Down syndrome preleukemia and leukemia.

Science.gov (United States)

Maloney, Kelly W; Taub, Jeffrey W; Ravindranath, Yaddanapudi; Roberts, Irene; Vyas, Paresh

2015-02-01

Children with Down syndrome (DS) and acute leukemias acute have unique biological, cytogenetic, and intrinsic factors that affect their treatment and outcome. Myeloid leukemia of Down syndrome (ML-DS) is associated with high event-free survival (EFS) rates and frequently preceded by a preleukemia condition, the transient abnormal hematopoiesis (TAM) present at birth. For acute lymphoblastic leukemia (ALL), their EFS and overall survival are poorer than non-DS ALL, it is important to enroll them on therapeutic trials, including relapse trials; investigate new agents that could potentially improve their leukemia-free survival; and strive to maximize the supportive care these patients need. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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

2016-03-01

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

Is complete resection of high-risk stage IV neuroblastoma associated with better survival?

Science.gov (United States)

Yeung, Fanny; Chung, Patrick Ho Yu; Tam, Paul Kwong Hang; Wong, Kenneth Kak Yuen

2015-12-01

The role of surgery in the management of stage IV neuroblastoma is controversial. In this study, we attempted to study if complete tumor resection had any impact on event-free survival (EFS) and overall survival (OS). A retrospective analysis of patients with stage IV neuroblastoma between November 2000 and July 2014 in a tertiary referral center was performed. Demographics data, extent of surgical resection, and outcomes were analyzed. A total of 34 patients with stage IV neuroblastoma according to International Neuroblastoma Staging System (INSS) were identified. The median age at diagnosis and operation was 3.5 (±1.9) years and 3.8 (±2.0) years, respectively. Complete gross tumor resection (CTR) was achieved in twenty-four patients (70.1%), in which one of the patients had nephrectomy and another had distal pancreatectomy. Gross total resection (GTR) with removal of >95% of tumor was performed in six patients (17.6%) and subtotal tumor resection (STR) with removal of >50%, but <95% of tumor was performed in four patients (11.8%). There was no statistical significance in terms of 5-year EFS and OS among the 3 groups. There was no surgery-related mortality or morbidity. From our center's experience, as there was no substantial survival benefit in stage IV neuroblastoma patients undergoing complete tumor resection, organ preservation and minimalization of morbidity should also be taken into consideration. Copyright © 2015. Published by Elsevier Inc.

Survival outcome of intermediate risk neuroblastoma at Children Cancer Hospital Egypt.

Science.gov (United States)

Elzomor, Hossam; Ahmed, Gehad; Elmenawi, Salma; Elkinaai, Naglaa; Refaat, Amal; Soliman, Sonya; Abdelwahab, Mai Amr; Zaghloul, Mohamed Saad; Fawzy, Mohamed

2018-03-01

The study aims to evaluate survival outcome in newly diagnosed pediatric intermediate risk neuroblastoma patients treated at the Children Cancer Hospital - Egypt and their relation to various clinical and pathological factors. The study included stage 3 patients INSS) stage 4 disease, stage 4 children 1-1.5 years with favorable biology, and infants stage 4 s (with unfavorable biologic features). Patients received systemic chemotherapy, in the form of etoposide and carboplatin alternating with cyclophosphamide, doxorubicin and vincristine, administered at 3-week intervals, with a total of 6 or 8 cycles guided by reaching objective overall response (complete/very good partial/partial response). The study included 136 patients, 67 males and 69 females. 101 patients had abdominal primary tumors, 28 had mediastinal masss and 7 with masses in the neck; 68% were stage 3 and the remaining (n = 44) had metastatic disease. The three-year overall survival (OS) and event-free survival (EFS) estimates were 94% ± 2% and 90.9% ± 2.5%, respectively. OS and EFS by gender, age, pathology and INPC were all statistically not significantly different. Moreover, OS for patients having surgery versus no surgery (inoperable residual only) was statistically significant (98.4% ± 1.6% & 88.7% ± 5.3%, respectively, p = .034). A very high rate of survival is currently achievable in patients with intermediate risk neuroblastoma by chemotherapy or chemotherapy and surgery. In addition to response, our plan is to adopt biologically-based treatment to reduce treatment-induced complications among survivors. Copyright © 2018 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

Minimal Loss of Lifetime for Patients With Diffuse Large B-Cell Lymphoma in Remission and Event Free 24 Months After Treatment

DEFF Research Database (Denmark)

Jakobsen, Lasse Hjort; Bøgsted, Martin; Brown, Peter de Nully

2017-01-01

Purpose The general outlook for patients with diffuse large B-cell lymphoma (DLBCL) in first remission is important information for patients and for planning post-treatment follow-up. The purpose of this study was to evaluate the survival of patients with DLBCL in remission compared with a matched......). During the first 8 years after pEFS24, the average loss of lifetime was 0.31 mo/y (95% CI, 0.11 to 0.50 mo/y). Excess mortality diminished when analyzing death from lymphoma as competing event to death from other causes, suggesting that early and late relapse is responsible for increased mortality...

Long-term outcomes of high dose treatment and autologous stem cell transplantation in follicular and mantle cell lymphomas – a single centre experience

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Boltezar Lucka

2016-06-01

Full Text Available Advanced follicular lymphoma (FL and mantle cell lymphoma (MCL are incurable diseases with conventional treatment. The high dose treatment (HDT with autologous stem cell transplantation (ASCT, however, offers a certain proportion of these patients the prospect of a prolonged disease-free and overall survival. The aim of this study was to investigate the event free survival (EFS and overall survival (OS in patients with FL and MCL treated with ASCT.

The Influence of the Toxin/Antitoxin mazEF on Growth and Survival of Listeria monocytogenes under Stress.

Science.gov (United States)

Curtis, Thomas D; Takeuchi, Ippei; Gram, Lone; Knudsen, Gitte M

2017-01-13

A major factor in the resilience of Listeria monocytogenes is the alternative sigma factor B (σ B ). Type II Toxin/Antitoxin (TA) systems are also known to have a role in the bacterial stress response upon activation via the ClpP or Lon proteases. Directly upstream of the σ B operon in L. monocytogenes is the TA system mazEF , which can cleave mRNA at UACMU sites. In this study, we showed that the mazEF TA locus does not affect the level of persister formation during treatment with antibiotics in lethal doses, but exerts different effects according to the sub-inhibitory stress added. Growth of a Δ mazEF mutant was enhanced relative to the wildtype in the presence of sub-inhibitory norfloxacin and at 42 °C, but was decreased when challenged with ampicillin and gentamicin. In contrast to studies in Staphylococcus aureus , we found that the mazEF locus did not affect transcription of genes within the σ B operon, but MazEF effected the expression of the σ B -dependent genes opuCA and lmo0880 , with a 0.22 and 0.05 fold change, respectively, compared to the wildtype under sub-inhibitory norfloxacin conditions. How exactly this system operates remains an open question, however, our data indicates it is not analogous to the system of S. aureus , suggesting a novel mode of action for MazEF in L. monocytogenes.

Education for Sustainability (EfS): Practice and Practice Architectures

Science.gov (United States)

Kemmis, Stephen; Mutton, Rebecca

2012-01-01

This paper reports some findings from an investigation of educational practice in ten (formal and informal) education for sustainability (EfS) initiatives, to characterise exemplary practice in school and community education for sustainability, considered crucial to Australia's future. The study focused on rural/regional Australia, specifically…

Heart Failure with Recovered EF and Heart Failure with Mid-Range EF: Current Recommendations and Controversies.

Science.gov (United States)

Unkovic, Peter; Basuray, Anupam

2018-04-03

This review explores key features and potential management controversies in two emerging populations in heart failure: heart failure with recovered ejection fraction (HF-recovered EF) and heart failure with mid-range ejection fraction (HFmrEF). While HF-recovered EF patients have better outcomes than heart failure with reduced ejection fraction (HFrEF), they continue to have symptoms, persistent biomarker elevations, and abnormal outcomes suggesting a continued disease process. HFmrEF patients appear to have features of HFrEF and heart failure with preserved ejection fraction (HFpEF), but have a high prevalence of ischemic heart disease and may represent a transitory phase between the HFrEF and HFpEF. Management strategies have insufficient data to warrant standardization at this time. HF-recovered EF and HFmrEF represent new populations with unmet needs and expose the pitfalls of an EF basis for heart failure classification.

Pneumocystis jiroveci pneumonia prophylaxis during maintenance therapy influences methotrexate/6-mercaptopurine dosing but not event-free survival for childhood acute lymphoblastic leukemia

DEFF Research Database (Denmark)

Levinsen, Mette; Shabaneh, Diana; Bohnstedt, Cathrine

2012-01-01

of maintenance therapy. The TMP/SMX2–7 group received lower oral 6MP doses than TMP/SMXnever patients (50.6 vs. 63.9 mg/m2/d; P ANC) (median 1.7 vs. 2.0 × 109/L; P ANC levels (P = 0.04) and male gender (P = 0.......06) were related to reduced EFS. ANC had no effect on EFS among TMP/SMX2–7 patients (P = 0.40) but did for TMP/SMXnever patients (P = 0.02). The difference in the effect on EFS between TMP/SMX2–7 and TMP/SMXnever patients was not significant (P = 0.46). EFS did not differ between TMP/SMX2–7 and TMP...

Overall survival and disease-free survival in endometrial cancer: prognostic factors in 276 patients

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Tejerizo-García A

2013-09-01

Full Text Available Álvaro Tejerizo-García,1 Jesús S Jiménez-López,1 José L Muñoz-González,1 Sara Bartolomé-Sotillos,1 Laura Marqueta-Marqués,1 Gregorio López-González,1 José F Pérez-Regadera Gómez21Service of Obstetrics and Gynecology, 2Radiation Oncology Service, Hospital Universitario 12 de Octubre, Madrid, SpainObjective: The aim of the study reported here was to assess the disease-free survival and overall survival of patients with endometrial cancer and to determine independent factors affecting the prognosis.Materials and methods: This was a retrospective study of a single-center clinical series of 276 patients (mean age 64 years with histologically confirmed cancer of the corpus uteri. The standard treatments were extrafascial total hysterectomy and bilateral salpingo-oophorectomy with selective pelvic/para-aortic node dissection, according to risk for recurrence. Actuarial overall survival and disease-free survival were estimated according to the Kaplan–Meier method. Univariate and multivariate Cox proportional hazards analyses were used to assess the prognostic significance of the different variables.Results: The estimated median follow-up, determined using the inverse Kaplan–Meier method, was 45 months (95% confidence interval [CI] 41.2–48.8 for disease-free survival and 46 months (95% CI 43.0–49.0 for overall survival. The statistically significant variables affecting disease-free survival and overall survival were age, serous-papillary and clear-cell histological types, outer-half myometrial invasion, advanced International Federation of Gynecology and Obstetrics (FIGO stage, tumor grades G2 and G3, incomplete surgical resection, positive lymph nodes, lymphovascular space invasion, tumor remnants of >1 cm after surgery, and high-risk group. In the multivariate Cox regression model, predictors of tumor recurrence included advanced FIGO stage (hazard ratio [HR] 4.90, 95% CI 2.57–9.36, P < 0.001 and tumor grades G2 (HR 4.79, 95

HFpEF and HFrEF Display Different Phenotypes as Assessed by IGF-1 and IGFBP-1.

Science.gov (United States)

Faxén, Ulrika Ljung; Hage, Camilla; Benson, Lina; Zabarovskaja, Stanislava; Andreasson, Anna; Donal, Erwan; Daubert, Jean-Claude; Linde, Cecilia; Brismar, Kerstin; Lund, Lars H

2017-04-01

Anabolic drive is impaired in heart failure with reduced ejection fraction (HFrEF) but insufficiently studied in heart failure with preserved ejection fraction (HFpEF). Insulin-like growth factor 1 (IGF-1) mediates growth hormone effects and IGF binding protein 1 (IGFBP-1) regulates IGF-1 activity. We tested the hypothesis that HFpEF and HFrEF are similar with regard to IGF-1 and IGFBP-1. In patients with HFpEF (n = 79), HFrEF (n = 85), and controls (n = 136), we analyzed serum IGF-1 and IGFBP-1 concentrations, correlations, and associations with outcome. Age-standardized scores of IGF-1 were higher in HFpEF, median arbitrary units (interquartile range); 1.21 (0.57-1.96) vs HFrEF, 0.09 (-1.40-1.62), and controls, 0.22 (-0.47-0.96), P overall IGF-1 was associated with outcomes in HFrEF, hazard ratio per natural logarithmic increase in IGF-1 SD score 0.51 (95% confidence interval 0.32-0.82, P = .005), but not significantly in HFpEF. IGFBP-1 was not associated with outcomes in either HFpEF nor HFrEF. HFpEF and HFrEF phenotypes were similar with regard to increased IGFBP-1 concentrations but differed regarding IGF-1 levels and prognostic role. HFrEF and HFpEF may display different impairment in anabolic drive. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of malnutrition on treatment-related morbidity and survival of children with cancer in Nicaragua.

Science.gov (United States)

Pribnow, Allison K; Ortiz, Roberta; Báez, Luis Fulgencio; Mendieta, Luvy; Luna-Fineman, Sandra

2017-11-01

Most children with cancer live in resource-limited countries where malnutrition is often prevalent. We identified the relationship between malnutrition and treatment-related morbidity (TRM), abandonment of therapy, and survival of children with cancer in Nicaragua to better inform targeted nutritional interventions. We conducted a retrospective review of patients aged 6 months to 18 years with newly diagnosed acute lymphoblastic leukemia, acute myeloid leukemia (AML), Wilms tumor, Hodgkin lymphoma, or Burkitt lymphoma (BL) who were treated between January 1, 2004, and December 31, 2007 at Children's Hospital Manuel de Jesus Rivera in Managua, Nicaragua. Statistical analysis examined the relations among nutritional status and cancer type, risk category, TRM, and event-free survival (EFS). Sixty-seven percent of patients (189/282) were malnourished at diagnosis. Malnutrition was highest among patients with Wilms tumor (85.7%), BL (75%), and AML (74.3%). A total of 92.2% of patients (225/244) experienced morbidity during the first 90 days. Malnutrition was associated with severe infection (P = 0.033). Severely malnourished patients had ≥grade 3 TRM on more days (P = 0.023) and were more likely to experience severe TRM on >50% of days (P = 0.032; OR, 3.27 [95% CI, 1.05-10.16]). Malnourished patients had inferior median EFS (2.25 vs. 5.58 years; P = 0.049), and abandoned therapy more frequently (P = 0.015). In Nicaragua, pediatric oncology patients with malnutrition at diagnosis experienced increased TRM, abandoned therapy more frequently, and had inferior EFS. Standardized nutritional evaluation of patients with newly diagnosed cancer and targeted provision of nutritional support are essential to decrease TRM and improve outcomes. © 2017 Wiley Periodicals, Inc.

Prognostic implications of post-stress ejection fraction decrease detected by gated SPECT in the absence of stress-induced perfusion abnormalities

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Dona, Manjola; Massi, Lucia; Settimo, Leonardo; Bartolini, Matteo; Gianni, Gianluca; Pupi, Alberto; Sciagra, Roberto [University of Florence, Nuclear Medicine Unit, Department of Clinical Physiopathology, Florence (Italy)

2011-03-15

The prognostic meaning of a post-stress ejection fraction (EF) decrease detected by perfusion gated SPECT is still unclear. We therefore followed up patients with post-stress EF decrease in the absence of stress-induced perfusion abnormalities. We prospectively enrolled 57 consecutive patients with post-stress EF drop {>=} 5 EF units and summed difference score (SDS) {<=} 1. They were followed up for more than 1 year and their outcome was compared with a group of sex- and age-matched controls with the same SDS but without EF decrease. During follow-up there were 13 events (1 cardiac death, 1 non-fatal myocardial infarction, 1 congestive heart failure and 10 late revascularizations). In the control group we registered six events. There was a significant difference (p < 0.0001) between the event-free survival curves of the two groups. The event rate of patients with post-stress EF decrease {>=} 5 EF units is relatively high and is significantly worse than that of a control group of patients with similarly normal SDS but without EF changes. Therefore, a post-stress EF decrease without stress-induced perfusion abnormalities should be cautiously interpreted. (orig.)

Factors influencing survival and recurrence-free intervals after treatment of primary breast cancer

International Nuclear Information System (INIS)

O'Higgins, N.; Brady, H.R.; Clark, C.G.

1984-01-01

A retrospective analysis of 739 patients with breast cancer is presented. Factors influencing overall survival, recurrence-free interval and survival after first recurrence are analysed and discussed. None of the factors was affected by age or menopausal status at the time of presentation. Overall survival and recurrence-free intervals varied significantly with tumour size, extent of nodal spread and tumour site. Medially situated tumours, large tumours and extensive nodal spread were associated with earlier first recurrence and poor prognosis. No difference in survival or recurrence-free interval was observed between different surgical operations. Although overall survival was longer in patients who received post-operative radiotherapy, no significant differences in survival or disease-free intervals were noted when patients were standardised for operation or tumour stage. Survival after local recurrence was longer than survival after distant metastases, although the time of onset of local and distant disease followed an identical pattern. These results suggest that the tumour characteristics of size, site and nodal spread are important determinants of survival and recurrence-free interval in primary breast cancer. Local recurrence should be regarded as a manifestation of systemic disease. (author)

Precision spectroscopy of high rotational states in H2 investigated by Doppler-free two-photon laser spectroscopy in the EF 1Σg+-X 1Σg+ system

Science.gov (United States)

Dickenson, G. D.; Salumbides, E. J.; Niu, M.; Jungen, Ch.; Ross, S. C.; Ubachs, W.

2012-09-01

Recently a high precision spectroscopic investigation of the EF1Σg+-X1Σg+ system of molecular hydrogen was reported yielding information on QED and relativistic effects in a sequence of rotational quantum states in the X1Σg+ ground state of the H2 molecule [Salumbides , Phys. Rev. Lett.PRLTAO0031-900710.1103/PhysRevLett.107.043005 107, 043005 (2011)]. The present paper presents a more detailed description of the methods and results. Furthermore, the paper serves as a stepping stone towards a continuation of the previous study by extending the known level structure of the EF1Σg+ state to highly excited rovibrational levels through Doppler-free two-photon spectroscopy. Based on combination differences between vibrational levels in the ground state, and between three rotational branches (O, Q, and S branches) assignments of excited EF1Σg+ levels, involving high vibrational and rotational quantum numbers, can be unambiguously made. For the higher EF1Σg+ levels, where no combination differences are available, calculations were performed using the multichannel quantum defect method, for a broad class of vibrational and rotational levels up to J=19. These predictions were used for assigning high-J EF levels and are found to be accurate within 5 cm-1.

Plasma Levels of Soluble HLA-E and HLA-F at Diagnosis May Predict Overall Survival of Neuroblastoma Patients

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Fabio Morandi

2013-01-01

Full Text Available The purpose of this study was to identify the plasma/serum biomarkers that are able to predict overall survival (OS of neuroblastoma (NB patients. Concentration of soluble (s biomarkers was evaluated in plasma (sHLA-E, sHLA-F, chromogranin, and B7H3 or serum (calprotectin samples from NB patients or healthy children. The levels of biomarkers that were significantly higher in NB patients were then analyzed considering localized or metastatic subsets. Finally, biomarkers that were significantly different in these two subsets were correlated with patient’s outcome. With the exception of B7H3, levels of all molecules were significantly higher in NB patients than those in controls. However, only chromogranin, sHLA-E, and sHLA-F levels were different between patients with metastatic and localized tumors. sHLA-E and -F levels correlated with each other but not chromogranin. Chromogranin levels correlated with different event-free survival (EFS, whereas sHLA-E and -F levels also correlated with different OS. Association with OS was also detected considering only patients with metastatic disease. In conclusion, low levels of sHLA-E and -F significantly associated with worse EFS/OS in the whole cohort of NB patients and in patients with metastatic NB. Thus, these molecules deserve to be tested in prospective studies to evaluate their predictive power for high-risk NB patients.

The Influence of the Toxin/Antitoxin mazEF on Growth and Survival of Listeria monocytogenes under Stress

DEFF Research Database (Denmark)

Curtis, Thomas; Takeuchi, Ippei; Gram, Lone

2017-01-01

A major factor in the resilience of Listeria monocytogenes is the alternative sigma factor B (σB). Type II Toxin/Antitoxin (TA) systems are also known to have a role in the bacterial stress response upon activation via the ClpP or Lon proteases. Directly upstream of the σB operon in L....... monocytogenes is the TA system mazEF, which can cleave mRNA at UACMU sites. In this study, we showed that the mazEF TA locus does not affect the level of persister formation during treatment with antibiotics in lethal doses, but exerts different effects according to the sub-inhibitory stress added. Growth...... it is not analogous to the system of S. aureus, suggesting a novel mode of action for MazEF in L. monocytogenes....

Centre characteristics and procedure-related factors have an impact on outcomes of allogeneic transplantation for patients with CLL: a retrospective analysis from the European Society for Blood and Marrow Transplantation (EBMT)

NARCIS (Netherlands)

Schetelig, J.; Wreede, L.C. de; Andersen, N.S.; Moreno, C.; Gelder, M. van; Vitek, A.; Karas, M.; Michallet, M.; Machaczka, M.; Gramatzki, M.; Beelen, D.; Finke, J.; Delgado, J.; Volin, L.; Passweg, J.; Dreger, P.; Schaap, N.P.; Wagner, E.; Henseler, A.; Biezen, A. van; Bornhauser, M.; Iacobelli, S.; Putter, H.; Schonland, S.O.; Kroger, N.

2017-01-01

The best approach for allogeneic haematopoietic stem cell transplantations (alloHCT) in patients with chronic lymphocytic leukaemia (CLL) is unknown. We therefore analysed the impact of procedure- and centre-related factors on 5-year event-free survival (EFS) in a large retrospective study. Data of

The development of hypothalamic obesity in craniopharyngioma patients: A risk factor analysis in a well-defined cohort

NARCIS (Netherlands)

van Iersel, Laura; Meijneke, Ruud W. H.; Schouten-van Meeteren, Antoinette Y. N.; Reneman, Liesbeth; de Win, Maartje M.; van Trotsenburg, A. S. Paul; Bisschop, Peter H.; Finken, Martijn J. J.; Vandertop, W. Peter; van Furth, Wouter R.; van Santen, Hanneke M.

2018-01-01

Hypothalamic obesity (HO) is a major concern in patients treated for craniopharyngioma (CP). The influence of degree of resection on development of HO, event-free survival (EFS), and neuroendocrine sequelae is an issue of debate. A retrospective cohort consisting of all CP patients treated between

Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial.

Science.gov (United States)

Dreger, Peter; Döhner, Hartmut; Ritgen, Matthias; Böttcher, Sebastian; Busch, Raymonde; Dietrich, Sascha; Bunjes, Donald; Cohen, Sandra; Schubert, Jörg; Hegenbart, Ute; Beelen, Dietrich; Zeis, Matthias; Stadler, Michael; Hasenkamp, Justin; Uharek, Lutz; Scheid, Christof; Humpe, Andreas; Zenz, Thorsten; Winkler, Dirk; Hallek, Michael; Kneba, Michael; Schmitz, Norbert; Stilgenbauer, Stephan

2010-10-07

The purpose of this prospective multicenter phase 2 trial was to investigate the long-term outcome of reduced-intensity conditioning allogeneic stem cell transplantation (alloSCT) in patients with poor-risk chronic lymphocytic leukemia. Conditioning was fludarabine/ cyclophosphamide-based. Longitudinal quantitative monitoring of minimal residual disease (MRD) was performed centrally by MRD-flow or real-time quantitative polymerase chain reaction. One hundred eligible patients were enrolled, and 90 patients proceeded to alloSCT. With a median follow-up of 46 months (7-102 months), 4-year nonrelapse mortality, event-free survival (EFS) and overall survival (OS) were 23%, 42%, and 65%, respectively. Of 52 patients with MRD monitoring available, 27 (52%) were alive and MRD negative at 12 months after transplant. Four-year EFS of this subset was 89% with all event-free patients except for 2 being MRD negative at the most recent assessment. EFS was similar for all genetic subsets, including 17p deletion (17p-). In multivariate analyses, uncontrolled disease at alloSCT and in vivo T-cell depletion with alemtuzumab, but not 17p-, previous purine analogue refractoriness, or donor source (human leukocyte antigen-identical siblings or unrelated donors) had an adverse impact on EFS and OS. In conclusion, alloSCT for poor-risk chronic lymphocytic leukemia can result in long-term MRD-negative survival in up to one-half of the patients independent of the underlying genomic risk profile. This trial is registered at http://clinicaltrials.gov as NCT00281983.

Is There a Role for Pelvic Irradiation in Localized Prostate Adenocarcinoma? Update of the Long-Term Survival Results of the GETUG-01 Randomized Study

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Pommier, Pascal, E-mail: Pascal.pommier@lyon.unicancer.fr [Department of Radiation Oncology, Centre Léon Bérard, Lyon (France); Chabaud, Sylvie [Department of Clinical Research and Innovation, Centre Léon Bérard, Lyon (France); Lagrange, Jean-Leon [Department of Radiation Oncology, Centre Hospitalo-Universitaire H. Mondor, Créteil (France); Richaud, Pierre [Department of Radiation Oncology, Institut Bergognié, Bordeaux (France); Le Prise, Elisabeth [Department of Radiation Oncology, Centre Eugène Marquis, Rennes (France); Wagner, Jean-Philippe [Department of Radiation Oncology, Institut Andrée Dutreix, Dunkerque (France); Azria, David [Department of Radiation Oncology, Institut de Cancérologie de Montpellier, Montpellier (France); Beckendorf, Veronique [Department of Radiation Oncology, Institut de Cancérologie de Lorraine, Nancy (France); Suchaud, Jean-Philippe [Department of Radiation Oncology, Centre Hospitalier de Roanne, Roanne (France); Bernier, Valerie [Department of Radiation Oncology, Centre Oscar Lambret, Lille (France); Perol, David [Department of Clinical Research and Innovation, Centre Léon Bérard, Lyon (France); Carrie, Christian [Department of Radiation Oncology, Centre Léon Bérard, Lyon (France)

2016-11-15

Purpose: To report the long-term results of the French Genitourinary Study Group (GETUG)-01 study in terms of event-free survival (EFS) and overall survival (OS) and assess the potential interaction between hormonotherapy and pelvic nodes irradiation. Patients and Methods: Between December 1998 and June 2004, 446 patients with T1b-T3, N0pNx, M0 prostate carcinoma were randomly assigned to either pelvic nodes and prostate or prostate-only radiation therapy. Patients were stratified into 2 groups: “low risk” (T1-T2 and Gleason score 6 and prostate-specific antigen <3× the upper normal limit of the laboratory) (92 patients) versus “high risk” (T3 or Gleason score >6 or prostate-specific antigen >3× the upper normal limit of the laboratory). Short-term 6-month neoadjuvant and concomitant hormonal therapy was allowed only for high-risk patients. Radiation therapy was delivered with a 3-dimensional conformal technique, using a 4-field technique for the pelvic volume (46 Gy). The total dose recommended to the prostate moved from 66 Gy to 70 Gy during the course of the study. Criteria for EFS included biologic prostate-specific antigen recurrences and/or a local or metastatic progression. Results: With a median follow-up of 11.4 years, the 10-year OS and EFS were similar in the 2 treatment arms. A higher but nonsignificant EFS was observed in the low-risk subgroup in favor of pelvic nodes radiation therapy (77.2% vs 62.5%; P=.18). A post hoc subgroup analysis showed a significant benefit of pelvic irradiation when the risk of lymph node involvement was <15% (Roach formula). This benefit seemed to be limited to patients who did not receive hormonal therapy. Conclusion: Pelvic nodes irradiation did not statistically improve EFS or OS in the whole population but may be beneficial in selected low- and intermediate-risk prostate cancer patients treated with exclusive radiation therapy.

Human survivability of extreme impacts in free-fall.

Science.gov (United States)

1963-08-01

Human deceleration tolerances beyond the limits imposed by voluntary experimental methods were studied by means of intensive case histories of 137 individuals who have survived extremely abrupt impacts in accidental, suicidal, and homicidal free-fall...

Telomere shortening and survival in free-living corvids

NARCIS (Netherlands)

Salomons, H.M.; Mulder, G.A.; Zande, L. van de; Haussmann, M.F.; Linskens, M.H.K.; Verhulst, S.

2009-01-01

Evidence accumulates that telomere shortening reflects lifestyle and predicts remaining lifespan, but little is known of telomere dynamics and their relation to survival under natural conditions. We present longitudinal telomere data in free-living jackdaws (Corvus monedula) and test hypotheses on

PSA response to cabazitaxel is associated with improved progression-free survival in metastatic castration-resistant prostate cancer: the non-interventional QoLiTime study.

Science.gov (United States)

Hammerer, Peter; Al-Batran, Salah-Eddin; Windemuth-Kieselbach, Christine; Keller, Martin; Hofheinz, Ralf-Dieter

2018-03-01

To evaluate the association between prostate-specific antigen (PSA) response and progression-free and overall survival in men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel. Men with mCRPC receiving cabazitaxel (25 mg/m 2 , every 3 weeks) plus oral prednis(ol)one (10 mg/day) were enrolled in the non-interventional, prospective QoLiTime study. Main outcome measures were progression-free survival and overall survival, in all patients and in those who showed a ≥ 50 or a ≥ 30% decrease in PSA relative to baseline after four cycles of cabazitaxel, as well as quality-of-life parameters. Of the 527 men (median age 72 years), 266 received ≥ 4 cycles of cabazitaxel and had PSA response data. After four cycles, 34.6% of men achieved a PSA decrease ≥ 50% and 49.6% a decrease ≥ 30%. Median progression-free survival was 7.7 (95% CI 6.2, 9.5) months, and overall survival was 19.5 (95% CI 16.0, 30.9) months, corresponding to 1-year event rates of 39.4 and 78.8%, respectively. Median progression-free survival was longer in PSA responders versus non-responders (15.7 vs 5.5 months at 50% cut-off; 15.7 vs 5.3 months for 30% cut-off; both P PSA response after four cycles of cabazitaxel is associated with improved progression-free survival in men with mCRPC treated with cabazitaxel plus prednis(ol)one.

Prevalence of Prediabetes and Undiagnosed Diabetes in Patients with HFpEF and HFrEF and Associated Clinical Outcomes

DEFF Research Database (Denmark)

Kristensen, Søren L; Jhund, Pardeep S; Lee, Matthew M Y

2017-01-01

PURPOSE: The prevalence and consequences of prediabetic dysglycemia and undiagnosed diabetes is unknown in patients with heart failure (HF) and preserved ejection fraction (HFpEF) and has not been compared to heart failure and reduced ejection fraction (HFrEF). METHODS: We examined the prevalence...... and outcomes associated with normoglycemia, prediabetic dysglycemia and diabetes (diagnosed and undiagnosed) among individuals with a baseline glycated hemoglobin (hemoglobin A1c, HbA1c) measurement stratified by HFrEF or HFpEF in the Candesartan in Heart failure Assessment of Reduction in Mortality...... and was available in 1072/3023 (35%) of patients with HFpEF and 1578/4576 (34%) patients with HFrEF. 18 and 16% had normoglycemia (HbA1c prediabetes (HbA1c 6.0-6.4), respectively. Finally among patients with HFpEF 22% had undiagnosed diabetes (HbA1c > 6.4), and 40% had known diabetes (any Hb...

The Potential of Devices for HFpEF

Directory of Open Access Journals (Sweden)

Andrew J Stewart Coats

2017-01-01

Full Text Available The 2016 ESC/HFA HF guidelines list the very many drug and device therapies that are proven to be beneficial in terms of life prolongation and hospitalisation prevention for HFrEF. The list of recommended therapies or devices for HFpEF and HFmrEF is limited to diuretics and the management of comorbidities and so far there is no clinical evidence for an electrical or mechanical device for HFpEF. The Cardiac Contractility Modulation (CCM device that may have a role in selected HFrEF and HFmrEF patients has been reviewed in another paper in this issue but here we survey the results so far of a novel device for patients with HFpEF. Despite lagging many years behind HFrEF, HFpEF patients are now being targeted with novel devices with the potential to improve symptoms, improve quality of life, reduce hospitalization and delay progression of the syndrome. The front-runner is a novel inter-atrial left atrial pressure decompression device the Corvia IASD, which currently enrolling patients in a randomized trial. This device is a CE-marked investigational, non- surgical transcatheter implant designed to provide continuous and dynamic decompression of the left atrium, in an effort to reduce symptoms, HF hospitalizations, and improve quality of life as well as potentially slowing the progression of HFpEF.

Postmenopausal women with a history of irregular menses and elevated androgen measurements at high risk for worsening cardiovascular event-free survival: results from the National Institutes of Health--National Heart, Lung, and Blood Institute sponsored Women's Ischemia Syndrome Evaluation.

Science.gov (United States)

Shaw, Leslee J; Bairey Merz, C Noel; Azziz, Ricardo; Stanczyk, Frank Z; Sopko, George; Braunstein, Glenn D; Kelsey, Sheryl F; Kip, Kevin E; Cooper-Dehoff, Rhonda M; Johnson, B Delia; Vaccarino, Viola; Reis, Steven E; Bittner, Vera; Hodgson, T Keta; Rogers, William; Pepine, Carl J

2008-04-01

Women with polycystic ovary syndrome (PCOS) have a greater clustering of cardiac risk factors. However, the link between PCOS and cardiovascular (CV) disease is incompletely described. The aim of this analysis was to evaluate the risk of CV events in 390 postmenopausal women enrolled in the National Institutes of Health-National Heart, Lung, and Blood Institute (NIH-NHLBI) sponsored Women's Ischemia Syndrome Evaluation (WISE) study according to clinical features of PCOS. A total of 104 women had clinical features of PCOS defined by a premenopausal history of irregular menses and current biochemical evidence of hyperandrogenemia. Hyperandrogenemia was defined as the top quartile of androstenedione (> or = 701 pg/ml), testosterone (> or = 30.9 ng/dl), or free testosterone (> or = 4.5 pg/ml). Cox proportional hazard model was fit to estimate CV death or myocardial infarction (n = 55). Women with clinical features of PCOS were more often diabetic (P < 0.0001), obese (P = 0.005), had the metabolic syndrome (P < 0.0001), and had more angiographic coronary artery disease (CAD) (P = 0.04) compared to women without clinical features of PCOS. Cumulative 5-yr CV event-free survival was 78.9% for women with clinical features of PCOS (n = 104) vs. 88.7% for women without clinical features of PCOS (n = 286) (P = 0.006). PCOS remained a significant predictor (P < 0.01) in prognostic models including diabetes, waist circumference, hypertension, and angiographic CAD as covariates. Among postmenopausal women evaluated for suspected ischemia, clinical features of PCOS are associated with more angiographic CAD and worsening CV event-free survival. Identification of postmenopausal women with clinical features of PCOS may provide an opportunity for risk factor intervention for the prevention of CAD and CV events.

Myostatin inhibits eEF2K-eEF2 by regulating AMPK to suppress protein synthesis.

Science.gov (United States)

Deng, Zhao; Luo, Pei; Lai, Wen; Song, Tongxing; Peng, Jian; Wei, Hong-Kui

2017-12-09

Growth of skeletal muscle is dependent on the protein synthesis, and the rate of protein synthesis is mainly regulated in the stage of translation initiation and elongation. Myostatin, a member of the transforming growth factor-β (TGF-β) superfamily, is a negative regulator of protein synthesis. C2C12 myotubes was incubated with 0, 0.01, 0.1, 1, 2, 3 μg/mL myostatin recombinant protein, and then we detected the rates of protein synthesis by the method of SUnSET. We found that high concentrations of myostatin (2 and 3 μg/mL) inhibited protein synthesis by blocking mTOR and eEF2K-eEF2 pathway, while low concentration of myostatin (0.01, 0.1 and 1 μg/mL) regulated eEF2K-eEF2 pathway activity to block protein synthesis without affected mTOR pathway, and myostatin inhibited eEF2K-eEF2 pathway through regulating AMPK pathway to suppress protein synthesis. It provided a new mechanism for myostatin regulating protein synthesis and treating muscle atrophy. Copyright © 2017. Published by Elsevier Inc.

Radical Nephrectomy for Primary Retroperitoneal Liposarcoma Near the Kidney has a Beneficial Effect on Disease-Free Survival.

Science.gov (United States)

Rhu, Jinsoo; Cho, Chan Woo; Lee, Kyo Won; Park, Hyojun; Park, Jae Berm; Choi, Yoon-La; Kim, Sung Joo

2018-01-01

The purpose of this study is to analyze the clinical impact of radical nephrectomy on retroperitoneal liposarcoma near the kidney. Data of patients who underwent surgery for unilateral primary retroperitoneal liposarcoma near the kidney were retrospectively collected. Patients were divided into four groups according to whether they underwent nephrectomy and combined resection of other organs. Kaplan-Meier survival analysis was used to estimate disease-free survival and overall survival. Multivariable Cox analysis was used to analyze factors related to disease-free survival and overall survival. Nephrectomy (HR = 0.260, CI = 0.078-0.873, p = 0.029) had a beneficial effect on disease-free survival, while interaction model of nephrectomy*other organ resection (HR = 4.655, CI = 1.767-12.263, p = 0.002) showed poor disease-free survival. Other organ resection was not related to disease-free survival (HR = 1.543, CI = 0.146-16.251, p = 0.718). Operation method (p = 0.007) and FNCLCC grade (p free survival. While combined organ resection without nephrectomy group (HR = 1.604, CI = 0.167-15.370, p = 0.682) and radical nephrectomy with combined organ resection group (HR = 1.309, CI = 0.448-3.825, p = 0.622) did not show significant difference in disease-free survival from the mass excision only group, radical nephrectomy without combined organ resection group (HR = 0.279, CI = 0.078-0.991, p = 0.048) showed superior disease-free survival. Radical nephrectomy of unilateral primary retroperitoneal liposarcoma near the kidney has a beneficial effect on disease-free survival.

Hypertension, Obesity, Diabetes, and Heart Failure-Free Survival: The Cardiovascular Disease Lifetime Risk Pooling Project.

Science.gov (United States)

Ahmad, Faraz S; Ning, Hongyan; Rich, Jonathan D; Yancy, Clyde W; Lloyd-Jones, Donald M; Wilkins, John T

2016-12-01

This study was designed to quantify the relationship between the absence of heart failure risk factors in middle age and incident heart failure, heart failure-free survival, and overall survival. Quantification of years lived free from heart failure in the context of risk factor burden in mid-life may improve risk communication and prevention efforts. We conducted a pooled, individual-level analysis sampling from communities across the United States as part of 4 cohort studies: the Framingham Heart, Framingham Offspring, Chicago Heart Association Detection Project in Industry, and ARIC (Atherosclerosis Risk In Communities) studies. Participants with and without hypertension (blood pressure ≥140/90 mm Hg or treatment), obesity (body mass index ≥30 kg/m 2 ), or diabetes (fasting glucose ≥126 mg/dl or treatment), and combinations of these factors, at index ages of 45 years and 55 years through 95 years. Competing risk-adjusted Cox models, a modified Kaplan-Meier estimator, and Irwin's restricted mean were used to estimate the association between the absence of risk factors at mid-life and incident heart failure, heart failure-free survival, and overall survival. For participants at age 45 years, over 516,537 person-years of follow-up, 1,677 incident heart failure events occurred. Men and women with no risk factors, compared to those with all 3, had 73% to 85% lower risks of incident heart failure. Men and women without hypertension, obesity, or diabetes at age 45 years lived on average 34.7 years and 38.0 years without incident heart failure, and they lived on average an additional 3 years to 15 years longer free of heart failure than those with 1, 2, or 3 risk factors. Similar trends were seen when stratified by race and at index age 55 years. Prevention of hypertension, obesity, and diabetes by ages 45 years and 55 years may substantially prolong heart failure-free survival, decrease heart failure-related morbidity, and reduce the public health impact of

Incident Atrial Fibrillation and Disability-Free Survival in the Cardiovascular Health Study.

Science.gov (United States)

Wallace, Erin R; Siscovick, David S; Sitlani, Colleen M; Dublin, Sascha; Mitchell, Pamela H; Odden, Michelle C; Hirsch, Calvin H; Thielke, Stephen; Heckbert, Susan R

2016-04-01

To assess the associations between incident atrial fibrillation (AF) and disability-free survival and risk of disability. Prospective cohort study. Cardiovascular Health Study. Individuals aged 65 and older and enrolled in fee-for-service Medicare followed between 1991 and 2009 (MN = 4,046). Individuals with prevalent AF, activity of daily living (ADL) disability, or a history of stroke or heart failure at baseline were excluded. Incident AF was identified according to annual study electrocardiogram, hospital discharge diagnosis, or Medicare claims. Disability-free survival was defined as survival free of ADL disability (any difficulty or inability in bathing, dressing, eating, using the toilet, walking around the home, or getting out of a bed or chair). ADLs were assessed at annual study visits or in a telephone interview. Association between incident AF and disability-free survival or risk of disability was estimated using Cox proportional hazards models. Over an average of 7.0 years of follow-up, 660 individuals (16.3%) developed incident AF, and 3,112 (77%) became disabled or died. Incident AF was associated with shorter disability-free survival (hazard ratio (HR) for death or ADL disability = 1.71, 95% confidence interval (CI) = 1.55-1.90) and a higher risk of ADL disability (HR = 1.36, 95% CI = 1.18-1.58) than in individuals with no history of AF. This association persisted after adjustment for interim stroke and heart failure. These results suggest that AF is a risk factor for shorter functional longevity in older adults, independent of other risk factors and comorbid conditions. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Postmenopausal Women with a History of Irregular Menses and Elevated Androgen Measurements at High Risk for Worsening Cardiovascular Event-Free Survival: Results from the National Institutes of Health—National Heart, Lung, and Blood Institute Sponsored Women’s Ischemia Syndrome Evaluation

Science.gov (United States)

Shaw, Leslee J.; Bairey Merz, C. Noel; Azziz, Ricardo; Stanczyk, Frank Z.; Sopko, George; Braunstein, Glenn D.; Kelsey, Sheryl F.; Kip, Kevin E.; Cooper-DeHoff, Rhonda M.; Johnson, B. Delia; Vaccarino, Viola; Reis, Steven E.; Bittner, Vera; Hodgson, T. Keta; Rogers, William; Pepine, Carl J.

2008-01-01

Background: Women with polycystic ovary syndrome (PCOS) have a greater clustering of cardiac risk factors. However, the link between PCOS and cardiovascular (CV) disease is incompletely described. Objective: The aim of this analysis was to evaluate the risk of CV events in 390 postmenopausal women enrolled in the National Institutes of Health–National Heart, Lung, and Blood Institute (NIH-NHLBI) sponsored Women’s Ischemia Syndrome Evaluation (WISE) study according to clinical features of PCOS. Methods: A total of 104 women had clinical features of PCOS defined by a premenopausal history of irregular menses and current biochemical evidence of hyperandrogenemia. Hyperandrogenemia was defined as the top quartile of androstenedione (≥701 pg/ml), testosterone (≥30.9 ng/dl), or free testosterone (≥4.5 pg/ml). Cox proportional hazard model was fit to estimate CV death or myocardial infarction (n = 55). Results: Women with clinical features of PCOS were more often diabetic (P < 0.0001), obese (P = 0.005), had the metabolic syndrome (P < 0.0001), and had more angiographic coronary artery disease (CAD) (P = 0.04) compared to women without clinical features of PCOS. Cumulative 5-yr CV event-free survival was 78.9% for women with clinical features of PCOS (n = 104) vs. 88.7% for women without clinical features of PCOS (n = 286) (P = 0.006). PCOS remained a significant predictor (P < 0.01) in prognostic models including diabetes, waist circumference, hypertension, and angiographic CAD as covariates. Conclusion: Among postmenopausal women evaluated for suspected ischemia, clinical features of PCOS are associated with more angiographic CAD and worsening CV event-free survival. Identification of postmenopausal women with clinical features of PCOS may provide an opportunity for risk factor intervention for the prevention of CAD and CV events. PMID:18182456

Optimizing Design Efficiency of Free Recall Events for fMRI

OpenAIRE

Öztekin, Ilke; Long, Nicole M.; Badre, David

2010-01-01

Free recall is a fundamental paradigm for studying memory retrieval in the context of minimal cue support. Accordingly, free recall has been extensively studied using behavioral methods. However, the neural mechanisms that support free recall have not been fully investigated due to technical challenges associated with probing individual recall events with neuroimaging methods. Of particular concern is the extent to which the uncontrolled latencies associated with recall events can confer suff...

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

Science.gov (United States)

Linden, Ariel; Yarnold, Paul R

2017-12-01

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

Function and structure in phage Qbeta RNA replicase. Association of EF-Tu-Ts with the other enzyme subunits

DEFF Research Database (Denmark)

Blumenthal, T; Young, R A; Brown, S

1976-01-01

alters its quaternary structure: the EF-Tu-Ts cannot be covalently attached to the other enzyme subunits with bifunctional cross-linking reagents in the presence of RNA. This conformational change is not influenced by ionic strength. The addition of Qbeta RNA to the enzyme, does not result in the release...... for one another increases with increasing ionic strength. The enzyme is capable of initiation of RNA synthesis with synthetic templates only when in the low ionic strength conformation. Elongation of initiated polynucleotide chains is not affectedby ionic strength. Addition of Qbeta RNA to the enzyme also...... of EF-Tu-Ts from the other enzyme subunits: whereas free EF-Tu-Ts binds GDP independently of salt concentration, this binding by Qbeta replicase is sensitive to high ionic strength and remains so in the presence of Qbeta RNA. Furthermore, RNA does not allow the release of EF-Ts from EF-Tu by GTP...

Summary curves for patients transplanted for chronic myeloid leukaemia salvaged by a donor lymphocyte infusion: the current leukaemia-free survival curve

DEFF Research Database (Denmark)

Klein, John P.; Keiding, Niels; Shu, Youyi

2000-01-01

CML, donor lymphocyte infusion, leukaemia-free survival, current leukaemia-free survival, statistical methods......CML, donor lymphocyte infusion, leukaemia-free survival, current leukaemia-free survival, statistical methods...

Progression-free Survival Following Stereotactic Body Radiotherapy for Oligometastatic Prostate Cancer Treatment-naive Recurrence: A Multi-institutional Analysis.

Science.gov (United States)

Ost, Piet; Jereczek-Fossa, Barbara Alicja; As, Nicholas Van; Zilli, Thomas; Muacevic, Alexander; Olivier, Kenneth; Henderson, Daniel; Casamassima, Franco; Orecchia, Roberto; Surgo, Alessia; Brown, Lindsay; Tree, Alison; Miralbell, Raymond; De Meerleer, Gert

2016-01-01

The literature on metastasis-directed therapy for oligometastatic prostate cancer (PCa) recurrence consists of small heterogeneous studies. This study aimed to reduce the heterogeneity by pooling individual patient data from different institutions treating oligometastatic PCa recurrence with stereotactic body radiotherapy (SBRT). We focussed on patients who were treatment naive, with the aim of determining if SBRT could delay disease progression. We included patients with three or fewer metastases. The Kaplan-Meier method was used to estimate distant progression-free survival (DPFS) and local progression-free survival (LPFS). Toxicity was scored using the Common Terminology Criteria for Adverse Events. In total, 163 metastases were treated in 119 patients. The median DPFS was 21 mo (95% confidence interval, 15-26 mo). A lower radiotherapy dose predicted a higher local recurrence rate with a 3-yr LPFS of 79% for patients treated with a biologically effective dose ≤100Gy versus 99% for patients treated with >100Gy (p=0.01). Seventeen patients (14%) developed toxicity classified as grade 1, and three patients (3%) developed grade 2 toxicity. No grade ≥3 toxicity occurred. These results should serve as a benchmark for future prospective trials. This multi-institutional study pools all of the available data on the use of stereotactic body radiotherapy for limited prostate cancer metastases. We concluded that this approach is safe and associated with a prolonged treatment progression-free survival. Copyright © 2015. Published by Elsevier B.V.

Embedding EfS in Teacher Education through a Multi-Level Systems Approach: Lessons from Queensland

Science.gov (United States)

Evans, Neus; Ferreira, Jo-Anne; Davis, Julie; Stevenson, Robert B.

2016-01-01

This article reports on the fourth stage of an evolving study to develop a systems model for embedding education for sustainability (EfS) into preservice teacher education. The fourth stage trialled the extension of the model to a comprehensive state-wide systems approach involving representatives from all eight Queensland teacher education…

Dual-Polarimetric Radar-Based Tornado Debris Paths Associated with EF-4 and EF-5 Tornadoes over Northern Alabama During the Historic Outbreak of 27 April 2011

Science.gov (United States)

Carey, Lawrence D.; Schultz, Chrstopher J.; Schultz, Elise V.; Petersen, Walter A.; Gatlin, Patrick N.; Knupp, Kevin R.; Molthan, Andrew L.; Jedlovec, Gary J.; Darden, Christopher B.

2012-01-01

An historic tornado and severe weather outbreak devastated much of the southeastern United States between 25 and 28 April 2011. On 27 April 2011, northern Alabama was particularly hard hit by a large number of tornadoes, including several that reached EF-4 and EF-5 on the Enhanced Fujita damage scale. In northern Alabama alone, there were approximately 100 fatalities and hundreds of more people who were injured or lost their homes during the havoc caused by these violent tornadic storms. Two long-track and violent (EF-4 and EF-5) tornadoes occurred within range of the University of Alabama in Huntsville (UAHuntsville) Advanced Radar for Meteorological and Operational Research (ARMOR, C-band dual-polarimetric). A unique capability of dual-polarimetric radar is the near-real time identification of lofted debris associated with ongoing tornadoes on the ground. The focus of this paper is to analyze the dual-polarimetric radar-inferred tornado debris signatures and identify the associated debris paths of the long-track EF-4 and EF-5 tornadoes near ARMOR. The relative locations of the debris and damage paths for each tornado will be ascertained by careful comparison of the ARMOR analysis with NASA MODIS (Moderate Resolution Imaging Spectroradiometer) and ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer) satellite imagery of the tornado damage scenes and the National Weather Service tornado damage surveys. With the ongoing upgrade of the WSR-88D (Weather Surveillance Radar 1988 Doppler) operational network to dual-polarimetry and a similar process having already taken place or ongoing for many private sector radars, dual-polarimetric radar signatures of tornado debris promise the potential to assist in the situational awareness of government and private sector forecasters and emergency managers during tornadic events. As such, a companion abstract (Schultz et al.) also submitted to this conference explores The use of dual-polarimetric tornadic debris

Progression-free survival: gaining on overall survival as a gold standard and accelerating drug development.

Science.gov (United States)

Lebwohl, David; Kay, Andrea; Berg, William; Baladi, Jean Francois; Zheng, Ji

2009-01-01

In clinical trials of oncology drugs, overall survival (OS) is a direct measure of clinical efficacy and is considered the gold standard primary efficacy end point. The purpose of this study was to discuss the difficulties in using OS as a primary efficacy end point in the setting of evolving cancer therapies. We suggest that progression-free survival is an appropriate efficacy end point in many types of cancer, specifically those for which OS is expected to be prolonged and for which subsequent treatments are expected to affect OS.

Preoperative radiation with concurrent chemotherapy for resectable rectal cancer: Effect of dose escalation on pathologic complete response, local recurrence-free survival, disease-free survival, and overall survival

International Nuclear Information System (INIS)

Wiltshire, Kirsty L.; Ward, Iain G.; Swallow, Carol; Oza, Amit M.; Cummings, Bernard; Pond, Gregory R.; Catton, Pamela; Kim, John; Ringash, Jolie; Wong, Chong S.; Wong, Rebecca; Siu, Lillian L.; Moore, Malcolm; Brierley, James

2006-01-01

Purpose: Three Phase II studies of preoperative radiotherapy and concurrent 5FU chemotherapy were undertaken. The primary endpoints were acute toxicity and pathologic complete response rate (pCR). Secondary endpoints were local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS). Methods and Materials: A total of 134 patients with adenocarcinoma of the rectum (clinical T3/T4 or N1/N2) were treated. The initial cohort received 40 Gy in 20 fractions, the second 46 Gy in 23 fractions, and the third 50 Gy in 25 fractions. 5FU (225 mg/m 2 /day) was given continuously throughout radiotherapy. A total of 121 patients underwent surgical resection. Results: Treatment was well tolerated. Grade 3/4 acute toxicity was observed in 13%, 4%, and 14% of patients in the 40 Gy, 46 Gy, and 50 Gy cohorts, respectively (p = 0.20). pCR was documented in 15%, 23%, and 33% of patients, respectively (p = 0.07). The 2-year actuarial LRFS was 72%, 90%, and 89% (p = 0.02); DFS was 62%, 84%, and 78% (p = 0.02); and OS was 72%, 94%, and 92%, respectively (p = 0.03). Conclusions: All treatment schedules were well tolerated. There was a trend toward increased pCR with higher doses. A statistically significant increase in LRFS, DFS, and OS was seen with radiation doses of 46 Gy and greater, but there was no difference between 46 Gy and 50 Gy

Contribution of effluent organic matter (EfOM) to ultrafiltration (UF) membrane fouling: Isolation, characterization, and fouling effect of EfOM fractions

KAUST Repository

Zheng, Xing; Khan, Muhammad; Croue, Jean-Philippe

2014-01-01

EfOM has been regarded as a major organic foulant resulting in UF membrane fouling in wastewater reclamation. To investigate fouling potential of different EfOM fractions, the present study isolated EfOM into hydrophobic neutrals (HPO-N), colloids

Preirradiation PSA predicts biochemical disease-free survival in patients treated with postprostatectomy external beam irradiation

International Nuclear Information System (INIS)

Crane, Christopher H.; Rich, Tyvin A.; Read, Paul W.; Sanfilippo, Nicholas J.; Gillenwater, Jay Y.; Kelly, Maria D.

1997-01-01

Purpose: To assess the clinical outcome and prostate-specific antigen (PSA) response and to determine prognostic factors for biochemical disease-free survival in patients treated with external beam radiotherapy following radical prostatectomy without hormonal therapy. Methods and Materials: Forty-eight patients were treated after prostatectomy with radiotherapy between March, 1988 and December, 1993. Seven patients had undetectable PSA ( 2.7. Five-year actuarial biochemical disease-free survival values were 71, 48, and 0%, respectively, for the three groups. Biochemical disease-free survival was not affected by preoperative PSA level, clinical stage, Gleason's score, pathologic stage, surgical margins, presence of undetectable PSA after surgery, surgery to radiation interval, total dose, or presence of clinically suspicious local disease. Based on digital rectal exam, there were no local failures. Conclusion: Biochemical disease-free survival after postprostatectomy radiation is predicted by the PSA at the time of irradiation. Clinical local control is excellent, but distant failure remains a significant problem in this population. The addition of concomitant systemic therapy should be investigated in patients with PSA >2.7

Development and Tests of the Event Filter for the ATLAS Experiment

CERN Document Server

Bosman, M; Negri, A; Segura, E; Sushkov, S; Touchard, F; Wheeler, S J; 14th IEEE - NPSS Real Time Conference 2005 Nuclear Plasma Sciences Society

2005-01-01

The Trigger and Data Acquisition (TDAQ) System of the ATLAS Experiment comprises three stages of event selection. The Event Filter (EF) is the third level trigger and is software implemented. Its primary goal is the final selection of interesting events with reduction of the event rate down to ~200 Hz acceptable by the mass storage. The EF System will be implemented as a set of independent commodity components Sub-Farms, each connected to the Event Builder subsystem to receive full events and on the other side to the Sub-Farm Output nodes, where the selected events are forwarded to mass storage. A distinctive feature of the Event Filter is its ability to use the full event data for selection directly based on the offline reconstruction and analysis algorithms. Besides the main duties on event triggering and data transportation, the EF is also able to provide additional functionalities, like monitoring of the selected events and online calibration of the ATLAS detectors. Significant design improvements are cur...

Seeding Event: Creating and Developing Spaces of Entrepreneurial Freedom

Directory of Open Access Journals (Sweden)

Gaëtan Mourmant

2012-12-01

Full Text Available This paper addresses the question of initiating, fostering and growing a vibrant economy by developing Spaces of Entrepreneurial Freedom (SoEF. Establishing and developing the SoEF is explained by a seeding event which is the core category of this grounded theory. In short, a seeding event leads to the patching of a potential, structural “hole”, which may prove valuable to an entrepreneurial network. Seeding events are started by an initiator who will recognize a network opportunity and exploit it. After event designing, the initiators implement the event through bold experimentation and using an adaptive structure. If the event is considered successful, the next stages are refining, growing, templating and finally replicating; these stages may occur one after the other or simultaneously. Through the development of SoEF, we suggest that entrepreneurs, governments, universities, large companies, and other players in the business world can improve the development of entrepreneurship at their respective levels.

Refractory Graft-Versus-Host Disease-Free, Relapse-Free Survival as an Accurate and Easy-to-Calculate Endpoint to Assess the Long-Term Transplant Success.

Science.gov (United States)

Kawamura, Koji; Nakasone, Hideki; Kurosawa, Saiko; Yoshimura, Kazuki; Misaki, Yukiko; Gomyo, Ayumi; Hayakawa, Jin; Tamaki, Masaharu; Akahoshi, Yu; Kusuda, Machiko; Kameda, Kazuaki; Wada, Hidenori; Ishihara, Yuko; Sato, Miki; Terasako-Saito, Kiriko; Kikuchi, Misato; Kimura, Shun-Ichi; Tanihara, Aki; Kako, Shinichi; Kanamori, Heiwa; Mori, Takehiko; Takahashi, Satoshi; Taniguchi, Shuichi; Atsuta, Yoshiko; Kanda, Yoshinobu

2018-02-21

The aim of this study was to develop a new composite endpoint that accurately reflects the long-term success of allogeneic hematopoietic stem cell transplantation (allo-HSCT), as the conventional graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) overestimates the impact of GVHD. First, we validated current GRFS (cGRFS), which recently was proposed as a more accurate endpoint of long-term transplant success. cGRFS was defined as survival without disease relapse/progression or active chronic GVHD at a given time after allo-HSCT, calculated using 2 distinct methods: a linear combination of a Kaplan-Meier estimates approach and a multistate modelling approach. Next, we developed a new composite endpoint, refractory GRFS (rGRFS). rGRFS was calculated similarly to conventional GRFS treating grade III to IV acute GVHD, chronic GVHD requiring systemic treatment, and disease relapse/progression as events, except that GVHD that resolved and did not require systemic treatment at the last evaluation was excluded as an event in rGRFS. The 2 cGRFS curves obtained using 2 different approaches were superimposed and both were superior to that of conventional GRFS, reflecting the proportion of patients with resolved chronic GVHD. Finally, the curves of cGRFS and rGRFS overlapped after the first 2 years of post-transplant follow-up. These results suggest that cGRFS and rGRFS more accurately reflect transplant success than conventional GRFS. Especially, rGRFS can be more easily calculated than cGRFS and analyzed with widely used statistical approaches, whereas cGRFS more accurately represents the burden of GVHD-related morbidity in the first 2 years after transplantation. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

The Event Chain of Survival in the Context of Music Festivals: A Framework for Improving Outcomes at Major Planned Events.

Science.gov (United States)

Lund, Adam; Turris, Sheila

2017-08-01

Despite the best efforts of event producers and on-site medical teams, there are sometimes serious illnesses, life-threatening injuries, and fatalities related to music festival attendance. Producers, clinicians, and researchers are actively seeking ways to reduce the mortality and morbidity associated with these events. After analyzing the available literature on music festival health and safety, several major themes emerged. Principally, stakeholder groups planning in isolation from one another (ie, in silos) create fragmentation, gaps, and overlap in plans for major planned events (MPEs). The authors hypothesized that one approach to minimizing this fragmentation may be to create a framework to "connect the dots," or join together the many silos of professionals responsible for safety, security, health, and emergency planning at MPEs. Adapted from the well-established literature regarding the management of cardiac arrests, both in and out of hospital, the "chain of survival" concept is applied to the disparate groups providing services that support event safety in the context of music festivals. The authors propose this framework for describing, understanding, coordinating and planning around the integration of safety, security, health, and emergency service for events. The adapted Event Chain of Survival contains six interdependent links, including: (1) event producers; (2) police and security; (3) festival health; (4) on-site medical services; (5) ambulance services; and (6) off-site medical services. The authors argue that adapting and applying this framework in the context of MPEs in general, and music festivals specifically, has the potential to break down the current disconnected approach to event safety, security, health, and emergency planning. It offers a means of shifting the focus from a purely reactive stance to a more proactive, collaborative, and integrated approach. Improving health outcomes for music festival attendees, reducing gaps in planning

Clinical efficacy of gamma knife and surgery treatment of mesial temporal lobe epilepsy and their effects on EF-Tumt and EF-Tsmt expression.

Science.gov (United States)

Wang, X-Q; Zhang, X-D; Han, Y-M; Shi, X-F; Lan, Z-B; Men, X-X; Pan, Y-W

2017-04-01

To study the clinical efficacy of gamma knife and surgery treatment of mesial temporal lobe epilepsy (MTLE) and their effects on EF-Tumt and EF-Tsmt expression. The data of 78 cases of MTLE patients treated in our hospital from April 2011 to March 2013 were retrospectively analyzed. The patients were divided into two groups according to the treatment methods: the surgery group (including 41 cases) and the gamma knife group (including 37 cases). The clinical efficacy, the occurrence and recurrence of complications were evaluated, respectively; meanwhile, the expression of the EF-Tumt protein and EF-Tsmt protein in brain tissue were analyzed. The difference between the efficacy rate of the two groups showed no statistical significance (χ2=0.960, p>0.05). The complication rate of the gamma knife group was significantly lower than that of the control group (χ2=6.430, pknife group was significantly lower than that of the patients in the surgery group (p>0.05). Within the two groups, the positive expression granum of EF-Tsmt protein and EF-Tumt protein of the two groups after treatment were significantly lower than that before treatment (pknife group was obviously more than that of the patients in the surgery group (p0.05). Before and after treatment within the group, the positive cell of EF-Tsmt protein and EF-Tumt protein of the two groups of patients after treatment were significantly lower than that before treatment (p0.05). Both surgery and gamma knife could treat MTLE effectively, and the efficacy may be related to the ability to reduce the expression of EF-Tsmt protein and EF-Tumt protein in brain tissue.

Single-molecule folding mechanism of an EF-hand neuronal calcium sensor

DEFF Research Database (Denmark)

Heiðarsson, Pétur Orri; Otazo, Mariela R.; Bellucci, Luca

2013-01-01

EF-hand calcium sensors respond structurally to changes in intracellular Ca2+ concentration, triggering diverse cellular responses and resulting in broad interactomes. Despite impressive advances in decoding their structure-function relationships, the folding mechanism of neuronal calcium sensors...... of the N domain, showing striking interdomain dependence. Molecular dynamics results reveal the atomistic details of the unfolding process and rationalize the different domain stabilities during mechanical unfolding. Through constant-force experiments and hidden Markov model analysis, the free energy...

Predictors of outcome and methodological issues in children with acute lymphoblastic leukaemia in El Salvador.

Science.gov (United States)

Bonilla, Miguel; Gupta, Sumit; Vasquez, Roberto; Fuentes, Soad L; deReyes, Gladis; Ribeiro, Raul; Sung, Lillian

2010-12-01

Most children with cancer live in low-income countries (LICs) where risk factors in paediatric acute lymphoblastic leukaemia (ALL) developed in high-income countries may not apply. We describe predictors of survival for children in El Salvador with ALL. We included patients El Salvador-Guatemala-Honduras II protocol. Demographic, disease-related, socioeconomic and nutritional variables were examined as potential predictors of event-free survival (EFS) and overall survival (OS). 260/443 patients (58.7%) were classified as standard risk. Standard- and high-risk 5-year EFS were 56.3 ± 4.5% and 48.6 ± 5.5%; 5-year OS were 77.7 ± 3.8% and 61.9 ± 5.8%, respectively. Among standard-risk children, socioeconomic variables such as higher monthly income (hazard ratio [HR] per $100 = 0.84 [95% confidence interval (CI) 0.70-0.99; P=0.04]) and parental secondary education (HR = 0.49, 95% CI 0.29-0.84; P = 0.01) were associated with better EFS. Among high-risk children, higher initial white blood cell (HR per 10×10(9)/L = 1.03, 95% CI 1.02-1.05; P<0.001) predicted worse EFS; socioeconomic variables were not predictive. The difference in EFS and OS appeared related to overestimating OS secondary to poor follow-up after abandonment/relapse. Socioeconomic variables predicted worse EFS in standard-risk children while disease-related variables were predictive in high-risk patients. Further studies should delineate pathways through which socioeconomic status affects EFS in order to design effective interventions. EFS should be the primary outcome in LIC studies. Copyright © 2010 Elsevier Ltd. All rights reserved.

Myositis-associated usual interstitial pneumonia has a better survival than idiopathic pulmonary fibrosis.

Science.gov (United States)

Aggarwal, Rohit; McBurney, Christine; Schneider, Frank; Yousem, Samuel A; Gibson, Kevin F; Lindell, Kathleen; Fuhrman, Carl R; Oddis, Chester V

2017-03-01

To compare the survival outcomes between myositis-associated usual interstitial pneumonia (MA-UIP) and idiopathic pulmonary fibrosis (IPF-UIP). Adult MA-UIP and IPF-UIP patients were identified using CTD and IPF registries. The MA-UIP cohort included myositis or anti-synthetase syndrome patients with interstitial lung disease while manifesting UIP on high-resolution CT chest and/or a lung biopsy revealing UIP histology. IPF subjects met American Thoracic Society criteria and similarly had UIP histopathology. Kaplan-Meier survival curves compared cumulative and pulmonary event-free survival (event = transplant or death) between (i) all MA-UIP and IPF-UIP subjects, (ii) MA-UIP with biopsy proven UIP (n = 25) vs IPF-UIP subjects matched for age, gender and baseline forced vital capacity (±10%). Cox proportional hazards ratios compared the survival controlling for co-variates. Eighty-one IPF-UIP and 43 MA-UIP subjects were identified. The median cumulative and event-free survival time in IPF vs MA-UIP was 5.25/1.8 years vs 16.2/10.8 years, respectively. Cumulative and event-free survival was significantly worse in IPF-UIP vs MA-UIP [hazards ratio of IPF-UIP was 2.9 (95% CI: 1.5, 5.6) and 5.0 (95% CI: 2.8, 8.7) (P < 0.001), respectively]. IPF-UIP event-free survival (but not cumulative) remained significantly worse than MA-UIP with a hazards ratio of 6.4 (95% CI: 3.0, 13.8) after controlling for age at interstitial lung disease diagnosis, gender, ethnicity and baseline forced vital capacity%. Respiratory failure was the most common cause of death in both groups. A sub-analysis of 25 biopsy-proven MA-UIP subjects showed similar results. MA-UIP patients demonstrated a significant survival advantage over a matched IPF cohort, suggesting that despite similar histological and radiographic findings at presentation, the prognosis of MA-UIP is superior to that of IPF-UIP. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology

The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction

DEFF Research Database (Denmark)

Boesgaard, Søren

2012-01-01

A substantial proportion of patients with heart failure have preserved left ventricular ejection fraction (HF-PEF). Previous studies have reported mixed results whether survival is similar to those patients with heart failure and reduced EF (HF-REF).......A substantial proportion of patients with heart failure have preserved left ventricular ejection fraction (HF-PEF). Previous studies have reported mixed results whether survival is similar to those patients with heart failure and reduced EF (HF-REF)....

A comparison of the conditional inference survival forest model to random survival forests based on a simulation study as well as on two applications with time-to-event data.

