao-Bo; Zong, Jing-Feng; Chen, Lei; Mao, Yan-Ping; Tang, Ling-Long; Li, Wen-Fei; Liu, Xu; Guo, Ying; Lin, Ai-Hua; Liu, Meng-Zhong; Sun, Ying; Ma, Jun

    2015-01-01

    The gold standard endpoint in trials of locoregionally advanced nasopharyngeal carcinoma (NPC) is overall survival (OS). Using data from a phase III randomized trial, we evaluated whether progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) or locoregional failure-free survival (LR-FFS) could be reliable surrogate endpoints for OS. Between July 2002 and September 2005, 316 eligible patients with stage III-IVB NPC were randomly assigned to receive either radiotherapy alone or chemoradiotherapy. 2- and 3-year PFS, FFS, D-FFS, and LR-FFS were tested as surrogate endpoints for 5-year OS using Prentice’s four criteria. The Spearman’s rank correlation coefficient was calculated to assess the strength of the associations. After a median follow-up time of 5.8 years, 2- and 3-year D-FFS and LR-FFS were not significantly different between treatment arms, in rejection of Prentice’s second criterion. Being consistent with all Prentice’s criteria, 2- and 3-year PFS and FFS were valid surrogate endpoints for 5-year OS; the rank correlation coefficient was highest (0.84) between 3-year PFS and 5-year OS. In conclusion, PFS and FFS at 2 and 3 years may be candidate surrogate endpoints for OS at 5 years; 3-year PFS may be more appropriate for early assessment of long-term survival. PMID:26219568

  12. Survival Rates for Thymus Cancer

    MedlinePlus

    ... staged? Next Topic How is thymus cancer treated? Survival rates for thymus cancer Survival rates are often ... into account. Stage of thymoma 5-year observed survival rate I 74% II 73% III 64% IV ...

  13. Concurrent Chemoradiotherapy Improves Survival in Patients With Hypopharyngeal Cancer

    PubMed Central

    Paximadis, Peter; Yoo, George; Lin, Ho-Sheng; Jacobs, John; Sukari, Ammar; Dyson, Greg; Christensen, Michael; Kim, Harold

    2013-01-01

    Purpose To retrospectively review our institutional experience with hypopharyngeal carcinoma with respect to treatment modality. Methods and Materials A total of 70 patients with hypopharyngeal cancer treated between 1999 and 2009 were analyzed for functional and survival outcomes. The treatments included surgery alone (n = 5), surgery followed by radiotherapy (RT) (n = 3), surgery followed by chemoradiotherapy (CRT) (n = 13), RT alone (n = 2), CRT alone (n = 22), induction chemotherapy followed by RT (n = 3), and induction chemotherapy followed by CRT (n = 22). Results The median follow-up was 18 months. The median overall survival and disease-free survival for all patients was 28.3 and 17.6 months, respectively. The 1- and 2-year local control rate for all patients was 87.1% and 80%. CRT, given either as primary therapy or in the adjuvant setting, improved overall survival and disease-free survival compared with patients not receiving CRT. The median overall survival and disease-free survival for patients treated with CRT was 36.7 and 17.6 months vs. 14.0 and 8.0 months, respectively (p <.01). Of the patients initially treated with an organ-preserving approach, 4 (8.2%) required salvage laryngectomy for local recurrence or persistent disease; 8 (16.3%) and 12 (24.5%) patients were dependent on a percutaneous gastrostomy and tracheostomy tube, respectively. The 2-year laryngoesophageal dysfunction-free survival rate for patients treated with an organ-preserving approach was estimated at 31.7%. Conclusions Concurrent CRT improves survival in patients with hypopharyngeal cancer. CRT given with conventional radiation techniques yields poor functional outcomes, and future efforts should be directed at determining the feasibility of pharyngeal-sparing intensity-modulated radiotherapy in patients with hypopharyngeal tumors. PMID:21658855

  14. Concurrent Chemoradiotherapy Improves Survival in Patients With Hypopharyngeal Cancer

    SciTech Connect

    Paximadis, Peter; Yoo, George; Lin, Ho-Sheng; Jacobs, John; Sukari, Ammar; Dyson, Greg; Christensen, Michael; Kim, Harold

    2012-03-15

    Purpose: To retrospectively review our institutional experience with hypopharyngeal carcinoma with respect to treatment modality. Methods and Materials: A total of 70 patients with hypopharyngeal cancer treated between 1999 and 2009 were analyzed for functional and survival outcomes. The treatments included surgery alone (n = 5), surgery followed by radiotherapy (RT) (n = 3), surgery followed by chemoradiotherapy (CRT) (n = 13), RT alone (n = 2), CRT alone (n = 22), induction chemotherapy followed by RT (n = 3), and induction chemotherapy followed by CRT (n = 22). Results: The median follow-up was 18 months. The median overall survival and disease-free survival for all patients was 28.3 and 17.6 months, respectively. The 1- and 2-year local control rate for all patients was 87.1% and 80%. CRT, given either as primary therapy or in the adjuvant setting, improved overall survival and disease-free survival compared with patients not receiving CRT. The median overall survival and disease-free survival for patients treated with CRT was 36.7 and 17.6 months vs. 14.0 and 8.0 months, respectively (p < .01). Of the patients initially treated with an organ-preserving approach, 4 (8.2%) required salvage laryngectomy for local recurrence or persistent disease; 8 (16.3%) and 12 (24.5%) patients were dependent on a percutaneous gastrostomy and tracheostomy tube, respectively. The 2-year laryngoesophageal dysfunction-free survival rate for patients treated with an organ-preserving approach was estimated at 31.7%. Conclusions: Concurrent CRT improves survival in patients with hypopharyngeal cancer. CRT given with conventional radiation techniques yields poor functional outcomes, and future efforts should be directed at determining the feasibility of pharyngeal-sparing intensity-modulated radiotherapy in patients with hypopharyngeal tumors.

  15. Cytogenetics and long-term survival of patients with refractory or relapsed and refractory multiple myeloma treated with pomalidomide and low-dose dexamethasone.

    PubMed

    Dimopoulos, Meletios A; Weisel, Katja C; Song, Kevin W; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Moreau, Philippe; Banos, Anne; Oriol, Albert; Garderet, Laurent; Cavo, Michele; Ivanova, Valentina; Alegre, Adrian; Martinez-Lopez, Joaquin; Chen, Christine; Spencer, Andrew; Knop, Stefan; Bahlis, Nizar J; Renner, Christoph; Yu, Xin; Hong, Kevin; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H; San Miguel, Jesus F

    2015-10-01

    Patients with refractory or relapsed and refractory multiple myeloma who no longer receive benefit from novel agents have limited treatment options and short expected survival. del(17p) and t(4;14) are correlated with shortened survival. The phase 3 MM-003 trial demonstrated significant progression-free and overall survival benefits from treatment with pomalidomide plus low-dose dexamethasone compared to high-dose dexamethasone among patients in whom bortezomib and lenalidomide treatment had failed. At an updated median follow-up of 15.4 months, the progression-free survival was 4.0 versus 1.9 months (HR, 0.50; P<0.001), and median overall survival was 13.1 versus 8.1 months (HR, 0.72; P=0.009). Pomalidomide plus low-dose dexamethasone, compared with high-dose dexamethasone, improved progression-free survival in patients with del(17p) (4.6 versus 1.1 months; HR, 0.34; P <0.001), t(4;14) (2.8 versus 1.9 months; HR, 0.49; P=0.028), and in standard-risk patients (4.2 versus 2.3 months; HR, 0.55; P<0.001). Although the majority of patients treated with high-dose dexamethasone took pomalidomide after discontinuation, the overall survival of patients treated with pomalidomide plus low-dose dexamethasone or high-dose dexamethasone was 12.6 versus 7.7 months (HR, 0.45; P=0.008) in patients with del(17p), 7.5 versus 4.9 months (HR, 1.12; P=0.761) in those with t(4;14), and 14.0 versus 9.0 months (HR, 0.85; P=0.380) in standard-risk subjects. The overall response rate was higher in patients treated with pomalidomide plus low-dose dexamethasone than in those treated with high-dose dexamethasone both among standard-risk patients (35.2% versus 9.7%) and those with del(17p) (31.8% versus 4.3%), whereas it was similar in patients with t(4;14) (15.9% versus 13.3%). The safety of pomalidomide plus low-dose dexamethasone was consistent with initial reports. In conclusion, pomalidomide plus low-dose dexamethasone is efficacious in patients with relapsed/refractory multiple myeloma

  16. 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.

  17. Weight Gain in Advanced Non-Small-Cell Lung Cancer Patients During Treatment With Split-Course Concurrent Chemoradiotherapy Is Associated With Superior Survival

    SciTech Connect

    Gielda, Benjamin T.; Mehta, Par; Khan, Atif; Marsh, James C.; Zusag, Thomas W.; Warren, William H.; Fidler, Mary Jo; Abrams, Ross A.; Bonomi, Philip; Liptay, Michael; Faber, L. Penfield

    2011-11-15

    Background: Preoperative concurrent chemoradiotherapy (CRT) is an accepted treatment for potentially resectable, locally advanced, non-small-cell lung cancer (NSCLC). We reviewed a decade of single institution experience with preoperative split-course CRT followed by surgical resection to evaluate survival and identify factors that may be helpful in predicting outcome. Methods and Materials: All patients treated with preoperative split-course CRT and resection at Rush University Medical Center (RUMC) between January 1999 and December 2008 were retrospectively analyzed. Endpoints included overall survival (OS), progression-free survival (PFS), local-regional progression-free survival (LRPFS), and distant metastasis-free survival (DMFS). Patient and treatment related variables were assessed for correlation with outcomes. Results: A total of 54 patients were analyzed, 76% Stage IIIA, 18% Stage IIIB, and 6% oligometastatic. The pathologic complete response (pCR) rate was 31.5%, and the absence of nodal metastases (pN0) was 64.8%. Median OS and 3-year actuarial survival were 44.6 months and 50%, respectively. Univariate analysis revealed initial stage (p < 0.01) and percent weight change during CRT (p < 0.01) significantly correlated with PFS/OS. On multivariate analysis initial stage (HR, 2.4; 95% CI, 1.18-4.90; p = 0.02) and percent weight change (HR, 0.79; 95% CI, 0.67-0.93; p < 0.01) maintained significance with respect to OS. There were no cases of Grade 3+ esophagitis, and there was a single case of Grade 3 febrile neutropenia. Conclusions: The strong correlation between weight change during CRT and OS/PFS suggests that this clinical parameter may be useful as a complementary source of predictive information in addition to accepted factors such as pathological response.

  18. 9 CFR 71.18 - Individual identification of certain cattle 2 years of age or over for movement in interstate...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... cattle 2 years of age or over for movement in interstate commerce. 71.18 Section 71.18 Animals and Animal... certain cattle 2 years of age or over for movement in interstate commerce. (a) No cattle 2 years of age or over, except steers and spayed heifers and cattle of any age which are being moved interstate...

  19. 9 CFR 71.18 - Individual identification of certain cattle 2 years of age or over for movement in interstate...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... cattle 2 years of age or over for movement in interstate commerce. 71.18 Section 71.18 Animals and Animal... certain cattle 2 years of age or over for movement in interstate commerce. (a) No cattle 2 years of age or...) of this chapter, shall be moved in interstate commerce other than in accordance with the...

  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. Patient factors predict functional outcomes after cruciate retaining TKA: a 2-year follow-up analysis.

    PubMed

    Roth, Justin S; Buehler, Knute C; Shen, Jianhua; Naughton, Marybeth

    2013-09-01

    We analyzed preoperative patient characteristics and postoperative functional outcomes to identify the most predictive preoperative characteristics of postoperative functional outcome for Cruciate Retaining (CR) TKA. In a prospective, multicenter study, 307 knees with minimum 2-year follow-up were first divided into groups based on 2-year functional performance. Logistic regression then determined SF-36 General Health Score (GHS) to be the most predictive preoperative patient characteristic. Subsequently, a second analysis was performed using preoperative SF-36 GHS to stratify patients into groups. Statistical significance was achieved in both analyses by gender, BMI and hypertension. Statistical significance was achieved in a single analysis by age, preoperative narcotic use, preoperative metabolic medication usage, preoperative pulmonary disease and preoperative use of medication for anxiety or depression. PMID:23523205

  2. Language experiences and vocabulary development in Dominican and Mexican infants across the first 2 years.

    PubMed

    Song, Lulu; Tamis-Lemonda, Catherine S; Yoshikawa, Hirokazu; Kahana-Kalman, Ronit; Wu, Irene

    2012-07-01

    We longitudinally investigated parental language context and infants' language experiences in relation to Dominican American and Mexican American infants' vocabularies. Mothers provided information on parental language context, comprising measures of parents' language background (i.e., childhood language) and current language use during interviews at infants' birth. Infants' language experiences were measured at ages 14 months and 2 years through mothers' reports of mothers' and fathers' engagement in English and Spanish literacy activities with infants and mothers' English and Spanish utterances during videotaped mother-infant interactions. Infants' vocabulary development at 14 months and 2 years was examined using standardized vocabulary checklists in English and Spanish. Both parental language context and infants' language experiences predicted infants' vocabularies in each language at both ages. Furthermore, language experiences mediated associations between parental language context and infants' vocabularies. However, the specific mediation mechanisms varied by language. PMID:22142187

  3. Tooth stain during 2 years' use of chlorhexidine- and fluoride-containing dentifrices.

    PubMed

    Dolles, O K; Eriksen, H M; Gjermo, P

    1979-08-01

    The purpose of the present study was to evaluate the effect of fluoride upon the stain-inducing capacity of chlorhexidine. Ninety-one children, 13 years of age, volunteered for the experiment. Three test dentifrices were used, containing 0.1% NaF, 0.1% NaF + 2% chlorhexidine, and 2% chlorhexidine respectively. The experiment was carried out as a double-blind test, and the degree of staining was recorded after 1 and 2 years. Four methods were used for stain scoring. The results after 1 year showed that chlorhexidine induced less stain when applied together with fluoride than when applied alone. After 2 years this difference disappeared, indicating that fluoride only retarded chlorhexidine-induced staining of teeth. PMID:295486

  4. Exenatide once weekly treatment maintained improvements in glycemic control and weight loss over 2 years

    PubMed Central

    2011-01-01

    Background The once-weekly (QW) formulation of the glucagon-like peptide-1 receptor agonist exenatide has been demonstrated to improve A1C, fasting plasma glucose (FPG), body weight, serum lipid profiles, and blood pressure in patients with type 2 diabetes through 52 weeks of treatment. In this report, we describe the 2-year results of the open-label, open-ended extension to the DURATION-1 trial of exenatide QW for type 2 diabetes. Methods A 2-stage protocol was used: patients received either exenatide QW (2 mg) or exenatide twice daily for 30 weeks (5 μg for the first 4 weeks and 10 μg thereafter), followed by 1.5 years of treatment with exenatide QW (2 mg), for a total of 2 years (104 weeks) of exenatide treatment. Of the 295 (intent-to-treat [ITT]) patients who entered the trial, 73% (n = 216) completed 2 years of treatment (completer population). Baseline characteristics (mean ± SE) for these patients were: A1C, 8.2 ± 0.1%; FPG, 168.4 ± 43.0 mg/dL; body weight, 101.1 ± 18.7 kg; and diabetes duration, 7 ± 5 years. Results In the completer population, significant improvements (LS mean ± SE [95% CI]) were maintained after 2 years of treatment in A1C (-1.71 ± 0.08% [-1.86 to -1.55%]), FPG (-40.1 ± 2.9 mg/dL [-45.7 to -34.5 mg/dL]), and body weight (-2.61 ± 0.52 kg [-3.64 to -1.58 kg]) compared with baseline. The percentages of patients who achieved an A1C of <7.0% and ≤6.5% at 2 years were 60% and 39%, respectively. A significant reduction in systolic blood pressure (SBP; -3.0 ± 1.0 mmHg [-4.9 to -1.1 mmHg]) was maintained through 2 years of treatment. Serum lipid profiles were also significantly improved, including triglycerides (geometric LS mean change from baseline, -15 ± 2.7% [-21% to -10%]), total cholesterol (-8.6 ± 2.8 mg/dL [-14.0 to -3.1 mg/dL]), and low-density lipoproteins (-4.5 ± 2.2 mg/dL [-8.9 to -0.01 mg/dL]). Changes in A1C, body weight, FPG, SBP, and lipids in the ITT population were similar to those seen in the completer

  5. A 2-Year-Old Child's Memory of Hospitalization during Early Infancy

    ERIC Educational Resources Information Center

    Solter, Aletha

    2008-01-01

    A child who had had surgery at 5 months of age, and who had been treated at the time for post-traumatic symptoms (reported in a previous paper by the author), was interviewed 2 years later and almost 3 years later to test for possible verbal recall of his hospitalization. He appeared to have some memories of the experience at 29 months of age, and…

  6. Complete paroxysmal atrioventricular block in a 2-year-old girl.

    PubMed

    Holst, Line M; Dixen, Ulrik; Jeppesen, Dorthe L

    2015-10-01

    We present a case of atypical syncope in a 2-year-old, otherwise healthy girl. The patient presented with three episodes of syncope without any precipitating factors and no family history of sudden unexpected death. Holter monitoring revealed 24 events of complete atrioventricular block lasting up to 6 seconds. A normal 12-lead electrocardiogram does not necessarily exclude cardiac disease, and Holter monitoring is warranted in children with atypical syncope. PMID:25428604

  7. Pial synangiosis in patients with moyamoya younger than 2 years of age.

    PubMed

    Jackson, Eric M; Lin, Ning; Manjila, Sunil; Scott, R Michael; Smith, Edward R

    2014-04-01

    Object Patients with moyamoya who are younger than 2 years of age represent a therapeutic challenge because of their frequent neurological instability and concomitant anesthetic risks. The authors report their experience with pial synangiosis revascularization in this population. Methods The authors reviewed the clinical and radiographic records of all patients with moyamoya in a consecutive series of patients under 2 years of age, who underwent cerebral revascularization surgery using pial synangiosis at a single institution. Results During a 12-year period (1994-2005), 34 procedures (bilateral in 15 patients, unilateral in 4) were performed in 19 patients younger than 2 years (out of a total of 456 procedures in 240 patients). Eighteen of these patients presented with either stroke or transient ischemic attack. The average age of the 19 patients at first surgery was 1.4 years (range 6 months-1.9 years). Unanticipated staged operations occurred in 3 patients, due to persistent electroencephalographic changes during the initial surgery in 2 cases and due to brain swelling during the procedure requiring ventriculostomy in the other. There were 2 perioperative strokes; both patients had postoperative seizures but made clinical recoveries. The average follow-up was 7 years (range 1-14 years). Long term, at follow-up, 13 patients (68%) were clinically independent for their age, with 8 (42%) having no significant deficit. Late complications included subdural hygroma evacuation (1), additional revascularization procedures performed years later for frontal lobe ischemia (2), late infarction (1), and asymptomatic ischemic change on routine follow-up MRI studies (1). All patients who had both pre- and postoperative angiography demonstrated progression of disease. Conclusions Despite the challenges inherent to this population, the majority of children with moyamoya under the age of 2 years have a good long-term prognosis. The data from this study support the use of pial

  8. A Comparison of Retention Rates among America's 2-Year Institutions of Higher Education

    ERIC Educational Resources Information Center

    Clark, Tampa J.

    2012-01-01

    The purpose of the study was first to calculate the full-time and part-time retention rates for each category of 2-year institution and to examine the differences, if they existed, between and among the three types of colleges. Secondly, the study explored the differences in the full-time and part-time retention rates of first-time students within…

  9. Natrelle 410 Extra-Full Projection Silicone Breast Implants: 2-Year Results from Two Prospective Studies

    PubMed Central

    McGuire, Patricia; Murphy, Diane K.

    2015-01-01

    Background: The safety and effectiveness of the Natrelle Style 410 highly cohesive silicone gel breast implant (Allergan, Inc., Irvine, Calif.) in full or moderate height and projection have been shown in a 10-year study. Extra-full projection implants may be an appropriate option for some women undergoing breast reconstruction. Methods: A total of 2795 women received at least one Natrelle 410 extra-full projection implant (X-style) for breast reconstruction in two similarly designed, prospective, multicenter studies. Data collected for 2 years after implantation in these studies were pooled to evaluate complication rates and subject and physician satisfaction. Results: Most subjects (76.0 percent) underwent bilateral reconstruction; a total of 4912 devices were implanted. Complication rates at 2 years were low. The most common complications were asymmetry (4.8 percent) and capsular contracture (3.3 percent). The cumulative risk of reoperation was 21.6 percent by subject and 16.6 percent by device; the most common reasons for reoperation were scarring (n = 97), asymmetry (n = 89), implant malposition (n = 78), and infection (n = 71). Subject and physician satisfaction rates exceeded 90 percent. At 2 years, 97 percent of physicians reported that the shape of the breast reflected the shape of the implant, and that the breast implant had maintained its original position. Conclusions: The safety profile of the Natrelle 410 extra-full projection implant mirrors that of its moderate projection and full projection counterparts. Both physicians and subjects were highly satisfied with the implants 2 years after surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID:26090764

  10. Isolated Hepatic Basidiobolomycosis in a 2-Year-Old Girl: The First Case Report

    PubMed Central

    Geramizadeh, Bita; Sanai Dashti, Anahita; Kadivar, Mohammad Rahim; Kord, Shirin

    2015-01-01

    Introduction: Gastrointestinal basidiobolomycosis is an emerging infection, with fewer than 80 cases reported in the English literature. Case Presentation: Also, a few cases of gastrointestinal basidiobolomycosis, accompanied by liver involvement as part of a disseminated disease, have been reported. Conclusions: This is the first case report of an isolated liver involvement of this fungal infection in a 2-year-old girl, who presented with a liver mass resembling a hepatic abscess. PMID:26322112

  11. Extrathoracic chronic heamatoma presenting as a chest wall tumor 2 years after a blunt thoracic injury.

    PubMed

    Kouritas, Vasileios K; Roussakis, Antonios G; Soultanis, Konstantinos; Bellenis, Ion

    2011-01-01

    Chronic expanding heamatomas may present as masses mimicking chest wall tumors. We report the case of a patient who was presented with a giant posterior extrathoracic chest wall tumor. The mass was proven to be a chronic heamatoma possibly developed after a blunt thoracic injury which took place 2 years before presentation and was growing thereafter. Clinicians should have high suspicion of rare entities which mimic tumors and consider any information reported by the patient's history in their diagnostic process. PMID:22112630

  12. Extrathoracic chronic heamatoma presenting as a chest wall tumor 2 years after a blunt thoracic injury

    PubMed Central

    2011-01-01

    Chronic expanding heamatomas may present as masses mimicking chest wall tumors. We report the case of a patient who was presented with a giant posterior extrathoracic chest wall tumor. The mass was proven to be a chronic heamatoma possibly developed after a blunt thoracic injury which took place 2 years before presentation and was growing thereafter. Clinicians should have high suspicion of rare entities which mimic tumors and consider any information reported by the patient's history in their diagnostic process. PMID:22112630

  13. 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

  14. Strabismus at Age 2 Years in Children Born Before 28 Weeks' Gestation: Antecedents and Correlates.

    PubMed

    VanderVeen, Deborah K; Allred, Elizabeth N; Wallace, David K; Leviton, Alan

    2016-03-01

    Children born very preterm are at greater risk of ophthalmic morbidities, including strabismus, than children born at term. We evaluated perinatal factors associated with strabismus at age 2 years in a large population of infants delivered before 28 weeks' gestation. A total of 996 infants in the multicenter ELGAN (Extremely Low Gestational Age Newborn) study who had a retinal exam in infancy and a developmental assessment at 2 years corrected age are included. Their mothers were interviewed about the pregnancy, and both mother and newborn charts were reviewed. Certified examiners administered the Bayley Scales of Infant Development-II and performed an examination of ocular alignment. Time-oriented logistic regression risk models were created to evaluate the associations of characteristics and exposures with the development of strabismus. Overall, 14% (n = 141) of the children had strabismus at 2 years, and 80% of strabismic children had esotropia. Characteristics associated with strabismus were birth before 26 weeks' gestation, severe fetal growth restriction, and maternal history of aspirin ingestion. Associated postnatal factors included a SNAP-II (Score for Neonatal Acute Physiology) illness severity value ≥ 30, brain ventriculomegaly, type I retinopathy of prematurity, and ventilator-dependent severe bronchopulmonary dysplasia. Strabismus in very preterm populations is associated with a number of antenatal and postnatal antecedents as well as clinical and imaging correlates indicative of brain damage in these children. Routine ophthalmologic assessments in the early years can allow appropriate and timely interventions. PMID:26350726

  15. Patient satisfaction and penile morphology changes with postoperative penile rehabilitation 2 years after Coloplast Titan prosthesis.

    PubMed

    Pryor, Michael B; Carrion, Rafael; Wang, Run; Henry, Gerard

    2016-01-01

    A common complaint after inflatable penile prosthesis surgery is reduced penile length. We previously reported how using the Coloplast Titan inflatable penile prosthesis with aggressive new length measurement technique (NLMT) coupled with postoperative IPP rehabilitation of the implant for 1-year helped to improve patient satisfaction and erectile penile measurements. This is a 2 years follow-up of a prospective, three-center, study of 40 patients who underwent Titan prosthesis placement, with new length measurement technique for erectile dysfunction. Patient instructions were to inflate daily for 6 months and then inflate maximally for 1-2 h daily for 6-24 months. Fifteen penile measurements were taken before and immediately after surgery and at follow-up visits. Measurement changes were improved at 24 months as compared to immediately postoperative and at 12 months. 67.8% of subjects were satisfied with their length at 2 years, and 77% had perceived penile length that was longer (30.8%) or the same (46.2%) as prior to the surgery. 64.3% and 17.9% of subjects had increased and unchanged satisfaction, respectively, with penile length as compared to prior to penile implant surgery. All but one subject (96.5%) was satisfied with the overall function of his implant. This study suggests using the Coloplast Titan with aggressive cylinder sizing, and a postoperative penile rehabilitation inflation protocol can optimize patient satisfaction and erectile penile measurements at 2 years postimplant. PMID:26459782

  16. Patient satisfaction and penile morphology changes with postoperative penile rehabilitation 2 years after Coloplast Titan prosthesis

    PubMed Central

    Pryor, Michael B; Carrion, Rafael; Wang, Run; Henry, Gerard

    2016-01-01

    A common complaint after inflatable penile prosthesis surgery is reduced penile length. We previously reported how using the Coloplast Titan inflatable penile prosthesis with aggressive new length measurement technique (NLMT) coupled with postoperative IPP rehabilitation of the implant for 1-year helped to improve patient satisfaction and erectile penile measurements. This is a 2 years follow-up of a prospective, three-center, study of 40 patients who underwent Titan prosthesis placement, with new length measurement technique for erectile dysfunction. Patient instructions were to inflate daily for 6 months and then inflate maximally for 1–2 h daily for 6–24 months. Fifteen penile measurements were taken before and immediately after surgery and at follow-up visits. Measurement changes were improved at 24 months as compared to immediately postoperative and at 12 months. 67.8% of subjects were satisfied with their length at 2 years, and 77% had perceived penile length that was longer (30.8%) or the same (46.2%) as prior to the surgery. 64.3% and 17.9% of subjects had increased and unchanged satisfaction, respectively, with penile length as compared to prior to penile implant surgery. All but one subject (96.5%) was satisfied with the overall function of his implant. This study suggests using the Coloplast Titan with aggressive cylinder sizing, and a postoperative penile rehabilitation inflation protocol can optimize patient satisfaction and erectile penile measurements at 2 years postimplant. PMID:26459782

  17. Prospective Study Evaluating Postoperative Radiotherapy Plus 2-Year Androgen Suppression for Post-Radical Prostatectomy Patients With Pathologic T3 Disease and/or Positive Surgical Margins

    SciTech Connect

    Choo, Richard Danjoux, Cyril; Gardner, Sandra; Morton, Gerard; Szumacher, Ewa; Loblaw, D. Andrew; Cheung, Patrick; Pearse, Maria

    2009-10-01

    Purpose: To determine the efficacy of a combined approach of postoperative radiotherapy (RT) plus 2-year androgen suppression (AS) for patients with pathologic T3 disease (pT3) and/or positive surgical margins (PSM) after radical prostatectomy (RP). Methods and Materials: A total of 78 patients with pT3 and/or PSM after RP were treated with RT plus 2-year AS, as per a pilot, prospective study. Androgen suppression started within 1 month after the completion of RT and consisted of nilutamide for 4 weeks and buserelin acetate depot subcutaneously every 2 months for 2 years. Relapse-free rate, including freedom from prostate-specific antigen (PSA) relapse, was estimated using the Kaplan-Meier method. A Cox regression analysis was performed to evaluate prognostic factors for relapse. Prostate-specific antigen relapse was defined as a PSA rise above 0.2 ng/mL, with two consecutive increases over a minimum of 3 months. Results: The median age was 61 years at the time of RP. The median interval between RP and postoperative RT was 4.2 months. Forty-nine patients had undetectable PSA (<0.2 ng/mL), and 29 had persistently detectable postoperative PSA at the time of the protocol treatment. Median follow-up from RT was 6.4 years. Relapse-free rates at 5 and 7 years were 94.4% and 86.3%, respectively. Survival rates were 96% at 5 years and 93.1% at 7 years. On Cox regression analysis, persistently detectable postoperative PSA and pT3b-T4 were significant predictors for relapse. Conclusion: The combined treatment of postoperative RT plus 2-year AS yielded encouraging results for patients with pT3 and/or PSM and warrants a confirmatory study.

  18. 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…

  19. 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,…

  20. A Profile of Survival.

    ERIC Educational Resources Information Center

    Zimrin, Hanita

    1986-01-01

    Abused children who survived the trauma of their childhood and grew up to be well-adjusted were compared with a matched group who showed a high degree of psychosocial pathology. The variables which distinguished the two groups were fatalism, self-esteem, cognitive abilities, self-destructiveness, hope and fantasy, behavior patterns and external…

  1. 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.

  2. 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…

  3. Survival Learning Materials.

    ERIC Educational Resources Information Center

    Wilson, Robert M.; Barnes, Marcia M.

