WorldWideScience

Sample records for survival responses final

  1. Role of Cell Cycle Regulation and MLH1, A Key DNA Mismatch Repair Protein, In Adaptive Survival Responses. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    David A. Boothman

    1999-08-11

    Due to several interesting findings on both adaptive survival responses (ASRs) and DNA mismatch repair (MMR), this grant was separated into two discrete Specific Aim sets (each with their own discrete hypotheses). The described experiments were simultaneously performed.

  2. Surviving Sepsis: Taming a Deadly Immune Response

    Science.gov (United States)

    ... Issues Subscribe August 2014 Print this issue Surviving Sepsis Taming a Deadly Immune Response En español Send ... Mouth? Looking at Lupus Wise Choices Signs of Sepsis Sepsis can be hard to spot, because its ...

  3. Emissions scenario: a final response

    Energy Technology Data Exchange (ETDEWEB)

    Gruebler, A.; Nakicenovic, N.; Alcamo, J. (and others)

    2004-01-01

    This note is a final response to the debate raised by Mr Castles and Mr Henderson (for brevity, we refer here to the two authors simply as C and H) in this Journal (vol. 14, no. 2 and 3, and no. 4) on the issue of economic growth in developing countries in some of the emissions scenarios published in the IPCC Special Report on Emissions Scenarios (SRES) (Nakicenovic et al., 2000). We first outline areas of agreement and then the remaining areas of disagreement. Two important areas of agreement have emerged from the debate according to our view. First, both parties agree that scenarios assuming a conditional convergence in income levels, i.e., a higher growth in per capita income in poorer countries when compared to countries with higher levels of affluence, are both ''plausible and well attested in economic history'' (C and H, p. 424). Thus, the fundamental, structural characteristic of some of the SRES scenarios contested by C and H are not challenged per se, but rather how fast such trends could unfold in the future. (author)

  4. Emissions scenarios: a final response

    Energy Technology Data Exchange (ETDEWEB)

    Gruebler, A.; Nakicenovic, N.; Alcamo, J. (and others)

    2004-01-01

    This note is a final response to the debate raised by Mr. Castles and Mr. Henderson (for brevity, we refer here to the two authors simply as C and H) in this Journal (vol 14, no 2 and 3, and no 4) on the issue of economic growth in developing countries in some of the emissions scenarios published in the IPCC Special Report on Emissions Scenarios (SRES) (Nakicenovic et al., 2000). We first outline areas of agreement and then the remaining areas of disagreement. Two important areas of agreement have emerged from the debate according to our view. First, both parties agree that scenarios assuming a conditional convergence in income levels, i.e., a higher growth in per capita income in poorer countries when compared to countries with higher levels of affluence, are both 'plausible and well attested in economic history' (C and H, p. 424). Thus, the fundamental, structural characteristic of some of the SRES scenarios contested by C and H are not challenged per se, but rather how fast such trends could unfold in the future. (author)

  5. Survival response of Sarotheron melanotheron (Ruppel, 1852 ...

    African Journals Online (AJOL)

    Survival response of Sarotheron melanotheron fingerlings to various concentration levels of perfkthion was studied under laboratory condition using five concentration levels, 0.0mg/l, 0.7mg/l, 1.4mg/l, 2.8mg/l, 5.5mg/l and 11.2mg/l. Mortality increased with increase in concentration level and exposure time. Ten percent ...

  6. Final disposal room structural response calculations

    International Nuclear Information System (INIS)

    Stone, C.M.

    1997-08-01

    Finite element calculations have been performed to determine the structural response of waste-filled disposal rooms at the WIPP for a period of 10,000 years after emplacement of the waste. The calculations were performed to generate the porosity surface data for the final set of compliance calculations. The most recent reference data for the stratigraphy, waste characterization, gas generation potential, and nonlinear material response have been brought together for this final set of calculations

  7. Topics in LIFE Target Survival: 11-SI-004 Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Miles, Robin [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Benett, Bill [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Bond, Tiziana [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Chang, Allan [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Dawson, David [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Fornasiero, Francesco [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Hamilton, Julie [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Havstad, Mark [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Kucheyev, Sergei [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); LeBlanc, Mary [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Rosso, Paul [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Schebler, Greg [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Van Cleve, Eli [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Worsley, Marcus [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2014-10-20

    The LIFE target design incorporates many considerations to generate the desired fusion gain including the physics design, the cost of manufacturing of the target, the injectability of the target, the aerodynamic flight characteristics of the target, the ability to track and engage the target and to maintain the structural and thermal integrity of the target. This document describes the effort that was made in support of issues of survivability of the target during injection which included issues massmanufactural materials and processes which could be used in the target.

  8. Growth response and survival of Heterobranchus longifilis ...

    African Journals Online (AJOL)

    In an effort to utilize feed efficiently, promote growth, increase survival and reduce labour costs associated with feeding, Heterobranchus longifilis ingerlings were placed on one of four feeding frequencies; once/day, twice/day; once every other day, and twice every other day for 56 days. They were fed with a commercial ...

  9. Survival And Growth Responses Of Frys Of The African Catfish ...

    African Journals Online (AJOL)

    Survival And Growth Responses Of Frys Of The African Catfish Hybrid ( Clarias gariepinus X Heterobranchus bidorsalis ) To Soluble Dietary Supplements Of ... The dietary treatments were fed to 4-weeks old hybrid of Clarias gariepinus × Heterobranchus bidorsalis (mean weight, 2.10 ± 0.14 g) at 5% body weight per day for ...

  10. AMPK regulates metabolism and survival in response to ionizing radiation

    International Nuclear Information System (INIS)

    Zannella, Vanessa E.; Cojocari, Dan; Hilgendorf, Susan; Vellanki, Ravi N.; Chung, Stephen; Wouters, Bradly G.; Koritzinsky, Marianne

    2011-01-01

    Background and purpose: AMPK is a metabolic sensor and an upstream inhibitor of mTOR activity. AMPK is phosphorylated by ionizing radiation (IR) in an ATM dependent manner, but the cellular consequences of this phosphorylation event have remained unclear. The objective of this study was to assess whether AMPK plays a functional role in regulating cellular responses to IR. Methods: The importance of AMPK expression for radiation responses was investigated using both MEFs (mouse embryo fibroblasts) double knockout for AMPK α1/α2 subunits and human colorectal carcinoma cells (HCT 116) with AMPK α1/α2 shRNA mediated knockdown. Results: We demonstrate here that IR results in phosphorylation of both AMPK and its substrate, ACC. IR moderately stimulated mTOR activity, and this was substantially exacerbated in the absence of AMPK. AMPK was required for IR induced expression of the mTOR inhibitor REDD1, indicating that AMPK restrains mTOR activity through multiple mechanisms. Likewise, cellular metabolism was deregulated following irradiation in the absence of AMPK, as evidenced by a substantial increase in oxygen consumption rates and lactate production. AMPK deficient cells showed impairment of the G1/S cell cycle checkpoint, and were unable to support long-term proliferation during starvation following radiation. Lastly, we show that AMPK proficiency is important for clonogenic survival after radiation during starvation. Conclusions: These data reveal novel functional roles for AMPK in regulating mTOR signaling, cell cycle, survival and metabolic responses to IR.

  11. Acid tolerance response and survival by oral bacteria.

    Science.gov (United States)

    Svensäter, G; Larsson, U B; Greif, E C; Cvitkovitch, D G; Hamilton, I R

    1997-10-01

    Using 21 species of oral bacteria, representing six acidogenic genera, we undertook to determine whether the pH-limiting exponential growth is related to the ability of the organisms to generate an acid-tolerance response that results in enhanced survival at low pH. The lower pH limit of exponential growth varied by more than two units with that of Neisseria A182 at pH 6.34; growth of Lactobacillus casei RB1014 stopped at pH 3.81, with species of Actinomyces, Enterococcus, Prevotella and Streptococcus falling between these limits. The working hypothesis was that the organisms with the higher pH limits for growth are unable to respond to acidic environments in order to survive, whereas the more aciduric organisms would possess or acquire acid tolerance. Adaptation to acid tolerance was tested by determining whether the prior exposure of exponential-phase cells to a low, sub-lethal pH would trigger the induction of a mechanism that would enhance survival at a pH killing pH 7.5 control cells. The killing pH varied from pH 4.5 for Prevotella intermedia ATCC 25611 to pH 2.3 for the three Lactobacillus casei strains in the study, with the three Streptococcus mutans strains killed at pH 3.0 for 3 h. The adaptation experiments revealed three groups of organisms: non-acid-responders, generally representing strains with the highest terminal pH values; weak acid-responders in the middle of the pH list, generating low numbers of survivors at one or two pH values, and the aciduric, strong responders generating a high number of survivors at pH values in the range 6.0 to 3.5, but not at pH 7.5. Predominant among the latter group were the S. mutans and Lactobacilli casei strains, with the most significant adaptive response exhibited by S. mutans LT11 and S. mutans Ingbritt, involving a process that required protein synthesis. Time course experiments with the latter organisms indicated that 90-120 min was required after exposure to the triggering pH before the acid response was

  12. Rapid Response Manufacturing (RRM). Final CRADA report

    Energy Technology Data Exchange (ETDEWEB)

    Cain, W.D. [Lockheed Martin Energy Systems, Inc., Oak Ridge, TN (United States); Waddell, W.L. [National Centers for Manufacturing Sciences, Ann Arbor, MI (United States)

    1997-08-28

    A major accomplishment of the Rapid Response Manufacturing (RRM) project was the development of a broad-based generic framework for automating and integrating the design-to-manufacturing activities associated with machined part products. Key components of the framework are a manufacturing model that integrates product and process data in a consistent, minimally redundant manner, an advanced computer-aided engineering working environment, knowledge-based software systems for design, process planning, and manufacturing and new production technologies for making products directly from design application software.

  13. Radiotherapy for esophageal carcinoma: dose, response and survival

    Directory of Open Access Journals (Sweden)

    Luo Y

    2017-12-01

    Full Text Available Yijun Luo,1,* Qingfeng Mao,2,3,* Xiaoli Wang,1 Jinming Yu,3 Minghuan Li3 1Department of Oncology, The People’s Hospital of Jiangxi, Nanchang, 2School of Medical and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, 3Department of Radiation Oncology and Radiology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China *These authors contributed equally to this work Abstract: Esophageal cancer (EC is an extremely aggressive, lethal malignancy that is increasing in incidence worldwide. At present, definitive chemoradiotherapy is accepted as the standard treatment for locally advanced EC. The EC guidelines recommend a radiation dose of 50.4 Gy for definitive treatment, yet the outcomes for patients who have received standard-dose radiotherapy remain unsatisfactory. However, some studies indicate that a higher radiation dose could improve local tumor control, and may also confer survival benefits. Some studies, however, suggest that high-dose radiotherapy does not bring survival benefit. The available data show that most failures occurred in the gross target volume (especially in the primary tumor after definitive chemoradiation. Based on those studies, we hypothesize that at least for some patients, more intense local therapy may lead to better local control and survival. The aim of this review is to evaluate the radiation dose, fractionation strategies, and predictive factors of response to therapy in functional imaging for definitive chemoradiotherapy in esophageal carcinoma, with an emphasis on seeking the predictive model of response to CRT and trying to individualize the radiation dose for EC patients. Keywords: esophageal cancer, radiation dose, altered fractionation, predictive factors, individualization 

  14. Rapid response manufacturing (RRM). Final CRADA report

    Energy Technology Data Exchange (ETDEWEB)

    Cain, W.D. [Lockheed Martin Energy Systems, Inc., Oak Ridge, TN (United States); Waddell, W.L. [National Centers for Manufacturing Sciences, Ann Arbor, MI (United States)

    1998-02-10

    US industry is fighting to maintain its competitive edge in the global market place. Markets fluctuate rapidly. Companies have to be able to respond quickly with improved, high quality, cost efficient products. Because companies and their suppliers are geographically distributed, rapid product realization is dependent on the development of a secure integrated concurrent engineering environment operating across multiple business entities. The way products are developed and brought to market can be improved and made more efficient through the proper incorporation of emerging technologies implemented in a secure environment. This documents the work done under this CRADA to develop capabilities, which permit the effective application, incorporation, and use of advanced technologies in a secure environment to facilitate the product realization process. Lockheed Martin Energy Systems (LMES), through a CRADA with the National Center for Manufacturing Sciences (NCMS), worked within a consortium of major industrial firms--Ford, General Motors, Texas Instruments, United Technologies, and Eastman Kodak--and several small suppliers of advanced manufacturing technology--MacNeal-Schwendler Corp., Teknowledge Corp., Cimplex Corp., Concentra, Spatial Technology, and Structural Dynamics Research Corp. (SDRC)--to create infrastructure to support the development and implementation of secure engineering environments for Rapid Response Manufacturing. The major accomplishment achieved under this CRADA was the demonstration of a prototypical implementation of a broad-based generic framework for automating and integrating the design-to-manufacturing activities associated with machined parts in a secure NWC compliant environment. Specifically, methods needed to permit the effective application, incorporation, and use of advanced technologies in a secure environment to facilitate the product realization process were developed and demonstrated. An important aspect of this demonstration was

  15. Survival interval in earthquake entrapments: research findings reinforced during the 2010 Haiti earthquake response.

    Science.gov (United States)

    Macintyre, Anthony G; Barbera, Joseph A; Petinaux, Bruno P

    2011-03-01

    Earthquakes can result in collapsed structures with the potential to entrap individuals. In some cases, people can survive entrapment for lengthy periods. The search for and rescue of entrapped people is resource intensive and competes with other postdisaster priorities. The decision to end search and rescue activities is often difficult and in some cases protracted. Medical providers participating in response may be consulted about the probability of continued survival in undiscovered trapped individuals. Historically, many espouse a rigid time frame for viability of entrapped living people (eg, 2 days, 4 days, 14 days). The available medical and engineering data and media reports demonstrate a wide variety in survival "time to rescue," arguing against the acceptance of a single time interval applicable to all incidents. This article presents historical evidence and reports from the 2010 Haiti earthquake. Factors that may contribute to survival after entombment are listed. Finally, a decision process for projecting viability that considers the critical factors in each incident rather than adhering to a single time frame for ceasing search and rescue activities is proposed. ©2011 American Medical Association. All rights reserved.

  16. Responsibility, coresponsibility and responsibility to the future in radiation protection and the question of final disposal

    International Nuclear Information System (INIS)

    Gellermann, R.

    2005-01-01

    Based on philosophical terms and concepts the responsibility, coresponsibility and responsibility to the future of people working in radiation protection are discussed and some resultant conclusions concerning finals disposal are derived. (orig.)

  17. Renal response assayed by survival of tubule epithelial cells

    International Nuclear Information System (INIS)

    Withers, H.R.; Mason, K.A.

    1985-01-01

    The epithelium of the renal tubules is essentially non-proliferative and hence is slow to be depleted after irradiation. Ultimately, however, depletion occurs. If cells survive within a tubule they regenerate the epithelial lining. After higher doses, e.g. greater than 12 Gy, some tubules are completely depopulated of epithelium giving rise to a histological picture of empty tubules interspersed with regenerated tubules. It is assumed that nephrons are all essentially the same size, that cell survival is a random probability and that, therefore, when a proportion of tubules are completely devoid of epithelium, those that aren't have regenerated from one or a few cells, the distribution of numbers of survivors per tubule following Poisson statistics. Based on these assumptions it is possible to determine a dose-survival relationship for renal tubule cells

  18. Student Entrepreneurship on Campus: A Survival Response or a ...

    African Journals Online (AJOL)

    The study shows that most of the respondents came from humble backgrounds and ran business mainly for survival. These results have useful implications on the effects of Structural Adjustment Programmes in financing university education in Kenya and elsewhere in Africa. Eastern Africa Social Science Research Review ...

  19. Survival in Response to Multimodal Therapy in Anaplastic Thyroid Cancer.

    Science.gov (United States)

    Prasongsook, Naiyarat; Kumar, Aditi; Chintakuntlawar, Ashish V; Foote, Robert L; Kasperbauer, Jan; Molina, Julian; Garces, Yolanda; Ma, Daniel; Wittich, Michelle A Neben; Rubin, Joseph; Richardson, Ronald; Morris, John; Hay, Ian; Fatourechi, Vahab; McIver, Bryan; Ryder, Mabel; Thompson, Geoffrey; Grant, Clive; Richards, Melanie; Sebo, Thomas J; Rivera, Michael; Suman, Vera; Jenkins, Sarah M; Smallridge, Robert C; Bible, Keith C

    2017-12-01

    Historical outcomes in anaplastic thyroid cancer (ATC) have been dismal. To determine whether an initial intensive multimodal therapy (MMT) is associated with improved ATC survival. MMT was offered to all patients with newly diagnosed ATC treated at the Mayo Clinic from 2003 through 2015; MMT vs care with palliative intent (PI) was individualized considering clinical status and patient preferences. Outcomes were retrospectively analyzed by American Joint Committee on Cancer stage and treatments compared with patient cohort data from 1949 through 1999. Forty-eight patients (60% male; median age, 62 years); 18 treated with PI, 30 with MMT. Overall survival (OS) and progression-free survival determined by Kaplan-Meier method. Median OS and 1-year survival for the later cohort were 9 months [95% confidence interval (CI), 4 to 22 months] and 42% (95% CI, 28% to 56%) vs 3 months and 10% for the earlier cohort. Median OS was 21 months compared with 3.9 months in the pooled MMT vs PI groups for the later cohort [hazard ratio (HR), 0.32; P = 0.0006]. Among only patients in the later cohort who had stage IVB disease, median OS was 22.4 vs 4 months (HR, 0.12; 95% CI, 0.03 to 0.44; P = 0.0001), with 68% vs 0% alive at 1 year (MMT vs PI). Among patients with stage IVC cancer, OS did not differ by therapy. MMT appears to convey longer survival in ATC among patients with stage IVA/B disease. Copyright © 2017 Endocrine Society

  20. Growth Responses and Survival of the Goldfish, Carassius auratus ...

    African Journals Online (AJOL)

    Five sets of 20-day old goldfish fry, Carassius auratus with average weights of 0.167 ± 0.003 g were reared for eight weeks in plastic bowls for growth and survival studies. One set (labelled MN) was fed Moina and Cyclops. A second set (labelled FM) was fed fishmeal, and a third set (labelled AF) was fed a 45% protein ...

  1. Platelet survival in idiopathic thrombocytopenic purpura and response to splenectomy

    International Nuclear Information System (INIS)

    Monteiro, M.E.; Verhaeghe, R.; Devos, P.

    Platelet survival combined with surface counting was performed in 9 patients with idiopathic thrombocytopenic purpura, resistent to steroid therapy. All patients had a markedly enhanced platelet turnover, five of them showed an augmented trapping of radioactivity over the spleen compared to liver and heart. These five patients underwent splenectomy: the platelet count increased in all of them but this increase was not always sustained. (Author) [pt

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

    Directory of Open Access Journals (Sweden)

    Hisao Imai

    2015-01-01

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

  3. Corporate social responsibility: An organizational tool for survival in ...

    African Journals Online (AJOL)

    Demonstrating socially responsible behaviour has become increasingly important for corporations. The study identifies the extent of participation of the banking industries in corporate social responsibility, the bank policies as it affects CRS and the impact of the bank the on the practice of CRS. The study utilized primary ...

  4. 205 Fulfillment of Social Responsibility as a Business Survival ...

    African Journals Online (AJOL)

    User

    2010-10-17

    Oct 17, 2010 ... impetus for executives to think through the society role of the enterprise they operate. Also, it is the belief by most ... responsibility as the duty of a business enterprise to ensure that it does not. Vol. 4 (4), Serial No. 17, October, 2010. .... Small Business Management. Fundamentals: McGraw-Hill Series in ...

  5. Fulfillment of Social Responsibility as a Business Survival Strategy ...

    African Journals Online (AJOL)

    InNigeria, too many oil corporations have been taken to court by either thegovernment or concerned citizens for the violation of EnvironmentalProtection Act. This work concludes that there is a significant relationshipbetween the practice of social responsibility and organization performanceand recommends that government ...

  6. 205 Fulfillment of Social Responsibility as a Business Survival ...

    African Journals Online (AJOL)

    User

    2010-10-17

    Oct 17, 2010 ... Nigeria, too many oil corporations have been taken to court by either the government or concerned citizens for the violation of Environmental. Protection Act. This work concludes that there is a significant relationship between the practice of social responsibility and organization performance.

  7. Elucidating the sponge stress response; lipids and fatty acids can facilitate survival under future climate scenarios.

    Science.gov (United States)

    Bennett, Holly; Bell, James J; Davy, Simon K; Webster, Nicole S; Francis, David S

    2018-03-05

    Ocean warming (OW) and ocean acidification (OA) are threatening coral reef ecosystems, with a bleak future forecast for reef-building corals, which are already experiencing global declines in abundance. In contrast, many coral reef sponge species are able to tolerate climate change conditions projected for 2100. To increase our understanding of the mechanisms underpinning this tolerance, we explored the lipid and fatty acid (FA) composition of four sponge species with differing sensitivities to climate change, experimentally exposed to OW and OA levels predicted for 2100, under two CO 2 Representative Concentration Pathways (RCPs). Sponges with greater concentrations of storage lipid, phospholipids, sterols and elevated concentrations of n-3 and n-6 long-chain polyunsaturated FA (LC PUFA), were more resistant to OW. Such biochemical constituents likely contribute to the ability of these sponges to maintain membrane function and cell homeostasis in the face of environmental change. Our results suggest that n-3 and n-6 LC PUFA are important components of the sponge stress response potentially via chain elongation and the eicosanoid stress-signalling pathways. The capacity for sponges to compositionally alter their membrane lipids in response to stress was also explored using a number of specific homeoviscous adaptation (HVA) indicators. This revealed a potential mechanism via which additional CO 2 could facilitate the resistance of phototrophic sponges to thermal stress through an increased synthesis of membrane-stabilising sterols. Finally, OW induced an increase in FA unsaturation in phototrophic sponges but a decrease in heterotrophic species, providing support for a difference in the thermal response pathway between the sponge host and the associated photosymbionts. Here we have shown that sponge lipids and FA are likely to be an important component of the sponge stress response and may play a role in facilitating sponge survival under future climate conditions

  8. Survival of the relocated population of the U. S. after a nuclear attack. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Haaland, C.M.; Chester, C.V.; Wigner, E.P.

    1976-06-01

    The feasibility of continued survival after a hypothetical nuclear attack is evaluated for people relocated from high-risk areas during the crisis period before the attack. The attack consists of 6559 MT, of which 5951 MT are ground bursts on military, industrial, and urban targets. Relocated people are assumed to be adequately protected from fallout radiation by shelters of various kinds. The major problems in the postattack situation will be the control of exposure to fallout radiation, and prevention of severe food shortages to several tens of millions of people.

  9. Parasitic infection improves survival from septic peritonitis by enhancing mast cell responses to bacteria in mice.

    Directory of Open Access Journals (Sweden)

    Rachel E Sutherland

    Full Text Available Mammals are serially infected with a variety of microorganisms, including bacteria and parasites. Each infection reprograms the immune system's responses to re-exposure and potentially alters responses to first-time infection by different microorganisms. To examine whether infection with a metazoan parasite modulates host responses to subsequent bacterial infection, mice were infected with the hookworm-like intestinal nematode Nippostrongylus brasiliensis, followed in 2-4 weeks by peritoneal injection of the pathogenic bacterium Klebsiella pneumoniae. Survival from Klebsiella peritonitis two weeks after parasite infection was better in Nippostrongylus-infected animals than in unparasitized mice, with Nippostrongylus-infected mice having fewer peritoneal bacteria, more neutrophils, and higher levels of protective interleukin 6. The improved survival of Nippostrongylus-infected mice depends on IL-4 because the survival benefit is lost in mice lacking IL-4. Because mast cells protect mice from Klebsiella peritonitis, we examined responses in mast cell-deficient Kit(W-sh/Kit(W-sh mice, in which parasitosis failed to improve survival from Klebsiella peritonitis. However, adoptive transfer of cultured mast cells to Kit(W-sh/Kit(W-sh mice restored survival benefits of parasitosis. These results show that recent infection with Nippostrongylus brasiliensis protects mice from Klebsiella peritonitis by modulating mast cell contributions to host defense, and suggest more generally that parasitosis can yield survival advantages to a bacterially infected host.

  10. [Pathological complete response: A predictive survival factor after neoadjuvant chemotherapy in lung cancer].

    Science.gov (United States)

    Milleron, Bernard; Westeel, Virginie; Gounant, Valérie; Wislez, Marie; Quoix, Elisabeth

    2016-01-01

    The phase III trials of adjuvant and neoadjuvant chemotherapy showed a 5 % increase survival but the clinical research in this area is difficult because the duration of the trials with overall survival as primary end point is around 10years. To shorten the duration of these studies, the use of surrogate end points such as disease-free survival or relapse-free survival is possible, but does not significantly reduce the duration of studies. Several studies in and outside the lung cancer showed histological complete response or the percentage of viable tumor cells after chemotherapy could be correlated with survival and thus become an interesting alternative criterion. If this is verified, clinical studies of preoperative chemotherapy should be shortened which would allow patients faster access to innovative treatment in the perioperative situation. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  11. Adaptive response and split-dose effect of radiation on the survival ...

    Indian Academy of Sciences (India)

    Unknown

    The findings have been discussed from a mechanistic point of view. The possible biological implications, potential medical benefits, uncertainties and controversies related to adaptive response have also been addressed. [Tiku A B and Kale R K 2004 Adaptive response and split-dose effect of radiation on the survival of ...

  12. A survey of pathogen survival during municipal solid waste and manure treatment processes. Final report

    International Nuclear Information System (INIS)

    Ware, S.A.

    1980-08-01

    Municipal solid waste (MSW) and animal manures may contain microorganisms that can cause disease in man and animals. These pathogenic microorganisms include enteric bacteria, fungi, viruses, and human and animal parasites. This report summarizes and discusses various research findings documenting the extent of pathogen survival during MSW treatment. The technologies discussed are composting, incineration, landfill, and anaerobic digestion. There is also a limited examination of the use of the oxidation ditch as a means of animal manure stabilization. High gradient magnetic separation (HGMS), and gamma radiation sterilization are mentioned as future options, especially for animal waste management. Several standard methods for the sampling, concentration, and isolation of microorganisms from raw and treated solid waste are also summarized

  13. In-Situ Survival Mechanisms of U and Tc Reducing Bacteria in Contaminated Sediments. Final Report

    International Nuclear Information System (INIS)

    Lee Krumholz Jimmy Ballard

    2005-01-01

    The proposed effort will identify genes and ultimately physiological mechanisms and pathways that are expressed under in situ conditions and are critical to functioning of aquifer dwelling anaerobic bacteria living in contaminated systems. The main objectives are: (1) Determine which Metal-reducer specific genes are important for activities in normal and contaminated subsurface sediment. To achieve these goals, we have generated a library of chromosomal mutants. These are introduced into contaminated sediments, incubated, allowed to grow, and then reisolated. A negative selection process allows us to determine which mutants have been selected against in sediments and thereby identify genes required for survival in subsurface sediments. (2) Delineate the function of these genes through GeneBank and Clusters of Orthologous Groups (COGs) comparisons and analyze other sediment microorganisms to determine if similar genes are present in these populations. After determining the sequence of the genes identified through the previous objectives, we delineate the role of those specific genes in the physiology of G20, MR-1 and perhaps other microorganisms. (3) Determine the loss in function of a select group of mutants. Cells with mutations in known genes with testable functions are assayed for the loss of that function if specific assays are available. Mutants with unknown loss of function and other mutants are run through a series of tests including motility, attachment, and rate of sulfate or iron reduction. These tests allow us to categorize mutants for subsequent more detailed study

  14. Noisy Response to Antibiotic Stress Predicts Subsequent Single-Cell Survival in an Acidic Environment.

    Science.gov (United States)

    Mitosch, Karin; Rieckh, Georg; Bollenbach, Tobias

    2017-04-26

    Antibiotics elicit drastic changes in microbial gene expression, including the induction of stress response genes. While certain stress responses are known to "cross-protect" bacteria from other stressors, it is unclear whether cellular responses to antibiotics have a similar protective role. By measuring the genome-wide transcriptional response dynamics of Escherichia coli to four antibiotics, we found that trimethoprim induces a rapid acid stress response that protects bacteria from subsequent exposure to acid. Combining microfluidics with time-lapse imaging to monitor survival and acid stress response in single cells revealed that the noisy expression of the acid resistance operon gadBC correlates with single-cell survival. Cells with higher gadBC expression following trimethoprim maintain higher intracellular pH and survive the acid stress longer. The seemingly random single-cell survival under acid stress can therefore be predicted from gadBC expression and rationalized in terms of GadB/C molecular function. Overall, we provide a roadmap for identifying the molecular mechanisms of single-cell cross-protection between antibiotics and other stressors. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  16. Survival patterns and hemopathological responses of dogs under continuous gamma irradiation

    International Nuclear Information System (INIS)

    Seed, T.M.; Fritz, T.E.; Tolle, D.V.; Poole, C.M.; Lombard, L.S.; Doyle, D.E.; Kaspar, L.V.; Cullen, S.M.; Carnes, B.A.

    1983-01-01

    Survival curves were constructed and analyzed relative to contributing hematopathological responses for groups of beagles exposed continuously for duration of life to low daily doses of whole body 60 Co gamma irradiation (27.3 rads/day to 4 rads/day). The survival curves versus time were progressively displaced toward longer survival as rates of exposure were reduced from the relatively high dose rate of 27.3 rads/day to the low dose rate of 4.0 rads/day. Average survival times increased from 57 days at 27.3 rads/day to 1830 days at 4.0 rads/day, representing fractional increased life-spans from 1.5% to 50.8%, respectively. Survival curves versus total dose were markedly displaced along the cumulative radiation dose axis at the extreme dose rates (i.e., 27.3 and 4.0 rads/day), but not at the intermediate dose rates (i.e., 13.4 and 7.9 rads/day) in which the upper linear portions of the survival curves are superimposed. From these dose-dependent survival curves, LD 50 values for whole body gamma irradiation, delivered chronically at 27.3, 13.4, 7.9, and 4.0 rads per day were estimated to be 1442, 2124, 2039, and 7161 rads, respectively. Both time- and dose-dependent survival curves for the intermediate dose rates, in contrast to the extreme dose rates, exhibited pronounced transitions in the lethality rate below the 50% survival level. These lethality rate transitions occurred at approx. 2500 rads of accumulated dose and were attributed to a shift in the spectrum of developing hematopathologies: namely, from a predominance of the acutely ablative radiation-induced lymphohematopoietic syndromes (i.e., septicemias and aplastic anemias) to a predominance of the late arising hematopoietic neoplasias (myelogenous leukemia and related myeloproliferative disorders)

  17. Exploring the impact of dysfunctional posttraumatic survival responses on crime revictimization.

    Science.gov (United States)

    Kunst, Maarten Jacob Johannes; Winkel, Frans Willem

    2013-01-01

    This study investigated the association between posttraumatic stress disorder (PTSD) symptoms and repeat victimization across crime types in survivors of traumatic interpersonal violence. An evolutionary psychological perspective was adopted to propose that symptoms of hyperarousal (particularly hypervigilance, exaggerated startle response, and irritability or outbursts of anger) and numbing predict revictimization. These symptoms may act as manifestations of dysfunctional survival responses. Survival responses are adaptive in life-threatening situations but may work counter-productive in the absence of immediate threat. Participants were recruited through the Dutch Victim Compensation Fund (DVCF; N = 233). PTSD symptomatology was assessed between October and December 2007. Revictimization was measured 6 months later. Results were partly in line with expectations. Exaggerated startle response and symptoms of irritability or outbursts of anger but not hypervigilance and numbing were related to revictimization.

  18. Adaptive response and split-dose effect of radiation on the survival ...

    Indian Academy of Sciences (India)

    Unknown

    Although the importance of radiation-induced adaptive response has been recognized in human health, risk assessment and clinical application, the phenomenon has not been understood well in terms of survival of ani- mals. To examine this aspect Swiss albino mice were irradiated with different doses (2–10 Gy) at 0⋅015 ...

  19. Adaptive response and split-dose effect of radiation on the survival ...

    Indian Academy of Sciences (India)

    Although the importance of radiation-induced adaptive response has been recognized in human health, risk assessment and clinical application, the phenomenon has not been understood well in terms of survival of animals. To examine this aspect Swiss albino mice were irradiated with different doses (2–10 Gy) at 0.015 ...

  20. Mesothelin-specific Immune Responses Predict Survival of Patients With Brain Metastasis

    Directory of Open Access Journals (Sweden)

    Liu Zhenjiang

    2017-09-01

    Interpretation: This is the first evidence that immune responses to mesothelin serve as a marker of increased overall survival in patients with brain metastases, regardless of the primary tumor origin. Analyses of immunological markers could potentially serve as prognostic markers in patients with brain metastases and help to select patients in need for adjunct, immunological, treatment strategies.

  1. Adaptive response and split-dose effect of radiation on the survival ...

    Indian Academy of Sciences (India)

    These results clearly showed the occurrence of adaptive response in terms of survival of animals. The conditioning dose given in small fractions seemed to be more effective. The findings have been discussed from a mechanistic point of view. The possible biological implications, potential medical benefits, uncertainties and ...

  2. HPV Integration in HNSCC Correlates with Survival Outcomes, Immune Response Signatures, and Candidate Drivers.

    Science.gov (United States)

    Koneva, Lada A; Zhang, Yanxiao; Virani, Shama; Hall, Pelle B; McHugh, Jonathan B; Chepeha, Douglas B; Wolf, Gregory T; Carey, Thomas E; Rozek, Laura S; Sartor, Maureen A

    2018-01-01

    The incidence of human papillomavirus (HPV)-related oropharynx cancer has steadily increased over the past two decades and now represents a majority of oropharyngeal cancer cases. Integration of the HPV genome into the host genome is a common event during carcinogenesis that has clinically relevant effects if the viral early genes are transcribed. Understanding the impact of HPV integration on clinical outcomes of head and neck squamous cell carcinoma (HNSCC) is critical for implementing deescalated treatment approaches for HPV + HNSCC patients. RNA sequencing (RNA-seq) data from HNSCC tumors ( n = 84) were used to identify and characterize expressed integration events, which were overrepresented near known head and neck, lung, and urogenital cancer genes. Five genes were recurrent, including CD274 (PD-L1) A significant number of genes detected to have integration events were found to interact with Tp63, ETS, and/or FOX1A. Patients with no detected integration had better survival than integration-positive and HPV - patients. Furthermore, integration-negative tumors were characterized by strongly heightened signatures for immune cells, including CD4 + , CD3 + , regulatory, CD8 + T cells, NK cells, and B cells, compared with integration-positive tumors. Finally, genes with elevated expression in integration-negative specimens were strongly enriched with immune-related gene ontology terms, while upregulated genes in integration-positive tumors were enriched for keratinization, RNA metabolism, and translation. Implications: These findings demonstrate the clinical relevancy of expressed HPV integration, which is characterized by a change in immune response and/or aberrant expression of the integration-harboring cancer-related genes, and suggest strong natural selection for tumor cells with expressed integration events in key carcinogenic genes. Mol Cancer Res; 16(1); 90-102. ©2017 AACR . ©2017 American Association for Cancer Research.

  3. Agency procedures for the NRC incident response plan. Final report

    International Nuclear Information System (INIS)

    1983-02-01

    The NRC Incident Response Plan, NUREG-0728/MC 0502 describes the functions of the NRC during an incident and the kinds of actions that comprise an NRC response. The NRC response plan will be activated in accordance with threshold criteria described in the plan for incidents occurring at nuclear reactors and fuel facilities involving materials licensees; during transportation of licensed material, and for threats against facilities or licensed material. In contrast to the general overview provided by the Plan, the purpose of these agency procedures is to delineate the manner in which each planned response function is performed; the criteria for making those response decisions which can be preplanned; and the information and other resources needed during a response. An inexperienced but qualified person should be able to perform functions assigned by the Plan and make necessary decisions, given the specified information, by becoming familiar with these procedures. This rule of thumb has been used to determine the amount of detail in which the agency procedures are described. These procedures form a foundation for the training of response personnel both in their normal working environment and during planned emergency exercises. These procedures also form a ready reference or reminder checklist for technical team members and managers during a response

  4. Mesothelin-specific Immune Responses Predict Survival of Patients With Brain Metastasis

    DEFF Research Database (Denmark)

    Zhenjiang, Liu; Rao, Martin; Luo, Xiaohua

    2017-01-01

    BACKGROUND: Patients with advanced malignancies, e.g. lung cancer, ovarian cancer or melanoma, frequently present with brain metastases. Clinical presentation and disease progression of cancer is in part shaped by the interaction of the immune system with malignant cells. Antigen-targeted immune......, prospective study the survival of patients with brain metastases in association with clinical parameters and cellular immune responses to molecularly defined TAAs or viral (control) target antigens. METHODS: Immune cells in peripheral blood obtained from thirty-six patients with brain metastases were tested...... or until death. FINDINGS: Univariate analysis identified age, gender, radiotherapy and mutational load as clinical parameters affecting survival of patients with brain metastases. Cox multivariate analysis showed that radiotherapy (P=0·004), age (P=0·029) and IFN-γ responses to mature mesothelin...

  5. Hidden survival heterogeneity of three Common eider populations in response to climate fluctuations.

    Science.gov (United States)

    Guéry, Loreleï; Descamps, Sébastien; Pradel, Roger; Hanssen, Sveinn Are; Erikstad, Kjell Einar; Gabrielsen, Geir W; Gilchrist, H Grant; Bêty, Joël

    2017-05-01

    Understanding how individuals and populations respond to fluctuations in climatic conditions is critical to explain and anticipate changes in ecological systems. Most such studies focus on climate impacts on single populations without considering inter- and intra-population heterogeneity. However, comparing geographically dispersed populations limits the risk of faulty generalizations and helps to improve ecological and demographic models. We aimed to determine whether differences in migration tactics among and within populations would induce inter- or intra-population heterogeneity in survival in relation to winter climate fluctuations. Our study species was the Common eider (Somateria mollissima), a marine duck with a circumpolar distribution, which is strongly affected by climatic conditions during several phases of its annual cycle. Capture-mark-recapture data were collected in two arctic (northern Canada and Svalbard) and one subarctic (northern Norway) population over a period of 18, 15, and 29 years respectively. These three populations have different migration tactics and experience different winter climatic conditions. Using multi-event and mixture modelling, we assessed the association between adult female eider survival and winter conditions as measured by the North Atlantic Oscillation (NAO) index. We found that winter weather conditions affected the survival of female eiders from each of these three populations. However, different mechanisms seemed to be involved. Survival of the two migrating arctic populations was impacted directly by changes in the NAO, whereas the subarctic resident population was affected by the NAO with time lags of 2-3 years. Moreover, we found evidence for intra-population heterogeneity in the survival response to the winter NAO in the Canadian eider population, where individuals migrate to distinct wintering areas. Our results illustrate how individuals and populations of the same species can vary in their responses to

  6. GENOMIC PREDICTOR OF RESPONSE AND SURVIVAL FOLLOWING TAXANE-ANTHRACYCLINE CHEMOTHERAPY FOR INVASIVE BREAST CANCER

    Science.gov (United States)

    Hatzis, Christos; Pusztai, Lajos; Valero, Vicente; Booser, Daniel J.; Esserman, Laura; Lluch, Ana; Vidaurre, Tatiana; Holmes, Frankie; Souchon, Eduardo; Martin, Miguel; Cotrina, José; Gomez, Henry; Hubbard, Rebekah; Chacón, J. Ignacio; Ferrer-Lozano, Jaime; Dyer, Richard; Buxton, Meredith; Gong, Yun; Wu, Yun; Ibrahim, Nuhad; Andreopoulou, Eleni; Ueno, Naoto T.; Hunt, Kelly; Yang, Wei; Nazario, Arlene; DeMichele, Angela; O’Shaughnessy, Joyce; Hortobagyi, Gabriel N.; Symmans, W. Fraser

    2017-01-01

    CONTEXT Accurate prediction of who will (or won’t) have high probability of survival benefit from standard treatments is fundamental for individualized cancer treatment strategies. OBJECTIVE To develop a predictor of response and survival from chemotherapy for newly diagnosed invasive breast cancer. DESIGN Development of different predictive signatures for resistance and response to neoadjuvant chemotherapy (stratified according to estrogen receptor (ER) status) from gene expression microarrays of newly diagnosed breast cancer (310 patients). Then prediction of breast cancer treatment-sensitivity using the combination of signatures for: 1) sensitivity to endocrine therapy, 2) chemo-resistance, and 3) chemo-sensitivity. Independent validation (198 patients) and comparison with other reported genomic predictors of chemotherapy response. SETTING Prospective multicenter study to develop and test genomic predictors for neoadjuvant chemotherapy. PATIENTS Newly diagnosed HER2-negative breast cancer treated with chemotherapy containing sequential taxane and anthracycline-based regimens then endocrine therapy (if hormone receptor-positive). MAIN OUTCOME MEASURES Distant relapse-free survival (DRFS) if predicted treatment-sensitive and absolute risk reduction (ARR, difference in DRFS of the two predicted groups) at median follow-up (3 years), and their 95% confidence intervals (CI). RESULTS Patients in the independent validation cohort (99% clinical Stage II–III) who were predicted to be treatment-sensitive (28% of total) had DRFS of 92% (CI 85–100) and survival benefit compared to others (absolute risk reduction (ARR) 18%; CI 6–28). Predictions were accurate if breast cancer was ER-positive (30% predicted sensitive, DRFS 97%, CI 91–100; ARR 11%, CI 0.1–21) or ER-negative (26% predicted sensitive, DRFS 83%, CI 68–100; ARR 26%, CI 4–28), and were significant in multivariate analysis after adjusting for relevant clinical-pathologic characteristics. Other

  7. Neoadjuvant Chemotherapy versus Chemoradiation Prior to Esophagectomy: Impact on Rate of Complete Pathologic Response and Survival in Esophageal Cancer Patients

    Science.gov (United States)

    Samson, Pamela; Robinson, Clifford; Bradley, Jeffrey; Lockhart, A. Craig; Puri, Varun; Broderick, Stephen; Kreisel, Daniel; Krupnick, A. Sasha; Patterson, G. Alexander; Meyers, Bryan; Crabtree, Traves

    2016-01-01

    Purpose To evaluate differences in pathologic complete response (pCR) rates and overall survival among patients receiving either neoadjuvant chemotherapy or chemoradiation prior to esophagectomy for locally advanced esophageal cancer. Patients and methods Esophageal cancer patients receiving either neoadjuvant chemotherapy or chemoradiation prior to esophagectomy were identified using the National Cancer Data Base (NCDB). Univariate analysis compared patient, tumor, and postoperative outcome characteristics. Logistic regression was performed to identify variables associated with achieving pCR. Kaplan-Meier analysis was performed to compare overall median survival by neoadjuvant therapy type and pCR status. Finally, a Cox proportional hazards model was fitted to identify variables associated with increased mortality hazard. Results From 2006 – 2012, 916/7,338 (12.5%) of patients received neoadjuvant chemotherapy while 6,422 (87.5%) received neoadjuvant chemoradiation. Neoadjuvant chemoradiation patients were more likely to achieve pCR (17.2% versus 6.4%, p<0.001) and less likely to have positive margins (5.6% versus 11.5%, p<0.001) than neoadjuvant chemotherapy patients, with no difference in 30- or 90-day mortality. Achieving pCR was associated with improved overall median survival (59.5 months ± 4.0 versus 30.1 months ± 0.76 for those with persistent disease, p<0.001). On logistic regression, neoadjuvant chemoradiation therapy was independently associated with achieving pCR (Odds Ratio 2.75, 2.01 – 3.77, p<0.001). Despite improvement in pCR rate with neoadjuvant chemoradiation, neoadjuvant therapy type was not independently associated with long-term survival (HR 1.12, 95% CI 0.97 – 1.30, p=0.12). Conclusion While neoadjuvant chemoradiation is more successful in downstaging esophageal cancer prior to esophagectomy, this therapy was not independently prognostic for improved long-term survival. Other factors affecting long-term survival among pathologic

  8. Early response as predictor of final remission in elderly depressed patients

    NARCIS (Netherlands)

    Kok, Rob M.; van Baarsen, Carlijn; Nolen, Willem A.; Heeren, Thea J.

    2009-01-01

    Background Several studies have attempted to predict the final response or remission based on improvement during the early Course of treatment of major depression. There is however a great variation in cut offs used to define early response and in the optimal week to predict final results. Objective

  9. Modulation of Dendritic Cell Responses by Parasites: A Common Strategy to Survive

    Directory of Open Access Journals (Sweden)

    César A. Terrazas

    2010-01-01

    Full Text Available Parasitic infections are one of the most important causes of morbidity and mortality in our planet and the immune responses triggered by these organisms are critical to determine their outcome. Dendritic cells are key elements for the development of immunity against parasites; they control the responses required to eliminate these pathogens while maintaining host homeostasis. However, there is evidence showing that parasites can influence and regulate dendritic cell function in order to promote a more permissive environment for their survival. In this review we will focus on the strategies protozoan and helminth parasites have developed to interfere with dendritic cell activities as well as in the possible mechanisms involved.

  10. Survey of system responsibility in the Nordic countries. Final report

    International Nuclear Information System (INIS)

    2005-02-01

    In September 2004 the Nordic Council of Ministers asked Nordel to perform some tasks and present the results to the Council on 1 March 2005. One of the tasks is to survey how system responsibility is defined and executed in the different Nordic countries. According to the Nordic Council of Ministers, the survey shall illuminate similarities and differences between the countries and assess the reasons for the differences. Nordel is asked to present a joint view system responsibility in the Nordic countries. Among other things, the responsibility for the system operators and the participants in the market shall be defined. The definition shall also include the distribution of costs between costs for network business and costs for business in competition. This shall be done in a way that creates a common platform for the further harmonisation work and continuous positive development of the Nordic electricity market. It is also important to identify the need for changes in e.g. legislation and guidelines in the different countries as a consequence of an implementation of a common definition in the Nordic countries. Areas to be included in the task are among others, balance settlement, security of supply, congestion management and system services. (BA)

  11. Homeopathy outperforms antibiotics treatment in juvenile scallop Argopecten ventricosus: effects on growth, survival, and immune response.

    Science.gov (United States)

    Mazón-Suástegui, José Manuel; García-Bernal, Milagro; Saucedo, Pedro Enrique; Campa-Córdova, Ángel; Abasolo-Pacheco, Fernando

    2017-02-01

    Mortality from vibriosis in mollusk production is attributed to pathogenic bacteria, particularly Vibrio alginolyticus. Use of increasingly potent antibiotics has led to bacterial resistance and increased pathogenicity. Alternatives in sanitation, safety, and environmental sustainability are currently under analysis. To-date, homeopathy has been investigated in aquaculture of freshwater fish, but not in marine mollusks. The effect of the homeopathic complexes in the growth, survival, and immune response of the Catarina scallop Argopecten ventricosus were assessed. A bioassay to assess the potential of homeopathy in improving cultivation of juvenile A. ventricosus was conducted for 21 days, with a final challenge of 120 h with V. alginolyticus. The experimental design included two homeopathic formulas The homeopathic complex Passival, consisting of Passiflora incarnata 30 CH, Valeriana officinalis 30 CH, Ignatia amara 30 CH and Zincum valerianicum 30 CH plus Phosphoricum acid 30 CH (treatment TH1) or Silicea terra 30 CH (TH2), two antibiotics (ampicillin = AMP, oxytetracycline = OXY), and two reference treatments (without homeopathic or antibiotic treatment = CTRL, ethanol 30° GL = ETH). Additionally, a negative control CTRL- (untreated/uninfected) is included in the challenge test. Juvenile scallops (4.14 ± 0.06 mm, 13.33 mg wet weight) were cultivated in 4 L tanks provided with aerated, filtered (1 μm), and UV-sterilized seawater that was changed every third day. They were fed a blend of the microalgae Isochrysis galbana and Chaetoceros calcitrans (150,000 cells mL -1 twice a day). All treatments were directly added to the tank water and then 500 mL challenge units were inoculated with 1 × 10 7  CFU/mL (LD 50 ) of V. alginolyticus. Juveniles grew significantly larger and faster in height and weight with TH2 compared to the ETH and CTRL (P homeopathy is a viable treatment for this mollusk to reduce use of antibiotics in scallops and its

  12. Role of X-ray-inducible genes and proteins in adaptive survival responses

    International Nuclear Information System (INIS)

    Meyers, M.; Schea, R.A.; Petrowski, A.E.; Seabury, H.; McLaughlin, P.W.; Lee, I.; Lee, S.W.; Boothman, D.A.

    1992-01-01

    Certain X-ray-inducible genes and their corresponding protein products, appearing following low priming doses of ionizing radiation may subsequently give rise to an adaptive survival response, ultimately leading to increased radioresistance. Further, this adaptive radioresistance may be due to increased DNA repair (or misrepair) processes. Ultimately, the function of low-dose-induced cDNA clones within the cell is hoped to elucidate to follow the effects of specific gene turn-off on adaptive responses. Future research must determine the various functions of adaptive response gene products so that the beneficial or deleterious consequences of adaptive responses, which increases resistance to ionizing radiation, can be determined. (author). 19 refs., 1 fig

  13. State and Employer: CERN faced with its responsibilities (final part)

    CERN Multimedia

    Association du personnel

    2009-01-01

    “The Organization must assume its responsibilities without reservation in both of its roles: as a State for our social security system (pensions, health insurance) and as an Employer (salaries, careers, contracts, etc.).” This is the key message passed on to you at the staff meetings last month. Our previous two editorials presented in detail the pensions and health insurance issues and the preparation for the 2010 five-yearly review. In this third part we talk about the contract policy and MARS.

  14. A new emergency response model for MACCS. Final report

    International Nuclear Information System (INIS)

    Chanin, D.I.

    1992-01-01

    Under DOE sponsorship, as directed by the Los Alamos National Laboratory (LANL), the MACCS code (version 1.5.11.1) [Ch92] was modified to implement a series of improvements in its modeling of emergency response actions. The purpose of this effort has been to aid the Westinghouse Savannah River Company (WSRC) in its performance of the Level III analysis for the Savannah River Site (SRS) probabilistic risk analysis (PRA) of K Reactor [Wo90]. To ensure its usefulness to WSRC, and facilitate the new model's eventual merger with other MACCS enhancements, close cooperation with WSRC and the MACCS development team at Sandia National Laboratories (SNL) was maintained throughout the project. These improvements are intended to allow a greater degree of flexibility in modeling the mitigative actions of evacuation and sheltering. The emergency response model in MACCS version 1.5.11.1 was developed to support NRC analyses of consequences from severe accidents at commercial nuclear power plants. The NRC code imposes unnecessary constraints on DOE safety analyses, particularly for consequences to onsite worker populations, and it has therefore been revamped. The changes to the code have been implemented in a manner that preserves previous modeling capabilities and therefore prior analyses can be repeated with the new code

  15. Final Report: Proteomic study of brassinosteroid responses in Arabidopsis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhiyong [Carnegie Inst. of Washington, Argonne, IL (United States); Burlingame, Alma [Univ. of California, San Francisco, CA (United States)

    2017-11-29

    The steroid hormone brassinosteroid (BR) is a major growth-promoting phytohormone. The specific aim of the current project is to identify BR-regulated proteins and characterize their functions in various aspects of plant growth, development, and adaptation. Our research has significantly advanced our understanding of how BR signal is transduced from the receptor at the cell surface to changes of nuclear gene expression and other cellular responses such as vesicle trafficking, as well as developmental transitions such as seed germination and flowering. We have also developed effective proteomic methods for quantitative analysis of protein phosphorylation and for identification of glycosylated proteins. Through this DOE funding, we have performed several proteomic experiments and made major discoveries.

  16. Decoy Receptor 3 Improves Survival in Experimental Sepsis by Suppressing the Inflammatory Response and Lymphocyte Apoptosis.

    Directory of Open Access Journals (Sweden)

    DongYu Liang

    Full Text Available Unbalanced inflammatory response and lymphocyte apoptosis is associated with high mortality in septic patients. Decoy receptor 3 (DcR3, a member of the tumor necrosis factor receptor superfamily, is an anti-inflammatory and anti-apoptotic factor. Recently, DcR3 expression was found to be increased in septic patients. This study evaluated the therapeutic effect and mechanisms of DcR3 on cecal ligation and puncture (CLP-induced sepsis in mice.C57BL/6 mice were subjected to CLP-induced polymicrobial sepsis. DcR3 Fc was intravenously injected 30 min before and 6 h after CLP. Bacterial clearance, cytokine production, histology, lymphocyte apoptosis and survival were evaluated. Furthermore, we investigated the systemic effects of DcR3 in in vitro lymphocyte apoptosis regulation.Our results demonstrated that DcR3 protein treatments significantly improved survival in septic mice (p <0.05. Treatment with DcR3 protein significantly reduced the inflammatory response and decreased lymphocyte apoptosis in the thymus and spleen. Histopathological findings of the lung and liver showed milder impairment after DcR3 administration. In vitro experiments showed that DcR3 Fc inhibited Fas-FasL mediated lymphocyte apoptosis.Treatment with the DcR3 protein protects mice from sepsis by suppressing the inflammatory response and lymphocyte apoptosis. DcR3 protein may be useful in treatment of sepsis.

  17. Late radiation response of kidney assayed by tubule-cell survival

    International Nuclear Information System (INIS)

    Withers, H.R.; Mason, K.A.

    1986-01-01

    An assay for the survival of renal tubule cells was developed using mice, analogous to other in-situ clonogenic cell survival assays. One kidney was irradiated using a 137 Cs irradiator and removed 60-68 weeks later for histological examination. In unirradiated animals there were about 370 tubules in contact with the capsule in a coronal cross section at the middle of the kidney. After irradiation, extensive tubular damage was the dominant lesion. The number of epithelialised tubules in contact with the capsule showed a dose-dependent logarithmic decline. The dose-survival relationship for the clonogenic cells responsible for the regeneration of tubule epithelium was described by a D 0 value of 1.5 Gy over the dose range 11-16 Gy. This radiosensitivity resembles that of stem cells in acutely responding tissues. The lack of histological evidence of damage to the arterial vasculature at the time the tubules are initially denuded of epithelium, and the similarity of renal tubule cell radiosensitivity to that of other mammalian cells, support the hypothesis that ''late'' radiation injury results primarily from depletion of parenchymal cells, not indirectly from injury to blood vessels, as has been the prevailing belief. (author)

  18. Sweet waste extract uptake by a mosquito vector: Survival, biting, fecundity responses, and potential epidemiological significance.

    Science.gov (United States)

    Dieng, Hamady; Satho, Tomomitsu; Abang, Fatimah; Meli, Nur Khairatun Khadijah Binti; Ghani, Idris A; Nolasco-Hipolito, Cirilo; Hakim, Hafijah; Miake, Fumio; Ahmad, Abu Hassan; Noor, Sabina; Zuharah, Wan Fatma; Ahmad, Hamdan; Majid, Abdul Hafiz A; Morales Vargas, Ronald E; Morales, Noppawan P; Attrapadung, Siriluck; Noweg, Gabriel Tonga

    2017-05-01

    In nature, adult mosquitoes typically utilize nectar as their main energy source, but they can switch to other as yet unidentified sugary fluids. Contemporary lifestyles, with their associated unwillingness to consume leftovers and improper disposal of waste, have resulted in the disposal of huge amounts of waste into the environment. Such refuse often contains unfinished food items, many of which contain sugar and some of which can collect water from rain and generate juices. Despite evidence that mosquitoes can feed on sugar-rich suspensions, semi-liquids, and decaying fruits, which can be abundant in garbage sites, the impacts of sweet waste fluids on dengue vectors are unknown. Here, we investigated the effects of extracts from some familiar sweet home waste items on key components of vectorial capacity of Aedes aegypti. Adult mosquitoes were fed one of five diets in this study: water (WAT); sucrose (SUG); bakery product (remnant of chocolate cake, BAK); dairy product (yogurt, YOG); and fruit (banana (BAN). Differences in survival, response time to host, and egg production were examined between groups. For both males and females, maintenance on BAK extract resulted in marked survival levels that were similar to those seen with SUG. Sweet waste extracts provided better substrates for survival compared to water, but this superiority was mostly seen with BAK. Females maintained on BAK, YOG, and BAN exhibited shorter response times to a host compared to their counterparts maintained on SUG. The levels of egg production were equivalent in waste extract- and SUG-fed females. The findings presented here illustrate the potential of sweet waste-derived fluids to contribute to the vectorial capacity of dengue vectors and suggest the necessity of readdressing the issue of waste disposal, especially that of unfinished sweet foods. Such approaches can be particularly relevant in dengue endemic areas where rainfall is frequent and waste collection infrequent. Copyright

  19. Do either early warning systems or emergency response teams improve hospital patient survival? A systematic review.

    Science.gov (United States)

    McNeill, G; Bryden, D

    2013-12-01

    For critical care to be effective it must have a system in place to achieve optimal care for the deteriorating ward patient. To systematically review the available literature to assess whether either early warning systems or emergency response teams improve hospital survival. In the event of there being a lack of evidence regarding hospital survival, secondary outcome measures were considered (unplanned ICU admissions, ICU mortality, length of ICU stay, length of hospital stay, cardiac arrest rates). The Ovid Medline, EMBASE, CINAHL, Web of Science, Cochrane library and NHS databases were searched in September 2012 along with non-catalogued resources for papers examining the effect of early warning systems or emergency response teams on hospital survival. Inclusion criteria were original clinical trials and comparative studies in adult inpatients that assessed either an early warning system or emergency response team against any of the predefined outcome measures. Exclusion criteria were previous systematic reviews, non-English abstracts and studies incorporating paediatric data. Studies were arranged in to sections focusing on the following interventions: Early warning systems - Single parameter systems - Aggregate weighted scoring systems (AWSS) Emergency response teams - Medical emergency teams - Multidisciplinary outreach services . In each section an appraisal of the level of evidence and a recommendation has been made using the SIGN grading system. 43 studies meeting the review criteria were identified and included for analysis. 2 studies assessed single parameter scoring systems and 4 addressed aggregate weighted scoring systems. A total of 20 studies examined medical emergency teams and 22 studies examined multidisciplinary outreach teams. The exclusion of non English studies and those including paediatric patients does limit the applicability of this review. Much of the available evidence is of poor quality. It is clear that a 'whole system' approach

  20. Habitat quality affects stress responses and survival in a bird wintering under extremely low ambient temperatures

    Science.gov (United States)

    Cīrule, Dina; Krama, Tatjana; Krams, Ronalds; Elferts, Didzis; Kaasik, Ants; Rantala, Markus J.; Mierauskas, Pranas; Luoto, Severi; Krams, Indrikis A.

    2017-12-01

    Animals normally respond to stressful environmental stimuli by releasing glucocorticoid hormones. We investigated whether baseline corticosterone (CORT), handling-induced corticosterone concentration(s), and body condition indices of members of willow tit ( Poecile montanus) groups differed while wintering in old growth forests and managed young forests in mild weather conditions and during cold spells. Willow tits spend the winter season in non-kin groups in which dominant individuals typically claim their priority to access resources, while subordinate individuals may experience greater levels of stress and higher mortality, especially during cold spells. We captured birds to measure baseline CORT and levels of handling-induced CORT secretion after 20 min of capture. Willow tits in the young forests had higher baseline CORT and a smaller increase in CORT in response to capture than individuals in the old forests. Baseline CORT was higher in females and juvenile birds compared to adult males, whereas handling-induced CORT secretion did not differ between birds of different ages. During cold spells, baseline CORT of willow tits increased and handling-induced CORT secretion decreased, especially in birds in young forests. Willow tits' survival was higher in the old forests, with dominant individuals surviving better than subordinates. Our results show that changes in CORT secretion reflect responses to habitat quality and climate harshness, indicating young managed coniferous forests as a suboptimal habitat for the willow tit.

  1. Laser Phototherapy Enhances Mesenchymal Stem Cells Survival in Response to the Dental Adhesives

    Directory of Open Access Journals (Sweden)

    Ivana Márcia Alves Diniz

    2015-01-01

    Full Text Available Background. We investigated the influence of laser phototherapy (LPT on the survival of human mesenchymal stem cells (MSCs submitted to substances leached from dental adhesives. Method. MSCs were isolated and characterized. Oral mucosa fibroblasts and osteoblast-like cells were used as comparative controls. Cultured medium conditioned with two adhesive systems was applied to the cultures. Cell monolayers were exposed or not to LPT. Laser irradiations were performed using a red laser (GaAlAs, 780 nm, 0.04 cm2, 40 mW, 1 W/cm2, 0.4 J, 10 seconds, 1 point, 10 J/cm2. After 24 h, cell viability was assessed by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide reduction assay. Data were statistically compared by ANOVA followed by Tukey’s test (P<0.05. Results. Different cell types showed different viabilities in response to the same materials. Substances leached from adhesives were less cytotoxic to MSCs than to other cell types. Substances leached from Clearfil SE Bond were highly cytotoxic to all cell types tested, except to the MSCs when applied polymerized and in association with LPT. LPT was unable to significantly increase the cell viability of fibroblasts and osteoblast-like cells submitted to the dental adhesives. Conclusion. LPT enhances mesenchymal stem cells survival in response to substances leached from dental adhesives.

  2. Initial Northwest Power Act Power Sales Contracts : Final Environmental Impact Statement. Volume 4, Comments and Responses.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration.

    1992-01-01

    This volume of the Initial Northwest Power Act Power Sales Contracts Final Environmental Impact Statement (Final EIS) contains public comments addressing the Initial Northwest Power Act Power Sales Contracts Draft EIS, August 1990 and Bonneville Power Administration`s (BPA) responses. The Introduction provides information about the process BPA follows in addressing these comments. Part I contains a listing of the Alternative Actions evaluated in the Final EIS; Part II is organized by Alternatives and includes summaries of the comments and BPA responses; Part III provides copies of the original comments letters, and, for ease of identification, are coded in the margins according to the alternative(s) addressed.

  3. Human response to nuclear and advanced technology weapons effects. Final report, January-December 1995

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, J.L.

    1996-05-01

    The purpose of this study is to help the system survivability analyst estimate hardness requirements for systems exposed to nuclear weapons and advanced technology weapons (ATWs). The system survivability analyst is often asked to make quick, order-of-magnitude estimates on the hardness requirements for existing or proposed systems based upon human responses to the effects of nuclear weapons and ATWs. The intent of this report is to identity the general range of human survivability to nuclear weapons and ATWs and to provide simple example calcuiations and scenarios that can give the reader rough estimates of the effects of these weapons. While high-powered microwave (HPM) and laser weapons are considered in this report, the main emphasis is on nuclear weapons and their ionizing radiation effects.

  4. Lymphoma development and survival in refractory coeliac disease type II: Histological response as prognostic factor.

    Science.gov (United States)

    Nijeboer, P; van Wanrooij, Rlj; van Gils, T; Wierdsma, N J; Tack, G J; Witte, B I; Bontkes, H J; Visser, O; Mulder, Cjj; Bouma, G

    2017-03-01

    Refractory coeliac disease type II (RCDII) frequently transforms into an enteropathy-associated T-cell lymphoma (EATL) and therefore requires intensive treatment. Current evaluated treatment strategies for RCDII include cladribine (2-CdA) and autologous stem cell transplantation (auSCT). The purpose of this study was to evaluate long-term survival and define clear prognostic criteria for EATL development comparing two treatment strategies. A total of 45 patients were retrospectively analysed. All patients received 2-CdA, after which they were either closely monitored (monotherapy, n  = 30) or a step-up approach was used including auSCT (step-up therapy, n  = 15). Ten patients (22%) ultimately developed EATL; nine of these had received monotherapy. Absence of histological remission after monotherapy was associated with EATL development ( p  = 0.010). Overall, 20 patients (44%) died with a median survival of 84 months. Overall survival (OS) within the monotherapy group was significantly worse in those without histological remission compared to those with complete histological remission( p  = 0.030). The monotherapy group who achieved complete histological remission showed comparable EATL occurrence and OS as compared to the step-up therapy group ( p  = 0.80 and p  = 0.14 respectively). Histological response is an accurate parameter to evaluate the effect of 2-CdA therapy and this parameter should be leading in the decisions whether or not to perform a step-up treatment approach in RCDII.

  5. Survival in Good Performance Malignant Pleural Mesothelioma Patients; Prognostic Factors and Predictors of Response

    Science.gov (United States)

    Rahouma, Mohamed; Aziz, Hala; Ghaly, Galal; Kamel, Mohamed; Loai, Iman; Mohamed, Abdelrahman

    2017-08-27

    Purpose: Malignant pleural mesothelioma (MPM) has a poor prognosis in general. Here we sought to evaluate prognostic factors and predictors of response to chemotherapy in good performance (PS=0-I) patients. Methods: We retrospectively reviewed our database and enrolled patients with MPM who received platinum containing chemotherapy (2012-2014). Clinico-pathological and laboratory data were retrieved and Cox and logistic regression multivariate analyses (MVA) were respectively used to identify predictors of survival and response to chemotherapy. Comparison of good vs poor performance status (PS≥II) was accomplished using the Chi (X2) test. Kaplan–Meier survival curves were also obtained and propensity-score matching was performed for survival comparison. Results: Among 114 patients listed during the study period, 82 had good PS=0-I (median age 45years, 43 men, 30 smokers, median weight=77Kg, pretreatment haemoglobin (Hb) level=12g/dL, platelet count=372,000/μL, leukocytes=9,700/μL, neutrophils=6,100/μL, lymphocytes=1,890/μL and neutrophil/lymphocyte ratio (NLR)=3.60 ). Some 65 had asbestosis, 23 had chronic disease, 55 (67.1%) were responders to platinum containing first line chemotherapy. A total of 49 (59.8%) had epithelial MPM. Median-OS and PFS in good PS cases were 17 and 9 months, respectively, as compared to 16 and 8 months for the poor PS group. After matching, better OS was observed among good PS vs poor PS patients (p=0.024) but there was no PFS difference (p=0.176). Significant decrease in PFS was observed among those with advanced nodal N disease (median PFS in N0 and N+ was 10 and 5 months, respectively), non-responders (p=0.012), NLR (p=0.026) and those with an epithelial pathology (p=0.062). MVA demonstrated that advanced (N) status (p=0.015), being a non-responder (pgood PS. Early detection before development of metastasis warrants greater focus to allow better responses to be obtained. Creative Commons Attribution License

  6. Survival, gene and metabolite responses of Litoria verreauxii alpina frogs to fungal disease chytridiomycosis

    Science.gov (United States)

    Grogan, Laura F.; Mulvenna, Jason; Gummer, Joel P. A.; Scheele, Ben C.; Berger, Lee; Cashins, Scott D.; McFadden, Michael S.; Harlow, Peter; Hunter, David A.; Trengove, Robert D.; Skerratt, Lee F.

    2018-03-01

    The fungal skin disease chytridiomycosis has caused the devastating decline and extinction of hundreds of amphibian species globally, yet the potential for evolving resistance, and the underlying pathophysiological mechanisms remain poorly understood. We exposed 406 naïve, captive-raised alpine tree frogs (Litoria verreauxii alpina) from multiple populations (one evolutionarily naïve to chytridiomycosis) to the aetiological agent Batrachochytrium dendrobatidis in two concurrent and controlled infection experiments. We investigated (A) survival outcomes and clinical pathogen burdens between populations and clutches, and (B) individual host tissue responses to chytridiomycosis. Here we present multiple interrelated datasets associated with these exposure experiments, including animal signalment, survival and pathogen burden of 355 animals from Experiment A, and the following datasets related to 61 animals from Experiment B: animal signalment and pathogen burden; raw RNA-Seq reads from skin, liver and spleen tissues; de novo assembled transcriptomes for each tissue type; raw gene expression data; annotation data for each gene; and raw metabolite expression data from skin and liver tissues. These data provide an extensive baseline for future analyses.

  7. Epigenetic Regulation of the Nitrosative Stress Response and Intracellular Macrophage Survival by Extraintestinal Pathogenic Escherichia coli

    Science.gov (United States)

    Bateman, Stacey L.; Seed, Patrick C.

    2013-01-01

    Summary Extraintestinal pathogenic Escherichia coli (ExPEC) reside in the enteric tract as a commensal reservoir, but can transition to a pathogenic state by invading normally sterile niches, establishing infection, and disseminating to invasive sites like the bloodstream. Macrophages are required for ExPEC dissemination, suggesting the pathogen has developed mechanisms to persist within professional phagocytes. Here, we report that FimX, an ExPEC-associated DNA invertase that regulates the major virulence factor type 1 pili (T1P), is also an epigenetic regulator of a LuxR-like response regulator HyxR. FimX regulated hyxR expression through bidirectional phase inversion of its promoter region at sites different from the type 1 pili promoter and independent of integration host factor IHF. In vitro, transition from high to low HyxR expression produced enhanced tolerance of reactive nitrogen intermediates (RNI), primarily through de-repression of hmpA, encoding a nitric oxide detoxifying flavohemoglobin. However, in the macrophage, HyxR produced large effects on intracellular survival in the presence and absence of RNI and independent of Hmp. Collectively, we have shown that the ability of ExPEC to survive in macrophages is contingent upon the proper transition from high to low HyxR expression through epigenetic regulatory control by FimX. PMID:22221182

  8. Systemic inflammatory response syndrome (SIRS) after extracorporeal membrane oxygenation (ECMO): Incidence, risks and survivals.

    Science.gov (United States)

    Thangappan, Karthik; Cavarocchi, Nicholas C; Baram, Michael; Thoma, Brandi; Hirose, Hitoshi

    2016-01-01

    Systemic inflammatory response syndrome (SIRS) is frequently observed after extracorporeal membrane oxygenation (ECMO) decannulation; however, these issues have not been investigated well in the past. Retrospective chart review was performed to identify post-ECMO SIRS phenomenon, defined by exhibiting 2/3 of the following criteria: fever, leukocytosis, and escalation of vasopressors. The patients were divided into 2 groups: patients with documented infections (Group I) and patients with true SIRS (Group TS) without any evidence of infection. Survival and pre-, intra- and post-ECMO risk factors were analyzed. Among 62 ECMO survivors, 37 (60%) patients developed the post-ECMO SIRS phenomenon, including Group I (n = 22) and Group TS (n = 15). The 30-day survival rate of Group I and TS was 77% and 100%, respectively (p = 0.047), although risk factors were identical. SIRS phenomenon after ECMO decannulation commonly occurs. Differentiating between the similar clinical presentations of SIRS and infection is important and will impact clinical outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Epigenetic regulation of the nitrosative stress response and intracellular macrophage survival by extraintestinal pathogenic Escherichia coli.

    Science.gov (United States)

    Bateman, Stacey L; Seed, Patrick C

    2012-03-01

    Extraintestinal pathogenic Escherichia coli (ExPEC) reside in the enteric tract as a commensal reservoir, but can transition to a pathogenic state by invading normally sterile niches, establishing infection and disseminating to invasive sites like the bloodstream. Macrophages are required for ExPEC dissemination, suggesting the pathogen has developed mechanisms to persist within professional phagocytes. Here, we report that FimX, an ExPEC-associated DNA invertase that regulates the major virulence factor type 1 pili (T1P), is also an epigenetic regulator of a LuxR-like response regulator HyxR. FimX regulated hyxR expression through bidirectional phase inversion of its promoter region at sites different from the type 1 pili promoter and independent of integration host factor (IHF). In vitro, transition from high to low HyxR expression produced enhanced tolerance of reactive nitrogen intermediates (RNIs), primarily through de-repression of hmpA, encoding a nitric oxide-detoxifying flavohaemoglobin. However, in the macrophage, HyxR produced large effects on intracellular survival in the presence and absence of RNI and independent of Hmp. Collectively, we have shown that the ability of ExPEC to survive in macrophages is contingent upon the proper transition from high to low HyxR expression through epigenetic regulatory control by FimX. © 2012 Blackwell Publishing Ltd.

  10. Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade

    Directory of Open Access Journals (Sweden)

    Michal Lotem

    2016-01-01

    Full Text Available Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival. Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p=0.0001 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2, MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p=0.007. Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity.