Science.gov (United States)

Nasejje, Justine B; Mwambi, Henry; Dheda, Keertan; Lesosky, Maia

2017-07-28

Random survival forest (RSF) models have been identified as alternative methods to the Cox proportional hazards model in analysing time-to-event data. These methods, however, have been criticised for the bias that results from favouring covariates with many split-points and hence conditional inference forests for time-to-event data have been suggested. Conditional inference forests (CIF) are known to correct the bias in RSF models by separating the procedure for the best covariate to split on from that of the best split point search for the selected covariate. In this study, we compare the random survival forest model to the conditional inference model (CIF) using twenty-two simulated time-to-event datasets. We also analysed two real time-to-event datasets. The first dataset is based on the survival of children under-five years of age in Uganda and it consists of categorical covariates with most of them having more than two levels (many split-points). The second dataset is based on the survival of patients with extremely drug resistant tuberculosis (XDR TB) which consists of mainly categorical covariates with two levels (few split-points). The study findings indicate that the conditional inference forest model is superior to random survival forest models in analysing time-to-event data that consists of covariates with many split-points based on the values of the bootstrap cross-validated estimates for integrated Brier scores. However, conditional inference forests perform comparably similar to random survival forests models in analysing time-to-event data consisting of covariates with fewer split-points. Although survival forests are promising methods in analysing time-to-event data, it is important to identify the best forest model for analysis based on the nature of covariates of the dataset in question.

A comparison of the conditional inference survival forest model to random survival forests based on a simulation study as well as on two applications with time-to-event data

Directory of Open Access Journals (Sweden)

Justine B. Nasejje

2017-07-01

Full Text Available Abstract Background Random survival forest (RSF models have been identified as alternative methods to the Cox proportional hazards model in analysing time-to-event data. These methods, however, have been criticised for the bias that results from favouring covariates with many split-points and hence conditional inference forests for time-to-event data have been suggested. Conditional inference forests (CIF are known to correct the bias in RSF models by separating the procedure for the best covariate to split on from that of the best split point search for the selected covariate. Methods In this study, we compare the random survival forest model to the conditional inference model (CIF using twenty-two simulated time-to-event datasets. We also analysed two real time-to-event datasets. The first dataset is based on the survival of children under-five years of age in Uganda and it consists of categorical covariates with most of them having more than two levels (many split-points. The second dataset is based on the survival of patients with extremely drug resistant tuberculosis (XDR TB which consists of mainly categorical covariates with two levels (few split-points. Results The study findings indicate that the conditional inference forest model is superior to random survival forest models in analysing time-to-event data that consists of covariates with many split-points based on the values of the bootstrap cross-validated estimates for integrated Brier scores. However, conditional inference forests perform comparably similar to random survival forests models in analysing time-to-event data consisting of covariates with fewer split-points. Conclusion Although survival forests are promising methods in analysing time-to-event data, it is important to identify the best forest model for analysis based on the nature of covariates of the dataset in question.

A comparison of HFrEF vs HFpEF's clinical workload and cost in the first year following hospitalization and enrollment in a disease management program.

Science.gov (United States)

Murphy, T M; Waterhouse, D F; James, S; Casey, C; Fitzgerald, E; O'Connell, E; Watson, C; Gallagher, J; Ledwidge, M; McDonald, K

2017-04-01

Admission with heart failure (HF) is a milestone in the progression of the disease, often resulting in higher intensity medical care and ensuing readmissions. Whilst there is evidence supporting enrolling patients in a heart failure disease management program (HF-DMP), not all reported HF-DMPs have systematically enrolled patients with HF with preserved ejection fraction (HFpEF) and there is a scarcity of literature differentiating costs based on HF-phenotype. 1292 consenting, consecutive patients admitted with a primary diagnosis of HF were enrolled in a hospital based HF-DMP and categorized as HFpEF (EF≥45%) or HFrEF (EFHospitalizations, primary care, medications, and DMP workload with associated costs were evaluated assessing DMP clinic-visits, telephonic contact, medication changes over 1year using a mixture of casemix and micro-costing techniques. The total average annual cost per patient was marginally higher in patients with HFrEF €13,011 (12,011, 14,078) than HFpEF, €12,206 (11,009, 13,518). However, emergency non-cardiovascular admission rates and average cost per patient were higher in the HFpEF vs HFrEF group (0.46 vs 0.31 per patient/12months) & €655 (318, 1073) vs €584 (396, 812). In the first 3months of the outpatient HF-DMP the HFrEF population cost more on average €791 (764, 819) vs €693 (660, 728). There are greater short-term (3-month) costs of HFrEF versus HFpEF as part of a HF-DMP following an admission. However, long-term (3-12month) costs of HFpEF are greater because of higher non-cardiovascular rehospitalisations. As HFpEF becomes the dominant form of HF, more work is required in HF-DMPs to address prevention of non-cardiovascular rehospitalisations and to integrate hospital based HF-DMPs into primary healthcare structures. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Impact of Socioeconomic Status on Timing of Relapse and Overall Survival for Children Treated on Dana-Farber Cancer Institute ALL Consortium Protocols (2000-2010).

Science.gov (United States)

Bona, Kira; Blonquist, Traci M; Neuberg, Donna S; Silverman, Lewis B; Wolfe, Joanne

2016-06-01

Population-based evidence suggests that lower socioeconomic status (SES) negatively impacts the overall survival (OS) of children with leukemia; however, the relationships between SES and treatment-related mortality, relapse, and timing of relapse remain unclear. We examined OS, event-free survival (EFS) and cumulative incidence (CI) and timing of relapse by community-level poverty for 575 children aged 1-18 years with newly diagnosed acute lymphoblastic leukemia (ALL) treated on consecutive phase III multicenter Dana-Farber Cancer Institute ALL Consortium Protocols between 2000 and 2010. Children were categorized into high- and low-poverty areas for the analysis using aggregate U.S. Census data linked to zip code. Children living in high-poverty areas experienced a 5-year OS of 85% as compared with 92% for those in low-poverty areas (P = 0.02); poverty remained marginally significant (P = 0.07) after adjustment for immunophenotype, age, and white blood cell count. There were no differences detected in EFS or CI relapse by poverty area. However, 92% of the relapses observed in children from high-poverty areas occurred <36 months from complete remission, compared to 48% of those in children from low-poverty areas (P = 0.008). U.S. children with ALL living in high-poverty areas have a higher risk of early relapse when compared with those living in low-poverty areas despite uniform treatment. This may in part explain decreased OS observed in these children. This finding highlights disparities in childhood cancer outcomes by SES despite uniform treatment. Further investigations of the mechanistic pathways underlying this finding are needed. © 2016 Wiley Periodicals, Inc.

Brownfields/IGD: EF_ACRES

Data.gov (United States)

U.S. Environmental Protection Agency — EF_ACRES is a subset of facilities from FRS_INTEREST and FRS_FACILITY_SITE which are updated on a monthly basis as part of the Locational Reference Tables (LRT)...

Superfund/IGD: EF_NPL

Data.gov (United States)

U.S. Environmental Protection Agency — EF_NPL is a subset of facilities from FRS_INTEREST and FRS_FACILITY_SITE which are updated on a monthly basis as part of the Locational Reference Tables (LRT)...

Relationship of peak serum methotrexate concentration to prognosis and drug tolerance in non-metastatic extremity osteosarcomas.

Science.gov (United States)

Wang, Bo; Yao, Hao; Xie, Xianbiao; Yin, Junqiang; Zou, Changye; Huang, Gang; Shen, Jingnan

2018-05-28

This study aimed to explore whether peak serum methotrexate concentration (C max ) correlated with adverse events, overall survival (OS) and event-free survival (EFS) in patients with primary extremity osteosarcoma. Patients with extremity osteosarcoma who were treated at our center between 2005 and 2015 were retrospectively studied. All the patients were Enneking stage II and had received standard perioperative chemotherapy composed of high-dose methotrexate, doxorubicin, cisplatin and ifosfamide. C max and treatment-associated toxicities of each cycle were recorded. OS and EFS were estimated and compared by Kaplan-Meier survival analysis, and Cox regression models were performed for univariate comparisons. In total, 567 patients were followed for an average of 53 months (24-104 months). The estimated 3- and 5-year EFS were 71.7 and 63.1%, and the 3- and 5-year OS were 78.2 and 72.9%, respectively. C max ranged from 527 to 2495 µmol/L with a mean value of 931 ± 106 µmol/L. No significant differences in EFS and OS (p = 0.18 and p = 0.28) were observed among patients with a mean C max  > 1500, > 1000, > 700 and  1500 µmol/L had significantly increased rates of grade 3-5 toxicity. In the univariate analysis, C max was not a prognostic factor for EFS (p = 0.08) or OS (p = 0.16). C max did not correlate significantly with the oncologic prognosis of non-metastatic extremity osteosarcoma patients treated by multi-agent chemotherapy; however, C max correlated closely with toxicities and complications. The persistent inclusion of methotrexate in classical multidisciplinary chemotherapy was questioned and should be examined in future trials.

75 FR 27986 - Electronic Filing System-Web (EFS-Web) Contingency Option

Science.gov (United States)

2010-05-19

...] Electronic Filing System--Web (EFS-Web) Contingency Option AGENCY: United States Patent and Trademark Office... contingency option when the primary portal to EFS-Web has an unscheduled outage. Previously, the entire EFS-Web system is not available to the users during such an outage. The contingency option in EFS-Web will...

Biochemical disease-free survival following I-125 prostate implantation

International Nuclear Information System (INIS)

Beyer, David C.; Priestley, Joseph B.

1995-01-01

Purpose/Objective: To assess the five-year clinical and biochemical results of ultrasound-guided permanent I-125 brachytherapy in early prostate cancer. Biochemical disease-free survival (BDFS) is reported, using PSA follow-up and is compared to the surgical and radiation therapy literature. Materials and Methods: From 12/88 through 12/93, ultrasound-guided brachytherapy was preplanned with I-125 and delivered 16,000 cGy as the sole treatment in 499 patients. All were clinically staged as T1 or T2 - N0M0 adenocarcinoma of the prostate. Within the first year, 19 patients were lost to follow-up and have been excluded from further study. The remaining 480 patients form the basis of this report. Clinical status and PSA values were systematically recorded before and after treatment. Results: With a median follow-up of 35 months (3-70) the actuarial clinical local control is 83%. Both stage and grade are shown to predict for this endpoint. Actuarial BDFS is also correlated with stage, grade, and PSA at presentation. Biochemical disease-free survival at five years is 94% for T1, 70% for unilateral T2, and 34% for T2c tumors. Grade is also predictive, ranging from 85% in low-grade tumors to 30% in high-grade tumors. In a multivariate analysis, the pretreatment PSA is most highly correlated (p 10 had a BDFS of 40%. Complications have been few, with severe urinary urgency or dysuria in 4% and both incontinence and proctitis seen in 1%. Conclusion: While biochemical disease-free survival reports in the literature are immature and have short follow-up, our data compares favorably with studies following radical prostatectomy or radiation therapy. Further follow-up of this cohort is required. The complication rate is low and patient acceptance excellent. Permanent implantation of I-125 as the sole treatment for early prostate cancer is a viable alternative for patients with early stage and low- to moderate-grade cancers. The PSA provides significant prognostic information and

Biochemical disease-free survival following I-125 prostate implantation

Energy Technology Data Exchange (ETDEWEB)

Beyer, David C; Priestley, Joseph B

1995-07-01

Purpose/Objective: To assess the five-year clinical and biochemical results of ultrasound-guided permanent I-125 brachytherapy in early prostate cancer. Biochemical disease-free survival (BDFS) is reported, using PSA follow-up and is compared to the surgical and radiation therapy literature. Materials and Methods: From 12/88 through 12/93, ultrasound-guided brachytherapy was preplanned with I-125 and delivered 16,000 cGy as the sole treatment in 499 patients. All were clinically staged as T1 or T2 - N0M0 adenocarcinoma of the prostate. Within the first year, 19 patients were lost to follow-up and have been excluded from further study. The remaining 480 patients form the basis of this report. Clinical status and PSA values were systematically recorded before and after treatment. Results: With a median follow-up of 35 months (3-70) the actuarial clinical local control is 83%. Both stage and grade are shown to predict for this endpoint. Actuarial BDFS is also correlated with stage, grade, and PSA at presentation. Biochemical disease-free survival at five years is 94% for T1, 70% for unilateral T2, and 34% for T2c tumors. Grade is also predictive, ranging from 85% in low-grade tumors to 30% in high-grade tumors. In a multivariate analysis, the pretreatment PSA is most highly correlated (p < 0.0001). Patients with a normal pretreatment PSA enjoyed 93% BDFS, while those presenting with PSA > 10 had a BDFS of 40%. Complications have been few, with severe urinary urgency or dysuria in 4% and both incontinence and proctitis seen in 1%. Conclusion: While biochemical disease-free survival reports in the literature are immature and have short follow-up, our data compares favorably with studies following radical prostatectomy or radiation therapy. Further follow-up of this cohort is required. The complication rate is low and patient acceptance excellent. Permanent implantation of I-125 as the sole treatment for early prostate cancer is a viable alternative for patients with

Isopropanolic black cohosh extract and recurrence-free survival after breast cancer.

Science.gov (United States)

Henneicke-von Zepelin, H H; Meden, H; Kostev, K; Schröder-Bernhardi, D; Stammwitz, U; Becher, H

2007-03-01

To investigate the influence of an isopropanolic Cimicifuga racemosa extract (iCR) on recurrence-free survival after breast cancer, including estrogen-dependent tumors. This pharmacoepidemiologic observational retrospective cohort study examined breast cancer patients treated at general, gynecological and internal facilities linked to a medical database in Germany. The main endpoint was disease-free survival following a diagnosis of breast cancer. The impact of treatment with iCR following diagnosis was analyzed by Cox-proportional hazards models, controlling for age and other confounders. Of 18,861 patients, a total of 1,102 had received an iCR therapy. The mean overall observation time was 3.6 years. Results showed that iCR was not associated with an increase in the risk of recurrence but associated with prolonged disease-free survival. After 2 years following initial diagnosis, 14% of the control group had developed a recurrence, while the iCR group reached this proportion after 6.5 years. The primary Cox regression model controlling for age, tamoxifen use and other confounders demonstrated a protractive effect of iCR on the rate of recurrence (hazard ratio 0.83, 95% confidence interval 0.69 0.99). This effect remained consistent throughout all variations of the statistical model, including subgroup analyses. TNM status was unknown but did not bias the iCR treatment decision as investigated separately. Hence, it was assumed to be equally distributed between treatment groups. Correlation analyses showed good internal and external validity of the database. An increase in the risk of breast cancer recurrence for women having had iCR treatment, compared to women not treated with iCR is unlikely.

Improved treatment results in high-risk pediatric acute myeloid leukemia patients after intensification with high-dose cytarabine and mitoxantrone: results of Study Acute Myeloid Leukemia-Berlin-Frankfurt-Münster 93.

Science.gov (United States)

Creutzig, U; Ritter, J; Zimmermann, M; Reinhardt, D; Hermann, J; Berthold, F; Henze, G; Jürgens, H; Kabisch, H; Havers, W; Reiter, A; Kluba, U; Niggli, F; Gadner, H

2001-05-15

To improve outcome in high-risk patients, high-dose cytarabine and mitoxantrone (HAM) was introduced into the treatment of children with acute myelogenous leukemia (AML) in study AML-BFM 93. Patients were randomized to HAM as either the second or third therapy block, for the purpose of evaluation of efficacy and toxicity. A total of 471 children with de novo AML were entered onto the trial; 161 were at standard risk and 310 were at high risk. After the randomized induction (daunorubicin v idarubicin), further therapy, with the exception of HAM, was identical in the two risk groups and also comparable to that in study Acute Myeloid Leukemia-Berlin-Frankfurt-Münster (AML-BFM) 87. Overall, 387 (82%) of 471 patients achieved complete remission, and 5-year survival, event-free survival (EFS), and disease-free survival rates were 60%, 51%, and 62%, respectively. Idarubicin induction resulted in a significantly better blast cell reduction in the bone marrow on day 15. Estimated survival and probability of EFS were superior in study AML-BFM 93 compared with study AML-BFM 87 (P =.01, log-rank test). This improvement, however, was restricted to the 310 high-risk patients (remission rate and probability of 5-year EFS in study AML-BFM 93 v study AML-BFM 87: 78% v 68%, P =.007; and 44% v 31%, P =.01, log-rank test). Probability of 5-year EFS among standard-risk patients in study AML-BFM 93 was similar to that in study AML-BFM 87 (65% v 63%, P = not significant). Whether HAM was placed as the second or third therapy block was of minor importance. However, patients who received the less intensive daunorubicin treatment during induction benefited from early HAM. Improved treatment results in children with high-risk AML in study AML-BFM 93 must be attributed mainly to the introduction of HAM.

Amputation-Free Survival after Crural Percutaneous Transluminal Angioplasty for Critical Limb Ischemia

DEFF Research Database (Denmark)

Strøm, M; Konge, L; Lönn, L

2016-01-01

BACKGROUND AND AIM: To evaluate the amputation-free survival after below the knee percutaneous transluminal angioplasty in a consecutive group of patients with critical ischemia of the lower extremity. MATERIALS AND METHODS: A total of 70 consecutive patients with critical ischemia were treated......-up clinical examinations were performed within 6 weeks and after 1 year. All medical records were crosschecked with the national vascular registry ensuring a valid 1-year status in 97% of the patients. RESULTS: A total of 15 major amputations were performed during follow-up, with 11 amputations performed...... within the first year. Complications after percutaneous transluminal angioplasty were rare. Cumulative mortality after 1 and 2 years was 22% and 34%, respectively. Amputation-free survival at 1 and 2 years of follow-up was 68% and 58%, respectively. There were no association between known risk factors...

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

Directory of Open Access Journals (Sweden)

Verduyn S

2012-09-01

Full Text Available Abstract 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

Extreme climatic events constrain space use and survival of a ground-nesting bird.

Science.gov (United States)

Tanner, Evan P; Elmore, R Dwayne; Fuhlendorf, Samuel D; Davis, Craig A; Dahlgren, David K; Orange, Jeremy P

2017-05-01

Two fundamental issues in ecology are understanding what influences the distribution and abundance of organisms through space and time. While it is well established that broad-scale patterns of abiotic and biotic conditions affect organisms' distributions and population fluctuations, discrete events may be important drivers of space use, survival, and persistence. These discrete extreme climatic events can constrain populations and space use at fine scales beyond that which is typically measured in ecological studies. Recently, a growing body of literature has identified thermal stress as a potential mechanism in determining space use and survival. We sought to determine how ambient temperature at fine temporal scales affected survival and space use for a ground-nesting quail species (Colinus virginianus; northern bobwhite). We modeled space use across an ambient temperature gradient (ranging from -20 to 38 °C) through a maxent algorithm. We also used Andersen-Gill proportional hazard models to assess the influence of ambient temperature-related variables on survival through time. Estimated available useable space ranged from 18.6% to 57.1% of the landscape depending on ambient temperature. The lowest and highest ambient temperature categories (35 °C, respectively) were associated with the least amount of estimated useable space (18.6% and 24.6%, respectively). Range overlap analysis indicated dissimilarity in areas where Colinus virginianus were restricted during times of thermal extremes (range overlap = 0.38). This suggests that habitat under a given condition is not necessarily a habitat under alternative conditions. Further, we found survival was most influenced by weekly minimum ambient temperatures. Our results demonstrate that ecological constraints can occur along a thermal gradient and that understanding the effects of these discrete events and how they change over time may be more important to conservation of organisms than are average and broad

Predictors and Prognostic Value of Worsening Renal Function During Admission in HFpEF Versus HFrEF: Data From the KorAHF (Korean Acute Heart Failure) Registry.

Science.gov (United States)

Kang, Jeehoon; Park, Jin Joo; Cho, Young-Jin; Oh, Il-Young; Park, Hyun-Ah; Lee, Sang Eun; Kim, Min-Seok; Cho, Hyun-Jai; Lee, Hae-Young; Choi, Jin Oh; Hwang, Kyung-Kuk; Kim, Kye Hun; Yoo, Byung-Su; Kang, Seok-Min; Baek, Sang Hong; Jeon, Eun-Seok; Kim, Jae-Joong; Cho, Myeong-Chan; Chae, Shung Chull; Oh, Byung-Hee; Choi, Dong-Ju

2018-03-13

Worsening renal function (WRF) is associated with adverse outcomes in patients with heart failure. We investigated the predictors and prognostic value of WRF during admission, in patients with preserved ejection fraction (HFpEF) versus those with reduced ejection fraction (HFrEF). A total of 5625 patients were enrolled in the KorAHF (Korean Acute Heart Failure) registry. WRF was defined as an absolute increase in creatinine of ≥0.3 mg/dL. Transient WRF was defined as recovery of creatinine at discharge, whereas persistent WRF was indicated by a nonrecovered creatinine level. HFpEF and HFrEF were defined as a left ventricle ejection fraction ≥50% and ≤40%, respectively. Among the total population, WRF occurred in 3101 patients (55.1%). By heart failure subgroup, WRF occurred more frequently in HFrEF (57.0% versus 51.3%; P failure subgroups. Among various predictors of WRF, chronic renal failure was the strongest predictor. WRF was an independent predictor of adverse in-hospital outcomes (HFrEF: odds ratio; 2.75; 95% confidence interval, 1.50-5.02; P =0.001; HFpEF: odds ratio, 9.48; 95% confidence interval, 1.19-75.89; P =0.034) and 1-year mortality (HFrEF: hazard ratio, 1.41; 95% confidence interval, 1.12-1.78; P =0.004 versus HFpEF: hazard ratio, 1.72; 95% confidence interval, 1.23-2.42; P =0.002). Transient WRF was a risk factor for 1-year mortality, whereas persistent WRF had no additive risk compared to transient WRF. In patients with acute heart failure patients, WRF is an independent predictor of adverse in-hospital and follow-up outcomes in both HFrEF and HFpEF, though with a different effect size. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01389843. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Consolidation chemoradiotherapy and autologous bone marrow transplantation versus continued chemotherapy for metastatic neuroblastoma: a report of two concurrent Children's Cancer Group studies.

Science.gov (United States)

Stram, D O; Matthay, K K; O'Leary, M; Reynolds, C P; Haase, G M; Atkinson, J B; Brodeur, G M; Seeger, R C

1996-09-01

To compare event-free survival (EFS) for patients with stage IV neuroblastoma who were treated with induction chemotherapy followed by additional courses of the same chemotherapy or by intensive chemoradiotherapy and autologous bone marrow transplantation (ABMT). Two hundred seven children who were diagnosed with stage IV neuroblastoma after 1 year of age were given five to seven courses of induction chemotherapy consisting of cisplatin, etoposide, doxorubicin, and cyclophosphamide (CCC-321-P2). This chemotherapy was continued for 13 total courses for some patients, whereas intensive chemoradiotherapy with ABMT was given to others (CCG-321-P3). The decision to continue chemotherapy versus to consolidate with chemoradiotherapy was not randomized but was made by parents and physicians. Marrow used for ABMT was purged ex vivo and was free of immunocytologically detectable neuroblastoma cells. One hundred fifty-nine of 207 patients (77%) remained event-free during induction therapy. Of these, 67 received chemoradiotherapy/ABMT (CCG-321-P3) and 74 continued chemotherapy (CCG-321-P2). Using Cox regression analysis, the relative risk (RR) of an event after chemoradiotherapy/ABMT was estimated to be 58% of that for patients who continued chemotherapy (P = .01). Similarly, Kaplan-Meier analysis estimated EFS at four years for the chemoradiotherapy/ABMT and chemotherapy groups to be 40% and 19% respectively (P = .019). Subgroups appearing to benefit from chemoradiotherapy/ABMT were those with only a partial tumor response to induction chemotherapy (RR = 0.43; P = .008; EFS, 29% v 6%) and those whose tumors had amplification of the N-myc gene (RR = 0.26; P = .112; EFS, 67% v 0%). Consolidation with intensive, myeloablative chemoradiotherapy followed by purged ABMT may be more effective than continuing chemotherapy for patients with stage IV neuroblastoma.

Influence of an extreme high water event on survival, reproduction, and distribution of snail kites in Florida, USA

Science.gov (United States)

Bennetts, R.E.; Kitchens, W.M.; Dreitz, V.J.

2002-01-01

Hydrology frequently has been reported as the environmental variable having the greatest influence on Florida snail kite (Rostrhamus sociabilis) populations. Although drought has received the most attention, high-water conditions also have been reported to affect kites. Years of high water generally have been reported to be favorable for nesting, although prolonged high water may be detrimental to sustaining suitable habitat. During 1994 and 1995, southern Florida experienced an extreme high water event. This event enabled us to compare survival, nesting success, number of young per successful nest, and spatial distribution of nesting before, during, and after the event. We found no evidence of an effect (either negative or positive) on survival of adult kites. In contrast, juvenile kites experienced the highest survival during the event, although our data suggest greater annual variability than can be explained by the event alone. We found no evidence of an effect of the high water event on nest success or number of young per successful nest. Nest success was highest during the event in the southern portion of the range but was quite similar to other years, both before and after the event. Our data do indicate a substantial shift in the spatial distribution of nesting birds. During the event, nesting activity shifted to higher elevations (i.e., shallower water) in the major nesting areas of the Everglades region. Nesting also occurred in Big Cypress National Preserve during the event, which is typically too dry to support nesting kites. Thus, our data indicate a potential short-term benefit of increased juvenile survival and an expansion of nesting habitat. However, the deterioration of habitat quality from prolonged high water precludes any recommendation for such conditions to be maintained for extended periods. ?? 2002, The Society of Wetland Scientists.

Analysis of audiometric relapse-free survival in patients with immune-mediated hearing loss exclusively treated with corticosteroids.

Science.gov (United States)

Mata-Castro, Nieves; García-Chilleron, Raimon; Gavilanes-Plasencia, Javier; Ramírez-Camacho, Rafael; García-Fernández, Alfredo; García-Berrocal, José Ramón

2017-10-12

To describe the results in terms of audiometric relapse-free survival and relapse rate in immunomediated hearing loss patients treated exclusively with corticosteroids. Retrospective study of patients with audiometric relapses, monitored from 1995 to 2014, in two centres of the Community of Madrid. We evaluated 31 patients with a mean age of 48.52 years (14.67 SD), of which 61.3% were women. Most hearing loss was fluctuating (48.4%). Only 16.1% of patients had systemic autoimmune disease. There is a moderate positive correlation between the sex variable and the systemic involvement variable (Spearman's correlation coefficient=0.356): specifically, between being female and systemic disease. The relative incidence rate of relapse in the first year was 2.01 relapses/year with a 95% CI (1.32 to 2.92). The mean survival time of the event (audiometric relapse) was 5.25 months (SD 0.756). With multivariate analysis, the only variable that achieved statistical significance was age, with a hazard ratio of 1.032 (95% CI; 1.001-1.063, P=.043). Immune-mediated disease of the inner ear is a chronic disease with relapses. Half of the patients with immunomediated hearing loss treated exclusively with corticosteroids relapse before 6 months of follow-up. In addition, if a patient has not relapsed, they are more likely to relapse as each year passes. Analysis of the of audiometric relapse- free survival will enable the effect of future treatments to be compared and their capacity to reduce the rhythm of relapses. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

Pathophysiological understanding of HFpEF: microRNAs as part of the puzzle.

Science.gov (United States)

Rech, Monika; Barandiarán Aizpurua, Arantxa; van Empel, Vanessa; van Bilsen, Marc; Schroen, Blanche

2018-05-01

Half of all heart failure patients have preserved ejection fraction (HFpEF). Comorbidities associated with and contributing to HFpEF include obesity, diabetes and hypertension. Still, the underlying pathophysiological mechanisms of HFpEF are unknown. A preliminary consensus proposes that the multi-morbidity triggers a state of systemic, chronic low-grade inflammation, and microvascular dysfunction, causing reduced nitric oxide bioavailability to adjacent cardiomyocytes. As a result, the cardiomyocyte remodels its contractile elements and fails to relax properly, causing diastolic dysfunction, and eventually HFpEF. HFpEF is a complex syndrome for which currently no efficient therapies exist. This is notably due to the current one-size-fits-all therapy approach that ignores individual patient differences. MicroRNAs have been studied in relation to pathophysiological mechanisms and comorbidities underlying and contributing to HFpEF. As regulators of gene expression, microRNAs may contribute to the pathophysiology of HFpEF. In addition, secreted circulating microRNAs are potential biomarkers and as such, they could help stratify the HFpEF population and open new ways for individualized therapies. In this review, we provide an overview of the ever-expanding world of non-coding RNAs and their contribution to the molecular mechanisms underlying HFpEF. We propose prospects for microRNAs in stratifying the HFpEF population. MicroRNAs add a new level of complexity to the regulatory network controlling cardiac function and hence the understanding of gene regulation becomes a fundamental piece in solving the HFpEF puzzle.

Ewing's sarcoma: only patients with 100% of necrosis after chemotherapy should be classified as having a good response.

Science.gov (United States)

Albergo, J I; Gaston, C L; Laitinen, M; Darbyshire, A; Jeys, L M; Sumathi, V; Parry, M; Peake, D; Carter, S R; Tillman, R; Abudu, A T; Grimer, R J

2016-08-01

The purpose of this study was to review a large cohort of patients and further assess the correlation between the histological response to chemotherapy in patients with Ewing's sarcoma with the overall (OS) and event-free survival (EFS). All patients treated for Ewing's sarcoma between 1980 and 2012 were reviewed. Of these, 293 patients without metastases at the time of diagnosis and treated with chemotherapy and surgery were included. Patients were grouped according to the percentage of necrosis after chemotherapy: Group I: 0% to 50%, Group II: 51% to 99% and Group III: 100%. The mean age at diagnosis was 16 years (1 to 62) and the mean follow-up was 9.1 years (six months to 32.6 years). The OS and EFS for the series were 75% and 65% at five years. There were significant differences in survival between the groups of necrosis: 0% to 50% (OS: 49% and EFS: 45% at five years, respectively) compared with 51% to 99% (OS: 72% and EFS: 59% at five years, respectively) and 100% (OS: 94% and EFS: 81% at five years, respectively) (p < 0.001). There were no significant differences in survival between patients treated between 1980 and 1989 compared with those treated between 1990 and 1999, and those treated between 2000 and 2012 (p = 0.55). Only patients with 100% necrosis after chemotherapy should be classified as having a good response to chemotherapy because they have significantly better rates of survival compared with those with any viable tumour in the surgical specimen. Cite this article: Bone Joint J 2016;98-B:1138-44. ©2016 The British Editorial Society of Bone & Joint Surgery.

The long-term clinical implications of clonal chromosomal abnormalities in newly diagnosed chronic phase chronic myeloid leukemia patients treated with imatinib mesylate.

Science.gov (United States)

Lee, Sung-Eun; Choi, Soo Young; Bang, Ju-Hee; Kim, Soo-Hyun; Jang, Eun-Jung; Byeun, Ji-Young; Park, Jin Eok; Jeon, Hye-Rim; Oh, Yun Jeong; Kim, Myungshin; Kim, Dong-Wook

2012-11-01

The aim of this study was to evaluate the long-term clinical significance of an additional chromosomal abnormality (ACA), variant Philadelphia chromosome (vPh) at diagnosis, and newly developed other chromosomal abnormalities (OCA) in patients with chronic myeloid leukemia (CML) on imatinib (IM) therapy. Sequential cytogenetic data from 281 consecutive new chronic phase CML patients were analyzed. With a median follow-up of 78.6 months, the 22 patients with vPh (P = 0.034) or ACA (P = 0.034) at diagnosis had more events of IM failure than did the patients with a standard Ph. The 5-year overall survival (OS), event-free survival (EFS), and failure-free survival (FFS) rates for patients with vPh at diagnosis were 77.8%, 75.0%, and 53.3%, respectively; for patients with ACA at diagnosis, 100%, 66.3%, and 52.1%, respectively; and for patients with a standard Ph, 96.0%, 91.3%, and 83.7%, respectively. During IM therapy, eight patients developed an OCA, which had no impact on outcomes as a time-dependent covariate in our Cox proportional hazards regression models. This study showed that vPh was associated with poor OS and FFS and that ACA had adverse effects on EFS and FFS. In addition, no OCA, except monosomy 7, had any prognostic impact, suggesting that the development of OCA may not require a change in treatment strategy. Copyright © 2012 Elsevier Inc. All rights reserved.

Velocity ratio predicts outcomes in patients with low gradient severe aortic stenosis and preserved EF

DEFF Research Database (Denmark)

Jander, Nikolaus; Hochholzer, Willibald; Kaufmann, Beat A

2014-01-01

OBJECTIVE: To evaluate the usefulness of velocity ratio (VR) in patients with low gradient severe aortic stenosis (LGSAS) and preserved EF. BACKGROUND: LGSAS despite preserved EF represents a clinically challenging entity. Reliance on mean pressure gradient (MPG) may underestimate stenosis severity...... for severe stenosis. We hypothesised that VR may have conceptual advantages over MPG and AVA, predict clinical outcomes and thereby be useful in the management of patients with LGSAS. METHODS: Patients from the prospective Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study with an AVA...≤40 mm Hg and EF≥55% and asymptomatic at baseline were stratified according to VR with a cut-off value of 0.25. Outcomes were evaluated according to aortic valve-related events and cardiovascular death. RESULTS: Of 435 patients with LGSAS, 197 (45%) had VRVR≥0...

TRIO-EF a general thermal hydraulics computer code applied to the Avlis process

International Nuclear Information System (INIS)

Magnaud, J.P.; Claveau, M.; Coulon, N.; Yala, P.; Guilbaud, D.; Mejane, A.

1993-01-01

TRIO(EF is a general purpose Fluid Mechanics 3D Finite Element Code. The system capabilities cover areas such as steady state or transient, laminar or turbulent, isothermal or temperature dependent fluid flows; it is applicable to the study of coupled thermo-fluid problems involving heat conduction and possibly radiative heat transfer. It has been used to study the thermal behaviour of the AVLIS process separation module. In this process, a linear electron beam impinges the free surface of a uranium ingot, generating a two dimensional curtain emission of vapour from a water-cooled crucible. The energy transferred to the metal causes its partial melting, forming a pool where strong convective motion increases heat transfer towards the crucible. In the upper part of the Separation Module, the internal structures are devoted to two main functions: vapor containment and reflux, irradiation and physical separation. They are subjected to very high temperature levels and heat transfer occurs mainly by radiation. Moreover, special attention has to be paid to electron backscattering. These two major points have been simulated numerically with TRIO-EF and the paper presents and comments the results of such a computation, for each of them. After a brief overview of the computer code, two examples of the TRIO-EF capabilities are given: a crucible thermal hydraulics model, a thermal analysis of the internal structures

Contrast in atomically resolved EF-SCEM imaging

Energy Technology Data Exchange (ETDEWEB)

Wang, Peng [National Laboratory of Solid State Microstructures and Department of Materials Science and Engineering, Nanjing University, Nanjing 210093 (China); D’Alfonso, Adrian J. [School of Physics, University of Melbourne, Parkville, Victoria 3010 (Australia); Hashimoto, Ayako [Surface Physics and Structure Unit, National Institute for Materials Science, 1-2-1 Sengen, Tsukuba 305-0047 (Japan); Global Research Center for Environment and Energy based on Nanomaterials Science, National Institute for Materials Science, 1-2-1 Sengen, Tsukuba, 305-0047 (Japan); Electron Microscopy Station, National Institute for Materials Science, 3-13 Sakura, Tsukuba 305-0003 (Japan); Morgan, Andrew J. [School of Physics, University of Melbourne, Parkville, Victoria 3010 (Australia); Takeguchi, Masaki [Surface Physics and Structure Unit, National Institute for Materials Science, 1-2-1 Sengen, Tsukuba 305-0047 (Japan); Electron Microscopy Station, National Institute for Materials Science, 3-13 Sakura, Tsukuba 305-0003 (Japan); Mitsuishi, Kazutaka [Surface Physics and Structure Unit, National Institute for Materials Science, 1-2-1 Sengen, Tsukuba 305-0047 (Japan); Global Research Center for Environment and Energy based on Nanomaterials Science, National Institute for Materials Science, 1-2-1 Sengen, Tsukuba, 305-0047 (Japan); Electron Microscopy Station, National Institute for Materials Science, 3-13 Sakura, Tsukuba 305-0003 (Japan); Shimojo, Masayuki [Department of Materials Science and Engineering, Shibaura Institute of Technology, 3-7-5, Toyosu, Koto-ku, Tokyo, 135-8548 (Japan); Kirkland, Angus I. [Department of Materials, University of Oxford, Parks Road, Oxford OX1 3PH (United Kingdom); Allen, Leslie J. [School of Physics, University of Melbourne, Parkville, Victoria 3010 (Australia); Nellist, Peter D., E-mail: peter.nellist@materials.ox.ac.uk [Department of Materials, University of Oxford, Parks Road, Oxford OX1 3PH (United Kingdom)

2013-11-15

Energy-filtered scanning confocal electron microscopy (EF-SCEM) is a technique that uses the reduced depth of field of an aberration-corrected transmission electron microscope to provide three-dimensional (3D) compositional information. Using a silicon sample in the <110> orientation, we show that EF-SCEM image data can be recorded that shows lattice resolution in the plane perpendicular to the incident beam direction. The confocal effect is demonstrated through the reduction of the mean intensity as the confocal plane is displaced from the sample mid-plane, unlike optical sectioning in high-angle annular dark-field scanning transmission electron microscopy (STEM). Simulations of the EF-SCEM data show agreement with the experimental data, and allow the interpretability of the data to be explored. The effects of channelling, absorption and delocalisation complicate the quantitative and qualitative interpretation of the data, highlighting the need for matching to simulations. Finally the effects of the finite detector pin-hole aperture size are explored, and we show that the EF-SCEM contrast in the plane perpendicular to the beam direction starts to resemble that of a STEM spectrum imaging experiment as the aperture size increases. - Highlights: • Atomically resolved energy-filtered scanning confocal electron microscopy (EF-SCEM) is demonstrated. • The confocal effect is demonstrated through the reduction of the mean intensity as the confocal plane is displaced from the sample mid-plane. • Simulations show agreement with the experimental data. • The effects of channelling, absorption and delocalisation complicate the quantitative and qualitative interpretation of the data. • The effects of the finite detector pin-hole aperture size are explored.

Contrast in atomically resolved EF-SCEM imaging

International Nuclear Information System (INIS)

Wang, Peng; D’Alfonso, Adrian J.; Hashimoto, Ayako; Morgan, Andrew J.; Takeguchi, Masaki; Mitsuishi, Kazutaka; Shimojo, Masayuki; Kirkland, Angus I.; Allen, Leslie J.; Nellist, Peter D.

2013-01-01

Energy-filtered scanning confocal electron microscopy (EF-SCEM) is a technique that uses the reduced depth of field of an aberration-corrected transmission electron microscope to provide three-dimensional (3D) compositional information. Using a silicon sample in the orientation, we show that EF-SCEM image data can be recorded that shows lattice resolution in the plane perpendicular to the incident beam direction. The confocal effect is demonstrated through the reduction of the mean intensity as the confocal plane is displaced from the sample mid-plane, unlike optical sectioning in high-angle annular dark-field scanning transmission electron microscopy (STEM). Simulations of the EF-SCEM data show agreement with the experimental data, and allow the interpretability of the data to be explored. The effects of channelling, absorption and delocalisation complicate the quantitative and qualitative interpretation of the data, highlighting the need for matching to simulations. Finally the effects of the finite detector pin-hole aperture size are explored, and we show that the EF-SCEM contrast in the plane perpendicular to the beam direction starts to resemble that of a STEM spectrum imaging experiment as the aperture size increases. - Highlights: • Atomically resolved energy-filtered scanning confocal electron microscopy (EF-SCEM) is demonstrated. • The confocal effect is demonstrated through the reduction of the mean intensity as the confocal plane is displaced from the sample mid-plane. • Simulations show agreement with the experimental data. • The effects of channelling, absorption and delocalisation complicate the quantitative and qualitative interpretation of the data. • The effects of the finite detector pin-hole aperture size are explored

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

Science.gov (United States)

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

2017-07-01

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

Roles of Protein Synthesis Elongation Factor EF-Tu in Heat Tolerance in Plants

Directory of Open Access Journals (Sweden)

Jianming Fu

2012-01-01

Full Text Available EF-Tu proteins of plastids, mitochondria, and the cytosolic counterpart EF-1α in plants, as well as EF-Tu proteins of bacteria, are highly conserved and multifunctional. The functions of EF-Tu include transporting the aminoacyl-tRNA complex to the A site of the ribosome during protein biosynthesis; chaperone activity in protecting other proteins from aggregation caused by environmental stresses, facilitating renaturation of proteins when conditions return to normal; displaying a protein disulfide isomerase activity; participating in the degradation of N-terminally blocked proteins by the proteasome; eliciting innate immunity and triggering resistance to pathogenic bacteria in plants; participating in transcription when an E. coli host is infected with phages. EF-Tu genes are upregulated by abiotic stresses in plants, and EF-Tu plays important role in stress responses. Expression of a plant EF-Tu gene confers heat tolerance in E. coli, maize knock-out EF-Tu null mutants are heat susceptible, and over-expression of an EF-Tu gene improves heat tolerance in crop plants. This review paper summarizes the current knowledge of EF-Tu proteins in stress responses in plants and progress on application of EF-Tu for developing crop varieties tolerant to abiotic stresses, such as high temperatures.

Simultaneous Binding of Multiple EF-Tu Copies to Translating Ribosomes in Live Escherichia coli.

Science.gov (United States)

Mustafi, Mainak; Weisshaar, James C

2018-01-16

In bacteria, elongation factor Tu is a translational cofactor that forms ternary complexes with aminoacyl-tRNA (aa-tRNA) and GTP. Binding of a ternary complex to one of four flexible L7/L12 units on the ribosome tethers a charged tRNA in close proximity to the ribosomal A site. Two sequential tests for a match between the aa-tRNA anticodon and the current mRNA codon then follow. Because one elongation cycle can occur in as little as 50 ms and the vast majority of aa-tRNA copies are not cognate with the current mRNA codon, this testing must occur rapidly. We present a single-molecule localization and tracking study of fluorescently labeled EF-Tu in live Escherichia coli Imaging at 2 ms/frame distinguishes 60% slowly diffusing EF-Tu copies (assigned as transiently bound to translating ribosome) from 40% rapidly diffusing copies (assigned as a mixture of free ternary complexes and free EF-Tu). Combining these percentages with copy number estimates, we infer that the four L7/L12 sites are essentially saturated with ternary complexes in vivo. The results corroborate an earlier inference that all four sites can simultaneously tether ternary complexes near the A site, creating a high local concentration that may greatly enhance the rate of testing of aa-tRNAs. Our data and a combinatorial argument both suggest that the initial recognition test for a codon-anticodon match occurs in less than 1 to 2 ms per aa-tRNA copy. The results refute a recent study (A. Plochowietz, I. Farrell, Z. Smilansky, B. S. Cooperman, and A. N. Kapanidis, Nucleic Acids Res 45:926-937, 2016, https://doi.org/10.1093/nar/gkw787) of tRNA diffusion in E. coli that inferred that aa-tRNAs arrive at the ribosomal A site as bare monomers, not as ternary complexes. IMPORTANCE Ribosomes catalyze translation of the mRNA codon sequence into the corresponding sequence of amino acids within the nascent polypeptide chain. Polypeptide elongation can be as fast as 50 ms per added amino acid. Each amino acid

Proteomic biomarkers for overall and progression-free survival in ovarian cancer patients

DEFF Research Database (Denmark)

Høgdall, Estrid; Fung, Eric T; Christensen, Ib Jarle

2010-01-01

To determine if the level of apolipoprotein A1, hepcidin, transferrin, inter-α trypsin IV internal fragment, transthyretin (TT), connective-tissue activating protein 3 (CTAP3), serum amyloid A1, β-2 microglobulin (B2M) might have impact on overall and progression-free survival for ovarian cancer...

Proteomic biomarkers for overall and progression-free survival in ovarian cancer patients

DEFF Research Database (Denmark)

Høgdall, Estrid; Fung, Eric T; Christensen, Ib Jarle

2010-01-01

To determine if the level of apolipoprotein A1, hepcidin, transferrin, inter-a trypsin IV internal fragment, transthyretin (TT), connective-tissue activating protein 3 (CTAP3), serum amyloid A1, ß-2 microglobulin (B2M) might have impact on overall and progression-free survival for ovarian cancer...

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

Science.gov (United States)

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

2018-05-01

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

Chronic myeloid leukemia patients in Tunisia: epidemiology and outcome in the imatinib era (a multicentric experience).

Science.gov (United States)

Ben Lakhal, Raihane; Ghedira, Hela; Bellaaj, Hatem; Ben Youssef, Yosra; Menif, Samia; Manai, Zeineb; Bedoui, Manel; Lakhal, Amel; M'Sadek, Fehmi; Elloumi, Moez; Khélif, Abderrahmane; Ben Romdhane, Neila; Laatiri, Mohamed Adnène; Ben Othmen, Tarek; Meddeb, Balkis

2018-04-01

Data are limited in developing countries regarding the clinicopathologic features and response to therapy of chronic myeloid leukemia (CML) in the era of imatinib (IM). The objective of this study is to report on the clinicoepidemiologic features of CML in Tunisia, to evaluate the long-term outcome of patients in chronic (CP) or accelerated phase (AP) treated with IM 400 mg daily as frontline therapy, and to determine imatinib's efficacy and safety. From October 2002 to December 2014, 410 CML patients were treated with IM in six Tunisian departments of hematology. Response (hematologic, cytogenetic, and molecular responses) and outcome-overall survival (OS), event-free survival (EFS), and progression-free survival (PFS)-were evaluated. The following prognostic factors were analyzed for their impact on the European leukemia net (ELN) response, OS, EFS, and PFS at 5 years: age, sex, leukocyte count, Sokal score, European Treatment and Outcome Study (EUTOS) score, CML phase, time to starting IM, and impact of adverse events. The median age was 45 years (3-85 years). Two hundred ten (51.2%) patients were male. Splenomegaly was present in 322 of the 410 (79%). Additional cytogenetic abnormalities were encountered in 25 (6.3%) patients. At diagnosis, 379 (92.4%) patients were in CP, 31 (7.6%) were in AP. The Sokal risk was low in 87 (22.5%), intermediate in 138 (35.7%), and high in 164 patients (41.9%). The EUTOS risk was low in 217 (74%), and high in 77 (26%) patients. The rates of cumulative complete cytogenetic response (CCyR), major molecular response (MMR), and molecular response 4/5 log (MR4.5) in CP/AP-CML patients were 72, 68.4, and 46.4%, respectively. The median time to reach CCyR, MMR, and MR4.5 was 6 months (3-51), 18 months (3-72), and 24 months (3-100), respectively. According to the ELN criteria, optimal, suboptimal response, and failure were noted in 206 (51.8%), 61 (15.3%), and 125 (31.4%) patients, respectively. Five-year event-free survival (EFS

Hazardous Waste/IGD: EF_RCRA

Data.gov (United States)

U.S. Environmental Protection Agency — EF_RCRA is a subset of facilities from FRS_INTEREST and FRS_FACILITY_SITE which are updated on a monthly basis as part of the Locational Reference Tables (LRT)...

Air Emissions/IGD: EF_AFS

Data.gov (United States)

U.S. Environmental Protection Agency — EF_AFS is a subset of facilities from FRS_INTEREST and FRS_FACILITY_SITE which are updated on a monthly basis as part of the Locational Reference Tables (LRT)...

Water Dischargers/IGD: EF_NPDES

Data.gov (United States)

U.S. Environmental Protection Agency — EF_NPDES is a subset of facilities from FRS_INTEREST and FRS_FACILITY_SITE which are updated on a monthly basis as part of the Locational Reference Tables (LRT)...

Toxic Releases/IGD: EF_TRI

Data.gov (United States)

U.S. Environmental Protection Agency — EF_TRI is a subset of facilities from FRS_INTEREST and FRS_FACILITY_SITE which are updated on a monthly basis as part of the Locational Reference Tables (LRT)...

Disease-free survival after hepatic resection in hepatocellular carcinoma patients: a prediction approach using artificial neural network.

Directory of Open Access Journals (Sweden)

Wen-Hsien Ho

Full Text Available BACKGROUND: A database for hepatocellular carcinoma (HCC patients who had received hepatic resection was used to develop prediction models for 1-, 3- and 5-year disease-free survival based on a set of clinical parameters for this patient group. METHODS: The three prediction models included an artificial neural network (ANN model, a logistic regression (LR model, and a decision tree (DT model. Data for 427, 354 and 297 HCC patients with histories of 1-, 3- and 5-year disease-free survival after hepatic resection, respectively, were extracted from the HCC patient database. From each of the three groups, 80% of the cases (342, 283 and 238 cases of 1-, 3- and 5-year disease-free survival, respectively were selected to provide training data for the prediction models. The remaining 20% of cases in each group (85, 71 and 59 cases in the three respective groups were assigned to validation groups for performance comparisons of the three models. Area under receiver operating characteristics curve (AUROC was used as the performance index for evaluating the three models. CONCLUSIONS: The ANN model outperformed the LR and DT models in terms of prediction accuracy. This study demonstrated the feasibility of using ANNs in medical decision support systems for predicting disease-free survival based on clinical databases in HCC patients who have received hepatic resection.

Disease-Free Survival after Hepatic Resection in Hepatocellular Carcinoma Patients: A Prediction Approach Using Artificial Neural Network

Science.gov (United States)

Ho, Wen-Hsien; Lee, King-Teh; Chen, Hong-Yaw; Ho, Te-Wei; Chiu, Herng-Chia

2012-01-01

Background A database for hepatocellular carcinoma (HCC) patients who had received hepatic resection was used to develop prediction models for 1-, 3- and 5-year disease-free survival based on a set of clinical parameters for this patient group. Methods The three prediction models included an artificial neural network (ANN) model, a logistic regression (LR) model, and a decision tree (DT) model. Data for 427, 354 and 297 HCC patients with histories of 1-, 3- and 5-year disease-free survival after hepatic resection, respectively, were extracted from the HCC patient database. From each of the three groups, 80% of the cases (342, 283 and 238 cases of 1-, 3- and 5-year disease-free survival, respectively) were selected to provide training data for the prediction models. The remaining 20% of cases in each group (85, 71 and 59 cases in the three respective groups) were assigned to validation groups for performance comparisons of the three models. Area under receiver operating characteristics curve (AUROC) was used as the performance index for evaluating the three models. Conclusions The ANN model outperformed the LR and DT models in terms of prediction accuracy. This study demonstrated the feasibility of using ANNs in medical decision support systems for predicting disease-free survival based on clinical databases in HCC patients who have received hepatic resection. PMID:22235270

Characterization of the 1st and 2nd EF-hands of NADPH oxidase 5 by fluorescence, isothermal titration calorimetry, and circular dichroism

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Wei Chin-Chuan

2012-04-01

Full Text Available Abstract Background Superoxide generated by non-phagocytic NADPH oxidases (NOXs is of growing importance for physiology and pathobiology. The calcium binding domain (CaBD of NOX5 contains four EF-hands, each binding one calcium ion. To better understand the metal binding properties of the 1st and 2nd EF-hands, we characterized the N-terminal half of CaBD (NCaBD and its calcium-binding knockout mutants. Results The isothermal titration calorimetry measurement for NCaBD reveals that the calcium binding of two EF-hands are loosely associated with each other and can be treated as independent binding events. However, the Ca2+ binding studies on NCaBD(E31Q and NCaBD(E63Q showed their binding constants to be 6.5 × 105 and 5.0 × 102 M-1 with ΔHs of -14 and -4 kJ/mol, respectively, suggesting that intrinsic calcium binding for the 1st non-canonical EF-hand is largely enhanced by the binding of Ca2+ to the 2nd canonical EF-hand. The fluorescence quenching and CD spectra support a conformational change upon Ca2+ binding, which changes Trp residues toward a more non-polar and exposed environment and also increases its α-helix secondary structure content. All measurements exclude Mg2+-binding in NCaBD. Conclusions We demonstrated that the 1st non-canonical EF-hand of NOX5 has very weak Ca2+ binding affinity compared with the 2nd canonical EF-hand. Both EF-hands interact with each other in a cooperative manner to enhance their Ca2+ binding affinity. Our characterization reveals that the two EF-hands in the N-terminal NOX5 are Ca2+ specific. Graphical abstract

Survival of patients with Ewing's sarcoma in Yazd-Iran.

Science.gov (United States)

Akhavan, Ali; Binesh, Fariba; Shamshiri, Hadi; Ghanadi, Fazllolah

2014-01-01

The Ewing's sarcoma family is a group of small round cell tumors which accounts for 10-15% of all primary bone neoplasms. The aim of this study was to evaluate the survival of Ewing's sarcoma patients in our province and to determine of influencing factors. All patients with documented Ewing's sarcoma/ primitive neuroectodermal tumor(PNET) family pathology were enrolled in this study during a period of eight years. For all of them local and systemic therapy were carried out. Overall and event free survival and prognostic factors were evaluated. Thirty two patients were enrolled in the study. The median age was 17.5 years. Twenty (65.2%) were male and 9 (28.1%) were aged 14 years or less. Mean disease free survival was 26.8 (95%CI; 13.8-39.9) months and five year disease free survival was 26%. Mean overall survival was 38.7 months (95%CI; 25.9-50.6) and median overall survival was 24 months. Five year overall survival was 25%. From the variables evaluated , only presence of metastatic disease at presentation (p value=0. 028) and complete response (p value =0. 006) had significant relations to overall survival. Survival of Ewing's sarcoma in our province is disappointing. It seems to be mostly due to less effective treatment. Administration of adequate chemotherapy dosage, resection of tumor with negative margins and precise assessment of irradiation volume may prove helpful.

Lightning Prediction using Electric Field Measurements Associated with Convective Events at a Tropical Location

Science.gov (United States)

Jana, S.; Chakraborty, R.; Maitra, A.

2017-12-01

Nowcasting of lightning activities during intense convective events using a single electric field monitor (EFM) has been carried out at a tropical location, Kolkata (22.65oN, 88.45oE). Before and at the onset of heavy lightning, certain changes of electric field (EF) can be related to high liquid water content (LWC) and low cloud base height (CBH). The present study discusses the utility of EF observation to show a few aspects of convective events. Large convective cloud showed by high LWC and low CBH can be detected from EF variation which could be a precursor of upcoming convective events. Suitable values of EF gradient can be used as an indicator of impending lightning events. An EF variation of 0.195 kV/m/min can predict lightning within 17.5 km radius with a probability of detection (POD) of 91% and false alarm rate (FAR) of 8% with a lead time of 45 min. The total number of predicted lightning strikes is nearly 9 times less than that measured by the lightning detector. This prediction technique can, therefore, give an estimate of cloud to ground (CG) and intra cloud (IC) lighting occurrences within the surrounding area. This prediction technique involving POD, FAR and lead time information shows a better prediction capability compared to the techniques reported earlier. Thus an EFM can be effectively used for prediction of lightning events at a tropical location.

Viability, biofilm formation, and MazEF expression in drug-sensitive and drug-resistant Mycobacterium tuberculosis strains circulating in Xinjiang, China.

Science.gov (United States)

Zhao, Ji-Li; Liu, Wei; Xie, Wan-Ying; Cao, Xu-Dong; Yuan, Li

2018-01-01

Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is one of the most common chronic infectious amphixenotic diseases worldwide. Prevention and control of TB are greatly difficult, due to the increase in drug-resistant TB, particularly multidrug-resistant TB. We speculated that there were some differences between drug-sensitive and drug-resistant MTB strains and that mazEF 3,6,9 toxin-antitoxin systems (TASs) were involved in MTB viability. This study aimed to investigate differences in viability, biofilm formation, and MazEF expression between drug-sensitive and drug-resistant MTB strains circulating in Xinjiang, China, and whether mazEF 3,6,9 TASs contribute to MTB viability under stress conditions. Growth profiles and biofilm-formation abilities of drug-sensitive, drug-resistant MTB strains and the control strain H37Rv were monitored. Using molecular biology experiments, the mRNA expression of the mazF 3, 6, and 9 toxin genes, the mazE 3, 6, and 9 antitoxin genes, and expression of the MazF9 protein were detected in the different MTB strains, H37RvΔ mazEF 3,6,9 mutants from the H37Rv parent strain were generated, and mutant viability was tested. Ex vivo culture analyses demonstrated that drug-resistant MTB strains exhibit higher survival rates than drug-sensitive strains and the control strain H37Rv. However, there was no statistical difference in biofilm-formation ability in the drug-sensitive, drug-resistant, and H37Rv strains. mazE 3,6 mRNA-expression levels were relatively reduced in the drug-sensitive and drug-resistant strains compared to H37Rv. Conversely, mazE 3,9 expression was increased in drug-sensitive strains compared to drug-resistant strains. Furthermore, compared with the H37Rv strain, mazF 3,6 expression was increased in drug-resistant strains, mazF 9 expression was increased in drug-sensitive strains, and mazF 9 exhibited reduced expression in drug-resistant strains compared with drug-sensitive strains. Protein expression of mazF9

A Prospective Study of Expectant Observation as Primary Therapy for Neuroblastoma in Young Infants, a Children’s Oncology Group Study

Science.gov (United States)

Nuchtern, Jed G.; London, Wendy B.; Barnewolt, Carol E.; Naranjo, Arlene; McGrady, Patrick W.; Geiger, James D.; Diller, Lisa; Schmidt, Mary Lou; Maris, John M.; Cohn, Susan L.; Shamberger, Robert C.

2015-01-01

Structured Abstract OBJECTIVE To demonstrate that expectant observation of young infants with small adrenal masses would result in excellent event-free and overall survival (EFS and OS). SUMMARY BACKGROUND DATA Neuroblastoma is the most common malignant tumor in infants, and in young infants, 90% are located in the adrenal gland. Although surgical resection is standard therapy, multiple observations suggest that expectant observation could be a safe alternative for infants 2 were referred for surgical resection. RESULTS 87 eligible patients were enrolled, 83 elected observation and 4 chose immediate surgery. 16 observation patients ultimately had surgery; 8 had INSS stage 1 neuroblastoma, 2 had higher stage neuroblastoma (2B and 4S), 2 had low grade adrenocortical neoplasm, 2 had adrenal hemorrhage and 2 had extralobar pulmonary sequestration. The two patients with adrenocortical tumors were resected because of a >50% increase in tumor volume. The 3-year EFS for a neuroblastoma event was 97.7±2.2% within the entire cohort of patients (n=87). The 3-year overall survival was 100% with median follow-up of 3.2 years. 81% of patients on the observation arm were spared resection. CONCLUSIONS Expectant observation of infants <6 months old with small adrenal masses led to excellent EFS and OS while avoiding surgical intervention in a large majority of the patients. PMID:22964741

Predictors for long-term survival free from whole brain radiation therapy in patients treated with radiosurgery for limited brain metastases

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Daniel eGorovets

2015-05-01

Full Text Available Purpose: To identify predictors for prolonged survival free from salvage whole brain radiation therapy (WBRT in patients with brain metastases treated with stereotactic radiosurgery (SRS as their initial radiotherapy approach. Material and Methods: Patients with brain metastases treated with SRS from 2001-2013 at our institution were identified. SRS without WBRT was typically offered to patients with 1-4 brain metastases, Karnofsky Performance Status ≥70, and life expectancy ≥3 mo. Three hundred and eight patients met inclusion criteria for analysis. Medical records were reviewed for patient, disease, and treatment information. Two comparison groups were identified: those with ≥1-yr WBRT-free survival (N=104, and those who died or required salvage WBRT within 3 mo of SRS (N=56. Differences between these groups were assessed by univariate and multivariate analyses.Results: Median survival for all patients was 11 mo. Among patients with ≥1-yr WBRT-free survival, median survival was 33 mo [12-107 mo] with only 21% requiring salvage WBRT. Factors significantly associated with prolonged WBRT-free survival on univariate analysis (p<0.05 included younger age, asymptomatic presentation, RTOG RPA class I, fewer brain metastases, surgical resection, breast primary, new or controlled primary, absence of extracranial metastatic disease, and oligometastatic disease burden (≤5 metastatic lesions. After controlling for covariates, asymptomatic presentation, breast primary, single brain metastasis, absence of extracranial metastases, and oligometastatic disease burden remained independent predictors for favorable WBRT-free survival.Conclusions: A subset of patients with brain metastases can achieve long-term survival after upfront SRS without the need for salvage WBRT. Predictors identified in this study can help select patients that might benefit most from a treatment strategy of SRS alone.

Effect of population size on prospect of species survival

Czech Academy of Sciences Publication Activity Database

Münzbergová, Zuzana

2006-01-01

Roč. 41, - (2006), s. 137-150 ISSN 1211-9520 R&D Projects: GA AV ČR KJB6111303 Institutional research plan: CEZ:AV0Z60050516 Keywords : population * size * survival Subject RIV: EF - Botanics Impact factor: 1.196, year: 2006

Labeled EF-Tus for rapid kinetic studies of pretranslocation complex formation

DEFF Research Database (Denmark)

Liu, Wei; Kavaliauskas, Darius; Schrader, Jared

2014-01-01

The universally conserved translation elongation factor EF-Tu delivers aminoacyl(aa)-tRNA in the form of an aa-tRNA·EF-Tu·GTP ternary complex (TC) to the ribosome where it binds to the cognate mRNA codon within the ribosomal A-site, leading to formation of a pretranslocation (PRE) complex. Here we...... describe preparation of QSY9 and Cy5 derivatives of the variant E348C-EF-Tu that are functional in translation elongation. Together with fluorophore derivatives of aa-tRNA and of ribosomal protein L11, located within the GTPase associated center (GAC), these labeled EF-Tus allow development of two new FRET...... assays that permit the dynamics of distance changes between EF-Tu and both L11 (Tu-L11 assay) and aa-tRNA (Tu-tRNA assay) to be determined during the decoding process. We use these assays to examine: (i) the relative rates of EF-Tu movement away from the GAC and from aa-tRNA during decoding, (ii...

Disease-free survival after complete mesocolic excision compared with conventional colon cancer surgery

DEFF Research Database (Denmark)

Bertelsen, Claus Anders; Neuenschwander, Anders Ulrich; Jansen, Jens Erik

2015-01-01

BACKGROUND: Application of the principles of total mesorectal excision to colon cancer by undertaking complete mesocolic excision (CME) has been proposed to improve oncological outcomes. We aimed to investigate whether implementation of CME improved disease-free survival compared with conventional...... consisted of patients who underwent CME surgery in a centre validated to perform such surgery; the control group consisted of patients undergoing conventional colon resection in three other hospitals. Data were collected from the Danish Colorectal Cancer Group (DCCG) database and medical charts. Patients...... updated by the National Central Office of Civil Registration. FINDINGS: The CME group consisted of 364 patients and the non-CME group consisted of 1031 patients. For all patients, 4-year disease-free survival was 85.8% (95% CI 81.4-90.1) after CME and 75.9% (72.2-79.7) after non-CME surgery (log-rank p=0...

Complete surgical resection improves outcome in INRG high-risk patients with localized neuroblastoma older than 18 months.

Science.gov (United States)

Fischer, Janina; Pohl, Alexandra; Volland, Ruth; Hero, Barbara; Dübbers, Martin; Cernaianu, Grigore; Berthold, Frank; von Schweinitz, Dietrich; Simon, Thorsten

2017-08-04

Although several studies have been conducted on the role of surgery in localized neuroblastoma, the impact of surgical timing and extent of primary tumor resection on outcome in high-risk patients remains controversial. Patients from the German neuroblastoma trial NB97 with localized neuroblastoma INSS stage 1-3 age > 18 months were included for retrospective analysis. Imaging reports were reviewed by two independent physicians for Image Defined Risk Factors (IDRF). Operation notes and corresponding imaging reports were analyzed for surgical radicality. The extent of tumor resection was classified as complete resection (95-100%), gross total resection (90-95%), incomplete resection (50-90%), and biopsy (Neuroblastoma Risk Group (INRG) staging system. Survival curves were estimated according to the method of Kaplan and Meier and compared by the log-rank test. A total of 179 patients were included in this study. 77 patients underwent more than one primary tumor operation. After best surgery, 68.7% of patients achieved complete resection of the primary tumor, 16.8% gross total resection, 14.0% incomplete surgery, and 0.5% biopsy only. The cumulative complication rate was 20.3% and the surgery associated mortality rate was 1.1%. Image defined risk factors (IDRF) predicted the extent of resection. Patients with complete resection had a better local-progression-free survival (LPFS), event-free survival (EFS) and OS (overall survival) than the other groups. Subgroup analyses showed better EFS, LPFS and OS for patients with complete resection in INRG high-risk patients. Multivariable analyses revealed resection (complete vs. other), and MYCN (non-amplified vs. amplified) as independent prognostic factors for EFS, LPFS and OS. In patients with localized neuroblastoma age 18 months or older, especially in INRG high-risk patients harboring MYCN amplification, extended surgery of the primary tumor site improved local control rate and survival with an acceptable risk of

Real-world outcomes of treatment for acute lymphoblastic leukemia during adolescence in a financially restricted environment: Results at a single center in Latin America.

Science.gov (United States)

Jaime-Pérez, José C; Jiménez-Castillo, Raúl A; Pinzón-Uresti, Mónica A; Cantú-Rodríguez, Olga G; Herrera-Garza, José L; Marfil-Rivera, Luis J; Gómez-Almaguer, David

2017-07-01

There is a paucity of the studies of adolescents with acute lymphoblastic leukemia (ALL). This is more noticeable in low- and middle-income countries. The international 5-year event-free survival (EFS) and overall survival (OS) for this age group is around 80%, with pediatric-inspired protocols offering better results. A retrospective analysis of adolescents aged 16-20 diagnosed with ALL during the period 2004-2015 treated with a high-risk pediatric protocol at an academic center from a middle-income country was performed. Five-year OS and EFS were estimated by the Kaplan-Meier analysis. Hazard ratios of relapse and death were estimated by the Cox regression model. Five-year EFS and OS for 57 adolescents were 23.3% and 48.9%, respectively. From the 41 patients who achieved complete remission, 24 (58.5%) relapsed. Bone marrow and central nervous system were the most frequent sites of relapse. Hazard ratio of treatment failure and death for patients with organomegaly at diagnosis was 2.026 and 2.970, respectively. Treatment-related toxicity developed in 31 (54.4%) patients and febrile neutropenia was the most frequent in 14 (24.6%) cases. Twelve patients (21.1%) had poor adherence to treatment. High relapse rate and low 5-year EFS compared with international standards, was documented. Use of intensified pediatric regimens, adherence to proven effective medications, improved supportive care, and prevention of abandonment are necessary to improve survival rates in these patients. © 2016 Wiley Periodicals, Inc.

Adjuvant interferon-α for the treatment of high-risk melanoma: An individual patient data meta-analysis.

Science.gov (United States)

Ives, Natalie J; Suciu, Stefan; Eggermont, Alexander M M; Kirkwood, John; Lorigan, Paul; Markovic, Svetomir N; Garbe, Claus; Wheatley, Keith

2017-09-01

Many randomised trials assessing interferon-α (IFN-α) as adjuvant therapy for high-risk malignant melanoma have been undertaken. To better assess the role of IFN-α, an individual patient data (IPD) meta-analysis of these trials was undertaken. IPD was sought from all randomised trials of adjuvant IFN-α versus no IFN-α for high-risk melanoma. Primary outcomes were event-free survival (EFS) and overall survival (OS). Standard methods for quantitative IPD meta-analysis were used. Subgroup analyses by dose, duration of treatment and various patient and disease-specific parameters were performed. Fifteen trials were included in the analysis (eleven with IPD). EFS was significantly improved with IFN-α (hazard ratio [HR] = 0.86, CI 0.81-0.91; P meta-analysis provides clear evidence that adjuvant IFN-α significantly reduces the risk of relapse and improves survival and shows no benefit for higher doses compared to lower doses. The increased benefit in patients with ulcerated tumours, and lack of benefit in patients without ulceration, needs further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Quantifying discrimination of Framingham risk functions with different survival C statistics.