    This booklet is designed to provide some starter ideas for teachers to use in developing their own packet of learning materials. The procedures suggested and the examples included are literally starters. "Introduction to Survival Learning Materials" presents some procedures to help teachers get started in developing materials. "Following…

  4. Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer’s disease

    PubMed Central

    Hager, Klaus; Baseman, Alan S; Nye, Jeffrey S; Brashear, H Robert; Han, John; Sano, Mary; Davis, Bonnie; Richards, Henry M

    2014-01-01

    Background Currently available treatments for Alzheimer’s disease (AD) can produce mild improvements in cognitive function, behavior, and activities of daily living in patients, but their influence on long-term survival is not well established. This study was designed to assess patient survival and drug efficacy following a 2-year galantamine treatment in patients with mild to moderately severe AD. Methods In this multicenter, double-blind study, patients were randomized 1:1 to receive galantamine or placebo. One primary end point was safety; mortality was assessed. An independent Data Safety Monitoring Board monitored mortality for the total deaths reaching prespecified numbers, using a time-to-event method and a Cox-regression model. The primary efficacy end point was cognitive change from baseline to month 24, as measured by the Mini-Mental State Examination (MMSE) score, analyzed using intent-to-treat analysis with the ‘last observation carried forward’ approach, in an analysis of covariance model. Results In all, 1,024 galantamine- and 1,021 placebo-treated patients received study drug, with mean age ~73 years, and mean (standard deviation [SD]) baseline MMSE score of 19 (4.08). A total of 32% of patients (661/2,045) completed the study, 27% (554/2,045) withdrew, and 41% (830/2,045) did not complete the study and were discontinued due to a Data Safety Monitoring Board-recommended early study termination. The mortality rate was significantly lower in the galantamine group versus placebo (hazard ratio [HR] =0.58; 95% confidence interval [CI]: 0.37; 0.89) (P=0.011). Cognitive impairment, based on the mean (SD) change in MMSE scores from baseline to month 24, significantly worsened in the placebo (−2.14 [4.34]) compared with the galantamine group (−1.41 [4.05]) (P<0.001). Functional impairment, based on mean (SD) change in the Disability Assessment in Dementia score (secondary end point), at month 24 significantly worsened in the placebo (−10.81 [18

  5. 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

  6. 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

  7. High mesothelin correlates with chemoresistance and poor survival in epithelial ovarian carcinoma

    PubMed Central

    Cheng, W-F; Huang, C-Y; Chang, M-C; Hu, Y-H; Chiang, Y-C; Chen, Y-L; Hsieh, C-Y; Chen, C-A

    2009-01-01

    The objective of this paper is to investigate the mesothelin expression level to the clinicopathological features, chemoresponse, and to the outcome of patients with epithelial ovarian carcinoma (EOC). Mesothelin mRNA was detected by real-time quantitative reverse-transcription PCR in 139 EOC patients. Clinical characteristics, histopathological items, responses to chemotherapy, progression-free survival (PFS), and overall survival (OS) were recorded. Tumours with advanced stages had higher mesothelin than those with early stages. The chemoresistant patients showed significantly higher mesothelin than did chemosensitive patients (2.81 vs 0.43, P<0.001), irrespective of optimal or suboptimal surgery in those with advanced stages. Highly expressed levels of mesothelin were an independent but poor prognostic factor in the PFS (2.03 (1.23–3.37) P=0.006) and OS (3.72 (1.64–8.45), P=0.002) of the 139 EOC patients in multivariate analysis. In addition, patients in advanced stages with highly expressed mesothelin also had significantly worse OS, regardless of whether they had undergone optimal (13.85 (1.76–125.60), P=0.013) or suboptimal (4.47 (1.83–10.88), P=0.001) debulking surgery in multivariate analysis. Out results provide new evidence that mesothelin expression is associated with chemoresistance and with shorter disease-free survival and worse OS of patients with EOC. PMID:19293794

  8. Preterm infant gut colonization in the neonatal ICU and complete restoration 2 years later.

    PubMed

    Moles, L; Gómez, M; Jiménez, E; Fernández, L; Bustos, G; Chaves, F; Cantón, R; Rodríguez, J M; Del Campo, R

    2015-10-01

    Preterm infants in a neonatal intensive care unit (NICU) are exposed to multidrug-resistant bacteria previously adapted to the hospital environment. The aim of the present study was to characterize the bacterial antibiotic-resistant high-risk lineages colonizing preterm infants during their NICU stay and their persistence in faeces after 2 years. A total of 26 preterm neonates were recruited between October 2009 and June 2010 and provided 144 faecal samples. Milk samples (86 mother's milk, 35 human donor milk and 15 formula milk) were collected at the same time as faecal samples. An additional faecal sample was recovered in 16 infants at the age of 2 years. Samples were plated onto different selective media, and one colony per morphology was selected. Isolates were identified by 16S rDNA nucleotide sequence and MALDI-TOF. Antibiotic susceptibility (agar dilution), genetic diversity (RAPD, PFGE and MLST) and virulence factors (only in enterococcal and staphylococcal isolates) were determined by PCR. A high proportion of antibiotic-resistant high-risk clones was detected in both faecal and milk samples during the NICU admittance. Almost all infants were colonized by Enterococcus faecalis ST64 and Enterococcus faecium ST18 clones, while a wider genetic diversity was observed for the Gram-negative isolates. Multidrug-resistant high-risk clones were not recovered from the faecal samples of the 2-year-olds. In conclusion, the gut of preterm infants admitted to the NICU might be initially colonized by antibiotic-resistant and virulent high-risk lineages, which are later replaced by antibiotic-susceptible community ones. PMID:26086569

  9. Altered corpus callosum morphology associated with autism over the first 2 years of life.

    PubMed

    Wolff, Jason J; Gerig, Guido; Lewis, John D; Soda, Takahiro; Styner, Martin A; Vachet, Clement; Botteron, Kelly N; Elison, Jed T; Dager, Stephen R; Estes, Annette M; Hazlett, Heather C; Schultz, Robert T; Zwaigenbaum, Lonnie; Piven, Joseph

    2015-07-01

    Numerous brain imaging studies indicate that the corpus callosum is smaller in older children and adults with autism spectrum disorder. However, there are no published studies examining the morphological development of this connective pathway in infants at-risk for the disorder. Magnetic resonance imaging data were collected from 270 infants at high familial risk for autism spectrum disorder and 108 low-risk controls at 6, 12 and 24 months of age, with 83% of infants contributing two or more data points. Fifty-seven children met criteria for ASD based on clinical-best estimate diagnosis at age 2 years. Corpora callosa were measured for area, length and thickness by automated segmentation. We found significantly increased corpus callosum area and thickness in children with autism spectrum disorder starting at 6 months of age. These differences were particularly robust in the anterior corpus callosum at the 6 and 12 month time points. Regression analysis indicated that radial diffusivity in this region, measured by diffusion tensor imaging, inversely predicted thickness. Measures of area and thickness in the first year of life were correlated with repetitive behaviours at age 2 years. In contrast to work from older children and adults, our findings suggest that the corpus callosum may be larger in infants who go on to develop autism spectrum disorder. This result was apparent with or without adjustment for total brain volume. Although we did not see a significant interaction between group and age, cross-sectional data indicated that area and thickness differences diminish by age 2 years. Regression data incorporating diffusion tensor imaging suggest that microstructural properties of callosal white matter, which includes myelination and axon composition, may explain group differences in morphology. PMID:25937563

  10. Food Variety at 2 Years of Age is Related to Duration of Breastfeeding

    PubMed Central

    Scott, Jane A.; Chih, Tsz Ying; Oddy, Wendy H.

    2012-01-01

    The aim of this study was to investigate the association of breastfeeding duration and food variety at 2 years of age. A secondary data analysis was undertaken of the Western Australian Pregnancy Cohort (Raine) Study, an ongoing longitudinal study. Data collected from a single 24 h dietary recall of 1905, 2 year-old children were used to calculate two food variety scores; a core food variety score (CFVS) and a fruit and vegetable variety score (FVVS). Multivariate linear regression analysis was used to identify those factors independently associated with the CFVS and FVVS. The mean CFVS was 7.52 (range 1–18) of a possible 34 food items or groups and the mean FVVS was 2.84 (range 0–10) of a possible 16 food items or groups. Breastfeeding duration was independently directly associated with the CFVS (p < 0.001) and FVVS (p < 0.001). In addition, maternal age was independently directly associated with the CFVS (p < 0.001) and FVVS (p = 0.001) as was maternal education (CFVS p < 0.001 and FVVS p = 0.043). The presence of older siblings was independently inversely associated with the CFVS (p = 0.003) and FVVS (p = 0.001). This study demonstrated a direct modest association between breastfeeding duration and food variety in 2 year-old children, independent of maternal demographic characteristics known to predict food variety in children. This finding supports the hypothesis that flavours transferred in breast milk provide repeated early exposure to different tastes and positively shape children’s food preferences and food variety. PMID:23201765

  11. Interdental papilla regeneration around implants: A novel window technique (2 years follow-up)

    PubMed Central

    Lambodharan, R.; Balaji, V. R.

    2015-01-01

    Reconstructing predictable and esthetic papilla is the most complex and challenging aspect of implant dentistry. To obtain an esthetic and predictable gingival architecture and implant restoration, interdental papilla plays an important role. The main objective of the surgeon during the second stage of implant treatment should be the creation of interdental papilla prior to prosthetic restoration. The aim of this case report was to demonstrate a novel window technique for developing predictable and esthetic papilla around dental implants, which was followed for 2 years with excellent esthetic results. PMID:26538979

  12. Dermestid Dermatitis in a 2-Year-Old Girl: Case Report and Review of the Literature.

    PubMed

    Hoverson, Kara; Wohltmann, Wendi E; Pollack, Richard J; Schissel, Daniel J

    2015-01-01

    Dermatitis from contact with carpet, larder, and hide beetles (family Dermestidae) is a seemingly uncommon or underrecognized hypersensitivity reaction to the specialized hairs on the larvae of certain dermestid beetles. The erythematous papulovesicular dermatitis that may result from such contact can be mistakenly construed as evidence of bites of bedbugs or other arthropods or infestation with scabies mites or can be the basis for a diagnosis of delusory parasitosis. We present a case of dermestid dermatitis in a 2-year-old girl and provide a review of the current literature. PMID:26250481

  13. Age-related light scattering in rat lenses observed in a 2-year inhalation toxicity study.

    PubMed

    Wegener, A; Kaegler, M; Stinn, W

    2002-01-01

    Normal light scattering in the eye is determined primarily by the size of alpha-crystalline molecules. Ageing effects appear as an increase in normal lens light scattering in distinct layers. Subliminal effects of toxins on lens transparency can also cause an increase in light scattering due to protein molecule aggregation before visible opacities appear. Scheimpflug photography of the anterior eye segment with subsequent densitometric image analysis is the method of choice to evaluate such effects. To gain more insight into normal ageing and the potential effects of complex aerosols, a subset of Wistar rats (both sexes) belonging to a larger chronic inhalation toxicity study was documented at baseline and after 2 years with a Topcon SL-45 Scheimpflug camera on Kodak T(max) 400 ISO film. The recording procedure, film development, and microdensitometric image analysis were all performed according to standard protocol. A second group from the same study was documented at the start and after 5 months of a 6-month posttreatment period immediately following the inhalation period. Rats were nose-only exposed for 6 h/day, 7 days/week, for 2 years to low (3 microg/l) or high (10 microg/l) concentrations of room-aged cigarette sidestream smoke or diesel engine exhaust. Control animals were exposed to filtered fresh air. At the baseline examination, there were no relevant differences between groups with respect to corneal density or density of defined layers in the lens capsule (1), epithelium and superficial cortex (2), deep cortex (3), supranuclear layer (4) and nucleus (5). At the 2-year examination, mean corneal density was significantly lower in females than in males. This same trend, although not significant, was also found in most layers of the lens. The most prominent differences in density over time were measured in lens layers 3 and 4, but neither corneal density nor lenticular density showed any consistent treatment-related effects in any of the layers. The data

  14. Practical prediction model for the risk of 2-year mortality of individuals in the general population.

    PubMed

    Goldfarb-Rumyantzev, Alexander; Gautam, Shiva; Brown, Robert S

    2016-04-01

    This study proposed to validate a prediction model and risk-stratification tool of 2-year mortality rates of individuals in the general population suitable for office practice use. A risk indicator (R) derived from data in the literature was based on only 6 variables: to calculate R for an individual, starting with 0, for each year of age above 60, add 0.14; for a male, add 0.9; for diabetes mellitus, add 0.7; for albuminuria >30 mg/g of creatinine, add 0.7; for stage ≥3 chronic kidney disease (CKD), add 0.9; for cardiovascular disease (CVD), add 1.4; or for both CKD and CVD, add 1.7. We developed a univariate logistic regression model predicting 2-year individual mortality rates. The National Health and Nutrition Examination Survey (NHANES) data set (1999-2004 with deaths through 2006) was used as the target for validation. These 12,515 subjects had a mean age of 48.9±18.1 years, 48% males, 9.5% diabetes, 11.7% albuminuria, 6.8% CVD, 5.4% CKD, and 2.8% both CKD and CVD. Using the risk indicator R alone to predict mortality demonstrated good performance with area under the receiver operating characteristic (ROC) curve of 0.84. Dividing subjects into low-risk (R=0-1.0), low intermediate risk (R>1.0-3.0), high intermediate risk (R>3.0-5.0) or high-risk (R>5.0) categories predicted 2-year mortality rates of 0.52%, 1.44%, 5.19% and 15.24%, respectively, by the prediction model compared with actual mortality rates of 0.29%, 2.48%, 5.13% and 13.40%, respectively. We have validated a model of risk stratification using easily identified clinical characteristics to predict 2-year mortality rates of individuals in the general population. The model demonstrated performance adequate for its potential use for clinical practice and research decisions. PMID:26951378

  15. Ten-year survival of hepatocellular carcinoma patients undergoing radiofrequency ablation as a first-line treatment

    PubMed Central

    Yang, Wei; Yan, Kun; Goldberg, S Nahum; Ahmed, Muneeb; Lee, Jung-Chieh; Wu, Wei; Zhang, Zhong-Yi; Wang, Song; Chen, Min-Hua

    2016-01-01

    AIM: To investigate the long-term survival and prognostic factors in hepatocellular carcinoma (HCC) patients undergoing radiofrequency ablation (RFA) as a first-line treatment. METHODS: From 2000 to 2013, 316 consecutive patients with 404 HCC (1.0-5.0 cm; mean: 3.2 ± 1.1 cm) underwent ultrasonography-guided percutaneous RFA as a first-line treatment. There were 250 males and 66 females with an average age of 60.1 ± 10.8 years (24-87 years). Patients were followed for 1 year to > 10 years after RFA (234, 181, 136, and 71 for 3, 5, 7, and 10 years, respectively). Overall local response rates and long-term survival rates were assessed. Survival results were generated using Kaplan-Meier estimates, and multivariate analysis was performed using the Cox regression model. RESULTS: In total, 548 RFA sessions were performed and major complications occurred in 10 sessions (1.8%). Local tumor progression and/or new tumor development were observed in 43.3% (132/305) of the patients during the follow-up period. Overall 5- and 10-year survival rates were 49.7% and 28.4%, respectively. Based on multivariate analysis, three factors were identified as independent prognostic factors for overall survival: Child-Pugh classification (HR = 4.054, P < 0.001), portal vein hypertension (HR = 2.743, P = 0.002), and tumor number (HR = 2.693, P = 0.003). The local progression-free 5- and 10-year survival rates were 42.7% and 19.5%. In addition to the Child-Pugh classification and the number of tumors, the number of RFA sessions (HR = 1.550, P = 0.002) was associated with local progression-free survival. CONCLUSION: RFA can achieve acceptable outcomes for HCC patients as a first-line treatment, especially for patients with Child-Pugh class A, patients with a single tumor and patients without portal vein hypertension. PMID:26973395

  16. Common raven juvenile survival in a human-augmented landscape

    USGS Publications Warehouse

    Webb, W.C.; Boarman, W.I.; Rotenberry, J.T.

    2004-01-01

    Anthropogenic resource subsidies have contributed to the dramatic increase in the abundance of Common Ravens (Corvus corax) in the western Mojave Desert, California, during the past 30 years. To better understand the effects of these subsidies on raven demography, we examined whether survival to juvenile departure from the natal territory could be predicted by a set of environmental and morphological variables, such as nest proximity to anthropogenic resources and juvenile condition. We captured 240 juvenile ravens over 2 years and marked them prior to fledging. Nest proximity to anthropogenic resources and earlier fledging dates significantly predicted raven juvenile survival to departure from the natal territory. The best-fitting mark-recapture models predicted postdeparture survival as a function of time since fledging, nest proximity to anthropogenic resources, and year hatched. The positive effect of nest proximity to anthropogenic resources influenced postdeparture survival for at least 9 months after fledging, as revealed by the mark-recapture analysis. Annual survival was 47% for first-year, 81% for second-year, and 83% for third-year birds. Our results support the hypothesis that anthropogenic resources contribute to increasing raven numbers via increased juvenile survival to departure as well as increased postdeparture survival. We expect raven numbers to grow in concert with the growing human presence in the Mojave Desert unless raven access to anthropogenic resources is diminished.

  17. 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.

  18. 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

  19. 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

  20. Cracking the survival code

    PubMed Central

    Füllgrabe, Jens; Heldring, Nina; Hermanson, Ola; Joseph, Bertrand

    2014-01-01

    Modifications of histones, the chief protein components of the chromatin, have emerged as critical regulators of life and death. While the “apoptotic histone code” came to light a few years ago, accumulating evidence indicates that autophagy, a cell survival pathway, is also heavily regulated by histone-modifying proteins. In this review we describe the emerging “autophagic histone code” and the role of histone modifications in the cellular life vs. death decision. PMID:24429873

  1. Survivable Optical WDM Networks

    NASA Astrophysics Data System (ADS)

    Ou, Canhui (Sam); Mukherjee, Biswanath

    Survivable Optical WDM Networks investigates different approaches for designing and operating an optical network with the objectives that (1) more connections can be carried by a given network, leading to more revenue, and (2) connections can recover faster in case of failures, leading to better services. Different networks - wavelength-routed WDM networks, wavelength-routed WDM networks with sub-wavelength granularity grooming, and data over next-generation SONET/SDH over WDM networks - are covered.

  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. Diabetic foot wounds in haemodialysis patients: 2-year outcome after percutaneous transluminal angioplasty and minor amputation.

    PubMed

    Matsuzaki, Kyoichi; Miyamoto, Akira; Hakamata, Naohiro; Fukuda, Masahiro; Yamauchi, Yasutaka; Akita, Takako; Kuhara, Ryoji; Tezuka, Shingo

    2012-12-01

    Critical limb ischaemia (CLI) is known to be associated with high mortality. In some patients, surgery cannot be performed due to high risk of perioperative death and complications. In other cases, there is only pain at rest but no wound. Therefore, it is difficult to accurately predict the prognosis of individual patients. We examined the prognosis of CLI cases in which therapeutic footwear was made for ambulation after wounds healed. The subjects were 31 haemodialysis patients with diabetic foot wounds, which were treated with percutaneous transluminal angioplasty and minor amputation. The subjects were 22 men and 9 women. Female patients were significantly older than male patients (P = 0.046). Two-year postoperative outcomes were survival in 19 patients and death in 12 patients. Eight of twelve deceased patients had a history of coronary intervention. There were 8 deaths among 13 patients with such history, indicating a marginally significant increase in the mortality rate (P = 0.060). Re-amputation was performed in 6 of 19 patients who survived. Two years postoperatively, 41.9% of patients overall survived without re-amputation. It is important to increase the number of cases for further study to improve the well-being of CLI patients and to examine medical economics. PMID:23095148

  4. Radiostereometric migration analysis of the Cerafit femoral stem: 28 patients followed for 2 years.

    PubMed

    Tschunko, Franz; Wagner, Benedikt; Hong, Yutong; Söder, Stephan; Wölfel, Rainer; Müller, Lutz A; Forst, Raimund; Sesselmann, Stefan

    2016-06-01

    Radiostereometric analysis (RSA) is the gold standard evaluating micromovements after total hip arthroplasty. The aim of this study was to investigate the migratory pattern of an uncemented femoral stem during the first 2 years after surgery. We followed 28 patients with a mean age of 57 (SD 13) years for the first two postoperative years. Radiostereometric analysis was used to measure the translation and rotation of the femoral component. The Harris hip score (HHS) was determined to evaluate the clinical outcome. No stem had to be revised. The mean HHS advanced from 35 (SD 11) preoperative to 89 (SD 10) 1 year after surgery. At the end of the observation period, mean subsidence of the stem was 0.26 mm (SD 0.82). Maximum total point motion (MTPM) was 1.23 mm (SD 1.22). The main distal migration took place up to 6 weeks after surgery with nearly no further subsidence up to 2 years postoperatively. All the measured migrations of the hip stem were very small. Results of the HHS demonstrate good clinical outcome. Long-term RSA is necessary to assess possible late migration of the Cerafit standard femoral stem. PMID:25996482

  5. A 2-year longitudinal analysis of the relationships between violent assault and substance use in women.

    PubMed

    Kilpatrick, D G; Acierno, R; Resnick, H S; Saunders, B E; Best, C L

    1997-10-01

    Women experience alarming levels of physical and sexual assault, which may lead to escalation of substance use. Reciprocally, evidence from cross-sectional studies indicates that substance use may increase risk of assault. To date, directionality of this relationship remains unclear. This issue is addressed by the present 3-wave longitudinal study in which a national probability sample of 3,006 women were followed for 2 years. Dependent measures were obtained at each wave of the study and included questions about lifetime and new assault status, alcohol abuse, and drug use. Wave 1 use of drugs, but not abuse of alcohol, increased odds of new assault in the subsequent 2 years. Reciprocally, after a new assault, odds of both alcohol abuse and drug use were significantly increased, even among women with no previous use or assault history. For illicit drug use, findings support a vicious cycle relationship in which substance use increases risk of future assault and assault increases risk of subsequent substance use. PMID:9337502

  6. A 2-year longitudinal nutritional survey of 405 Northumberland children initially aged 11.5 years.

    PubMed

    Hackett, A F; Rugg-Gunn, A J; Appleton, D R; Eastoe, J E; Jenkins, G N

    1984-01-01

    Children (405), initially of average age 11.5 years, recorded all food and drinks consumed for three consecutive days (with an interview on the fourth day) on five separate occasions over a 2-year period. Food tables (Paul & Southgate, 1978) enabled nutrient intakes to be calculated. The data collected were found to be of high reliability (Hackett et al. 1983). The mean energy intakes showed broad agreement with other recent British dietary surveys but were well below those recorded in the prewar study by Widdowson (1947) and the FAO/WHO (1973) recommended levels. They were slightly below the current Department of Health and Social Security (DHSS; 1979) recommended intakes. Over the 2-year period, the energy intake of the boys increased by 13% compared with an increase of only 7% in the girls. The iron and vitamin A intakes of all groups of children were low compared with current recommendations (DHSS, 1979). This seems to be a result of falling energy intake. Mean calcium intakes were also only marginally in excess of the recommended intake, and those of most of the girls would fall below the recommendation if the proposal to end the fortification of flour (DHSS, 1981) is implemented. PMID:6317011

  7. Vitamin D Status in Botswana Children Under 2 Years Old With and Without Active Tuberculosis.

    PubMed

    Ludmir, Jonathan; Mazhani, Loeto; Cary, Mark S; Chakalisa, Unoda A; Pettifor, John M; Molefi, Mooketsi; Redwood, Abiona; Stallings, Virginia A; Gross, Robert; Steenhoff, Andrew P

    2016-05-01

    Additional strategies are needed to prevent and treat tuberculosis (TB). Although vitamin D may have antimycobacterial effects, it is unknown whether low vitamin D status confers a risk for active TB in African children. This case-control study assessed serum 25-hydroxyvitamin D (25(OH)D) concentration in children with and without active TB in Gaborone, Botswana. A total of 80 children under 2 years old with and without active TB, seen at hospitals and clinics in the greater Gaborone area between September 2010 and November 2012, were enrolled. Of these, 39 cases did not differ from the 41 controls in median 25(OH)D levels (P = 0.84). The 25(OH)D was < 20 ng/mL in 8/39 (21%) cases and 7/41 (17%) controls (P = 0.69, χ(2)). Univariate analyses of subject clinical characteristics (other than 25(OH)D levels) showed that any degree of weight loss was associated with a diagnosis of TB (P = 0.047). Other clinical characteristics, including age (P = 0.08) or weight below third percentile (P = 0.58), showed no association with TB. There was no significant difference in vitamin D status between children under 2 years old with and without active TB. Lower vitamin D status did not appear to be a risk factor for TB in this small Gaborone cohort. PMID:26976889

  8. Sleep/wake patterns of breast-fed infants in the first 2 years of life.

    PubMed

    Elias, M F; Nicolson, N A; Bora, C; Johnston, J

    1986-03-01

    Published norms for infant sleep/wake patterns during the first 2 years of life include an increase in length of maximum sleep bout from four to five to eight to ten hours by 4 months but little decrease in total sleep in 24 hours from 13 to 15 hours. Thirty-two breast-fed infants were followed for 2 years and data collected on 24-hour patterns of nursing and sleep. Infants who were breast-fed into the second year did not develop sleep/wake patterns in conformance with the norms. Instead of having long unbroken night sleep, they continued to sleep in short bouts with frequent wakings. Their total sleep in 24 hours was less than that of weaned infants. This pattern was most pronounced in infants who both nursed and shared a bed with the mother, common practices in many nonwestern cultures. The sleep/wake development accepted as the physiologic norm may be attributable to the early weaning and separated sleeping practiced in western culture. As prolonged breast-feeding becomes more popular in our society, the norms of sleep/wake patterns in infancy will have to be revised. PMID:3951913

  9. Patients Awaiting Heart Transplantation on HVAD Support for Greater Than 2 Years.

    PubMed

    Aaronson, Keith D; Silvestry, Scott C; Maltais, Simon; Mallidi, Hari R; Frazier, O H; Boyce, Steven W; Leadley, Katrin; Najarian, Kevin B; Slaughter, Mark S; Pagani, Francis D

    2016-01-01

    Advanced heart failure patients who are classified as bridge to transplant (BTT) often remain on mechanical circulatory support (MCS) for long durations because of the limited supply of donor organs. Here, we present the outcomes of patients who have been supported by the HeartWare ventricular assist device system for more than 2 years. In the HeartWare BTT and continued access protocol trial, 74 of the 382 total patients (19.4%) had more than 2 years of MCS with a mean time of 1,045 days on device. The long-term group was more frequently female, was nonwhite, and had Interagency Registry for Mechanically Assisted Circulatory Support profiles 4-7. Postimplant adverse event rates including bleeding, cardiac arrhythmia, infection, stroke, renal dysfunction, and right heart failure were less frequent in the long-term cohort. In addition, the long-term cohort displayed significant improvements in Kansas City Cardiomyopathy Questionnaire Overall Summary Score, EuroQOL-5D Overall Health State Score, and 6 minute walk scores from baseline values. The rate of heart transplantation was lower for the long-term cohort, which may have been a result of their sex and blood type. However, most of these patients are still listed for cardiac transplantation and maintained their quality of life profiles through 3 years of support. PMID:27111739

  10. Brain activity during a visuospatial working memory task predicts arithmetical performance 2 years later.

    PubMed

    Dumontheil, Iroise; Klingberg, Torkel

    2012-05-01

    Visuospatial working memory (WM) capacity is highly correlated with mathematical reasoning abilities and can predict future development of arithmetical performance. Activity in the intraparietal sulcus (IPS) during visuospatial WM tasks correlates with interindividual differences in WM capacity. This region has also been implicated in numerical representation, and its structure and activity reflect arithmetical performance impairments (e.g., dyscalculia). We collected behavioral (N = 246) and neuroimaging data (N = 46) in a longitudinal sample to test whether IPS activity during a visuospatial WM task could provide more information than psychological testing alone and predict arithmetical performance 2 years later in healthy participants aged 6-16 years. Nonverbal reasoning and verbal and visuospatial WM measures were found to be independent predictors of arithmetical outcome. In addition, WM activation in the left IPS predicted arithmetical outcome independently of behavioral measures. A logistic model including both behavioral and imaging data showed improved sensitivity by correctly classifying more than twice as many children as poor arithmetical performers after 2 years than a model with behavioral measures only. These results demonstrate that neuroimaging data can provide useful information in addition to behavioral assessments and be used to improve the identification of individuals at risk of future low academic performance. PMID:21768226

  11. Hospital admissions before the age of 2 years in Western Australia.

    PubMed Central

    Read, A W; Gibbins, J; Stanley, F J; Morich, P

    1994-01-01

    A linked data file of birth records and hospital admissions was used to investigate inpatient hospital morbidity before 2 years of age for all non-Aboriginal and Aboriginal children born in Western Australia in 1986. Of the non-Aboriginal children, 31.8% were admitted to hospital at least once before the age of 2 years, with an overall admission rate of 526/1000 live births; the corresponding figures for Aboriginal children were 68.7% and 2797. The mean number of days in hospital for each non-Aboriginal child admitted was 7.4, and 26.5 for Aboriginal children. Of the total cohort, 21% of non-Aboriginal and 20% of Aboriginal children were admitted only once, and 4% of non-Aboriginal and 36% of Aboriginal children were admitted at least three times; 23% of non-Aboriginal and 24% of Aboriginal children were admitted for only one major disease category, and 1% of non-Aboriginal and 16% of Aboriginal children were in at least four categories. The highest admission rates and highest percentages of the cohort admitted were for gastrointestinal and respiratory diseases and social admissions. These results illustrate the importance for both descriptive and analytical research of relating admissions to hospital for the total population to the individual child, and of using clinically relevant disease classifications. PMID:8135564

  12. Live Pups from Evaporatively Dried Mouse Sperm Stored at Ambient Temperature for up to 2 Years

    PubMed Central

    Liu, Jie; Lee, Gloria Y.; Lawitts, Joel A.; Toner, Mehmet; Biggers, John D.

    2014-01-01

    The purpose of this study is to develop a mouse sperm preservation method based on evaporative drying. Mouse sperm were evaporatively dried and stored at 4°C and ambient temperature for 3 months to 2 years. Upon rehydration, a single sperm was injected into a mature oocyte to develop into a blastocyst after culture or a live birth after embryo transfer to a recipient female. For the samples stored at 4°C for 3, 6, 12, 18, and 24 months, the blastocyst formation rate was 61.5%, 49.1%, 31.5%, 32.2%, and 41.4%, respectively. The blastocyst rate for those stored at ambient temperature (∼22°C) for 3, 6, 12, and 18 months was 57.8%, 36.2%, 33.6%, and 34.4%, respectively. Fifteen, eight and three live pups were produced from sperm stored at room temperature for 12, 18, and 24 months, respectively. This is the first report of live offspring produced from dried mouse sperm stored at ambient temperature for up to 2 years. Based on these results, we suggest that evaporative drying is a potentially useful method for the routine preservation of mouse sperm. PMID:24924588

  13. A model of Earth's magnetic field derived from 2 years of Swarm satellite constellation data

    NASA Astrophysics Data System (ADS)

    Olsen, Nils; Finlay, Christopher C.; Kotsiaros, Stavros; Tøffner-Clausen, Lars

    2016-07-01

    More than 2 years of magnetic field data taken by the three-satellite constellation mission Swarm are used to derive a model of Earth's magnetic field and its time variation. This model is called SIFMplus. In addition to the magnetic field observations provided by each of the three Swarm satellites, explicit advantage is taken of the constellation aspect of Swarm by including East-West magnetic intensity and vector field gradient information from the lower satellite pair. Along-track differences of the magnetic intensity as well as of the vector components provide further information concerning the North-South gradient. The SIFMplus model provides a description of the static lithospheric field that is very similar to models determined from CHAMP data, up to at least spherical harmonic degree n=75. Also the core field part of SIFMplus, with a quadratic time dependence for n ≤ 6 and a linear time dependence for n=7-15, demonstrates the possibility to determine high-quality field models from only 2 years of Swarm data, thanks to the unique constellation aspect of Swarm. To account for the magnetic signature caused by ionospheric electric currents at polar latitudes we co-estimate, together with the model of the core, lithospheric and large-scale magnetospheric fields, a magnetic potential that depends on quasi-dipole latitude and magnetic local time.

  14. The 2-year stability of parental perceptions of child vulnerability and parental overprotection.

    PubMed

    Thomasgard, M; Metz, W P

    1996-08-01

    Clinicians often identify parent-child relationships that are believed to be problematic for the child's future emotional growth, yet there are minimal outcome data on which to base anticipatory guidance. This 2-year follow-up study examined the stability and child behavioral correlates of parental perceptions of increased child vulnerability and parental overprotection. Of 192 potential participants, 114 parents (93% mothers, 86% white, 75% married, 90% middle-upper socioeconomic status) with children age 4 to 7 years successfully completed the Parent Protection Scale, Child Vulnerability Scale, Child Behavior Checklist 4-18, and the Parental Bonding Instrument. The 2-year stability of high parental overprotection was 37%; for high parental perception of child vulnerability, it was 31%. High perceived vulnerability at enrollment was significantly associated with both internalizing (somatic complaints, anxious/depressed) and externalizing (aggressive) behaviors at follow-up. A history of overprotection in the parent's childhood was not associated with current parental report of overprotective behaviors toward the child. PMID:8856517

  15. Translating theory into practice: results of a 2-year trial for the LEAD programme.

    PubMed

    Shelton, D

    2008-05-01

    This paper presents data for 2 years of a continuing study aimed to reduce the risk of first-time involvement by minority youth with the juvenile justice system. A quasi-experimental design was used to test a 14-week expressive art curriculum (LEAD: leadership, education, achievement and development) implemented in two rural communities. A total of 70 African American youth participated in the programme over a 2-year period. Pre- and post-test differences were examined for protective factors, behavioural self-control, self-esteem and resilience measures. When compared with the after-school programme (control group), youth in the LEAD programme in both communities had more dramatic increases in post-test scores following the intervention. The combined data from year 1 and year 2 provide positive findings in support of LEAD as a prevention programme for young offenders. The placement of the programme within an African American church in year 2 improved the processes of the LEAD programme and seemed to provide a better fit with the original design of the programme, highlighting the importance of the context, in which the programme was provided. PMID:18387150

  16. Phonetic Modification of Vowel Space in Storybook Speech to Infants up to 2 Years of Age

    PubMed Central

    Burnham, Evamarie B.; Wieland, Elizabeth A.; Kondaurova, Maria V.; McAuley, J. Devin; Bergeson, Tonya R.

    2015-01-01

    Purpose A large body of literature has indicated vowel space area expansion in infant-directed (ID) speech compared with adult-directed (AD) speech, which may promote language acquisition. The current study tested whether this expansion occurs in storybook speech read to infants at various points during their first 2 years of life. Method In 2 studies, mothers read a storybook containing target vowels in ID and AD speech conditions. Study 1 was longitudinal, with 11 mothers recorded when their infants were 3, 6, and 9 months old. Study 2 was cross-sectional, with 48 mothers recorded when their infants were 3, 9, 13, or 20 months old (n = 12 per group). The 1st and 2nd formants of vowels /i/, /ɑ/, and /u/ were measured, and vowel space area and dispersion were calculated. Results Across both studies, 1st and/or 2nd formant frequencies shifted systematically for /i/ and /u/ vowels in ID compared with AD speech. No difference in vowel space area or dispersion was found. Conclusions The results suggest that a variety of communication and situational factors may affect phonetic modifications in ID speech, but that vowel space characteristics in speech to infants stay consistent across the first 2 years of life. PMID:25659121

  17. Age-specific survival estimates of King Eiders derived from satellite telemetry

    USGS Publications Warehouse

    Oppel, Steffen; Powell, Abby N.

    2010-01-01

    Age- and sex-specific survival and dispersal are important components in the dynamics and genetic structure of bird populations. For many avian taxa survival rates at the adult and juvenile life stages differ, but in long-lived species juveniles' survival is logistically challenging to study. We present the first estimates of hatch-year annual survival rates for a sea duck, the King Eider (Somateria spectabilis), estimated from satellite telemetry. From 2006 to 2008 we equipped pre-fiedging King Eiders with satellite transmitters on breeding grounds in Alaska and estimated annual survival rates during their first 2 years of life with known-fate models. We compared those estimates to survival rates of adults marked in the same area from 2002 to 2008. Hatch-year survival varied by season during the first year of life, and model-averaged annual survival rate was 0.67 (95% CI: 0.48–0.80). We did not record any mortality during the second year and were therefore unable to estimate second-year survival rate. Adults' survival rate was constant through the year (0.94, 95% CI: 0.86–0.97). No birds appeared to breed during their second summer. While 88% of females with an active transmitter (n = 9) returned to their natal area at the age of 2 years, none of the 2-year old males (n = 3) did. This pattern indicates that females' natal philopatry is high and suggests that males' higher rates of dispersal may account for sex-specific differences in apparent survival rates of juvenile sea ducks when estimated with mark—recapture methods.