  11. YAP enhances autophagic flux to promote breast cancer cell survival in response to nutrient deprivation.

    Directory of Open Access Journals (Sweden)

    Qinghe Song

    Full Text Available The Yes-associated protein (YAP, a transcriptional coactivator inactivated by the Hippo tumor suppressor pathway, functions as an oncoprotein in a variety of cancers. However, its contribution to breast cancer remains controversial. This study investigated the role of YAP in breast cancer cells under nutrient deprivation (ND. Here, we show that YAP knockdown sensitized MCF7 breast cancer cells to nutrient deprivation-induced apoptosis. Furthermore, in response to ND, YAP increased the autolysosome degradation, thereby enhancing the cellular autophagic flux in breast cancer cells. Of note, autophagy is crucial for YAP to protect MCF7 cells from apoptosis under ND conditions. In addition, the TEA domain (TEAD family of growth-promoting transcription factors was indispensable for YAP-mediated regulation of autophagy. Collectively, our data reveal a role for YAP in promoting breast cancer cell survival upon ND stress and uncover an unappreciated function of YAP/TEAD in the regulation of autophagy.

  12. Altered G{sub 1} checkpoint control determines adaptive survival responses to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Boothman, David A.; Meyers, Mark; Odegaard, Eric; Wang, Meizhi [Department of Human Oncology, University of Wisconsin-Madison, Madison, WI (United States)

    1996-11-04

    Adaptive survival responses (ASRs) are observed when cells become more resistant to a high dose of a cytotoxic agent after repeated low dose exposures to that agent or another genotoxic agent. Confluent (G{sub 0}/G{sub 1}) human normal (GM2936B, GM2937A, AG2603, IMR-90), cancer-prone (XPV2359), and neoplastic (U1-Mel, HEp-2, HTB-152) cells were primed with repeated low doses of X-rays (ranging from 0.05-10 cGy/day for 4 days), then challenged with a high dose (290-450 cGy) on day 5. U1-Mel and HEp-2 cells showed greater than 2-fold transient survival enhancement when primed with 1-10 cGy. ASRs in U1-Mel or HEp-2 cells were blocked by cycloheximide or actinomycin D. Increases in cyclins A and D1 mRNAs were noted in primed compared to unirradiated U1-Mel and HEp-2 cells; however, only cyclin A protein levels increased. Cyclin D1 and proliferating cell nuclear antigen (PCNA) protein levels were constitutively elevated in HEp-2 and U1-Mel cells, compared to the other human normal and neoplastic cells examined, and were not altered by low or high doses of radiation. Low dose primed U1-Mel cells entered S-phase 4-6 h faster than unprimed U1-Mel cells upon low-density replating. Similar responses in terms of survival recovery, transcript and protein induction, and altered cell cycle regulation were not observed in the other human normal, cancer-prone or neoplastic cells examined. We hypothesize that only certain human cells can adapt to ionizing radiation by progressing to a point later in G{sub 1} (the A point) where DNA repair processes and radioresistance can be induced. ASRs in human cells correlated well with constitutively elevated levels of PCNA and cyclin D1, as well as inducibility of cyclin A. We propose that a protein complex composed of cyclin D1, PCNA, and possibly cyclin A may play a role in cell cycle regulation and DNA repair, which determine ASRs in human cells.

  13. Altered G1 checkpoint control determines adaptive survival responses to ionizing radiation

    International Nuclear Information System (INIS)

    Boothman, David A.; Meyers, Mark; Odegaard, Eric; Wang, Meizhi

    1996-01-01

    Adaptive survival responses (ASRs) are observed when cells become more resistant to a high dose of a cytotoxic agent after repeated low dose exposures to that agent or another genotoxic agent. Confluent (G 0 /G 1 ) human normal (GM2936B, GM2937A, AG2603, IMR-90), cancer-prone (XPV2359), and neoplastic (U1-Mel, HEp-2, HTB-152) cells were primed with repeated low doses of X-rays (ranging from 0.05-10 cGy/day for 4 days), then challenged with a high dose (290-450 cGy) on day 5. U1-Mel and HEp-2 cells showed greater than 2-fold transient survival enhancement when primed with 1-10 cGy. ASRs in U1-Mel or HEp-2 cells were blocked by cycloheximide or actinomycin D. Increases in cyclins A and D1 mRNAs were noted in primed compared to unirradiated U1-Mel and HEp-2 cells; however, only cyclin A protein levels increased. Cyclin D1 and proliferating cell nuclear antigen (PCNA) protein levels were constitutively elevated in HEp-2 and U1-Mel cells, compared to the other human normal and neoplastic cells examined, and were not altered by low or high doses of radiation. Low dose primed U1-Mel cells entered S-phase 4-6 h faster than unprimed U1-Mel cells upon low-density replating. Similar responses in terms of survival recovery, transcript and protein induction, and altered cell cycle regulation were not observed in the other human normal, cancer-prone or neoplastic cells examined. We hypothesize that only certain human cells can adapt to ionizing radiation by progressing to a point later in G 1 (the A point) where DNA repair processes and radioresistance can be induced. ASRs in human cells correlated well with constitutively elevated levels of PCNA and cyclin D1, as well as inducibility of cyclin A. We propose that a protein complex composed of cyclin D1, PCNA, and possibly cyclin A may play a role in cell cycle regulation and DNA repair, which determine ASRs in human cells

  14. Guidebook for preparation of aircraft-system survivability requirements for procurement documents. Final report, October 1975-October 1976

    Energy Technology Data Exchange (ETDEWEB)

    Morrow, J.J.; Burris, R.A.; Watson, D.J.

    1977-05-01

    This report is intended to provide guidelines for the preparation of procurements specifications for aircraft survivability enhancement equipment, for the survivability/vulnerability (S/V) tasks associated with the procurement of a total aircraft system or its relate subsystems, and also for the modification of current fleet aircraft to their related subsystems. It is intended that these S/V procurement guidelines be applied to the procurement of all military aircraft, aircraft subsystems, and aircraft componenets which can either lose their functional capability of have their performance degraded as a result of interactions with the damage mechanisms of threat weapons. The guidelines should be applied to preliminary design programs, to production programs, and to programs that will retrofit or modify existing systems. These guidelines include general requirements statements for the establishment of an S/V program, requirements statements for reducing the susceptibility of the system to the threat weapons, and requirements for the reduction of vulnerability to nonnuclear, nuclear, and laser weapon effects. Requirements for S/V assessments and the verification of vulnerability levels and survival enhancement features are also included. Although nuclear and laser weapon effects are included, the major emphasis is on the reduction of susceptibility and vulnerability to conventional weapons and the establishment of the S/V program.

  15. Preradiation chemotherapy may improve survival in pediatric diffuse intrinsic brainstem gliomas: final results of BSG 98 prospective trial.

    Science.gov (United States)

    Frappaz, Didier; Schell, Matthias; Thiesse, Philippe; Marec-Bérard, Perrine; Mottolese, Carmine; Perol, David; Bergeron, Christophe; Philip, Thierry; Ricci, Anne Claire; Galand-Desme, Sophie; Szathmari, Alexandru; Carrie, Christian

    2008-08-01

    Radiation therapy remains the only treatment that provides clinical benefit to children with diffuse brainstem tumors. Their median survival, however, rarely exceeds 9 months. The authors report a prospective trial of frontline chemotherapy aimed at delaying radiation until time of clinical progression. The aim was to investigate the possibility that radiotherapy would maintain its activity in children whose disease progressed after chemotherapy. Twenty-three patients took part in this protocol, the BSG 98 protocol, which consisted of frontline chemotherapy alternating hematotoxic and nonhematotoxic schedules. Each cycle included three courses delivered monthly; the first course was 1,3-bis(2-chloroethyl)-1-nitrosoureacisplatin, and the second and third were high-dose methotrexate. Three patients underwent one cycle; 5 patients each, two and three cycles; and 10 patients, four cycles. Twenty of the 23 patients eventually received local radiation therapy. A historical cohort of 14 patients who received at least local radiation therapy served as controls. Four patients experienced severe iatrogenic infections, and 11 patients required platelet transfusions. Median survival increased significantly in patients participating in the protocol compared to that in the historical controls (17 months, 95% confidence interval [CI], 10-23 months, vs. 9 months, 95% CI, 8-10 months; p = 0.022), though hospitalization was prolonged (57 vs. 25 days, p = 0.001). Although frontline chemotherapy alternating hematotoxic and nonhematotoxic schedules significantly increases overall median survival, its cost from infection and hospitalization deserves honest discussion with the children and their parents.

  16. Pathologic complete response predicts long-term survival following preoperative radiation therapy for rectal cancer

    International Nuclear Information System (INIS)

    Ahmad, Neelofur R.; Nagle, Deborah A.; Topham, Allan

    1997-01-01

    Purpose: The finding of a pathologic complete response (pCR) after preoperative radiation therapy (RT) for rectal cancer is frequently used as a surrogate endpoint for treatment outcome. In most reported series, the pCR rate ranges from 10 to 25%. An underlying assumption is that pCR relates to favorable long-term patient outcome; however, such results are rarely reported. The purpose of this study was to determine the long-term outcome of patients having pCR's following preoperative RT and surgery for rectal cancer. Materials and Methods: Between 1978 and 1993, 49 of 315 patients (16%) were found to have pCR's following 40 to 65 Gy of preoperative RT for rectal cancer (median RT dose 55.8 Gy). Six complete responders also received concurrent 5-FU chemotherapy with RT. Follow-up time ranged from 7 to 224 months (median 52 months). Actuarial overall survival (OS), disease-free survival (DFS), and local control (LC) rates were calculated. Patient outcome was analyzed with respect to pretreatment clinical stage (mobile vs. tethered/fixed on digital exam), tumor level in the rectum as measured from the anorectal ring (0-3 cm vs. >3 cm), type of surgery (local excision, APR, or other), and use of concurrent chemotherapy vs. RT alone. Results: Prior to treatment, clinical stage tumor stage was 43% mobile ((21(49))) and 35% tethered/fixed ((17(49))). Twenty-two percent ((11(49))) did not have palpable tumor at presentation to our institution due to prior local excision of an invasive cancer. Tumor level in the rectum was 74% 0-3 cm, 16% >3 to 6 cm, and 10% > 6 cm. Surgical procedures were 12% APR, 24% LAR, 6% combined abdominal transsacral resection (CATS), 27% coloanal anastamosis, and 31% full thickness local excision. Overall, 2 of 49 patients (4%) developed a local tumor recurrence, and 4 of 49 (8%) developed distant metastases. The overall 5- and 10-year actuarial survival rates were 91% and 86%, respectively. The 5- and 10-year actuarial DFS rate was 85%, and the

  17. Circulating Vitamin D and Overall Survival in Breast Cancer Patients: A Dose-Response Meta-Analysis of Cohort Studies.

    Science.gov (United States)

    Hu, Kejia; Callen, David Frederick; Li, Jiayuan; Zheng, Hong

    2017-05-01

    Studies have shown that vitamin D could have a role in breast cancer survival; however, the evidence of the relationship between patients' vitamin D levels and their survival has been inconsistent. This meta-analysis explores possible dose-response relationships between vitamin D levels and overall survival by allowing for differences in vitamin D levels among populations of the various studies. Studies relating vitamin D (25-OH-D [25-hydroxyvitamin D]) levels in breast cancer patients with their survival were identified by searching PubMed and Embase. A pooled HR (hazard ratio) comparing the highest with the lowest category of circulating 25-OH-D levels were synthesized using the Mantel-Haenszel method under a fixed-effects model. A two-stage fixed-effects dose-response model including both linear (a log-linear dose-response regression) and nonlinear (a restricted cubic spline regression) models were used to further explore possible dose-response relationships. Six studies with a total number of 5984 patients were identified. A pooled HR comparing the highest with the lowest category of circulating 25-OH-D levels under a fixed-effects model was 0.67 (95% confidence interval = 0.56-0.79, P response meta-analysis, the pooled HR for overall survival in breast cancer patients was 0.994 (per 1 nmol/L), P for linear trend response relationship between circulating 25-OH-D levels and overall survival in patients with breast cancer. However, better designed prospective cohort studies and clinical trials are needed to further confirm these findings.

  18. Inherited Inflammatory Response Genes Are Associated with B-Cell Non-Hodgkin's Lymphoma Risk and Survival.

    Directory of Open Access Journals (Sweden)

    Kaspar René Nielsen

    Full Text Available Malignant B-cell clones are affected by both acquired genetic alterations and by inherited genetic variations changing the inflammatory tumour microenvironment.We investigated 50 inflammatory response gene polymorphisms in 355 B-cell non-Hodgkin's lymphoma (B-NHL samples encompassing 216 diffuse large B cell lymphoma (DLBCL and 139 follicular lymphoma (FL and 307 controls. The effect of single genes and haplotypes were investigated and gene-expression analysis was applied for selected genes. Since interaction between risk genes can have a large impact on phenotype, two-way gene-gene interaction analysis was included.We found inherited SNPs in genes critical for inflammatory pathways; TLR9, IL4, TAP2, IL2RA, FCGR2A, TNFA, IL10RB, GALNT12, IL12A and IL1B were significantly associated with disease risk and SELE, IL1RN, TNFA, TAP2, MBL2, IL5, CX3CR1, CHI3L1 and IL12A were, associated with overall survival (OS in specific diagnostic entities of B-NHL. We discovered noteworthy interactions between DLBCL risk alleles on IL10 and IL4RA and FL risk alleles on IL4RA and IL4. In relation to OS, a highly significant interaction was observed in DLBCL for IL4RA (rs1805010 * IL10 (rs1800890 (HR = 0.11 (0.02-0.50. Finally, we explored the expression of risk genes from the gene-gene interaction analysis in normal B-cell subtypes showing a different expression of IL4RA, IL10, IL10RB genes supporting a pathogenetic effect of these interactions in the germinal center.The present findings support the importance of inflammatory genes in B-cell lymphomas. We found association between polymorphic sites in inflammatory response genes and risk as well as outcome in B-NHL and suggest an effect of gene-gene interactions during the stepwise oncogenesis.

  19. Modeling the survival responses of a multi-component biofilm to environmental stress

    Science.gov (United States)

    Carles Brangarí, Albert; Manzoni, Stefano; Sanchez-Vila, Xavier; Fernàndez-Garcia, Daniel

    2017-04-01

    Biofilms are consortia of microorganisms embedded in self-produced matrices of biopolymers. The survival of such communities depends on their capacity to improve the environmental conditions of their habitat by mitigating, or even benefitting from some adverse external factors. The mechanisms by which the microbial habitat is regulated remain mostly unknown. However, many studies have reported physiological responses to environmental stresses that include the release of extracellular polymeric substances (EPS) and the induction of a dormancy state. A sound understanding of these capacities is required to enhance the knowledge of the microbial dynamics in soils and its potential role in the carbon cycle, with significant implications for the degradation of contaminants and the emission of greenhouse gases, among others. We present a numerical analysis of the dynamics of soil microbes and their responses to environmental stresses. The conceptual model considers a multi-component heterotrophic biofilm made up of active cells, dormant cells, EPS, and extracellular enzymes. Biofilm distribution and properties are defined at the pore-scale and used to determine nutrient availability and water saturation via feedbacks of biofilm on soil hydraulic properties. The pore space micro-habitat is modeled as a simplified pore-network of cylindrical tubes in which biofilms proliferate. Microbial compartments and most of the carbon fluxes are defined at the bulk level. Microbial processes include the synthesis, decay and detachment of biomass, the activation/deactivation of cells, and the release and reutilization of EPS. Results suggest that the release of EPS and the capacity to enter a dormant state offer clear evolutionary advantages in scenarios characterized by environmental stress. On the contrary, when the conditions are favorable, the diversion of carbon into the production of the aforementioned survival mechanisms does not confer any additional benefit and the population

  20. Survival and Passage of Yearling Chinook Salmon and Steelhead at The Dalles Dam, Spring 2011 - FINAL REPORT

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Gary E.; Hennen, Matthew J.; Zimmerman, Shon A.; Batten, G.; Carpenter, Scott M.; Deng, Zhiqun; Fu, Tao; Hughes, James S.; Martinez, Jayson J.; Ploskey, Gene R.; Royer, Ida M.; Townsend, Richard L.; Woodley, Christa M.; Kim, Jeongkwon; Etherington, D. J.; Skalski, J. R.; Carlson, Thomas J.; Cushing, Aaron W.; Fisher, Erik J.; Greiner, Michael J.; Khan, Fenton; Mitchell, T. D.; Rayamajhi, Bishes; Seaburg, Adam; Weiland, Mark A.

    2012-10-01

    The study reported herein was conducted by the Pacific Northwest National Laboratory (PNNL) and the University of Washington (UW) for the U.S. Army Corps of Engineers, Portland District (USACE). The PNNL and UW project managers were Drs. Thomas J. Carlson and John R. Skalski, respectively. The USACE technical lead was Mr. Brad Eppard. The study was designed to estimate dam passage survival and other performance measures at The Dalles Dam as stipulated by the 2008 Federal Columbia River Power System Biological Opinion (BiOp) and the 2008 Columbia Basin Fish Accords. The study is being documented in two types of reports: compliance and technical. A compliance report is delivered within 6 months of the completion of the field season and focuses on results of the performance metrics outlined in the 2008 BiOp and Fish Accords. A technical report is produced within the 18 months after field work, providing comprehensive documentation of a given study and results on route-specific survival estimates and fish passage distributions, which are not included in compliance reports. This technical report concerns the 2011 acoustic telemetry study at The Dalles Dam.

  1. Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab.

    Science.gov (United States)

    McDermott, David F; Drake, Charles G; Sznol, Mario; Choueiri, Toni K; Powderly, John D; Smith, David C; Brahmer, Julie R; Carvajal, Richard D; Hammers, Hans J; Puzanov, Igor; Hodi, F Stephen; Kluger, Harriet M; Topalian, Suzanne L; Pardoll, Drew M; Wigginton, Jon M; Kollia, Georgia D; Gupta, Ashok; McDonald, Dan; Sankar, Vindira; Sosman, Jeffrey A; Atkins, Michael B

    2015-06-20

    Blockade of the programmed death-1 inhibitory cell-surface molecule on immune cells using the fully human immunoglobulin G4 antibody nivolumab mediates tumor regression in a portion of patients with advanced treatment-refractory solid tumors. We report clinical activity, survival, and long-term safety in patients with advanced renal cell carcinoma (RCC) treated with nivolumab in a phase I study with expansion cohorts. A total of 34 patients with previously treated advanced RCC, enrolled between 2008 and 2012, received intravenous nivolumab (1 or 10 mg/kg) in an outpatient setting once every two weeks for up to 96 weeks and were observed for survival and duration of response after treatment discontinuation. Ten patients (29%) achieved objective responses (according to RECIST [version 1.0]), with median response duration of 12.9 months; nine additional patients (27%) demonstrated stable disease lasting > 24 weeks. Three of five patients who stopped treatment while in response continued to respond for ≥ 45 weeks. Median overall survival in all patients (71% with two to five prior systemic therapies) was 22.4 months; 1-, 2-, and 3-year survival rates were 71%, 48%, and 44%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 18% of patients; all were reversible. Patients with advanced treatment-refractory RCC treated with nivolumab demonstrated durable responses that in some responders persisted after drug discontinuation. Overall survival is encouraging, and toxicities were generally manageable. Ongoing randomized clinical trials will further assess the impact of nivolumab on overall survival in patients with advanced RCC. © 2015 by American Society of Clinical Oncology.

  2. Enhancing Organizational Survivability in a Crisis: Perceived Organizational Crisis Responsibility, Stance, and Strategy

    Directory of Open Access Journals (Sweden)

    JiYeon Jeong

    2015-08-01

    Full Text Available For the purpose of enhancing organizational sustainability during a crisis, an organization takes a position in decision-making, how to respond toward its public, and that is supposed to determine which stance or tactic to employ. This study aims to examine whether publics’ perceptions of organizational crisis responsibility affect their expectations that an organization should choose certain stances and strategies toward the public in a crisis. To address these concerns, an experiment was conducted. As the specific public of this research, health journalists were selected, since they affect public perceptions significantly and public opinion can ultimately put pressure on an organization. Results from an analysis of the experimental data with health journalists confirm that they expect a more accommodative stance/strategy when they perceive that the organization is highly responsible for a health-related crisis. Conversely, when the journalists perceive that an organization has a low level of responsibility for a crisis, they expect a more advocative stance/strategy. By taking into account the health journalists’ expectations along with the needs of the organization, public relations practitioners are better able to make optimal decisions regarding their client organizations’ adopted stance and strategy, and finally, enhance organizational sustainability in a crisis.

  3. EQ-5D utility, response and drug survival in rheumatoid arthritis patients on biologic monotherapy

    DEFF Research Database (Denmark)

    Jørgensen, Tanja Schjødt; Turesson, Carl; Kapetanovic, Meliha C

    2017-01-01

    OBJECTIVES: Biologic agents have dramatically changed treatment of rheumatoid arthritis (RA). To date only scarce head-to-head data exist especially when the biological therapies are given as monotherapy without concomitant disease modifying drugs (DMARDs). Thus the objective of the current study...... is to evaluate treatment response of all available biological therapies with special focus on utility (EQ-5D-3L) and drug survival of biologic DMARDs (bDMARDs) prescribed as monotherapy in RA patients in southern Sweden. MATERIALS AND METHODS: All RA patients registered in a regional database as initiating b......-5D-3L was 0.34. Most patients had moderate to high disease activity, with a mean DAS28 of 5.0, and were substantially disabled, with an average HAQ score of 1.4. At 6 months´ follow-up, the EQ-5D-3L in patients still on the biologic drug had increased by mean 0.23 (SD 0.4) with no differences...

  4. Oosorption in response to poor food: complexity in the trade-off between reproduction and survival

    Science.gov (United States)

    Moore, Patricia J; Attisano, Alfredo

    2011-01-01

    Plasticity in reproductive physiology is one avenue by which environmental signals, such as poor quality food, can be coordinated with adaptive responses. Insects have the ability to resorb oocytes that are not oviposited. Oosorption is proposed to be an adaptive mechanism to optimize fitness in hostile environments, recouping resources that might otherwise be lost, and reinvesting them into future reproductive potential. We tested the hypothesis that oosorption is an evolved mechanism by which females can reallocate resources from current reproductive effort to survival and future reproduction, when conditions for reproduction are poor, by examining the reproductive physiology and life-history outcome under poor quality food in populations of the milkweed bug (Oncopeltus fasciatus) that have adapted to live on sunflower seed. Females fed a diet of pumpkin seeds, known to be a poor host food, had higher levels of ovarian apoptosis (oosorption), lower reproductive output, but no reduction in life span under poor nutrition, as predicted under the oosorption hypothesis. However, the schedule of reproduction was surprising given the “wait to reproduce” assumption of oosorption as early fecundity was unaffected. PMID:22393481

  5. Root based responses account for Psidium guajava survival at high nickel concentration.

    Science.gov (United States)

    Bazihizina, Nadia; Redwan, Mirvat; Taiti, Cosimo; Giordano, Cristiana; Monetti, Emanuela; Masi, Elisa; Azzarello, Elisa; Mancuso, Stefano

    2015-02-01

    The presence of Psidium guajava in polluted environments has been reported in recent studies, suggesting that this species has a high tolerance to the metal stress. The present study aims at a physiological characterization of P. guajava response to high nickel (Ni) concentrations in the root-zone. Three hydroponic experiments were carried out to characterize the effects of toxic Ni concentrations on morphological and physiological parameters of P. guajava, focusing on Ni-induced damages at the root-level and root ion fluxes. With up to 300μM NiSO4 in the root-zone, plant growth was similar to that in control plants, whereas at concentrations higher than 1000μM NiSO4 there was a progressive decline in plant growth and leaf gas exchange parameters; this occurred despite, at all considered concentrations, plants limited Ni(2+) translocation to the shoot, therefore avoiding shoot Ni(2+) toxicity symptoms. Maintenance of plant growth with 300μM Ni(2+) was associated with the ability to retain K(+) in the roots meanwhile 1000 and 3000μM NiSO4 led to substantial K(+) losses. In this study, root responses mirror all plant performances suggesting a direct link between root functionality and Ni(2+) tolerance mechanisms and plant survival. Considering that Ni was mainly accumulated in the root system, the potential use of P. guajava for Ni(2+) phytoextraction in metal-polluted soils is limited; nevertheless, the observed physiological changes indicate a good Ni(2+) tolerance up to 300μM NiSO4 suggesting a potential role for the phytostabilization of polluted soils. Copyright © 2014 Elsevier GmbH. All rights reserved.

  6. Emmprin and survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer

    DEFF Research Database (Denmark)

    Als, Anne B; Dyrskjøt, Lars; von der Maase, Hans

    2007-01-01

    PURPOSE: Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is approximately 50% and tumor-derived molecular prognostic markers are desirable for improved estimation of respon...... independent prognostic factors for response and survival after cisplatin-containing chemotherapy in patients with advanced bladder cancer.......PURPOSE: Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is approximately 50% and tumor-derived molecular prognostic markers are desirable for improved estimation of response...... in an independent material of 124 patients receiving cisplatin-containing therapy. RESULTS: Fifty-five differentially expressed genes correlated significantly to survival time. Two of the protein products (emmprin and survivin) were validated using immunohistochemistry. Multivariate analysis identified emmprin...

  7. Emmprin and Survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer

    DEFF Research Database (Denmark)

    Als, Anne Birgitte; Andersen, Lars Dyrskjøt; Maase, Hans von der

    2007-01-01

    PURPOSE: Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is approximately 50% and tumor-derived molecular prognostic markers are desirable for improved estimation of respon...... independent prognostic factors for response and survival after cisplatin-containing chemotherapy in patients with advanced bladder cancer.......PURPOSE: Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is approximately 50% and tumor-derived molecular prognostic markers are desirable for improved estimation of response...... in an independent material of 124 patients receiving cisplatin-containing therapy. RESULTS: Fifty-five differentially expressed genes correlated significantly to survival time. Two of the protein products (emmprin and survivin) were validated using immunohistochemistry. Multivariate analysis identified emmprin...

  8. Culture conditions affecting the survival response of Chinese hamster ovary cells treated by hyperthermia

    International Nuclear Information System (INIS)

    Highfield, D.P.; Holahan, E.V.; Dewey, W.C.

    1982-01-01

    Using lethally irradiated feeder cells to control cell population densities, researchers investigated the survival of Chinese hamster ovary cells heated between 42.2 and 45.5 degrees C. Test cells were plated into T25 flasks with or without feeder cells, incubated 2 hours at 37 degrees C, and then given various heat treatments. Under all heating conditions, survival increased in those flasks containing feeder cells. Increased survival (by as much as a factor of 100 for cells heated at 42.4 degrees C for 6-10 hr) was most apparent when cells were heated to thermotolerance. By adjustment of test and feeder cell numbers, survival increased as density increased; however, maximum survival followed a transition period that occurred between the plating of 1 X 10(4) and 6 X 10(4) cells. Experimental artifacts due to improper control of cell density was demonstrated

  9. Prognostic nutritional index serves as a predicative marker of survival and associates with systemic inflammatory response in metastatic intrahepatic cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Zhang C

    2016-10-01

    Full Text Available Chenyue Zhang,1,2 Haiyong Wang,1,3 Zhouyu Ning,1,2 Litao Xu,1,2 Liping Zhuang,1,2 Peng Wang,1,2 Zhiqiang Meng1,2 1Department of Integrative Oncology, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 3Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, People’s Republic of China Objective: The significance of the prognostic nutritional index (PNI has been widely reported and confirmed in many types of cancers. However, few studies are available indicating its prognostic power in patients with intrahepatic cholangiocarcinoma (ICC. Thus, we investigated its relationship with overall survival (OS to evaluate its role in predicting survival in patients with ICC. Patients and methods: Between October 2011 and October 2015, 173 consecutive patients with pathologically confirmed locally advanced or metastatic ICC were enrolled. First, the correlations between PNI and clinical factors were analyzed among these patients. Next, univariate and multivariate analyses were conducted to evaluate the association between PNI and OS among these patients with ICC. In addition, the relationships between PNI and three typical systemic inflammatory response (SIR markers – the neutrophil/lymphocyte ratio (NLR, the platelet/lymphocyte ratio (PLR, and the lymphocyte/monocyte ratio (LMR – were also assessed. Results: A lower PNI was linked with a shorter OS in patients with ICC, as reflected obviously in the Kaplan–Meier analyses. The patients with ICC were divided into the locally advanced group and the metastatic group. Further analyses revealed that PNI is not associated with OS in the locally advanced group. However, in the subgroup of patients with metastatic ICC, a lower PNI significantly correlated with a worsened OS. The OS for patients with a low PNI is 5 months, whereas the OS is 10.17 months for patients with a high PNI. Multivariate analyses revealed

  10. Response of the microtubular cytoskeleton following hyperthermia as a prognostic indicator of survival of Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    Coss, Ronald A.; Alden, Mark E.; Wachsberger, Phyllis R.; Smith, Nancy N.

    1996-01-01

    Purpose: The response of the microtubular (MT) cytoskeleton to hyperthermia was assessed as a prognostic indicator of cytotoxicity. Methods and Materials: Heat-induced collapse and subsequent recovery of the MT system were compared with survival for both nonthermotolerant (NT) and thermotolerant (TT) G1 populations of Chinese hamster ovary (CHO) cells. The response of the MT system was monitored using immunofluorescence staining. The G1 populations of NT and TT cells were heated by submersion in 45.0 and 43.0 deg. C waterbaths. Results: Heat-induced perinuclear collapse of the MT system did not correlate with survival for the NT and TT populations. However, recovery of the organization of the MT cytoskeleton was correlatable with survival. The regression line of survival plotted as a function of MT recovery is fit by: y = -0.43 + 1.03x, r 2 = 0.95 (p < 0.0005). Conclusion: Restoration of the organization of the MT cytoskeleton following hyperthermia may be used as a prognostic indicator of survival of CHO cells heated in G1

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

    OpenAIRE

    Facon, Thierry; Dimopoulos, Meletios A.; Dispenzieri, Angela; Catalano, John V.; Belch, Andrew; Cavo, Michele; Pinto, Antonello; Weisel, Katja; Ludwig, Heinz; Bahlis, Nizar J.; Banos, Anne; Tiab, Mourad; Delforge, Michel; Cavenagh, Jamie D.; Geraldes, Catarina

    2018-01-01

    Rd continuous significantly extended OS compared with MPT and resulted in comparable OS to that with Rd18 in patients with multiple myeloma.Patients achieving complete or very good partial response with Rd benefited greatly from continuous vs fixed treatment in terms of PFS.

  12. Validated Models for Radiation Response and Signal Generation in Scintillators: Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Kerisit, Sebastien N.; Gao, Fei; Xie, YuLong; Campbell, Luke W.; Van Ginhoven, Renee M.; Wang, Zhiguo; Prange, Micah P.; Wu, Dangxin

    2014-12-01

    This Final Report presents work carried out at Pacific Northwest National Laboratory (PNNL) under the project entitled “Validated Models for Radiation Response and Signal Generation in Scintillators” (Project number: PL10-Scin-theor-PD2Jf) and led by Drs. Fei Gao and Sebastien N. Kerisit. This project was divided into four tasks: 1) Electronic response functions (ab initio data model) 2) Electron-hole yield, variance, and spatial distribution 3) Ab initio calculations of information carrier properties 4) Transport of electron-hole pairs and scintillation efficiency Detailed information on the results obtained in each of the four tasks is provided in this Final Report. Furthermore, published peer-reviewed articles based on the work carried under this project are included in Appendix. This work was supported by the National Nuclear Security Administration, Office of Nuclear Nonproliferation Research and Development (DNN R&D/NA-22), of the U.S. Department of Energy (DOE).

  13. The regrowth kinetic of the surviving population is independent of acute and chronic responses to temozolomide in glioblastoma cell lines

    International Nuclear Information System (INIS)

    Silva, Andrew Oliveira; Dalsin, Eloisa; Onzi, Giovana Ravizzoni; Filippi-Chiela, Eduardo Cremonese; Lenz, Guido

    2016-01-01

    Chemotherapy acts on cancer cells by producing multiple effects on a cell population including cell cycle arrest, necrosis, apoptosis and senescence. However, often a subpopulation of cells survives and the behavior of this subpopulation, which is responsible for cancer recurrence, remains obscure. Here we investigated the in vitro short- and long-term responses of six glioblastoma cell lines to clinically relevant doses of temozolomide for 5 days followed by 23 days of recovery, mimicking the standard schedule used in glioblastoma patient for this drug. These cells presented different profiles of sensitivity to temozolomide with varying levels of cell cycle arrest, autophagy and senescence, followed by a regrowth of the surviving cells. The initial reduction in cell number and the subsequent regrowth was analyzed with four new parameters applied to Cumulative Population Doubling (CPD) curves that describe the overall sensitivity of the population and the characteristic of the regrowth: the relative end point CPD (RendCPD); the relative Area Under Curve (rAUC); the Relative Time to Cross a Threshold (RTCT); and the Relative Proliferation Rate (RPR). Surprisingly, the kinetics of regrowth were not predicted by the mechanisms activated after treatment nor by the acute or overall sensitivity. With this study we added new parameters that describe key responses of glioblastoma cell populations to temozolomide treatment. These parameters can also be applied to other cell types and treatments and will help to understand the behavior of the surviving cancer cells after treatment and shed light on studies of cancer resistance and recurrence. - Highlights: • Little is known about the behavior of the glioma cells surviving to TMZ. • The short- and long-term response of six glioma cells lines to TMZ varies considerably. • These glioma cells lines recovered proliferation after therapeutic levels of TMZ. • The growth velocity of the surviving cells was different from the

  14. The regrowth kinetic of the surviving population is independent of acute and chronic responses to temozolomide in glioblastoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Andrew Oliveira, E-mail: andrewbiomed@gmail.com [Department of Biophysics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil); Dalsin, Eloisa, E-mail: dalsineloisa@gmail.com [Department of Biophysics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil); Onzi, Giovana Ravizzoni, E-mail: gioonzi@gmail.com [Department of Biophysics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil); Center of Biotechnology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil); Filippi-Chiela, Eduardo Cremonese, E-mail: eduardochiela@gmail.com [Department of Biophysics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil); Lenz, Guido, E-mail: lenz@ufrgs.br [Department of Biophysics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil); Center of Biotechnology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil)

    2016-11-01

    Chemotherapy acts on cancer cells by producing multiple effects on a cell population including cell cycle arrest, necrosis, apoptosis and senescence. However, often a subpopulation of cells survives and the behavior of this subpopulation, which is responsible for cancer recurrence, remains obscure. Here we investigated the in vitro short- and long-term responses of six glioblastoma cell lines to clinically relevant doses of temozolomide for 5 days followed by 23 days of recovery, mimicking the standard schedule used in glioblastoma patient for this drug. These cells presented different profiles of sensitivity to temozolomide with varying levels of cell cycle arrest, autophagy and senescence, followed by a regrowth of the surviving cells. The initial reduction in cell number and the subsequent regrowth was analyzed with four new parameters applied to Cumulative Population Doubling (CPD) curves that describe the overall sensitivity of the population and the characteristic of the regrowth: the relative end point CPD (RendCPD); the relative Area Under Curve (rAUC); the Relative Time to Cross a Threshold (RTCT); and the Relative Proliferation Rate (RPR). Surprisingly, the kinetics of regrowth were not predicted by the mechanisms activated after treatment nor by the acute or overall sensitivity. With this study we added new parameters that describe key responses of glioblastoma cell populations to temozolomide treatment. These parameters can also be applied to other cell types and treatments and will help to understand the behavior of the surviving cancer cells after treatment and shed light on studies of cancer resistance and recurrence. - Highlights: • Little is known about the behavior of the glioma cells surviving to TMZ. • The short- and long-term response of six glioma cells lines to TMZ varies considerably. • These glioma cells lines recovered proliferation after therapeutic levels of TMZ. • The growth velocity of the surviving cells was different from the

  15. Transarterial hepatic chemoperfusion of uveal melanoma metastases. Survival and response to treatment

    Energy Technology Data Exchange (ETDEWEB)

    Heusner, T.A.; Wittkowski-Sterczewski, A.; Ladd, S.C.; Forsting, M.; Verhagen, R. [Universitaetsklinik Essen, Duisburg-Essen Univ. (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie; Antoch, G. [Duesseldorf Univ. (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie; Scheulen, M. [Duisburg-Essen Univ., Essen (DE). Klinik fuer Innere Medizin (Tumorforschung)

    2011-12-15

    Purpose: To assess the survival of patients with hepatic uveal melanoma metastases undergoing sequential transarterial hepatic chemoperfusion. Materials and Methods: 61 patients (mean age, 60.3 {+-} 13.8y) underwent a total of 249 hepatic chemoperfusion procedures (mean: 4 chemoperfusion procedures; range, 1 - 7 chemoperfusion procedures; standard deviation, 2.3 chemoperfusion procedures). All patients started with melphalan. In the case of progressive disease, melphalan was replaced by a different chemoperfusion agent. 38 patients were treated with melphalan only, 23 patients were treated with a combination of melphalan and other drugs. The median overall survival time was calculated for the overall population and several sub-groups. Differences in the survival rate between the sub-groups were assessed for statistical significance. The complication rate was assessed. Results: The median overall survival of the entire population was 10 months. The patients in the subgroups with a maximum number of 9 hepatic metastases as well as the patients in the subgroup without extrahepatic metastases at the beginning of therapy survived significantly longer than patients with more than 9 metastases/extrahepatic metastases (p = 0.019, p = 0.008). One patient (0.4 %) died from liver failure after initial infusion of melphalan. Conclusion: Intraarterial sequential hepatic chemoperfusion offers a minimally invasive treatment in patients with hepatic uveal melanoma metastases with good survival times and an acceptable major complication rate. (orig.)

  16. 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

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

    Directory of Open Access Journals (Sweden)

    Southey Bruce R

    2011-06-01

    . Biological processes associated glioblastoma survival included morphogenesis, cell cycle, aging, response to stimuli, and programmed cell death. Conclusions Known biomarkers of glioblastoma survival were confirmed, and new general and clinical-dependent gene profiles were uncovered. The comparison of biomarkers across glioblastoma phases and functional analyses offered insights into the role of genes. These findings support the development of more accurate and personalized prognostic tools and gene-based therapies that improve the survival and quality of life of individuals afflicted by glioblastoma multiforme.

  18. Population density, call-response interval, and survival of out-of-hospital cardiac arrest

    Science.gov (United States)

    2011-01-01

    Background Little is known about the effects of geographic variation on outcomes of out-of-hospital cardiac arrest (OHCA). The present study investigated the relationship between population density, time between emergency call and ambulance arrival, and survival of OHCA, using the All-Japan Utstein-style registry database, coupled with geographic information system (GIS) data. Methods We examined data from 101,287 bystander-witnessed OHCA patients who received emergency medical services (EMS) through 4,729 ambulatory centers in Japan between 2005 and 2007. Latitudes and longitudes of each center were determined with address-match geocoding, and linked with the Population Census data using GIS. The endpoints were 1-month survival and neurologically favorable 1-month survival defined as Glasgow-Pittsburgh cerebral performance categories 1 or 2. Results Overall 1-month survival was 7.8%. Neurologically favorable 1-month survival was 3.6%. In very low-density (population size may lead to inequality in health outcomes between urban and rural areas. PMID:21489299

  19. Columbia River System Operation Review final environmental impact statement. Appendix T: Comments and responses

    International Nuclear Information System (INIS)

    1995-11-01

    The System Operation Review (SOR) is a study and environmental compliance process being used by the three Federal agencies to analyze future operations of the system and river use issues. The goal of the SOR is to achieve a coordinated system operation strategy for the river that better meets the needs of all river users. This technical appendix addresses only the effects of alternative system operating strategies for managing the Columbia River system. This appendix documents the public and agency review of the SOR Draft EIS and how the SOR agencies used the review to formulate the FINAL EIS. The appendix includes a summary of the review process, a discussion of the nature of the comments, a list of all commentors, reproductions of comment letters, and responses to all comments. Changes in the EIS text in response to comments are noted in the responses

  20. Survival and growth of eucalypts clones seedlings in response to organic fertilizer application

    Directory of Open Access Journals (Sweden)

    Sula Janaína de Oliveira Fernandes

    2011-12-01

    Full Text Available This work aimed to evaluate the effect of Fert-Bokashi® on survival and seedlings growth of two Eucalyptus urophylla clones propagated by minicutting technique. The experiment was conducted over a period of 28 days using a randomized block design and three replicates in an 6 x 2 factorial arrangement, with six Fert-Bokashi® concentrations (0.0%, 0.1%, 0.3%, 0.5%, 0.7% and 0.9% and two clones. Seedlings survival, height growth and shoot, root and total dry matter were evaluated. Experimental results demonstrated no significant effect of Fert- Bokashi® on survival and seedlings growth of two Eucalyptus urophylla clones.

  1. No survival benefit for patients with melanoma undergoing sentinel lymph node biopsy: critical appraisal of the Multicenter Selective Lymphadenectomy Trial-I final report.

    Science.gov (United States)

    Sladden, M; Zagarella, S; Popescu, C; Bigby, M

    2015-03-01

    Sentinel lymph node biopsy (SLNB) was developed in the hope that it would improve outcomes for patients with melanoma. SLNB is an area of discussion and controversy in melanoma medicine. The final trial results of the Multicenter Selective Lymphadenectomy Trial (MSLT-I) have now been published and the authors suggest their long-term results 'clearly validate the use of sentinel-node biopsy in patients with intermediate-thickness or thick primary melanomas'. An accompanying editorial states that MSLT-I is a practice-changing trial. However, critical appraisal of MSLT-I data does not support the claims of the final report. On the contrary, MSLT-I failed to demonstrate that there is a significant treatment-related difference in the 10-year melanoma-specific survival rate in the overall study population. Furthermore, there was no improvement in overall or melanoma-specific survival of the intermediate-thickness group (1·2-3·5 mm). Completion lymphadenectomy can result in complications in about a third of patients, with a rate of clinically significant lymphoedema following axillary or groin dissection of 5-10%. Unnecessary lymphadenectomy can therefore have a major effect on patient quality of life. The evidence provided by Morton et al. does not support the claim that sentinel lymph node biopsy followed by lymphadenectomy in patients with positive sentinel nodes should be the standard of care in patients with melanoma. Readers are encouraged to check with registration sites to make sure declared primary outcomes are fairly reported. Post-hoc analyses are at best exploratory and cannot be used to form the principal conclusions of a trial. © 2015 British Association of Dermatologists.

  2. Telephone Flat Geothermal Development Project Environmental Impact Statement Environmental Impact Report. Final: Comments and Responses to Comments

    Energy Technology Data Exchange (ETDEWEB)

    None

    1999-02-01

    This document is the Comments and Responses to Comments volume of the Final Environmental Impact Statement and Environmental Impact Report prepared for the proposed Telephone Flat Geothermal Development Project (Final EIS/EIR). This volume of the Final EIS/EIR provides copies of the written comments received on the Draft EIS/EIR and the leady agency responses to those comments in conformance with the requirements of the National Environmental Policy Act (NEPA) and the California Environmental Quality Act (CEQA).

  3. Systems for arctic spill response. Volume I. Final report, August 1977--March 1978

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, L.A.; Deslauriers, P.C.; DeBord, F.W.; Voelker, R.P.

    1978-03-01

    This final report summarizes the work accomplished under the program entitled 'Study to Define Arctic Pollution Response Systems and Develop Arctic Oil Pollution Response Project Plans.' The objective of the program was to determine the most cost effective, environmentally compatible, and technically feasible Coast Guard arctic pollution response system that can be used in projected oil spill scenarios to recover and dispose of spilled oil. The optimum arctic pollution response system was determined by establishing the cost and effectiveness of response for sixteen oil spill response situations, and developing six alternative Coast Guard arctic pollution response systems based on these situations. These six systems were developed with a recognition of three distinctly different types of operational requirements, those for thick stable ice, dynamic hummocky ice, and open water or light ice conditions. The optimum system was then identified as the result of a cost effectiveness analysis. The six arctic oil spill scenarios consisted of a gathering pipeline rupture in the nearshore Beaufort Sea, an oil well blowout from a very large reservoir in the nearshore Chukchi Sea, crude oil tanker casualties in Norton Sound and in the Navarin Basin region of the Bering Sea, an oil well blowout from an average sized reservoir in Bristol Bay, and a fuel oil spill resulting from the collision of a fuel oil barge in Unimak Pass. The optimum system provides for a 25% response level for the Norton Sound, Navarin Basin, Bristol Bay, and Unimak Pass scenarios, and a 50% response level for the Beaufort Sea and Chukchi Sea scenarios.

  4. Systems for arctic spill response. Volume II. Appendices. Final report, August 1977--March 1978

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, L.A.; Deslauriers, P.C.; DeBord, F.W.; Voelker, R.P.

    1978-03-01

    This final report summarizes the work accomplished under Phase I of the program entitled 'Study to Define Arctic Pollution Response Systems and Develop Arctic Oil Pollution Response Project Plans.' The objective of Phase I of the program was to determine the most cost effective, environmentally compatible, and technically feasible Coast Guard arctic pollution response system that can be used in projected oil spill scenarios to recover and dispose of spilled oil. The optimum arctic pollution response system was determined by establishing the cost and effectiveness of response for sixteen oil spill response situations, and developing six alternative Coast Guard arctic pollution response systems based on these situations. The optimum system was then identified as the result of a cost effectiveness analysis. The six arctic oil spill scenarios consisted of a gathering pipeline rupture in the nearshore Beaufort Sea, an oil well blowout from a very large reservoir in the nearshore Chukchi Sea, crude oil tanker casualties in Norton Sound and in the Navarin Basin region of the Bering Sea, an oil well blowout from an average sized reservoir in Bristol Bay, and a fuel oil spill resulting from the collision of a fuel oil barge in Unimak Pass. The optimum system provides for a 25% response level for the Norton Sound, Navarin Basin, Bristol Bay, and Unimak Pass scenarios, and a 50% response level for the Beaufort Sea and Chukchi Sea scenarios. Modifications in the optimum system required to extend its capability to subarctic applications in the Great Lakes, the northern rivers, and the northern coastal region were also identified.

  5. Final report: Hydraulic mechanisms of survival and mortality during drought in pinon-juniper woodlands of southwestern USA

    Energy Technology Data Exchange (ETDEWEB)

    Pockman, William [Univ. of New Mexico, Albuquerque, NM (United States)

    2016-11-23

    The goal of this project was to use rainfall manipulation of an intact pinon-juniper woodland in central New Mexico to understand the mechanisms that control the response of these species to extremes of rainfall. Experimental plots were installed in a pinon-juniper woodland at the Sevilleta National Wildlife Refuge and treatments were imposed in August 2007. Treatments consisted of 1) a Drought treatment imposed by diverting approximately 45% of precipitation away from the plot, 2) and Irrigation treatment imposed by applying six 19 mm simulated rainfall events at regular intervals during the growing season, 3) a Cover Control treatment designed to assess the impact of the plastic troughs constructed on Drought plots without imposing the rainfall diversion, and 4) an untreated control that received no modification. Extensive pinon mortality was observed beginning one year after the start of drought treatment on hillslope plots, while a third drought plot on deeper soils did not exhibit pinon mortality until the fifth year of drought treatment. Pinon mortality occurred in the context of high levels of bark beetle activity, motivating the installation of two additional plots in 2010: a control plot and a drought plot built to the same standards as the original treatments but with bark beetle control maintained by pesticide application to the bole of target trees from 2010 - 2016. Although the drought treatment created similar conditions to those experienced on hillslope drought plots, the drought plot with bark beetle control exhibited no pinon mortality for 5 years even in the presence of high regional bark beetle activity in 2012/13. One of the goals of the research was to identify the mechanism of drought-induced mortality in pinon and juniper: 1) mortality due to catastrophic failure of water transport through plant tissues (hydraulic failure), 2) mortality due to limitations in carbon uptake (carbon starvation) and 3) either of the first two mechanisms with the

  6. Tumor Necrosis Factor-α Inhibition in Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis: Treatment Response, Drug Survival, and Patient Outcome.

    Science.gov (United States)

    Corli, Justine; Flipo, René-Marc; Philippe, Peggy; Bera-Louville, Anne; Béhal, Hélène; Wibaux, Cécile; Paccou, Julien

    2015-12-01

    The purpose of this study was to (1) evaluate baseline characteristics of nonradiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) treated with tumor necrosis factor-α inhibitors (TNFi), (2) assess the response to first TNFi treatment, and (3) compare drug-survival duration and rates. Inclusion criteria were patients with axSpA who initiated first TNFi treatment between April 2001 and July 2014 and were followed up for at least 3 months. Efficacy criteria were an improvement of at least 2 points (on a 0-10 scale) or a 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Baseline characteristics, responses at 12 months, and drug survival were compared between AS and nr-axSpA. A total of 361 patients were included in the study (AS, n = 263 and nr-axSpA, n = 98). Patients with AS were more often men (65.02% vs 45.92%, p = 0.001) and had longer symptom duration (11.71 ± 9.52 vs 7.34 ± 9.30 yrs, p Treatment response and drug survival were similar in patients with AS and nr-axSpA after first TNFi initiation.

  7. Survival and growth response of white spruce stock types to site preparation in Alaska

    Science.gov (United States)

    Andrew Youngblood; Elizabeth Cole; Michael Newton

    2011-01-01

    To identify suitable methods for reforestation, we evaluated the interacting effects of past disturbance, stock types, and site preparation treatments on white spruce (Picea glauca (Moench) Voss) seedling survival and growth across a range of sites in Alaska. Replicated experiments were established in five regions. At each site, two complete...

  8. Migration tendency delays distributional response to differential survival prospects along a flyway.

    Science.gov (United States)

    Lok, Tamar; Overdijk, Otto; Piersma, Theunis

    2013-04-01

    When populations grow or decline, habitat selection may change due to local density-dependent processes, such as site dependence and interference. In seasonally migrating animals, nonbreeding distributions may be determined through these mechanisms of density dependence, which we examine here at a hemispheric scale for a long-distance migrating bird. Using summer and winter resightings of 2,095 Eurasian spoonbills Platalea leucorodia leucorodia that were ringed in the Netherlands during 16 years of fast population growth, we show that neither site dependence nor interference fully explains their patterns of survival and winter distribution. Within their three main wintering areas, annual survival decreased with an increase in population size. While survival was consistently higher in the two European wintering areas (France, Iberia), most spoonbills migrated onward to winter in west Africa. The number of birds wintering in Europe increased, but not enough to maximize annual survival. We conclude that a constraint of tradition (their "migration tendency") inhibits birds from changing their migratory habits. We pose that this phenomenon may similarly constrain other migratory populations from rapidly responding to large-scale climate- and/or human-driven habitat changes at their wintering grounds.

  9. Surviving without a Brain: A response to McMahan on Personal ...

    African Journals Online (AJOL)

    In his Ethics of Killing: Problems at the Margins of Life, Jeff McMahan defends what he calls the embodied mind view of identity, and then puts forward several arguments in support of the view that physical continuity of the brain is crucial to our survival. He ultimately denies that psychological continuity is of any importance.

  10. Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival.

    Science.gov (United States)

    Salem, Riad; Lewandowski, Robert J; Atassi, Bassel; Gordon, Stuart C; Gates, Vanessa L; Barakat, Omar; Sergie, Ziad; Wong, Ching-Yee O; Thurston, Kenneth G

    2005-12-01

    To present safety and efficacy results obtained in treatment of a cohort of patients with unresectable hepatocellular carcinoma (HCC) with use of 90Y microspheres (TheraSphere). Forty-three consecutive patients with HCC were treated with 90Y microspheres over a 4-year period. Patients were treated by liver segment or lobe on one or more occasions based on tumor distribution, liver function, and vascular flow dynamics. Patients were followed for adverse events, objective tumor response, and survival. Patients were stratified into three risk groups according to method of treatment and risk stratification (group 0, segmental; group 1, lobar low-risk; group 2, lobar high-risk) and Okuda and Child-Pugh scoring systems. Based on follow-up data from 43 treated patients, 20 patients (47%) had an objective tumor response based on percent reduction in tumor size and 34 patients (79%) had a tumor response when percent reduction and/or tumor necrosis were used as a composite measure of tumor response. There was no statistical difference among the three risk groups with respect to tumor response. Survival times from date of diagnosis were different among the risk groups (P TheraSpheres) provides a safe and effective method of treatment for a broad spectrum of patients presenting with unresectable HCC. Further investigation is warranted.

  11. Cell therapy for Parkinson's disease: Functional role of the host immune response on survival and differentiation of dopaminergic neuroblasts.

    Science.gov (United States)

    Wenker, Shirley D; Leal, María Celeste; Farías, María Isabel; Zeng, Xianmin; Pitossi, Fernando J

    2016-05-01

    Parkinson's disease (PD) is a neurodegenerative disorder, whose cardinal pathology is the loss of dopaminergic neurons in the substantia nigra. Current treatments for PD have side effects in the long term and do not halt disease progression or regenerate dopaminergic cell loss. Attempts to compensate neuronal cell loss by transplantation of dopamine-producing cells started more than 30 years ago, leading to several clinical trials. These trials showed safety and variable efficacy among patients. In addition to variability in efficacy, several patients developed graft-induced dyskinesia. Nevertheless, they have provided a proof of concept that motor symptoms could be improved by cell transplantation. Cell transplantation in the brain presents several immunological challenges. The adaptive immune response should be abolished to avoid graft rejection by the host. In addition, the innate immune response will always be present after transplanting cells into the brain. Remarkably, the innate immune response can have dramatic effects on the survival, differentiation and proliferation of the transplanted cells, but has been hardly investigated. In this review, we analyze data on the functional effects of signals from the innate immune system on dopaminergic differentiation, survival and proliferation. Then, we discussed efforts on cell transplantation in animal models and PD patients, highlighting the immune response and the immunomodulatory treatment strategies performed. The analysis of the available data lead us to conclude that the modulation of the innate immune response after transplantation can increase the success of future clinical trials in PD by enhancing cell differentiation and survival. This article is part of a Special Issue entitled SI: PSC and the brain. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Understanding the Response of Photosynthetic Metabolism in Tropical Forests to Seasonal Climate Variations. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Dye, Dennis [U.S. Geological Survey, Menlo Park, CA (United States); Ivanov, Valeriy [Univ. of Michigan, Ann Arbor, MI (United States); Saleska, Scott [Univ. of Arizona, Tucson, AZ (United States); Huete, Alfredo [Univ. of Arizona, Tucson, AZ (United States); Univ. of Technology, Sydney NSW (Australia)

    2017-03-31

    This U.S-Brazil collaboration for GOAmazon has investigated a deceptively simple question: what controls the response of photosynthesis in Amazon tropical forests to seasonal variations in climate? In the past this question has been difficult to answer with modern earth system process models. We hypothesized that observed dry season increases in photosynthetic capacity are controlled by the phenology of leaf flush and litter fall, from which the seasonal pattern of LAI emerges. Our results confirm this hypothesis (Wu et al., 2016). Synthesis of data collected throughout the 3-year project period continues through December 31, 2017 under no-cost extensions granted to the project teams at University of Michigan and University of Arizona (Award 2). The USGS component (Award 1) ceased on the final date of the project performance period, December 31, 2016. This report summarizes the overall activities and achievements of the project, and constitutes the final project report for the USGS component. The University of Michigan will submit a separate final report that includes additional results and deliverables achieved during the period of their and the University of Arizona’s no-cost extension, which will end on December 31, 2017.

  13. Tumor Surface Regularity at MR Imaging Predicts Survival and Response to Surgery in Patients with Glioblastoma.

    Science.gov (United States)

    Pérez-Beteta, Julián; Molina-García, David; Ortiz-Alhambra, José A; Fernández-Romero, Antonio; Luque, Belén; Arregui, Elena; Calvo, Manuel; Borrás, José M; Meléndez, Bárbara; Rodríguez de Lope, Ángel; Moreno de la Presa, Raquel; Iglesias Bayo, Lidia; Barcia, Juan A; Martino, Juan; Velásquez, Carlos; Asenjo, Beatriz; Benavides, Manuel; Herruzo, Ismael; Revert, Antonio; Arana, Estanislao; Pérez-García, Víctor M

    2018-04-03

    Purpose To evaluate the prognostic and predictive value of surface-derived imaging biomarkers obtained from contrast material-enhanced volumetric T1-weighted pretreatment magnetic resonance (MR) imaging sequences in patients with glioblastoma multiforme. Materials and Methods A discovery cohort from five local institutions (165 patients; mean age, 62 years ± 12 [standard deviation]; 43% women and 57% men) and an independent validation cohort (51 patients; mean age, 60 years ± 12; 39% women and 61% men) from The Cancer Imaging Archive with volumetric T1-weighted pretreatment contrast-enhanced MR imaging sequences were included in the study. Clinical variables such as age, treatment, and survival were collected. After tumor segmentation and image processing, tumor surface regularity, measuring how much the tumor surface deviates from a sphere of the same volume, was obtained. Kaplan-Meier, Cox proportional hazards, correlations, and concordance indexes were used to compare variables and patient subgroups. Results Surface regularity was a powerful predictor of survival in the discovery (P = .005, hazard ratio [HR] = 1.61) and validation groups (P = .05, HR = 1.84). Multivariate analysis selected age and surface regularity as significant variables in a combined prognostic model (P surface regularity was a predictor of survival for patients who underwent complete resection (P = .01, HR = 1.90). Tumors with irregular surfaces did not benefit from total over subtotal resections (P = .57, HR = 1.17), but those with regular surfaces did (P = .004, HR = 2.07). Conclusion The surface regularity obtained from high-resolution contrast-enhanced pretreatment volumetric T1-weighted MR images is a predictor of survival in patients with glioblastoma. It may help in classifying patients for surgery. © RSNA, 2018 Online supplemental material is available for this article.

  14. Effects of decabromodiphenyl ether (BDE-209) on the avoidance response, survival, growth and reproduction of earthworms (Eisenia fetida).

    Science.gov (United States)

    Xie, Xianchuan; Qian, Yan; Wu, Yingxin; Yin, Jun; Zhai, Jianping

    2013-04-01

    The effects of decabromodiphenyl ether (BDE-209) on avoidance response, survival, growth, and reproduction of earthworms (Eisenia fetida) were investigated under laboratory conditions using natural and artificial soils as substrate. Results showed that no significant avoidance response was observed when earthworms were exposed to 0.1-1000 mg/kg of BDE-209 for 48 h. After 28-days exposure, no significant effects on survival and growth of adult earthworms was induced by 0.1-1000 mg/kg of BDE-209 indicating the Lowest Observed Effect Level (LOEL) of BDE-209 on their survival and body weight was more than 1000 mg/kg. Except for a significant decrease in the number of juveniles per hatched cocoon in artificial soils at 1000 mg/kg of BDE-209, no significant effects on reproductive parameters (e.g. cocoon production per earthworms, weight per cocoon and cocoon hatchability) were observed. These results suggest that adult earthworms have a strong tolerance for BDE-209 exposure in soils, but a potential toxicity does exist for earthworm embryos or juveniles. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Dual axis radiographic hydrodynamic test facility. Final environmental impact statement, Volume 2: Public comments and responses

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-08-01

    On May 12, 1995, the U.S. Department of Energy (DOE) issued the draft Dual Axis Radiographic Hydrodynamic Test Facility Environmental Impact Statement (DARHT EIS) for review by the State of New Mexico, Indian Tribes, local governments, other Federal agencies, and the general public. DOE invited comments on the accuracy and adequacy of the draft EIS and any other matters pertaining to their environmental reviews. The formal comment period ran for 45 days, to June 26, 1995, although DOE indicated that late comments would be considered to the extent possible. As part of the public comment process, DOE held two public hearings in Los Alamos and Santa Fe, New Mexico, on May 31 and June 1, 1995. In addition, DOE made the draft classified supplement to the DARHT EIS available for review by appropriately cleared individuals with a need to know the classified information. Reviewers of the classified material included the State of New Mexico, the U.S. Environmental Protection Agency, the Department of Defense, and certain Indian Tribes. Volume 2 of the final DARHT EIS contains three chapters. Chapter 1 includes a collective summary of the comments received and DOE`s response. Chapter 2 contains the full text of the public comments on the draft DARHT EIS received by DOE. Chapter 3 contains DOE`s responses to the public comments and an indication as to how the comments were considered in the final EIS.

  16. Nutritional factors as predictors of response to radio-chemotherapy and survival in unresectable squamous head and neck carcinoma

    International Nuclear Information System (INIS)

    Salas, Sebastien; Deville, Jean-Laurent; Giorgi, Roch; Pignon, Thierry; Bagarry, Danielle; Barrau, Karine; Zanaret, Michel; Giovanni, Antoine; Bourgeois, Aude; Favre, Roger; Duffaud, Florence

    2008-01-01

    Background and purpose: This study sought to evaluate nutritional prognostic factors before treatment in patients with unresectable head and neck cancer treated by concomitant radio-chemotherapy. Methods and materials: Seventy-two consecutive patients were treated. We studied the potential effects of CRP, Alb, preAlb, orosomucoid, weight, weight history, BMI, PINI, OPR and NRI on response to treatment, Event-Free Survival (EFS) and Overall Survival (OS). Effects of potential risk factors on OS and on EFS were analyzed by computing Kaplan-Meier estimates, and curves were compared using the log-rank test. Results: All biological nutritional factors were statistically correlated with the response to radio-chemotherapy. In multivariate analysis, only CRP (p = 0.004) remained statistically significant. A statistical correlation was found between Alb and EFS in multivariate analysis (p = 0.04). The factors influencing OS in univariate analysis were Alb (p = 0.008), CRP (p = 0.004), orosomucoid (p = 0.01) and NRI (p = 0.01), response to radio-chemotherapy (p < 0.001) and staging (p = 0.04). In multivariate analysis, only the response to radio-chemotherapy (p < 0.001) remained significant. Conclusions: This study illustrates the prognostic value of nutritional status. CRP and Alb may be useful in the assessment of advanced head and neck cancer patients at diagnosis and for stratifying patients taking part in randomized trials

  17. Dose response severity functions for acoustic disturbance in cetaceans using recurrent event survival analysis

    NARCIS (Netherlands)

    Harris, C.M.; Sadykova, D.; DeRuiter, S.L.; Tyack, P.L.; Miller, P.J.O.; Kvadsheim, P.H.; Lam, F.P.A.; Thomas, L.

    2015-01-01

    Behavioral response studies (BRSs) aim to enhance our understanding of the behavior changes made by animals in response to specific exposure levels of different stimuli, often presented in an increasing dosage. Here, we focus on BRSs that aim to understand behavioral responses of free-ranging whales

  18. Survival and behavior of Chinese mystery snails (Bellamya chinensis) in response to simulated water body drawdowns and extended air exposure

    Science.gov (United States)

    Unstad, Kody M.; Uden, Daniel R.; Allen, Craig R.; Chaine, Noelle M.; Haak, Danielle M.; Kill, Robert A.; Pope, Kevin L.; Stephen, Bruce J.; Wong, Alec

    2013-01-01

    Nonnative invasive mollusks degrade aquatic ecosystems and induce economic losses worldwide. Extended air exposure through water body drawdown is one management action used for control. In North America, the Chinese mystery snail (Bellamya chinensis) is an invasive aquatic snail with an expanding range, but eradication methods for this species are not well documented. We assessed the ability of B. chinensis to survive different durations of air exposure, and observed behavioral responses prior to, during, and following desiccation events. Individual B. chinensis specimens survived air exposure in a laboratory setting for > 9 weeks, and survivorship was greater among adults than juveniles. Several B. chinensis specimens responded to desiccation by sealing their opercula and/or burrowing in mud substrate. Our results indicate that drawdowns alone may not be an effective means of eliminating B. chinensis. This study lays the groundwork for future management research that may determine the effectiveness of drawdowns when combined with factors such as extreme temperatures, predation, or molluscicides.

  19. Survival and behavior of Chinese mystery snails (Bellamya chinensis in response to simulated water body drawdowns and extended air exposure

    Directory of Open Access Journals (Sweden)

    Kody M. Unstad

    2013-04-01

    Full Text Available Nonnative invasive mollusks degrade aquatic ecosystems and induce economic losses worldwide. Extended air exposure through water bodydrawdown is one management action used for control. In North America, the Chinese mystery snail (Bellamya chinensis is an invasiveaquatic snail with an expanding range, but eradication methods for this species are not well documented. We assessed the ability ofB. chinensis to survive different durations of air exposure, and observed behavioral responses prior to, during, and following desiccationevents. Individual B. chinensis specimens survived air exposure in a laboratory setting for > 9 weeks, and survivorship was greater amongadults than juveniles. Several B. chinensis specimens responded to desiccation by sealing their opercula and/or burrowing in mud substrate.Our results indicate that drawdowns alone may not be an effective means of eliminating B. chinensis. This study lays the groundwork forfuture management research that may determine the effectiveness of drawdowns when combined with factors such as extreme temperatures,predation, or molluscicides.

  20. Artichoke compound cynarin differentially affects the survival, growth and stress response of normal, immortalized and cancerous human cells

    DEFF Research Database (Denmark)

    Gezer, Ceren; Yücecan, Sevinç; Rattan, Suresh Inder Singh

    2015-01-01

    of CYN on the proliferative potential, survival, morphology, and stress response (SR) markers haemoxygenase-1 (HO-1) and heat shock protein-70 (HSP70) in normal human skin fibroblasts (FSF-1), telomerase-immortalized mesenchymal stem cells (hTERT-MSC) and cervical cancer cells, HeLa. Effects of CYN....... Furthermore, CYN induced oxidative SR marker HO-1 in both fibroblasts and stem cells in a biphasic manner, but a slight induction of HSP70 was observed only in the stem cells. Thus, CYN may be useful as a protection against the growth and survival of potentially cancerous cells and may promote longevity...... of normal cells by induction of SR proteins. Further advanced researches related with CYN and artichoke are recommended....

  1. Late Release of Circulating Endothelial Cells and Endothelial Progenitor Cells after Chemotherapy Predicts Response and Survival in Cancer Patients

    Directory of Open Access Journals (Sweden)

    Jeanine M. Roodhart

    2010-01-01

    Full Text Available We and others have previously demonstrated that the acute release of progenitor cells in response to chemotherapy actually reduces the efficacy of the chemotherapy. Here, we take these data further and investigate the clinical relevance of circulating endothelial (progenitor cells (CE(PCs and modulatory cytokines in patients after chemotherapy with relation to progression-free and overall survival (PFS/OS. Patients treated with various chemotherapeutics were included. Blood sampling was performed at baseline, 4 hours, and 7 and 21 days after chemotherapy. The mononuclear cell fraction was analyzed for CE(PC by FACS analysis. Plasma was analyzed for cytokines by ELISA or Luminex technique. CE(PCs were correlated with response and PFS/OS using Cox proportional hazard regression analysis. We measured CE(PCs and cytokines in 71 patients. Only patients treated with paclitaxel showed an immediate increase in endothelial progenitor cell 4 hours after start of treatment. These immediate changes did not correlate with response or survival. After 7 and 21 days of chemotherapy, a large and consistent increase in CE(PC was found (P < .01, independent of the type of chemotherapy. Changes in CE(PC levels at day 7 correlated with an increase in tumor volume after three cycles of chemotherapy and predicted PFS/OS, regardless of the tumor type or chemotherapy. These findings indicate that the late release of CE(PC is a common phenomenon after chemotherapeutic treatment. The correlation with a clinical response and survival provides further support for the biologic relevance of these cells in patients' prognosis and stresses their possible use as a therapeutic target.

  2. Combined effect of temperature and ammonia on molecular response and survival of the freshwater crustacean Gammarus pulex.

    Science.gov (United States)

    Henry, Y; Piscart, C; Charles, S; Colinet, H

    2017-03-01

    Freshwater ecosystems are experiencing mounting pressures from agriculture, urbanization, and climate change, which could drastically impair aquatic biodiversity. As nutrient inputs increase and temperatures rise, ammonia (NH 3 ) concentration is likely to be associated with stressful temperatures. To investigate the interaction between NH 3 and temperature on aquatic invertebrate survival, we performed a factorial experiment on the survival and molecular response of Gammarus pulex, with temperature (10, 15, 20, and 25°C) and NH 3 (0, 0.5, 1, 2, 3, and 4mg NH 3 /L) treatments. We observed an unexpected antagonistic interaction between temperature and NH 3 concentration, meaning survival in the 4mg NH 3 /L treatment was higher at 25°C than at the control temperature of 10°C. A toxicokinetic-toxicodynamic (TK-TD) model was built to describe this antagonistic interaction. While the No Effect Concentration showed no significant variation across temperatures, the 50% lethal concentration at the end of the experiment increased from 2.7 (2.1-3.6) at 10°C to 5.5 (3.5- 23.4) mg NH 3 /L at 25°C. Based on qPCR data, we associated these survival patterns to variations in the expression of the hsp70 gene, a generic biomarker of stress. However, though there was a 14-fold increase in hsp70 mRNA expression for gammarids exposed to 25°C compared to controls, NH 3 concentration had no effect on hsp70 mRNA synthesis across temperatures. Our results demonstrate that the effects of combined environmental stressors, like temperature and NH 3 , may strongly differ from simple additive effects, and that stress response to temperature can actually increase resilience to nutrient pollution in some circumstances. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. The innate immune response may be important for surviving plague in wild Gunnison's prairie dogs

    Science.gov (United States)

    Busch, Joseph D.; Van Andel, Roger; Stone, Nathan E.; Cobble, Kacy R.; Nottingham, Roxanne; Lee, Judy; VerSteeg, Michael; Corcoran, Jeff; Cordova, Jennifer; Van Pelt, William E.; Shuey, Megan M.; Foster, Jeffrey T.; Schupp, James M.; Beckstrom-Sternberg, Stephen; Beckstrom-Sternberg, James; Keim, Paul; Smith, Susan; Rodriguez-Ramos, Julia; Williamson, Judy L.; Rocke, Tonie E.; Wagner, David M.

    2013-01-01

    Prairie dogs (Cynomys spp.) are highly susceptible to Yersinia pestis, with ≥99% mortality reported from multiple studies of plague epizootics. A colony of Gunnison's prairie dogs (Cynomys gunnisoni) in the Aubrey Valley (AV) of northern Arizona appears to have survived several regional epizootics of plague, whereas nearby colonies have been severely affected by Y. pestis. To examine potential mechanisms accounting for survival in the AV colony, we conducted a laboratory Y. pestis challenge experiment on 60 wild-caught prairie dogs from AV and from a nearby, large colony with frequent past outbreaks of plague, Espee (n = 30 per colony). Test animals were challenged subcutaneously with the fully virulent Y. pestis strain CO92 at three doses: 50, 5,000, and 50,000 colony-forming units (cfu); this range is lethal in black-tailed prairie dogs (Cynomys ludovicianus). Contrary to our expectations, only 40% of the animals died. Although mortality trended higher in the Espee colony (50%) compared with AV (30%), the differences among infectious doses were not statistically significant. Only 39% of the survivors developed moderate to high antibody levels to Y. pestis, indicating that mechanisms other than humoral immunity are important in resistance to plague. The ratio of neutrophils to lymphocytes was not correlated with plague survival in this study. However, several immune proteins with roles in innate immunity (VCAM-1, CXCL-1, and vWF) were upregulated during plague infection and warrant further inquiry into their role for protection against this disease. These results suggest plague resistance exists in wild populations of the Gunnison's prairie dog and provide important directions for future studies.

  4. The innate immune response may be important for surviving plague in wild Gunnison's prairie dogs.

    Science.gov (United States)

    Busch, Joseph D; Van Andel, Roger; Stone, Nathan E; Cobble, Kacy R; Nottingham, Roxanne; Lee, Judy; VerSteeg, Michael; Corcoran, Jeff; Cordova, Jennifer; Van Pelt, William; Shuey, Megan M; Foster, Jeffrey T; Schupp, James M; Beckstrom-Sternberg, Stephen; Beckstrom-Sternberg, James; Keim, Paul; Smith, Susan; Rodriguez-Ramos, Julia; Williamson, Judy L; Rocke, Tonie E; Wagner, David M

    2013-10-01

    Prairie dogs (Cynomys spp.) are highly susceptible to Yersinia pestis, with ≥99% mortality reported from multiple studies of plague epizootics. A colony of Gunnison's prairie dogs (Cynomys gunnisoni) in the Aubrey Valley (AV) of northern Arizona appears to have survived several regional epizootics of plague, whereas nearby colonies have been severely affected by Y. pestis. To examine potential mechanisms accounting for survival in the AV colony, we conducted a laboratory Y. pestis challenge experiment on 60 wild-caught prairie dogs from AV and from a nearby, large colony with frequent past outbreaks of plague, Espee (n = 30 per colony). Test animals were challenged subcutaneously with the fully virulent Y. pestis strain CO92 at three doses: 50, 5,000, and 50,000 colony-forming units (cfu); this range is lethal in black-tailed prairie dogs (Cynomys ludovicianus). Contrary to our expectations, only 40% of the animals died. Although mortality trended higher in the Espee colony (50%) compared with AV (30%), the differences among infectious doses were not statistically significant. Only 39% of the survivors developed moderate to high antibody levels to Y. pestis, indicating that mechanisms other than humoral immunity are important in resistance to plague. The ratio of neutrophils to lymphocytes was not correlated with plague survival in this study. However, several immune proteins with roles in innate immunity (VCAM-1, CXCL-1, and vWF) were upregulated during plague infection and warrant further inquiry into their role for protection against this disease. These results suggest plague resistance exists in wild populations of the Gunnison's prairie dog and provide important directions for future studies.