Science.gov (United States)

Pencina, Michael J; D'Agostino, Ralph B; Song, Linye

2012-07-10

Cardiovascular risk prediction functions offer an important diagnostic tool for clinicians and patients themselves. They are usually constructed with the use of parametric or semi-parametric survival regression models. It is essential to be able to evaluate the performance of these models, preferably with summaries that offer natural and intuitive interpretations. The concept of discrimination, popular in the logistic regression context, has been extended to survival analysis. However, the extension is not unique. In this paper, we define discrimination in survival analysis as the model's ability to separate those with longer event-free survival from those with shorter event-free survival within some time horizon of interest. This definition remains consistent with that used in logistic regression, in the sense that it assesses how well the model-based predictions match the observed data. Practical and conceptual examples and numerical simulations are employed to examine four C statistics proposed in the literature to evaluate the performance of survival models. We observe that they differ in the numerical values and aspects of discrimination that they capture. We conclude that the index proposed by Harrell is the most appropriate to capture discrimination described by the above definition. We suggest researchers report which C statistic they are using, provide a rationale for their selection, and be aware that comparing different indices across studies may not be meaningful. Copyright © 2012 John Wiley & Sons, Ltd.

Survival analysis using S analysis of time-to-event data

CERN Document Server

Tableman, Mara

2003-01-01

Survival Analysis Using S: Analysis of Time-to-Event Data is designed as a text for a one-semester or one-quarter course in survival analysis for upper-level or graduate students in statistics, biostatistics, and epidemiology. Prerequisites are a standard pre-calculus first course in probability and statistics, and a course in applied linear regression models. No prior knowledge of S or R is assumed. A wide choice of exercises is included, some intended for more advanced students with a first course in mathematical statistics. The authors emphasize parametric log-linear models, while also detailing nonparametric procedures along with model building and data diagnostics. Medical and public health researchers will find the discussion of cut point analysis with bootstrap validation, competing risks and the cumulative incidence estimator, and the analysis of left-truncated and right-censored data invaluable. The bootstrap procedure checks robustness of cut point analysis and determines cut point(s). In a chapter ...

Prognostic value of 18F-FDG-PET/CT in patients with nasopharyngeal carcinoma: a systematic review and meta-analysis.

Science.gov (United States)

Lin, Jie; Xie, Guozhu; Liao, Guixiang; Wang, Baiyao; Yan, Miaohong; Li, Hui; Yuan, Yawei

2017-05-16

The prognostic role of 18F-fluorodeoxyglucose positron emission tomography CT (18F-FDG PET/CT) parameters is still controversial in nasopharyngeal carcinoma patients. We sought to perform a systematic review and meta-analysis to explore the prognostic value of maximal standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on event-free survival (EFS) and overall survival (OS) in nasopharyngeal carcinoma patients. Fifteen studies comprising 1,938 patients were included in this study. The combined hazard ratios (HRs) for EFS were 2.63 (95%CI 1.71-4.05) for SUVmax, 2.55 (95%CI 1.49-4.35) for MTV, and 3.32 (95%CI 1.23-8.95) for TLG. The pooled HRs for OS were 2.07 (95%CI 1.54-2.79) for SUVmax, 3.86 (95%CI 1.85-8.06) for MTV, and 2.60 (95%CI 1.55-4.34) for TLG. The prognostic role of SUVmax, MTV and TLG remained similar in the sub-group analyses. A systematic literature search was performed to identify studies which associated 18F-FDG PET/CT to clinical survival outcomes of nasopharyngeal carcinoma patients. The summarized HRs for EFS and OS were estimated by using fixed- or random-effect models according to heterogeneity between trials. The present meta-analysis confirms that high values of SUVmax, MTV and TLG predicted a higher risk of adverse events or death in patients with nasopharyngeal carcinoma, despite clinically heterogeneous nasopharyngeal carcinoma patients and the various methods adopted between these studies.

The prognostic role of controlling nutritional status scores in patients with solid tumors.

Science.gov (United States)

Liang, Ruo-Fei; Li, Jun-Hong; Li, Mao; Yang, Yuan; Liu, Yan-Hui

2017-11-01

We conducted a meta-analysis to investigate the association between preoperative controlling nutritional status (CONUT) scores in various solid tumors and clinical outcomes. Relevant studies published up to August 12, 2017 were identified using electronic databases, including PubMed, Embase, and Web of Science. The pooled hazard ratios (HR) and their corresponding 95% confidence intervals (CI) for overall survival (OS) and event-free survival (EFS) were calculated to explore the relationship between preoperative CONUT score and prognosis. In total, 674 patients with solid tumors from four published studies were included in this meta-analysis. The pooled HR for OS was 1.98 (95% CI, 1.34-2.91, p=0.001), indicating that patients with high CONUT scores had worse OS. The pooled HR for EFS was 1.98 (95% CI, 1.34-2.93, p=0.001), revealing that high CONUT scores were significantly associated with short EFS. Our data suggest that high preoperative CONUT scores indicate poor prognosis for patients with solid tumors. Further studies are needed to verify the significance of CONUT scores in clinical practice. Copyright © 2017. Published by Elsevier B.V.

Contribution of effluent organic matter (EfOM) to ultrafiltration (UF) membrane fouling: Isolation, characterization, and fouling effect of EfOM fractions

KAUST Repository

Zheng, Xing

2014-11-01

EfOM has been regarded as a major organic foulant resulting in UF membrane fouling in wastewater reclamation. To investigate fouling potential of different EfOM fractions, the present study isolated EfOM into hydrophobic neutrals (HPO-N), colloids, hydrophobic acids (HPO-A), transphilic neutrals and acids (TPI), and hydrophilics (HPI), and tested their fouling effect in both salt solution and pure water during ultrafiltration (UF). Major functional groups and chemical structure of the isolates were identified using Fourier transform infrared spectroscopy (FT-IR) and solid-state carbon nuclear magnetic resonance (13C NMR) analysis. The influence of the isolation process on the properties of EfOM fractions was minor because the raw and reconstituted secondary effluents were found similar with respect to UV absorbance, molecular size distribution, and fluorescence character. In membrane filtration tests, unified membrane fouling index (UMFI) and hydraulic resistance were used to quantify irreversible fouling potential of different water samples. Results show that under similar DOC level in feed water, colloids present much more irreversible fouling than other fractions. The fouling effect of the isolates is related to their size, chemical properties, and solution chemistry. Further investigations have identified that the interaction between colloids and other fractions also influences the performance of colloids in fouling phenomena. © 2014 Elsevier Ltd.

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

Directory of Open Access Journals (Sweden)

Beauchemin C

2014-06-01

Full Text Available Catherine Beauchemin,1 Dan Cooper,2 Marie-Ève Lapierre,1 Louise Yelle,3 Jean Lachaine11Université de Montréal, Faculté de pharmacie, Montreal, 2Institut national d'excellence en santé et en services sociaux (INESSS, 3Centre Hospitalier de l'Université de Montréal – Hôpital Notre-Dame, Département de médecine, Université de Montréal, Montreal, QC, CanadaBackground: 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

Electrostatics effects on Ca(2+) binding and conformational changes in EF-hand domains: Functional implications for EF-hand proteins.

Science.gov (United States)

Ababou, Abdessamad; Zaleska, Mariola

2015-12-01

Mutations of Gln41 and Lys75 with nonpolar residues in the N-terminal domain of calmodulin (N-Cam) revealed the importance of solvation energetics in conformational change of Ca(2+) sensor EF-hand domains. While in general these domains have polar residues at these corresponding positions yet the extent of their conformational response to Ca(2+) binding and their Ca(2+) binding affinity can be different from N-Cam. Consequently, here we address the charge state of the polar residues at these positions. The results show that the charge state of these polar residues can affect substantially the conformational change and the Ca(2+) binding affinity of our N-Cam variants. Since all the variants kept their conformational activity in the presence of Ca(2+) suggests that the differences observed among them mainly originate from the difference in their molecular dynamics. Hence we propose that the molecular dynamics of Ca(2+) sensor EF-hand domains is a key factor in the multifunctional aspect of EF-hand proteins. Copyright © 2015 Elsevier Inc. All rights reserved.

Prognostic value of tumour blood flow, [18F]EF5 and [18F]FDG PET/CT imaging in patients with head and neck cancer treated with radiochemotherapy

International Nuclear Information System (INIS)

Komar, Gaber; Eskola, Olli; Sipilae, Hannu; Solin, Olof; Lehtioe, Kaisa; Levola, Helena; Lindholm, Paula; Seppaelae, Jan; Seppaenen, Marko; Grenman, Reidar; Minn, Heikki

2014-01-01

In order to improve the treatment of squamous cell carcinoma of the head and neck, precise information on the treated tumour's biology is required and the prognostic importance of different biological parameters needs to be determined. The aim of our study was to determine the predictive value of pretreatment PET/CT imaging using [ 18 F]FDG, a new hypoxia tracer [ 18 F]EF5 and the perfusion tracer [ 15 O]H 2 O in patients with squamous cell cancer of the head and neck treated with radiochemotherapy. The study group comprised 22 patients with confirmed squamous cell carcinoma of the head and neck who underwent a PET/CT scan using the above tracers before any treatment. Patients were later treated with a combination of radiochemotherapy and surgery. Parametric blood flow was calculated from dynamic [ 15 O]H 2 O PET images using a one-tissue compartment model. [ 18 F]FDG images were analysed by calculating standardized uptake values (SUV) and metabolically active tumour volumes (MATV). [ 18 F]EF5 images were analysed by calculating tumour-to-muscle uptake ratios (T/M ratio). A T/M ratio of 1.5 was considered a significant threshold and used to determine tumour hypoxic subvolumes (HS) and hypoxic fraction area. The findings were finally correlated with the pretreatment clinical findings (overall stage and TNM stage) as well as the outcome following radiochemotherapy in terms of local control and overall patient survival. Tumour stage and T-classification did not show any significant differences in comparison to the patients' metabolic and functional characteristics measured on PET. Using the Cox proportional hazards model, a shorter overall survival was associated with MATV (p = 0.008, HR = 1.108), maximum [ 18 F]EF5 T/M ratio (p = 0.0145, HR = 4.084) and tumour HS (p = 0.0047, HR = 1.112). None of the PET parameters showed a significant effect on patient survival in the log-rank test, although [ 18 F]EF5 maximum T/M ratio was the closest (p = 0.109). By contrast

Corticosterone levels predict survival probabilities of Galapagos marine iguanas during El Nino events.

Science.gov (United States)

Romero, L M; Wikelski, M

2001-06-19

Plasma levels of corticosterone are often used as a measure of "stress" in wild animal populations. However, we lack conclusive evidence that different stress levels reflect different survival probabilities between populations. Galápagos marine iguanas offer an ideal test case because island populations are affected differently by recurring El Niño famine events, and population-level survival can be quantified by counting iguanas locally. We surveyed corticosterone levels in six populations during the 1998 El Niño famine and the 1999 La Niña feast period. Iguanas had higher baseline and handling stress-induced corticosterone concentrations during famine than feast conditions. Corticosterone levels differed between islands and predicted survival through an El Niño period. However, among individuals, baseline corticosterone was only elevated when body condition dropped below a critical threshold. Thus, the population-level corticosterone response was variable but nevertheless predicted overall population health. Our results lend support to the use of corticosterone as a rapid quantitative predictor of survival in wild animal populations.

Fifteen-Year Biochemical Relapse-Free Survival, Cause-Specific Survival, and Overall Survival Following I125 Prostate Brachytherapy in Clinically Localized Prostate Cancer: Seattle Experience

International Nuclear Information System (INIS)

Sylvester, John E.; Grimm, Peter D.; Wong, Jason; Galbreath, Robert W.; Merrick, Gregory; Blasko, John C.

2011-01-01

Purpose: To report 15-year biochemical relapse-free survival (BRFS), cause-specific survival (CSS), and overall survival (OS) outcomes of patients treated with I 125 brachytherapy monotherapy for clinically localized prostate cancer early in the Seattle experience. Methods and Materials: Two hundred fifteen patients with clinically localized prostate cancer were consecutively treated from 1988 to 1992 with I 125 monotherapy. They were prospectively followed as a tight cohort. They were evaluated for BRFS, CSS, and OS. Multivariate analysis was used to evaluate outcomes by pretreatment clinical prognostic factors. BRFS was analyzed by the Phoenix (nadir + 2 ng/mL) definition. CSS and OS were evaluated by chart review, death certificates, and referring physician follow-up notes. Gleason scoring was performed by general pathologists at a community hospital in Seattle. Time to biochemical failure (BF) was calculated and compared by Kaplan-Meier plots. Results: Fifteen-year BRFS for the entire cohort was 80.4%. BRFS by D'Amico risk group classification cohort analysis was 85.9%, 79.9%, and 62.2% for low, intermediate, and high-risk patients, respectively. Follow-up ranged from 3.6 to 18.4 years; median follow-up was 15.4 years for biochemically free of disease patients. Overall median follow-up was 11.7 years. The median time to BF in those who failed was 5.1 years. CSS was 84%. OS was 37.1%. Average age at time of treatment was 70 years. There was no significant difference in BRFS between low and intermediate risk groups. Conclusion: I 125 monotherapy results in excellent 15-year BRFS and CSS, especially when taking into account the era of treatment effect.

Pathological 99mTc-sestamibi myocardial perfusion scintigraphy is independently associated with emerging cardiac events in elderly patients with known or suspected coronary artery disease

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Bucerius, Jan; Joe, Alexius Y.; Herder, Ellen; Brockmann, Holger; Biermann, Kim; Palmedo, Holger; Biersack, Hans-Juergen (Dept. of Nuclear Medicine, Univ. of Bonn (Germany)), e-mail: jan.bucerius@ukb.uni-bonn.de; Tiemann, Klaus (Dept. of Internal Medicine II, Univ. of Bonn (Germany))

2011-02-15

Background: Only few data are available regarding the prognostic impact of myocardial perfusion scintigraphy with 99mTc-sestamibi (MPS) regarding emerging cardiac events in elderly patients Purpose: To evaluate the prognostic value of MPS regarding emerging cardiac events in patients aged =70 years with known or suspected coronary artery disease (CAD). Material and Methods: One hundred and thirty-three patients (74.6 +- 3.7 years) who underwent exercise or pharmacological stress/rest MPS were included in this analysis. Semi-quantitative visual interpretation of MPS images was performed and Summed-Stress- (SSS), Summed-Difference- (SDS), and Summed-Rest Scores (SRS) were calculated. Multivariate logistic regression analyses were calculated for evaluation of the independent prognostic impact of MPS results and several cardiac-related patient characteristics with regard to emerging cardiac events. Kaplan-Meier survival- and log rank analyses were calculated for assessment of cardiac event-free survival. Results: Pathological SSS (OR: 3.3), angina (OR: 2.7) and ischemic ECG (OR: 3.0) were independently associated with cardiac events. Patients with pathological SSS (p = 0.005) and ischemic ECG (p = 0.012) had a significantly lower incidence of cardiac event-free survival. Conclusion: Pathological MPS is independently associated with emerging cardiac events predicting a significantly lower incidence of cardiac event-free survival in patients aged =70 years

Long-term disease-free survival in advanced melanomas treated with nitrosoureas: mechanisms and new perspectives.

Science.gov (United States)

Durando, Xavier; Thivat, Emilie; D'Incan, Michel; Sinsard, Anne; Madelmont, Jean-Claude; Chollet, Philippe

2005-11-15

Median survival of metastatic malignant melanoma is 6.0 to 7.5 months, with a 5-year survival of approximately 6.0%. Although long-term complete remissions are rare, few reports describe cases after chemotherapy. Fifty-three patients with metastatic melanoma were treated with Cystemustine, a chloroethyl nitrosourea (CENU) (60 or 90 mg/m2). We describe 5 cases, presenting with complete response with long-term disease-free survival of long-term remission of 14, 12, 9, 7 and 6 years after Cystemustine therapy alone. Long-term survival has already been described in literature, but in all cases they have been obtained after chemotherapy associated with or followed by surgery. But despite these noteworthy and encouraging but also rare results, it appears essential to increase Cystemustine efficiency.

An Overview of the ATLAS High Level Trigger Dataflow and Supervision

CERN Document Server

Wheeler, S; Baines, J T M; Bee, C P; Biglietti, M; Bogaerts, A; Boisvert, V; Bosman, M; Brandt, S; Caron, B; Casado, M P; Cataldi, G; Cavalli, D; Cervetto, M; Comune, G; Corso-Radu, A; Di Mattia, A; Díaz-Gómez, M; Dos Anjos, A; Drohan, J; Ellis, Nick; Elsing, M; Epp, B; Etienne, F; Falciano, S; Farilla, A; George, S; Ghete, V M; González, S; Grothe, M; Kaczmarska, A; Karr, K M; Khomich, A; Konstantinidis, N P; Krasny, W; Li, W; Lowe, A; Luminari, L; Meessen, C; Mello, A G; Merino, G; Morettini, P; Moyse, E; Nairz, A; Negri, A; Nikitin, N V; Nisati, A; Padilla, C; Parodi, F; Pérez-Réale, V; Pinfold, J L; Pinto, P; Polesello, G; Qian, Z; Resconi, S; Rosati, S; Scannicchio, D A; Schiavi, C; Schörner-Sadenius, T; Segura, E; De Seixas, J M; Shears, T G; Sivoklokov, S Yu; Smizanska, M; Soluk, R A; Stanescu, C; Tapprogge, Stefan; Touchard, F; Vercesi, V; Watson, A; Wengler, T; Werner, P; Wickens, F J; Wiedenmann, W; Wielers, M; Zobernig, G; RT 2003 13th IEEE-NPSS Real Time Conference

2004-01-01

The ATLAS High Level Trigger (HLT) system provides software-based event selection after the initial LVL1 hardware trigger. It is composed of two stages, the LVL2 trigger and the Event Filter (EF). The LVL2 trigger performs event selection with optimized algorithms using selected data guided by Region of Interest pointers provided by the LVL1 trigger. Those events selected by LVL2, are built into complete events, which are passed to the EF for a further stage of event selection and classification using off-line algorithms. Events surviving the EF selection are passed for off-line storage. The two stages of HLT are implemented on processor farms. The concept of distributing the selection process between LVL2 and EF is a key element in the architecture, which allows it to be flexible to changes (luminosity, detector knowledge, background conditions etc.) Although there are some differences in the requirements between these sub-systems there are many commonalities. An overview of the dataflow (event selection) an...

Comparison of total body irradiation-based or non-total body irradiation-based conditioning regimens for allogeneic stem cell transplantation in pediatric leukemia patients

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Sang Jeong Kim

2010-04-01

Full Text Available Purpose : This study aims to compare the outcome of total body irradiation (TBI- or non-TBI-containing conditioning regimens for leukemia in children. Methods : We retrospectively evaluated 77 children conditioned with TBI (n=40 or non-TBI (n=37 regimens, transplanted at Chonnam National University Hospital between January 1996 and December 2007. The type of transplantation, disease status at the time of transplant, conditioning regimen, engraftment kinetics, development of graft-versus-host disease (GVHD, complications, cause of deaths, overall survival (OS, and event-free survival (EFS were compared between the 2 groups. Results : Among 34 patients with acute lymphoblastic leukemia (ALL, 28 (82.4% were in the TBI group, while 72.7% (24/33 of patients with myeloid leukemia were in the non-TBI group. Although the 5-year EFS of the 2 groups was similar for all patients (62% vs 63%, the TBI group showed a better 5-year EFS than the non-TBI group when only ALL patients were analyzed (65% vs 17%; P =0.005. In acute myelogenous leukemia patients, the non-TBI group had better survival tendency (73% vs 38%; P=0.089. The incidence of GVHD, engraftment, survival, cause of death, and late complications was not different between the 2 groups. Conclusion : The TBI and non-TBI groups showed comparable results, but the TBI group showed a significantly higher 5-year EFS than the non-TBI group in ALL patients. Further prospective, randomized controlled studies involving larger number of patients are needed to assess the late-onset complications and to compare the socioeconomic quality of life.

Embryonal Fyn-associated substrate (EFS) and CASS4: The lesser-known CAS protein family members.

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Deneka, Alexander; Korobeynikov, Vladislav; Golemis, Erica A

2015-10-01

The CAS (Crk-associated substrate) adaptor protein family consists of four members: CASS1/BCAR1/p130Cas, CASS2/NEDD9/HEF1/Cas-L, CASS3/EFS/Sin and CASS4/HEPL. While CAS proteins lack enzymatic activity, they contain specific recognition and binding sites for assembly of larger signaling complexes that are essential for cell proliferation, survival, migration, and other processes. All family members are intermediates in integrin-dependent signaling pathways mediated at focal adhesions, and associate with FAK and SRC family kinases to activate downstream effectors regulating the actin cytoskeleton. Most studies of CAS proteins to date have been focused on the first two members, BCAR1 and NEDD9, with altered expression of these proteins now appreciated as influencing disease development and prognosis for cancer and other serious pathological conditions. For these family members, additional mechanisms of action have been defined in receptor tyrosine kinase (RTK) signaling, estrogen receptor signaling or cell cycle progression, involving discrete partner proteins such as SHC, NSP proteins, or AURKA. By contrast, EFS and CASS4 have been less studied, although structure-function analyses indicate they conserve many elements with the better-known family members. Intriguingly, a number of recent studies have implicated these proteins in immune system function, and the pathogenesis of developmental disorders, autoimmune disorders including Crohn's disease, Alzheimer's disease, cancer and other diseases. In this review, we summarize the current understanding of EFS and CASS4 protein function in the context of the larger CAS family group. Copyright © 2015 Elsevier B.V. All rights reserved.

$l l \\gamma \\gamma$ events at LEP

CERN Document Server

Chang, Yuan-Hann

1993-01-01

The results of studies on the ef.7-y events with high 'Y'Y mass from the L3 experiment at LEP is reported. A clustering of events with 'Y'Y invariant mass around 60 GeV is observed. The clustering could come from decay of a heavy particle, however, QED fluctuation cannot be ruled out. More data are needed to ascertain the origin of these events.

Centre characteristics and procedure-related factors have an impact on outcomes of allogeneic transplantation for patients with CLL

DEFF Research Database (Denmark)

Schetelig, Johannes; de Wreede, Liesbeth C; Andersen, Niels S

2017-01-01

The best approach for allogeneic haematopoietic stem cell transplantations (alloHCT) in patients with chronic lymphocytic leukaemia (CLL) is unknown. We therefore analysed the impact of procedure- and centre-related factors on 5-year event-free survival (EFS) in a large retrospective study. Data...... of 684 CLL patients who received a first alloHCT between 2000 and 2011 were analysed by multivariable Cox proportional hazards models with a frailty component to investigate unexplained centre heterogeneity. Five-year EFS of the whole cohort was 37% (95% confidence interval [CI], 34-42%). Larger numbers...... of CLL alloHCTs (hazard ratio [HR] 0·96, P = 0·002), certification of quality management (HR 0·7, P = 0·045) and a higher gross national income per capita (HR 0·4, P = 0·04) improved EFS. In vivo T-cell depletion (TCD) with alemtuzumab compared to no TCD (HR 1·5, P = 0·03), and a female donor compared...

Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial.

Science.gov (United States)

Bonnefoi, H; Litière, S; Piccart, M; MacGrogan, G; Fumoleau, P; Brain, E; Petit, T; Rouanet, P; Jassem, J; Moldovan, C; Bodmer, A; Zaman, K; Cufer, T; Campone, M; Luporsi, E; Malmström, P; Werutsky, G; Bogaerts, J; Bergh, J; Cameron, D A

2014-06-01

Pathological complete response (pCR) following chemotherapy is strongly associated with both breast cancer subtype and long-term survival. Within a phase III neoadjuvant chemotherapy trial, we sought to determine whether the prognostic implications of pCR, TP53 status and treatment arm (taxane versus non-taxane) differed between intrinsic subtypes. Patients were randomized to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel then three cycles of eprirubicin/docetaxel (T-ET). pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in primary tumour and lymph nodes. We used a simplified intrinsic subtypes classification, as suggested by the 2011 St Gallen consensus. Interactions between pCR, TP53 status, treatment arm and intrinsic subtype on event-free survival (EFS), distant metastasis-free survival (DMFS) and overall survival (OS) were studied using a landmark and a two-step approach multivariate analyses. Sufficient data for pCR analyses were available in 1212 (65%) of 1856 patients randomized. pCR occurred in 222 of 1212 (18%) patients: 37 of 496 (7.5%) luminal A, 22 of 147 (15%) luminal B/HER2 negative, 51 of 230 (22%) luminal B/HER2 positive, 43 of 118 (36%) HER2 positive/non-luminal, 69 of 221(31%) triple negative (TN). The prognostic effect of pCR on EFS did not differ between subtypes and was an independent predictor for better EFS [hazard ratio (HR) = 0.40, P analysis. EORTC 10994/BIG 1-00 Trial registration number NCT00017095. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Number of infection events per cell during HIV-1 cell-free infection.

Science.gov (United States)

Ito, Yusuke; Remion, Azaria; Tauzin, Alexandra; Ejima, Keisuke; Nakaoka, Shinji; Iwasa, Yoh; Iwami, Shingo; Mammano, Fabrizio

2017-07-26

HIV-1 accumulates changes in its genome through both recombination and mutation during the course of infection. For recombination to occur, a single cell must be infected by two HIV strains. These coinfection events were experimentally demonstrated to occur more frequently than would be expected for independent infection events and do not follow a random distribution. Previous mathematical modeling approaches demonstrated that differences in target cell susceptibility can explain the non-randomness, both in the context of direct cell-to-cell transmission, and in the context of free virus transmission (Q. Dang et al., Proc. Natl. Acad. Sci. USA 101:632-7, 2004: K. M. Law et al., Cell reports 15:2711-83, 2016). Here, we build on these notions and provide a more detailed and extensive quantitative framework. We developed a novel mathematical model explicitly considering the heterogeneity of target cells and analysed datasets of cell-free HIV-1 single and double infection experiments in cell culture. Particularly, in contrast to the previous studies, we took into account the different susceptibility of the target cells as a continuous distribution. Interestingly, we showed that the number of infection events per cell during cell-free HIV-1 infection follows a negative-binomial distribution, and our model reproduces these datasets.

Bevacizumab for the treatment of nonsquamous non-small-cell lung cancer in Portugal: a retrospective, multicenter study

International Nuclear Information System (INIS)

Estevinho, Fernanda; Soares, Marta; Azevedo, Isabel; Queiroga, Henrique; Parente, Bárbara; Brito, Ulisses; Teixeira, Encarnação; Sotto-Mayor, Renato; Araújo, António

2012-01-01

Lung cancer is the leading cause of cancer-related mortality. In patients with nonsquamous non-small-cell lung cancer (NSCLC) stage IIIB/IV treatment with chemotherapy plus bevacizumab led to significant improvements in progression-free and median overall survival (OS). To report the experience of five Portuguese centers in treating patients with nonsquamous NSCLC in stage IIIB or IV with bevacizumab and chemotherapy regarding survival and toxicity outcomes. This was a retrospective, multicenter study on patients with nonsquamous stage IIIB/IV NSCLC treated with bevacizumab and chemotherapy from November 2007 to August 2010 through special use permits. We reviewed the medical records, registry of demographic characteristics, treatments provided, treatment responses, adverse events, and dates of death. Statistical analysis was performed with SPSS statistics software. Median OS and event-free survival (EFS) were calculated using the Kaplan–Meier method. From an eligible population of 41 patients, 37 participants were registered. Study participants were predominantly male (78.4%) with a median age of 53 years (29–75 years). In total, 83.8% patients had stage IV disease (TNM, 6th Ed.). The OS was 21.5 months (95% confidence interval [CI]: 12.6–30.5] and median EFS was 9.4 months (95% CI9: 7.1–11.7). Hematologic toxicity grade 3/4 occurred in 35.1% of patients, and nonhematologic toxicity in 24.3% patients. One fatal thromboembolic event was recorded (2.7%). The results of chemotherapy plus bevacizumab treatment for nonsquamous NSCLC obtained from the daily clinical practice of the centers involved in this study were similar to those of published clinical trials. Collaboration between the different Portuguese centers is crucial for this kind of study

Sordarin derivatives induce a novel conformation of the yeast ribosome translocation factor eEF2

DEFF Research Database (Denmark)

Søe, Rikke; Mosley, R.T.; Justice, M.

2007-01-01

EF2 that form the ligand binding pocket are oriented in a different manner relative to the rest of eEF2 compared to our previous structure of eEF2 in complex with the parent natural product sordarin. Yeast eEF2 is also shown to bind adenylic nucleotides, which can be displaced by sordarin, suggesting...... that ADP or ATP also bind to the three C-terminal domains of eEF2. Fusidic acid is a universal inhibitor of translation that targets EF-G or eEF2, and is widely used as an antibiotic against gram positive bacteria. Based on mutations conferring resistance to fusidic acid, cryo-EM reconstructions, and X...

Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival

Science.gov (United States)

van Besien, Koen; Hari, Parameswaran; Zhang, Mei-Jie; Liu, Hong-Tao; Stock, Wendy; Godley, Lucy; Odenike, Olatoyosi; Larson, Richard; Bishop, Michael; Wickrema, Amittha; Gergis, Usama; Mayer, Sebastian; Shore, Tsiporah; Tsai, Stephanie; Rhodes, Joanna; Cushing, Melissa M.; Korman, Sandra; Artz, Andrew

2016-01-01

Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, Pdisease (HR=0.26, Pdisease (HR=0.06, Pdisease-free, relapse-free survival was superior with haplo-cord (HR 0.63, P=0.002) but not overall survival (HR=0.97, P=0.85). Haplo-cord transplantation using fludarabine-melphalan-thymoglobulin conditioning hastens hematopoietic recovery with a lower risk of relapse relative to double umbilical cord blood transplantation using the commonly used fludarabine-cyclophosphamide-low-dose total body irradiation conditioning. Graft-versus-host disease-free and relapse-free survival is significantly improved. Haplo-cord is a readily available graft source that improves outcomes and access to transplant for those lacking HLA-matched donors. Trials registered at clinicaltrials.gov identifiers 00943800 and 01810588. PMID:26869630

Treatment results and prognostic factors of pediatric neuroblastoma: a retrospective study.

Science.gov (United States)

El-Sayed, Mohamed I; Ali, Amany M; Sayed, Heba A; Zaky, Eman M

2010-12-24

We conducted a retrospective analysis to investigate treatment results and prognostic factors of pediatric neuroblastoma patients. This retrospective study was carried out analyzing the medical records of patients with the pathological diagnosis of neuroblastoma seen at South Egypt Cancer Institute, Assiut University during the period from January 2001 and January 2010. After induction chemotherapy, response according to international neuoblastoma response criteria was assessed. Radiotherapy to patients with residual primary tumor was applied. Overall and event free survival (OAS and EFS) rates were estimated using Graphed prism program. The Log-rank test was used to examine differences in OAS and EFS rates. Cox-regression multivariate analysis was done to determine the independent prognostic factors affecting survival rates. Fifty three cases were analyzed. The median follow-up duration was 32 months and ranged from 2 to 84 months. The 3-year OAS and EFS rates were 39.4% and 29.3% respectively. Poor prognostic factors included age >1 year of age, N-MYC amplification, and high risk group. The majority of patients (68%) presented in high risk group, where treatment outcome was poor, as only 21% of patients survived for 3 year. Multivariate analysis confirmed only the association between survival and risk group. However, in univariate analysis, local radiation therapy resulted in significant survival improvement. Therefore, radiotherapy should be given to patients with residual tumor evident after induction chemotherapy and surgery. Future attempts to improve OAS in high risk group patients with aggressive chemotherapy and bone marrow transplantation should be considered.

Treatment results and prognostic factors of pediatric neuroblastoma: a retrospective study

Directory of Open Access Journals (Sweden)

El-Sayed Mohamed I

2010-12-01

Full Text Available Abstract Background We conducted a retrospective analysis to investigate treatment results and prognostic factors of pediatric neuroblastoma patients. Methods This retrospective study was carried out analyzing the medical records of patients with the pathological diagnosis of neuroblastoma seen at South Egypt Cancer Institute, Assiut University during the period from January 2001 and January 2010. After induction chemotherapy, response according to international neuoblastoma response criteria was assessed. Radiotherapy to patients with residual primary tumor was applied. Overall and event free survival (OAS and EFS rates were estimated using Graphed prism program. The Log-rank test was used to examine differences in OAS and EFS rates. Cox-regression multivariate analysis was done to determine the independent prognostic factors affecting survival rates. Results Fifty three cases were analyzed. The median follow-up duration was 32 months and ranged from 2 to 84 months. The 3-year OAS and EFS rates were 39.4% and 29.3% respectively. Poor prognostic factors included age >1 year of age, N-MYC amplification, and high risk group. The majority of patients (68% presented in high risk group, where treatment outcome was poor, as only 21% of patients survived for 3 year. Conclusion Multivariate analysis confirmed only the association between survival and risk group. However, in univariate analysis, local radiation therapy resulted in significant survival improvement. Therefore, radiotherapy should be given to patients with residual tumor evident after induction chemotherapy and surgery. Future attempts to improve OAS in high risk group patients with aggressive chemotherapy and bone marrow transplantation should be considered.

Long-Term Outcomes of 107 Cases of Primary Thyroid Mucosa-Associated Lymphoid Tissue Lymphoma at a Single Medical Institution in Japan.

Science.gov (United States)

Watanabe, Natsuko; Narimatsu, Hiroto; Noh, Jaeduk Yoshimura; Iwaku, Kenji; Kunii, Yo; Suzuki, Nami; Ohye, Hidemi; Suzuki, Miho; Matsumoto, Masako; Yoshihara, Ai; Kameyama, Kaori; Kobayashi, Kazuhiko; Kami, Masahiro; Sugino, Kiminori; Ito, Koichi

2018-02-01

Thyroid mucosa-associated lymphoid tissue (MALT) lymphoma is a type of extranodal lymphoma with a favorable prognosis. To provide information on long-term outcomes that would facilitate establishment of the optimal management strategy for thyroid lymphoma. Medical records of 107 patients (median age 67 years, 20 males, 87 females) who were diagnosed with localized thyroid MALT lymphoma stage IE or IIE at Ito Hospital were retrospectively reviewed. Overall and event-free survival (EFS). Initial treatments included radiation therapy (RT) alone (n = 58), combined modality therapy (CMT) (n = 48), or chemotherapy alone (n = 1). All 107 patients responded to the treatment, six of whom experienced relapse. Only one patient died of lymphoma. The 5-year overall survival (OS) and EFS rates were 94% [95% confidence interval (CI), 87% to 97%] and 92% (95% CI, 85% to 95%), respectively, and the 10-year OS and EFS rates were 91% (95% CI, 83% to 95%) and 84% (95% CI, 74% to 90%), respectively. Of the 106 patients with information available on adverse events, 71 patients (67%) developed hypothyroidism after primary thyroid lymphoma treatment. The CMT group showed additional chemotherapy-induced adverse reactions in the form of neutropenia, neuropathy, constipation, and pneumonia. The 5-year OS rates of patients treated with CMT and RT were 93% (95% CI, 81% to 98%) and 94% (95% CI, 84% to 98%), respectively. Long-term outcomes of localized thyroid MALT lymphoma are favorable with all initial treatment modalities. Copyright © 2017 Endocrine Society

Mapping the human translation elongation factor eEF1H complex using the yeast two-hybrid system

DEFF Research Database (Denmark)

Mansilla, Francisco; Friis, Irene; Jadidi, Mandana

2002-01-01

In eukaryotes, the eukaryotic translation elongation factor eEF1A responsible for transporting amino-acylated tRNA to the ribosome forms a higher-order complex, eEF1H, with its guanine-nucleotide-exchange factor eEF1B. In metazoans, eEF1B consists of three subunits: eEF1B alpha, eEF1B eta and eEF1B...... of in vitro experiments have been proposed for the macromolecular organization of the eEF1H complex. However, these models differ in various aspects. This might be due to the difficulties of handling, particularly the eEF1B beta and eEF1B gamma subunits in vitro. Here, the human eEF1H complex is for the first...... gamma:eEF1B beta, where the last was observed using a three-hybrid approach. Surprisingly, eEF1A2 showed no or only little affinity for the guanine-nucleotide-exchange factors. Truncated versions of the subunits of eEF1B were used to orientate these subunits within the resulting model. The model unit...

Long-term disease-free survival in advanced melanomas treated with nitrosoureas: mechanisms and new perspectives

Directory of Open Access Journals (Sweden)

Sinsard Anne

2005-11-01

Full Text Available Abstract Background Median survival of metastatic malignant melanoma is 6.0 to 7.5 months, with a 5-year survival of ~6.0%. Although long-term complete remissions are rare, few reports describe cases after chemotherapy. Fifty-three patients with metastatic melanoma were treated with Cystemustine, a chloroethyl nitrosourea (CENU (60 or 90 mg/m2. Case presentation We describe 5 cases, presenting with complete response with long-term disease-free survival of long-term remission of 14, 12, 9, 7 and 6 years after Cystemustine therapy alone. Conclusion Long-term survival has already been described in literature, but in all cases they have been obtained after chemotherapy associated with or followed by surgery. But despite these noteworthy and encouraging but also rare results, it appears essential to increase cystemustine efficiency.

Multi-institutional Nomogram Predicting Survival Free From Salvage Whole Brain Radiation After Radiosurgery in Patients With Brain Metastases

International Nuclear Information System (INIS)

Gorovets, Daniel; Ayala-Peacock, Diandra; Tybor, David J.; Rava, Paul; Ebner, Daniel; Cielo, Deus; Norén, Georg; Wazer, David E.; Chan, Michael; Hepel, Jaroslaw T.

2017-01-01

Purpose: Optimal patient selection for stereotactic radiosurgery (SRS) as the initial treatment for brain metastases is complicated and controversial. This study aimed to develop a nomogram that predicts survival without salvage whole brain radiation therapy (WBRT) after upfront SRS. Methods and Materials: Multi-institutional data were analyzed from 895 patients with 2095 lesions treated with SRS without prior or planned WBRT. Cox proportional hazards regression model was used to identify independent pre-SRS predictors of WBRT-free survival, which were integrated to build a nomogram that was subjected to bootstrap validation. Results: Median WBRT-free survival was 8 months (range, 0.1-139 months). Significant independent predictors for inferior WBRT-free survival were age (hazard ratio [HR] 1.1 for each 10-year increase), HER2(−) breast cancer (HR 1.6 relative to other histologic features), colorectal cancer (HR 1.4 relative to other histologic features), increasing number of brain metastases (HR 1.09, 1.32, 1.37, and 1.87 for 2, 3, 4, and 5+ lesions, respectively), presence of neurologic symptoms (HR 1.26), progressive systemic disease (HR 1.35), and increasing extracranial disease burden (HR 1.31 for oligometastatic and HR 1.56 for widespread). Additionally, HER2(+) breast cancer (HR 0.81) and melanoma (HR 1.11) trended toward significance. The independently weighted hazard ratios were used to create a nomogram to display estimated probabilities of 6-month and 12-month WBRT-free survival with a corrected Harrell's C concordance statistic of 0.62. Conclusions: Our nomogram can be used at initial evaluation to help select patients best suited for upfront SRS for brain metastases while reducing expense and morbidity in patients who derive minimal or no benefit.

Multi-institutional Nomogram Predicting Survival Free From Salvage Whole Brain Radiation After Radiosurgery in Patients With Brain Metastases

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Gorovets, Daniel [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Department of Radiation Oncology, Perlmutter Cancer Center, NYU School of Medicine, New York, New York (United States); Ayala-Peacock, Diandra [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Tybor, David J. [Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts (United States); Rava, Paul [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Department of Radiation Oncology, UMass Memorial Medical Center, University of Massachusetts School of Medicine, Worcester, Massachusetts (United States); Ebner, Daniel [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Cielo, Deus; Norén, Georg [Department of Neurosurgery, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Wazer, David E. [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Chan, Michael [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Hepel, Jaroslaw T., E-mail: jhepel@lifespan.org [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States)

2017-02-01

Purpose: Optimal patient selection for stereotactic radiosurgery (SRS) as the initial treatment for brain metastases is complicated and controversial. This study aimed to develop a nomogram that predicts survival without salvage whole brain radiation therapy (WBRT) after upfront SRS. Methods and Materials: Multi-institutional data were analyzed from 895 patients with 2095 lesions treated with SRS without prior or planned WBRT. Cox proportional hazards regression model was used to identify independent pre-SRS predictors of WBRT-free survival, which were integrated to build a nomogram that was subjected to bootstrap validation. Results: Median WBRT-free survival was 8 months (range, 0.1-139 months). Significant independent predictors for inferior WBRT-free survival were age (hazard ratio [HR] 1.1 for each 10-year increase), HER2(−) breast cancer (HR 1.6 relative to other histologic features), colorectal cancer (HR 1.4 relative to other histologic features), increasing number of brain metastases (HR 1.09, 1.32, 1.37, and 1.87 for 2, 3, 4, and 5+ lesions, respectively), presence of neurologic symptoms (HR 1.26), progressive systemic disease (HR 1.35), and increasing extracranial disease burden (HR 1.31 for oligometastatic and HR 1.56 for widespread). Additionally, HER2(+) breast cancer (HR 0.81) and melanoma (HR 1.11) trended toward significance. The independently weighted hazard ratios were used to create a nomogram to display estimated probabilities of 6-month and 12-month WBRT-free survival with a corrected Harrell's C concordance statistic of 0.62. Conclusions: Our nomogram can be used at initial evaluation to help select patients best suited for upfront SRS for brain metastases while reducing expense and morbidity in patients who derive minimal or no benefit.

The eEF1A proteins: at the crossroads of oncogenesis, apoptosis and viral infections.

Directory of Open Access Journals (Sweden)

Georges eHerbein

2015-04-01

Full Text Available Eukaryotic translation elongation factors 1 alpha, eEF1A1 and eEF1A2, are not only translation factors, but also pleiotropic proteins that are highly expressed in human tumors, including breast cancer, ovarian cancer and lung cancer. eEF1A1 modulates cytoskeleton, exhibits chaperone-like activity and also controls cell proliferation and cell death. By contrast eEF1A2 protein favors oncogenesis as shown by the fact that overexpression of eEF1A2 leads to cellular transformation and gives rise to tumors in nude mice. The eEF1A2 protein stimulates the phospholipid signaling and activates the Akt-dependent cell migration and actin remodeling that ultimately favors tumorigenesis. By contrast, inactivation of eEF1A proteins leads to immunodeficiency, neural and muscular defects, and favors apoptosis. Finally, eEF1A proteins interact with several viral proteins resulting in enhanced viral replication, decreased apoptosis and increased cellular transformation. This review summarizes the recent findings on eEF1A proteins indicating that eEF1A proteins play a critical role in numerous human diseases through enhancement of oncogenesis, blockade of apoptosis and increased viral pathogenesis.

Bacterial translation elongation factor EF-Tu interacts and colocalizes with actin-like MreB protein.

Science.gov (United States)

Defeu Soufo, Hervé Joël; Reimold, Christian; Linne, Uwe; Knust, Tobias; Gescher, Johannes; Graumann, Peter L

2010-02-16

We show that translation initiation factor EF-Tu plays a second important role in cell shape maintenance in the bacterium Bacillus subtilis. EF-Tu localizes in a helical pattern underneath the cell membrane and colocalizes with MreB, an actin-like cytoskeletal element setting up rod cell shape. The localization of MreB and of EF-Tu is interdependent, but in contrast to the dynamic MreB filaments, EF-Tu structures are more static and may serve as tracks for MreB filaments. In agreement with this idea, EF-Tu and MreB interact in vivo and in vitro. Lowering of the EF-Tu levels had a minor effect on translation but a strong effect on cell shape and on the localization of MreB, and blocking of the function of EF-Tu in translation did not interfere with the localization of MreB, showing that, directly or indirectly, EF-Tu affects the cytoskeletal MreB structure and thus serves two important functions in a bacterium.

Prognostic value of tumour blood flow, [{sup 18}F]EF5 and [{sup 18}F]FDG PET/CT imaging in patients with head and neck cancer treated with radiochemotherapy

Energy Technology Data Exchange (ETDEWEB)

Komar, Gaber; Eskola, Olli; Sipilae, Hannu; Solin, Olof [Turku PET Centre, Turku (Finland); Lehtioe, Kaisa; Levola, Helena; Lindholm, Paula; Seppaelae, Jan [Turku University Hospital and University of Turku, Department of Oncology and Radiotherapy, Turku (Finland); Seppaenen, Marko [Turku PET Centre, Turku (Finland); Turku University Hospital and University of Turku, Department of Nuclear Medicine, Turku (Finland); Grenman, Reidar [Turku University Hospital and University of Turku, Department of Otorhinolaryngology, Head and Neck Surgery, Turku (Finland); Minn, Heikki [Turku PET Centre, Turku (Finland); Turku University Hospital and University of Turku, Department of Oncology and Radiotherapy, Turku (Finland)

2014-11-15

In order to improve the treatment of squamous cell carcinoma of the head and neck, precise information on the treated tumour's biology is required and the prognostic importance of different biological parameters needs to be determined. The aim of our study was to determine the predictive value of pretreatment PET/CT imaging using [{sup 18}F]FDG, a new hypoxia tracer [{sup 18}F]EF5 and the perfusion tracer [{sup 15}O]H{sub 2}O in patients with squamous cell cancer of the head and neck treated with radiochemotherapy. The study group comprised 22 patients with confirmed squamous cell carcinoma of the head and neck who underwent a PET/CT scan using the above tracers before any treatment. Patients were later treated with a combination of radiochemotherapy and surgery. Parametric blood flow was calculated from dynamic [{sup 15}O]H{sub 2}O PET images using a one-tissue compartment model. [{sup 18}F]FDG images were analysed by calculating standardized uptake values (SUV) and metabolically active tumour volumes (MATV). [{sup 18}F]EF5 images were analysed by calculating tumour-to-muscle uptake ratios (T/M ratio). A T/M ratio of 1.5 was considered a significant threshold and used to determine tumour hypoxic subvolumes (HS) and hypoxic fraction area. The findings were finally correlated with the pretreatment clinical findings (overall stage and TNM stage) as well as the outcome following radiochemotherapy in terms of local control and overall patient survival. Tumour stage and T-classification did not show any significant differences in comparison to the patients' metabolic and functional characteristics measured on PET. Using the Cox proportional hazards model, a shorter overall survival was associated with MATV (p = 0.008, HR = 1.108), maximum [{sup 18}F]EF5 T/M ratio (p = 0.0145, HR = 4.084) and tumour HS (p = 0.0047, HR = 1.112). None of the PET parameters showed a significant effect on patient survival in the log-rank test, although [{sup 18}F]EF5 maximum T

Murine elongation factor 1 alpha (EF-1 alpha) is posttranslationally modified by novel amide-linked ethanolamine-phosphoglycerol moieties. Addition of ethanolamine-phosphoglycerol to specific glutamic acid residues on EF-1 alpha

International Nuclear Information System (INIS)

Whiteheart, S.W.; Shenbagamurthi, P.; Chen, L.; Cotter, R.J.; Hart, G.W.

1989-01-01

Elongation Factor 1 alpha (EF-1 alpha), an important eukaryotic translation factor, transports charged aminoacyl-tRNA from the cytosol to the ribosomes during poly-peptide synthesis. Metabolic radiolabeling with [ 3 H] ethanolamine shows that, in all cells examined, EF-1 alpha is the major radiolabeled protein. Radiolabeled EF-1 alpha has an apparent Mr = 53,000 and a basic isoelectric point. It is cytosolic and does not contain N-linked oligosaccharides. Trypsin digestion of murine EF-1 alpha generated two major [ 3 H]ethanolamine-labeled peptides. Three peptides were sequenced and were identical to two distinct regions of the human EF-1 alpha protein. Blank sequencing cycles coinciding with glutamic acid in the human cDNA-derived sequence were also found to release [ 3 H]ethanolamine, and compositional analysis of these peptides confirmed the presence of glutamic acid. Dansylation analysis demonstrates that the amine group of the ethanolamine is blocked. These results indicate that EF-1 alpha is posttranslationally modified by the covalent attachment of ethanolamine via an amide bond to at least two specific glutamic acid residues (Glu-301 and Glu-374). The hydroxyl group of the attached ethanolamine was shown by mass spectrometry and compositional analysis, to be further modified by the addition of a phosphoglycerol unit. This novel posttranslational modification may represent an important alteration of EF-1 alpha, comparable to the regulatory effects of posttranslational methylation of EF-1 alpha lysine residues

PKA spectral effects on subcascade structures and free defect survival ratio as estimated by cascade-annealing computer simulation

International Nuclear Information System (INIS)

Muroga, Takeo

1990-01-01

The free defect survival ratio is calculated by ''cascade-annealing'' computer simulation using the MARLOWE and modified DAIQUIRI codes in various cases of Primary Knock-on Atom (PKA) spectra. The number of subcascades is calculated by ''cut-off'' calculation using MARLOWE. The adequacy of these methods is checked by comparing the results with experiments (surface segregation measurements and Transmission Electron Microscope cascade defect observations). The correlation using the weighted average recoil energy as a parameter shows that the saturation of the free defect survival ratio at high PKA energies has a close relation to the cascade splitting into subcascades. (author)

Heat-Killed Enterococcus faecalis EF-2001 Ameliorates Atopic Dermatitis in a Murine Model

Science.gov (United States)

Choi, Eun-Ju; Iwasa, Masahiro; Han, Kwon-Il; Kim, Wan-Jae; Tang, Yujiao; Hwang, Young Joung; Chae, Jeong Ryong; Han, Weon Cheol; Shin, Yu-Su; Kim, Eun-Kyung

2016-01-01

Recent reports have shown the immunomodulatory effect of heat-killed lactic acid bacteria. Atopic dermatitis (AD) is an allergic skin disease, caused by immune dysregulation among other factors. The aim of this study was to assess the effect of heat-killed Enterococcus faecalis EF-2001 (EF-2001) on AD. We established an in vivo AD model by repeated local exposure of Dermatophagoides farinae extract (DFE; house dust mite extract) and 2,4-dinitrochlorobenzene (DNCB) to the ears of mice. After oral administration of EF-2001 for four weeks, the epidermal and dermal ear thickness, mast cell infiltration, and serum immunoglobulin levels were measured. In addition, the gene expression levels of pathogenic cytokines in the ears, lymph nodes, and splenocytes were assayed. EF-2001 attenuated AD symptoms based on the ear thickness, histopathological analysis, and serum immunoglobulin levels. Moreover, EF-2001 decreased the DFE/DNCB-induced expression of various pathogenic cytokines in the ears, lymph nodes, and splenocytes. These results suggest that EF-2001 has therapeutic potential in the treatment of AD owing to its immunomodulatory effects. PMID:26959058

Heat-Killed Enterococcus faecalis EF-2001 Ameliorates Atopic Dermatitis in a Murine Model

Directory of Open Access Journals (Sweden)

Eun-Ju Choi

2016-03-01

Full Text Available Recent reports have shown the immunomodulatory effect of heat-killed lactic acid bacteria. Atopic dermatitis (AD is an allergic skin disease, caused by immune dysregulation among other factors. The aim of this study was to assess the effect of heat-killed Enterococcus faecalis EF-2001 (EF-2001 on AD. We established an in vivo AD model by repeated local exposure of Dermatophagoides farinae extract (DFE; house dust mite extract and 2,4-dinitrochlorobenzene (DNCB to the ears of mice. After oral administration of EF-2001 for four weeks, the epidermal and dermal ear thickness, mast cell infiltration, and serum immunoglobulin levels were measured. In addition, the gene expression levels of pathogenic cytokines in the ears, lymph nodes, and splenocytes were assayed. EF-2001 attenuated AD symptoms based on the ear thickness, histopathological analysis, and serum immunoglobulin levels. Moreover, EF-2001 decreased the DFE/DNCB-induced expression of various pathogenic cytokines in the ears, lymph nodes, and splenocytes. These results suggest that EF-2001 has therapeutic potential in the treatment of AD owing to its immunomodulatory effects.

Prostate-Specific Antigen Persistence After Radical Prostatectomy as a Predictive Factor of Clinical Relapse-Free Survival and Overall Survival: 10-Year Data of the ARO 96-02 Trial

Energy Technology Data Exchange (ETDEWEB)

Wiegel, Thomas, E-mail: thomas.wiegel@uniklinik-ulm.de [Department of Radiation Oncology, University Hospital Ulm (Germany); Bartkowiak, Detlef; Bottke, Dirk; Thamm, Reinhard [Department of Radiation Oncology, University Hospital Ulm (Germany); Hinke, Axel [WiSP, Research Institute Pharma GmbH, Langenfeld (Germany); Stöckle, Michael [Department of Urology, University Hospital Homburg/Saar (Germany); Rübe, Christian [Department of Radiation Oncology, University Hospital Homburg/Saar (Germany); Semjonow, Axel [Department of Urology, University Hospital Münster (Germany); Wirth, Manfred [Department of Urology, University Hospital Dresden (Germany); Störkel, Stephan; Golz, Reinhard [Department of Pathology, HELIOS Hospital Wuppertal (Germany); Engenhart-Cabillic, Rita [Department of Radiation Oncology, University Hospital Giessen-Marburg (Germany); Hofmann, Rainer [Department of Urology, University Hospital Giessen-Marburg (Germany); Feldmann, Horst-Jürgen [Department of Radiation Oncology, General Hospital Fulda (Germany); Kälble, Tilman [Department of Urology, General Hospital Fulda (Germany); Siegmann, Alessandra; Hinkelbein, Wolfgang [Department of Radiation Oncology, University Hospital Berlin (Germany); Steiner, Ursula; Miller, Kurt [Department of Urology, University Hospital Berlin (Germany)

2015-02-01

Objective: The ARO 96-02 trial primarily compared wait-and-see (WS, arm A) with adjuvant radiation therapy (ART, arm B) in prostate cancer patients who achieved an undetectable prostate-specific antigen (PSA) after radical prostatectomy (RP). Here, we report the outcome with up to 12 years of follow-up of patients who retained a post-RP detectable PSA and received salvage radiation therapy (SRT, arm C). Methods and Materials: For the study, 388 patients with pT3-4pN0 prostate cancer with positive or negative surgical margins were recruited. After RP, 307 men achieved an undetectable PSA (arms A + B). In 78 patients the PSA remained above thresholds (median 0.6, range 0.05-5.6 ng/mL). Of the latter, 74 consented to receive 66 Gy to the prostate bed, and SRT was applied at a median of 86 days after RP. Clinical relapse-free survival, metastasis-free survival, and overall survival were determined by the Kaplan-Meier method. Results: Patients with persisting PSA after RP had higher preoperative PSA values, higher tumor stages, higher Gleason scores, and more positive surgical margins than did patients in arms A + B. For the 74 patients, the 10-year clinical relapse-free survival rate was 63%. Forty-three men had hormone therapy; 12 experienced distant metastases; 23 patients died. Compared with men who did achieve an undetectable PSA, the arm-C patients fared significantly worse, with a 10-year metastasis-free survival of 67% versus 83% and overall survival of 68% versus 84%, respectively. In Cox regression analysis, Gleason score ≥8 (hazard ratio [HR] 2.8), pT ≥ 3c (HR 2.4), and extraprostatic extension ≥2 mm (HR 3.6) were unfavorable risk factors of progression. Conclusions: A persisting PSA after prostatectomy seems to be an important prognosticator of clinical progression for pT3 tumors. It correlates with a higher rate of distant metastases and with worse overall survival. A larger prospective study is required to determine which patient subgroups

Option A improved HIV-free infant survival and mother to child HIV transmission at 9-18 months in Zimbabwe.

Science.gov (United States)

Buzdugan, Raluca; Kang Dufour, Mi-Suk; McCoy, Sandra I; Watadzaushe, Constancia; Dirawo, Jeffrey; Mushavi, Angela; Mujuru, Hilda Angela; Mahomva, Agnes; Kangwende, Rugare Abigail; Hakobyan, Anna; Mugurungi, Owen; Cowan, Frances M; Padian, Nancy S

2016-06-19

We evaluated the impact of Option A on HIV-free infant survival and mother-to-child transmission (MTCT) in Zimbabwe. Serial cross-sectional community-based serosurveys. We analyzed serosurvey data collected in 2012 and 2014 among mother-infant pairs from catchment areas of 132 health facilities from five of 10 provinces in Zimbabwe. Eligible infants (alive or deceased) were born 9-18 months before each survey to mothers at least 16 years old. We randomly selected mother-infant pairs and conducted questionnaires, verbal autopsies, and collected blood samples. We estimated the HIV-free infant survival and MTCT rate within each catchment area and compared the 2012 and 2014 estimates using a paired t test and number of HIV infections averted because of the intervention. We analyzed 7249 mother-infant pairs with viable maternal specimens collected in 2012 and 8551 in 2014. The mean difference in the catchment area level MTCT between 2014 and 2012 was -5.2 percentage points (95% confidence interval = -8.1, -2.3, P Option A regimen. The association between HIV-free infant survival and duration of Option A implementation was NS at the multivariate level (P = 0.093). We found a substantial and statistically significant increase in HIV-free survival and decrease in MTCT among infants aged 9-18 months following Option A rollout in Zimbabwe. This is the only evaluation of Option A and shows the effectiveness of Option A and Zimbabwe's remarkable progress toward eMTCT.

Development and internal validation of a prognostic model to predict recurrence free survival in patients with adult granulosa cell tumors of the ovary

NARCIS (Netherlands)

van Meurs, Hannah S.; Schuit, Ewoud; Horlings, Hugo M.; van der Velden, Jacobus; van Driel, Willemien J.; Mol, Ben Willem J.; Kenter, Gemma G.; Buist, Marrije R.

2014-01-01

Models to predict the probability of recurrence free survival exist for various types of malignancies, but a model for recurrence free survival in individuals with an adult granulosa cell tumor (GCT) of the ovary is lacking. We aimed to develop and internally validate such a prognostic model. We

The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse

DEFF Research Database (Denmark)

Schmiegelow, K; Donovan, Martin Heyman; Sherson, Maiken Gustafsson

2010-01-01

Drug doses, blood levels of drug metabolites and myelotoxicity during 6-mercaptopurine/methotrexate (MTX) maintenance therapy were registered for 59 adolescents (10 years) and 176 non-adolescents (leukemia (ALL) and a white blood cell count (WBC......) diagnosis. Event-free survival was lower for adolescents than non-adolescents (pEFS12y:0.71 vs 0.83, P=0.04). For adolescents staying in remission, the mean WBC during maintenance therapy (mWBC) was related to age (rS=0.36, P=0.02), which became nonsignificant for those who relapsed (r...

Volumetric FDG-PET predicts overall and progression- free survival after 14 days of targeted therapy in metastatic renal cell carcinoma

International Nuclear Information System (INIS)

Farnebo, Jacob; Grybäck, Per; Harmenberg, Ulrika; Laurell, Anna; Wersäll, Peter; Blomqvist, Lennart K; Ullén, Anders; Sandström, Per

2014-01-01

To determine whether changes in the metabolism of metastatic renal cell carcinoma (mRCC) assessed by F18-FDG-PET after 14 and 28 days of treatment with tyrosine kinase inhibitors can predict overall and progression- free patient survival. Thirty-nine consecutive patients with mRCC were included prospectively and underwent PET examinations prior to and after 14 and 28 days of standard treatment with sunitinib (n = 18), sorafenib (n = 19) or pazopanib (n = 2). The PET response was analyzed in terms of SUVmax, SULpeak, and total lesion glycolysis and a positive response (defined as a 30% reduction) compared to overall and progression- free survival. Thirty-five patients with at least one metabolically active metastatic lesion prior to treatment underwent additional FDG-PET examinations after 14 (n = 32) and/or 28 days (n = 30) of treatment. Changes in either SULpeak or total lesion glycolysis were correlated to both progression-free and overall survival (for TLG2.5 responders, HR = 0.38 (95% CI: 0.18-0.83) and 0.22 (95% CI: 0.09-0.53), and for TLG50 responders, HR = 0.25 (0.10-0.62) and 0.25 (95% CI: 0.11-0.57) and for SULpeak responders, HR = 0.39 (95% CI: 0.17-0.91) and 0.38 (95% CI: 0.15-0.93), respectively). In contrast SUVmax response did not predict progression- free or overall survival (HR = 0.43 (95% CI: 0.18-1.01) and 0.50 (95% CI: 0.21-1.19), respectively). Assessment of early changes in SULpeak and total lesion glycolysis undergoing treatment with tyrosine kinase inhibitors by FDG-PET can possibly predict progression- free and overall survival in patients with mRCC

CD20 positivity and white blood cell count predict treatment outcomes in Philadelphia chromosome-negative acute lymphoblastic leukemia patients ineligible for pediatric-inspired chemotherapy.

Science.gov (United States)

Isshiki, Yusuke; Ohwada, Chikako; Sakaida, Emiko; Onoda, Masahiro; Aotsuka, Nobuyuki; Tanaka, Hiroaki; Fukazawa, Motoharu; Cho, Ryuko; Sugawara, Takeaki; Kawaguchi, Takeharu; Hara, Satoru; Yokota, Akira

2017-11-01

The efficacy of conventional chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been controversial as post-remission therapies for adult Philadelphia chromosome-negative acute lymphoblastic leukemia patients. We retrospectively analyzed 96 adolescent and adult cases of Philadelphia chromosome-negative acute lymphoblastic leukemia to evaluate whether allo-HSCT should be performed after first complete remission (1CR). In total, 34 patients received chemotherapy followed by allo-HSCT (HSCT group) and 62 received chemotherapy alone (chemotherapy group). No significant differences in the event-free survival (EFS) or overall survival were observed between the two groups. In the chemotherapy group, use of pediatric regimens was significantly associated with favorable EFS, while high white blood cell (WBC) count and CD20 positivity were associated with poor outcome. In patients who received pediatric regimens, subsequent allo-HSCT did not influence EFS. In patients who received conventional chemotherapy (adult regimen), subsequent allo-HSCT did not improve EFS. High WBC count and CD20 positivity were also significantly associated with poor EFS in patients who received adult regimens. Patients with low WBC count and absence of CD20 who received adult regimens did not benefit from allo-HSCT. Allo-HSCT may not be required in the pediatric regimen-eligible patients; however, pediatric regimen-ineligible patients with either CD20 positivity or high WBC count should receive allo-HSCT after achieving 1CR. This study was registered at http://www.umin.ac.jp/ctr/ as #C000016287. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Comparison of survival outcome between donor types or stem cell sources for childhood acute myeloid leukemia after allogenic hematopoietic stem cell transplantation: A multicenter retrospective study of Study Alliance of Yeungnam Pediatric Hematology-oncology.

Science.gov (United States)

Shim, Ye Jee; Lee, Jae Min; Kim, Heung Sik; Jung, Nani; Lim, Young Tak; Yang, Eu Jeen; Hah, Jeong Ok; Lee, Young-Ho; Chueh, Hee Won; Lim, Jae Young; Park, Eun Sil; Park, Jeong A; Park, Ji Kyoung; Park, Sang Kyu

2018-06-19

We compared transplant outcomes between donor types and stem cell sources for childhood acute myeloid leukemia (AML). The medical records of children with AML in the Yeungnam region of Korea from January 2000 to June 2017 were reviewed. In all, 76 children with AML (male-to-female ratio = 46:30) received allogenic hematopoietic stem cell transplantation (allo-HSCT). In total, 29 patients received HSCT from either a matched-related donor or a mismatched-related donor, 32 patients received an unrelated donor, and 15 patients received umbilical cord blood. In term of stem cell sources, bone marrow was used in 15 patients and peripheral blood in 46 patients. For all HSCT cases, the 5-year overall survival (OS) was 73.1% (95% CI: 62.7-83.5) and the 5-year event-free survival (EFS) was 66.1% (95% CI: 54.5-77.7). There was no statistical difference in 5-year OS according to the donor types or stem cell sources (P = .869 and P = .911). There was no statistical difference in 5-year EFS between donor types or stem cell sources (P = .526 and P = .478). For all HSCT cases, the 5-year relapse rate was 16.1% (95% CI: 7.3-24.9) and the 5-year non-relapse mortality (NRM) was 13.3% (95% CI: 5.1-21.5). There was no statistical difference in the 5-year relapse rate according to the donor types or stem cell sources (P = .971 and P = .965). There was no statistical difference in the 5-year NRM between donor types or stem cell sources (P = .461 and P = .470). © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prognostic value of myocardial perfusion and ventricular function in a Japanese multicenter cohort study (J-ACCESS). The first-year total events and hard events

International Nuclear Information System (INIS)

Nakajima, Kenichi; Kusuoka, Hideo; Nishimura, Shigeyuki; Yamashina, Akira; Nishimura, Tsunehiko

2009-01-01

The objective of this study was to determine the prognostic value of myocardial ischemia, function and coronary risk factors on total and hard cardiac events using myocardial perfusion imaging in a Japanese population. A prospective cohort study was performed in 117 Japanese hospitals, each with a nuclear cardiology facility. A total of 4,031 patients with suspected or confirmed ischemic heart disease were registered. The patients were followed up for a year to investigate total and hard events, and those who had any events were followed up for 3 years to evaluate subsequent hard events. A stress-rest gated myocardial perfusion study was performed with 99m Tc-tetrofosmin using gated single-photon emission computed tomography (SPECT) and analyzed by semi-quantitative scores. During the 1-year follow-up period, 263 (6.5%) patients had total events comprising all-cause death, non-fatal myocardial infarction (MI), heart failure, unstable angina, angina pectoris and coronary revascularization. Cardiac death occurred in 23 patients (0.6%) and non-fatal MI in 11 (0.3%). Among patients with ejection fraction (EF) of <45% and a summed difference score (SDS) of ≥2, 18.7% (2.4% for cardiac death and 0.6% for non-fatal MI) experienced total events compared with 3.9% (0.3% for cardiac death and 0.2% for non-fatal MI; P<0.0001) of those with EF≥45% and SDS<2. Multivariate analysis identified EF, SDS, age, history of revascularization and diabetes as significant predictors of all events, while the significant predictors were age and EF for hard events. When the patients who had heart failure in the first year were followed up, 9 of 41 (22.0%) experienced cardiac death in the subsequent 3-year follow-up period. Myocardial ischemia defined by SDS and ventricular function were the main predictors of total events despite the relatively low incidence of hard events in this Japanese population. In patients with cardiac events in a year, closer attention should be paid to subsequent

High-energy cosmic ray nuclei from tidal disruption events: Origin, survival, and implications

Science.gov (United States)

Zhang, B. Theodore; Murase, Kohta; Oikonomou, Foteini; Li, Zhuo

2017-09-01

Tidal disruption events (TDEs) by supermassive or intermediate mass black holes have been suggested as candidate sources of ultrahigh-energy cosmic rays (UHECRs) and high-energy neutrinos. Motivated by the recent measurements from the Pierre Auger Observatory, which indicates a metal-rich cosmic-ray composition at ultrahigh energies, we investigate the fate of UHECR nuclei loaded in TDE jets. First, we consider the production and survival of UHECR nuclei at internal shocks, external forward and reverse shocks, and nonrelativistic winds. Based on the observations of Swift J 1644 +57 , we show that the UHECRs can survive for external reverse and forward shocks, and disk winds. On the other hand, UHECR nuclei are significantly disintegrated in internal shocks, although they could survive for low-luminosity TDE jets. Assuming that UHECR nuclei can survive, we consider implications of different composition models of TDEs. We find that the tidal disruption of main sequence stars or carbon-oxygen white dwarfs does not successfully reproduce UHECR observations, namely the observed composition or spectrum. The observed mean depth of the shower maximum and its deviation could be explained by oxygen-neon-magnesium white dwarfs, although they may be too rare to be the sources of UHECRs.

eEF-2 Phosphorylation Down-Regulates P-Glycoprotein Over-Expression in Rat Brain Microvessel Endothelial Cells.