  18. Surrogate clinical endpoints to predict overall survival in non-small cell lung cancer trials—are we in a new era?

    PubMed Central

    Wang, Xiaofei; Ready, Neal E.

    2015-01-01

    Surrogate endpoints for clinical trials in oncology offer an alternative metric for measuring clinical benefit, allowing for shorter trial duration, smaller patient cohorts, and single arm design. The correlation of surrogate endpoints with overall survival (OS) in therapeutic studies is a central consideration to their validity. The Food and Drug Administration (FDA) recently published an analysis of fourteen clinical trials in advanced non-small cell lung cancer (NSCLC), and discovered a strong association between response rate and progression free survival. Furthermore, a correlation between response rate and OS is demonstrated when analyzing the experimental treatment arm separately, minimizing bias from patient crossover. We also highlight multiple, important considerations when using response as an endpoint in clinical trials involving NSCLC patients. PMID:26798592

  19. Effectiveness of a tinnitus management programme: a 2-year follow-up study

    PubMed Central

    Gudex, Claire; Skellgaard, Preben H; West, Torben; Sørensen, Jan

    2009-01-01

    Background Tinnitus impairs the possibility of leading a normal life in 0.5–1% of the population. While neither medical nor surgical treatment appears effective, counselling may offer some relief. An intervention combining counselling and hearing devices is offered to clients referred to the Centre for Help Aids and Communication (CHC) in southern Denmark. The aims of this exploratory study were to examine i) the characteristics of CHC's clients and their tinnitus, ii) the effectiveness of the treatment, and iii) whether particular client groups benefit more than others. Methods One hundred new clients presenting with tinnitus completed the Tinnitus Handicap Inventory (THI) three times – before their first consultation, after one month and after 1–2 years. The scores were tested for significant differences over time using tests for paired data. Logistic regression was used to examine factors associated with a clinically important difference (i.e. THI score improvement of at least 20 points). Results At final follow-up, total THI score was significantly lower than baseline, i.e. 29.8 (CI 25.5–34.2) vs. 37.2 (CI 33.1–37.2), p < 0.01. The programme achieved a clinically important difference for 27% and 24% of the clients one month and 1–2 years after the first consultation, respectively. It appeared that greater improvement in THI score was related to higher baseline THI score and possibly also to treatment by a particular CHC therapist. The absolute reduction in mean THI score after 1–2 years for clients with moderate and severe handicap was 14 and 20 points, respectively, i.e. similar to that previously reported for TRT (14–28 points). The cost of the current programme was approximately 200 EUR per client. Conclusion The tinnitus management programme appeared to provide significant benefit to many clients at a relatively low cost. It would be useful to conduct a randomised controlled study comparing the current programme with alternative forms of

  20. Higher Tetanus Toxoid Immunity 2 Years After PsA-TT Introduction in Mali

    PubMed Central

    Basta, Nicole E.; Borrow, Ray; Berthe, Abdoulaye; Onwuchekwa, Uma; Dembélé, Awa Traoré Eps; Almond, Rachael; Frankland, Sarah; Patel, Sima; Wood, Daniel; Nascimento, Maria; Manigart, Olivier; Trotter, Caroline L.; Greenwood, Brian; Sow, Samba O.

    2015-01-01

    Background. In 2010, mass vaccination with a then-new meningococcal A polysaccharide–tetanus toxoid protein conjugate vaccine (PsA-TT, or MenAfriVac) was undertaken in 1- to 29-year-olds in Bamako, Mali. Whether vaccination with PsA-TT effectively boosts tetanus immunity in a population with heterogeneous baseline tetanus immunity is not known. We assessed the impact of PsA-TT on tetanus toxoid (TT) immunity by quantifying age- and sex-specific immunity prior to and 2 years after introduction. Methods. Using a household-based, age-stratified design, we randomly selected participants for a prevaccination serological survey in 2010 and a postvaccination survey in 2012. TT immunoglobulin G (IgG) antibodies were quantified and geometric mean concentrations (GMCs) pre- and postvaccination among all age groups targeted for vaccination were compared. The probability of TT IgG levels ≥0.1 IU/mL (indicating short-term protection) and ≥1.0 IU/mL (indicating long-term protection) by age and sex was determined using logistic regression models. Results. Analysis of 793 prevaccination and 800 postvaccination sera indicated that while GMCs were low pre–PsA-TT, significantly higher GMCs in all age–sex strata were observed 2 years after PsA-TT introduction. The percentage with short-term immunity increased from 57.1% to 88.4% (31.3-point increase; 95% confidence interval [CI], 26.6–36.0;, P < .0001) and with long-term immunity increased from 20.0% to 58.5% (38.5-point increase; 95% CI, 33.7–43.3; P < .0001) pre- and postvaccination. Conclusions. Significantly higher TT immunity was observed among vaccine-targeted age groups up to 2 years after Mali's PsA-TT mass vaccination campaign. Our results, combined with evidence from clinical trials, strongly suggest that conjugate vaccines containing TT such as PsA-TT should be considered bivalent vaccines because of their ability to boost tetanus immunity. PMID:26553691

  1. Surgery of colorectal cancer lung metastases: analysis of survival, recurrence and re-surgery

    PubMed Central

    Guerrera, Francesco; Mossetti, Claudio; Ceccarelli, Manuela; Bruna, Maria Cristina; Bora, Giulia; Olivetti, Stefania; Lausi, Paolo Olivo; Solidoro, Paolo; Ciccone, Giovannino; Ruffini, Enrico; Oliaro, Alberto

    2016-01-01

    Background Surgery is considered an effective therapeutic option for patients with lung metastasis (MTS) of colorectal cancer (CRC). The purpose of the study was to evaluate efficacy and feasibility of lung metastasectomy in CRC patients and to explore factors of prognostic relevance. Methods This is a retrospective study of patients operated for lung MTS of CRC from 2004 to 2012 in a single Institution. Overall survival (OS) was the primary endpoint. Secondary endpoints were progression free survival (PFS) in resection status R0 and OS in in patients submitted to re-resections. In order to evaluate prognostic factors, a multivariable Cox proportional hazard model was performed. Results One-hundred eighty-eight consecutive patients were included in the final analysis. The median follow-up (FU) was 45 months. The 5-year OS and PFS were 53% (95% CI: 44–60%) and 33% (95% CI: 25–42%), respectively. Two- and 5-year survival after re-resection were 79% (95% CI: 63–89%) and 49% (95% CI: 31–65%), respectively. Multivariate adjusted analysis showed that primary CRC pathological TNM stages (P=0.019), number of resected MTS ≥5 (P=0.009) and lymph nodal involvement (P<0.0001) are independent predictors of poor prognosis. Conclusions Patients operated and re-operated for lung MTS from CRC cancers showed encouraging survival rates. Our results indicated that primary CRC stage, number of MTS and lymph nodal involvement are strong predictive factors. Prognosis after surgery remained comforting up to four resected MTS. Adjuvant chemotherapy seems to have a benefit on survival in patients affected by multiple metastases. Finally, according to the high rate of unidentified lymph node involvement in pre-operative setting, lymph node sampling should be advisable for a correct staging. PMID:27499967

  2. Understanding Cancer: Survivability and Hope

    MedlinePlus

    ... Bar Home Current Issue Past Issues Special Section Survivability and Hope Past Issues / Spring 2007 Table of ... More "Understanding Cancer" Articles Understanding Cancer / Cancer Today / Survivability and Hope / Sam Donaldson: Tips From a Cancer ...

  3. Classification Schemes: Developments and Survival.

    ERIC Educational Resources Information Center

    Pocock, Helen

    1997-01-01

    Discusses the growth, survival and future of library classification schemes. Concludes that to survive, a scheme must constantly update its policies, and readily adapt itself to accommodate growing disciplines and changing terminology. (AEF)

  4. 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

  5. Inoculation of Pinus halepensis Mill. with selected ectomycorrhizal fungi improves seedling establishment 2 years after planting in a degraded gypsum soil.

    PubMed

    Rincón, Ana; de Felipe, M R; Fernández-Pascual, M

    2007-12-01

    Vegetative inoculum of Amanita ovoidea (Bull.) Link and three isolates of Suillus collinitus (Fr.) Kuntze, as well as spore inoculum of Rhizopogon roseolus (Corda) Th. M. Fr. and S. collinitus, were evaluated for the production of Pinus halepensis Mill. in nursery and for the establishment of seedlings in a degraded gypsum soil. In nursery, most of the fungi significantly improved the height of seedlings and modified the accumulation of nutrients in needles. The percentage of ectomycorrhizas (ESR) per seedling ranged from 25 to 78%, depending on the fungi. One and 2 years after planting in the field, the survival of seedlings was significantly improved by inoculation with two isolates of S. collinitus and with spores of the same fungus. Inoculation with A. ovoidea had no significant effect on seedling survival, whilst R. roseolus caused a significant mortality of seedlings. Seedling height was significantly improved by inoculation with all fungi except R. roseolus and isolate CCMA-1 of S. collinitus. One year after planting, mycorrhization of control seedlings was negligible, and percentages of ESR were under 38% for the rest of treatments. In spring of the second year, seedlings in all treatments, including the control, became highly mycorrhizal (60-77% of ESR). Low ectomycorrhizal diversity (five morphotypes described) and seasonal variation on morphotype composition were detected 2 years after plantation. From a perspective of soil restoration management under limiting environmental conditions, nursery inoculation with selected fungi can be a key advantage for tree seedlings to surmount the initial transplant stress, assuring their establishment in the field. Our results emphasise the importance of selecting compatible fungal-host species combinations for nursery inoculation and sources of inoculum adapted to the environmental conditions of the transplantation site. PMID:17874144

  6. Functional outcomes of proximal row carpectomy: 2-year follow-up

    PubMed Central

    Mandarano-Filho, Luiz Garcia; Campioto, Débora Schalge; Bezuti, Márcio Takey; Mazzer, Nilton; Barbieri, Cláudio Henrique

    2015-01-01

    ABSTRACT OBJECTIVE : To evaluate functional outcomes of patients submit-ted to proximal row carpectomy for the treatment of wrist arthri-tis METHODS : This is a retrospective study using wrist motion and grip strenght of patients diagnosed with Kienböck disease and scaphoid non-union surgically treated by this technique RESULTS : Eleven patients with 2-year follow-up were evaluated. Wrist motion (flexion, extension and ulnar deviation) and grip strength were significantly better from preoperative values. Ho-wever, no difference in radial deviation was observed in these patients CONCLUSION : Proximal row carpectomy provides an alternative option for treatment of wrist arthritis, resulting in better active range of motion and grip strength in the long run. Level of Evidence IV, Case Series. PMID:27057144

  7. Speech identification in Spanish- and English-learning 2-year-olds.

    PubMed

    Oller, D K; Eilers, R E

    1983-03-01

    English- and Spanish-learning 2-year-olds were tested for speech skills in a real speech context. Each child was tested in his/her native language on one native and one nonnative contrast. The nonnative contrast consisted of a real native word paired with a nonsense word containing a nonnative element. The native contrast consisted of a native word paired with a nonsense word containing a minimally paired native element. The results showed that both groups of children found identification of native contrasts much easier than identification of nonnative contrasts. The results suggest that by age 2, normal children may have achieved an awareness of their native phonology, an awareness that encourages them to ignore certain distinctions that are not part of their language's contrastive meaning system. PMID:6865381

  8. Health-Engagement Control Strategies and 2-Year Changes in Older Adults’ Physical Health

    PubMed Central

    Wrosch, Carsten; Schulz, Richard

    2009-01-01

    This study examined the associations between older adults’ daily physical symptoms (e.g., chest pain or difficulty breathing) and 2-year changes in chronic health problems (e.g., cardiovascular disease or cancer) and in functional problems (e.g., difficulty dressing or moving around at home). We reasoned that these associations depend on a person’s active control processes aimed at counteracting physical health problems (i.e., health-engagement control strategies, or HECS). In particular, we hypothesized that high levels of HECS buffer the adverse effect of daily physical symptoms on increases in chronic and functional health problems. We found that daily physical symptoms were associated with declines in chronic and functional health among older adults who were not engaged in addressing their health problems, but not among their counterparts who reported high levels of HECS. These findings suggest that active control strategies play an important role in the maintenance of older adults’ physical health. PMID:18578842

  9. Stressful work, psychological job strain, and turnover: a 2-year prospective cohort study of truck drivers.

    PubMed

    de Croon, Einar M; Sluiter, Judith K; Blonk, Roland W B; Broersen, Jake P J; Frings-Dresen, Monique H W

    2004-06-01

    Based on a model that combines existing organizational stress theory and job transition theory, this 2-year longitudinal study examined antecedents and consequences of turnover among Dutch truck drivers. For this purpose, self-reported data on stressful work (job demands and control), psychological strain (need for recovery after work and fatigue), and turnover were obtained from 820 drivers in 1998 and 2000. In agreement with the model, the results showed that strain mediates the influence of stressful work on voluntary turnover. Also in conformity with the model, job movement to any job outside the trucking industry (i.e., interoccupational turnover) resulted in a larger strain reduction as compared to job movement within the trucking industry (intraoccupational turnover). Finally, strain was found to stimulate interoccupational turnover more strongly than it stimulated intraoccupational turnover. These findings provide a thorough validation of existing turnover theory and give new insights into the turnover (decision) process. PMID:15161404

  10. Restrictive Strabismus and Diplopia 2 Years After Conjunctivodacryocystorhinostomy With Medpor-Coated Tear Drain.

    PubMed

    Shin, Dong Hoon; Kim, Yoon-Duck; Lee, Chung-Hyun; Johnson, Owen N; Woo, Kyung In

    2015-01-01

    A 19-year-old woman who underwent conjunctivodacryocystorhinostomy with Medpor-Coated Tear Drain 2 years ago presented with diplopia on left gaze for 4 months. Limitation of extraocular movement of OS on left gaze was observed on duction test. The forced duction test revealed restriction of the left medial rectus muscle. Orbital MRI demonstrated an enhancing soft tissue lesion surrounding the tube in inferomedial aspect of left orbit. Removal of the tube and adhesiolysis were performed. Histologic findings were consistent with a chronic inflammation with fibrosis. After surgery, limitation of extraocular movement and diplopia were completely resolved. Jones tube coated with a thin layer of porous polyethylene allows the ingrowth of fibrovascular tissue into the coating, decreasing the probability of tube extrusion, but can also accelerate fibrotic changes around the tube causing restrictive strabismus. PMID:24914690

  11. A case with reversible neurotoxicity after 2 years of dementia secondary to maintenance lithium treatment.

    PubMed

    Soriano-Barceló, Juan; Alonso, María Tajes; Traba, María Begoña Portela; Vilar, Alberte Araúxo; Kahn, David A

    2015-03-01

    Chronic neurotoxicity caused by lithium salts can be reversible or irreversible and may appear after years of treatment, even at serum levels considered within the usual therapeutic range. The authors present the case of a patient with bipolar disorder who developed dementia at the age of 54 after being treated with lithium carbonate at therapeutic levels for 4 years. Nevertheless, lithium treatment was continued. At age 56, the patient presented with an acute encephalopathy caused by toxic lithium levels, which resolved only after lithium carbonate was discontinued. Full recovery from the dementia, which had started 2 years earlier, occurred only after cessation of lithium. The authors conclude that when patients treated with lithium develop subacute cognitive impairment, the possibility of lithium toxicity should be considered, even if the serum levels are considered within the therapeutic range. A long duration of neurotoxicity associated with lithium treatment does not necessarily indicate an irreversible prognosis. PMID:25782766

  12. Attention to Multiple Events Helps 2 1/2-Year-Olds Extend New Verbs

    PubMed Central

    Childers, Jane B.

    2013-01-01

    An important question in verb learning is how children extend new verbs to new situational contexts. In Study 1, 2 1/2-year-old children were shown a complex event followed by new events that preserved only the action from the initial event, only the result, or no new events. Children seeing events that preserved either the action or the result produced appropriate verb extensions at test while children without this information did not. In a follow-up study, children hearing new verbs produced more extensions than did children hearing nonlabeling speech. These studies suggest that attention to related events is helpful to young verb learners, perhaps because they structurally align these events (e.g., Gentner, 1983; 1989) during verb learning. PMID:24324284

  13. A worksite smoking intervention: a 2 year assessment of groups, incentives and self-help.

    PubMed

    Jason, L A; Salina, D; McMahon, S D; Hedeker, D; Stockton, M

    1997-03-01

    Sixty-three companies in the Chicago area were recruited to participate in a worksite smoking cessation program. Participants in each worksite received a television program and newspaper supplement (part of a community-wide media campaign), and one of three conditions: (1) self-help manuals alone (M), (2) self-help manuals and incentives for 6 months (IM) or (3) maintenance manuals, incentives and cognitive-behavioral support groups for 6 months (GIM). Results at the 2 year assessment are examined using a random-effects regression model. In addition, various definitions of quit-rate commonly used in smoking cessation research are explored and the advantages of using a public health approach in the worksite are examined. PMID:10166900

  14. The Histological Changes of the Great Saphenous Vein at 2 Years after Cryosclerosis

    PubMed Central

    Balint, Istvan Bence; Bali, Ottilia; Vargovics, Eszter; Simon, Eva; Vizsy, Laszlo

    2014-01-01

    Cryosclerosis was developed at the end of the last decade. It is the endovenous cryoablation of the great saphenous vein and has been forgotten before the era of the endovenous ablation techniques began. The caused histomorphological changes of the vein weren’t described before, especially, years after the procedure. A 31-year-old female patient underwent cryosclerosis 2 years ago. Because of the recanalization of the great saphenous vein and recurrent varicosity, high ligation, cryostripping and phlebectomy of varices were performed. During surgery, a saphenous vein piece was harvested to investigate the histomorphological effect of cryosclerosis. Histological findings verified that recanalization had occurred, the vein wall had undergone remodeling, and the picro-sirius red stain showed collagen deposition in the whole vein wall. Cryosclerosis seems to result in the remodeling of the vein wall. PMID:26217627

  15. Occlusal glass ionomer cermet, resin sandwich and amalgam restorations: a 2-year clinical study.

    PubMed

    Lidums, A; Wilkie, R; Smales, R

    1993-08-01

    This study compared the clinical behavior of a glass ionomer silver cermet (Ketac-Silver), a posterior resin composite (Visio-Molar) used with the "sandwich" technique, and a high-copper amalgam (Dispersalloy) for restoring conventional Class I occlusal cavity preparations. Two dentists placed 116 restorations in the posterior permanent teeth of 35 adults treated at a dental hospital. Restorations were assessed at 6-month intervals over 2 years for bulk loss of material and occlusal wear, surface voids, roughness and cracking, surface and marginal staining, and marginal fracture. Losses of material and surface voids were obvious with the cermet material, with surface crazing or cracking being present in 33% of the restorations. The cermet cannot be recommended as a long-term permanent restorative material if the restorations are likely to be subjected to heavy occlusal stresses and abrasive wear. PMID:7803005

  16. Gesture and Symbolic Representation in Italian and English-Speaking Canadian 2-Year-Olds.

    PubMed

    Marentette, Paula; Pettenati, Paola; Bello, Arianna; Volterra, Virginia

    2016-05-01

    Analyses of elicited pantomime, primarily of English-speaking children, show that preschool-aged children are more likely to symbolically represent an object with gestures depicting an object's form rather than its function. In contrast, anecdotal reports of spontaneous gesture production in younger children suggest that children use multiple representational techniques. This study examined the spontaneous gestures of sixty-four 2-year-old Italian children and English-speaking Canadian children, primarily from middle-class Caucasian families. The Italian children produced twice as many gestures as Canadian children in a picture-naming task but produced a similar range of representational techniques. Two-year-olds were equally likely to produce gestures depicting function as form. These data suggest young children's communicative skills are supported by a symbolic capacity that reflects contextual communicative demands. PMID:27079825

  17. Weight and Weight-Related Behaviors Among 2-Year College Students

    PubMed Central

    Nanney, Marilyn S.; Lytle, Leslie A.; Farbakhsh, Kian; Moe, Stacey G.; Linde, Jennifer A.; Gardner, Jolynn K.; Laska, Melissa N.

    2015-01-01

    Objectives and Participants The purpose of this paper is to describe weight indicators and weight-related behaviors of students enrolled in 2-year colleges, including sex differences. Methods During Fall 2011 and Spring 2012, 441 students from 3 Minnesota community colleges enrolled in the Choosing Healthy Options in College Environments and Settings (CHOICES) Study and completed baseline assessments. Participants completed a baseline survey evaluating eating and activity patterns, sleep, and stress and measures of height, weight, waist circumference, and body fat. Results Participants were primarily female (68%), white (73%), with a mean age of 22.8 years and 66.2% reporting an annual income <$12,000. Almost half (47%) were overweight or obese. Young males appeared to engage the most in risky health behaviors and had higher levels of overweight or obesity, compared to young females. Conclusions Findings confirm the need for innovative interventions targeting this understudied and underserved young adult population. PMID:25692380

  18. [Influence of sport on isoinertial trunk muscle performance development: a 2 years prospective study].

    PubMed

    Rosset, E Bibbo; Mélot, C; Szpalski, M; Keller, T S; Balagué, F

    2013-07-17

    In this study, we investigate the relationship between either regular sports practice or a non sportive way of life, development of trunk muscle performance and occurrence of lower back pain between male schoolchildren. 93 schoolchildren were recruited, then stratified in 4 groups, according to sport practice or sedentary way of life. Participants were evaluated twice at an interval of 2 years with an interview, a physical examination and an evaluation of trunk muscle performance. We identified that basketball players have significantly better results and perfomance concerning isometric and isoinertial tests of trunk muscles than the other groups. Differences in trunk muscle performance exist following the practice of different types of sport. We can deduce that trunk muscle performance has some sport specificity. PMID:23971327

  19. Inaugural cerebral sinovenous thrombosis revealing homocystinuria in a 2-year-old boy.

    PubMed

    Saboul, Cécile; Darteyre, Stéphane; Ged, Cécile; Fichtner, Christine; Gay, Claire; Stephan, Jean-Louis

    2015-01-01

    Cerebral sinovenous thrombosis is unusual during childhood and requires early and accurate management because of its detrimental consequences. We report on the case of a 2-year-old boy with mild psychomotor delay, who presented with nonfebrile acute ataxia. A brain computed tomographic (CT) scan showed complete thrombosis of the superior sagittal sinus, confirmed by magnetic resonance angiography and associated with a right frontal hemorrhagic infarction. Systematic screening for thrombophilia revealed homocystinuria linked to cystathionine β-synthase deficiency with underlying compound heterozygosity. The evolution was favorable after anticoagulant therapy, specific diet, and vitamin supplementation. This case is of interest because of the unusual clinical presentation as a pediatric cerebral sinovenous thrombosis. Furthermore, homocystinuria is rarely revealed by cerebral sinovenous thrombosis at the onset of the disease and should systematically be ruled out in pediatric stroke. PMID:24598125

  20. Comparison of wear and clinical performance between amalgam, composite and open sandwich restorations: 2-year results.

    PubMed

    Sachdeo, A; Gray, Gordon B; Sulieman, M A; Jagger, Daryll C

    2004-03-01

    There has been some disquiet over the use of mercury containing restorative materials. The most commonly used alternative is composite resin but this has the potential disadvantage associated with wear and marginal leakage, which in turn, has proven to result in secondary caries and sensitivity. To overcome the shortcomings of a directly placed composite restoration, the glass-ionomer/composite open sandwich technique was introduced followed by the subsequent introduction of compomer systems. The aims of this study were to evaluate the wear and clinical performance of a control group of amalgam restorations compared with that of a group of posterior composite resin restorations fillings and a group of compomer/composite open sandwich restorations placed by a single general dental practitioner. The duration of the study was 2 years. One hundred and thirty three (71.4%) patients were successfully recalled and the wear and clinical performance of each restoration after 6, 12 and 24 months was measured, indirectly. There was no statistically significant difference recorded between the groups at 6 months or 1 year (p > 0.05). However, at the end of the 2-year study, there was a significantly lower rate of wear recorded for the control amalgam restorations compared with other two groups (p = 0.033). There was no statistically significant difference in wear recorded between the two groups of tooth-coloured restorations (p > 0.05). With regards to clinical performance of the restorations, occlusal and proximal contacts in each group of restoration remained satisfactory throughout the study. PMID:15058177

  1. A 2-year longitudinal study of prospective predictors of pathological Internet use in adolescents.

    PubMed

    Strittmatter, Esther; Parzer, Peter; Brunner, Romuald; Fischer, Gloria; Durkee, Tony; Carli, Vladimir; Hoven, Christina W; Wasserman, Camilla; Sarchiapone, Marco; Wasserman, Danuta; Resch, Franz; Kaess, Michael

    2016-07-01

    Longitudinal studies of prospective predictors for pathological Internet use (PIU) in adolescents as well as its course are lacking. This three-wave longitudinal study was conducted within the framework of the European Union-funded project "Saving and Empowering Young Lives in Europe" over a 2-year period. The sample consisted of 1444 students at the baseline investigation (T0); 1202 students after 1 year (T1); and 515 students after 2 years (T2). Structured self-report questionnaires were administered at all three time points. PIU was assessed using the Young Diagnostic Questionnaire (YDQ). In addition, demographic (i.e., gender), social (i.e., parental involvement), psychological (i.e., emotional problems), and Internet use-related factors (i.e., online activities) were assessed as prospective predictors. The prevalence of PIU was 4.3 % at T0, 2.7 % at T1 and 3.1 % at T2. However, only 3 students (0.58 %) had persistent categorical PIU (YDQ score of ≥5) over the 2-year period. In univariate models, a variety of variables that have been previously identified in cross-sectional investigations predicted PIU at T2. However, multivariate regression demonstrated that only previous PIU symptoms and emotional problems were significant predictors of PIU 2 years later (adjusted R (2) 0.23). The stability of categorical PIU in adolescents over 2 years was lower than previously reported. However, current PIU symptoms were the best predictor of later PIU; emotional symptoms also predicted PIU over and above the influence of previous problematic Internet use. Both PIU symptoms and emotional problems may contribute to the vicious cycle that supports the perpetuation of PIU. PMID:26526444

  2. 2-year follow-up report on micromotion of a short tibia stem

    PubMed Central

    Toksvig-Larsen, Sören

    2015-01-01

    Background and purpose A shortened tibial stem could influence the early prosthetic fixation. We therefore compared the short stem to the standard-length stem using radiostereometric analysis (RSA) as primary outcome measure. Patients and methods 60 patients were randomized to receive a cemented Triathlon total knee arthroplasty (TKA) with a tibial tray of either standard or short stem length. The patients were blinded regarding treatment allocation. The micromotion of the tibial component was measured by RSA postoperatively, at 3 months, and after 1 and 2 years; clinical outcome was measured with the American Knee Society score (AKSS) and the knee osteoarthritis and injury outcome score (KOOS). Results The maximum total point motion (MTPM) for the standard stem was 0.36 (SD 0.16) mm at 3 months, 0.51 (SD 0.27) mm at 1 year, and 0.54 (SD 0.28) mm at 2 years. For the short stem, it was 0.42 (0.24) mm, 0.59 (0.43) mm, and 0.61 (0.39) mm. 4 short-stemmed components and 2 standard-stemmed components had more than 0.2 mm of migration between the first- and second-year follow-up, and were classified as continuously migrating. Interpretation The short-stemmed cemented tibial prosthesis showed an early prosthetic migratory pattern similar to that of the standard-stemmed cemented Triathlon knee prosthesis. The number of continuously migrating tibial plates in each group is predictive of a lower revision rate than 5% at 10 years. PMID:25809183

  3. Learning, Memory, and Executive Function in New MDMA Users: A 2-Year Follow-Up Study

    PubMed Central

    Wagner, Daniel; Tkotz, Simon; Koester, Philip; Becker, Benjamin; Gouzoulis-Mayfrank, Euphrosyne; Daumann, Joerg

    2015-01-01

    3,4-Methylenedioxymethamphetamine (MDMA) is associated with changes in neurocognitive performance. Recent studies in laboratory animals have provided additional support for the neurodegeneration hypothesis. However, results from animal research need to be applied to humans with caution. Moreover, several of the studies that examine MDMA users suffer from methodological shortcomings. Therefore, a prospective cohort study was designed in order to overcome these previous methodological shortcomings and to assess the relationship between the continuing use of MDMA and cognitive performance in incipient MDMA users. It was hypothesized that, depending on the amount of MDMA taken, the continued use of MDMA over a 2-year period would lead to further decreases in cognitive performance, especially in visual paired association learning tasks. Ninety-six subjects were assessed, at the second follow-up assessment: 31 of these were non-users, 55 moderate-users, and 10 heavy-users. Separate repeated measures analyses of variance were conducted for each cognitive domain, including attention and information processing speed, episodic memory, and executive functioning. Furthermore, possible confounders including age, general intelligence, cannabis use, alcohol use, use of other concomitant substances, recent medical treatment, participation in sports, level of nutrition, sleep patterns, and subjective well-being were assessed. The Repeated measures analysis of variance (rANOVA) revealed that a marginally significant change in immediate and delayed recall test performances of visual paired associates learning had taken place within the follow-up period of 2 years. No further deterioration in continuing MDMA-users was observed in the second follow-up period. No significant differences with the other neuropsychological tests were noted. It seems that MDMA use can impair visual paired associates learning in new users. However, the groups differed in their use of concomitant use of

  4. Study of 2 years follow-up of referral patients with abnormal Pap smear

    PubMed Central

    Behnamfar, Fariba; Zafarbakhsh, Azam; Allameh, Taj-Alsadat

    2015-01-01

    Background: Abnormal Pap smear consists of premalignant or malignant cervical lesions. Many of premalignant cervical lesions will never progress to invasive malignancy, or even may regress over the time. Thus, there is always a risk of overtreatment of patients with an abnormal Pap smear. A long-term follow-up of these patients can reveal final events associated with each subtype of abnormal Pap smear, and, therefore, help us to prevent unnecessary interventions. The aim of our study was to present 2 years follow-up of referral patients with abnormal Pap smear. Materials and Methods: A total of 334 consecutive women aged more than 16 who were referred with an abnormal Pap smear were entered into the study. Patients were followed with biannual Pap smear and annual colposcopy and biopsy for 2 years. Results: At baseline, the majority of patients with abnormal Pap smear were normal on colposcopy and biopsy (68% and 86%, respectively). Six months after first abnormal Pap smear majority of patients in each group showed a significant regress to normal or less invasive lesion (P < 0.001). Twelve patients (4%) had no change in Pap smear, whereas 313 (94%) had at least one stage improvement. Only nine (3%) patients had deteriorated Pap smear after 6 months. All 308 patients who underwent colposcopy and biopsy had normal Pap smear 24 months after the first abnormal Pap smear. Conclusion: Pap smear is associated with a high rate of false-positive results. In addition, the majority of low-grade cervical lesions can spontaneously regress. A long-term follow-up of a patient with abnormal Pap smear can help us to avoid needless interventions. PMID:26958048

  5. Resistance training over 2 years increases bone mass in calcium-replete postmenopausal women.

    PubMed

    Kerr, D; Ackland, T; Maslen, B; Morton, A; Prince, R

    2001-01-01

    Understanding the stress/strain relationship between exercise and bone is critical to understanding the potential benefit of exercise in preventing postmenopausal bone loss. This study examined the effect of a 2-year exercise intervention and calcium supplementation (600 mg) on bone mineral density (BMD) in 126 postmenopausal women (mean age, 60 +/- 5 years). Assignment was by block randomization to one of three groups: strength (S), fitness (F), or nonexercise control (C). The two exercise groups completed three sets of the same nine exercises, three times a week. The S group increased the loading, while the F group had additional stationary bicycle riding with minimal increase in loading. Retention at 2 years was 71% (59% in the S group, 69% in the F group, and 83% in the C group), while the exercise compliance did not differ between the exercise groups (S group, 74 +/- 13%; F group, 77 +/- 14%). BMD was measured at the hip, lumbar spine, and forearm sites every 6 months using a Hologic 4500. Whole body BMD also was measured every 6 months on a Hologic 2000. There was no difference between the groups at the forearm, lumbar spine, or whole body sites. There was a significant effect of the strength program at the total (0.9 +/- 2.6%; p < 0.05) and intertrochanter hip site (1.1 +/- 3.0%; p < 0.01). There was a significant time and group interaction (p < 0.05) at the intertrochanter site by repeated measures. This study shows the effectiveness of a progressive strength program in increasing bone density at the clinically important hip site. We concluded that a strength program could be recommended as an adjunct lifestyle approach to osteoporosis treatment or used in combination with other therapies. PMID:11149482

  6. In Utero Pesticide Exposure and Leukemia in Brazilian Children < 2 Years of Age

    PubMed Central

    Ferreira, Jeniffer Dantas; Couto, Arnaldo Cézar; Pombo-de-Oliveira, Maria S.