  5. Final heights of boys with normal growth hormone responses to provocative tests following priming.

    Science.gov (United States)

    Gonc, E Nazli; Kandemir, Nurgun; Ozon, Alev; Alikasifoglu, Ayfer

    2008-10-01

    Priming with sex steroids prior to growth hormone (GH) stimulation tests for the diagnosis of GH deficiency is still debatable. We analyzed the auxological data of boys with growth retardation who had normal GH responses to stimulation tests only after priming to establish the validity of priming in the diagnosis of GH deficiency. We also analyzed the effect of different protocols for priming and their efficiency in the diagnosis of GH deficiency. Fifty boys with growth retardation who failed to respond to unprimed GH stimulation tests but responded normally to primed tests were included in the study. Thirty-one of 50 boys responded to GH stimulation tests after single low dose testosterone, 11/50 boys after single conventional dose, and 8/50 boys with multiple-dose testosterone. The study group was followed till final height; height velocity, final height and height SDS were compared to parental and mid-parental heights to determine whether or not the children achieved their height potential. Mean final height SDS of the study group (-1.27 +/- 0.72 SDS) was similar to mid-parental (-1.38 +/- 0.72 SDS) (p = 0.249) and maternal height SDS (-1.26 +/- 1.05 SDS) (p = 0.941), whereas it was greater than the paternal height SDS (-1.7 +/- 0.86) (p = 0.001). The final height SDS of the study group was correlated to maternal, paternal and mid-parental height SDS. Height velocity after the test was greater than the previous height velocity. Final height SDS of the boys who responded to the GH stimulation tests with different priming protocols were compared and found to be similar. Normal responders in primed GH tests grow normally to their target height, suggesting that priming might be a valuable method in the assessment of GH status. Use of priming in the GH stimulation tests of peripubertal boys with decreased growth rate may help avoid unnecessary GH therapy. Multiple-dose testing might exclude GHD in a patient population who failed to respond to a single dose of

  6. Hematological Responses, Survival, and Respiratory Exchange in the Olive Flounder, , during Starvation

    Directory of Open Access Journals (Sweden)

    I.-S. Park

    2012-09-01

    Full Text Available A 12-wk experiment was conducted to examine the hematological changes, survival, and respiratory exchange in the olive flounder, Paralichthys olivaceus, during starvation. The growth, survival and respiratory exchange rates of the starved group were lower than those of the fed group during the experiment. Blood analysis, including hematocrit, hemoglobin, red blood cells, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and mean corpuscular volume, did not differ significantly (p>0.05 between the fed and starved groups at the end of the experiment. There were no significant differences in plasma cortisol, glucose, Na+, Cl−, K+, or aspartate aminotransferase between the fed and starved groups (p>0.05. Alanine aminotransferase levels were higher in the starved group than in the fed group, whereas plasma osmolality was lower in the starved group than in the fed group. It was shown that starved fish had various problems after four weeks, which did not occur in the fed group. Long-term starvation is infrequent in aquaculture farms. However, starvation studies of this kind are very useful for a basic understanding of how physiological changes affect fish health, life expectancy, and growth.

  7. Hematological Responses, Survival, and Respiratory Exchange in the Olive Flounder, Paralichthys olivaceus, during Starvation.

    Science.gov (United States)

    Park, I-S; Hur, J W; Choi, J W

    2012-09-01

    A 12-wk experiment was conducted to examine the hematological changes, survival, and respiratory exchange in the olive flounder, Paralichthys olivaceus, during starvation. The growth, survival and respiratory exchange rates of the starved group were lower than those of the fed group during the experiment. Blood analysis, including hematocrit, hemoglobin, red blood cells, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and mean corpuscular volume, did not differ significantly (p>0.05) between the fed and starved groups at the end of the experiment. There were no significant differences in plasma cortisol, glucose, Na(+), Cl(-), K(+), or aspartate aminotransferase between the fed and starved groups (p>0.05). Alanine aminotransferase levels were higher in the starved group than in the fed group, whereas plasma osmolality was lower in the starved group than in the fed group. It was shown that starved fish had various problems after four weeks, which did not occur in the fed group. Long-term starvation is infrequent in aquaculture farms. However, starvation studies of this kind are very useful for a basic understanding of how physiological changes affect fish health, life expectancy, and growth.

  8. Evaluation of factors affecting tumor response and survival in patients with primary and metastatic liver cancer treated with microspheres.

    Science.gov (United States)

    Demirelli, Serkan; Erkilic, Metin; Oner, Ali Ozan; Budak, Evrim Surer; Gunduz, Seyda; Ozgur, Ozhan; Bozcuk, Hakan; Sindel, Hakki Timur; Boz, Adil

    2015-04-01

    Radioembolization with the yttrium-90 (Y-90) microspheres is being used increasingly more often in the treatment of patients with primary or metastatic liver cancer. Although technetium-99m macroaggregated albumin (Tc-99m MAA) scintigraphy performed following diagnostic angiography has an important role in predicting the effectiveness of treatment and in dose estimation, the number of studies using quantitative assessment of Tc-99m MAA scintigraphy is limited in this field. In the present study, the aim was to assess whether a tumor dose is required to obtain objective tumor response and to check whether this threshold value is predictive in terms of tumor response, survival, and liver toxicity by using Tc-99m MAA single-photon emission computed tomography (SPECT) images. Overall, 54 patients (20 women and 34 men; median age: 60 years) who underwent Y-90 Resin (SIR-Spheres) and Glass (TheraSphere) microsphere treatment with a diagnosis of unresectable liver cancer between August 2010 and April 2013 were included in the study. The mean doses to normal liver and tumor were estimated for each patient using Tc-99m MAA SPECT images and the medical internal radiation dosimetry method. The responses were assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) and European Organisation for Research and Treatment of Cancer (EORTC) criteria. Kaplan-Meier survival curves and univariate Cox regression analysis were used in survival analysis. The relationship between treatment response and other parameters included was assessed using logistic regression analysis. The variables with a P value less than 0.01 in univariate analysis were assessed with multivariate analysis. Fifty-four Y-90 microsphere treatments (eight by using a Y-90 glass microsphere and 46 by using a Y-90 resin microsphere) were performed. In the multivariate analysis, the only parameter related to response was tumor dose (P<0.01). With a tumor dose of 280 Gy or higher, objective tumor

  9. UV light-induced survival response in a highly radiation-resistant isolate of the Moraxella-acinetobacter group

    International Nuclear Information System (INIS)

    Keller, L.C.; Thompson, T.L.; Maxcy, R.B.

    1982-01-01

    A highly radiation-resistant member of the Moraxella-Acinetobacter group, isolate 4, obtained from meat, was studied to determine the effect of preexposure to UV radiation on subsequent UV light resistance. Cultures that were preexposed to UV light and incubated for a short time in plate count broth exhibited increased survival of a UV light challenge dose. This response was inhibited in the presence of chloramphenicol. Frequencies of mutation to streptomycin, trimethoprim, and sulfanilamide resistance remained the same after the induction of this survival response and were not altered by treatment with mutagens, with the exception of mutation to streptomycin resistance after γ-irradiation or nitrosoguanidine or methyl methane sulfonate treatment. The results indicated that isolate 4 has a UV light-inducible UV light resistance mechanism which is not associated with increased mutagenesis. The characteristics of the radiation resistance response in this organism are similar to those of certain other common food contaminants. Therefore, considered as part of the total microflora of meat, isolate 4 and the other radiation-resistant Moraxella-Acinetobacter isolates should not pose unique problems in a proposed radappertizaton process

  10. Early Response of Protein Quality Control in Gills Is Associated with Survival of Hypertonic Shock in Mozambique tilapia

    Science.gov (United States)

    Tang, Cheng-Hao; Lee, Tsung-Han

    2013-01-01

    The protein quality control (PQC) mechanism is essential for cell function and viability. PQC with proper biological function depends on molecular chaperones and proteases. The hypertonicity-induced protein damage and responses of PQC mechanism in aquatic organisms, however, are poorly understood. In this study, we examine the short-term effects of different hypertonic shocks on the levels of heat shock proteins (HSPs, e.g., HSP70 and HSP90), ubiquitin-conjugated proteins and protein aggregation in gills of the Mozambique tilapia (Oreochromis mossambicus). Following transfer from fresh water (FW) to 20‰ hypertonicity, all examined individuals survived to the end of experiment. Moreover, the levels of branchial HSPs and ubiquitin-conjugated proteins significantly increased at 3 and 24 h post-transfer, respectively. Up-regulation of HSPs and ubiquitin-conjugated proteins was sufficient to prevent the accumulation of aggregated proteins. However, the survival rate of tilapia dramatically declined at 5 h and all fish died within 7 h after direct transfer to 30‰ hypertonicity. We presumed that this result was due to the failed activation of gill PQC system, which resulted in elevating the levels of aggregated proteins at 3 and 4 h. Furthermore, in aggregated protein fractions, the amounts of gill Na+/K+-ATPase (NKA) remained relatively low when fish were transferred to 20‰ hypertonicity, whereas abundant NKA was found at 4 h post-transfer to 30‰ hypertonicity. This study demonstrated that the response of PQC in gills is earlier than observable changes in localization of ion-secreting transport proteins upon hypertonic challenge. To our knowledge, this is the first study to investigate the regulation of PQC mechanism in fish and characterize its important role in euryhaline teleost survival in response to hypertonic stress. PMID:23690986

  11. Impact of different infliximab dose regimens on treatment response and drug survival in 462 patients with psoriatic arthritis

    DEFF Research Database (Denmark)

    Glintborg, Bente; Gudbjornsson, Bjorn; Krogh, Niels Steen

    2014-01-01

    OBJECTIVE: The aim of this study was to describe dose regimens, dose escalation and clinical outcomes in TNF-α inhibitor (TNFi)-naive patients with PsA treated with infliximab in routine rheumatology care. METHODS: We conducted an observational cohort study based on the nationwide Danish Rheumato......OBJECTIVE: The aim of this study was to describe dose regimens, dose escalation and clinical outcomes in TNF-α inhibitor (TNFi)-naive patients with PsA treated with infliximab in routine rheumatology care. METHODS: We conducted an observational cohort study based on the nationwide Danish...... Icelandic patients at baseline [median 3.1 (interquartile range 3.0-3.8) vs 2.3 (2.1-2.9) mg/kg, P drug survival than...... Icelandic patients (1183 vs 483 days). In univariate analyses stratified by country, time until dose escalation, response rates, drug survival and 1-year's disease activity were independent of starting dose. Drug survival was shorter among patients not receiving concomitant MTX. CONCLUSION: In clinical...

  12. Response to growth hormone treatment and final height after cranial or craniospinal irradiation

    International Nuclear Information System (INIS)

    Sulmont, V.; Brauner, R.; Fontoura, M.; Rappaport, R.

    1990-01-01

    Growth hormone (GH) deficiency (GHD) induced by cranial irradiation has become a frequent indication of hGH substitutive therapy. This study analyses the growth response to hGH therapy and the factors involved in the decrease in growth velocity observed after cranial irradiation. One hundred children given cranial radiation for pathology distant from the hypothalamo-pituitary area were studied. Fifty-six of them received hGH therapy for GHD resulting in decreased growth velocity. The initial annual height gain in the cranial-irradiated group was comparable to that of patients treated for idiopathic GHD; additional spinal irradiation significantly reduced the growth response. Twenty-eight hGH-treated patients reached final heights which were compared to those of 2 untreated irradiated groups, one with GHD (n=27) and the other with normal GH secretion (n=17). The height SD score changes observed in hGH therapy were +0.3 in the cranial (n=10) and -1.2 SD in the craniospinal (n=18) groups. GH deficiency had contributed to a mean height loss of 1 SD and spinal irradiation to a loss of 1.4SD. The small effect of hGH therapy on final height is probably linked to the small bone age retardation at onset of hGH therapy and to the fact that irradiated children entered puberty at a younger age in terms of chronological age and bone age than the idiopathic GHD patients. These data suggest that the results of gGH therapy in irradiated children might be improved with higher and more fractionated hGH doses and, in some patients, by delaying puberty using luteinizing hormone releasing hormone analogs

  13. Factors Predictive of Tumor Recurrence and Survival After Initial Complete Response of Esophageal Squamous Cell Carcinoma to Definitive Chemoradiotherapy

    International Nuclear Information System (INIS)

    Ishihara, Ryu; Yamamoto, Sachiko; Iishi, Hiroyasu; Takeuchi, Yoji; Sugimoto, Naotoshi; Higashino, Koji; Uedo, Noriya; Tatsuta, Masaharu; Yano, Masahiko; Imai, Atsushi; Nishiyama, Kinji

    2010-01-01

    Purpose: To assess factors predictive of recurrent disease and survival after achieving initial complete response (CR) to chemoradiotherapy (CRT) for esophageal cancer. Methods and Materials: Patients who had clinical Stage I-IVA esophageal cancer and received definitive CRT between 2001 and 2007 were retrospectively analyzed. Results: Of 269 patients with esophageal cancer, 110 who achieved CR after definitive CRT were included in the analyses. Chemoradiotherapy mainly consisted of 2 cycles of cisplatin and fluorouracil with concurrent radiotherapy of 60 Gy in 30 fractions. We identified 28 recurrences and 28 deaths during follow-up. The cumulative 1- and 3-year recurrence rates were 18% and 32%, respectively. By univariate and multivariate analyses, tumor category (hazard ratio [HR] 6.6; 95% confidence interval [CI] 1.4-30.2; p = 0.015) was an independent risk factor for local recurrence, whereas age (HR 3.9; 95% CI 1.1-14.0; p = 0.034) and primary tumor location (HR 4.5; 95% CI 1.6-12.4; p = 0.004) were independent risk factors for regional lymph node or distant recurrences. The cumulative overall 1- and 3-year survival rates were 91% and 66%, respectively. As expected, recurrence was associated with poor survival (p = 0.019). By univariate and multivariate analyses, primary tumor location (HR 3.8; 95% CI 1.2-12.0; p = 0.024) and interval to recurrence (HR 4.3; 95% CI 1.3-14.4; p = 0.018) were independent factors predictive of survival after recurrence. Conclusion: Risk of recurrence after definitive CRT for esophageal cancer was associated with tumor category, age, and primary tumor location; this information may help in improved prognostication for these patients.

  14. Survivin-specific T-cell reactivity correlates with tumor response and patient survival

    DEFF Research Database (Denmark)

    Becker, Jürgen C; Andersen, Mads H; Hofmeister-Müller, Valeska

    2012-01-01

    Therapeutic vaccination directed to induce an anti-tumoral T-cell response is a field of extensive investigation in the treatment of melanoma. However, many vaccination trials in melanoma failed to demonstrate a correlation between the vaccine-specific immune response and therapy outcome. This has...... been mainly attributed to immune escape by antigen loss, rendering us in the need of new vaccination targets....

  15. Association Between Survival and Time of Day for Rapid Response Team Calls in a National Registry.

    Science.gov (United States)

    Churpek, Matthew Michael; Edelson, Dana P; Lee, Ji Yeon; Carey, Kyle; Snyder, Ashley

    2017-10-01

    Decreased staffing at nighttime is associated with worse outcomes in hospitalized patients. Rapid response teams were developed to decrease preventable harm by providing additional critical care resources to patients with clinical deterioration. We sought to determine whether rapid response team call frequency suffers from decreased utilization at night and how this is associated with patient outcomes. Retrospective analysis of a prospectively collected registry database. National registry database of inpatient rapid response team calls. Index rapid response team calls occurring on the general wards in the American Heart Association Get With The Guidelines-Medical Emergency Team database between 2005 and 2015 were analyzed. None. The primary outcome was inhospital mortality. Patient and event characteristics between the hours with the highest and lowest mortality were compared, and multivariable models adjusting for patient characteristics were fit. A total of 282,710 rapid response team calls from 274 hospitals were included. The lowest frequency of calls occurred in the consecutive 1 AM to 6:59 AM period, with 266 of 274 (97%) hospitals having lower than expected call volumes during those hours. Mortality was highest during the 7 AM hour and lowest during the noon hour (18.8% vs 13.8%; adjusted odds ratio, 1.41 [1.31-1.52]; p response team activation is less frequent during the early morning and is followed by a spike in mortality in the 7 AM hour. These findings suggest that failure to rescue deteriorating patients is more common overnight. Strategies aimed at improving rapid response team utilization during these vulnerable hours may improve patient outcomes.

  16. Extracellular histones reduce survival and angiogenic responses of late outgrowth progenitor and mature endothelial cells.

    Science.gov (United States)

    Mena, H A; Carestia, A; Scotti, L; Parborell, F; Schattner, M; Negrotto, S

    2016-02-01

    ESSENTIALS: Extracellular histones are highly augmented in sites of neovessel formation, such as regeneration tissues. We studied histone effect on survival and angiogenic activity of mature and progenitor endothelial cells. Extracellular histones trigger apoptosis and pyroptosis and reduce angiogenesis in vivo and in vitro. Histone blockade can be useful as a therapeutic strategy to improve angiogenesis and tissue regeneration. Extracellular histones are highly augmented in sites of neovessel formation, like regeneration tissues. Their cytotoxic effect has been studied in endothelial cells, although the mechanism involved and their action on endothelial colony-forming cells (ECFCs) remain unknown. To study the effect of histones on ECFC survival and angiogenic functions and compare it with mature endothelial cells. Nuclear morphology analysis showed that each human recombinant histone triggered both apoptotic-like and necrotic-like cell deaths in both mature and progenitor endothelial cells. While H1 and H2A exerted a weak toxicity, H2B, H3 and H4 were the most powerful. The percentage of apoptosis correlated with the percentage of ECFCs exhibiting caspase-3 activation and was zeroed by the pan-caspase inhibitor Z-VAD-FMK. Necrotic-like cell death was also suppressed by this compound and the caspase-1 inhibitor Ac-YVAD-CMK, indicating that histones triggered ECFC pyroptosis. All histones, at non-cytotoxic concentrations, reduced migration and H2B, H3 and H4 induced cell cycle arrest and impaired tubulogenesis via p38 activation. Neutrophil-derived histones exerted similar effects. In vivo blood vessel formation in the quail chorioallantoic membrane was also reduced by H2B, H3 and H4. Their cytotoxic and antiangiogenic effects were suppressed by unfractioned and low-molecular-weight heparins and the combination of TLR2 and TLR4 blocking antibodies. Histones trigger both apoptosis and pyroptosis of ECFCs and inhibit their angiogenic functions. Their cytotoxic and

  17. Influence of pre- and post-transplantation responses on outcome of patients with multiple myeloma: sequential improvement of response and achievement of complete response are associated with longer survival.

    Science.gov (United States)

    Lahuerta, Juan José; Mateos, Maria Victoria; Martínez-López, Joaquin; Rosiñol, Laura; Sureda, Anna; de la Rubia, Javier; García-Laraña, José; Martínez-Martínez, Rafael; Hernández-García, Miguel T; Carrera, Dolores; Besalduch, Joan; de Arriba, Felipe; Ribera, José María; Escoda, Lourdes; Hernández-Ruiz, Belén; García-Frade, Javier; Rivas-González, Concepción; Alegre, Adrían; Bladé, Joan; San Miguel, Jesús F

    2008-12-10

    Complete response (CR) is considered an important goal in most hematologic malignancies. However, in multiple myeloma (MM), there is no consensus regarding whether immunofixation (IF)-negative CR, IF-positive near-CR (nCR), and partial response (PR) are associated with different survivals. We evaluated the prognostic influence on event-free survival (EFS) and overall survival (OS) of these responses pre- and post-transplantation in newly diagnosed patients with MM. We analyzed 632 patients from the prospective Grupo Español de Mieloma 2000 protocol who were uniformly treated with vincristine, carmustine, cyclophosphamide, melphalan, and predisone/vincristine, carmustine, adryamcine, and dexamethasone induction followed by high-dose therapy and autologous stem-cell transplantation. Post-transplantation response markedly influenced outcomes. Patients achieving CR had significantly longer EFS (median, 61 v 40 months; P < 10(-5)) and OS (medians not reached; P = .01) versus patients achieving nCR, who likewise had somewhat better outcomes compared with patients achieving PR (median EFS, 34 months, P = .07 v nCR; median OS, 61 months, P = .04). EFS and OS and influence of response were similar among older (age 65 to 70 years) and younger (age < 65 years) patients. Similar findings were observed with pretransplantation response, with trends toward EFS (P = .1; P = .05) and OS (P = .1; P = .07) benefit in patients achieving CR versus nCR and PR, respectively. Post-transplantation response was markedly influenced by pretransplantation response; improvements in response were associated with prolonged survival. Quality of response post-transplantation, notably CR, is significantly associated with EFS and OS prolongation in newly diagnosed patients with MM. There were trends toward similar associations with pretransplantation response status.

  18. 78 FR 59726 - Interim Final Appendix D of OMB Circular No. A-123, “Management's Responsibility for Internal...

    Science.gov (United States)

    2013-09-27

    ... Management Systems'' September 27, 2013. ACTION: Notice. SUMMARY: OMB Circular No. A-123, ``Management's Responsibility for Internal Control,'' defines management's responsibility for internal control in Federal... OFFICE OF MANAGEMENT AND BUDGET Interim Final Appendix D of OMB Circular No. A-123, ``Management's...

  19. Recovery of endo-CFU-S in radio-adaptive survival response in mice

    International Nuclear Information System (INIS)

    Yonezawa, Morio; Horie, Kiyohito; Kubo, Kihei

    2003-01-01

    A priming irradiation with 0.45 Gy of X-rays, given 2 weeks prior to the challenging exposures, induces radio-resistance (decrease in bone marrow death rate after mid-lethal irradiations) in mice of C57BL/6 mice. This acquired radio-resistance appeared on day 9 and continued till day 17 after the priming irradiation, with a maximal on days 12-14 and diminished on day 21. The priming irradiation, given 14 days prior to the challenging exposure, increased endogenous spleen colonies on days 12-13 after exposure to 5.0 Gy. Effect of interval time between the priming and the challenging irradiations on the increase in endogenous spleen colonies was also examined. Significant increase of the colonies by the priming irradiation was observed when the interval time was 12-17 and 21 days. The results correspond to the increase of the survival rates on days 12-17 after the challenging irradiations. (author)

  20. Radio-adaptive survival response in mice: Hematological studies on the acquired radio-resistance

    International Nuclear Information System (INIS)

    Morio Yonezawa

    1997-01-01

    We have reported that X-ray pre-irradiation induced two types of radio-resistance (improved 30-day survival rate after mid-lethal irradiation) in C57BL and ICR strains of mice. The dose- effects were distinguished into the following 4 dose ranges in ICR mice: (1) below 2.5 cGy: no radio-resistance is induced 2 months later, (2) 5 to 10 cGy: significant radio-resistance 2 to 2.5 months later by whole-body pre-irradiation, (3) 15 to 20 cGy: no radio-resistance at any time between 2 weeks to 2 months later, and (4) 30 to 50 cGy: significant radio-resistance 2 weeks later by partial-body pre-irradiation of the trunk as well as whole-body pre-irradiation. We previously reported that the recovery of blood cell counts of erythrocytes, leukocytes and thrombocytes was enhanced by the pre-irradiation in C57BL, but not in ICR mice. In the present study, hematological changes were examined on blood coagulation time and hemorrhaging tendency in case of pre-irradiation with 45 cGy in ICR mice. Blood coagulation time prolonged on day 12 after sub-lethal irradiation, but it was not restored by the pre- irradiation, while occult blood appearance in feces collected on days 10 to 12 after sub-lethal irradiation was decreased by the pre-irradiation in ICR mice. (author)

  1. Biologic therapy response and drug survival for females compared to males with rheumatoid arthritis: a cohort study.

    Science.gov (United States)

    Lee, Jeffrey; Mason, Randal; Martin, Liam; Barnabe, Cheryl

    2014-10-01

    Prior research has identified differences between sexes in rheumatoid arthritis (RA) disease characteristics and treatment response, but not how these differences affect therapeutic decision making to switch therapy. Our objective was to assess for sex differences in RA disease activity during the course of biologic therapy and how these differences impact drug survival and therapeutic switching. Data from the Alberta Biologics Pharmacosurveillance Program, a population-based observational cohort of patients receiving biologic therapy for RA, were used for a sex-stratified analysis of disease activity. Linear mixed-model analysis was applied to compare continuous effectiveness outcomes (DAS28, HAQ scores, visual analogue scales of patient-reported outcomes). Chi-squared tests and log-rank tests were used to determine differences in the frequency of switching and drug survival between females and males. At biologic initiation, females (n = 419) and males (n = 148) had similar disease activity (DAS28 in females 5.83, males 5.72), but females reported worse function (HAQ 1.64 vs 1.51, p = 0.037) and more fatigue (6.7 vs 5.9/10, p = 0.013), but the same global score as males (6.9 vs 6.8/10). During biologic therapy, females reported more fatigue (β = -0.454, 95 % CI -0.852, -0.056, p = 0.0252), worse function (β = -0.183, 95 % CI -0.291, -0.074, p = 0.0010) and higher DAS28 scores (β = -0.401, 95 % CI -0.617, -0.184, p = 0.0003). A new composite disease activity index, the HUPI, eliminated the observed differences in disease activity scores between females and males. Median survival for biologic-naïve patients was similar between sexes (3.7 years males, 3.3 years females, log-rank test p = 0.25). The frequency of switching and survival on subsequent biologics were the same between females and males. Guided by traditional outcome measurement tools, worse disease activity and patient-reported outcomes through the course of therapy did not translate into differences

  2. Immune Response of Mormon Crickets that Survived Infection by Beauveria Bassiana

    Science.gov (United States)

    Beauveria bassiana is an entomopathogenic Ascomycete fungus that serves as a biological control agent of Mormon crickets (Anabrus simplex Haldeman) and other grasshopper pests. To measure the dose dependent response of Mormon crickets to fungal attack, we applied B. bassiana strain GHA topically to...

  3. The time dimension in stress responses : relevance for survival and health

    NARCIS (Netherlands)

    Eriksen, HR; Olff, M; Murison, R; Ursin, H

    1999-01-01

    Within the Cognitive Activation Theory of Stress (CATS), the stress response occurs whenever there is a discrepancy between what the organism is expecting, and what really exists. It affects the biochemistry of the brain, mobilizes resources, affects performance, and endocrine, vegetative, and

  4. Survival in early breast cancer patients is favorably influenced by a natural humoral immune response to polymorphic epithelial mucin.

    Science.gov (United States)

    von Mensdorff-Pouilly, S; Verstraeten, A A; Kenemans, P; Snijdewint, F G; Kok, A; Van Kamp, G J; Paul, M A; Van Diest, P J; Meijer, S; Hilgers, J

    2000-02-01

    Polymorphic epithelial mucin (PEM or MUC1) is being studied as a vaccine substrate for the immunotherapy of patients with adenocarcinoma. The present study analyzes the incidence of naturally occurring MUC1 antibodies in early breast cancer patients and relates the presence of these antibodies in pretreatment serum to outcome of disease. We measured immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies to MUC1 with an enzyme-linked immunoassay (PEM.CIg), which uses a MUC1 triple-tandem repeat peptide conjugated to bovine serum albumin, in pretreatment serum samples obtained from 154 breast cancer patients (52 with stage I disease and 102 with stage II) and 302 controls. The median disease-specific survival time of breast cancer patients was 74 months (range, 15 to 118 months). A positive test result was defined as MUC1 IgG or IgM antibody levels equal to or greater than the corresponding rounded-up median results obtained in the total breast cancer population. A positive test result for both MUC1 IgG and IgM antibodies in pretreatment serum was associated with a significant benefit in disease-specific survival in stage I and II (P =.0116) breast cancer patients. Positive IgG and IgM MUC1 antibody levels had significant additional prognostic value to stage (P =.0437) in multivariate analysis. Disease-free survival probability did not differ significantly. However, stage II patients who tested positive for MUC1 IgG and IgM antibody and who relapsed had predominantly local recurrences or contralateral disease, as opposed to recurrences at distant sites in the patients with a negative humoral response (P =.026). Early breast cancer patients with a natural humoral response to MUC1 have a higher probability of freedom from distant failure and a better disease-specific survival. MUC1 antibodies may control hematogenic tumor dissemination and outgrowth by aiding the destruction of circulating or seeded MUC1-expressing tumor cells. Vaccination of breast cancer

  5. Potential density and tree survival: an analysis based on South ...

    African Journals Online (AJOL)

    Finally, we present a tree survival analysis, based on the Weibull distribution function, for the Nelshoogte replicated CCT study, which has been observed for almost 40 years after planting and provides information about tree survival in response to planting espacements ranging from 494 to 2 965 trees per hectare.

  6. Surviving anoxia in marine sediments: The metabolic response of ubiquitous benthic foraminifera (Ammonia tepida)

    Science.gov (United States)

    Spangenberg, Jorge E.; Mabilleau, Guillaume; Escrig, Stéphane; Meibom, Anders; Geslin, Emmanuelle

    2017-01-01

    High input of organic carbon and/or slowly renewing bottom waters frequently create periods with low dissolved oxygen concentrations on continental shelves and in coastal areas; such events can have strong impacts on benthic ecosystems. Among the meiofauna living in these environments, benthic foraminifera are often the most tolerant to low oxygen levels. Indeed, some species are able to survive complete anoxia for weeks to months. One known mechanism for this, observed in several species, is denitrification. For other species, a state of highly reduced metabolism, essentially a state of dormancy, has been proposed but never demonstrated. Here, we combined a 4 weeks feeding experiment, using 13C-enriched diatom biofilm, with correlated TEM and NanoSIMS imaging, plus bulk analysis of concentration and stable carbon isotopic composition of total organic matter and individual fatty acids, to study metabolic differences in the intertidal species Ammonia tepida exposed to oxic and anoxic conditions. Strongly contrasting cellular-level dynamics of ingestion and transfer of the ingested biofilm components were observed between the two conditions. Under oxic conditions, within a few days, intact diatoms were ingested, degraded, and their components assimilated, in part for biosynthesis of different cellular components: 13C-labeled lipid droplets formed after a few days and were subsequently lost (partially) through respiration. In contrast, in anoxia, fewer diatoms were initially ingested and these were not assimilated or metabolized further, but remained visible within the foraminiferal cytoplasm even after 4 weeks. Under oxic conditions, compound specific 13C analyses showed substantial de novo synthesis by the foraminifera of specific polyunsaturated fatty acids (PUFAs), such as 20:4(n-6). Very limited PUFA synthesis was observed under anoxia. Together, our results show that anoxia induced a greatly reduced rate of heterotrophic metabolism in Ammonia tepida on a time

  7. Biology of the fire blight pathogen Erwinia amylovora in oligotrophic environments: survival responses and virulence

    OpenAIRE

    Delgado Santander, Ricardo

    2016-01-01

    Erwinia amylovora es una bacteria fitopatógena de la familia Enterobacteriaceae, responsable del fuego bacteriano de las rosáceas. Los efectos destructivos de este patógeno sobre frutos, flores y prácticamente todos los órganos de las plantas hospedadoras afectadas constituyen una amenaza importante para la producción de pera y manzana, y suponen graves pérdidas económicas anuales en todo el mundo. E. amylovora está clasificada como un organismo de cuarentena en la Unión Europea y en otros pa...

  8. Survival pathways under stress

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. Survival pathways under stress. Bacteria survive by changing gene expression. pattern. Three important pathways will be discussed: Stringent response. Quorum sensing. Proteins performing function to control oxidative damage.

  9. Is cell survival a determinant of the in situ response of 9L tumours

    International Nuclear Information System (INIS)

    Wheeler, K.T.; Wallen, C.A.

    1980-01-01

    The influence of growth rate, location, size and potential lethal damage (PLD) recovery on the cellular radiosensitivity and the tumour response was studied in 9L/Ro and 9L/SF rat tumours. The median day of death of rats bearing the intracerebral (i.c.) 9L/Ro tumours was 16-18 days; for i.c. 9L/SF tumours it was 23-25 days. The doubling time of 9L/Ro cells was slightly faster than for 9L/SF cells both in culture and in the brain. The cellular radiosensitivity of both i.c. tumour cell sublines was identical. However, subcutaneous (s.c.) 9L/Ro tumour cells were more resistant. There was no evidence of a substantial hypoxic fraction in either site. When i.c. 9L/Ro and 9L/SF tumours of similar size were treated with fractionated doses of BCNU, X-rays or combinations of the two, the responses of the two tumours were essentially identical. The rate of recovery from radiation-induced PLD was identical in the two sublines and the two sites. Increase in life-span of rats bearing i.c. 9L/Ro tumours appeared to be correlated with the tumour cell kill measured after completion of PLD recovery rather than with the tumour cell kill determined immediately after irradiation. (author)

  10. Imaging response is highly predictive of survival of malignant glioma patients treated with standard or hyperfractionated RT and carmustine in RTOG 9006

    International Nuclear Information System (INIS)

    Curran, Walter J.; Scott, Charles B.; Yung, W.K. Alfred; Scarantino, Charles; Urtasun, Raul; Movsas, Benjamin; Jones, Christopher; Simpson, Joseph; Fischbach, A. Jennifer; Petito, Carol; Nelson, James

    1996-01-01

    Objectives: Limited information is available correlating response to initial therapy and survival outcome among malignant glioma patients. This analysis was conducted to determine the response rate of malignant glioma patients to either standard (STN) or hyperfractionated (HFX) RT and carmustine and to correlate the tumor response status with survival. Patients and Methods: From (11(90)) to (3(94)), 712 newly diagnosed malignant glioma patients were registered on RTOG 9006 and randomized between hyperfractionated RT of 72.0 Gy in 1.2 Gy twice-daily fractions and 60.0 Gy in 2.0 Gy daily fractions. All patients received 80 mg/m-2 of carmustine D 1-3 q 8 wks. As reported in the 1996 Proceedings of the Amer Soc Clin Oncol (Abstr no. 280), there was no survival benefit observed for the HFX regimen. 529 of the 686 eligible patients had pre-operative, post-operative, and post-RT contrast-enhanced MR and/or CT scans available for central review of tumor and peritumoral edema measurements. Response status was judged by applying standard response criteria to a comparison of tumor measurements on follow-up and post-operative films. Results: Of the 529 patients evaluated for imaging response, the complete and partial response rates were 14% and 20%, respectively. A significant correlation between response and survival was observed (P<0.0001). Variables which predicted for a better tumor response were anaplastic astrocytoma vs glioblastoma multiforme histology, better performance status, more extensive resection, and a more favorable Recursive Partitioning and Amalgamation class assignment (JNCI 85:704-710, 1993). Conclusion: The objective response rate for malignant glioma patients to RTOG 9006 therapy was 34%, and survival outcome is strongly correlated with tumor response status. These observations justify the testing of aggressive salvage strategies for patients without imaging evidence of response following initial therapy

  11. The Final 24-Item Early Onset Scoliosis Questionnaires (EOSQ-24): Validity, Reliability and Responsiveness.

    Science.gov (United States)

    Matsumoto, Hiroko; Williams, Brendan; Park, Howard Y; Yoshimachi, Julie Y; Roye, Benjamin D; Roye, David P; Akbarnia, Behrooz A; Emans, John; Skaggs, David; Smith, John T; Vitale, Michael G

    2018-03-01

    The goal of early-onset scoliosis (EOS) treatment is to improve health-related quality of life (HRQoL) for patients and to reduce the burden on their parents or caregivers. The purpose of this study is to develop and finalize the 24-item Early-Onset Scoliosis Questionnaire (EOSQ-24), and examine the validity, reliability, and responsiveness of the EOSQ-24 in measuring patients' HRQoL, the burden on their caregivers, and the burden on their caregiver's finances. The study also established aged-matched normative values for the EOSQ-24. The EOSQ-24 was administered to caregivers of male and female patients aged 0 to 18 years with EOS. Patients with EOS are diagnosed before 10 years of age. Criterion validity was investigated by measuring agreement between its scores and pulmonary function testing. Construct validity was established by comparing values across different etiology groups using the known-group method, and measuring internal consistency reliability. Content validity was confirmed by reviewing caregiver and health provider ratings for the relativity and clarity of the EOSQ-24 questions. Test-retest reliability was examined through intraclass correlation coefficients. Responsiveness of the EOSQ-24 before and after surgical interventions was also investigated. Age-matched, healthy patients, without spinal deformity, were enrolled to establish normative EOSQ-24 values. The pulmonary function subdomain score in the EOSQ-24 was positively correlated with pulmonary function testing values, establishing criterion validity. The EOSQ-24 scores for neuromuscular patients were significantly decreased compared with idiopathic or congenital/structural patients, demonstrating known-group validity. Internal consistency reliability of patients' HRQoL was excellent (0.92), but Family Burden was questionable (0.64) indicating that Parental Burden and Financial Burden should be in separate domains. All 24 EOSQ items were rated as essential and clear, confirming content

  12. Evaluation of 60Co radiation effect in the survival of different mouse strains. Radiomodifiers and celular response

    International Nuclear Information System (INIS)

    Villavicencio, A.L.C.H.

    1988-01-01

    The radiomodifier capacity of proteose-peptone (PP), imidazole derivatives such as azomycin and levamisole against an 8 or 9 Gy single dose of 60 Co irradiation of mice from IPEN animal house was evaluated, being the biological responses compared with other mouse strains. It is concluded that PP, azomycin and PP + azomycin behaved as radioprotectors, while lavamisole appeared as a radiossensitizer. The various strains showed differences in their survival indexes. The changes in body weight curves of mice from all the experiments were followed during 30 days. Qualitative and quantitative analysis 2 hours, 3 and 6 days after irradiation of typical macrophages, mononuclear cells (monocytes and lymphocytes), polimorphonuclear and mast cells from peritonium of test animals showed that radiation interfered in a differential way in the kinetics of peritoneal cells. (author) [pt

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

    Science.gov (United States)

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

    2015-06-15

    To investigate the predictive and prognostic value of O(6) -methylguanine DNA methyltransferase (MGMT) inactivation by analyses of promoter methylation in pretreatment tumor biopsies from patients with cutaneous melanoma treated with dacarbazine (DTIC) or temozolomide (TMZ) were performed. The patient cohorts consisted of Belgian and Swedish disseminated melanoma patients. Patients were subdivided into those receiving single-agent treatment with DTIC/TMZ (cohort S, n = 74) and those treated with combination chemotherapy including DTIC/TMZ (cohort C, n = 79). Median follow-up was 248 and 336 days for cohort S and cohort C, respectively. MGMT promoter methylation was assessed by three methods. The methylation-related transcriptional silencing of MGMT mRNA expression was assessed by real-time RT-PCR. Response to chemotherapy and progression-free survival (PFS) and overall survival were correlated to MGMT promoter methylation status. MGMT promoter methylation was detected in tumor biopsies from 21.5 % of the patients. MGMT mRNA was found to be significantly lower in tumors positive for MGMT promoter methylation compared to tumors without methylation in both treatment cohorts (p MGMT promoter methylation in cohort S (p = 0.0005), but did not reach significance in cohort C (p = 0.16). Significantly longer PFS was observed among patients with MGMT promoter-methylated tumors (p = 0.002). Multivariate Cox regression analysis identified presence of MGMT promoter methylation as an independent variable associated with longer PFS. Together, this implies that MGMT promoter methylation is associated with response to single-agent DTIC/TMZ and longer PFS in disseminated cutaneous melanoma. © 2014 UICC.

  14. Identification of a novel Francisella tularensis factor required for intramacrophage survival and subversion of innate immune response.

    Science.gov (United States)

    Mahawar, Manish; Atianand, Maninjay K; Dotson, Rachel J; Mora, Vanessa; Rabadi, Seham M; Metzger, Dennis W; Huntley, Jason F; Harton, Jonathan A; Malik, Meenakshi; Bakshi, Chandra Shekhar

    2012-07-20

    Francisella tularensis, the causative agent of tularemia, is one of the deadliest agents of biological warfare and bioterrorism. Extremely high virulence of this bacterium is associated with its ability to dampen or subvert host innate immune response. The objectives of this study were to identify factors and understand the mechanisms of host innate immune evasion by F. tularensis. We identified and explored the pathogenic role of a mutant interrupted at gene locus FTL_0325, which encodes an OmpA-like protein. Our results establish a pathogenic role of FTL_0325 and its ortholog FTT0831c in the virulent F. tularensis SchuS4 strain in intramacrophage survival and suppression of proinflammatory cytokine responses. This study provides mechanistic evidence that the suppressive effects on innate immune responses are due specifically to these proteins and that FTL_0325 and FTT0831c mediate immune subversion by interfering with NF-κB signaling. Furthermore, FTT0831c inhibits NF-κB activity primarily by preventing the nuclear translocation of p65 subunit. Collectively, this study reports a novel F. tularensis factor that is required for innate immune subversion caused by this deadly bacterium.

  15. Identification of a Novel Francisella tularensis Factor Required for Intramacrophage Survival and Subversion of Innate Immune Response*

    Science.gov (United States)

    Mahawar, Manish; Atianand, Maninjay K.; Dotson, Rachel J.; Mora, Vanessa; Rabadi, Seham M.; Metzger, Dennis W.; Huntley, Jason F.; Harton, Jonathan A.; Malik, Meenakshi; Bakshi, Chandra Shekhar

    2012-01-01

    Francisella tularensis, the causative agent of tularemia, is one of the deadliest agents of biological warfare and bioterrorism. Extremely high virulence of this bacterium is associated with its ability to dampen or subvert host innate immune response. The objectives of this study were to identify factors and understand the mechanisms of host innate immune evasion by F. tularensis. We identified and explored the pathogenic role of a mutant interrupted at gene locus FTL_0325, which encodes an OmpA-like protein. Our results establish a pathogenic role of FTL_0325 and its ortholog FTT0831c in the virulent F. tularensis SchuS4 strain in intramacrophage survival and suppression of proinflammatory cytokine responses. This study provides mechanistic evidence that the suppressive effects on innate immune responses are due specifically to these proteins and that FTL_0325 and FTT0831c mediate immune subversion by interfering with NF-κB signaling. Furthermore, FTT0831c inhibits NF-κB activity primarily by preventing the nuclear translocation of p65 subunit. Collectively, this study reports a novel F. tularensis factor that is required for innate immune subversion caused by this deadly bacterium. PMID:22654100

  16. Sirtuin 7 promotes cellular survival following genomic stress by attenuation of DNA damage, SAPK activation and p53 response

    Energy Technology Data Exchange (ETDEWEB)

    Kiran, Shashi; Oddi, Vineesha [Laboratory of Cancer Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, 500001 (India); Ramakrishna, Gayatri, E-mail: gayatrirama1@gmail.com [Laboratory of Cancer Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, 500001 (India); Laboratory of Cancer Cell Biology, Department of Research, Institute of Liver and Biliary Sciences, Delhi 110070 (India)

    2015-02-01

    Maintaining the genomic integrity is a constant challenge in proliferating cells. Amongst various proteins involved in this process, Sirtuins play a key role in DNA damage repair mechanisms in yeast as well as mammals. In the present work we report the role of one of the least explored Sirtuin viz., SIRT7, under conditions of genomic stress when treated with doxorubicin. Knockdown of SIRT7 sensitized osteosarcoma (U2OS) cells to DNA damage induced cell death by doxorubicin. SIRT7 overexpression in NIH3T3 delayed cell cycle progression by causing delay in G1 to S transition. SIRT7 overexpressing cells when treated with low dose of doxorubicin (0.25 µM) showed delayed onset of senescence, lesser accumulation of DNA damage marker γH2AX and lowered levels of growth arrest markers viz., p53 and p21 when compared to doxorubicin treated control GFP expressing cells. Resistance to DNA damage following SIRT7 overexpression was also evident by EdU incorporation studies where cellular growth arrest was significantly delayed. When treated with higher dose of doxorubicin (>1 µM), SIRT7 conferred resistance to apoptosis by attenuating stress activated kinases (SAPK viz., p38 and JNK) and p53 response thereby shifting the cellular fate towards senescence. Interestingly, relocalization of SIRT7 from nucleolus to nucleoplasm together with its co-localization with SAPK was an important feature associated with DNA damage. SIRT7 mediated resistance to doxorubicin induced apoptosis and senescence was lost when p53 level was restored by nutlin treatment. Overall, we propose SIRT7 attenuates DNA damage, SAPK activation and p53 response thereby promoting cellular survival under conditions of genomic stress. - Highlights: • Knockdown of SIRT7 sensitized cells to DNA damage induced apoptosis. • SIRT7 delayed onset of premature senescence by attenuating DNA damage response. • Overexpression of SIRT7 delayed cell cycle progression by delaying G1/S transition. • Upon DNA damage SIRT

  17. Interactions between SNPs affecting inflammatory response genes are associated with multiple myeloma disease risk and survival

    DEFF Research Database (Denmark)

    Nielsen, Kaspar René; Rodrigo-Domingo, Maria; Steffensen, Rudi

    2017-01-01

    -nucleotide polymorphisms (SNPs) involved in the immune response and a subsequent statistical analysis that focusses on the association of SNPs, certain haplotypes or SNP-SNP interactions with MM risk and prognosis. We genotyped 348 Danish patients and 355 controls for 13 SNPs located in the TNFA, IL-4, IL-6, IL-10 and CHI...... were studied for expression in normal B-cell subsets and myeloma plasma cells. We observed a significantly reduced risk when harboring the TNFA-238A allele (OR = 0.51 (0.29-0.86)) and interactions between the TNFA-1031T/C * and IL-10 -3575T/A (p = .007) as well as the TNFA-308G/A * and IL-10-1082G/A (p...... = .008) allels. By statistical approaches, we observed association between prognosis and the TNFA-857CC genotype (HR = 2.80 (1.29-6.10)) and IL-10-1082GG + GA genotypes (HR = 1.93 (1.07-3.49)) and interactions between IL-6-174G/C and IL-10-3575T/A (p = .001) and between TNFA-308G/A and IL-4-1098T/G (p...

  18. Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers.

    Science.gov (United States)

    Imhof, Anna; Brunner, Philippe; Marincek, Nicolas; Briel, Matthias; Schindler, Christian; Rasch, Helmut; Mäcke, Helmut R; Rochlitz, Christoph; Müller-Brand, Jan; Walter, Martin A

    2011-06-10

    To investigate response, survival, and safety profile of the somatostatin-based radiopeptide (90)yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([(90)Y-DOTA]-TOC) in neuroendocrine cancers. In a clinical phase II single-center open-label trial, patients with neuroendocrine cancers were treated with repeated cycles of [(90)Y-DOTA]-TOC. Each cycle consisted of a single intravenous injection of 3.7GBq/m(2) body-surface [(90)Y-DOTA]-TOC. Additional cycles were withheld in case of tumor progression and/or permanent toxicity. Overall, 1,109 patients received 2,472 cycles of [(90)Y-DOTA]-TOC (median, two; range, one to 10 cycles per patient). Of the 1,109 patients, 378 (34.1%) experienced morphologic response; 172 (15.5%), biochemical response; and 329 (29.7%), clinical response. During a median follow-up of 23 months, 491 patients (44.3%) died. Longer survival was correlated with each: morphologic (hazard ratio [HR], 0.46; 95% CI, 0.38 to 0.56; median survival, 44.7 v 18.3 months; P TOC treatment in a large cohort. Response to [(90)Y-DOTA]-TOC is associated with longer survival. Somatostatin receptor imaging is predictive for both survival after [(90)Y-DOTA]-TOC treatment and occurrence of renal toxicity.

  19. Waste Isolation Pilot Plant disposal phase final supplemental environmental impact statement. Volume 3: Comment response document

    International Nuclear Information System (INIS)

    1997-09-01

    The purpose of the Waste Isolation Pilot Plant Disposal Final Supplemental Environmental Impact Statement (SEIS-II) is to provide information on environmental impacts regarding the Department of Energy''s (DOE) proposed disposal operations at WIPP. The Proposed Action describes the treatment and disposal of the Basic inventory of TRU waste over a 35-year period. The Action Alternatives proposed the treatment of the Basic Inventory and an Additional Inventory as well as the transportation of the treated waste to WIPP for disposal over a 150- to 190-year period. The three Action Alternatives include the treatment of TRU waste at consolidation sites to meet WIPP planning-basic Waste Acceptance Criteria, the thermal treatment of TRU waste to meet Land Disposal Restrictions, and the treatment of TRU waste by a shred and grout process. SEIS-II evaluates environmental impacts resulting from the various treatment options; the transportation of TRU waste to WIPP using truck, a combination of truck and regular rail service, and a combination of truck and dedicated rail service; and the disposal of this waste in the repository. Evaluated impacts include those to the general environment and to human health. Additional issues associated with the implementation of the alternatives are discussed to provide further understanding of the decisions to be reached and to provide the opportunity for public input on improving DOE''s Environmental Management Program. This volume provides responses to public comments on the Draft SEIS-II. Comments are related to: Alternatives; TRU waste; DOE credibility; Editorial; Endorsement/opposition; Environmental justice; Facility accidents; Generator site operations; Health and safety; Legal and policy issues; NEPA process; WIPP facilities; WIPP waste isolation performance; Purpose and need; WIPP operations; Site characterization; Site selection; Socioeconomics; and Transportation

  20. Whole-brain radiotherapy with or without efaproxiral for the treatment of brain metastases: Determinants of response and its prognostic value for subsequent survival

    International Nuclear Information System (INIS)

    Stea, Baldassarre; Suh, John H.; Boyd, Adam P. M.S.; Cagnoni, Pablo J.; Shaw, Edward

    2006-01-01

    Purpose: To determine the prognostic factors for radiographic response and its prognostic value for subsequent survival in patients undergoing whole-brain radiotherapy (WBRT) for brain metastases. Methods and Materials: Five hundred fifteen eligible patients were randomized in a phase III trial evaluating WBRT and supplemental oxygen with or without efaproxiral, an allosteric modifier of hemoglobin that reduces hemoglobin oxygen-binding affinity and enhances tumor oxygenation, potentially increasing tumor radiosensitivity. Brain images were obtained at baseline and at scheduled follow-up visits after WBRT. Landmark analysis was used to assess the ability of response at selected time points to predict subsequent survival. Logistic regression was used to assess determinants of response at 3 months. Results: Treatment arm, Karnofsky Performance Status, presence or absence of liver metastases, and primary site were all determinants of response at the 3-month follow-up visit, with patients in the efaproxiral arm experiencing a 67% greater odds of response at this visit (p = 0.02). Response at 3 and 6 months was a significant prognostic factor for longer subsequent survival. Conclusions: The 3-month scan is a valuable prognostic factor for subsequent survival in patients with brain metastases treated with WBRT. Patients in the efaproxiral arm had a higher response rate at 3 and 6 months than those in the control arm

  1. Surviving the crisis: Adaptive wisdom, coping mechanisms and local responses to avian influenza threats in Haining, China.

    Science.gov (United States)

    Zhang, Letian; Pan, Tianshu

    2008-04-01

    Based on ethnographic research conducted in the summer of 2006, this paper examines local responses to the imminent threat of avian flu in Haining County of Zhejiang Province. During our field investigation, we conducted interviews with officials from local medical institutions (including the hospitals, the animal husbandry and veterinary station, and health clinics), to bureaus of public health and agro-economy. We also visited chicken farms, restaurants and farming households. We address the following factors that commonly structured the perceptions and actions of different social actors in the area of study: The changing mode of information-sharing and communication practices in the local communities; the official drive to professionalize the emergency response management system in the county; and the coping mechanisms that helped the villagers and town residents to weather the storm of avian flu. Our field research suggests that collective survival consciousness was translated into a spirit of voluntarism during the crisis. One important practical lesson we have learned from this study is that the adaptive wisdom embedded in local memories demonstrated its operational worth as a resourceful knowledge base for ordinary farmers to deal with food shortage, famine, plague and future pandemics.

  2. Acrolein activates cell survival and apoptotic death responses involving the endoplasmic reticulum in A549 lung cells.

    Science.gov (United States)

    Tanel, André; Pallepati, Pragathi; Bettaieb, Ahmed; Morin, Patrick; Averill-Bates, Diana A

    2014-05-01

    Acrolein, a highly reactive α,β-unsaturated aldehyde, is a product of endogenous lipid peroxidation. It is a ubiquitous environmental pollutant that is generated mainly by smoke, overheated cooking oil and vehicle exhaust. Acrolein damages cellular proteins, which could lead to accumulation of aberrantly-folded proteins in the endoplasmic reticulum (ER). This study determines the mechanisms involved in acrolein-induced apoptosis mediated by the ER and possible links with the ER stress response in human A549 lung cells. The exposure of cells to acrolein (15-50μM) for shorter times of 15 to 30min activated several ER stress markers. These included the ER chaperone protein BiP and the three ER sensors: (i) the survival/rescue molecules protein kinase RNA (PKR)-like ER kinase (PERK) and eukaryotic initiation factor 2 alpha (eIF2α) were phosphorylated; (ii) cleavage of activating transcription factor 6 (ATF6) occurred, and (iii) inositol-requiring protein-1 alpha (IRE1α) was phosphorylated. Acrolein (25-50μM) caused apoptotic cell death mediated by the ER after 2h, which was characterised by the induction of CHOP and activation of ER proteases calpain and caspase-4. Calpain and caspase-7 were the initiating factors for caspase-4 activation in acrolein-induced apoptosis. These results increase our knowledge about cellular responses to acrolein in lung cells, which have implications for human health. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Dietary nucleotide supplementation enhances immune responses and survival to Streptococcus iniae in hybrid tilapia fed diet containing low fish meal

    Directory of Open Access Journals (Sweden)

    Shi-Yen Shiau

    2015-11-01

    Full Text Available A feeding trial was conducted to evaluate the effects of nucleotide (NT supplementation in diet on immune responses and disease resistance of juvenile hybrid tilapia, Oreochromis niloticus × Oreochromis aureus. Nucleotide was added at 0, 120, 240, 360, 480 and 600 mg NT/kg to low fish meal (6% and high soybean meal (56% basal diet for a total of 6 experimental diets. Each diet was fed to triplicate groups of tilapia (initial body weight 0.15 ± 0.005 g in a recirculated freshwater rearing system for 10 weeks. Head kidney leukocyte superoxide anion production ratio was higher (P 80% were observed in fish fed diets supplemented with NT than fish fed the NT unsupplemented control diet (56.7%. These results suggest that nucleotides supplemented at 120–240 mg NT/kg in diet enhances immune responses and survival of tilapia fed low fish meal and high soybean meal diet.

  4. Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy.

    Science.gov (United States)

    Seiler, Roland; Ashab, Hussam Al Deen; Erho, Nicholas; van Rhijn, Bas W G; Winters, Brian; Douglas, James; Van Kessel, Kim E; Fransen van de Putte, Elisabeth E; Sommerlad, Matthew; Wang, Natalie Q; Choeurng, Voleak; Gibb, Ewan A; Palmer-Aronsten, Beatrix; Lam, Lucia L; Buerki, Christine; Davicioni, Elai; Sjödahl, Gottfrid; Kardos, Jordan; Hoadley, Katherine A; Lerner, Seth P; McConkey, David J; Choi, Woonyoung; Kim, William Y; Kiss, Bernhard; Thalmann, George N; Todenhöfer, Tilman; Crabb, Simon J; North, Scott; Zwarthoff, Ellen C; Boormans, Joost L; Wright, Jonathan; Dall'Era, Marc; van der Heijden, Michiel S; Black, Peter C

    2017-10-01

    An early report on the molecular subtyping of muscle-invasive bladder cancer (MIBC) by gene expression suggested that response to neoadjuvant chemotherapy (NAC) varies by subtype. To investigate the ability of molecular subtypes to predict pathological downstaging and survival after NAC. Whole transcriptome profiling was performed on pre-NAC transurethral resection specimens from 343 patients with MIBC. Samples were classified according to four published molecular subtyping methods. We developed a single-sample genomic subtyping classifier (GSC) to predict consensus subtypes (claudin-low, basal, luminal-infiltrated and luminal) with highest clinical impact in the context of NAC. Overall survival (OS) according to subtype was analyzed and compared with OS in 476 non-NAC cases (published datasets). Gene expression analysis was used to assign subtypes. Receiver-operating characteristics were used to determine the accuracy of GSC. The effect of GSC on survival was estimated by Cox proportional hazard regression models. The models generated subtype calls in expected ratios with high concordance across subtyping methods. GSC was able to predict four consensus molecular subtypes with high accuracy (73%), and clinical significance of the predicted consensus subtypes could be validated in independent NAC and non-NAC datasets. Luminal tumors had the best OS with and without NAC. Claudin-low tumors were associated with poor OS irrespective of treatment regimen. Basal tumors showed the most improvement in OS with NAC compared with surgery alone. The main limitations of our study are its retrospective design and comparison across datasets. Molecular subtyping may have an impact on patient benefit to NAC. If validated in additional studies, our results suggest that patients with basal tumors should be prioritized for NAC. We discovered the first single-sample classifier to subtype MIBC, which may be suitable for integration into routine clinical practice. Different molecular

  5. The effects of drought-induced mortality on the response of surviving trees in piñon-juniper woodlands

    Science.gov (United States)

    Huang, C. W.; Pockman, W.; Litvak, M. E.

    2017-12-01

    AbstractAlthough it is well-established that land cover change influences water and carbon cycles across different spatiotemporal scales, the impact of climate-driven mortality events on site energy and water balance and subsequently on vegetation dynamics is more variable among studies. In semi-arid ecosystems globally, mortality events following severe drought are increasingly common. We used long-term observations (i.e., from 2009 to present) in two piñon-juniper (i.e., Pinus edulis and Juniperus monosperma) woodlands located at central New Mexico USA to explore the consequence of mortality events in such water-stressed environments. We compared a pinon-juniper woodland site where girdling was used to mimic mortality of adult pinon (PJG) with a nearby untreated woodland site (PJC). Our primary goal is to disentangle the reduction in water loss via biological pathway (i.e., leaf and sapwood area) introduced by girdling manipulation from other effects contributing to the response of surviving trees such as modifications in surface reflectivity (i.e., albedo and emissivity) and surface roughness impacting the partitioning between components in both energy and water balance at canopy level. To achieve this goal, we directly measured sap flux, environmental factors and ecosystem-atmosphere exchange of carbon, water and energy fluxes using eddy-covariance systems at both sites. We found that 1) for each component of the energy balance the difference between PJC and PJG was surprisingly negligible such that the canopy-level surface temperature (i.e., both radiometric and aerodynamic temperature) remains nearly identical for the two sites; 2) the surface reflectivity and roughness are mainly dominated by the soil surface especially when the foliage coverage in semi-arid regions is small; 3) the increase in soil evaporation after girdling manipulation outcompetes the surviving trees for the use of water in the soil. These results suggest that the so-called `water

  6. Phase II trial of anticarcinoembryonic antigen pretargeted radioimmunotherapy in progressive metastatic medullary thyroid carcinoma: biomarker response and survival improvement.

    Science.gov (United States)

    Salaun, Pierre-Yves; Campion, Loïc; Bournaud, Claire; Faivre-Chauvet, Alain; Vuillez, Jean-Philippe; Taieb, David; Ansquer, Catherine; Rousseau, Caroline; Borson-Chazot, Françoise; Bardet, Stéphane; Oudoux, Aurore; Cariou, Bertrand; Mirallié, Eric; Chang, Chien-Hsing; Sharkey, Robert M; Goldenberg, David M; Chatal, Jean-François; Barbet, Jacques; Kraeber-Bodéré, Françoise

    2012-08-01

    The prognosis of medullary thyroid carcinoma (MTC) varies from long- to short-term survival based on such prognostic factors as serum calcitonin and carcinoembryonic antigen (CEA) doubling times (DTs). This prospective phase II multicenter trial evaluated the efficacy and safety of anti-CEA pretargeted radioimmunotherapy (pRAIT) in rapidly progressing metastatic MTC patients and also how serum biomarker DTs correlate with clinical outcome. From June 2004 to January 2008, 42 patients were treated with anti-CEA × anti-diethylenetriaminepentaacetic acid (DTPA) bispecific antibody (hMN-14 × m734) (40 mg/m(2)), followed by (131)I-di-DTPA-indium bivalent hapten (1.8 GBq/m(2)) 4-6 d later. The disease control rate (durable stabilization plus objective response) was 76.2%. Grade 3-4 hematologic toxicity was observed in 54.7% of patients and myelodysplastic syndrome in 2, including 1 heavily treated previously. After pRAIT, 21 of 37 assessed patients (56.7%) showed a significant impact on DT (≥100% increase of pre-pRAIT calcitonin or CEA DT or prolonged decrease of the biomarker concentration after pRAIT). Pre-pRAIT DT and post-pRAIT DT were significant independent predictors for overall survival (OS) from pRAIT (pre-pRAIT: hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.24-0.86; P = 0.016; and post-pRAIT: HR, 5.32; 95% CI, 1.63-17.36; P = 0.006) and OS from diagnosis (pre-pRAIT: HR, 0.21; 95% CI, 0.08-0.51; P = 0.001; and post-pRAIT: HR, 6.16; 95% CI, 1.81-20.98; P = 0.004). pRAIT showed antitumor activity, with manageable hematologic toxicity in progressive MTC. Increased biomarker DT after treatment correlated with increased OS.

  7. Linking Biological Responses of Terrestrial N Eutrophication to the Final Ecosystem Goods and Services Classification System

    Science.gov (United States)

    Bell, M. D.; Clark, C.; Blett, T.

    2015-12-01

    The response of a biological indicator to N deposition can indicate that an ecosystem has surpassed a critical load and is at risk of significant change. The importance of this exceedance is often difficult to digest by policy makers and public audiences if the change is not linked to a familiar ecosystem endpoint. A workshop was held to bring together scientists, resource managers, and policy makers with expertise in ecosystem functioning, critical loads, and economics in an effort to identify the ecosystem services impacted by air pollution. This was completed within the framework of the Final Ecosystem Goods and Services (FEGS) Classification System to produce a product that identified distinct interactions between society and the effects of nitrogen pollution. From each change in a biological indicator, we created multiple ecological production functions to identify the cascading effects of the change to a measureable ecosystem service that a user interacts with either by enjoying, consuming, or appreciating the good or service, or using it as an input in the human economy. This FEGS metric was then linked to a beneficiary group that interacts with the service. Chains detailing the links from the biological indicator to the beneficiary group were created for aquatic and terrestrial acidification and eutrophication at the workshop, and here we present a subset of the workshop results by highlighting for 9 different ecosystems affected by terrestrial eutrophication. A total of 213 chains that linked to 37 unique FEGS metrics and impacted 15 beneficiary groups were identified based on nitrogen deposition mediated changes to biological indicators. The chains within each ecosystem were combined in flow charts to show the complex, overlapping relationships among biological indicators, ecosystem services, and beneficiary groups. Strength of relationship values were calculated for each chain based on support for the link in the scientific literature. We produced the

  8. Personalized peptide vaccine-induced immune response associated with long-term survival of a metastatic cholangiocarcinoma patient.

    Science.gov (United States)

    Löffler, Markus W; Chandran, P Anoop; Laske, Karoline; Schroeder, Christopher; Bonzheim, Irina; Walzer, Mathias; Hilke, Franz J; Trautwein, Nico; Kowalewski, Daniel J; Schuster, Heiko; Günder, Marc; Carcamo Yañez, Viviana A; Mohr, Christopher; Sturm, Marc; Nguyen, Huu-Phuc; Riess, Olaf; Bauer, Peter; Nahnsen, Sven; Nadalin, Silvio; Zieker, Derek; Glatzle, Jörg; Thiel, Karolin; Schneiderhan-Marra, Nicole; Clasen, Stephan; Bösmüller, Hans; Fend, Falko; Kohlbacher, Oliver; Gouttefangeas, Cécile; Stevanović, Stefan; Königsrainer, Alfred; Rammensee, Hans-Georg

    2016-10-01

    We report a novel experimental immunotherapeutic approach in a patient with metastatic intrahepatic cholangiocarcinoma. In the 5year course of the disease, the initial tumor mass, two local recurrences and a lung metastasis were surgically removed. Lacking alternative treatment options, aiming at the induction of anti-tumor T cells responses, we initiated a personalized multi-peptide vaccination, based on in-depth analysis of tumor antigens (immunopeptidome) and sequencing. Tumors were characterized by immunohistochemistry, next-generation sequencing and mass spectrometry of HLA ligands. Although several tumor-specific neo-epitopes were predicted in silico, none could be validated by mass spectrometry. Instead, a personalized multi-peptide vaccine containing non-mutated tumor-associated epitopes was designed and applied. Immunomonitoring showed vaccine-induced T cell responses to three out of seven peptides administered. The pulmonary metastasis resected after start of vaccination showed strong immune cell infiltration and perforin positivity, in contrast to the previous lesions. The patient remains clinically healthy, without any radiologically detectable tumors since March 2013 and the vaccination is continued. This remarkable clinical course encourages formal clinical studies on adjuvant personalized peptide vaccination in cholangiocarcinoma. Metastatic cholangiocarcinomas, cancers that originate from the liver bile ducts, have very limited treatment options and a fatal prognosis. We describe a novel therapeutic approach in such a patient using a personalized multi-peptide vaccine. This vaccine, developed based on the characterization of the patient's tumor, evoked detectable anti-tumor immune responses, associating with long-term tumor-free survival. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  9. Development and field test of a responsible alcohol service program. Volume 3, Final results

    Science.gov (United States)

    1988-08-01

    A Program of Responsible Alcohol Service was developed to enable servers and managers in establishments selling alcoholic beverages to exercise responsibility in their service of alcohol in order to prevent injury to and by intoxicated patrons. The P...

  10. Very Early PSA Response to Abiraterone in mCRPC Patients: A Novel Prognostic Factor Predicting Overall Survival.

    Science.gov (United States)

    Facchini, Gaetano; Caffo, Orazio; Ortega, Cinzia; D'Aniello, Carmine; Di Napoli, Marilena; Cecere, Sabrina C; Della Pepa, Chiara; Crispo, Anna; Maines, Francesca; Ruatta, Fiorella; Iovane, Gelsomina; Pisconti, Salvatore; Montella, Maurizio; Berretta, Massimiliano; Pignata, Sandro; Cavaliere, Carla

    2016-01-01

    Abiraterone Acetate (AA) is approved for the treatment of mCRPC after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated and for treatment of mCRPC progressed during or after docetaxel-based chemotherapy regimen. The aim of this study is to evaluate the role of early PSA decline for detection of therapy success or failure in mCRPC patients treated with AA in post chemotherapy setting. We retrospectively evaluated 87 patients with mCRPC treated with AA. Serum PSA levels were evaluated after 15, 90 days and then monthly. The PSA flare phenomenon was evaluated, according to a confirmation value at least 1 week apart. The primary endpoint was to demonstrate that an early PSA decline correlates with a longer progression free survival (PFS) and overall survival (OS). The secondary endpoind was to demonstrate a correlation between better outcome and demographic and clinical patient characteristics. We have collected data of 87 patients between Sep 2011 and Sep 2014. Early PSA response (≥50% from baseline at 15 days) was found in 56% evaluated patients and confirmed in 29 patients after 90 days. The median PFS was 5.5 months (4.6-6.5) and the median OS was 17.1 months (8.8-25.2). In early responders patients (PSA RR ≥ 50% at 15 days), we found a significant statistical advantage in terms of PFS at 1 year, HR 0.28, 95%CI 0.12-0.65, p = 0.003, and OS, HR 0.21 95% CI 0.06-0.72, p = 0.01. The results in PFS at 1 years and OS reached statistical significance also in the evaluation at 90 days. A significant proportion (78.6%) of patients achieved a rapid response in terms of PSA decline. Early PSA RR (≥50% at 15 days after start of AA) can provide clinically meaningful information and can be considered a surrogate of longer PFS and OS.

  11. Targeting Ongoing DNA Damage in Multiple Myeloma: Effects of DNA Damage Response Inhibitors on Plasma Cell Survival

    Directory of Open Access Journals (Sweden)

    Ana Belén Herrero

    2017-05-01

    Full Text Available Human myeloma cell lines (HMCLs and a subset of myeloma patients with poor prognosis exhibit high levels of replication stress (RS, leading to DNA damage. In this study, we confirmed the presence of DNA double-strand breaks (DSBs in several HMCLs by measuring γH2AX and RAD51 foci and analyzed the effect of various inhibitors of the DNA damage response on MM cell survival. Inhibition of ataxia telangiectasia and Rad3-related protein (ATR, the main kinase mediating the response to RS, using the specific inhibitor VE-821 induced more cell death in HMCLs than in control lymphoblastoid cells and U266, an HMCL with a low level of DNA damage. The absence of ATR was partially compensated by ataxia telangiectasia-mutated protein (ATM, since chemical inhibition of both kinases using VE-821 and KU-55933 significantly increased the death of MM cells with DNA damage. We found that ATM and ATR are involved in DSB repair by homologous recombination (HR in MM. Inhibition of both kinases resulted in a stronger inhibition that may underlie cell death induction, since abolition of HR using two different inhibitors severely reduced survival of HMCLs that exhibit DNA damage. On the other hand, inhibition of the other route involved in DSB repair, non-homologous end joining (NHEJ, using the DNA-PK inhibitor NU7441, did not affect MM cell viability. Interestingly, we found that NHEJ inhibition did not increase cell death when HR was simultaneously inhibited with the RAD51 inhibitor B02, but it clearly increased the level of cell death when HR was inhibited with the MRE11 inhibitor mirin, which interferes with recombination before DNA resection takes place. Taken together, our results demonstrate for the first time that MM cells with ongoing DNA damage rely on an intact HR pathway, which thereby suggests therapeutic opportunities. We also show that inhibition of HR after the initial step of end resection might be more appropriate for inducing MM cell death, since it

  12. Survival and immune response of the Chagas vector Meccus pallidipennis (Hemiptera: Reduviidae) against two entomopathogenic fungi, Metarhizium anisopliae and Isaria fumosorosea.

    Science.gov (United States)

    Flores-Villegas, A Laura; Cabrera-Bravo, Margarita; Toriello, Conchita; Bucio-Torres, Martha I; Salazar-Schettino, Paz María; Córdoba-Aguilar, Alex

    2016-03-24

    Chagas disease is a key health problem in Latin America and is caused and transmitted by Trypanosoma cruzi and triatomine bugs, respectively. Control of triatomines has largely relied on the use pyrethroids, which has proved to be ineffective in the long term. Alternatively, the use of entomopathogenic fungi has been implemented to control triatomine bugs. These fungi are highly efficient as they induce a reduction in immune response on insects. Meccus pallidipennis is the main triatomine vector of Chagas disease in Mexico. In this work we investigated the effects of two entomopathogenic fungi, Metarhizium anisopliae and Isaria fumosorosea, on M. pallidipennis nymphs in terms of insect survival and immune response. We had an infected and a control group for each fungal species and assessed: a) insect survival during 30 days; and, b) phenoloxidase (PO) and prophenoloxidase (proPO; two key traits in insect immune response) at 24, 48, 96 and 144 h. For survival we used Kaplan-Meier survival analysis while for immune response we used factorial, repeated-measures ANOVA for each fungal species. Animals treated with M. anisopliae died sooner than animals treated with I. fumosorosea. Infected animals showed lower PO and proPO values than sham individuals, with a clear decrease in these parameters at 24 h with no further changes after this time. Our study widens the possibility of entomopathogenic fungi being used for triatomine control. The negative effect on PO and proPO seems mediated by a down-regulation of the triatomine immune response.

  13. Human and Autologous Adipose-derived Stromal Cells Increase Flap Survival in Rats Independently of Host Immune Response

    DEFF Research Database (Denmark)

    Toyserkani, Navid Mohamadpour; Jensen, Charlotte Harken; Andersen, Ditte Caroline

    2018-01-01

    evaluated after 7 days. RESULTS: The mean survival rates for SVF treatment regardless of human or autologous origin were significantly increased as compared with the control group. Adipose stem/stromal cell and SVF lysate injection did not increase flap survival. Vessel density was increased for human...... injections lead to increased vessel density, but it did not necessarily lead to increased flap survival. Further research should elaborate which molecular events make SVF treatment more efficacious than ASC....