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Xing Hua Tang

Full Text Available We investigated whether glutamate, NMDA receptors, and eukaryote elongation factor-2 kinase (eEF-2K/eEF-2 regulate P-glycoprotein expression, and the effects of the eEF-2K inhibitor NH125 on the expression of P-glycoprotein in rat brain microvessel endothelial cells (RBMECs.Cortex was obtained from newborn Wistar rat brains. After surface vessels and meninges were removed, the pellet containing microvessels was resuspended and incubated at 37°C in culture medium. Cell viability was assessed by the MTT assay. RBMECs were identified by immunohistochemistry with anti-vWF. P-glycoprotein, phospho-eEF-2, and eEF-2 expression were determined by western blot analysis. Mdr1a gene expression was analyzed by RT-PCR.Mdr1a mRNA, P-glycoprotein and phospho-eEF-2 expression increased in L-glutamate stimulated RBMECs. P-glycoprotein and phospho-eEF-2 expression were down-regulated after NH125 treatment in L-glutamate stimulated RBMECs.eEF-2K/eEF-2 should have played an important role in the regulation of P-glycoprotein expression in RBMECs. eEF-2K inhibitor NH125 could serve as an efficacious anti-multidrug resistant agent.

Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the Study Alliance Leukemia.

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Müller-Tidow, C; Tschanter, P; Röllig, C; Thiede, C; Koschmieder, A; Stelljes, M; Koschmieder, S; Dugas, M; Gerss, J; Butterfaß-Bahloul, T; Wagner, R; Eveslage, M; Thiem, U; Krause, S W; Kaiser, U; Kunzmann, V; Steffen, B; Noppeney, R; Herr, W; Baldus, C D; Schmitz, N; Götze, K; Reichle, A; Kaufmann, M; Neubauer, A; Schäfer-Eckart, K; Hänel, M; Peceny, R; Frickhofen, N; Kiehl, M; Giagounidis, A; Görner, M; Repp, R; Link, H; Kiani, A; Naumann, R; Brümmendorf, T H; Serve, H; Ehninger, G; Berdel, W E; Krug, U

2016-03-01

DNA methylation changes are a constant feature of acute myeloid leukemia. Hypomethylating drugs such as azacitidine are active in acute myeloid leukemia (AML) as monotherapy. Azacitidine monotherapy is not curative. The AML-AZA trial tested the hypothesis that DNA methyltransferase inhibitors such as azacitidine can improve chemotherapy outcome in AML. This randomized, controlled trial compared the efficacy of azacitidine applied before each cycle of intensive chemotherapy with chemotherapy alone in older patients with untreated AML. Event-free survival (EFS) was the primary end point. In total, 214 patients with a median age of 70 years were randomized to azacitidine/chemotherapy (arm-A) or chemotherapy (arm-B). More arm-A patients (39/105; 37%) than arm-B (25/109; 23%) showed adverse cytogenetics (P=0.057). Adverse events were more frequent in arm-A (15.44) versus 13.52 in arm-B, (P=0.26), but early death rates did not differ significantly (30-day mortality: 6% versus 5%, P=0.76). Median EFS was 6 months in both arms (P=0.96). Median overall survival was 15 months for patients in arm-A compared with 21 months in arm-B (P=0.35). Azacitidine added to standard chemotherapy increases toxicity in older patients with AML, but provides no additional benefit for unselected patients.

A pilot study of daunorubicin-augmented hyper-CVAD induction chemotherapy for adults with acute lymphoblastic leukemia.

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Kim, Sung-Yong; Park, Ji Hyun; Yoon, So Young; Cho, Yo-Han; Lee, Mark Hong

2018-02-01

Induction of complete remission (CR) is imperative for long-term survival in adult acute lymphoblastic leukemia (ALL) patients regardless of transplantation eligibility. Hyper-CVAD chemotherapy is a widely-used frontline remission induction regimen for these patients. We conducted a pilot trial of frontline remission induction using daunorubicin-augmented hyper-CVAD regimen (hyper-CVDD) in adult ALL patients (n = 15). The CR rate after this modified regimen was 100% (n = 15). Twelve patients were able to proceed to allogeneic hematopoietic cell transplantation, two patients died before transplantation due to infection, and the remaining one who was ineligible for transplant due to her age received an additional five courses of consolidation chemotherapy. Overall survival (OS) and event-free survival (EFS) of the study patients was 61.0 and 47.5% at 3 years. OS and relapse-free survival of transplanted patients was 66.8 and 55.0% at 3 years. This pilot trial demonstrates the favorable efficacy of the hyper-CVDD chemotherapy as a frontline remission induction regimen. Further clinical trials using this regimen are warranted.

Survival rates in the Czech Republic of introduced plants known as wool aliens

Czech Academy of Sciences Publication Activity Database

Pyšek, Petr

2005-01-01

Roč. 7, - (2005), s. 567-576 ISSN 1387-3547 R&D Projects: GA ČR(CZ) GA526/00/1443 Institutional research plan: CEZ:AV0Z60050516 Keywords : wool aliens * survival rate * naturalization Subject RIV: EF - Botanics

Up-regulation of eEF1A2 promotes proliferation and inhibits apoptosis in prostate cancer

International Nuclear Information System (INIS)

Sun, Yue; Du, Chengli; Wang, Bo; Zhang, Yanling; Liu, Xiaoyan; Ren, Guoping

2014-01-01

Highlights: • The expression of eEF1A2 is up-regulated in prostate cancer tissues. • Suppression of eEF1A2 inhibits the proliferation and promotes apoptosis. • Inhibition of eEF1A2 enhances the expression of apoptotic relevant proteins. • The expressions of eEF1A2 and cleavage-caspase3 are inversely correlated. - Abstract: Background: eEF1A2 is a protein translation factor involved in protein synthesis, which possesses important function roles in cancer development. This study aims at investigating the expression pattern of eEF1A2 in prostate cancer and its potential role in prostate cancer development. Methods: We examined the expression level of eEF1A2 in 30 pairs of prostate cancer tissues by using RT-PCR and immunohistochemical staining (IHC). Then we applied siRNA specifically targeting eEF1A2 to down-regulate its expression in DU-145 and PC-3 cells. Flow cytometer was used to explore apoptosis and Western-blot was used to detect the pathway proteins of apoptosis. Results: Our results showed that the expression level of eEF1A2 in prostate cancer tissues was significantly higher compared to their corresponding normal tissues. Reduction of eEF1A2 expression in DU-145 and PC-3 cells led to a dramatic inhibition of proliferation accompanied with enhanced apoptosis rate. Western blot revealed that apoptosis pathway proteins (caspase3, BAD, BAX, PUMA) were significantly up-regulated after suppression of eEF1A2. More importantly, the levels of eEF1A2 and caspase3 were inversely correlated in prostate cancer tissues. Conclusion: Our data suggests that eEF1A2 plays an important role in prostate cancer development, especially in inhibiting apoptosis. So eEF1A2 might serve as a potential therapeutic target in prostate cancer

In vivo and in vitro suppression of hepatocellular carcinoma by EF24, a curcumin analog.

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Haitao Liu

Full Text Available The synthetic compound 3,5-bis(2-flurobenzylidenepiperidin-4-one (EF24 is a potent analog of curcumin that exhibits enhanced biological activity and bioavailability without increasing toxicity. EF24 exerts antitumor activity by arresting the cell cycle and inducing apoptosis, suppressing many types of cancer cells in vitro. The antiproliferative and antiangiogenic properties of EF24 provide theoretical support for its development and application to liver cancers. We investigated the in vitro and in vivo activities of EF24 on liver cancer to better understand its therapeutic effects and mechanisms. EF24 induced significant apoptosis and G2/M-phase cell cycle arrest in mouse liver cancer cell lines, Hepa1-6 and H22. The expression levels of G2/M cell cycle regulating factors, cyclin B1 and Cdc2, were significantly decreased, pp53, p53, and p21 were significantly increased in EF24-treated cells. In addition, EF24 treatment significantly reduced Bcl-2 concomitant with an increase in Bax, enhanced the release of cytochrome c from the mitochondria into the cytosol, resulting in an upregulation of cleaved-caspase-3, which promoted poly (ADP-ribose polymerase cleavage. EF24-treated cells also displayed decreases in phosphorylated Akt, phosphorylated extracellular signal-regulated kinase and vascular endothelial growth factor. Our in vitro protein expression data were confirmed in vivo using a subcutaneous hepatocellular carcinoma (HCC tumor model. This mouse HCC model confirmed that total body weight was unchanged following EF24 treatment, although tumor weight was significantly decreased. Using an orthotopic HCC model, EF24 significantly reduced the liver/body weight ratio and relative tumor areas compared to the control group. In situ detection of apoptotic cells and quantification of Ki-67, a biomarker of cell proliferation, all indicated significant tumor suppression with EF24 treatment. These results suggest that EF24 exhibits anti-tumor activity

Combined external beam therapy (EBT) and brachytherapy in the treatment of localized prostate carcinoma : The 1979-1993 Centre Francois Baclesse experience

International Nuclear Information System (INIS)

Brune, D.; Coueette, J-E.; Lesaunier, F.; Benabib, D.; Mace-Lesec'h, J.; Henry-Amar, M.

1996-01-01

Purpose: To improve efficacy and minimize rectal, vesical and urethral morbidity. Patients and Methods: Three 192 Ir brachytherapy (BT) techniques were developed: transurethral BT and interstitial BT with low dose rate (TBT-LDR and IBT-LDR), and IBT with high DR (IBT-HDR). EBT delivered 43.2 Gy in 18 fr/32 d in pelvic volume. BT-LDR delivered 15 Gy with mean urethral dose 80-90 Gy and maximal rectal dose 50-60 Gy to rectum. BT-HDR delivered 9.4 Gy in 2 fractions over a 2-3 days period, with urethral dose 18 Gy and rectal dose 9.4 Gy. 161 pts were treated with TBT-LDR, 185 with IBT-LDR and 40 with IBT-HDR. Mean age was 69 yrs; 90% were T2-T3; 76% had Gleason grade 10 ng/ml (IEA). Results: IBT induced better event-free survival (EFS) than TBT, with no difference between IBT-LDR and IBT-HDR. While IBT and TBT were equivalent in T1 (5-yr EFS 88% vs 83%) pts, IBT was superior to TBT in T2 (64% vs 51%) and T3 (43% vs 31%) pts. In IBT, very localized tumour (T1 a T1 b T2 a , n=51) pts had better 5-yr EFS, local recurrence-free survival and distant recurrence-free survival than pts with more advanced tumour (T2 b T3T4, n=141), 77%, 92% and 85% vs 41%, 78% and 61%, respectively. EFS highly correlated with initial PSA (p<0.001). PSA returned to normal value within 7 mo (maxi 2 yrs) in 78% of pts with very localized tumour vs 44% in other pts; EFS also highly correlated with normalization of PSA (p<0.001). Rectal morbidity was very low in both techniques (4 grade 3 in IBT pts). Urinary morbidity was limited: 5-yr cumulative rate of grade 2 haematuria 3%, grade 2-3 dysuria 7%, grade 2-3 incontinence 28% (mostly after prostate resection, 44% vs 18%). Sexual function at diagnosis was documented in 129 pts in whom it was well preserved in 27%. Among the latter, the cumulative risk of impotency was 11% at 1 yr, 21% at 2 yrs and 35% at 3 yrs. Conclusions: In locally advanced prostate tumour, IBT appears to induce better results than TBT because the overall prostate volume is

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

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Hisao Imai

2015-01-01

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

Management of Primary Tectal Plate Low-Grade Glioma in Pediatric Patients: Results of the Multicenter Treatment Study SIOP-LGG 2004.

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Kaufmann, Ariane; Gerber, Nicolas U; Kandels, Daniela; Azizi, Amedeo A; Schmidt, Rene; Warmuth-Metz, Monika; Pietsch, Torsten; Kortmann, Rolf-Dieter; Gnekow, Astrid K; Grotzer, Michael A

2018-06-11

 Tectal plate low-grade gliomas (LGGs) most often present with increased intracranial pressure and sometimes as incidental findings from brain imaging. Prognostic factors predicting outcome are largely unknown.  From 2004 until 2012, 71 patients with tectal plate LGG from Germany and Switzerland were followed within the SIOP-LGG 2004 study. Median age at diagnosis was 9.7 (range: 0.1-17.5) years, and median follow-up time of surviving patients was 6.3 (interquartile range: 4.9-8.3) years.  A total of 41 out of 71 patients received no tumor treatment (12 with and 29 without biopsy). The 10-year event-free survival (EFS) rate (± standard error ) for patients with an initial tumor volume of ≤3 cm 3 was 56% (±7%), as opposed to 12% (±8%) for those with tumors >3 cm 3 ( p  < 0.001). The 10-year EFS for patients without contrast enhancement on initial magnetic resonance imaging (MRI) was 52% (±9%), and for those with enhancement, it was 23% (±9%) ( p  = 0.003). The 10-year overall survival rate was 96% (±3%) (death due to disease, 1; ventriculoperitoneal shunt infection, 1). Sixty-three (89%) patients had at least one cerebrospinal fluid diversion procedure.  More than half of patients were managed without tumor treatment. Favorable prognostic factors for EFS were small initial tumor volume (≤3cm 3 ) and the absence of initial contrast enhancement on MRI. Overall survival was excellent. Georg Thieme Verlag KG Stuttgart · New York.

Evolution of EF-hand calcium-modulated proteins. IV. Exon shuffling did not determine the domain compositions of EF-hand proteins

Science.gov (United States)

Kretsinger, R. H.; Nakayama, S.

1993-01-01

In the previous three reports in this series we demonstrated that the EF-hand family of proteins evolved by a complex pattern of gene duplication, transposition, and splicing. The dendrograms based on exon sequences are nearly identical to those based on protein sequences for troponin C, the essential light chain myosin, the regulatory light chain, and calpain. This validates both the computational methods and the dendrograms for these subfamilies. The proposal of congruence for calmodulin, troponin C, essential light chain, and regulatory light chain was confirmed. There are, however, significant differences in the calmodulin dendrograms computed from DNA and from protein sequences. In this study we find that introns are distributed throughout the EF-hand domain and the interdomain regions. Further, dendrograms based on intron type and distribution bear little resemblance to those based on protein or on DNA sequences. We conclude that introns are inserted, and probably deleted, with relatively high frequency. Further, in the EF-hand family exons do not correspond to structural domains and exon shuffling played little if any role in the evolution of this widely distributed homolog family. Calmodulin has had a turbulent evolution. Its dendrograms based on protein sequence, exon sequence, 3'-tail sequence, intron sequences, and intron positions all show significant differences.

Complex distribution of EFL and EF-1α proteins in the green algal lineage

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Keeling Patrick J

2007-05-01

Full Text Available Abstract Background EFL (or elongation factor-like is a member of the translation superfamily of GTPase proteins. It is restricted to eukaryotes, where it is found in a punctate distribution that is almost mutually exclusive with elongation factor-1 alpha (EF-1α. EF-1α is a core translation factor previously thought to be essential in eukaryotes, so its relationship to EFL has prompted the suggestion that EFL has spread by horizontal or lateral gene transfer (HGT or LGT and replaced EF-1α multiple times. Among green algae, trebouxiophyceans and chlorophyceans have EFL, but the ulvophycean Acetabularia and the sister group to green algae, land plants, have EF-1α. This distribution singles out green algae as a particularly promising group to understand the origin of EFL and the effects of its presence on EF-1α. Results We have sampled all major lineages of green algae for both EFL and EF-1α. EFL is unexpectedly broad in its distribution, being found in all green algal lineages (chlorophyceans, trebouxiophyceans, ulvophyceans, prasinophyceans, and mesostigmatophyceans, except charophyceans and the genus Acetabularia. The presence of EFL in the genus Mesostigma and EF-1α in Acetabularia are of particular interest, since the opposite is true of all their closest relatives. The phylogeny of EFL is poorly resolved, but the Acetabularia EF-1α is clearly related to homologues from land plants and charophyceans, demonstrating that EF-1α was present in the common ancestor of the green lineage. Conclusion The distribution of EFL and EF-1α in the green lineage is not consistent with the phylogeny of the organisms, indicating a complex history of both genes. Overall, we suggest that after the introduction of EFL (in the ancestor of green algae or earlier, both genes co-existed in green algal genomes for some time before one or the other was lost on multiple occasions.

Towards real-time eruption forecasting in the Auckland Volcanic Field: application of BET_EF during the New Zealand National Disaster Exercise `Ruaumoko'

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Lindsay, Jan; Marzocchi, Warner; Jolly, Gill; Constantinescu, Robert; Selva, Jacopo; Sandri, Laura

2010-03-01

The Auckland Volcanic Field (AVF) is a young basaltic field that lies beneath the urban area of Auckland, New Zealand’s largest city. Over the past 250,000 years the AVF has produced at least 49 basaltic centers; the last eruption was only 600 years ago. In recognition of the high risk associated with a possible future eruption in Auckland, the New Zealand government ran Exercise Ruaumoko in March 2008, a test of New Zealand’s nation-wide preparedness for responding to a major disaster resulting from a volcanic eruption in Auckland City. The exercise scenario was developed in secret, and covered the period of precursory activity up until the eruption. During Exercise Ruaumoko we adapted a recently developed statistical code for eruption forecasting, namely BET_EF (Bayesian Event Tree for Eruption Forecasting), to independently track the unrest evolution and to forecast the most likely onset time, location and style of the initial phase of the simulated eruption. The code was set up before the start of the exercise by entering reliable information on the past history of the AVF as well as the monitoring signals expected in the event of magmatic unrest and an impending eruption. The average probabilities calculated by BET_EF during Exercise Ruaumoko corresponded well to the probabilities subjectively (and independently) estimated by the advising scientists (differences of few percentage units), and provided a sound forecast of the timing (before the event, the eruption probability reached 90%) and location of the eruption. This application of BET_EF to a volcanic field that has experienced no historical activity and for which otherwise limited prior information is available shows its versatility and potential usefulness as a tool to aid decision-making for a wide range of volcano types. Our near real-time application of BET_EF during Exercise Ruaumoko highlighted its potential to clarify and possibly optimize decision-making procedures in a future AVF eruption

Management plan for deep sternal wound infection targeting to survival free of recurrence: A prospective evaluation study

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Ibrahim Kasb

2016-10-01

Conclusion: Management of DSWI is tedious, has prolonged hospital stay and is associated with high morbidity and mortality rates. Management of DSWI must be personalized according to findings on exploration of the sternal wound and flap coverage must be initiated only when the patient is bacteriologically free. Both PMF and/or VOF provided high acceptable success rate defined as survival free of DSWI recurrence.

Extremely low-frequency magnetic fields and survival from childhood acute lymphoblastic leukemia

DEFF Research Database (Denmark)

Schüz, J; Grell, K; Kinsey, S

2012-01-01

A previous US study reported poorer survival in children with acute lymphoblastic leukemia (ALL) exposed to extremely low-frequency magnetic fields (ELF-MF) above 0.3 μT, but based on small numbers. Data from 3073 cases of childhood ALL were pooled from prospective studies conducted in Canada......, Denmark, Germany, Japan, UK and US to determine death or relapse up to 10 years from diagnosis. Adjusting for known prognostic factors, we calculated hazard ratios (HRs) and 95% confidence intervals (CI) for overall survival and event-free survival for ELF-MF exposure categories and by 0.1 μT increases...

Whole-brain radiotherapy and high-dose methylprednisolone for elderly patients with primary central nervous system lymphoma: Results of North Central Cancer Treatment Group (NCCTG) 96-73-51

International Nuclear Information System (INIS)

Laack, Nadia N.; Ballman, Karla V.; Brown, Paul B.; O'Neill, Brian Patrick

2006-01-01

Purpose: The aim of this study was to evaluate the efficacy, toxicity, and survival of whole-brain radiotherapy-treated (WBRT) and high-dose methylprednisolone (HDMP)-treated in elderly patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Patients with PCNSL who were 70 years and older received 1 g of methylprednisolone daily for 5 days, 30 days after WBRT. Patients then received 1 g of methylprednisolone every 28 days until progression. The primary endpoint was overall survival (OS) at 6 months. Results were compared with those in patients on the previous North Central Cancer Treatment Group (NCCTG) trial who received pre-WBRT cytoxan, adriamycin, vincristine, prednisone (CHOP) and high-dose cytarabine (CHOP-WBRT). A planned interim analysis was performed. The current regimen would be considered inactive if survival was not improved from patients treated with CHOP-WBRT. Results: Nineteen patients were accrued between 1998 and 2003. Median age was 76 years. Interim analysis revealed a 6-month survival of 33%, resulting in closure of the trial. Toxicity, OS, and event-free survival (EFS) were similar to those in patients more than 70 years of age who received CHOP-WBRT. The subgroup of patients who received HDMP had longer OS (12.1 vs. 7.0 months, p = 0.76) and EFS (11.7 vs. 4.0 months, p = 0.04) compared with the CHOP-WBRT patients alive 60 days after the start of treatment. Conclusions: Patients on-study long enough to receive HDMP had prolongation of OS and EFS compared to patients receiving CHOP-WBRT. Although the numbers of patients are too small for statistical conclusions, the HDMP regimen deserves further study

delta-EF1 is a negative regulator of Ihh in the developing growth plate.

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Bellon, Ellen; Luyten, Frank P; Tylzanowski, Przemko

2009-11-30

Indian hedgehog (Ihh) regulates proliferation and differentiation of chondrocytes in the growth plate. Although the biology of Ihh is currently well documented, its transcriptional regulation is poorly understood. delta-EF1 is a two-handed zinc finger/homeodomain transcriptional repressor. Targeted inactivation of mouse delta-EF1 leads to skeletal abnormalities including disorganized growth plates, shortening of long bones, and joint fusions, which are reminiscent of defects associated with deregulation of Ihh signaling. Here, we show that the absence of delta-EF1 results in delayed hypertrophic differentiation of chondrocytes and increased cell proliferation in the growth plate. Further, we demonstrate that delta-EF1 binds to the putative regulatory elements in intron 1 of Ihh in vitro and in vivo, resulting in down-regulation of Ihh expression. Finally, we show that delta-EF1 haploinsufficiency leads to a postnatal increase in trabecular bone mass associated with enhanced Ihh expression. In summary, we have identified delta-EF1 as an in vivo negative regulator of Ihh expression in the growth plate.

Structure of eEF3 and the mechanism of transfer RNA release from the E-site

DEFF Research Database (Denmark)

Andersen, Christian Brix Folsted; Becker, T.; Blau, M.

2006-01-01

Elongation factor eEF3 is an ATPase, which, in addition to the two canonical factors eEF1A and eEF2, serves an essential function in the translation cycle of fungi. eEF3 is required for the binding of the aatRNA-eEF1A-GTP ternary complex to the ribosomal A-site and has been suggested to facilitate...... the clearance of deacyl-tRNA from the E-site. Here, we present the crystal structure of eEF3 showing that it consists of an N-terminal HEAT repeat domain, followed by a four-helix bundle and two ABC-type ATPase domains with a chromo-domain inserted in ABC2. Moreover, we present the cryo-EM structure of the ATP......-bound form of eEF3 in complex with the post-translocational state 80S ribosome from yeast. eEF3 uses an entirely new factor binding site near the ribosomal E-site, with the chromodomain stabilizing the ribosomal L1 stalk in an open conformation, thus, allowing tRNA release....

Assessment of early response biomarkers in relation to long‐term survival in patients with HER2‐negative breast cancer receiving neoadjuvant chemotherapy plus bevacizumab: Results from the Phase II PROMIX trial

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Kimbung, Siker; Markholm, Ida; Bjöhle, Judith; Lekberg, Tobias; von Wachenfeldt, Anna; Azavedo, Edward; Saracco, Ariel; Hellström, Mats; Veerla, Srinivas; Paquet, Eric; Bendahl, Pär‐Ola; Fernö, Mårten; Bergh, Jonas; Loman, Niklas

2017-01-01

Pathologic complete response (pCR) is a predictor for favorable outcome after neoadjuvant treatment in early breast cancer. Modulation of gene expression may also provide early readouts of biological activity and prognosis, offering the possibility for timely response‐guided treatment adjustment. The role of early transcriptional changes in predicting response to neoadjuvant chemotherapy plus bevacizumab was investigated. One‐hundred‐and‐fifty patients with large, operable and locally advanced HER2‐negative breast cancer received epirubicin and docetaxel, with the addition of bevacizumab. Patients underwent tumor biopsies at baseline, after Cycle 2 and at the time of surgery. The primary end point, pCR, and its relation with the secondary endpoints event‐free survival (EFS), overall survival (OS) and gene expression profiles, are reported. The pCR rate was 13% (95% CI 8.6–20.2), with significantly more pCRs among triple‐negative [28% (95% CI 14.8–45.4)] than among hormone receptor positive (HR+) tumors [9% (95% CI 4.6–16.3); (OR = 3.9 [CI = 1.5–10.3])]. pCR rates were not associated with EFS or OS. PAM50 subtypes significantly changed after Cycle 2 (p = 0.03) and an index of absolute changes in PAM50 correlations between these time‐points was associated with EFS [HR = 0.62 (CI = 0.3–1.1)]. In univariable analyses, signatures for angiogenesis, proliferation, estrogen receptor signaling, invasion and metastasis, and immune response, measured after Cycle 2, were associated with pCR in HR+ tumors. Evaluation of changes in molecular subtypes and other signatures early in the course of neoadjuvant treatment may be predictive of pCR and EFS. These factors may help guide further treatment and should be considered when designing neoadjuvant trials. PMID:28940389

Guidelines for the definition of time-to-event end points in renal cell cancer clinical trials: results of the DATECAN project†.

Science.gov (United States)

Kramar, A; Negrier, S; Sylvester, R; Joniau, S; Mulders, P; Powles, T; Bex, A; Bonnetain, F; Bossi, A; Bracarda, S; Bukowski, R; Catto, J; Choueiri, T K; Crabb, S; Eisen, T; El Demery, M; Fitzpatrick, J; Flamand, V; Goebell, P J; Gravis, G; Houédé, N; Jacqmin, D; Kaplan, R; Malavaud, B; Massard, C; Melichar, B; Mourey, L; Nathan, P; Pasquier, D; Porta, C; Pouessel, D; Quinn, D; Ravaud, A; Rolland, F; Schmidinger, M; Tombal, B; Tosi, D; Vauleon, E; Volpe, A; Wolter, P; Escudier, B; Filleron, T

2015-12-01

In clinical trials, the use of intermediate time-to-event end points (TEEs) is increasingly common, yet their choice and definitions are not standardized. This limits the usefulness for comparing treatment effects between studies. The aim of the DATECAN Kidney project is to clarify and recommend definitions of TEE in renal cell cancer (RCC) through a formal consensus method for end point definitions. A formal modified Delphi method was used for establishing consensus. From a 2006-2009 literature review, the Steering Committee (SC) selected 9 TEE and 15 events in the nonmetastatic (NM) and metastatic/advanced (MA) RCC disease settings. Events were scored on the range of 1 (totally disagree to include) to 9 (totally agree to include) in the definition of each end point. Rating Committee (RC) experts were contacted for the scoring rounds. From these results, final recommendations were established for selecting pertinent end points and the associated events. Thirty-four experts scored 121 events for 9 end points. Consensus was reached for 31%, 43% and 85% events during the first, second and third rounds, respectively. The expert recommend the use of three and two endpoints in NM and MA setting, respectively. In the NM setting: disease-free survival (contralateral RCC, appearance of metastases, local or regional recurrence, death from RCC or protocol treatment), metastasis-free survival (appearance of metastases, regional recurrence, death from RCC); and local-regional-free survival (local or regional recurrence, death from RCC). In the MA setting: kidney cancer-specific survival (death from RCC or protocol treatment) and progression-free survival (death from RCC, local, regional, or metastatic progression). The consensus method revealed that intermediate end points have not been well defined, because all of the selected end points had at least one event definition for which no consensus was obtained. These clarified definitions of TEE should become standard practice in

Surrogate marker analysis in cancer clinical trials through time-to-event mediation techniques.

Science.gov (United States)

Vandenberghe, Sjouke; Duchateau, Luc; Slaets, Leen; Bogaerts, Jan; Vansteelandt, Stijn

2017-01-01

The meta-analytic approach is the gold standard for validation of surrogate markers, but has the drawback of requiring data from several trials. We refine modern mediation analysis techniques for time-to-event endpoints and apply them to investigate whether pathological complete response can be used as a surrogate marker for disease-free survival in the EORTC 10994/BIG 1-00 randomised phase 3 trial in which locally advanced breast cancer patients were randomised to either taxane or anthracycline based neoadjuvant chemotherapy. In the mediation analysis, the treatment effect is decomposed into an indirect effect via pathological complete response and the remaining direct effect. It shows that only 4.2% of the treatment effect on disease-free survival after five years is mediated by the treatment effect on pathological complete response. There is thus no evidence from our analysis that pathological complete response is a valuable surrogate marker to evaluate the effect of taxane versus anthracycline based chemotherapies on progression free survival of locally advanced breast cancer patients. The proposed analysis strategy is broadly applicable to mediation analyses of time-to-event endpoints, is easy to apply and outperforms existing strategies in terms of precision as well as robustness against model misspecification.

Complete Surgical Excision Is Essential for the Management of Patients With Breast Implant-Associated Anaplastic Large-Cell Lymphoma.

Science.gov (United States)

Clemens, Mark W; Medeiros, L Jeffrey; Butler, Charles E; Hunt, Kelly K; Fanale, Michelle A; Horwitz, Steven; Weisenburger, Dennis D; Liu, Jun; Morgan, Elizabeth A; Kanagal-Shamanna, Rashmi; Parkash, Vinita; Ning, Jing; Sohani, Aliyah R; Ferry, Judith A; Mehta-Shah, Neha; Dogan, Ahmed; Liu, Hui; Thormann, Nora; Di Napoli, Arianna; DiNapoli, Arianna; Lade, Stephen; Piccolini, Jorge; Reyes, Ruben; Williams, Travis; McCarthy, Colleen M; Hanson, Summer E; Nastoupil, Loretta J; Gaur, Rakesh; Oki, Yasuhiro; Young, Ken H; Miranda, Roberto N

2016-01-10

Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is a rare type of T-cell lymphoma that arises around breast implants. The optimal management of this disease has not been established. The goal of this study is to evaluate the efficacy of different therapies used in patients with BI-ALCL to determine an optimal treatment approach. In this study, we applied strict criteria to pathologic findings, assessed therapies used, and conducted a clinical follow-up of 87 patients with BI-ALCL, including 50 previously reported in the literature and 37 unreported. A Prentice, Williams, and Peterson model was used to assess the rate of events for each therapeutic intervention. The median and mean follow-up times were 45 and 30 months, respectively (range, 3 to 217 months). The median overall survival (OS) time after diagnosis of BI-ALCL was 13 years, and the OS rate was 93% and 89% at 3 and 5 years, respectively. Patients with lymphoma confined by the fibrous capsule surrounding the implant had better event-free survival (EFS) and OS than did patients with lymphoma that had spread beyond the capsule (P = .03). Patients who underwent a complete surgical excision that consisted of total capsulectomy with breast implant removal had better OS (P = .022) and EFS (P = .014) than did patients who received partial capsulectomy, systemic chemotherapy, or radiation therapy. Surgical management with complete surgical excision is essential to achieve optimal EFS in patients with BI-ALCL. © 2015 by American Society of Clinical Oncology.

Complete Surgical Excision Is Essential for the Management of Patients With Breast Implant–Associated Anaplastic Large-Cell Lymphoma

Science.gov (United States)

Clemens, Mark W.; Medeiros, L. Jeffrey; Butler, Charles E.; Hunt, Kelly K.; Fanale, Michelle A.; Horwitz, Steven; Weisenburger, Dennis D.; Liu, Jun; Morgan, Elizabeth A.; Kanagal-Shamanna, Rashmi; Parkash, Vinita; Ning, Jing; Sohani, Aliyah R.; Ferry, Judith A.; Mehta-Shah, Neha; Dogan, Ahmed; Liu, Hui; Thormann, Nora; Di Napoli, Arianna; Lade, Stephen; Piccolini, Jorge; Reyes, Ruben; Williams, Travis; McCarthy, Colleen M.; Hanson, Summer E.; Nastoupil, Loretta J.; Gaur, Rakesh; Oki, Yasuhiro; Young, Ken H.

2016-01-01

Purpose Breast implant–associated anaplastic large-cell lymphoma (BI-ALCL) is a rare type of T-cell lymphoma that arises around breast implants. The optimal management of this disease has not been established. The goal of this study is to evaluate the efficacy of different therapies used in patients with BI-ALCL to determine an optimal treatment approach. Patients and Methods In this study, we applied strict criteria to pathologic findings, assessed therapies used, and conducted a clinical follow-up of 87 patients with BI-ALCL, including 50 previously reported in the literature and 37 unreported. A Prentice, Williams, and Peterson model was used to assess the rate of events for each therapeutic intervention. Results The median and mean follow-up times were 45 and 30 months, respectively (range, 3 to 217 months). The median overall survival (OS) time after diagnosis of BI-ALCL was 13 years, and the OS rate was 93% and 89% at 3 and 5 years, respectively. Patients with lymphoma confined by the fibrous capsule surrounding the implant had better event-free survival (EFS) and OS than did patients with lymphoma that had spread beyond the capsule (P = .03). Patients who underwent a complete surgical excision that consisted of total capsulectomy with breast implant removal had better OS (P = .022) and EFS (P = .014) than did patients who received partial capsulectomy, systemic chemotherapy, or radiation therapy. Conclusion Surgical management with complete surgical excision is essential to achieve optimal EFS in patients with BI-ALCL. PMID:26628470

Outcomes and long-term survival of coronary artery surgery: The controversial role of opium as risk marker

Science.gov (United States)

Najafi, Mahdi; Jahangiry, Leila; Mortazavi, Seyedeh Hamideh; Jalali, Arash; Karimi, Abbasali; Bozorgi, Ali

2016-01-01

AIM To study survival in isolated coronary artery bypass graft (CABG) patients and to evaluate the impact of preoperative chronic opium consumption on long-term outcome. METHODS Cohort of 566 isolated CABG patients as Tehran Heart Center cardiac output measurement was conducted. Daily evaluation until discharge as well as 4- and 12-mo and 6.5-year follow-up information for survival status were fulfilled for all patients. Long-term 6.5-year overall and opium-stratified survival, adjusted survival curves based on opium consumption as well as possible predictors of all-cause mortality using multiple cox regression were determined by statistical analysis. RESULTS Six point five-year overall survival was 91.8%; 86.6% in opium consumers and 92.7% in non-opium consumers (P = 0.035). Patients with positive history of opium consumption significantly tended to have lower ejection fraction (EF), higher creatinine level and higher prevalence of myocardial infarction. Multiple predictors of all-cause mortality included age, body mass index, EF, diabetes mellitus and cerebrovascular accident. The hazard ratio (HR) of 2.09 for the risk of mortality in opium addicted patients with a borderline P value (P = 0.052) was calculated in this model. Further adjustment with stratification based on smoking and opium addiction reduced the HR to 1.20 (P = 0.355). CONCLUSION Simultaneous impact of smoking as a confounding variable in most of the patients prevents from definitive judgment on the role of opium as an independent contributing factor in worse long-term survival of CABG patients in addition to advanced age, low EF, diabetes mellitus and cerebrovascular accident. Meanwhile, our findings do not confirm any cardio protective role for opium to improve outcome in coronary patients with the history of smoking. Further studies are needed to clarify pure effect of opium and warrant the aforementioned findings. PMID:27957254

Benefit from prolonged dose-intensive chemotherapy for infants with malignant brain tumors is restricted to patients with ependymoma: a report of the Pediatric Oncology Group randomized controlled trial 9233/34.

Science.gov (United States)

Strother, Douglas R; Lafay-Cousin, Lucie; Boyett, James M; Burger, Peter; Aronin, Patricia; Constine, Louis; Duffner, Patricia; Kocak, Mehmet; Kun, Larry E; Horowitz, Marc E; Gajjar, Amar

2014-03-01

The randomized controlled Pediatric Oncology Group study 9233 tested the hypothesis that dose-intensive (DI) chemotherapy would improve event-free survival (EFS) for children chemotherapy (Regimen A, n = 162) or DI chemotherapy (Regimen B, n = 166). Radiation therapy (RT) was recommended for patients with evidence of disease at completion of chemotherapy or who relapsed within 6 months of chemotherapy completion. Distributions of EFS for Regimens A and B were not significantly different (P = 0.32) with 2- and 10-year rates of 22.8% ± 3.3% and 15.4% ± 3.7%, and 27.1% ± 3.4% and 20.8% ± 3.8%, respectively. Thus, the study hypothesis was rejected. While distributions of EFS and OS were not significantly different between Regimens A and B for patients with medulloblastoma and sPNET, DI chemotherapy resulted in significantly improved EFS distribution (P = .0011) (2-year EFS rates of 42.1% vs. 19.6% with SD chemotherapy), but not OS distribution, for patients with centrally confirmed ependymoma. The degree of surgical resection affected EFS, OS or both for most tumor groups. Approximately 20%, 40% and 20% of patients with medulloblastoma, ependymoma treated with DI chemotherapy, and sPNET, respectively appear to have been cured without RT. Of 11 toxic deaths on study, 10 occurred on the DI chemotherapy arm. Prolonged dose-intensive chemotherapy given to infants with malignant brain tumors resulted in increased EFS only for patients with ependymoma.

Droop-Free Distributed Control with Event-Triggered Communication in DC Micro-Grid

DEFF Research Database (Denmark)

Han, Renke; Aldana, Nelson Leonardo Diaz; Meng, Lexuan

2017-01-01

A novel nonlinear droop-free distributed controller is proposed to achieve accurate current sharing and eliminate voltage drops in dc Micro-Grid (MG). Then by introducing the sample and holding scheme, the proposed controller is extended to the event-triggered-based controller which is designed...

The difference in blood pressure readings between arms and survival: primary care cohort study

OpenAIRE

Clark, Christopher E; Taylor, Rod S; Shore, Angela C; Campbell, John L

2012-01-01

Objective To determine whether a difference in systolic blood pressure readings between arms can predict a reduced event free survival after 10 years. Design Cohort study. Setting Rural general practice in Devon, United Kingdom. Participants 230 people receiving treatment for hypertension in primary care. Intervention Bilateral blood pressure measurements recorded at three successive surgery attendances. Main outcome measures Cardiovascular events and deaths from all causes during a median fo...

Option A Improved HIV-free Infant Survival and Mother to Child HIV Transmission at 9–18 Months in Zimbabwe

Science.gov (United States)

BUZDUGAN, Raluca; KANG DUFOUR, Mi-Suk; MCCOY, Sandra I; WATADZAUSHE, Constancia; DIRAWO, Jeffrey; MUSHAVI, Angela; MUJURU, Hilda Angela; MAHOMVA, Agnes; KANGWENDE, Rugare Abigail; HAKOBYAN, Anna; MUGURUNGI, Owen; COWAN, Frances M; PADIAN, Nancy S

2016-01-01

Objective We evaluated the impact of Option A on HIV-free infant survival and mother-to-child transmission (MTCT) in Zimbabwe. Design Serial cross-sectional community-based serosurveys. Methods We analyzed serosurvey data collected in 2012 and 2014 among mother-infant pairs from catchment areas (CAs) of 132 health facilities from 5 of 10 provinces in Zimbabwe. Eligible infants (alive or deceased) were born 9–18 months before each survey to mothers ≥16 years old. We randomly selected mother-infant pairs and conducted questionnaires, verbal autopsies and collected blood samples. We estimated: 1) the HIV-free infant survival and MTCT rate within each CA and compared the 2012 and 2014 estimates using a paired t-test, 2) number of HIV infections averted due to the intervention. Results We analyzed 7,249 mother-infant pairs with viable maternal specimens collected in 2012 and 8,551 in 2014. The mean difference in the CA-level MTCT between 2014 and 2012 was −5.2 percentage points (95% confidence interval (CI)=−8.1, −2.3, pOption A regimen. The association between HIV-free infant survival and duration of Option A implementation was not significant at the multivariate level (p=0.093). Conclusions We found a substantial and statistically significant increase in HIV-free survival and decrease in MTCT among infants aged 9–18 months following Option A rollout in Zimbabwe. This is the only impact evaluation of Option A and shows the effectiveness of Option A and Zimbabwe’s remarkable progress towards eMTCT. PMID:27058354

A new Leukemia Prognostic Scoring System for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study.

Science.gov (United States)

Chevallier, P; Labopin, M; Turlure, P; Prebet, T; Pigneux, A; Hunault, M; Filanovsky, K; Cornillet-Lefebvre, P; Luquet, I; Lode, L; Richebourg, S; Blanchet, O; Gachard, N; Vey, N; Ifrah, N; Milpied, N; Harousseau, J-L; Bene, M-C; Mohty, M; Delaunay, J

2011-06-01

A simplified prognostic score is presented based on the multivariate analysis of 138 refractory/relapsed acute myeloid leukaemia (AML) patients (median age 55 years, range: 19-70) receiving a combination of intensive chemotherapy+Gemtuzumab as salvage regimen. Overall, 2-year event-free survival (EFS) and overall survival (OS) were 29±4% and 36±4%, respectively. Disease status (relapse Leukemia Prognostic Scoring System was then validated on an independent cohort of 111 refractory/relapsed AML patients. This new simplified prognostic score, using three clinical and biological parameters routinely applied, allow to discriminate around two third of the patients who should benefit from a salvage intensive regimen in the setting of refractory/relapsed AML patients. The other one third of the patients should receive investigational therapy.

Interleukin-11 binds specific EF-hand proteins via their conserved structural motifs.

Science.gov (United States)

Kazakov, Alexei S; Sokolov, Andrei S; Vologzhannikova, Alisa A; Permyakova, Maria E; Khorn, Polina A; Ismailov, Ramis G; Denessiouk, Konstantin A; Denesyuk, Alexander I; Rastrygina, Victoria A; Baksheeva, Viktoriia E; Zernii, Evgeni Yu; Zinchenko, Dmitry V; Glazatov, Vladimir V; Uversky, Vladimir N; Mirzabekov, Tajib A; Permyakov, Eugene A; Permyakov, Sergei E

2017-01-01

Interleukin-11 (IL-11) is a hematopoietic cytokine engaged in numerous biological processes and validated as a target for treatment of various cancers. IL-11 contains intrinsically disordered regions that might recognize multiple targets. Recently we found that aside from IL-11RA and gp130 receptors, IL-11 interacts with calcium sensor protein S100P. Strict calcium dependence of this interaction suggests a possibility of IL-11 interaction with other calcium sensor proteins. Here we probed specificity of IL-11 to calcium-binding proteins of various types: calcium sensors of the EF-hand family (calmodulin, S100B and neuronal calcium sensors: recoverin, NCS-1, GCAP-1, GCAP-2), calcium buffers of the EF-hand family (S100G, oncomodulin), and a non-EF-hand calcium buffer (α-lactalbumin). A specific subset of the calcium sensor proteins (calmodulin, S100B, NCS-1, GCAP-1/2) exhibits metal-dependent binding of IL-11 with dissociation constants of 1-19 μM. These proteins share several amino acid residues belonging to conservative structural motifs of the EF-hand proteins, 'black' and 'gray' clusters. Replacements of the respective S100P residues by alanine drastically decrease its affinity to IL-11, suggesting their involvement into the association process. Secondary structure and accessibility of the hinge region of the EF-hand proteins studied are predicted to control specificity and selectivity of their binding to IL-11. The IL-11 interaction with the EF-hand proteins is expected to occur under numerous pathological conditions, accompanied by disintegration of plasma membrane and efflux of cellular components into the extracellular milieu.

Frontline low-dose alemtuzumab with fludarabine and cyclophosphamide prolongs progression-free survival in high-risk CLL

DEFF Research Database (Denmark)

Geisler, Christian H; van T' Veer, Mars B; Jurlander, Jesper

2014-01-01

.3%). FCA improves progression-free survival in high-risk chronic lymphocytic leukemia. As anticipated, FCA is more immunosuppressive than FC, but with due vigilance, does not lead to a higher treatment-related mortality. This study was registered at www.trialregister.nl as trial no. NTR529....

POTENTIAL MARKETING PLAN FOR EF, REGARDING LANGUAGE COURSES IN CHINA

OpenAIRE

Saarni, Helena

2017-01-01

This bachelor’s thesis was conducted as a potential marketing plan for EF. The aim and purpose of the project was to create a marketing plan for a company called EF regarding their Chinese language courses in China, where they offer these courses to young adults already. These courses however are not marketed in Finland as much as the other language courses. The theoretical part was gathered by collecting information and theories from various sources including books and e-books about mark...

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

Science.gov (United States)

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

2018-01-01

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

Liposome-encapsulated EF24-HPβCD inclusion complex: a preformulation study and biodistribution in a rat model

International Nuclear Information System (INIS)

Agashe, H.; Lagisetty, P.; Sahoo, K.; Bourne, D.; Grady, B.; Awasthi, V.

2011-01-01

3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a “drug-in-CD-in liposome” approach. An aqueous solution of EF24 and hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze–thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HPβCD mixture provided k 1:1 value of 9.9 M −1 . The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HPβCD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 ± 2.6 nm) by dehydration–rehydration technique. With extrusion technique, the size of 177 ± 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 μM dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an α-t 1/2 of 21.4 min and β-t 1/2 of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using “drug-in-CD-in liposome” approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.

Liposome-encapsulated EF24-HPβCD inclusion complex: a preformulation study and biodistribution in a rat model

Science.gov (United States)

Agashe, H.; Lagisetty, P.; Sahoo, K.; Bourne, D.; Grady, B.; Awasthi, V.

2011-06-01

3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a "drug-in-CD-in liposome" approach. An aqueous solution of EF24 and hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze-thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HPβCD mixture provided k 1:1 value of 9.9 M-1. The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HPβCD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 ± 2.6 nm) by dehydration-rehydration technique. With extrusion technique, the size of 177 ± 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 μM dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an α- t 1/2 of 21.4 min and β- t 1/2 of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using "drug-in-CD-in liposome" approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.

Duplication of Drosophila melanogaster mitochondrial EF-Tu: pre-adaptation to T-arm truncation and exclusion of bulky aminoacyl residues.

Science.gov (United States)

Sato, Aya; Suematsu, Takuma; Aihara, Koh-Ki; Kita, Kiyoshi; Suzuki, Tsutomu; Watanabe, Kimitsuna; Ohtsuki, Takashi; Watanabe, Yoh-Ichi

2017-03-07

Translation elongation factor Tu (EF-Tu) delivers aminoacyl-tRNA (aa-tRNA) to ribosomes in protein synthesis. EF-Tu generally recognizes aminoacyl moieties and acceptor- and T-stems of aa-tRNAs. However, nematode mitochondrial (mt) tRNAs frequently lack all or part of the T-arm that is recognized by canonical EF-Tu. We previously reported that two distinct EF-Tu species, EF-Tu1 and EF-Tu2, respectively, recognize mt tRNAs lacking T-arms and D-arms in the mitochondria of the chromadorean nematode Caenorhabditis elegans C. elegans EF-Tu2 specifically recognizes the seryl moiety of serylated D-armless tRNAs. Mitochondria of the enoplean nematode Trichinella possess three structural types of tRNAs: T-armless tRNAs, D-armless tRNAs, and cloverleaf tRNAs with a short T-arm. Trichinella mt EF-Tu1 binds to all three types and EF-Tu2 binds only to D-armless Ser-tRNAs, showing an evolutionary intermediate state from canonical EF-Tu to chromadorean nematode (e.g. C. elegans ) EF-Tu species. We report here that two EF-Tu species also participate in Drosophila melanogaster mitochondria. Both D. melanogaster EF-Tu1 and EF-Tu2 bound to cloverleaf and D-armless tRNAs. D. melanogaster EF-Tu1 has the ability to recognize T-armless tRNAs that do not evidently exist in D. melanogaster mitochondria, but do exist in related arthropod species. In addition, D. melanogaster EF-Tu2 preferentially bound to aa-tRNAs carrying small amino acids, but not to aa-tRNAs carrying bulky amino acids. These results suggest that the Drosophila mt translation system could be another intermediate state between the canonical and nematode mitochondria-type translation systems. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Pretreatment PSA predicts for biochemical disease free survival in patients treated with post-prostatectomy external beam irradiation

International Nuclear Information System (INIS)

Crane, C.H.; Kelly, M.; Rich, T.A.

1996-01-01

Objective: To assess the outcome and determine prognostic factors for patients treated with external beam radiotherapy following radical prostatectomy. Methods and Materials: Forty-four patients were treated after prostatectomy with radiotherapy between March 1988 and October 1993. All patients were free from clinically or radiographically suspicious local or distant disease. One patient underwent neoadjuvant hormonal therapy, but no other patients received hormonal therapy prior to radiation. Pre-radiotherapy PSA and follow-up PSA data were available in all patients. Four patients had undetectable PSA ( 7, and 11% had nodal involvement. Survival was analyzed using the life table method. Actuarial freedom from biochemical (BCM) failure, defined as a rise of greater than 10% or an undetectable PSA becoming detectable, was the primary endpoint studied. Results: Fifty-nine percent of patients had a detectable PSA return to undetectable levels after XRT. The actuarial five year freedom from biochemical failure for all patients was 24%. A significant difference in BCM disease free survival was seen for patients irradiated with a pre-XRT PSA ≤2.7 versus a pre-XRT PSA >2.7 (p=0.0001). Sixty percent of the former group were BCM disease free versus 0% in the latter. Biochemical disease free survival was not affected by preoperative PSA level, presence of undetectable PSA after surgery, surgery to radiation interval, seminal vesicle invasion, clinical stage, pathologic stage, Gleasons grade, or total dose. There were no symptomatic or clinically suspicious local failures, and there were no grade 3, 4, or 5 acute or late complications. There were 69% grade 1 and 2 acute reactions and one grade 2 late complication. Conclusions: Pelvic radiotherapy for patients with a PSA of ≤2.7 after prostatectomy was effective in biochemically controlling 60% of the patients with four years median follow up. To our knowledge these data represent the longest follow-up for this patient

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

LENUS (Irish Health Repository)

2012-02-01

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

A retrospective analysis of the results of p(65) + Be neutron therapy for the treatment of prostate adenocarcinoma at the cyclotron of Louvain-la-Neuve. Part I: survival and progression-free survival

International Nuclear Information System (INIS)

Scalliet, P.G.M.; Remouchamps, V.; Wambersie, A.; Richard, F.; Lhoas, F.; Van Glabbeke, M.; Curran, D.; Van Cangh, P.; Ledent, T.

2001-01-01

Purpose. -To retrospectively evaluate survival, progression free survival (PFS) and biological response in a series of patients irradiated with mixed neutron/photon beams for locally advanced prostate cancer in our institution. Patients and methods. - Three hundred and eight patients were treated between January 1990 and December 1996. Fifty-five of these were recruited for pT3 or pN1 tumors after radical prostatectomy. Neo-adjuvant androgen deprivation was given in 106 patients. The treatment protocol consisted of a mixed photon/neutron irradiation in a two-to-three proportion, up to a total equivalent dose of 66 Gy (assuming a clinical RBE value of 2.8). Pre- and post-treatment PSA determinations were available in practically all cases. Study endpoints were overall survival (OAS) and progression-free survival (PFS). The Cox proportional hazard regression model was used to investigate the prognostic value of baseline characteristics on survival and progression-free survival were a progression was defined as local, regional, metastatic or biological progression. Mean age was 69 years (49-86); mean pretreatment PSA was 15 (0.5-330) in all patients and 14 (0.5-160) in those receiving neo-adjuvant hormonotherapy; seven patients only had an initial PSA S 4 ng/mL; 15% were T1, 46% were T2, 28% were T3 or pT3 and 4% were T4 (7% unspecified); WHO grade of differentiation was I in 38%, II in 38% and III in 14% (5% unspecified). Results. -The median follow-up was 2.8 years (0-7.8). Five year overall survival (OAS) was 79% (95% CI: 71-87%) and 5-year progression-free survival (PFS) was 64% (95% Cl: 54-74%) for the entire series. PFS in patients with an initial PSA >- 20 ng/mL was the same. PFS could be predicted by two optimal Cox regression models, one including histological grade (p = 0.003) and initial PSA (p = 0.0009) as cofactors, the other including histological grade (p = 0.003) and T stage (p = 0.02). The main prognostic factors for overall survival were PSA and age

Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

NARCIS (Netherlands)

Gast, M.C.; van Tinteren, H.; Bontenbal, M.; van Hoesel, R.Q.; Nooij, M.A.; Rodenhuis, S.; Span, P.N.; Tjan-Heijnen, V.C.; de Vries, E.G.; Harris, N.; Twisk, J.W.R.; Schellens, J.H.; Beijnen, J.H.

2008-01-01

Background: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. Methods: Two

Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

NARCIS (Netherlands)

M.C.W. Gast; H. van Tinteren (Harm); M. Bontenbal (Marijke); R.Q.G.C.M. van Hoesel (René); M.A. Nooij; S. Rodenhuis (Sjoerd); P.N. Span (Paul); V.C.G. Tjan-Heijnen (Vivianne); E. de Vries (Esther); N. Harris (Nathan); J.W.R. Twisk (Jos); J.H.M. Schellens (Jan); J.H. Beijnen (Jos)

2008-01-01

textabstractBackground: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival.

Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

NARCIS (Netherlands)

Gast, Marie-Christine W.; van Tinteren, Harm; Bontenbal, Marijke; van Hoesel, Rene Q. G. C. M.; Nooij, Marianne A.; Rodenhuis, Sjoerd; Span, Paul N.; Tjan-Heijnen, Vivianne C. G.; de Vries, Elisabeth G. E.; Harris, Nathan; Twisk, Jos W. R.; Schellens, Jan H. M.; Beijnen, Jos H.

2008-01-01

ABSTRACT: BACKGROUND: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival.

Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients.

NARCIS (Netherlands)

Gast, M.C.; Tinteren, H. van; Bontenbal, M.; Hoesel, R.Q. van; Nooij, M.A.; Rodenhuis, S.; Span, P.N.; Tjan-Heijnen, V.C.; Vries, E.G.F. de; Harris, N.; Twisk, J.W.R.; Schellens, J.H.; Beijnen, J.H.

2008-01-01

BACKGROUND: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. METHODS: Two

The Effect of dcEFs on migration behavior of A549 cells and Integrin beta1 expression

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Yunjie WANG

2008-04-01

Full Text Available Background and objective The effect of direct-current electric fields (dcEFs on cells attracted extensive attention. Moreover the metastasis and its potential are considered to be related to dcEFs. The aim is to study the effect of dcEFs on migration behavior of A549 cells, Integrin ?1 and its signal pathways. Methods According to exposure to 5 V/cm dcEFs or not and the time of exposure, the A549 cells were divided into 4 groups. Images were taken per 5 min within 2 h to recode the migration of the cells. The data of results were analyzed statistically. Results Most of A549cells exposed to the dcEFs aligned and elongated perpendicularly to the electric field lines and migrated to the cathode continually during 2 h. On the contrary, cells unexposed to dcEFs showed slightly random movements. Immunofluorescence showed that Integrin ?1 on plasma membrane polarized to the cathode of the dcEFs. Western blot showed that Integrin beta1 downstream signal pathways p-FAK and p-ERK were overexpressed in the dcEFs. Conclusion A549 cells have a galvanotatic feature of cathodal directed migration while exposed to the dcEFs. The polarization of Integrin beta1 and the promotion of its downstream signal pathways may play an important roles in the galvanotaxis of A549 cells.

Magnetic field power density spectra during 'scatter-free' solar particle events

Science.gov (United States)

Tan, L. C.; Mason, G. M.

1993-01-01

We have examined interplanetary magnetic field power spectral density during four previously identified 3He-rich flare periods when the about 1 MeV nucleon-1 particles exhibited nearly scatter-free transport from the sun to 1 AU. Since the scattering mean free path A was large, it might be expected that interplanetary turbulence was low, yet the spectral density value was low only for one of the four periods. For the other three, however, the spectral index q of the power density spectrum was near 2.0, a value at which quasi-linear theories predict an increase in the scattering mean free path. Comparing the lambda values from the energetic particles with that computed from a recent quasi-linear theory which includes helicity and the propagation direction of waves, we find lambda(QLT)/lambda(SEP) = 0.08 +/- 0.03 for the four events. Thus, the theory fits the q-dependence of lambda; however, as found for previous quasi-linear theories, the absolute value is low.

MicroRNA expression in multiple myeloma is associated with genetic subtype, isotype and survival

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Pezzella Francesco

2011-05-01

Full Text Available Abstract Background MicroRNAs are small RNA species that regulate gene expression post-transcriptionally and are aberrantly expressed in many cancers including hematological malignancies. However, the role of microRNAs in the pathogenesis of multiple myeloma (MM is only poorly understood. We therefore used microarray analysis to elucidate the complete miRNome (miRBase version 13.0 of purified tumor (CD138+ cells from 33 patients with MM, 5 patients with monoclonal gammopathy of undetermined significance (MGUS and 9 controls. Results Unsupervised cluster analysis revealed that MM and MGUS samples have a distinct microRNA expression profile from control CD138+ cells. The majority of microRNAs aberrantly expressed in MM (109/129 were up-regulated. A comparison of these microRNAs with those aberrantly expressed in other B-cell and T-cell malignancies revealed a surprising degree of similarity (~40% suggesting the existence of a common lymphoma microRNA signature. We identified 39 microRNAs associated with the pre-malignant condition MGUS. Twenty-three (59% of these were also aberrantly expressed in MM suggesting common microRNA expression events in MM progression. MM is characterized by multiple chromosomal abnormalities of varying prognostic significance. We identified specific microRNA signatures associated with the most common IgH translocations (t(4;14 and t(11;14 and del(13q. Expression levels of these microRNAs were distinct between the genetic subtypes (by cluster analysis and correctly predicted these abnormalities in > 85% of cases using the support vector machine algorithm. Additionally, we identified microRNAs associated with light chain only myeloma, as well as IgG and IgA-type MM. Finally, we identified 32 microRNAs associated with event-free survival (EFS in MM, ten of which were significant by univariate (logrank survival analysis. Conclusions In summary, this work has identified aberrantly expressed microRNAs associated with the

Outcome of high-risk stage 3 neuroblastoma with myeloablative therapy and 13-cis-retinoic acid: a report from the Children's Oncology Group.

Science.gov (United States)

Park, Julie R; Villablanca, Judith G; London, Wendy B; Gerbing, Robert B; Haas-Kogan, Daphne; Adkins, E Stanton; Attiyeh, Edward F; Maris, John M; Seeger, Robert C; Reynolds, C Patrick; Matthay, Katherine K

2009-01-01

The components of therapy required for patients with INSS Stage 3 neuroblastoma and high-risk features remain controversial. A retrospective cohort design was used to determine if intensive chemoradiotherapy with purged autologous bone marrow rescue (ABMT) and/or 13-cis-retinoic acid (13-cis-RA) improved outcome for patients with high-risk neuroblastoma that was not metastatic to distant sites. We identified 72 patients with INSS Stage 3 neuroblastoma enrolled between 1991 and 1996 on the Phase 3 CCG-3891 randomized trial. Patients were analyzed on an intent-to-treat basis using a log-rank test. The 5-year event-free survival (EFS) and overall survival (OS) rates for patients with Stage 3 neuroblastoma were 55 +/- 6% and 59 +/- 6%, respectively (n = 72). Patients randomized to ABMT (n = 20) had 5-year EFS of 65 +/- 11% and OS of 65 +/- 11% compared to 41 +/- 11 (P = 0.21) and 46 +/- 11% (P = 0.23) for patients randomized to CC (n = 23), respectively. Patients randomized to 13-cis-RA (n = 23) had 5-year EFS of 70 +/- 10% and OS of 78 +/- 9% compared to 63 +/- 12% (P = 0.67) and 67 +/- 12% (P = 0.55) for those receiving no further therapy (n = 16), respectively. Patients randomized to both ABMT and 13-cis-RA (n = 6) had a 5-year EFS of 80 +/- 11% and OS of 100%. Patients with high-risk Stage 3 neuroblastoma have an overall poor prognosis despite aggressive chemoradiotherapy. Further studies are warranted to determine if myeloablative consolidation followed by 13-cis-RA maintenance therapy statistically significantly improves outcome.

Accelerated Total Lymphoid Irradiation-containing Salvage Regimen for Patients With Refractory and Relapsed Hodgkin Lymphoma: 20 Years of Experience

Energy Technology Data Exchange (ETDEWEB)

Rimner, Andreas; Lovie, Shona [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Hsu, Meier [Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Chelius, Monica [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Chau, Karen [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Moskowitz, Alison J.; Matasar, Matthew; Moskowitz, Craig H. [Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Yahalom, Joachim, E-mail: yahalomj@mskcc.org [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States)

2017-04-01

Purpose: We report the long-term results of integrated accelerated involved field radiation therapy (IFRT) followed by total lymphoid irradiation (TLI) as part of the high-dose salvage regimen followed by autologous bone marrow transplantation or autologous stem cell transplantation in patients with relapsed or refractory Hodgkin lymphoma (HL). Methods and Materials: From November 1985 to July 2008, 186 previously unirradiated patients with relapsed or refractory HL underwent salvage therapy on 4 consecutive institutional review board–approved protocols. All patients had biopsy-proven primary refractory or relapsed HL. After standard-dose salvage chemotherapy (SC), accelerated IFRT (18-20 Gy) was given to relapsed or refractory sites, followed by TLI (15-18 Gy) and high-dose chemotherapy. Overall survival (OS) and event-free survival (EFS) were analyzed by Cox analysis and disease-specific survival (DSS) by competing-risk regression. Results: With a median follow-up period of 57 months among survivors, 5- and 10-year OS rates were 68% and 56%, respectively; 5- and 10-year EFS rates were 62% and 56%, respectively; and 5- and 10-year cumulative incidences of HL-related deaths were 21% and 29%, respectively. On multivariate analysis, complete response to SC was independently associated with improved OS and EFS. Primary refractory disease and extranodal disease were independently associated with poor DSS. Eight patients had grade 3 or higher cardiac toxicity, with 3 deaths. Second malignancies developed in 10 patients, 5 of whom died. Conclusions: Accelerated IFRT followed by TLI and high-dose chemotherapy is an effective, feasible, and safe salvage strategy for patients with relapsed or refractory HL with excellent long-term OS, EFS, and DSS. Complete response to SC is the most important prognostic factor.

Accelerated Total Lymphoid Irradiation-containing Salvage Regimen for Patients With Refractory and Relapsed Hodgkin Lymphoma: 20 Years of Experience

International Nuclear Information System (INIS)

Rimner, Andreas; Lovie, Shona; Hsu, Meier; Chelius, Monica; Zhang, Zhigang; Chau, Karen; Moskowitz, Alison J.; Matasar, Matthew; Moskowitz, Craig H.; Yahalom, Joachim

2017-01-01

Purpose: We report the long-term results of integrated accelerated involved field radiation therapy (IFRT) followed by total lymphoid irradiation (TLI) as part of the high-dose salvage regimen followed by autologous bone marrow transplantation or autologous stem cell transplantation in patients with relapsed or refractory Hodgkin lymphoma (HL). Methods and Materials: From November 1985 to July 2008, 186 previously unirradiated patients with relapsed or refractory HL underwent salvage therapy on 4 consecutive institutional review board–approved protocols. All patients had biopsy-proven primary refractory or relapsed HL. After standard-dose salvage chemotherapy (SC), accelerated IFRT (18-20 Gy) was given to relapsed or refractory sites, followed by TLI (15-18 Gy) and high-dose chemotherapy. Overall survival (OS) and event-free survival (EFS) were analyzed by Cox analysis and disease-specific survival (DSS) by competing-risk regression. Results: With a median follow-up period of 57 months among survivors, 5- and 10-year OS rates were 68% and 56%, respectively; 5- and 10-year EFS rates were 62% and 56%, respectively; and 5- and 10-year cumulative incidences of HL-related deaths were 21% and 29%, respectively. On multivariate analysis, complete response to SC was independently associated with improved OS and EFS. Primary refractory disease and extranodal disease were independently associated with poor DSS. Eight patients had grade 3 or higher cardiac toxicity, with 3 deaths. Second malignancies developed in 10 patients, 5 of whom died. Conclusions: Accelerated IFRT followed by TLI and high-dose chemotherapy is an effective, feasible, and safe salvage strategy for patients with relapsed or refractory HL with excellent long-term OS, EFS, and DSS. Complete response to SC is the most important prognostic factor.

Risk of Recurrence or Contralateral Breast Cancer More than 5 Years After Diagnosis of Hormone Receptor-Positive Early-Stage Breast Cancer.

Science.gov (United States)

Wilson, Sheridan; Speers, Caroline; Tyldesley, Scott; Chia, Stephen; Kennecke, Hagen; Ellard, Susan; Lohrisch, Caroline

2016-08-01

Three large studies have shown a survival benefit from 10 years of adjuvant hormone therapy (AHT). We evaluated the risk of an event 5 years after the initial breast cancer (BC) diagnosis and identified the prognostic factors to assist clinicians considering extended AHT. Patients newly referred to the BC Cancer Agency with stage I to III estrogen receptor-positive BC diagnosed from 1989 to 2004 who had undergone AHT were identified by the BC Cancer Agency's Breast Cancer Outcomes Unit. Cases with recurrence, death, or contralateral BC occurring within the first 5 years were excluded. The 10-year event-free survival (EFS) and 95% confidence intervals (CIs) were calculated using the Kaplan-Meier method. This provided estimates of recurrence risk after the fifth year following the diagnosis. The histopathologic and age variables were examined for prognostic value by univariate analysis. Within our cohort, 6615 women were postmenopausal and 1886 were premenopausal at the BC diagnosis. The median follow-up period was 11 years. The 10-year EFS for women aged cancer (any grade) and for stage II (node-negative and node-positive), grade I cancer. Our data have identified BCs associated with a very low recurrence risk 5 to 10 years after diagnosis, providing women with such cancers confidence about a decision to discontinue AHT after 5 years. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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Rui Guo

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

Free-field ground motions for the nonproliferation experiment: Preliminary comparisons with nearby nuclear events

International Nuclear Information System (INIS)

Olsen, K.H.; Peratt, A.L.