    2012-01-01

    Background: An association between pesticide exposure and cancer has been suggested. Infant leukemia is a rare neoplasm and its association with maternal pesticide exposure has been poorly explored. Objectives: We investigated the association between pesticide exposure during pregnancy and leukemia in children < 2 years of age. Methods: A hospital-based case–control study was carried out in 13 Brazilian states during 1999–2007. Mothers of 252 cases and those of 423 controls were interviewed. Information on pesticide exposures 3 months before pregnancy, throughout pregnancy, and during breastfeeding was obtained. Unconditional logistic regression was used to estimate adjusted odds ratios (aORs) for associations between pesticide exposures and leukemia. Results: Associations with ever use of pesticides during pregnancy were observed for acute lymphoid leukemia (ALL) (aOR = 2.10; 95% CI: 1.14, 3.86) and acute myeloid leukemia (AML) (aOR = 5.01; 95% CI: 1.97, 12.7) in children 0–11 months of age, and with ALL (aOR = 1.88; 95% CI: 1.05, 5.23) at 12–23 months of age. According to reported maternal exposure to permethrin, higher risk estimates were verified for children 0–11 months of age (aOR = 2.47; 95% CI: 1.17, 5.25 for ALL; and aOR = 7.28; 95% CI: 2.60, 20.38 for AML). Maternal pesticide exposure related to agricultural activities showed an aOR of 5.25 (95% CI: 1.83, 15.08) for ALL, and an aOR of 7.56 (95% CI: 1.83, 31.23) for AML. Conclusions: These results support the hypothesis that pesticide exposure during pregnancy may be involved in the etiology of acute leukemia in children < 2 years of age. PMID:23092909

  7. Learning, Memory, and Executive Function in New MDMA Users: A 2-Year Follow-Up Study.

    PubMed

    Wagner, Daniel; Tkotz, Simon; Koester, Philip; Becker, Benjamin; Gouzoulis-Mayfrank, Euphrosyne; Daumann, Joerg

    2015-01-01

    3,4-Methylenedioxymethamphetamine (MDMA) is associated with changes in neurocognitive performance. Recent studies in laboratory animals have provided additional support for the neurodegeneration hypothesis. However, results from animal research need to be applied to humans with caution. Moreover, several of the studies that examine MDMA users suffer from methodological shortcomings. Therefore, a prospective cohort study was designed in order to overcome these previous methodological shortcomings and to assess the relationship between the continuing use of MDMA and cognitive performance in incipient MDMA users. It was hypothesized that, depending on the amount of MDMA taken, the continued use of MDMA over a 2-year period would lead to further decreases in cognitive performance, especially in visual paired association learning tasks. Ninety-six subjects were assessed, at the second follow-up assessment: 31 of these were non-users, 55 moderate-users, and 10 heavy-users. Separate repeated measures analyses of variance were conducted for each cognitive domain, including attention and information processing speed, episodic memory, and executive functioning. Furthermore, possible confounders including age, general intelligence, cannabis use, alcohol use, use of other concomitant substances, recent medical treatment, participation in sports, level of nutrition, sleep patterns, and subjective well-being were assessed. The Repeated measures analysis of variance (rANOVA) revealed that a marginally significant change in immediate and delayed recall test performances of visual paired associates learning had taken place within the follow-up period of 2 years. No further deterioration in continuing MDMA-users was observed in the second follow-up period. No significant differences with the other neuropsychological tests were noted. It seems that MDMA use can impair visual paired associates learning in new users. However, the groups differed in their use of concomitant use of

  8. 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.

  9. Survival in MS

    PubMed Central

    Reder, A.T.; Ebers, G.C.; Cutter, G.; Kremenchutzky, M.; Oger, J.; Langdon, D.; Rametta, M.; Beckmann, K.; DeSimone, T.M.; Knappertz, V.

    2012-01-01

    Objective: To examine the effects of interferon beta (IFNβ)-1b on all-cause mortality over 21 years in the cohort of 372 patients who participated in the pivotal randomized clinical trial (RCT), retaining (in the analysis) the original randomized treatment-assignments. Methods: For this randomized long-term cohort study, the primary outcome, defined before data collection, was the comparison of all-cause mortality between the IFNβ-1b 250 μg and placebo groups from the time of randomization through the entire 21-year follow-up interval (intention-to-treat, log-rank test for Kaplan-Meier survival curves). All other survival outcomes were secondary. Results: After a median of 21.1 years from RCT enrollment, 98.4%(366 of 372) of patients were identified, and, of these, 81 deaths were recorded (22.1% [81 of 366]). Patients originally randomly assigned to IFNβ-1b 250 μg showed a significant reduction in all-cause mortality over the 21-year period compared with placebo (p = 0.0173), with a hazard ratio of 0.532 (95% confidence interval 0.314–0.902). The hazard rate of death at long-term follow-up by Kaplan-Meier estimates was reduced by 46.8% among IFNβ-1b 250 μg–treated patients (46.0% among IFNβ-1b 50 μg–treated patients) compared with placebo. Baseline variables did not influence the observed treatment effect. Conclusions: There was a significant survival advantage in this cohort of patients receiving early IFNβ-1b treatment at either dose compared with placebo. Near-complete ascertainment, together with confirmatory findings from both active treatment groups, strengthens the evidence for an IFNβ-1b benefit on all-cause mortality. Classification of Evidence: This study provides Class III evidence that early treatment with IFNβ-1b is associated with prolonged survival in initially treatment-naive patients with relapsing-remitting multiple sclerosis. PMID:22496198

  10. Nocturnality and species survival.

    PubMed Central

    Daily, G C; Ehrlich, P R

    1996-01-01

    Surveys of butterfly and moth diversity in tropical forest fragments suggest that nocturnality confers a dispersal, and possibly a survival, advantage. The butterfly faunas of smaller fragments were depauperate; in contrast, the species richness of nocturnal moths was similar in all fragments and even in pasture. The lack of correlation between butterfly and moth species richness among fragments (r2 = 0.005) is best explained by movements of moths at night when ambient conditions in forest and pasture are most similar; butterflies face substantial daytime temperature, humidity, and solar radiation barriers. This interpretation is supported by information on birds, beetles, and bats. PMID:8876201

  11. Does cancer survivors' health-related quality of life depend on cancer type? Findings from a large French national sample 2 years after cancer diagnosis.

    PubMed

    Le Corroller-Soriano, A-G; Bouhnik, A-D; Preau, M; Malavolti, L; Julian-Reynier, C; Auquier, P; Moatti, J-P

    2011-01-01

    We investigated whether health-related quality of life (HRQL) depends on cancer type, after adjustment for demographic and medical variables. A French national population-based survey was conducted between November and December 2004 to assess surviving cancer patients' HRQL 2 years after diagnosis. HRQL was measured by the 36-Item Short Form Survey scale. The sample included 3900 persons. All cancer diagnoses were entered in the study. We demonstrated that medical and treatment variables have an impact on patients' physical HRQL but not on mental HRQL. Cancer type impacted on physical HRQL, with those suffering from upper aerodigestive tract /lung cancers and haematological malignancies being affected to a greater degree. Disturbing side effects impacted both HRQL domains. Socio-demographic variables had statistically significant effects but not clinically meaningful ones. Socio-economic variables led to potentially clinically meaningful differences for cancer patients' HRQL and represented a socio-economic gradient in HRQL among cancer survivors. From our results, we may assert that cancer survivors, 2 years after cancer diagnosis, share a similar pattern of psychological morbidity, independent of cancer type. Patients disproportionately affected by cancer, such as those with lower educational levels and income, need to be identified and targeted and interventions which address their unique needs and concerns need to be developed. PMID:20345457

  12. Perceptions Concerning Occupational Survival Skills.

    ERIC Educational Resources Information Center

    Nelson, Robert E.

    This volume presents the reports of a series of interrelated studies which were part of a study that developed curriculum materials for teaching occupational survival skills. The first of six sections, Need for Teaching Occupational Survival Skills and Attitudes, discusses the importance of survival skills and describes twelve general topics which…

  13. SURVIV for survival analysis of mRNA isoform variation.

    PubMed

    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

  14. 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

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

    PubMed Central

    Mauro, Michael J.; Martinelli, Giovanni; Kim, Dong-Wook; Soverini, Simona; Müller, Martin C.; Hochhaus, Andreas; Cortes, Jorge; Chuah, Charles; Dufva, Inge H.; Apperley, Jane F.; Yagasaki, Fumiharu; Pearson, Jay D.; Peter, Senaka; Sanz Rodriguez, Cesar; Preudhomme, Claude; Giles, Francis; Goldman, John M.; Zhou, Wei

    2009-01-01

    The BCR–ABL T315I mutation represents a major mechanism of resistance to tyrosine kinase inhibitors (TKIs). The objectives of this retrospective observational study were to estimate overall and progression-free survival for chronic myeloid leukemia in chronic-phase (CP), accelerated-phase (AP), or blastic-phase (BP) and Philadelphia chromosome—positive (Ph)+ acute lymphoblastic leukemia (ALL) patients with T315I mutation. Medical records of 222 patients from 9 countries were reviewed; data were analyzed using log-rank tests and Cox proportional hazard models. Median age at T315I mutation detection was 54 years; 57% cases were men. Median time between TKI treatment initiation and T315I mutation detection was 29.2, 15.4, 5.8, and 9.1 months, respectively, for CP, AP, BP, and Ph+ ALL patients. After T315I mutation detection, second-generation TKIs were used in 56% of cases, hydroxyurea in 39%, imatinib in 35%, cytarabine in 26%, MK-0457 in 11%, stem cell transplantation in 17%, and interferon-α in 6% of cases. Median overall survival from T315I mutation detection was 22.4, 28.4, 4.0, and 4.9 months, and median progression-free survival was 11.5, 22.2, 1.8, and 2.5 months, respectively, for CP, AP, BP, and Ph+ ALL patients. These results confirm that survival of patients harboring a T315I mutation is dependent on disease phase at the time of mutation detection. PMID:19843886

  16. Couple and Individual Adjustment for 2 Years Following a Randomized Clinical Trial Comparing Traditional versus Integrative Behavioral Couple Therapy

    ERIC Educational Resources Information Center

    Christensen, Andrew; Atkins, David C.; Yi, Jean; Baucom, Donald H.; George, William H.

    2006-01-01

    Follow-up data across 2 years were obtained on 130 of 134 couples who were originally part of a randomized clinical trial comparing traditional versus integrative behavioral couple therapy (TBCT vs. IBCT; A. Christensen et al., 2004). Both treatments produced similar levels of clinically significant improvement at 2 years posttreatment (69% of…

  17. Hispanic Student Enrollment and Educational Attainment in Texas 2-Year Colleges: A Multi-Year Statewide Analysis

    ERIC Educational Resources Information Center

    Hernandez, Jack

    2012-01-01

    Purpose: The purpose of the study was to examine the numbers and percentages of Hispanic college students enrolled in Texas 2-year colleges from the 2000 through the 2011 academic years and to examine the numbers and percentages of Hispanic students obtaining associate degrees from Texas 2-year colleges for the 2000 through the 2011 academic…

  18. Cognitive and Linguistic Sources of Variance in 2-Year-Olds' Speech-Sound Discrimination: A Preliminary Investigation

    ERIC Educational Resources Information Center

    Lalonde, Kaylah; Holt, Rachael Frush

    2014-01-01

    Purpose: This preliminary investigation explored potential cognitive and linguistic sources of variance in 2- year-olds' speech-sound discrimination by using the toddler change/no-change procedure and examined whether modifications would result in a procedure that can be used consistently with younger 2-year-olds. Method: Twenty typically…

  19. IDH1 mutation and MGMT methylation status predict survival in patients with anaplastic astrocytoma treated with temozolomide-based chemoradiotherapy.

    PubMed

    Minniti, Giuseppe; Scaringi, Claudia; Arcella, Antonella; Lanzetta, Gaetano; Di Stefano, Domenica; Scarpino, Stefania; Bozzao, Alessandro; Pace, Andrea; Villani, Veronica; Salvati, Maurizio; Esposito, Vincenzo; Giangaspero, Felice; Enrici, Riccardo Maurizi

    2014-06-01

    Several molecular markers have been proposed as predictors of outcome in patients with high grade gliomas. We report a retrospective multicenter study of 97 consecutive adult patients with anaplastic astrocytoma (AA) treated with radiation therapy (RT) plus concomitant and adjuvant temozolomide (TMZ) between October 2004 and March 2012. Correlations between the isocitrate dehydrogenase 1 (IDH1) mutation and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with survival outcomes have been analyzed. At a median follow-up time of 46 months (range 12-89 months), median and 5-year overall survival rates were 50.5 months (95 % CI, 37.8-63.2) and 38% (95 % CI, 25.7-50.7%), and median and 5-year progression-free survival rates were 36 months (95% CI, 28.5-44.0) and 22 % (95 % CI, 10-34%), respectively. IDH1 mutation and MGMT promoter methylation were present in 54 and 60% of evaluable patients, respectively. Multivariate Cox proportional hazards regression analysis showed that IDH1 mutation (P = 0.001), MGMT methylation (P = 0.01), age < 50 years (P = 0.02), and extent of resection (P = 0.04) were significantly associated with longer survival. Our study confirms the favorable prognostic value of IDH1 mutation and MGMT methylation in patients with AA treated with RT plus concomitant and adjuvant TMZ. The superiority of combined radiochemotherapy over other treatment modalities remains to be demonstrated. PMID:24748470

  20. 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. PMID:22570412

  1. Growth of containerized loblolly pine with specific ectomycorrhizae after 2 years on an amended borrow pit

    SciTech Connect

    Ruehle, J.L.

    1980-01-01

    A borrow pit with exposed subsoil in South Carolina was graded level and deep subsoiled. Plots were amended with processed sewage sludge or commercial fertilizer followed by a seeding with fescue. Container-grown loblolly pines colonized with Pisolithus tinctorius, Thelephora terrestris, or no ectomycorrhizae were planted by hand on the plots one year after site preparation. Two years after planting on sludge-amended plots, seedlings initially colonized with Pisolithus had greater height, root-collar diameter, and seedling volume (D/sup 2/H) than Thelephora or control seedlings. The means for these three growth parameters on seedlings planted on fertilized plots were no different between Pisolithus and Thelephora seedlings, but Pisolithus seedlings were greater than controls. There was no difference in survival among mycorrhizal treatments on the sludge plots. Survival and seedling volume were integrated into plot volume indices (PVI). Seedlings on sludge plots had greater PVI than seedlings on fertilized plots. Pisolithus seedlings on sludge plots had 265 and 528% greater PVI after two years than Thelephora or control seedlings. Containerized loblolly seedlings tailored with Pisolithus can be successfully established and rapid growth obtained on a subsoiled borrow pit amended with sewage sludge. This procedure may be applicable to thousands of acres of similar borrow pits left by highway and construction work.

  2. 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

  3. 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.

  4. Near-Infrared Spectroscopy Monitoring, Superior Vena Cava Flow, and Neurodevelopmental Outcome at 2 years in a Cohort of Very Low-Birth-Weight Infants.

    PubMed

    Cerbo, Rosa Maria; Orcesi, Simona; Scudeller, Luigia; Borellini, Martina; Croci, Carolina; Ravelli, Claudia; Masa, Giulia; Paolillo, Piermichele; Manzoni, Paolo; Balottin, Umberto; Stronati, Mauro

    2016-09-01

    Objective We aimed at assessing the association between superior vena cava flow (SVCf), regional (cerebral) tissue oxygen saturation (rSO2), and cerebral fractional oxygen extraction (CFOE) during the first 48 hours of life and 2-years neurodevelopmental outcome of very low-birth-weight infants (VLBW). Methods We prospectively studied 60 VLBW infants admitted to our neonatal intensive care unit; rSO2 was continuously monitored with near-infrared spectroscopy during the first 48 hours of life, SVCf was measured at 4 to 6, 12, 24, and 48 hours, and CFOE was calculated. Neurodevelopmental outcome was assessed at 24 months corrected age. Results The mean gestational age at birth was 27.9 weeks (standard deviation: 2.4); 8 infants died in the first 3 months of life, 6 were lost to follow-up, 46 survived and were followed up. At 24 months, 6 (13%) and 7 (15.2%) infants developed minor and major sequelae, respectively. Infants who died had higher CFOE (p < 0.001) and lower SVCf (p < 0.001) than infants surviving with sequelae. In turn, these had higher SVCf between 24 and 48 hours than those without sequelae (p < 0.001). Conclusion SVCf, rSO2, and CFOE patterns in the first days of life suggest cerebral hyperperfusion, related to loss of autoregulation and/or use of inotropic drugs, as a potential mechanism of cerebral injury. PMID:27603543

  5. Peginterferon beta-1a in multiple sclerosis: 2-year results from ADVANCE

    PubMed Central

    Arnold, Douglas L; Balcer, Laura J; Boyko, Alexey A; Pelletier, Jean; Liu, Shifang; Zhu, Ying; Seddighzadeh, Ali; Hung, Serena; Deykin, Aaron; Sheikh, Sarah I; Calabresi, Peter A

    2015-01-01

    Objective: To evaluate the efficacy and safety of subcutaneous peginterferon beta-1a over 2 years in patients with relapsing–remitting multiple sclerosis in the ADVANCE study. Methods: Patients were randomized to placebo or 125 µg peginterferon beta-1a every 2 or 4 weeks. For Year 2 (Y2), patients originally randomized to placebo were re-randomized to peginterferon beta-1a every 2 weeks or every 4 weeks. Patients randomized to peginterferon beta-1a in Year 1 (Y1) remained on the same dosing regimen in Y2. Results: Compared with Y1, annualized relapse rate (ARR) was further reduced in Y2 with every 2 week dosing (Y1: 0.230 [95% CI 0.183–0.291], Y2: 0.178 [0.136–0.233]) and maintained with every 4 week dosing (Y1: 0.286 [0.231–0.355], Y2: 0.291 [0.231–0.368]). Patients starting peginterferon beta-1a from Y1 displayed improved efficacy versus patients initially assigned placebo, with reductions in ARR (every 2 weeks: 37%, p<0.0001; every 4 weeks: 17%, p=0.0906), risk of relapse (every 2 weeks: 39%, p<0.0001; every 4 weeks: 19%, p=0.0465), 12-week disability progression (every 2 weeks: 33%, p=0.0257; every 4 weeks: 25%, p=0.0960), and 24-week disability progression (every 2 weeks: 41%, p=0.0137; every 4 weeks: 9%, p=0.6243). Over 2 years, greater reductions were observed with every 2 week versus every 4 week dosing for all endpoints and peginterferon beta-1a was well tolerated. Conclusions: Peginterferon beta-1a efficacy is maintained beyond 1 year, with greater effects observed with every 2 week versus every 4 week dosing, and a similar safety profile to Y1. Clinicaltrials.gov Registration Number: NCT00906399. PMID:25432952

  6. Evolution of nonspecific duodenal lymphocytosis over 2 years of follow-up

    PubMed Central

    Losurdo, Giuseppe; Piscitelli, Domenico; Giangaspero, Antonio; Principi, Mariabeatrice; Buffelli, Francesca; Giorgio, Floriana; Montenegro, Lucia; Sorrentino, Claudia; Amoruso, Annacinzia; Ierardi, Enzo; Di Leo, Alfredo

    2015-01-01

    AIM: To assess the evolution of duodenal lymphocytosis (DL), a condition characterized by increased intraepithelial lymphocytes (IELs), over 2 years of follow-up. METHODS: Consecutive patients undergoing upper endoscopy/histology for abdominal pain, diarrhea, weight loss, weakness or other extraintestinal features compatible with celiac disease (CD) were included. Evaluation of IELs infiltrate in duodenal biopsy samples was carried out by CD3-immunohistochemistry and expressed as number of positive cells/100 enterocytes. Diagnostic agreement on the IELs count was tested by calculating the weighted k coefficient. All patients underwent serological detection of autoantibodies associated with CD: IgG and IgA anti-tissue transglutaminase and endomysium. Each patient underwent further investigations to clarify the origin of DL at baseline and/or in the course of 2 years of follow-up every six months. Autoimmune thyroiditis, intestinal infections, parasitic diseases, bacterial intestinal overgrowth, hypolactasia and wheat allergy were detected. Colonoscopy and enteric magnetic resonance imaging were performed when necessary. Risk factors affecting the final diagnosis were detected by multinomial logistic regression and expressed as OR. RESULTS: Eighty-five patients (16 males, 69 females, aged 34.1 ± 12.5 years) were followed up for a mean period of 21.7 ± 11.7 mo. At baseline, endoscopy/duodenal biopsy, CD3 immunohistochemistry revealed: > 25 IELs/100 enterocytes in 22 subjects, 15-25 IELs in 37 and < 15 IELs in 26. They all had negative serum anti-transglutaminase and anti-endomysium, whilst 5 showed IgG anti-gliadin positivity. In the course of follow-up, 23 developed CD seropositivity and gluten sensitivity (GS) was identified in 19. Other diagnoses were: 5 Helicobacter pylori infections, 4 jejunal Crohn’s disease, 1 lymphocytic colitis and 1 systemic sclerosis. The disease in the remaining 32 patients was classified as irritable bowel syndrome because of the lack

  7. TLR4/TIRAP polymorphisms are associated with progression and survival of patients with symptomatic myeloma.

    PubMed

    Bagratuni, Tina; Terpos, Evangelos; Eleutherakis-Papaiakovou, Evangelos; Kalapanida, Despoina; Gavriatopoulou, Maria; Migkou, Magdalini; Liacos, Christine-Ivy; Tasidou, Anna; Matsouka, Charis; Mparmparousi, Despoina; Dimopoulos, Meletios A; Kastritis, Efstathios

    2016-01-01

    Myeloma cells thrive in an environment of sustained inflammation, which impacts the development and evolution of the disease, as well as drug resistance. We evaluated the impact of genetic polymorphisms in the Toll-like receptor 4 (TLR4) pathway, which have been implicated in different inflammatory responses in the outcomes of patients with symptomatic multiple myeloma (MM) who have received contemporary therapies. We found that the presence of single nucleotide polymorphisms (SNPs) in both the TLR4 and toll/interleukin-1 receptor (TIR)-associated protein (TIRAP) genes was associated with lower response to primary therapy mainly for patients who received immunomodulatory drugs but not in patients treated with bortezomib-based therapies. Furthermore, TIRAP SNP was associated with a significantly shorter progression-free survival and overall survival, independently of other prognostic factors, such as age, transplant, International Staging System stage, lactate dehydrogenase and cytogenetics. This is the first study to demonstrate the effect of SNPs in TLR4/TIRAP in MM. Our data indicate that genetic variability in the immune system may be associated with different responses to antimyeloma therapies and may be a critical component affecting the natural history of the disease, providing the basis for further investigation of the role of these pathways in myeloma. PMID:26564000

  8. Minimal residual disease in myeloma by flow cytometry: independent prediction of survival benefit per log reduction

    PubMed Central

    Rawstron, Andy C.; Gregory, Walter M.; de Tute, Ruth M.; Davies, Faith E.; Bell, Sue E.; Drayson, Mark T.; Cook, Gordon; Jackson, Graham H.; Morgan, Gareth J.; Child, J. Anthony

    2015-01-01

    The detection of minimal residual disease (MRD) in myeloma using a 0.01% threshold (10−4) after treatment is an independent predictor of progression-free survival (PFS), but not always of overall survival (OS). However, MRD level is a continuous variable, and the predictive value of the depth of tumor depletion was evaluated in 397 patients treated intensively in the Medical Research Council Myeloma IX study. There was a significant improvement in OS for each log depletion in MRD level (median OS was 1 year for ≥10%, 4 years for 1% to <10%, 5.9 years for 0.1% to <1%, 6.8 years for 0.01% to <0.1%, and more than 7.5 years for <0.01% MRD). MRD level as a continuous variable determined by flow cytometry independently predicts both PFS and OS, with approximately 1 year median OS benefit per log depletion. The trial was registered at www.isrctn.com as #68454111. PMID:25645353

  9. 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

  10. 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.

  11. 1- and 2-year-olds' expectations about third-party communicative actions.

    PubMed

    Thorgrimsson, Gudmundur B; Fawcett, Christine; Liszkowski, Ulf

    2015-05-01

    Infants expect people to direct actions toward objects, and they respond to actions directed to themselves, but do they have expectations about actions directed to third parties? In two experiments, we used eye tracking to investigate 1- and 2-year-olds' expectations about communicative actions addressed to a third party. Experiment 1 presented infants with videos where an adult (the Emitter) either uttered a sentence or produced non-speech sounds. The Emitter was either face-to-face with another adult (the Recipient) or the two were back-to-back. The Recipient did not respond to any of the sounds. We found that 2-, but not 1-year-olds looked quicker and longer at the Recipient following speech than non-speech, suggesting that they expected her to respond to speech. These effects were specific to the face-to-face context. Experiment 2 presented 1-year-olds with similar face-to-face exchanges but modified to engage infants and minimize task demands. The infants looked quicker to the Recipient following speech than non-speech, suggesting that they expected a response to speech. The study suggests that by 1 year of age infants expect communicative actions to be directed at a third-party listener. PMID:25766104

  12. Prescription Disposal Practices: A 2-Year Ecological Study of Drug Drop Box Donations in Appalachia

    PubMed Central

    Hagemeier, Nicholas; Brooks, Billy; Alamian, Arsham

    2015-01-01

    Objectives. We quantified controlled substance donations via permanent drug donation boxes over 2 years in a region with high prescription abuse, assessing medication characteristics, time between dispensing and donation, and weight of medications donated per capita. Methods. In partnership with Drug Enforcement Administration and local law enforcement, we analyzed permanent drug donation box collections in 8 Northeast Tennessee locations from June 2012 to April 2014. We recorded controlled substance dosage units along with the product dispensing date. Results. We collected 4841 pounds of pharmaceutical waste, 4.9% (238.5 pounds) of which were controlled substances, totaling 106 464 controlled substance doses. Analysis of dispensing dates for controlled substances indicated a median of 34 months lapsed from dispensing to donation (range = 1–484 months). The mean controlled substance donation rate was 1.39 pounds per 1000 residents. Communities with fewer than 10 000 residents had a statistically higher controlled substance donation rate (P = .002) compared with communities with 10 000 or more residents. Conclusions. Permanent drug donation boxes can be an effective mechanism to remove controlled substances from community settings. Rural and urban community residents should be provided convenient and timely access to drug disposal options. PMID:26180956

  13. Time and again: effects of repetition and retention interval on 2 year olds' event recall.

    PubMed

    Fivush, R; Hamond, N R

    1989-04-01

    How and what very young children remember is a central question for understanding the course of memory development. In this research, we examined the effects of two factors on 2-year-old children's ability to recall novel events: repetition of the experience and time since experience. Twenty 24-month-old and twenty 28-month-old children participated in unusual laboratory play events. Half of the children returned after a 2-week delay and again after a 3-month delay (repeated experience condition); the remaining children returned only after 3 months (single experience condition). Memory was assessed by asking children to reenact the events. Recall was generally accurate, and there were no significant effects of age. All children recalled more information about the activities associated with the event than about the objects. Surprisingly, children in the repeated experience condition recalled as much about the events at the 3-month retention interval as at the 2-week retention interval. Further, children in this condition recalled more information at the 3-month retention interval than children in the single experience condition, suggesting that reexperiencing an event may guard against long-term forgetting. PMID:2703807

  14. Caudal epidural anesthesia for a 2-year old child with congenital myasthenia gravis.

    PubMed

    Calişkan, Esra; Koçum, Aysu; Sener, Mesut; Bozdoğan, Nesrin; Ariboğan, Aniş

    2008-10-01

    Myasthenia gravis is an autoimmune disease with antibodies directed against the acetylcholine receptor at the neuromuscular junction. Anesthetists have a special interest in myasthenia gravis because of its interaction with various anesthetic agents. Unlike adult myasthenic patients; very little report has been written about the anesthetic management in children, other than in relation to thymectomy. Although the use of caudal anesthesia in pediatric patients is common, have not seen any report concerning its use in a myasthenic child. In this case report, we represented a 2 year-old boy was performed caudal anesthesia for orchiopexy operation. He had presented difficulty in breathing, generalized weakness and droopy eyes due to congenital myasthenia gravis. In the operating room, following the routine monitoring, the patient was sedated with intravenous 1mg midazolam and 10 mg ketamine. Then caudal block was performed. 17 minutes later from the local anesthetic injection; operation was started and lasted 45 minutes. The patient did not require intraoperative supplemental analgesia and postoperative course was uneventful. Specific attention should be paid to voluntary and respiratory muscle strength in myasthenia gravis patients. Caudal anesthesia allowed airway control of myasthenia gravis patients without endotracheal intubations and muscle relaxant. In conclusion, we think that caudal anesthetic technique may be considered as a safe and suitable for the myasthenic child and it may represent a valid alternative to general anesthesia for these patients. PMID:19117157

  15. Seismicity location from analysis of a 2 years passive seismological experiment around Ulaanbaatar

    NASA Astrophysics Data System (ADS)

    Batkhuu, Battulga; Munkhuu, Ulziibat; Sebe, Olivier; Monfret, Tony; Deschamps, Anne; Gao, Mengtan; Wu, Qingju

    2014-05-01

    We analyse broadband seismological records from a 2 years temporary array deployed over a 400x600km2 region in central Mongolia, including Ulaanbaatar region, by a Sino-Mongolian cooperation. The dataset is completed with all available regional data, mostly recorded by Mongolian National Seismic Network (MNSN) operated by Research Center for Astronomy and Geophysics (RCAG). The seismic activity of the covered area is not very high, except SW of Ulaanbaatar. To obtain as good as possible image of this seismicity, we have first to determine a regional velocity model. The development of mining activity in Mongolia, allows us to record a large set of quarry blasts. Due to the very continental position of Mongolia, micro-seismic noise level is low and the signal of these human made sources are very often recorded at distances as far as 200km. Travel time information of direct, reflected and refracted waves are used to produce crustal information (Moho depth and mean crustal P wave velocity, and velocity below the Moho, Vp/Vs ratio) over the area of observation. We show that the crust of the studied area is relatively homogeneous which allows us to improve this very simple model, searching the best crustal model with Velest software. The experiment was supported by Sino-Mongolian joint project titled "The Geophysical Investigation and Deep Structure Modeling for Seismic Hazard Assessment in the Far East", Project code: 2011DFB20120.

  16. FORGE Canada Consortium: outcomes of a 2-year national rare-disease gene-discovery project.

    PubMed

    Beaulieu, Chandree L; Majewski, Jacek; Schwartzentruber, Jeremy; Samuels, Mark E; Fernandez, Bridget A; Bernier, Francois P; Brudno, Michael; Knoppers, Bartha; Marcadier, Janet; Dyment, David; Adam, Shelin; Bulman, Dennis E; Jones, Steve J M; Avard, Denise; Nguyen, Minh Thu; Rousseau, Francois; Marshall, Christian; Wintle, Richard F; Shen, Yaoqing; Scherer, Stephen W; Friedman, Jan M; Michaud, Jacques L; Boycott, Kym M

    2014-06-01

    Inherited monogenic disease has an enormous impact on the well-being of children and their families. Over half of the children living with one of these conditions are without a molecular diagnosis because of the rarity of the disease, the marked clinical heterogeneity, and the reality that there are thousands of rare diseases for which causative mutations have yet to be identified. It is in this context that in 2010 a Canadian consortium was formed to rapidly identify mutations causing a wide spectrum of pediatric-onset rare diseases by using whole-exome sequencing. The FORGE (Finding of Rare Disease Genes) Canada Consortium brought together clinicians and scientists from 21 genetics centers and three science and technology innovation centers from across Canada. From nation-wide requests for proposals, 264 disorders were selected for study from the 371 submitted; disease-causing variants (including in 67 genes not previously associated with human disease; 41 of these have been genetically or functionally validated, and 26 are currently under study) were identified for 146 disorders over a 2-year period. Here, we present our experience with four strategies employed for gene discovery and discuss FORGE's impact in a number of realms, from clinical diagnostics to the broadening of the phenotypic spectrum of many diseases to the biological insight gained into both disease states and normal human development. Lastly, on the basis of this experience, we discuss the way forward for rare-disease genetic discovery both in Canada and internationally. PMID:24906018

  17. A 2-year-old with 4 weeks of daily fever.

    PubMed

    Darby, John B; Liddell, Lucette; DeGuzman, Marietta; McClain, Kenneth L; Rubenstein, Jared; Chase, Lindsay; Marquez, Lucila

    2015-05-01

    A 2-year-old female presents for evaluation of 4 weeks of daily fevers. When the fevers began, she had mild upper respiratory tract symptoms, which quickly resolved. The fevers persisted, however, with a maximum of 40°C. The child's review of symptoms was significant for a 1-kg weight loss over the past month. Ten months before presentation, she had moved from Saudi Arabia with her family. One week before the onset of symptoms, she had visited a petting zoo. During episodes of fever, the patient was ill-appearing and had an elevated heart rate and respiratory rate. On examination, she was found to be thin, febrile, tachycardic, and with scattered lymphadenopathy. Results of laboratory tests were remarkable for an elevated white blood cell count of 16,100 cells per uL with a neutrophilic predominance. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were elevated at 99 mm/h and 27 mg/dL, respectively. A chest radiograph indicated a small amount of fluid in the interlobar fissures. Our expert panel examines her case, offers a definition of fever of unknown origin, and makes diagnostic considerations. PMID:25917994

  18. How many well-baby visits are necessary in the first 2 years of life?

    PubMed Central

    Gilbert, J. R.; Feldman, W.; Siegel, L. S.; Mills, D. A.; Dunnett, C.; Stoddart, G.