  14. 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.

  15. Magnetic resonance imaging in breast cancer treated with neoadjuvant chemotherapy: radiologic-pathologic correlation of the response and disease-free survival depending on molecular subtype.

    Science.gov (United States)

    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.

  16. Anuran larval developmental plasticity and survival in response to variable salinity of ecologically relevant timing and magnitude.

    Science.gov (United States)

    Kearney, Brian D; Pell, Rebecca J; Byrne, Phillip G; Reina, Richard D

    2014-12-01

    Salinity in affected freshwater ecosystems fluctuates with seasonal rainfall, tidal flux, rates of evaporation, chemical runoff and the influence of secondary salinization. Environmental stressors such as salinity can have lasting effects on anuran development, yet little is known about the effects of fluctuating salinity on tadpole ontogeny or the effects of differing magnitudes of salinity exposure, as would occur in natural wetland systems. We examined how salinity fluctuations affected survival, growth and development of Litoria ewingii by exposing tadpoles to a range of salinity concentrations (5.6-10.85 ppt) at three different stages of development (hind limb-bud formation; toe differentiation and forearm development). We also investigated the plasticity of tadpole growth rates in response to non-lethal, transient salinity influxes, specifically examining the capacity for compensatory growth and its relationship to the timing, magnitude or frequency of salinity exposure. Our results show that later-stage tadpoles are more tolerant to elevated salinity than those exposed at a younger age, and that exposure to high salinity later in life suppresses the potential for compensatory growth. Tadpoles exposed to transient low salinity lost less mass during metamorphosis than animals in constant salinity treatments, indicating a possible alternate to compensatory growth. Exposure to near-lethal salinities early in development did not alter tadpole responses to subsequent salinity stress. Our results provide some of the first evidence that both the timing and magnitude of transient environmental stressors can have an effect on anuran development and developmental trade-offs in a stressful environment. © 2014 Wiley Periodicals, Inc.

  17. Final Report: Optimal Model Complexity in Geological Carbon Sequestration: A Response Surface Uncertainty Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ye [Univ. of Wyoming, Laramie, WY (United States)

    2018-01-17

    The critical component of a risk assessment study in evaluating GCS is an analysis of uncertainty in CO2 modeling. In such analyses, direct numerical simulation of CO2 flow and leakage requires many time-consuming model runs. Alternatively, analytical methods have been developed which allow fast and efficient estimation of CO2 storage and leakage, although restrictive assumptions on formation rock and fluid properties are employed. In this study, an intermediate approach is proposed based on the Design of Experiment and Response Surface methodology, which consists of using a limited number of numerical simulations to estimate a prediction outcome as a combination of the most influential uncertain site properties. The methodology can be implemented within a Monte Carlo framework to efficiently assess parameter and prediction uncertainty while honoring the accuracy of numerical simulations. The choice of the uncertain properties is flexible and can include geologic parameters that influence reservoir heterogeneity, engineering parameters that influence gas trapping and migration, and reactive parameters that influence the extent of fluid/rock reactions. The method was tested and verified on modeling long-term CO2 flow, non-isothermal heat transport, and CO2 dissolution storage by coupling two-phase flow with explicit miscibility calculation using an accurate equation of state that gives rise to convective mixing of formation brine variably saturated with CO2. All simulations were performed using three-dimensional high-resolution models including a target deep saline aquifer, overlying caprock, and a shallow aquifer. To evaluate the uncertainty in representing reservoir permeability, sediment hierarchy of a heterogeneous digital stratigraphy was mapped to create multiple irregularly shape stratigraphic models of decreasing geologic resolutions: heterogeneous (reference), lithofacies, depositional environment, and a (homogeneous) geologic formation. To ensure model

  18. Projecting demographic responses to climate change: adult and juvenile survival respond differently to direct and indirect effects of weather in a passerine population.

    Science.gov (United States)

    Dybala, Kristen E; Eadie, John M; Gardali, Thomas; Seavy, Nathaniel E; Herzog, Mark P

    2013-09-01

    Few studies have quantitatively projected changes in demography in response to climate change, yet doing so can provide important insights into the processes that may lead to population declines and changes in species distributions. Using a long-term mark-recapture data set, we examined the influence of multiple direct and indirect effects of weather on adult and juvenile survival for a population of Song Sparrows (Melospiza melodia) in California. We found evidence for a positive, direct effect of winter temperature on adult survival, and a positive, indirect effect of prior rainy season precipitation on juvenile survival, which was consistent with an effect of precipitation on food availability during the breeding season. We used these relationships, and climate projections of significantly warmer and slightly drier winter weather by the year 2100, to project a significant increase in mean adult survival (12-17%) and a slight decrease in mean juvenile survival (4-6%) under the B1 and A2 climate change scenarios. Together with results from previous studies on seasonal fecundity and postfledging survival in this population, we integrated these results in a population model and projected increases in the population growth rate under both climate change scenarios. Our results underscore the importance of considering multiple, direct, and indirect effects of weather throughout the annual cycle, as well as differences in the responses of each life stage to climate change. Projecting demographic responses to climate change can identify not only how populations will be affected by climate change but also indicate the demographic process(es) and specific mechanisms that may be responsible. This information can, in turn, inform climate change adaptation plans, help prioritize future research, and identify where limited conservation resources will be most effectively and efficiently spent. © 2013 John Wiley & Sons Ltd.

  19. Initial Stage Affects Survival Even After Complete Pathologic Remission is Achieved in Locally Advanced Esophageal Cancer: Analysis of 70 Patients With Pathologic Major Response After Preoperative Chemoradiotherapy

    International Nuclear Information System (INIS)

    Kim, Min Kyoung; Cho, Kyung-Ja; Park, Seung-Il; Kim, Yong Hee; Kim, Jong Hoon; Song, Ho-Young; Shin, Ji Hoon; Jung, Hwoon Yong; Lee, Gin Hyug; Choi, Kee Don; Song, Ho June; Ryu, Jin-Sook; Kim, Sung-Bae

    2009-01-01

    Purpose: To analyze outcomes and factors predictive for recurrence and survival in patients with operable esophageal carcinoma who achieved pathologic complete response (PCR) or microscopic residual disease (MRD) after preoperative chemoradiotherapy (CRT). Materials and Methods: Outcomes were assessed in 70 patients with locally advanced esophageal cancer who achieved pathologic major response (53 with PCR and 17 with MRD) after preoperative CRT. Results: At a median follow-up of 38.6 months for surviving patients, 17 of 70 patients (24.3%) experienced disease recurrence and 31 (44.3%) died. Clinical stage (II vs III; p = 0.013) and pathologic response (PCR vs. MRD; p = 0.014) were independent predictors of disease recurrence. Median overall survival (OS) was 99.6 months (95% CI, 44.1-155.1 months) and the 5-year OS rate was 57%. Median recurrence-free survival (RFS) was 71.5 months (95% CI, 39.5-103.6 months) and the 5-year RFS rate was 51.3%. Median OS of patients with Stage II and Stage III disease was 108.8 months and 39.9 months, respectively, and the 5-year OS rates were 68.2% and 27.0%, respectively (p = 0.0003). In a subgroup of patients with PCR, median OS and RFS were also significantly different according to clinical stage. Multivariate analysis showed that clinical stage was an independent predictor of RFS (p = 0.01) and OS (p = 0.008). Conclusions: Even though patients achieved major response after preoperative CRT, pretreatment clinical stage is an important prognostic marker for recurrence and survival. Patients with MRD have an increased recurrence risk but similar survival compared with patients achieved PCR.

  20. Treatment response, drug survival, and predictors thereof in 764 patients with psoriatic arthritis treated with anti-tumor necrosis factor α therapy

    DEFF Research Database (Denmark)

    Glintborg, Bente; Østergaard, Mikkel; Dreyer, Lene

    2011-01-01

    Score. Male sex, CRP level >10 mg/liter, concomitant methotrexate use, and low patient health visual analog scale score at baseline were associated with longer drug survival. Improvement was achieved by 59%, 45%, 24%, and 54% of patients according to the ACR20, ACR50, ACR70 response criteria and EULAR...

  1. Final diagnosis of patients with clinically suspected vestibular neuritis showing normal caloric response.

    Science.gov (United States)

    Ahn, Sung Hwan; Shin, Jung Eun; Kim, Chang-Hee

    2017-07-01

    Vestibular neuritis is one of the most common peripheral causes of acute vestibular syndrome, of which the diagnosis is generally based on a comprehensive interpretation of clinical and laboratory findings following reasonable exclusion of other disorders. This study aimed to investigate the final diagnosis of patients admitted to hospital under the clinical impression of vestibular neuritis who showed no unilateral caloric paresis. Forty-five patients who visited the emergency department with isolated acute spontaneous vertigo were included. Among them, six patients (13%) developed definitive spontaneous vertigo lasting longer than 20min again after discharge from hospital, accompanied by hearing loss, which was audiometrically documented, leading to a final diagnosis of definite Ménière's disease. Nine patients (20%) revisited our clinic with recurrent episodic vertigo without any documented hearing loss or auditory symptoms such as hearing loss, tinnitus or ear fullness, which led to a final diagnosis of possible Ménière's disease. In four patients (9%), initial spontaneous vertigo and nystagmus changed to positional vertigo and nystagmus on the second hospital day. In 26 patients (58%), neither another episode of vertigo nor auditory symptoms developed during follow-up period (7-92months), a condition to which the authors gave an arbitrary diagnosis of "mild unilateral vestibular deficit". In conclusion, patients admitted to hospital under clinical impression of vestibular neuritis may have various final diagnoses, and "mild unilateral vestibular deficit" was the most common final diagnosis among patients who did not meet the diagnostic criteria of vestibular neuritis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. CT Perfusion Imaging Can Predict Patients' Survival and Early Response to Transarterial Chemo-Lipiodol Infusion for Liver Metastases from Colorectal Cancers

    OpenAIRE

    Lv, Wei-Fu; Han, Jian-Kui; Cheng, De-Lei; Zhou, Chun-Ze; Ni, Ming; Lu, Dong

    2015-01-01

    Objective To prospectively evaluate the performance of computed tomography perfusion imaging (CTPI) in predicting the early response to transarterial chemo-lipiodol infusion (TACLI) and survival of patients with colorectal cancer liver metastases (CRLM). Materials and Methods Computed tomography perfusion imaging was performed before and 1 month after TACLI in 61 consecutive patients. Therapeutic response was evaluated on CT scans 1 month and 4 months after TACLI; the patients were classified...

  3. Survivability enhancement study for C/sup 3/I/BM (communications, command, control and intelligence/battle management) ground segments: Final report

    Energy Technology Data Exchange (ETDEWEB)

    1986-10-30

    This study involves a concept developed by the Fairchild Space Company which is directly applicable to the Strategic Defense Initiative (SDI) Program as well as other national security programs requiring reliable, secure and survivable telecommunications systems. The overall objective of this study program was to determine the feasibility of combining and integrating long-lived, compact, autonomous isotope power sources with fiber optic and other types of ground segments of the SDI communications, command, control and intelligence/battle management (C/sup 3/I/BM) system in order to significantly enhance the survivability of those critical systems, especially against the potential threats of electromagnetic pulse(s) (EMP) resulting from high altitude nuclear weapon explosion(s). 28 figs., 2 tabs.

  4. Assessment of the flow-survival relationship obtained by Sims and Ossiander (1981) for Snake River spring/summer chinook salmon smolts. Final report

    International Nuclear Information System (INIS)

    Steward, C.R.

    1994-04-01

    There has been much debate recently among fisheries professionals over the data and functional relationships used by Sims and Ossiander to describe the effects of flow in the Snake River on the survival and travel time of chinook salmon and steelhead smolts. The relationships were based on mark and recovery experiments conducted at various Snake and Columbia River sites between 1964 and 1979 to evaluate the effects of dams and flow regulation on the migratory characteristic's chinook sa mon and steelhead trout smolts. The reliability of this information is crucial because it forms the logical basis for many of the flow management options being considered today to protect,upriver populations of chinook salmon and steelhead trout. In this paper I evaluate the primary data, assumptions, and calculations that underlie the flow-survival relationship derived by Sims and Ossiander (1981) for chinook salmon smolts

  5. Assessment of the Flow-Survival Relationship Obtained by Sims and Ossiander (1981) for Snake River Spring/Summer Chinook Salmon Smolts, Final Report.

    Energy Technology Data Exchange (ETDEWEB)

    Steward, C.R. (Cleveland R.)

    1994-04-01

    There has been much debate recently among fisheries professionals over the data and functional relationships used by Sims and Ossiander to describe the effects of flow in the Snake River on the survival and travel time of chinook salmon and steelhead smolts. The relationships were based on mark and recovery experiments conducted at various Snake and Columbia River sites between 1964 and 1979 to evaluate the effects of dams and flow regulation on the migratory characteristic`s chinook sa mon and steelhead trout smolts. The reliability of this information is crucial because it forms the logical basis for many of the flow management options being considered today to protect,upriver populations of chinook salmon and steelhead trout. In this paper I evaluate the primary data, assumptions, and calculations that underlie the flow-survival relationship derived by Sims and Ossiander (1981) for chinook salmon smolts.

  6. Pre-cultivation with Selected Prebiotics Enhances the Survival and the Stress Response of Lactobacillus rhamnosus Strains in Simulated Gastrointestinal Transit

    Directory of Open Access Journals (Sweden)

    Mariantonietta Succi

    2017-06-01

    pre-cultivated with mannitol. Among the up-regulated stress proteins, P7 resulted involved in the response to the starvation. Finally, it is possible to conclude that the pre-cultivation with certain prebiotics as a unique carbon source represents a strain-specific, sub-lethal stress able to enhance the resistance of Lb. rhamnosus strains and consequently their viability under simulated GI transit.

  7. Pre-cultivation with Selected Prebiotics Enhances the Survival and the Stress Response of Lactobacillus rhamnosus Strains in Simulated Gastrointestinal Transit.

    Science.gov (United States)

    Succi, Mariantonietta; Tremonte, Patrizio; Pannella, Gianfranco; Tipaldi, Luca; Cozzolino, Autilia; Romaniello, Rossana; Sorrentino, Elena; Coppola, Raffaele

    2017-01-01

    -cultivated with mannitol. Among the up-regulated stress proteins, P7 resulted involved in the response to the starvation. Finally, it is possible to conclude that the pre-cultivation with certain prebiotics as a unique carbon source represents a strain-specific, sub-lethal stress able to enhance the resistance of Lb. rhamnosus strains and consequently their viability under simulated GI transit.

  8. Early survival prediction after intra-arterial therapies: a 3D quantitative MRI assessment of tumour response after TACE or radioembolization of colorectal cancer metastases to the liver

    Energy Technology Data Exchange (ETDEWEB)

    Chapiro, Julius; Savic, Lynn Jeanette [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); Charite Universitaetsmedizin, Department of Diagnostic and Interventional Radiology, Berlin (Germany); Duran, Rafael; Schernthaner, Ruediger; Wang, Zhijun; Geschwind, Jean-Francois [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); Lin, MingDe [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); U/S Imaging and Interventions (UII), Philips Research North America, Briarcliff Manor, NY (United States); Lesage, David [Philips Research, Medisys, Suresnes (France)

    2015-07-15

    This study evaluated the predictive role of 1D, 2D and 3D quantitative, enhancement-based MRI regarding overall survival (OS) in patients with colorectal liver metastases (CLM) following intra-arterial therapies (IAT). This retrospective analysis included 29 patients who underwent transarterial chemoembolization (TACE) or radioembolization and received MRI within 6 weeks after therapy. Tumour response was assessed using 1D and 2D criteria (such as European Association for the Study of the Liver guidelines [EASL] and modified Response Evaluation Criteria in Solid Tumors [mRECIST]). In addition, a segmentation-based 3D quantification of overall (volumetric [v] RECIST) and enhancing lesion volume (quantitative [q] EASL) was performed on portal venous phase MRI. Accordingly, patients were classified as responders (R) and non-responders (NR). Survival was evaluated using Kaplan-Meier analysis and compared using Cox proportional hazard ratios (HR). Only enhancement-based criteria identified patients as responders. EASL and mRECIST did not predict patient survival (P = 0.27 and P = 0.44, respectively). Using uni- and multivariate analysis, qEASL was identified as the sole predictor of patient survival (9.9 months for R, 6.9 months for NR; P = 0.038; HR 0.4). The ability of qEASL to predict survival early after IAT provides evidence for potential advantages of 3D quantitative tumour analysis. (orig.)

  9. Early survival prediction after intra-arterial therapies: a 3D quantitative MRI assessment of tumour response after TACE or radioembolization of colorectal cancer metastases to the liver

    International Nuclear Information System (INIS)

    Chapiro, Julius; Savic, Lynn Jeanette; Duran, Rafael; Schernthaner, Ruediger; Wang, Zhijun; Geschwind, Jean-Francois; Lin, MingDe; Lesage, David

    2015-01-01

    This study evaluated the predictive role of 1D, 2D and 3D quantitative, enhancement-based MRI regarding overall survival (OS) in patients with colorectal liver metastases (CLM) following intra-arterial therapies (IAT). This retrospective analysis included 29 patients who underwent transarterial chemoembolization (TACE) or radioembolization and received MRI within 6 weeks after therapy. Tumour response was assessed using 1D and 2D criteria (such as European Association for the Study of the Liver guidelines [EASL] and modified Response Evaluation Criteria in Solid Tumors [mRECIST]). In addition, a segmentation-based 3D quantification of overall (volumetric [v] RECIST) and enhancing lesion volume (quantitative [q] EASL) was performed on portal venous phase MRI. Accordingly, patients were classified as responders (R) and non-responders (NR). Survival was evaluated using Kaplan-Meier analysis and compared using Cox proportional hazard ratios (HR). Only enhancement-based criteria identified patients as responders. EASL and mRECIST did not predict patient survival (P = 0.27 and P = 0.44, respectively). Using uni- and multivariate analysis, qEASL was identified as the sole predictor of patient survival (9.9 months for R, 6.9 months for NR; P = 0.038; HR 0.4). The ability of qEASL to predict survival early after IAT provides evidence for potential advantages of 3D quantitative tumour analysis. (orig.)

  10. Development of an Effective Transport Media for Juvenile Spring Chinook Salmon to Mitigate Stress and Improve Smolt Survival During Columbia River Fish Hauling Operations, 1985 Final Report.

    Energy Technology Data Exchange (ETDEWEB)

    Wedemeyer, Gary A.

    1985-02-01

    Selected transport media consisting of mineral salt additions (Na/sup +/, Cl/sup -/, Ca/sup + +/, PO/sub 4//sup -3/, HCO/sub 3//sup -/, and Mg/sup + +/), mineral salts plus tranquilizing concentrations of tricaine methane sulfonate (MS-222), or MS-222 alone were tested for their ability to mitigate stress and increase smolt survival during single and mixed species hauling of Columbia River spring chinook salmon (Oncorhynchus tshawytscha) and steelhead trout (Salmo gairdneri). Successful stress mitigation was afforded by several formulations as indicated by protection against life-threatening osmoregulatory and other physiological dysfunctions, and against immediate and delayed hauling mortality. Effects on the seawater survival and growth of smolts hauled in transport media were used as the overall criterion of success. Of the fourteen chemical formulations tested, 10 ppM MS-222 emerged as top-rated in terms of ability to mitigate physiological stress during single and mixed species transport of juvenile spring chinook salmon at hauling densities of 0.5 or 1.0 lb/gallon. Immediate and delayed mortalities from hauling stress were also reduced, but benefits to early marine growth and survival were limited to about the first month in seawater. The two physical factors tested (reduced light intensity and water temperature) were generally less effective than mineral salt additions in mitigating hauling stress, but the degree of protection afforded by reduced light intensity was nevertheless judged to be physiologically beneficial. 36 refs., 1 fig., 19 tabs.

  11. The response of the Government of Ontario to the final report of the Royal Commission on Electric Power Planning

    International Nuclear Information System (INIS)

    1981-05-01

    In March 1980, after nearly five years of hearings and research, the Ontario Royal Commission on Electric Power Planning submitted the first volume of its final report. The remaining eight volumes were submitted in April 1980. The Commission made 88 recommendations on technical, operational, and policy issues. The present document sets out the Ontario government's response to the recommendations. The government accepts and is implementing 77 recommendations. Four recommendations require further study, and six have been rejected

  12. Long-Term Survival According to Histology and Radiologic Response to Preoperative Chemotherapy in 126 Patients Undergoing Resection of Non-GIST Sarcoma Liver Metastases.

    Science.gov (United States)

    Goumard, Claire; Marcal, Leonardo P; Wang, Wei-Lien; Somaiah, Neeta; Okuno, Masayuki; Roland, Christina L; Tzeng, Ching-Wei D; Chun, Yun Shin; Feig, Barry W; Vauthey, Jean-Nicolas; Conrad, Claudius

    2018-01-01

    Non-gastrointestinal stromal tumor sarcomas (NGSs) have heterogeneous histology, and this heterogeneity may lead to uncertainty regarding the prognosis of patients with liver metastases from NGS (NGSLM) and decision regarding their surgical management. Furthermore, the role of preoperative chemotherapy in treatment of NGSLM remains poorly defined. We investigated long-term survival and its correlation to response to preoperative chemotherapy in patients with NGSLM. Patients who underwent liver resection for NGSLM during 1998-2015 were identified. Clinical, histopathologic, and survival data were analyzed. Multivariate analysis was performed using a Cox proportional hazards model. 126 patients [62 (49%) with leiomyosarcoma] were included. Five-year overall survival (OS) and recurrence-free survival (RFS) rates were 49.3 and 14.9%, respectively. Survival did not differ by histologic subtype, primary tumor location, or use of preoperative or postoperative chemotherapy. NGSLM ≥ 10 cm and extrahepatic metastases at NGSLM diagnosis were the only independent risk factors for OS. In the 83 (66%) patients with metachronous NSGLM, disease-free interval > 6 months was associated with improved OS and RFS. Among the 65 patients (52%) who received preoperative chemotherapy, radiologic response according to Choi criteria specifically was associated with improved OS (p = 0.04), but radiologic response according to RECIST 1.1 criteria was not. Resection of NGSLM led to a 5-year OS rate of 49%, independent of histologic subtype and primary tumor location. Choi criteria (which take into account tumor density) are superior to RECIST 1.1 in assessing radiologic response and should be used to assess response to preoperative chemotherapy.

  13. [(90)Yttrium-DOTA]-TOC response is associated with survival benefit in iodine-refractory thyroid cancer: long-term results of a phase 2 clinical trial.

    Science.gov (United States)

    Iten, Fabienne; Muller, Beat; Schindler, Christian; Rasch, Helmut; Rochlitz, Christoph; Oertli, Daniel; Maecke, Helmut R; Muller-Brand, Jan; Walter, Martin A

    2009-05-15

    The authors aimed to explore the efficacy of (90)Yttrium-1,4,7,10-tetra-azacyclododecane N,N',N'',N'''-tetraacetic acid [(90)Y-DOTA]-Tyr(3)-octreotide (TOC) in advanced iodine-refractory thyroid cancer. In a phase 2 trial, the authors investigated biochemical response (assessed by serum thyroglobulin levels), survival, and the long-term safety profile of systemic [(90)Y-DOTA]-TOC treatment in metastasized iodine-refractory thyroid cancer. Adverse events were assessed according to the National Cancer Institute criteria. Survival analyses were performed by using multiple regression models. A total of 24 patients were enrolled. A median cumulative activity of 13.0 GBq (range, 1.7-30.3 GBq) was administered. Response was found in 7 (29.2%) patients. Eight (33.3%) patients developed hematologic toxicity grade 1-3, and 4 (16.7%) patients developed renal toxicity grade 1-4. The median survival was 33.4 months (range, 3.6-126.8 months) from time of diagnosis and 16.8 months (range, 1.8-99.1 months) from time of first [(90)Y-DOTA]-TOC treatment. Response to treatment was associated with longer survival from time of diagnosis (hazard ratio [HR], 0.17; 95% confidence interval [CI], 0.03-0.92; P = .04) and from time of first [(90)Y-DOTA]-TOC therapy (HR, 0.20; 95% CI, 0.04-0.94; P = .04). The visual grade of scintigraphic tumor uptake was not associated with treatment response (odds ratio [OR], 0.98; 95% CI, 0.26-3.14; P = 1.00). Response to [(90)Y-DOTA]-TOC in metastasized iodine-refractory thyroid cancer was associated with longer survival. Upcoming trials should aim to increase the number of treatment cycles.

  14. Seismic Safety Margins Research Program. Phase I final report - Subsystem response (Project V)

    International Nuclear Information System (INIS)

    Shieh, L.C.; Chuang, T.Y.; O'Connell, W.J.

    1981-10-01

    This document reports on (1) the computation of the responses of subsystems, given the input subsystem support motion for components and systems whose failure can lead to an accident sequence (radioactive release), and (2) the results of a sensitivity study undertaken to determine the contributions of the several links in the seismic methodology chain (SMC) - seismic input (SI), soil-structure interaction (SSI), structure response (STR), and subsystem response (SUB) - to the uncertainty in subsystem response. For the singly supported subsystems (e.g., pumps, turbines, electrical control panels, etc.), we used the spectral acceleration response of the structure at the point where the subsystem components were mounted. For the multiple supported subsystems, we developed 13 piping models of five safety-related systems, and then used the pseudostatic-mode method with multisupport input motion to compute the response parameters in terms of the parameters used in the fragility descriptions (i.e., peak resultant accelerations for valves and peak resultant moments for piping). Damping and frequency were varied to represent the sources of modeling and random uncertainty. Two codes were developed: a modified version of SAPIV which assembles the piping supports into groups depending on the support's location relative to the attached structure, and SAPPAC a stand-alone modular program from which the time-history analysis module is extracted. On the basis of our sensitivity study, we determined that the variability in the combined soil-structure interaction, structural response, and subsystem response areas contribute more to uncertainty in subsystem response than does the variability in the seismic input area, assuming an earthquake within the limited peak ground acceleration range, i.e., 0.15 to 0.30g. The seismic input variations were in terms of different earthquake time histories. (author)

  15. Seismic site coefficients and acceleration design response spectra based on conditions in South Carolina : final report.

    Science.gov (United States)

    2014-11-15

    The simplified procedure in design codes for determining earthquake response spectra involves : estimating site coefficients to adjust available rock accelerations to site accelerations. Several : investigators have noted concerns with the site coeff...

  16. 76 FR 69052 - Final Response to Petition From New Jersey Regarding SO2

    Science.gov (United States)

    2011-11-07

    ... Source Owner Opts To Cease Operations 1. What the EPA Proposed 2. Public Comments and the EPA's Responses... Appalachian Power Co. v. EPA, 49 F.3d 1032 (2001), on the theories that the agency was required to refrain...

  17. p53/Surviving Ratio as a Parameter for Chemotherapy Induction Response in Children with Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Rinaldi Lenggana

    2016-11-01

    Full Text Available Acute myeloid leukemia (AML is a malignancy that is often found in children. Many studies into the failure of apoptosis function, or programmed cell death, is one of the most important regulatory mechanisms of cellular hemostasis which is closely linked to the development of cancer, are important. Also, regulation of the apoptotic (p53 and anti-apoptotic (surviving proteins influence treatment outcome. One role of p53 is to monitor cellular stress necessary to induce apoptosis. Surviving (BIRC5 is a group of proteins in the apoptosis inhibitor which works by inhibiting caspase-3. The role of surviving is considered very important in oncogenesis proliferation and cell growth regulation. Chemotherapy in childhood AML can inhibit cell growth and induce slowing as well as stopping the cell cycle. Thus, the aim of this study was to compare p53 and surviving before and after receiving induction chemotherapy in children with AML and also to determine the p53/surviving ratio. Peripheral blood mononuclear cells were collected from AML children before treatment and three months after starting their induction therapy. p53 and surviving were measured by flowcytometry using monoclonal antibodies. Data were analyzed by t-test for comparison between groups and Spearman’s test to find out the correlation between variables with a significant value of p < 0.05. A total of 8 children were evaluated. The intensity of p53 expression was not significantly increased after induction phase chemotherapy (p = 0.224, but surviving expression and the ratio of p53/surviving were significantly increased in the treatment group compared with the levels prior to chemotherapy (p = 0.002, p = 0.034, and there was a strong negative correlation between p53 and surviving after chemotherapy (r = −0.63, p = 0.049.

  18. Seismic safety margins research program. Phase I final report - Major structure response (Project IV)

    International Nuclear Information System (INIS)

    Benda, B.J.; Johnson, J.J.; Lo, T.Y.

    1981-08-01

    The primary task of the Major Structure Response Project within the Seismic Safety Margins Research Program (SSMRP) was to develop detailed finite element models of the Zion Nuclear Power Plant's containment building and auxiliary-fuel-turbine (AFT) complex. The resulting models served as input to the seismic methodology analysis chain. The containment shell was modeled as a series of beam elements with the shear and bending characteristics of a circular cylindrical shell. Masses and rotary inertias were lumped at nodal points; thirteen modes were included in the analysis. The internal structure was modeled with three-dimensional finite elements, with masses again lumped at selected nodes; sixty modes were included in the analysis. The model of the AFT complex employed thin plate and shell elements to represent the concrete shear walls and floor diaphragms, and beam and truss elements to model the braced frames. Because of the size and complexity of the model, and the potentially large number of degrees of freedom, masses were lumped at a limited number of node points. These points were selected so as to minimize the effect of the discrete mass distribution on structural response. One hundred and thirteen modes were extracted. A second objective of Project IV was to investigate the effects of uncertainty and variability on structural response. To this end, four side studies were conducted. Three of them, briefly summarized in this volume, addressed themselves respectively to an investigation of sources of random variability in the dynamic response of nuclear power plant structures; formulation of a methodology for modeling and evaluating the effects of structural uncertainty on predicted modal characteristics of major nuclear power plant structures and substructures; and a preliminary evaluation of nonlinear responses in shear-wall structures. A fourth side study, reported in detail in this volume, quantified variations in dynamic characteristics and seismic

  19. Increased cell survival by inhibition of BRCA1 using an antisense approach in an estrogen responsive ovarian carcinoma cell line

    International Nuclear Information System (INIS)

    Annab, Lois A; Hawkins, Rebecca E; Solomon, Greg; Barrett, J Carl; Afshari, Cynthia A

    2000-01-01

    phosphoprotein that is regulated in response to DNA damaging agents [5,6,7] and in response to estrogen-induced growth [8,9,10,11]. Germline mutations that cause breast and ovarian cancer predisposition frequently result in truncated and presumably inactive BRCA1 protein [12]. BG-1 cells were derived from a patient with stage III, poorly differentiated ovarian adenocarcinoma [13]. This cell line, which expresses wild-type BRCA1, is estrogen responsive and withdrawal of estrogen results in eventual cell death. Previous studies suggest that BRCA1 is stimulated as a result of estrogen treatment [8,9,10,11], and also that BRCA1 may be involved in the cell death process [14]. Therefore, we examined the effect of reduction of BRCA1 levels in BG-1 cells on the cellular response to hormone depletion as well as estrogen stimulation. The results suggest that reduced levels of BRCA1 correlates with a survival advantage when BG-1 cells are placed under growth-restrictive and hormone-depleted conditions. In optimum growth conditions, significantly reduced levels of BRCA1 correlates with enhanced growth both in vitro and in vivo. To test the hypothesis that BRCA1 may play a role in the regulation of ovarian tumor cell death as well as in the inhibition of ovarian cell proliferation. The estrogen receptor-positive, BG-1 cell line [13], which contains an abundant amount of estrogen receptors (600 fmoles/100 μg DNA), was infected using a pLXSN retroviral vector (provided by AD Miller) containing an inverted partial human cDNA 900-base-pair sequence of BRCA1 (from nucleotide 121 in exon 1 to nucleotide 1025 in exon 11, accession #U14680). After 2 weeks of selection in 800 μg/ml of geneticin-G418 (Gibco/Life Technologies, Gaithersburg, MD, USA), BG-1 G418-resistant colonies were pooled, or individually isolated, and assayed for growth in the presence or absence of supplemented estrogen. Virally infected pooled populations of BG-1 cells were examined for BRCA1 message levels by ribonuclease

  20. Salivary Biomarker Responses to Two Final Matches in Women’s Professional Football

    Directory of Open Access Journals (Sweden)

    Javiera Maya, Pablo Marquez, Luis Peñailillo, Ariel Contreras-Ferrat, Louise Deldicque, Hermann Zbinden-Foncea

    2016-06-01

    Full Text Available The aim of this study was to examine the link between salivary concentrations of cortisol, testosterone, immunoglobulin A (IgA and the rate of perceived exertion (RPE as a measure of internal load after two final matches played 3 days apart by professional women football players. Saliva samples were taken before and after the two matches (M1, M2. RPE was used to monitor the exercise intensity after each match. Testosterone concentrations increased after each match (M1: +42%, p = 0.002; M2: +50%, p < 0.001 while cortisol increased only after M1 (+116%, p < 0.001. The testosterone-to-cortisol ratio decreased only after M1 (-32.4%, p < 0.001. IgA concentration did not change after any match. Testosterone concentrations were correlated with IgA concentrations after each match (M1: R = 0.59, p = 0.008; M2: R=0.51, p = 0.02. RPE was correlated with cortisol concentrations after M1 (R = 0.57; p = 0.01, but not after M2 (R = 0.38; p = 0.07. All these results suggest that salivary cortisol and testosterone concentrations increase especially after the first match of a final, without affecting IgA levels. We speculate that increased testosterone concentration in women after football matches may play a protecting role against immune suppression usually observed after intense exercise.

  1. Migrational Characteristics, Biological Observations, and Relative Survival of Juvenile Salmonids Entering the Columbia River Estuary, 1966-1983, 1985 Final Report of Research.

    Energy Technology Data Exchange (ETDEWEB)

    Dawley, Earl M.

    1986-04-01

    Natural runs of salmonids in the Columbia River basin have decreased as a result of hydroelectric-dam development, poor land- and forest-management, and over-fishing. This has necessitated increased salmon culture to assure adequate numbers of returning adults. Hatchery procedures and facilities are continually being modified to improve both the efficiency of production and the quality of juveniles produced. Initial efforts to evaluate changes in hatchery procedures were dependent upon adult contributions to the fishery and returns to the hatchery. Procedures were developed for sampling juvenile salmon and steelhead entering the Columbia River estuary and ocean plume. The sampling of hatchery fish at the terminus of their freshwater migration assisted in evaluating hatchery production techniques and identifying migrational or behavioral characteristics that influence survival to and through the estuary. The sampling program attempted to estimate survival of different stocks and define various aspects of migratory behavior in a large river, with flows during the spring freshet from 4 to 17 thousand cubic meters per second (m/sup 3//second).

  2. GLP-1 analogs reduce hepatocyte steatosis and improve survival by enhancing the unfolded protein response and promoting macroautophagy.

    Directory of Open Access Journals (Sweden)

    Shvetank Sharma

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a known outcome of hepatosteatosis. Free fatty acids (FFA induce the unfolded protein response (UPR or endoplasmic reticulum (ER stress that may induce apoptosis. Recent data indicate ER stress to be a major player in the progression of fatty liver to more aggressive lesions. Autophagy on the other hand has been demonstrated to be protective against ER stress-induced cell death. We hypothesized that exendin-4 (GLP-1 analog treatment of fat loaded hepatocytes can reduce steatosis by autophagy which leads to reduced ER stress-related hepatocyte apoptosis.Primary human hepatocytes were loaded with saturated, cis- and trans-unsaturated fatty acids (palmitic, oleic and elaidic acid respectively. Steatosis, induced with all three fatty acids, was significantly resolved after exendin-4 treatment. Exendin-4 sustained levels of GRP78 expression in fat-loaded cells when compared to untreated fat-loaded cells alone. In contrast, CHOP (C/EBP homologous protein; the penultimate protein that leads to ER stress-related cell death was significantly decreased by exendin-4 in hepatocytes loaded with fatty acids. Finally, exendin-4 in fat loaded hepatocytes clearly promoted gene products associated with macroautophagy as measured by enhanced production of both Beclin-1 and LC3B-II, markers for autophagy; and visualized by transmission electron microscopy (TEM. Similar observations were made in mouse liver lysates after mice were fed with high fat high fructose diet and treated with a long acting GLP-1 receptor agonist, liraglutide.GLP-1 proteins appear to protect hepatocytes from fatty acid-related death by prohibition of a dysfunctional ER stress response; and reduce fatty acid accumulation, by activation of both macro-and chaperone-mediated autophagy. These findings provide a novel role for GLP-1 proteins in halting the progression of more aggressive lesions from underlying steatosis in humans afflicted with NAFLD.

  3. Work Scope for Developing Standards for Emergency Preparedness and Response: Fiscal Year 2004 Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Stenner, Robert D.

    2005-09-28

    Summarizes the fiscal year 2004 work completed on PNNL's Department of Homeland Security Emergency Preparedness and Response Standards Development Project. Also, the report includes key draft standards, in various stages of development and publication, that were associated with various tasks of the fiscal year 2004 scope of the project.

  4. Comparative Analysis and Predictors of 10-year Tumor Necrosis Factor Inhibitors Drug Survival in Patients with Spondyloarthritis: First-year Response Predicts Longterm Drug Persistence.

    Science.gov (United States)

    Flouri, Irini D; Markatseli, Theodora E; Boki, Kyriaki A; Papadopoulos, Ioannis; Skopouli, Fotini N; Voulgari, Paraskevi V; Settas, Loukas; Zisopoulos, Dimitrios; Iliopoulos, Alexios; Geborek, Pierre; Drosos, Alexandros A; Boumpas, Dimitrios T; Sidiropoulos, Prodromos

    2018-04-01

    To evaluate the 10-year drug survival of the first tumor necrosis factor inhibitor (TNFi) administered to patients with spondyloarthritis (SpA) overall and comparatively between SpA subsets, and to identify predictors of drug retention. Patients with SpA in the Hellenic Registry of Biologic Therapies, a prospective multicenter observational cohort, starting their first TNFi between 2004-2014 were analyzed. Kaplan-Meier curves and Cox regression models were used. Overall, 404 out of 1077 patients (37.5%) discontinued treatment (followup: 4288 patient-yrs). Ten-year drug survival was 49%. In the unadjusted analyses, higher TNFi survival was observed in patients with ankylosing spondylitis (AS) compared to undifferentiated SpA and psoriatic arthritis [PsA; significant beyond the first 2.5 (p = 0.003) years and 7 years (p < 0.001), respectively], and in patients treated for isolated axial versus peripheral arthritis (p = 0.001). In all multivariable analyses, male sex was a predictor for longer TNFi survival. Use of methotrexate (MTX) was a predictor in PsA and in patients with peripheral arthritis. Absence of peripheral arthritis and use of a monoclonal antibody (as opposed to non-antibody TNFi) independently predicted longer TNFi survival in axial disease because of lower rates of inefficacy. Achievement of major responses during the first year in either axial or peripheral arthritis was the strongest predictor of longer therapy retention (HR 0.33, 95% CI 0.26-0.41 for Ankylosing Spondylitis Disease Activity Score inactive disease, and HR 0.35, 95% CI 0.24-0.50 for 28-joint Disease Activity Score remission). The longterm retention of the first TNFi administered to patients with SpA is high, especially for males with axial disease. The strongest predictor of longterm TNFi survival is a major response within the first year of treatment.

  5. Final programmatic environmental impact statement for stockpile stewardship and management. Comment response document. Volume 4

    International Nuclear Information System (INIS)

    1996-09-01

    In response to the end of the Cold War and changes in the world's political regimes, the United States is not producing new-design nuclear weapons. Instead, the emphasis on the U.S. nuclear weapons program is on reducing the size of the Nation's nuclear stockpile by dismantling existing nuclear weapons. The Department of Energy (DOE) has been directed by the President and Congress to maintain the safety and reliability of the reduced nuclear weapons stockpile in the absence of underground nuclear testing. In order to fulfill that responsibility, DOE has developed a Stockpile Stewardship and Management Program to provide a single highly integrated program for maintaining the continued safety and reliability of the nuclear stockpile. The Stockpile Stewardship and Management PEIS describes and analyzes alternative ways to implement the proposed actions for the Stockpile Stewardship and Management Program

  6. Apparent diffusion coefficient quantification as an early imaging biomarker of response and predictor of survival following yttrium-90 radioembolization for unresectable infiltrative hepatocellular carcinoma with portal vein thrombosis.

    Science.gov (United States)

    Kokabi, Nima; Camacho, Juan C; Xing, Minzhi; Qiu, Deqiang; Kitajima, Hiroumi; Mittal, Pardeep K; Kim, Hyun S

    2014-10-01

    To investigate early diffusion-weighted imaging (DWI) at 30-days post-yttrium-90 (Y-90) radioembolization as a predictor of treatment response and survival in unresectable infiltrative hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT). In a prospective study, 18 consecutive patients with unresectable infiltrative HCC and PVT underwent Y-90 therapy. MR imaging was obtained pre Y-90, and at 1 and 3 months post-therapy with DWI fat-suppressed tri-directional diffusion gradient (b = 50, 400, 800 s/mm(2)). Response was evaluated using target mRECIST and EASL. Relative change in apparent diffusion coefficient (ADC) value of tumors was evaluated. Statistical analysis using receiver operator characteristic curves was performed. Paired t test and Pearson correlation coefficient (r) were used to assess intra- and inter-observer variability. Survival analysis was performed using Kaplan-Meier estimation and log-rank test. Mean ADC values of all HCC's at baseline and at 30-days post-Y90 therapy was 0.86 × 10(-3) and 1.17×10(-3) mm(2)/s, respectively (p 30% increase in ADC value at 30-days was found to be at least 90% sensitive in predicting response at 90 days. A >30% increase in ADC value at 30-days predicted significantly prolonged survival. A 30% increase in ADC value at 30-days measured post Y90 is a reproducible early imaging response biomarker predicting tumor response and prolonged survival following Y-90 therapy in infiltrative HCC with PVT.

  7. The Ratio of Leaf to Total Photosynthetic Area Influences Shade Survival and Plastic Response to Light of Green‐stemmed Leguminous Shrub Seedlings

    Science.gov (United States)

    VALLADARES, FERNANDO; HERNÁNDEZ, LIBERTAD G.; DOBARRO, IKER; GARCÍA‐PÉREZ, CRISTINA; SANZ, RUBÉN; PUGNAIRE, FRANCISCO I.

    2003-01-01

    Different plant species and organs within a plant differ in their plastic response to light. These responses influence their performance and survival in relation to the light environment, which may range from full sunlight to deep shade. Plasticity, especially with regard to physiological features, is linked to a greater capacity to exploit high light and is usually low in shade‐tolerant species. Among photosynthetic organs, green stems, which represent a large fraction of the total photosynthetic area of certain species, are hypothesized to be less capable of adjustment to light than leaves, because of biomechanical and hydraulic constraints. The response to light by leaves and stems of six species of leguminous, green‐stemmed shrubs from dry and high‐light environments was studied by growing seedlings in three light environments: deep shade, moderate shade and sun (3, 30 and 100 % of full sunlight, respectively). Survival in deep shade ranged from 2 % in Retama sphaerocarpa to 74 % in Ulex europaeus. Survival was maximal at moderate shade in all species, ranging from 80 to 98 %. The six species differed significantly in their ratio of leaf to total photosynthetic area, which influenced their light response. Survival in deep shade increased significantly with increasing ratio of leaf to total photosynthetic area, and decreased with increasing plasticity in net photosynthesis and dark respiration. Responses to light differed between stems and leaves within each species. Mean phenotypic plasticity for the variables leaf or stem specific mass, chlorophyll content, chlorophyll a/b ratio, and carotenoid to chlorophyll ratio of leaves, was inversely related to that of stems. Although mean plasticity of stems increased with the ratio of leaf to total photosynthetic area, the mean plasticity of leaves decreased. Shrubs with green stems and a low ratio of leaf to total photosynthetic area are expected to be restricted to well‐lit habitats, at least during the

  8. Growth, water relations, and survival of drought-exposed seedlings from six maternal families of honey mesquite (Prosopis glandulosa): responses to CO(2) enrichment.

    Science.gov (United States)

    Polley, H. Wayne; Tischler, Charles R.; Johnson, Hyrum B.; Pennington, Rodney E.

    1999-05-01

    Low water availability is a leading contributor to mortality of woody seedlings on grasslands, including those of the invasive shrub Prosopis. Increasing atmospheric CO(2) concentration could favor some genotypes of this species over others if there exists intraspecific variation in the responsiveness of survivorship to CO(2). To investigate such variation, we studied effects of CO(2) enrichment on seedling survival in response to uniform rates of soil water depletion in six maternal families of honey mesquite (P. glandulosa Torr. var. glandulosa). Three families each from the arid and mesic extremes of the species' distribution in the southwestern United States were studied in environmentally controlled glasshouses. Relative water content at turgor loss and osmotic potential were not affected by CO(2) treatment. Increased atmospheric CO(2) concentration, however, increased growth, leaf production and area, and midday xylem pressure potential, and apparently reduced transpiration per unit leaf area of seedlings as soil dried. Consequently, CO(2) enrichment about doubled the fraction of seedlings that survived soil water depletion. Maternal families of honey mesquite differed in percentage survival of drought and in several other characteristics, but differences were of similar or of smaller magnitude compared with differences between CO(2) treatments. There was no evidence for genetic variation in the responsiveness of survivorship to CO(2). By increasing seedling survival of drought, increasing atmospheric CO(2) concentration could increase the abundance of honey mesquite where establishment is limited by water availability. Genetic types with superior ability to survive drought today, however, apparently will maintain that advantage in the future.

  9. STRUCTURAL FLUCTUATIONS, ELECTRICAL RESPONSE AND THE RELIABILITY OF NANOSTRUCTURES (FINAL REPORT)

    Energy Technology Data Exchange (ETDEWEB)

    Philip J. Rous; Ellen D. Williams; Michael S. Fuhrer

    2006-07-31

    The goal of the research supported by DOE-FG02-01ER45939 was to synthesize a number of experimental and theoretical approaches to understand the relationship between morphological fluctuations, the electrical response and the reliability (failure) of metallic nanostructures. The primary focus of our work was the study of metallic nanowires which we regard as prototypical of nanoscale interconnects. Our research plan has been to link together these materials properties and behaviors by understanding the phenomenon of, and the effects of electromigration at nanometer length scales. The thrust of our research has been founded on the concept that, for nanostructures where the surface-to-volume ratio is necessarily high, surface diffusion is the dominant mass transport mechanism that governs the fluctuations, electrical properties and failure modes of nanostructures. Our approach has been to develop experimental methods that permit the direct imaging of the electromagnetic distributions within nanostructures, their structural fluctuations and their electrical response. This experimental research is complemented by a parallel theoretical and computational program that describes the temporal evolution of nanostructures in response to current flow.

  10. High RBM3 expression is associated with an improved survival and oxaliplatin response in patients with metastatic colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Christina Siesing

    Full Text Available High expression of the RNA-binding motif protein 3 (RBM3 has been shown to correlate, with prolonged survival in several malignant diseases and with the benefit of platinum-based chemotherapy in ovarian cancer. The aim of this study was to evaluate RBM3 in metastatic colorectal cancer (mCRC as a prognostic factor for overall survival and in relation to benefit of first-line chemotherapy.Immunohistochemical staining was conducted and evaluated in tumours from 455 mCRC patients. Kaplan-Meier analysis and Cox regression proportional hazards models were used to access the impact of RBM3 expression on overall survival (OS and progression-free survival (PFS.High RBM3 expression, both nuclear and cytoplasmic, was an independent prognostic factor for prolonged OS (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.50-0.90 and HR 0.66, 95% CI 0.48-0.91, respectively. PFS was significantly longer in patients with high RBM3 expression who had received first-line oxaliplatin based treatment, compared to those who had received irinotecan based treatment, both regarding nuclear and cytoplasmic expression (p-value 0.020 and 0.022 respectively.High RBM3 expression is an independent predictor of prolonged survival in mCRC patients, in particular in patients treated with first-line oxaliplatin based chemotherapy.

  11. 2025 California Demand Response Potential Study - Charting California’s Demand Response Future. Final Report on Phase 2 Results

    Energy Technology Data Exchange (ETDEWEB)

    Alstone, Peter [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Potter, Jennifer [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Piette, Mary Ann [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Schwartz, Peter [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Berger, Michael A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Dunn, Laurel N. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Smith, Sarah J. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sohn, Michael D. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Aghajanzadeh, Aruab [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Stensson, Sofia [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Szinai, Julie [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Walter, Travis [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); McKenzie, Lucy [Energy and Environmental Economics, Inc. (E3), San Francisco, CA (United States); Lavin, Luke [Energy and Environmental Economics, Inc. (E3), San Francisco, CA (United States); Schneiderman, Brendan [Energy and Environmental Economics, Inc. (E3), San Francisco, CA (United States); Mileva, Ana [Energy and Environmental Economics, Inc. (E3), San Francisco, CA (United States); Cutter, Eric [Energy and Environmental Economics, Inc. (E3), San Francisco, CA (United States); Olson, Arne [Energy and Environmental Economics, Inc. (E3), San Francisco, CA (United States); Bode, Josh [Nexant, Inc., Nashville, TN (United States); Ciccone, Adriana [Nexant, Inc., Nashville, TN (United States); Jain, Ankit [Nexant, Inc., Nashville, TN (United States)

    2017-03-01

    California’s legislative and regulatory goals for renewable energy are changing the power grid’s dynamics. Increased variable generation resource penetration connected to the bulk power system, as well as, distributed energy resources (DERs) connected to the distribution system affect the grid’s reliable operation over many different time scales (e.g., days to hours to minutes to seconds). As the state continues this transition, it will require careful planning to ensure resources with the right characteristics are available to meet changing grid management needs. Demand response (DR) has the potential to provide important resources for keeping the electricity grid stable and efficient, to defer upgrades to generation, transmission and distribution systems, and to deliver customer economic benefits. This study estimates the potential size and cost of future DR resources for California’s three investor-owned utilities (IOUs): Pacific Gas and Electric Company (PG&E), Southern California Edison Company (SCE), and San Diego Gas & Electric Company (SDG&E). Our goal is to provide data-driven insights as the California Public Utilities Commission (CPUC) evaluates how to enhance DR’s role in meeting California’s resource planning needs and operational requirements. We address two fundamental questions: 1. What cost-competitive DR service types will meet California’s future grid needs as it moves towards clean energy and advanced infrastructure? 2. What is the size and cost of the expected resource base for the DR service types?

  12. Inter-Individual Variability in Human Response to Low-Dose Ionizing Radiation, Final Report

    International Nuclear Information System (INIS)

    Rocke, David

    2016-01-01

    In order to investigate inter-individual variability in response to low-dose ionizing radiation, we are working with three models, 1) in-vivo irradiated human skin, for which we have a realistic model, but with few subjects, all from a previous project, 2) ex-vivo irradiated human skin, for which we also have a realistic model, though with the limitations involved in keeping skin pieces alive in media, and 3) MatTek EpiDermFT skin plugs, which provides a more realistic model than cell lines, which is more controllable than human samples.

  13. Inter-Individual Variability in Human Response to Low-Dose Ionizing Radiation, Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Rocke, David [Univ. of California, Davis, CA (United States)

    2016-08-01

    In order to investigate inter-individual variability in response to low-dose ionizing radiation, we are working with three models, 1) in-vivo irradiated human skin, for which we have a realistic model, but with few subjects, all from a previous project, 2) ex-vivo irradiated human skin, for which we also have a realistic model, though with the limitations involved in keeping skin pieces alive in media, and 3) MatTek EpiDermFT skin plugs, which provides a more realistic model than cell lines, which is more controllable than human samples.

  14. Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck

    DEFF Research Database (Denmark)

    Lassen, Pernille; Eriksen, Jesper Grau; Hamilton-Dutoit, Stephen

    2009-01-01

    PURPOSE: A subset of head and neck cancers is associated with the human papillomavirus (HPV). Viral infection is closely correlated with expression of p16(INK4A) in these tumors. We evaluated p16(INK4A) as a prognostic marker of treatment response and survival in a well-defined and prospectively...... (hazard ratio [HR], 0.35; 95% CI, 0.19 to 0.64), disease-specific death (HR, 0.36; 95% CI, 0.20 to 0.64), and overall death (HR, 0.44; 95% CI, 0.28 to 0.68). CONCLUSION: Expression of p16(INK4A) has a major impact on treatment response and survival in patients with head and neck cancer treated...

  15. The relationship between survival of Columbia River fall chinook salmon and in-river environmental factors -- Analysis of historic data for juvenile and adult salmonid production: Phase 2. Final report

    International Nuclear Information System (INIS)

    Skalski, J.R.; Townsend, R.L.; Donnelly, R.F.; Hilborn, R.W.

    1996-12-01

    This project analyzes in greater detail the coded-wire-tag (CWT) returns of Priest Rapids Hatchery fall chinook for the years 1976--1989 initially begun by Hilborn et al. (1993a). These additional analyses were prompted by suggestions made by peer reviews of the initial draft report. The initial draft and the peer review comments are included in this final report (Appendices A and B). The statistical analyses paired Priest Rapids stock with potential downriver reference stocks to isolate in-river survival rates. Thirty-three potential reference stocks were initially examined for similar ocean recovery rates; the five stocks with the most similar recovery patterns (i.e., Bonneville Brights, Cowlitz, Gray's River, Tanner Creek, and Washougal) to the Priest Rapids stock were used in the subsequent analysis of in-river survival. Three alternate forms of multiple regression models were used to investigate the relationship between predicted in-river survival and ambient conditions. Analyses were conducted with and without attempts to adjust for smolt transportation at McNary Dam. Independent variables examined in the analysis included river flows, temperature, turbidity, and spill along with the total biomass of hatchery releases in the Columbia-Snake River Basin

  16. Grassland/atmosphere response to changing climate: Coupling regional and local scales. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Coughenour, M.B.; Kittel, T.G.F.; Pielke, R.A.; Eastman, J.

    1993-10-01

    The objectives of the study were: to evaluate the response of grassland ecosystems to atmospheric change at regional and site scales, and to develop multiscaled modeling systems to relate ecological and atmospheric models with different spatial and temporal resolutions. A menu-driven shell was developed to facilitate use of models at different temporal scales and to facilitate exchange information between models at different temporal scales. A detailed ecosystem model predicted that C{sub 3} temperate grasslands wig respond more strongly to elevated CO{sub 2} than temperate C{sub 4} grasslands in the short-term while a large positive N-PP response was predicted for a C{sub 4} Kenyan grassland. Long-term climate change scenarios produced either decreases or increases in Colorado plant productivity (NPP) depending on rainfall, but uniform increases in N-PP were predicted in Kenya. Elevated CO{sub 2} is likely to have little effect on ecosystem carbon storage in Colorado while it will increase carbon storage in Kenya. A synoptic climate classification processor (SCP) was developed to evaluate results of GCM climate sensitivity experiments. Roughly 80% agreement was achieved with manual classifications. Comparison of lx and 2xCO{sub 2} GCM Simulations revealed relatively small differences.

  17. Bridging the Divide: Linking Genomics to Ecosystem Responses to Climate Change: Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Melinda D.

    2014-03-15

    Over the project period, we have addressed the following objectives: 1) assess the effects of altered precipitation patterns (i.e., increased variability in growing season precipitation) on genetic diversity of the dominant C4 grass species, Andropogon gerardii, and 2) experimentally assess the impacts of extreme climatic events (heat wave, drought) on responses of the dominant C4 grasses, A. gerardii and Sorghastrum nutans, and the consequences of these response for community and ecosystem structure and function. Below is a summary of how we have addressed these objectives. Objective 1 After ten years of altered precipitation, we found the number of genotypes of A. gerardii was significantly reduced compared to the ambient precipitation treatments (Avolio et al., 2013a). Although genotype number was reduced, the remaining genotypes were less related to one another indicating that the altered precipitation treatment was selecting for increasingly dissimilar genomes (based on mean pairwise Dice distance among individuals). For the four key genotypes that displayed differential abundances depending on the precipitation treatment (G1, G4, and G11 in the altered plots and G2 in the ambient plots), we identified phenotypic differences in the field that could account for ecological sorting (Avolio & Smith, 2013a). The three altered rainfall genotypes also have very different phenotypic traits in the greenhouse in response to different soil moisture availabilities (Avolio and Smith, 2013c). Two of the genotypes that increased in abundance in the altered precipitation plots had greater allocation to root biomass (G4 and G11), while G1 allocated more biomass aboveground. These phenotypic differences among genotypes suggests that changes in genotypic structure between the altered and the ambient treatments has likely occurred via niche differentiation, driven by changes in soil moisture dynamics (reduced mean, increased variability and changes in the depth distribution of

  18. Site-specific earthquake response analysis for Paducah Gaseous Diffusion Plant, Paducah, Kentucky. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Sykora, D.W.; Davis, J.J.

    1993-08-01

    The Paducah Gaseous Diffusion Plant (PGDP), owned by the US Department of Energy (DOE) and operated under contract by Martin Marietta Energy systems, Inc., is located southwest of Paducah, Kentucky. An aerial photograph and an oblique sketch of the plant are shown in Figures 1 and 2, respectively. The fenced portion of the plant consists of 748 acres. This plant was constructed in the 1950`s and is one of only two gaseous diffusion plants in operation in the United States; the other is located near Portsmouth, Ohio. The facilities at PGDP are currently being evaluated for safety in response to natural seismic hazards. Design and evaluation guidelines to evaluate the effects of earthquakes and other natural hazards on DOE facilities follow probabilistic hazard models that have been outlined by Kennedy et al. (1990). Criteria also established by Kennedy et al. (1990) classify diffusion plants as ``moderate hazard`` facilities. The US Army Engineer Waterways Experiment Station (WES) was tasked to calculate the site response using site-specific design earthquake records developed by others and the results of previous geotechnical investigations. In all, six earthquake records at three hazard levels and four individual and one average soil columns were used.

  19. Final Scientific Technical Report: INTEGRATED PREDICTIVE DEMAND RESPONSE CONTROLLER FOR COMMERCIAL BUILDINGS

    Energy Technology Data Exchange (ETDEWEB)

    Wenzel, Mike

    2013-10-14

    This project provides algorithms to perform demand response using the thermal mass of a building. Using the thermal mass of the building is an attractive method for performing demand response because there is no need for capital expenditure. The algorithms rely on the thermal capacitance inherent in the building?s construction materials. A near-optimal ?day ahead? predictive approach is developed that is meant to keep the building?s electrical demand constant during the high cost periods. This type of approach is appropriate for both time-of-use and critical peak pricing utility rate structures. The approach uses the past days data in order to determine the best temperature setpoints for the building during the high price periods on the next day. A second ?model predictive approach? (MPC) uses a thermal model of the building to determine the best temperature for the next sample period. The approach uses constant feedback from the building and is capable of appropriately handling real time pricing. Both approaches are capable of using weather forecasts to improve performance.

  20. The effect of radiosensitizers on the survival response of hypoxic mammalian cells: The low X-ray dose region, hypersensitivity and induced radioresistance

    International Nuclear Information System (INIS)

    Skov, K.A.; MacPhail, H.S.; Marples, B.

    1994-01-01

    It has been shown previously that the extent of chemical modification of the hypoxic radiation response is dependent on dose. Some types of sensitizer are more effective at low doses (to 4 Gy) than at higher doses. Since such drugs are possible adjuvants to radiotherapy, the mechanisms responsible for the variable response at clinical doses are summarized, and the effects of cisplatin and buthionine sulfoximine on the purported induced response to radiation in hypoxic cells are presented. Cisplatin at a low, nontoxic concentration (1 μM) appears to abolish the increased radioresistant portion of the survival response. A role for high-mobility-group protein binding by platinum drugs is hypothesized to explain their interaction with radiation, and conversely, it is suggested that the heretofore unexplained different behavior of certain hypoxic sensitizers at low doses could be, at least in part, an effect on the induction of resistance. 36 refs., 2 figs

  1. Percutaneous cholecystostomy for gallbladder perforation : early response and final outcome in 10 patients

    International Nuclear Information System (INIS)

    Lee, Jeong Min; Han, Young Min; Lee, Mi Suk; Kim, Jin; Kowk, Hyo Seong; Lee, Sang Young; Chung, Gyung Ho; Kim, Chong Soo

    1998-01-01

    To evaluate the efficacy of percutaneous cholecystostomy (PC) as a therapeutic maneuver for patients with spontaneous gallbladder (GB) perforation. All procedures were technically successful, and no major procedure-related complications occurred. Eight patients (80%) responded favorably to PC. One, who did not respond, underwent emergency cholecystectomy next day due to worsening peritonitis, and the other who failed to respond within 72hr showed delayed response after drainage of a coexistent liver abscess at seven days after the procedure. A patient who responded to PC experience catheter dislodgement four days after the procedure but reinsertion was not required. Five of eight patients who responded positively underwent elective cholecystecomy after the improvement of clinical symptoms, and the three remaining patients improved without further surgery. (author). 23 refs., 4 figs

  2. Percutaneous cholecystostomy for gallbladder perforation : early response and final outcome in 10 patients

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Min; Han, Young Min; Lee, Mi Suk [Namwon Medical Center, Namwon (Korea, Republic of ); Kim, Jin; Kowk, Hyo Seong; Lee, Sang Young; Chung, Gyung Ho; Kim, Chong Soo [Chonbuk Univ., Chonju (Korea, Republic of). Coll. of Medicine; Han, Hyeun Young; Chung, Jin Young [Eulgi Medical College, Seoul (Korea, Republic of)

    1998-01-01

    To evaluate the efficacy of percutaneous cholecystostomy (PC) as a therapeutic maneuver for patients with spontaneous gallbladder (GB) perforation. All procedures were technically successful, and no major procedure-related complications occurred. Eight patients (80%) responded favorably to PC. One, who did not respond, underwent emergency cholecystectomy next day due to worsening peritonitis, and the other who failed to respond within 72hr showed delayed response after drainage of a coexistent liver abscess at seven days after the procedure. A patient who responded to PC experience catheter dislodgement four days after the procedure but reinsertion was not required. Five of eight patients who responded positively underwent elective cholecystecomy after the improvement of clinical symptoms, and the three remaining patients improved without further surgery. (author). 23 refs., 4 figs.

  3. Fast Response, Load-Matching Hybrid Fuel Cell: Final Technical Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Key, T. S.; Sitzlar, H. E.; Geist, T. D.

    2003-06-01

    Hybrid DER technologies interconnected with the grid can provide improved performance capabilities compared to a single power source, and, add value, when matched to appropriate applications. For example, in a typical residence, the interconnected hybrid system could provide power during a utility outage, and also could compensate for voltage sags in the utility service. Such a hybrid system would then function as a premium power provider and eliminate the potential need for an uninterruptible power supply. In this research project, a proton exchange membrane (PEM) fuel cell is combined with an asymmetrical ultracapacitor to provide robust power response to changes in system loading. This project also considers the potential of hybrid DER technologies to improve overall power system compatibility and performance. This report includes base year accomplishments of a proposed 3-year-option project.

  4. A Prospective Study Assessing Tumour Response, Survival, and Palliative Care Outcomes in Patients with HIV-Related Kaposi's Sarcoma at Queen Elizabeth Central Hospital, Blantyre, Malawi

    Directory of Open Access Journals (Sweden)

    H. Francis

    2012-01-01

    Full Text Available Background. Human-Immunodeficiency-Virus- (HIV- related Kaposi's sarcoma (KS has a high prevalence in Africa; however, there is minimal published data on treatment and outcomes in this population. Objective and Design. This was a prospective study of 50 patients, aiming to assess the impact of vincristine therapy on tumour response and survival and to assess palliative care outcomes in patients with HIV-related KS. Methods. 50 consecutive patients were recruited during 2008. Vincristine therapy and highly active antiretroviral therapy (HAART were given. Tumour response, survival, and chemotherapy-related toxicities were documented. Palliative care outcomes were assessed using the African Palliative Care Association (APCA Palliative Outcome Scale (POS. Results. The majority of patients were male, and the median age was 33 years. At baseline assessment, the median CD4 T-cell count was 263, and 50% patients had evidence of peripheral neuropathy. The overall response rate was 64% at 6 weeks, and median progression-free survival was 30 weeks. Treatment was generally well tolerated, with peripheral neuropathy the main dose-limiting toxicity. Conclusion. The combination of vincristine and HAART is feasible and effective in a low resource setting, although peripheral neuropathy is a dose-limiting factor. This patient group carries a high mortality and as such adequate access to palliative care is crucial.

  5. Anoxic or aerial survival of bivalves and other euryoxic invertebrates as a useful response to environmental stress - A comprehensive review

    NARCIS (Netherlands)

    De Zwaan, A.; Eertman, R.H.M.

    1996-01-01

    Laboratory and field studies have demonstrated the applicability of anoxic/aerial survival as an early warning indicator of contaminant induced stress. The effects of xenobiotics, including heavy metals, organometals and organics as well as contaminated field sediments have been investigated. The

  6. Photosynthetic response, survival, and growth of three ponderosa pine stocktypes under water stress enhanced by vegetative competition

    Science.gov (United States)

    Jeremiah R. Pinto; John D. Marshall; R. Kasten Dumroese; Anthony S. Davis; Douglas R. Cobos

    2012-01-01

    Selecting the proper stock type for reforestation on dry sites can be critical for the long-term survival and growth of seedlings. In this study, we use a novel approach to understand stock type selection on a site where drought was induced with vegetative competition. Three ponderosa pine (Pinus ponderosa Lawson & C. Lawson var. ponderosa C. Lawson) seedling stock...

  7. The Role of RUB (related to ubiquitin) Family of Proteins in the Hormone Response. Final Report.

    Energy Technology Data Exchange (ETDEWEB)

    Callis, Judy [Univ. of California, Davis, CA (United States). Dept. of Molecular and Cellular Biology

    2013-03-22

    The Rub pathway is a conserved protein modification pathway. RUB (called Rubp1 in budding yeast, Nedd8 in animals and RUB in plants) is a ubiquitin-like 76-amino acid protein. It covalently attaches to protein using an enzymatic machinery analogous to the enzymes that attach ubiquitin to its substrate proteins. However, the nature of the complement of Rub-modified proteins in organisms was not clear. From bioinformatics analyses, one can identify a Rub activating enzymes and Rub conjugating enzymes. However, in many cases, their biochemical properties were not described. In DOE-funded work, we made major advances in our understanding of the Rub pathway in yeast and plants, work that is applicable to other organisms as well. There is a multi-subunit enzyme called SCF in all eukaryotes. The SCF consists of several subunits that serve as a scaffold (the cullin, SKP and RBX subunits) and one subunit that interacts with the substrate. This cullin protein (called Cdc53p in yeast and CULLIN 1 in plants and animals) was a known Rub target. In this work, we identified additional Rub targets in yeast as the other cullin-like proteins Cul3p and Rtt101p. Additionally we described the conservation of the Rub pathway because plant RUB1 can conjugated to yeast Cdc53p- in yeast. In the model plant Arabidopsis thaliana, we characterized the Rub activating enzymes and showed that they are not biochemically equivalent. We also showed that the Rub pathway is essential in plants and characterized plants with reduced levels of rub proteins. These plants are affected in multiple developmental processes. We discovered that they over-produce ethylene as dark-grown seedlings. We characterized a mutant allele of CULLIN1 in Arabidopsis with impaired interaction with RBX and showed that it is unstable in vivo. We used our knowledge of monitoring protein degradation to map the degradation determinants in a plant transcription factor. Finally, we took a mass spectrometric approach to identify

  8. Assessment of predictors of response and long-term survival of patients with neuroendocrine tumour treated with peptide receptor chemoradionuclide therapy (PRCRT)

    Energy Technology Data Exchange (ETDEWEB)

    Kong, G.; Thompson, M.; Johnston, V.; Eu, P. [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, East Melbourne, VIC (Australia); Collins, M.; Herschtal, A. [Peter MacCallum Cancer Centre, Department of Biostatistics and Clinical Trials, Melbourne, VIC (Australia); Hofman, M.S.; Hicks, Rodney J. [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, East Melbourne, VIC (Australia); The University of Melbourne, Department of Medicine, Melbourne, VIC (Australia); Michael, M. [The University of Melbourne, Department of Medicine, Melbourne, VIC (Australia); Peter MacCallum Cancer Centre, Division of Cancer Medicine, Neuroendocrine Tumour Unit, Melbourne, VIC (Australia)

    2014-10-15

    To review the response and outcomes of {sup 177}Lu-DOTA-octreotate chemoradionuclide therapy (LuTate PRCRT) in patients with neuroendocrine tumour (NET) expressing high levels of somatostatin receptors with uncontrolled symptoms or disease progression. A total of 68 patients (39 men; 17 - 76 years of age) who had completed an induction course of at least three cycles of LuTate PRCRT between January 2006 and June 2010 were reviewed. Ten patients were treated for uncontrolled symptoms and 58 had disease progression despite conventional treatment. The majority had four induction LuTate cycles (median treatment duration 5 months and cumulative activity 31 GBq), and 63 patients had concomitant 5-FU radiosensitizing infusional chemotherapy. Factors predicting overall survival were assessed using the log-rank test and Cox proportional hazards regression. Of those treated for uncontrolled symptoms, 70 % received benefit maintained for at least 6 months after treatment. Among patients with progressive disease 68 % showed stabilization or regression on CT, 67 % on molecular imaging and 56 % biochemically up to 12 months after treatment; 32 patients died. Overall survival rates at 2 and 5 year were 72.1 % and 52.1 %, respectively. Median overall survival was not estimable at a median follow-up of 60 months (range 5 - 86 months). Nonpancreatic primary sites, dominant liver metastases, lesion size <5 cm and the use of 5-FU chemotherapy were statistically significantly associated with objective response. A disseminated pattern and a high disease burden (whole-body retention index) were associated with an increased risk of death. Objective biochemical, molecular imaging and CT responses were all associated with longer overall survival. A high proportion of patients with progressive NET or uncontrolled symptoms received therapeutic benefit from LuTate with concomitant 5-FU chemotherapy. The achievement of objective biochemical, molecular or CT responses within 12 months was

  9. Assessment of private sector anticipatory response to greenhouse gas market development : Final analysis

    International Nuclear Information System (INIS)

    Forrister, D.; Marsh, D.; Varilek, M.

    2002-01-01

    Some active markets in greenhouse gases are beginning to emerge, which will lead to actual data concerning market performance becoming available and rendering the prediction of future prices for global greenhouse gas reductions more accurate. Market participants use studies as a starting point for the calibration of their understanding then seize opportunities in the external market and therefore refine their price expectations. In addition, they attempt to outperform their competitors. In this study, the authors reviewed the results of some of the most recent economic modeling results, synthesized pricing data, assessed the price and risk expectations of a broad range of corporate market players and examined their response strategies. The authors also took advantage of their expertise as market brokers to offer their views. The representatives of 35 companies operating in Canada, the United States, Japan, the European Union and Russia were interviewed for this study. Their price expectations were just over 5 dollars per tonne of carbon dioxide equivalent in 2005 before the implementation of the Kyoto Protocol, and raised to an average of 11 dollars per tonne of carbon dioxide equivalent in 2010. The major assumption was that the Kyoto Protocol would begin to take effect in 2002, and also that the United States would fail to ratify the Protocol. The respondents believed that some demand would force state and/or local programs to be implemented for a carbon reduction program. Poorly harmonized or delayed national policies, the potential costs of the Clean Development Mechanism projects and national pressure to take action at home are some of the concerns expressed which could prevent prices from becoming fully efficient. 41 refs., 6 tabs., 4 figs

  10. Final Report Systems Level Analysis of the Function and Adaptive Responses of Methanogenic Consortia

    Energy Technology Data Exchange (ETDEWEB)

    Lovley, Derek R. [Univ. of Massachusetts, Amherst, MA (United States)

    2015-03-09

    performance of DIET may be strongly influenced by environmental factors. These studies have significantly modified conceptual models for carbon and electron flow in methane-producing environments and have developed a computational framework for predictive modeling the influence of environmental perturbations on methane-producing microbial communities. The results have important implications for modeling the response of methane-producing microbial communities to climate change as well as for the bioenergy strategy of converting wastes and biomass to methane.