1994-01-01

Since 1987, we have installed fixed arrays of tri-axial accelerometers in the fire-field near the shot horizons for low-yield (≤ 20 kt) nuclear events in the N-tunnel complex beneath Rainier Mesa. For the Nonproliferation Experiment (NPE) we augmented the array to achieve 23 free-field stations. Goals are: (a) to examine robustness and stability of various free-field source function estimates -- e.g., reduced displacement potentials (RDP) and spectra; (b) to compare close-in with regional estimates to test whether detailed close-in free-field and/or surface ground motion data can improve predictability of regional-teleseismic source functions; (c) to provide experimental data for checking two-dimensional numerical simulations. We report preliminary comparisons between experimental free-field data for NPE (1993) and three nearby nuclear events (MISTY ECHO, 1988; MINERAL QUARRY, 1990; HUNTERS TROPHY, 1992). All four working points are within 1 km of each other in the same wet tuff bed, thus reducing concerns about possible large differences in material properties between widely separated shots. Initial comparison of acceleration and velocity seismograms for the four events reveals: (1) There is a large departure from the spherical symmetry commonly assumed in analytic treatments of source theory; both vertical and tangential components are surprisingly large. (2) All shots show similar first-peak particle-velocity amplitude decay rates suggesting significant attenuation even in the supposedly purely elastic region. (3) Sharp (>20 Hz) arrivals are not observed at tunnel level from near-surface pP reflections or spall-closure sources -- but broadened peaks are seen that suggest more diffuse reflected energy from the surface and from the Paleozoic limestone basement below tunnel level

Liposome-encapsulated EF24-HP{beta}CD inclusion complex: a preformulation study and biodistribution in a rat model

Energy Technology Data Exchange (ETDEWEB)

Agashe, H; Lagisetty, P; Sahoo, K; Bourne, D [University of Oklahoma Health Sciences Center, Department of Pharmaceutical Sciences (United States); Grady, B [School of Chemical, Biological and Materials Engineering (United States); Awasthi, V [University of Oklahoma Health Sciences Center, Department of Pharmaceutical Sciences (United States)

2011-06-15

3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a 'drug-in-CD-in liposome' approach. An aqueous solution of EF24 and hydroxypropyl-{beta}-cyclodextrin (HP{beta}CD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze-thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HP{beta}CD mixture provided k{sub 1:1} value of 9.9 M{sup -1}. The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HP{beta}CD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 {+-} 2.6 nm) by dehydration-rehydration technique. With extrusion technique, the size of 177 {+-} 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 {mu}M dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an {alpha}-t{sub 1/2} of 21.4 min and {beta}-t{sub 1/2} of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using 'drug-in-CD-in liposome' approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.

Liposome-encapsulated EF24-HP{beta}CD inclusion complex: a preformulation study and biodistribution in a rat model

Energy Technology Data Exchange (ETDEWEB)

Agashe, H.; Lagisetty, P.; Sahoo, K.; Bourne, D. [University of Oklahoma Health Sciences Center, Department of Pharmaceutical Sciences (United States); Grady, B. [School of Chemical, Biological and Materials Engineering (United States); Awasthi, V., E-mail: vawasthi@ouhsc.edu [University of Oklahoma Health Sciences Center, Department of Pharmaceutical Sciences (United States)

2011-06-15

3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a 'drug-in-CD-in liposome' approach. An aqueous solution of EF24 and hydroxypropyl-{beta}-cyclodextrin (HP{beta}CD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze-thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HP{beta}CD mixture provided k{sub 1:1} value of 9.9 M{sup -1}. The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HP{beta}CD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 {+-} 2.6 nm) by dehydration-rehydration technique. With extrusion technique, the size of 177 {+-} 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 {mu}M dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an {alpha}-t{sub 1/2} of 21.4 min and {beta}-t{sub 1/2} of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using 'drug-in-CD-in liposome' approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.

A Medicago truncatula EF-hand family gene, MtCaMP1, is involved in drought and salt stress tolerance.

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Tian-Zuo Wang

Full Text Available BACKGROUND: Calcium-binding proteins that contain EF-hand motifs have been reported to play important roles in transduction of signals associated with biotic and abiotic stresses. To functionally characterize genes of EF-hand family in response to abiotic stress, an MtCaMP1 gene belonging to EF-hand family from legume model plant Medicago truncatula was isolated and its function in response to drought and salt stress was investigated by expressing MtCaMP1 in Arabidopsis. METHODOLOGY/PRINCIPAL FINDINGS: Transgenic Arabidopsis seedlings expressing MtCaMP1 exhibited higher survival rate than wild-type seedlings under drought and salt stress, suggesting that expression of MtCaMP1 confers tolerance of Arabidopsis to drought and salt stress. The transgenic plants accumulated greater amounts of Pro due to up-regulation of P5CS1 and down-regulation of ProDH than wild-type plants under drought stress. There was a less accumulation of Na(+ in the transgenic plants than in WT plants due to reduced up-regulation of AtHKT1 and enhanced regulation of AtNHX1 in the transgenic plants compared to WT plants under salt stress. There was a reduced accumulation of H2O2 and malondialdehyde in the transgenic plants than in WT plants under both drought and salt stress. CONCLUSIONS/SIGNIFICANCE: The expression of MtCaMP1 in Arabidopsis enhanced tolerance of the transgenic plants to drought and salt stress by effective osmo-regulation due to greater accumulation of Pro and by minimizing toxic Na(+ accumulation, respectively. The enhanced accumulation of Pro and reduced accumulation of Na(+ under drought and salt stress would protect plants from water default and Na(+ toxicity, and alleviate the associated oxidative stress. These findings demonstrate that MtCaMP1 encodes a stress-responsive EF-hand protein that plays a regulatory role in response of plants to drought and salt stress.

Fluctuations between multiple EF-G-induced chimeric tRNA states during translocation on the ribosome

Science.gov (United States)

Adio, Sarah; Senyushkina, Tamara; Peske, Frank; Fischer, Niels; Wintermeyer, Wolfgang; Rodnina, Marina V.

2015-06-01

The coupled translocation of transfer RNA and messenger RNA through the ribosome entails large-scale structural rearrangements, including step-wise movements of the tRNAs. Recent structural work has visualized intermediates of translocation induced by elongation factor G (EF-G) with tRNAs trapped in chimeric states with respect to 30S and 50S ribosomal subunits. The functional role of the chimeric states is not known. Here we follow the formation of translocation intermediates by single-molecule fluorescence resonance energy transfer. Using EF-G mutants, a non-hydrolysable GTP analogue, and fusidic acid, we interfere with either translocation or EF-G release from the ribosome and identify several rapidly interconverting chimeric tRNA states on the reaction pathway. EF-G engagement prevents backward transitions early in translocation and increases the fraction of ribosomes that rapidly fluctuate between hybrid, chimeric and posttranslocation states. Thus, the engagement of EF-G alters the energetics of translocation towards a flat energy landscape, thereby promoting forward tRNA movement.

Influence of activated carbon preloading by EfOM fractions from treated wastewater on adsorption of pharmaceutically active compounds.

Science.gov (United States)

Hu, Jingyi; Shang, Ran; Heijman, Bas; Rietveld, Luuk

2016-05-01

In this study, the preloading effects of different fractions of wastewater effluent organic matter (EfOM) on the adsorption of trace-level pharmaceutically active compounds (PhACs) onto granular activated carbon (GAC) were investigated. A nanofiltration (NF) membrane was employed to separate the EfOM by size, and two GACs with distinct pore structures were chosen for comparison. The results showed that preloading with EfOM substantially decreased PhAC uptake of the GACs; however, comparable PhAC adsorption capacities were achieved on GACs preloaded by feed EfOM and the NF-permeating EfOM. This indicates that: (1) the NF-rejected, larger EfOM molecules with an expectation to block the PhAC adsorption pores exerted little impact on the adsorbability of PhACs; (2) the smaller EfOM molecules present in the NF permeate contributed mainly to the decrease in PhAC uptake, mostly due to site competition. Of the two examined GACs, the wide pore-size-distributed GAC was found to be more susceptible to EfOM preloading than the microporous GAC. Furthermore, among the fourteen investigated PhACs, the negatively charged hydrophilic PhACs were generally subjected to a greater EfOM preloading impact. Copyright © 2016 Elsevier Ltd. All rights reserved.

Kidney-Sparing Methods for Extended-Field Intensity-Modulated Radiotherapy (EF-IMRT) in Cervical Carcinoma Treatment.

Science.gov (United States)

Kunogi, Hiroaki; Yamaguchi, Nanae; Terao, Yasuhisa; Sasai, Keisuke

2016-01-01

Coplanar extended-field intensity-modulated radiation therapy (EF-IMRT) targeting the whole-pelvic and para-aortic lymph nodes in patients with advanced cervical cancer results in impaired creatinine clearance. An improvement in renal function cannot be expected unless low-dose (approximately 10 Gy) kidney exposure is reduced. The dosimetric method should be considered during EF-IMRT planning to further reduce low-dose exposure to the kidneys. To assess the usefulness of non-coplanar EF-IMRT with kidney-avoiding beams to spare the kidneys during cervical carcinoma treatment in dosimetric analysis between non-coplanar and coplanar EF-IMRT, we compared the doses of the target organ and organs at risk, including the kidney, in 10 consecutive patients. To estimate the influence of EFRT on renal dysfunction, creatinine clearance values after treatment were also examined in 18 consecutive patients. Of these 18 patients, 10 patients who were included in the dosimetric analysis underwent extended field radiation therapy (EFRT) with concurrent chemotherapy, and eight patients underwent whole-pelvis radiation therapy with concurrent chemotherapy to treat cervical carcinoma between April 2012 and March 2015 at our institution. In the dosimetric analysis, non-coplanar EF-IMRT was effective at reducing low-dose (approximately 10 Gy) exposure to the kidneys, thus maintaining target coverage and sparing other organs at risk, such as the small bowel, rectum, and bladder, compared with coplanar EF-IMRT. Renal function in all 10 patients who underwent EFRT, including coplanar EF-IMRT (with kidney irradiation), was low after treatment, and differed significantly from that of the eight patients who underwent WPRT (no kidney irradiation) 6 months after the first day of treatment (P = 0.005). In conclusion, non-coplanar EF-IMRT should be considered in patients with advanced cervical cancer, particularly in patients with a long life expectancy or with pre-existing renal dysfunction.

Application of BET_EF at Mount Etna: a retrospective analysis (years 2001-2005

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Jacopo Selva

2011-12-01

Full Text Available Advances in volcano monitoring and forecasting need a multidisciplinary collaborative framework. In light of this, a Bayesian Event Tree (BET approach was performed by the application of the BET for Eruption Forecasting (BET_EF code to analyze the space-time distribution of the volcanic activity of Mount Etna from 2001-2005. First, a reliable monitoring dataset was set up after some sessions to elicit geophysical, volcanological and geochemical ‘precursor’ parameters. A constant unrest probability of 100%, with a magma involvement usually greater than 95%, was computed throughout the time period analyzed. Eruption probabilities higher than 90% were estimated a few days before the onsets of the 2001 and 2002-2003 flank eruptions. Values slightly higher than 75% were observed during the lava fountaining period in June-July 2001. However, the probabilities flattened to around 30% for the 2004-2005 flank eruption. With suitable data, a good depiction of the actual location of the eruptive scenario for the 2001 and 2002-2003 events was provided. Conversely, the size of the eruptions was not indicated.

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

Science.gov (United States)

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

2014-01-01

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

In-hospital resuscitation: opioids and other factors influencing survival

Directory of Open Access Journals (Sweden)

Karamarie Fecho

2009-12-01

Full Text Available Karamarie Fecho1, Freeman Jackson1, Frances Smith1, Frank J Overdyk21Department of Anesthesiology, University of North Carolina, Chapel Hill, North Carolina, USA; 2Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina, Charleston, South Carolina, USAPurpose: “Code Blue” is a standard term used to alertt hospital staff that a patient requires resuscitation. This study determined rates of survival from Code Blue events and the role of opioids and other factors on survival.Methods: Data derived from medical records and the Code Blue and Pharmacy databases were analyzed for factors affecting survival.Results: During 2006, rates of survival from the code only and to discharge were 25.9% and 26.4%, respectively, for Code Blue events involving cardiopulmonary resuscitation (CPR; N = 216. Survival rates for events not ultimately requiring CPR (N = 77 were higher, with 32.5% surviving the code only and 62.3% surviving to discharge. For CPR events, rates of survival to discharge correlated inversely with time to chest compressions and defibrillation, precipitating event, need for airway management, location and age. Time of week, witnessing, postoperative status, gender and opioid use did not influence survival rates. For non-CPR events, opioid use was associated with decreased survival. Survival rates were lowest for patients receiving continuous infusions (P < 0.01 or iv boluses of opioids (P < 0.05.Conclusions: One-quarter of patients survive to discharge after a CPR Code Blue event and two-thirds survive to discharge after a non-CPR event. Opioids may influence survival from non-CPR events.Keywords: code blue, survival, opioids, cardiopulmonary resuscitation, cardiac arrest, patient safety

Measuring coverage in MNCH: population HIV-free survival among children under two years of age in four African countries.

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Jeffrey S A Stringer

Full Text Available Population-based evaluations of programs for prevention of mother-to-child HIV transmission (PMTCT are scarce. We measured PMTCT service coverage, regimen use, and HIV-free survival among children ≤24 mo of age in Cameroon, Côte D'Ivoire, South Africa, and Zambia.We randomly sampled households in 26 communities and offered participation if a child had been born to a woman living there during the prior 24 mo. We tested consenting mothers with rapid HIV antibody tests and tested the children of seropositive mothers with HIV DNA PCR or rapid antibody tests. Our primary outcome was 24-mo HIV-free survival, estimated with survival analysis. In an individual-level analysis, we evaluated the effectiveness of various PMTCT regimens. In a community-level analysis, we evaluated the relationship between HIV-free survival and community PMTCT coverage (the proportion of HIV-exposed infants in each community that received any PMTCT intervention during gestation or breastfeeding. We also compared our community coverage results to those of a contemporaneous study conducted in the facilities serving each sampled community. Of 7,985 surveyed children under 2 y of age, 1,014 (12.7% were HIV-exposed. Of these, 110 (10.9% were HIV-infected, 851 (83.9% were HIV-uninfected, and 53 (5.2% were dead. HIV-free survival at 24 mo of age among all HIV-exposed children was 79.7% (95% CI: 76.4, 82.6 overall, with the following country-level estimates: Cameroon (72.6%; 95% CI: 62.3, 80.5, South Africa (77.7%; 95% CI: 72.5, 82.1, Zambia (83.1%; 95% CI: 78.4, 86.8, and Côte D'Ivoire (84.4%; 95% CI: 70.0, 92.2. In adjusted analyses, the risk of death or HIV infection was non-significantly lower in children whose mothers received a more complex regimen of either two or three antiretroviral drugs compared to those receiving no prophylaxis (adjusted hazard ratio: 0.60; 95% CI: 0.34, 1.06. Risk of death was not different for children whose mothers received a more complex regimen

Efficacy Comparison of Six Chemotherapeutic Combinations for Osteosarcoma and Ewing's Sarcoma Treatment: A Network Meta-Analysis.

Science.gov (United States)

Zhang, Tao; Zhang, Song; Yang, Feifei; Wang, Lili; Zhu, Sigang; Qiu, Bing; Li, Shunhua; Deng, Zhongliang

2018-01-01

This study aimed to address the insufficiency of traditional meta-analysis and provide improved guidelines for the clinical practice of osteosarcoma treatment. The heterogeneity of the fixed-effect model was calculated, and when necessary, a random-effect model was adopted. Furthermore, the direct and indirect evidence was pooled together and exhibited in the forest plot and slash table. The surface under the cumulative ranking curve (SUCRA) value was also measured to rank each intervention. Finally, heat plot was introduced to demonstrate the contribution of each intervention and the inconsistency between direct and indirect comparisons. This network meta-analysis included 32 trials, involving a total of 5,626 subjects reported by 28 articles. All the treatments were classified into six chemotherapeutic combinations: dual agent with or without ifosfamide (IFO), multi-agent with or without IFO, and dual agent or multi-agent with IFO and etoposide. For the primary outcomes, both overall survival (OS) and event-free survival (EFS) rates were considered. The multi-agent integrated with IFO and etoposide showed an optimal performance for 5-year OS, 10-year OS, 3-year EFS, 5-year EFS, and 10-year EFS when compared with placebo. The SUCRA value of this treatment was also the highest of these six interventions. However, multi-drug with IFO alone had the highest SUCRA value of 0.652 and 0.516 when it came to relapse and lung-metastasis. It was efficient to some extent, but no significant difference was observed in both outcomes. Chemotherapy, applied as induction or adjuvant treatment with radiation therapy or surgery, is able to increase the survival rate of patients, especially by combining multi-drug with IFO and etoposide, which demonstrated the best performance in both OS and EFS. As for relapse and the lung-metastasis, multiple agents with IFO alone seemed to have the optimal efficiency, although no significant difference was observed here. J. Cell. Biochem. 119: 250

Survival of Free and Encapsulated Human and Rat Islet Xenografts Transplanted into the Mouse Bone Marrow

Science.gov (United States)

Meier, Raphael P. H.; Seebach, Jörg D.; Morel, Philippe; Mahou, Redouan; Borot, Sophie; Giovannoni, Laurianne; Parnaud, Geraldine; Montanari, Elisa; Bosco, Domenico; Wandrey, Christine; Berney, Thierry; Bühler, Leo H.; Muller, Yannick D.

2014-01-01

Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow) and 10 days (kidney capsule). Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation. PMID:24625569

Survival of free and encapsulated human and rat islet xenografts transplanted into the mouse bone marrow.

Directory of Open Access Journals (Sweden)

Raphael P H Meier

Full Text Available Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow and 10 days (kidney capsule. Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation.

Virtual HDR CyberKnife SBRT for Localized Prostatic Carcinoma: 5-year Disease-free Survival and Toxicity Observations

Directory of Open Access Journals (Sweden)

Donald Blake Fuller

2014-11-01

Full Text Available PURPOSEProstate stereotactic body radiotherapy (SBRT may substantially recapitulate the dose distribution of high-dose-rate (HDR brachytherapy, representing an externally delivered Virtual HDR treatment method. Herein we present 5-year outcomes from a cohort of consecutively treated Virtual HDR SBRT prostate cancer patients.METHODSSeventy-nine patients were treated from 2006 - 2009, 40 low-risk and 39 intermediate-risk, under IRB-approved clinical trial, to 38 Gy in 4 fractions. The planning target volume (PTV included prostate plus a 2-mm volume expansion in all directions, with selective use of a 5-mm prostate-to-PTV expansion and proximal seminal vesicle coverage in intermediate-risk patients, to better cover potential extraprostatic disease; rectal PTV margin reduced to zero in all cases. The prescription dose covered > 95% of the PTV (V100 >= 95%, with a minimum 150% PTV dose escalation to create HDR-like PTV dose distribution.RESULTSMedian pre-SBRT PSA level of 5.6 ng/mL decreased to 0.05 ng/mL 5 years out and 0.02 ng/mL 6 years out. At least one PSA bounce was seen in 55 patients (70% but only 3 of them subsequently relapsed, Biochemical-relapse-free survival was 100% and 92% for low-risk and intermediate-risk patients, respectively, by ASTRO definition (98% and 92% by Phoenix definition. Local relapse did not occur, distant metastasis-free survival was 100% and 95% by risk-group, and disease-specific survival was 100%. Acute and late grade 2 GU toxicity incidence was 10% and 9%, respectively; with 6% late grade 3 GU toxicity. Acute urinary retention did not occur. Acute and late grade 2 GI toxicity was 0% and 1%, respectively, with no grade 3 or higher toxicity. Of patients potent pre-SBRT, 65% remained so at 5 years.CONCLUSIONSVirtual HDR prostate SBRT creates a very low PSA nadir, a high rate of 5-year disease-free survival and an acceptable toxicity incidence, with results closely resembling those reported post-HDR brachytherapy.

Translation elongation factor EF-Tu modulates filament formation of actin-like MreB protein in vitro.

Science.gov (United States)

Defeu Soufo, Hervé Joël; Reimold, Christian; Breddermann, Hannes; Mannherz, Hans G; Graumann, Peter L

2015-04-24

EF-Tu has been shown to interact with actin-like protein MreB and to affect its localization in Escherichia coli and in Bacillus subtilis cells. We have purified YFP-MreB in an active form, which forms filaments on glass slides in vitro and was active in dynamic light-scattering assays, polymerizing in milliseconds after addition of magnesium. Purified EF-Tu enhanced the amount of MreB filaments, as seen by sedimentation assays, the speed of filament formation and the length of MreB filaments in vitro. EF-Tu had the strongest impact on MreB filaments in a 1:1 ratio, and EF-Tu co-sedimented with MreB filaments, revealing a stoichiometric interaction between both proteins. This was supported by cross-linking assays where 1:1 species were well detectable. When expressed in E. coli cells, B. subtilis MreB formed filaments and induced the formation of co-localizing B. subtilis EF-Tu structures, indicating that MreB can direct the positioning of EF-Tu structures in a heterologous cell system. Fluorescence recovery after photobleaching analysis showed that MreB filaments have a higher turnover in B. subtilis cells than in E. coli cells, indicating different filament kinetics in homologous or heterologous cell systems. The data show that MreB can direct the localization of EF-Tu in vivo, which in turn positively affects the formation and dynamics of MreB filaments. Thus, EF-Tu is a modulator of the activity of a bacterial actin-like protein. Copyright © 2015. Published by Elsevier Ltd.

Effects of Exergame Play on EF in Children and Adolescents at a Summer Camp for Low Income Youth.

Science.gov (United States)

Flynn, Rachel M; Richert, Rebekah A; Staiano, Amanda E; Wartella, Ellen; Calvert, Sandra L

2014-01-01

Past research has suggested exergame play improves adolescents' executive function (EF) skills. EF change in 70 African American and Hispanic/Latino 10- to 16-year-olds participating in an inner-city summer camp was assessed following five 30-minute exergame play sessions. Children's EF scores improved from pre- to posttest, and factors related to this change were examined. The number of exergame sessions the participants attended predicted posttest scores. In addition, level of achievement during game play was related to EF scores. Finally, the children's level of enjoyment was not related to EF; however, frustration and boredom during game play were negatively related to EF. The findings are discussed in terms of their implications for the relationship between exergame play and cognitive benefits for adolescent players.

Hyperdiploidy with 58-66 chromosomes in childhood B-acute lymphoblastic leukemia is highly curable: 58951 CLG-EORTC results.

Science.gov (United States)

Dastugue, Nicole; Suciu, Stefan; Plat, Geneviève; Speleman, Frank; Cavé, Hélène; Girard, Sandrine; Bakkus, Marleen; Pagès, Marie Pierre; Yakouben, Karima; Nelken, Brigitte; Uyttebroeck, Anne; Gervais, Carine; Lutz, Patrick; Teixeira, Manuel R; Heimann, Pierre; Ferster, Alice; Rohrlich, Pierre; Collonge, Marie Agnès; Munzer, Martine; Luquet, Isabelle; Boutard, Patrick; Sirvent, Nicolas; Karrasch, Matthias; Bertrand, Yves; Benoit, Yves

2013-03-28

The aim of our study was to analyze the factors contributing to heterogeneity of prognosis in patients with hyperdiploidy>50 chromosomes (HD>50), a group of B-cell precursor acute lymphoblastic leukemia with favorable outcome. The 541 HD>50 patients registered prospectively in the 58951 European Organisation for Research and Treatment of Cancer (EORTC) Children's Leukemia Group (CLG) trial, identified by karyotype (446 patients) and by DNA index (DI) (490 patients), had a 6-year event-free survival (EFS) of 89.0% (standard error [SE] = 1.5%) and a 6-year overall survival (OS) of 95.9% (SE = 0.9%). The strongest prognostic factor was the modal number of chromosomes (MNC): the 6-year EFS of 51-53, 54-57, and 58-66 MNC groups were 80%, 89%, and 99%, respectively (P best indicator for excellent outcome was ploidy assessed by karyotype because patients with 58-66 chromosomes stood every chance of being cured (OS of 100% at 6-year follow-up) with less-intensive therapy. This trial was registered at www.clinicaltrials.gov as #NCT00003728. Registered: http://www.eortc.org/, http://clinicaltrials.gov/show/NCT00003728.

The Impact of Splenectomy in Myelofibrosis Patients before Allogeneic Hematopoietic Stem Cell Transplantation.

Science.gov (United States)

Robin, Marie; Zine, Maryem; Chevret, Sylvie; Meignin, Véronique; Munoz-Bongrand, Nicolas; Moatti, Hannah; Xhaard, Aliénor; Sicre de Fontbrune, Flore; Peffault de Latour, Régis; Sarfati, Emile; Socié, Gérard

2017-06-01

Performing a pretransplantation splenectomy in patients with myelofibrosis (MF) is a matter of debate, as while the procedure improves hematological recovery, it may lead to severe morbidities. We retrospectively analyzed data from 85 consecutive patients who underwent transplantation in our center for MF, including 39 patients who underwent splenectomy before their transplantation. A majority of them had primary MF (78%), were considered high-risk patients (84% dynamic international prognostic scoring system intermediate-2 or higher), and had received transplants from HLA-matched sibling donors (56%) after a reduced-intensity conditioning regimen (82%). One-half of all splenectomized patients presented surgical or postsurgical morbidities, most frequently thrombosis and hemorrhage. After adjustment using Cox models, pretransplantation splenectomy was not associated with nonrelapse mortality or post-transplantation relapse but with an improved overall survival (OS) and event-free survival (EFS). We conclude that some patients with huge splenomegaly may undergo pretransplantation splenectomy without a deleterious impact on post-transplantation outcomes. OS and EFS improvement should in confirmed in controlled study. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Survival Response of .i.Larix Sibirica./i. to the Tunguska Explosion

Czech Academy of Sciences Publication Activity Database

Kletetschka, Günther; Procházka, V.; Fantucci, R.; Trojek, T.

2017-01-01

Roč. 73, č. 2 (2017), s. 75-90 ISSN 1536-1098 Institutional support: RVO:67985831 Keywords : airburst * defoliation * impact * PGAA * tree rings * Tunguska event * XRF * xylem Subject RIV: EF - Botanics OBOR OECD: Plant sciences, botany Impact factor: 1.769, year: 2016

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

International Nuclear Information System (INIS)

Chen, James X.; Rose, Steven; White, Sarah B.; El-Haddad, Ghassan; Fidelman, Nicholas; Yarmohammadi, Hooman; Hwang, Winifred; Sze, Daniel Y.; Kothary, Nishita; Stashek, Kristen; Wileyto, E. Paul; Salem, Riad; Metz, David C.; Soulen, Michael C.

2017-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2017-01-15

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

Energy-filtered Photoelectron Emission Microscopy (EF-PEEM) for imaging nanoelectronic materials

International Nuclear Information System (INIS)

Renault, Olivier; Chabli, Amal

2007-01-01

Photoelectron-Emission Microscopy (PEEM) is the most promising approach to photoemission-based (XPS, UPS) imaging techniques with high lateral resolution, typically below 100 nm. It has now reached its maturity with a new generation of instruments with energy-filtering capabilities. Therefore UPS and XPS imaging with energy-filtered PEEM (EF-PEEM) can be applied to technologically-relevant samples. UPS images with contrast in local work function, obtained with laboratory UV sources, are obtained in ultra-high vacuum environment with lateral resolutions better than 50 nm and sensitivies of 20 meV. XPS images with elemental and bonding state contrast can show up lateral resolution better than 200 nm with synchrotron excitation. In this paper, we present the principles and capabilities of EF-PEEM and nanospectroscopy. Then, we focus on an example of application to non-destructive work-function imaging of polycrystalline copper for advanced interconnects, where it is shown that EF-PEEM is an alternative to Kelvin probes

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

Science.gov (United States)

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

2015-02-01

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

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

Science.gov (United States)

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

2015-01-01

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

Proteomic analysis of trichloroethylene-induced alterations in expression, distribution, and interactions of SET/TAF-Iα and two SET/TAF-Iα-binding proteins, eEF1A1 and eEF1A2, in hepatic L-02 cells

Energy Technology Data Exchange (ETDEWEB)

Hong, Wen-Xu; Yang, Liang; Chen, Moutong; Yang, Xifei; Ren, Xiaohu; Fang, Shisong; Ye, Jinbo; Huang, Haiyan; Peng, Chaoqiong; Zhou, Li; Huang, Xinfeng; Yang, Fan; Wu, Desheng; Zhuang, Zhixiong; Liu, Jianjun, E-mail: bio-research@hotmail.com

2012-09-01

Emerging evidence indicates that trichloroethylene (TCE) exposure causes severe hepatotoxicity. However, the mechanisms of TCE hepatotoxicity remain unclear. Recently, we reported that TCE exposure up-regulated the expression of the oncoprotein SET/TAF-Iα and SET knockdown attenuated TCE-induced cytotoxicity in hepatic L-02 cells. To decipher the function of SET/TAF-Iα and its contributions to TCE-induced hepatotoxicity, we employed a proteomic analysis of SET/TAF-Iα with tandem affinity purification to identify SET/TAF-Iα-binding proteins. We identified 42 novel Gene Ontology co-annotated SET/TAF-Iα-binding proteins. The identifications of two of these proteins (eEF1A1, elongation factor 1-alpha 1; eEF1A2, elongation factor 1-alpha 2) were confirmed by Western blot analysis and co-immunoprecipitation (Co-IP). Furthermore, we analyzed the effects of TCE on the expression, distribution and interactions of eEF1A1, eEF1A2 and SET in L-02 cells. Western blot analysis reveals a significant up-regulation of eEF1A1, eEF1A2 and two isoforms of SET, and immunocytochemical analysis reveals that eEF1A1 and SET is redistributed by TCE. SET is redistributed from the nucleus to the cytoplasm, while eFE1A1 is translocated from the cytoplasm to the nucleus. Moreover, we find by Co-IP that TCE exposure significantly increases the interaction of SET with eEF1A2. Our data not only provide insights into the physiological functions of SET/TAF-Iα and complement the SET interaction networks, but also demonstrate that TCE exposure induces alterations in the expression, distribution and interactions of SET and its binding partners. These alterations may constitute the mechanisms of TCE cytotoxicity. -- Highlights: ► Identify 62 SET/TAF-Iα-associated proteins in human L-02 cells ► Trichloroethylene (TCE) alters the interaction of SET with eEF1A1 and eEF1A2. ► TCE induces the translocation and up-regulation of SET. ► TCE induces the translocation and up-regulation of eEF1A.

Proteomic analysis of trichloroethylene-induced alterations in expression, distribution, and interactions of SET/TAF-Iα and two SET/TAF-Iα-binding proteins, eEF1A1 and eEF1A2, in hepatic L-02 cells

International Nuclear Information System (INIS)

Hong, Wen-Xu; Yang, Liang; Chen, Moutong; Yang, Xifei; Ren, Xiaohu; Fang, Shisong; Ye, Jinbo; Huang, Haiyan; Peng, Chaoqiong; Zhou, Li; Huang, Xinfeng; Yang, Fan; Wu, Desheng; Zhuang, Zhixiong; Liu, Jianjun

2012-01-01

Emerging evidence indicates that trichloroethylene (TCE) exposure causes severe hepatotoxicity. However, the mechanisms of TCE hepatotoxicity remain unclear. Recently, we reported that TCE exposure up-regulated the expression of the oncoprotein SET/TAF-Iα and SET knockdown attenuated TCE-induced cytotoxicity in hepatic L-02 cells. To decipher the function of SET/TAF-Iα and its contributions to TCE-induced hepatotoxicity, we employed a proteomic analysis of SET/TAF-Iα with tandem affinity purification to identify SET/TAF-Iα-binding proteins. We identified 42 novel Gene Ontology co-annotated SET/TAF-Iα-binding proteins. The identifications of two of these proteins (eEF1A1, elongation factor 1-alpha 1; eEF1A2, elongation factor 1-alpha 2) were confirmed by Western blot analysis and co-immunoprecipitation (Co-IP). Furthermore, we analyzed the effects of TCE on the expression, distribution and interactions of eEF1A1, eEF1A2 and SET in L-02 cells. Western blot analysis reveals a significant up-regulation of eEF1A1, eEF1A2 and two isoforms of SET, and immunocytochemical analysis reveals that eEF1A1 and SET is redistributed by TCE. SET is redistributed from the nucleus to the cytoplasm, while eFE1A1 is translocated from the cytoplasm to the nucleus. Moreover, we find by Co-IP that TCE exposure significantly increases the interaction of SET with eEF1A2. Our data not only provide insights into the physiological functions of SET/TAF-Iα and complement the SET interaction networks, but also demonstrate that TCE exposure induces alterations in the expression, distribution and interactions of SET and its binding partners. These alterations may constitute the mechanisms of TCE cytotoxicity. -- Highlights: ► Identify 62 SET/TAF-Iα-associated proteins in human L-02 cells ► Trichloroethylene (TCE) alters the interaction of SET with eEF1A1 and eEF1A2. ► TCE induces the translocation and up-regulation of SET. ► TCE induces the translocation and up-regulation of eEF1A.

Survival and cardiovascular events after coarctation-repair in long-term follow-up (COAFU): Predictive value of clinical variables.

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Bambul Heck, P; Pabst von Ohain, J; Kaemmerer, H; Ewert, P; Hager, A

2017-02-01

Long-term sequelae and events after coarctation repair are well described. However, the predictive value of variables from clinical follow-up investigation for late events and survival has rarely been investigated. All patients who participated in the prospective cross-sectional COALA Study in 2000 with a structural clinical investigation including blood pressure measurement and symptom-limited exercise test were contacted for reevaluation of survival, current clinical status and major cardiovascular events. Of 273 eligible patients, 209 were available for follow-up. Nine patients had died at a median age of 46years (range 30-64years), five of them due to cardiovascular complications. Late mortality after surgical intervention was 5.7% with a median age of 41years (range 16-64years). Twenty-five patients had a major cardiovascular event: 12 had procedures at the aortic valve or aortic arch, 8 had procedures for restenosis, 2 had endocarditis, 2 had a cerebrovascular insult and 1 an aortic dissection. The presence of bicuspid aortic valve (p=0.009), brachial-ankle blood pressure gradient >20mmHg (p<0.001) and reduced left ventricular function (p=0.002) correlated with major cardiovascular events. Surgical correction of coarctation of the aorta shows fairly low mortality in the long-term follow-up. Late morbidities include recoarctation, but also the consequences of the hemodynamics produced by a congenital bicuspid aortic valve, presence of which is predictive for aortic valve procedures: however the predictive value of clinical variables is limited. Copyright © 2016. Published by Elsevier Ireland Ltd.

SURVIVAL OF CONTINUOUS AMBULATORY PERITONEAL DIALYSIS CATHETERS: AN EVALUATION OF SURGICAL AND NON-SURGICAL FACTORS (SINGLE CENTER STUDY

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A. Keshvari

2006-06-01

Full Text Available Peritoneal dialysis is an established form of renal replacement therapy used in many patients with end-stage renal disease. The key to a successful chronic peritoneal dialysis is a permanent and safe access to the peritoneal cavity. This study was conducted in order to evaluate the catheter survival and its related factors in Imam Khomeini Hospital. A total of 80 catheters were inserted into 69 patients (52 men and 28 women with end-stage chronic renal failure during a period of 84 months. Retrospectively the correlation between catheter survival (overall and event free with demographic factors (sex and age, surgical factors (surgeons and surgical methods, nephrologic factors (the causes of peritoneal dialysis selection and the history of hemodialysis and peritonitis factors (the history and number of peritonitis has been evaluated. The mean age of the patients was 48.35 years (16 to 79 years. The overall survival of catheters or the probability of having a functioning catheter after one, two and three years was 53%, 41%, 22%, respectively. The event free survival of the catheter or the probability of having a functioning catheter without any problems after one year was 14%. It has been found out that among all factors in this study only history of hemodialysis had statistically significant effect on the overall survival of continuous ambulatory peritoneal dialysis catheter (P = 0.04. It seems that the overall survival of catheters is better when CAPD is started before any other attempts for hemodialysis.

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

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Rolf Warta

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

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

International Nuclear Information System (INIS)

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

2009-01-01

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

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

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

2009-09-15

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

Corticosterone levels predict survival probabilities of Galápagos marine iguanas during El Niño events

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Romero, L. Michael; Wikelski, Martin

2001-01-01

Plasma levels of corticosterone are often used as a measure of “stress” in wild animal populations. However, we lack conclusive evidence that different stress levels reflect different survival probabilities between populations. Galápagos marine iguanas offer an ideal test case because island populations are affected differently by recurring El Niño famine events, and population-level survival can be quantified by counting iguanas locally. We surveyed corticosterone levels in six populations during the 1998 El Niño famine and the 1999 La Niña feast period. Iguanas had higher baseline and handling stress-induced corticosterone concentrations during famine than feast conditions. Corticosterone levels differed between islands and predicted survival through an El Niño period. However, among individuals, baseline corticosterone was only elevated when body condition dropped below a critical threshold. Thus, the population-level corticosterone response was variable but nevertheless predicted overall population health. Our results lend support to the use of corticosterone as a rapid quantitative predictor of survival in wild animal populations. PMID:11416210

Cardiovascular event-free survival after adjuvant radiation therapy in breast cancer patients stratified by cardiovascular risk

International Nuclear Information System (INIS)

Onwudiwe, Nneka C; Kwok, Young; Onukwugha, Eberechukwu; Sorkin, John D; Zuckerman, Ilene H; Shaya, Fadia T; Daniel Mullins, C

2014-01-01

The objective of this study was to estimate the risk of a cardiovascular event or death associated with modern radiation in a population of elderly female breast cancer patients with varying baseline cardiovascular risk. The data used for this analysis are from the linked Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. The retrospective cohort study included women aged 66 years and older with stage 0–III breast cancer diagnosed between 2000 and 2005. Women were grouped as low, intermediate, or high cardiovascular risk based on the presence of certain clinical diagnoses. The risk for the combined outcome of a hospitalization for a cardiovascular event or death within 6 months and 24 months of diagnosis was estimated using a multivariable Cox model. The median follow-up time was 24 months. Among the 91,612 women with American Joint Committee on Cancer (AJCC) stage 0–III breast cancer: 39,555 (43.2%) were treated with radiation therapy and 52,057 (56.8%) were not. The receipt of radiation therapy in the first 6 months was associated with a statistically significant increased risk for the combined outcome in women categorized as high risk (HR = 1.510; 95% CI, 1.396–1.634) or intermediate risk (HR = 1.415; 95% CI, 1.188–1.686) but not low risk (HR = 1.027; 95% CI, 0.798–1.321). Women with a prior medical history of cardiovascular disease treated with radiation therapy are at increased risk for an event and should be monitored for at least 6 months following treatment with radiation therapy

The Fic protein Doc uses an inverted substrate to phosphorylate and inactivate EF-Tu.

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Castro-Roa, Daniel; Garcia-Pino, Abel; De Gieter, Steven; van Nuland, Nico A J; Loris, Remy; Zenkin, Nikolay

2013-12-01

Fic proteins are ubiquitous in all of the domains of life and have critical roles in multiple cellular processes through AMPylation of (transfer of AMP to) target proteins. Doc from the doc-phd toxin-antitoxin module is a member of the Fic family and inhibits bacterial translation by an unknown mechanism. Here we show that, in contrast to having AMPylating activity, Doc is a new type of kinase that inhibits bacterial translation by phosphorylating the conserved threonine (Thr382) of the translation elongation factor EF-Tu, rendering EF-Tu unable to bind aminoacylated tRNAs. We provide evidence that EF-Tu phosphorylation diverged from AMPylation by antiparallel binding of the NTP relative to the catalytic residues of the conserved Fic catalytic core of Doc. The results bring insights into the mechanism and role of phosphorylation of EF-Tu in bacterial physiology as well as represent an example of the catalytic plasticity of enzymes and a mechanism for the evolution of new enzymatic activities.

Clinical Significance of Serum Ferritin at Diagnosis in Patients With Acute Myeloid Leukemia: A YACHT Multicenter Retrospective Study.

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Tachibana, Takayoshi; Andou, Taiki; Tanaka, Masatsugu; Ito, Satomi; Miyazaki, Takuya; Ishii, Yoshimi; Ogusa, Eriko; Koharazawa, Hideyuki; Takahashi, Hiroyuki; Motohashi, Kenji; Aoki, Jun; Nakajima, Yuki; Matsumoto, Kenji; Hagihara, Maki; Hashimoto, Chizuko; Taguchi, Jun; Fujimaki, Katsumichi; Fujita, Hiroyuki; Fujisawa, Shin; Kanamori, Heiwa; Nakajima, Hideaki

2018-06-01

A multicenter retrospective analysis was performed to evaluate the clinical significance of serum ferritin at diagnosis in patients with acute myeloid leukemia (AML). The study cohort included 305 patients who were newly diagnosed with AML from 2000 to 2015 and received standard induction chemotherapy. Transplantation was performed in 168 patients. The median ferritin value was 512 ng/mL (range, 8-9475 ng/mL). Ferritin correlated with lactate dehydrogenase, C-reactive protein, white blood cell count, and blast count, and elevation of ferritin was associated with poor performance status. The median follow-up period was 58 months (range, 4-187 months) among survivors. The high ferritin group (≥ 400 ng/mL) demonstrated inferior event-free survival (EFS) at the 5-year interval (30% vs. 40%; P = .033) compared to the low ferritin group. Multivariate analysis in the high-risk karyotype revealed that high ferritin levels predicted worse EFS (hazard ratio = 2.07; 95% confidence interval, 1.28-3.33; P = .003). Elevated ferritin at diagnosis may indicate tumor burden in patients with AML and predict worse EFS in the high-risk group. Copyright © 2018 Elsevier Inc. All rights reserved.

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

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

2009-01-01

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

Case of Six-Year Disease-Free Survival with Undifferentiated Carcinoma of the Pancreas

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Hiroyuki Saito

2016-08-01

Full Text Available Undifferentiated carcinoma of the pancreas (UDC is rare and has a dismal prognosis. Here, we report a case of 6-year disease-free survival with a mixed type of UDC and UDC with osteoclast-like giant cells, with a high mitotic index as well as perineural, lymphatic, vessel, and diaphragmatic invasion. The patient underwent radical distal pancreatectomy and was subsequently treated with adjuvant chemotherapy using gemcitabine plus S-1 followed by maintenance chemotherapy with oral tegafur-uracil. The patient has been doing well with no evidence of recurrence for more than 6 years after surgery.

Outcome of children with acute myeloid leukaemia (AML) experiencing primary induction failure in the AIEOP AML 2002/01 clinical trial.

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Quarello, Paola; Fagioli, Franca; Basso, Giuseppe; Putti, Maria C; Berger, Massimo; Luciani, Matteo; Rizzari, Carmelo; Menna, Giuseppe; Masetti, Riccardo; Locatelli, Franco

2015-11-01

Paediatric patients with acute myeloid leukaemia (AML) who fail induction due to primary resistance to chemotherapy account for a significant proportion of cases and have a particularly dismal prognosis. We report the clinical and biological data, and final outcome of 48 paediatric patients with primary-resistant AML enrolled in the Associazione Italiana di Ematologia e Oncologia Pediatrica AML 2002/01 clinical trial. These patients had a significantly higher white blood cell count at diagnosis compared to other AML patients. Cytogenetic and molecular features did not differ between patients with primary induction failure and patients allocated to the high-risk group. For the whole patient population, the probability of overall survival, event-free survival (EFS) and disease-free survival (DFS) was 21·8% ± 6·2, 20·4% ± 5·9, and 49·5% ± 11·3, respectively. Twenty-eight (58%) patients received haematopoietic stem cell transplantation (HSCT); 3 were autologous and 25 were allogeneic. Patients who underwent HSCT had improved EFS (31·2% vs. 5%, P < 0·0001). Only one of the 20 patients who did not receive HSCT is alive and disease free. The 19 patients in complete remission at time of HSCT showed significantly better DFS than the 9 with active disease (46% vs. 0%, P = 0·02). This study represents one of the largest series with long-term follow up of paediatric AML patients with primary refractory disease. Children who underwent transplantation had an encouraging long-term outcome. Disease recurrence remains the major cause of treatment failure; a better understanding of the disease biology is desirable to develop more effective treatment strategies. © 2015 John Wiley & Sons Ltd.

Early Postoperative Low Expression of RAD50 in Rectal Cancer Patients Associates with Disease-Free Survival

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Vincent Ho

2017-11-01

Full Text Available Background: Molecular biomarkers have the potential to predict response to the treatment of rectal cancer. In this study, we aimed to evaluate the prognostic and clinicopathological implication of RAD50 (DNA repair protein RAD50 homolog expression in rectal cancer. Methods: A total of 266 rectal cancer patients who underwent surgery and received chemo- and radiotherapy between 2000 and 2011 were involved in the study. Postoperative RAD50 expression was determined by immunohistochemistry in surgical samples (n = 266. Results: Using Kaplan–Meier survival analysis, we found that low RAD50 expression in postoperative samples was associated with worse disease free survival (p = 0.001 and overall survival (p < 0.001 in early stage/low-grade tumors. In a comparison of patients with low vs. high RAD50 expression, we found that low levels of postoperative RAD50 expression in rectal cancer tissues were significantly associated with perineural invasion (p = 0.002. Conclusion: Expression of RAD50 in rectal cancer may serve as a prognostic biomarker for long-term survival of patients with perineural invasion-positive tumors and for potential use in early stage and low-grade rectal cancer assessment.

MRE11-Deficiency Associated with Improved Long-Term Disease Free Survival and Overall Survival in a Subset of Stage III Colon Cancer Patients in Randomized CALGB 89803 Trial

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Pavelitz, Thomas; Renfro, Lindsay; Foster, Nathan R.; Caracol, Amber; Welsch, Piri; Lao, Victoria Valinluck; Grady, William B.; Niedzwiecki, Donna; Saltz, Leonard B.; Bertagnolli, Monica M.; Goldberg, Richard M.; Rabinovitch, Peter S.; Emond, Mary; Monnat, Raymond J.; Maizels, Nancy

2014-01-01

Purpose Colon cancers deficient in mismatch repair (MMR) may exhibit diminished expression of the DNA repair gene, MRE11, as a consequence of contraction of a T11 mononucleotide tract. This study investigated MRE11 status and its association with prognosis, survival and drug response in patients with stage III colon cancer. Patients and Methods Cancer and Leukemia Group B 89803 (Alliance) randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly adjuvant bolus 5-fluorouracil/leucovorin (FU/LV) or irinotecan+FU/LV (IFL), with 8 year follow-up. Tumors from these patients were analyzed to determine stability of a T11 tract in the MRE11 gene. The primary endpoint was overall survival (OS), and a secondary endpoint was disease-free survival (DFS). Non-proportional hazards were addressed using time-dependent covariates in Cox analyses. Results Of 625 tumor cases examined, 70 (11.2%) exhibited contraction at the T11 tract in one or both MRE11 alleles and were thus predicted to be deficient in MRE11 (dMRE11). In pooled treatment analyses, dMRE11 patients showed initially reduced DFS and OS but improved long-term DFS and OS compared with patients with an intact MRE11 T11 tract. In the subgroup of dMRE11 patients treated with IFL, an unexplained early increase in mortality but better long-term DFS than IFL-treated pMRE11 patients was observed. Conclusions Analysis of this relatively small number of patients and events showed that the dMRE11 marker predicts better prognosis independent of treatment in the long-term. In subgroup analyses, dMRE11 patients treated with irinotecan exhibited unexplained short-term mortality. MRE11 status is readily assayed and may therefore prove to be a useful prognostic marker, provided that the results reported here for a relatively small number of patients can be generalized in independent analyses of larger numbers of samples. Trial Registration ClinicalTrials.gov NCT00003835 PMID:25310185

MRE11-deficiency associated with improved long-term disease free survival and overall survival in a subset of stage III colon cancer patients in randomized CALGB 89803 trial.

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Thomas Pavelitz

Full Text Available Colon cancers deficient in mismatch repair (MMR may exhibit diminished expression of the DNA repair gene, MRE11, as a consequence of contraction of a T11 mononucleotide tract. This study investigated MRE11 status and its association with prognosis, survival and drug response in patients with stage III colon cancer.Cancer and Leukemia Group B 89803 (Alliance randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly adjuvant bolus 5-fluorouracil/leucovorin (FU/LV or irinotecan+FU/LV (IFL, with 8 year follow-up. Tumors from these patients were analyzed to determine stability of a T11 tract in the MRE11 gene. The primary endpoint was overall survival (OS, and a secondary endpoint was disease-free survival (DFS. Non-proportional hazards were addressed using time-dependent covariates in Cox analyses.Of 625 tumor cases examined, 70 (11.2% exhibited contraction at the T11 tract in one or both MRE11 alleles and were thus predicted to be deficient in MRE11 (dMRE11. In pooled treatment analyses, dMRE11 patients showed initially reduced DFS and OS but improved long-term DFS and OS compared with patients with an intact MRE11 T11 tract. In the subgroup of dMRE11 patients treated with IFL, an unexplained early increase in mortality but better long-term DFS than IFL-treated pMRE11 patients was observed.Analysis of this relatively small number of patients and events showed that the dMRE11 marker predicts better prognosis independent of treatment in the long-term. In subgroup analyses, dMRE11 patients treated with irinotecan exhibited unexplained short-term mortality. MRE11 status is readily assayed and may therefore prove to be a useful prognostic marker, provided that the results reported here for a relatively small number of patients can be generalized in independent analyses of larger numbers of samples.ClinicalTrials.gov NCT00003835.

Prognostic Value of Normal Perfusion but Impaired Left Ventricular Function in the Diabetic Heart on Quantitative Gated Myocardial Perfusion SPECT

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Jeong, Hwanjeong; Choi, Sehun; Han, Yeonhee [Research Institute of Chonbuk National Univ. Medical School and Hospitial, Jeonju (Korea, Republic of); Lee, Dong Soo; Lee, Hoyoung; Chung, Junekey [Seoul National Univ., Seoul (Korea, Republic of)

2013-09-15

This study aimed at identifying the predictive parameters on quantitative gated myocardial perfusion single-photon emission computed tomography (QG-SPECT) in diabetic patients with normal perfusion but impaired function. Methods Among the 533 consecutive diabetic patients, 379 patients with normal perfusion on rest Tl-201/dipyridamole-stress Tc-{sup 99m} sestamibi Gated SPECT were enrolled. Patients were grouped into those with normal post-stress left ventricular function (Group I) and those with impaired function (EF <50 or impaired regional wall motion, Group II). We investigated cardiac events and cause of death by chart review and telephone interview. Survival analysis and Cox proportional hazard model analysis were performed. Between the Group I and II, cardiac events as well as chest pain symptoms, smoking, diabetic complications were significantly different (P<0.05). On survival analysis, event free survival rate in Group II was significantly lower than in Group I (P=0.016). In univariate Cox proportional hazard analysis on overall cardiac event, Group (II over I), diabetic nephropathy, summed motion score (SMS), summed systolic thickening score (STS), numbers of abnormal segmental wall motion and systolic thickening predicted more cardiac events (P<0.05). Multivariate analysis showed that STS was the only independent predictor cardiac event. The functional parameter, especially summed systolic thickening score on QG-SPECT had prognostic values, despite normal perfusion, in predicting cardiac events in diabetic patients, and QG-SPECT provides clinically useful risk stratification in diabetic patients with normal perfusion.

24-month HIV-free survival among infants born to HIV-positive women enrolled in Option B+ program in Kigali, Rwanda: The Kabeho Study.

Science.gov (United States)

Gill, Michelle M; Hoffman, Heather J; Ndatimana, Dieudonne; Mugwaneza, Placidie; Guay, Laura; Ndayisaba, Gilles F; Bobrow, Emily A; Asiimwe, Anita; Mofenson, Lynne M

2017-12-01

Lifelong antiretroviral therapy (ART) provision to all pregnant HIV-positive women ("Option B+") has been recommended by the World Health Organization since 2013, but there remain limited data on the effects of Option B+ on long-term HIV-free survival in breastfeeding HIV-exposed infants. The Kigali Antiretroviral and Breastfeeding Assessment for the Elimination of HIV (Kabeho) study enrolled HIV-positive women from the third trimester of pregnancy to 2 weeks postpartum in 14 heath facilities implementing Option B+ in Kigali, Rwanda. Mother-child pairs in the longitudinal observational cohort were followed until 24 months postpartum, with HIV diagnostic testing at 6 weeks, and 9, 18 and 24 months. The Kaplan-Meier method was used to estimate HIV transmission, survival, and HIV-free survival through 24 months. We enrolled 608 HIV-positive women in 2013-2014; birth outcome data were available for 600 women and 597 live-born infants. By 6 weeks, 11 infants had died and 3 infants had confirmed HIV infection (0.5% transmission; 95% confidence interval [CI] 0.2-1.6). At 9 months, there were 9 additional deaths and 2 new infections (cumulative transmission 0.9%, 95% CI 0.4-2.2). At 18 months, there were 6 additional deaths and no new infant infections. At 24 months, there were no additional child deaths and 1 new infection (cumulative 2.2%, 95% CI 0.7-7.0), for an overall 24-month HIV-free survival of 93.2% (95% CI 89.5-95.6). Low transmission rates and high HIV-free survival at 24 months were achieved in breastfeeding infants of HIV-positive mothers receiving universal ART in urban health facilities in Rwanda, though vigilance on maintaining viral suppression for ART-experienced women is needed. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Additional androgen deprivation makes the difference. Biochemical recurrence-free survival in prostate cancer patients after HDR brachytherapy and external beam radiotherapy

International Nuclear Information System (INIS)

Schiffmann, Jonas; Tennstedt, Pierre; Beyer, Burkhard; Boehm, Katharina; Tilki, Derya; Salomon, Georg; Graefen, Markus; Lesmana, Hans; Platz, Volker; Petersen, Cordula; Kruell, Andreas; Schwarz, Rudolf

2015-01-01

The role of additional androgen deprivation therapy (ADT) in prostate cancer (PCa) patients treated with combined HDR brachytherapy (HDR-BT) and external beam radiotherapy (EBRT) is still unknown. Consecutive PCa patients classified as D'Amico intermediate and high-risk who underwent HDR-BT and EBRT treatment ± ADT at our institution between January 1999 and February 2009 were assessed. Multivariable Cox regression models predicting biochemical recurrence (BCR) were performed. BCR-free survival was assessed with Kaplan-Meier analyses. Overall, 392 patients were assessable. Of these, 221 (56.4 %) underwent trimodality (HDR-BT and EBRT and ADT) and 171 (43.6 %) bimodality (HDR-BT and EBRT) treatment. Additional ADT administration reduced the risk of BCR (HR: 0.4, 95 % CI: 0.3-0.7, p < 0.001). D'Amico high-risk patients had superior BCR-free survival when additional ADT was administered (log-rank p < 0.001). No significant difference for BCR-free survival was recorded when additional ADT was administered to D'Amico intermediate-risk patients (log-rank p = 0.2). Additional ADT administration improves biochemical control in D'Amico high-risk patients when HDR-BT and EBRT are combined. Physicians should consider the oncological benefit of ADT administration for these patients during the decision-making process. (orig.) [de

Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses

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Todorovic Balint, Milena; Jelicic, Jelena; Mihaljevic, Biljana; Kostic, Jelena; Stanic, Bojana; Balint, Bela; Pejanovic, Nadja; Lucic, Bojana; Tosic, Natasa; Marjanovic, Irena; Stojiljkovic, Maja; Karan-Djurasevic, Teodora; Perisic, Ognjen; Rakocevic, Goran; Popovic, Milos; Raicevic, Sava; Bila, Jelena; Antic, Darko; Andjelic, Bosko; Pavlovic, Sonja

2016-01-01

The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach. PMID:27164089

Heterologous expression of a plastid EF-Tu reduces protein thermal aggregation and enhances CO2 fixation in wheat (Triticum aestivum) following heat stress.

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Fu, Jianming; Momcilović, Ivana; Clemente, Thomas E; Nersesian, Natalya; Trick, Harold N; Ristic, Zoran

2008-10-01

Heat stress is a major constraint to wheat production and negatively impacts grain quality, causing tremendous economic losses, and may become a more troublesome factor due to global warming. At the cellular level, heat stress causes denaturation and aggregation of proteins and injury to membranes leading to alterations in metabolic fluxes. Protein aggregation is irreversible, and protection of proteins from thermal aggregation is a strategy a cell uses to tolerate heat stress. Here we report on the development of transgenic wheat (Triticum aestivum) events, expressing a maize gene coding for plastidal protein synthesis elongation factor (EF-Tu), which, compared to non-transgenic plants, display reduced thermal aggregation of leaf proteins, reduced heat injury to photosynthetic membranes (thylakoids), and enhanced rate of CO(2) fixation after exposure to heat stress. The results support the concept that EF-Tu ameliorates negative effects of heat stress by acting as a molecular chaperone. This is the first demonstration of the introduction of a plastidal EF-Tu in plants that leads to protection against heat injury and enhanced photosynthesis after heat stress. This is also the first demonstration that a gene other than HSP gene can be used for improvement of heat tolerance and that the improvement is possible in a species that has a complex genome, hexaploid wheat. The results strongly suggest that heat tolerance of wheat, and possibly other crop plants, can be improved by modulating expression of plastidal EF-Tu and/or by selection of genotypes with increased endogenous levels of this protein.

Increased tumour ascorbate is associated with extended disease-free survival and decreased hypoxia-inducible factor-1 activation in human colorectal cancer

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Caroline eKuiper

2014-02-01

Full Text Available Ascorbate is a co-factor for the hydroxylases that regulate the transcription factor hypoxia-inducible factor (HIF-1, which provides cancer cells with a metabolic and survival advantage in the hypoxic environment of solid tumors. However, whether ascorbate affects tumor development is a highly debated issue. We aimed to determine whether tumor ascorbate was associated with HIF-1 activation and patient disease-free survival. In this study we undertook a retrospective observational analysis of tissue-banked tumor and paired normal tissue from 49 colorectal cancer patients, measuring ascorbate levels, HIF-1α and its downstream gene products BNIP3 and VEGF. Patient survival was monitored for the first six years after surgery. We found that ascorbate levels were lower in tumor tissue compared to normal tissue (p< 0.001 but overall levels varied considerably. HIF-1α, VEGF and BNIP3 were elevated in tumor samples (p< 0.01. There was an inverse relationship between tumor ascorbate content and HIF-1 pathway activation (p=0.002 and tumor size (p=0.018. Higher tumor ascorbate content was associated with significantly improved disease-free survival in the first 6 years after surgery (p=0.006, with 141 - 1,094 additional disease free days. This was independent of tumor grade and stage. Survival advantage was associated with the amount of ascorbate in the tumor, but not with the amount in adjacent normal tissue. Our results demonstrate that higher tumor ascorbate content is associated decreased HIF-1 activation, most likely due to the co-factor activity of ascorbate for the regulatory HIF hydroxylases. Our findings support the need for future studies to determine whether raising tumor ascorbate is possible with clinical intervention and whether this results in modification of hydroxylase-dependent pathways in the tumor.

Tick exposure and extreme climate events impact survival and threaten the persistence of a long-lived lizard.

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Jones, Alice R; Bull, C Michael; Brook, Barry W; Wells, Konstans; Pollock, Kenneth H; Fordham, Damien A

2016-03-01

Assessing the impacts of multiple, often synergistic, stressors on the population dynamics of long-lived species is becoming increasingly important due to recent and future global change. Tiliqua rugosa (sleepy lizard) is a long-lived skink (>30 years) that is adapted to survive in semi-arid environments with varying levels of parasite exposure and highly seasonal food availability. We used an exhaustive database of 30 years of capture-mark-recapture records to quantify the impacts of both parasite exposure and environmental conditions on the lizard's survival rates and long-term population dynamics. Lizard abundance was relatively stable throughout the study period; however, there were changing patterns in adult and juvenile apparent survival rates, driven by spatial and temporal variation in levels of tick exposure and temporal variation in environmental conditions. Extreme weather events during the winter and spring seasons were identified as important environmental drivers of survival. Climate models predict a dramatic increase in the frequency of extreme hot and dry winter and spring seasons in our South Australian study region; from a contemporary probability of 0.17 up to 0.47-0.83 in 2080 depending on the emissions scenario. Our stochastic population model projections showed that these future climatic conditions will induce a decline in the abundance of this long-lived reptile of up to 67% within 30 years from 2080, under worst case scenario modelling. The results have broad implications for future work investigating the drivers of population dynamics and persistence. We highlight the importance of long-term data sets and accounting for synergistic impacts between multiple stressors. We show that predicted increases in the frequency of extreme climate events have the potential to considerably and negatively influence a long-lived species, which might previously have been assumed to be resilient to environmental perturbations. © 2015 The Authors. Journal of

Treatment outcome and prognostic factor analysis in transplant-eligible Chinese myeloma patients receiving bortezomib-based induction regimens including the staged approach, PAD or VTD

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Chim Chor

2012-06-01

Full Text Available Abstract Background We have reported promising outcomes using a staged approach, in which bortezomib/thalidomide/dexamethasone was used only in 14 patients with suboptimal response to VAD (vincristine/adriamycin/dexamethasone before autologous stem cell transplantation (ASCT. Here we compared the outcomes of the staged approach with frontline PAD (bortezomib/doxorubicin/dexamethasone or VTD (bortezomib/thalidomide/dexamethasone induction, and analysed prognostic factors for outcome. Patients and methods Ninety-one transplant-eligible Chinese patients received three induction regimens prior to ASCT [staged approach (N = 25, PAD (N = 31, VTD (N = 35]. and received thalidomide maintenance for 2 years post-ASCT. Results 43 (47.3% patients had International Staging System (ISS III disease. By an intention-to-treat analysis, the overall CR/nCR rate were 37.4% post-induction, and 62.6% post-ASCT. Five-year overall (OS and event-free (EFS survivals were 66% and 45.1%. There was no difference of the post-induction CR/nCR rate, EFS or OS between patients induced by these three regimens. Moreover, ISS III disease did not affect CR/nCR rates. Multivariate analysis showed that ISS and post-ASCT CR/nCR impacted OS while ISS and post-induction CR/nCR impacted EFS. Conclusions These three induction regimens produced comparable and favorable outcomes in myeloma. The unfavorable outcome of ISS stage III persisted despite upfront/early use of bortezomib. CR/nCR predicted favorable survivals.

75 FR 41894 - Wapakoneta Machine Company, Currently Known as EF Industrial Technologies, Inc., Wapakoneta, OH...

Science.gov (United States)

2010-07-19

... of early 2010, Wapakoneta Machine Company is currently known as EF Industrial Technologies, Inc. Some... Wapakoneta Machine Company, currently known as EF Industrial Technologies, Inc., Wapakoneta, Ohio became... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-73,211] Wapakoneta Machine...

Outcome of High-Risk Stage 3 Neuroblastoma with Myeloablative Therapy and 13-cis-Retinoic Acid: A Report from the Children’s Oncology Group

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Park, Julie R.; Villablanca, Judith G.; London, Wendy B.; Gerbing, Robert B.; Haas-Kogan, Daphne; Stanton Adkins, E.; Attiyeh, Edward F.; Maris, John M.; Seeger, Robert C.; Patrick Reynolds, C.; Matthay, Katherine K.

2009-01-01

Background The components of therapy required for patients with INSS Stage 3 neuroblastoma and high risk features remain controversial. Procedure A retrospective cohort design was used to determine if intensive chemoradiotherapy with purged autologous bone marrow rescue (ABMT) and/or 13-cis-retinoic acid (13-cis-RA) improved outcome for patients with high-risk neuroblastoma that was not metastatic to distant sites. We identified 72 patients with INSS Stage 3 neuroblastoma enrolled between 1991 and 1996 on the Phase III CCG 3891 randomized trial. Patients were analyzed on an intent-to-treat basis using a log-rank test. Results The 5-year event-free survival (EFS) and overall survival (OS) rates for patients with Stage 3 neuroblastoma were 55 +/- 6% and 59% +/- 6%, respectively (n=72). Patients randomized to ABMT (n=20) had 5-year EFS of 65% +/- 11% and OS of 65% +/- 11% compared to 41% +/- 11 (p=0.21) and 46% +/- 11% (p=0.23) for patients randomized to CC (n=23), respectively. Patients randomized to 13-cis-RA (n=23) had 5-year EFS of 70% +/- 10% and OS of 78% +/- 9% compared to 63% +/- 12% (p=0.67) and 67% +/- 12% (p=0.55) for those receiving no further therapy (n=16), respectively. Patients randomized to both ABMT and 13-cis-RA (n=6) had a 5-year EFS of 80% ± 11% and OS of 100%. Conclusion Patients with high-risk Stage 3 neuroblastoma have an overall poor prognosis despite aggressive chemoradiotherapy. Further studies are warranted to determine if myeloablative consolidation followed by 13-cis-RA maintenance therapy statistically significantly improves outcome. PMID:18937318

High-dose-rate stereotactic body radiation therapy for postradiation therapy locally recurrent prostatic carcinoma: Preliminary prostate-specific antigen response, disease-free survival, and toxicity assessment.

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Fuller, Donald B; Wurzer, James; Shirazi, Reza; Bridge, Stephen S; Law, Jonathan; Mardirossian, George

2015-01-01

Patients with locally recurrent adenocarcinoma of the prostate following radiation therapy (RT) present a challenging problem. We prospectively evaluated the use of "high-dose-rate-like" prostate stereotactic body RT (SBRT) salvage for this circumstance, evaluating prostate-specific antigen response, disease-free survival, and toxicity. Between February 2009 and March 2014, 29 patients with biopsy-proven recurrent locally prostate cancer >2 years post-RT were treated. Median prior RT dose was 73.8 Gy and median interval to SBRT salvage was 88 months. Median recurrence Gleason score was 7 (79% was ≥7). Pre-existing RT toxicity >grade 1 was a reason for exclusion. Magnetic resonance imaging-defined prostate volume including any suspected extraprostatic extension, comprising the planning target volume. A total of 34 Gy/5 fractions was given, delivering a heterogeneous, high-dose-rate-like dose-escalation pattern. Toxicities were assessed using Common Terminology Criteria for Adverse Events, version 3.0, criteria. Twenty-nine treated patients had a median 24-month follow-up (range, 3-60 months). A median pre-SBRT salvage baseline prostate-specific antigen level of 3.1 ng/mL decreased to 0.65 ng/mL and 0.16 ng/mL at 1 and 2 years, respectively. Actuarial 2-year biochemical disease-free survival measured 82%, with no local failures. Toxicity >grade 1 was limited to the genitourinary domain, with 18% grade 2 or higher and 7% grade 3 or higher. No gastrointestinal toxicity >grade 1 occurred. Two-year disease-free survival is encouraging, and the prostate-specific antigen response kinetic appears comparable with that seen in de novo patients treated with SBRT, albeit still a preliminary finding. Grade ≥2 genitourinary toxicity was occasionally seen with no obvious predictive factor. Noting that our only brachytherapy case was 1 of the 2 cases with ≥grade 3 genitourinary toxicity, caution is recommended treating these patients. SBRT salvage of post-RT local recurrence

Biostatistics series module 9: Survival analysis

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Avijit Hazra

2017-01-01

Full Text Available Survival analysis is concerned with “time to event“ data. Conventionally, it dealt with cancer death as the event in question, but it can handle any event occurring over a time frame, and this need not be always adverse in nature. When the outcome of a study is the time to an event, it is often not possible to wait until the event in question has happened to all the subjects, for example, until all are dead. In addition, subjects may leave the study prematurely. Such situations lead to what is called censored observations as complete information is not available for these subjects. The data set is thus an assemblage of times to the event in question and times after which no more information on the individual is available. Survival analysis methods are the only techniques capable of handling censored observations without treating them as missing data. They also make no assumption regarding normal distribution of time to event data. Descriptive methods for exploring survival times in a sample include life table and Kaplan–Meier techniques as well as various kinds of distribution fitting as advanced modeling techniques. The Kaplan–Meier cumulative survival probability over time plot has become the signature plot for biomedical survival analysis. Several techniques are available for comparing the survival experience in two or more groups – the log-rank test is popularly used. This test can also be used to produce an odds ratio as an estimate of risk of the event in the test group; this is called hazard ratio (HR. Limitations of the traditional log-rank test have led to various modifications and enhancements. Finally, survival analysis offers different regression models for estimating the impact of multiple predictors on survival. Cox's proportional hazard model is the most general of the regression methods that allows the hazard function to be modeled on a set of explanatory variables without making restrictive assumptions concerning the

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

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

2012-02-01

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

Radiographic Progression-Free Survival as a Clinically Meaningful End Point in Metastatic Castration-Resistant Prostate Cancer: The PREVAIL Randomized Clinical Trial.