    1984-01-01

    Since we could find no scientific basis for the 10 well-baby visits recommended in the first 2 years of life in Ontario, we carried out a randomized trial in 570 healthy, low-risk newborns to determine the efficacy and safety of decreasing the number of scheduled well-baby visits from 10 to 5. Among the 466 babies still in the trial at the end of the study period those in the 10-visit group had had a mean of 7.63 scheduled and 0.26 unscheduled well-baby visits and those in the 5-visit group a mean of 4.77 scheduled and 1.42 unscheduled well-baby visits. Reducing the recommended number of visits did not result in an increased incidence of illness or an increased prevalence of undetected abnormality, and the physical development of the babies in the two groups was almost identical. The mean scores of the two groups in assessments of mental development, maternal-child relations, maternal anxiety and parental satisfaction with health care were close. The results suggest that the recommended number of well-baby visits for healthy, low-risk newborns can be reduced to five for children of multiparas and six for children of primiparas. Any additional well-baby visits should be scheduled according to the needs and experience of the parents. PMID:6704838

  19. Longitudinal development of cortical and subcortical gray matter from birth to 2 years.

    PubMed

    Gilmore, John H; Shi, Feng; Woolson, Sandra L; Knickmeyer, Rebecca C; Short, Sarah J; Lin, Weili; Zhu, Hongtu; Hamer, Robert M; Styner, Martin; Shen, Dinggang

    2012-11-01

    Very little is known about cortical development in the first years of life, a time of rapid cognitive development and risk for neurodevelopmental disorders. We studied regional cortical and subcortical gray matter volume growth in a group of 72 children who underwent magnetic resonance scanning after birth and at ages 1 and 2 years using a novel longitudinal registration/parcellation approach. Overall, cortical gray matter volumes increased substantially (106%) in the first year of life and less so in the second year (18%). We found marked regional differences in developmental rates, with primary motor and sensory cortices growing slower in the first year of life with association cortices growing more rapidly. In the second year of life, primary sensory regions continued to grow more slowly, while frontal and parietal regions developed relatively more quickly. The hippocampus grew less than other subcortical structures such as the amygdala and thalamus in the first year of life. It is likely that these patterns of regional gray matter growth reflect maturation and development of underlying function, as they are consistent with cognitive and functional development in the first years of life. PMID:22109543

  20. Avascular necrosis of the femoral head at 2 years after pertrochanteric fracture surgery: Case report

    PubMed Central

    Deleanu, Bogdan; Prejbeanu, Radu; Vermesan, Dinu; Honcea, Lucian; Mioc, Mihail Lazar; Tsiridis, Eleftherios; Predescu, Vlad

    2015-01-01

    Introduction The avascular necrosis of the femoral head represents the death of bone tissue due to the lack of blood supply. The disease has a progressive evolution and left untreated leads to femoral head collapse and severe arthritis. Case presentation We present a case of a pertrochanteric fracture which has been successfully operated with a dynamic interlocking trochanteric gamma nail on the right hip. At 2 years after surgery the patient developed an incipient avascular necrosis of the femoral head. Despite the good positioning of the implant, we considered that the source of the pain was an intolerance of the implant, and thus we removed it. After implant removal, the patient was kept under observation and conservative treatment, to prevent further damage to the right hip and allow the healing to occur. At 6 months after the gamma nail was removed the X-rays revealed advanced avascular necrosis of the femoral head and secondary osteoarthritis on the right hip. The patient underwent surgery with an uncemented total hip arthroplasty. Discussion There are a few discussions regarding the avascular necrosis of the femoral head. These discussions may include the predisposing risk factors, the treatment of choice and the postoperative complications. Conclusion The avascular necrosis of the femoral head is a complication of pertrochanteric fractures that can not be foreseen or avoided. The optimal treatment in these cases is uncemented total hip arthroplasty. PMID:26900462

  1. Chronic intermittent form of isovaleric aciduria in a 2-year-old boy

    PubMed Central

    Cho, Jin Min; Lee, Beom Hee; Kim, Gu-Hwan; Kim, Yoo-Mi; Choi, Jin-Ho

    2013-01-01

    Isovaleric aciduria (IVA) is caused by an autosomal recessive deficiency of isovaleryl-CoA dehydrogenase (IVD). IVA presents either in the neonatal period as an acute episode of fulminant metabolic acidosis, which may lead to coma or death, or later as a "chronic intermittent form" that is associated with developmental delays, with or without recurrent acidotic episodes during periods of stress, such as infections. Here, we report the case of a 2-year old boy with IVA who presented with the chronic intermittent form. He was admitted to Asan Medical Center Children's Hospital with recurrent vomiting. Metabolic acidosis, hyperammonemia, elevated serum lactate and isovalerylcarnitine levels, and markedly increased urine isovalerylglycine concentration were noted. Sequence analysis of the IVD gene in the patient revealed the novel compound mutations-a missense mutation, c.986T>C (p.Met329Thr) and a frameshift mutation, c.1083del (p.Ile361fs*11). Following stabilization during the acute phase, the patient has remained in a stable condition on a low-leucine diet. PMID:24019846

  2. Complete Traumatic Separation of Proximal Femoral Epiphysis in A 2 Year Old Child

    PubMed Central

    Pal, Chandra Prakash; Kumar, Deepak; Singh, Pulkesh; Gaurav, Vishal

    2014-01-01

    Introduction: Hip fractures are very common in adults, but are rare in children, comprising less than 1% of all pediatric fractures. Separation of the proximal femoral epiphysis can occur in a child with a traumatic hip dislocation and an open epiphysis. Regardless of the mechanism of proximal femoral epiphyseal separation, the prognosis is poor secondary to the development of osteonecrosis. Case Report: Here we are reporting a case of complete separation of the proximal epiphysis of the femur in a 2 year old female child. She was treated by open reduction and internal fixation by a single k-wire of proximal femoral epiphysis. Regular follow up showed fusion of proximal femoral epiphysis at about 3 months of post operative period. After 8 months of follow up she can stand and walk without support. Long term outcome is awaited. Conclusion: Traumatic separation of the proximal femoral epiphysis is a rare but devastating injury because osteonecrosis occurs in most cases. In our study we found fusion of the proximal femoral epiphysis to the neck after 3 months of postoperative period. But to comment upon the final outcome a long follow up is awaited.

  3. Artificial-recharge investigation near Aurora, Nebraska: 2-year progress report

    USGS Publications Warehouse

    Lichtler, William F.; Stannard, David I.; Kouma, Edwin

    1979-01-01

    This report presents the results of the first 2 years of a 4-year investigation of potential for artificial recharge and recharge methods that might be used to mitigate excessive aquifer depletion in Nebraska. A Quaternary sand-and-gravel aquifer near Aurora, Nebr., was recharged by injecting water through a well at a rate of approximately 730 gallons per minute for nearly 6 months. Total recharge was 530 acre-feet. Recharge was intermittent during the first 2 months, but was virtually continuous during the last 4 months. Buildup of the water level in the recharge well was 17 feet. The rate of buildup indicates that the well could have accepted water by gravity flow at more than 3,000 gallons per minute for at least 1 year. The cause of a continuing slow rise in water levels in the recharge well in contrast to nearly stable water levels in observation wells as close as 10 feet from the recharge well is as yet uncertain. The recharge water and the native ground water appeared to be chemically compatible. Infiltration rates from 24-foot-diameter surface impoundments ranged from 0.04 to 0.66 feet per day. The higher rates may have resulted in part from leakage down incompletely sealed holes that were drilled to install monitoring equipment. The investigation, including a report on the entire project, is scheduled for completion by 1980.

  4. Physical Education, Obesity, and Academic Achievement: A 2-Year Longitudinal Investigation of Australian Elementary School Children

    PubMed Central

    Cunningham, Ross B.; Fitzgerald, Robert; Olive, Lisa S.; Prosser, Laurence; Jiang, Xiaoli; Telford, Rohan M.

    2012-01-01

    Objectives. We determined whether physical education (PE) taught by specialists contributed to academic development and prevention of obesity in elementary school children. Methods. Our 2-year longitudinal study involved 620 boys and girls initially in grade 3 in Australia, all receiving 150 minutes per week of PE. One group (specialist-taught PE; n = 312) included 90 minutes per week of PE from visiting specialists; the other (common-practice PE; n = 308) received all PE from generalist classroom teachers. Measurements included percentage of body fat (measured by dual-emission x-ray absorptiometry) and writing, numeracy, and reading proficiency (by government tests). Results. Compared with common-practice PE, specialist-taught PE was associated with a smaller increase in age-related percentage of body fat (P = .02). Specialist-taught PE was also associated with greater improvements in numeracy (P < .03) and writing (P = .13) scores. There was no evidence of a reading effect. Conclusions. The attenuated age-related increases in percentage of body fat and enhanced numeracy development among elementary school children receiving PE from specialists provides support for the role of PE in both preventive medicine and academic development. PMID:21940922

  5. Class II glass ionomer cermet tunnel, resin sandwich and amalgam restorations over 2 years.

    PubMed

    Wilkie, R; Lidums, A; Smales, R

    1993-08-01

    This study compared the clinical behavior of a glass ionomer (polyalkenoate) silver cermet, a posterior resin composite used with the "tunnel" technique, a posterior resin composite used with the "closed sandwich" technique, and a high-copper amalgam for restoring small, proximal surface carious lesions. Two dentists placed 86 restorations in the posterior permanent teeth of 26 adults treated at a dental hospital. Restorations were assessed at 6-month intervals over 2 years for gingivitis adjacent to them, the tightness of proximal contacts, occlusal wear, surface voids, roughness and cracking, surface and marginal staining, and marginal fracture. Small filling defects, surface voids and occlusal wear were obvious with the cermet material, with surface crazing and cracking present in 48% of the tunnel restorations. Two of the posterior resin composites, but none of the amalgam restorations, also failed. The cermet cannot be recommended as a long-term permanent restorative material in situations where it is likely to be subjected to heavy occlusal stresses and abrasive wear. PMID:7803004

  6. Mechanical Properties of Cranial Bones and Sutures in 1–2-Year-Old Infants

    PubMed Central

    Wang, Jiawen; Zou, Donghua; Li, Zhengdong; Huang, Ping; Li, Dongri; Shao, Yu; Wang, Huijun; Chen, Yijiu

    2014-01-01

    Background The mechanical properties of 1–2-year-old pediatric cranial bones and sutures and their influential factors were studied to better understand how the pediatric calvarium reacts to loading. Material/Methods Cranial bone and suture specimens were extracted from seven fresh-frozen human infant cadavers (1.5±0.5 years old). Eight specimens were obtained from each subject: two frontal bones, two parietal bones, two sagittal suture samples, and two coronal suture samples. The specimens were tested in a three-point bend setup at 1.5 mm/s. The mechanical properties, such as ultimate stress, elastic modulus, and ultimate strain, were calculated for each specimen. Results The ultimate stress and elastic modulus of the frontal bone were higher than those of the parietal bone (P<0.05). No differences were found between the coronal and sagittal sutures in ultimate stress, elastic modulus, or ultimate strain (P>0.05). The ultimate stress and elastic modulus of the frontal and parietal bones were higher than those of the sagittal and coronal sutures (P<0.05), whereas the opposite ultimate strain findings were revealed (P<0.05). Conclusions There was no significant difference in ultimate stress, elastic modulus, or ultimate strain between the sagittal and coronal sutures. However, there were significant differences in ultimate stress, elastic modulus, and ultimate strain between the frontal and parietal bones as well as between the cranial bones and sutures. PMID:25279966

  7. Early intervention and prevention of anxiety disorders in children: results at 2-year follow-up.

    PubMed

    Dadds, M R; Holland, D E; Laurens, K R; Mullins, M; Barrett, P M; Spence, S H

    1999-02-01

    The Queensland Early Intervention and Prevention of Anxiety Project evaluated a child- and family-focused group intervention for preventing anxiety problems in children. This article reports on 12- and 24-month follow-up data to previously reported outcomes at posttreatment and at 6-month follow-up. A total of 1,786 7- to 14-year-olds were screened for anxiety problems using teacher nominations and children's self-report. After diagnostic interviews, 128 children were selected and assigned to either a 10-week school-based child- and parent-focused psychosocial intervention or a monitoring group. Both groups showed improvements immediately at postintervention and at 6-month follow-up; the improvement was maintained in the intervention group only reducing the rate of existing anxiety disorder and preventing the onset of new anxiety disorders. At 12 months, the groups converged, but the superiority of the intervention group was evident again at 2-year follow-up. Severity of pretreatment diagnoses, gender, and parental anxiety predicted poor initial response to intervention, whereas pretreatment severity was the only predictor of chronicity at 24 months. Overall, follow-up results show that a brief school-based intervention for children can produce durable reductions in anxiety problems. PMID:10028219

  8. A 3 1/2 year old girl with distal trisomy 19q defined by FISH.

    PubMed Central

    James, C; Jauch, A; Robson, L; Watson, N; Smith, A

    1996-01-01

    A 3 1/2 year old girl was evaluated because of developmental delay. Short stature was evident with height between the 3rd and 10th centiles, while weight and head circumference were on the 50th centile. Dysmorphic features consisted of a high bossed forehead, pointed short ear lobes, small nose, bilateral convergent strabismus, left simian crease, a gap between the first and second toes bilaterally, mild clinodactyly, and a broad, barrel shaped thorax. Cytogenetic investigations showed an unbalanced karyotype, 46,XX,10q+, which was de novo in origin. Fluorescence in situ hybridisation (FISH) using three library probes (from chromosomes 10, 19, and 19q) and a YAC probe (from 10q telomere) showed that the additional material on 10q was derived from chromosome 19q. The patient had an unbalanced translocation, 46,XX,-10,+der(10)t(10;19)(q26.3; q13.3), which resulted in distal trisomy 19q. Few other cases of proven distal trisomy 19q are available for comparison of clinical features. Images PMID:8880586

  9. Remediation by 2-PHASE {trademark} extraction-A 2-year success story

    SciTech Connect

    Koerner, C.; Dee, P.E.; Baxter, J.; Huber, S.

    1996-12-31

    Radian has used the Xerox 2-PHASE{trademark} Extraction technology at several facilities worldwide to remove VOCs and petroleum hydrocarbons from subsurface soils and groundwater. The use of high vacuum with 2-PHASE{trademark} causes greater forces to be applied to the subsurface than do other dual-phase methods. 2-PHASE{trademark} improves dewatering, increases vacuum and groundwater radii of influence, deepens vadose zone development, enhances vapor stripping of soil contamination, improves vaporflow, and expedites remediation timeframes. This paper describes the successful 2-year application of 2-PHASE{trademark} to, remediate soil and several groundwater contamination. Contamination occurred under a floor slab near a former solvent spray booth and several underground storage tanks. Contaminants were primarily chlorinated VOCs and mineral spirits ranging to 330 mg/kg in soil and 1,070 mg/L in groundwater. The 2-PHASE{trademark} system was installed in October 1993; business constraints necessitated the completion of remediation within two years. The system was modified and expanded to optimize the removal effectiveness and extend the area of influence. Subsurface soil data obtained 8 and 11 months into the remediation program were used with soil gas data to predict future soil concentrations. VOC concentrations in the soil and groundwater were reduced by over 95 percent, and remediation goals were met within 18 months following start of in situ 2-PHASE{trademark} remediation. The system has been decommissioned following agency and landowner approval.

  10. Remediation by 2-PHASE [trademark] extraction-A 2-year success story

    SciTech Connect

    Koerner, C.; Dee, P.E. ); Baxter, J. ); Huber, S. )

    1996-01-01

    Radian has used the Xerox 2-PHASE[trademark] Extraction technology at several facilities worldwide to remove VOCs and petroleum hydrocarbons from subsurface soils and groundwater. The use of high vacuum with 2-PHASE[trademark] causes greater forces to be applied to the subsurface than do other dual-phase methods. 2-PHASE[trademark] improves dewatering, increases vacuum and groundwater radii of influence, deepens vadose zone development, enhances vapor stripping of soil contamination, improves vaporflow, and expedites remediation timeframes. This paper describes the successful 2-year application of 2-PHASE[trademark] to, remediate soil and several groundwater contamination. Contamination occurred under a floor slab near a former solvent spray booth and several underground storage tanks. Contaminants were primarily chlorinated VOCs and mineral spirits ranging to 330 mg/kg in soil and 1,070 mg/L in groundwater. The 2-PHASE[trademark] system was installed in October 1993; business constraints necessitated the completion of remediation within two years. The system was modified and expanded to optimize the removal effectiveness and extend the area of influence. Subsurface soil data obtained 8 and 11 months into the remediation program were used with soil gas data to predict future soil concentrations. VOC concentrations in the soil and groundwater were reduced by over 95 percent, and remediation goals were met within 18 months following start of in situ 2-PHASE[trademark] remediation. The system has been decommissioned following agency and landowner approval.

  11. Progressive supranuclear palsy: progression and survival.

    PubMed

    Arena, Julieta E; Weigand, Stephen D; Whitwell, Jennifer L; Hassan, Anhar; Eggers, Scott D; Höglinger, Günter U; Litvan, Irene; Josephs, Keith A

    2016-02-01

    Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder characterized by postural instability and falls, vertical supranuclear gaze palsy, parkinsonism with poor levodopa response, pseudobulbar palsy, and frontal release signs. The natural history of the disease has been previously described. However, the time frame of appearance of clinical milestones and how these symptoms may relate to survival in PSP are unknown. The primary objective was to determine the prevalence of symptoms at different stages of PSP and to estimate the time of appearance of clinical symptoms characteristic of the disease. Second, we determined the association between clinical symptoms and survival. We prospectively studied 35 PSP patients during assessments scheduled every 6 months for up to 2 years. We estimated symptoms prevalence and the association between symptoms and survival. The median age of onset was 65.9 years (IQR 60.6-70.0), and the median time from onset to first assessment was 3.0 years (IQR 2.4-3.9). The most commonly reported symptoms at baseline were: motor (100%) followed by cognitive/behavioral (89%), systemic and bulbar (80%), and sleep disturbances (60%). Slowness of movement, falls, neck stiffness and difficulty looking up/down had high prevalence from baseline, while balance and gait impairment were less common at baseline but increased in prevalence over time. The presence of sleep disturbances, and possibly hallucinations, was associated with increased death risk. Improved recognition of the clinical spectrum and milestones of PSP advances knowledge of the disease, helps earlier diagnosis, and allows prognostic predictions. PMID:26705121

  12. Basic Student Charges at Postsecondary Institutions: Academic Year 1992-93. Tuition and Required Fees and Room and Board Charges at 4-year, 2-year, and Public Less-than-2-year Institutions. Statistical Analysis Report.

    ERIC Educational Resources Information Center

    Broyles, Susan G.; Morgan, Frank B.

    This report lists the typical tuition and required fees and room and board charges for academic year 1992-93 at nearly 5,000 4-year, 2-year, and public less-than-2-year postsecondary institutions in the United States and its outlying areas. Included are tuition and fee charges to in-state and out-of-state students at the undergraduate and graduate…

  13. The value of surrogate endpoints for predicting real-world survival across five cancer types.

    PubMed

    Shafrin, Jason; Brookmeyer, Ron; Peneva, Desi; Park, Jinhee; Zhang, Jie; Figlin, Robert A; Lakdawalla, Darius N

    2016-04-01

    Objective It is unclear how well different outcome measures in randomized controlled trials (RCTs) perform in predicting real-world cancer survival. We assess the ability of RCT overall survival (OS) and surrogate endpoints - progression-free survival (PFS) and time to progression (TTP) - to predict real-world OS across five cancers. Methods We identified 20 treatments and 31 indications for breast, colorectal, lung, ovarian, and pancreatic cancer that had a phase III RCT reporting median OS and median PFS or TTP. Median real-world OS was determined using a Kaplan-Meier estimator applied to patients in the Surveillance and Epidemiology End Results (SEER)-Medicare database (1991-2010). Performance of RCT OS and PFS/TTP in predicting real-world OS was measured using t-tests, median absolute prediction error, and R(2) from linear regressions. Results Among 72,600 SEER-Medicare patients similar to RCT participants, median survival was 5.9 months for trial surrogates, 14.1 months for trial OS, and 13.4 months for real-world OS. For this sample, regression models using clinical trial OS and trial surrogates as independent variables predicted real-world OS significantly better than models using surrogates alone (P = 0.026). Among all real-world patients using sample treatments (N = 309,182), however, adding trial OS did not improve predictive power over predictions based on surrogates alone (P = 0.194). Results were qualitatively similar using median absolute prediction error and R(2) metrics. Conclusions Among the five tumor types investigated, trial OS and surrogates were each independently valuable in predicting real-world OS outcomes for patients similar to trial participants. In broader real-world populations, however, trial OS added little incremental value over surrogates alone. PMID:26743800

  14. 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

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

    PubMed

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

    2016-09-01

    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

  16. The Lymphocyte-Monocyte Ratio Predicts Patient Survival and Aggressiveness of Ovarian Cancer

    PubMed Central

    Eo, Wan Kyu; Chang, Hye Jung; Kwon, Sang Hoon; Koh, Suk Bong; Kim, Young Ok; Ji, Yong Il; Kim, Hong-Bae; Lee, Ji Young; Suh, Dong Soo; Kim, Ki Hyung; Chang, Ik Jin; Kim, Heung Yeol; Chang, Suk Choo

    2016-01-01

    Objective: To measure the prognostic value of the lymphocyte-monocyte ratio (LMR) in patients with epithelial ovarian cancer (EOC). Methods: We retrospectively examined the LMR as a prognosticator in a cohort of 234 patients with EOC who underwent surgical resection. Patients were categorized into two different groups based on the LMR (LMR-low and LMR-high) using cut-off values determined by receiver operating characteristic (ROC) curve analysis. The objective of the study was to assess the effect of the LMR on progression-free survival (PFS) and overall survival (OS), and to validate the LMR as an independent predictor of survival. Results: Using the data collected from the whole cohort, the optimized LMR cut-off value selected on the ROC curve was 2.07 for both PFS and OS. The LMR-low and LMR-high groups included 48 (20.5%) and 186 patients (79.5%), respectively. The 5-year PFS rates in the LMR-low and LMR-high groups were 40.0 and 62.5% (P < 0.0001), respectively, and the 5-year OS rates in these two groups were 42.2 and 67.2% (P < 0.0001), respectively. On multivariate analysis, we identified age, International Federation of Gynecology and Obstetrics (FIGO) stage, and cancer antigen 125 levels to be the strongest valuable prognostic factors affecting PFS (P = 0.0421, P = 0.0012, and P = 0.0313, respectively) and age, FIGO stage, and the LMR as the most valuable prognostic factors predicting OS (P = 0.0064, P = 0.0029, and P = 0.0293, respectively). Conclusion: The LMR is an independent prognostic factor affecting the survival of patients with EOC. PMID:26918042

  17. Lung response to ultrafine Kevlar aramid synthetic fibrils following 2-year inhalation exposure in rats.

    PubMed

    Lee, K P; Kelly, D P; O'Neal, F O; Stadler, J C; Kennedy, G L

    1988-07-01

    Four groups of 100 male and 100 female rats were exposed to ultrafine Kevlar fibrils at concentrations of 0, 2.5, 25, and 100 fibrils/cc for 6 hr/day, 5 days/week for 2 years. One group was exposed to 400 fibrils/cc for 1 year and allowed to recover for 1 year. At 2.5 fibrils/cc, the lungs had normal alveolar architecture with a few dust-laden macrophages (dust cell response) in the alveolar airspaces. At 25 fibrils/cc, the lungs showed a dust cell response, slight Type II pneumocyte hyperplasia, alveolar bronchiolarization, and a negligible amount of collagenized fibrosis in the alveolar duct region. At 100 fibrils/cc, the same pulmonary responses were seen as at 25 fibrils/cc. In addition, cystic keratinizing squamous cell carcinoma (CKSCC) was found in 4 female rats, but not in male rats. Female rats had more prominent foamy alveolar macrophages, cholesterol granulomas, and alveolar bronchiolarization. These pulmonary lesions were related to the development of CKSCC. The lung tumors were derived from metaplastic squamous cells in areas of alveolar bronchiolarization. At 400 fibrils/cc following 1 year of recovery, the lung dust content, average fiber length, and the pulmonary lesions were markedly reduced, but slight centriacinar emphysema and minimal collagenized fibrosis were found in the alveolar duct region. One male and 6 female rats developed CKSCC. The lung tumors were a unique type of experimentally induced tumors in the rats and have not been seen as spontaneous tumors in man or animals. Therefore, the relevance of this type of lung tumor to the human situation is minimal. PMID:3209007

  18. Epidemiology of 577 pediatric firearm fatalities: a 2-year review of the National Trauma Data Bank.

    PubMed

    Oyetunji, Tolulope A; Haider, Adil H; Obirieze, Augustine C; Fisher, Michael; Cornwell, Edward E; Qureshi, Faisal G; Abdullah, Fizan; Nwomeh, Benedict C

    2014-04-01

    The purpose of this study was to delineate the epidemiology of pediatric firearm injuries, including ethno-demographic patterns with impact on years of potential life lost (YPLL). A 2-year review of the National Trauma Data Bank (2007 to 2008) was conducted. Firearm fatalities in records of patients younger than 18 years were identified. Data were analyzed by demographic and injury characteristics and YPLL was calculated by ethnicity. A total of 577 deaths were identified in the pediatric group. Blacks accounted for 49.7 per cent of the fatalities; Hispanics, 19.2 per cent; whites, 17.7 per cent, and other ethnicity, 13.4 per cent. Median Injury Severity Score was 25 with a median Glasgow Coma Scale score of 3. Traumatic brain injury was present in 84.2 per cent of the records. Assault accounted for 72.8 per cent, self-inflicted injury 12.7 per cent, and unintentional injuries were 8.2 per cent. Most firearm fatalities occurred at home (33.6%). By emergency department (ED) disposition, 29.3 per cent died in the ED, 32.9 per cent were admitted to the intensive care unit, and 30.0 per cent taken to the operating room. Blacks had a total of 17,446 YPLL, Hispanics 6,776 YPLL, and whites 6,718 YPLL. Pediatric firearm fatalities still remain an important public health concern. Inclusive gun control policies focused on primary prevention of accidental injuries may be more effective in mitigating its impact. PMID:24887667

  19. Ankle Sprain Injuries: A 2-Year Prospective Cohort Study in Female Greek Professional Basketball Players

    PubMed Central

    Kofotolis, Nikolaos; Kellis, Eleftherios

    2007-01-01

    Context: Ankle sprains are a common basketball injury. Therefore, examination of risk factors for injury in female professional basketball players is worthwhile. Objective: To examine rates of ankle sprains, associated time missed from participation, and risk factors for injury during 2 consecutive seasons. Design: Prospective cohort study. Setting: Eighteen professional basketball facilities. Patients or Other Participants: We observed 204 players from 18 female professional basketball teams for 2 consecutive seasons during a 2-year period. Main Outcome Measure(s): Using questionnaires, we recorded the incidence of ankle sprains, participation time missed, and mechanisms of injury in games and practice sessions. Potential risk factors, such as age, body mass, height, training experience, and history of ankle sprain, were examined using multivariate logistic regression. Results: Fifty of the 204 participants sustained ankle injuries; injuries included 32 ankle sprains, which translated to an ankle sprain rate of 1.12 per 1000 hours of exposure to injury. The 32 players missed 224.4 training and game sessions and an average of 7.01 sessions per injury. Most injuries occurred in the key area of the basketball court and were the result of contact. Injury rates during games were higher than injury rates during practice sessions. Centers, followed by guards and forwards, had the highest rate of injury. Players who did not wear an external ankle support had an odds ratio of 2.481 for sustaining an ankle sprain. Conclusions: Female professional basketball athletes who did not wear an external ankle support, who played in the key area, or who functioned as centers had a higher risk for ankle sprain than did other players. PMID:18059995

  20. Global calibration/validation of 2 years of SARAL/AltiKa data

    NASA Astrophysics Data System (ADS)

    Scharroo, Remko; Lillibridge, John; Leuliette, Eric; Bonekamp, Hans

    2015-04-01

    The AltiKa altimeter flying onboard the French/Indian SARAL satellite provides the first opportunity to examine Ka-band measurements of sea surface height, significant wave height and ocean surface wind speed. In this presentation we provide the results from our global calibration/validation analysis of the AltiKa measurements, with an emphasis on near real-time applications of interest to both EUMETSAT and NOAA. Traditional along-track SSHA, and single as well as dual-satellite crossover assessments of the AltiKa performance are be provided. Unique aspects of the AltiKa mission such as improved along-track resolution, reduced ionospheric path delay corrections, mission-specific wind speed and sea state bias corrections, and sensitivity to liquid moisture and rain are also explored. In February 2014, a major update to the ground processing was introduced. "Patch-2" improved the way wind speed was derived from altimeter backscatter, as suggested by Lillibridge et al. (1). The backscatter attenuation is now derived from the radiometer measurements via neural network algorithms, which also determine the wet tropospheric correction. We emphasize these improvements in our analysis. After 2 years in flight, SARAL/AltiKa is already providing a significant contribution to the constellation of operational radar altimetry missions, demonstrating the large benefits of high-rate Ka-band altimetry. (1) Lillibridge, John, Remko Scharroo, Saleh Abdalla, Doug Vandemark, 2014: One- and Two-Dimensional Wind Speed Models for Ka-Band Altimetry. J. Atmos. Oceanic Technol., 31, 630-638. doi: http://dx.doi.org/10.1175/JTECH-D-13-00167.1

  1. Residue level and dissipation pattern of spiromesifen in cabbage and soil from 2-year field study.

    PubMed

    Siddamallaiah, Lekha; Mohapatra, Soudamini

    2016-03-01

    Spiromesifen is a new class of insecticide used for the control of whiteflies and mites which have developed resistance to the more commonly used neonicotinoids. Dissipation pattern of spiromesifen on cabbage was evaluated over 2 years by conducting supervised field studies as per good agricultural practices. Cabbage and soil samples were extracted and purified using modified QuEChERS method and analyzed through gas chromatography (GC). Confirmatory studies were carried out by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The recoveries of spiromesifen from cabbage and soil were between 85.44 and 103.37% with the relative standard deviation (RSD) between 3.2 and 9.4% (n = 6). The limit of detection (LOD) and limit of quantification (LOQ) were 0.003 μg mL(-1) and 0.01 mg kg(-1), respectively. The measurement uncertainties (MUs) were within 9.9-14.9%. Initial residues of spiromesifen on cabbage were 0.640 and 1.549 mg kg(-1) during 2013 and 0.723 and 1.438 mg kg(-1) during 2014 from treatments at standard and double doses of 125 and 250 g active ingredient (a.i.) ha(-1), respectively. Spiromesifen residue dissipation followed first-order rate kinetics, and it degraded within the half-lives of 2.9 and 3.9 days during 2013 and 3.2 and 4.5 days during 2014. The residue levels reached below the maximum residue limit (MRL; 0.02 mg kg(-1)) within 15-17 days at the standard dose and 24-27 days at the double dose. The field soil analyzed at harvest (30 days) was free from spiromesifen residues. Metabolite spiromesifen-enol was not detected in any sample which was confirmed through LC-MS/MS analysis. PMID:26869045

  2. Dental treatment of a 2-year-old victim of a suicide bomb attack.

    PubMed

    Katz-Sagi, Hadas; Gozal, David; Ram, Diana

    2007-10-01

    The purpose of this report was to describe the diagnosis and dental treatment of a 2-year-old girl that was involved in a suicide bomb attack. A 14-months-old infant was severely injured when a suicide bomber detonated an explosive device inside a crowded bus. Her injury was 'multi-system', mainly burns and fragments in her face, eyes and other parts of the body. Fifteen months later, she was brought to the Department of Pediatric Dentistry of the Hadassah School of Dental Medicine and the clinical and radiographic examination showed that she was caries free but there were dental trauma injuries to many teeth. Due to her non-cooperative behavior and the extent of treatment the girl was scheduled for a one appointment treatment under deep sedation. Three days later, she was brought to the Emergency Room of the Department of Pediatric Dentistry complaining of pain on the lower left side of the mouth and a swollen vestibule and face could clinically be observed. The lower left first molar that apparently revealed only an enamel fracture and cracks at the time of treatment, actually revealed a necrotic pulp as a result of the blast. As this girl was caries free, and with no history of dental trauma due to any accident, the only explanation for the response of the pulp was the impact of the blast. In conclusion, the reaction of the dental pulp to the blast of an explosion is different than the reaction to other kind of insult and this should be taken in consideration when treating children after this kind of dental trauma. PMID:17803491

  3. Natural Course of Allergic and Nonallergic Rhinitis After 2 Years in Korean Children

    PubMed Central

    Lee, Seung-Hoon; Choi, Ji Ho; Suh, Jeffrey D.; Chung, Sochung; Hong, Seok-Chan; Kim, Jin Kook; Cho, Jae Hoon

    2016-01-01

    Objectives. Allergic and nonallergic rhinitis are very common disease for children, however, little is known about their natural courses in the general population. The purpose is to evaluate the natural course of allergic and nonallergic rhinitis in children. Methods. We analyzed data from Snoring Child Cohort of 178 children (107 boys and 71 girls). All children entered the study at the age of 7 years (range, 6.5 to 7.4 years). Questionnaires regarding chronic rhinitis, a skin prick test (SPT) for 5 inhalent allergens, and specific IgE for 2 dust mites were administered. Children were classified into 4 groups: allergic rhinitis (rhinitis, positive SPT), nonallergic rhinitis (rhinitis, negative SPT), sensitization only (no rhinitis, positive SPT), and control (no rhinitis, negative SPT). We repeated follow them annually, and analyzed the data of first and third year for this study. Results. Finally, the data of 122 children were analyzed. Among 18 children with allergic rhinitis at 7 year, 13 (72%) became sensitization only after 2 years and 5 (28%) were remained having allergic rhinitis. Five out of 19 children (26%) with nonallergic rhinitis developed into allergic rhinitis and 7 (37%) into control at 9 years. Twenty-four out of 28 children (86%) with sensitization only at 7 years remained the same at 9 years. Among 57 control children at 7 year, 2 (4%) developed into allergic rhinitis, 7 (12%) with nonallergic rhinitis, and 16 (28%) with sensitization only at 9 years. Conclusion. The status of chronic rhinitis and allergen sensitization is ever-changing in children. PMID:27095517

  4. Survival by Stage of Soft Tissue Sarcoma

    MedlinePlus

    ... Next Topic How are soft tissue sarcomas treated? Survival by stage of soft tissue sarcoma Survival rates ... observed, not relative survival): Stage 5-year observed survival rate I 90% II 81% III 56% IV ...