  11. Response of thyroid follicular cells to gamma irradiation compared to proton irradiation. I. Initial characterization of DNA damage, micronucleus formation, apoptosis, cell survival, and cell cycle phase redistribution

    Science.gov (United States)

    Green, L. M.; Murray, D. K.; Bant, A. M.; Kazarians, G.; Moyers, M. F.; Nelson, G. A.; Tran, D. T.

    2001-01-01

    .12 Gy(-1) for protons), which suggests that the higher level of survival of gamma-irradiated cells could be attributed to the persistence of nonlethally irradiated thyrocytes and/or the capacity to repair damage more effectively than cells exposed to equal physical doses of protons. The final assessment in this study was radiation-induced cell cycle phase redistribution. Gamma rays and protons produced a similar dose-dependent redistribution toward a predominantly G(2)-phase population. From our cumulative results, it seems likely that a majority of the proton-irradiated cells would not continue to divide. In conclusion, these findings suggest that there are quantitative and qualitative differences in the biological effects of proton beams and gamma rays. These differences could be due to structured energy deposition from the tracks of primary protons and the associated high-LET secondary particles produced in the targets. The results suggest that a simple dose-equivalent approach to dosimetry may be inadequate to compare the biological responses of cells to photons and protons.

  12. Survival analysis

    International Nuclear Information System (INIS)

    Badwe, R.A.

    1999-01-01

    The primary endpoint in the majority of the studies has been either disease recurrence or death. This kind of analysis requires a special method since all patients in the study experience the endpoint. The standard method for estimating such survival distribution is Kaplan Meier method. The survival function is defined as the proportion of individuals who survive beyond certain time. Multi-variate comparison for survival has been carried out with Cox's proportional hazard model

  13. CT Perfusion Imaging Can Predict Patients' Survival and Early Response to Transarterial Chemo-Lipiodol Infusion for Liver Metastases from Colorectal Cancers.

    Science.gov (United States)

    Lv, Wei-Fu; Han, Jian-Kui; Cheng, De-Lei; Zhou, Chun-Ze; Ni, Ming; Lu, Dong

    2015-01-01

    To prospectively evaluate the performance of computed tomography perfusion imaging (CTPI) in predicting the early response to transarterial chemo-lipiodol infusion (TACLI) and survival of patients with colorectal cancer liver metastases (CRLM). Computed tomography perfusion imaging was performed before and 1 month after TACLI in 61 consecutive patients. Therapeutic response was evaluated on CT scans 1 month and 4 months after TACLI; the patients were classified as responders and non-responders based on 4-month CT scans after TACLI. The percentage change of CTPI parameters of target lesions were compared between responders and non-responders at 1 month after TACLI. The optimal parameter and cutoff value were determined. The patients were divided into 2 subgroups according to the cutoff value. The log-rank test was used to compare the survival rates of the 2 subgroups. Four-month images were obtained from 58 patients, of which 39.7% were responders and 60.3% were non-responders. The percentage change in hepatic arterial perfusion (HAP) 1 month after TACLI was the optimal predicting parameter (p = 0.003). The best cut-off value was -21.5% and patients who exhibited a ≥ 21.5% decrease in HAP had a significantly higher overall survival rate than those who exhibited a HAP after TACLI with a cutoff value of -21.5% is the optimal predictor.

  14. Early response of C-reactive protein as a predictor of survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors.

    Science.gov (United States)

    Yasuda, Yosuke; Saito, Kazutaka; Yuasa, Takeshi; Uehara, Sho; Kawamura, Naoko; Yokoyama, Minato; Ishioka, Junichiro; Matsuoka, Yoh; Yamamoto, Shinya; Okuno, Tetsuo; Yonese, Junji; Kihara, Kazunori; Fujii, Yasuhisa

    2017-12-01

    Pretreatment C-reactive protein (CRP) has been shown to be an independent prognostic factor for metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs). We further evaluated the early response of CRP after the initiation of TKIs. A total of 103 patients (80 men and 23 women) were treated with TKIs for mRCC from 2008-2013. Patients were divided into three groups according to their early CRP kinetics-patients whose baseline CRP levels were 20% at 4 weeks after the initiation of TKIs (early CRP responder), and the remaining patients (non-early CRP responder). The endpoints were progression-free survival (PFS) and overall survival (OS). The median follow-up period was 21 (interquartile range 10-34) months. The numbers of patients classified as non-elevated, early CRP responder, and non-early CRP responder were 62, 19, and 22, respectively. The 1-year PFS rates of patients in the non-elevated, early CRP responder, and non-early CRP responder groups were 50, 23, and 9.7%, respectively (p < 0.001). The 1-year OS rates of patients in these three groups were 79, 62, and 36%, respectively (p < 0.001). In multivariate analysis, the early CRP kinetics assessment was a significant independent factor for PFS and OS. Early CRP response at 4 weeks is predictive of survival for patients with mRCC treated with TKI.

  15. RESPONSE PROTOCOL TOOLBOX: PLANNING FOR AND RESPONDING TO DRINKING WATER CONTAMINATION THREATS AND INCIDENTS. MODULE 1: WATER UTILITIES PLANNING GUIDE - INTERIM FINAL - DECEMBER 2003

    Science.gov (United States)

    The interim final Response Protocol Toolbox: Planning for and Responding to Contamination Threats to Drinking Water Systems is designed to help the water sector effectively and appropriately respond to intentional contamination threats and incidents. It was produced by EPA, buil...

  16. Revised Interim Final Consolidated Enforcement Response and Penalty Policy for the Pre-Renovation Education Rule; Renovation, Repair and Painting Rule; and Lead-Based Paint Activities Rule

    Science.gov (United States)

    This is the revised version of the Interim Final Consolidated Enforcement Response and Penalty Policy for the Pre-Renovation Education Rule; Renovation, Repair and Painting Rule; and Lead-Based Paint Activities Rule.

  17. Effects of Upgrade Versus De Novo Cardiac Resynchronization Therapy on Clinical Response and Long-Term Survival: Results from a Multicenter Study.

    Science.gov (United States)

    Vamos, Mate; Erath, Julia W; Bari, Zsolt; Vagany, Denes; Linzbach, Sven P; Burmistrava, Tatsiana; Israel, Carsten W; Duray, Gabor Z; Hohnloser, Stefan H

    2017-02-01

    Benefits of cardiac resynchronization therapy (CRT) on morbidity and mortality in selected patients are well known. Although the number of upgrade procedures from single- or dual-chamber devices to CRT is increasing, there are only sparse data on the outcomes of upgrade procedures compared with de novo CRT. This study aimed to evaluate clinical response and survival in patients receiving de novo versus upgrade CRT defibrillator therapy. Prospectively collected outcome data were compared in patients undergoing de novo or upgrade CRT defibrillator implantation at 3 implant centers in Germany and Hungary. Clinical response was defined as an improvement by at least one New York Heart Association (NYHA) functional class. CRT implantation was performed in 552 consecutive patients of whom 375 underwent a de novo and 177 an upgrade procedure. Upgrade patients were more often implanted for secondary prevention, suffered more often from atrial fibrillation, chronic kidney disease, diabetes mellitus, and dyslipidemia, and had more often a non-LBBB (left bundle branch block) wide QRS complex, and lower left ventricular ejection fraction. Upgrade procedures were associated with a lower response rate compared to the de novo group (57% versus 69%, P univariate=0.008, P multivariate=0.021). During the follow-up of 37±28 months, survival was worse after upgrade compared with de novo CRT defibrillator implantations (hazard ratio, 1.65; 95% confidence interval, 1.22-2.24; P =0.001) even after careful adjustment for important baseline variables (adjusted hazard ratio, 1.68; 95% confidence interval, 1.20-2.34; P =0.002) and after propensity-score matching (propensity-adjusted hazard ratio, 1.79; 95% confidence interval, 1.08-2.95; P =0.023). Both clinical response and long-term survival were less favorable in patients undergoing CRT upgrade compared to de novo implantations. © 2017 American Heart Association, Inc.

  18. Integrative analysis of deep sequencing data identifies estrogen receptor early response genes and links ATAD3B to poor survival in breast cancer.

    Directory of Open Access Journals (Sweden)

    Kristian Ovaska

    Full Text Available Identification of responsive genes to an extra-cellular cue enables characterization of pathophysiologically crucial biological processes. Deep sequencing technologies provide a powerful means to identify responsive genes, which creates a need for computational methods able to analyze dynamic and multi-level deep sequencing data. To answer this need we introduce here a data-driven algorithm, SPINLONG, which is designed to search for genes that match the user-defined hypotheses or models. SPINLONG is applicable to various experimental setups measuring several molecular markers in parallel. To demonstrate the SPINLONG approach, we analyzed ChIP-seq data reporting PolII, estrogen receptor α (ERα, H3K4me3 and H2A.Z occupancy at five time points in the MCF-7 breast cancer cell line after estradiol stimulus. We obtained 777 ERa early responsive genes and compared the biological functions of the genes having ERα binding within 20 kb of the transcription start site (TSS to genes without such binding site. Our results show that the non-genomic action of ERα via the MAPK pathway, instead of direct ERa binding, may be responsible for early cell responses to ERα activation. Our results also indicate that the ERα responsive genes triggered by the genomic pathway are transcribed faster than those without ERα binding sites. The survival analysis of the 777 ERα responsive genes with 150 primary breast cancer tumors and in two independent validation cohorts indicated the ATAD3B gene, which does not have ERα binding site within 20 kb of its TSS, to be significantly associated with poor patient survival.

  19. Immunological and biological changes during ipilimumab treatment and their potential correlation with clinical response and survival in patients with advanced melanoma.

    Science.gov (United States)

    Simeone, Ester; Gentilcore, Giusy; Giannarelli, Diana; Grimaldi, Antonio M; Caracò, Corrado; Curvietto, Marcello; Esposito, Assunta; Paone, Miriam; Palla, Marco; Cavalcanti, Ernesta; Sandomenico, Fabio; Petrillo, Antonella; Botti, Gerardo; Fulciniti, Franco; Palmieri, Giuseppe; Queirolo, Paola; Marchetti, Paolo; Ferraresi, Virginia; Rinaldi, Gaetana; Pistillo, Maria Pia; Ciliberto, Gennaro; Mozzillo, Nicola; Ascierto, Paolo A

    2014-07-01

    Ipilimumab can induce durable disease control and long-term survival in patients with metastatic melanoma. Identification of a biomarker that correlates with clinical benefit and potentially provides an early marker of response is an active area of research. Ipilimumab was available upon physician request for patients aged ≥16 years with stage III (unresectable) or IV cutaneous, ocular or mucosal melanoma, who had failed or did not tolerate previous treatments and had no other therapeutic option available. Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. Tumour assessments were conducted at baseline, Week 12 and Week 24 using immune-related response criteria. Patients were monitored continuously for adverse events (AEs), including immune-related AEs. Candidate immunological markers were evaluated in peripheral blood and sera samples collected at baseline and Weeks 4, 7, 10 and 12. Among 95 patients treated with ipilimumab 3 mg/kg, the immune-related disease control rate at Week 24 was 38 %. With a median follow-up of 24 months, median overall survival was 9.6 months. Both disease control and survival were significantly associated with decreasing levels of lactate dehydrogenase, C-reactive protein and FoxP3/regulatory T cells, and increasing absolute lymphocyte count, between baseline and the end of dosing (Week 12). Ipilimumab is a feasible treatment option for heavily pretreated patients with metastatic melanoma. Changes in some immunological markers between baseline and the fourth ipilimumab infusion appear to be associated with disease control and survival, but verification in prospective clinical trials is required.

  20. The natural killer cell response and tumor debulking are associated with prolonged survival in recurrent glioblastoma patients receiving dendritic cells loaded with autologous tumor lysates

    Science.gov (United States)

    Pellegatta, Serena; Eoli, Marica; Frigerio, Simona; Antozzi, Carlo; Bruzzone, Maria Grazia; Cantini, Gabriele; Nava, Sara; Anghileri, Elena; Cuppini, Lucia; Cuccarini, Valeria; Ciusani, Emilio; Dossena, Marta; Pollo, Bianca; Mantegazza, Renato; Parati, Eugenio A.; Finocchiaro, Gaetano

    2013-01-01

    Recurrent glioblastomas (GBs) are highly aggressive tumors associated with a 6–8 mo survival rate. In this study, we evaluated the possible benefits of an immunotherapeutic strategy based on mature dendritic cells (DCs) loaded with autologous tumor-cell lysates in 15 patients affected by recurrent GB. The median progression-free survival (PFS) of this patient cohort was 4.4 mo, and the median overall survival (OS) was 8.0 mo. Patients with small tumors at the time of the first vaccination (< 20 cm3; n = 8) had significantly longer PFS and OS than the other patients (6.0 vs. 3.0 mo, p = 0.01; and 16.5 vs. 7.0 mo, p = 0.003, respectively). CD8+ T cells, CD56+ natural killer (NK) cells and other immune parameters, such as the levels of transforming growth factor β, vascular endothelial growth factor, interleukin-12 and interferon γ (IFNγ), were measured in the peripheral blood and serum of patients before and after immunization, which enabled us to obtain a vaccination/baseline ratio (V/B ratio). An increased V/B ratio for NK cells, but not CD8+ T cells, was significantly associated with prolonged PFS and OS. Patients exhibiting NK-cell responses were characterized by high levels of circulating IFNγ and E4BP4, an NK-cell transcription factor. Furthermore, the NK cell V/B ratio was inversely correlated with the TGFβ2 and VEGF V/B ratios. These results suggest that tumor-loaded DCs may increase the survival rate of patients with recurrent GB after effective tumor debulking, and emphasize the role of the NK-cell response in this therapeutic setting. PMID:23802079

  1. Bioclimatic thresholds, thermal constants and survival of mealybug, Phenacoccus solenopsis (hemiptera: pseudococcidae) in response to constant temperatures on hibiscus.

    Science.gov (United States)

    Sreedevi, Gudapati; Prasad, Yenumula Gerard; Prabhakar, Mathyam; Rao, Gubbala Ramachandra; Vennila, Sengottaiyan; Venkateswarlu, Bandi

    2013-01-01

    Temperature-driven development and survival rates of the mealybug, Phenacoccussolenopsis Tinsley (Hemiptera: Pseudococcidae) were examined at nine constant temperatures (15, 20, 25, 27, 30, 32, 35 and 40°C) on hibiscus (Hibiscusrosa -sinensis L.). Crawlers successfully completed development to adult stage between 15 and 35°C, although their survival was affected at low temperatures. Two linear and four nonlinear models were fitted to describe developmental rates of P. solenopsis as a function of temperature, and for estimating thermal constants and bioclimatic thresholds (lower, optimum and upper temperature thresholds for development: Tmin, Topt and Tmax, respectively). Estimated thresholds between the two linear models were statistically similar. Ikemoto and Takai's linear model permitted testing the equivalence of lower developmental thresholds for life stages of P. solenopsis reared on two hosts, hibiscus and cotton. Thermal constants required for completion of cumulative development of female and male nymphs and for the whole generation were significantly lower on hibiscus (222.2, 237.0, 308.6 degree-days, respectively) compared to cotton. Three nonlinear models performed better in describing the developmental rate for immature instars and cumulative life stages of female and male and for generation based on goodness-of-fit criteria. The simplified β type distribution function estimated Topt values closer to the observed maximum rates. Thermodynamic SSI model indicated no significant differences in the intrinsic optimum temperature estimates for different geographical populations of P. solenopsis. The estimated bioclimatic thresholds and the observed survival rates of P. solenopsis indicate the species to be high-temperature adaptive, and explained the field abundance of P. solenopsis on its host plants.

  2. Survival and growth responses of Jatropha curcas L. to three restoration techniques on degraded soils in Burkina Faso

    Directory of Open Access Journals (Sweden)

    François Wenemi Kagambèga

    2013-12-01

    Full Text Available Land degradation is a major problem in the Sahelian countries. Erosion control through establishment of vegetation cover is at important strategy to reverse the trend. Our research objective was to analyse the e-ffects of three restoration techniques on Jatropha curcas L. seedlings growth and survivorship. Were conducted two separate field trials, involving the sowing and planting of J. curcas, in which several different soil restoration techniques were applied. The trial was monitored using a ran-domized block study design over a period of two years. The design included ten different treatments, six in the sowing trial and four in the planting trial, each with three replicates. In the first experiment, growth rate was found to be significantly higher in the Sub-Soiling treatment, that received additional organic matter than other treatments. However, overall survival rate was low (18%. In the second experiment, the Half-moon treatment yielded a significantly higher growth both in height (df = 3, F = 56.74, p < 0.05 and diameter (df = 3, F = 31.76, p < 0.05 and survival rate compared to those of the other treatments (df = 3, F = 50.4, p < 0.05. In conclusion, planting seedlings produced a greater survival rate than sowing seeds. Among tested the soil restoration and water conservation techniques the Half-moon technique was found as the most effective. This is recommended to be used for improving the revegetation of J. curcas in the future. 

  3. Frequency of Class I and II HLA alleles in patients with lung cancer according to chemotherapy response and 5-year survival.

    Science.gov (United States)

    Araz, Omer; Ucar, Elif Yilmazel; Meral, Mehmet; Yalcin, Aslıhan; Acemoglu, Hamit; Dogan, Hasan; Karaman, Adem; Aydin, Yener; Gorguner, Metin; Akgun, Metin

    2015-07-01

    Lung cancer is the most common cause of cancer death in the world, and the most common type is non-small-cell lung cancer (NSCLC). At present, surgical resection, chemotherapy, and radiation therapy are the main treatments for patients with NSCLC, but unfortunately outcome remains unsatisfactory. This study aimed to determine whether Class I and II histocompatibility leukocyte antigen (HLA) alleles are related with response to chemotherapy and survival of lung cancer. A total of 65 NSCLC patients (56 men and 9 women, mean age 58.4 ± 11 years) were included in the study. Patient groups were compared with a control group of 88 unrelated healthy kidney or bone marrow donors in order to clearly identify susceptible and protective HLA alleles in lung cancer. Target lesions and tumor response were assessed using the Response Evaluation Criteria for Solid Tumors (RECIST) guidelines. Results were classified into two groups: complete-partial response and stable-progressive disease. We found that expression of HLA-A32, HLA-B41, HLA-B57, HLA-DRB1*13, and HLA-DQ5 were more frequent in the complete and partial response groups to chemotherapy than in the control group. The frequency of HLA-A11, HLA-A29, HLA-BW6, HLA-CW3, HLA-DR1*1, and HLA-DRB1*3 were determined to be higher in the stable and progressive disease groups taking chemotherapy than in the control group. Additionally, expressions of HLA-A2 and HLA-B49 were statistically related with 5-year survival. Our results suggested that expressions of HLA-BW6 and HLA-DRB1*13 alleles may be predictable markers for response to chemotherapy in lung cancer patients. © 2014 John Wiley & Sons Ltd.

  4. Survival, growth, detoxifying and antioxidative responses of earthworms (Eisenia fetida) exposed to soils with industrial DDT contamination.

    Science.gov (United States)

    Shi, Yajuan; Zhang, Qiangbin; Huang, Dunqi; Zheng, Xiaoqi; Shi, Yajing

    2016-03-01

    The survival, growth, activity of the biotransformation system phase II enzyme glutathione-S-transferase (GST) and the oxidative defense enzyme catalase (CAT) of earthworms exposed to the contaminated soils from a former DDT plant and reference soils were investigated, and compared with the corresponding indicators in simulated soil-earthworm system, unpolluted natural soils with spiked-in DDT series, to identify the toxic effects of DDT on earthworms and their cellular defense system in complex soil system. The results indicated that DDT level in the contaminated soils was significantly higher than that in the reference soils with similar level of other pollutants and soil characters. The mortality, growth inhibition rates, GST and CST activities of earthworms exposed to the contaminated soils were significantly higher than that in reference soils. The contribution of historical DDT in contaminated soils to earthworms was confirmed by the DDT spiked tests. DDT spiked in soils at rates of higher than 200 mg·kg(-1) was significantly toxic to both the survival and the growth of earthworms. DDT significantly stimulated GST and CAT activity in earthworms after 14 days. The CAT and GST activities were also stimulated by DDT exposure at rates of 100 mg·kg(-1) after chronic exposure (42 days). The results provide implications for validating the extrapolation from laboratory simulated soils criteria to contaminated soils and for making site risk assessments. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Molecular response assessed by {sup 68}Ga-DOTANOC and survival after {sup 90}Y microsphere therapy in patients with liver metastases from neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Filippi, Luca; Salvatori, Rita; Bagni, Oreste [Santa Maria Goretti Hospital, Department of Nuclear Medicine, Latina (Italy); Scopinaro, Francesco [Sant' Andrea Hospital, Department of Nuclear Medicine, Rome (Italy); Pelle, Giuseppe; Cianni, Roberto [Santa Maria Goretti Hospital, Department of Interventional Radiology, Latina (Italy); Schillaci, Orazio [University Tor Vergata, Department of Biomedicine and Prevention, Rome (Italy)

    2016-03-15

    We investigated the prognostic role of {sup 68}Ga-DOTANOC in patients affected by hepatic metastases from neuroendocrine tumours (NET) undergoing {sup 90}Y radioembolization ({sup 90}Y-RE). A group of 15 consecutive patients with unresectable NET liver metastases underwent {sup 68}Ga-DOTANOC PET at baseline and 6 weeks after {sup 90}Y-RE. Molecular response was defined as a reduction of >50 % in the tumour-to-spleen ratio (ΔT/S). The patients were divided into two groups (responders with ΔT/S >50 % and nonresponders with ΔT/S <50 %) Patients were followed up by imaging and laboratory tests every 3 months until death or for at least 36 months following {sup 90}Y-RE. Statistical analysis was performed to identify factors predicting overall survival (OS) and progression-free survival (PFS). A decrease in T/S ratio was seen in all patients on {sup 68}Ga-DOTANOC PET scans performed after {sup 90}Y-RE. Nine patients were classified as responders and six as nonresponders. The mean OS in all patients was 31.0 months. Responders had a significantly (p < 0.001) longer OS (mean 36.0 ± 2.5 months) and PFS (mean 29.7 ± 3.4 months) than nonresponders. In a multivariate analysis, none of the other examined variables including age, unilobar vs. bilobar locations, bilirubin levels, radiological response or the presence of extrahepatic disease significantly predicted patient outcome. Molecular response assessed with {sup 68}Ga-DOTANOC PET might be a useful predictor of survival in patients affected by NET liver metastases treated with {sup 90}Y-RE. (orig.)

  6. Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival

    NARCIS (Netherlands)

    Chang, Howard Y.; Nuyten, Dimitry S. A.; Sneddon, Julie B.; Hastie, Trevor; Tibshirani, Robert; Sørlie, Therese; Dai, Hongyue; He, Yudong D.; van't Veer, Laura J.; Bartelink, Harry; van de Rijn, Matt; Brown, Patrick O.; van de Vijver, Marc J.

    2005-01-01

    Based on the hypothesis that features of the molecular program of normal wound healing might play an important role in cancer metastasis, we previously identified consistent features in the transcriptional response of normal fibroblasts to serum, and used this "wound-response signature" to reveal

  7. Predominance of Th1 response, increase of megakaryocytes and Kupffer cells are related to survival in Trypanosoma cruzi infected mice treated with Lycopodium clavatum.

    Science.gov (United States)

    Falkowski-Temporini, Gislaine Janaina; Lopes, Carina Ribeiro; Massini, Paula Fernanda; Brustolin, Camila Fernanda; Sandri, Patricia Flora; Ferreira, Érika Cristina; Aleixo, Denise Lessa; Pala, Nelson Roberto; de Araújo, Silvana Marques

    2016-12-01

    We investigated the number of megakaryocytes, Kupffer cells and ratios of Th1/Th2 and Th1/Th17 cytokines in survival of mice infected with Y strain of Trypanosoma cruzi and treated with Lycopodium clavatum. In a blind, randomized and controlled assay, Swiss male mice, 8weeks-old, infected with 1400 trypomastigotes (Y strain) were divided into groups and treated with: GLy - Lycopodium clavatum dynamization13c and GCI - alcohol solution 7° GL (vehicle medicine). The treatment was offered two days before infection and on the 2nd, 4th and 6th days after infection, overnight (1mL/100mL) and ad libitum. Parameters assessed were: survival rate, number of megakaryocytes and Kupffer cells, cytokines dosage (TNF-α, IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-17), Th1/Th2 and Th1/Th17 ratios. The increase in megakaryocytes, Kupffer cells, predominance of Th1 response, with increased TNF-α, IL-10, TNF-α/IL-4, TNF-α/IL-17 and decreased IL-6 IL-6/IL-4, are related to increased survival in mice infected with T. cruzi and treated with Lycopodium clavatum 13c. This result demonstrates the possibility of an alternative approach for the treatment of Chagas disease with dynamized drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Acid tolerance response induced in the biocontrol agent Pantoea agglomerans CPA-2 and effect on its survival ability in acidic environments.

    Science.gov (United States)

    Cañamás, T P; Viñas, I; Abadias, M; Usall, J; Torres, R; Teixidó, N

    2009-01-01

    The aim of this work was to optimize acid stress conditions for induction of acid tolerance response (ATR) in the biocontrol agent Pantoea agglomerans and study the effect of ATR induced on the ability to survive under acidic conditions. Initially, Pantoea agglomerans was grown in mild acidic conditions (pH 6.0, 5.5, 5.0 and 4.0) in order to induce ATR. The highest ATR was induced at initial pH of 5 using malic or citric acid. A first in vitro experiment was carried out. Thus, basal liquid medium at different pHs (3.0, 3.5, 4.0 and non-acidified) were then inoculated with acid-adapted and non-adapted inocula of P. agglomerans and survivals were examined during incubation at 25 or 4 degrees C. It was found that acid adaptation enhanced the survivals of Pantoea agglomerans CPA-2 cells at pH levels at which the cells were unable to grow (Pantoea agglomerans to mild acidic conditions could induce acid resistance in this biocontrol agent.

  9. Radiation dose ≥54 Gy and CA 19–9 response are associated with improved survival for unresectable, non-metastatic pancreatic cancer treated with chemoradiation

    Directory of Open Access Journals (Sweden)

    Golden Daniel W

    2012-09-01

    Full Text Available Abstract Background Unresectable pancreatic cancer (UPC has low survival. With improving staging techniques and systemic therapy, local control in patients without metastatic disease may have increasing importance. We investigated whether the radiation dose used in chemoradiation (CRT as definitive treatment for UPC and the CA 19–9 response to therapy have an impact on overall survival (OS. Methods From 1997–2009 46 patients were treated with CRT for non-metastatic UPC. Median prescribed RT dose was 54 Gy (range 50.4-59.4 Gy. All patients received concurrent chemotherapy (41: 5-fluorouracil, 5: other and 24 received adjuvant chemotherapy. Results 41 patients were inoperable due to T4 disease and 5 patients with T3 disease were medically inoperable. Five patients did not complete CRT due to progressive disease or treatment-related toxicity (median RT dose 43.2 Gy. Overall, 42 patients were dead of disease at the time of last follow-up. The median and 12 month OS were 8.8 months and 35%, respectively. By univariate analysis, minimum CA 19–9 post-CRT Conclusions CRT as definitive treatment for UPC had low survival. However, our retrospective data suggest that patients treated to ≥54 Gy or observed to have a minimum post-CRT CA 19–9

  10. 1988 Underground Storage Tanks; Technical Requirements; Final Rule and Underground Storage Tanks Containing Petroleum-Financial Responsibility Requirements and State Program Approval Objective; Final Rule

    Science.gov (United States)

    EPA's 1988 regulations concerning USTs are contained in 40 CFR Part 280, 40 CFR Part 281 and 40 CFR Parts 282.50-282.105 and divided into three sections: technical requirements, financial responsibility requirements, and state program approval objectives.

  11. Stress Survival Islet 2, Predominantly Present in Listeria monocytogenes Strains of Sequence Type 121, Is Involved in the Alkaline and Oxidative Stress Responses.

    Science.gov (United States)

    Harter, Eva; Wagner, Eva Maria; Zaiser, Andreas; Halecker, Sabrina; Wagner, Martin; Rychli, Kathrin

    2017-08-15

    The foodborne pathogen Listeria monocytogenes is able to survive a variety of stress conditions leading to the colonization of different niches like the food processing environment. This study focuses on the hypervariable genetic hot spot lmo0443 to lmo0449 haboring three inserts: the stress survival islet 1 (SSI-1), the single-gene insert LMOf2365_0481 , and two homologous genes of the nonpathogenic species Listeria innocua : lin0464 , coding for a putative transcriptional regulator, and lin0465 , encoding an intracellular PfpI protease. Our prevalence study revealed a different distribution of the inserts between human and food-associated isolates. The lin0464-lin0465 insert was predominantly found in food-associated strains of sequence type 121 (ST121). Functional characterization of this insert showed that the putative PfpI protease Lin0465 is involved in alkaline and oxidative stress responses but not in acidic, gastric, heat, cold, osmotic, and antibiotic stresses. In parallel, deletion of lin0464 decreased survival under alkaline and oxidative stresses. The expression of both genes increased significantly under oxidative stress conditions independently of the alternative sigma factor σ B Furthermore, we showed that the expression of the protease gene lin0465 is regulated by the transcription factor lin0464 under stress conditions, suggesting that lin0464 and lin0465 form a functional unit. In conclusion, we identified a novel stress survival islet 2 (SSI-2), predominantly present in L. monocytogenes ST121 strains, beneficial for survival under alkaline and oxidative stresses, potentially supporting adaptation and persistence of L. monocytogenes in food processing environments. IMPORTANCE Listeria monocytogenes strains of ST121 are known to persist for months and even years in food processing environments, thereby increasing the risk of food contamination and listeriosis. However, the molecular mechanism underlying this remarkable niche-specific adaptation

  12. Stress Survival Islet 2, Predominantly Present in Listeria monocytogenes Strains of Sequence Type 121, Is Involved in the Alkaline and Oxidative Stress Responses

    Science.gov (United States)

    Harter, Eva; Wagner, Eva Maria; Zaiser, Andreas; Halecker, Sabrina; Wagner, Martin

    2017-01-01

    ABSTRACT The foodborne pathogen Listeria monocytogenes is able to survive a variety of stress conditions leading to the colonization of different niches like the food processing environment. This study focuses on the hypervariable genetic hot spot lmo0443 to lmo0449 haboring three inserts: the stress survival islet 1 (SSI-1), the single-gene insert LMOf2365_0481, and two homologous genes of the nonpathogenic species Listeria innocua: lin0464, coding for a putative transcriptional regulator, and lin0465, encoding an intracellular PfpI protease. Our prevalence study revealed a different distribution of the inserts between human and food-associated isolates. The lin0464-lin0465 insert was predominantly found in food-associated strains of sequence type 121 (ST121). Functional characterization of this insert showed that the putative PfpI protease Lin0465 is involved in alkaline and oxidative stress responses but not in acidic, gastric, heat, cold, osmotic, and antibiotic stresses. In parallel, deletion of lin0464 decreased survival under alkaline and oxidative stresses. The expression of both genes increased significantly under oxidative stress conditions independently of the alternative sigma factor σB. Furthermore, we showed that the expression of the protease gene lin0465 is regulated by the transcription factor lin0464 under stress conditions, suggesting that lin0464 and lin0465 form a functional unit. In conclusion, we identified a novel stress survival islet 2 (SSI-2), predominantly present in L. monocytogenes ST121 strains, beneficial for survival under alkaline and oxidative stresses, potentially supporting adaptation and persistence of L. monocytogenes in food processing environments. IMPORTANCE Listeria monocytogenes strains of ST121 are known to persist for months and even years in food processing environments, thereby increasing the risk of food contamination and listeriosis. However, the molecular mechanism underlying this remarkable niche

  13. Baicalin improves survival in a murine model of polymicrobial sepsis via suppressing inflammatory response and lymphocyte apoptosis.

    Directory of Open Access Journals (Sweden)

    Jiali Zhu

    Full Text Available BACKGROUND: An imbalance between overwhelming inflammation and lymphocyte apoptosis is the main cause of high mortality in patients with sepsis. Baicalin, the main active ingredient of the Scutellaria root, exerts anti-inflammatory, anti-apoptotic, and even antibacterial properties in inflammatory and infectious diseases. However, the therapeutic effect of baicalin on polymicrobial sepsis remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: Polymicrobial sepsis was induced by cecal ligation and puncture (CLP in C57BL/6 mice. Mice were infused with baicalin intraperitoneally at 1 h, 6 h and 12 h after CLP. Survival rates were assessed over the subsequent 8 days. Bacterial burdens in blood and peritoneal cavity were calculated to assess the bacterial clearance. Neutrophil count in peritoneal lavage fluid was also calculated. Injuries to the lung and liver were detected by hematoxylin and eosin staining. Levels of cytokines, including tumor necrosis factor (TNF-alpha, interleukin (IL-6, IL-10 and IL-17, in blood and peritoneum were measured by enzyme-linked immunosorbent assay. Adaptive immune function was assessed by apoptosis of lymphocytes in the thymus and counts of different cell types in the spleen. Baicalin significantly enhanced bacterial clearance and improved survival of septic mice. The number of neutrophils in peritoneal lavage fluid was reduced by baicalin. Less neutrophil infiltration of the lung and liver in baicalin-treated mice was associated with attenuated injuries to these organs. Baicalin significantly reduced the levels of proinflammatory cytokines but increased the level of anti-inflammatory cytokine in blood and peritoneum. Apoptosis of CD3(+ T cell was inhibited in the thymus. The numbers of CD4(+, CD8(+ T lymphocytes and dendritic cells (DCs were higher, while the number of CD4(+CD25(+ regulatory T cells was lower in the baicalin group compared with the CLP group. CONCLUSIONS/SIGNIFICANCE: Baicalin improves survival of mice

  14. T3SS effector VopL inhibits the host ROS response, promoting the intracellular survival of Vibrio parahaemolyticus.

    Science.gov (United States)

    de Souza Santos, Marcela; Salomon, Dor; Orth, Kim

    2017-06-01

    The production of antimicrobial reactive oxygen species by the nicotinamide dinucleotide phosphate (NADPH) oxidase complex is an important mechanism for control of invading pathogens. Herein, we show that the gastrointestinal pathogen Vibrio parahaemolyticus counteracts reactive oxygen species (ROS) production using the Type III Secretion System 2 (T3SS2) effector VopL. In the absence of VopL, intracellular V. parahaemolyticus undergoes ROS-dependent filamentation, with concurrent limited growth. During infection, VopL assembles actin into non-functional filaments resulting in a dysfunctional actin cytoskeleton that can no longer mediate the assembly of the NADPH oxidase at the cell membrane, thereby limiting ROS production. This is the first example of how a T3SS2 effector contributes to the intracellular survival of V. parahaemolyticus, supporting the establishment of a protective intracellular replicative niche.

  15. T3SS effector VopL inhibits the host ROS response, promoting the intracellular survival of Vibrio parahaemolyticus.

    Directory of Open Access Journals (Sweden)

    Marcela de Souza Santos

    2017-06-01

    Full Text Available The production of antimicrobial reactive oxygen species by the nicotinamide dinucleotide phosphate (NADPH oxidase complex is an important mechanism for control of invading pathogens. Herein, we show that the gastrointestinal pathogen Vibrio parahaemolyticus counteracts reactive oxygen species (ROS production using the Type III Secretion System 2 (T3SS2 effector VopL. In the absence of VopL, intracellular V. parahaemolyticus undergoes ROS-dependent filamentation, with concurrent limited growth. During infection, VopL assembles actin into non-functional filaments resulting in a dysfunctional actin cytoskeleton that can no longer mediate the assembly of the NADPH oxidase at the cell membrane, thereby limiting ROS production. This is the first example of how a T3SS2 effector contributes to the intracellular survival of V. parahaemolyticus, supporting the establishment of a protective intracellular replicative niche.

  16. Change in contrast enhancement of HCC on 1-month follow-up CT after local radiotherapy: An early predictor of final treatment response

    International Nuclear Information System (INIS)

    Kim, Eun Young; Choi, Dongil; Lim, Do Hoon; Lee, Won Jae; Yoo, Byung Chul; Paik, Seung Woon

    2009-01-01

    Background: The purpose of this study was to evaluate the change in contrast enhancement of HCC on 1-month follow-up CT after local radiotherapy (RT) as an early predictor of final treatment response. Materials: Fifty patients who underwent local RT for HCCs had both pre-RT and post-RT CT scans including 1-month follow-up CT. We assessed the final treatment response by using the change in maximal tumor size on 6-12-month follow-up CT scan after RT. We also evaluated the change in tumor enhancement between pre-RT and 1-month follow-up CT scans. Results: A final treatment response was achieved in 27 (54%) of 50 patients, who showed either a complete response (n = 11) or a partial response (n = 16). Compared with non-responsive patients (n = 23), responsive patients showed a significant decrease in tumor enhancement on 1-month follow-up CT after RT in both objective and subjective analyses (each P < 0.001). Conclusion: The change in contrast enhancement of HCC seen on the 1-month follow-up CT in patients after local RT may be used as an early predictor of final treatment response.

  17. Review and Response to the Final Report of the National Black Health Providers Task Force on High Blood Pressure Education and Control.

    Science.gov (United States)

    Public Health Service (DHHS), Rockville, MD.

    This report presents the National Heart, Lung, and Blood Institute's (NHLBI) review of and response to the final report of the National Black Health Providers Task Force on High Blood Pressure Education and Control. The response includes a statement of NHLBI's involvement in health research, and descriptions of what steps can be taken to solve the…

  18. Predictive factors for response and prognostic factors for long-term survival in consecutive, single institution patients with locally advanced and/or metastatic transitional cell carcinoma following cisplatin-based chemotherapy

    DEFF Research Database (Denmark)

    Jessen, Christian; Agerbaek, Mads; Von Der Maase, Hans

    2009-01-01

    PURPOSE: The study was undertaken to identify pre-treatment clinical and histopathological factors of importance for response and survival after cisplatin-based combination chemotherapy, in patients with locally advanced or metastatic transitional cell carcinoma of the urothelium. PATIENTS...

  19. Multinationals and plant survival

    DEFF Research Database (Denmark)

    Bandick, Roger

    2010-01-01

    -parametric estimates show that domestic MNE plants are more likely to exit the market than other plants, also when controlling for plant-specific differences. Finally, foreign presence in the market seems to have had a negative impact on the survival rate of plants in non-exporting non- MNEs, but not to have affected...

  20. Relationship between the temporal changes in positron-emission-tomography-imaging-based textural features and pathologic response and survival in esophageal cancer patients

    Directory of Open Access Journals (Sweden)

    Stephen ShingFan Yip

    2016-03-01

    Full Text Available Purpose: Although change in SUV measures and PET-based textural features during treatment have shown promise in tumor response prediction, it is unclear which quantitative measure is the most predictive. We compared the relationship between PET-based features and pathologic response and overall survival with the SUV measures in esophageal cancer. Methods: Fifty-four esophageal cancer patients received PET/CT scans before and after chemo-radiotherapy. Of these, 45 patients underwent surgery and were classified into complete, partial, and non-responders to the preoperative chemoradiation. SUVmax and SUVmean, two co-occurrence matrix (Entropy and Homogeneity, two run-length-matrix (High-gray-run-emphasis and Short-run-high-gray-run-emphasis, and two size-zone-matrix (High-gray-zone-emphasis and Short-zone-high-gray-emphasis textures were computed. The relationship between the relative difference of each measure at different treatment time points and the pathologic response and overall survival was assessed using the area under the receiver-operating-characteristic curve (AUC and Kaplan-Meier statistics respectively. Results: All Textures, except Homogeneity, were better related to pathologic response than SUVmax and SUVmean. Entropy was found to significantly distinguish non-responders from the complete (AUC=0.79, p=1.7x10^-4 and partial (AUC=0.71, p=0.01 responders. Non-responders can also be significantly differentiated from partial and complete responders by the change in the run length and size zone matrix textures (AUC=0.71‒0.76, p≤0.02. Homogeneity, SUVmax and SUVmean failed to differentiate between any of the responders (AUC=0.50‒0.57, p≥0.46. However, none of the measures were found to significantly distinguish between complete and partial responders with AUC0.25. Conclusions: For the patients studied, temporal change in Entropy and all Run length matrix were better correlated with pathological response and survival than the SUV

  1. Oleate protects beta-cells from the toxic effect of palmitate by activating pro-survival pathways of the ER stress response.

    Science.gov (United States)

    Sargsyan, Ernest; Artemenko, Konstantin; Manukyan, Levon; Bergquist, Jonas; Bergsten, Peter

    2016-09-01

    Long-term exposure of beta cells to saturated fatty acids impairs insulin secretion and increases apoptosis. In contrast, unsaturated fatty acids protect beta-cells from the long-term negative effects of saturated fatty acids. We aimed to identify the mechanisms underlying this protective action of unsaturated fatty acids. To address the aim, insulin-secreting MIN6 cells were exposed to palmitate in the absence or presence of oleate and analyzed by using nano-LC MS/MS based proteomic approach. Important findings were validated by using alternative approaches. Proteomic analysis identified 34 proteins differentially expressed in the presence of palmitate compared to control samples. These proteins play a role in insulin processing, mitochondrial function, metabolism of biomolecules, calcium homeostasis, exocytosis, receptor signaling, ER protein folding, antioxidant activity and anti-apoptotic function. When oleate was also present during culture, expression of 15 proteins was different from the expression in the presence of palmitate alone. Most of the proteins affected by oleate are targets of the ER stress response and play a pro-survival role in beta cells such as protein folding and antioxidative defence. We conclude that restoration of pro-survival pathways of the ER stress response is a major mechanism underlying the protective effect of unsaturated fatty acids in beta-cells treated with saturated fatty acids. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Growth, water relations, and survival of drought-exposed seedlings from six families of honey mesquite (Prosopis glandulosa): responses to CO{sub 2} enrichment

    Energy Technology Data Exchange (ETDEWEB)

    Polley, H. W.; Tischler, C. R.; Johnson, H. B.; Pennington, R. E. [USDA, ARS, Grassland, Soil and Water Research Laboratory, Temple, TX (United States)

    1999-05-01

    The effects of carbon dioxide enrichment on seedling survival in response to uniform rates of water depletion were studied in six maternal families of the shrub honey mesquite (Prosopis glandulosa). Three families were selected each from the arid and mesic extremes of the species distribution in the United States. Results showed that relative water content at turgor loss and osmotic potential were not affected by CO{sub 2} treatment, however, increased atmospheric CO{sub 2} concentrations increased growth, leaf production and areas, as well as midday xylem pressure potential. Transpiration per unit leaf area of seedlings decreased as the soil dried. Maternal families differed in drought resistance and several other characteristics, but differences were of similar or of smaller magnitude compared with differences between CO{sub 2} treatments. No evidence as to genetic variation in responsiveness to CO{sub 2} survivorship was discovered. It was concluded that honey mesquite abundance could be increased by elevated atmospheric CO{sub 2} concentration, assuming that seedling survival of drought can be increased. 36 refs., 4 tabs., 4 figs.

  3. Sequential transition of the injury phenotype, temperature-dependent survival and transcriptional response in Listeria monocytogenes following lethal H2O2 exposure.

    Science.gov (United States)

    Ochiai, Yoshitsugu; Yamada, Fumiya; Yoshikawa, Yuko; Mochizuki, Mariko; Takano, Takashi; Hondo, Ryo; Ueda, Fukiko

    2017-10-16

    The food-borne pathogen Listeria monocytogenes is present persistently in food processing environments, where this bacterium is exposed to various stress factors, including oxidative stress. This study aimed to elucidate the temperature-dependent response of L. monocytogenes to H 2 O 2 exposure and the phenotypic changes in colony formation by H 2 O 2 -treated bacteria. Survival curves indicated an increase in the resistance to H 2 O 2 in L. monocytogenes as the temperature decreased during the stress exposure procedure. Transcriptional induction of genes with key roles in response to H 2 O 2 , including sigB and kat, was observed at 37°C, but not at 20°C, whereas other stress response genes were induced at both temperatures. Following H 2 O 2 exposure, L. monocytogenes produced small colony phenotypes and the colony size decreased in a stress exposure duration-dependent manner. Resuscitated cells with no ability to form colonies in the absence of sodium pyruvate were also found. Our findings show the possibility that a sequential transition in the injury phenotype from small colony phenotype to resuscitated cells occurred during the course of exposure to H 2 O 2 . The higher H 2 O 2 resistance at 20°C than 37°C suggests further investigation of the response to H 2 O 2 exposure under the lower temperatures, including refrigeration temperature, which may contribute to elucidation of bacterial survival over extended time periods in food-processing environments. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Atg7 deficiency impairs host defense against Klebsiella pneumoniae by impacting bacterial clearance, survival and inflammatory responses in mice.

    Science.gov (United States)

    Ye, Yan; Li, Xuefeng; Wang, Wenxue; Ouedraogo, Kiswendsida Claude; Li, Yi; Gan, Changpei; Tan, Shirui; Zhou, Xikun; Wu, Min

    2014-09-01

    Klebsiella pneumoniae (Kp) is a Gram-negative bacterium that can cause serious infections in humans. Autophagy-related gene 7 (Atg7) has been implicated in certain bacterial infections; however, the role of Atg7 in macrophage-mediated immunity against Kp infection has not been elucidated. Here we showed that Atg7 expression was significantly increased in murine alveolar macrophages (MH-S) upon Kp infection, indicating that Atg7 participated in host defense. Knocking down Atg7 with small-interfering RNA increased bacterial burdens in MH-S cells. Using cell biology assays and whole animal imaging analysis, we found that compared with wild-type mice atg7 knockout (KO) mice exhibited increased susceptibility to Kp infection, with decreased survival rates, decreased bacterial clearance, and intensified lung injury. Moreover, Kp infection induced excessive proinflammatory cytokines and superoxide in the lung of atg7 KO mice. Similarly, silencing Atg7 in MH-S cells markedly increased expression levels of proinflammatory cytokines. Collectively, these findings reveal that Atg7 offers critical resistance to Kp infection by modulating both systemic and local production of proinflammatory cytokines. Copyright © 2014 the American Physiological Society.

  5. Essential role for cyclic-AMP responsive element binding protein 1 (CREB) in the survival of acute lymphoblastic leukemia

    NARCIS (Netherlands)

    van der Sligte, Naomi E.; Kampen, Kim R.; ter Elst, Arja; Scherpen, Frank J. G.; Meeuwsen-de Boer, Tiny G. J.; Guryev, Victor; van Leeuwen, Frank N.; Kornblau, Steven M.; de Bont, Eveline S. J. M.

    2015-01-01

    Acute lymphoblastic leukemia (ALL) relapse remains a leading cause of cancer related death in children, therefore, new therapeutic options are needed. Recently, we showed that a peptide derived from Cyclic-AMP Responsive Element Binding Protein (CREB) was highly phosphorylated in pediatric

  6. Retinoblastoma protein expression is an independent predictor of both radiation response and survival in muscle-invasive bladder cancer

    DEFF Research Database (Denmark)

    Agerbaek, M; Alsner, J; Marcussen, N

    2003-01-01

    The objective of the study was to investigate the predictive value of various clinical, biochemical, and histopathological parameters, with special emphasis on the expression of the retinoblastoma protein (pRB), on the radiation response in bladder cancer. In order to obtain a truly objective...

  7. Survival and immune response of drones of a Nosemosis tolerant honey bee strain towards N. ceranae infections.

    Science.gov (United States)

    Huang, Qiang; Kryger, Per; Le Conte, Yves; Moritz, Robin F A

    2012-03-01

    Honey bee colonies (Apis mellifera) have been selected for low level of Nosema in Denmark over decades and Nosema is now rarely found in bee colonies from these breeding lines. We compared the immune response of a selected and an unselected honey bee lineage, taking advantage of the haploid males to study its potential impact on the tolerance toward Nosema ceranae, a novel introduced microsporidian pathogen. After artificial infections of the N. ceranae spores, the lineage selected for Nosema tolerance showed a higher N. ceranae spore load, a lower mortality and an up-regulated immune response. The differences in the response of the innate immune system between the selected and unselected lineage were strongest at day six post infection. In particular genes of the Toll pathway were up-regulated in the selected strain, probably is the main immune pathway involved in N. ceranae infection response. After decades of selective breeding for Nosema tolerance in the Danish strain, it appears these bees are tolerant to N. ceranae infections. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Virtual Institute of Microbial Stress and Survival: Deduction of Stress Response Pathways in Metal and Radionuclide Reducing Microorganisms

    Energy Technology Data Exchange (ETDEWEB)

    None

    2004-04-17

    The projects application goals are to: (1) To understand bacterial stress-response to the unique stressors in metal/radionuclide contamination sites; (2) To turn this understanding into a quantitative, data-driven model for exploring policies for natural and biostimulatory bioremediation; (3) To implement proposed policies in the field and compare results to model predictions; and (4) Close the experimental/computation cycle by using discrepancies between models and predictions to drive new measurements and construction of new models. The projects science goals are to: (1) Compare physiological and molecular response of three target microorganisms to environmental perturbation; (2) Deduce the underlying regulatory pathways that control these responses through analysis of phenotype, functional genomic, and molecular interaction data; (3) Use differences in the cellular responses among the target organisms to understand niche specific adaptations of the stress and metal reduction pathways; (4) From this analysis derive an understanding of the mechanisms of pathway evolution in the environment; and (5) Ultimately, derive dynamical models for the control of these pathways to predict how natural stimulation can optimize growth and metal reduction efficiency at field sites.

  9. Transcriptome analysis of the spalax hypoxia survival response includes suppression of apoptosis and tight control of angiogenesis

    Directory of Open Access Journals (Sweden)

    Malik Assaf

    2012-11-01

    Full Text Available Abstract Background The development of complex responses to hypoxia has played a key role in the evolution of mammals, as inadequate response to this condition is frequently associated with cardiovascular diseases, developmental disorders, and cancers. Though numerous studies have used mice and rats in order to explore mechanisms that contribute to hypoxia tolerance, these studies are limited due to the high sensitivity of most rodents to severe hypoxia. The blind subterranean mole rat Spalax is a hypoxia tolerant rodent, which exhibits unique longevity and therefore has invaluable potential in hypoxia and cancer research. Results Using microarrays, transcript abundance was measured in brain and muscle tissues from Spalax and rat individuals exposed to acute and chronic hypoxia for varying durations. We found that Spalax global gene expression response to hypoxia differs from that of rat and is characterized by the activation of functional groups of genes that have not been strongly associated with the response to hypoxia in hypoxia sensitive mammals. Using functional enrichment analysis of Spalax hypoxia induced genes we found highly significant overrepresentation of groups of genes involved in anti apoptosis, cancer, embryonic/sexual development, epidermal growth factor receptor binding, coordinated suppression and activation of distinct groups of transcription factors and membrane receptors, in addition to angiogenic related processes. We also detected hypoxia induced increases of different critical Spalax hub gene transcripts, including antiangiogenic genes associated with cancer tolerance in Down syndrome human individuals. Conclusions This is the most comprehensive study of Spalax large scale gene expression response to hypoxia to date, and the first to use custom Spalax microarrays. Our work presents novel patterns that may underlie mechanisms with critical importance to the evolution of hypoxia tolerance, with special relevance to

  10. Long-term survival of patients with critical limb ischemia treated with iloprost: response rate and predictive criteria. A retrospective analysis of 102 patients.

    Science.gov (United States)

    Melillo, E; Lucaccini, E; Berchiolli, R; Adami, D; Nuti, M; Dell'Omo, G; Farina, A; Panigada, G; Roberts, A T; Meini, S

    2016-12-01

    Critical limb ischemia (CLI) patients have poor long-term prognosis. We showed that iloprost improves outcomes (major amputation and survival) up a 5-year follow-up, but it is not known if in this length of time the survival curves, of clinical responders and non-responders, differ. A retrospective study enrolling 102 consecutive patients between 2004-2008, with clinical and instrumental (ultrasound, angiography, transcutaneous tensiometry of oxygen TcpO2 and carbon dioxide TcpCO2 in the affected and contralateral limbs) diagnosis of critical ischemia. All patients received the best medical therapy. Iloprost was administered (0.5-2 ng/kg/min 6 hours/day for 2-4 weeks) in all patients initially considered unsuitable for revascularization, repeating it regularly in time every six-twelve months in the case of positive response. The minimum expected follow-up was 4 years. 71.5% of patients were treated with iloprost and the responder rate was 71.2%. Most of the patients were regularly retreated with repeated cycles. Initial median supine TcpCO2 in symptomatic limb was higher in untreated patients than those treated (58 vs. 49 mmHg; p TcpCO2 directly and significantly correlated with the highest risk of mortality and seems to represent a new accurate prognostic criterion of unfavourable short and long-term response to prostanoid. In iloprost group, major amputations were significantly reduced. Revascularization was significantly higher in non-responders (57.1% vs. 11.5%; p < 0.05). There was a significantly higher prevalence of subsequent myocardial infarction in the non-iloprost group (27.6% vs. 9.6%; p < 0.05). The survival rate of non-responders was higher than untreated up until the second year (76.2% vs. 62%; p < 0.05). At 4 years we found higher survival in patients treated with iloprost (64.3% vs. 41% in untreated; p < 0.05) and in responders (75% vs. 38.1% in non-responders; p < 0.05). Our results confirm the favourable role of iloprost on the long-term outcome

  11. Sublethal pesticide doses negatively affect survival and the cellular responses in American foulbrood-infected honeybee larvae

    Science.gov (United States)

    López, Javier Hernández; Krainer, Sophie; Engert, Antonia; Schuehly, Wolfgang; Riessberger-Gallé, Ulrike; Crailsheim, Karl

    2017-02-01

    Disclosing interactions between pesticides and bee infections is of most interest to understand challenges that pollinators are facing and to which extent bee health is compromised. Here, we address the individual and combined effect that three different pesticides (dimethoate, clothianidin and fluvalinate) and an American foulbrood (AFB) infection have on mortality and the cellular immune response of honeybee larvae. We demonstrate for the first time a synergistic interaction when larvae are exposed to sublethal doses of dimethoate or clothianidin in combination with Paenibacillus larvae, the causative agent of AFB. A significantly higher mortality than the expected sum of the effects of each individual stressor was observed in co-exposed larvae, which was in parallel with a drastic reduction of the total and differential hemocyte counts. Our results underline that characterizing the cellular response of larvae to individual and combined stressors allows unmasking previously undetected sublethal effects of pesticides in colony health.

  12. DNA mismatch repair protein MSH2 dictates cellular survival in response to low dose radiation in endometrial carcinoma cells.

    LENUS (Irish Health Repository)

    Martin, Lynn M

    2013-07-10

    DNA repair and G2-phase cell cycle checkpoint responses are involved in the manifestation of hyper-radiosensitivity (HRS). The low-dose radioresponse of MSH2 isogenic endometrial carcinoma cell lines was examined. Defects in cell cycle checkpoint activation and the DNA damage response in irradiated cells (0.2 Gy) were evaluated. HRS was expressed solely in MSH2+ cells and was associated with efficient activation of the early G2-phase cell cycle checkpoint. Maintenance of the arrest was associated with persistent MRE11, γH2AX, RAD51 foci at 2 h after irradiation. Persistent MRE11 and RAD51 foci were also evident 24 h after 0.2 Gy. MSH2 significantly enhances cell radiosensitivity to low dose IR.

  13. EBOV Protection Is Supported by T Cell-Dependent Humoral Responses But Is Not Requisite for Survival

    Science.gov (United States)

    2016-06-03

    Sabrina Stronsky, David Langan, Jesse Steffens, Sean Van 2 Tongeren, and Sina Bavari 3 Abstract 4 Despite agreement across Ebola virus (EBOV) vaccine...of antibodies can be achieved; however, B cells are obligate. 17 18 Introduction 19 Humoral immune responses are a hallmark for successful...pathogens have been limited. The recent 2014 Western Africa Ebola virus (EBOV) epidemic, 31 which affected nearly 28,000 individuals and claimed a reported

  14. Global Activities and Plant Survival

    DEFF Research Database (Denmark)

    Bandick, Roger

    2014-01-01

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

  15. General response of Salmonella enterica serovar Typhimurium to desiccation: A new role for the virulence factors sopD and sseD in survival.

    Directory of Open Access Journals (Sweden)

    Alice Maserati

    Full Text Available Salmonella can survive for long periods under extreme desiccation conditions. This stress tolerance poses a risk for food safety, but relatively little is known about the molecular and cellular regulation of this adaptation mechanism. To determine the genetic components involved in Salmonella's cellular response to desiccation, we performed a global transcriptomic analysis comparing S. enterica serovar Typhimurium cells equilibrated to low water activity (aw 0.11 and cells equilibrated to high water activity (aw 1.0. The analysis revealed that 719 genes were differentially regulated between the two conditions, of which 290 genes were up-regulated at aw 0.11. Most of these genes were involved in metabolic pathways, transporter regulation, DNA replication/repair, transcription and translation, and, more importantly, virulence genes. Among these, we decided to focus on the role of sopD and sseD. Deletion mutants were created and their ability to survive desiccation and exposure to aw 0.11 was compared to the wild-type strain and to an E. coli O157:H7 strain. The sopD and sseD mutants exhibited significant cell viability reductions of 2.5 and 1.3 Log (CFU/g, respectively, compared to the wild-type after desiccation for 4 days on glass beads. Additional viability differences of the mutants were observed after exposure to aw 0.11 for 7 days. E. coli O157:H7 lost viability similarly to the mutants. Scanning electron microscopy showed that both mutants displayed a different morphology compared to the wild-type and differences in production of the extracellular matrix under the same conditions. These findings suggested that sopD and sseD are required for Salmonella's survival during desiccation.

  16. Comparative Analysis of Matrix Metalloproteinase Family Members Reveals That MMP9 Predicts Survival and Response to Temozolomide in Patients with Primary Glioblastoma.

    Directory of Open Access Journals (Sweden)

    Qingbin Li

    Full Text Available Glioblastoma multiform (GBM is the most common malignant primary brain tumor in adults. Radiotherapy plus concomitant and adjuvant TMZ chemotherapy is the current standard of care for patients with GBM. Matrix metalloproteinases (MMPs, a family of zinc-dependent endopeptidases, are key modulators of tumor invasion and metastasis due to their ECM degradation capacity. The aim of the present study was to identify the most informative MMP member in terms of prognostic and predictive ability for patients with primary GBM.The mRNA expression profiles of all MMP genes were obtained from the Chinese Glioma Genome Atlas (CGGA, the Repository for Molecular Brain Neoplasia Data (REMBRANDT and the GSE16011 dataset. MGMT methylation status was also examined by pyrosequencing. The correlation of MMP9 expression with tumor progression was explored in glioma specimens of all grades. Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the association of MMP9 expression with survival and response to temozolomide.MMP9 was the only significant prognostic factor in three datasets for primary glioblastoma patients. Our results indicated that MMP9 expression is correlated with glioma grade (p<0.0001. Additionally, low expression of MMP9 was correlated with better survival outcome (OS: p = 0.0012 and PFS: p = 0.0066, and MMP9 was an independent prognostic factor in primary GBM (OS: p = 0.027 and PFS: p = 0.032. Additionally, the GBM patients with low MMP9 expression benefited from temozolomide (TMZ chemotherapy regardless of the MGMT methylation status.Patients with primary GBMs with low MMP9 expression may have longer survival and may benefit from temozolomide chemotherapy.

  17. Human CD6 Down-Modulation following T-Cell Activation Compromises Lymphocyte Survival and Proliferative Responses

    Directory of Open Access Journals (Sweden)

    Esther Carrasco

    2017-06-01

    Full Text Available Available evidence indicates that the CD6 lymphocyte surface receptor is involved in T-cell developmental and activation processes, by facilitating cell-to-cell adhesive contacts with antigen-presenting cells and likely modulating T-cell receptor (TCR signaling. Here, we show that in vitro activation of human T cells under different TCR-ligation conditions leads to surface downregulation of CD6 expression. This phenomenon was (i concomitant to increased levels of soluble CD6 (sCD6 in culture supernatants, (ii partially reverted by protease inhibitors, (iii not associated to CD6 mRNA down-regulation, and (iv reversible by stimulus removal. CD6 down-modulation inversely correlated with the upregulation of CD25 in both FoxP3− (Tact and FoxP3+ (Treg T-cell subsets. Furthermore, ex vivo analysis of peripheral CD4+ and CD8+ T cells with activated (CD25+ or effector memory (effector memory T cell, CD45RA−CCR7− phenotype present lower CD6 levels than their naïve or central memory (central memory T cell, CD45RA−CCR7+ counterparts. CD6lo/− T cells resulting from in vitro T-cell activation show higher apoptosis and lower proliferation levels than CD6hi T cells, supporting the relevance of CD6 in the induction of proper T-cell proliferative responses and resistance to apoptosis. Accordingly, CD6 transfectants also showed higher viability when exposed to TCR-independent apoptosis-inducing conditions in comparison with untransfected cells. Taken together, these results provide insight into the origin of sCD6 and the previously reported circulating CD6-negative T-cell subset in humans, as well as into the functional consequences of CD6 down-modulation on ongoing T-cell responses, which includes sensitization to apoptotic events and attenuation of T-cell proliferative responses.

  18. Overall survival and response pattern of castration-resistant metastatic prostate cancer to multiple cycles of radioligand therapy using [{sup 177}Lu]Lu-PSMA-617

    Energy Technology Data Exchange (ETDEWEB)

    Ahmadzadehfar, Hojjat; Wegen, Simone; Yordanova, Anna; Kuerpig, Stefan; Eppard, Elisabeth; Wei, Xiao; Schlenkhoff, Carl; Essler, Markus [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Fimmers, Rolf [University of Bonn, Institute for Medical Biometry, Informatics and Epidemiology, Bonn (Germany); Hauser, Stefan [University Hospital Bonn, Department of Urology, Bonn (Germany)

    2017-08-15

    Up to 30% of patients with castration-resistant prostate cancer (CRPC) do not show any response to the first cycle of radioligand therapy (RLT) with [{sup 177}Lu]Lu-PSMA-617 (Lu-PSMA). We evaluated patient response to the second and third cycles of RLT in patients that underwent at least three cycles. The second aim of this study was to calculate the median overall survival (OS) of responders and non-responders after the first cycle and after all three cycles of RLT. CRPC patients were treated with Lu-PSMA, with a median interval of 8 weeks between each cycle. The tumour marker prostate-specific antigen (PSA) was used as the marker for response evaluation. Fifty-two patients underwent a total of 190 cycles of RLT (3-6 cycles per patient). Of these, 80.8% showed a decline in PSA 2 months after the first cycle, with 44.2% showing a PSA decline of ≥50%. When compared to baseline PSA, 73.1% showed a PSA decline after the third cycle. 50% of patients that did not show any response to the first cycle also did not respond to the second and third cycles. The median OS was 60 weeks in all patients. The median OS was significantly longer for patients that showed any PSA decline after the first cycle compared to patients without PSA decline (68 vs. 33 weeks). There was a significant difference in median OS between responders and non-responders for a change in PSA after the third cycle compared to baseline PSA. Patients with a positive response to RLT, regardless of the rate of decline, had a significantly longer median OS. Of the patients that did not show any response to the first cycle, 50% responded to the second or third cycles. (orig.)

  19. Pathological Complete Response and Long-Term Survival in a Very Elderly Patient after Neoadjuvant Chemotherapy for Locally Advanced, Unresectable Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Kunihiko Izuishi

    2014-01-01

    Full Text Available We address the pathological complete response and long-term survival of elderly patients after neoadjuvant chemotherapy in locally advanced, unresectable gastric cancer. An 83-year-old man was hospitalized for upper abdominal pain. Gastrointestinal endoscopy showed a large tumor spanning from the gastric angle to the antrum, and extending to the duodenum. Histological analysis of the biopsy specimen revealed a poorly differentiated adenocarcinoma. Computed tomography images showed thickening of the gastric wall and invasion of the body and head of the pancreas, but did not show distant metastases. The patient was diagnosed with unresectable gastric cancer, and was treated with neoadjuvant chemotherapy using S-1 (80 mg/m2 and paclitaxel (60 mg/m2. After the third course of chemotherapy, gastrointestinal endoscopy and abdominal computed tomography revealed a remarkable reduction in tumor size. This reduction allowed distal gastrectomy to be conducted. Histological examination of the specimen revealed no cancer cells in the primary lesion or lymph nodes. The patient was treated with adjuvant chemotherapy of oral tegafur-uracil (300 mg/day for one year after surgery. He lived for five years after surgery without recurrence. Neoadjuvant chemotherapy using S-1 and paclitaxel is a potent strategy for improving survival in very elderly patients with unresectable gastric cancer.

  20. Accelerated phase chronic myeloid leukemia: evaluation of clinical criteria as predictors of survival, major cytogenetic response and progression to blast phase

    Directory of Open Access Journals (Sweden)

    Vanessa Fiorini Furtado

    2015-10-01

    Full Text Available BACKGROUND: Published criteria defining the accelerated phase in chronic myeloid leukemia are heterogeneous and little is known about predictors of poor outcome.METHODS: This is a retrospective study of 139 subjects in the accelerated phase of chronic myeloid leukemia treated with imatinib at a single center in Brazil. The objective was to identify risk factors for survival, major cytogenetic response and progression to blast phase in this population. The factors analyzed were: blasts 10-29%, basophils ≥ 20%, platelets > 1 × 106/µL or 1 × 105/µL in the peripheral blood, as well as clonal evolution, splenomegaly, hemoglobin 12 months (p-value = 0.030.CONCLUSION: These data indicate that patients with the above risk factors have a worse prognosis. This information can guide the therapy to be used.

  1. Multi-omics Analyses of Starvation Responses Reveal a Central Role for Lipoprotein Metabolism in Acute Starvation Survival in C. elegans

    DEFF Research Database (Denmark)

    Harvald, Eva Bang; Sprenger, Richard R; Dall, Kathrine Brændgaard

    2017-01-01

    Starvation causes comprehensive metabolic changes, which are still not fully understood. Here, we used quantitative proteomics and RNA sequencing to examine the temporal starvation responses in wild-type Caenorhabditis elegans and animals lacking the transcription factor HLH-30. Our findings show...... that starvation alters the abundance of hundreds of proteins and mRNAs in a temporal manner, many of which are involved in central metabolic pathways, including lipoprotein metabolism. We demonstrate that premature death of hlh-30 animals under starvation can be prevented by knockdown of either vit-1 or vit-5......, encoding two different lipoproteins. We further show that the size and number of intestinal lipid droplets under starvation are altered in hlh-30 animals, which can be rescued by knockdown of vit-1. Taken together, this indicates that survival of hlh-30 animals under starvation is closely linked...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  3. Survival Rate and Transcriptional Response upon Infection with the Generalist Parasite Beauveria bassiana in a World-Wide Sample of Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Francesco Paparazzo

    Full Text Available The ability to cope with infection by a parasite is one of the major challenges for any host species and is a major driver of evolution. Parasite pressure differs between habitats. It is thought to be higher in tropical regions compared to temporal ones. We infected Drosophila melanogaster from two tropical (Malaysia and Zimbabwe and two temperate populations (the Netherlands and North Carolina with the generalist entomopathogenic fungus Beauveria bassiana to examine if adaptation to local parasite pressures led to differences in resistance. Contrary to previous findings we observed increased survival in temperate populations. This, however, is not due to increased resistance to infection per se, but rather the consequence of a higher general vigor of the temperate populations. We also assessed transcriptional response to infection within these flies eight and 24 hours after infection. Only few genes were induced at the earlier time point, most of which are involved in detoxification. In contrast, we identified more than 4,000 genes that changed their expression state after 24 hours. This response was generally conserved over all populations with only few genes being uniquely regulated in the temperate populations. We furthermore found that the American population was transcriptionally highly diverged from all other populations concerning basal levels of gene expression. This was particularly true for stress and immune response genes, which might be the genetic basis for their elevated vigor.

  4. Ensuring survival.

    Science.gov (United States)

    Sadik, N

    1992-12-01

    The global population growth rate has been 1.7% since 1975, while for developing countries it is 2.1%. UN projections are for population to grow from 5.5 billion in 1992 to 10 billion by 2050. Sustainable development is only possible when population growth is balanced with available resources. UN medium population projections of 7.8 billion by 2050 can be reached with 187 million more couples practicing family planning (FP) by the year 2000. Within the past 20 years, 1 billion people, mostly from developed countries, have enjoyed economic growth, but have contributed polluting technologies, excessive waste, and environmentally dangerous economic practices. The generations to come will be affected by the continuance of these practices by the 1 billion affluent population. The bottom billion are mired in poverty and high population growth and survival, needs that hinder their country's economic development, upset fragile ecosystems, and destroy the balance between human beings and the environment. International migration on a large scale could be the by-product of population growth. Progress has been made since the 1974 UN Conference on Population in Bucharest. There are still, however, vulnerable populations, the poorest households, the landless and small-holder families, urban squatters and slum dwellers, those living in low lying deltas and along coasts, and women. Women control family resources and their micro environment. Sustainable development is not possible without the elimination of prejudice against women. Reproductive freedom for women must be a priority. High quality, readily available FP services are also needed for those desiring this. The difficulty is in providing FP services that conform to a woman's social and cultural background and personal needs; success is dependent on involving women in the process and holding men more responsible for FP. Development means allowing for the legitimate aspirations of the majority not just the specialized

  5. HLA superfamily assignment is a predictor of immune response to cancer testis antigens and survival in ovarian cancer.

    Science.gov (United States)

    Szender, J Brian; Eng, Kevin H; Matsuzaki, Junko; Miliotto, Anthony; Gnjatic, Sacha; Tsuji, Takemasa; Odunsi, Kunle

    2016-07-01

    To characterize the association between major histocompatibility complex (MHC) types and spontaneous antibody development to the cancer testis (CT) antigen NY-ESO-1. Tumor expression of NY-ESO-1 and serum antibodies to NY-ESO-1 were characterized in addition to human leukocyte antigen (HLA) type for patients with epithelial ovarian cancer. HLA types were assigned to structure-based superfamilies and statistical associations were examined. HLA types were compared to existing reference libraries of HLA frequencies in a European-Caucasian American population. Out of 126 patients identified, 81% were expression positive and 48% had spontaneous antibody responses to NY-ESO-1. There was an association between HLA-B superfamily and seropositivity among patients with tumors expressing NY-ESO-1 (pHLA-B superfamily assignment were driven by HLA-B44. Among all patients, the B27 superfamily was over-represented compared with the general population (pHLA type appears to be associated with spontaneous anti-CT antigen antibodies, as well as with the overall risk of ovarian cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Pretreatment with Cry1Ac Protoxin Modulates the Immune Response, and Increases the Survival of Plasmodium-Infected CBA/Ca Mice

    Directory of Open Access Journals (Sweden)

    Martha Legorreta-Herrera

    2010-01-01

    Full Text Available Malaria is a major global health problem that kills 1-2 million people each year. Despite exhaustive research, naturally acquired immunity is poorly understood. Cry1A proteins are potent immunogens with adjuvant properties and are able to induce strong cellular and humoral responses. In fact, it has been shown that administration of Cry1Ac protoxin alone or with amoebic lysates induces protection against the lethal infection caused by the protozoa Naegleria fowleri. In this work, we studied whether Cry1Ac is able to activate the innate immune response to induce protection against Plasmodium berghei ANKA (lethal and P. chabaudi AS (nonlethal parasites in CBA/Ca mice. Treatment with Cry1Ac induced protection against both Plasmodium species in terms of reduced parasitaemia, longer survival time, modulation of pro- and anti-inflammatory cytokines, and increased levels of specific antibodies against Plasmodium. Understanding how to boost innate immunity to Plasmodium infection should lead to immunologically based intervention strategies.

  7. Modelling survival

    DEFF Research Database (Denmark)

    Ashauer, Roman; Albert, Carlo; Augustine, Starrlight

    2016-01-01

    well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates...

  8. Survival Analysis

    CERN Document Server

    Miller, Rupert G

    2011-01-01

    A concise summary of the statistical methods used in the analysis of survival data with censoring. Emphasizes recently developed nonparametric techniques. Outlines methods in detail and illustrates them with actual data. Discusses the theory behind each method. Includes numerous worked problems and numerical exercises.

  9. DNA Damage Response and Repair Gene Alterations Are Associated with Improved Survival in Patients with Platinum-Treated Advanced Urothelial Carcinoma.