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Rathkopf, Dana E; Beer, Tomasz M; Loriot, Yohann; Higano, Celestia S; Armstrong, Andrew J; Sternberg, Cora N; de Bono, Johann S; Tombal, Bertrand; Parli, Teresa; Bhattacharya, Suman; Phung, De; Krivoshik, Andrew; Scher, Howard I; Morris, Michael J

2018-05-01

Drug development for metastatic castration-resistant prostate cancer has been limited by a lack of clinically relevant trial end points short of overall survival (OS). Radiographic progression-free survival (rPFS) as defined by the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) is a candidate end point that represents a clinically meaningful benefit to patients. To demonstrate the robustness of the PCWG2 definition and to examine the relationship between rPFS and OS. PREVAIL was a phase 3, randomized, double-blind, placebo-controlled multinational study that enrolled 1717 chemotherapy-naive men with metastatic castration-resistant prostate cancer from September 2010 through September 2012. The data were analyzed in November 2016. Patients were randomized 1:1 to enzalutamide 160 mg or placebo until confirmed radiographic disease progression or a skeletal-related event and initiation of either cytotoxic chemotherapy or an investigational agent for prostate cancer treatment. Sensitivity analyses (SAs) of investigator-assessed rPFS were performed using the final rPFS data cutoff (May 6, 2012; 439 events; SA1) and the interim OS data cutoff (September 16, 2013; 540 events; SA2). Additional SAs using investigator-assessed rPFS from the final rPFS data cutoff assessed the impact of skeletal-related events (SA3), clinical progression (SA4), a confirmatory scan for soft-tissue disease progression (SA5), and all deaths regardless of time after study drug discontinuation (SA6). Correlations between investigator-assessed rPFS (SA2) and OS were calculated using Spearman ρ and Kendall τ via Clayton copula. In the 1717 men (mean age, 72.0 [range, 43.0-93.0] years in enzalutamide arm and 71.0 [range, 42.0-93.0] years in placebo arm), enzalutamide significantly reduced risk of radiographic progression or death in all SAs, with hazard ratios of 0.22 (SA1; 95% CI, 0.18-0.27), 0.31 (SA2; 95% CI, 0.27-0.35), 0.21 (SA3; 95% CI, 0.18-0.26), 0.21 (SA4; 95% CI, 0.17-0.26), 0

Proteomic analysis of trichloroethylene-induced alterations in expression, distribution, and interactions of SET/TAF-Iα and two SET/TAF-Iα-binding proteins, eEF1A1 and eEF1A2, in hepatic L-02 cells.

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Hong, Wen-Xu; Yang, Liang; Chen, Moutong; Yang, Xifei; Ren, Xiaohu; Fang, Shisong; Ye, Jinbo; Huang, Haiyan; Peng, Chaoqiong; Zhou, Li; Huang, Xinfeng; Yang, Fan; Wu, Desheng; Zhuang, Zhixiong; Liu, Jianjun

2012-09-01

Emerging evidence indicates that trichloroethylene (TCE) exposure causes severe hepatotoxicity. However, the mechanisms of TCE hepatotoxicity remain unclear. Recently, we reported that TCE exposure up-regulated the expression of the oncoprotein SET/TAF-Iα and SET knockdown attenuated TCE-induced cytotoxicity in hepatic L-02 cells. To decipher the function of SET/TAF-Iα and its contributions to TCE-induced hepatotoxicity, we employed a proteomic analysis of SET/TAF-Iα with tandem affinity purification to identify SET/TAF-Iα-binding proteins. We identified 42 novel Gene Ontology co-annotated SET/TAF-Iα-binding proteins. The identifications of two of these proteins (eEF1A1, elongation factor 1-alpha 1; eEF1A2, elongation factor 1-alpha 2) were confirmed by Western blot analysis and co-immunoprecipitation (Co-IP). Furthermore, we analyzed the effects of TCE on the expression, distribution and interactions of eEF1A1, eEF1A2 and SET in L-02 cells. Western blot analysis reveals a significant up-regulation of eEF1A1, eEF1A2 and two isoforms of SET, and immunocytochemical analysis reveals that eEF1A1 and SET is redistributed by TCE. SET is redistributed from the nucleus to the cytoplasm, while eFE1A1 is translocated from the cytoplasm to the nucleus. Moreover, we find by Co-IP that TCE exposure significantly increases the interaction of SET with eEF1A2. Our data not only provide insights into the physiological functions of SET/TAF-Iα and complement the SET interaction networks, but also demonstrate that TCE exposure induces alterations in the expression, distribution and interactions of SET and its binding partners. These alterations may constitute the mechanisms of TCE cytotoxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

Combination of baseline metabolic tumour volume and early response on PET/CT improves progression-free survival prediction in DLBCL

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Mikhaeel, N.G.; Smith, Daniel [Guy' s and St Thomas' NHS Foundation Trust, Department of Clinical Oncology, London (United Kingdom); Dunn, Joel T.; Phillips, Michael; Barrington, Sally F. [King' s College London, PET Imaging Centre at St Thomas' Hospital, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Moeller, Henrik [King' s College London, Department of Cancer Epidemiology and Population Health, London (United Kingdom); Fields, Paul A.; Wrench, David [Guy' s and St Thomas' NHS Foundation Trust, Department of Haematology, London (United Kingdom)

2016-07-15

The study objectives were to assess the prognostic value of quantitative PET and to test whether combining baseline metabolic tumour burden with early PET response could improve predictive power in DLBCL. A total of 147 patients with DLBCL underwent FDG-PET/CT scans before and after two cycles of RCHOP. Quantitative parameters including metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were measured, as well as the percentage change in these parameters. Cox regression analysis was used to test the relationship between progression-free survival (PFS) and the study variables. Receiver operator characteristics (ROC) analysis determined the optimal cut-off for quantitative variables, and Kaplan-Meier survival analysis was performed. The median follow-up was 3.8 years. As MTV and TLG measures correlated strongly, only MTV measures were used for multivariate analysis (MVA). Baseline MTV (MTV-0) was the only statistically significant predictor of PFS on MVA. The optimal cut-off for MTV-0 was 396 cm{sup 3}. A model combing MTV-0 and Deauville score (DS) separated the population into three distinct prognostic groups: good (MTV-0 < 400; 5-year PFS > 90 %), intermediate (MTV-0 ≥ 400+ DS1-3; 5-year PFS 58.5 %) and poor (MTV-0 ≥ 400+ DS4-5; 5-year PFS 29.7 %) MTV-0 is an important prognostic factor in DLBCL. Combining MTV-0 and early PET/CT response improves the predictive power of interim PET and defines a poor-prognosis group in whom most of the events occur. (orig.)

Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials).

Science.gov (United States)

Bonnetain, Franck; Bonsing, Bert; Conroy, Thierry; Dousseau, Adelaide; Glimelius, Bengt; Haustermans, Karin; Lacaine, François; Van Laethem, Jean Luc; Aparicio, Thomas; Aust, Daniela; Bassi, Claudio; Berger, Virginie; Chamorey, Emmanuel; Chibaudel, Benoist; Dahan, Laeticia; De Gramont, Aimery; Delpero, Jean Robert; Dervenis, Christos; Ducreux, Michel; Gal, Jocelyn; Gerber, Erich; Ghaneh, Paula; Hammel, Pascal; Hendlisz, Alain; Jooste, Valérie; Labianca, Roberto; Latouche, Aurelien; Lutz, Manfred; Macarulla, Teresa; Malka, David; Mauer, Muriel; Mitry, Emmanuel; Neoptolemos, John; Pessaux, Patrick; Sauvanet, Alain; Tabernero, Josep; Taieb, Julien; van Tienhoven, Geertjan; Gourgou-Bourgade, Sophie; Bellera, Carine; Mathoulin-Pélissier, Simone; Collette, Laurence

2014-11-01

Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Management and outcome of stage 3 neuroblastoma

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Modak, Shakeel; Kushner, Brian H.; LaQuaglia, Michael P.; Kramer, Kim; Cheung, Nai-Kong V.

2013-01-01

Purpose The management of patients with International Neuroblastoma Staging System (INSS) stage 3 neuroblastoma (NB) is not consistent worldwide. We describe a single centre approach at Memorial Sloan-Kettering Cancer Centre (MSKCC) from 1991 to 2007 that minimizes therapy except for those patients with MYCN-amplified NB. Methods In this retrospective analysis of 69 patients, tumour MYCN was not amplified in 53 and amplified in 16. Event-free survival (EFS) and overall survival (OS) were determined by Kaplan–Meier analysis. Results Fourteen patients with non-MYCN-amplified tumours were treated with surgery alone (group A) and the remaining 39 (group B) with surgery following chemotherapy that was initiated and administered at non-MSKCC institutions. Chemotherapy was discontinued after surgery in 38/39 of the latter. The 10-year EFS and OS for all patients with MYCN-non-amplified NB were 74.9 ± 16.9% and 92.6 ± 5.5%, respectively. There was no difference in OS between groups A and B (p = 0.2; 10-year OS for groups A and B was 84.6 ± 14% and 97.1 ± 2.9%, respectively). Patients with MYCN-amplified disease (group C) underwent dose-intensive induction, tumour resection and local radiotherapy: 13 achieved complete or very good partial remission, and 10 received myeloablative chemotherapy. 11/16 patients also received 3F8-based immunotherapy: 10 remain free of disease. The 10-year EFS and OS for patients with MYCN-amplified neuroblastoma treated with immunotherapy were both 90.9 ± 8.7%. Conclusion Patients with MYCN-non-amplified stage 3 NB can be successfully treated with surgery without the need for radiotherapy or continuation of chemotherapy. Combination of dose-intensive chemotherapy, surgery, radiotherapy and immunotherapy was associated with a favourable outcome for most patients with MYCN-amplified stage 3 NB. PMID:18996003

The predictive value of early molecular response in chronic myeloid leukaemia patients treated with imatinib in a single real-world medical centre in a developing country.

Science.gov (United States)

Bee, Ping Chong; Sekaran, Veera; Ng, Richard Rui Jie; Kweh, Ting Yi; Gan, Gin Gin

2017-03-01

The prognosis of patients with chronic myeloid leukaemia (CML) has improved since the introduction of imatinib. However, patients who do not achieve complete cytogenetic response (CCyR) and major molecular response (MMR) have poorer prognosis. Recent clinical trials have demonstrated that early and deeper cytogenetic and molecular responses predict a better long-term outcome. This study aimed to analyse the relationship between early molecular response and clinical outcome in a real-life setting. This retrospective study included all patients with CML, in chronic or accelerated phase, who were treated with imatinib at University of Malaya Medical Centre, Malaysia. A total of 70 patients were analysed. The median follow-up duration was 74 months, and the cumulative percentages of patients with CCyR and MMR were 80.0% and 65.7%, respectively. Overall survival (OS) and event-free survival (EFS) at ten years were 94.3% and 92.9%, respectively. Patients who achieved CCyR and MMR had significantly better OS and EFS than those who did not. At six months, patients who had a BCR-ABL level ≤ 10% had significantly better OS and EFS than those who had a BCR-ABL level > 10%. The target milestone of CCyR at 12 months and MMR at 18 months showed no survival advantage in our patients. Our data showed that imatinib is still useful as first-line therapy. However, vigilant monitoring of patients who have a BCR-ABL level > 10% at six months of treatment should be implemented so that prompt action can be taken to provide the best outcome for these patients. Copyright: © Singapore Medical Association

Progression-free survival/time to progression as a potential surrogate for overall survival in HR+, HER2– metastatic breast cancer

Directory of Open Access Journals (Sweden)

Forsythe A

2018-05-01

Full Text Available Anna Forsythe,1 David Chandiwana,2 Janina Barth,3 Marroon Thabane,4 Johan Baeck,2 Gabriel Tremblay1 1Purple Squirrel Economics, New York, NY, 2Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 3Novartis Pharma GmbH, Nuremberg, Germany; 4Novartis Pharmaceuticals Incorporated, Dorval, QC, Canada Background: Several recent randomized controlled trials (RCTs in hormone receptor-positive (HR+, human epidermal growth factor receptor 2-negative (HER2– metastatic breast cancer (MBC have demonstrated significant improvements in progression-free survival (PFS; however, few have reported improvement in overall survival (OS. The surrogacy of PFS or time to progression (TTP for OS has not been formally investigated in HR+, HER2– MBC.Methods: A systematic literature review of RCTs in HR+, HER2– MBC was conducted to identify studies that reported both median PFS/TTP and OS. The correlation between PFS/TTP and OS was evaluated using Pearson’s product–moment correlation and Spearman’s rank correlation. Subgroup analyses were performed to explore possible reasons for heterogeneity. Errors-in-variables weighted least squares regression (LSR was used to model incremental OS months as a function of incremental PFS/TTP months. An exploratory analysis investigated the impact of three covariates (chemotherapy vs hormonal/targeted therapy, PFS vs TTP, and first-line therapy vs second-line therapy or greater on OS prediction. The lower 95% prediction band was used to determine the minimum incremental PFS/TTP months required to predict OS benefit (surrogate threshold effect [STE].Results: Forty studies were identified. There was a statistically significant correlation between median PFS/TTP and OS (Pearson =0.741, P=0.000; Spearman =0.650, P=0.000. These results proved consistent for chemotherapy and hormonal/targeted therapy. Univariate LSR analysis yielded an R2 of 0.354 with 1 incremental PFS/TTP month corresponding to 1.13 incremental OS months

Regulation of eukaryotic elongation factor 1 alpha (eEF1A) by dynamic lysine methylation

DEFF Research Database (Denmark)

Jakobsson, Magnus E; Małecki, Jędrzej; Falnes, Pål Ø

2018-01-01

Lysine methylation is a frequent post-translational protein modification, which has been intensively studied in the case of histone proteins. Lysine methylations are also found on many non-histone proteins, and one prominent example is eukaryotic elongation factor 1 alpha (eEF1A). Besides its...... essential role in the protein synthesis machinery, a number of non-canonical functions have also been described for eEF1A, such as regulation of the actin cytoskeleton and the promotion of viral replication. The functional significance of the extensive lysine methylations on eEF1A, as well as the identity...

Susceptibility of Ph-positive all to TKI therapy associated with Bcr-Abl rearrangement patterns: a retrospective analysis.

Directory of Open Access Journals (Sweden)

Yu Jing

Full Text Available BACKGROUND: Tyrosine kinase inhibitors (TKIs have demonstrated success in the treatment of acute lymphoblastic leukemia (ALL in patients that express BCR-ABL rearrangements (Philadelphia chromosome [Ph]. The current study aimed to assess the efficacy of TKIs and prognostic factors in the treatment of adults with Ph+-ALL. METHODS: In this multicenter retrospective study, the relationship between Ph+-ALL and treatment outcomes among Chinese patients receiving TKI-containing induction/consolidation chemotherapy was examined. A total of 86 Ph+-ALL patients were included and followed for 3.85 (0.43-9.30 years. Overall survival (OS and event-free survival (EFS were analyzed. RESULTS: A total of 86 Ph+-ALL patients (40 females and 46 males; median age: 34.0 years were enrolled, including those with BCR/ABL transcripts 190 (n = 52, 210 (n = 25, and 230 (n = 2; BCR/ABL isoform determination was not available for 7 patients. Mortality was influenced by variable BCR/ABL transcripts and TKI administration, and BCR/ABL transcripts, hematopoietic stem cell transplantation (HSCT, and TKI administration were associated with the occurrence of events. The OS rate in the TKI administration group during steady state was significantly higher compared with those patients who did not receive TKI administration (P = 0.008, the EFS rate in the TKI administration group during steady state was significantly higher compared with those patients who did not receive TKIs (P = 0.012, and also higher than those with TKI salvage administration (P = 0.004. BCR/ABL transcripts 210 showed preferable OS and EFS compared with BCR/ABL transcripts 190 and 230 (P<0.05 for each. CONCLUSIONS: The susceptibility of Ph+-ALL to TKI associated with the patterns of BCR-ABL rearrangement is demonstrated for the first time, thus adding another risk-stratifying molecular prognostic tool for the management of patients with Ph+-ALL.

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

NARCIS (Netherlands)

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

Vaccination of free-living juvenile wild rabbits (Oryctolagus cuniculus) against myxomatosis improved their survival.

Science.gov (United States)

Guitton, Jean-Sébastien; Devillard, Sébastien; Guénézan, Michel; Fouchet, David; Pontier, Dominique; Marchandeau, Stéphane

2008-04-17

For several decades, the populations of the European wild rabbit (Oryctolagus cuniculus) have declined, which is partly due to myxomatosis. Vaccination against this disease is expected to contribute to restoration of rabbit populations but the actual impact of myxomatosis is not well known and vaccination might have some negative effects. We analyzed the capture-mark-recapture data obtained in a 4-year field experiment (1991-1994) in a park near Paris, France wherein 300 out of 565 seronegative juvenile rabbits were vaccinated at first capture against myxomatosis with the nontransmissible Dervaximyxo SG33 vaccine. After accounting for weight at first capture, age-class (juvenile/adult), "trap-happiness" and season (spring/autumn) of the capture event, vaccinated rabbits had 1.8-fold greater odds of surviving than the unvaccinated rabbits. The average summer survival risk for vaccinated juveniles was 0.63 (+/-0.08 S.E.) whereas it was 0.48 (+/-0.08 S.E.) for unvaccinated juvenile rabbits.

Flow cytometric minimal residual disease monitoring in children with acute lymphoblastic leukemia treated by regimens with reduced intensity

Directory of Open Access Journals (Sweden)

A. M. Popov

2015-01-01

Full Text Available 191 consecutive unselected children with acute lymphoblastic leukemia aged from 1 to 16 years were enrolled in the study. Bone marrow samples were obtained at the time of initial diagnostics as well as at days 15 (n = 188, 36 (n = 191, and 85 (n = 187 of remission induction. Minimal residual disease (MRD was assessed by 6–10-color flow cytometry. Flow cytometry data at day 15 allowed distinguishing three patients groups with significantly different outcome (p ˂ 0.0001: 35.64 % patients with MRD < 0.1 % represented 5-year event-free survival (EFS of 100 %; 48.40 % cases with 0.1 % ≤ MRD< 10 % had EFS 84.6 ± 4.2 %; 15.96 % patients with very high MRD (≥ 10 % belonged to group with poor outcome (EFS 56.7 ± 9.0 %. At the end of remission induction (day 36 36 children (18.85 % with MRD higher than 0.1 % had significantly worse outcome compared to remaining ones (EFS 49.4 ± 9.0 and 93.5 ± 2.1 % respectively; p ˂ 0.0001. From a clinical standpoint it is relevant to evaluate both low-risk and high-risk criteria. Multivariate analysis showed that day 15 MRD data is better for low-risk patients definition while end-induction MRD is the strongest unfavorable prognostic factor.

Risk factors for treatment failure after allogeneic transplantation of patients with CLL: a report from the European Society for Blood and Marrow Transplantation.

Science.gov (United States)

Schetelig, J; de Wreede, L C; van Gelder, M; Andersen, N S; Moreno, C; Vitek, A; Karas, M; Michallet, M; Machaczka, M; Gramatzki, M; Beelen, D; Finke, J; Delgado, J; Volin, L; Passweg, J; Dreger, P; Henseler, A; van Biezen, A; Bornhäuser, M; Schönland, S O; Kröger, N

2017-04-01

For young patients with high-risk CLL, BTK-/PI3K-inhibitors or allogeneic stem cell transplantation (alloHCT) are considered. Patients with a low risk of non-relapse mortality (NRM) but a high risk of failure of targeted therapy may benefit most from alloHCT. We performed Cox regression analyses to identify risk factors for 2-year NRM and 5-year event-free survival (using EFS as a surrogate for long-term disease control) in a large, updated EBMT registry cohort (n= 694). For the whole cohort, 2-year NRM was 28% and 5-year EFS 37%. Higher age, lower performance status, unrelated donor type and unfavorable sex-mismatch had a significant adverse impact on 2-year NRM. Two-year NRM was calculated for good- and poor-risk reference patients. Predicted 2-year-NRM was 11 and 12% for male and female good-risk patients compared with 42 and 33% for male and female poor-risk patients. For 5-year EFS, age, performance status, prior autologous HCT, remission status and sex-mismatch had a significant impact, whereas del(17p) did not. The model-based prediction of 5-year EFS was 55% and 64%, respectively, for male and female good-risk patients. Good-risk transplant candidates with high-risk CLL and limited prognosis either on or after failure of targeted therapy should still be considered for alloHCT.

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

Science.gov (United States)

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

2017-10-01

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

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

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Guyot Patricia

2012-02-01

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

Executive function (EF) in dyslexia: examining an EF profile associated with dyslexia and comorbid dyslexia-ADHD and exploring the near and far transfer effects of EF training in dyslexia alone.

OpenAIRE

Doyle, Caoilainn

2017-01-01

Although there are several competing theories to explain dyslexia, no clear causal pathway has been established. Current theories also fail to address associated socio-emotional difficulties and high co-occurrence of dyslexia with ADHD. Executive function (EF), an umbrella term for a triad of high-level cognitive processes associated with pre-frontal brain regions – response inhibition (RI), working memory updating and switching, is a candidate factor for explaining the overlap between dyslex...

Translation elongation factor eEF1A2 is a potential oncoprotein that is overexpressed in two-thirds of breast tumours

International Nuclear Information System (INIS)

Tomlinson, Victoria AL; Newbery, Helen J; Wray, Naomi R; Jackson, Juliette; Larionov, Alexey; Miller, William R; Dixon, J Michael; Abbott, Catherine M

2005-01-01

The tissue-specific translation elongation factor eEF1A2 was recently shown to be a potential oncogene that is overexpressed in ovarian cancer. Although there is no direct evidence for an involvement of eEF1A2 in breast cancer, the genomic region to which EEF1A2 maps, 20q13, is frequently amplified in breast tumours. We therefore sought to establish whether eEF1A2 expression might be upregulated in breast cancer. eEF1A2 is highly similar (98%) to the near-ubiquitously expressed eEF1A1 (formerly known as EF1-α) making analysis with commercial antibodies difficult. We have developed specific anti-eEF1A2 antibodies and used them in immunohistochemical analyses of tumour samples. We report the novel finding that although eEF1A2 is barely detectable in normal breast it is moderately to strongly expressed in two-thirds of breast tumours. This overexpression is strongly associated with estrogen receptor positivity. eEF1A2 should be considered as a putative oncogene in breast cancer that may be a useful diagnostic marker and therapeutic target for a high proportion of breast tumours. The oncogenicity of eEF1A2 may be related to its role in protein synthesis or to its potential non-canonical functions in cytoskeletal remodelling or apoptosis

Effect of time interval between capecitabine intake and radiotherapy on local recurrence-free survival in preoperative chemoradiation for locally advanced rectal cancer

Energy Technology Data Exchange (ETDEWEB)

Kim, Yeon Joo; Kim, Jong Hoon; Yu, Chang Sik; Kim, Tae Won; Jang, Se Jin; Choi, Eun Kyung; Kim, Jin Cheon [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Won Sik [University of Ulsan College of Medicine, Gangneung (Korea, Republic of)

2017-06-15

The concentration of capecitabine peaks at 1–2 hours after administration. We therefore assumed that proper timing of capecitabine administration and radiotherapy would maximize radiosensitization and influence survival among patients with locally advanced rectal cancer. We retrospectively reviewed 223 patients with locally advanced rectal cancer who underwent preoperative chemoradiation, followed by surgery from January 2002 to May 2006. All patients underwent pelvic radiotherapy (50 Gy/25 fractions) and received capecitabine twice daily at 12-hour intervals (1,650 mg/m2/day). Patients were divided into two groups according to the time interval between capecitabine intake and radiotherapy. Patients who took capecitabine 1 hour before radiotherapy were classified as Group A (n = 109); all others were classified as Group B (n = 114). The median follow-up period was 72 months (range, 7 to 149 months). Although Group A had a significantly higher rate of good responses (44% vs. 25%; p = 0.005), the 5-year local recurrence-free survival rates of 93% in Group A and 97% in Group B did not differ significantly (p = 0.519). The 5-year disease-free survival and overall survival rates were also comparable between the groups. Despite the better pathological response in Group A, the time interval between capecitabine and radiotherapy administration did not have a significant effect on survivals. Further evaluations are needed to clarify the interaction of these treatment modalities.

Free Base Lysine Increases Survival and Reduces Metastasis in Prostate Cancer Model.

Science.gov (United States)

Ibrahim-Hashim, Arig; Wojtkowiak, Jonathan W; de Lourdes Coelho Ribeiro, Maria; Estrella, Veronica; Bailey, Kate M; Cornnell, Heather H; Gatenby, Robert A; Gillies, Robert J

2011-11-19

Malignant tumor cells typically metabolize glucose anaerobically to lactic acid even under normal oxygen tension, a phenomenon called aerobic glycolysis or the Warburg effect. This results in increased acid production and the acidification of the extracellular microenvironment in solid tumors. H + ions tend to flow along concentration gradients into peritumoral normal tissue causing extracellular matrix degradation and increased tumor cell motility thus promoting invasion and metastasis. We have shown that reducing this acidity with sodium bicarbonate buffer decreases the metastatic fitness of circulating tumor cells in prostate cancer and other cancer models. Mathematical models of the tumor-host dynamics predicted that buffers with a pka around 7 will be more effective in reducing intra- and peri-tumoral acidosis and, thus, and possibly more effective in inhibiting tumor metastasis than sodium bicarbonate which has a pKa around 6. Here we test this prediction the efficacy of free base lysine; a non-bicarbonate/non-volatile buffer with a higher pKa (~10), on prostate tumor metastases model. Oxygen consumption and acid production rate of PC3M prostate cancer cells and normal prostate cells were determined using the Seahorse Extracellular Flux (XF-96) analyzer. In vivo effect of 200 mM lysine started four days prior to inoculation on inhibition of metastasis was examined in PC3M-LUC-C6 prostate cancer model using SCID mice. Metastases were followed by bioluminescence imaging. PC3M prostate cancer cells are highly acidic in comparison to a normal prostate cell line indicating that reduction of intra- and perit-tumoral acidosis should inhibit metastases formation. In vivo administration of 200 mM free base lysine increased survival and reduced metastasis. PC3M prostate cancer cells are highly glycolytic and produce large amounts of acid when compared to normal prostate cells. Administration of non-volatile buffer decreased growth of metastases and improved survival

Translation elongation factor eEF1A2 is a potential oncoprotein that is overexpressed in two-thirds of breast tumours

Directory of Open Access Journals (Sweden)

Miller William R

2005-09-01

Full Text Available Abstract Background The tissue-specific translation elongation factor eEF1A2 was recently shown to be a potential oncogene that is overexpressed in ovarian cancer. Although there is no direct evidence for an involvement of eEF1A2 in breast cancer, the genomic region to which EEF1A2 maps, 20q13, is frequently amplified in breast tumours. We therefore sought to establish whether eEF1A2 expression might be upregulated in breast cancer. Methods eEF1A2 is highly similar (98% to the near-ubiquitously expressed eEF1A1 (formerly known as EF1-α making analysis with commercial antibodies difficult. We have developed specific anti-eEF1A2 antibodies and used them in immunohistochemical analyses of tumour samples. We report the novel finding that although eEF1A2 is barely detectable in normal breast it is moderately to strongly expressed in two-thirds of breast tumours. This overexpression is strongly associated with estrogen receptor positivity. Conclusion eEF1A2 should be considered as a putative oncogene in breast cancer that may be a useful diagnostic marker and therapeutic target for a high proportion of breast tumours. The oncogenicity of eEF1A2 may be related to its role in protein synthesis or to its potential non-canonical functions in cytoskeletal remodelling or apoptosis.

Bacterial elongation factors EF-Tu, their mutants, chimeric forms, and domains: isolation and purification

Czech Academy of Sciences Publication Activity Database

Jonák, Jiří

2007-01-01

Roč. 849, 1-2 (2007), s. 141-153 ISSN 1570-0232 R&D Projects: GA AV ČR IAA5052206; GA AV ČR KJB500520503; GA MŠk 2B06065 Institutional research plan: CEZ:AV0Z50520514 Keywords : bacterial elongation factors EF-Tu, , G-domain * recombinant EF-Tus * preparation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.935, year: 2007

Risk strata-based therapy and outcome in stage Ib-IIa carcinoma cervix: single-centre ten-year experience.

Science.gov (United States)

Kundargi, Rajshekar S; Guruprasad, B; Rathod, Praveen Shankar; Shakuntala, Pn; Shobha, K; Pallavi, Vr; Uma Devi, K; Bafna, Ud

2013-01-01

To review the outcome of stage (Ib, IIa), cervical cancer patients were primarily treated with radical hysterectomy and risk-based postoperative therapy. Between January 2001 and December 2011, 601 cases underwent surgery followed by tailored therapy. Patients were classified into low risk (pelvic lymph node negative, tumour less than 4 cm, no evidence of lympho-vascular invasion, less than one-third of thickness of surgical stoma involved), intermediate risk (positive lympho-vascular space invasion, tumour size more than 4 cm, and deep invasion of cervical stroma), and high risk (pelvic lymph node involved, positive parametrial, or vaginal margins) groups. Postoperative adju-vant therapy in the form of radiotherapy alone to those with intermediate risk and chemo-radiotherapy to those with high risk was given to patients. The median follow-up was 60 months. The majority of patients had intermediate risk. The overall event-free survival (EFS) at five years was 74.37%, with EFS of 86.5% in those from the low-risk group, 73% in those from the intermediate-risk group, and 64% in those from the high-risk group. In conclusion, risk strata-based adjuvant postoperative therapy is able to provide a favourable outcome in patients with stage Ib-IIa cervical cancer with a nearly 11% improvement in survival compared with historical control.

Mammalian translation elongation factor eEF1A2: X-ray structure and new features of GDP/GTP exchange mechanism in higher eukaryotes.

Science.gov (United States)

Crepin, Thibaut; Shalak, Vyacheslav F; Yaremchuk, Anna D; Vlasenko, Dmytro O; McCarthy, Andrew; Negrutskii, Boris S; Tukalo, Michail A; El'skaya, Anna V

2014-11-10

Eukaryotic elongation factor eEF1A transits between the GTP- and GDP-bound conformations during the ribosomal polypeptide chain elongation. eEF1A*GTP establishes a complex with the aminoacyl-tRNA in the A site of the 80S ribosome. Correct codon-anticodon recognition triggers GTP hydrolysis, with subsequent dissociation of eEF1A*GDP from the ribosome. The structures of both the 'GTP'- and 'GDP'-bound conformations of eEF1A are unknown. Thus, the eEF1A-related ribosomal mechanisms were anticipated only by analogy with the bacterial homolog EF-Tu. Here, we report the first crystal structure of the mammalian eEF1A2*GDP complex which indicates major differences in the organization of the nucleotide-binding domain and intramolecular movements of eEF1A compared to EF-Tu. Our results explain the nucleotide exchange mechanism in the mammalian eEF1A and suggest that the first step of eEF1A*GDP dissociation from the 80S ribosome is the rotation of the nucleotide-binding domain observed after GTP hydrolysis. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Callous-unemotional traits moderate executive function in children with ASD and ADHD: A pilot event-related potential study

Directory of Open Access Journals (Sweden)

C. Tye

2017-08-01

Full Text Available Attention deficit hyperactivity disorder (ADHD and autism spectrum disorder (ASD are associated with varied executive function (EF difficulties. Callous-unemotional (CU traits, a proposed antecedent of adult psychopathy, are often associated with intact or enhanced EF. Here we test whether CU traits may therefore modulate EF in ASD and ADHD, in which EF is typically impaired. We collected CU traits and measured event-related potentials (ERPs that index EF during a cued-continuous performance test (CPT-OX in boys with ASD, ADHD, comorbid ASD + ADHD and typical controls. We examined attentional orienting at cues (Cue-P3, inhibitory processing at non-targets (NoGo-P3 and conflict monitoring between target and non-target trials (Go-N2 vs. NoGo-N2. In children with ASD, higher CU traits were associated with an enhanced increase in N2 amplitude in NoGo trials compared to Go trials, which suggests relatively superior conflict monitoring and a potential cognitive strength associated with CU traits. The results emphasise the importance of considering the effects of co-occurring traits in the assessment of heterogeneity of EF profiles in neurodevelopmental disorders.

Is progression-free survival a more relevant endpoint than overall survival in first-line HR+/HER2− metastatic breast cancer?

Directory of Open Access Journals (Sweden)

Forsythe A

2018-05-01

Full Text Available Anna Forsythe,1 David Chandiwana,2 Janina Barth,3 Marroon Thabane,4 Johan Baeck,5 Anastasiya Shor,1 Gabriel Tremblay6 1Health Technology Assessment Evidence, Purple Squirrel Economics, New York, NY, USA; 2Global Value and Access, Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 3German Market Access, Novartis Pharma GmbH, Nuremberg, Germany; 4Health Policy and Patient Access, Novartis Pharmaceuticals Incorporated, Dorval, QC, Canada; 5Global Medical Affairs (Oncology Business Unit, Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 6Health Economics, Purple Squirrel Economics, New York, NY, USA Background: Hormone receptor-positive (HR+, human epidermal growth factor receptor 2- negative (HER2−, metastatic breast cancer (MBC accounts for 73% of all MBCs. Endocrine therapy (ET is the basis of first-line (1L therapy for patients with HR+/HER2− MBC. Novel therapies have demonstrated improvements in progression-free survival (PFS compared to ET. The clinical relevance of PFS is being debated, as there is no proven direct correlation with overall survival (OS benefit to date. We reviewed studies of HR+/HER2− MBC to assess PFS and other factors that influence OS and treatment response, and health-related quality of life (HRQoL. Methods: The Embase®, Medline®, and Cochrane databases were systematically searched to identify studies in adult women with HR+/HER2− MBC, published between January 2006 and January 2017, and written in English. Phase II and III randomized controlled trials (RCTs, observational, and retrospective studies were included. Results: Seventy-nine RCTs were identified: 58 (73% in the 1L+ setting and 21 (27% in second-line or greater settings. PFS hazard ratios (HRs were reported in 61 (77% studies; 31 (39% reported significant PFS improvements. OS was reported in 44 (41% studies; 12 (15% reported significant OS improvements. Significant improvements in both PFS and OS were reported in only 6 (8% studies

Whole Lung Irradiation for Adults With Pulmonary Metastases From Ewing Sarcoma

International Nuclear Information System (INIS)

Casey, Dana L.; Alektiar, Kaled M.; Gerber, Naamit K.; Wolden, Suzanne L.

2014-01-01

Purpose: To evaluate feasibility and patterns of failure in adult patients with Ewing sarcoma (ES) treated with whole lung irradiation (WLI) for pulmonary metastases. Methods and Materials: Retrospective review of all ES patients treated at age 18 or older with 12-15 Gy WLI for pulmonary metastases at a single institution between 1990 and 2014. Twenty-six patients met the study criteria. Results: The median age at WLI was 23 years (range, 18-40). The median follow-up time of the surviving patients was 3.8 years (range, 1.0-9.6). The 3-year cumulative incidence of pulmonary relapse (PR) was 55%, with a 3-year cumulative incidence of PR as the site of first relapse of 42%. The 3-year event-free survival (EFS) and overall survival (OS) were 38 and 45%, respectively. Patients with exclusively pulmonary metastases had better outcomes than did those with extrapulmonary metastases: the 3-year PR was 45% in those with exclusively lung metastases versus 76% in those with extrapulmonary metastases (P=.01); the 3-year EFS was 49% versus 14% (P=.003); and the 3-year OS was 61% versus 13% (P=.009). Smoking status was a significant prognostic factor for EFS: the 3-year EFS was 61% in nonsmokers versus 11% in smokers (P=.04). Two patients experienced herpes zoster in the radiation field 6 and 12 weeks after radiation. No patients experienced pneumonitis or cardiac toxicity, and no significant acute or late sequelae were observed among the survivors. Conclusion: WLI in adult patients with ES and lung metastases is well tolerated and is associated with freedom from PR of 45% at 3 years. Given its acceptable toxicity and potential therapeutic effect, WLI for pulmonary metastases in ES should be considered for adults, as it is in pediatric patients. All patients should be advised to quit smoking before receiving WLI

Whole Lung Irradiation for Adults With Pulmonary Metastases From Ewing Sarcoma

Energy Technology Data Exchange (ETDEWEB)

Casey, Dana L.; Alektiar, Kaled M.; Gerber, Naamit K.; Wolden, Suzanne L., E-mail: woldens@mskcc.org

2014-08-01

Purpose: To evaluate feasibility and patterns of failure in adult patients with Ewing sarcoma (ES) treated with whole lung irradiation (WLI) for pulmonary metastases. Methods and Materials: Retrospective review of all ES patients treated at age 18 or older with 12-15 Gy WLI for pulmonary metastases at a single institution between 1990 and 2014. Twenty-six patients met the study criteria. Results: The median age at WLI was 23 years (range, 18-40). The median follow-up time of the surviving patients was 3.8 years (range, 1.0-9.6). The 3-year cumulative incidence of pulmonary relapse (PR) was 55%, with a 3-year cumulative incidence of PR as the site of first relapse of 42%. The 3-year event-free survival (EFS) and overall survival (OS) were 38 and 45%, respectively. Patients with exclusively pulmonary metastases had better outcomes than did those with extrapulmonary metastases: the 3-year PR was 45% in those with exclusively lung metastases versus 76% in those with extrapulmonary metastases (P=.01); the 3-year EFS was 49% versus 14% (P=.003); and the 3-year OS was 61% versus 13% (P=.009). Smoking status was a significant prognostic factor for EFS: the 3-year EFS was 61% in nonsmokers versus 11% in smokers (P=.04). Two patients experienced herpes zoster in the radiation field 6 and 12 weeks after radiation. No patients experienced pneumonitis or cardiac toxicity, and no significant acute or late sequelae were observed among the survivors. Conclusion: WLI in adult patients with ES and lung metastases is well tolerated and is associated with freedom from PR of 45% at 3 years. Given its acceptable toxicity and potential therapeutic effect, WLI for pulmonary metastases in ES should be considered for adults, as it is in pediatric patients. All patients should be advised to quit smoking before receiving WLI.

Retropubic radical prostatectomy: Clinicopathological observations and outcome analysis of 428 consecutive patients

Directory of Open Access Journals (Sweden)

Jagdeesh N Kulkarni

2011-01-01

Full Text Available Aim : We report the outcome analysis of retropubic radical prostatectomy (RRP performed in 428 patients in terms of pathological findings, complications, and survival. Materials and Methods : Systematically recorded case reports forms of consecutive 428 RRPs done over a 14-year period were analyzed using the SPSS 14 software. Secondary analysis was done to evaluate era specific (pre and post 2002 changes in clinical features and survivals. Results : Seven-year overall survival (OAS, cancer-specific survival (CSS, and event-free survival (EFS was 83.2%, 82.8%, and 69.8% respectively in our series. Era-specific survival showed higher CSS post 2002, and there was an increase in presentation with organ-confined disease. Univariate and multivariate analysis showed statistically significant impact on era specific outcome. With the improvement in techniques decrease in complications rate and increase in quality of life was noted. Conclusions : Our series spanning over decade demonstrates that RRP is viable option to offer cure to organ-confined carcinoma prostate. Further, there is evidence of stage migration and improvements in outcome in post 2002 patients. Although our series is modest in number, the success rates and outcome data matches those reported in the literature.

Is the mazEF toxin-antitoxin system responsible for vancomycin resistance in clinical isolates of Enterococcus faecalis?

Science.gov (United States)

Sadeghifard, Nourkhoda; Soheili, Sara; Sekawi, Zamberi; Ghafourian, Sobhan

2014-01-01

The current study was conducted to investigate the relationship between vancomycin-resistant Enterococcus faecalis (VRE) and the presence of mazEF toxin-antitoxin (TA) system, which may be useful as target for novel antimicrobial therapy concepts. The susceptibility of E. faecalis was determined by MIC, and the presence of the mazEF TA system was evaluated by PCR. Among 200 E. faecalis isolates 39.5% showed resistance to vancomycin (VRE), while 60.5% were susceptible strains (VSE). The mazEF TA system was positive in all VRE isolates (100%), but less prevalent (38/121, 31.4%) among the 121 VSE strains. In conclusion, our study demonstrated a positive relationship between the presence of vancomycin resistance and mazEF TA system. This observation may introduce therapeutic options against a novel antimicrobial target in enterococci.

Functional role of EF-hands 3 and 4 in membrane-binding of KChIP1

Indian Academy of Sciences (India)

The aim of the present study is to explore whether membrane targeting of K+ channel-interacting protein 1 (KChIP1) is associated with its EF-hand motifs and varies with specific phospholipids. Truncated KChIP1, in which the EF-hands 3 and 4 were deleted, retained the -helix structure, indicating that the N-terminal half of ...

Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study.

Science.gov (United States)

Güngör, Tayfun; Teira, Pierre; Slatter, Mary; Stussi, Georg; Stepensky, Polina; Moshous, Despina; Vermont, Clementien; Ahmad, Imran; Shaw, Peter J; Telles da Cunha, José Marcos; Schlegel, Paul G; Hough, Rachel; Fasth, Anders; Kentouche, Karim; Gruhn, Bernd; Fernandes, Juliana F; Lachance, Silvy; Bredius, Robbert; Resnick, Igor B; Belohradsky, Bernd H; Gennery, Andrew; Fischer, Alain; Gaspar, H Bobby; Schanz, Urs; Seger, Reinhard; Rentsch, Katharina; Veys, Paul; Haddad, Elie; Albert, Michael H; Hassan, Moustapha

2014-02-01

In chronic granulomatous disease allogeneic haemopoietic stem-cell transplantation (HSCT) in adolescents and young adults and patients with high-risk disease is complicated by graft-failure, graft-versus-host disease (GVHD), and transplant-related mortality. We examined the effect of a reduced-intensity conditioning regimen designed to enhance myeloid engraftment and reduce organ toxicity in these patients. This prospective study was done at 16 centres in ten countries worldwide. Patients aged 0-40 years with chronic granulomatous disease were assessed and enrolled at the discretion of individual centres. Reduced-intensity conditioning consisted of high-dose fludarabine (30 mg/m(2) [infants HLA-matched related-donors or HLA-9/10 or HLA-10/10 matched unrelated-donors were infused. The primary endpoints were overall survival and event-free survival (EFS), probabilities of overall survival and EFS at 2 years, incidence of acute and chronic GVHD, achievement of at least 90% myeloid donor chimerism, and incidence of graft failure after at least 6 months of follow-up. 56 patients (median age 12·7 years; IQR 6·8-17·3) with chronic granulomatous disease were enrolled from June 15, 2003, to Dec 15, 2012. 42 patients (75%) had high-risk features (ie, intractable infections and autoinflammation), 25 (45%) were adolescents and young adults (age 14-39 years). 21 HLA-matched related-donor and 35 HLA-matched unrelated-donor transplants were done. Median time to engraftment was 19 days (IQR 16-22) for neutrophils and 21 days (IQR 16-25) for platelets. At median follow-up of 21 months (IQR 13-35) overall survival was 93% (52 of 56) and EFS was 89% (50 of 56). The 2-year probability of overall survival was 96% (95% CI 86·46-99·09) and of EFS was 91% (79·78-96·17). Graft-failure occurred in 5% (three of 56) of patients. The cumulative incidence of acute GVHD of grade III-IV was 4% (two of 56) and of chronic graft-versus-host disease was 7% (four of 56). Stable (≥90%) myeloid

Involved-Node Proton Therapy in Combined Modality Therapy for Hodgkin Lymphoma: Results of a Phase 2 Study

International Nuclear Information System (INIS)

Hoppe, Bradford S.; Flampouri, Stella; Zaiden, Robert; Slayton, William; Sandler, Eric; Ozdemir, Savas; Dang, Nam H.; Lynch, James W.; Li, Zuofeng; Morris, Christopher G.; Mendenhall, Nancy P.

2014-01-01

Purpose: This study describes the early clinical outcomes of a prospective phase 2 study of consolidative involved-node proton therapy (INPT) as a component of combined-mode therapy in patients with stages I to III Hodgkin lymphoma (HL) with mediastinal involvement. Methods and Materials: Between September 2009 and June 2013, 15 patients with newly diagnosed HL received INPT after completing chemotherapy in an institutional review board-approved protocol comparing the dosimetric impact of PT with those of three-dimensional conformal radiation therapy (3DCRT) and intensity modulated RT. Based on 18 F-Fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) response, 5 children received 15 to 25.5 cobalt Gy equivalent (CGE) of INPT after receiving 4 cycles of Adriamycin, Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide or Vincristine, adriamycin, methotrexate, Prednisone chemotherapy, and 10 adults received 30.6 to 39.6 CGE of INPT after 3 to 6 cycles of Adriamycin, Bleomycine, Vinblastine, Dacarbazine. Patients were routinely evaluated for toxicity during and after treatment, using Common Terminology Criteria for Adverse Events, version 3.0, and for relapse by physical examination and routine imaging. Relapse-free survival (RFS) and event-free survival (EFS) rates were calculated using the Kaplan-Meier method from the time of diagnosis. Results: The median follow-up was 37 months (range, 26-55). Two events occurred during follow-up: 1 relapse (inside and outside the targeted field) and 1 transformation into a primary mediastinal large B cell lymphoma. The 3-year RFS rate was 93%, and the 3-year EFS rate was 87%. No acute or late grade 3 nonhematologic toxicities were observed. Conclusions: Although decades of follow-up will be needed to realize the likely benefit of PT in reducing the risk of radiation-induced late effects, PT following chemotherapy in patients with HL is well-tolerated, and disease outcomes were similar

Involved-Node Proton Therapy in Combined Modality Therapy for Hodgkin Lymphoma: Results of a Phase 2 Study

Energy Technology Data Exchange (ETDEWEB)

Hoppe, Bradford S., E-mail: bhoppe@floridaproton.org [Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida (United States); Flampouri, Stella [Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida (United States); Zaiden, Robert [Department of Medicine, Division of Hematology and Oncology, University of Florida College of Medicine, Jacksonville, Florida (United States); Slayton, William [Department of Pediatrics, Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville, Florida (United States); Sandler, Eric [Department of Pediatrics, Division of Hematology/Oncology Nemours Children' s Clinic, Jacksonville, Florida (United States); Ozdemir, Savas [Department of Radiology, Division of Functional and Molecular Imaging, University of Florida College of Medicine, Jacksonville, Florida (United States); Dang, Nam H.; Lynch, James W. [Department of Medicine, Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville, Florida (United States); Li, Zuofeng; Morris, Christopher G.; Mendenhall, Nancy P. [Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida (United States)

2014-08-01

Purpose: This study describes the early clinical outcomes of a prospective phase 2 study of consolidative involved-node proton therapy (INPT) as a component of combined-mode therapy in patients with stages I to III Hodgkin lymphoma (HL) with mediastinal involvement. Methods and Materials: Between September 2009 and June 2013, 15 patients with newly diagnosed HL received INPT after completing chemotherapy in an institutional review board-approved protocol comparing the dosimetric impact of PT with those of three-dimensional conformal radiation therapy (3DCRT) and intensity modulated RT. Based on {sup 18}F-Fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) response, 5 children received 15 to 25.5 cobalt Gy equivalent (CGE) of INPT after receiving 4 cycles of Adriamycin, Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide or Vincristine, adriamycin, methotrexate, Prednisone chemotherapy, and 10 adults received 30.6 to 39.6 CGE of INPT after 3 to 6 cycles of Adriamycin, Bleomycine, Vinblastine, Dacarbazine. Patients were routinely evaluated for toxicity during and after treatment, using Common Terminology Criteria for Adverse Events, version 3.0, and for relapse by physical examination and routine imaging. Relapse-free survival (RFS) and event-free survival (EFS) rates were calculated using the Kaplan-Meier method from the time of diagnosis. Results: The median follow-up was 37 months (range, 26-55). Two events occurred during follow-up: 1 relapse (inside and outside the targeted field) and 1 transformation into a primary mediastinal large B cell lymphoma. The 3-year RFS rate was 93%, and the 3-year EFS rate was 87%. No acute or late grade 3 nonhematologic toxicities were observed. Conclusions: Although decades of follow-up will be needed to realize the likely benefit of PT in reducing the risk of radiation-induced late effects, PT following chemotherapy in patients with HL is well-tolerated, and disease outcomes

Surgical versus non-surgical approach in primary desmoid-type fibromatosis patients: A nationwide prospective cohort from the French Sarcoma Group.

Science.gov (United States)

Penel, Nicolas; Le Cesne, Axel; Bonvalot, Sylvie; Giraud, Antoine; Bompas, Emmanuelle; Rios, Maria; Salas, Sébastien; Isambert, Nicolas; Boudou-Rouquette, Pascaline; Honore, Charles; Italiano, Antoine; Ray-Coquard, Isabelle; Piperno-Neumann, Sophie; Gouin, François; Bertucci, François; Ryckewaert, Thomas; Kurtz, Jean-Emmanuel; Ducimetiere, Françoise; Coindre, Jean-Michel; Blay, Jean-Yves

2017-09-01

The outcome of desmoid-type fibromatosis (DTF) is unpredictable. Currently, a wait-and-see approach tends to replace large en bloc resection as the first therapeutic approach. Nevertheless, there are no validated factors to guide the treatment choice. We conducted a prospective study of 771 confirmed cases of DTF. We analysed event-free survival (EFS) based on the occurrence of relapse after surgery, progressive disease during the wait-and-see approach, or change in therapeutic strategy. Identification of prognostic factors was performed using classical methods (log-rank test and Cox model). Overall, the 2-year EFS was 56%; this value did not differ between patients undergoing an operation and those managed by the wait-and-see approach (53% versus 58%, p = 0.415). In univariate analysis, two prognostic factors significantly influenced the outcome: the nature of diagnostic sampling (p = 0.466) and primary location (p = 0.0001). The 2-year EFS was only 32% after open biopsy. The 2-year EFS was 66% for favourable locations (abdominal wall, intra-abdominal, breast, digestive viscera and lower limb) and 41% for unfavourable locations. Among patients with favourable locations, the 2-year EFS was similar in patients treated by both surgery (70%) and the wait-and-see approach (63%; p = 0.413). Among patients with unfavourable locations, the 2-year EFS was significantly enhanced in patients initially managed with the wait-and-see approach (52%) compared with those who underwent initial surgery (25%; p = 0.001). The location of DTF is a major prognostic factor for EFS. If these findings are confirmed by independent analysis, personalised management of DTF must consider this easily obtained parameter. Copyright © 2017 Elsevier Ltd. All rights reserved.

The value of exercise radionuclide ventriculography in risk stratification in patients with known or suspected coronary artery disease

International Nuclear Information System (INIS)

Iskandrian, A.S.; Hakki, A.H.; Kane, S.; Schenk, C.

1985-01-01

This study examined the value of rest and exercise (EX) radionuclide ventriculography (RNV) in risk stratification in 392 pts with suspected or known coronary artery disease who were being evaluated for anginal symptoms. There were 289 men and 203 women, aged 55 +- 12 years (mean +- SD). There were 20 cardiac events in the followup period of up to 4 years (19 +- 10 months): 14 pts died of cardiac causes and 6 had non-fatal acute myocardial infarctions. The pts with and without events did not differ in age, clinical presentation, risk factors, and rest and EX ECGs. However, pts with events had lower EX systolic blood pressure (p < 0.02); lower EX duration; (5.5 +- 2.5 vs 7.6 +- 3.7 minutes, p < 0.0l), lower resting left ventricular (LV) ejection fraction (EF) (p = 0.001), and lower EX EF (35 +- 17% vs 56 +- 15%, p = 0.0001). The change in EF from rest to EX was not significantly different (-0.1 +- 6.1 vs 3 +- 9.9). Univariate survival analysis (Cox model) showed several descriptors related to prognosis: EX EF, rest EF, wall motion and EX duration. Multivariate analysis, however, identified the EX EF as the only significant predictor (X/sup 2/ = 19.9). None of the other variables added independent information to that provided by the EX EF. Actuarial lie table analysis showed that the risk increased as the EX EF decreased, when pts were grouped into those with EXEF ≥ 50%, 30-49%, and <30%., (p = 0.001, Mantel-Cox). Thus, the EX RNV is useful in risk stratification; the EX EF is the best descriptor that categorizes pts into different risk groups

Therapy reduction in patients with Down syndrome and myeloid leukemia: the international ML-DS 2006 trial.

Science.gov (United States)

Uffmann, Madita; Rasche, Mareike; Zimmermann, Martin; von Neuhoff, Christine; Creutzig, Ursula; Dworzak, Michael; Scheffers, Lenie; Hasle, Henrik; Zwaan, C Michel; Reinhardt, Dirk; Klusmann, Jan-Henning

2017-06-22

Children with myeloid leukemia associated with Down syndrome (ML-DS) have superior outcome compared with non-DS patients, but suffer from higher constitutional cytotoxic drug susceptibility. We analyzed the outcome of 170 pediatric patients with ML-DS enrolled in the prospective, multicenter, open-label, nonrandomized ML-DS 2006 trial by Nordic Society for Pediatric Hematology and Oncology (NOPHO), Dutch Childhood Oncology Group (DCOG), and Acute Myeloid Leukemia-Berlin-Frankfurt-Münster (AML-BFM) study group. Compared with the historical control arm (reduced-intensity protocol for ML-DS patients from the AML-BFM 98 trial), treatment intensity was reduced by lowering the cumulative dose of etoposide (950 to 450 mg/m 2 ) and intrathecal central nervous system prophylaxis while omitting maintenance therapy. Still, 5-year overall survival (89% ± 3% vs 90% ± 4%; P log-rank = .64), event-free survival (EFS; 87% ± 3% vs 89% ± 4%; P log-rank = .71), and cumulative incidence of relapse/nonresponse (CIR/NR; 6% ± 3% vs 6% ± 2%; P Gray = .03) did not significantly differ between the ML-DS 2006 trial and the historical control arm. Poor early treatment response (5-year EFS, 58% ± 16% vs 88% ± 3%; P log rank = .0008) and gain of chromosome 8 (CIR/NR, 16% ± 7% vs 3% ± 2%, P Gray = .02; 5-year EFS, 73% ± 8% vs 91% ± 4%, P log rank = .018) were identified as independent prognostic factors predicting a worse EFS. Five of 7 relapsed patients (71%) with cytogenetic data had trisomy 8. Our study reveals prognostic markers for children with ML-DS and illustrates that reducing therapy did not impair excellent outcome. The trial was registered at EudraCT as #2007-006219-2. © 2017 by The American Society of Hematology.

Decoding the biosynthesis and function of diphthamide, an enigmatic modification of translation elongation factor 2 (EF2

Directory of Open Access Journals (Sweden)

Raffael Schaffrath

2014-05-01

Full Text Available Diphthamide is a highly conserved modification of archaeal and eukaryal translation elongation factor 2 (EF2 and yet why cells need EF2 to contain diphthamide is unclear. In yeast, the first steps of diphthamide synthesis and the genes (DPH1-DPH5 required to form the intermediate diphthine are well-documented. However, the last step, amidadation of diphthine to diphthamide, had largely been ill-defined. Remarkably, through mining genome-wide synthetic gene array (SGA and chemical genomics databases, recent studies by Uthman et al. [PLoS Genetics (2013 9, e1003334] and Su et al. [Proc. Natl. Acad. Sci. USA (2012 109, 19983-19987] have identified two more diphthamide players, DPH6 and DPH7. Consistent with roles in the amidation step, dph6 and dph7 deletion strains fail to complete diphthamide synthesis and accumulate diphthine-modified EF2. In contrast to Dph6, the catalytically relevant amidase, Dph7 appears to be regulatory. As shown by Uthman et al., it promotes dissociation of diphthine synthase (Dph5 from EF2, allowing diphthine amidation by Dph6 to occur and thereby coupling diphthine synthesis to the terminal step in the pathway. Remarkably, the study by Uthman et al. suggests that Dph5 has a novel role as an EF2 inhibitor that affects cell growth when diphthamide synthesis is blocked or incomplete and, importantly, shows that diphthamide promotes the accuracy of EF2 performance during translation.

General practitioners' home visit tendency and readmission-free survival after COPD hospitalisation

DEFF Research Database (Denmark)

Lykkegaard, Jesper; Larsen, Pia V; Paulsen, Maja S

2014-01-01

Background:The tendency of general practitioners (GPs) to conduct home visits is considered an important aspect of practices' accessibility and quality of care.Aims:To investigate whether GPs' tendency to conduct home visits affects 30-day readmission or death after hospitalisation with chronic...... obstructive pulmonary disease.Methods:All Danish patients first-time hospitalised with COPD during the years 2006-2008 were identified. The association between the GP's tendency to conduct home visits and the time from hospital discharge until death or all-cause readmission was analysed by means of Cox...... been readmitted and 1.6% had died without readmission. A U-shaped dose-response relationship was found between GP home visit tendency and readmission-free survival. The lowest adjusted risk of readmission or death was recorded among patients who were listed with a general practice in which >20...

Treatment Adherence and Its Impact on Disease-Free Survival in the Breast International Group 1-98 Trial of Tamoxifen and Letrozole, Alone and in Sequence

DEFF Research Database (Denmark)

Chirgwin, Jacquie H; Giobbie-Hurder, Anita; Coates, Alan S

2016-01-01

PURPOSE: To investigate adherence to endocrine treatment and its relationship with disease-free survival (DFS) in the Breast International Group (BIG) 1-98 clinical trial. METHODS: The BIG 1-98 trial is a double-blind trial that randomly assigned 6,193 postmenopausal women with hormone receptor......-positive early breast cancer in the four-arm option to 5 years of tamoxifen (Tam), letrozole (Let), or the agents in sequence (Let-Tam, Tam-Let). This analysis included 6,144 women who received at least one dose of study treatment. Conditional landmark analyses and marginal structural Cox proportional hazards......). Sequential treatments were associated with higher rates of nonpersistence (Tam-Let, 20.8%; Let-Tam, 20.3%; Tam 16.9%; Let 17.6%). Adverse events were the reason for most trial treatment early discontinuations (82.7%). Apart from sequential treatment assignment, reduced adherence was associated with older age...

Preoperative Tracheostomy Is Associated with Poor Disease-Free Survival in Recurrent Laryngeal Cancer.

Science.gov (United States)

Birkeland, Andrew C; Rosko, Andrew J; Beesley, Lauren; Bellile, Emily; Chinn, Steven B; Shuman, Andrew G; Prince, Mark E; Wolf, Gregory T; Bradford, Carol R; Brenner, J Chad; Spector, Matthew E

2017-09-01

Objectives It is unknown if preoperative tracheostomy for persistent/recurrent laryngeal squamous cell carcinoma (LSCC) plays a role in unrecognized local disease spread and disease recurrence after salvage laryngectomy. The goals of this study were to determine the effect of preoperative tracheostomy on disease-free survival (DFS) in patients with recurrent/persistent LSCC undergoing salvage laryngectomy. Study Design Retrospective case series derived from prospectively maintained database. Setting Tertiary care academic center. Subjects Patients with recurrent/persistent LSCC after radiation/chemoradiation (RT/CRT) who underwent salvage laryngectomy at the University of Michigan from 1997 to 2015. Methods Demographic, clinical, pathologic, and survival data were collected. Kaplan-Meier survival estimates were performed. Results DFS was worse for patients with tracheostomy prior to laryngectomy than patients without a tracheostomy (5 year: 39% vs 67%; P tracheostomy prior to RT/CRT compared to patients with tracheostomy after RT/CRT or patients without a tracheostomy had worse DFS (5-year: 25%, 49%, and 67%, respectively; P tracheostomy was associated with worse DFS. In multivariable analysis, presence of a preoperative tracheostomy had a worse DFS (hazard ratio, 1.63; 95% confidence interval, 1.00-2.67; P = .048). Conclusion Preoperative tracheostomy is associated with disease recurrence in patients with persistent/recurrent LSCC undergoing salvage laryngectomy, particularly in patients who had tracheostomy prior to completion of initial RT/CRT. Notably, preoperative tracheostomy as a causal factor vs marker for disease recurrence is difficult to ascertain. Nevertheless, clinicians should be aware of the increased risk of locoregional recurrence in patients with preoperative tracheostomy when counseling on surgical salvage and when considering the role of additional therapy.

Myeloid Sarcoma Predicts Superior Outcome in Pediatric AML; Can Cytogenetics Solve the Puzzle?

Science.gov (United States)

Pramanik, Raja; Tyagi, Anudishi; Chopra, Anita; Kumar, Akash; Vishnubhatla, Sreenivas; Bakhshi, Sameer

2018-06-01

The purpose of our study was to evaluate the clinical, cytogenetic, and molecular features, and survival outcomes in patients with acute myeloid leukemia (AML) with myeloid sarcoma (MS) and compare them with patients with AML without MS. This was a retrospective analysis of de novo pediatric AML patients with or without MS diagnosed at our cancer center between June 2003 and June 2016. MS was present in 121 of 570 (21.2%), the most frequent site being the orbit. Patients with MS had a younger median age (6 years vs. 10 years) and presented with higher hemoglobin and platelet but lower white blood cell count compared with patients without MS. Further, t (8; 21) (P < .01), loss of Y chromosome (P < .01), and deletion 9q (P = .03) were significantly higher in patients with AML with MS. Event-free survival (EFS; P = .003) and overall survival (OS; P = .001) were better among patients with AML with MS (median EFS 21.0 months and median OS 37.1 months) compared with those with AML without MS (median EFS 11.2 months and median OS 16.2 months). The t (8; 21) was significantly associated with MS (odds ratio, 3.92). In a comparison of the 4 groups divided according to the presence or absence of MS and t (8; 21), the subgroup of patients having MS without concomitant t (8; 21) was the only group to have a significantly better OS (hazard ratio, 0.53; 95% confidence interval, 0.34-0.82; P = .005). Although t (8; 21) was more frequently associated with MS, it did not appear to be the reason for better outcome. Copyright © 2018 Elsevier Inc. All rights reserved.

The value of exercise radionuclide ventriculography in risk stratification after coronary arterial bypass grafting

International Nuclear Information System (INIS)

Iskandrian, A.S.; Hakki, A.H.; Goel, I.P.; Mundth, E.D.; Kane, S.; Schenk, C.

1985-01-01

Cardiac events after coronary artery bypass surgery (CABG) may be related to left ventricular (LV) function, residual coronary artery diseases (CAD), graft occlusion, and progression of CAD. This study examined the value of rest and exercise (EX) radionuclide ventriculography (RNV) done 3-6 mos after CABG in risk stratification in 212 pts. There were 185 men and 27 women, aged 57 +- 8 years (mean +- SD). During a followup period of up to 4 years, (15 +- 10 months), there were 23 cardiac events; 13 pts died of cardiac causes and 20 had non-fatal acute myocardial infarctions. The pts with and without events did not differ in: clinical presentation after CABG (most were asymptomatic), medications and ECG findings at rest and EX. The pts with events had lower EX systolic blood pressure (p < 0.01); resting LV ejection fraction (EF) (p = 0.002), and EX EF (40 +- 18% vs 54 +- 16%, p = 0.002). The change in EF (rest to EX) was not significantly different (l.6 +- 8.2%, vs 2.1 +- 9.2%). Survival analysis (Cox model) identified the EX EF as the best predictor of death and total events (X/sup 2/ = 4.3 and 2.4, p = 0.04 and 0.07 respectively). Actuarial life table analysis showed that the risk increased as the EX EF decreased when pts were grouped into EX EF ≥ 50, 30-49, and <30%, (p < 0.001, Mantel-Cox). Thus, EX RNA is useful in risk stratification after CABG. The EX LVEF is an important descriptor that categorizes pts into different risks groups. The pts at high risk probably require more aggressive followup and continued medical therapy

Survival chance in papillary thyroid cancer in Hungary: individual survival probability estimation using the Markov method

International Nuclear Information System (INIS)

Esik, Olga; Tusnady, Gabor; Daubner, Kornel; Nemeth, Gyoergy; Fuezy, Marton; Szentirmay, Zoltan

1997-01-01

Purpose: The typically benign, but occasionally rapidly fatal clinical course of papillary thyroid cancer has raised the need for individual survival probability estimation, to tailor the treatment strategy exclusively to a given patient. Materials and methods: A retrospective study was performed on 400 papillary thyroid cancer patients with a median follow-up time of 7.1 years to establish a clinical database for uni- and multivariate analysis of the prognostic factors related to survival (Kaplan-Meier product limit method and Cox regression). For a more precise prognosis estimation, the effect of the most important clinical events were then investigated on the basis of a Markov renewal model. The basic concept of this approach is that each patient has an individual disease course which (besides the initial clinical categories) is affected by special events, e.g. internal covariates (local/regional/distant relapses). On the supposition that these events and the cause-specific death are influenced by the same biological processes, the parameters of transient survival probability characterizing the speed of the course of the disease for each clinical event and their sequence were determined. The individual survival curves for each patient were calculated by using these parameters and the independent significant clinical variables selected from multivariate studies, summation of which resulted in a mean cause-specific survival function valid for the entire group. On the basis of this Markov model, prediction of the cause-specific survival probability is possible for extrastudy cases, if it is supposed that the clinical events occur within new patients in the same manner and with the similar probability as within the study population. Results: The patient's age, a distant metastasis at presentation, the extent of the surgical intervention, the primary tumor size and extent (pT), the external irradiation dosage and the degree of TSH suppression proved to be

Survival of falling robots

Science.gov (United States)

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.

Survival of falling robots

Science.gov (United States)

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.

Biochemical response to ursodeoxycholic acid predicts survival in a North American cohort of primary biliary cirrhosis patients.

Science.gov (United States)

Lammert, Craig; Juran, Brian D; Schlicht, Erik; Chan, Landon L; Atkinson, Elizabeth J; de Andrade, Mariza; Lazaridis, Konstantinos N

2014-10-01

Biochemical response to ursodeoxycholic acid among patients with primary biliary cirrhosis remains variable, and there is no agreement of an ideal model. Novel assessment of response coupled to histologic progression was recently defined by the Toronto criteria. We retrospectively assessed transplant-free survival and clinical outcomes associated with ursodeoxycholic acid response to evaluate the Toronto criteria using a large North American cohort of PBC patients. Three hundred and ninety-eight PBC patients from the Mayo Clinic PBC Genetic Epidemiology Registry were assessed for ursodeoxycholic acid treatment and biochemical response per the Toronto criteria. Responders were defined by reduction in alkaline phosphatase to less than or equal to 1.67 times the upper normal limit by 2 years of treatment, whereas non-responders had alkaline phosphatase values greater than 1.67 times the upper normal limit. Probability of survival was estimated using the Kaplan-Meier method. Three hundred and two (76 %) patients were responders and 96 (24 %) were non-responders. Significantly more non-responders developed adverse events related to chronic liver disease compared to responders (hazard ratio (HR) 2.77, P = 0.001). Biochemical responders and early-stage disease at treatment start was associated with improved overall transplant-free survival compared to non-responders (HR 1.9) and patients with late-stage disease (HR 2.7) after age and sex adjustment. The Toronto criteria are capable of identifying ursodeoxycholic acid-treated primary biliary cirrhosis patients at risk of poor transplant-free survival and adverse clinical outcomes. Our data reveal that despite advanced disease at diagnosis, biochemical response per the Toronto criteria associates with improved overall transplant-free survival.

18F-Fluoride PET/CT tumor burden quantification predicts survival in breast cancer.