  5. A Prospective Noninterventional Study to Evaluate Survival and Success of Reduced Diameter Implants Made From Titanium-Zirconium Alloy.

    PubMed

    Al-Nawas, Bilal; Domagala, Peter; Fragola, Giuliano; Freiberger, Philip; Ortiz-Vigón, Alberto; Rousseau, Paul; Tondela, João

    2015-08-01

    Narrow diameter implants may be at increased risk of overload due to occlusal forces; therefore, implants with higher fatigue strength may be beneficial. The aim of this observational study was to evaluate survival and success of narrow diameter (Ø 3.3 mm) TiZr alloy (Roxolid, Institut Straumann AG, Basel, Switzerland) implants for 2 years in daily dental practice. This was a prospective, non-interventional, multicenter study; no specific patient inclusion or exclusion criteria were applied. Each patient received at least one TiZr implant; the treatment plan, including implant loading and final restoration, was at the investigator's discretion. The primary outcome was implant survival and success after 1 year. Secondary outcomes included 2-year survival and success and marginal bone level change. A total of 603 implants were placed in 357 patients. Cumulative survival and success rates were 97.8% and 97.6%, respectively, after 1 year and 97.6% and 97.4%, respectively, after 2 years. Bone levels remained stable in the majority of patients, and soft tissue remained stable up to 2 years. Within the limitations of a non-interventional study design, TiZr implants showed excellent survival and success with minimal bone loss up to 2 years in daily dental practice. The results compare favorably with those of small-diameter implants in controlled clinical trials. PMID:24666383

  6. 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

  7. 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.

  8. 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

  9. Improvement in High-Grade Osteosarcoma Survival: Results from 202 Patients Treated at a Single Institution in Taiwan.

    PubMed

    Hung, Giun-Yi; Yen, Hsiu-Ju; Yen, Chueh-Chuan; Wu, Po-Kuei; Chen, Cheng-Fong; Chen, Paul C-H; Wu, Hung-Ta H; Chiou, Hong-Jen; Chen, Wei-Ming

    2016-04-01

    The aim of this study was to compare survival before and after 2004 and define the prognostic factors for high-grade osteosarcomas beyond those of typical young patients with localized extremity disease.Few studies have reported the long-term treatment outcomes of high-grade osteosarcoma in Taiwan.A total of 202 patients with primary high-grade osteosarcoma who received primary chemotherapy at Taipei Veterans General Hospital between January 1995 and December 2011 were retrospectively evaluated and compared by period (1995-2003 vs 2004-2011). Patients of all ages and tumor sites and those following or not following controlled protocols were included in analysis of demographic, tumor-related, and treatment-related variables and survival.Overall survival and progression-free survival at 5 years were, respectively, 67.7% and 48% for all patients (n = 202), 77.3% and 57.1% for patients without metastasis (n = 157), and 33.9% and 14.8% for patients with metastasis (n = 45). The survival rates of patients treated after 2004 were significantly higher (by 13%-16%) compared with those of patients treated before 2004, with an accompanying 30% increase in histological good response rate (P = .002). Factors significantly contributing to inferior survival in univariate and multivariate analyses were diagnosis before 2004, metastasis at diagnosis, and being a noncandidate for a controlled treatment protocol.By comparison with the regimens used at our institution before 2004, the current results support the effectiveness of the post-2004 regimens, which consisted of substantially reduced cycles of high-dose methotrexate and a higher dosage of ifosfamide per cycle, cisplatin, and doxorubicin, for treating high-grade osteosarcoma in Asian patients. PMID:27082623

  10. Improved tumor vascularization after anti-VEGF therapy with carboplatin and nab-paclitaxel associates with survival in lung cancer

    PubMed Central

    Heist, Rebecca S.; Duda, Dan G.; Sahani, Dushyant V.; Ancukiewicz, Marek; Fidias, Panos; Sequist, Lecia V.; Temel, Jennifer S.; Shaw, Alice T.; Pennell, Nathan A.; Neal, Joel W.; Gandhi, Leena; Lynch, Thomas J.; Engelman, Jeffrey A.; Jain, Rakesh K.

    2015-01-01

    Addition of anti-VEGF antibody therapy to standard chemotherapies has improved survival and is an accepted standard of care for advanced non–small cell lung cancer (NSCLC). However, the mechanisms by which anti-VEGF therapy increases survival remain unclear. We evaluated dynamic CT-based vascular parameters and plasma cytokines after bevacizumab alone and after bevacizumab plus chemotherapy with carboplatin and nab-paclitaxel in advanced NSCLC patients to explore potential biomarkers of treatment response and resistance to this regimen. Thirty-six patients were enrolled in this study. The primary end point was 6-mo progression-free survival rate, which was 74% (95% CI: 57, 97). This regimen has a promising overall response rate of 36% and median time to progression of 8.5 (6.0, 38.7) mo and overall survival of 12.2 (9.6, 44.1) mo. We found that anti-VEGF therapy led to a sustained increase in plasma PlGF, a potential pharmacodynamic marker. We also found that higher levels of soluble VEGFR1 measured before starting bevacizumab with chemotherapy were associated with worse survival, supporting its potential role as biomarker of treatment resistance. Our imaging biomarker studies indicate that bevacizumab-based treatment—while reducing blood flow, volume, and permeability in the overall population—may be associated with improved survival in patients with improved tumor vasculature and blood perfusion after treatment. This hypothesis-generating study supports the notion that excessively decreasing vascular permeability and pruning/rarefaction after bevacizumab therapy may negatively impact the outcome of combination therapy in NSCLC patients. This hypothesis warrants further dose-titration studies of bevacizumab to examine the dose effect on tumor vasculature and treatment efficacy. PMID:25605928

  11. 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

  12. Prolonged survival in adult neurofibromatosis type I patients with recurrent high-grade gliomas treated with bevacizumab.

    PubMed

    Theeler, Brett J; Ellezam, Benjamin; Yust-Katz, Shlomit; Slopis, John M; Loghin, Monica E; de Groot, John F

    2014-08-01

    Astrocytic tumors, especially optic pathway pilocytic astrocytomas, are common in pediatric NF1 patients. High-grade gliomas (HGGs) appear to be rare in adult and pediatric NF1 patients. This is a series of five consecutive, adult NF1 patients with recurrent HGGs treated at The University of Texas MD Anderson Cancer Center. Four patients met consensus clinical criteria for NF1 and one patient had presumed segmental NF1. Three patients had glioblastomas, one gliosarcoma, and one progressive, enhancing optic pathway glioma which was not biopsied. Two tumors had molecular testing performed; both were IDH wild type and activating oncogene mutations (1 BRAFV600E and 1 PIK3CA mutation) were found in these tumors. All five patients received bevacizumab-containing regimens at tumor recurrence. The median number of 4-week cycles of bevacizumab was 20. All five patients experienced prolonged post-recurrence survival following bevacizumab treatment ranging from ten to 72 months. The median overall survival from HGG diagnosis was 72.6 months with three patients alive and progression free at last follow-up. Three out of five patients developed vascular complications leading to bevacizumab discontinuation. In this case series, adult NF1 patients with recurrent HGGs had prolonged, post-recurrence survival after treatment with bevacizumab-containing regimens. Based on these results, further study of antiangiogenic therapy in NF1 patients with HGGs and bevacizumab-response in sporadic HGG patients with NF1-mutated tumors is warranted. PMID:24859329

  13. Minimum 2-Year Outcomes after Resection Arthroplasty of the Sternoclavicular Joint

    PubMed Central

    Katthagen, Jan Christoph; Tahal, Dimitri S.; Menge, Travis; Horan, Marilee P.; Millett, Peter J.

    2016-01-01

    Objectives: Injuries of the sternoclavicular (SC) joint are rare and are usually caused by high energy mechanisms, such as collision sports or motor vehicle accidents. The aims of this study were to assess functional outcomes and return to sport following resection arthroplasty for osteoarthritis of the sternoclavicular joint. Methods: 20 SC joints (18 patients) had undergone resection arthroplasty of up to a maximum of 10 mm of the medial end of the clavicle for painful osteoarthritis, without instability, between November 2006 and November 2013. Patients at least two years out from surgery and living in the U.S. were included in the study. This was an IRB-approved retrospective outcomes study with prospectively collected data. Preoperative and postoperative function and pain levels were assessed with the ASES, SF-12 PCS, QuickDASH and SANE scores. Additionally, the level of sport intensity and the pain levels during activities of daily living, work and recreation were assessed pre- and postoperatively. The results of the functional outcome scores were normally distributed and were compared with the paired sample t-test. The results of pain level assessment were not normally distributed and were compared with the paired Wilcoxon signed-rank test. Results: 19 SC joints in 17 patients (9 female, 8 male; mean age at time of surgery 39.5±17.1 years) met inclusion criteria. One patient refused participation in the study. Two patients (10.5%) were considered failures as they required additional SC joint surgery (one patient with revision resection of the medial clavicle for persistent symptoms and one patient with secondary figure-of-eight graft stabilization for instability). Minimum 2-year outcomes data were available for 14 of the remaining 16 SC joints (88%). The mean time to follow-up was 3.1 years (range, 2.0-8.8 years). The ASES score, QuickDASH, and pain levels demonstrated significant improvement postoperatively (p<0.05; Table 1). No significant differences

  14. Spectroscopy of High-Redshift Supernovae from the ESSENCE Project: The First 2 Years

    NASA Astrophysics Data System (ADS)

    Matheson, Thomas; Blondin, Stéphane; Foley, Ryan J.; Chornock, Ryan; Filippenko, Alexei V.; Leibundgut, Bruno; Smith, R. Chris; Sollerman, Jesper; Spyromilio, Jason; Kirshner, Robert P.; Clocchiatti, Alejandro; Aguilera, Claudio; Barris, Brian; Becker, Andrew C.; Challis, Peter; Covarrubias, Ricardo; Garnavich, Peter; Hicken, Malcolm; Jha, Saurabh; Krisciunas, Kevin; Li, Weidong; Miceli, Anthony; Miknaitis, Gajus; Prieto, Jose Luis; Rest, Armin; Riess, Adam G.; Salvo, Maria Elena; Schmidt, Brian P.; Stubbs, Christopher W.; Suntzeff, Nicholas B.; Tonry, John L.

    2005-05-01

    We present the results of spectroscopic observations of targets discovered during the first 2 years of the ESSENCE project. The goal of ESSENCE is to use a sample of ~200 Type Ia supernovae (SNe Ia) at moderate redshifts (0.2<~z<~0.8) to place constraints on the equation of state of the universe. Spectroscopy not only provides the redshifts of the objects but also confirms that some of the discoveries are indeed SNe Ia. This confirmation is critical to the project, as techniques developed to determine luminosity distances to SNe Ia depend on the knowledge that the objects at high redshift have the same properties as the ones at low redshift. We describe the methods of target selection and prioritization, the telescopes and detectors, and the software used to identify objects. The redshifts deduced from spectral matching of high-redshift SNe Ia with low-redshift SNe Ia are consistent with those determined from host-galaxy spectra. We show that the high-redshift SNe Ia match well with low-redshift templates. We include all spectra obtained by the ESSENCE project, including 52 SNe Ia, five core-collapse SNe, 12 active galactic nuclei, 19 galaxies, four possibly variable stars, and 16 objects with uncertain identifications. Based in part on observations obtained at the Cerro Tololo Inter-American Observatory, which is operated by the Association of Universities for Research in Astronomy (AURA), Inc., under a cooperative agreement with the National Science Foundation (NSF); the European Southern Observatory, Chile (ESO Programme 170.A-0519) the Gemini Observatory, which is operated by AURA under a cooperative agreement with the NSF on behalf of the Gemini partnership (the NSF [United States], the Particle Physics and Astronomy Research Council [United Kingdom], the National Research Council [Canada], CONICYT [Chile], the Australian Research Council [Australia], CNPq [Brazil], and CONICET [Argentina] [programs GN-2002B-Q-14, GN-2003B-Q-14, and GS-2003B-Q-11]) the

  15. Serum insulin profiles in consecutive children 2 years after the diagnosis of IDDM.

    PubMed

    Simell, T; Mäenpää, J; Kaprio, E A; Hakulinen, A; Hakalax, J; Sipilä, I; Akerblom, H K; Simell, O

    1995-01-01

    We studied associations of 24-h serum insulin profiles with insulin dose, age, gender, haemoglobin A1c (HbA1c) and C-peptide values, as well as blood glucose profiles in 77 consecutive children-nine aged 2-4, 14 aged 5-8, 26 aged 9-12, and 28 aged 13-17 years--2 years after the onset of insulin-dependent diabetes mellitus (IDDM). Mean weight-based insulin doses in the four age groups were similar (0.7 +/- 0.2 U.kg-1.day-1 in all); body surface-area-based doses differed. Insulin doses correlated significantly with the 24-h mean and area-under-the-curve (AUC) values, and with mean values at 03.00 hours of serum insulin in the children aged 5-8 and 13-17 years. The mean insulin concentrations of the age groups (95% confidence intervals) increased with age [6.1 (3.8, 9.7), 7.6 (5.9, 9.8), 10.4 (8.6, 12.4), and 14.0 (11.6, 16.8) mU/l; p < 0.0002]. The 24-h mean of serum insulin together with HbA1c concentration predicted 32% of the variation of mean blood glucose concentrations. Of children aged less than 9 years, 50% had insulin values less than 5 mU/l (healthy subjects' lower reference limit), and 14% were of less than 2 mU/l (detection limit of the assay) at 03.00 hours. At 07.00 hours, 82% had insulin values of less than 5 mU/l, and 36% were of less than 2 mU/l, respectively. Some young children had night-time hypoglycaemia with simultaneous hypoinsulinaemia. Insulin profiles correlated poorly with the HbA1c and peak C-peptide values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7744234

  16. 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

  17. Survival of Planetary Systems

    NASA Astrophysics Data System (ADS)

    Ward, William R.

    1996-06-01

    Recent low frequency results from attempts to detect Jupiter-sized planets around nearby stars have raised a question as to whether such objects are all that common. In the over 200 stars observed so far, the yield has been 3%. And, the close orbit (0.05 AU) of the nearly Jupiter-sized object around Peg 51 places the object in an environment where the current paradigm of planetary formation would not predict planets to form at all. Other newly discovered candidates, such a Vir 70 and HR3522, also have suspiciously small semi-major axes for gas giants. Of course, the low yield may be strongly influenced by selection effects since massive planets close to their primaries are more easily detected. Nevertheless, given the results to date, it is natural to wonder whether a planetary system like ours is such a natural outgrowth of a circumplantary disk. In particular, could there be forces absent from the existing paradigm that tend to destroy a planetary system once formed? We point out that strong gravitational interactions (i.e., disk tides) between a newly formed protoplanet and its precursor disk give rise to a net torque that drains angular momentum from the protoplanet's orbit. As a result, protoplanetary objects suffer orbital decay as the disk attempts to destroy the very system it spawns. Strong interaction (type I) leads to gap formation and co-evolution with the disk; weak inter- action (type II) leads to drift relative to the disk and in some cases, a much more rapid decay. Survival of a planetary system may be a comparatively uncommon outcome. Newly discovered planets such as Peg 51b may be evidence of such large-scale orbit migration due to disk tidal torques (i.e., Lin et al., 1996).

  18. 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

  19. Survival After Relapse of Medulloblastoma.

    PubMed

    Koschmann, Carl; Bloom, Karina; Upadhyaya, Santhosh; Geyer, J Russell; Leary, Sarah E S

    2016-05-01

    Survival after recurrence of medulloblastoma has not been reported in an unselected cohort of patients in the contemporary era. We reviewed 55 patients diagnosed with medulloblastoma between 2000 and 2010, and treated at Seattle Children's Hospital to evaluate patterns of relapse treatment and survival. Fourteen of 47 patients (30%) over the age of 3 experienced recurrent or progressive medulloblastoma after standard therapy. The median time from diagnosis to recurrence was 18.0 months (range, 3.6 to 62.6 mo), and site of recurrence was metastatic in 86%. The median survival after relapse was 10.3 months (range, 1.3 to 80.5 mo); 3-year survival after relapse was 18%. There were trend associations between longer survival and having received additional chemotherapy (median survival 12.8 vs. 1.3 mo, P=0.16) and radiation therapy (15.4 vs. 5.9 mo, P=0.20). Isolated local relapse was significantly associated with shorter survival (1.3 vs. 12.8 mo, P=0.009). Recurrence of medulloblastoma is more likely to be metastatic than reported in previous eras. Within the limits of our small sample, our data suggest a potential survival benefit from retreatment with cytotoxic chemotherapy and radiation even in heavily pretreated patients. This report serves as a baseline against which to evaluate novel therapy combinations. PMID:26907655

  20. Validation of survivability validation protocols

    SciTech Connect

    Stringer, T.A. )

    1993-05-01

    Issues associated with the validation of survivability protocols are discussed. Both empirical and analytical approaches to protocol validation are included. The use of hybrid simulations (hardware-in-the-loop, scene generators, software generators, man-in-the-loop, etc.) for the validation of survivability protocols is discussed.

  1. CAD/CAM ZIRCONIA VS. SLIP-CAST GLASS-INFILTRATED ALUMINA/ZIRCONIA ALL-CERAMIC CROWNS: 2-YEAR RESULTS OF A RANDOMIZED CONTROLLED CLINICAL TRIAL

    PubMed Central

    Çehreli, Murat Cavit; Kökat, Ali Murat; Akça, Kivanç

    2009-01-01

    The aim of this randomized controlled clinical trial was to compare the early clinical outcome of slip-cast glass-infiltrated Alumina/Zirconia and CAD/CAM Zirconia all-ceramic crowns. A total of 30 InCeram® Zirconia and Cercon® Zirconia crowns were fabricated and cemented with a glass ionomer cement in 20 patients. At baseline, 6-month, 1-year, and 2-year recall appointments, Californian Dental Association (CDA) quality evaluation system was used to evaluate the prosthetic replacements, and plaque and gingival index scores were used to explore the periodontal outcome of the treatments. No clinical sign of marginal discoloration, persistent pain and secondary caries was detected in any of the restorations. All InCeram® Zirconia crowns survived during the 2-year period, although one nonvital tooth experienced root fracture coupled with the fracture of the veneering porcelain of the restoration. One Cercon® Zirconia restoration fractured and was replaced. According to the CDA criteria, marginal integrity was rated excellent for InCeram® Zirconia (73%) and Cercon® Zirconia (80%) restorations, respectively. Slight color mismatch rate was higher for InCeram® Zirconia restorations (66%) than Cercon® Zirconia (26%) restorations. Plaque and gingival index scores were mostly zero and almost constant over time. Time-dependent changes in plaque and gingival index scores within and between groups were statistically similar (p>0.05). This clinical study demonstrates that single-tooth InCeram® Zirconia and Cercon® Zirconia crowns have comparable early clinical outcome, both seem as acceptable treatment modalities, and most importantly, all-ceramic alumina crowns strengthened by 25% zirconia can sufficiently withstand functional load in the posterior zone. PMID:19148406

  2. TP53 Mutations and Survival in Osteosarcoma Patients: A Meta-Analysis of Published Data

    PubMed Central

    Chen, Zhe; Guo, Jiayi; Zhang, Kun; Guo, Yanxing

    2016-01-01

    Several research groups have examined the association between TP53 mutations and prognosis in human osteosarcoma. However, the results were controversial. The purpose of this study was to evaluate the prognostic value of TP53 mutations in osteosarcoma patients. A meta-analysis was conducted with all eligible studies which quantitatively evaluated the relationship between TP53 mutations and clinical outcome of osteosarcoma patients. Eight studies with a total of 210 patients with osteosarcoma were included in this meta-analysis. The risk ratio (RR) with a 95% confidence interval (95% CI) was calculated to assess the effect of TP53 mutations on 2-year overall survival. The quantitative synthesis of 8 published studies showed that TP53 mutations were associated with 2-year overall survival in osteosarcoma patients. These data suggested that TP53 mutations had an unfavorable impact on 2-year overall survival when compared to the counterparts with wild type (WT) TP53 (RR: 1.79; 95% CI: 1.12 to 2.84; P = 0.01; I2 = 0%). There was no between-study heterogeneity. TP53 mutations are an effective prognostic marker for survival of patients with osteosarcoma. However, further large-scale prospective trials should be performed to clarify the prognostic value of TP53 mutations on 3- or 5-year survival in osteosarcoma patients. PMID:27239089

  3. CA-125–indicated asymptomatic relapse confers survival benefit to ovarian cancer patients who underwent secondary cytoreduction surgery

    PubMed Central

    2013-01-01

    Background There is no consensus regarding the management of ovarian cancer patients, who have shown complete clinical response (CCR) to primary therapy and have rising cancer antigen CA-125 levels but have no symptoms of recurrent disease. The present study aims to determine whether follow-up CA-125 levels can be used to identify the need for imaging studies and secondary cytoreductive surgery (CRS). Methods We identified 410 ovarian cancer patients treated at The University of Texas MD Anderson Cancer Center between 1984 and 2011. These patients had shown CCR to primary therapy. Follow-up was conducted based on the surveillance protocol of the MD Anderson Cancer Center. We used the Cox proportional hazards model and log-rank test to assess the associations between the follow-up CA-125 levels and secondary CRS and survival duration. Results The CA-125 level of 1.68 × nadir was defined as the indicator of recurrent disease (p < 0.001). The specificity and sensitivity of this criterion were 82.9% and 85.6%, respectively, and the median lead-time of the CA-125 biochemical progression prior to clinically-defined relapse was 31 days (ranging from 1 to 391 days). The median number of the negative imaging studies for the clinical relapse findings in patients with a CA-125 level of < 1.68 × nadir was 3 (ranging from 0 to 24 times). The increase of CA-125 level at relapse was an independent predictor of overall and progression free survival in patients who had shown CCR to primary therapy (p = 0.04 and 0.02 respectively). The overall and progression free survival durations in patients with a CA-125 level ≤ 1.68 × nadir at relapse (69.4 and 13.8 months) were longer than those with a CA-125 level > 1.68 × nadir at relapse (55.7 and 10.4 months; p = 0.04 and 0.01, respectively). The overall and progression free survival duration of patients with asymptomatic relapse and underwent a secondary CRS was longer than that of

  4. Correlation between array-comparative genomic hybridization-defined genomic gains and losses and survival: identification of 1p31-32 deletion as a prognostic factor in myeloma

    PubMed Central

    Chng, WJ; Gertz, MA; Chung, T-H; Van Wier, S; Keats, JJ; Baker, A; Bergsagel, PL; Carpten, J; Fonseca, R

    2010-01-01

    In this study, we correlated array-comparative genomic hybridization-defined abnormalities with survival in two different cohorts of patients treated with therapy based on high-dose melphalan with autologous stem-cell transplantation (64 from the Mayo Clinic and 67 from the University of Arkansas Medical School) and identified that several regions of genomic gains and losses were significantly associated with poorer survival. Three noncontiguous survival relevant regions covering 1p31-33 and two noncontiguous regions covering 20p12.3-12.1 were common between the two datasets. The prognostic relevance of these hotspots was validated in an independent cohort using fluorescent in situ hybridization, which showed that 1p31-32 loss is significantly associated with shorter survival (24.5 months versus 40 months, log-rank P-value=0.01), whereas 20p12 loss has a trend toward shorter survival (26.3 months versus 40 months, log-rank P-value=0.06). On multivariate analysis, 1p31-32 loss is an independent prognostic factor. On further analysis, the prognostic impact of 1p31-32 loss is due to shortening of post-relapse survival as there is no impact on complete response rates and progression-free survival. PMID:20220778

  5. Incidence of Second ACL Injuries 2 Years After Primary ACL Reconstruction and Return to Sport

    PubMed Central

    Paterno, Mark V.; Rauh, Mitchell J.; Schmitt, Laura C.; Ford, Kevin R.; Hewett, Timothy E.

    2014-01-01

    Background The incidence of second anterior cruciate ligament (ACL) injuries in the first 12 months after ACL reconstruction (ACLR) and return to sport (RTS) in a young, active population has been reported to be 15 times greater than that in a previously uninjured cohort. There are no reported estimates of whether this high relative rate of injury continues beyond the first year after RTS and ACLR. Hypothesis The incidence rate of a subsequent ACL injury in the 2 years after ACLR and RTS would be less than the incidence rate reported within the first 12 months after RTS but greater than the ACL injury incidence rate in an uninjured cohort of young athletes. Study Design Cohort study; Level of evidence, 2. Methods Seventy-eight patients (mean age, 17.1 ± 3.1 years) who underwent ACLR and were ready to return to a pivoting/ cutting sport and 47 controls (mean age, 17.2 ± 2.6 years) who also participated in pivoting/cutting sports were prospectively enrolled. Each participant was followed for injury and athlete exposure (AE) data for a 24-month period after RTS. Twenty-three ACLR and 4 control participants suffered an ACL injury during this time. Incidence rate ratios (IRRs) were calculated to compare the rates (per 1000 AEs) of ACL injury in athletes in the ACLR and control groups. For the ACLR group, similar comparisons were conducted for side of injury by sex. Results The overall incidence rate of a second ACL injury within 24 months after ACLR and RTS (1.39/1000 AEs) was nearly 6 times greater (IRR, 5.71; 95% CI, 2.0–22.7; P = .0003) than that in healthy control participants (0.24/1000 AEs). The rate of injury within 24 months of RTS for female athletes in the ACLR group was almost 5 times greater (IRR, 4.51; 95% CI, 1.5–18.2; P = .0004) than that for female controls. Although only a trend was observed, female patients within the ACLR group were twice as likely (IRR, 2.43; 95% CI, 0.8–8.6) to suffer a contralateral injury (1.13/1000 AEs) than an

  6. Satellite Survivability Module

    NASA Astrophysics Data System (ADS)

    Buehler, P.; Smith, J.

    The Satellite Survivability Module (SSM) is an end-to-end, physics-based, performance prediction model for directed energy engagement of orbiting spacecraft. SSM was created as an add-on module for the Satellite Tool Kit (STK). Two engagement types are currently supported: laser engagement of the focal plane array of an imaging spacecraft; and Radio Frequency (RF) engagement of spacecraft components. This paper will focus on the laser engagement scenario, the process by which it is defined, and how we use this tool to support a future laser threat detection system experiment. For a laser engagement, the user creates a spacecraft, defines its optical system, adds any protection techniques used by the optical system, introduces a laser threat, and then defines the atmosphere through which the laser will pass. SSM models the laser engagement and its impact on the spacecraft's optical system using four impact levels: degradation, saturation, damage, and destruction. Protection techniques, if employed, will mitigate engagement effects. SSM currently supports two laser protection techniques. SSM allows the user to create and implement a variety of "what if" scenarios. Satellites can be placed in a variety of orbits. Threats can be placed anywhere on the Earth or, for version 2.0, on other satellites. Satellites and threats can be mixed and matched to examine possibilities. Protection techniques for a particular spacecraft can be turned on or off individually; and can be arranged in any order to simulate more complicated protection schemes. Results can be displayed as 2-D or 3-D visualizations, or as textual reports. A new report feature available in version 2.0 will allow laser effects data to be displayed dynamically during scenario execution. In order to test SSM capabilities, the Ball team used SSM to model several engagement scenarios for our future laser threat detection system experiment. Actual test sites, along with actual laser, optics, and detector

  7. 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

  8. Functional deterioration from the premorbid period to 2 years after the first episode of psychosis in early-onset psychosis.

    PubMed

    Del Rey-Mejías, Ángel; Fraguas, David; Díaz-Caneja, Covadonga M; Pina-Camacho, Laura; Castro-Fornieles, Josefina; Baeza, Inmaculada; Espliego, Ana; Merchán-Naranjo, Jessica; González-Pinto, Ana; de la Serna, Elena; Payá, Beatriz; Graell, Montserrat; Arango, Celso; Parellada, Mara

    2015-12-01

    The aim of the study was to analyze changes in functional adjustment from childhood to 2 years after the first episode of psychosis (FEP) in patients with early-onset schizophrenia spectrum disorders (SSD) and affective psychoses (AFP) and a good or intermediate level of premorbid adjustment. We followed 106 adolescents (aged 12-17 years) with FEP for 2 years after recruitment. Premorbid adjustment in childhood was assessed in 98 patients with the childhood subscale of the Cannon-Spoor Premorbid Adjustment Scale (c-PAS). Global functioning was assessed 2 years after the FEP with the Children's Global Assessment Scale (c-GAS) or the Global Assessment of Functioning scale (GAF), as appropriate. Functional deterioration was defined as a downward shift in the level of functional adjustment from childhood to 2 years after the FEP. In patients with good or intermediate premorbid adjustment, functional deterioration was observed in 28.2 % (26.5 % of the AFP group, 29.4 % of the SSD group). Longer duration of untreated psychosis (Beta = 0.01; P = 0.01) and higher symptom severity at the FEP, as measured with the Clinical Global Impression Scale (Beta = 1.12; P = 0.02), significantly predicted the presence of functional deterioration, accounting for 21.4 % of the variance. Irrespective of diagnosis (SSD or AFP), almost one-third of adolescents with FEP and good or intermediate premorbid adjustment showed functional deterioration from the premorbid period to 2 years after the FEP. PMID:25726022

  9. Inbreeding impact on litter size and survival in selected canine breeds.

    PubMed

    Leroy, Grégoire; Phocas, Florence; Hedan, Benoit; Verrier, Etienne; Rognon, Xavier

    2015-01-01

    Data obtained from the French Kennel Club and the Fichier National Canin were used to estimate the effect of inbreeding on average litter size and survival in seven French breeds of dog. Depending on the breed, litter sizes were 3.5-6.3 puppies and longevities were 7.7-12.2 years. Estimated heritabilities were 6.0-10.9% for litter size and 6.1-10.1% for survival at 2 years of age. Regression coefficients indicated a negative effect of inbreeding on both individual survival and litter size. Although the impact of baseline inbreeding within breeds appears to be limited, the improper mating of close relatives will reduce biological fitness through significant reduction of litter size and longevity. PMID:25475165

  10. Intraocular lymphoma in Korea: the Consortium for Improving Survival of Lymphoma (CISL) study

    PubMed Central

    Lee, Seul; Kim, Moon Jin; Kim, Jin Seok; Kim, Seok Jin; Kwon, Yoon Hyung; Chung, In Young; Kang, Jung Hun; Yang, Deok-Hwan; Kang, Hye Jin; Yoon, Dok Hyun; Kim, Won Seog; Kim, Hyo-Jin

    2015-01-01

    Background Intraocular lymphoma (IOL) is a rare malignant lymphoma that most closely resembles a diffuse large B-cell lymphoma, and it is a subtype of primary central nervous system lymphoma (PCNSL). IOL is located inside the eye in the retina, uvea, and/or optic nerve. We retrospectively analyzed IOL patient data to identify treatment patterns and survival rates in Korea. Methods Cytological confirmation for a diagnosis of IOL was performed for all patients. The clinical data collected from medical records included Ann Arbor stage, International Prognostic Index, performance status, date of diagnosis, treatment modality and response, date of relapse, and date of last follow-up. Results Twenty patients who were diagnosed with IOL, between December 2007 and June 2014 at multiple centers in Korea, were included in the analysis. Four patients were diagnosed with IOL alone, not involving the CNS. Two patients with isolated IOL later developed PCNSL. Nine patients developed CNS lesions before the onset of ocular lymphoma. Five patients had simultaneous onset in the eye and CNS. Twelve patients were treated by intravitreal injection of methotrexate for IOL. The median progression-free survival (PFS) for patients was 19.7 months (95% CI, 8.7-30.7 mo). The estimated 3-year overall survival (OS) for all patients was 75.1%. Conclusion Treatment for IOL patients included radiotherapy and intraocular chemotherapy. IOL patients showed favorable PFS and OS. These patients would require long-term follow-up to identify relapse and adverse effects of radiotherapy or intraocular chemotherapy. PMID:26770952

  11. Hypertension and overall survival in metastatic colorectal cancer patients treated with bevacizumab-containing chemotherapy

    PubMed Central

    Österlund, P; Soveri, L-M; Isoniemi, H; Poussa, T; Alanko, T; Bono, P

    2011-01-01

    Background: Hypertension (HTN) is a common toxicity of anti-VEGF (vascular endothelial growth factor) antibody treatment. It may be a marker of VEGF signalling pathway inhibition and therefore represent a cancer biomarker in metastatic colorectal cancer (mCRC) patients treated with chemotherapy and bevacizumab. Methods: A total of 101 consecutive patients with mCRC were treated with standard chemotherapy combined with bevacizumab at dose of 2.5 mg kg−1 per week in a single centre. The median follow-up time of the patients alive was 64 months. Blood pressure was measured before each bevacizumab infusion, and HTN was graded according to common toxicity criteria for adverse events version 3.0. Results: Overall, 57 patients (56%) developed ⩾grade 1 HTN (median blood pressure 168/97 mm Hg), whereas 44 (44%) remained normotensive when treated with bevacizumab-containing chemotherapy regimen. Overall response rate was higher among patients with HTN (30 vs 20% P=0.025). Hypertension was associated with improved progression-free survival (10.5 vs 5.3 months; P=0.008) and overall survival (25.8 vs 11.7 months; P<0.001), and development of HTN within 3 months had an independent, prognostic influence in a multivariate landmark survival analysis together with other known mCRC prognostic factors (P=0.007). There was no association between HTN and development of thromboembolic complications. Conclusion: Hypertension may predict outcome of bevacizumab-containing chemotherapy in mCRC. These data require confirmation in prospective studies including pharmacodynamic and pharmacokinetic analyses. PMID:21304526