    Science.gov (United States)

    Teo, Min Yuen; Bambury, Richard M; Zabor, Emily C; Jordan, Emmet; Al-Ahmadie, Hikmat; Boyd, Mariel E; Bouvier, Nancy; Mullane, Stephanie A; Cha, Eugene K; Roper, Nitin; Ostrovnaya, Irina; Hyman, David M; Bochner, Bernard H; Arcila, Maria E; Solit, David B; Berger, Michael F; Bajorin, Dean F; Bellmunt, Joaquim; Iyer, Gopakumar; Rosenberg, Jonathan E

    2017-07-15

    Purpose: Platinum-based chemotherapy remains the standard treatment for advanced urothelial carcinoma by inducing DNA damage. We hypothesize that somatic alterations in DNA damage response and repair (DDR) genes are associated with improved sensitivity to platinum-based chemotherapy. Experimental Design: Patients with diagnosis of locally advanced and metastatic urothelial carcinoma treated with platinum-based chemotherapy who had exon sequencing with the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay were identified. Patients were dichotomized based on the presence/absence of alterations in a panel of 34 DDR genes. DDR alteration status was correlated with clinical outcomes and disease features. Results: One hundred patients were identified, of which 47 harbored alterations in DDR genes. Patients with DDR alterations had improved progression-free survival (9.3 vs. 6.0 months, log-rank P = 0.007) and overall survival (23.7 vs. 13.0 months, log-rank P = 0.006). DDR alterations were also associated with higher number mutations and copy-number alterations. A trend toward positive correlation between DDR status and nodal metastases and inverse correlation with visceral metastases were observed. Different DDR pathways also suggested variable impact on clinical outcomes. Conclusions: Somatic DDR alteration is associated with improved clinical outcomes in platinum-treated patients with advanced urothelial carcinoma. Once validated, it can improve patient selection for clinical practice and future study enrollment. Clin Cancer Res; 23(14); 3610-8. ©2017 AACR . ©2017 American Association for Cancer Research.

  10. A Chimeric Antibody against ACKR3/CXCR7 in Combination with TMZ Activates Immune Responses and Extends Survival in Mouse GBM Models.

    Science.gov (United States)

    Salazar, Nicole; Carlson, Jeffrey C; Huang, Kexin; Zheng, Yayue; Oderup, Cecilia; Gross, Julia; Jang, Andrew D; Burke, Thomas M; Lewén, Susanna; Scholz, Alexander; Huang, Serina; Nease, Leona; Kosek, Jon; Mittelbronn, Michel; Butcher, Eugene C; Tu, Hua; Zabel, Brian A

    2018-03-06

    Glioblastoma (GBM) is the least treatable type of brain tumor, afflicting over 15,000 people per year in the United States. Patients have a median survival of 16 months, and over 95% die within 5 years. The chemokine receptor ACKR3 is selectively expressed on both GBM cells and tumor-associated blood vessels. High tumor expression of ACKR3 correlates with poor prognosis and potential treatment resistance, making it an attractive therapeutic target. We engineered a single chain FV-human FC-immunoglobulin G1 (IgG 1 ) antibody, X7Ab, to target ACKR3 in human and mouse GBM cells. We used hydrodynamic gene transfer to overexpress the antibody, with efficacy in vivo. X7Ab kills GBM tumor cells and ACKR3-expressing vascular endothelial cells by engaging the cytotoxic activity of natural killer (NK) cells and complement and the phagocytic activity of macrophages. Combining X7Ab with TMZ allows the TMZ dosage to be lowered, without compromising therapeutic efficacy. Mice treated with X7Ab and in combination with TMZ showed significant tumor reduction by MRI and longer survival overall. Brain-tumor-infiltrating leukocyte analysis revealed that X7Ab enhances the activation of M1 macrophages to support anti-tumor immune response in vivo. Targeting ACKR3 with immunotherapeutic monoclonal antibodies (mAbs) in combination with standard of care therapies may prove effective in treating GBM. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Therapeutic administration of IL-15 superagonist complex ALT-803 leads to long-term survival and durable antitumor immune response in a murine glioblastoma model.

    Science.gov (United States)

    Mathios, Dimitrios; Park, Chul-Kee; Marcus, Warren D; Alter, Sarah; Rhode, Peter R; Jeng, Emily K; Wong, Hing C; Pardoll, Drew M; Lim, Michael

    2016-01-01

    Glioblastoma is the most aggressive primary central nervous system malignancy with a poor prognosis in patients. Despite the need for better treatments against glioblastoma, very little progress has been made in discovering new therapies that exhibit superior survival benefit than the standard of care. Immunotherapy has been shown to be a promising treatment modality that could help improve clinical outcomes of glioblastoma patients by assisting the immune system to overcome the immunosuppressive tumor environment. Interleukin-15 (IL-15), a cytokine shown to activate several effector components of the immune system, may serve as an excellent immunotherapeutic candidate for the treatment of glioblastoma. Thus, we evaluated the efficacy of an IL-15 superagonist complex (IL-15N72D:IL-15RαSu-Fc; also known as ALT-803) in a murine GL261-luc glioblastoma model. We show that ALT-803, as a single treatment as well as in combination with anti-PD-1 antibody or stereotactic radiosurgery, exhibits a robust antitumor immune response resulting in a prolonged survival including complete remission in tumor bearing mice. In addition, ALT-803 treatment results in long-term immune memory against glioblastoma tumor rechallenge. Flow cytometric analysis of tumor infiltrating immune cells shows that ALT-803 leads to increased percentage of CD8+-cell infiltration, but not the NK cells, and IFN-γ production into the tumor microenvironment. Cell depletion studies, in accordance with the flow cytometric results, show that the ALT-803 therapeutic effect is dependent on CD4+ and CD8+ cells. These results provide a rationale for evaluating the therapeutic activity of ALT-803 against glioblastoma in the clinical setting. © 2015 UICC.

  12. Prediction of neoadjuvant radiation chemotherapy response and survival using pretreatment [{sup 18}F]FDG PET/CT scans in locally advanced rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Ji-In; Ha, Seunggyun; Kim, Sang Eun [Seoul National University Bundang Hospital, Department of Nuclear Medicine, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Kang, Sung-Bum; Oh, Heung-Kwon [Seoul National University Bundang Hospital, Department of Surgery, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Lee, Keun-Wook [Seoul National University Bundang Hospital, Department of Internal Medicine, Seongnam (Korea, Republic of); Lee, Hye-Seung [Seoul National University Bundang Hospital, Department of Pathology, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Kim, Jae-Sung [Seoul National University Bundang Hospital, Department of Radiation Oncology, Seongnam (Korea, Republic of); Lee, Ho-Young [Seoul National University Bundang Hospital, Department of Nuclear Medicine, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Seoul National University, Cancer Research Institute, Seoul (Korea, Republic of)

    2016-03-15

    The aim of this study was to investigate metabolic and textural parameters from pretreatment [{sup 18}F]FDG PET/CT scans for the prediction of neoadjuvant radiation chemotherapy response and 3-year disease-free survival (DFS) in patients with locally advanced rectal cancer (LARC). We performed a retrospective review of 74 patients diagnosed with LARC who were initially examined with [{sup 18}F]FDG PET/CT, and who underwent neoadjuvant radiation chemotherapy followed by complete resection. The standardized uptake value (mean, peak, and maximum), metabolic volume (MV), and total lesion glycolysis of rectal cancer lesions were calculated using the isocontour method with various thresholds. Using three-dimensional textural analysis, about 50 textural features were calculated for PET images. Response to neoadjuvant radiation chemotherapy, as assessed by histological tumour regression grading (TRG) after surgery and 3-year DFS, was evaluated using univariate/multivariate binary logistic regression and univariate/multivariate Cox regression analyses. MVs calculated using the thresholds mean standardized uptake value of the liver + two standard deviations (SDs), and mean standard uptake of the liver + three SDs were significantly associated with TRG. Textural parameters from histogram-based and co-occurrence analysis were significantly associated with TRG. However, multivariate analysis revealed that none of these parameters had any significance. On the other hand, MV calculated using various thresholds was significantly associated with 3-year DFS, and MV calculated using a higher threshold tended to be more strongly associated with 3-year DFS. In addition, textural parameters including kurtosis of the absolute gradient (GrKurtosis) were significantly associated with 3-year DFS. Multivariate analysis revealed that GrKurtosis could be a prognostic factor for 3-year DFS. Metabolic and textural parameters from initial [{sup 18}F]FDG PET/CT scans could be indexes to assess

  13. TLR-4/miRNA-32-5p/FSTL1 signaling regulates mycobacterial survival and inflammatory responses in Mycobacterium tuberculosis-infected macrophages.

    Science.gov (United States)

    Zhang, Zhi-Min; Zhang, Ai-Rong; Xu, Min; Lou, Jun; Qiu, Wei-Qiang

    2017-03-15

    Macrophages play a pivotal role in host immune response against mycobacterial infection, which is tightly modulated by multiple factors, including microRNAs. The purpose of the present study was to investigate the biological function and potential mechanism of miR-32-5p in human macrophages during Mycobacterium tuberculosis (M.tb) infection. The results demonstrated that miR-32-5p was robustly enhanced in THP-1 and U937 cells in response to M.tb infection. TLR-4 signaling was required for upregulation of miR-32-5p induced by M.tb infection. Additionally, the introduction of miR-32-5p strongly increased the survival rate of intracellular mycobacteria, whereas inhibition of miR-32-5p suppressed intracellular growth of mycobacteria during M.tb challenged. Furthermore, forced expression of miR-32-5p dramatically attenuated the accumulation of inflammatory cytokines IL-1β, IL-6 and TNF-α induced by M.tb infection. Conversely, downregulated expression of miR-32-5p led to enhancement in these inflammatory cytokines. More importantly, our study explored that Follistatin-like protein 1 (FSTL1) was a direct and functional target of miR-32-5p. qRT-PCR and western blot analysis further validated that miR-32-5p negatively regulated the expression of FSTL1. Mechanistically, re-expression of FSTL1 attenuated the ability of miR-32-5p to promote mycobacterial survival. Meanwhile, miR-32-5p-mediated inhibition of the inflammatory cytokine production were completely reversed by overexpression of FSTL1. Collectively, our findings demonstrated a novel role of TLR-4/miRNA-32-5p/FSTL1 in the modulation of host defense against mycobacterial infection, which may provide a better understanding of the pathogenesis of tuberculosis and useful information for developing potential therapeutic interventions against the disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2

    Directory of Open Access Journals (Sweden)

    Anders Carey

    2007-09-01

    Full Text Available Abstract Background The HER2-inhibiting antibody trastuzumab, in combination with chemotherapy, significantly improves survival of women with resected, HER2-overexpressing breast cancers, but is associated with toxicities including a risk of cardiomyopathy. Additionally, the beneficial effect of trastuzumab is expected to decrease once the drug is discontinued. We proposed to address these concerns by using cancer vaccines to stimulate HER2 intracellular domain (ICD-specific T cell and antibody responses. Methods Subjects with stage II (≥ 6 +LN, III, or stage IV breast cancerwith > 50% HER2 overexpressing tumor cells who were disease-free after surgery and adjuvant therapy were eligible. Vaccines consisted of immature, cultured DC (n = 3, mature cultured DC (n = 3, or mature Flt3-ligand mobilized peripheral blood DC (n = 1 loaded with ICD, or tetanus toxoid, keyhole limpet hemocyanin or CMV peptide as controls, and were administered intradermally/subcutaneously four times at 3 week intervals. ICD-specific T cell and antibody responses were measured. Cardiac function was determined by MUGA or ECHO; long term disease status was obtained from patient contact. Results All seven patients successfully underwent DC generation and five received all 4 immunizations. There were no toxicities greater than grade 1 or ejection fraction decrements below normal. Delayed-type hypersensitivity (DTH reactions at the injection site occurred in 6/7 patients and HER2 specificity was detected by cytokine flow cytometry or ELISPOT in 5 patients. At more than 5 years of follow-up, 6/7 had detectable anti-ICD antibodies. One patient experienced a pulmonary recurrence at 4 years from their study immunizations. This recurrence was resected and they are without evidence of disease. All patients are alive and disease-free at 4.6–6.7 years of follow-up. Conclusion Although this was a small pilot study, the well-tolerated nature of the vaccines, the lack of cardiac

  15. Ki67 and lymphocytes in the pretherapeutic core biopsy of primary invasive breast cancer: positive markers of therapy response prediction and superior survival.

    Science.gov (United States)

    Schlotter, Claus M; Tietze, Lothar; Vogt, Ulf; Heinsen, Carlos Villena; Hahn, Antje

    2017-09-22

    Background Core needle biopsy plays a crucial role as diagnostic tool for BC. Both Ki67 and likely tumor-infiltrating lymphocytes (TILs) in the near future are determining the kind of systemic therapy. The role of TILs in BC is still an issue for clinical research, albeit preliminary results of neoadjuvant and adjuvant clinical studies already now highlight the crucial impact of TILs on therapy response and survival. Methods Evaluation of related publications (pubmed) and meeting abstracts (ASCO, SABCS). Results The monoclonal antibody Ki67 recognizing a nuclear antigene in proliferating cells is a positive marker of therapy response and superior survival. Endocrine responsive tumors of low proliferation (Ki67 19%) vs. tumors with lower proliferation after neoadjuvant chemotherapy (NAC). pCR-rates of up to 60% can be seen in TNBC and HR-, HER2+BC, lower pCR-rates, however, in HR+, HER2- BC. Increased stromal TILs are found in 30% of TNBC and in 19% of HR-, HER2+BC. The percentage of TILs is a significant independent parameter for pCR after NAC. Lymphocyte-predominant BC (LPBC) respond with higher pCR-rates than non-LPBC or tumors without any TILs. Increased TILs in TN and HR-, HER2+ subtypes predict benefit from addition of carboplatin to NAC. TILs are also associated with improved DFS and OS among patients with TNBC and HR-, HER2+ BC. Conversly and interestingly increased TILs in patients with HR+, HER2-(luminal) BC are associated with a 10% higher risk of death per 10% increase of TILs. Interactions between immune system and cancer are complex. The cancer-immunity cycle characterizes these interactions. BC subtypes with higher number of mutations such as TNBC and HR-, HER2+BC are considered to provide a raising number of tumor-associated antigens, thereby capable to build up a higher endogenous immune response. TILs may serve as surrogate marker of both an existing endogenous immune response and the probability to respond to cancer immune therapies. As cancer co

  16. Non-Linear Dose Response Relationships in Biology, Toxicology, and Medicine (June 8-10, 2004). Final Report

    International Nuclear Information System (INIS)

    Calabrese, Edward J.

    2004-01-01

    The conference attracts approximately 500 scientists researching in the area of non-linear low dose effects. These scientists represent a wide range of biological/medical fields and technical disciplines. Observations that biphasic dose responses are frequently reported in each of these areas but that the recognition of similar dose response relationships across disciplines is very rarely appreciated and exploited. By bringing scientist of such diverse backgrounds together who are working on the common area of non-linear dose response relationships this will enhance our understanding of the occurrence, origin, mechanism, significance and practical applications of such dose response relationships

  17. SARA: Survivable Autonomic Response Architecture

    Science.gov (United States)

    2001-03-23

    Rossey Lincoln Laboratory, Massachusetts Institute of Technology 244 Wood Street Lexington, Massachusetts 02420-9108 {scl,dvanhook, oleary ,jhaines...discussed, and these motivate the presentation of the SARA architecture. Substantial analysis indicates that the SARA architecture will be successful in...threat to the system. • Detectors. Detectors determine if sensor output (event and state data) indicates a threat to the defended system by

  18. 78 FR 19879 - Final Order in Response to a Petition From Certain Independent System Operators and Regional...

    Science.gov (United States)

    2013-04-02

    ... provisions of the CEA and Commission regulations, with the exception of the Commission's general anti-fraud... ``electricity'' and ``electric power.'' For the sake of consistency in the Final Order, the term ``electric..., an amount based solely on the difference between the price for electricity, established on an...

  19. 76 FR 68210 - United States v. George's Foods, LLC, et al.; Public Comment and Response on Proposed Final Judgment

    Science.gov (United States)

    2011-11-03

    ..., was not a term--either express or implied--of the settlement between the United States and George's... processors benefitted growers in terms of better prices for their services.\\23\\ The processers, however, also...., et. al., 76 FR 38419; and summaries of the terms of the proposed Final Judgment and CIS, together...

  20. Improved Estimation Procedures for Item Response Functions. Final Report on Project NR150-464. Research Report 84-2.

    Science.gov (United States)

    Tsutakawa, Robert K.

    This report describes new statistical procedures for item response analysis using estimation of item response curves used in mental testing with ability parameters treated as a random sample. Modern computer technology and the EM algorithm make this solution possible. The research focused on the theoretical formulation and solution of maximum…

  1. 17 CFR 171.42 - Notice of a final decision of the National Futures Association in a member responsibility action.

    Science.gov (United States)

    2010-04-01

    ... the National Futures Association in a member responsibility action. 171.42 Section 171.42 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION RULES RELATING TO REVIEW OF NATIONAL FUTURES ASSOCIATION DECISIONS IN DISCIPLINARY, MEMBERSHIP DENIAL, REGISTRATION AND MEMBER RESPONSIBILITY...

  2. The rs16906252:C>T SNP is not associated with increased overall survival or temozolomide response in a Han-Chinese glioma cohort.

    Directory of Open Access Journals (Sweden)

    Kuo-Chen Wei

    Full Text Available The methylation status of O-6-methylguanine-DNA methyltransferase (MGMT is associated with the prognosis in gliomas and in other cancers. Recent studies showed that rs16906252, an SNP in the MGMT promoter, is associated with promoter methylation and is a predictor of the overall survival time (OST and the response to temozolomide (TMZ treatment. However, these findings haven't been systematically investigated in the Han-Chinese population. We analyzed the relevance between rs16906252 polymorphisms, the MGMT methylation status, and the OST in 72 Han-Chinese gliomas patients. The MGMT promoter methylation was measured by bisulfite conversion followed by pyro-sequencing, while rs16906252 was measured by restriction endonuclease digestion. Contrary to the previous findings, we found no association between rs16906252 genotypes and promoter methylation on MGMT. The lower-grade glioma (LGGs patients carrying the C allele with rs16906252 showed a surprisingly better OST (P = 0.04. Furthermore, the LGG patients carrying hypo-methylated MGMT promoter and rs16906252 T allele showed significantly poorer prognosis. The prognostic benefit of MGMT promoter methylation and genotypes on gliomas patients is marginal. A new molecular stratified patient grouping of LGGs is potentially associated with poorer OST. Active MGMT might have a protective role in LGG tumors, enabling evolution to severe malignancy.

  3. Improving hydrologic disaster forecasting and response for transportation by assimilating and fusing NASA and other data sets : final report.

    Science.gov (United States)

    2017-04-15

    In this 3-year project, the research team developed the Hydrologic Disaster Forecast and Response (HDFR) system, a set of integrated software tools for end users that streamlines hydrologic prediction workflows involving automated retrieval of hetero...

  4. Neuroglobin-deficiency exacerbates Hif1A and c-FOS response, but does not affect neuronal survival during severe hypoxia in vivo

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Luuk, Hendrik; Ilmjärv, Sten

    2011-01-01

    Neuroglobin (Ngb), a neuron-specific globin that binds oxygen in vitro, has been proposed to play a key role in neuronal survival following hypoxic and ischemic insults in the brain. Here we address whether Ngb is required for neuronal survival following acute and prolonged hypoxia in mice...

  5. Finally Making Good on the Promise of Qualitative Research in Special Education? A Response to the Special Issue

    Science.gov (United States)

    Pugach, Marleen C.; Mukhopadhyay, Ananya; Gomez-Najarro, Joyce

    2014-01-01

    In this response to the special issue, we would like to offer two additional considerations to the discourse on qualitative research and special education this issue is meant to catalyze. First, we would like to further problematize the question of why qualitative research continues to be so sparsely represented in most prominent publications of…

  6. Specific TP53 Mutants Overrepresented in Ovarian Cancer Impact CNV, TP53 Activity, Responses to Nutlin-3a, and Cell Survival

    Directory of Open Access Journals (Sweden)

    Lisa K. Mullany

    2015-10-01

    Full Text Available Evolutionary Action analyses of The Cancer Gene Atlas data sets show that many specific p53 missense and gain-of-function mutations are selectively overrepresented and functional in high-grade serous ovarian cancer (HGSC. As homozygous alleles, p53 mutants are differentially associated with specific loss of heterozygosity (R273; chromosome 17; copy number variation (R175H; chromosome 9; and up-stream, cancer-related regulatory pathways. The expression of immune-related cytokines was selectively related to p53 status, showing for the first time that specific p53 mutants impact, and are related to, the immune subtype of ovarian cancer. Although the majority (31% of HGSCs exhibit loss of heterozygosity, a significant number (24% maintain a wild-type (WT allele and represent another HGSC subtype that is not well defined. Using human and mouse cell lines, we show that specific p53 mutants differentially alter endogenous WT p53 activity; target gene expression; and responses to nutlin-3a, a small molecular that activates WT p53 leading to apoptosis, providing “proof of principle” that ovarian cancer cells expressing WT and mutant alleles represent a distinct ovarian cancer subtype. We also show that siRNA knock down of endogenous p53 in cells expressing homozygous mutant alleles causes apoptosis, whereas cells expressing WT p53 (or are heterozygous for WT and mutant p53 alleles are highly resistant. Therefore, despite different gene regulatory pathways associated with specific p53 mutants, silencing mutant p53 might be a suitable, powerful, global strategy for blocking ovarian cancer growth in those tumors that rely on mutant p53 functions for survival. Knowing p53 mutational status in HGSC should permit new strategies tailored to control this disease.

  7. Final Technical Report [Scalable methods for electronic excitations and optical responses of nanostructures: mathematics to algorithms to observables

    Energy Technology Data Exchange (ETDEWEB)

    Saad, Yousef

    2014-03-19

    The master project under which this work is funded had as its main objective to develop computational methods for modeling electronic excited-state and optical properties of various nanostructures. The specific goals of the computer science group were primarily to develop effective numerical algorithms in Density Functional Theory (DFT) and Time Dependent Density Functional Theory (TDDFT). There were essentially four distinct stated objectives. The first objective was to study and develop effective numerical algorithms for solving large eigenvalue problems such as those that arise in Density Functional Theory (DFT) methods. The second objective was to explore so-called linear scaling methods or Methods that avoid diagonalization. The third was to develop effective approaches for Time-Dependent DFT (TDDFT). Our fourth and final objective was to examine effective solution strategies for other problems in electronic excitations, such as the GW/Bethe-Salpeter method, and quantum transport problems.

  8. Effects on quality of life, anti-cancer responses, breast conserving surgery and survival with neoadjuvant docetaxel: a randomised study of sequential weekly versus three-weekly docetaxel following neoadjuvant doxorubicin and cyclophosphamide in women with primary breast cancer

    Directory of Open Access Journals (Sweden)

    Wiseman Janice

    2011-05-01

    Full Text Available Abstract Background Weekly docetaxel has occasionally been used in the neoadjuvant to downstage breast cancer to reduce toxicity and possibly enhance quality of life. However, no studies have compared the standard three weekly regimen to the weekly regimen in terms of quality of life. The primary aim of our study was to compare the effects on QoL of weekly versus 3-weekly sequential neoadjuvant docetaxel. Secondary aims were to determine the clinical and pathological responses, incidence of Breast Conserving Surgery (BCS, Disease Free Survival (DFS and Overall Survival (OS. Methods Eighty-nine patients receiving four cycles of doxorubicin and cyclophosphamide were randomised to receive twelve cycles of weekly docetaxel (33 mg/m2 or four cycles of 3-weekly docetaxel (100 mg/m2. The Functional Assessment of Cancer Therapy-Breast and psychosocial questionnaires were completed. Results At a median follow-up of 71.5 months, there was no difference in the Trial Outcome Index scores between treatment groups. During weekly docetaxel, patients experienced less constipation, nail problems, neuropathy, tiredness, distress, depressed mood, and unhappiness. There were no differences in overall clinical response (93% vs. 90%, pathological complete response (20% vs. 27%, and breast-conserving surgery (BCS rates (49% vs. 42%. Disease-free survival and overall survival were similar between treatment groups. Conclusions Weekly docetaxel is well-tolerated and has less distressing side-effects, without compromising therapeutic responses, Breast Conserving Surgery (BCS or survival outcomes in the neoadjuvant setting. Trial registration ISRCTN: ISRCTN09184069

  9. Repair and cell cycle response in cells exposed to environmental biohazards. Final report, January 1, 1973-December 31, 1984

    International Nuclear Information System (INIS)

    Hadden, C.T.; Billen, D.

    1986-01-01

    These studies have focussed on agents which cause damage to DNA leading to inhibition of DNA synthesis or faulty DNA replication or repair. The overall goal of this project has been to understand how environmental agents interact with the DNA of cells and how cells cope with any resulting damage. In particular we have been concerned with the nature of the repair systems involved in restoration of damaged DNA and the cellular responses to radiation or chemical damage

  10. 77 FR 44271 - United States v. Apple, Inc., et al.; Public Comments and Response on Proposed Final Judgment

    Science.gov (United States)

    2012-07-27

    ... States v. Armour and Co., 402 U.S. 673 (1971) 46 United States v. Bechtel, 648 F.2d 660 (9th Cir. 9-10... any issue not already addressed in this Response to Comments. \\2\\ As of this writing, that letter is... consideration of the public benefit, if any, to be derived from a determination of the issues at trial. 15 U.S.C...

  11. Behavioral Responses Of Fish To A Current-Based Hydrokinetic Turbine Under Mutlipe Operational Conditions: Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Grippo, Mark A. [Argonne National Lab. (ANL), Argonne, IL (United States); Shen, Haixue [Univ. of Maine, Orono, ME (United States); Zydlewski, Gayle [Univ. of Maine, Orono, ME (United States); Rao, Shivanesh [Univ. of Maine, Orono, ME (United States); Goodwin, Andy [United States Army Engineer R & D Center, Vicksburg, MI (United States)

    2017-02-01

    There is significant interest in the interaction of aquatic organisms with current-based marine and hydrokinetic (MHK) technologies. Determining the potential impacts of MHK devices on fish behavior is critical to addressing the environmental concerns that could act as barriers to the permitting and deployment of MHK devices. To address these concerns, we use field monitoring and fish behavior models to characterize the behavioral responses of fish to MHK turbines and infer potential stimuli that may have elicited the observed behavioral changes.

  12. Final technical report. Can microbial functional traits predict the response and resilience of decomposition to global change?

    Energy Technology Data Exchange (ETDEWEB)

    Allison, Steven D. [Univ. of California, Irvine, CA (United States)

    2015-09-24

    The role of specific micro-organisms in the carbon cycle, and their responses to environmental change, are unknown in most ecosystems. This knowledge gap limits scientists’ ability to predict how important ecosystem processes, like soil carbon storage and loss, will change with climate and other environmental factors. The investigators addressed this knowledge gap by transplanting microbial communities from different environments into new environments and measuring the response of community composition and carbon cycling over time. Using state-of-the-art sequencing techniques, computational tools, and nanotechnology, the investigators showed that microbial communities on decomposing plant material shift dramatically with natural and experimentally-imposed drought. Microbial communities also shifted in response to added nitrogen, but the effects were smaller. These changes had implications for carbon cycling, with lower rates of carbon loss under drought conditions, and changes in the efficiency of decomposition with nitrogen addition. Even when transplanted into the same conditions, microbial communities from different environments remained distinct in composition and functioning for up to one year. Changes in functioning were related to differences in enzyme gene content across different microbial groups. Computational approaches developed for this project allowed the conclusions to be tested more broadly in other ecosystems, and new computer models will facilitate the prediction of microbial traits and functioning across environments. The data and models resulting from this project benefit the public by improving the ability to predict how microbial communities and carbon cycling functions respond to climate change, nutrient enrichment, and other large-scale environmental changes.

  13. Retinoid-X-receptors (α/β in melanocytes modulate innate immune responses and differentially regulate cell survival following UV irradiation.

    Directory of Open Access Journals (Sweden)

    Daniel J Coleman

    2014-05-01

    Full Text Available Understanding the molecular mechanisms of ultraviolet (UV induced melanoma formation is becoming crucial with more reported cases each year. Expression of type II nuclear receptor Retinoid-X-Receptor α (RXRα is lost during melanoma progression in humans. Here, we observed that in mice with melanocyte-specific ablation of RXRα and RXRβ, melanocytes attract fewer IFN-γ secreting immune cells than in wild-type mice following acute UVR exposure, via altered expression of several chemoattractive and chemorepulsive chemokines/cytokines. Reduced IFN-γ in the microenvironment alters UVR-induced apoptosis, and due to this, the survival of surrounding dermal fibroblasts is significantly decreased in mice lacking RXRα/β. Interestingly, post-UVR survival of the melanocytes themselves is enhanced in the absence of RXRα/β. Loss of RXRs α/β specifically in the melanocytes results in an endogenous shift in homeostasis of pro- and anti-apoptotic genes in these cells and enhances their survival compared to the wild type melanocytes. Therefore, RXRs modulate post-UVR survival of dermal fibroblasts in a "non-cell autonomous" manner, underscoring their role in immune surveillance, while independently mediating post-UVR melanocyte survival in a "cell autonomous" manner. Our results emphasize a novel immunomodulatory role of melanocytes in controlling survival of neighboring cell types besides controlling their own, and identifies RXRs as potential targets for therapy against UV induced melanoma.

  14. Lesser prairie-chicken nest site selection, microclimate, and nest survival in association with vegetation response to a grassland restoration program

    Science.gov (United States)

    Boal, Clint W.; Grisham, Blake A.; Haukos, David A.; Zavaleta, Jennifer C.; Dixon, Charles

    2014-01-01

    Climate models predict that the region of the Great Plains Landscape Conservation Cooperative (GPLCC) will experience increased maximum and minimum temperatures, reduced frequency but greater intensity of precipitation events, and earlier springs. These climate changes along with different landscape management techniques may influence the persistence of the lesser prairie-chicken (Tympanuchus pallidicinctus), a candidate for protection under the Endangered Species Act and a priority species under the GPLCC, in positive or negative ways. The objectives of this study were to conduct (1) a literature review of lesser prairie-chicken nesting phenology and ecology, (2) an analysis of thermal aspects of lesser prairie-chicken nest microclimate data, and (3) an analysis of nest site selection, nest survival, and vegetation response to 10 years of tebuthiuron and/or grazing treatments. We found few reports in the literature containing useful data on the nesting phenology of lesser prairie-chickens; therefore, managers must rely on short-term observations and measurements of parameters that provide some predictive insight into climate impacts on nesting ecology. Our field studies showed that prairie-chickens on nests were able to maintain relatively consistent average nest temperature of 31 °C and nest humidities of 56.8 percent whereas average external temperatures (20.3–35.0 °C) and humidities (35.2–74.9 percent) varied widely throughout the 24 hour (hr) cycle. Grazing and herbicide treatments within our experimental areas were designed to be less intensive than in common practice. We determined nest locations by radio-tagging hen lesser prairie-chickens captured at leks, which are display grounds at which male lesser prairie-chickens aggregate and attempt to attract a female for mating. Because nest locations selected by hen lesser prairie-chicken are strongly associated with the lek at which they were captured, we assessed nesting habitat use on the basis of hens

  15. Response of a tundra ecosystem to elevated atmospheric carbon dioxide and CO{sub 2}-induced climate change. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Oechel, W.C.

    1996-11-01

    The overall objective of this research was to document current patterns of CO{sub 2} flux in selected locations of the circumpolar arctic, and to develop the information necessary to predict how these fluxes may be affected by climate change. In fulfillment of these objectives, net CO{sub 2} flux was measured at several sites on the North Slope of Alaska during the 1990--94 growing season (June--August) to determine the local and regional patterns of seasonal CO{sub 2} exchange. In addition, net CO{sub 2} flux was measured in the Russian and Icelandic Arctic to determine if the patterns of CO{sub 2} exchange observed in Arctic Alaska were representative of the circumpolar Arctic, while cold-season CO{sub 2} flux measurements were carried out during the 1993--94 winter season to determine the magnitude of CO{sub 2} efflux not accounted for by the growing season measurements. Manipulations of soil water table depth and surface temperature, which were identified from the extensive measurements as being the most important variables in determining the magnitude and direction of net CO{sub 2} exchange, were carried out during the 1993--94 growing seasons in tussock and wet sedge tundra ecosystems. Finally, measurements of CH{sub 4} flux were also measured at several of the North Slope study sites during the 1990--91 growing seasons.

  16. Response of a tundra ecosytem to elevated atmospheric carbon dioxide and CO2-induced climate change. Final report

    International Nuclear Information System (INIS)

    Oechel, W.C.

    1996-11-01

    The overall objective of this research was to document current patterns of CO 2 flux in selected locations of the circumpolar arctic, and to develop the information necessary to predict how these fluxes may be affected by climate change. In fulfillment of these objectives, net CO 2 flux was measured at several sites on the North Slope of Alaska during the 1990-94 growing season (June-August) to determine the local and regional patterns, of seasonal CO 2 exchange. In addition, net CO 2 flux was measured in the Russian and Icelandic Arctic to determine if the patterns of CO 2 exchange observed in Arctic Alaska were representative of the circumpolar arctic, while cold-season CO 2 flux measurements were carried out during the 1993-94 winter season to determine the magnitude of CO 2 efflux not accounted for by the growing season measurements. Manipulations of soil water table depth and surface temperature, which were identified from the extensive measurements as being the most important variables in determining the magnitude and direction of net CO 2 exchange, were carried out during the 1993-94 growing seasons in tussock and wet sedge tundra ecosystems. Finally, measurements of CH 4 flux were also measured at several of the North Slope study sites during the 1990-91 growing seasons. Measurements were made on small (e.g. 0.5 m 2 ) plots using a portable gas-exchange system and cuvette. The sample design allowed frequent measurements of net CO 2 exchange and respiration over diurnal and seasonal cycles, and a large spatial extent that incorporated both locally and regionally diverse tundra surface types. Measurements both within and between ecosystem types typically extended over soil water table depth and temperature gradients, allowing for the indirect analysis of the effects of anticipated climate change scenarios on net CO 2 exchange. In situ experiments provided a direct means for testing hypotheses

  17. Final Technical Report: Response of Mediterranean-Type Ecosystems to Elevated Atmospheric CO2 and Associated Climate Change

    Energy Technology Data Exchange (ETDEWEB)

    Oechel, Walter C

    2002-08-15

    This research incorporated an integrated hierarchical approach in space, time, and levels of biological/ecological organization to help understand and predict ecosystem response to elevated CO{sub 2} and concomitant environmental change. The research utilized a number of different approaches, and collaboration of both PER and non-PER investigators to arrive at a comprehensive, integrative understanding. Central to the work were the CO{sub 2}-controlled, ambient Lit, Temperature controlled (CO{sub 2}LT) null-balance chambers originally developed in the arctic tundra, which were re-engineered for the chaparral with treatment CO{sub 2} concentrations of from 250 to 750 ppm CO{sub 2} in 100 ppm increments, replicated twice to allow for a regression analysis. Each chamber was 2 meters on a side and 2 meters tall, which were installed over an individual shrub reprouting after a fire. This manipulation allowed study of the response of native chaparral to varying levels of CO{sub 2}, while regenerating from an experimental burn. Results from these highly-controlled manipulations were compared against Free Air CO{sub 2} Enrichment (FACE) manipulations, in an area adjacent to the CO{sub 2}LT null balance greenhouses. These relatively short-term results (5-7 years) were compared to long-term results from Mediterranean-type ecosystems (MTEs) surrounding natural CO{sub 2} springs in northern Italy, near Laiatico, Italy. The springs lack the controlled experimental rigor of our CO{sub 2}LT and FACE manipulation, but provide invaluable validation of our long-term predictions.

  18. Response of a tundra ecosytem to elevated atmospheric carbon dioxide and CO{sub 2}-induced climate change. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Oechel, W.C.

    1996-11-01

    The overall objective of this research was to document current patterns of CO{sub 2} flux in selected locations of the circumpolar arctic, and to develop the information necessary to predict how these fluxes may be affected by climate change. In fulfillment of these objectives, net CO{sub 2} flux was measured at several sites on the North Slope of Alaska during the 1990-94 growing season (June-August) to determine the local and regional patterns, of seasonal CO{sub 2} exchange. In addition, net CO{sub 2} flux was measured in the Russian and Icelandic Arctic to determine if the patterns of CO{sub 2} exchange observed in Arctic Alaska were representative of the circumpolar arctic, while cold-season CO{sub 2} flux measurements were carried out during the 1993-94 winter season to determine the magnitude of CO{sub 2} efflux not accounted for by the growing season measurements. Manipulations of soil water table depth and surface temperature, which were identified from the extensive measurements as being the most important variables in determining the magnitude and direction of net CO{sub 2} exchange, were carried out during the 1993-94 growing seasons in tussock and wet sedge tundra ecosystems. Finally, measurements of CH{sub 4} flux were also measured at several of the North Slope study sites during the 1990-91 growing seasons. Measurements were made on small (e.g. 0.5 m{sup 2}) plots using a portable gas-exchange system and cuvette. The sample design allowed frequent measurements of net CO{sub 2} exchange and respiration over diurnal and seasonal cycles, and a large spatial extent that incorporated both locally and regionally diverse tundra surface types. Measurements both within and between ecosystem types typically extended over soil water table depth and temperature gradients, allowing for the indirect analysis of the effects of anticipated climate change scenarios on net CO{sub 2} exchange. In situ experiments provided a direct means for testing hypotheses.

  19. Survival probability of larval sprat in response to decadal changes in diel vertical migration behavior and prey abundance in the Baltic Sea

    DEFF Research Database (Denmark)

    Hinrichsen, Hans-Harald; Peck, Myron A.; Schmidt, Jörn

    2010-01-01

    distribution and climate-driven abiotic and biotic environmental factors including variability in the abundance of different, key prey species (calanoid copepods) as well as seasonal changes, long-term trends, and spatial differences in water temperature. Climate forcing affected Baltic sprat larval survival...... both directly (via changes in temperature) and indirectly (via changes in prey populations). By incorporating observed changes in larval diel vertical migration, decadal changes in modeled and observed survival of Baltic sprat agreed well. Higher larval survival (spawning stock biomass) was predicted...... in the 1990s compared to the 1980s. After changing their foraging strategy by shifting from mid-depth, low prey environment to near-surface waters, first-feeding larvae encountered much higher rates of prey encounter and almost optimal feeding conditions and had a much higher growth potential. Consequently...

  20. On the road to becoming a responsible leader: A simulation-based training approach for final year medical students.

    Science.gov (United States)

    Schmidt-Huber, Marion; Netzel, Janine; Kiesewetter, Jan

    2017-01-01

    Background and objective: There is a need for young physicians to take a responsible role in clinical teams, comparable to a leadership role. However, today's medical curricula barely consider the development of leadership competencies. Acquisition of leadership skills are currently a by-product of medical education, even though it seems to be a competency relevant for physicians' success. Therefore, an innovative leadership training program for young physicians was developed and validated. Training conceptualisation were based upon findings of critical incidents interviews ( N =19) with relevant personnel (e.g. experienced doctors/nurses, residents) and upon evidence-based leadership contents focusing on ethical leadership behaviors. Method: The training consists of four sessions (3-4 hours each) and provided evidence-based lectures of leadership theory and effective leader behaviors, interactive training elements and a simulation-based approach with professional role players focusing on interprofessional collaboration with care staff. Training evaluation was assessed twice after completion of the program ( N =37). Assessments included items from validated and approved evaluation instruments regarding diverse learning outcomes (satisfaction/reaction, learning, self-efficacy, and application/transfer) and transfer indicators. Furthermore, training success predictors were assessed based on stepwise regression analysis. In addition, long-term trainings effects and behavioral changes were analysed. Results: Various learning outcomes are achieved (self-reported training satisfaction, usefulness of the content and learning effects) and results show substantial transfer effects of the training contents and a strengthened awareness for the leadership role (e.g. self-confidence, ideas dealing with work-related problems in a role as responsible physician). We identified competence of trainer, training of applied tools, awareness of job expectations, and the opportunity to

  1. On the road to becoming a responsible leader: A simulation-based training approach for final year medical students

    Directory of Open Access Journals (Sweden)

    Schmidt-Huber, Marion

    2017-08-01

    Full Text Available Background and objective: There is a need for young physicians to take a responsible role in clinical teams, comparable to a leadership role. However, today’s medical curricula barely consider the development of leadership competencies. Acquisition of leadership skills are currently a by-product of medical education, even though it seems to be a competency relevant for physicians’ success. Therefore, an innovative leadership training program for young physicians was developed and validated. Training conceptualisation were based upon Method: The training consists of four sessions (3-4 hours each and provided evidence-based lectures of leadership theory and effective leader behaviors, interactive training elements and a simulation-based approach with professional role players focusing on interprofessional collaboration with care staff. Training evaluation was assessed twice after completion of the program (=37. Assessments included items from validated and approved evaluation instruments regarding diverse learning outcomes (satisfaction/reaction, learning, self-efficacy, and application/transfer and transfer indicators. Furthermore, training success predictors were assessed based on stepwise regression analysis. In addition, long-term trainings effects and behavioral changes were analysed. Results: Various learning outcomes are achieved (self-reported training satisfaction, usefulness of the content and learning effects and results show substantial transfer effects of the training contents and a strengthened awareness for the leadership role (e.g. self-confidence, ideas dealing with work-related problems in a role as responsible physician. We identified competence of trainer, training of applied tools, awareness of job expectations, and the opportunity to learn from experiences of other participants as predictors of training success. Additionally, we found long-term training effects and participants reported an increase in specific

  2. Switching to nilotinib in patients with chronic myeloid leukemia in chronic phase with molecular suboptimal response to frontline imatinib: SENSOR final results and BIM polymorphism substudy.

    Science.gov (United States)

    Miyamura, Koichi; Miyamoto, Toshihiro; Tanimoto, Mitsune; Yamamoto, Kazuhito; Kimura, Shinya; Kawaguchi, Tatsuya; Matsumura, Itaru; Hata, Tomoko; Tsurumi, Hisashi; Saito, Shigeki; Hino, Masayuki; Tadokoro, Seiji; Meguro, Kuniaki; Hyodo, Hideo; Yamamoto, Masahide; Kubo, Kohmei; Tsukada, Junichi; Kondo, Midori; Aoki, Makoto; Okada, Hikaru; Yanada, Masamitsu; Ohyashiki, Kazuma; Taniwaki, Masafumi

    2016-12-01

    Optimal management of patients with chronic myeloid leukemia in chronic phase with suboptimal molecular response (MR) to frontline imatinib is undefined. We report final results from SENSOR, which evaluated efficacy/safety of nilotinib in this setting. A substudy assessed whether BIM polymorphisms impacted response to nilotinib. In this single-arm, multicenter study, Japanese patients with suboptimal MR per European LeukemiaNet 2009 criteria (complete cytogenetic response, but not major MR [MMR]) after ≥18 months of frontline imatinib received nilotinib 400mg twice daily for 24 months. MR, BCR-ABL1 mutations/variants, and BIM polymorphisms were evaluated in a central laboratory. Primary endpoint was the MMR rate at 12 months (null hypothesis of 40%). Of 45 patients (median exposure, 22.08 months), 39 completed the study and six discontinued. At 12 and 24 months, 51.1% (95% CI, 35.8%-66.3%) and 66.7% (95% CI, 51.0%-80.0%) achieved MMR, respectively. Cumulative MMR incidence by 24 months was 75.6%. Of 40 patients analyzed, 10 of 12 (83.3%) with and 17 of 28 (60.7%) without BIM polymorphisms achieved MMR at 24 months. The safety profile was manageable with dose reductions and interruptions. Nilotinib provided clinical benefit for patients with suboptimal response to imatinib, and BIM polymorphisms did not influence MMR achievement. ClinicalTrials.gov: NCT01043874. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Final programmatic environmental impact statement for alternative strategies for the long-term management and use of depleted uranium hexafluoride. Volume 3: Responses to public comments

    International Nuclear Information System (INIS)

    1999-04-01

    This PEIS assesses the potential impacts of alternative management strategies for depleted uranium hexafluoride (UF 6 ) currently stored at three DOE sites: Paducah site near Paducah, Kentucky, Portsmouth site near Portsmouth, Ohio; and K-25 site on the Oak Ridge Reservation, Oak Ridge, Tennessee. The alternatives analyzed in the PEIS include no action, long-term storage as UF 6 , long-term storage as uranium oxide, use as uranium oxide, use as uranium metal, and disposal. DOE's preferred alternative is to begin conversion of the depleted UF 6 inventory as soon as possible, either to uranium oxide, uranium metal, or a combination of both, while allowing for use of as much of this inventory as possible. This volume of the Final PEIS contains the comments and DOE's responses to comments received during the comment period. Chapter 2 contains photocopies of written submissions received by DOE on the Draft PEIS; DOE's responses to those comments are listed in Chapter 3. Chapter 4 provides the oral comments received at the public hearings and DOE's responses. Chapter 5 provides indices to comments and responses arranged by commentor name and by comment number

  4. Interactions of CO{sub 2} with temperature and other climate variables: response of vegetation. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Knipling, E.B.

    1995-02-28

    The overall objectives of this project were: (1) to examine experimentally, for major crop species, the interacting effects of CO{sub 2} concentration, temperature, and water availability on plant growth and development, (2) to model these interactions, and (3) to continue developing physiologically-based mechanistic models for predicting crop response to increased CO{sub 2} concentration and future global climate change. To meet these objectives, controlled-environment studies were conducted on cotton, lemon, rice, and soybean and a long-term open-top chamber study was continued on orange. Much progress was made on development of plant growth models for cotton, wheat, rice, and soybean. In addition, there were two special modeling efforts which have the potential for contributing to all of the crop models. These efforts are concerned with modeling root growth and physical and chemical processes in soil and with modeling the effect of stomatal aperture on photosynthesis and transpiration rates as a function of CO{sub 2} concentration, temperature, and vapor pressure deficit. The root growth and soil process modeling is important because it enables us to estimate the water available to the plant. The modeling of effects of stomatal aperture on photosynthesis and transpiration rates enables them to estimate dry weight gain and water use by the plant. These are both important components of the interaction of CO{sub 2} concentration with temperature and water availability. The work on stomatal aperture, photosynthesis, and transpiration has the added benefit of allowing us to improve predictions of energy partitioning by the terrestrial biosphere. The lack of realistic energy partitioning is a serious deficiency of the present general circulation models which are used to predict how climate will change. An additional important aspect of the rice experiments is a study of methane emissions of paddy-grown (i.e., flooded) rice grown under two levels of CO{sub 2} and three

  5. Influence of surface polysaccharides of Escherichia coli O157:H7 on plant defense response and survival of the human enteric pathogen on Arabidopsis thaliana and lettuce (Lactuca sativa).

    Science.gov (United States)

    Jang, Hyein; Matthews, Karl R

    2018-04-01

    This study aimed to determine the influence of bacterial surface polysaccharides (cellulose, colanic acid, and lipopolysaccharide; LPS) on the colonization or survival of Escherichia coli O157:H7 on plants and the plant defense response. Survival of E. coli O157:H7 were evaluated on Arabidopsis thaliana and romaine lettuce as a model plant and an edible crop (leafy vegetable), respectively. The population of the wild-type strain of E. coli O157:H7 on Arabidopsis plants and lettuce was significantly (P < 0.05) greater compared with the colanic acid-deficient and LPS-truncated mutants on day 1 and day 5 post-inoculation. This result indicates that colanic acid and LPS structures may contribute to the ability of bacterial survival or persistence on plants. The wild-type strain of E. coli O157:H7 produced approximately twice the amount (P < 0.05) of capsular polysaccharide (CPS) than the colanic acid and LPS-truncated mutants. The significantly lower production of CPS was associated with significantly greater (2-fold) expression of pathogenesis-related gene (PR1) compared with the wild-type and cellulose-deficient mutant (P < 0.05). Collectively, the results of this study may suggest that specific surface polysaccharides of E. coli O157:H7 differentially induce the plant defense response, consequently affecting the survival of the human pathogen on plants. The survival and persistence of E. coli O157:H7 was similar on Arabidopsis and lettuce regardless of day post-inoculation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Black-chinned hummingbird nest-site selection and nest survival in response to fuel reduction in a southwestern riparian forest

    Science.gov (United States)

    D. Max Smith; Deborah M. Finch; David L. Hawksworth

    2009-01-01

    Despite widespread efforts to avert wildfire by reducing the density of flammable vegetation, little is known about the effects of this practice on the reproductive biology of forest birds. We examined nest-site selection and nest survival of the Black-chinned Hummingbird (Archilochus alexandri) in New Mexico riparian forests treated or not for fuel...

  7. Surviving death

    DEFF Research Database (Denmark)

    Gerstroem, Anna

    2013-01-01

    by another bank to which bankers needed to adapt. Even in the acquiring organization, the legacy organizational identity continued to play a significant role. The paper contributes to the important and timely emergence of theory on legacy organizational identity by showing how members of a dead organization...... such phases. The aim of this paper is to explore how an organization’s identity is re-constructed after organizational death. Based on interviews with members of a bankrupted bank who narrate their bankruptcy experiences, the paper explores how legacy organizational identity is constructed after...... organizational death. The paper shows how members draw on their legacy organizational identity to justify their past interpretations and responses to the intensifying bankruptcy threats. Members refer to their firm belief in the bank’s solid and robust identity claim when they explain how they disregarded...

  8. Determination of an optimal response cut-off able to predict progression-free survival in patients with well-differentiated advanced pancreatic neuroendocrine tumours treated with sunitinib: an alternative to the current RECIST-defined response.

    Science.gov (United States)

    Lamarca, Angela; Barriuso, Jorge; Kulke, Matthew; Borbath, Ivan; Lenz, Heinz-Josef; Raoul, Jean Luc; Meropol, Neal J; Lombard-Bohas, Catherine; Posey, James; Faivre, Sandrine; Raymond, Eric; Valle, Juan W

    2018-01-01

    Sunitinib prolongs progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumours (pNET). Response Evaluation Criteria in Solid Tumors (RECIST)-defined partial responses (PR; classically defined as ⩾30% size decrease from baseline) are infrequent. Individual data of pNET patients from the phase II [NCT00056693] and pivotal phase III [NCT00428597] trials of sunitinib were analysed in this investigator-initiated, post hoc study. The primary objective was to determine the optimal RECIST (v.1.0) response cut-off value to identify patients who were progression-free at 11 months (median PFS in phase III trial); and the most informative time-point (highest area under the curve (AUC) by receiver operating characteristic (ROC) analysis and logistic regression) for prediction of benefit (PFS) from sunitinib. Data for 237 patients (85 placebo; 152 sunitinib (n=66.50 mg '4-weeks on/2-weeks off' schedule; n=86 '37.5 mg continuous daily dosing (CDD)')) and 788 scans were analysed. The median PFS for sunitinib and placebo were 9.3 months (95% CI 7.6-12.2) and 5.4 months (95% CI 3.5-6.01), respectively (hazard ratio (HR) 0.43 (95% CI 0.29-0.62); P<0.001). A PR was seen in 19 patients (13%) on sunitinib; the median change in the sum of the lesions (vs baseline) was -12.8% (range -100 to +36.4). Month 7 was the most informative time-point (AUC 0.78 (95% CI 0.66-0.9); odds ratio 1.05 (95% CI 1.01-1.08), P=0.002). Reduction of 10% (vs baseline) achieved the highest sensitivity (50%) and specificity (82%), amongst cut-offs tested. A 10% reduction in marker lesions was associated with improved PFS in the whole sunitinib population (HR 0.55 (95 CI 0.3-0.9); P=0.04); mostly in patients on sunitinib CDD (HR 0.33 (95% CI 0.2-0.7); P=0.005). A 10% reduction in marker lesions (P=0.034) and sunitinib treatment (P=0.012) independently impacted on PFS (multivariable analysis). A 10% reduction within marker lesions identifies pNET patients benefiting from

  9. Modified response evaluation criteria in solid tumors and European Association for The Study of the Liver criteria using delayed-phase imaging at an early time point predict survival in patients with unresectable intrahepatic cholangiocarcinoma following yttrium-90 radioembolization.

    Science.gov (United States)

    Camacho, Juan C; Kokabi, Nima; Xing, Minzhi; Prajapati, Hasmukh J; El-Rayes, Bassel; Kim, Hyun S

    2014-02-01

    To investigate early imaging prognostic factors in unresectable intrahepatic cholangiocarcinoma (ICC) refractory to standard chemotherapy after yttrium-90 ((90)Y) radioembolization therapy. In an institutional review board-approved prospective correlative study, 21 consecutive patients with ICC refractory to standard chemotherapy underwent (90)Y radioembolization therapy. Target and overall Response Evaluation Criteria In Solid Tumors (RECIST), modified RECIST (mRECIST), and European Association for the Study of the Liver (EASL) treatment responses were assessed. The mRECIST and EASL criteria were modified for application on delayed phases of dynamic contrast-enhanced cross-sectional imaging studies. Conventional definitions for complete and partial response were applied; these responses comprised objective response. Restaging imaging was obtained at 1- and 3-month intervals until patient death. Survival analyses by Kaplan-Meier and log-rank proportional models including application of the landmark method to avoid lead-time bias were performed from the day of treatment. Significance was set at P 90)Y therapy was 16.3 months (95% confidence interval, 7.2-25.4 mo). Significant differences between mRECIST and EASL versus RECIST were found when categorizing patients into responders and nonresponders (P 90)Y radioembolization therapy for ICC predicted OS. RECIST did not correlate with survival. © 2014 Published by SIR on behalf of SIR.

  10. Responses to comments received on the draft final report of the Secretary of Energy Advisory Board Task Force on Radioactive Waste Management

    Energy Technology Data Exchange (ETDEWEB)

    1994-10-01

    The Task Force solicited comments on its Draft Final Report from a variety of sources. Letters were sent to over 400 individuals who had expressed interest in the interest in the Department`s radioactive waste, management programs, a notice was placed in the Federal Register, the morning session of the January 1993 meeting of the full Secretary of Energy Advisory Board was given over to discussion of the draft, and Task Force members and staff presented the effort at several professional meetings. Altogether 32 written comments were received. They are reproduced here, followed in each case by the Task Force`s response to specific suggestions made to improve the draft. (The panel did not respond to comments that simply reflected policy preferences or that praised the group`s effort.) With one exception, those specific suggestions are highlighted and given a letter designation from {open_quotes}A{close_quotes} to {open_quotes}Z{close_quotes}. The Task Force`s responses, written in the Fall 1993, are labeled in a like manner. For the one exception, a comments submitted by Judy Treichel, the Task Force`s response is printed on copies of her annotated pages.

  11. Responses to comments received on the draft final report of the Secretary of Energy Advisory Board Task Force on Radioactive Waste Management

    International Nuclear Information System (INIS)

    1994-01-01

    The Task Force solicited comments on its Draft Final Report from a variety of sources. Letters were sent to over 400 individuals who had expressed interest in the interest in the Department's radioactive waste, management programs, a notice was placed in the Federal Register, the morning session of the January 1993 meeting of the full Secretary of Energy Advisory Board was given over to discussion of the draft, and Task Force members and staff presented the effort at several professional meetings. Altogether 32 written comments were received. They are reproduced here, followed in each case by the Task Force's response to specific suggestions made to improve the draft. (The panel did not respond to comments that simply reflected policy preferences or that praised the group's effort.) With one exception, those specific suggestions are highlighted and given a letter designation from open-quotes Aclose quotes to open-quotes Zclose quotes. The Task Force's responses, written in the Fall 1993, are labeled in a like manner. For the one exception, a comments submitted by Judy Treichel, the Task Force's response is printed on copies of her annotated pages

  12. Interactions of CO{sub 2} with temperature and other climate variables: Response of vegetation. Final report, September 1, 1988--August 31, 1993

    Energy Technology Data Exchange (ETDEWEB)

    Acock, B.; Kimball, B.A.

    1995-02-01

    The current project was initiated in 1991, and full details of the scope of the project are contained in the original proposal. that original proposal was reviewed and approved for three years funding. Progress made in 1991-92 and 1992-93 was described in annual Progress Reports and Statements of Work. This document summarizes progress made over the duration of the project, but with an emphasis on the final year`s (1993-94) results. Several of the important experiments are ongoing, to the extent that alternative funding could be arranged, and analyses of data from several of the earlier completed experiments is continuing. Therefore, this Final Report is also intermediary in nature, and additional results from this project will be reported in the open literature in the future. The overall objectives of the project were: (1) to examine experimentally, for major crop species, the interacting effects of CO{sub 2} concentration, temperature, and water availability on plant growth and development, (2) to model these interactions, and (3) to continue developing physiologically-based mechanistic models for predicting crop response to increased CO{sub 2} concentration and future global climate change.

  13. INTERNATIONAL JOURNAL FINAL FINALweb

    African Journals Online (AJOL)

    hp

    duty etc are critical to his survival which are his bible which his family must teach him and zealously too. What might be considered the most important role of the family in fashioning an individual's moral life is to educate him that he has to accept limitations upon his life that moral responsibilities impose. The family has to ...

  14. Alternative barging strategies to improve survival of salmonids transported from Lower Granite Dam: Final report from the 2006-2008 spring/summer Chinook salmon and Steelhead juvenile migrations

    Science.gov (United States)

    Marsh, Tiffani M.; Muir, William D.; Sandford, Benjamin P.; Smith, Steven G.; Elliott, Diane G.

    2012-01-01

    In 2011, the final year class of adult salmon Oncorhynchus spp. returned from smolt groups released for a multi-year study to evaluate an alternate release site for transported fish. Smolts were collected and tagged at Lower Granite Dam, transported, and released at the alternate site near Astoria, Oregon (river kilometer 10) or at the traditional release site near Skamania Landing (rkm 225) just downstream of Bonneville Dam.

  15. Expression of DNA Damage Response Molecules PARP1, γH2AX, BRCA1, and BRCA2 Predicts Poor Survival of Breast Carcinoma Patients

    Directory of Open Access Journals (Sweden)

    See-Hyoung Park

    2015-08-01

    Full Text Available BACKGROUND: Poly(ADP-ribose polymerase 1 (PARP1, γH2AX, BRCA1, and BRCA2 are conventional molecular indicators of DNA damage in cells and are often overexpressed in various cancers. In this study, we aimed, using immunohistochemical detection, whether the co-expression of PARP1, γH2AX, BRCA1, and BRCA2 in breast carcinoma (BCA tissue can provide more reliable prediction of survival of BCA patients. MATERIALS AND METHODS: We investigated immunohistochemical expression and prognostic significance of the expression of PARP1, γH2AX, BRCA1, and BRCA2 in 192 cases of BCAs. RESULTS: The expression of these four molecules predicted earlier distant metastatic relapse, shorter overall survival (OS, and relapse-free survival (RFS by univariate analysis. Multivariate analysis revealed the expression of PARP1, γH2AX, and BRCA2 as independent poor prognostic indicators of OS and RFS. In addition, the combined expressional pattern of BRCA1, BRCA2, PARP1, and γH2AX (CSbbph was an additional independent prognostic predictor for OS (P < .001 and RFS (P < .001. The 10-year OS rate was 95% in the CSbbph-low (CSbbph scores 0 and 1 subgroup, but that was only 35% in the CSbbph-high (CSbbph score 4 subgroup. CONCLUSION: This study has demonstrated that the individual and combined expression patterns of PARP1, γH2AX, BRCA1, and BRCA2 could be helpful in determining an accurate prognosis for BCA patients and for the selection of BCA patients who could potentially benefit from anti-PARP1 therapy with a combination of genotoxic chemotherapeutic agents.

  16. Phase I trial of anti-GD2 monoclonal antibody hu3F8 plus GM-CSF: Impact of body weight, immunogenicity and anti-GD2 response on pharmacokinetics and survival.

    Science.gov (United States)

    Cheung, Irene Y; Kushner, Brian H; Modak, Shakeel; Basu, Ellen M; Roberts, Stephen S; Cheung, Nai-Kong V

    2017-01-01

    Fifty-seven stage 4 patients with refractory/relapsed neuroblastoma were enrolled in a phase I trial (Clinicaltrials.gov NCT01757626) using humanized anti-GD2 monoclonal antibody hu3F8 in combination with granulocyte-macrophage colony-stimulating factor. The influence of body weight and human anti-human antibody (HAHA) on the pharmacokinetics (PK) of hu3F8, and the effect of de novo anti-GD2 response on patient outcome were explored. Serum samples before hu3F8 infusion, and serially up to day 12 during treatment cycle #1, and at 5 min after each hu3F8 infusion for all subsequent cycles were collected. PK was analyzed using non-compartmental modeling. Immunogenicity was assayed by HAHA response, and vaccination effect by induced host anti-GD2 response measured periodically until disease progression or last followup. Progression-free and overall survival was estimated by the Kaplan-Meier method. Despite dosing being based on body weight, smaller patients had consistently lower area-under-the-curve and faster clearance over the 15 dose levels (0.9 to 9.6 mg/kg per treatment cycle) in this trial. Positive HAHA, defined by the upper limit of normal, when measured within 10 days from the last hu3F8 dose received, was associated with significantly lower serum hu3F8. Despite prior sensitization to other anti-GD2 antibody, e.g. mouse 3F8 or ch14.18, 75% of the patients never developed HAHA response even after getting more treatment cycles. Hu3F8 induced a de novo anti-GD2 response in patients, which was prognostic of progression-free survival. We conclude that hu3F8 had low immunogenicity. During treatment, positive HAHA and low body weight affected PK adversely, whereas induced anti-GD2 response was an outcome predictor.

  17. Caspase-10 Negatively Regulates Caspase-8-Mediated Cell Death, Switching the Response to CD95L in Favor of NF-κB Activation and Cell Survival

    Directory of Open Access Journals (Sweden)

    Sebastian Horn

    2017-04-01

    Full Text Available Formation of the death-inducing signaling complex (DISC initiates extrinsic apoptosis. Caspase-8 and its regulator cFLIP control death signaling by binding to death-receptor-bound FADD. By elucidating the function of the caspase-8 homolog, caspase-10, we discover that caspase-10 negatively regulates caspase-8-mediated cell death. Significantly, we reveal that caspase-10 reduces DISC association and activation of caspase-8. Furthermore, we extend our co-operative/hierarchical binding model of caspase-8/cFLIP and show that caspase-10 does not compete with caspase-8 for binding to FADD. Utilizing caspase-8-knockout cells, we demonstrate that caspase-8 is required upstream of both cFLIP and caspase-10 and that DISC formation critically depends on the scaffold function of caspase-8. We establish that caspase-10 rewires DISC signaling to NF-κB activation/cell survival and demonstrate that the catalytic activity of caspase-10, and caspase-8, is redundant in gene induction. Thus, our data are consistent with a model in which both caspase-10 and cFLIP coordinately regulate CD95L-mediated signaling for death or survival.

  18. Modification by preirradiation growth conditions of the shoulder of the UV fluence-survival curve of Escherichia coli B/r WP2 thy trp and changes in mutagenic response toward tryptophan prototrophy

    International Nuclear Information System (INIS)

    Doudney, C.O.

    1978-01-01

    The distinct three-section UV fluence-mutation frequency response (MFR) curve demonstrated in Escherichia coli strain B/r WP2 thy trp and its uvrA derivative supports the SOS hypothesis and suggests that trp + revertants can arise either from isolated lesions (1DM) plus SOS induction or from two lesions in proximity (2DM). Preirradiation growth on arabinose instead of glucose converted the fluence-survival curve from highly shouldered to exponential but did not affect the three-section MFR curve. Prestarvation of the uvrA + strain for typtophan, which drastically increases the expanse of the shoulder of the survival curve, greatly decreased both 1DM and 2DM. With the uvrA strain the increase in shoulder expanse after typtophan prestarvation was accompanied by greatly increased 2DM but no change in 1DM. Preincubation with chloramphenicol induced an even greater increase in 2DM response than amino acid prestarvation. Nalidixic acid, which prevents DNA accumulation, eliminated the response. (Auth.)

  19. TIMP-1 Is Significantly Associated with Objective Response and Survival in Metastatic Colorectal Cancer Patients Receiving Combination of Irinotecan, 5-Fluorouracil, and Folinic Acid

    DEFF Research Database (Denmark)

    Sørensen, Nanna M; Byström, Per; Christensen, Ib Jarle

    2007-01-01

    with metastatic colorectal cancer were included in the study. PlasmaTIMP-1and serum carcinoembryonic antigen (CEA) were measured in samples obtainedbef ore the first cycle of chemotherapy. Results: Analysis of best objective response (complete or partial response versus stable or progressive disease) showed...

  20. Probabilistic Survivability Versus Time Modeling

    Science.gov (United States)

    Joyner, James J., Sr.

    2015-01-01

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

  1. Focal radiation therapy combined with 4-1BB activation and CTLA-4 blockade yields long-term survival and a protective antigen-specific memory response in a murine glioma model.

    Directory of Open Access Journals (Sweden)

    Zineb Belcaid

    Full Text Available Glioblastoma (GBM is the most common malignant brain tumor in adults and is associated with a poor prognosis. Cytotoxic T lymphocyte antigen -4 (CTLA-4 blocking antibodies have demonstrated an ability to generate robust antitumor immune responses against a variety of solid tumors. 4-1BB (CD137 is expressed by activated T lymphocytes and served as a co-stimulatory signal, which promotes cytotoxic function. Here, we evaluate a combination immunotherapy regimen involving 4-1BB activation, CTLA-4 blockade, and focal radiation therapy in an immune-competent intracranial GBM model.GL261-luciferace cells were stereotactically implanted in the striatum of C57BL/6 mice. Mice were treated with a triple therapy regimen consisted of 4-1BB agonist antibodies, CTLA-4 blocking antibodies, and focal radiation therapy using a small animal radiation research platform and mice were followed for survival. Numbers of brain-infiltrating lymphocytes were analyzed by FACS analysis. CD4 or CD8 depleting antibodies were administered to determine the relative contribution of T helper and cytotoxic T cells in this regimen. To evaluate the ability of this immunotherapy to generate an antigen-specific memory response, long-term survivors were re-challenged with GL261 glioma en B16 melanoma flank tumors.Mice treated with triple therapy had increased survival compared to mice treated with focal radiation therapy and immunotherapy with 4-1BB activation and CTLA-4 blockade. Animals treated with triple therapy exhibited at least 50% long-term tumor free survival. Treatment with triple therapy resulted in a higher density of CD4+ and CD8+ tumor infiltrating lymphocytes. Mechanistically, depletion of CD4+ T cells abrogated the antitumor efficacy of triple therapy, while depletion of CD8+ T cells had no effect on the treatment response.Combination therapy with 4-1BB activation and CTLA-4 blockade in the setting of focal radiation therapy improves survival in an orthotopic mouse

  2. Solar Energy Grid Integration Systems. Final Report of the Princeton Power Systems Development of the 100kW Demand Response Inverter.

    Energy Technology Data Exchange (ETDEWEB)

    Bower, Ward Isaac; Heavener, Paul (Princeton Power Systems, Inc., Princeton, NJ); Sena-Henderson, Lisa; Hammell, Darren (Princeton Power Systems, Inc., Princeton, NJ); Holveck, Mark (Princeton Power Systems, Inc., Princeton, NJ); David, Carolyn; Akhil, Abbas Ali; Gonzalez, Sigifredo

    2012-01-01

    Initiated in 2008, the Solar Energy Grid Integration (SEGIS) program is a partnership involving the U.S. Department of Energy, Sandia National Laboratories, electric utilities, academic institutions and the private sector. Recognizing the need to diversify the nation's energy portfolio, the SEGIS effort focuses on specific technologies needed to facilitate the integration of large-scale solar power generation into the nation's power grid Sandia National Laboratories (SNL) awarded a contract to Princeton Power Systems, Inc., (PPS) to develop a 100kW Advanced AC-link SEGIS inverter prototype under the Department of Energy Solar Energy Technologies Program for near-term commercial applications. This SEGIS initiative emphasizes the development of advanced inverters, controllers, communications and other balance-of-system components for photovoltaic (PV) distributed power applications. The SEGIS Stage 3 Contract was awarded to PPS on July 28, 2010. PPS developed and implemented a Demand Response Inverter (DRI) during this three-stage program. PPS prepared a 'Site Demonstration Conference' that was held on September 28, 2011, to showcase the cumulative advancements. This demo of the commercial product will be followed by Underwriters Laboratories, Inc., certification by the fourth quarter of 2011, and simultaneously the customer launch and commercial production sometime in late 2011 or early 2012. This final report provides an overview of all three stages and a full-length reporting of activities and accomplishments in Stage 3.

  3. Bt-maize (MON810) and Non-GM Soybean Meal in Diets for Atlantic Salmon (Salmo salar L.) Juveniles – Impact on Survival, Growth Performance, Development, Digestive Function, and Transcriptional Expression of Intestinal Immune and Stress Responses

    Science.gov (United States)

    Gu, Jinni; Bakke, Anne Marie; Valen, Elin C.; Lein, Ingrid; Krogdahl, Åshild

    2014-01-01

    Responses in Atlantic salmon (Salmo salar L.) juveniles (fry) fed diets containing genetically modified maize (Bt-maize, MON810) expressing Cry1Ab protein from first-feeding were investigated during a 99-day feeding trial. Four experimental diets were made; each diet contained ∼20% maize, either Bt-maize or its near-isogenic maternal line (non-GM maize). One pair was fishmeal-based while the other pair included standard (extracted) soybean meal (SBM; 16.7% inclusion level), with the intention of investigating responses to the maize varieties in healthy fish as well as in immunologically challenged fish with SBM-induced distal intestinal inflammation, respectively. Three replicate tanks of fry (0.17±0.01 g; initial mean weight ± SEM) were fed one of the four diets and samples were taken on days 15, 36, 48 and 99. Survival, growth performance, whole body composition, digestive function, morphology of intestine, liver and skeleton, and mRNA expression of some immune and stress response parameters in the distal intestine were evaluated. After 99 days of feeding, survival was enhanced and the intended SBM-induced inflammatory response in the distal intestine of the two groups of SBM-fed fish was absent, indicating that the juvenile salmon were tolerant to SBM. Mortality, growth performance and body composition were similar in fish fed the two maize varieties. The Bt-maize fed fish, however, displayed minor but significantly decreased digestive enzyme activities of leucine aminopeptidase and maltase, as well as decreased concentration of gut bile salts, but significantly increased amylase activity at some sampling points. Histomorphological, radiographic and mRNA expression evaluations did not reveal any biologically relevant effects of Bt-maize in the gastrointestinal tract, liver or skeleton. The results suggest that the Cry1Ab protein or other compositional differences in GM Bt-maize may cause minor alterations in intestinal responses in juvenile salmon, but

  4. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    DeTar, Carleton [P.I.

    2012-12-10

    This document constitutes the Final Report for award DE-FC02-06ER41446 as required by the Office of Science. It summarizes accomplishments and provides copies of scientific publications with significant contribution from this award.

  5. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Gurney, Kevin R. [Arizona Univ., Mesa, AZ (United States)

    2015-01-12

    This document constitutes the final report under DOE grant DE-FG-08ER64649. The organization of this document is as follows: first, I will review the original scope of the proposed research. Second, I will present the current draft of a paper nearing submission to Nature Climate Change on the initial results of this funded effort. Finally, I will present the last phase of the research under this grant which has supported a Ph.D. student. To that end, I will present the graduate student’s proposed research, a portion of which is completed and reflected in the paper nearing submission. This final work phase will be completed in the next 12 months. This final workphase will likely result in 1-2 additional publications and we consider the results (as exemplified by the current paper) high quality. The continuing results will acknowledge the funding provided by DOE grant DE-FG-08ER64649.

  6. Dose-dependent effects of NY-ESO-1 protein vaccine complexed with cholesteryl pullulan (CHP-NY-ESO-1) on immune responses and survival benefits of esophageal cancer patients.