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Brito, Ana E; Santos, Allan; Sasse, André Deeke; Cabello, Cesar; Oliveira, Paulo; Mosci, Camila; Souza, Tiago; Amorim, Barbara; Lima, Mariana; Ramos, Celso D; Etchebehere, Elba

2017-05-30

In bone-metastatic breast cancer patients, there are no current imaging biomarkers to identify which patients have worst prognosis. The purpose of our study was to investigate if skeletal tumor burden determined by 18F-Fluoride PET/CT correlates with clinical outcomes and may help define prognosis throughout the course of the disease. Bone metastases were present in 49 patients. On multivariable analysis, skeletal tumor burden was significantly and independently associated with overall survival (p breast cancer patients (40 for primary staging and the remainder for restaging after therapy). Clinical parameters, primary tumor characteristics and skeletal tumor burden were correlated to overall survival, progression free-survival and time to bone event. The median follow-up time was 19.5 months. 18F-Fluoride PET/CT skeletal tumor burden is a strong independent prognostic imaging biomarker in breast cancer patients.

Incidence of cardiovascular events and associated risk factors in kidney transplant patients: a competing risks survival analysis.

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Seoane-Pillado, María Teresa; Pita-Fernández, Salvador; Valdés-Cañedo, Francisco; Seijo-Bestilleiro, Rocio; Pértega-Díaz, Sonia; Fernández-Rivera, Constantino; Alonso-Hernández, Ángel; González-Martín, Cristina; Balboa-Barreiro, Vanesa

2017-03-07

The high prevalence of cardiovascular risk factors among the renal transplant population accounts for increased mortality. The aim of this study is to determine the incidence of cardiovascular events and factors associated with cardiovascular events in these patients. An observational ambispective follow-up study of renal transplant recipients (n = 2029) in the health district of A Coruña (Spain) during the period 1981-2011 was completed. Competing risk survival analysis methods were applied to estimate the cumulative incidence of developing cardiovascular events over time and to identify which characteristics were associated with the risk of these events. Post-transplant cardiovascular events are defined as the presence of myocardial infarction, invasive coronary artery therapy, cerebral vascular events, new-onset angina, congestive heart failure, rhythm disturbances, peripheral vascular disease and cardiovascular disease and death. The cause of death was identified through the medical history and death certificate using ICD9 (390-459, except: 427.5, 435, 446, 459.0). The mean age of patients at the time of transplantation was 47.0 ± 14.2 years; 62% were male. 16.5% had suffered some cardiovascular disease prior to transplantation and 9.7% had suffered a cardiovascular event. The mean follow-up period for the patients with cardiovascular event was 3.5 ± 4.3 years. Applying competing risk methodology, it was observed that the accumulated incidence of the event was 5.0% one year after transplantation, 8.1% after five years, and 11.9% after ten years. After applying multivariate models, the variables with an independent effect for predicting cardiovascular events are: male sex, age of recipient, previous cardiovascular disorders, pre-transplant smoking and post-transplant diabetes. This study makes it possible to determine in kidney transplant patients, taking into account competitive events, the incidence of post-transplant cardiovascular events and

Impact of 9p deletion and p16, Cyclin D1, and Myc hyperexpression on the outcome of anaplastic oligodendrogliomas.

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Karine Michaud

Full Text Available To study the presence of 9p deletion and p16, cyclin D1 and Myc expression and their respective diagnostic and prognostic interest in oligodendrogliomas.We analyzed a retrospective series of 40 consecutive anaplastic oligodendrogliomas (OIII from a single institution and compared them to a control series of 10 low grade oligodendrogliomas (OII. Automated FISH analysis of chromosome 9p status and immunohistochemistry for p16, cyclin D1 and Myc was performed for all cases and correlated with clinical and histological data, event free survival (EFS and overall survival (OS.Chromosome 9p deletion was observed in 55% of OIII (22/40 but not in OII. Deletion was highly correlated to EFS (median = 29 versus 53 months, p<0.0001 and OS (median = 48 versus 83 months, p<0.0001 in both the total cohort and the OIII population. In 9p non-deleted oligodendrogliomas, p16 hyperexpression correlated with a shorter OS (p = 0.02 in OII and p = 0.0001 in OIII whereas lack of p16 expression was correlated to a shorter EFS and OS in 9p deleted OIII (p = 0.001 and p = 0.0002 respectively. Expression of Cyclin D1 was significantly higher in OIII (median expression 45% versus 14% for OII, p = 0.0006 and was correlated with MIB-1 expression (p<0.0001, vascular proliferation (p = 0.002, tumor necrosis (p = 0.04 and a shorter EFS in the total cohort (p = 0.05. Hyperexpression of Myc was correlated to grade (median expression 27% in OII versus 35% in OIII, p = 0.03, and to a shorter EFS in 9p non-deleted OIII (p = 0.01.Chromosome 9p deletion identifies a subset of OIII with significantly worse prognosis. The combination of 9p status and p16 expression level identifies two distinct OIII populations with divergent prognosis. Hyperexpression of Bcl1 and Myc appears highly linked to anaplasia but the prognostic value is unclear and should be investigated further.

Outcomes following autologous hematopoietic stem cell transplant for patients with relapsed Wilms’ Tumor: A CIBMTR retrospective analysis

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Malogolowkin, Marcio H.; Hemmer, Michael T.; Le-Rademacher, Jennifer; Hale, Gregory A; Metha, Parinda A.; Smith, Angela R.; Kitko, Carrie; Abraham, Allistair; Abdel-Azim, Hisham; Dandoy, Christopher; Diaz, Miguel Angel; Gale, Robert Peter; Guilcher, Greg; Hayashi, Robert; Jodele, Sonata; Kasow, Kimberly A.; MacMillian, Margaret L.; Thakar, Monica; Wirk, Baldeep M.; Woolfrey, Ann; Thiel, E L

2017-01-01

Despite the dramatic improvement in the overall survival for patients diagnosed with Wilms’ tumor (WT), the outcomes for those that experience relapse have remained disappointing. We describe the outcomes of 253 patients with relapsed WT who received high-dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplant (HCT) between 1990 and 2013, and reported to the Center for International Blood and Marrow Transplantation Research (CIBMTR). The 5-year estimates for event free survival (EFS) and overall survival (OS) were 36% (95% CI; 29 – 43%) and 45% (95% CI; 38 – 51%) respectively. Relapse of primary disease was the cause of death in 81% of the population. EFS, OS, relapse and transplant-related mortality (TRM) showed no significant differences when broken down by disease status at transplant, time from diagnosis to transplant, year of transplant or conditioning regimen. Our data suggest that HDT followed by autologous HCT for relapsed WT is well tolerated and outcomes are similar to those reported in the literature. Since attempts to conduct a randomized trial comparing maintenance chemotherapy with consolidation versus high-dose chemotherapy followed by stem cell transplant have failed, one should balance the potential benefits with the yet unknown long-term risks. Since disease recurrence continues to be the most common cause of death, future research should focus on the development of consolidation therapies for those patients achieving complete response to therapy. PMID:28869618

Major clinical events, signs and severity assessment scores related to actual survival in patients who died from primary biliary cirrhosis. A long-term historical cohort study

NARCIS (Netherlands)

van Dam, GM; Gips, CH; Reisman, Y; Maas, KW; Purmer, IM; Huizenga, [No Value; Verbaan, BW

1999-01-01

BACKGROUND/AIMS: One of the prognostic methods for survival in primary biliary cirrhosis (PBC) is the Mayo model, with a time-scale limited to 7 years. The aim of our study was to assess how major clinical events, signs, several severity assessment methods and Mayo survival probabilities fit in with

A comparative study of machine learning methods for time-to-event survival data for radiomics risk modelling.

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Leger, Stefan; Zwanenburg, Alex; Pilz, Karoline; Lohaus, Fabian; Linge, Annett; Zöphel, Klaus; Kotzerke, Jörg; Schreiber, Andreas; Tinhofer, Inge; Budach, Volker; Sak, Ali; Stuschke, Martin; Balermpas, Panagiotis; Rödel, Claus; Ganswindt, Ute; Belka, Claus; Pigorsch, Steffi; Combs, Stephanie E; Mönnich, David; Zips, Daniel; Krause, Mechthild; Baumann, Michael; Troost, Esther G C; Löck, Steffen; Richter, Christian

2017-10-16

Radiomics applies machine learning algorithms to quantitative imaging data to characterise the tumour phenotype and predict clinical outcome. For the development of radiomics risk models, a variety of different algorithms is available and it is not clear which one gives optimal results. Therefore, we assessed the performance of 11 machine learning algorithms combined with 12 feature selection methods by the concordance index (C-Index), to predict loco-regional tumour control (LRC) and overall survival for patients with head and neck squamous cell carcinoma. The considered algorithms are able to deal with continuous time-to-event survival data. Feature selection and model building were performed on a multicentre cohort (213 patients) and validated using an independent cohort (80 patients). We found several combinations of machine learning algorithms and feature selection methods which achieve similar results, e.g. C-Index = 0.71 and BT-COX: C-Index = 0.70 in combination with Spearman feature selection. Using the best performing models, patients were stratified into groups of low and high risk of recurrence. Significant differences in LRC were obtained between both groups on the validation cohort. Based on the presented analysis, we identified a subset of algorithms which should be considered in future radiomics studies to develop stable and clinically relevant predictive models for time-to-event endpoints.

Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

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Harris Nathan

2008-12-01

Full Text Available Abstract Background Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. Methods Two sample sets of high-risk primary breast cancer patients participating in a randomised national trial investigating the effectiveness of high-dose chemotherapy were analysed. Sera in set I (n = 63 were analysed by surface enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS for biomarker finding. Initial results were validated by analysis of sample set II (n = 371, using one-dimensional gel-electrophoresis. Results In sample set I, the expression of a peak at mass-to-charge ratio 9198 (relative intensity ≤ 20 or > 20, identified as haptoglobin (Hp alpha-1 chain, was strongly associated with recurrence free survival (global Log-rank test; p = 0.0014. Haptoglobin is present in three distinct phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2, of which only individuals with phenotype Hp 1-1 or Hp 2-1 express the haptoglobin alpha-1 chain. As the expression of the haptoglobin alpha-1 chain, determined by SELDI-TOF MS, corresponds to the phenotype, initial results were validated by haptoglobin phenotyping of the independent sample set II by native one-dimensional gel-electrophoresis. With the Hp 1-1 phenotype as the reference category, the univariate hazard ratio for recurrence was 0.87 (95% CI: 0.56 – 1.34, p = 0.5221 and 1.03 (95% CI: 0.65 – 1.64, p = 0.8966 for the Hp 2-1 and Hp 2-2 phenotypes, respectively, in sample set II. Conclusion In contrast to our initial results, the haptoglobin phenotype was not identified as a predictor of recurrence free survival in high-risk primary breast cancer in our validation set. Our initial observation in the discovery set was probably the result of a type I error (i.e. false positive

Survival analysis models and applications

CERN Document Server

Liu, Xian

2012-01-01

Survival analysis concerns sequential occurrences of events governed by probabilistic laws.  Recent decades have witnessed many applications of survival analysis in various disciplines. This book introduces both classic survival models and theories along with newly developed techniques. Readers will learn how to perform analysis of survival data by following numerous empirical illustrations in SAS. Survival Analysis: Models and Applications: Presents basic techniques before leading onto some of the most advanced topics in survival analysis.Assumes only a minimal knowledge of SAS whilst enablin

Expression of Myc, but not pSTAT3, is an adverse prognostic factor for diffuse large B-cell lymphoma treated with epratuzumab/R-CHOP.

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Gupta, Mamta; Maurer, Matthew J; Wellik, Linda E; Law, Mark E; Han, Jing Jing; Ozsan, Nazan; Micallef, Ivana N; Dogan, Ahmet; Witzig, Thomas E

2012-11-22

STAT3 regulates cell growth by up-regulating downstream targets, such as Myc. The frequency of phosphorylated STAT3 (pSTAT3) and Myc expression and their prognostic relevance is unknown within diffuse large B-cell lymphoma (DLBCL) germinal center B-cell (GCB) and non-GCB subtypes. pSTAT3 and Myc were studied by immunohistochemistry (IHC) on tumors from 40 DLBCL patients uniformly treated on a clinical trial of epratuzumab/rituximab-CHOP. A total of 35% of cases were pSTAT3-positive, and pSTAT3 positivity was more frequent in the non-GCB (P = .06) type but did not correlate with event-free survival (EFS). Myc expression was observed in 50% of cases and was more frequent in non-GCB type (P = .07). Myc-positive cases had inferior EFS in all patients, including the GCB and pSTAT3-positive cases, were more likely to express Myc (P = .06). Myc translocations involving the major breakpoint regions were found in 10% (3 of 29) of cases, and all 3 cases were GCB and had an inferior EFS (P = .09). pSTAT3, but not Myc expression, was correlated with elevated pretreatment serum cytokines, such as IL-10 (P = .05), G-CSF (P = .03), and TNF-α (P = .04). pSTAT3 IHC in DLBCL tumors has the potential to identify patients for STAT3 pathway-directed therapy; Myc IHC is a potential marker for inferior EFS in GCB patients.

Centre characteristics and procedure-related factors have an impact on outcomes of allogeneic transplantation for patients with CLL: a retrospective analysis from the European Society for Blood and Marrow Transplantation (EBMT).

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Schetelig, Johannes; de Wreede, Liesbeth C; Andersen, Niels S; Moreno, Carol; van Gelder, Michel; Vitek, Antonin; Karas, Michal; Michallet, Mauricette; Machaczka, Maciej; Gramatzki, Martin; Beelen, Dietrich; Finke, Jürgen; Delgado, Julio; Volin, Liisa; Passweg, Jakob; Dreger, Peter; Schaap, Nicolaas; Wagner, Eva; Henseler, Anja; van Biezen, Anja; Bornhäuser, Martin; Iacobelli, Simona; Putter, Hein; Schönland, Stefan O; Kröger, Nicolaus

2017-08-01

The best approach for allogeneic haematopoietic stem cell transplantations (alloHCT) in patients with chronic lymphocytic leukaemia (CLL) is unknown. We therefore analysed the impact of procedure- and centre-related factors on 5-year event-free survival (EFS) in a large retrospective study. Data of 684 CLL patients who received a first alloHCT between 2000 and 2011 were analysed by multivariable Cox proportional hazards models with a frailty component to investigate unexplained centre heterogeneity. Five-year EFS of the whole cohort was 37% (95% confidence interval [CI], 34-42%). Larger numbers of CLL alloHCTs (hazard ratio [HR] 0·96, P = 0·002), certification of quality management (HR 0·7, P = 0·045) and a higher gross national income per capita (HR 0·4, P = 0·04) improved EFS. In vivo T-cell depletion (TCD) with alemtuzumab compared to no TCD (HR 1·5, P = 0·03), and a female donor compared to a male donor for a male patient (HR 1·4, P = 0·02) had a negative impact on EFS, but not non-myeloablative versus more intensive conditioning. After correcting for patient-, procedure- and centre-characteristics, significant variation in centre outcomes persisted. In conclusion, further research on the impact of centre and procedural characteristics is warranted. Non-myeloablative conditioning appears to be the preferable approach for patients with CLL. © 2017 John Wiley & Sons Ltd.

Attendance at cultural events, reading books or periodicals, and making music or singing in a choir as determinants for survival: Swedish interview survey of living conditions.

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Bygren, L O; Konlaan, B B; Johansson, S E

To investigate the possible influence of attendance at cultural events, reading books or periodicals, making music or singing in a choir as determinants for survival. A simple random sample was drawn of 15,198 individuals aged 16-74 years. Of these, 85% (12,982) were interviewed by trained non-medical interviewers between 1982 and 1983 about cultural activities. They were followed up with respect to survival until 31 December 1991. Swedish interview survey of living conditions comprising a random sample of the adult Swedish population. 12,675 people interviewed between 1982 and 1983. Survival of subjects after controlling for eight confounding variables: age, sex, education level, income, long term disease, social network, smoking, and physical exercise. 6,301 men and 6,374 women were followed up; 533 men and 314 women died during this period. The control variables influenced survival in the expected directions except for social network for men; a significant negative effective was found when the analysis was made separately for men and women. We found an influence on mortality when the eight control variables were controlled for in people who rarely attended events compared with those attending most often, the relative risk being 1.57 (95% confidence interval 1.18 to 2.09). Attendance at cultural events may have a positive influence on survival. Long term follow up of large samples with confounders that are well controlled for and with the cultural stimulation more highly specified should be used to try to falsify the hypothesis before experiments start.

The mazEF toxin-antitoxin system as a novel antibacterial target in Acinetobacter baumannii.

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Ghafourian, Sobhan; Good, Liam; Sekawi, Zamberi; Hamat, Rukman Awang; Soheili, Sara; Sadeghifard, Nourkhoda; Neela, Vasanthakumari

2014-07-01

Although analysis of toxin-antitoxin (TA) systems can be instructive, to date, there is no information on the prevalence and identity of TA systems based on a large panel of Acinetobacter baumannii clinical isolates. The aim of the current study was to screen for functional TA systems among clinical isolates of A. baumannii and to identify the systems' locations. For this purpose, we screened 85 A. baumannii isolates collected from different clinical sources for the presence of the mazEF, relBE and higBA TA genes. The results revealed that the genes coding for the mazEF TA system were commonly present in all clinical isolates of A. baumannii. Reverse transcriptase-polymerase chain reaction analysis showed that transcripts were produced in the clinical isolates. Our findings showed that TA genes are prevalent, harboured by chromosomes and transcribed within A. baumannii. Hence, activation of the toxin proteins in the mazEF TA system should be investigated further as an effective antibacterial strategy against this bacterium.

Flux balance modeling to predict bacterial survival during pulsed-activity events

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Jose, Nicholas A.; Lau, Rebecca; Swenson, Tami L.; Klitgord, Niels; Garcia-Pichel, Ferran; Bowen, Benjamin P.; Baran, Richard; Northen, Trent R.

2018-04-01

Desert biological soil crusts (BSCs) are cyanobacteria-dominated surface soil microbial communities common to plant interspaces in arid environments. The capability to significantly dampen their metabolism allows them to exist for extended periods in a desiccated dormant state that is highly robust to environmental stresses. However, within minutes of wetting, metabolic functions reboot, maximizing activity during infrequent permissive periods. Microcoleus vaginatus, a primary producer within the crust ecosystem and an early colonizer, initiates crust formation by binding particles in the upper layer of soil via exopolysaccharides, making microbial dominated biological soil crusts highly dependent on the viability of this organism. Previous studies have suggested that biopolymers play a central role in the survival of this organism by powering resuscitation, rapidly forming compatible solutes, and fueling metabolic activity in dark, hydrated conditions. To elucidate the mechanism of this phenomenon and provide a basis for future modeling of BSCs, we developed a manually curated, genome-scale metabolic model of Microcoleus vaginatus (iNJ1153). To validate this model, gas chromatography-mass spectroscopy (GC-MS) and liquid chromatography-mass spectroscopy (LC-MS) were used to characterize the rate of biopolymer accumulation and depletion in in hydrated Microcoleus vaginatus under light and dark conditions. Constraint-based flux balance analysis showed agreement between model predictions and experimental reaction fluxes. A significant amount of consumed carbon and light energy is invested into storage molecules glycogen and polyphosphate, while β-polyhydroxybutyrate may function as a secondary resource. Pseudo-steady-state modeling suggests that glycogen, the primary carbon source with the fastest depletion rate, will be exhausted if M. vaginatus experiences dark wetting events 4 times longer than light wetting events.

Postoperative radiotherapy appeared to improve the disease free survival rate of patients with extrahepatic bile duct cancer at high risk of loco-regional recurrence

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Kim, Mi Young; Kim, Jin Hee; Kim, Yong Hoon [Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of); Byun, Sang Jun [Dept. of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

2016-12-15

To investigate the outcomes of postoperative radiotherapy (RT), in patients with extrahepatic bile duct (EHBD) cancer by comparing the survival rate between patients undergoing surgery alone or surgery plus postoperative RT, and to identify the prognostic factors affecting survival. Between 2000 and 2013, 52 patients with EHBD cancer underwent surgical resection. Of these, 33 patients did not receive postoperative RT (group I), and 19 patients did (group II). R1 resection was significantly more frequent in group II. The median radiation dose was 5,040 cGy. The 3-year overall survival (OS) rate for group I and group II was 38% and 56%, respectively (p = 0.274). The 3-year disease free survival (DFS) rate for group I and group II was 20% and 31%, respectively (p = 0.049), and the 3-year loco-regional recurrence free survival (LRFS) rates were 19% and 58%, respectively (p = 0.002). Multivariate analyses showed that postoperative RT and lymphovascular invasion were independent prognostic factors for DFS and LRFS. Overall, 42 patients (80%) experienced treatment failure. Distant metastasis was the predominant pattern of failure in group II. Postoperative RT after surgical resection appeared to improve the loco-regional control and DFS rate. More effort is needed to reduce distant metastasis, the major pattern of failure, in patients who receive postoperative RT.

The SOS response is permitted in Escherichia coli strains deficient in the expression of the mazEF pathway.

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Kalderon, Ziva; Kumar, Sathish; Engelberg-Kulka, Hanna

2014-01-01

The Escherichia coli (E. coli) SOS response is the largest, most complex, and best characterized bacterial network induced by DNA damage. It is controlled by a complex network involving the RecA and LexA proteins. We have previously shown that the SOS response to DNA damage is inhibited by various elements involved in the expression of the E. coli toxin-antitoxin mazEF pathway. Since the mazEF module is present on the chromosomes of most E. coli strains, here we asked: Why is the SOS response found in so many E. coli strains? Is the mazEF module present but inactive in those strains? We examined three E. coli strains used for studies of the SOS response, strains AB1932, BW25113, and MG1655. We found that each of these strains is either missing or inhibiting one of several elements involved in the expression of the mazEF-mediated death pathway. Thus, the SOS response only takes place in E. coli cells in which one or more elements of the E. coli toxin-antitoxin module mazEF or its downstream pathway is not functioning.

Free Testosterone During Androgen Deprivation Therapy Predicts Castration-Resistant Progression Better Than Total Testosterone.

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Regis, Lucas; Planas, Jacques; Carles, Joan; Maldonado, Xavier; Comas, Inma; Ferrer, Roser; Morote, Juan

2017-01-01

The optimal degree of testosterone suppression in patients with prostate cancer undergoing androgen deprivation therapy remains in question. Furthermore, serum free testosterone, which is the active form of testosterone, seems to correlate with intraprostatic testosterone. Here we compared free and total serum testosterone as predictors of survival free of castration resistance. Total testosterone (chemiluminescent assay, lower sensitivity 10 ng/dl) and free testosterone (analogue-ligand radioimmunoassay, lower sensitivity 0.05 pg/ml) were determined at 6 months of LHRH agonist treatment in a prospective cohort of 126 patients with prostate cancer. During a mean follow-up of 67 months (9-120), 75 (59.5%) events of castration-resistant progression were identified. Multivariate analysis and survival analysis according to total testosterone cutoffs of 50, 32, and 20 ng/dl, and free testosterone cutoffs of 1.7, 1.1, and 0.7 pg/ml were performed. Metastatic spread was the most powerful predictor of castration resistance, HR: 2.09 (95%CI: 1.18-3.72), P = 0.012. Gleason score, baseline PSA and PSA at 6 months were also independents predictors, but not free and total testosterone. Stratified analysis was conducted on the basis of the status of metastatic diseases and free testosterone was found to be an independent predictor of survival free of castration resistance in the subgroup of patients without metastasis, HR: 2.12 (95%CI: 1.16-3.85), P = 0.014. The lowest threshold of free testosterone which showed significant differences was 1.7 pg/ml, P = 0.003. Free testosterone at 6 months of LHRH agonist treatment seems to be a better surrogate than total testosterone to predict castration resistance in no metastatic prostate cancer patients. Prostate 77:114-120, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Early life events carry over to influence pre-migratory condition in a free-living songbird.

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Greg W Mitchell

Full Text Available Conditions experienced during development can have long-term consequences for individual success. In migratory songbirds, the proximate mechanisms linking early life events and survival are not well understood because tracking individuals across stages of the annual cycle can be extremely challenging. In this paper, we first use a 13 year dataset to demonstrate a positive relationship between 1(st year survival and nestling mass in migratory Savannah sparrows (Passerculus sandwichensis. We also use a brood manipulation experiment to show that nestlings from smaller broods have higher mass in the nest relative to individuals from larger broods. Having established these relationships, we then use three years of field data involving multiple captures of individuals throughout the pre-migratory period and a multi-level path model to examine the hypothesis that conditions during development limit survival during migration by affecting an individual's ability to accumulate sufficient lean tissue and fat mass prior to migration. We found a positive relationship between fat mass during the pre-migratory period (Sept-Oct and nestling mass and a negative indirect relationship between pre-migratory fat mass and fledging date. Our results provide the first evidence that conditions during development limit survival during migration through their effect on fat stores. These results are particularly important given recent evidence showing that body condition of songbirds at fledging is affected by climate change and anthropogenic changes to landscape structure.

Results of a Prospective Study of High-Dose or Conventional Anthracycline-Cyclophosphamide Regimen Plus Radiotherapy for Localized Adult Non-Hodgkin’s Primary Bone Lymphoma

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A. Schmidt-Tanguy

2014-01-01

Full Text Available Background. Primary bone lymphoma (PBL is a rare entity that has only been reviewed in one prospective and small retrospective studies, from which it is difficult to establish treatment guidelines. We prospectively evaluated high-dose or conventional anthracycline-cyclophosphamide dose and radiotherapy for PBL. Patients and Methods. The GOELAMS prospective multicenter study (1986–1998 enrolled adults with localized high-grade PBL according to age and performance status (PS. Patients <60 years received a high-dose CHOP regimen (VCAP and those ≥60 years a conventional anthracycline-cyclophosphamide regimen (VCEP-bleomycin; all received intrathecal chemotherapy and local radiotherapy. Results. Among the 26 patients included (VCAP: 19; VCEP-bleomycin: 7, 39% had poor PS ≥2. With a median follow-up of 8 years, overall survival, event-free survival, and relapse-free survival were 64%, 62%, and 65%, respectively, with no significant difference between treatment groups. Poor PS was significantly associated with shorter OS and EFS. Conclusions. Our results confirm the efficacy of our age-based therapeutic strategy. High-doses anthracycline-cyclophosphamide did not improve the outcome. VCEP-bleomycin is effective and well tolerated for old patients. The intensification must be considered for patients with PS ≥2, a poor prognostic factor.

Recurrence-free survival, but not surgical therapy per se, determines 583 patients' long-term satisfaction following primary pilonidal sinus surgery.

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Doll, Dietrich; Luedi, Markus M; Evers, Theo; Kauf, Peter; Matevossian, Edouard

2015-05-01

With pilonidal sinus disease (PSD) incidence increasing and patients freely choosing their surgeon, patients' interest issues have been brought forward estimating patient satisfaction following pilonidal sinus surgery. The influence of wound healing time and long-term recurrence rate on patient satisfaction in primary PSD surgery has not been investigated yet. Five hundred eighty-three patients (German military cohort) were interviewed, compiling wound healing time, aesthetic satisfaction, long-term recurrence-free survival and patient satisfaction having undergone primary open (PO) treatment, marsupialization (MARS) or primary midline closure (PMC) treatment. Recurrence rate was determined by Kaplan-Meier calculation following up to 20 years after primary PSD surgery. Patient satisfaction ranking from 1 to 10 (10 = max. satisfied) showed an average satisfaction of 8.2 (range 0-10; 95% confidence interval (CI) 7891-8250). In-hospital stay time was significantly longer in primary open (PO) and marsupialization (MARS) group as compared to primary midline closure (PMC; p < 0.0001, Kruskal-Wallis test). Satisfaction was comparable between treatment groups, and was neither linked to in-hospital stay time nor to longer outpatient wound care period or total treatment time. Recurrence-free survival, as seen in the PO and PMC treatment group, revealed a highly significant difference for all patients. Improvement in MARS patients with versus without recurrence was low, as satisfaction with primary treatment was lower as the other groups. Neither choice of surgical treatment nor treatment duration within hospital or after hospital influences patient satisfaction, as long as recurrence-free survival can be provided. Marsupialization was ranked lower in both groups (with or without recurrence), and should be abandoned, as patients are significantly less satisfied with either results, independent of recurrence.

End points for adjuvant therapy trials: has the time come to accept disease-free survival as a surrogate end point for overall survival?

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Gill, Sharlene; Sargent, Daniel

2006-06-01

The intent of adjuvant therapy is to eradicate micro-metastatic residual disease following curative resection with the goal of preventing or delaying recurrence. The time-honored standard for demonstrating efficacy of new adjuvant therapies is an improvement in overall survival (OS). This typically requires phase III trials of large sample size with lengthy follow-up. With the intent of reducing the cost and time of completing such trials, there is considerable interest in developing alternative or surrogate end points. A surrogate end point may be employed as a substitute to directly assess the effects of an intervention on an already accepted clinical end point such as mortality. When used judiciously, surrogate end points can accelerate the evaluation of new therapies, resulting in the more timely dissemination of effective therapies to patients. The current review provides a perspective on the suitability and validity of disease-free survival (DFS) as an alternative end point for OS. Criteria for establishing surrogacy and the advantages and limitations associated with the use of DFS as a primary end point in adjuvant clinical trials and as the basis for approval of new adjuvant therapies are discussed.

A neutron scattering study of the ternary complex EF-Tu.GTP-valyl-tRNAVal1A

DEFF Research Database (Denmark)

Österberg, R.; Elias, P.; Kjems, Jørgen

1986-01-01

The complex formation between elongation factor Tu (EF-Tu), GTP, and valyl-tRNAVal1A has been investigated in a hepes buffer of "pH" 7.4 and 0.2 M ionic strength using the small-angle neutron scattering method at concentrations of D2O where EF-Tu (42% D2O) and tRNA (71% D2O) are successively...

Evaluation of {sup 18}F-BCPP-EF for mitochondrial complex 1 imaging in the brain of conscious monkeys using PET

Energy Technology Data Exchange (ETDEWEB)

Tsukada, Hideo; Ohba, Hiroyuki; Kanazawa, Masakatsu; Kakiuchi, Takeharu; Harada, Norihiro [Hamamatsu Photonics K.K., Central Research Laboratory, Hamamatsu, Shizuoka (Japan)

2014-04-15

We have reported on the development of a novel PET probe, {sup 18}F-2-tert-butyl-4-chloro-5-{6-[2-(2-fluoroethoxy)-ethoxy] -pyridin-3-ylmethoxy}-2H-pyridazin-3-one ({sup 18}F-BCPP-EF), for quantitative imaging of mitochondrial complex 1 (MC-1) activity in the brain of the living rat. For clinical application in humans, translational research in the monkey was conducted. PET measurements with {sup 18}F-BCPP-EF were performed in young and old monkeys (Macaca mulatta) in a conscious state with arterial blood sampling. The binding specificity of {sup 18}F-BCPP-EF was evaluated with rotenone, a specific MC-1 inhibitor, in young animals. The binding (total distribution volume, V{sub T}) of {sup 18}F-BCPP-EF was calculated using Logan graphical analysis, and one-tissue compartment model (1-TC) and two-tissue compartment model (2-TC) analyses using a metabolite-corrected plasma input function. F-BCPP-EF was rapidly taken up into the brain just after intravenous injection, peaked between 10 and 20 min after injection, and was then gradually eliminated. The 2-TC analysis provided a better fit than the 1-TC analysis, and the V{sub T} values from the 2-TC analysis correlated well with those from the Logan plot. With predosing with rotenone, {sup 18}F-BCPP-EF showed a higher uptake peak in the brain, followed by more rapid elimination thereafter than in the vehicle condition, resulting in significant reductions in 2-TC V{sub T} values in all regions. In old animals, the kinetics of {sup 18}F-BCPP-EF were slightly slower with lower peak levels than in young animals, resulting age-related reductions in {sup 18}F-BCPP-EF binding in all brain regions. The present study demonstrated that {sup 18}F-BCPP-EF may be a potential PET probe for quantitative imaging MC-1 activity in the living brain using PET. (orig.)

Being treated in higher volume hospitals leads to longer progression-free survival for epithelial ovarian carcinoma patients in the Rhone-Alpes region of France

OpenAIRE

Huguet, Marius; Perrier, Lionel; Bally, Olivia; Benayoun, David; De Saint Hilaire, Pierre; Beal Ardisson, Dominique; Morelle, Magali; Havet, Nathalie; Joutard, Xavier; Meeus, Pierre; Gabelle, Philippe; Provençal, Jocelyne; Chauleur, Céline; Glehen, Olivier; Charreton, Amandine

2018-01-01

Background To investigate the relationship between hospital volume activities and the survival for Epithelial Ovarian Carcinoma (EOC) patients in France. Methods This retrospective study using prospectively implemented databases was conducted on an exhaustive cohort of 267 patients undergoing first-line therapy during 2012 in the Rhone-Alpes Region of France. We compared Progression-Free Survival for Epithelial Ovarian Carcinoma patients receiving first-line therapy in high- (i.e. ≥ 12 cases/...

Evidence of MexT-independent overexpression of MexEF-OprN multidrug efflux pump of Pseudomonas aeruginosa in presence of metabolic stress.

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Ayush Kumar

Full Text Available The Pseudomonas aeruginosa MexEF-OprN efflux pump confers resistance to clinically significant antibiotics. Regulation of mexEF-oprN operon expression is multifaceted with the MexT activator being one of the most prominent regulatory proteins.We have exploited the impaired metabolic fitness of a P. aeruginosa mutant strain lacking several efflux pump of the resistance nodulation cell division superfamily and the TolC homolog OpmH, and isolated derivatives (large colony variants that regained fitness by incubation on nutrient-rich medium in the absence of antibiotics. Although the mexEF-oprN operon is uninducible in this mutant due to a 8-bp mexT insertion present in some P. aeruginosa PAO1 strains, the large colony variants expressed high levels of MexEF-OprN. Unlike large colony variants obtained after plating on antibiotic containing medium which expressed mexEF-oprN in a MexT-dependent fashion as evidenced by clean excision of the 8-bp insertion from mexT, mexEF-oprN expression was MexT-independent in the large colony variants obtained by plating on LB alone since the mexT gene remained inactivated. A search for possible regulators of mexEF-oprN expression using transposon mutagenesis and genomic library expression approaches yielded several candidates but proved inconclusive.Our results show that antibiotic and metabolic stress lead to up-regulation of MexEF-OprN expression via different mechanisms and that MexEF-OprN does not only extrude antimicrobials but rather serves other important metabolic functions.

Safety aspects of the emergency filtration system (EFS) for NRU reactor

International Nuclear Information System (INIS)

Hickey, D.L.; Lounsbury, R.I.

1990-01-01

A description of the NRU emergency filter system (EFS) is presented, including operation, testing and hazards. Operation of the NRU EFS reduces the dose to the thyroid for members of the public and site personnel by a factor of 100. The calculated thyroid doses for off-site and on-site locations for the current system configuration are 91 and 160 mSv, respectively. An unavailability analysis was performed on the control system which recognized subtle problems in the current system. Modifications to the system result in a system unavailability of 2.0 E-3. The thyroid risk analysis revealed that these improvements in system availability result in risk reduction by approximately a factor of three. Improvements beyond the availability analysis recommendations do not result in substantial risk benefit for members of the public or on-site personnel

Effects of mercury on health and first-year survival of free-ranging great egrets (Ardea albus) from southern Florida.

Science.gov (United States)

Sepúlveda, M S; Williams, G E; Frederick, P C; Spalding, M G

1999-10-01

The objectives of this study were to determine whether elevated mercury (Hg) concentrations have a negative impact on the health and survival of nestling and juvenile free-ranging great egrets (Ardea albus) from southern Florida. During 1994, when health and survival was monitored in a cohort of young birds with naturally variable concentrations of Hg, packed cell volume was positively correlated with blood Hg concentrations, and high Hg concentration in blood was not related to the probability of surviving during the first 10.5 months of life. During 1995, 70 first-hatched great egret chicks were included in a Hg field-dosing experiment to compare the effects of elevated Hg on health and survival. Birds were dosed while in the nest orally every 2.5 days for 15 days with 0.5 mg of methyl mercury chloride (MeHgCl) for an estimated intake of 1.54 mg MeHgCl/kg food intake. These birds were compared with controls, which received an estimated 0.41 mg MeHgCl/kg food. No differences were observed in health parameters or in the probability of surviving during the first 8 months of age between egrets that were dosed with Hg and those that were not. A likely explanation for the lack of any effects on health and survival between both groups could be that chicks at this age were eliminating most of the dietary Hg through the production of new feathers.

Arbuscular mycorrhizal fungus inoculation reduces the drought-resistance advantage of endophyte-infected versus endophyte-free Leymus chinensis.

Science.gov (United States)

Liu, Hui; Chen, Wei; Wu, Man; Wu, Rihan; Zhou, Yong; Gao, Yubao; Ren, Anzhi

2017-11-01

Grasses can be infected simultaneously by endophytic fungi and arbuscular mycorrhizal (AM) fungi. In this study, we tested the hypothesis that endophyte-associated drought resistance of a native grass was affected by an AM fungus. In a greenhouse experiment, we compared the performance of endophyte-infected (EI) and endophyte-free (EF) Leymus chinensis, a dominant species native to the Inner Mongolia steppe, under altered water and AM fungus availability. The results showed that endophyte infection significantly increased drought resistance of the host grass, but the beneficial effects were reduced by AM fungus inoculation. In the mycorrhizal-non-inoculated (MF) treatment, EI plants accumulated significantly more biomass, had greater proline and total phenolic concentration, and lower malondialdehyde concentration than EF plants. In the mycorrhizal-inoculation (MI) treatment, however, no significant difference occurred in either growth or physiological characters measured between EI and EF plants. AM fungus inoculation enhanced drought resistance of EF plants but had no significant effect on drought resistance of EI plants, thus AM fungus inoculation reduced the difference between EI and EF plants. Our findings highlight the importance of interactions among multiple microorganisms for plant performance under drought stress.

Improved Metastasis- and Disease-Free Survival With Preoperative Sequential Short-Course Radiation Therapy and FOLFOX Chemotherapy for Rectal Cancer Compared With Neoadjuvant Long-Course Chemoradiotherapy: Results of a Matched Pair Analysis.

Science.gov (United States)

Markovina, Stephanie; Youssef, Fady; Roy, Amit; Aggarwal, Sonya; Khwaja, Shariq; DeWees, Todd; Tan, Benjamin; Hunt, Steven; Myerson, Robert J; Chang, Daniel T; Parikh, Parag J; Olsen, Jeffrey R

2017-10-01

To compare treatment and toxicity outcomes between a phase 2 institutional trial of near total neoadjuvant therapy (nTNT) for locally advanced rectal cancer and a similar historical control cohort treated at Washington University in St. Louis with the current US standard of care, defined as neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant FOLFOX chemotherapy; to expand the comparison to an additional institution, patients treated with similar NCRT at Stanford University were included. Sixty-nine patients with cT3-4N0-2M0 rectal adenocarcinoma enrolled on the Washington University in St. Louis phase 2 study of nTNT were included for analysis. Patients treated at the same institution with conventional NCRT and adjuvant FOLFOX were matched for exact cTNM stage. Forty-one patients treated with NCRT at Stanford University were included in a second analysis. Kaplan-Meier analysis with log-rank test was used to compare local control, distant metastasis-free survival, disease-free survival, and overall survival. Median follow-up was 49 and 54 months for nTNT and NCRT, respectively. Pathologic complete response and T-downstaging rates were 28% versus 16% (P=.21) and 75% versus 41% (P<.001) in the nTNT and NCRT cohorts, respectively. Three-year disease-free survival (85% vs 68%, P=.032) was significantly better in the nTNT group. Actuarial 3-year local control (92% vs 96%, P=.36) and overall survival (96% vs 88%, P=.67) were similar. The Stanford cohort had significantly lower clinical stage. After controlling for clinical stage, age, tumor location, institution, and number of chemotherapy cycles, nTNT treatment remained significantly associated with lower risk of recurrence (P=.006). Patients treated with nTNT had higher T-downstaging and superior distant metastasis-free survival and disease-free survival compared with conventional NCRT when matched for tumor location and exact cTNM stage. Near total neoadjuvant therapy remained a

Equation-free analysis of agent-based models and systematic parameter determination

Science.gov (United States)

Thomas, Spencer A.; Lloyd, David J. B.; Skeldon, Anne C.

2016-12-01

Agent based models (ABM)s are increasingly used in social science, economics, mathematics, biology and computer science to describe time dependent systems in circumstances where a description in terms of equations is difficult. Yet few tools are currently available for the systematic analysis of ABM behaviour. Numerical continuation and bifurcation analysis is a well-established tool for the study of deterministic systems. Recently, equation-free (EF) methods have been developed to extend numerical continuation techniques to systems where the dynamics are described at a microscopic scale and continuation of a macroscopic property of the system is considered. To date, the practical use of EF methods has been limited by; (1) the over-head of application-specific implementation; (2) the laborious configuration of problem-specific parameters; and (3) large ensemble sizes (potentially) leading to computationally restrictive run-times. In this paper we address these issues with our tool for the EF continuation of stochastic systems, which includes algorithms to systematically configuration problem specific parameters and enhance robustness to noise. Our tool is generic and can be applied to any 'black-box' simulator and determines the essential EF parameters prior to EF analysis. Robustness is significantly improved using our convergence-constraint with a corrector-repeat (C3R) method. This algorithm automatically detects outliers based on the dynamics of the underlying system enabling both an order of magnitude reduction in ensemble size and continuation of systems at much higher levels of noise than classical approaches. We demonstrate our method with application to several ABM models, revealing parameter dependence, bifurcation and stability analysis of these complex systems giving a deep understanding of the dynamical behaviour of the models in a way that is not otherwise easily obtainable. In each case we demonstrate our systematic parameter determination stage for

A comparison of EF-18 agar and modified brilliant green agar with lutensit for isolation of Salmonella from poultry samples

DEFF Research Database (Denmark)

Petersen, Line Hedegård

1997-01-01

-Vassiliadis broth, and 3) Plating onto EF-18 agar and BGA/L simultaneously. From a total of 1101 samples, Salmonella was isolated from 158, 157 of which were faecal samples. Thirtyone of these isolates were recovered on one medium only, 18 could not be found on BGA/L and 13 could not be found on EF-18 agar....... The relative specificity and sensitivity of each plating agar was determined by enumeration of false-positive and false-negative reactions. EF-18 agar compared favourably with BGA/L, displaying a sensitivity of 0.92 as opposed to 0.89 for BGA/L, calculated for the ''fecal samples'' group only. The calculated...... specificities for each group of samples were likewise considerably higher for EF-18 agar (0.75-0.91) than for BGA/L (0.35-0.55). Though EF-18 agar is slightly more expensive than BGA/L, the routine use of the former may result in a considerable reduction in overall laboratory costs due to its superior...

A Ca2+-calmodulin-eEF2K-eEF2 signalling cascade, but not AMPK, contributes to the suppression of skeletal muscle protein synthesis during contractions

DEFF Research Database (Denmark)

Rose, Adam John; Alsted, Thomas Junker; Jensen, Thomas Elbenhardt

2009-01-01

Skeletal muscle protein synthesis rate decreases during contractions but the underlying regulatory mechanisms are poorly understood. It was hypothesised that there would be a coordinated regulation of eukaryotic elongation factor 2 (eEF2) and eukaryotic initiation factor 4E-binding protein 1 (4EBP1......) phosphorylation by signalling cascades downstream of rises in intracellular [Ca(2+)] and decreased energy charge via AMP activated protein kinase (AMPK) in contracting skeletal muscle. When fast-twitch skeletal muscles were contracted ex vivo using different protocols, the suppression of protein synthesis...... correlated more closely with changes in eEF2 rather than 4EBP1 phosphorylation. Using a combination of Ca(2+) release agents and ATPase inhibitors it was shown that the 60-70% suppression of fast-twitch skeletal muscle protein synthesis during contraction was equally distributed between Ca(2+) and energy...

Central Hemodynamics Measured During 5 Repetition Maximum Free Weight Resistance Exercise.

Science.gov (United States)

Howard, Jonathan S; McLester, Cherilyn N; Evans, Thomas W; McLester, John R; Calloway, Jimmy P

2018-01-01

The PhysioFlow™ is a piece of equipment that uses bioimpedance cardiography to measure central hemodynamics. The purpose of this research was to explore the novel approach of monitoring central hemodynamics during free weight resistance exercise using bioimpedance cardiography throughout a 5 repetition maximum (5RM). Thirty participants ranging from beginner to advanced lifters (16 males and 14 females) completed a 5RM for back squat, seated push press, and bicep curl while connected to the PhysioFlow™ to assess the response of heart rate (HR), stroke volume (SV), cardiac output (Q), and ejection fraction (EF). Participants were cued for form and to breathe normally throughout the lifts. The PhysioFlow™ detected an increase in HR and Q for all lifts between rest and each repetition ( p 0.05) and no changes in EF or SV were detected when all repetitions were compared to each other for all lifts ( p > 0.05). In conclusion, the PhysioFlow™ was able to detect changes in HR and Q during dynamic free weight resistance exercise. This novel approach may provide a mechanism for monitoring central hemodynamics during free weight resistance training. However, more research needs to be conducted as the exercise protocol for this investigation did not allow for a comparison to a reference method.

Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System.

Science.gov (United States)

Baer, Matthew L; Henderson, Scott C; Colello, Raymond J

2015-01-01

Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50-100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair.

Elucidating the Role of Injury-Induced Electric Fields (EFs in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System.

Directory of Open Access Journals (Sweden)

Matthew L Baer

Full Text Available Injury to the vertebrate central nervous system (CNS induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs at the injury site, which are 50-100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair.

Lymphadenectomy extent and survival of patients with gastric carcinoma: a systematic review and meta-analysis of time-to-event data from randomized trials.

Science.gov (United States)

Mocellin, Simone; Nitti, Donato

2015-05-01

The extent of lymph node dissection in patients with resectable non-metastatic primary carcinoma of the stomach is still a controversial matter of debate, with special regard to its effect on survival. We conducted a systematic review and meta-analysis of time-to-event data from randomized controlled trials (RCTs) comparing the three main types of lymphadenectomy (D1, D2, and D3) for gastric cancer. Hazard ratio (HR) was considered the effect measure for both overall (OS), disease-specific (DSS) and disease-free survival (DFS). The quality of the available evidence was assessed using the GRADE system. Eight RCTs enrolling 2515 patients were eligible. The meta-analysis of four RCTs (n=1599) showed a significant impact of D2 versus D1 lymphadenectomy on DSS (summary HR=0.807, CI: 0.705-0.924, P=0.002), the corresponding number-to-treat being equal to ten. This effect remained clinically valuable even after adjustment for postoperative mortality. However, the quality of evidence was graded as moderate due to inconsistency issues. When OS and DFS were considered, the meta-analysis of respectively five (n=1653) and three RCTs (n=1332) found no significant difference between D2 and D1 lymph node dissection (summary HR=0.911, CI: 0.708-1.172, P=0.471, and summary HR=0.946, CI: 0.840-1.066, P=0.366, respectively). However, at subgroup analysis D2 type resulted superior to D1 type lymphadenectomy in terms of OS considering the two RCTs carried out in Eastern countries (summary HR=0.627, CI: 0.396-0.994, P=0.047). As regards the D3 vs D2 comparison, the meta-analysis of the three available RCTs (n=862) showed no significant impact of more extended lymphadenectomy on OS (summary HR=0.990, CI: 0.814-1.205, P=0.924). Our findings support the superiority of D2 versus D1 lymphadenectomy in terms of survival benefit. However, this advantage is mainly limited to DSS, the level of evidence is moderate, and the interaction with other factors affecting patient survival (such as

Prognostic significance of Epstein-Barr virus in nodal peripheral T-cell lymphoma, unspecified: A Groupe d'Etude des Lymphomes de l'Adulte (GELA) study.

Science.gov (United States)

Dupuis, Jehan; Emile, Jean-François; Mounier, Nicolas; Gisselbrecht, Christian; Martin-Garcia, Nadine; Petrella, Tony; Bouabdallah, Reda; Berger, Françoise; Delmer, Alain; Coiffier, Bertrand; Reyes, Félix; Gaulard, Philippe

2006-12-15

Peripheral T-cell lymphomas (PTCLs) are rare and have a dismal prognosis. The most frequent subtype is PTCL, unspecified. Epstein-Barr virus (EBV) has been detected in around 40% of cases, but its prognostic significance is not fully established. Lymph node samples from 110 patients with PTCL, unspecified included in LNH87 and LNH93 trials were available. EBV status was studied by EBV-encoded small RNA in situ hybridization (EBER-ISH). EBER-ISH showed positive cells in 45 (41%) of 110 patients. Pretreatment characteristics were comparable between positive and negative cases, except for male sex (80% versus 60%, respectively, P = .02). Only 50% of patients achieved complete remission with a 5-year event-free survival (EFS) and overall survival (OS) of 21% and 30%, respectively. EBER-ISH positivity was the sole factor linked with worse EFS, with a 5-year probability of 11% for positive patients. In univariate analysis, factors affecting OS were EBER-ISH positivity, high LDH level, and age older than 60 years. In multivariate analysis, EBER-ISH was associated with a worse OS in the elderly population. Time-dependent analysis showed that the negative impact of EBV was essentially seen in the first 2 years following diagnosis. These results warrant further studies regarding pathogenesis and specific treatment approaches for EBV-associated PTCL patients.

Prognostic Significance of Serum Alkaline Phosphatase Level in Osteosarcoma: A Meta-Analysis of Published Data

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Hai-Yong Ren

2015-01-01

Full Text Available Background. Serum alkaline phosphatase (SALP is commonly elevated in osteosarcoma patients. A number of studies have investigated the prognostic role of SALP level in patients with osteosarcoma but yielded inconsistent results. Method. Systematic computerized searches were performed in PubMed, Embase, and Web of Science databases for relevant original articles. The pooled hazard ratios (HRs and relative risks (RRs with corresponding confidence intervals (CIs were calculated to assess the prognostic value of SALP level. Results. Finally, 21 studies comprising 3228 patients were included. Overall, the pooled HRs of SALP suggested that elevated level had an unfavorable impact on osteosarcoma patients’ overall survival (OS (HR = 1.82; 95% CI: 1.61–2.06; p<0.001 and event-free survival (EFS (HR = 1.97; 95% CI: 1.61–2.42; p<0.001. Combined RRs of SALP indicated that elevated level was associated with presence of metastasis at diagnosis (RR = 5.55; 95% CI: 1.61–9.49; p=0.006. No significantly different results were obtained after stratified by variables of age range, cancer stage, sample size, and geographic region. Conclusion. This meta-analysis demonstrated that high SALP level is significantly associated with poor OS or EFS rate and presence of metastasis at diagnosis. SALP level is a convenient and effective biomarker of prognosis for osteosarcoma.

Outcome of relapse after allogeneic HSCT in children with ALL enrolled in the ALL-SCT 2003/2007 trial.

Science.gov (United States)

Kuhlen, Michaela; Willasch, Andre M; Dalle, Jean-Hugues; Wachowiak, Jacek; Yaniv, Isaac; Ifversen, Marianne; Sedlacek, Petr; Guengoer, Tayfun; Lang, Peter; Bader, Peter; Sufliarska, Sabina; Balduzzi, Adriana; Strahm, Brigitte; von Luettichau, Irene; Hoell, Jessica I; Borkhardt, Arndt; Klingebiel, Thomas; Schrappe, Martin; von Stackelberg, Arend; Glogova, Evgenia; Poetschger, Ulrike; Meisel, Roland; Peters, Christina

2018-01-01

Relapse remains the major cause of treatment failure in children with high-risk acute lymphoblastic leukaemia (ALL) undergoing allogeneic haematopoietic stem-cell transplantation (allo-SCT). Prognosis is considered dismal but data on risk factors and outcome are lacking from prospective studies. We analysed 242 children with recurrence of ALL after first allo-SCT enrolled in the Berlin-Frankfurt-Munster (BFM) ALL-SCT-BFM 2003 and ALL-SCT-BFM international 2007 studies. Median time from allo-SCT to relapse was 7·7 months; median follow-up from relapse after allo-SCT until last follow-up was 3·4 years. The 3-year event-free survival (EFS) was 15% and overall survival (OS) was 20%. The main cause of death was disease progression or relapse (86·5%). The majority of children (48%) received salvage therapy without second allo-SCT, 26% of the children underwent a second allo-SCT and 25% received palliative treatment only. In multivariate analyses, age, site of relapse, time to relapse and type of salvage therapy were identified as significant prognostic factors for OS and EFS, whereas factors associated with first SCT were not statistically significant. Combined approaches incorporating novel immunotherapeutic treatment options and second allo-SCT hold promise to improve outcome in children with post allo-SCT relapse. © 2017 John Wiley & Sons Ltd.

Prognostic Factors for Survival in Patients with Gastric Cancer using a Random Survival Forest

Science.gov (United States)

Adham, Davoud; Abbasgholizadeh, Nategh; Abazari, Malek

2017-01-01

Background: Gastric cancer is the fifth most common cancer and the third top cause of cancer related death with about 1 million new cases and 700,000 deaths in 2012. The aim of this investigation was to identify important factors for outcome using a random survival forest (RSF) approach. Materials and Methods: Data were collected from 128 gastric cancer patients through a historical cohort study in Hamedan-Iran from 2007 to 2013. The event under consideration was death due to gastric cancer. The random survival forest model in R software was applied to determine the key factors affecting survival. Four split criteria were used to determine importance of the variables in the model including log-rank, conversation?? of events, log-rank score, and randomization. Efficiency of the model was confirmed in terms of Harrell’s concordance index. Results: The mean age of diagnosis was 63 ±12.57 and mean and median survival times were 15.2 (95%CI: 13.3, 17.0) and 12.3 (95%CI: 11.0, 13.4) months, respectively. The one-year, two-year, and three-year rates for survival were 51%, 13%, and 5%, respectively. Each RSF approach showed a slightly different ranking order. Very important covariates in nearly all the 4 RSF approaches were metastatic status, age at diagnosis and tumor size. The performance of each RSF approach was in the range of 0.29-0.32 and the best error rate was obtained by the log-rank splitting rule; second, third, and fourth ranks were log-rank score, conservation of events, and the random splitting rule, respectively. Conclusion: Low survival rate of gastric cancer patients is an indication of absence of a screening program for early diagnosis of the disease. Timely diagnosis in early phases increases survival and decreases mortality. Creative Commons Attribution License

The mazEF toxin-antitoxin system as a novel antibacterial target in Acinetobacter baumannii

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Sobhan Ghafourian

2014-07-01

Full Text Available Although analysis of toxin-antitoxin (TA systems can be instructive, to date, there is no information on the prevalence and identity of TA systems based on a large panel of Acinetobacter baumannii clinical isolates. The aim of the current study was to screen for functional TA systems among clinical isolates of A. baumannii and to identify the systems’ locations. For this purpose, we screened 85 A. baumannii isolates collected from different clinical sources for the presence of the mazEF, relBE and higBA TA genes. The results revealed that the genes coding for the mazEF TA system were commonly present in all clinical isolates of A. baumannii. Reverse transcriptase-polymerase chain reaction analysis showed that transcripts were produced in the clinical isolates. Our findings showed that TA genes are prevalent, harboured by chromosomes and transcribed within A. baumannii. Hence, activation of the toxin proteins in the mazEF TA system should be investigated further as an effective antibacterial strategy against this bacterium.

Isoforms of elongation factor eEF1A may be differently regulated at post-transcriptional level in breast cancer progression

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Vislovukh A. A.

2013-01-01

Full Text Available Eukaryotic translation elongation factor 1A exists as two 98 % homologous isoforms: eEF1A1 (A1 and eEF1A2 (A2 which are tissue and development specific. Despite high homology in an open reading frame (ORF region, mRNAs coding for eEF1A1 and eEF1A2 are different in their untranslated regions (UTR, suggesting a possibility of their dissimilar post-transcriptional regulation. Aim. To analyze the existence of cis-acting motifs in the UTRs of EEF1A1/A2 mRNAs, to confirm the possibility of post-transcriptional control of eEF1A1 and eEF1A2 expression. Methods. An ensemble of bioinformatic methods was applied to predict regulatory motifs in the UTRs of EEF1A1/A2 mRNAs. Dual-luciferase reporter assay was employed to detect post-transcriptional regulation of eEF1A1/A2 expression. Results. Numerous regulatory motifs in the UTR of EEF1A1/A2 mRNAs were found bioinformatically. The experimental evidence was obtained for the existence of negative regulation of EEF1A1 and positive regulation of EEF1A2 mRNA in the model of breast cancer development. Conclusions. EEF1A1 and EEF1A2 mRNAs contain distinct motifs in the UTRs and are differently regulated in cancer suggesting the possibility of their control by different cellular signals.

The influence of disturbance events on survival and dispersal rates of Florida box turtles

Science.gov (United States)

Dodd, C.K.; Ozgul, A.; Oli, M.K.

2006-01-01

Disturbances have the potential to cause long-term effects to ecosystem structure and function, and they may affect individual species in different ways. Long-lived vertebrates such as turtles may be at risk from such events, inasmuch as their life histories preclude rapid recovery should extensive mortality occur. We applied capture–mark–recapture models to assess disturbance effects on a population of Florida box turtles (Terrapene carolina bauri) on Egmont Key, Florida, USA. Near the midpoint of the study, a series of physical disturbances affected the island, from salt water overwash associated with several tropical storms to extensive removal of nonindigenous vegetation. These disturbances allowed us to examine demographic responses of the turtle population and to determine if they affected dispersal throughout the island. Adult survival rates did not vary significantly either between sexes or among years of the study. Survival rates did not vary significantly between juvenile and adult turtles, or among years of the study. Furthermore, neither adult nor juvenile survival rates differed significantly between pre- and post-disturbance. However, dispersal rates varied significantly among the four major study sites, and dispersal rates were higher during the pre-disturbance sampling periods compared to post-disturbance. Our results suggest few long-term effects on the demography of the turtle population. Florida box turtles responded to tropical storms and vegetation control by moving to favorable habitats minimally affected by the disturbances and remaining there. As long as turtles and perhaps other long-lived vertebrates can disperse to non-disturbed habitat, and high levels of mortality do not occur in a population, a long life span may allow them to wait out the impact of disturbance with potentially little effect on long-term population processes.

Postmastectomy radiotherapy improves disease-free survival of high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

Directory of Open Access Journals (Sweden)

Zhen-Yu He

Full Text Available The indications for post-mastectomy radiotherapy (PMRT with T1-2 breast cancer and 1-3 positive axillary lymph nodes is still controversial. The purpose of this study was to investigate the role of PMRT in T1-2 breast cancer with 1-3 positive axillary lymph node.We retrospectively reviewed the file records of 79 patients receiving PMRT and not receiving PMRT (618 patients.The median follow-up was 65 months. Multivariate analysis showed that PMRT was an independent prognostic factor of locoregional recurrence-free survival (LRFS (P = 0.010. Subgroup analysis of patients who did not undergo PMRT showed that pT stage, number of positive axillary lymph nodes, and molecular subtype were independent prognostic factors of LRFS. PMRT improved LRFS in the entire group (P = 0.005, but did not affect distant metastasis-free survival (DMFS (P = 0.494, disease-free survival (DFS (P = 0.215, and overall survival (OS (P = 0.645. For patients without PMRT, the 5-year LRFS of low-risk patients (0-1 risk factor for locoregional recurrence of 94.5% was significantly higher than that of high-risk patients (2-3 risk factors for locoregional recurrence (80.9%, P < 0.001. PMRT improved LRFS (P = 0.001 and DFS (P = 0.027 in high-risk patients, but did not improve LRFS, DMFS, DFS, and OS in low-risk patients.PMRT is beneficial in patients with high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

Solvent-free enzymatic synthesis of feruloylated structured lipids by the transesterification of ethyl ferulate with castor oil.

Science.gov (United States)

Sun, Shangde; Zhu, Sha; Bi, Yanlan

2014-09-01

A novel enzymatic route of feruloylated structured lipids synthesis by the transesterification of ethyl ferulate (EF) with castor oil, in solvent-free system, was investigated. The transesterification reactions were catalysed by Novozym 435, Lipozyme RMIM, and Lipozyme TLIM, among which Novozym 435 showed the best catalysis performance. Effects of feruloyl donors, reaction variables, and ethanol removal on the transesterification were also studied. High EF conversion (∼100%) was obtained under the following conditions: enzyme load 20% (w/w, relative to the weight of substrates), reaction temperature 90 °C, substrate molar ratio 1:1 (EF/castor oil), 72 h, vacuum pressure 10 mmHg, and 200 rpm. Under these conditions, the transesterification product consisted of 62.6% lipophilic feruloylated structured lipids and 37.3% hydrophilic feruloylated lipids. Copyright © 2014 Elsevier Ltd. All rights reserved.

Outcome of relapse after allogeneic HSCT in children with ALL enrolled in the ALL-SCT 2003/2007 trial

DEFF Research Database (Denmark)

Kuhlen, Michaela; Willasch, Andre M; Dalle, Jean-Hugues

2018-01-01

Relapse remains the major cause of treatment failure in children with high-risk acute lymphoblastic leukaemia (ALL) undergoing allogeneic haematopoietic stem-cell transplantation (allo-SCT). Prognosis is considered dismal but data on risk factors and outcome are lacking from prospective studies. We...... analysed 242 children with recurrence of ALL after first allo-SCT enrolled in the Berlin-Frankfurt-Munster (BFM) ALL-SCT-BFM 2003 and ALL-SCT-BFM international 2007 studies. Median time from allo-SCT to relapse was 7·7 months; median follow-up from relapse after allo-SCT until last follow-up was 3·4 years....... The 3-year event-free survival (EFS) was 15% and overall survival (OS) was 20%. The main cause of death was disease progression or relapse (86·5%). The majority of children (48%) received salvage therapy without second allo-SCT, 26% of the children underwent a second allo-SCT and 25% received palliative...

Classical and anaplastic seminoma: Difference in survival

International Nuclear Information System (INIS)

Bobba, V.S.; Mittal, B.B.; Hoover, S.V.; Kepka, A.

1987-01-01

The authors undertook a retrospective study of seminoma patients treated with radiation therapy between 1961 and 1985. The classical group consisted of 66 patients, of whom 47 were stage I and 19 were stage II. The anaplastic group consisted of 21 patients, of whom 11 were stage I, nine were stage II, and one was stage III. The median follow-up was 66 months. The five-year crude survival rate for the entire group was 92%, for classical 96%, and for anaplastic 78% (P<.005). Similarly, there was a significant difference (P<.005) in actuarial relapse-free survival at 5 years between classical and anaplastic seminoma. For classical stage I, the relapse-free actuarial 5-year survival rate was 96; for classical stage II, 84%. For anaplastic stage I the relapse-free actuarial 5-year survival rate was 82%, and for stage II 75%. Six patients in the classical group (9%) failed treatment. In the anaplastic group, five patients or 24 failed treatment. Therefore, the authors' data suggest a difference in survival and failure rate between classical and anaplastic seminoma. Extratesticular seminoma with anaplastic histology has an even worse prognosis

Fabrication and tests of EF conductors for JT-60SA

Energy Technology Data Exchange (ETDEWEB)

Kizu, Kaname, E-mail: kizu.kaname@jaea.go.jp [Japan Atomic Energy Agency, Naka, Ibaraki 311-0193 (Japan); Kashiwa, Yoshitoshi; Murakami, Haruyuki [Japan Atomic Energy Agency, Naka, Ibaraki 311-0193 (Japan); Obana, Tetsuhiro; Takahata, Kazuya [National Institute for Fusion Science, Toki, Gifu 509-5292 (Japan); Tsuchiya, Katsuhiko; Yoshida, Kiyoshi [Japan Atomic Energy Agency, Naka, Ibaraki 311-0193 (Japan); Hamaguchi, Shinji [National Institute for Fusion Science, Toki, Gifu 509-5292 (Japan); Matsui, Kunihiro [Japan Atomic Energy Agency, Naka, Ibaraki 311-0193 (Japan); Nakamura, Kazuya; Takao, Tomoaki [Sophia University, Tokyo 102-8554 (Japan); Yanagi, Nagato; Imagawa, Shinsaku; Mito, Toshiyuki [National Institute for Fusion Science, Toki, Gifu 509-5292 (Japan)

2011-10-15

The conductors for plasma equilibrium field (EF) coils of JT-60SA are NbTi cable-in-conduit (CIC) conductor with stainless steel 316L jacket. The production of superconductors for actual EF coils started from February 2010. Nine superconductors with 444 m in length were produced up to July 2010. More than 300 welding of jackets were performed. Six nonconformities were found by inspections as go gauge, visual inspection and X-ray test. In order to shorten the manufacturing time schedule, helium leak test was conducted at once after connecting the long length jacket not just after the welding. The maximum force to pull the cable into jacket was about 7.6 kN on average. The mass flow rates of 9 conductors showed almost same values indicating that there are no blockages in the conductors. The measured current sharing temperature agreed with the expectation values from strand performance indicating that no degradation was caused by production process. The coupling time constants of conductors ranged from 80 to 90 ms which are much smaller than the design value of 200 ms.

Clinical trials of CCLSG L874 and I874 protocols without cranial irradiation for standard-risk acute lymphoblastic leukemia in childhood

International Nuclear Information System (INIS)

Koizumi, Shoichi; Fujimoto, Takeo; Tsurusawa, Masahito

1992-01-01

In the CCLSG-874 protocol for children with low-risk (LR) and intermediate-risk (IR) acute lymphoblastic leukemia (ALL), two regimens with or without cranial irradiation (CI) were compared with respect to their ability to prevent central nervous system (CNS) leukemia and to improve overall outcome of ALL. From 1987 to 1990, 82 and 109 evaluable patients were registered into L874 and I874 protocols for LR and IR patients, respectively. All responders to induction therapy were randomized to treatment with 18 Gy of CI plus intrathecal methotrexate (MTX it) or to treatment with high-dose MTX plus MTX it. Patients were then treated with standard maintenance regimens of L874 and I874. At a median follow-up of 39 months (range 14-58 months) there was no difference in the rate of hematologic relapse between the CI group and MTX group. The rate of CNS relapse in the MTX group seemed to be higher (3 of 39 in L874 and 2 of 54 in I874) than that in the CI group (1 of 43 in L874 and 0 of 55 in I874), but these data were not statistically significant. The rates of 4-year event-free survival (EFS) in L874 were 81.1±7.6% (mean±SE) and 75.2±7.9% (ns) for the CI and MTX group, respectively, and the rates of EFS in I874 were 70.0±13.6% and 70.0±9.0% (ns) for the CI and MTX group, respectively. These data suggest that MTX alone may be as effective as CI to prolong disease-free survival in LR and IR ALL although further continuous studies are needed. Analysis of serial CCLSG protocols for ALL from 1981 revealed that the rate of EFS of ALL allover including all risk groups has gradually been increasing from 44.2±3.6% for 811 protocol and 53.1±3.5% for 841 to 65.5±3.6% for the present 874 protocol. (author)

Repeatability of tumour hypoxia imaging using [{sup 18}F]EF5 PET/CT in head and neck cancer

Energy Technology Data Exchange (ETDEWEB)

Silvoniemi, Antti [University of Turku, Turku PET Centre (Finland); Turku University Hospital, Department of Otorhinolaryngology - Head and Neck Surgery (Finland); Suilamo, Sami [Turku University Hospital, Department of Oncology and Radiotherapy (Finland); Turku University Hospital, Department of Medical Physics (Finland); Laitinen, Timo; Forsback, Sarita; Solin, Olof [University of Turku, Turku PET Centre (Finland); Loeyttyniemi, Eliisa [University of Turku, Department of Biostatistics, Turku (Finland); Vaittinen, Samuli [Turku University Hospital, Department of Pathology (Finland); Saunavaara, Virva [University of Turku, Turku PET Centre (Finland); Turku University Hospital, Department of Medical Physics (Finland); Groenroos, Tove J.; Minn, Heikki [University of Turku, Turku PET Centre (Finland); Turku University Hospital, Department of Oncology and Radiotherapy (Finland)

2018-02-15

Hypoxia contributes to radiotherapy resistance and more aggressive behaviour of several types of cancer. This study was designed to evaluate the repeatability of intratumour uptake of the hypoxia tracer [{sup 18}F]EF5 in paired PET/CT scans. Ten patients with newly diagnosed head and neck cancer (HNC) received three static PET/CT scans before chemoradiotherapy: two with [{sup 18}F]EF5 a median of 7 days apart and one with [{sup 18}F]FDG. Metabolically active primary tumour volumes were defined in [{sup 18}F]FDG images and transferred to co-registered [{sup 18}F]EF5 images for repeatability analysis. A tumour-to-muscle uptake ratio (TMR) of 1.5 at 3 h from injection of [{sup 18}F]EF5 was used as a threshold representing hypoxic tissue. In 10 paired [{sup 18}F]EF5 PET/CT image sets, SUVmean, SUVmax, and TMR showed a good correlation with the intraclass correlation coefficients of 0.81, 0.85, and 0.87, respectively. The relative coefficients of repeatability for these parameters were 15%, 17%, and 10%, respectively. Fractional hypoxic volumes of the tumours in the repeated scans had a high correlation using the Spearman rank correlation test (r = 0.94). In a voxel-by-voxel TMR analysis between the repeated scans, the mean of Pearson correlation coefficients of individual patients was 0.65. The mean (± SD) difference of TMR in the pooled data set was 0.03 ± 0.20. Pretreatment [{sup 18}F]EF5 PET/CT within one week shows high repeatability and is feasible for the guiding of hypoxia-targeted treatment interventions in HNC. (orig.)