  12. High risk of peripheral arterial disease in the United Kingdom: 2-year results of a prospective registry.

    PubMed

    Stansby, Gerard; Mister, Rebecca; Fowkes, Gerry; Roughton, Michael; Nugara, Fiona; Brittenden, Julie; Bradbury, Andrew; Ashley, Simon; Shearman, Cliff; Hannon, Ray; Flather, Marcus

    2011-02-01

    We report a prospective 2-year, multicenter study of patients presenting with intermittent claudication (IC; ankle brachial blood pressure index, ABPI ≤ 0.9). Mean age of the 473 patients enrolled was 68 years, 20% were diabetics, 30% had prior symptomatic coronary heart disease (CHD), 7% had prior stroke, and 39% were current smokers. At baseline, 26.2% of patients had BP ≤ 140/85 mm Hg or lower and at 2 years this figure was 32.5% (P = .01). Current smokers had fallen to 27% (from 39%) at 2 years (P < .001). Use of antiplatelet agents, statins, and angiotensin converting enzyme inhibitors increased significantly during the course of the study as did claudication distance. Death and the composite of death, stroke or myocardial infarction (MI), occurred in 8.4% and 11.6% of patients, respectively. Prognosis was worse in patients with prior history of CHD, older age, those with diabetes and a lower ABPI. PMID:21220371

  13. Patterns of Improved Survival in Patients With Multiple Myeloma in the Twenty-First Century: A Population-Based Study

    PubMed Central

    Turesson, Ingemar; Velez, Ramon; Kristinsson, Sigurdur Y.; Landgren, Ola

    2010-01-01

    Purpose Randomized multiple myeloma (MM) studies show improved response rates and better progression-free survival for newer therapies. However, a less pronounced effect has been found for overall survival (OS). Using population-based data including detailed treatment information for individual patients, we assessed survival patterns for all patients diagnosed with MM in Malmö, Sweden from 1950 to 2005. Patients and Methods We identified 773 patients with MM (48% males). On the basis of the age limit used for treatment with high-dose melphalan with autologous stem-cell support (HDM-ASCT; ≤ 65 years old) in Sweden, we constructed Kaplan-Meier curves and used the Breslow generalized Wilcoxon test to evaluate OS patterns (diagnosed in six calendar periods) for patients 65 years old or younger and patients older than 65 years. Results Including all age groups, patients diagnosed from 1960 to 1969 had a better survival than patients diagnosed from 1950 to 1959. In subsequent 10-year calendar periods, median OS increased from 24.3 to 56.3 months (P = .036) in patients ≤ 65 years old. In contrast, OS did not improve among patients older than age 65 years (21.2 to 26.7 months, P = .7). Conclusion With the establishment of HDM-ASCT as the standard therapy for younger patients with MM, OS has improved significantly for this age group in the general MM population. With novel therapies being commonly used at disease progression, presumably it becomes increasingly difficult to confirm survival differences between defined induction, consolidation, and maintenance therapies in the future. Consequently, in the era of novel MM therapies, population-based studies will serve as a necessary complement to randomized trials. PMID:20038719

  14. High XRCC1 Protein Expression Is Associated with Poorer Survival in Patients with Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Ang, Mei-Kim; Patel, Mihir R.; Yin, Xiao-Ying; Sundaram, Sneha; Fritchie, Karen; Zhao, Ni; Liu, Yufeng; Freemerman, Alex J.; Wilkerson, Matthew D.; Walter, Vonn; Weissler, Mark C.; Shockley, William W.; Couch, Marion E.; Zanation, Adam M.; Hackman, Trevor; Chera, Bhishamjit S.; Harris, Stephen L.; Miller, C. Ryan; Thorne, Leigh B.; Hayward, Michele C.; Funkhouser, William K.; Olshan, Andrew F.; Shores, Carol G.; Makowski, Liza; Hayes, D. Neil

    2012-01-01

    Purpose We evaluated X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) protein in head and neck squamous cell carcinoma (HNSCC) patients in association with outcome. Experimental Design XRCC1 protein expression was assessed by immunohistochemical (IHC) staining of pretreatment tissue samples in 138 consecutive HNSCC patients treated with surgery (n = 31), radiation (15), surgery and radiation (23), surgery and adjuvant chemoradiation (17), primary chemoradiation (51), and palliative measures (1). Results Patients with high XRCC1 expression by IHC (n = 77) compared with patients with low XRCC1 expression (n = 60) had poorer median overall survival (OS; 41.0 months vs. OS not reached, P = 0.009) and poorer progression-free survival (28.0 months vs. 73.0 months, P = 0.031). This association was primarily due to patients who received chemoradiation (median OS of high- and low-XRCC1 expression patients, 35.5 months and not reached respectively, HR 3.48; 95% CI: 1.44–8.38; P = 0.006). In patients treated with nonchemoradiation modalities, there was no survival difference by XRCC1 expression. In multivariable analysis, high XRCC1 expression and p16INK4a-positive status were independently associated with survival in the overall study population (HR = 2.62; 95% CI: 1.52–4.52; P < 0.001 and HR = 0.21; 95% CI: 0.06–0.71; P = 0.012, respectively) and among chemoradiation patients (HR = 6.02; 95% CI: 2.36–15.37; P < 0.001 and HR = 0.26; 95% CI: 0.08–0.92, respectively; P = 0.037). Conclusions In HNSCC, high XRCC1 protein expression is associated with poorer survival, particularly in patients receiving chemoradiation. Future validation of these findings may enable identification of HNSCC expressing patients who benefit from chemoradiation treatment. PMID:21908577

  15. High ERCC1 expression is associated with platinum-resistance, but not survival in patients with epithelial ovarian cancer

    PubMed Central

    Du, Pei; Wang, Yifeng; Chen, Liquan; Gan, Yaping; Wu, Qinian

    2016-01-01

    The present study aimed to investigate the association between excision repair cross-complementation group 1 (ERCC1) expression and clinical resistance to platinum-based chemotherapy or clinical characteristics, including survival time, in patients with epithelial ovarian cancer (EOC). ERCC1 expression was determined by immunohistochemical staining in 92 tumor specimens from patients with EOC. The effect of ERCC1 expression on progression-free survival time (PFS) or overall survival time (OS), and its association with clinical resistance to platinum-based chemotherapy was investigated by Kaplan-Meier survival analysis, Cox regression analysis and the χ2 test. Of 92 patients with EOC, 89.13% (82/92) had ERCC1-positive tumors. The positive rate was significantly higher in platinum-resistant patients compared with those who were platinum-responding (P<0.05). The PFS and median OS were 12 and 30 months, respectively, in ERCC1 high expression patients, and 17 and 39 months, respectively, in ERCC1 low expression patients. However, there was no statistically significant difference in PFS (P=0.099) or OS (P=0.103) between the high and low expression groups. Furthermore, it was identified that ERCC1 was not an independent factor affecting the prognosis of patients with EOC based on Cox proportional hazards regression analysis. These results demonstrate that high ERCC1 expression is associated with resistance to platinum-based chemotherapy, but not with survival time, and ERCC1 protein expression is not an independent factor or the only factor affecting the prognosis of patients with EOC. PMID:27446360

  16. Economic evaluation of nivolumab for the treatment of second-line advanced squamous NSCLC in Canada: a comparison of modeling approaches to estimate and extrapolate survival outcomes.

    PubMed

    Goeree, Ron; Villeneuve, Julie; Goeree, Jeff; Penrod, John R; Orsini, Lucinda; Tahami Monfared, Amir Abbas

    2016-06-01

    Background Lung cancer is the most common type of cancer in the world and is associated with significant mortality. Nivolumab demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients with advanced squamous non-small cell lung cancer (NSCLC) who were previously treated. The cost-effectiveness of nivolumab has not been assessed in Canada. A contentious component of projecting long-term cost and outcomes in cancer relates to the modeling approach adopted, with the two most common approaches being partitioned survival (PS) and Markov models. The objectives of this analysis were to estimate the cost-utility of nivolumab and to compare the results using these alternative modeling approaches. Methods Both PS and Markov models were developed using docetaxel and erlotinib as comparators. A three-health state model was used consisting of progression-free, progressed disease, and death. Disease progression and time to progression were estimated by identifying best-fitting survival curves from the clinical trial data for PFS and OS. Expected costs and health outcomes were calculated by combining health-state occupancy with medical resource use and quality-of-life assigned to each of the three health states. The health outcomes included in the model were survival and quality-adjusted-life-years (QALYs). Results Nivolumab was found to have the highest expected per-patient cost, but also improved per-patient life years (LYs) and QALYs. Nivolumab cost an additional $151,560 and $140,601 per QALY gained compared to docetaxel and erlotinib, respectively, using a PS model approach. The cost-utility estimates using a Markov model were very similar ($152,229 and $141,838, respectively, per QALY gained). Conclusions Nivolumab was found to involve a trade-off between improved patient survival and QALYs, and increased cost. It was found that the use of a PS or Markov model produced very similar estimates of expected cost

  17. Surviving Small-Town Practice

    PubMed Central

    Johnson, Merv

    1987-01-01

    To cope and to survive family medicine in a small town has been, and continues to be, a problem. This article presents one physician's means and methods of staying in a difficult, but extremely exciting, profession. PMID:21263791

  18. Secretarial Administration: Secretarial Survival Skills.

    ERIC Educational Resources Information Center

    Banks, Jane M.

    1978-01-01

    Secretarial survival skills of communication, organization, and decision making should be incorporated into the secretarial training program, according to the author. She discusses these skills in relation to career mobility. (MF)

  19. SURVIVAL OF BACTERIA DURING AEROSOLIZATION

    EPA Science Inventory

    One form of commercial application of microorganisms, including genetically engineered microorganisms is as an aerosol. To study the effect of aerosol-induced stress on bacterial survival, nonrecombinant spontaneous antibiotic-resistant mutants of four organisms, Enterobacter clo...

  20. 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

  1. 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.

  2. 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)

  3. 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

  4. Fine sediment affects on survival to emergence of robust redhorse

    USGS Publications Warehouse

    Jennings, C.A.; Dilts, E.W.; Shelton, J.L., Jr.; Peterson, Ronald C.

    2009-01-01

    Robust redhorse (Moxostoma robustum) is a rare riverine sucker for which life history information is scarce. Spawning occurs over loose gravel substrate and eggs and larvae may be adversely affected by fine sediments among the gravel. A 2-year study was conducted to determine the threshold at which fine sediments are detrimental to successful egg incubation and larval emergence. Year 1 gravel treatments contained 0, 25, 50, and 75% fine sediments. Mean survival during Year 1 ranged from 63.5% in the 0% fine sediment treatment to 0% in the 75% fine sediment treatment. The results also indicated an adverse affect threshold between 0 and 25% fine sediment. Year 2 gravel treatments contained 0, 5, 10, 15, 20, and 25% fine sediments. Mean survival during Year 2 ranged from 69.8% in the 0% treatment to 9.1% in the 25% treatment. Year 2 results also identified the 15% fine sediment treatment as the threshold at which survival began to decline. Substrates at one known spawning area used by robust redhorse typically contain 25 to 50% fine sediment, but the spawning act cleans some fines from the egg pocket. Whether the "cleaning" that results from the spawning act reduces the fines sufficiently to avoid adverse effects is unknown. According to our results, survival rates of robust redhorse eggs and larvae are predicted to be about 8.0% or less when fine sediment is >25%. ?? US Government 2009.

  5. 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? PMID:10623133

  6. Comparison of Immediate and 2-Year Outcomes between Excimer Laser-Assisted Angioplasty with Spot Stent and Primary Stenting in Intermediate to Long Femoropopliteal Disease

    PubMed Central

    Chou, Hsin-Hua; Chang, Shang-Hung; Tsai, Yueh-Ju; Hsieh, Chien-An; Cheng, Shih-Tsung; Yeh, Kuan-Hung; Chang, Hern-Jia; Ko, Yu-Lin; Huang, Hsuan-Li

    2013-01-01

    Background. To compare the clinical outcomes between excimer laser-assisted angioplasty (ELA) with spot stent (group A) and primary stenting (group B) in intermediate to long femoropopliteal disease. Methods. Outcomes of 105 patients totaling 119 legs treated with two different strategies were analyzed retrospectively in a prospectively maintained database. Results. Baseline characteristics were similar in both groups. Better angiographic results and lesser increase of serum C-reactive protein levels (0.60 ± 0.72 versus 2.98 ± 0.97 mg/dL, P < 0.001) after the intervention were obtained in Group B. Group A had inferior 1-year outcomes due to higher rate of binary restenosis (67% versus 32%, P = 0.001) and lower rate of primary patency (40% versus 58%, P = 0.039). Rates of amputation-free survival, target vessel revascularization, assisted primary patency, and stent fracture at 24 months were similar in both groups (80% versus 82%, P = 0.979, 65% versus 45%, P = 0.11, 78% versus 80%, P = 0.75 and 6.3% versus 6.8%, P = 0.71, resp.). Conclusion. Greater vascular inflammation after ELA with spot stent resulted in earlier restenosis and inferior 1-year clinical outcomes than primary stenting. This benefit was lost in the primary stenting group at 2 years due to late catch-up restenosis. Active surveillance with prompt intervention was required to maintain the vessel patency. PMID:24381515

  7. The Use of Botulinum Toxin for the Treatment of Muscle Spasticity in the First 2 Years of Life

    ERIC Educational Resources Information Center

    Bakheit, Abdel Magid

    2010-01-01

    Although there are sound theoretical reasons for the use of botulinum toxin (Btx) as early as possible in the management of severe childhood muscle spasticity, the experience with its safety in children younger than 2 years of age is limited and information about its possible effects on the development and maturation of the human motor system…

  8. Early infant diet is not a predictor of body mass index and macronutrient intake at 2 years

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many retrospective studies have suggested that breast feeding during the first year of life may provide protection against overweight and obesity during childhood and later in life. We compared body mass index (BMI) and macronutrient composition in 2-year-old children who were fed breast milk (BF, ...

  9. Stability and Change among High-Functioning Children with Pervasive Developmental Disorders: A 2-Year Outcome Study.

    ERIC Educational Resources Information Center

    Starr, Elizabeth; Szatmari, Peter; Bryson, Susan; Zwaigenbaum, Lonnie

    2003-01-01

    This study compared the 2-year outcomes of 68 children diagnosed with autism or Asperger syndrome at age 6-8 years in terms of symptoms from the Autism Diagnostic Interview. Significant differences were seen in the domains of social interaction, communication, and repetitive activities, with the Asperger group demonstrating fewer and/or less…

  10. Very Pre-Term Infants' Behaviour at 1 and 2 Years of Age and Parental Stress Following Basic

    ERIC Educational Resources Information Center

    van der Pal, Sylvia M.; Maguire, Celeste M.; Bruil, Jeanet; le Cessie, Saskia; van Zwieten, Paul; Veen, Sylvia; Wit, Jan M.; Walther, Frans J.

    2008-01-01

    This study explored the effects of basic developmental care on the behaviour of very pre-term infants and parental stress at 1 and 2 years of corrected age. A randomized controlled trial was done to compare basic Developmental Care (standardized nests and incubator covers) and controls (standard care). Parents of infants born less than 32 weeks of…

  11. Outcomes of a New Residential Scheme for Adults with Intellectual Disabilities in Taiwan: A 2-Year Follow-Up

    ERIC Educational Resources Information Center

    Chou, Y-C.; Pu, C.; Kroger, T.; Lee, W.; Chang, S.

    2011-01-01

    Background: The Taiwanese government launched a new programme in November 2004 to support adults with intellectual disabilities living in smaller facilities. This paper aims to evaluate the service outcomes of this new residential scheme over 2 years including those residents who moved from an institution and those who moved from their family.…

  12. Finnish Parental Involvement Ethos, Health Support, Health Education Knowledge and Participation: Results from a 2-Year School Health Intervention

    ERIC Educational Resources Information Center

    Sormunen, Marjorita; Tossavainen, Kerttu; Turunen, Hannele

    2013-01-01

    A 2-year, participatory action research school health study focused on developing components for home-school partnerships to support children's health learning process. Two intervention schools implemented strengthened health and collaboration-orientated activities; two control schools followed the national core curriculum without extracurricular…

  13. Interest Level in 2-Year-Olds with Autism Spectrum Disorder Predicts Rate of Verbal, Nonverbal, and Adaptive Skill Acquisition

    ERIC Educational Resources Information Center

    Klintwall, Lars; Macari, Suzanne; Eikeseth, Svein; Chawarska, Katarzyna

    2015-01-01

    Recent studies have suggested that skill acquisition rates for children with autism spectrum disorders receiving early interventions can be predicted by child motivation. We examined whether level of interest during an Autism Diagnostic Observation Schedule assessment at 2?years predicts subsequent rates of verbal, nonverbal, and adaptive skill…

  14. 41 CFR 302-11.22 - May the 2-year time limitation be extended by my agency?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 4 2010-07-01 2010-07-01 false May the 2-year time... Federal Travel Regulation System RELOCATION ALLOWANCES RESIDENCE TRANSACTION ALLOWANCES 11-ALLOWANCES FOR EXPENSES INCURRED IN CONNECTION WITH RESIDENCE TRANSACTIONS General Rules Time Limitations § 302-11.22...

  15. Parental Retrospective Assessment of Development and Behavior in Asperger Syndrome during the First 2 Years of Life

    ERIC Educational Resources Information Center

    Dewrang, Petra; Sandberg, Annika Dahlgren

    2010-01-01

    Development and behavior during the first 2 years of life was assessed retrospectively by the parents to 23 adolescents and young adults with Asperger syndrome and 13 typically developing adolescents and young adults. The groups were matched on chronological age and the participants were within the normal range of intelligence. The questionnaire,…

  16. Mapping Longitudinal Hemispheric Structural Asymmetries of the Human Cerebral Cortex From Birth to 2 Years of Age

    PubMed Central

    Li, Gang; Nie, Jingxin; Wang, Li; Shi, Feng; Lyall, Amanda E.; Lin, Weili; Gilmore, John H.; Shen, Dinggang

    2014-01-01

    Mapping cortical hemispheric asymmetries in infants would increase our understanding of the origins and developmental trajectories of hemispheric asymmetries. We analyze longitudinal cortical hemispheric asymmetries in 73 healthy subjects at birth, 1, and 2 years of age using surface-based morphometry of magnetic resonance images with a specific focus on the vertex position, sulcal depth, mean curvature, and local surface area. Prominent cortical asymmetries are found around the peri-Sylvian region and superior temporal sulcus (STS) at birth that evolve modestly from birth to 2 years of age. Sexual dimorphisms of cortical asymmetries are present at birth, with males having the larger magnitudes and sizes of the clusters of asymmetries than females that persist from birth to 2 years of age. The left supramarginal gyrus (SMG) is significantly posterior to the right SMG, and the maximum position difference increases from 10.2 mm for males (6.9 mm for females) at birth to 12.0 mm for males (8.4 mm for females) by 2 years of age. The right STS and parieto-occipital sulcus are significantly larger and deeper than those in the left hemisphere, and the left planum temporale is significantly larger and deeper than that in the right hemisphere at all 3 ages. Our results indicate that early hemispheric structural asymmetries are inherent and gender related. PMID:23307634

  17. THE FREQUENCY OF T(14;18) IN BLOOD LYMPHOCYTES IS STABLE OVER A 2 YEAR PERIOD IN ADULTS

    EPA Science Inventory

    The Frequency of t(14;18) in Blood Lymphocytes Is Stable over a 2 Year Period in Adults

    As part of a multi-endpoint molecular epidemiology study on in utero environmental exposures, umbilical cord and adult blood lymphocytes were examined for the frequency of t(14;18) by ...

  18. Percutaneous laser disc decompression (PLDD): 352 cases with an 8 1/2-year follow-up.

    PubMed

    Choy, D S

    1995-02-01

    Percutaneous laser disc decompression (PLDD) was pioneered by Dr. Peter Ascher and myself in 1986. This report describes patient selection, operative technique, laser dosimetry, and results in 352 cases with an 8 1/2-year follow-up. The conclusion is that PLDD is relatively non-invasive, safe, simple and effective. PMID:10150569

  19. Latino Adolescents' Experiences of Discrimination across the First 2 Years of High School: Correlates and Influences on Educational Outcomes

    ERIC Educational Resources Information Center

    Benner, Aprile D.; Graham, Sandra

    2011-01-01

    Changes in perceptions of discrimination were examined with 668 Latino students (62% Mexican American; 56% female; M[subscript age] = 14.6 years). Adolescents' reports of discrimination increased across the first 2 years of high school. Perceptions of discrimination were higher for boys and for primary language brokers, as well as for adolescents…

  20. Restricted Consonant Inventories of 2-Year-Old Finnish Children with a History of Recurrent Acute Otitis Media

    ERIC Educational Resources Information Center

    Haapala, Sini; Niemitalo-Haapola, Elina; Raappana, Antti; Kujala, Tiia; Kujala, Teija; Jansson-Verkasalo, Eira

    2015-01-01

    Many children experience recurrent acute otitis media (RAOM) in early childhood. In a previous study, 2-year-old children with RAOM were shown to have immature neural patterns for speech sound discrimination. The present study further investigated the consonant inventories of these same children using natural speech samples. The results showed…

  1. A FreeSurfer-compliant consistent manual segmentation of infant brains spanning the 0–2 year age range

    PubMed Central

    de Macedo Rodrigues, Katyucia; Ben-Avi, Emma; Sliva, Danielle D.; Choe, Myong-sun; Drottar, Marie; Wang, Ruopeng; Fischl, Bruce; Grant, Patricia E.; Zöllei, Lilla

    2015-01-01

    We present a detailed description of a set of FreeSurfer compatible segmentation guidelines tailored to infant MRI scans, and a unique data set of manually segmented acquisitions, with subjects nearly evenly distributed between 0 and 2 years of age. We believe that these segmentation guidelines and this dataset will have a wide range of potential uses in medicine and neuroscience. PMID:25741260

  2. Sluggish Cognitive Tempo and ADHD Inattention as Predictors of Externalizing, Internalizing, and Impairment Domains: A 2-Year Longitudinal Study.

    PubMed

    Bernad, Maria del Mar; Servera, Mateu; Becker, Stephen P; Burns, G Leonard

    2016-05-01

    Although sluggish cognitive tempo (SCT) is distinct from attention-deficit/hyperactivity disorder inattention (ADHD-IN), few studies have examined whether SCT longitudinally predicts other symptom or impairment dimensions. This study used 4 sources (mothers, fathers, primary teachers, and secondary teachers) and 3 occasions of measurement (first, second, and third grades) with 758 first grade (55 % boys), 718 second grade (54 % boys), and 585 third grade (53 % boys) children from Spain to determine SCT's and ADHD-IN's unique longitudinal relationships with psychopathology, academic impairment, and social impairment over the 1- and 2-year intervals (i.e., first to third grade, second to third grade). For 1- and 2-year intervals using both mothers' and fathers' ratings, higher levels of SCT uniquely predicted higher levels of anxiety, depression, academic impairment, and social impairment whereas higher levels of ADHD-IN uniquely predicted higher levels of ADHD-HI, ODD, and academic impairment. For 1- and 2-year intervals across different primary and secondary teachers (i.e., first/second and third grade ratings were provided by different teachers), higher scores on ADHD-IN uniquely predicted poorer outcomes across domains whereas higher scores on SCT uniquely predicted lower levels of ADHD-HI and ODD for both intervals in addition to higher levels of depression (for primary teachers only), academic impairment (for 1-year interval only), and peer rejection (2-year interval only for primary teachers). Overall, SCT was significantly associated with important outcomes independent of ADHD-IN over 1- and 2-year intervals and across four different raters. This study provides further evidence for distinguishing between SCT and ADHD-IN in home and school settings. PMID:26278273

  3. Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies

    PubMed Central

    Licht, Christoph; Greenbaum, Larry A; Muus, Petra; Babu, Sunil; Bedrosian, Camille L; Cohen, David J; Delmas, Yahsou; Douglas, Kenneth; Furman, Richard R; Gaber, Osama A; Goodship, Timothy; Herthelius, Maria; Hourmant, Maryvonne; Legendre, Christophe M; Remuzzi, Giuseppe; Sheerin, Neil; Trivelli, Antonella; Loirat, Chantal

    2015-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a rare, possibly life-threatening disease characterized by platelet activation, hemolysis and thrombotic microangiopathy (TMA) leading to renal and other end-organ damage. We originally conducted two phase 2 studies (26 weeks and 1 year) evaluating eculizumab, a terminal complement inhibitor, in patients with progressing TMA (trial 1) and those with long duration of aHUS and chronic kidney disease (trial 2). The current analysis assessed outcomes after 2 years (median eculizumab exposure 100 and 114 weeks, respectively). At all scheduled time points, eculizumab inhibited terminal complement activity. In trial 1 with 17 patients, the platelet count was significantly improved from baseline, and hematologic normalization was achieved in 13 patients at week 26, and in 15 patients at both 1 and 2 years. The estimated glomerular filtration rate (eGFR) was significantly improved compared with baseline and year 1. In trial 2 with 20 patients, TMA event-free status was achieved by 16 patients at week 26, 17 patients at year 1, and 19 patients at year 2. Criteria for hematologic normalization were met by 18 patients at each time point. Improvement of 15 ml/min per 1.73 m2 or more in eGFR was achieved by 1 patient at week 26, 3 patients at 1 year, and 8 patients at 2 years. The mean change in eGFR was not significant compared with baseline, week 26, or year 1. Eculizumab was well tolerated, with no new safety concerns or meningococcal infections. Thus, a 2-year analysis found that the earlier clinical benefits achieved by eculizumab treatment of aHUS were maintained at 2 years of follow-up. PMID:25651368

  4. 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.

  5. Survival Response and Rearrangement of Plasmid DNA of Lactococcus lactis during Long-Term Starvation

    PubMed Central

    Kim, Woojin S.; Park, Ji Hyeon; Ren, Jun; Su, Ping; Dunn, Noel W.

    2001-01-01

    The survival response of Lactococcus lactis during long-term starvation was investigated. The cells were cultured with different levels of glucose (the sole energy source) and either were kept in the resultant spent medium or transferred to fresh medium (without glucose) for up to 2 years. The survival of the cells during starvation was not dependent on the nature of transition phase, as expected, but on the nature of medium in which the cells were kept. The proliferation of cells, despite the apparent lack of glucose, could have been due to some cells being able to utilize the small amounts of peptides still present in the spent medium or to use energy sources provided by the breakup of dead cells. The 1- and 2-year-old cultures contained cells with vastly changed morphotypes. When these isolates were examined, it was revealed that the original plasmids present in the parent were rearranged in a certain way, and an entirely new plasmid was generated. Changes were also evident in the chromosomal DNA and in gene expression. Furthermore, all of the isolates exhibited a growth advantage relative to the parent cells when grown in energy-limiting media. When they were tested against different types of stresses, they exhibited a higher resistance against the bile salt and hydrogen peroxide stresses compared to the parent. Because of the similar changes observed in the 2-year-old isolates, a similar survival strategy may be operational in those cells that survive for that length of time. PMID:11571161

  6. Regional Chemotherapy for Unresectable Intrahepatic Cholangiocarcinoma: A Potential Role for Dynamic Magnetic Resonance Imaging as an Imaging Biomarker and a Survival Update from Two Prospective Clinical Trials

    PubMed Central

    Konstantinidis, Ioannis T.; Gultekin, David H.; Gönen, Mithat; Schwartz, Lawrence H.; Fong, Yuman; Allen, Peter J.; D'Angelica, Michael I.; DeMatteo, Ronald P.; Klimstra, David S.; Kemeny, Nancy E.; Jarnagin, William R.

    2015-01-01

    Background For patients with unresectable intrahepatic cholangiocarcinoma (ICC), treatment options are limited and survival is poor. This study summarizes the long-term outcome of two previously reported clinical trials using hepatic arterial infusion (HAI) with floxuridine and dexamethasone (with or without bevacizumab) in advanced ICC. Methods Prospectively collected clinicopathologic and survival data were retrospectively reviewed. Response was based on Response Evaluation Criteria in Solid Tumors (RECIST). Pre-HAI dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) images were reviewed, and tumor perfusion data correlated with outcome. Results Forty-four patients were analyzed (floxuridine, 26; floxuridine/bevacizumab, 18). At a median follow-up of 29.3 months, 41 patients had died of disease. Partial response by RECIST was observed in 48 %, and 50 % had stable disease. Three patients underwent resection after response, and 82 % received additional HAI after removal from the trials. Median survival was similar in both trials (floxuridine 29.3 months vs. floxuridine/bevacizumab 28.5 months; p = 0.96). Ten (23 %) patients survived ≥3 years, including 5 (11 %) who survived ≥5 years. Tumor perfusion measured on pre-treatment DCE-MRI [area under the gadolinium concentration curve at 90 and 180 s (AUC90 and AUC180, respectively)] was significantly higher in ≥3-year survivors and was the only factor that distinguished this group from <3-year survivors (mean AUC90 22.6 vs. 15.9 mM s, p = 0.025, and mean AUC180 48.9 vs. 32.3 mM s, p = 0.003, respectively). Median hepatic progression-free survival was longer in ≥3-year survivors (12.9 vs. 9.3 months, respectively; p = 0.008). Conclusions HAI chemotherapy can result in prolonged survival in unresectable ICC. Pre-HAI DCE-MRI may predict treatment outcome. PMID:24664624

  7. 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

  8. 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. PMID:26348890

  9. Tumor-Associated Macrophages Associate with Cerebrospinal Fluid Interleukin-10 and Survival in Primary Central Nervous System Lymphoma (PCNSL).

    PubMed

    Sasayama, Takashi; Tanaka, Kazuhiro; Mizowaki, Takashi; Nagashima, Hiroaki; Nakamizo, Satoshi; Tanaka, Hirotomo; Nishihara, Masamitsu; Mizukawa, Katsu; Hirose, Takanori; Itoh, Tomoo; Kohmura, Eiji

    2016-07-01

    Increased tumor-associated macrophages (TAMs) have been reported to be associated with poor prognosis in various tumors; however, the importance of TAMs in primary central nervous system lymphoma (PCNSL) has not been clarified. In 47 patients with PCNSL who were treated with high-dose methotrexate (MTX) and radiotherapy, the relationships between the infiltration levels of TAMs and the clinicopathological parameters were analyzed. Univariate analysis of the Cox proportional hazards model using continuous scales revealed that increased CD68 positive (+) TAMs was significantly associated with inferior progression-free survival (PFS) (P = 0.04), and trends were observed for the increased CD163(+)  TAMs and having shorter PFS (P = 0.05). However, increased TAMs were not associated with overall survival. Because TAMs are known to produce various cytokines, we examined the relationships between cerebrospinal fluid (CSF) cytokines and TAMs. CSF interleukin-6 (IL-6) and soluble IL-2 receptor were not correlated with the infiltration rate of TAMs; however, CSF IL-10 level was correlated with infiltration levels of CD68 and CD163(+)  TAMs. We also confirmed the expression of IL-10 in CD68(+)  and CD163(+)  TAMs by double immunostaining analysis. Our results indicate that a high level of IL-10 in CSF may be positively associated with the infiltration level of TAMs in PCNSLs. PMID:26314692

  10. Overall survival should be the primary endpoint in clinical trials for advanced non-small-cell lung cancer

    PubMed Central

    Cheema, P.K.; Burkes, R.L.