    Science.gov (United States)

    Kageyama, Shinichi; Wada, Hisashi; Muro, Kei; Niwa, Yasumasa; Ueda, Shugo; Miyata, Hiroshi; Takiguchi, Shuji; Sugino, Sahoko H; Miyahara, Yoshihiro; Ikeda, Hiroaki; Imai, Naoko; Sato, Eiichi; Yamada, Tomomi; Osako, Masaharu; Ohnishi, Mami; Harada, Naozumi; Hishida, Tadashi; Doki, Yuichiro; Shiku, Hiroshi

    2013-10-05

    Cholesteryl pullulan (CHP) is a novel antigen delivery system for cancer vaccines. This study evaluated the safety, immune responses and clinical outcomes of patients who received the CHP-NY-ESO-1 complex vaccine, Drug code: IMF-001. Patients with advanced/metastatic esophageal cancer were enrolled and subcutaneously vaccinated with either 100 μg or 200 μg of NY-ESO-1 protein complexed with CHP. The primary endpoints were safety and humoral immune responses, and the secondary endpoint was clinical efficacy. A total of 25 patients were enrolled. Thirteen and twelve patients were repeatedly vaccinated with 100 μg or 200 μg of CHP-NY-ESO-1 with a median of 8 or 9.5 doses, respectively. No serious adverse events related to the vaccine were observed. Three out of 13 patients in the 100-μg cohort and 7 out of 12 patients in the 200-μg cohort were positive for anti-NY-ESO-1 antibodies at baseline. In the 100-μg cohort, an antibody response was observed in 5 out of 10 pre-antibody-negatives patients, and the antibody levels were augmented in 2 pre-antibody-positive patients after vaccination. In the 200-μg cohort, all 5 pre-antibody-negative patients became seropositive, and the antibody level was amplified in all 7 pre-antibody-positive patients. No tumor shrinkage was observed. The patients who received 200 μg of CHP-NY-ESO-1 survived longer than patients receiving 100 μg of CHP-NY-ESO-1, even those who exhibited unresponsiveness to previous therapies or had higher tumor burdens. The safety and immunogenicity of CHP-NY-ESO-1 vaccine were confirmed. The 200 μg dose more efficiently induced immune responses and suggested better survival benefits. (Clinical trial registration number NCT01003808).

  7. CD8+ T-cell responses to tumor-associated antigens correlate with superior relapse-free survival after allo-SCT.

    Science.gov (United States)

    Kapp, M; Stevanović, S; Fick, K; Tan, S M; Loeffler, J; Opitz, A; Tonn, T; Stuhler, G; Einsele, H; Grigoleit, G U

    2009-03-01

    The GVL effect following allo-SCT is one of the most prominent examples showing the ability of the immune system to eliminate malignant hematological diseases. Tumor-associated Ags (TAA), for instance WT1 and proteinase-3, have been proposed as targets for T cells to establish a GVL effect. Here, we examined an additional TAA (MUC1) as a possible T-cell target of GVL-related immune responses. We have defined new peptide epitopes from the MUC1 Ag to broaden patients' screening and to expand the repertoire of immunologic monitoring as well as for therapeutic approaches in the future. Twenty-eight patients after allo-SCT have been screened for T-cell responses toward TAA (proteinase-3, WT1, MUC1). We could detect a significant relationship between relapse and the absence of a TAA-specific T-cell response, whereby only 2/13 (15%) patients with TAA-specific CTL relapsed, in contrast to 9/15 (60%) patients without TAA-specific CTL responses (P<0.05). In conclusion, CD8(+) T-cell responses directed to TAA might contribute to the GVL effect. These observations highlight both the importance and the potential of immunotherapeutic approaches after allo-SCT.

  8. Effects of α,β-unsaturated lactones on larval survival and gut trypsin as well as oviposition response of Aedes aegypti.

    Science.gov (United States)

    Barros, Maria Ester S B; Freitas, Juliano C R; Santos, Geanne K N; da Silva, Rayane Cristine Santos; Pontual, Emmanuel V; Paiva, Patrícia M G; Napoleão, Thiago H; Navarro, Daniela M A F; Menezes, Paulo H

    2015-09-01

    Lactones are organic cyclic esters that have been described as larvicides against Aedes aegypti and as components of oviposition pheromone of Culex quinquefasciatus. This work describes the effect of six α,β-unsaturated lactones (5a-5f) on survival of A. aegypti fourth instar larvae (L4). It is also reported the effects of the lactones on L4 gut trypsin activity and oviposition behavior of A. aegypti females. Five lactones were able to kill L4 being the lactones 5a (LC50 of 39.05 ppm), 5e (LC50 of 36.30 ppm) and 5f (LC50 of 40.46 ppm) the most promising larvicides. Only the lactone 5a inhibited L4 gut trypsin activity, with an IC50 of 115.15 µg/mL. Lactones 5a, 5c, 5d and 5e did not exert deterrent or stimulatory effects on oviposition, whereas lactone 5b exhibited a strong deterrent oviposition activity. In conclusion, this work introduces new α,β-unsaturated lactones as promising alternatives to control A. aegypti dissemination. The larvicidal mechanism of the lactone 5a can involve the disruption of proteolysis at larval gut. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Improved tumor response and survival outcomes with post-transplant bortezomib (Btz) consolidation versus observation (Obs) alone in patients with newly diagnosed multiple myeloma (MM)

    DEFF Research Database (Denmark)

    Sezer, O.; Terpos, E.; Hajek, R.

    2015-01-01

    Background: Induction therapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a standard frontline treatment for eligible MM patients (pts). Post- ASCT consolidation can improve depth of response and long-term outcomes. This phase 2 study evaluated the effect...

  10. Survival and immune response of drones of a Nosemosis tolerant honey bee strain towards N. ceranae infections

    DEFF Research Database (Denmark)

    Huanga, Qiang; Kryger, Per; Le Conte, Yves

    2012-01-01

    Honey bee colonies (Apis mellifera) have been selected for low level of Nosema in Denmark over decades and Nosema is now rarely found in bee colonies from these breeding lines. We compared the immune response of a selected and an unselected honey bee lineage, taking advantage of the haploid males...

  11. Cell Survival Signaling in Neuroblastoma

    Science.gov (United States)

    Megison, Michael L.; Gillory, Lauren A.; Beierle, Elizabeth A.

    2013-01-01

    Neuroblastoma is the most common extracranial solid tumor of childhood and is responsible for over 15% of pediatric cancer deaths. Neuroblastoma tumorigenesis and malignant transformation is driven by overexpression and dominance of cell survival pathways and a lack of normal cellular senescence or apoptosis. Therefore, manipulation of cell survival pathways may decrease the malignant potential of these tumors and provide avenues for the development of novel therapeutics. This review focuses on several facets of cell survival pathways including protein kinases (PI3K, AKT, ALK, and FAK), transcription factors (NF-κB, MYCN and p53), and growth factors (IGF, EGF, PDGF, and VEGF). Modulation of each of these factors decreases the growth or otherwise hinders the malignant potential of neuroblastoma, and many therapeutics targeting these pathways are already in the clinical trial phase of development. Continued research and discovery of effective modulators of these pathways will revolutionize the treatment of neuroblastoma. PMID:22934706

  12. Narrative Finality

    Directory of Open Access Journals (Sweden)

    Armine Kotin Mortimer

    1981-01-01

    Full Text Available The cloturai device of narration as salvation represents the lack of finality in three novels. In De Beauvoir's Tous les hommes sont mortels an immortal character turns his story to account, but the novel makes a mockery of the historical sense by which men define themselves. In the closing pages of Butor's La Modification , the hero plans to write a book to save himself. Through the thrice-considered portrayal of the Paris-Rome relationship, the ending shows the reader how to bring about closure, but this collective critique written by readers will always be a future book. Simon's La Bataille de Pharsale , the most radical attempt to destroy finality, is an infinite text. No new text can be written. This extreme of perversion guarantees bliss (jouissance . If the ending of De Beauvoir's novel transfers the burden of non-final world onto a new victim, Butor's non-finality lies in the deferral to a future writing, while Simon's writer is stuck in a writing loop, in which writing has become its own end and hence can have no end. The deconstructive and tragic form of contemporary novels proclaims the loss of belief in a finality inherent in the written text, to the profit of writing itself.

  13. Final Environmental Impact Statement for the construction and operation of Claiborne Enrichment Center, Homer, Louisiana (Docket No. 70-3-70). Volume 2, Public comments and NRC response

    Energy Technology Data Exchange (ETDEWEB)

    Zeitoun, A. [Science Applications International Corp., Germantown, MD (United States)

    1994-08-01

    The Final Environmental Impact Statement (FEIS) (Volume 1), was prepared by the Nuclear Regulatory Commission (NRC) in accordance with regulation 10 CFR Part 51, which implements the National Environmental Policy Act (NEPA), to assess the potential environmental impacts for licensing the construction and operation of a proposed gaseous centrifuge enrichment facility to be built in Claiborne Parish, Louisiana by Louisiana Energy Services, L.P. (LES). The proposed facility would have a production capacity of about 866 metric tons annually of up to 5 weight percent enriched UF{sub 6}, using a proven centrifuge technology. Included in the assessment are co on, both normal operations and potential accidents (internal and external events), and the eventual decontamination and decommissioning of the site. In order to help assure that releases from the operation of the facility and potential impacts on the public are as low as reasonably achievable, an environmental monitoring program was developed by LES to detect significant changes in the background levels of uranium around the site. Other issues addressed include the purpose and need for the facility, the alternatives to the proposed action, potential disposition of the tails, the site selection process, and environmental justice. The NRC staff concludes that the facility can be constructed and operated with small and acceptable impacts on the public and the environment, and proposes to issue a license to the applicant, Louisiana Energy Services, to authorize construction and operation of the proposed facility. The letters in this Appendix have been divided into three sections. Section One contains letters to which the NRC responded by addressing specific comments. Section Two contains the letters that concerned the communities of Forest Grove and Center Springs. Section Three is composed of letters that required no response. These letters were generally in support of the facility.

  14. Final Environmental Impact Statement for the construction and operation of Claiborne Enrichment Center, Homer, Louisiana (Docket No. 70-3-70). Volume 2, Public comments and NRC response

    International Nuclear Information System (INIS)

    Zeitoun, A.

    1994-08-01

    The Final Environmental Impact Statement (FEIS) (Volume 1), was prepared by the Nuclear Regulatory Commission (NRC) in accordance with regulation 10 CFR Part 51, which implements the National Environmental Policy Act (NEPA), to assess the potential environmental impacts for licensing the construction and operation of a proposed gaseous centrifuge enrichment facility to be built in Claiborne Parish, Louisiana by Louisiana Energy Services, L.P. (LES). The proposed facility would have a production capacity of about 866 metric tons annually of up to 5 weight percent enriched UF 6 , using a proven centrifuge technology. Included in the assessment are co on, both normal operations and potential accidents (internal and external events), and the eventual decontamination and decommissioning of the site. In order to help assure that releases from the operation of the facility and potential impacts on the public are as low as reasonably achievable, an environmental monitoring program was developed by LES to detect significant changes in the background levels of uranium around the site. Other issues addressed include the purpose and need for the facility, the alternatives to the proposed action, potential disposition of the tails, the site selection process, and environmental justice. The NRC staff concludes that the facility can be constructed and operated with small and acceptable impacts on the public and the environment, and proposes to issue a license to the applicant, Louisiana Energy Services, to authorize construction and operation of the proposed facility. The letters in this Appendix have been divided into three sections. Section One contains letters to which the NRC responded by addressing specific comments. Section Two contains the letters that concerned the communities of Forest Grove and Center Springs. Section Three is composed of letters that required no response. These letters were generally in support of the facility

  15. Response to long-term growth hormone therapy in patients affected by RASopathies and growth hormone deficiency: Patterns of growth, puberty and final height data.

    Science.gov (United States)

    Tamburrino, Federica; Gibertoni, Dino; Rossi, Cesare; Scarano, Emanuela; Perri, Annamaria; Montanari, Francesca; Fantini, Maria Pia; Pession, Andrea; Tartaglia, Marco; Mazzanti, Laura

    2015-11-01

    RASopathies are developmental disorders caused by heterozygous germline mutations in genes encoding proteins in the RAS-MAPK signaling pathway. Reduced growth is a common feature. Several studies generated data on growth, final height (FH), and height velocity (HV) after growth hormone (GH) treatment in patients with these disorders, particularly in Noonan syndrome, the most common RASopathy. These studies, however, refer to heterogeneous cohorts in terms of molecular information, GH status, age at start and length of therapy, and GH dosage. This work reports growth data in 88 patients affected by RASopathies with molecularly confirmed diagnosis, together with statistics on body proportions, pubertal pattern, and FH in 33, including 16 treated with GH therapy for proven GH deficiency. Thirty-three patients showed GH deficiency after pharmacological tests, and were GH-treated for an average period of 6.8 ± 4.8 years. Before starting therapy, HV was -2.6 ± 1.3 SDS, and mean basal IGF1 levels were -2.0 ± 1.1 SDS. Long-term GH therapy, starting early during childhood, resulted in a positive height response compared with untreated patients (1.3 SDS in terms of height-gain), normalizing FH for Ranke standards but not for general population and Target Height. Pubertal timing negatively affected pubertal growth spurt and FH, with IGF1 standardized score increased from -2.43 to -0.27 SDS. During GH treatment, no significant change in bone age velocity, body proportions, or cardiovascular function was observed. © 2015 Wiley Periodicals, Inc.

  16. Structural features of the two-component system LisR/LisK suggests multiple responses for the adaptation and survival of Listeria monocytogenes

    Directory of Open Access Journals (Sweden)

    Nelson Enrique Arenas Suarez

    2013-08-01

    Full Text Available Here, we characterized the structure of the two-component regulatory system, LisR/LisK, in Listeria monocytogenes. To predict the structure of both proteins and the relationship between them, we employed several bioinformatic tools and databases. Based on our results, LisK protein is embedded in the cell membrane and its modular composition (HAMP, histidine kinase and ATPase domains is associated with its autophosphorylation (His-266. A stimulus-response likely determines the sequential signal propagation from the bacterial cell surface to its cytoplasmic components. According to our results, LisR is a cytoplasmic protein with a receptor domain (homologous to CheY that comprises a phosphoacceptor residue (Asp-52 and a DNA-binding domain, which may allow the transmission of a specific transcriptional response. LisR/LisK has been experimentally characterized both biochemically andfunctionally in other Bacilli pathophysiology; our structure-function approach may facilitate the design of suitable inhibitors.

  17. Long-term effects of neonatal malnutrition on microbicide response, production of cytokines, and survival of macrophages infected by Staphylococcus aureus sensitive/resistant to methicillin

    Directory of Open Access Journals (Sweden)

    Natália Gomes de Morais

    2014-10-01

    Full Text Available OBJECTIVE: To assess microbicide function and macrophage viability after in vitro cellular infection by methicillin-sensitive/resistant Staphylococcus aureus in nourished rats and rats subjected to neonatal malnutrition. METHODS: Male Wistar rats (n=40 were divided in two groups: Nourished (rats suckled by dams consuming a 17% casein diet and Malnourished (rats suckled by dams consuming an 8% casein diet. Macrophages were recovered after tracheotomy, by bronchoalveolar lavage. After mononuclear cell isolation, four systems were established: negative control composed exclusively of phagocytes; positive control composed of macrophages plus lipopolysaccharide; and two testing systems, macrophages plus methicillin-sensitive Staphylococcus aureus and macrophages plus methicillin-resistant Staphylococcus aureus. The plates were incubated in a humid atmosphere at 37 degrees Celsius containing 5% CO2 for 24 hours. After this period tests the microbicidal response, cytokine production, and cell viability were analyzed. The statistical analysis consisted of analysis of variance (p<0.05. RESULTS: Malnutrition reduced weight gain, rate of phagocytosis, production of superoxide anion and nitric oxide, and macrophage viability. Production of nitrite and interleukin 18, and viability of macrophages infected with methicillin-resistant Staphylococcus aureus were lower. CONCLUSION: The neonatal malnutrition model compromised phagocyte function and reduced microbicidal response and cell viability. Interaction between malnutrition and the methicillin-resistant strain decreased the production of inflammatory mediators by effector cells of the immune response, which may compromise the immune system's defense ability.

  18. Individual and Combined Expression of DNA Damage Response Molecules PARP1, γH2AX, BRCA1, and BRCA2 Predict Shorter Survival of Soft Tissue Sarcoma Patients.

    Directory of Open Access Journals (Sweden)

    Kyoung Min Kim

    Full Text Available DNA damage response (DDR molecules are protective against genotoxic stresses. DDR molecules are also involved in the survival of cancer cells in patients undergoing anti-cancer therapies. Therefore, DDR molecules are potential markers of cancer progression in addition to being potential therapeutic targets. In this study, we evaluated the immunohistochemical expression of PARP1, γH2AX, BRCA1, and BRCA2 and their prognostic significance in 112 cases of soft tissue sarcoma (STS. The expression of PARP1, γH2AX, BRCA1, and BRCA2 were significantly associated with each other and were associated with higher tumor stage and presence of distant metastasis. The expression of PARP1, γH2AX, and BRCA2 were significantly associated with shorter disease-specific survival (DSS and event-free survival (EFS by univariate analysis. BRCA1 expression was associated with shorter DSS. Multivariate analysis revealed the expression of PARP1 and γH2AX to be independent indicators of poor prognosis of DSS and EFS. BRCA2 expression was an independent indicator of poor prognosis of DSS. In addition, the combined expressional patterns of PARP1, γH2AX, BRCA1, and BRCA2 (CSddrm were independent prognostic predictors of DSS (P < 0.001 and EFS (P = 0.016. The ten-year DSS rate of the CSddrm-low, CSddrm-intermediate, and CSddrm-high subgroups were 81%, 26%, and 0%, respectively. In conclusion, this study demonstrates that the individual and combined expression patterns of the DDR molecules PARP1, γH2AX, BRCA1, and BRCA2 could be predictive of the prognosis of STS patients and suggests that controlling the activity of these DDR molecules could be employed in new therapeutic stratagems for the treatment of STS.

  19. Prostate cancer: net survival and cause-specific survival rates after multiple imputation.

    Science.gov (United States)

    Morisot, Adeline; Bessaoud, Faïza; Landais, Paul; Rébillard, Xavier; Trétarre, Brigitte; Daurès, Jean-Pierre

    2015-07-28

    Estimations of survival rates are diverse and the choice of the appropriate method depends on the context. Given the increasing interest in multiple imputation methods, we explored the interest of a multiple imputation approach in the estimation of cause-specific survival, when a subset of causes of death was observed. By using European Randomized Study of Screening for Prostate Cancer (ERSPC), 20 multiply imputed datasets were created and analyzed with a Multivariate Imputation by Chained Equation (MICE) algorithm. Then, cause-specific survival was estimated on each dataset with two methods: Kaplan-Meier and competing risks. The two pooled cause-specific survival and confidence intervals were obtained using Rubin's rules after complementary log-log transformation. Net survival was estimated using Pohar-Perme's estimator and was compared to pooled cause-specific survival. Finally, a sensitivity analysis was performed to test the robustness of our constructed multiple imputation model. Cause-specific survival performed better than net survival, since this latter exceeded 100 % for almost the first 2 years of follow-up and after 9 years whereas the cause-specific survival decreased slowly and than stabilized at around 94 % at 9 years. Sensibility study results were satisfactory. On our basis of prostate cancer data, the results obtained by cause-specific survival after multiple imputation appeared to be better and more realistic than those obtained using net survival.

  20. 17Beta-estradiol affects the response of complement components and survival of rainbow trout (Oncorhynchus mykiss) challenged by bacterial infection.

    Science.gov (United States)

    Wenger, Michael; Sattler, Ursula; Goldschmidt-Clermont, Elinor; Segner, Helmut

    2011-07-01

    Research on the endocrine role of estrogens has focused on the reproductive system, while other potential target systems have been less studied. Here, we investigated the possible immunomodulating role of 17β-estradiol (E2) using rainbow trout (Oncorhynchus mykiss) as a model. The aims of the study were to examine a) whether estrogens can modulate immune gene transcription levels, and b) whether this has functional implications for the resistance of trout towards pathogens. Trout were reared from fertilization until 6 months of age under (1) control conditions, (2) short-term E2-treatment (6-month-old juveniles were fed a diet containing 20 mg E2/kg for 2 weeks), or c) long-term E2-treatment (twice a 2-h-bath-exposure of trout embryos to 400 μg 17β-estradiol (E2)/L, followed by rearing on the E2-spiked diet from start-feeding until 6 months of age). Analysis of plasma estrogen levels indicated that the internal estrogen concentrations of E2-exposed fish were within the physiological range and analysis of hepatic vitellogenin mRNA levels indicated that the E2 administration was effective in activating the endogenous estrogen receptor pathway. However, expression levels of the hepatic complement components C3-1, C3-3, and Factor H were not affected by E2-treatment. In a next step, 6-month-old juveniles were challenged with pathogenic bacteria (Yersinia ruckeri). In control fish, this bacterial infection resulted in significant up-regulation of the mRNA levels of hepatic complement genes (C3-1, C3-3, Factor B, Factor H), while E2-treated fish showed no or significantly lower up-regulation of the complement gene transcription levels. Apparently, the E2-treated trout had a lower capacity to activate their immune system to defend against the bacterial infection. This interpretation is corroborated by the finding that survival of E2-treated fish under bacterial challenge was significantly lower than in the control group. In conclusion, the results from this study

  1. Human papillomavirus serologic follow-up response and relationship to survival in head and neck cancer: a case-comparison study

    Directory of Open Access Journals (Sweden)

    Hamšíková Eva

    2011-07-01

    Full Text Available Abstract Background Human papillomavirus high risk (HPV-HR type 16 is a significant risk factor for head and neck cancers (HNC independent of tobacco and alcohol. The purpose of this study was to determine whether antibody levels to the HPV-16 oncoproteins E6 and E7 measured in sera collected at baseline (BL prior to treatment and at two post-treatment follow-up (FU visits were associated with HNC risk factors or prognosis. Methods Presence of antibodies to HPV-16 E6 and E7 was evaluated in 109 newly diagnosed HNC cases with BL and FU blood samples, using the enzyme-linked immunosorbent assay (ELISA. Results HPV-16 E6 and/or E7 seropositive HNC cases were associated with higher risk in younger patients (≤ 55 years, more sexual partners (≥ 10, oropharyngeal cancer, worse stage at diagnosis, poorer grade, and nodal involvement. Between BL and FU (median = 8.3 months, there were decreased antibody levels for seropositive E6 (73% vs. 27%, p = 0.02 and seropositive E7 patients (65% vs. 35%, p = 0.09 with 5% of BL E6 and 35% of BL E7 seropositive patients converting to negative status at FU. Overall mortality (OM was significantly worse among BL E6 seronegative patients than among BL seropositive patients (40.2% vs.13.6%, p = 0.01. There were no disease specific (DS deaths among BL E6 seropositive vs. 24% in BL E6 seronegative patients (p = 0.01. BL E7 seronegative patients also had higher mortality than BL seropositive patients (OM: 38.2% vs. 20.0%, p = 0.04; DS: 22.5% vs. 5.6%, p = 0.07. Conclusion These findings are the first to follow post-treatment OD levels of HPV-16 E6 and E7 in HNC and suggest that these HPV antibodies may be potential prognostic markers of survival in HNC patients.

  2. Final Report

    DEFF Research Database (Denmark)

    Heiselberg, Per; Brohus, Henrik; Nielsen, Peter V.

    This final report for the Hybrid Ventilation Centre at Aalborg University describes the activities and research achievement in the project period from August 2001 to August 2006. The report summarises the work performed and the results achieved with reference to articles and reports published...

  3. Prediction error variance and expected response to selection, when selection is based on the best predictor – for Gaussian and threshold characters, traits following a Poisson mixed model and survival traits

    Directory of Open Access Journals (Sweden)

    Jensen Just

    2002-05-01

    Full Text Available Abstract In this paper, we consider selection based on the best predictor of animal additive genetic values in Gaussian linear mixed models, threshold models, Poisson mixed models, and log normal frailty models for survival data (including models with time-dependent covariates with associated fixed or random effects. In the different models, expressions are given (when these can be found – otherwise unbiased estimates are given for prediction error variance, accuracy of selection and expected response to selection on the additive genetic scale and on the observed scale. The expressions given for non Gaussian traits are generalisations of the well-known formulas for Gaussian traits – and reflect, for Poisson mixed models and frailty models for survival data, the hierarchal structure of the models. In general the ratio of the additive genetic variance to the total variance in the Gaussian part of the model (heritability on the normally distributed level of the model or a generalised version of heritability plays a central role in these formulas.

  4. TolC is important for bacterial survival and oxidative stress response in Salmonella enterica serovar Choleraesuis in an acidic environment.

    Science.gov (United States)

    Lee, Jen-Jie; Wu, Ying-Chen; Kuo, Chih-Jung; Hsuan, Shih-Ling; Chen, Ter-Hsin

    2016-09-25

    The outer membrane protein TolC, which is one of the key components of several multidrug efflux pumps, is thought to be involved in various independent systems in Enterobacteriaceae. Since the acidic environment of the stomach is an important protection barrier against foodborne pathogen infections in hosts, we evaluated whether TolC played a role in the acid tolerance of Salmonella enterica serovar Choleraesuis. Comparison of the acid tolerance of the tolC mutant and the parental wild-type strain showed that the absence of TolC limits the ability of Salmonella to sustain life under extreme acidic conditions. Additionally, the mutant exhibited morphological changes during growth in an acidic medium, leading to the conflicting results of cell viability measured by spectrophotometry and colony-forming unit counting. Reverse-transcriptional-PCR analysis indicated that acid-related molecules, apparatus, or enzymes and oxidation-induced factors were significantly affected by the acidic environment in the null-tolC mutant. The elongated cellular morphology was restored by adding antioxidants to the culture medium. Furthermore, we found that increased cellular antioxidative activity provides an overlapping protection against acid killing, demonstrating the complexity of the bacterial acid stress response. Our findings reinforce the multifunctional characteristics of TolC in acid tolerance or oxidative stress resistance and support the correlative protection mechanism between oxygen- and acid-mediated stress responses in Salmonella enterica serovar Choleraesuis. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Impact of feed restriction and housing hygiene conditions on specific and inflammatory immune response, the cecal bacterial community and the survival of young rabbits.

    Science.gov (United States)

    Combes, S; Massip, K; Martin, O; Furbeyre, H; Cauquil, L; Pascal, G; Bouchez, O; Le Floc'h, N; Zemb, O; Oswald, I P; Gidenne, T

    2017-05-01

    Limiting the post-weaning intake of the young rabbit is known to improve its resistance to digestive disorders, whereas a degradation of its housing hygiene is assumed to have a negative impact on its health. This study aims at providing insights into the mechanism of digestive health preservation regarding both host (growth and immune response) and its symbiotic digestive microbiota. A 2×2 factorial design from weaning (day 28) to day 64 was set up: ad libitum intake or restricted intake at 70% of ad libitum, and high v. low hygiene of housing (n=105 per group). At day 36 and day 45, 15 animals/group were subcutaneously immunized with ovalbumin (OVA) to assess their specific immune response. Blood was sampled at 36, 45, 57 and 64 days of age to determine total and anti-OVA immunoglobulin type G (IgG) and haptoglobin levels. The cecal bacterial community was explored (18 per group) by 454 pyrosequencing of genes coding for the 16S ribosomal RNA, whereas cecal pH, NH3 and volatile fatty acid (VFA) concentrations were measured to characterize fermentative activity. A 30% reduction in feed intake reduced the growth by only 17% (Pratio by 15% (Pratio (3.7 v. 2.4; Phighest in animals raised in poor hygiene conditions after 8 days of restriction, but decreased after 19 days of restriction in high hygiene conditions (-2.15%; Presponse in rabbit, but reduced morbidity instead. Our results suggest that the microbiota composition would be a helpful source of biomarkers of digestive health.

  6. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Issen, Kathleen [Clarkson Univ., Potsdam, NY (United States)

    2017-06-05

    This project employed a continuum approach to formulate an elastic constitutive model for Castlegate sandstone. The resulting constitutive framework for high porosity sandstone is thermodynamically sound, (i.e., does not violate the 1st and 2nd law of thermodynamics), represents known material constitutive response, and is able to be calibrated using available mechanical response data. To authenticate the accuracy of this model, a series of validation criteria were employed, using an existing mechanical response data set for Castlegate sandstone. The resulting constitutive framework is applicable to high porosity sandstones in general, and is tractable for scientists and researchers endeavoring to solve problems of practical interest.

  7. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Stinis, Panos [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-08-07

    This is the final report for the work conducted at the University of Minnesota (during the period 12/01/12-09/18/14) by PI Panos Stinis as part of the "Collaboratory on Mathematics for Mesoscopic Modeling of Materials" (CM4). CM4 is a multi-institution DOE-funded project whose aim is to conduct basic and applied research in the emerging field of mesoscopic modeling of materials.

  8. The Final Frontier

    DEFF Research Database (Denmark)

    Baron, Christian

    2017-01-01

    The concept of the ‘frontier’ plays an important role in understanding the themes that connect survival-oriented science fiction with American history. Building partly on this tradition of the frontier, this chapter seeks to develop the notion of ‘frontier ethics’ as a way of facing moral dilemmas...... premises for making moral judgments that is often not recognized in ethical discussions. In a frontier situation, the failure to respond adequately to life-threatening situations may quickly be interpreted as a moral failure per se – disregarding whether this failure is a result of neglect, recklessness...... moral dilemmas. Disagreements about the severity of a situation (in term of potential threats to survival or loss of vital resources) may easily facilitate moral disagreement about which kind of response is morally defensible....

  9. Conclusiones finales

    OpenAIRE

    Guerrero Gaitán, Manuel

    2016-01-01

    La investigación realizada permite extraer las siguientes conclusiones finales que serán agrupadas según los principales problemas abordados: 1. En relación a las cláusulas que impiden una adecuada transferencia de tecnología, en la presente investigación se demuestra: Primero. Que las cláusulas más frecuentes recogidas en los contratos internacionales de transferencia de tecnología son: la fijación de precios, las restricciones a la investigación y adaptación de la tecnología objeto del cont...

  10. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    R Paul Drake

    2004-01-12

    OAK-B135 This is the final report from the project Hydrodynamics by High-Energy-Density Plasma Flow and Hydrodynamics and Radiation Hydrodynamics with Astrophysical Applications. This project supported a group at the University of Michigan in the invention, design, performance, and analysis of experiments using high-energy-density research facilities. The experiments explored compressible nonlinear hydrodynamics, in particular at decelerating interfaces, and the radiation hydrodynamics of strong shock waves. It has application to supernovae, astrophysical jets, shock-cloud interactions, and radiative shock waves.

  11. Suppression of survival in human SKBR3 breast carcinoma in response to metal-chelator complexes is preferential for copper-dithiocarbamate.

    Science.gov (United States)

    Viola-Rhenals, Maricela; Rieber, Mary Strasberg; Rieber, Manuel

    2006-03-14

    Since diethyl dithiocarbamate (DEDTC) forms complexes with either zinc or copper, and 8-hydroxyquinoline (8-OHQ) also complexes with copper, we now compared the cytotoxic activity of Cu[DEDTC]2, Zn[DEDTC]2 and Cu[8-OHQ]2. This report shows that at nanomolar levels, only copper-[DEDTC]2, suppresses proliferation and clonogenicity of SKBR3 human breast carcinoma, concurrently with induction of apoptosis-associated PARP fragmentation. Susceptibility to these agents was paralleled by reactive oxygen generation (ROS) and greater expression of anti-oxidant enzymes like MnSOD and catalase, with no comparable effect on Cu/Zn superoxide dismutase. The lethal effects of Cu[DEDTC]2 manifested when adding the two separate aqueous components or the preformed synthetic complexes in DMSO, was prevented by N-acetyl cysteine or glutathione, with no comparable protection afforded by non-thiol anti-oxidants like mannitol or DMSO. Exogenously added catalase also protected cells from Cu[DEDTC]2, suggesting that this complex may kill after the levels of superoxide anion [O2*-] dismutated by MnSOD increase hydrogen peroxide-related stress. Cu[DEDTC]2 also induced p21WAF1, a cdk inhibitor usually not inducible in mutant p53 tumors like SKBR3 carcinoma, correlating with dephosphorylation of the Sp1 transcription factor. Concentrations of Cu[DEDTC]2 cytotoxic for SKBR3 carcinoma did not induce comparable damage versus normal diploid human WI-38 fibroblasts. In contrast to the cytotoxic effect of nM levels of Cu[DEDTC]2 against SKBRR3 cells, no response was seen in the same cells exposed to 20 microM cis-platin. Since neither DEDTC bound to zinc, nor copper bound to 8-OHQ showed comparable cytotoxicity, our results suggest that the greater activity of copper-DEDTC reflects a specific structure-activity relationship for the active complex. Since Cu[DEDTC]2 shows more effectiveness than other metal-chelator complexes, it may be worth further investigation as an alternative to cancer therapies.

  12. S.O.S. Surviving or Surviving

    Science.gov (United States)

    Hersh, Richard H.; Whiteman, James

    1973-01-01

    A High School course, General Studies Survival Curriculum, was designed to aid students in problem solving in a complex society. Areas of concern were psychology, consumer economics, environmental studies, law and society, religion and values, ethnic studies, applied aesthetics, creative studies, occupations and futurism. (JB)

  13. Associação entre transientes inicial e final de frequência cardíaca no teste de exercício Asociación entre transientes inicial y final de frecuencia cardiaca en la prueba de ejercicio Association between initial and final transient heart rate responses in exercise testing

    Directory of Open Access Journals (Sweden)

    Gisele Messias Mattioli

    2009-08-01

    variaciones de la FC en los primeros minutos del ejercicio (ΔFC y de la recuperación (dFC. RESULTADO: Hay simples asociaciones entre el TVC y las tres formas de medir el ΔFC, r entre 0,27 y 0,31 (pBACKGROUND: The rest-exercise-rest transition is accompanied by rapid and slow heart rate (HR changes modulated by the branches of the autonomic nervous system. Vagal participation seems to be distinct in these different transitions. Additionally, it is methodologically difficult to determine the best moment and how to measure resting HR. OBJECTIVE: To determine the association between initial (rapid and slow and final transient HR responses during exercise, considering different forms of measuring resting HR. METHODS: We retrospectively studied 103 non-athlete adults (76 males who underwent 4-second exercise test to obtain the rapid transient HR response as measured by the cardiac vagal index (CVI, and completed a maximal cardiopulmonary exercise test in exactly 10 minutes. HR changes were measured in the first few minutes of exercise (ΔHR and recovery (dHR. RESULTS: Modest associations were found between CVI and the three forms of measuring ΔHR, r between 0.27 and 0.31 (p<0.05, and a more significant association between dHR and CVI, r=0.53 (p<0.05. The means of the three measurements of resting HR were different (p<0.05 and showed only reasonable correlations between them (r between 0.64 and 0.76; p<0.05. CONCLUSION: It is important to standardize the measurement of resting HR for the analysis of transient HR responses; small or moderate association between the results of the different transients suggests that partially distinct autonomic mechanisms are involved and that their measurements may provide different and potentially complementary clinical information.

  14. MicroRNA profiling of the bovine alveolar macrophage response to Mycobacterium bovis infection suggests pathogen survival is enhanced by microRNA regulation of endocytosis and lysosome trafficking.

    Science.gov (United States)

    Vegh, Peter; Magee, David A; Nalpas, Nicolas C; Bryan, Kenneth; McCabe, Matthew S; Browne, John A; Conlon, Kevin M; Gordon, Stephen V; Bradley, Daniel G; MacHugh, David E; Lynn, David J

    2015-01-01

    Mycobacterium bovis, the causative agent of bovine tuberculosis, a major problem for global agriculture, spreads via an airborne route and is taken up by alveolar macrophages (AM) in the lung. Here, we describe the first next-generation sequencing (RNA-seq) approach to temporally profile miRNA expression in primary bovine AMs post-infection with M. bovis. One, six, and forty miRNAs were identified as significantly differentially expressed at 2, 24 and 48 h post-infection, respectively. The differential expression of three miRNAs (bta-miR-142-5p, bta-miR-146a, and bta-miR-423-3p) was confirmed by RT-qPCR. Pathway analysis of the predicted mRNA targets of differentially expressed miRNAs suggests that these miRNAs preferentially target several pathways that are functionally relevant for mycobacterial pathogenesis, including endocytosis and lysosome trafficking, IL-1 signalling and the TGF-β pathway. Over-expression studies using a bovine macrophage cell-line (Bomac) reveal the targeting of two key genes in the innate immune response to M. bovis, IL-1 receptor-associated kinase 1 (IRAK1) and TGF-β receptor 2 (TGFBR2), by miR-146. Taken together, our study suggests that miRNAs play a key role in tuning the complex interplay between M. bovis survival strategies and the host immune response.

  15. Platform-Independent Genome-Wide Pattern of DNA Copy-Number Alterations Predicting Astrocytoma Survival and Response to Treatment Revealed by the GSVD Formulated as a Comparative Spectral Decomposition

    Science.gov (United States)

    Aiello, Katherine A.; Alter, Orly

    2016-01-01

    We use the generalized singular value decomposition (GSVD), formulated as a comparative spectral decomposition, to model patient-matched grades III and II, i.e., lower-grade astrocytoma (LGA) brain tumor and normal DNA copy-number profiles. A genome-wide tumor-exclusive pattern of DNA copy-number alterations (CNAs) is revealed, encompassed in that previously uncovered in glioblastoma (GBM), i.e., grade IV astrocytoma, where GBM-specific CNAs encode for enhanced opportunities for transformation and proliferation via growth and developmental signaling pathways in GBM relative to LGA. The GSVD separates the LGA pattern from other sources of biological and experimental variation, common to both, or exclusive to one of the tumor and normal datasets. We find, first, and computationally validate, that the LGA pattern is correlated with a patient’s survival and response to treatment. Second, the GBM pattern identifies among the LGA patients a subtype, statistically indistinguishable from that among the GBM patients, where the CNA genotype is correlated with an approximately one-year survival phenotype. Third, cross-platform classification of the Affymetrix-measured LGA and GBM profiles by using the Agilent-derived GBM pattern shows that the GBM pattern is a platform-independent predictor of astrocytoma outcome. Statistically, the pattern is a better predictor (corresponding to greater median survival time difference, proportional hazard ratio, and concordance index) than the patient’s age and the tumor’s grade, which are the best indicators of astrocytoma currently in clinical use, and laboratory tests. The pattern is also statistically independent of these indicators, and, combined with either one, is an even better predictor of astrocytoma outcome. Recurring DNA CNAs have been observed in astrocytoma tumors’ genomes for decades, however, copy-number subtypes that are predictive of patients’ outcomes were not identified before. This is despite the growing number

  16. Bacillus sp. LT3 improves the survival of gnotobiotic brine shrimp (Artemia franciscana) larvae challenged with Vibrio campbellii by enhancing the innate immune response and by decreasing the activity of shrimp-associated vibrios.

    Science.gov (United States)

    Niu, Yufeng; Defoirdt, Tom; Baruah, Kartik; Van de Wiele, Tom; Dong, Shuanglin; Bossier, Peter

    2014-10-10

    Bacteria belonging to the genus Bacillus are amongst the most intensively studied group of bacteria for use as probiotics in aquaculture. However, the exact mechanism of action of these bacteria is often not well described, and the microbiota that are naturally present in cultures of test organisms often compromise the interpretation of the results. The present study aimed to evaluate the putative probiotic effect of Bacillus sp. LT3 in a model system with gnotobiotic brine shrimp Artemia franciscana larvae. The strain significantly increased the survival of brine shrimp larvae challenged with Vibrio campbellii when administered 6h before the challenge. Under these conditions, LT3 was able to colonize the brine shrimp gastrointestinal tract and to decrease the in vivo pathogen activity as indicated by the bioluminescence of the V. campbellii associated with brine shrimp larvae. In order to investigate the effect of the Bacillus strain on the innate immune system of the brine shrimp larvae, prophenoloxidase and transglutaminase mRNA levels were monitored, while heat shock protein 70 mRNA levels were measured as an indicator of physiological stress. Interestingly, 12h after challenge, the prophenoloxidase mRNA level in the larvae pre-treated with LT3 and challenged with V. campbellii was approximately 8-fold higher than in the other treatments. Further, a decreased mRNA level of transglutaminase gene and heat shock protein 70 gene suggested that pretreatment with LT3 results in less stress and tissue damage in the brine shrimp larvae upon V. campbellii challenge. These results indicated that Bacillus sp. LT3 could improve the survival of brine shrimp larvae when challenged with pathogenic V. campbellii, both by decreasing the in vivo activity of the pathogen and by priming the innate immune response through activating the prophenoloxidase system. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Genome Wide Evaluation of Normal Human Tissue in Response to Controlled, In vivo Low-Dose Low LET Ionizing Radiation Exposure: Pathways and Mechanisms Final Report, September 2013

    Energy Technology Data Exchange (ETDEWEB)

    Rocke, David M. [University of California Davis

    2013-09-09

    During course of this project, we have worked in several areas relevant to low-dose ionizing radiation. Using gene expression to measure biological response, we have examined the response of human skin exposed in-vivo to radation, human skin exposed ex-vivo to radiation, and a human-skin model exposed to radiation. We have learned a great deal about the biological response of human skin to low-dose ionizing radiation.

  18. Aircraft Survivability. Spring 2011

    Science.gov (United States)

    2011-01-01

    panel exhibiting telltale signs and critical fragments were identified and collected. The weapon employed against the aircraft was correctly assessed...701C engines (for FCR- equipped Apache Longbows), and a fully integrated cockpit. In addition, the aircraft received improved survivability...sustained analytical contributions to improve the survivability and effectiveness of US military aircraft and weapon systems. These contributions

  19. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Jarillo-Herrero, Pablo [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

    2017-02-07

    This is the final report of our research program on electronic transport experiments on Topological Insulator (TI) devices, funded by the DOE Office of Basic Energy Sciences. TI-based electronic devices are attractive as platforms for spintronic applications, and for detection of emergent properties such as Majorana excitations , electron-hole condensates , and the topological magneto-electric effect . Most theoretical proposals envision geometries consisting of a planar TI device integrated with materials of distinctly different physical phases (such as ferromagnets and superconductors). Experimental realization of physics tied to the surface states is a challenge due to the ubiquitous presence of bulk carriers in most TI compounds as well as degradation during device fabrication.

  20. Saudi sands, SCUDS, and survival.

    Science.gov (United States)

    Glendon, M P

    1993-01-01

    SCUD attacks were one of many challenges this pediatric nurse practitioner (NP) and Air Force Reserve flight nurse faced daily during Desert Shield and Desert Storm. Providing nursing care to sick and injured patients on board a C141 transport plane en route from Saudi Arabia to Germany was her primary responsibility. Additionally, many hours were spent filling sandbags, attending in-service classes, and practicing putting on a gas mask and protective suit. Although the war has been over for almost 3 years, the effects are long lasting. The author was able to use her wartime experience positively to gain insight into survival in today's violent society. As violence increases, NPs must reshape their focus and educate their clients about survival.

  1. Campylobacter virulence and survival factors.

    Science.gov (United States)

    Bolton, Declan J

    2015-06-01

    Despite over 30 years of research, campylobacteriosis is the most prevalent foodborne bacterial infection in many countries including in the European Union and the United States of America. However, relatively little is known about the virulence factors in Campylobacter or how an apparently fragile organism can survive in the food chain, often with enhanced pathogenicity. This review collates information on the virulence and survival determinants including motility, chemotaxis, adhesion, invasion, multidrug resistance, bile resistance and stress response factors. It discusses their function in transition through the food processing environment and human infection. In doing so it provides a fundamental understanding of Campylobacter, critical for improved diagnosis, surveillance and control. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Efficient Methods of Estimating the Operating Characteristics of Item Response Categories and Challenge to a New Model for the Multiple-Choice Item. Final Report.

    Science.gov (United States)

    Samejima, Fumiko

    In defense of retaining the "latent trait theory" term, instead of replacing it with "item response theory" as some recent research would have it, the following objectives are outlined: (1) investigation of theory and method for estimating the operating characteristics of discrete item responses using a minimum number of…

  3. Leishmania donovani Activates Hypoxia Inducible Factor-1α and miR-210 for Survival in Macrophages by Downregulation of NF-κB Mediated Pro-inflammatory Immune Response

    Directory of Open Access Journals (Sweden)

    Vinod Kumar

    2018-03-01

    Full Text Available Micro RNAs (miRNAs have emerged as a critical regulator of several biological processes in both animals and plants. They have also been associated with regulation of immune responses in many human diseases during recent years. Visceral leishmaniasis (VL is the most severe form of leishmaniasis, which is characterized by impairment of both innate and adaptive immune responses. In the present study, we observed that Leishmania establishes hypoxic environment in host macrophages that induces the expression of hypoxia inducible factor-1α (HIF-1α and miRNA-210. Further, the expression of miRNA-210 was found to be dependent on activation of HIF-1α expression. The HIF-1α silencing by siRNA resulted in significantly (p < 0.001 decreased expression of miR-210 in parasites infected macrophages. We also observed that in siHIF-1α or antagomir-210 treated L. donovani infected macrophages, the parasitic load and percentage infectivity were significantly (p < 0.001 decreased. Furthermore, we found that inhibition of miR-210 leads to activation of NF-κB subunit p50, and it forms heterodimer with p65 and translocates into the nucleus from the cytoplasm. This significantly (p < 0.05 induced the transcription of pro-inflammatory cytokines genes such as TNF-α and IL-12 in miRNA-210 inhibited macrophages compared to uninhibited macrophages whereas the level of IL-10, an anti-inflammatory cytokine, was found to be significantly decreased (p < 0.001. These findings suggested that L. donovani infection induces hypoxic environment inside the macrophages that activates HIF-1α. Further, HIF-1α upregulates miR-210, which eventually establishes a suitable environment for the survival of parasite inside the host macrophages by downregulating NF-κB mediated pro-inflammatory immune responses.

  4. Predictive factors of tumour response after neo-adjuvant chemo-radiation for locally advanced rectal cancer and correlation of these factors with survival; Facteurs predictifs de reponse a la radiochimiotherapie neoaduvante dans les cancers rectaux localement evolues et correlation de ces facteurs avec la survie

    Energy Technology Data Exchange (ETDEWEB)

    Farnault, B.; Moureau-Zabotto, L.; Resbeut, M. [Departement de radiotherapie, institut Paoli-Calmettes, 232, boulevard Sainte-Marguerite, 13009 Marseille (France); De Chaisemartin, C.; Lelong, B.; Delpero, J.R.; Turrini, O. [Departement de chirurgie digestive, institut Paoli-Calmettes, 232, boulevard Sainte-Marguerite, 13009 Marseille (France); Esterni, B. [Departement de statistiques, institut Paoli-Calmettes, 232, boulevard Sainte-Marguerite, 13009 Marseille (France); Viret, F.; Viens, P. [Departement d' oncologie medicale, institut Paoli-Calmettes, 232, boulevard Sainte-Marguerite, 13009 Marseille (France); Giovannini, M.; Bories, E. [Departement d' endoscopie digestive, institut Paoli-Calmettes, 232, boulevard Sainte-Marguerite, 13009 Marseille (France); Monges, G. [Departement d' anatomopathologie, institut Paoli-Calmettes, 232, boulevard Sainte-Marguerite, 13009 Marseille (France)

    2011-07-15

    Purpose. - neo-adjuvant chemo-radiation followed by surgery is the standard of care for locally advanced rectal cancer. The aim of this study was to correlate tumour response to survival and to identify predictive factors for tumour response after chemo-radiation. Patients and methods. - From 1998 to 2008, 168 patients with histologically-proven locally advanced adenocarcinoma treated by preoperative chemo-radiation before total meso-rectal excision were retrospectively studied. They received a radiation dose of 45 Gy with a concomitant 5-fluoro-uracil-based chemotherapy. Analysis of tumour response was based on the lowering of T stage between pre-treatment endorectal ultrasound and pathologic specimens. Overall and progression-free survival was correlated with tumour response. Tumour response was analysed with predictive factors. (authors)

  5. Survival after in-hospital Cardiopulmonary Resuscitation

    Directory of Open Access Journals (Sweden)

    M Adib Hajbaghery

    2005-05-01

    Full Text Available Background: During recent years, cardiopulmonary resuscitation (CPR in hospital has received much attention. However, the survival rate of CPR in Iran’s hospitals is unknown. This study was designed to evaluate outcome of in-hospital CPR in Kashan. Methods: A longitudinal case registry study was conducted on all cases of in-hospital CPR during 6 months at 2002. Necessary data including; age, sex, underlying disease, working shift, time from cardiac arrest until initiating of CPR and until defibrillation, duration and result of CPR, frequency of tracheal intubations and time served for it were collected in a checklist. Results: In six months study, 206 cases of cardiopulmonary resuscitation attempted. The survival rate was similar for both sexes. Short-term survival observed in19.9% of cases and only 5.3% survived to discharge. Conclusions: Duration of CPR, time of the first defibrillation, response time and the location of cardiac arrest are the key predictors of survival to hospital discharge and in-hospital CPR strategies require improvement. This study promotes a national study on post CPR survival for accurate data on our performance in attention to chain of survival. KeyWords: Cardiopulmonary Resuscitation (CPR, Survival rate, Iran

  6. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Webb, Robert C. [Texas A& M University; Kamon, Teruki [Texas A& M University; Toback, David [Texas A& M University; Safonov, Alexei [Texas A& M University; Dutta, Bhaskar [Texas A& M University; Dimitri, Nanopoulos [Texas A& M University; Pope, Christopher [Texas A& M University; White, James [Texas A& M University

    2013-11-18

    Overview The High Energy Physics Group at Texas A&M University is submitting this final report for our grant number DE-FG02-95ER40917. This grant has supported our wide range of research activities for over a decade. The reports contained here summarize the latest work done by our research team. Task A (Collider Physics Program): CMS & CDF Profs. T. Kamon, A. Safonov, and D. Toback co-lead the Texas A&M (TAMU) collider program focusing on CDF and CMS experiments. Task D: Particle Physics Theory Our particle physics theory task is the combined effort of Profs. B. Dutta, D. Nanopoulos, and C. Pope. Task E (Underground Physics): LUX & NEXT Profs. R. Webb and J. White(deceased) lead the Xenon-based underground research program consisting of two main thrusts: the first, participation in the LUX two-phase xenon dark matter search experiment and the second, detector R&D primarily aimed at developing future detectors for underground physics (e.g. NEXT and LZ).

  7. Not from my world. Responsibility for future generations in the final disposal of nuclear waste; Nicht von meiner Welt. Zukunftsverantwortung bei der Endlagerung von radioaktiven Reststoffen

    Energy Technology Data Exchange (ETDEWEB)

    Ott, Konrad [Kiel Univ. (Germany). Philosophisches Seminar; Semper, Franziska [TU Braunschweig (Germany). Inst. fuer Rechtswissenschaften

    2017-09-01

    In Germany the decision on a final repository for nuclear wastes is intended for 2031. The consequences of this decision will concern many generations in the future. Today there is a contradiction between the request of reversibility of all measures and the avoidance of the necessity of continuous activities for future generations. There is no way for a simple solution. The interests of future generations have to be considered as well as the interests of the actual living society.

  8. Growth response and survival of Heterobranchus longifilis ...

    African Journals Online (AJOL)

    GRACE

    2006-05-02

    May 2, 2006 ... quadratic regression analysis observed that rainbow trout. Oncorhynchus mykiss had higher growth rates when fed. 3 times/day compared to fish fed once/day or twice/day, but were not different from fish fed four times/day. The results of this study of fish fed twice daily also agree with those of Noeske-Hallin ...

  9. The Procalcitonin And Survival Study (PASS) – A Randomised multi-center investigator-initiated trial to investigate whether daily measurements biomarker Procalcitonin and pro-active diagnostic and therapeutic responses to abnormal Procalcitonin levels, can improve survival in intensive care unit patients. Calculated sample size (target population): 1000 patients

    Science.gov (United States)

    Jensen, Jens-Ulrik; Lundgren, Bettina; Hein, Lars; Mohr, Thomas; Petersen, Pernille L; Andersen, Lasse H; Lauritsen, Anne Ø; Hougaard, Sine; Mantoni, Teit; Bømler, Bonnie; Thornberg, Klaus J; Thormar, Katrin; Løken, Jesper; Steensen, Morten; Carl, Peder; Petersen, J Asger; Tousi, Hamid; Søe-Jensen, Peter; Bestle, Morten; Hestad, Søren; Andersen, Mads H; Fjeldborg, Paul; Larsen, Kim M; Rossau, Charlotte; Thomsen, Carsten B; Østergaard, Christian; Kjær, Jesper; Grarup, Jesper; Lundgren, Jens D

    2008-01-01

    Background Sepsis and complications to sepsis are major causes of mortality in critically ill patients. Rapid treatment of sepsis is of crucial importance for survival of patients. The infectious status of the critically ill patient is often difficult to assess because symptoms cannot be expressed and signs may present atypically. The established biological markers of inflammation (leucocytes, C-reactive protein) may often be influenced by other parameters than infection, and may be unacceptably slowly released after progression of an infection. At the same time, lack of a relevant antimicrobial therapy in an early course of infection may be fatal for the patient. Specific and rapid markers of bacterial infection have been sought for use in these patients. Methods Multi-centre randomized controlled interventional trial. Powered for superiority and non-inferiority on all measured end points. Complies with, "Good Clinical Practice" (ICH-GCP Guideline (CPMP/ICH/135/95, Directive 2001/20/EC)). Inclusion: 1) Age ≥ 18 years of age, 2) Admitted to the participating intensive care units, 3) Signed written informed consent. Exclusion: 1) Known hyper-bilirubinaemia. or hypertriglyceridaemia, 2) Likely that safety is compromised by blood sampling, 3) Pregnant or breast feeding. Computerized Randomisation: Two arms (1:1), n = 500 per arm: Arm 1: standard of care. Arm 2: standard of care and Procalcitonin guided diagnostics and treatment of infection. Primary Trial Objective: To address whether daily Procalcitonin measurements and immediate diagnostic and therapeutic response on day-to-day changes in procalcitonin can reduce the mortality of critically ill patients. Discussion For the first time ever, a mortality-endpoint, large scale randomized controlled trial with a biomarker-guided strategy compared to the best standard of care, is conducted in an Intensive care setting. Results will, with a high statistical power answer the question: Can the survival of critically ill

  10. The Procalcitonin And Survival Study (PASS – A Randomised multi-center investigator-initiated trial to investigate whether daily measurements biomarker Procalcitonin and pro-active diagnostic and therapeutic responses to abnormal Procalcitonin levels, can improve survival in intensive care unit patients. Calculated sample size (target population: 1000 patients

    Directory of Open Access Journals (Sweden)

    Fjeldborg Paul

    2008-07-01

    Full Text Available Abstract Background Sepsis and complications to sepsis are major causes of mortality in critically ill patients. Rapid treatment of sepsis is of crucial importance for survival of patients. The infectious status of the critically ill patient is often difficult to assess because symptoms cannot be expressed and signs may present atypically. The established biological markers of inflammation (leucocytes, C-reactive protein may often be influenced by other parameters than infection, and may be unacceptably slowly released after progression of an infection. At the same time, lack of a relevant antimicrobial therapy in an early course of infection may be fatal for the patient. Specific and rapid markers of bacterial infection have been sought for use in these patients. Methods Multi-centre randomized controlled interventional trial. Powered for superiority and non-inferiority on all measured end points. Complies with, "Good Clinical Practice" (ICH-GCP Guideline (CPMP/ICH/135/95, Directive 2001/20/EC. Inclusion: 1 Age ≥ 18 years of age, 2 Admitted to the participating intensive care units, 3 Signed written informed consent. Exclusion: 1 Known hyper-bilirubinaemia. or hypertriglyceridaemia, 2 Likely that safety is compromised by blood sampling, 3 Pregnant or breast feeding. Computerized Randomisation: Two arms (1:1, n = 500 per arm: Arm 1: standard of care. Arm 2: standard of care and Procalcitonin guided diagnostics and treatment of infection. Primary Trial Objective: To address whether daily Procalcitonin measurements and immediate diagnostic and therapeutic response on day-to-day changes in procalcitonin can reduce the mortality of critically ill patients. Discussion For the first time ever, a mortality-endpoint, large scale randomized controlled trial with a biomarker-guided strategy compared to the best standard of care, is conducted in an Intensive care setting. Results will, with a high statistical power answer the question: Can the survival

  11. Surviving Sepsis Campaign

    DEFF Research Database (Denmark)

    Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed

    2017-01-01

    OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meeting...

  12. Modulation of cell proliferation, survival and gene expression by RAGE and TLR signaling in cells of the innate and adaptive immune response: role of p38 MAPK and NF-KB

    Directory of Open Access Journals (Sweden)

    Marcell Costa de MEDEIROS

    2014-06-01

    Full Text Available Objective: The aim of this study was to evaluate a possible synergism between AGE-RAGE and TLR4 signaling and the role of p38 MAPK and NF-kB signaling pathways on the modulation of the expression of inflammatory cytokines and proliferation of cells from the innate and adaptive immune response. Material and Methods: T lymphocyte (JM and monocyte (U937 cell lines were stimulated with LPS and AGE-BSA independently and associated, both in the presence and absence of p38 MAPK and NF-kB inhibitors. Proliferation was assessed by direct counting and viability was assessed by a biochemical assay of mitochondrial function. Cytokine gene expression for RAGe, CCL3, CCR5, IL-6 and TNF-α was studied by RT-PCR and RT-qPCR. Results: RAGE mRNA expression was detected in both cell lines. LPS and AGE-BSA did not influence cell proliferation and viability of either cell line up to 72 hours. LPS and LPS associated with AGE induced expression of IL-6 and TNF-α in monocytes and T cells, respectively. Conclusions: There is no synergistic effect between RAGE and TLR signaling on the expression of IL-6, TNF-α , RAGE, CCR5 and CCL3 by monocytes and lymphocytes. Activation of RAGE associated or not with TLR signaling also had no effect on cell proliferation and survival of these cell types.

  13. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Joseph H. Simmons; Tracie J. Bukowski

    2002-08-07

    This grant was a continuation of research conducted at the University of Florida under Grant No. DE-FG05-91ER45462 in which we investigated the energy bandgap shifts produced in semiconductor quantum dots of sizes between 1.5 and 40 nm. The investigated semiconductors consisted of a series of Column 2-6 compounds (CdS, CdSe, CdTe) and pure Column IV elements (Si and Ge). It is well-known of course that the 2-6 semiconductors possess a direct-gap electronic structure, while the Column IV elements possess an indirect-gap structure. The investigation showed a major difference in quantum confinement behavior between the two sets of semiconductors. This difference is essentially associated with the change in bandgap energy resulting from size confinement. In the direct-gap semiconductors, the change in energy (blue shift) saturates when the crystals approach 2-3 nm in diameter. This limits the observed shift in energy to less than 1 eV above the bulk value. In the indirect-gap semiconductors, the energy shift does not show any sign of saturation and in fact, we produced Si and Ge nanocrystals with absorption edges in the UV. The reason for this difference has not been determined and will require additional experimental and theoretical studies. In our work, we suggest, but do not prove that mixing of conduction band side valleys with the central valley under conditions of size confinement may be responsible for the saturation in the blue-shift of direct-gap semiconductors. The discovery of large bandgap energy shifts with crystal size prompted us to suggest that these materials may be used to form photovoltaic cells with multi-gap layers for high efficiency in a U.S. Patent issued in 1998. However, this possibility depends strongly on the ability to collect photoexcited carriers from energy-confined crystals. The research conducted at the University of Arizona under the subject grant had a major goal of testing an indirect gap semiconductor in size-confined structures to

  14. Does early response to intravenous glucocorticoids predict the final outcome in patients with moderate-to-severe and active Graves' orbitopathy?

    NARCIS (Netherlands)

    Bartalena, L.; Veronesi, G.; Krassas, G. E.; Wiersinga, W. M.; Marcocci, C.; Marinò, M.; Salvi, M.; Daumerie, C.; Bournaud, C.; Stahl, M.; Sassi, L.; Azzolini, C.; Boboridis, K. G.; Mourits, M. P.; Soeters, M. R.; Baldeschi, L.; Nardi, M.; Currò, N.; Boschi, A.; Bernard, M.; von Arx, G.; Perros, P.; Kahaly, G. J.

    2017-01-01

    Intravenous glucocorticoids (ivGCs) given as 12-weekly infusions are the first-line treatment for moderate-to-severe and active Graves' orbitopathy (GO), but they are not always effective. In this study, we evaluated whether response at 6 weeks correlated with outcomes at 12 (end of intervention)

  15. Final Scientific Report DE-FGO3-97ER62460 Stomatal Responses to CO2: A Comparison of Woody and Herbaceous Species in Arid and Humid Climates

    Energy Technology Data Exchange (ETDEWEB)

    Koch, George W.

    2003-12-19

    OAK-B135 The project involved a study of a fundamental response of terrestrial vegetation to rising atmospheric carbon dioxide (CO2) concentration, namely, the change in leaf conductance to gas diffusion associated with a change in the aperture of the microscopic pores (stomata) on the surface of leaves.

  16. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    J. K. Blasie; W.F. DeGrado; J.G. Saven; M.J. Therien

    2012-05-24

    The overall objective is to create robust artificial protein modules as scaffolds to control both (a) the conformation of novel cofactors incorporated into the modules thereby making the modules possess a desired functionality and (b) the organization of these functional modules into ordered macroscopic ensembles, whose macroscopic materials properties derive from the designed microscopic function of the modules. We focus on two specific types of cofactors for imparting functionality in this project; primarily nonlinear optical (NLO) chromophores designed to exhibit extraordinary molecular hyperpolarizabilities, as well as donor-bridge-acceptor cofactors designed to exhibit highly efficient, 'through-bonds' light-induced electron transfer (LIET) over nano-scale distances. The ensembles range from 2-D to 3-D, designed to possess the degree of orientational and positional order necessary to optimize their macroscopic response, the latter ranging from liquid-crystalline or glass-like to long-range periodic. Computational techniques, firmly based in statistical thermodynamics, are utilized for the design the artificial protein modules, based on robust {alpha}-helical bundle motifs, necessarily incorporating the desired conformation, location, and environment of the cofactor. Importantly, this design approach also includes optimization of the interactions between the modules to promote their organization into ordered macroscopic ensembles in 2-D and 3-D via either directed-assembly or self-assembly. When long-range periodic order is required, the design can be optimized to result a specified lattice symmetry. The structure and functionality of the individual modules are fully characterized at the microscopic level, as well as that of the ensembles at the macroscopic level, employing modern experimental physical-chemical and computational techniques. These include, for example, multi-dimensional NMR, various pump-probe transient spectroscopies to ultrafast time

  17. Modeling the response of plants and ecosystems to CO{sub 2} and climate change. Final technical report, September 1, 1992--August 31, 1996

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, J.F.

    1998-04-10

    Objectives can be divided into those for plant modeling and those for ecosystem modeling and experimental work in support of both. The author worked in a variety of ecosystem types, including pine, arctic, desert, and grasslands. Plant modeling objectives are: (1) to construct generic models of leaf, canopy, and whole-plant response to elevated CO{sub 2} and climate change; (2) to validate predictions of whole-plant response against various field studies of elevated CO{sub 2} and climate change; (3) to use these models to test specific hypotheses and to make predictions about primary, secondary and tertiary effects of elevated CO{sub 2} and climate change on individual plants for conditions and time frames beyond those used to calibrate the model; and (4) to provide information to higher-level models, such as community models and ecosystem models. Ecosystem level modeling objectives are: (1) to incorporate models of plant responses to elevated CO{sub 2} into a generic ecosystem model in order to predict the direct and indirect effects of elevated CO{sub 2} and climate change on ecosystems; (2) to validate model predictions of total system-level response (including decomposition) against various ecosystem field studies of elevated CO{sub 2} and climate change; (3) to use the ecosystem model to test specific hypotheses and to make predictions about primary, secondary and tertiary effects of elevated CO{sub 2} and climate change on ecosystems for conditions and time frames beyond those used to calibrate the model; and (4) to use the ecosystem model to study effects of change in CO{sub 2} and climate at regional and global scales. Occasionally the author conducted some experimental work that was deemed important to the development of the models. This work was mainly physiological work that could be performed in the Duke University Phytotron, using existing facilities.

  18. Approaches to the final disposal of radioactive waste in the Federal Republic of Germany. Will responsibility be shifted to future generations?

    International Nuclear Information System (INIS)

    Thomauske, B.

    2004-01-01

    The analysis presented shows that an operational repository for heat generating radioactive waste can be realised only by resumption of the underground exploration work at Gorleben and demonstration of the suitability of that site and subsequent construction of the repository. Acting responsibly means to build the Konrad repository speedily after completion of the legal proceedings about the license and, in this way, avoid the erection of additional interim storage facilities for waste with negligible heat generation. (orig.) [de

  19. Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: final results of the RNS System Pivotal trial.

    Science.gov (United States)

    Heck, Christianne N; King-Stephens, David; Massey, Andrew D; Nair, Dileep R; Jobst, Barbara C; Barkley, Gregory L; Salanova, Vicenta; Cole, Andrew J; Smith, Michael C; Gwinn, Ryder P; Skidmore, Christopher; Van Ness, Paul C; Bergey, Gregory K; Park, Yong D; Miller, Ian; Geller, Eric; Rutecki, Paul A; Zimmerman, Richard; Spencer, David C; Goldman, Alica; Edwards, Jonathan C; Leiphart, James W; Wharen, Robert E; Fessler, James; Fountain, Nathan B; Worrell, Gregory A; Gross, Robert E; Eisenschenk, Stephan; Duckrow, Robert B; Hirsch, Lawrence J; Bazil, Carl; O'Donovan, Cormac A; Sun, Felice T; Courtney, Tracy A; Seale, Cairn G; Morrell, Martha J

    2014-03-01

    To demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci. Randomized multicenter double-blinded controlled trial of responsive focal cortical stimulation (RNS System). Subjects with medically intractable partial onset seizures from one or two foci were implanted, and 1 month postimplant were randomized 1:1 to active or sham stimulation. After the fifth postimplant month, all subjects received responsive stimulation in an open label period (OLP) to complete 2 years of postimplant follow-up. All 191 subjects were randomized. The percent change in seizures at the end of the blinded period was -37.9% in the active and -17.3% in the sham stimulation group (p = 0.012, Generalized Estimating Equations). The median percent reduction in seizures in the OLP was 44% at 1 year and 53% at 2 years, which represents a progressive and significant improvement with time (p < 0.0001). The serious adverse event rate was not different between subjects receiving active and sham stimulation. Adverse events were consistent with the known risks of an implanted medical device, seizures, and of other epilepsy treatments. There were no adverse effects on neuropsychological function or mood. Responsive stimulation to the seizure focus reduced the frequency of partial-onset seizures acutely, showed improving seizure reduction over time, was well tolerated, and was acceptably safe. The RNS System provides an additional treatment option for patients with medically intractable partial-onset seizures. © 2014 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

  20. Final environmental impact statement for the continued operation of the Pantex Plant and associated storage of nuclear weapon components. Volume 3 -- Comment response

    International Nuclear Information System (INIS)

    1996-11-01

    The Draft Environmental Impact Statement (EIS) for the continued operation of Pantex Plant was published in March 1996. The document assessed the alternatives of no action, relocation of the storage of plutonium components resulting from nuclear weapon disassemble activities at Pantex Plant to another site, and the proposed action (preferred alternative) of continuing operations and increasing the quantity of pits in interim storage at Pantex Plant. This report contains the comments and responses received on the Draft EIS

  1. Final generic environmental statement on the use of recycle plutonium in mixed oxide fuel in light water cooled reactors. Volume 5. Public comments and Nuclear Regulatory Commission responses

    International Nuclear Information System (INIS)

    1976-08-01

    Copies of 69 letters are presented commenting on the Draft Generic Environmental Statement (GESMO) WASH-1327 and the NRC's responses to the comments received from Federal, State and local agencies; environmental and public interest groups, members of the academic and industrial communities, and individual citizens. An index to these letters indicating the number assigned to each letter, the author, and organization represented, is provided in the Table of Contents

  2. Marketing child survival.

    Science.gov (United States)

    Grant, J P

    1984-01-01

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

  3. Quantify Plasma Response to Non-Axisymmetric (3D) Magnetic Fields in Tokamaks, Final Report for FES (Fusion Energy Sciences) FY2014 Joint Research Target

    Energy Technology Data Exchange (ETDEWEB)

    Strait, E. J. [General Atomics, San Diego, CA (United States); Park, J. -K. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Marmar, E. S. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Ahn, J. -W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Berkery, J. W. [Columbia Univ., New York, NY (United States); Burrell, K. H. [General Atomics, San Diego, CA (United States); Canik, J. M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Delgado-Aparicio, L. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Ferraro, N. M. [General Atomics, San Diego, CA (United States); Garofalo, A. M. [General Atomics, San Diego, CA (United States); Gates, D. A. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Greenwald, M. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Kim, K. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); King, J. D. [General Atomics, San Diego, CA (United States); Lanctot, M. J. [General Atomics, San Diego, CA (United States); Lazerson, S. A. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Liu, Y. Q. [Culham Science Centre, Abingdon (United Kingdom). Euratom/CCFE Association; Logan, N. C. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Lore, J. D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Menard, J. E. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Nazikian, R. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Shafer, M. W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Paz-Soldan, C. [General Atomics, San Diego, CA (United States); Reiman, A. H. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Rice, J. E. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Sabbagh, S. A. [Columbia Univ., New York, NY (United States); Sugiyama, L. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Turnbull, A. D. [General Atomics, San Diego, CA (United States); Volpe, F. [Columbia Univ., New York, NY (United States); Wang, Z. R. [Princeton Plasma Physics Lab. (PPPL), Princeton, NJ (United States); Wolfe, S. M. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

    2014-09-30

    The goal of the 2014 Joint Research Target (JRT) has been to conduct experiments and analysis to investigate and quantify the response of tokamak plasmas to non-axisymmetric (3D) magnetic fields. Although tokamaks are conceptually axisymmetric devices, small asymmetries often result from inaccuracies in the manufacture and assembly of the magnet coils, or from nearby magnetized objects. In addition, non-axisymmetric fields may be deliberately applied for various purposes. Even at small amplitudes of order 10-4 of the main axisymmetric field, such “3D” fields can have profound impacts on the plasma performance. The effects are often detrimental (reduction of stabilizing plasma rotation, degradation of energy confinement, localized heat flux to the divertor, or excitation of instabilities) but may in some case be beneficial (maintenance of rotation, or suppression of instabilities). In general, the magnetic response of the plasma alters the 3D field, so that the magnetic field configuration within the plasma is not simply the sum of the external 3D field and the original axisymmetric field. Typically the plasma response consists of a mixture of local screening of the external field by currents induced at resonant surfaces in the plasma, and amplification of the external field by stable kink modes. Thus, validated magnetohydrodynamic (MHD) models of the plasma response to 3D fields are crucial to the interpretation of existing experiments and the prediction of plasma performance in future devices. The non-axisymmetric coil sets available at each facility allow well-controlled studies of the response to external 3D fields. The work performed in support of the 2014 Joint Research Target has included joint modeling and analysis of existing experimental data, and collaboration on new experiments designed to address the goals of the JRT. A major focus of the work was validation of numerical models through quantitative comparison to experimental data, in

  4. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Weissman, Jon B

    2006-04-30

    High performance computational science and engineering simulations have become an increasingly important part of the scientist's problem solving toolset. A key reason is the development of widely used codes and libraries that support these applications, for example, Netlib, a collection of numerical libraries [33]. The term community codes refers to those libraries or applications that have achieved some critical level of acceptance by a user community. Many of these applications are on the high-end in terms of required resources: computation, storage, and communication. Recently, there has been considerable interest in putting such applications on-line and packaging them as network services to make them available to a wider user base. Applications such as data mining [22], theorem proving and logic [14], parallel numerical computation [8][32] are example services that are all going on-line. Transforming applications into services has been made possible by advances in packaging and interface technologies including component systems [2][6][13][28][37], proposed communication standards [34], and newer Web technologies such as Web Services [38]. Network services allow the user to focus on their application and obtain remote service when needed by simply invoking the service across the network. The user can be assured that the most recent version of the code or service is always provided and they do not need to install, maintain, and manage significant infrastructure to access the service. For high performance applications in particular, the user is still often required to install a code base (e.g. MPI), and therefore become involved with the tedious details of infrastructure management. In the network service model, the service provider is responsible for all of these activities and not the user. The user need not become an expert in high performance computing. An additional advantage of high-end network services is that the user need not have specialized

  5. Always follow your nose: the functional significance of social chemosignals in human reproduction and survival.

    Science.gov (United States)

    Lübke, Katrin T; Pause, Bettina M

    2015-02-01

    This article is part of a Special Issue "Chemosignals and Reproduction" Across phyla, chemosensory communication is crucial for mediating a variety of social behaviors, which form the basis for ontogenetic and phylogenetic survival. In the present paper, evidence on chemosensory communication in humans, with special reference to reproduction and survival, will be presented. First, the impact of chemosignals on human reproduction will be reviewed. Work will be presented, showing how chemosensory signals are involved in mate choice and partnership formation by communicating attractiveness and facilitating a partner selection, which is of evolutionary advantage, and furthermore providing information about the level of sexual hormones. In addition to direct effects on phylogenetic survival, chemosignals indirectly aid reproductive success by fostering harm protection. Results will be presented, showing that chemosensory communication aids the emotional bond between mother and child, which in turn motivates parental caretaking and protection, leading to infant survival. Moreover, the likelihood of group survival can be increased through the use of stress-related chemosignals. Stress-related chemosignals induce a stress-related physiology in the perceiver, thereby priming a fight-flight-response, which is necessary for an optimum adaption to environmental harm. Finally, effects of sexual orientation on chemosensory communication will be discussed in terms of their putative role in stabilizing social groups, which might indirectly provide harm protection and foster survival. An integrative model of the presented data will be introduced. In conclusion, an outlook, focusing on the involvement of chemosensory communication in human social behavior and illustrating a novel approach to the significance of chemosensory signals in human survival, will be given. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Treatment and final disposal of nuclear waste. Supplement to the 1992 programme in response to the government decision of December 16, 1993

    International Nuclear Information System (INIS)

    1994-08-01

    In response to criticism from the regulatory authorities, SKB has made this supplementary account to the 1992 R,D and D programme. The report describes the criteria and methods that form the basis for selection of a site suitable for a nuclear waste repository; a programme for specification of the design of a waste encapsulation plant and the repository; a programme for the safety assessments SKB intends to prepare; and an analysis of how different measures and decisions influence later decisions within the repository programme. 71 refs, 19 figs, 6 tabs

  7. Final report: Initial ecosystem response of salt marshes to ditch plugging and pool creation: Experiments at Rachel Carson National Wildlife Refuge (Maine)

    Science.gov (United States)

    Adamowicz, S.C.; Roman, C.T.