Equivalent biochemical failure-free survival after external beam radiation therapy or radical prostatectomy in patients with a pretreatment prostate specific antigen of > 4-20 ng/ml

International Nuclear Information System (INIS)

D'Amico, Anthony V.; Whittington, Richard; Kaplan, Irving; Beard, Clair; Jiroutek, Michael; Malkowicz, S. Bruce; Wein, Alan; Coleman, C. Norman

1997-01-01

Purpose: Biochemical failure-free survival stratified by the pretreatment prostate-specific antigen (PSA) and biopsy Gleason score (bGl) is determined for prostate cancer patients managed definitively with external beam radiation therapy or radical retropubic prostatectomy. Methods and Materials: A Cox regression multivariable analysis evaluating the variables of PSA, bGl, and clinical stage was used to evaluate the end point of time to PSA failure in 867 and 757 consecutive prostate cancer patients managed definitively with external beam radiation therapy or radical retropubic prostatectomy, respectively. PSA failure-free survival was determined using Kaplan-Meier analysis. Comparisons were made using the log rank test. Results: The pretreatment PSA, bGl, and clinical stage (T3,4 vs. T1,T2) were found to be independent predictors of time to post-treatment PSA failure for both surgically and radiation managed patients using Cox regression multivariable analysis. Patients with a pretreatment PSA of > 4 ng/ml and ≤ 20 ng/ml could be classified into risk groups for time to post-therapy PSA failure: low = PSA > 4-10 ng/ml and bGl ≤ 4; intermediate = PSA > 4-10 and bGl 5-7; or PSA > 10-20 ng/ml and bGl ≤ 7; high = PSA > 4-20 ng/ml and bGl ≥ 8. Two-year PSA failure-free survival for surgically managed and radiation-managed patients, respectively, were 98% vs. 92% (p = 0.45), 77% vs. 81% (p = 0.86), and 51% vs. 53% (p = 0.48) for patients at low, intermediate, and high risk for post-therapy PSA failure. Conclusions: There was no statistical difference in the 2-year PSA failure-free survival for potentially curable patients managed definitively with surgery or radiation therapy when a retrospective comparison stratifying for the pretreatment PSA and bGl was performed

IKZF1 deletion is associated with a poor outcome in pediatric B-cell precursor acute lymphoblastic leukemia in Japan

International Nuclear Information System (INIS)

Asai, Daisuke; Imamura, Toshihiko; Suenobu, So-ichi; Saito, Akiko; Hasegawa, Daiichiro; Deguchi, Takao; Hashii, Yoshiko; Matsumoto, Kimikazu; Kawasaki, Hirohide; Hori, Hiroki; Iguchi, Akihiro; Kosaka, Yoshiyuki; Kato, Koji; Horibe, Keizo; Yumura-Yagi, Keiko; Hara, Junichi; Oda, Megumi

2013-01-01

Genetic alterations of Ikaros family zinc finger protein 1 (IKZF1), point mutations in Janus kinase 2 (JAK2), and overexpression of cytokine receptor-like factor 2 (CRLF2) were recently reported to be associated with poor outcomes in pediatric B-cell precursor (BCP)-ALL. Herein, we conducted genetic analyses of IKZF1 deletion, point mutation of JAK2 exon 16, 17, and 21, CRLF2 expression, the presence of P2RY8-CRLF2 fusion and F232C mutation in CRLF2 in 202 pediatric BCP-ALL patients newly diagnosed and registered in Japan Childhood Leukemia Study ALL02 protocol to find out if alterations in these genes are determinants of poor outcome. All patients showed good response to initial prednisolone (PSL) treatment. Ph + , infantile, and Down syndrome–associated ALL were excluded. Deletion of IKZF1 occurred in 19/202 patients (9.4%) and CRLF2 overexpression occurred in 16/107 (15.0%), which are similar to previous reports. Patients with IKZF1 deletion had reduced event-free survival (EFS) and overall survival (OS) compared to those in patients without IKZF1 deletion (5-year EFS, 62.7% vs. 88.8%, 5-year OS, 71.8% vs. 90.2%). Our data also showed significantly inferior 5-year EFS (48.6% vs. 84.7%, log rank P = 0.0003) and 5-year OS (62.3% vs. 85.4%, log rank P = 0.009) in NCI-HR patients (n = 97). JAK2 mutations and P2RY8-CRLF2 fusion were rarely detected. IKZF1 deletion was identified as adverse prognostic factor even in pediatric BCP-ALL in NCI-HR showing good response to PSL

High-dose chemotherapy with stem cell rescue in the primary treatment of metastatic and pelvic osteosarcoma: final results of the ISG/SSG II study.

Science.gov (United States)

Boye, Kjetil; Del Prever, Adalberto Brach; Eriksson, Mikael; Saeter, Gunnar; Tienghi, Amelia; Lindholm, Paula; Fagioli, Franca; Skjeldal, Sigmund; Ferrari, Stefano; Hall, Kirsten Sundby

2014-05-01

Patients with metastatic osteosarcoma at diagnosis or axial primary tumors have a poor prognosis. The aim of the study was to evaluate the feasibility and efficacy of intensified treatment with high-dose chemotherapy (HDCT) and stem cell rescue in this group. From May 1996 to August 2004, 71 patients were included in a Scandinavian-Italian single arm phase II study. Preoperative chemotherapy included methotrexate, doxorubicin, cisplatin and ifosfamide, and postoperative treatment consisted of two cycles of doxorubicin, one cycle of cyclophosphamide and etoposide and two courses of high-dose etoposide and carboplatin with stem cell rescue. Twenty-nine patients (43%) received two courses and 10 patients (15%) received one course of HDCT. HDCT was associated with significant toxicity, but no treatment-related deaths were recorded. Fourteen patients (20%) had disease progression before completion of the study protocol, and only 29/71 patients (41%) received the full planned treatment. Median event-free survival (EFS) was 18 months, and estimated 5-year EFS was 27%. Median overall survival (OS) was 34 months, and estimated 5-year OS was 31%. When patients who did not receive HDCT due to disease progression were excluded, there was no difference in EFS (P = 0.72) or OS (P = 0.49) between patients who did or did not receive HDCT. The administration of high-dose chemotherapy with stem cell rescue was feasible, but associated with significant toxicity. Patient outcome seemed comparable to previous studies using conventional chemotherapy. We conclude that HDCT with carboplatin and etoposide should not be further explored as a treatment strategy in high-risk osteosarcoma. © 2013 Wiley Periodicals, Inc.

Survival of extrasolar giant planet moons in planet-planet scattering

Science.gov (United States)

CIAN HONG, YU; Lunine, Jonathan; Nicholson, Phillip; Raymond, Sean

2015-12-01

Planet-planet scattering is the best candidate mechanism for explaining the eccentricity distribution of exoplanets. Here we study the survival and dynamics of exomoons under strong perturbations during giant planet scattering. During close encounters, planets and moons exchange orbital angular momentum and energy. The most common outcomes are the destruction of moons by ejection from the system, collision with the planets and the star, and scattering of moons onto perturbed but still planet-bound orbits. A small percentage of interesting moons can remain bound to ejected (free-floating) planets or be captured by a different planet. Moons' survival rate is correlated with planet observables such as mass, semi-major axis, eccentricity and inclination, as well as the close encounter distance and the number of close encounters. In addition, moons' survival rate and dynamical outcomes are predetermined by the moons' initial semi-major axes. The survival rate drops quickly as moons' distances increase, but simulations predict a good chance of survival for the Galilean moons. Moons with different dynamical outcomes occupy different regions of orbital parameter space, which may enable the study of moons' past evolution. Potential effects of planet obliquity evolution caused by close encounters on the satellites’ stability and dynamics will be reported, as well as detailed and systematic studies of individual close encounter events.

[Disease-free survival related factors in breast cancer].

Science.gov (United States)

Dávila-Arias, Cristina; Ocón, Olga; Fernández, Mariana F; Arrebola, Juan Pedro; Sánchez, María José; Aneiros, José; Torné, Pablo; Olea, Nicolás

2014-10-07

To evaluate the relationship between the clinical and pathological parameters of the primary tumor and disease-free survival (DFS) in a sample of hospital cases of invasive breast cancer. We performed a retrospective cohort study in 635 patients recruited at San Cecilio University Hospital in Granada (Spain) between 1994 and 2006. Information on the primary tumor and the outcomes of patients was collected by reviewing the medical records. Predictors of recurrence and/or metastasis and DFS (follow up of 3, 5 and 10 years) were analyzed by using Cox regression analysis. Multivariate models adjusted for age, tumor size, lymph nodal status, histological grade and estrogen and progesterone receptor expression showed a higher risk of recurrence and/or metastasis and lower DFS (adjusted relative risk, 95% confidence intervals) with tumor size (3 yrs: 3.00, 1.79-5.03; 5 yrs: 2.56, 1.65-3.98; 10 yrs: 2.16, 1.44-3.24), lymph nodal status (3 yrs: 4.58, 2.42-8.65; 5 yrs: 3.84, 2.35-6.30; 10 yrs: 3.08, 2.05-4.61), lymphovascular invasion (5 yrs: 1.88, 1.16-3.04; 10 yrs: 2.19, 1.43-3.35), multifocal and/or multicenter tumors (3 yrs: 2.69, 1.46-4.96; 5 yrs: 1.90, 1.08-3.35) and p53 protein expression (3 yrs: 2.03, 1.00-4.09). DFS was positively associated with an increased expression of progesterone receptor (3 yr: 0.48, 0.26-0.89; 5 yrs: 0.58, 0.35-0.97; 10 yrs: 0.59, 0.38-0.90). The biological characteristics of the primary tumor can be used to identify patients with distinctive prognoses and DFS, and could be helpful in making individual follow up strategies. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

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

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

2015-01-01

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

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

Directory of Open Access Journals (Sweden)

Daniel Willian Lustosa de Sousa

2015-08-01

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

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.

Science.gov (United States)

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

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. 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 R(2) 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. 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 (R(2), 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy. 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. © 2014 by American Society of Clinical Oncology.

Understanding survival analysis: Kaplan-Meier estimate.

Science.gov (United States)

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

2010-10-01

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

Elevated HERV-K Expression in Soft Tissue Sarcoma Is Associated with Worsened Relapse-Free Survival.

Science.gov (United States)

Giebler, Maria; Staege, Martin S; Blauschmidt, Sindy; Ohm, Lea I; Kraus, Matthias; Würl, Peter; Taubert, Helge; Greither, Thomas

2018-01-01

A wide variety of endogenous retroviral sequences has been demonstrated in the human genome so far, divided into several different families according to the sequence homology to viral strains. While increased expression of human endogenous retrovirus (HERV) elements has already been linked to unfavorable prognosis in hepatocellular carcinoma, breast cancer, and ovarian carcinoma yet less is known about the impact of the expression of different HERV elements on sarcomagenesis in general as well as the outcome of soft tissue sarcoma (STS) patients. Therefore, in this study the association between expression of HERV-K and HERV-F and the clinicopathological characteristics in a cohort of STSs as well as the patients' prognosis was evaluated. HERV-K and HERV-F expression was assessed by quantitative real-time PCR in 120 patient specimens. HERV-K and HERV-F expression was significantly correlated ( r S = 0.5; p = 6.4 × 10 -9 ; Spearman's rank bivariate correlation). Also, tumor diameter exhibited a significant negative association to HERV-K and HERV-F expression. Levels of several hypoxia-related RNAs like HIF-1α and miR-210 showed a significant positive correlation with both HERV-K and HERV-F expression. Although in survival analyses no impact of HERV expression on disease-specific survival could be detected, patients with elevated HERV-K expression had a significantly shorter relapse-free survival ( p = 0.014, log-rank analysis). In conclusion, we provide evidence for the first time that the increased expression of HERV-K in tumors is associated with STS patients' prognosis.

Membrane Fouling Potential of Secondary Effluent Organic Matter (EfOM) from Conventional Activated Sludge Process

KAUST Repository

Wei, Chunhai; Amy, Gary L.

2012-01-01

Secondary effluent organic matter (EfOM) from a conventional activated sludge process was filtered through constant-pressure dead-end filtration tests with a sequential ultrafiltration (UF, molecular weight cut-off (MWCO) of 10k Dalton) and nanofiltration (NF, MWCO of 200 Dalton) array to investigate its membrane fouling potential. Advanced analytical methods including liquid chromatography with online carbon detection (LC-OCD) and fluorescent excitation-emission matrix (F-EEM) were employed for EfOM characterization. EfOM consisted of humic substances and building blocks, low molecular weight (LMW) neutrals, biopolymers (mainly proteins) and hydrophobic organics according to the sequence of their organic carbon fractions. The UF rejected only biopolymers and the NF rejected most humics and building blocks and a significant part of LMW neutrals. Simultaneous occurrence of cake layer and standard blocking during the filtration process of both UF and NF was identified according to constant-pressure filtration equations, which was possibly caused by the heterogeneous nature of EfOM with a wide MW distribution (several ten to several million Dalton). Thus the corresponding two fouling indices (kc for cake layer and ks for standard blocking) from UF and NF could characterize the fouling potential of macromolecular biopolymers and low to intermediate MW organics (including humics, building blocks, LMW neutrals), respectively. Compared with macromolecular biopolymers, low to intermediate MW organics exhibited a much higher fouling potential due to their lower molecular weight and higher concentration.

Predictive potential of macrophage migration inhibitory factor (MIF) in patients with heart failure with preserved ejection fraction (HFpEF).

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Luedike, Peter; Alatzides, Georgios; Papathanasiou, Maria; Heisler, Martin; Pohl, Julia; Lehmann, Nils; Rassaf, Tienush

2018-05-04

Prognostication in heart failure with preserved ejection fraction (HFpEF) is challenging and novel biomarkers are urgently needed. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that plays a crucial role in cardiovascular and various inflammatory diseases. Whether MIF is involved in HFpEF is unknown. Sixty-two patients with HFpEF were enrolled and followed up for 180 days. MIF plasma levels as well as natriuretic peptide (NP) levels were assessed. High MIF levels significantly predicted the combined end-point of all-cause death or hospitalization at 180 days in the univariate analysis (HR 2.41, 95% CI 1.12-5.19, p = 0.025) and after adjustment for relevant covariates in a Cox proportional hazard regression model (HR 2.35, 95% CI 1.05-5.27, p = 0.0374). Furthermore, MIF levels above the median were associated with higher pulmonary artery systolic pressure (PASP) as assessed by echocardiography (PASP 31 mmHg vs 48 mmHg in the low- and high-MIF group, respectively, p = 0.017). NPs significantly correlated with MIF in HFpEF patients (BNP p = 0.011; r = 0.32; NT-proBNP p = 0.027; r = 0.28). MIF was associated with clinical outcomes and might be involved in the pathophysiology of pulmonary hypertension in patients with HFpEF. These first data on MIF in HFpEF should stimulate further research to elucidate the role of this cytokine in heart failure. Trial registration NCT03232671.

Fat-free muscle mass in magnetic resonance imaging predicts acute-on-chronic liver failure and survival in decompensated cirrhosis

DEFF Research Database (Denmark)

Praktiknjo, Michael; Book, Marius; Luetkens, Julian

2018-01-01

of sarcopenia using magnetic resonance imaging (MRI) in decompensated cirrhotic patients with transjugular intrahepatic portosystemic shunt (TIPS). METHODS: The total erector spinae muscle area and the intramuscular fat tissue area were measured and subtracted to calculate the fat-free muscle area (FFMA) in 116...... in a validation cohort of 45 patients. RESULTS: FFMA correlated with follistatin and TPMT and showed slightly better association with survival than TPMT. Gender-specific cut-off values for FFMA were determined for sarcopenia. Decompensation (ascites, overt hepatic encephalopathy) persisted after TIPS...... in the sarcopenia group but resolved in the non-sarcopenia group. Sarcopenic patients showed no clinical improvement after TIPS as well as higher mortality, mainly due to development of acute-on-chronic liver failure (ACLF). FFMA was an independent predictor of survival in these patients. CONCLUSION: This study...

Magnetic resonance imaging in breast cancer treated with neoadjuvant chemotherapy: radiologic-pathologic correlation of the response and disease-free survival depending on molecular subtype.

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Cruz Ciria, S; Jiménez Aragón, F; García Mur, C; Esteban Cuesta, H; Gros Bañeres, B

2014-01-01

To evaluate the radiologic and pathologic responses to neoadjuvant chemotherapy and their correlation in the molecular subtypes of breast cancer and to analyze their impact in disease-free survival. We included 205 patients with breast cancer treated with neoadjuvant chemotherapy. We evaluated the radiologic response by comparing MRI images acquired before and after chemotherapy. The pathologic response was classified on the Miller and Payne scale. For each subtype (HER2+, TN, luminal A, luminal B HER2-, and luminal B HER2+), we used the χ(2) test, Student's t-test, ANOVA, and Kendall's Tau-b to evaluate the radiologic response and the pathologic response, the radiologic-pathologic correlation, and the disease-free survival. The subtypes HER2+ (62.1%) and TN (45.2%) had higher rates of complete radiologic response. The pathologic response was 65.5% in the HER2+ subtype, 38.1% in the TN subtype, 2.6% in the luminal A subtype, 8.2% in the luminal B HER2- subtype, and 31% in the luminal B HER2+ subtype. The rate of radiologic-pathologic correlation was significant in all subtypes, higher in TN and HER2 (Tau-b coefficients 0.805 and 0.717, respectively). Disease-free survival was higher in HER2+ (91.9±3.3 months) and lower in TN (69.5±6.3 months), with significant differences between the cases with poor and good radiologic responses (P=.040). Survival was greater in cases with good radiologic response, except in cases with luminal A subtype. MRI can be a useful tool that provides information about the evolution of breast cancer treated with neoadjuvant chemotherapy, which varies with the immunohistochemical subtype. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

Survival of free and microencapsulated human-derived oral probiotic Lactobacillus paracasei SD1 in orange and aloe vera juices

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Rawee Teanpaisan

2015-06-01

Full Text Available Microencapsulation was evaluated as a means of preserving Lactobacillus paracasei SD1, a human-derived strain with probiotic potential, in orange and aloe vera juices. The microencapsulation parameters included alginate concentration, calcium chloride concentration and hardening-time, and the efficacy of microencapsulation to preserve the survival of microencapsulated bacteria compared to free cells during exposure in fruit juices were determined. The results revealed that the viable count of free-cell form markedly decreased compared to microencapsulated form. The microencapsulation of 2% alginate (w/v and 0.05 M CaCl2 gave the best result to preserve the probiotic. It was found that viability of microencapsulated probiotic bacteria was significantly higher than free-cell in fruit juices during 8 weeks of storage time in the refrigerator. The potential probiotic trait related to inhibitory effect was not affected after microencapsulation process. In summary, the microencapsulation method may be an alternative way of preserving the viability of probiotic L. paracasei SD1.

46 CFR 117.130 - Stowage of survival craft.

Science.gov (United States)

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Stowage of survival craft. 117.130 Section 117.130... AND ARRANGEMENTS Survival Craft Arrangements and Equipment § 117.130 Stowage of survival craft. (a) Each survival craft must be: (1) Secured to the vessel by a painter with a float-free link permanently...

Clinical efficacy of preoperative chemotherapy with or without ifosfamide in patients with osteosarcoma of the extremity: meta-analysis of randomized controlled trials.

Science.gov (United States)

Su, Wenmei; Lai, Zhennan; Wu, Fenping; Lin, Yanming; Mo, Yanli; Yang, Zhixiong; Wu, Jiayuan

2015-02-01

Ifosfamide has been used in neoadjuvant chemotherapy since the mid-1980s. Although several studies have been conducted, the results remain controversial. Randomized controlled trials have an improved balance of confounding factors and reliable results. Thus, we performed a meta-analysis based on randomized controlled trials to gather more evidence of the effect of ifosfamide on neoadjuvant chemotherapy for patients with osteosarcoma of the extremity. An electronic search was conducted via the Internet retrieval system to identify eligible trials until September 2014. Odds ratios (ORs) and 95 % confidence interval (CI) were calculated to compare the results of ifosfamide and ifosfamide-free therapies. Four trials with a total of 1,378 patients were eligible for our meta-analysis. Overall, compared with neoadjuvant chemotherapy without ifosfamide, the use of ifosfamide had no advantage in terms of histological response to chemotherapy (cHR; OR 1.36; 95 % CI 0.90-2.03, P = 0.140), 5-year event-free survival (EFS; OR 1.16; 95 % CI 0.789-1.75, P = 0.464), and 5-year overall survival (OS; OR 1.06; 95 % CI 0.70-1.59, P = 0.794). However, improvement was noted in the rate of limb salvage (OR 4.06; 95 % CI 2.04-8.10, P chemotherapy with ifosfamide for patients with extremity osteosarcoma might not increase the cHR and exhibited no significant effect on either EFS or OS. However, ifosfamide therapy could significantly increase the rate of limb salvage for osteosarcoma of the extremity, which suggests that the preoperative use of ifosfamide could increase the success rate of limb salvage operation.

Designing sequence to control protein function in an EF-hand protein.

Science.gov (United States)

Bunick, Christopher G; Nelson, Melanie R; Mangahas, Sheryll; Hunter, Michael J; Sheehan, Jonathan H; Mizoue, Laura S; Bunick, Gerard J; Chazin, Walter J

2004-05-19

The extent of conformational change that calcium binding induces in EF-hand proteins is a key biochemical property specifying Ca(2+) sensor versus signal modulator function. To understand how differences in amino acid sequence lead to differences in the response to Ca(2+) binding, comparative analyses of sequence and structures, combined with model building, were used to develop hypotheses about which amino acid residues control Ca(2+)-induced conformational changes. These results were used to generate a first design of calbindomodulin (CBM-1), a calbindin D(9k) re-engineered with 15 mutations to respond to Ca(2+) binding with a conformational change similar to that of calmodulin. The gene for CBM-1 was synthesized, and the protein was expressed and purified. Remarkably, this protein did not exhibit any non-native-like molten globule properties despite the large number of mutations and the nonconservative nature of some of them. Ca(2+)-induced changes in CD intensity and in the binding of the hydrophobic probe, ANS, implied that CBM-1 does undergo Ca(2+) sensorlike conformational changes. The X-ray crystal structure of Ca(2+)-CBM-1 determined at 1.44 A resolution reveals the anticipated increase in hydrophobic surface area relative to the wild-type protein. A nascent calmodulin-like hydrophobic docking surface was also found, though it is occluded by the inter-EF-hand loop. The results from this first calbindomodulin design are discussed in terms of progress toward understanding the relationships between amino acid sequence, protein structure, and protein function for EF-hand CaBPs, as well as the additional mutations for the next CBM design.

SEMI-COMPETING RISKS ON A TRIVARIATE WEIBULL SURVIVAL MODEL

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Jenq-Daw Lee

2008-07-01

Full Text Available A setting of a trivairate survival function using semi-competing risks concept is proposed, in which a terminal event can only occur after other events. The Stanford Heart Transplant data is reanalyzed using a trivariate Weibull distribution model with the proposed survival function.

What doesn’t kill them makes them stronger: an association between elongation factor 1-α overdominance in the sea star Pisaster ochraceus and “sea star wasting disease”

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John P. Wares

2016-03-01

Full Text Available In recent years, a massive mortality event has killed millions of sea stars, of many different species, along the Pacific coast of North America. This disease event, known as ‘sea star wasting disease’ (SSWD, is linked to viral infection. In one affected sea star (Pisaster ochraceus, previous work had identified that the elongation factor 1-α locus (EF1A harbored an intronic insertion allele that is lethal when homozygous yet appears to be maintained at moderate frequency in populations through increased fitness for heterozygotes. The environmental conditions supporting this increased fitness are unknown, but overdominance is often associated with disease. Here, we evaluate populations of P. ochraceus to identify the relationship between SSWD and EF1A genotype. Our data suggest that there may be significantly decreased occurrence of SSWD in individuals that are heterozygous at this locus. These results suggest further studies are warranted to understand the functional relationship between diversity at EF1A and survival in P. ochraceus.

Cross-cultural adaptation and validity of the "Edmonton Frail Scale - EFS" in a Brazilian elderly sample Adaptación cultural y validez de la Edmonton Frail Scale - EFS en una muestra de ancianos brasileños Adaptação cultural e validade da Edmonton Frail Scale - EFS em uma amostra de idosos brasileiros

Directory of Open Access Journals (Sweden)

Suzele Cristina Coelho Fabrício-Wehbe

2009-12-01

Full Text Available This study aimed to assess the cross-cultural adaptation of the Edmonton Frail Scale (EFS and its validity in a Brazilian elderly sample. Translation and back-translation were performed, as well as discussion with professionals and elderly for conceptual equivalence, semantic validation and pre-test of the scale. The scale was applied to 137 elderly aged 65 years or older who lived in the community. In the know-groups validation of the frailty diagnosis between gender, age and cognitive deficit, elder elderly, female and with a cognitive deficit scored higher on the frailty diagnosis. A negative convergent correlation was found between the EFS and the Functional Independence Measure (FIM (-0.53, pEl objetivo de este estudio fue evaluar la adaptación cultural de la Edmonton Frail Scale (EFS y su validez en una muestra de ancianos brasileños. Fueron realizadas las etapas de traducción y retrotraducción, discusión con profesionales y ancianos para equivalencia conceptual, validación semántica y prueba piloto de la escala. El instrumento fue aplicado en 137 ancianos, con 65 años o más de edad, que vivían en la comunidad. En la validación de grupos conocidos, del diagnóstico de fragilidad entre sexo, edad y déficit cognitivo, los ancianos con edad más avanzada, sexo femenino y con déficit cognitivo tuvieron mayor puntuación en el diagnóstico de fragilidad. Hubo una correlación convergente negativa de la EFS con la Medida de Independencia Funcional (MIF (-0,53, pO objetivo deste estudo foi avaliar a adaptação cultural da Edmonton Frail Scale (EFS e sua validade em uma amostra de idosos brasileiros. Foram realizadas as etapas de tradução e retrotradução, discussão com profissionais e idosos para equivalência conceitual, validação semântica e pré-teste da escala. O instrumento foi aplicado em 137 idosos, com 65 anos ou mais de idade, que viviam na comunidade. Na validação de grupos conhecidos, do diagnóstico de

eEF1A Mediates the Nuclear Export of SNAG-Containing Proteins via the Exportin5-Aminoacyl-tRNA Complex

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José Manuel Mingot

2013-11-01

Full Text Available Exportin5 mediates the nuclear export of double-stranded RNAs, including pre-microRNAs, adenoviral RNAs, and tRNAs. When tRNAs are aminoacylated, the Exportin5-aminoacyl (aa-tRNA complex recruits and coexports the translation elongation factor eEF1A. Here, we show that eEF1A binds to Snail transcription factors when bound to their main target, the E-cadherin promoter, facilitating their export to the cytoplasm in association with the aa-tRNA-Exportin5 complex. Snail binds to eEF1A through the SNAG domain, a protein nuclear export signal present in several transcription factor families, and this binding is regulated by phosphorylation. Thus, we describe a nuclear role for eEF1A and provide a mechanism for protein nuclear export that attenuates the activity of SNAG-containing transcription factors.

Validation of Progression‐Free Survival as a Surrogate Endpoint for Overall Survival in Malignant Mesothelioma: Analysis of Cancer and Leukemia Group B and North Central Cancer Treatment Group (Alliance) Trials

Science.gov (United States)

Wang, Xiaoyi; Hodgson, Lydia; George, Stephen L.; Sargent, Daniel J.; Foster, Nate R.; Ganti, Apar Kishor; Stinchcombe, Thomas E.; Crawford, Jeffrey; Kratzke, Robert; Adjei, Alex A.; Kindler, Hedy L.; Vokes, Everett E.; Pang, Herbert

2017-01-01

Abstract Purpose. The aim of this study was to investigate whether progression‐free survival (PFS) can be considered a surrogate endpoint for overall survival (OS) in malignant mesothelioma. Materials and Methods. Individual data were collected from 15 Cancer and Leukemia Group B (615 patients) and 2 North Central Cancer Treatment Group (101 patients) phase II trials. The effects of 5 risk factors for OS and PFS, including age, histology, performance status (PS), white blood cell count, and European Organisation for Research and Treatment of Cancer (EORTC) risk score, were used in the analysis. Individual‐level surrogacy was assessed by Kendall's tau through a Clayton bivariate Copula survival (CBCS) model. Summary‐level surrogacy was evaluated via the association between logarithms of the hazard ratio (log HR)—log HROS and log HRPFS—measured in R2 from a weighted least‐square (WLS) regression model and the CBCS model. Results. The median PFS for all patients was 3.0 months (95% confidence interval [CI], 2.8–3.5 months) and the median OS was 7.2 months (95% CI, 6.5–8.0 months). Moderate correlations between PFS and OS were observed across all risk factors at the individual level, with Kendall's tau ranging from 0.46 to 0.47. The summary‐level surrogacy varied among risk factors. The Copula R2 ranged from 0.51 for PS to 0.78 for histology. The WLS R2 ranged from 0.26 for EORTC and PS to 0.67 for age. Conclusions. The analyses demonstrated low to moderate individual‐level surrogacy between PFS and OS. At the summary level, the surrogacy between PFS and OS varied significantly across different risk factors. With a short postprogression survival and a moderate correlation between PFS and OS, there is no evidence that PFS is a valid surrogate endpoint for OS in malignant mesothelioma. Implications for Practice. For better disease management and for more efficient clinical trial designs, it is important to know if progression‐free survival (PFS) is

Concurrent Chemoradiotherapy Improves Survival in Patients With Hypopharyngeal Cancer

Energy Technology Data Exchange (ETDEWEB)

Paximadis, Peter, E-mail: ppaximad@med.wayne.edu [Department of Radiation Oncology, Wayne State University, Detroit, MI (United States); Yoo, George; Lin, Ho-Sheng; Jacobs, John [Department of Otolaryngology, Barbara Ann Karmanos Cancer Institute, Detroit, MI (United States); Sukari, Ammar [Department of Medical Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI (United States); Dyson, Greg [Department of Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI (United States); Christensen, Michael; Kim, Harold [Department of Radiation Oncology, Wayne State University, Detroit, MI (United States)

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.

Survival of infants born to HIV-positive mothers, by feeding modality, in Rakai, Uganda.

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Joseph Kagaayi

Full Text Available BACKGROUND: Data comparing survival of formula-fed to breast-fed infants in programmatic settings are limited. We compared mortality and HIV-free of breast and formula-fed infants born to HIV-positive mothers in a program in rural, Rakai District Uganda. METHODOLOGY/PRINCIPAL FINDINGS: One hundred eighty two infants born to HIV-positive mothers were followed at one, six and twelve months postpartum. Mothers were given infant-feeding counseling and allowed to make informed choices as to whether to formula-feed or breast-feed. Eligible mothers and infants received antiretroviral therapy (ART if indicated. Mothers and their newborns received prophylaxis for prevention of mother-to-child HIV transmission (pMTCT if they were not receiving ART. Infant HIV infection was detected by PCR (Roche Amplicor 1.5 during the follow-up visits. Kaplan Meier time-to-event methods were used to compare mortality and HIV-free survival. The adjusted hazard ratio (Adjusted HR of infant HIV-free survival was estimated by Cox regression. Seventy-five infants (41% were formula-fed while 107 (59% were breast-fed. Exclusive breast-feeding was practiced by only 25% of breast-feeding women at one month postpartum. The cumulative 12-month probability of infant mortality was 18% (95% CI = 11%-29% among the formula-fed compared to 3% (95% CI = 1%-9% among the breast-fed infants (unadjusted hazard ratio (HR = 6.1(95% CI = 1.7-21.4, P-value < 0.01. There were no statistically significant differentials in HIV-free survival by feeding choice (86% in the formula-fed compared to 96% in breast-fed group (Adjusted RH = 2.8[95%CI = 0.67-11.7, P-value = 0.16] CONCLUSIONS/SIGNIFICANCE: Formula-feeding was associated with a higher risk of infant mortality than breastfeeding in this rural population. Our findings suggest that formula-feeding should be discouraged in similar African settings.

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

Science.gov (United States)

Poynor, Valerie; Kottas, Athanasios

2018-01-19

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

Prospective, Randomized, Double-Blind, Phase III Clinical Trial of Anti-T-Lymphocyte Globulin to Assess Impact on Chronic Graft-Versus-Host Disease-Free Survival in Patients Undergoing HLA-Matched Unrelated Myeloablative Hematopoietic Cell Transplantation.

Science.gov (United States)

Soiffer, Robert J; Kim, Haesook T; McGuirk, Joseph; Horwitz, Mitchell E; Johnston, Laura; Patnaik, Mrinal M; Rybka, Witold; Artz, Andrew; Porter, David L; Shea, Thomas C; Boyer, Michael W; Maziarz, Richard T; Shaughnessy, Paul J; Gergis, Usama; Safah, Hana; Reshef, Ran; DiPersio, John F; Stiff, Patrick J; Vusirikala, Madhuri; Szer, Jeff; Holter, Jennifer; Levine, James D; Martin, Paul J; Pidala, Joseph A; Lewis, Ian D; Ho, Vincent T; Alyea, Edwin P; Ritz, Jerome; Glavin, Frank; Westervelt, Peter; Jagasia, Madan H; Chen, Yi-Bin

2017-12-20

Purpose Several open-label randomized studies have suggested that in vivo T-cell depletion with anti-T-lymphocyte globulin (ATLG; formerly antithymocyte globulin-Fresenius) reduces chronic graft-versus-host disease (cGVHD) without compromising survival. We report a prospective, double-blind phase III trial to investigate the effect of ATLG (Neovii Biotech, Lexington, MA) on cGVHD-free survival. Patients and Methods Two hundred fifty-four patients 18 to 65 years of age with acute leukemia or myelodysplastic syndrome who underwent myeloablative HLA-matched unrelated hematopoietic cell transplantation (HCT) were randomly assigned one to one to placebo (n =128 placebo) or ATLG (n = 126) treatment at 27 sites. Patients received either ATLG or placebo 20 mg/kg per day on days -3, -2, -1 in addition to tacrolimus and methotrexate as GVHD prophylaxis. The primary study end point was moderate-severe cGVHD-free survival. Results Despite a reduction in grade 2 to 4 acute GVHD (23% v 40%; P = .004) and moderate-severe cGVHD (12% v 33%; P < .001) in ATLG recipients, no difference in moderate-severe cGVHD-free survival between ATLG and placebo was found (2-year estimate: 48% v 44%, respectively; P = .47). Both progression-free survival (PFS) and overall survival (OS) were lower with ATLG (2-year estimate: 47% v 65% [ P = .04] and 59% v 74% [ P = .034], respectively). Multivariable analysis confirmed that ATLG was associated with inferior PFS (hazard ratio, 1.55; 95% CI, 1.05 to 2.28; P = .026) and OS (hazard ratio, 1.74; 95% CI, 1.12 to 2.71; P = .01). Conclusion In this prospective, randomized, double-blind trial of ATLG in unrelated myeloablative HCT, the incorporation of ATLG did not improve moderate-severe cGVHD-free survival. Moderate-severe cGVHD was significantly lower with ATLG, but PFS and OS also were lower. Additional analyses are needed to understand the appropriate role for ATLG in HCT.

Active smoking may negatively affect response rate, progression-free survival, and overall survival of patients with metastatic renal cell carcinoma treated with sunitinib.

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

2014-01-01

Obesity, smoking, hypertension, and diabetes are risk factors for renal cell carcinoma development. Their presence has been associated with a worse outcome in various cancers. We sought to determine their association with outcome of sunitinib treatment in metastatic renal cell carcinoma (mRCC). An international multicenter retrospective study of sunitinib-treated mRCC patients was performed. Multivariate analyses were performed to determine the association between outcome and the pretreatment status of smoking, body mass index, hypertension, diabetes, and other known prognostic factors. Between 2004 and 2013, 278 mRCC patients were treated with sunitinib: 59 were active smokers, 67 were obese, 73 were diabetic, and 165 had pretreatment hypertension. Median progression-free survival (PFS) was 9 months, and overall survival (OS) was 22 months. Factors associated with PFS were smoking status (past and active smokers: hazard ratio [HR]: 1.17, p = .39; never smokers: HR: 2.94, p non-clear cell histology (HR: 1.62, p = .011), pretreatment neutrophil-to-lymphocyte ratio >3 (HR: 3.51, p smoking status (past and active smokers: HR: 1.25, p = .29; never smokers: HR: 2.7, p 3 (HR: 2.95, p smoking may negatively affect the PFS and OS of sunitinib-treated mRCC. Clinicians should consider advising patients to quit smoking at initiation of sunitinib treatment for mRCC.

Impaired left ventricular systolic function reserve limits cardiac output and exercise capacity in HFpEF patients due to systemic hypertension.

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Henein, Michael; Mörner, Stellan; Lindmark, Krister; Lindqvist, Per

2013-09-30

Heart failure (HF) patients with preserved left ventricular (LV) ejection fraction (EF) (HFpEF) due to systemic hypertension (SHT) are known to have limited exercise tolerance. Despite having normal EF at rest, we hypothesize that these patients have abnormal systolic function reserve limiting their exercise capacity. Seventeen patients with SHT (mean age 68 ± 9 years) but no valve disease and 14 healthy individuals (mean age of 65 ± 10 years) underwent resting and peak exercise echocardiography using conventional, tissue Doppler and speckle tracking techniques. The differences between resting and peak exercise values were also analyzed (Δ). Exercise capacity was determined as the workload divided by body surface area. Resting values for left atrial (LA) volume/BSA (r=-0.66, pexercise capacity. LVEF increased during exercise in normals (mean Δ EF=10 ± 8%) but failed to do so in patients (mean Δ EF=0.6 ± 9%, pexercise in patients, to the same extent as it did in normals (0.2 ± 0.2 vs. 0.6 ± 0.3 1/s, pexercise (Δ) in LV lateral wall systolic velocity from tissue Doppler (s') (0.71, pexercise capacity independent of changes in heart rate. HFpEF patients with hypertensive LV disease have significantly limited exercise capacity which is related to left atrial enlargement as well as compromised LV systolic function at the time of the symptoms. The limited myocardial systolic function reserve seems to be underlying important explanation for their limited exercise capacity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Prognostic impact of pre-transplantation computed tomography and 67gallium scanning in chemosensitive diffuse large B cell lymphoma patients undergoing hematopoietic stem-cell transplantation

International Nuclear Information System (INIS)

Escobar, Ignacio G.; Alonso, Pilar T.; Barrigon, Dolores C.; Perez-Simon, Jose A.; Mateos Manteca, Maria V.; San Miguel Izquierdo, Jesus F.

2008-01-01

In the present study, we evaluated computed tomography (CT) and 67 gallium scanning ( 67 Ga scan) pre-transplant as prognostic factors for overall survival (OS) and event-free survival (EFS) in patients with diffuse large B cell lymphoma, undergoing high-dose chemotherapy and stem-cell transplantation. Forty-two patients were included. Of these, 9 (21%) had both positive CT and 67 Ga scans, 17 (41%) negative results with both techniques, and 16 (38%) positive CT/negative 67 Ga scan. Whole-body planar imaging and single-photon emission computed tomography (SPECT) were performed 72 h after an intravenous administration of 67 Ga citrate measuring between 7 mCi and 10 mCi (259-370 MBq). Patients with positive CT/positive 67 Ga scan had a significantly worse EFS and OS at 5 years than those with negative 67 Ga scan regardless of whether it was associated with a positive or a negative CT scan (29% and 16% vs. 81% and 93% vs. 88% and 100%, respectively, P 67 Ga scan and those with positive CT/negative 67 Ga scan, with an EFS and OS at 5 years of 88% versus 81% and 100% versus 93%, respectively. In multivariate analysis, the presence of a pre-transplant positive CT/ 67 Ga scans adversely influenced both EFS and OS [HR 8, 95% confidence interval (CI) (1.4-38), P=0.03 and HR 2; 95% CI (1.3-8), P=0.02, respectively]. 67 Ga scan helps to identify, in the pre-transplant evaluation, two groups with a different outcome: one group of patients with positive CT and negative 67 Ga scans pre-transplant, who showed a favorable outcome with a low rate of relapse, and the other group of patients with both positive CT and 67 Ga scans pre-transplant, who showed a poor prognosis and did not benefit from autologous stem-cell transplantation. They should have been offered other therapeutic strategies. (author)

Neuroblastoma mRNAs predict outcome in children with stage 4 neuroblastoma: a European HR-NBL1/SIOPEN study.

Science.gov (United States)

Viprey, Virginie F; Gregory, Walter M; Corrias, Maria V; Tchirkov, Andrei; Swerts, Katrien; Vicha, Ales; Dallorso, Sandro; Brock, Penelope; Luksch, Roberto; Valteau-Couanet, Dominique; Papadakis, Vassilios; Laureys, Genevieve; Pearson, Andrew D; Ladenstein, Ruth; Burchill, Susan A

2014-04-01

To evaluate the hypothesis that detection of neuroblastoma mRNAs by reverse transcriptase quantitative polymerase chain reaction (RTqPCR) in peripheral blood (PB) and bone marrow aspirates (BM) from children with stage 4 neuroblastoma are clinically useful biomarkers of risk. RTqPCR for paired-like homeobox 2b (PHOX2B), tyrosine hydroxylase (TH), and doublecortin (DCX) mRNA in PB and BM of children enrolled onto the High-Risk Neuroblastoma Trial-1 of the European Society of Pediatric Oncology Neuroblastoma Group (HR-NBL1/SIOPEN) was performed at diagnosis and after induction therapy. High levels of TH, PHOX2B, or DCX mRNA in PB or BM at diagnosis strongly predicted for worse event-free survival (EFS) and overall survival (OS) in a cohort of 290 children. After induction therapy, high levels of these mRNAs predicted worse EFS and OS in BM but not in PB. Combinations of mRNAs in BM did not add to the predictive power of any single mRNA. However, in the original (n = 182) and validation (n = 137) PB cohorts, high TH (log10TH > 0.8) or high PHOX2B (log10PHOX2B > 0.28) identify 19% of children as ultrahigh risk, with 5-year EFS and OS rates of 0%; OS rate was 25% (95% CI, 16% to 36%) and EFS rate was 38% (95% CI, 28% to 49%) in the remaining children. The magnitude of reduction in mRNA level between diagnosis and postinduction therapy in BM or PB was not of additional predictive value. High levels of TH and PHOX2B mRNA in PB at diagnosis objectively identify children with ultrahigh-risk disease who may benefit from novel treatment approaches. The level of TH, PHOX2B, and DCX mRNA in BM and/or PB at diagnosis might contribute to an algorithm to improve stratification of children for treatment.

Neurite outgrowth mediated by translation elongation factor eEF1A1: a target for antiplatelet agent cilostazol.

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Kenji Hashimoto

Full Text Available Cilostazol, a type-3 phosphodiesterase (PDE3 inhibitor, has become widely used as an antiplatelet drug worldwide. A recent second Cilostazol Stroke Prevention Study demonstrated that cilostazol is superior to aspirin for prevention of stroke after an ischemic stroke. However, its precise mechanisms of action remain to be determined. Here, we report that cilostazol, but not the PDE3 inhibitors cilostamide and milrinone, significantly potentiated nerve growth factor (NGF-induced neurite outgrowth in PC12 cells. Furthermore, specific inhibitors for the endoplasmic reticulum protein inositol 1,4,5-triphosphate (IP(3 receptors and several common signaling pathways (PLC-γ, PI3K, Akt, p38 MAPK, and c-Jun N-terminal kinase (JNK, and the Ras/Raf/ERK/MAPK significantly blocked the potentiation of NGF-induced neurite outgrowth by cilostazol. Using a proteomics analysis, we identified that levels of eukaryotic translation elongation factor eEF1A1 protein were significantly increased by treatment with cilostazol, but not cilostamide, in PC12 cells. Moreover, the potentiating effects of cilostazol on NGF-induced neurite outgrowth were significantly antagonized by treatment with eEF1A1 RNAi, but not the negative control of eEF1A1. These findings suggest that eEF1A1 and several common cellular signaling pathways might play a role in the mechanism of cilostazol-induced neurite outgrowth. Therefore, agents that can increase the eEF1A1 protein may have therapeutic relevance in diverse conditions with altered neurite outgrowth.

Estimating Finite Source Effects in Microlensing Events due to Free-Floating Planets with the Euclid Survey

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Lindita Hamolli

2015-01-01

Full Text Available In recent years free-floating planets (FFPs have drawn a great interest among astrophysicists. Gravitational microlensing is a unique and exclusive method for their investigation which may allow obtaining precious information about their mass and spatial distribution. The planned Euclid space-based observatory will be able to detect a substantial number of microlensing events caused by FFPs towards the Galactic bulge. Making use of a synthetic population algorithm, we investigate the possibility of detecting finite source effects in simulated microlensing events due to FFPs. We find a significant efficiency for finite source effect detection that turns out to be between 20% and 40% for a FFP power law mass function index in the range [0.9, 1.6]. For many of such events it will also be possible to measure the angular Einstein radius and therefore constrain the lens physical parameters. These kinds of observations will also offer a unique possibility to investigate the photosphere and atmosphere of Galactic bulge stars.

Applied survival analysis using R

CERN Document Server

Moore, Dirk F

2016-01-01

Applied Survival Analysis Using R covers the main principles of survival analysis, gives examples of how it is applied, and teaches how to put those principles to use to analyze data using R as a vehicle. Survival data, where the primary outcome is time to a specific event, arise in many areas of biomedical research, including clinical trials, epidemiological studies, and studies of animals. Many survival methods are extensions of techniques used in linear regression and categorical data, while other aspects of this field are unique to survival data. This text employs numerous actual examples to illustrate survival curve estimation, comparison of survivals of different groups, proper accounting for censoring and truncation, model variable selection, and residual analysis. Because explaining survival analysis requires more advanced mathematics than many other statistical topics, this book is organized with basic concepts and most frequently used procedures covered in earlier chapters, with more advanced topics...

Characterization of novel peptide-specific antibodies against the translation elongation factor eEF1A2 and their application for cancer research

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Shalak V. F.

2014-11-01

Full Text Available Aim. We intend to characterize the new peptide-specific antibodies against the isoform 2 of translation elongation factor 1A (eEF1A2 and determine its presence in the postoperative samples of human breast, lung and stomach tumor tissues. Methods. The analysis of antibody specificity was performed by enzyme-linked immunosorbent assay, immunoblotting and immunohistochemistry. Immunoblotting and immunohistochemistry were used for the determination of the eEF1A2 in the human tumor samples, as well as in the samples of normal tissues surrounding tumors. Results. The antibodies obtained against the eEF1A2 specifically recognized this protein in the cell extracts and histological sections and did not cross-react with the elongation factor 1A isoform 1. eEF1A2 was revealed in the postoperative samples of breast, lung and stomach tumors as well as in the putative normal tissues surrounding tumors. Conclusions. The antibodies obtained against eEF1A2 are highly specific for the antigen and can be used for the immunological studies of tumors.

Influence of complete administration of adjuvant chemotherapy cycles on overall and disease-free survival in locally advanced rectal cancer: post hoc analysis of a randomized, multicenter, non-inferiority, phase 3 trial.

Science.gov (United States)

Sandra-Petrescu, Flavius; Herrle, Florian; Burkholder, Iris; Kienle, Peter; Hofheinz, Ralf-Dieter

2018-04-03

A randomized trial demonstrated that capecitabine is at least as effective as fluorouracil in the adjuvant treatment of patients with locally advanced rectal cancer. However, not all patients receive all planned cycles of chemotherapy. Therefore it is of interest how complete or partial administration of chemotherapy influences oncological outcome. A post hoc analysis of a trial with 401 randomized patients, nine being excluded because of missing data, was performed. 392 patients (197 - capecitabine, 195 - fluorouracil) could be analyzed regarding the number of administered adjuvant chemotherapy cycles. In the subgroup of 361 patients with an overall survival of at least six months, five-year overall and disease-free survival were analyzed in respect to completion (complete vs. incomplete) of chemotherapy cycles. Survival rates and curves were calculated and compared using the log-rank test. The effect of completion of chemotherapy was adjusted for relevant confounding factors. Two hundred fifty-one (64.0%) of analyzed patients received all postoperative scheduled cycles. Five-year overall survival was significantly better in these patients compared to the incomplete group (76.0 vs. 60.6%, p cycles. Five-year overall survival was also significantly better than in the incomplete group (76.0 vs. 66.4%, p = 0.0073). Five-year disease free survival was numerically better (64.9 vs. 58.7%, p = 0.0646; HR [not all cycles vs. all cycles] = 1.42 95% CI: [0.98, 2.07]). Cox regression models show a non-significant better OS (p = 0.061) and DFS (p = 0.083), if chemotherapy cycles were administered completely. Complete administration of chemotherapy cycles was associated with improved five-year overall and disease-free survival in patients with locally advanced rectal cancer.

Development of the finite element method in the thermal field. TRIO-EF software for thermal and radiation analysis

International Nuclear Information System (INIS)

Casalotti, N.; Magnaud, J.P.

1989-01-01

The possibilities of the TRIO-EF software in the thermal field are presented. The TRIO-EF is a computer program based on the finite element method and used for three-dimensional incompressible flow analysis. It enables the calculation of three-dimensional heat transfer and the fluid/structure analysis. The geometrically complex radiative reactor systems are taken into account in the form factor calculation. The implemented algorithms are described [fr

Endogenous TSH levels at the time of 131I ablation do not influence ablation success, recurrence-free survival or differentiated thyroid cancer-related mortality

International Nuclear Information System (INIS)

Vrachimis, Alexis; Riemann, Burkhard; Maeder, Uwe; Reiners, Christoph; Verburg, Frederik A.

2016-01-01

Based on a single older study it is established dogma that TSH levels should be ≥30 mU/l at the time of postoperative 131 I ablation in differentiated thyroid cancer (DTC) patients. We sought to determine whether endogenous TSH levels, i.e. after levothyroxine withdrawal, at the time of ablation influence ablation success rates, recurrence-free survival and DTC-related mortality. A total of 1,873 patients without distant metastases referred for postoperative adjuvant 131 I therapy were retrospectively included from 1991 onwards. Successful ablation was defined as stimulated Tg <1 μg/l. Age, gender and the presence of lymph node metastases were independent determinants of TSH levels at the time of ablation. TSH levels were not significantly related to ablation success rates (p = 0.34), recurrence-free survival (p = 0.29) or DTC -elated mortality (p = 0.82), but established risk factors such as T-stage, lymph node metastases and age were. Ablation was successful in 230 of 275 patients (83.6 %) with TSH <30 mU/l and in 1,359 of 1,598 patients (85.0 %) with TSH ≥30 mU/l. The difference was not significant (p = 0.55). Of the whole group of 1,873 patients, 21 had recurrent disease. There were no significant differences in recurrence rates between patients with TSH <30 mU/l and TSH ≥30 mU/l (p = 0.16). Ten of the 1,873 patients died of DTC. There were no significant differences in DTC-specific survival between patients with TSH <30 mU/l and TSH ≥30 mU/l (p = 0.53). The precise endogenous TSH levels at the time of 131 I ablation are not related to the ablation success rates, recurrence free survival and DTC related mortality. The established dogma that TSH levels need to be ≥30 mU/l at the time of 131 I ablation can be discarded. (orig.)

The eukaryotic translation elongation factor eEF1A2 induces neoplastic properties and mediates tumorigenic effects of ZNF217 in precursor cells of human ovarian carcinomas

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Sun, Yu; Wong, Nicholas; Guan, Yinghui; Salamanca, Clara M.; Cheng, Jung Chien; Lee, Jonathan M.; Gray, Joe W.; Auersperg, Nelly

2008-04-25

Ovarian epithelial carcinomas (OEC) frequently exhibit amplifications at the 20q13 locus which is the site of several oncogenes, including the eukaryotic elongation factor EEF1A2 and the transcription factor ZNF217. We reported previously that overexpressed ZNF217 induces neoplastic characteristics in precursor cells of OEC. Unexpectedly, ZNF217, which is a transcriptional repressor, enhanced expression of eEF1A2. In this study, array comparative genomic hybridization, single nucleotide polymorphism and Affymetrix analysis of ZNF217-overexpressing cell lines confirmed consistently increased expression of eEF1A2 but not of other oncogenes, and revealed early changes in EEF1A2 gene copy numbers and increased expression at crisis during immortalization. We defined the influence of eEF1A2 overexpression on immortalized ovarian surface epithelial cells, and investigated interrelationships between effects of ZNF217 and eEF1A2 on cellular phenotypes. Lentivirally induced eEF1A2 overexpression caused delayed crisis, apoptosis resistance and increases in serum-independence, saturation densities, and anchorage independence. siRNA to eEF1A2 reversed apoptosis resistance and reduced anchorage independence in eEF1A2-overexpressing lines. Remarkably, siRNA to eEF1A2 was equally efficient in inhibiting both anchorage independence and resistance to apoptosis conferred by ZNF217 overexpression. Our data define neoplastic properties that are caused by eEF1A2 in nontumorigenic ovarian cancer precursor cells, and suggest that eEF1A2 plays a role in mediating ZNF217-induced neoplastic progression.

A safe potential juice clarifying pectinase from Trichoderma viride EF-8 utilizing Egyptian onion skins

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Abdel-Mohsen S. Ismail

2016-06-01

Full Text Available The production of a notable, safe and highly active pectinase by the local fungal strain Trichoderma viride EF-8 utilizing the abundant pigmented Egyptian onion (Allium cepa L. skins (6.5%, w/v was achieved in 4 days submerged fermentation (SMF cultures, at temperature and pH of 30 °C and 4.0, respectively. The indigenously produced pectinase was partially purified by 50% batch ethanol precipitation and its general properties were studied following the standard procedures. The lyophilized enzyme preparation was free of any ochra or aflatoxins. The optimum conditions for the partially purified enzyme form were 2 mg/mL and 1% (w/v enzyme protein and substrate (citrus pectin concentrations, reaction pH and temperature of 7.0 and 40 °C, respectively. The results presented the low cost onion skins waste as the major substrate for the fungal pectinase production and its subsequent use in perfect fruit (apple, lemon and orange juices clarification with remarkable stability during and after this process, which certainly enhance fruit juices processing in the tropics.

Progressive rise in red blood cell distribution width predicts mortality and cardiovascular events in end-stage renal disease patients.

Science.gov (United States)

Yoon, Hye Eun; Kim, Sung Jun; Hwang, Hyeon Seok; Chung, Sungjin; Yang, Chul Woo; Shin, Seok Joon

2015-01-01

Red blood cell distribution width (RDW) is a robust marker of adverse clinical outcomes in various populations. However, the clinical significance of a progressive rise in RDW is undetermined in end-stage renal disease (ESRD) patients. The purpose of this study was to determine the prognostic importance of a change in RDW in ESRD patients. Three hundred twenty-six incident dialysis patients were retrospectively analyzed. Temporal changes in RDW during 12 months after dialysis initiation were assessed by calculating the coefficients by linear regression. Patients were divided into two groups: an RDW-decreased group who had negative coefficient values (n = 177) and an RDW-increased group who had positive values (n = 149). The associations between rising RDW and mortality and cardiovascular (CV) events were investigated. During a median follow-up of 2.7 years (range, 1.0-7.7 years), 75 deaths (24.0%) and 60 non-fatal CV events (18.4%) occurred. The event-free survival rate for the composite of end-points was lower in the RDW-increased group (P = 0.004). After categorizing patients according to baseline RDW, the event-free survival rate was lowest in patients with a baseline RDW >14.9% and increased RDW, and highest in patients with a baseline RDW ≤14.9% and decreased RDW (P = 0.02). In multivariate analysis, rising RDW was independently associated with the composite of end-points (hazard ratio = 1.75, P = 0.007), whereas the baseline RDW was not. This study shows that a progressive rise in RDW independently predicted mortality and CV events in ESRD patients. Rising RDW could be an additive predictor for adverse CV outcomes ESRD patients.

Interaction between the cellular protein eEF1A and the 3'-terminal stem-loop of West Nile virus genomic RNA facilitates viral minus-strand RNA synthesis.

Science.gov (United States)

Davis, William G; Blackwell, Jerry L; Shi, Pei-Yong; Brinton, Margo A

2007-09-01

RNase footprinting and nitrocellulose filter binding assays were previously used to map one major and two minor binding sites for the cell protein eEF1A on the 3'(+) stem-loop (SL) RNA of West Nile virus (WNV) (3). Base substitutions in the major eEF1A binding site or adjacent areas of the 3'(+) SL were engineered into a WNV infectious clone. Mutations that decreased, as well as ones that increased, eEF1A binding in in vitro assays had a negative effect on viral growth. None of these mutations affected the efficiency of translation of the viral polyprotein from the genomic RNA, but all of the mutations that decreased in vitro eEF1A binding to the 3' SL RNA also decreased viral minus-strand RNA synthesis in transfected cells. Also, a mutation that increased the efficiency of eEF1A binding to the 3' SL RNA increased minus-strand RNA synthesis in transfected cells, which resulted in decreased synthesis of genomic RNA. These results strongly suggest that the interaction between eEF1A and the WNV 3' SL facilitates viral minus-strand synthesis. eEF1A colocalized with viral replication complexes (RC) in infected cells and antibody to eEF1A coimmunoprecipitated viral RC proteins, suggesting that eEF1A facilitates an interaction between the 3' end of the genome and the RC. eEF1A bound with similar efficiencies to the 3'-terminal SL RNAs of four divergent flaviviruses, including a tick-borne flavivirus, and colocalized with dengue virus RC in infected cells. These results suggest that eEF1A plays a similar role in RNA replication for all flaviviruses.

Can histopathologic assessment of circumferential margin after preoperative pelvic chemoradiotherapy for T3-T4 rectal cancer predict for 3-year disease-free survival?

International Nuclear Information System (INIS)

Mawdsley, Suzannah; Glynne-Jones, Rob; Grainger, Juliet; Richman, Paul; Makris, Andreas; Harrison, Mark; Ashford, Richard; Harrison, Richard A.; Osborne, Melanie; Livingstone, Jeremy I.; MacDonald, Peter; Mitchell, Ian C.; Meyrick-Thomas, John; Northover, John; Windsor, Alastair; Novell, Richard; Wallace, Marina

2005-01-01

Purpose: This study set out to determine the impact of a positive circumferential resection margin (CRM) (R1-R2) and pathologic downstaging on local recurrence and survival in patients with borderline resectable or unresectable rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy (CRT). Methods and Materials: A total of 150 patients with locally advanced rectal cancer were treated with long-course neoadjuvant CRT using low-dose folinic acid and 5-fluorouracil. CRT was followed 6-12 weeks later by surgical excision. The CRM rate and incidence, site, and pattern of local and systemic recurrences were recorded. The median follow-up was 25 months. Results: The overall median survival was 37 months, with a 5-year overall survival rate of 34%. Of the 150 patients, 122 underwent curative resection; 12% had a complete pathologic response, and downstaging to pT1-T2 occurred in an additional 16%. A negative CRM (R0) was achieved in 65% overall (98 of 150). Local recurrence occurred in 10% of those with R0 resection and 62% of those with R1-R2 resections. Distant metastases occurred in 29% of those with R0 resections and 75% of those with R1-R2 resections. The 3-year disease-free and 3-year overall survival rate was 9% and 25% and 52% and 64%, respectively, for patients with and without a histologically positive CRM. Conclusion: After 5-fluorouracil-based CRT, a positive CRM predicted for a high risk of subsequent local recurrence and a 3-year disease-free survival rate of only 9%. For this reason, the CRM should be considered a major prognostic factor and should be validated in future trials as an early alternative clinical endpoint

Treatment results of the Tokai-POSG 8610HR pilot protocol for children with high-risk acute lymphoblastic leukemia

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Hongo, Teruaki; Inoue, Noriko [Hamamatsu Medical Univ., Shizuoka (Japan); Horibe, Keizo [and others

1997-10-01

We reported the treatment results of Tokai-POSG 8610HR pilot protocol for children with high-risk acute lymphoblastic leukemia (ALL). From Oct. 1986 to Jan. 1991, 43 eligible children were enrolled, who had one or more following high-risk factors: age{>=}10 years old, initial white blood cell count (WBC) of 50,000/{mu}l or more, and extramedullary leukemia. All patients received induction therapy consisting of vincristine, dexamethasone, cyclophosphamide and daunorubicin, followed by central nervous system prophylaxis by 24 Gy cranial irradiation, consolidation therapy and cyclic maintenance by multidrugs for 3 years after diagnosis. Complete remission was achieved in 39 patients. The 5-year event-free survival (EFS) rate was 72.6{+-}7.1%. The only factor of an adverse association with EFS was a initial WBC of 10,000/{mu}l or more (p=0.002) in the 24 patients who were 10 years old or over. The factors related to a negative survival were male gender (p=0.031) and an initial WBC of 10,000/{mu}l or more (p=0.0012) in 43 patients. The major toxicities of the therapy were pancreatitis and allergic reaction due to{sub L}-ASP administration, and growth hormone deficiency due to cranial irradiation. Tokai 8610HR pilot protocol was a promising regimen, but further intensive chemotherapy was needed for improvement or the prognosis of the older patients with high initial WBC greater than 10,000/{mu}l. (author)

Glypican-3 mRNA expression level in Wilms tumor: correlation with histological type, stage, and outcome.

Science.gov (United States)

Wari, Md Nahidul; Vallonthaiel, Archana George; Ahmed, Aijaz; Saxena, Deepali; Iyer, Venkateswaran K; Mathur, Sandeep R; Agarwala, Sandeep; Bakhshi, Sameer; Srinivas, V; Chattopadhyaya, P; Sharma, Arundhati; Gupta, S Datta; Dinda, Amit

2017-06-01

To correlate expression of Glypican-3 in Wilms tumor with histopathology, stage, and outcome. Glypican-3 mRNA expression by real-time PCR on tumor and normal germline samples from 75 fresh nephrectomies for Wilms tumor with fold change after normalization against GAPDH was compared. Survival analysis for event-free and overall survival (EFS, OS) with 2-year follow-up for Glypican-3 overexpression (>1.5 times) and clinicopathological parameters was performed. Glypican-3 was overexpressed in 37/75 (49.3%). It was overexpressed in 77% (10/13) cases with blastema predominance or anaplastic histology, as compared to 44% of other histologies (27/62) (p = 0.03). OS was 73 and 93%, respectively (p = 0.016), for those with and without GPC-3 overexpression. EFS was not significantly different with Glypican-3 overexpression (p = 0.11). All 5 deaths among blastema predominant tumors and 4/5 deaths among triphasic tumors had overexpressed Glypican-3. Most deaths in Stage IV, Stage III, and Stage I + II (5/7, 3/3, 1/1) had GPC-3 overexpression. On multivariate analysis, only histology and stage were found to have independent prognostic value. Glypican-3 overexpression in Wilms tumor correlates with poor OS on univariate analysis. However, only histology and stage have independent prognostic value. Glypican-3 levels may help to stratify intermediate outcome histology (triphasic) and Stage III Wilms tumors.

Treatment results of the Tokai-POSG 8610HR pilot protocol for children with high-risk acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Hongo, Teruaki; Inoue, Noriko; Horibe, Keizo

1997-01-01

We reported the treatment results of Tokai-POSG 8610HR pilot protocol for children with high-risk acute lymphoblastic leukemia (ALL). From Oct. 1986 to Jan. 1991, 43 eligible children were enrolled, who had one or more following high-risk factors: age≥10 years old, initial white blood cell count (WBC) of 50,000/μl or more, and extramedullary leukemia. All patients received induction therapy consisting of vincristine, dexamethasone, cyclophosphamide and daunorubicin, followed by central nervous system prophylaxis by 24 Gy cranial irradiation, consolidation therapy and cyclic maintenance by multidrugs for 3 years after diagnosis. Complete remission was achieved in 39 patients. The 5-year event-free survival (EFS) rate was 72.6±7.1%. The only factor of an adverse association with EFS was a initial WBC of 10,000/μl or more (p=0.002) in the 24 patients who were 10 years old or over. The factors related to a negative survival were male gender (p=0.031) and an initial WBC of 10,000/μl or more (p=0.0012) in 43 patients. The major toxicities of the therapy were pancreatitis and allergic reaction due to L -ASP administration, and growth hormone deficiency due to cranial irradiation. Tokai 8610HR pilot protocol was a promising regimen, but further intensive chemotherapy was needed for improvement or the prognosis of the older patients with high initial WBC greater than 10,000/μl. (author)

Favorable outcome in non-infant children with MLL-AF4-positive acute lymphoblastic leukemia: a report from the Tokyo Children's Cancer Study Group.

Science.gov (United States)

Tomizawa, Daisuke; Kato, Motohiro; Takahashi, Hiroyuki; Fujimura, Junya; Inukai, Takeshi; Fukushima, Takashi; Kiyokawa, Nobutaka; Koh, Katsuyoshi; Manabe, Atsushi; Ohara, Akira

2015-11-01

Unlike acute lymphoblastic leukemia (ALL) in infants, MLL gene rearrangement (MLL-r) is rare in ALL children (≥1 year old). The outcome and optimal treatment options for MLL-r ALL remain controversial. Among the 1827 children enrolled in the Tokyo Children's Cancer Study Group ALL studies L95-14, L99-15, L99-1502, L04-16, and L07-1602 (1995-2009), 25 MLL-r ALL patients (1.3 %) were identified. Their median age and leukocyte count at diagnosis was 2 years old (range 1-15 years) and 27,690/μL (range 1800-1,113,000/μL), respectively. All but one patient achieved complete remission (CR) after induction therapy, and 19 underwent allogeneic hematopoietic stem cell transplantation (HSCT) in first CR according to the protocol. The 5-year event-free survival (EFS) and overall survival (OS) rate were 60.0 % [standard error (SE), 9.7 %] and 64.0 % (SE 9.6 %), respectively. Notably, 9/12 cases with MLL-AF4-positive ALL are alive in continuous CR with a 75.0 % (SE 12.5 %) EFS rate. The causes of treatment failure were as follows: one induction failure, five relapses, and five transplant-related deaths. With intensive chemotherapy and allogeneic HSCT, favorable outcome of children (≥1 year old) with MLL-AF4-positive ALL was observed. However, considering the risk of acute and late toxicities associated with HSCT, its indication should be restricted.