    2013-01-01

    An article in a recent edition of Current Oncology explored the validation of progression-free survival (pfs) as an endpoint in clinical trials of antineoplastic agents for metastatic colorectal cancer, metastatic renal cell carcinoma, and ovarian cancer. The support for pfs as a surrogate endpoint for overall survival (os) was elucidated. As with the aforementioned tumour types, advanced non-small-cell lung cancer (nsclc) has seen a rise in active agents since the year 2000. Those agents range from improved cytotoxics such as pemetrexed, to targeted therapies such as tyrosine kinase inhibitors of the epidermal growth factor receptor and agents that target the EML4–ALK gene mutation. More recently, it has also become apparent that histology plays an important role in the response to and outcomes of treatment. With the therapeutic options for patients with advanced nsclc increasing, concerns are being raised that the efficacy of drugs measured by os may be diluted in clinical trials, thereby underestimating their true clinical benefit. That possibility, together with the need to have efficacious drugs available to patients earlier, has resulted in the search for a surrogate to the os endpoint in advanced nsclc. The present article follows up the recent article on pfs as a surrogate. Although advances in identifying pfs as a valid surrogate endpoint for os have been made in other tumour types, in advanced nsclc, such surrogacy has not been formally validated. Until it has, os should remain the primary endpoint of clinical trials in advanced nsclc. PMID:23559882

  11. Clinical effectiveness of a one-step self-etch adhesive in non-carious cervical lesions at 2 years.

    PubMed

    Ermis, R Banu; Van Landuyt, Kirsten L; Cardoso, Marcio Vivan; De Munck, Jan; Van Meerbeek, Bart; Peumans, Marleen

    2012-06-01

    A 2-year randomized, controlled prospective study evaluated the clinical effectiveness of a one-step self-etch adhesive and a "gold-standard" three-step etch-and-rinse adhesive in non-carious Class-V lesions. The null hypothesis tested was that the one-step self-etch adhesive does perform clinically equally well as the three-step etch-and-rinse adhesive. A total of 161 lesions in 26 patients were restored with Clearfil AP-X (Kuraray). The restorations were bonded either with the "all-in-one" adhesive Clearfil S3 Bond (Kuraray) or with the three-step etch-and-rinse adhesive Optibond FL (Kerr). The restorations were evaluated at baseline and after 6 months, 1 and 2 years, regarding their retention, marginal adapation, marginal discoloration, caries occurrence, preservation of tooth vitality and post-operative sensivity. Retention loss, severe marginal defects and/or discoloration that needed intervention (repair or replacement) and the occurrence of caries were considered as clinical failures. The recall rate at 2 years was 93.8%. Only one Clearfil S3 Bond restoration was lost at the 2-year recall. All other restorations were clinically acceptable. The number of restorations with defect-free margins decreased severely during the 2-year study period (to 6.7% and 25.3% for Clearfil S3 Bond and Optibond FL, respectively). The Clearfil S3 Bond restorations presented significantly more small marginal defects at the enamel side than the Optibond FL restorations (Clearfil S3 Bond: 93.3%; Optibond FL: 73.3%; p = 0.000). Superficial marginal discoloration increased in both groups (to 53.3% and 36% for Clearfil S3 Bond and Optibond FL, respectively) and was also more pronounced in the Clearfil S3 Bond group (p = 0.007). After 2 years, the simplified one-step self-etch adhesive Clearfil S3 Bond and the three-step etch-and-rinse adhesive Optibond FL were clinically equally successful, even though both adhesives were characterized by progressive degradation in marginal

  12. Effects of a 2-Year Supervised Exercise Program Upon the Body Composition and Muscular Performance of HIV-Infected Patients

    PubMed Central

    Paes, Lorena da Silva; Borges, Juliana Pereira; dos Santos, Fernanda Monteiro; de Oliveira, Taciana Pinto; Dupin, Jaciara Gomes; Harris, Elizabeth Assumpção; Farinatti, Paulo

    2015-01-01

    Background : There is a lack of research investigating long-term effects of exercise training upon the body composition and muscle function in HIV-infected patients (PHIV). The study investigated the influence of a 2-year supervised exercise program on body composition and strength of PHIV under highly active antiretroviral therapy (HAART). Methods : A training program including aerobic, strength and flexibility exercises was performed by 27 PHIV (17 men/ 10 women; age: 48.7±7.0 years; HAART: 150.7±65.3 months) during 1 year and 18 PHIV (10 men/ 8 women; age: 50.6±5.2 years; HAART: 176.6±53.1 months) during 2 years. Body composition and knee isokinetic strength were assessed at baseline and at the end of each year of intervention. Results : Body composition remained stable along the whole experiment vs baseline (1-year - total muscle mass: Δ men=1.1%, P=0.21; Δ women=1.4%, P=0.06; trunk fat: Δ men=-0.1%, P=0.65; Δ women=-1.5%, P=0.45; 2 years - total muscle mass: Δ men=2.7%, P=0.54; Δ women=-1.9%, P=0.71; trunk fat: Δ men=4.4%, P=0.96; Δ women=10.0%, P=0.30). After 1-year, peak torque increased in men (Δ extension=4.2%, P=0.01; Δ flexion=12.2%, P=0.04) and total work reduced in women (Δ extension=-15.4%, P=0.01, Δ flexion=-17.5%, P=0.05). All strength markers remained stable vs baseline after 2 years of intervention (P>0.05). Only men showed significant reduction in the risk of disability due to sarcopenia (P=0.05) after 1 year of intervention, which remained stable after 2 years. Conclusion : Long-term exercise training preserved strength and muscle mass in PHIV under HAART. Exercise programs should be part of HIV therapy to prevent sarcopenia of this population along the years. Trial Registration : ACTRN12610000683033; UTN U1111-1116-4416. PMID:26587076

  13. 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

  14. 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

  15. 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

  16. The experience of fatigue in the first 2 years after moderate-to-severe traumatic brain injury: a preliminary report.

    PubMed

    Bushnik, Tamara; Englander, Jeffrey; Wright, Jerry

    2008-01-01

    Fatigue is a well-recognized issue for individuals with traumatic brain injury (TBI). This prospective study examined the rate and types of fatigue that are experienced by a cohort of individuals with TBI within the first 2 years, using a multidimensional fatigue scale. The impact of factors such as demographics, injury severity indices, and concomitant psychosocial variables was also examined. Using 2 measures of overall fatigue, 16%-32% at Year 1 and 21%-34% at Year 2 reported significant levels of fatigue. Fatigue did not appear to change between 1 and 2 years post-TBI. Sleep quality was the most prevalent concomitant disturbance followed by depression and pain. PMID:18219231

  17. Hyperkeratosis of the nipple and areola: 2 years of remission with low-dose acitretin and topical calcipotriol therapy.

    PubMed

    Kartal Durmazlar, Selda Pelin; Eskioglu, Fatma; Bodur, Zeliha

    2008-01-01

    Hyperkeratosis of the nipple and areola is a rare disorder characterized by verrucous thickening and brown pigmentation of the nipple and areola with unknown etiology. Although it is a generally asymptomatic disorder, cosmetic disfiguring creates a real psychological problem for young women. Moreover, treatment regimens are not satisfactory. Surgical treatment has been suggested as an initial treatment in resistant and recurrent cases because of the relapses seen after medical treatment. We report a case who responded satisfactorily to low-dose acitretin and topical calcipotriol treatment with no relapses during 2 years of follow-up. Among all reported medical treatments and interventional approaches, including surgery, this is the first patient reported with 2 years of remission. PMID:18608736

  18. Are immunoglobulin A anti-gliadin antibodies helpful in diagnosing coeliac disease in children younger than 2 years?

    PubMed

    Foucher, Barbara; Johanet, Catherine; Jégo-Desplat, Sophie; Sanmarco, Marielle; Dubucquoi, Sylvain; Fily-Nalewajk, Sandrine; Olsson, Nils-Olivier; Lakomy, Daniela; Escande, Andrée; Chrétien, Pascale; Fortenfant, Françoise; Chevailler, Alain; André, Chantal; Goetz, Joëlle; Humbel, René-Louis; Monier, Jean-Claude; Sibilia, Jean; Taillefer, Marie-France; Abreu, Isabelle; Fabien, Nicole

    2012-01-01

    The usefulness of immumoglobulin (Ig) A antibodies to gliadin (AGA-IgA) in addition to IgA anti-endomysium and tissue transglutaminase antibodies was evaluated in 4122 children younger than 2 years with a suspicion of coeliac disease (CD). Eight percent (312/4122) displayed IgA anti-endomysium and/or IgA anti-tissue transglutaminase, whereas 2.1% (85/4122) displayed only AGA-IgA. Clinical data were obtained for 62 of 85 children with isolated AGA-IgA, and 33 children underwent a duodenal biopsy. Histologically proven CD was established for 5 patients, whereas 57 children were diagnosed to experience other diseases. The systematic detection of AGA-IgA using native gliadin conferred no additional diagnostic benefit for the diagnosis of CD in children younger than 2 years of age, except for rare cases. PMID:21857243

  19. 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

  20. Association of single nucleotide polymorphisms in the MVP gene with platinum resistance and survival in patients with epithelial ovarian cancer

    PubMed Central

    ZHAO, YA-NAN; HE, DONG-NING; WANG, YA-DI; LI, JUN-JIE; HA, MIN-WEN

    2016-01-01

    The human major vault protein (MVP) has been linked to the development of multidrug resistance in cancer cells, and overexpression of MVP has been observed in ovarian cancer tissues. The aim of the present study was to investigate the association between single nucleotide polymorphisms (SNPs) in the MVP gene and the tumor response to platinum-based chemotherapy and survival of patients affected by epithelial ovarian cancer (EOC), in addition to confirm whether tetra-primer amplification-refractory mutation system (ARMS)-polymerase chain reaction (PCR) is an accurate genotyping method. For this purpose, two polymorphisms in the MVP gene, namely reference SNP (rs)1057451 and rs4788186, were selected from the data obtained by the International haplotype map (HapMap) Project regarding Chinese Han population, and were evaluated by tetra-primer ARMS-PCR. Upon validation by DNA sequencing, the association of these polymorphisms with platinum resistance, progression-free survival (PFS) and overall survival (OS) in patients with EOC was assessed. The results of tetra-primer ARMS-PCR were in agreement with those derived from DNA sequencing. No significant differences were observed between platinum-sensitive and platinum-resistant cohorts in terms of allele and genotype distribution of these two polymorphisms in the MVP gene, which were not associated with PFS or OS. However, a trend toward prolonged PFS was observed in patients carrying the heterozygous AG allele at the rs4788186 locus. These results suggest that rs1057451 and rs4788186 variants in the MVP gene are not associated with favorable therapeutic response to platinum or longer survival in Chinese Han patients affected by EOC. In addition, the data of the present study confirm that tetra-primer ARMS-PCR is a trustworthy and economical genotyping method. PMID:27073578

  1. Factors Predicting Patient Dissatisfaction 2 Years After Discectomy for Lumbar Disc Herniation in a Chinese Older Cohort

    PubMed Central

    Wang, Hui; Zhang, Di; Ma, Lei; Shen, Yong; Ding, Wenyuan

    2015-01-01

    Abstract We aim to identify factors predicting patient dissatisfaction 2 years after discectomy for lumbar disc herniation (LDH) in a Chinese older cohort. Preoperative and 2-year follow-up data for 843 patients were analyzed. After 2 years of discectomy, the patients rated their satisfaction by Patient Satisfaction Index (PSI), with response of 1 or 2 defining satisfaction and a PSI response of 3 or 4 defining dissatisfaction. Associations between perioperative variables and satisfaction with the results of surgery were examined in univariate and multivariate analysis. Six hundred fifty-seven patients had a PSI of 1 or 2 and were enrolled as satisfied group, 186 patients had a PSI of 3 or 4 and were enrolled as dissatisfied group. At baseline, no significant differences were found between the 2 groups in age, occupation, Oswestry Disability Index (ODI), Visual Analog Scale (VAS)-leg, and VAS-back. Compared to satisfied group, dissatisfied group had a significantly higher BMI and a higher incidence of depression. Two years after discectomy, no significant differences were found between the 2 groups in decrease of ODI, decrease of VAS-back, decrease of VAS-leg, surgery complications. Compared to satisfied group, dissatisfied group experienced higher incidence of symptom recurrence and depression. Logistic regression analysis showed that obesity, pre- and postoperative depression, symptom recurrence were independently associated with patient dissatisfaction 2 years after discectomy. In conclusion, more than 70% patients expressed satisfaction with discectomy for LDH. Two factors could predict patient dissatisfaction and be assessed before surgery: obesity and preoperative depression. Symptom recurrence and postoperative depression are also associated with diminished patient satisfaction. PMID:26448005

  2. Echinococcus granulosus infection of the liver and lung in an 8 1/2-year-old boy.

    PubMed

    Meyer, V; Morger, R; Müller, M

    1992-06-01

    We report on an 8 1/2-year-old boy with an echinococcus granulosus infection of the liver and lung, drawing particular attention to the therapy applied. This therapy consists on the one hand of medicinal treatment with Mebendazol and on the other hand of two subsequent operations with resection of the cysts. The course of the illness is illustrated by means of the most important laboratory parameters; an indication of the present serological diagnostic is also given. PMID:1498102

  3. Investigation of Respiratory Syncytial Virus-Associated Deaths Among US Children Aged <2 Years, 2004-2007.

    PubMed

    Prill, Mila M; Iwane, Marika K; Little, Delmar; Gerber, Susan I

    2016-09-01

    We validated the respiratory syncytial virus-coded deaths of children aged <2 years in 2004-2007 using national/state death data and medical records. There were 48 deaths in 4 states, and hospital records for 32 of them were available; 26 of those 32 (81%) had a laboratory finding of respiratory syncytial virus, and 21 of those 26 (81%) had a potential high-risk condition, most commonly preterm birth (35%). PMID:27534673

  4. [Arthroplasty of the cervical disks using artificial prodisc C(tm) in 54 patients with 2-year follow-up].

    PubMed

    Sukhomel, P; Byval'tsev, V A

    2008-01-01

    Aim of the study was to analyze results of arthroplasty using artificial discs Prodisc C(tm) ("Synthes, Inc., Paoli, PA) during a 2-year period. 54 patients with degenerative cervical disk disease were included in the study. 65 artificial disks Prodisc C(tm) were implanted. Results were assessed by neurological examination, neuroradiological techniques and Neck Disability Index (NDI). Significance of differences in parameters was evaluated using Student and Fischer tests (p < 0.05). Results of treatment were the following parameters: timing of surgery--82 minutes, blood loss--81 ml, hospital stay--4 days. Significant decrease of frequency and intensity of pain in cervical spine and upper extremities was observed after surgery (according to Visual Analog Scale (VAS) data). VAS assessment revealed discovered reduction of cervical pain severity from 4.5 to 2.8 points and its frequency from 6.1 to 3.2 points, and intensity of pain in arms decreased from 5.6 to 2.5 points while frequency changed from 7.0 to 2.7 points. 2-year of postoperative follow-up discovered decrease of NDI from 32 to 22. Full preservation of movement range in operated segments after 2 years was observed in 76.9% patients, stage 0, I and II limitation of movements--in 15.4%, absence of movements (stage IV)--in 7.7% (p < 0.05). Spontaneous heterotopy of bone tissue after implantation of artificial disks was encountered in 61.5% cases (stages I-IV) (p < 0.05). 2 intraoperative complications (splitting of vertebral body during insertion of implant) occurred. Arthroplasty using artificial disks Prodisc C(tm) is a perspective innovation of modem spinal surgery. Analysis of results of treatment during 2-year follow-up demonstrates necessity of further investigations in this area of neurosurgery. PMID:19062591

  5. Color-Object Interference in Young Children: A Stroop Effect in Children 31/2-61/2 Years Old

    ERIC Educational Resources Information Center

    Prevor, M.B.; Diamond, A.

    2005-01-01

    The Stroop color-word task cannot be administered to children who are unable to read. However, our color-object Stroop task can. One hundred and sixty-eight children of 31/2-61/2 years (50% female; 24 children at each 6-month interval) were shown line drawings of familiar objects in a color that was congruent (e.g., an orange carrot), incongruent…

  6. Spatial Patterns, Longitudinal Development, and Hemispheric Asymmetries of Cortical Thickness in Infants from Birth to 2 Years of Age.

    PubMed

    Li, Gang; Lin, Weili; Gilmore, John H; Shen, Dinggang

    2015-06-17

    Cortical thickness (CT) is related to normal development and neurodevelopmental disorders. It remains largely unclear how the characteristic patterns of CT evolve in the first 2 years. In this paper, we systematically characterized for the first time the detailed vertex-wise patterns of spatial distribution, longitudinal development, and hemispheric asymmetries of CT at 0, 1, and 2 years of age, via surface-based analysis of 219 longitudinal magnetic resonance images from 73 infants. Despite the dynamic increase of CT in the first year and the little change of CT in the second year, we found that the overall spatial distribution of thin and thick cortices was largely present at birth, and evolved only modestly during the first 2 years. Specifically, the precentral gyrus, postcentral gyrus, occipital cortex, and superior parietal region had thin cortices, whereas the prefrontal, lateral temporal, insula, and inferior parietal regions had thick cortices. We revealed that in the first year thin cortices exhibited low growth rates of CT, whereas thick cortices exhibited high growth rates. We also found that gyri were thicker than sulci, and that the anterior bank of the central sulcus was thicker than the posterior bank. Moreover, we showed rightward hemispheric asymmetries of CT in the lateral temporal and posterior insula regions at birth, which shrank gradually in the first 2 years, and also leftward asymmetries in the medial prefrontal, paracentral, and anterior cingulate cortices, which expanded substantially during this period. This study provides the first comprehensive picture of early patterns and evolution of CT during infancy. PMID:26085637

  7. Construction work practices and conditions improved after 2-years' participation in the HomeSafe pilot program.

    PubMed

    Gilkey, David P; Hautaluoma, Jacob E; Ahmed, Taslim P; Keefe, Thomas J; Herron, Robert E; Bigelow, Philip L

    2003-01-01

    This study reevaluated changes in job-site safety audit scores for a cohort of residential construction workers that had protracted exposure to the HomeSafe pilot program for 2(1/2) years. The investigation was a repeated measure of a cohort study underway in the six-county metro area of Denver, Colo. The larger study was a longitudinal, quasi-experimental design with a cohort of residential construction workers within the HomeSafe strategic partnership between Occupational Safety and Health Administration Region VIII and the Home Builders Association of Metropolitan Denver (HBA). Audits were conducted on residential construction sites. Study subjects were construction workers employed by partner or control companies within the study. Repeated measures of 41 companies showed significant improvement (p=.01) in audit scores, increasing from 71.8 to 76.8 after 2(1/2) years in the program. HomeSafe companies out-performed controls (p=.01) for both the retest group and previously unaudited HomeSafe companies. Prolonged exposure in the HomeSafe pilot program resulted in improved audit scores for companies within the program for at least 2 years. PMID:12809540

  8. Clinical Features and Treatment Outcomes of Primary Immune Thrombocytopenic Purpura in Hospitalized Children Under 2-Years Old

    PubMed Central

    Farhangi, H; Ghasemi, A; Banihashem, A; Badiei, Z; Jarahi, L; Eslami, G; Langaee, T

    2016-01-01

    Background Immune thrombocytopenic purpura (ITP) is the most prevalent cause of thrombocytopenia in children. Despite the importance of ITP in children under 2-years old, only a few publications are available in the literature.ITP usually presents itself as isolated thrombocytopenia and mucocutaneous bleeding. Materials and Methods This study was conducted on 187 under 2-year-old children diagnosed with ITP and treated at Dr. Sheikh Hospital from 2004 to 2011.In this retrospective study, clinical symptoms, laboratory findings, history of viral infections, vaccination history, and treatment efficacy in children under 2-years old with ITP were investigated.Patients were followed for one year after being discharged from the hospital. Results The risk of the disease developing into chronic form was higher in older children (0.001). ITP in children under 3-months old was significantly associated with vaccination (p=0.007). There was no significant differences between male and female patients in regards to newly diagnosed ITP, persistent, and chronic disease status (p = 0.21). No significant difference in bleeding symptoms was observed between patients under 3-months old and 3 to 24-months old (p=0.18). Conclusion Infantile ITP respond favorably to treatment. The risk of the disease developing into chronic form is higher in 3-to-24-month-old children compared to under-three-month olds. PMID:27222699

  9. Environmental Modifications and 2-Year Measured and Self-reported Stair-Use: A Worksite Randomized Trial

    PubMed Central

    Linde, Jennifer A.; Cousins, Julie M.; Jeffery, Robert W.

    2014-01-01

    Environmental modifications have been shown to increase short-term stair use, longer-term success is unclear. This study assessed the 2-year effectiveness of an environmental intervention promoting worksite stair use. We assessed stair use at work by means of self-reports and infrared beam counters (which send a safe and invisible beam of infrared light from one side of a stairwell to a reflector on the other side; when an individual uses the stairs, the infrared beam is disrupted and an instance of stair use is recorded) at six worksites (three intervention, three control) in a group randomized, controlled worksite weight-gain prevention trial in Minneapolis/St. Paul, MN. Intervention modifications were signs encouraging stair use, music, and art posters in stairwells. We collected data before environmental modifications (2006–2007) and at the end of the 2-year intervention (2008–2009). The intervention had a significant positive effect on stair use measured both objectively and via self-report, with greatest increases reported among those participants who used the stairs least at baseline. Following 2-years of continuously-maintained stairwell modifications, increases in both objectively-measured and self-reported stair use were significantly larger at intervention than control worksites. Study findings suggest that the positive impact of environmental modifications on stair use persist over a longer time period than has been previously demonstrated. Results also indicate that infrequent stair users may be most amenable to the behavior changes encouraged by these environmental enhancements. PMID:23979097

  10. Unaffected family members report improvements in daily routine sun-protection 2 years following melanoma genetic testing

    PubMed Central

    Aspinwall, Lisa G.; Taber, Jennifer M.; Kohlmann, Wendy; Leaf, Samantha L.; Leachman, Sancy A.

    2014-01-01

    Purpose Reducing ultraviolet radiation (UVR) exposure may decrease melanoma risk in the hereditary melanoma setting. It is unknown whether genetic counseling and test reporting of CDKN2A/p16 mutation status promote long-term compliance with photoprotection recommendations, especially in unaffected mutation carriers. Methods This study evaluated changes 2 years following melanoma genetic testing in self-reported practice of sun-protection (sunscreen, photoprotective clothing, UVR avoidance) among 37 members of two CDKN2A/p16 kindreds (10 unaffected carriers, 11 affected carriers, 16 unaffected noncarriers; response rate=64.9% of eligible participants). Results Multivariate profile analysis indicated that all 3 participant groups reported increased daily routine practice of sun-protection 2 years following melanoma genetic testing (p<.02), with 96.9% reporting that at least 1 sun-protection behavior was part of their daily routine, up from 78.1% at baseline (p<.015). Unaffected carriers (p<.024) and unaffected noncarriers (p<.027) reported significantly more frequent use of photoprotective clothing. Affected carriers maintained adherence to all sun-protection behaviors. Reported sunburns in the past 6 months decreased significantly (p<.018). Conclusion Members of high-risk families reported increased daily routine sun-protection and decreased sunburns 2 years following melanoma genetic testing, with no net decline in sun-protection following negative test results. Thus, genetic testing and counseling may motivate sustained improvements in prevention behaviors. PMID:24763292

  11. Violent Reinjury and Mortality Among Youth Seeking Emergency Department Care for Assault-Related Injury A 2-Year Prospective Cohort Study

    PubMed Central

    Cunningham, Rebecca M.; Carter, Patrick M.; Ranney, Megan; Zimmerman, Marc A.; Blow, Fred C.; Booth, Brenda M.; Goldstick, Jason; Walton, Maureen A.

    2015-01-01

    IMPORTANCE Violence is a leading cause of morbidity and mortality among youth, with more than 700 000 emergency department (ED) visits annually for assault-related injuries. The risk for violent reinjury among high-risk, assault-injured youth is poorly understood. OBJECTIVE To compare recidivism for violent injury and mortality outcomes among drug-using, assault-injured youth (AI group) and drug-using, non–assault-injured control participants (non-AI group) presenting to an urban ED for care. DESIGN, SETTING, AND PARTICIPANTS Participants were enrolled in a prospective cohort study from December 2, 2009, through September 30, 2011, at an urban level I ED and followed up for 24 months. We administered validated measures of violence and substance use and mental health diagnostic interviews and reviewed medical records at baseline and at each point of follow-up (6, 12, 18, and 24 months). EXPOSURE Follow-up over 24 months. MAIN OUTCOMES AND MEASURES Use of ED services for assault or mortality measured from medical record abstraction supplemented with self-report. RESULTS We followed 349 AI and 250 non-AI youth for 24 months. Youth in the AI group had almost twice the risk for a violent injury requiring ED care within 2 years compared with the non-AI group (36.7% vs 22.4%; relative risk [RR], 1.65 [95% CI, 1.25-2.14]; P < .001). Two-year mortality was 0.8%. Poisson regression modeling identified female sex (RR, 1.30 [95% CI, 1.02-1.65]), assault-related injury (RR, 1.57 [95% CI, 1.19-2.04), diagnosis of a drug use disorder (RR, 1.29 [95% CI, 1.01-1.65]), and posttraumatic stress disorder (RR, 1.47 [95% CI, 1.09-1.97]) at the index visit as predictive of ED recidivism or death within 24 months. Parametric survival models demonstrated that assault-related injury (P < .001), diagnosis of posttraumatic stress disorder (P = .008), and diagnosis of a drug use disorder (P = .03) significantly shortened the expected waiting time until the first ED return visit for violence

  12. 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.

  13. 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

  14. 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

  15. The influence of intraoperative resection control modalities on survival following gross total resection of glioblastoma.

    PubMed

    Neidert, Marian C; Hostettler, Isabel C; Burkhardt, Jan-Karl; Mohme, Malte; Held, Ulrike; Kofmehl, Reto; Eisele, Günter; Woernle, Christoph M; Regli, Luca; Bozinov, Oliver

    2016-07-01

    The purpose of the present study is to analyze the impact of intraoperative resection control modalities on overall survival (OS) and progression-free survival (PFS) following gross total resection (GTR) of glioblastoma. We analyzed data of 76 glioblastoma patients (30f, mean age 57.4 ± 11.6 years) operated at our institution between 2009 and 2012. Patients were only included if GTR was achieved as judged by early postoperative high-field MRI. Intraoperative technical resection control modalities comprised intraoperative ultrasound (ioUS, n = 48), intraoperative low-field MRI (ioMRI, n = 22), and a control group without either modality (n = 11). The primary endpoint of our study was OS, and the secondary endpoint was PFS-both analyzed in Kaplan-Meier plots and Cox proportional hazards models. Median OS in all 76 glioblastoma patients after GTR was 20.4 months (95 % confidence interval (CI) 18.5-29.0)-median OS in patients where GTR was achieved using ioUS was prolonged (21.9 months) compared to those without ioUS usage (18.8 months). A multiple Cox model adjusting for age, preop Karnofsky performance status, tumor volume, and the use of 5-aminolevulinic acid showed a beneficial effect of ioUS use, and the estimated hazard ratio was 0.63 (95 % CI 0.31-1.2, p = 0.18) in favor of ioUS, however not reaching statistical significance. A similar effect was found for PFS (hazard ratio 0.59, p = 0.072). GTR of glioblastoma performed with ioUS guidance was associated with prolonged OS and PFS. IoUS should be compared to other resection control devices in larger patient cohorts. PMID:26860420

  16. Survival of Atlantic salmon Salmo salar smolts through a hydropower complex.

    PubMed

    Stich, D S; Bailey, M M; Zydlewski, J D

    2014-10-01

    This study evaluated Atlantic salmon Salmo salar smolt survival through the lower Penobscot River, Maine, U.S.A., and characterized relative differences in proportional use and survival through the main-stem of the river and an alternative migration route, the Stillwater Branch. The work was conducted prior to removal of two main-stem dams and operational changes in hydropower facilities in the Stillwater Branch. Survival and proportional use of migration routes in the lower Penobscot were estimated from multistate (MS) models based on 6 years of acoustic telemetry data from 1669 smolts and 2 years of radio-telemetry data from 190 fish. A small proportion (0·12, 95% c.i. = 0·06-0·25) of smolts used the Stillwater Branch, and mean survival through the two operational dams in this part of the river was relatively high (1·00 and 0·97). Survival at Milford Dam, the dam that will remain in the main-stem of the Penobscot River, was relatively low (0·91), whereas survival through two dams that were removed was relatively high (0·99 and 0·98). Smolt survival could decrease in the Stillwater Branch with the addition of two new powerhouses while continuing to meet fish passage standards. The effects of removing two dams in the main-stem are expected to be negligible for smolt survival based on high survival observed from 2005 to 2012 at those locations. Survival through Milford Dam was been well below current regulatory standards, and thus improvement of passage at this location offers the best opportunity for improving overall smolt survival in the lower river. PMID:25130320

  17. Medieval Sport: Quest for Survival.

    ERIC Educational Resources Information Center

    Wiseman, Douglas C.

    Since the Middle Ages, sport has survived because of its masochistic and sadistic components. The Greeks, who organized athletic contests into the Olympic Games in 776 B.C., emphasized the relationship between the mind and the body and fair competition, rather than putting emphasis on winning or losing. The Romans preferred the spectacle of…

  18. 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

  19. GPS survivability - A military overview

    NASA Astrophysics Data System (ADS)

    Burgess, Alan

    The major features contributing to the military survivability of GPS during war are discussed. Possible threats to the various segments of GPS are examined, including the effects of attack, sabotage, and nuclear war. Consideration is given to applicable countermeasures to enable GPS to provide continuous service during war.

  20. Tale of survival tails off.

    PubMed

    Pallarito, K

    1991-02-25

    When Reader's Digest wove the tale of a scrappy rural hospital in Montana that raised enough in donations to keep from going under, it looked like a happy ending. But the last chapter on Sweet Grass Community Hospital's fight to survive is still being written, and it's a cliffhanger. PMID:10109267

  1. 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)

  2. 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,…

  3. 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…

  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. 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

    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

    2016-02-01

    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

  6. The effect of sediment on survival, growth, reproductive success and bioaccumulation in Neanthes: Summary report

    SciTech Connect

    Gerlinger, T.V.; Fanizzi, M.; Soong, K.; Armstrong, J.; Reish, D.J.

    1995-12-31

    Sediments taken from the vicinity of the County Sanitation Districts of Orange County ocean outfall were tested for survival, growth, reproduction and bioaccumulation of toxicants on the polychaete, Neanthes arenaceodentata. The end points were survival, growth (dry weight), reproductive success (as number of emerged larvae) and bioaccumulation (metals, DDT, PCBs). Ten experiments have been conducted over a 2 year period of which 2 measured reproductive success. The experiments for survival and growth utilized 2--3 week old post-emergence juvenile worms and subjected them to different test sediments including an inert sediment and plain sea water control. Worms were fed during the experiments. Experiments for reproductive success and bioaccumulation consisted of placing 100 juvenile worms each in 10 gallon aquaria together with test sediment for a 35--40 day period. After which, 10--15 pairs were made and each pair was placed in a separate 1 liter beaker together with sediment for the reproductive experiment. The remaining worms in each aquarium were used for chemical analysis. No toxic responses, as measured by survival, growth and reproductive success, were noted at any station during the 2 year study. Growth was generally lower in the inert sediment and sea water controls compared to test sediments indicating that worms were obtaining some nutrients from the sediment. No difference was noted in the number of emerged juveniles in any test container. While worms accumulated metals and organics in their tissue, there was neither a relationship to the station location nor to survival, growth or reproduction.

  7. Effect of spaying and timing of spaying on survival of dogs with mammary carcinoma.

    PubMed

    Sorenmo, K U; Shofer, F S; Goldschmidt, M H

    2000-01-01

    The risk of developing mammary gland tumors in dogs is significantly decreased by ovariohysterectomy at an early age. However, previous studies have not found a benefit to ovariohysterectomy concurrent with tumor removal in dogs with established mammary gland tumors, suggesting that the progression of these tumors is independent of continued estrogen stimulation. The purpose of this study was to evaluate the effect of spaying and of the timing of spaying on survival in dogs with mammary gland carcinoma. Signalment, spay status and spay age, tumor characteristics, treatment. survival, and cause of death of 137 dogs with mammary gland carcinoma were analyzed. The dogs were classified into 3 groups according to spay status and spay time: intact dogs, dogs spayed less than 2 years before tumor surgery (SPAY 1), and dogs spayed more than 2 years before their tumor surgery (SPAY 2). Dogs in the SPAY 1 group lived significantly longer than dogs in SPAY 2 and intact dogs (median survival of 755 days, versus 301 and 286 days, respectively, P = .02 and .03). After adjusting for differences between the spay groups with regard to age, histologic differentiation, and vascular invasion, SPAY 1 dogs survived 45% longer compared to dogs that were either intact or in the SPAY 2 group (RR = .55; 95% CI .32-.93; P = .03). This study reveals ovariohysterectomy to be an effective adjunct to tumor removal in dogs with mammary gland carcinoma and that the timing of ovariohysterectomy is important in influencing survival. PMID:10830539

  8. 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

  9. Survival of children with brain tumors: SEER Program, 1973-1980.

    PubMed

    Duffner, P K; Cohen, M E; Myers, M H; Heise, H W

    1986-05-01

    Eight hundred eighty-seven children with brain tumors were identified by the SEER registries (1973-1980). Twenty-five percent were low-grade supratentorial astrocytomas, medulloblastomas were 23%, cerebellar astrocytomas 12%, high-grade supratentorial astrocytomas 11%, brainstem gliomas 9%, and ependymomas 8%. The worst survivals were in children less than 2 years of age, and the best were in those aged 10 to 14 years. Five-year survivals of children with cerebellar astrocytomas were 91%, low-grade supratentorial astrocytomas 71%, high-grade supratentorial astrocytomas 35%, medulloblastomas 39%, ependymomas 28%, and brainstem gliomas 18%. PMID:3703257

  10. 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

  11. 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.

  12. Submaxillary gland androgen-regulated protein 3A expression is an unfavorable risk factor for the survival of oropharyngeal squamous cell carcinoma patients after surgery.

    PubMed

    Koffler, Jennifer; Holzinger, Dana; Sanhueza, Gustavo Acuña; Flechtenmacher, Christa; Zaoui, Karim; Lahrmann, Bernd; Grabe, Niels; Plinkert, Peter K; Hess, Jochen

    2013-03-01

    Recently, increased expression of the submaxillary gland androgen-regulated protein 3A (SMR3A) was found in recurrent tumors of an orthotopic floor-of-mouth mouse tumor model after surgery. However, SMR3A expression in the pathogenesis of human malignancy and its correlation with the clinical outcome have not been addressed so far. We analyzed tissue microarrays with specimens from oropharyngeal squamous cell carcinoma (OPSCC) patients (n = 157) by immunohistochemistry and compared SMR3A expression with clinical and pathological features by statistical analysis. Strong SMR3A expression was found in almost 36 % of all primary OPSCCs. Although, SMR3A protein levels were not associated with any clinical or histopathological feature tested, univariate Kaplan-Meier analysis revealed a significant correlation between high SMR3A protein expression and poor progression-free (p = 0.02) and overall survival (p = 0.03). Furthermore, high SMR3A expression was an independent marker for poor clinical outcome [HR (SMR3A(high) vs. SMR3(low)) = 2.32; 95 % CI = 1.03-5.23] concerning overall survival in a multivariate analysis of OPSCC patients with surgery as primary therapy (n = 100). Our data demonstrate for the first time increased SMR3A protein expression in the pathogenesis of OPSCC, which serves as an unfavorable risk factor for patient survival. PMID:23053383