    2002-01-01

    This study evaluates the response of three salt marshes, associated with the Rachel Carson National Wildlife Refuge (Maine), to the practice of ditch plugging. Drainage ditches, originally dug to drain the marsh for mosquito control or to facilitate salt hay farming, are plugged with marsh peat in an effort to impound water upstream of the plug, raise water table levels in the marsh, and increase surface water habitat. At two study sites, Moody Marsh and Granite Point Road Marsh, ditch plugs were installed in spring 2000. Monitoring of hydrology, vegetation, nekton and bird utilization, and marsh development processes was conducted in 1999, before ditch plugging, and then in 2000 and 2001 (all parameters except nekton), after ditch plugging. Each study site had a control marsh that was monitored simultaneously with the plugged marsh, and thus, we employed a BACI study design (before, after, control, impact). A third site, Marshall Point Road Marsh, was plugged in 1998. Monitoring of the plugged and control sites was conducted in 1999 and 2000, with limited monitoring in 2001, thus there was no ?before? plug monitoring. With ditch plugging, water table levels increased toward the marsh surface and the areal extent of standing water increased. Responding to a wetter substrate, a vegetation change from high marsh species (e.g., Spartina patens) to those more tolerant of flooded conditions (e.g., Spartina alterniflora) was noted at two of the three ditch plugged sites. Initial response of the nekton community (fishes and decapod crustaceans) was evaluated by monitoring utilization of salt marsh pools using a 1m2 enclosure trap. In general, nekton species richness, density, and community structure remained unchanged following ditch plugging at the Moody and Granite Point sites. At Marshall Point, species richness and density (number of individuals per m2) were significantly greater in the experimental plugged marsh than the control marsh (control marsh was open water

  8. Starvation-Survival in Haloarchaea

    Directory of Open Access Journals (Sweden)

    Yaicha D. Winters

    2015-11-01

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

  9. Starvation-Survival in Haloarchaea.

    Science.gov (United States)

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

    2015-11-12

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

  10. Network ties and survival

    DEFF Research Database (Denmark)

    Acheampong, George; Narteh, Bedman; Rand, John

    2017-01-01

    of the SCPFs in Ghana. Distribution ties are associated with negative survival chances and this is not even reversed if the human capital of the owner increases although managers with higher human capital and higher distribution ties experience positive effects. Industry ties are associated with positive ties...

  11. Education for Survival

    Science.gov (United States)

    Aldrich, Richard

    2010-01-01

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

  12. Artists’ Survival Rate

    DEFF Research Database (Denmark)

    Bille, Trine; Jensen, Søren

    2017-01-01

    The literature of cultural economics generally finds that an artistic education has no significant impact on artists’ income and careers in the arts. In our research, we have readdressed this question by looking at the artists’ survival in the arts occupations. The results show that an artistic...... education has a significant impact on artists’ careers in the arts and we find important industry differences....

  13. Survivability via Control Objectives

    Energy Technology Data Exchange (ETDEWEB)

    CAMPBELL,PHILIP L.

    2000-08-11

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

  14. Flexible survival regression modelling

    DEFF Research Database (Denmark)

    Cortese, Giuliana; Scheike, Thomas H; Martinussen, Torben

    2009-01-01

    Regression analysis of survival data, and more generally event history data, is typically based on Cox's regression model. We here review some recent methodology, focusing on the limitations of Cox's regression model. The key limitation is that the model is not well suited to represent time-varyi...

  15. Education for Survival.

    Science.gov (United States)

    Allen, James E., Jr.

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

  16. [The Waste Package Project. Final report, July 1, 1995--February 27, 1996]: Volume 2, Experimental verification of structural response of a flexible three-link hydraulic steel robot

    International Nuclear Information System (INIS)

    Ladkany, S.G.; Channarayapatna, S.S.

    1996-01-01

    This report presents experimental techniques for determining the static and dynamic response, in three dimensional space, of a flexible three-link hydraulic steel robot. The flexible robot was originally built under a grant from the Army Research Office (ARO) and has been the subject of a six year research project involving 12 graduate students and four faculty members. The research was continued under grant from the U.S. Department of Energy which is considering the use of robot in remote handling, placement and retrievability of H.L.N.W. canisters in geological formations. A series of static and dynamic experiments was conducted under two different loads at various angular positions of the robot links

  17. American Recovery and Reinvestment Act of 2009: Final Report on Customer Acceptance, Retention, and Response to Time-Based Rates from Consumer Behavior Studies

    Energy Technology Data Exchange (ETDEWEB)

    Cappers, Peter [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Energy Analysis and Environmental Impacts Division; Scheer, Rich [Scheer Ventures LLC, Takoma Park, MD (United States)

    2018-03-07

    Time-based rate programs, enabled by utility investments in advanced metering infrastructure (AMI), are increasingly being considered by utilities as tools to reduce peak demand and enable customers to better manage consumption and costs. Under the Smart Grid Investment Grant Program (SGIG), the U.S. Department of Energy (DOE) partnered with several electric utilities to conduct consumer behavior studies (CBS). The goals involved applying randomized and controlled experimental designs for estimating customer responses more precisely and credibly to advance understanding of time-based rates and customer systems, and provide new information for improving program designs, implementation strategies, and evaluations. The intent was to produce more robust and credible analysis of impacts, costs, benefits, and lessons learned and assist utility and regulatory decision makers in evaluating investment opportunities involving time-based rates.

  18. Surviving the War--And the Peace

    Science.gov (United States)

    Thompson, Doug

    2012-01-01

    This article presents the author's response to "Surviving the War: A College Counselor's Journal" by Philip Clinton. He argues that Clinton's engrossing account of the 1990-91 school year at Cairo American College (CAC) gives individuals wonderful insights into the unusual challenges occasionally encountered by an international…

  19. The formula for survival in resuscitation.

    Science.gov (United States)

    Søreide, Eldar; Morrison, Laurie; Hillman, Ken; Monsieurs, Koen; Sunde, Kjetil; Zideman, David; Eisenberg, Mickey; Sterz, Fritz; Nadkarni, Vinay M; Soar, Jasmeet; Nolan, Jerry P

    2013-11-01

    The International Liaison Committee on Resuscitation (ILCOR) Advisory Statement on Education and Resuscitation in 2003 included a hypothetical formula--'the formula for survival' (FfS)--whereby three interactive factors, guideline quality (science), efficient education of patient caregivers (education) and a well-functioning chain of survival at a local level (local implementation), form multiplicands in determining survival from resuscitation. In May 2006, a symposium was held to discuss the validity of the formula for survival hypothesis and to investigate the influence of each of the multiplicands on survival. This commentary combines the output from this symposium with an updated illustration of the three multiplicands in the FfS using rapid response systems (RRS) for medical science, therapeutic hypothermia (TH) for local implementation, and bystander cardiopulmonary resuscitation (CPR) for educational efficiency. International differences between hospital systems made it difficult to assign a precise value for the multiplicand medical science using RRS as an example. Using bystander CPR as an example for the multiplicand educational efficiency, it was also difficult to provide a precise value, mainly because of differences between compression-only and standard CPR. The local implementation multiplicand (exemplified by therapeutic hypothermia) is probably the easiest to improve, and is likely to have the most immediate improvement in observed survival outcome in most systems of care. Despite the noted weaknesses, we believe that the FfS will be useful as a mental framework when trying to improve resuscitation outcome in communities worldwide. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. Lead exposures and biological responses in military weapons systems: Aerosol characteristics and acute lead effects among US Army artillerymen: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharyya, M.H.; Stebbings, J.H.; Peterson, D.P.; Johnson, S.A.; Kumar, R.; Goun, B.D.; Janssen, I.; Trier, J.E.

    1993-03-01

    This study was to determine the concentration and chemical nature of lead (Pb) aerosols produced during the firing of artillery and to determine the exposures and biological responses of crew members exposed to lead aerosols during such firing. The concentrations of lead-containing aerosols at crew positions depended on wind conditions, with higher concentrations when firing into a head wind. Aerosol concentrations were highest in the muzzle blast zone. Concentrations of lead in the blood of crew members rose during the first 12 days of exposure to elevated airborne lead concentrations and then leveled off. There was no rapid decrease in blood lead concentrations after completion of firing. Small decreases in hematocrit and small increases in free erythrocyte porphyrin were correlated with increasing exposure to airborne lead. These changes were reversed by seven weeks after firing. Changes in nerve conduction velocity had borderline statistical significance to airborne lead exposure. In measuring nerve conduction velocity, differences in skin temperature must be taken into account.

  1. Abrupt Climate Change and the Atlantic Meridional Overturning Circulation: sensitivity and non-linear response to Arctic/sub-Arctic freshwater pulses. Collaborative research. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Hill, Christopher [MIT (Massachusetts Inst. of Technology), Cambridge, MA (United States)

    2015-06-15

    This project investigated possible mechanisms by which melt-water pulses can induce abrupt change in the Atlantic Meridional Overturning Circulation (AMOC) magnitude. AMOC magnitude is an important ingredient in present day climate. Previous studies have hypothesized abrupt reduction in AMOC magnitude in response to influxes of glacial melt water into the North Atlantic. Notable fresh-water influxes are associated with the terminus of the last ice age. During this period large volumes of melt water accumulated behind retreating ice sheets and subsequently drained rapidly when the ice weakened sufficiently. Rapid draining of glacial lakes into the North Atlantic is a possible origin of a number of paleo-record abrupt climate shifts. These include the Younger-Dryas cooling event and the 8,200 year cooling event. The studies undertaken focused on whether the mechanistic sequence by which glacial melt-water impacts AMOC, which then impacts Northern Hemisphere global mean surface temperature, is dynamically plausible. The work has implications for better understanding past climate stability. The work also has relevance for today’s environment, in which high-latitude ice melting in Greenland appears to be driving fresh water outflows at an accelerating pace.

  2. Adolescent IQ and Survival in the Wisconsin Longitudinal Study

    Science.gov (United States)

    Hauser, Robert M.; Palloni, Alberto

    2011-01-01

    Objective. This study attempts to explain the ubiquitous positive correlation between cognitive ability (IQ) and survival. Methods. A sample of 10,317 Wisconsin high school graduates of 1957 was followed until 2009, from ages 18 to 68 years. Mortality was analyzed using a Weibull survival model that includes gender, social background, Henmon–Nelson IQ, and rank in high school class. Results. Rank in high school class, a cumulative measure of responsible performance during high school, entirely mediates the relationship between adolescent IQ and survival. Its effect on survival is 3 times greater than that of IQ, and it accounts for about 10% of the female advantage in survival. Discussion. Cognitive functioning may improve survival by promoting responsible and timely patterns of behavior that are firmly in place by late adolescence. Prior research suggests that conscientiousness, one of the “Big Five” personality characteristics, plays a key role in this relationship. PMID:21743056

  3. Survivability of a metapopulation under local extinctions

    Science.gov (United States)

    Kundu, Srilena; Majhi, Soumen; Sasmal, Sourav Kumar; Ghosh, Dibakar; Rakshit, Biswambhar

    2017-12-01

    A metapopulation structure in landscape ecology comprises a group of interacting spatially separated subpopulations or patches of the same species that may experience several local extinctions. This makes the investigation of survivability (in the form of global oscillation) of a metapopulation on top of diverse dispersal topologies extremely crucial. However, among various dispersal topologies in ecological networks, which one can provide higher metapopulation survivability under local extinction is still not well explored. In this article, we scrutinize the robustness of an ecological network consisting of prey-predator patches having Holling type I functional response, against progressively extinct population patches. We present a comprehensive study on this while considering global, small-world, and scale-free dispersal of the subpopulations. Furthermore, we extend our work in enhancing survivability in the form of sustained global oscillation by introducing asymmetries in the dispersal rates of the considered species. Our findings affirm that the asynchrony among the patches plays an important role in the survivability of a metapopulation. In order to demonstrate the model independence of the observed phenomenon, we perform a similar analysis for patches exhibiting Holling type II functional response. On the grounds of the obtained results, our work is expected to provide a better perception of the influence of dispersal arrangements on the global survivability of ecological networks.

  4. [Final clinical indications and etiology in 1,023 enucleations. Descriptive databank evaluation with SPSS software in variable response mode with dummy variables].

    Science.gov (United States)

    Becker, H; Bialasiewicz, A A; Schaudig, U; Schäfer, H; von Domarus, D

    2002-05-01

    A new data bank developed for ophthalmopathology using a computer-generated, multidigital data code is expected to be able to accomplish complex clinicopathologic correlations of diagnoses and signs, as provided by (multiple) clinical events and histopathologically proven etiologies, and to facilitate the documentation of new data. In the ophthalmopathology laboratory 2890 eyes were examined between January 20, 1975 and December 12, 1996. The main diagnoses and patient data from this 22-year period were recorded. To facilitate the presentation of data, a 10-year period with eyes of 976 patients enucleated from December, 1986 to December, 1996 was chosen. Principal and secondary diagnoses served for establishing the data bank. The frequencies of successive histologic and clinical diagnoses were evaluated by a descriptive computing program using an SPSS-multi-response mode with dummy variables and a categorical variable listing of the software (SPSS version 10.0) classified as (a) non-filtered random, (b) filtered by multiple etiologies, and (c) filtered by multiple events. The principal groups (e.g., histologic diagnoses concerning etiology) and subgroups (e.g., trauma, neoplasia, surgery, systemic diseases, and inflammations) were defined and correlated with 798 separate diagnoses. From 11 diagnoses/events ascribed to the clinical cases, 11,198 namings resulted. Thus, a comparative study of complex etiologies and events leading to enucleation in different hospitals of a specific area may be performed using this electronic ophthalmopathologic data bank system. The complexity of rare disease and integration into a superimposed structure can be managed with this custom-made data bank. A chronologically and demographically oriented consideration of reasons for enucleation is thus feasible.

  5. Survival after blood transfusion

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Ahlgren, Martin; Rostgaard, Klaus

    2008-01-01

    of transfusion recipients in Denmark and Sweden followed for up to 20 years after their first blood transfusion. Main outcome measure was all-cause mortality. RESULTS: A total of 1,118,261 transfusion recipients were identified, of whom 62.0 percent were aged 65 years or older at the time of their first...... the SMR remained significantly 1.3-fold increased. CONCLUSION: The survival and relative mortality patterns among blood transfusion recipients were characterized with unprecedented detail and precision. Our results are relevant to assessments of the consequences of possible transfusion-transmitted disease......BACKGROUND: Long-term survival of transfusion recipients has rarely been studied. This study examines short- and long-term mortality among transfusion recipients and reports these as absolute rates and rates relative to the general population. STUDY DESIGN AND METHODS: Population-based cohort study...

  6. The Procalcitonin And Survival Study (PASS) - a randomised multi-center investigator-initiated trial to investigate whether daily measurements biomarker Procalcitonin and pro-active diagnostic and therapeutic responses to abnormal Procalcitonin levels, can improve survival in intensive care unit patients. Calculated sample size (target population): 1000 patients

    DEFF Research Database (Denmark)

    Jensen, Jens-Ulrik; Lundgren, Bettina; Hein, Lars

    2008-01-01

    BACKGROUND: Sepsis and complications to sepsis are major causes of mortality in critically ill patients. Rapid treatment of sepsis is of crucial importance for survival of patients. The infectious status of the critically ill patient is often difficult to assess because symptoms cannot be express...

  7. 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

  8. Combining parametric, semi-parametric, and non-parametric survival models with stacked survival models.

    Science.gov (United States)

    Wey, Andrew; Connett, John; Rudser, Kyle

    2015-07-01

    For estimating conditional survival functions, non-parametric estimators can be preferred to parametric and semi-parametric estimators due to relaxed assumptions that enable robust estimation. Yet, even when misspecified, parametric and semi-parametric estimators can possess better operating characteristics in small sample sizes due to smaller variance than non-parametric estimators. Fundamentally, this is a bias-variance trade-off situation in that the sample size is not large enough to take advantage of the low bias of non-parametric estimation. Stacked survival models estimate an optimally weighted combination of models that can span parametric, semi-parametric, and non-parametric models by minimizing prediction error. An extensive simulation study demonstrates that stacked survival models consistently perform well across a wide range of scenarios by adaptively balancing the strengths and weaknesses of individual candidate survival models. In addition, stacked survival models perform as well as or better than the model selected through cross-validation. Finally, stacked survival models are applied to a well-known German breast cancer study. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Immune investment impairs growth, female reproduction and survival in the house cricket, Acheta domesticus.

    Science.gov (United States)

    Bascuñán-García, Ana Priscila; Lara, Carlos; Córdoba-Aguilar, Alex

    2010-02-01

    We investigated whether an immune response is associated with growth, female reproduction and survival costs in the house cricket. Using different intensities of challenge immune (implantation of one piece of nylon (1N) and two nylons (2N), with their respective sham-challenge and control groups) with body size and exoskeleton thickness as response variables, growth costs were determined for both sexes. A similar methodology was followed for reproduction costs, in which egg number and size, and female survival were measured as response variables. It was also determined whether mated and virgin females showed different immune responses. Body size decreased with immune challenge but only in the 2N treatment. Exoskeleton thickness increased in both sham-challenge groups and the 1N group but decreased in the 2N group. Egg number decreased more in the sham-challenge groups followed by the 1N and 2N groups. The 2N group showed the largest egg size at the end of the experiment. In these females, 2N group died first followed by the 1N, two nylon sham and one nylon sham groups. Finally, mated females showed a lower immune response than virgin females. These results are consistent with ecological immunity theory. The discovery of exoskeleton-related costs of immunity and injury may have important implications for experimental design in studies of the cost of immunity. Copyright 2009 Elsevier Ltd. All rights reserved.

  10. Final Scientific/Technical Report: Characterizing the Response of the Cascadia Margin Gas Hydrate Reservoir to Bottom Water Warming Along the Upper Continental Slope

    Energy Technology Data Exchange (ETDEWEB)

    Solomon, Evan A. [Univ. of Washington, Seattle, WA (United States); Johnson, H. Paul [Univ. of Washington, Seattle, WA (United States); Salmi, Marie [Univ. of Washington, Seattle, WA (United States); Whorley, Theresa [Univ. of Washington, Seattle, WA (United States)

    2017-11-10

    The objective of this project is to understand the response of the WA margin gas hydrate system to contemporary warming of bottom water along the upper continental slope. Through pre-cruise analysis and modeling of archive and recent geophysical and oceanographic data, we (1) inventoried bottom simulating reflectors along the WA margin and defined the upper limit of gas hydrate stability, (2) refined margin-wide estimates of heat flow and geothermal gradients, (3) characterized decadal scale temporal variations of bottom water temperatures at the upper continental slope of the Washington margin, and (4) used numerical simulations to provide quantitative estimates of how the shallow boundary of methane hydrate stability responds to modern environmental change. These pre-cruise results provided the context for a systematic geophysical and geochemical survey of methane seepage along the upper continental slope from 48° to 46°N during a 10-day field program on the R/V Thompson from October 10-19, 2014. This systematic inventory of methane emissions along this climate-sensitive margin corridor and comprehensive sediment and water column sampling program provided data and samples for Phase 3 of this project that focused on determining fluid and methane sources (deep-source vs. shallow; microbial, thermogenic, gas hydrate dissociation) within the sediment, and how they relate to contemporary intermediate water warming. During the 2014 research expedition, we sampled nine seep sites between ~470 and 520 m water depth, within the zone of predicted methane hydrate retreat over the past 40 years. We imaged 22 bubble plumes with heights commonly rising to ~300 meters below sea level with one reaching near the sea surface. We collected 22 gravity cores and 20 CTD/hydrocasts from the 9 seeps and at background locations (no acoustic evidence of seepage) within the depth interval of predicted downslope retreat of the methane hydrate stability zone. Approximately 300 pore water

  11. When perception reflects reality: Non-native grass invasion alters small mammal risk landscapes and survival

    Science.gov (United States)

    Ceradnini, Joseph P.; Chalfoun, Anna

    2017-01-01

    Modification of habitat structure due to invasive plants can alter the risk landscape for wildlife by, for example, changing the quality or availability of refuge habitat. Whether perceived risk corresponds with actual fitness outcomes, however, remains an important open question. We simultaneously measured how habitat changes due to a common invasive grass (cheatgrass, Bromus tectorum) affected the perceived risk, habitat selection, and apparent survival of a small mammal, enabling us to assess how well perceived risk influenced important behaviors and reflected actual risk. We measured perceived risk by nocturnal rodents using a giving-up density foraging experiment with paired shrub (safe) and open (risky) foraging trays in cheatgrass and native habitats. We also evaluated microhabitat selection across a cheatgrass gradient as an additional assay of perceived risk and behavioral responses for deer mice (Peromyscus maniculatus) at two spatial scales of habitat availability. Finally, we used mark-recapture analysis to quantify deer mouse apparent survival across a cheatgrass gradient while accounting for detection probability and other habitat features. In the foraging experiment, shrubs were more important as protective cover in cheatgrass-dominated habitats, suggesting that cheatgrass increased perceived predation risk. Additionally, deer mice avoided cheatgrass and selected shrubs, and marginally avoided native grass, at two spatial scales. Deer mouse apparent survival varied with a cheatgrass–shrub interaction, corresponding with our foraging experiment results, and providing a rare example of a native plant mediating the effects of an invasive plant on wildlife. By synthesizing the results of three individual lines of evidence (foraging behavior, habitat selection, and apparent survival), we provide a rare example of linkage between behavioral responses of animals indicative of perceived predation risk and actual fitness outcomes. Moreover, our results

  12. 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...

  13. Generation of a convalescent model of virulent Francisella tularensis infection for assessment of host requirements for survival of tularemia.

    Directory of Open Access Journals (Sweden)

    Deborah D Crane

    Full Text Available Francisella tularensis is a facultative intracellular bacterium and the causative agent of tularemia. Development of novel vaccines and therapeutics for tularemia has been hampered by the lack of understanding of which immune components are required to survive infection. Defining these requirements for protection against virulent F. tularensis, such as strain SchuS4, has been difficult since experimentally infected animals typically die within 5 days after exposure to as few as 10 bacteria. Such a short mean time to death typically precludes development, and therefore assessment, of immune responses directed against virulent F. tularensis. To enable identification of the components of the immune system that are required for survival of virulent F. tularensis, we developed a convalescent model of tularemia in C57Bl/6 mice using low dose antibiotic therapy in which the host immune response is ultimately responsible for clearance of the bacterium. Using this model we demonstrate αβTCR(+ cells, γδTCR(+ cells, and B cells are necessary to survive primary SchuS4 infection. Analysis of mice deficient in specific soluble mediators shows that IL-12p40 and IL-12p35 are essential for survival of SchuS4 infection. We also show that IFN-γ is required for survival of SchuS4 infection since mice lacking IFN-γR succumb to disease during the course of antibiotic therapy. Finally, we found that both CD4(+ and CD8(+ cells are the primary producers of IFN-γand that γδTCR(+ cells and NK cells make a minimal contribution toward production of this cytokine throughout infection. Together these data provide a novel model that identifies key cells and cytokines required for survival or exacerbation of infection with virulent F. tularensis and provides evidence that this model will be a useful tool for better understanding the dynamics of tularemia infection.

  14. Prediction error variance and expected response to selection, when selection is based on the best predictor - for Gaussian and threshold characters, traits following a Poisson mixed model and survival traits

    DEFF Research Database (Denmark)

    Andersen, Anders Holst; Korsgaard, Inge Riis; Jensen, Just

    2002-01-01

    In this paper, we consider selection based on the best predictor of animal additive genetic values in Gaussian linear mixed models, threshold models, Poisson mixed models, and log normal frailty models for survival data (including models with time-dependent covariates with associated fixed...

  15. Consultant survival guide.

    Science.gov (United States)

    Haque, Sahena

    2014-04-01

    Taking up a new consultant post can be both exciting and daunting. Once the elation of completing years of training and successfully securing a valued position has subsided, the reality of the task ahead becomes apparent. A new consultant needs to develop a number of skills to develop as a clinical leader and understand the processes within the National Health Service (NHS) that enable service development and innovation. In a programme packed with esteemed speakers, the Royal College of Physicians' one-day conference, Consultants' survival guide: how to succeed as a new consultant provided practical tips and advice for senior trainees and new consultants.

  16. Nuclear War Survival Skills

    Energy Technology Data Exchange (ETDEWEB)

    Kearny, C.H.

    2002-06-24

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

  17. Survival curves for irradiated cells

    International Nuclear Information System (INIS)

    Gibson, D.K.

    1975-01-01

    The subject of the lecture is the probability of survival of biological cells which have been subjected to ionising radiation. The basic mathematical theories of cell survival as a function of radiation dose are developed. A brief comparison with observed survival curves is made. (author)

  18. Final environmental impact statement for the Nevada test site and off-site locations in the State of Nevada. Public comment and response document, Volume 3, Part A comments

    International Nuclear Information System (INIS)

    1996-08-01

    On February 2, 1996, the U.S. Department of Energy (DOE) issued the Draft Environmental Impact Statement for the Nevada Test Site and Off-Site Locations in the State of Nevada (NTS EIS) for review by the state of Nevada, Indian tribes, local governments, other federal agencies, groups and organizations, and the general public. The formal comment period lasted 90 days, ending May 3, 1996. As part of the comment process, the DOE held public hearings in St. George, Utah, and in Pahrump, Reno, and Las Vegas, Nevada. Community Workshops were held in Caliente, Tonopah, Boulder City, and North Las Vegas, Nevada, in conjunction with the University of Nevada Las Vegas to discuss the Draft NTS EIS. Volume 3 of the Final NTS EIS contains 3 chapters. Chapter 1 summarizes the major issues raised by the public. Chapter 2 contains the full text of the public comments on the Draft NTS EIS received by the DOE; it includes public hearing transcripts, written comments, and comments received via a toll-free comment open-quotes hot line.close quotes Chapter 3 contains the DOE's responses to the public comments and describes how the comments were considered in the Final NTS EIS

  19. Nuclear war survival skills

    International Nuclear Information System (INIS)

    Kearney, C.H.

    1979-09-01

    This book includes chapters on psychological preparations, warning and communications, and evacuation. It describes the building of expedient shelters, their ventilation and cooling, the purification and storage of adequate water, the processing and cooking of whole grains and legumes, fallout meters, protection against fires and carbon monoxide, and expedient furnishings for shelters. Other chapters cover sanitation and preventive medicine, medical advice for nuclear survivors lacking the help of doctors, improvised footwear and clothing, and advice on minimum preparations that can be made at low cost and should be made before a crisis arises. One appendix of the handbook gives detailed, field-tested instructions for building six types of earth-covered expedient fallout shelters, with criteria to guide the choice of which shelter to build. Others contain instructions for making an efficient shelter-ventilating pump and a homemade fallout meter that is accurate and dependable with inexpensive materials found in most households. This report is primarily a compilation and summary of civil defense measures and inventions developed at ORNL over the past 14 years and field-tested in six states, from Florida to Utah. It is the first comprehensive handbook of survival information for use by untrained citizens who want to improve their chances of surviving a possible nuclear attack. Sections may be easily excerpted and reproduced for mass distribution through news media

  20. Particle production and survival in muon acceleration

    Energy Technology Data Exchange (ETDEWEB)

    Noble, R.J.

    1992-06-01

    Because of the relative immunity of muons to synchrotron radiation, the idea of using them instead of electrons as probes in high-energy physics experiments has existed for some time, but applications were limited by the short muon lifetime. The production and survival of an adequate supply of low-emittance muons will determine the available luminosity in a high-energy physics collider. In this paper the production of pions by protons, their decay to muons and the survival of muons during acceleration are studied. Based on a combination of the various efficiencies, the number of protons needed at the pion source for every muon required in the final high-energy collider is estimated.

  1. Particle production and survival in muon acceleration

    International Nuclear Information System (INIS)

    Noble, R.J.

    1992-06-01

    Because of the relative immunity of muons to synchrotron radiation, the idea of using them instead of electrons as probes in high-energy physics experiments has existed for some time, but applications were limited by the short muon lifetime. The production and survival of an adequate supply of low-emittance muons will determine the available luminosity in a high-energy physics collider. In this paper the production of pions by protons, their decay to muons and the survival of muons during acceleration are studied. Based on a combination of the various efficiencies, the number of protons needed at the pion source for every muon required in the final high-energy collider is estimated

  2. Surviving relatives after suicide

    DEFF Research Database (Denmark)

    Nørrelykke, Helle; Cohrt, Pernille

    We would like to focus on the surviving relatives after suicides, because it is generally accepted that it is especially difficult to recover after the loss from suicide and because we know as a fact that one suicide affects five persons on average. Every year approximately 700 people commit...... suicide in Denmark. This means that at least 400 people undergo the trauma it is when one of their near relatives commits suicide. We also know that the loss from suicide involves a lot of conflicting feelings - like anger, shame, guilt and loss and that the lack of therapy/treatment of these difficult...... for treatment for the relatives. In the wake of this policy document a national organization for relatives after suicide and a national network for those who attempt suicide occurred. Both organizations are formed by voluntary subscription and both organizations offer acute emergency relief, conversation groups...

  3. Le survivant sans le syndrome Schreber

    Directory of Open Access Journals (Sweden)

    Richard Figuier

    2006-09-01

    Full Text Available On a pensé la catastrophe, mais a-t-on suffisamment pensé la survivance et la figure du survivant ? Ce n'est pas un hasard si celle-ci est au centre de Masse et puissance, oeuvre dans laquelle Canetti interroge la « mauvaise » survivance responsable de la poursuite de la logique de guerre. Mais où trouver la « bonne » ? Revenir de la catastrophe ne suffit pas pour être un « survivant authentique », selon l'expression de Kafka. Il faut avoir dépassé, avec Primo Levi et Robert Antelme, l'opposition de la vie comme croissance continue et de la mort comme son horrible contraire, par le don, dans la pauvreté solidaire, de cette vie retrouvée.Hemos reflexionado acerca de la catástrofe, pero ¿hemos meditado lo suficiente sobre la supervivencia y el superviviente? No es una coincidencia si el superviviente es el tema principal de Masse et puissance, obra en la cual Canetti analiza la «mala» supervivencia responsable de la persistencia de la lógica de guerra ¿Dónde sin embargo podemos encontrar la «buena» supervivencia? Superar la catástrofe no es suficiente para ser un «auténtico superviviente», según Kafka. Es fundamental ir más allá, con Primo Levi y Robert Antelme, de la oposición entre la vida, como crecimiento continuo, y la muerte, como su espantoso contrario, mediante la donación de forma solidaria de esta vida reencontrada.Disaster is the theme of many studies, but what about survival and of the figure of the survivor? This issue is central in Mass and power, work in which Canetti questions the “bad” survival, responsible for the continuation of the logic of war. But is there any “good” survival? Coming back from the catastrophe is not enough to be an “authentic survivor”, according to Kafka’s expression. To achieve this, it is necessary to have exceeded, with PrimoLevi and Robert Antelme, the opposition of life as a continuous growth and of death as its horrible opposite, by the gift, in a

  4. A taylor series approach to survival analysis

    International Nuclear Information System (INIS)

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

    1984-09-01

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

  5. Final environmental impact statement for the Nevada test site and off-site locations in the State of Nevada. Public comment and response document, Volume 3, Part B responses

    International Nuclear Information System (INIS)

    1996-08-01

    This sitewide EIS evaluates the potential environmental impacts of four possible land-use alternatives being considered for the Nevada Test Site (NTS), the Tonopah Test Range, and the formerly operated DOE sites in the state of Nevada: the Project Shoal Area, the Central Nevada Test Area, and portions of the Nellis Air Force Range Complex. Three additional sites in Nevada-Eldorado Valley, Dry Lake Valley, and Coyote Spring Valley-are evaluated for collocation of solar energy production facilities. The four alternatives include Continue Current Operations (No Action, continue to operate at the level maintained for the past 3 to 5 years); Discontinue Operations 1 (discontinue operations and interagency programs); Expanded Use (increased use of NTS and its resources to support defense and nondefense programs); and Alternate Use of Withdrawn Lands (discontinue all defense-related activities at NTS; continue waste management operations in support of NTS environmental restoration efforts; expand nondefense research). Environmental impacts were assessed for each alternative by analyzing, to the extent possible, the discrete and cumulative environmental impacts associated with Defense Waste Management, Environmental Restoration, Nondefense Research and Development, and Work for Others Programs. A framework for a Resource Management Plan is included as Volume 2 of this EIS and represents the development of an ecosystem based planning process closely integrated with the National Environmental Policy Act process. This EIS, among other things, analyzed the impacts of transportation of low level waste, and site characterization activities related to the Yucca Mountain Project but did not analyze the suitability of the site as a repository. This EIS does not analyze the suitability of the Yucca Mountain site as a repository as this is an action beyond the scope of the EIS. Volume 3 of this EIS contains the public comments and the responses to the comments

  6. Impact of fermentation pH and temperature on freeze-drying survival and membrane lipid composition of Lactobacillus coryniformis Si3.

    Science.gov (United States)

    Schoug, Asa; Fischer, Janett; Heipieper, Hermann J; Schnürer, Johan; Håkansson, Sebastian

    2008-03-01

    During the industrial stabilization process, lactic acid bacteria are subjected to several stressful conditions. Tolerance to dehydration differs among lactic acid bacteria and the determining factors remain largely unknown. Lactobacillus coryniformis Si3 prevents spoilage by mold due to production of acids and specific antifungal compounds. This strain could be added as a biopreservative in feed systems, e.g. silage. We studied the survival of Lb. coryniformis Si3 after freeze-drying in a 10% skim milk and 5% sucrose formulation following different fermentation pH values and temperatures. Initially, a response surface methodology was employed to optimize final cell density and growth rate. At optimal pH and temperature (pH 5.5 and 34 degrees C), the freeze-drying survival of Lb. coryniformis Si3 was 67% (+/-6%). The influence of temperature or pH stress in late logarithmic phase was dependent upon the nature of the stress applied. Heat stress (42 degrees C) did not influence freeze-drying survival, whereas mild cold- (26 degrees C), base- (pH 6.5), and acid- (pH 4.5) stress significantly reduced survival. Freeze-drying survival rates varied fourfold, with the lowest survival following mild cold stress (26 degrees C) prior to freeze-drying and the highest survival after optimal growth or after mild heat (42 degrees C) stress. Levels of different membrane fatty acids were analyzed to determine the adaptive response in this strain. Fatty acids changed with altered fermentation conditions and the degree of membrane lipid saturation decreased when the cells were subjected to stress. This study shows the importance of selecting appropriate fermentation conditions to maximize freeze-drying viability of Lb. coryniformis as well as the effects of various unfavorable conditions during growth on freeze-drying survival.

  7. Final storage of radioactive waste

    International Nuclear Information System (INIS)

    Ziehm, Cornelia

    2015-01-01

    As explained in the present article, operators of nuclear power plants are responsible for the safe final disposal of the radioactive wastes they produce on the strength of the polluter pays principle. To shift the burden of responsibility for safe disposal to society as a whole would violate this principle and is therefore not possible. The polluter pays principle follows from more general principles of the fair distribution of benefits and burdens. Instances of its implementation are to be found in the national Atomic Energy Law as well as in the European Radioactive Waste and Spent Fuel Management Directive. The polluters in this case are in particular responsible for financing the installation and operation of final disposal sites. The reserves accumulated so far for the decommissioning and dismantling of nuclear power plants and disposal of radioactive wastes, including the installation and operation of final disposal sites, should be transferred to a public-law fund. This fund should be supplemented by the polluters to cover further foreseeable costs not covered by the reserves accumulated so far, including a realistic cost increase factor, appropriate risk reserves as well as the costs of the site selection procedure and a share in the costs for the safe closure of the final disposal sites of Morsleben and Asse II. This would merely be implementing in the sphere of atomic law that has long been standard practice in other areas of environmental law involving environmental hazards.

  8. Modification of UV-induced mutation frequency and cell survival of Escherichia coli B/r WP2 trpE65 by treatment before irradiation

    International Nuclear Information System (INIS)

    Doudney, C.O.; Rinaldi, C.N.

    1984-01-01

    The UV radiation survival curve of exponentially growing cultures of Escherichia coli B/r WP2 trpE65 was modified by pretreatment for short incubation periods (up to 20 min) with chloramphenicol such that an extended exponential section of intermediate slope appeared between the shoulder and the final exponential slope. Surges of mutation to tryptophan independence occurred with each increase in slope of the survival curve. These surges were separated by extended sections of little mutation. Nalidixic acid prevented both the changes in survival and mutation. Mutation curves obtained with overnight cultures had three extended sections of little mutation alternating with section of high mutation. Reincubation for 60 min in fresh medium reduced or eliminated the low-response sections. These reappeared after 80 to 90 min, when DNA had doubled in the culture and before the initial synchronous cell divisions had occurred. Nalidixic acid prevented this reappearance

  9. Ship Systems Survivability Test Site

    Data.gov (United States)

    Federal Laboratory Consortium — Area for testing survivability of shipboard systems to include electrical, communications, and fire suppression. Multipurpose test range for supporting gun firing,...

  10. Atrial fibrillation and survival in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Justin Timothy A

    2004-11-01

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

  11. Weight, physical activity and breast cancer survival.

    Science.gov (United States)

    McTiernan, Anne

    2018-02-26

    Weight, weight change and physical activity may affect prognosis among women who are diagnosed with breast cancer. Observational studies show associations between overweight/obesity and weight gain with several measures of reduced prognosis in women with breast cancer, and some suggestions of lower survival in women who are underweight or who experience unexplained weight loss after diagnosis. Observational studies have also shown an association between higher levels of physical activity and reduced breast cancer-specific and all-cause mortality, although a dose-response relationship has not been established. The effects of purposive dietary weight loss and increase in physical activity on survival or recurrence in breast cancer are not yet established, and randomised controlled trials are needed for definitive data. This paper presents the epidemiologic evidence on weight status, weight change, and physical activity and breast cancer survival; suggests potential mediating mechanisms; summarises evidence on weight loss interventions in breast cancer survivors; describes ongoing randomised clinical trials designed to test the effects of weight loss or physical activity on breast cancer survival; and provides information on available guidelines on weight and physical activity for cancer survivors.

  12. Survival by Dialysis Modality-Who Cares?

    Science.gov (United States)

    Lee, Martin B; Bargman, Joanne M

    2016-06-06

    In light of the recent emphasis on patient-centered outcomes and quality of life for patients with kidney disease, we contend that the nephrology community should no longer fund, perform, or publish studies that compare survival by dialysis modality. These studies have become redundant; they are methodologically limited, unhelpful in practice, and therefore a waste of resources. More than two decades of these publications show similar survival between patients undergoing peritoneal dialysis and those receiving thrice-weekly conventional hemodialysis, with differences only for specific subgroups. In clinical practice, modality choice should be individualized with the aim of maximizing quality of life, patient-reported outcomes, and achieving patient-centered goals. Expected survival is often irrelevant to modality choice. Even for the younger and fitter home hemodialysis population, quality of life, not just duration of survival, is a major priority. On the other hand, increasing evidence suggests that patients with ESRD continue to experience poor quality of life because of high symptom burden, unsolved clinical problems, and unmet needs. Patients care more about how they will live instead of how long. It is our responsibility to align our research with their needs. Only by doing so can we meet the challenges of ESRD patient care in the coming decades. Copyright © 2016 by the American Society of Nephrology.

  13. Survival and chlamydospore production of Phytophthora ramorum in California bay laurel leaves

    Science.gov (United States)

    E. Fichtner; D. Rizzo; S. Lynch; D. Rizzo; G. Buckles; J. Parke

    2009-01-01

    Sudden oak death manifests as non-lethal foliar lesions on bay laurel (Umbellularia californica), which support sporulation and survival of Phytophthora ramorum in forest ecosystems. The pathogen survives the dry summers in a proportion of attached bay leaves, but the propagules responsible for survival are...

  14. Survival of Staphylococcus aureus on fomites.

    Science.gov (United States)

    Cuesta, Alicia; Nastri, Natalia; Bernat, Maria; Brusca, Maria; Turcot, Liliana; Nastri, Maria; Rosa, Alcira C

    2008-01-01

    The aim of this study was to evaluate duration of survival of Staphylococcus aureus on contaminated standardized fomites, such as sterilization paper (SP) and polyester previously sterilized in a steam autoclave, and to determine the potential inhibitory effects of the substrates (fabrics used to manufacture garments and special wrapping paper used in the dental setting) using the bacteriostasis test. The test was performed on two types of sterile standardized samples (T1 and T2). Sterility of the samples was validated following the protocol in use at the Department of Microbiology, after which the samples were inoculated with 50 microl of a calibrated suspension of Staphylococcus aureus (reference strain ATCC 25923) in the exponential growth phase, in a final concentration of 10(7) cfu/ml and 10(6) cfu/ml). The samples were incubated at 27 degrees C and survival and concentration of microorganisms attached to the surface of the substrates was determined at the following experimental time points: immediately post-contamination, and 3 hours, 24 hours, 3 days, and 7 days post-contamination. Recovery was determined and expressed as a percentage; the bacteriostasis test was performed and showed negative results. Our results suggest that the quantity of recovered microorganisms varies according to the type of substrate and that there is a relation between survival and incubation time of the inoculated substrate serving as an artificial niche.

  15. Thioredoxin priming prolongs lung allograft survival by promoting immune tolerance.

    Science.gov (United States)

    Hu, Hanbo; Zhu, Xiaoyan; Joshi, Sunil; Lu, Li; Xia, Chang-Qing; Patel, Jawaharlal M

    2015-01-01

    Tolerance to allograft antigen is the major challenge and final goal of transplant medicine. Our previous study demonstrated that thioredoxin-1 (Trx) priming of donor lung significantly protected allogeneic lung graft. To determine whether Trx priming of donor lung inhibits allograft rejection, extends allograft survival and induces immune tolerance, orthotopic left lung transplantation was performed from Lewis to Sprague-Dawley rats without immunosuppression. Donor lungs were primed with Trx at 4°C for 4 hr prior to transplantation. After up to 37 days post-transplantation, allograft lung morphology, recipient T cell and humoral alloantigen-specific immune responses were examined. We found that Trx-primed lungs exhibited much reduced acute rejection and associated lung injuries resulting in loss of graft functional area at 5-37 days post-transplant in contrast to the control groups. CD4+ T cells from the recipients with Trx-primed grafts responded to the stimulation of dendritic cells (DCs) of donor origin, in contrast to DCs from the third party, with significantly reduced proliferation. Consistent with above findings, we observed that CD4+Foxp3+ regulatory T cells in spleen cells from the recipients with Trx-primed grafts were significantly increased compared to controls, and CD4+ T cells from the recipients with Trx-primed grafts produced much higher levels of immunosuppressive cytokine, IL-10 when stimulated with allogeneic donor DCs. In addition, humoral immune tolerance was also induced as there was no significant increase levels of serum antibodies against donor antigens in Trx-lung recipients when re-challenged with allogeneic donor antigens. Our results demonstrate that one-time Trx-priming of donor lung grafts prior to transplantation significantly prolongs the survival of the grafts through inducing or promoting cellular and humoral alloantigen-specific immune tolerance, which might be associated with the induction of immunosuppressive regulatory T

  16. Thioredoxin priming prolongs lung allograft survival by promoting immune tolerance.

    Directory of Open Access Journals (Sweden)

    Hanbo Hu

    Full Text Available Tolerance to allograft antigen is the major challenge and final goal of transplant medicine. Our previous study demonstrated that thioredoxin-1 (Trx priming of donor lung significantly protected allogeneic lung graft. To determine whether Trx priming of donor lung inhibits allograft rejection, extends allograft survival and induces immune tolerance, orthotopic left lung transplantation was performed from Lewis to Sprague-Dawley rats without immunosuppression. Donor lungs were primed with Trx at 4°C for 4 hr prior to transplantation. After up to 37 days post-transplantation, allograft lung morphology, recipient T cell and humoral alloantigen-specific immune responses were examined. We found that Trx-primed lungs exhibited much reduced acute rejection and associated lung injuries resulting in loss of graft functional area at 5-37 days post-transplant in contrast to the control groups. CD4+ T cells from the recipients with Trx-primed grafts responded to the stimulation of dendritic cells (DCs of donor origin, in contrast to DCs from the third party, with significantly reduced proliferation. Consistent with above findings, we observed that CD4+Foxp3+ regulatory T cells in spleen cells from the recipients with Trx-primed grafts were significantly increased compared to controls, and CD4+ T cells from the recipients with Trx-primed grafts produced much higher levels of immunosuppressive cytokine, IL-10 when stimulated with allogeneic donor DCs. In addition, humoral immune tolerance was also induced as there was no significant increase levels of serum antibodies against donor antigens in Trx-lung recipients when re-challenged with allogeneic donor antigens. Our results demonstrate that one-time Trx-priming of donor lung grafts prior to transplantation significantly prolongs the survival of the grafts through inducing or promoting cellular and humoral alloantigen-specific immune tolerance, which might be associated with the induction of

  17. Radionuclide blood cell survival studies

    International Nuclear Information System (INIS)

    Bentley, S.A.; Miller, D.T.

    1986-01-01

    Platelet and red cell survival studies are reviewed. The use of 51 Cr and di-isopropylfluoridate labelled with tritium or 32 P is discussed for red cell survival study and 51 Cr and 111 In-oxine are considered as platelet labels. (UK)

  18. The Role of Lipid Metabolism in T Lymphocyte Differentiation and Survival

    Directory of Open Access Journals (Sweden)

    Duncan Howie

    2018-01-01

    Full Text Available The differentiation and effector functions of both the innate and adaptive immune system are inextricably linked to cellular metabolism. The features of metabolism which affect both arms of the immune system include metabolic substrate availability, expression of enzymes, transport proteins, and transcription factors which control catabolism of these substrates, and the ability to perform anabolic metabolism. The control of lipid metabolism is central to the appropriate differentiation and functions of T lymphocytes, and ultimately to the maintenance of immune tolerance. This review will focus on the role of fatty acid (FA metabolism in T cell differentiation, effector function, and survival. FAs are important sources of cellular energy, stored as triglycerides. They are also used as precursors to produce complex lipids such as cholesterol and membrane phospholipids. FA residues also become incorporated into hormones and signaling moieties. FAs signal via nuclear receptors and their channeling, between storage as triacyl glycerides or oxidation as fuel, may play a role in survival or death of the cell. In recent years, progress in the field of immunometabolism has highlighted diverse roles for FA metabolism in CD4 and CD8 T cell differentiation and function. This review will firstly describe the sensing and modulation of the environmental FAs and lipid intracellular signaling and will then explore the key role of lipid metabolism in regulating the balance between potentially damaging pro-inflammatory and anti-inflammatory regulatory responses. Finally the complex role of extracellular FAs in determining cell survival will be discussed.

  19. Final Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Schuur, Edward [Northern Arizona Univ., Flagstaff, AZ (United States); Luo, Yiqi [Univ. of Oklahoma, Norman, OK (United States)

    2016-12-01

    This final grant report is a continuation of the final grant report submitted for DE-SC0006982 as the Principle Investigator (Schuur) relocated from the University of Florida to Northern Arizona University. This report summarizes the original project goals, as well as includes new project activities that were completed in the final period of the project.

  20. Survival after elective surgery for colonic cancer in Denmark

    DEFF Research Database (Denmark)

    Perdawid, S K; Hemmingsen, L; Boesby, S

    2012-01-01

    AIM: Total mesorectal excision (TME) has been shown to improve the outcome for patients with rectal cancer. In contrast, there are fewer data on complete mesocolic excision (CME) for colonic cancer. METHOD: Data from the National Colorectal Cancer Database were analysed. This includes about 95......% of all patients with colorectal cancer in Denmark. Only patients having elective surgery for colonic cancer in the period 2001-2008 were included. Overall and relative survival analyses were carried out. The study period was divided into the periods 2001-2004 and 2005-2008. RESULTS: 9149 patients were...... included for the final analysis. The overall 5-year survival rates were 0.65 in 2001-2004 and 0.66 in 2005-2008. The relative 5-year survival rates were also within 1% of each other. None of these comparisons was statistically significant. CONCLUSION: Survival following elective colon cancer surgery has...

  1. Dying to remember, remembering to survive: mortality salience and survival processing.

    Science.gov (United States)

    Burns, Daniel J; Hart, Joshua; Kramer, Melanie E; Burns, Amy D

    2014-01-01

    Processing items for their relevance to survival improves recall for those items relative to numerous other deep processing encoding techniques. Perhaps related, placing individuals in a mortality salient state has also been shown to enhance retention of items encoded after the morality salience manipulation (e.g., in a pleasantness rating task), a phenomenon we dubbed the "dying-to-remember" (DTR) effect. The experiments reported here further explored the effect and tested the possibility that the DTR effect is related to survival processing. Experiment 1 replicated the effect using different encoding tasks, demonstrating that the effect is not dependent on the pleasantness task. In Experiment 2 the DTR effect was associated with increases in item-specific processing, not relational processing, according to several indices. Experiment 3 replicated the main results of Experiment 2, and tested the effects of mortality salience and survival processing within the same experiment. The DTR effect and its associated difference in item-specific processing were completely eliminated when the encoding task required survival processing. These results are consistent with the interpretation that the mechanisms responsible for survival processing and DTR effects are overlapping.

  2. Final Focus Test Stand final report

    CERN Document Server

    Jeremie, A; Burrows, P

    2013-01-01

    Future Linear colliders will need particle beam sizes in the nanometre range. The beam also needs to be stable all along the beam line and especially at the Final Focus section. A dedicated Final Focus test stand has been used for this study and is comprised of several sub-parts. First there is the Stabilisation/Isolation system with sensors and actuators stabilizing down to sub-nanometre level. Then the Magnet itself needs to comply with very specific design constraints. In addition to the mechanical items, the beam can be stabilized acting on the trajectory directly and Beam-based controls have been developed and tested on different accelerator facilities.

  3. Effect of environmental stress factors on the uptake and survival of Campylobacter jejuni in Acanthamoeba castellanii

    Directory of Open Access Journals (Sweden)

    Bui Xuan

    2012-10-01

    Full Text Available Abstract Background Campylobacter jejuni is a major cause of bacterial food-borne illness in Europe and North America. The mechanisms allowing survival in the environment and transmission to new hosts are not well understood. Environmental free-living protozoa may facilitate both processes. Pre-exposure to heat, starvation, oxidative or osmotic stresses encountered in the environment may affect the subsequent interaction of C. jejuni with free-living protozoa. To test this hypothesis, we examined the impact of environmental stress on expression of virulence-associated genes (ciaB, dnaJ, and htrA of C. jejuni and on its uptake by and intracellular survival within Acanthamoeba castellanii. Results Heat, starvation and osmotic stress reduced the survival of C. jejuni significantly, whereas oxidative stress had no effect. Quantitative RT-PCR experiments showed that the transcription of virulence genes was slightly up-regulated under heat and oxidative stresses but down-regulated under starvation and osmotic stresses, the htrA gene showing the largest down-regulation in response to osmotic stress. Pre-exposure of bacteria to low nutrient or osmotic stress reduced bacterial uptake by amoeba, but no effect of heat or oxidative stress was observed. Finally, C. jejuni rapidly lost viability within amoeba cells and pre-exposure to oxidative stress had no significant effect on intracellular survival. However, the numbers of intracellular bacteria recovered 5 h post-gentamicin treatment were lower with starved, heat treated or osmotically stressed bacteria than with control bacteria. Also, while ~1.5 × 103 colony forming unit/ml internalized bacteria could typically be recovered 24 h post-gentamicin treatment with control bacteria, no starved, heat treated or osmotically stressed bacteria could be recovered at this time point. Overall, pre-exposure of C. jejuni to environmental stresses did not promote intracellular survival in A. castellanii

  4. Hibernation Based Therapy to Improve Survival of Severe Blood Loss

    Science.gov (United States)

    2016-06-01

    AWARD NUMBER: W81XWH-10-2-0121 TITLE: Hibernation -Based Therapy to Improve Survival of Severe Blood Loss PRINCIPAL INVESTIGATOR: Greg Beilman... Hibernation -Based Therapy to Improve Survival of Severe Blood 5a. CONTRACT NUMBER Loss 5b. GRANT NUMBER W81XWH-10-2-0121 5c. PROGRAM ELEMENT NUMBER...patients who are risk for bleeding to death. Our overall strategy in this series of studies is to use physiologic adaptive responses in hibernating

  5. Requirements Engineering for Survivable Systems. Networked Systems Survivability

    National Research Council Canada - National Science Library

    Mead, Nancy

    2003-01-01

    This report describes the current state of requirements engineering for survivable systems, that is, systems that are able to complete their mission in a timely manner, even if significant portions...

  6. Aircraft Survivability: Unmanned Aircraft Systems Survivability. Fall 2008

    Science.gov (United States)

    2008-01-01

    airspace coordination, command and control, and reliability are driving UAS use and design. 25 JASP 2008 Survivability Short Courseby Dr. Mark Couch The...Mark Couch , Research Staff Member at the Institute for Defense Analyses. 27 Warfighters Need a Joint Survivability Libraryby Maj Trenton Alexander...best MAC conference in the past two years.” 1stLt James Stephenson, USAF, headed home in May 2008. During his tour, James did a great job

  7. Cardiovascular disease incidence and survival

    DEFF Research Database (Denmark)

    Byberg, Stine; Agyemang, Charles; Zwisler, Ann-Dorthe

    2016-01-01

    Studies on cardiovascular disease (CVD) incidence and survival show varying results between different ethnic groups. Our aim was to add a new dimension by exploring the role of migrant status in combination with ethnic background on incidence of-and survival from-CVD and more specifically acute...... of some types of cardiovascular disease compared to Danish-born. Family-reunified migrants on the other hand had lower rates of CVD. All migrants had better survival than Danish-born indicating that migrants may not always be disadvantaged in health....

  8. Trichoderma: sensing the environment for survival and dispersal.

    Science.gov (United States)

    Carreras-Villaseñor, Nohemí; Sánchez-Arreguín, José Alejandro; Herrera-Estrella, Alfredo H

    2012-01-01

    Species belonging to the genus Trichoderma are free-living fungi common in soil and root ecosystems, and have a broad range of uses in industry and agricultural biotechnology. Some species of the genus are widely used biocontrol agents, and their success is in part due to mycoparasitism, a lifestyle in which one fungus is parasitic on another. In addition Trichoderma species have been found to elicit plant defence responses and to stimulate plant growth. In order to survive and spread, Trichoderma switches from vegetative to reproductive development, and has evolved with several sophisticated molecular mechanisms to this end. Asexual development (conidiation) is induced by light and mechanical injury, although the effects of these inducers are influenced by environmental conditions, such as nutrient status and pH. A current appreciation of the links between the molecular participants is presented in this review. The photoreceptor complex BLR-1/BLR-2, ENVOY, VELVET, and NADPH oxidases have been suggested as key participants in this process. In concert with these elements, conserved signalling pathways, such as those involving heterotrimeric G proteins, mitogen-activated protein kinases (MAPKs) and cAMP-dependent protein kinase A (cAMP-PKA) are involved in this molecular orchestration. Finally, recent comparative and functional genomics analyses allow a comparison of the machinery involved in conidiophore development in model systems with that present in Trichoderma and a model to be proposed for the key factors involved in the development of these structures.

  9. The effect of donor gender on renal allograft survival.

    Science.gov (United States)

    Neugarten, J; Srinivas, T; Tellis, V; Silbiger, S; Greenstein, S

    1996-02-01

    Donor gender plays a role in the outcome of renal transplantation, but the mechanisms responsible for this effect are unclear. In this study, actuarial graft survival in 1049 recipients transplanted at Montefiore Medical Center between 1979 and 1994 was examined. It was found that donor gender had no influence on graft survival in recipients treated with precyclosporine immunosuppressive agents. In contrast, graft survival time was greater in cyclosporine-treated recipients of male donor kidneys compared with female kidneys (p demand results in hyperfiltration-mediated glomerular injury and that this is responsible for reduced survival time of female allografts. Any hypothesis purporting to explain gender-related differences in graft survival time must take into account this study's observations that the donor-gender effect was observed only in cyclosporine-treated recipients, was not seen in African-American donors, appeared soon after renal transplantation, and did not increase progressively with time. These observations are most consistent with the hypothesis that gender-related differences in graft survival time may reflect differences in susceptibility to cyclosporine nephrotoxicity or differences in the therapeutic response to cyclosporine.

  10. Struggling to survive in Russia.

    Science.gov (United States)

    Gadasina, A

    1997-01-01

    Abortion has long been the traditional method of family planning (FP) in Russia. Today, abortions are free, but contraception is not. The birth rate has decreased between 1989 and 1995, and the death rate has increased. The present economic situation has had a marked adverse effect on women who are expected to juggle jobs, household duties, and child care responsibilities. In order to survive, women sometimes must engage in work that compromises their health. Many women have resorted in prostitution, and this has caused an unprecedented explosion in the incidence of sexually transmitted diseases, especially syphilis. The number of people newly registered as HIV-positive in the first half of 1997 exceeded the total for 1996. While sex education is still restricted, erotica and pornography is widely available. Cases of syphilis are increasing among the young, and, in 1996, about 2500 girls under age 15 gave birth and an equal number had abortions. Only 12% of all pregnant women and 25% of newborn infants can be considered healthy. In 1994, the government launched a FP program that is being carried out by a few public and private organizations. One of these, the Russian FP Association, has created more than 50 branches in different regions, opened youth centers, and provided sex education and reproductive health counseling. The overall effort has led to a 27% reduction in abortions, and a 25% reduction in abortion mortality. These efforts, however, have been opposed by "pro-life" forces and by the Communist wing of the government that reduced the budget. The FP Association is fighting back by lobbying and explaining the need for its work.

  11. Providing Survivable Real-Time Communication Service for Distributed Mission Critical Systems

    National Research Council Canada - National Science Library

    Zhao, Wei; Bettati, Riccardo; Vaidya, Nitin

    2005-01-01

    This document is the final report for Providing Survivable Real-Time Communication Service for Distributed Mission Critical Systems, a Texas A AND M project funded through the DARPA Fault Tolerant Networks Program...

  12. The Survival of the Wisest

    Science.gov (United States)

    Salk, Jonas

    1975-01-01

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

  13. Probabilistic Survivability Versus Time Modeling

    Science.gov (United States)

    Joyner, James J., Sr.

    2016-01-01

    This presentation documents Kennedy Space Center's Independent Assessment work completed on three assessments for the Ground Systems Development and Operations (GSDO) Program to assist the Chief Safety and Mission Assurance Officer during key programmatic reviews and provided the GSDO Program with analyses of how egress time affects the likelihood of astronaut and ground worker survival during an emergency. For each assessment, a team developed probability distributions for hazard scenarios to address statistical uncertainty, resulting in survivability plots over time. The first assessment developed a mathematical model of probabilistic survivability versus time to reach a safe location using an ideal Emergency Egress System at Launch Complex 39B (LC-39B); the second used the first model to evaluate and compare various egress systems under consideration at LC-39B. The third used a modified LC-39B model to determine if a specific hazard decreased survivability more rapidly than other events during flight hardware processing in Kennedy's Vehicle Assembly Building.

  14. Customer service skills for survival.

    Science.gov (United States)

    McAtee, L F

    1999-11-01

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

  15. The Survival of Tuscan Firms

    OpenAIRE

    Filippo Randelli; Giorgio Ricchiuti

    2015-01-01

    In this paper we analyze the survival probability of firms in Tuscany (Italy) in the first decade of the $21^{st}$ century. Using the Official Register of Firms, held by Unioncamere Toscany, we build a panel for the period 1998-2010. Taking into account both individual and context variables, we find that a higher institutional complexity and a lower population density have a positive and significant effect on probability to survive. Moreover, both MAR and Jacob externalities have a nonlinear ...

  16. Vet Centers. Final rule.

    Science.gov (United States)

    2016-03-02

    The Department of Veterans Affairs (VA) adopts as final an interim final rule that amends its medical regulation that governs Vet Center services. The National Defense Authorization Act for Fiscal Year 2013 (the 2013 Act) requires Vet Centers to provide readjustment counseling services to broader groups of veterans, members of the Armed Forces, including a member of a reserve component of the Armed Forces, and family members of such veterans and members. This final rule adopts as final the regulatory criteria to conform to the 2013 Act, to include new and revised definitions.

  17. Micrograft size and subsequent survival.

    Science.gov (United States)

    Seager, D J

    1997-09-01

    Micrograft survival rates in hair transplantation have been frequently described in private conversations by hair transplant doctors as variable at best. References in medical literature may grossly underestimate the prevalence and magnitude of poor growth. This is probably because most hair transplant surgeons are concerned that publication of a significant incidence of poor growth would reflect negatively on their practice. The purpose of this research was to study micrograft survival rates using microscopic dissection techniques. The author also presents a hypothesis regarding the relatively poor survival rates reported by hair transplant physicians. Two different groups of micrografts were prepared. One group, mainly single-haired with tissue trimmed close to the hair shaft, was planted into one test patch in the bald crown of a patient's scalp. Another group of intact follicular clumps, prepared with more dermis, subcutaneous fat, and intact sebaceous glands, was planted into another test patch. These test patches and their growth were documented with close-up photography. The micrografts prepared as existing follicular clumps had a much higher survival rate (over 100%) than the micrografts cut as slender single hairs. Extremely high survival rates of micrografts are obtainable by transplanting intact follicular clumps with protective tissue around the micrograft, and preserving the follicular clump's sebaceous gland. These survival rates were not achieved when micrografts were produced by splitting individual hairs away from a naturally occurring follicular clump.

  18. Thermodynamics of miracidial survival and metabolism.

    Science.gov (United States)

    Morley, N J

    2012-10-01

    Miracidia are short-lived, non-feeding (lecithotrophic) free-living stages of trematodes, whose survival is potentially influenced by temperature. Climate change may result in elevated temperatures affecting trematode transmission. Therefore understanding their thermobiology forms an important step in determining the future dynamics of parasite populations. An empirical relationship exists between the mean expected life span of lecithotrophic larvae and the half life of their population (t(0·5)) and therefore t(0·5) is a good indicator of glycogen utilization. In this study experimental data on the effects of temperature on miracidial survival were compiled from the scientific literature and evaluated in terms of metabolism using Q 10 and Arrhenius activation energy (E* or μ). Temperature poorly influenced survival/metabolism with all miracidia having distinct zone(s) of thermostability. Overall there were few differences in Q(10) and E* values between most species temperature ranges whilst there were only limited strain-specific variations in thermal responses of laboratory-maintained Schistosoma mansoni. Miracidia demonstrated a trend of greater thermal resistance than cercariae. In particular, comparative studies on 4 strains of the same species of miracidia and cercariae showed little correlation in thermal biology between the 2 life-history stages. The importance of these results for trematode transmission under global climate change is discussed.

  19. The effect of interspecific variation in photosynthetic plasticity on 4-year growth rate and 8-year survival of understorey tree seedlings in response to gap formations in a cool-temperate deciduous forest.

    Science.gov (United States)

    Oguchi, Riichi; Hiura, Tsutom; Hikosaka, Kouki

    2017-08-01

    Gap formation increases the light intensity in the forest understorey. The growth responses of seedlings to the increase in light availability show interspecific variation, which is considered to promote biodiversity in forests. At the leaf level, some species increase their photosynthetic capacity in response to gap formation, whereas others do not. Here we address the question of whether the interspecific difference in the photosynthetic response results in the interspecific variation in the growth response. If so, the interspecific difference in photosynthetic response would also contribute to species coexistence in forests. We also address the further relevant question of why some species do not increase their photosynthetic capacity. We assumed that some cost of photosynthetic plasticity may constrain acquisition of the plasticity in some species, and hypothesized that species with larger photosynthetic plasticity exhibit better growth after gap formation and lower survivorship in the shade understorey of a cool-temperate deciduous forest. We created gaps by felling canopy trees and studied the relationship between the photosynthetic response and the subsequent growth rate of seedlings. Naturally growing seedlings of six deciduous woody species were used and their mortality was examined for 8 years. The light-saturated rate of photosynthesis (Pmax) and the relative growth rate (RGR) of the seedlings of all study species increased at gap plots. The extent of these increases varied among the species. The stimulation of RGR over 4 years after gap formation was strongly correlated with change in photosynthetic capacity of newly expanded leaves. The increase in RGR and Pmax correlated with the 8-year mortality at control plots. These results suggest a trade-off between photosynthetic plasticity and the understorey shade tolerance. Gap-demanding species may acquire photosynthetic plasticity, sacrificing shade tolerances, whereas gap-independent species may acquire

  20. Hacia la Realizacion de la Autoestima. Informe Definitivo del Comite Estatal en Pro de la Autoestima y de la Responsabilidad Personal y Social (Toward a State of Esteem. Final Report of the State Committee to Promote Self-Esteem and Personal and Social Responsibility).

    Science.gov (United States)

    California State Dept. of Education, Sacramento.

    This is the Spanish version of the final report of a California Task Force created to promote self-esteem and personal responsibility. It begins with an executive summary listing key principles of the task force and providing recommendations and discussions in each of six major areas upon which the report focuses. The next section presents the…

  1. Final Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Glasser, Alan H. [Fusion Theory and Computation Inc., Kingston, WA (United States)

    2018-02-02

    Final technical report on DE-SC0016106. This is the final technical report for a portion of the multi-institutional CEMM project. This report is centered around 3 publications and a seminar presentation, which have been submitted to E-Link.

  2. Survival prediction among nursing home residents: A longitudinal study.

    Science.gov (United States)

    Lai, Claudia Kam Yuk; Ho, Lily Yuen Wah; Chin, Kenny Chi Wing; Kwong, Enid Wai Yung

    2018-03-01

    To determine the survival time and predictors of survival of residents in a nursing home. Nursing home residents admitted from June 2008 (when the nursing home started operating) to December 2012 (n = 230) to a new nursing home in Hong Kong were prospectively followed. The predictors of survival in the residents were assessed annually, with the exception of those who did not want to continue with the study, or were hospitalized, discharged from the nursing home or died, to compare changes occurring from 2008 to 2012. Cox's regression analysis was used to examine the predictors of survival. A total of 66 of the nursing home residents (28.7%) died during the study period. The median length of survival was 20.46 months. Sex, the number of diseases, depressive symptoms, cognitive status and nutritional status were found to be significant predictors of survival. It is crucial for healthcare providers to offer quality care to residents in long-term care to enhance their well-being in the final sojourn of their lives. Although there are no consistent reports of predictors in the international literature, it is important to address the modifiable predictors, as this might lead to improvements in the quality of life of the residents. Geriatr Gerontol Int 2018; 18: 428-433. © 2017 Japan Geriatrics Society.

  3. Effect of chicken meat environment on gene expression of Campylobacter jejuni and its relevance to survival in food.

    Science.gov (United States)

    Ligowska, Małgorzata; Cohn, Marianne Thorup; Stabler, Richard A; Wren, Brendan W; Brøndsted, Lone

    2011-03-01

    Poultry meat is the major food source responsible for gastrointestinal infections caused by the human pathogen Campylobacter jejuni. Even though C. jejuni does not grow below 30 °C, the bacterium survives on raw meat surfaces at refrigerated temperatures and thus poses a risk to the consumer. Previously, we have shown that chicken meat juice prolongs survival of C. jejuni at 5 °C compared to laboratory medium, suggesting that compounds present in meat juice influence adaptation to low temperatures. In the present study we have used chicken meat juice to identify C. jejuni genes that are differentially expressed in a typical chicken meat environment encountered by consumers. The analysis showed that chicken meat juice increased expression of luxS involved in quorum sensing, as well as a gene involved in O-linked flagellin glycosylation in C. jejuni, while expression of haemin uptake and the peroxide stress response genes were reduced. Furthermore, we propose that LuxS may play a key role in adaptation to the chicken meat juice environment, as lack of the luxS gene reduces the ability of C. jejuni to survive in chicken meat juice at low temperature. Finally, our data suggest that part of an ABC transport system is induced and we speculate that uptake of cryoprotectants may be important for C. jejuni to adapt to low temperature. In summary, we found that C. jejuni has a specific but limited transcriptional response to chicken meat juice and that luxS has an impact on the prolonged survival of C. jejuni in this important environment in the food chain. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. Survival and personal identity in orphism

    Directory of Open Access Journals (Sweden)

    Carlos Megino Rodríguez

    2016-10-01

    Full Text Available The aim of the article is to clarify the conditions which are fulfilled by the soul in orphism in order to base on it the possibility of self-survival. To this end, we study what the soul consists of in orphism, analyzing all orphic testimonies that allow us to draw conclusions in connection with the role of the soul in the orphic conception of personal identity. We also take into account the role played by other factors in orphism, like the body and memory, as possible criteria for personal identity. Finally, we conclude that the soul in orphism is the bearer of the personal identity, because it is a substantive, individual and independent entity, of a unique and permanent nature, immortal and the subject of a unique and untransferable vital history.

  5. Estimating haplotype effects for survival data.

    Science.gov (United States)

    Scheike, Thomas H; Martinussen, Torben; Silver, Jeremy D

    2010-09-01

    Genetic association studies often investigate the effect of haplotypes on an outcome of interest. Haplotypes are not observed directly, and this complicates the inclusion of such effects in survival models. We describe a new estimating equations approach for Cox's regression model to assess haplotype effects for survival data. These estimating equations are simple to implement and avoid the use of the EM algorithm, which may be slow in the context of the semiparametric Cox model with incomplete covariate information. These estimating equations also lead to easily computable, direct estimators of standard errors, and thus overcome some of the difficulty in obtaining variance estimators based on the EM algorithm in this setting. We also develop an easily implemented goodness-of-fit procedure for Cox's regression model including haplotype effects. Finally, we apply the procedures presented in this article to investigate possible haplotype effects of the PAF-receptor on cardiovascular events in patients with coronary artery disease, and compare our results to those based on the EM algorithm. © 2009, The International Biometric Society.

  6. Climate policy, asymmetric information and firm survival

    International Nuclear Information System (INIS)

    Hagem, C.

    2001-02-01

    The purpose of this paper is to compare the effect of different domestic climate policy instruments under asymmetric information when the regulator wants to secure the survival of a specific firm. It is a well-known result from economic theory that emission taxes lead to a cost-effective distribution of abatement across polluters. However, if the regulator wants to ensure the survival of a specific firm, it may need to design policy instruments that reduce the firm's cost of complying with an emission tax regime. The climate policy instruments considered in this paper are tradable emission permits with distribution of free permits, emission taxes in combination with a fixed subsidy, and two types of voluntary agreements. It demonstrates first that if distributing free tradable permits shall have a preventing effect, the allocation of permits has to be made contingent on production. It further shows that a voluntary agreement where a specific abatement target is set by the regulator can prevent a shutdown but leads to lower welfare than the use of emission taxes in combination with a fixed subsidy. And finally it illustrates that a voluntary agree